2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
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The data below in the left column is taken directly from the Guidelines document while the data in the right hand column is intended to clarify the information for patients, lay people and those who are not accustomed to reading scientific documents. This data is provided by the HCMA and should you have any questions or comments regarding the RIGHT column, please direct them to Lisa Salberg, CEO HCMA –lisa@4hcm.org
A complete copy of the Guidelines document can be downloaded on the right side of your screen – all citations are located within the document – as there are 453 citations in this article, for the purpose of space, we simply included them in the attached PDF. This data is also included as a PDF to the right – we would NOT suggest printing this screen as it is a very long document. To print a copy of this information click here and download the PDF Download Complete PDF of Guidelines Download Complete PDF of the HCMA's patient friendly version of the Guidelines
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2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines |
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Preamble |
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It is essential that the medical profession play a central role in critically evaluating the evidence related to drugs, devices, and procedures for the detection, management, or prevention of disease. Properly applied, rigorous, expert analysis of the available data documenting absolute and relative benefits and risks of these therapies and procedures can improve the effectiveness of care, optimize patient outcomes, and favorably affect the cost of care by focusing resources on the most effective strategies. One important use of such data is the production of clinical practice guidelines that, in turn, can provide a foundation for a variety of other applications such as performance measures, appropriateness use criteria, clinical decision support tools, and quality improvement tools. The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly engaged in the production of guidelines in the area of cardiovascular disease since 1980. The ACCF/AHA Task Force on Practice Guidelines (Task Force) is charged with developing, updating, and revising practice guidelines for cardiovascular diseases and procedures, and the Task Force directs and oversees this effort. Writing committees are charged with assessing the evidence as an independent group of authors to develop, update, or revise recommendations for clinical practice. Experts in the subject under consideration have been selected from both organizations to examine subject-specific data and write guidelines in partnership with representatives from other medical practitioner and specialty groups. Writing committees are specifically charged to perform a formal literature review, weigh the strength of evidence for or against particular tests, treatments, or procedures, and include estimates of expected health outcomes where data exist. Patient-specific modifiers, co-morbidities, and issues of patient preference that may influence the choice of tests or therapies are considered. When available, information from studies on cost is considered, but data on efficacy and clinical outcomes constitute the primary basis for recommendations in these guidelines. In analyzing the data and developing the recommendations and supporting text, the writing committee used evidence-based methodologies developed by the Task Force, which are described elsewhere.' The committee reviewed and ranked evidence supporting current recommendations with the weight of evidence ranked as Level A if the data were derived from multiple randomized clinical trials or meta-analyses. The committee ranked available evidence as Level B when data were derived from a single randomized trial or nonrandomized studies. Evidence was ranked as Level C when the primary source of the recommendation was consensus opinion, case studies, or standard of care. In the narrative portions of these guidelines, evidence is generally presented in chronological order of development. Studies are identified as observational, retrospective, prospective, or randomized when appropriate. For certain conditions for which inadequate data are available, recommendations are based on expert consensus and clinical experience and ranked as Level C. An example is the use of penicillin for pneumococcal pneumonia, for which there are no randomized trials and treatment is based on clinical experience. When recommendations at Level C are supported by historical clinical data, appropriate references (including clinical reviews) are cited if available. For issues where sparse data are available, a survey of current practice among the clinicians on the writing committee was the basis for Level C recommendations and no references are cited. The schema for Classification of Recommendations and Level of Evidence is summarized in T1 Table 1, which also illustrates how the grading system provides an estimate of the size and the certainty of the treatment effect. A new addition to the ACCF/AHA methodology is a separation of the Class III recommendations to delineate whether the recommendation is determined to be of “no benefit” or associated with “harm” to the patient. In addition, in view of the increasing number of comparative effectiveness studies, comparator verbs and suggested phrases for writing recommendations for the comparative effectiveness of one treatment/strategy with respect to another for Class of Recommendation I and IIa, Level of Evidence A or B only have been added.
The Task Force makes every effort to avoid actual, potential, or perceived conflicts of interest that may arise as a result of industry relationships with industry and other entities (RWI) among the writing committee. Specifically, all members of the writing committee, as well as peer reviewers of the document, are asked to disclose all relevant relationships and those 12 months prior to initiation of the writing effort. The policies and procedures for RWI for this guideline were those in effect at the initial meeting of this committee (March 28, 2009), which included 50% of the writing committee with no relevant RWI. All guideline recommendations require a confidential vote by the writing committee and must be approved by a consensus of the members voting. Members who were recused from voting are indicated on the title page of this document with detailed information included in Appendix 1. Members must recuse themselves from voting on any recommendations where their RWI apply. If a writing committee member develops a new RWI during his/her tenure, he/she is required to notify guideline staff in writing. These statements are reviewed by the Task Force and all members during each conference call and/or meeting of the writing committee and are updated as changes occur. For detailed information regarding guideline policies and procedures, please refer to the ACCF/AHA methodology and policies manual.1 RWI pertinent to this guideline for authors and peer reviewers are disclosed in Appendixes 1 and 2, respectively. Disclosure information for the Task Force is also available online at http://www.cardiosource.org/ACC/About-ACC/Leadership/ Guidelines-and-Documents-Task-Forces.aspx. The work of the writing group was supported exclusively by the ACCF and AHA without commercial support. Writing group members volunteered their time for this effort.
The ACCF/AHA practice guidelines address patient populations (and healthcare providers) residing in North America. As such, drugs that are currently unavailable in North America are discussed in the text without a specific class of recommendation. For studies performed in large numbers of subjects outside of North America, each writing group reviews the potential impact of different practice patterns and patient populations on the treatment effect and on the relevance to the ACCF/AHA target population to determine whether the findings should inform a specific recommendation.
The ACCF/AHA practice guidelines are intended to assist healthcare providers in clinical decision making by describing a range of generally acceptable approaches for the diagnosis, management, and prevention of specific diseases or conditions. These practice guidelines represent a consensus of expert opinion after a thorough review of the available current scientific evidence and are intended to improve patient care. The guidelines attempt to define practices that meet the needs of most patients in most circumstances. The ultimate judgment regarding care of a particular patient must be made by the healthcare provider and patient in light of all the circumstances presented by that patient. Thus, there are situations in which deviations from these guidelines may be appropriate. Clinical decision making should consider the quality and availability of expertise in the area where care is provided. When these guidelines are used as the basis for regulatory or payer decisions, the goal should be improvement in quality of care. The Task Force recognizes that situations arise for which additional data are needed to better inform patient care; these areas will be identified within each respective guideline when appropriate.
Prescribed courses of treatment in accordance with these recommendations are effective only if they are followed. Because lack of patient understanding and adherence may adversely affect outcomes, physicians and other healthcare providers should make every effort to engage the patient’s active participation in prescribed medical regimens and lifestyles.
The guidelines will be reviewed annually by the Task Force and considered current unless they are updated, revised, or withdrawn from distribution. The Executive Summary and recommendations are published in the â—â—â— issue of the Journal of the American College of Cardiology and the â—â—â— issue of Circulation. The full-text version of the guidelines is e-published in the same issue of these journals and is posted on the ACC (www.cardiosource.org) and AHA (my. americanheart.org) World Wide Web sites.
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The purpose of this document is to provide understandable and usable information for patients and their families when making decisions regarding the treatment options, surveillance and management of hypertrophic cardiomyopathy. The American Heart Association, in partnership with the American College of Cardiology, in collaboration with American Association of Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons have all contributed to this document and this will be used as the standard of care for the treatment of those with hypertrophic cardiomyopathy and those with a family history of HCM requiring screening for the condition for the foreseeable future. The purpose of the patient guideline is to break down the technical language of the document and place it in layman’s terms so that patients may have articulate and scientifically-valid discussions with their healthcare providers when choosing screening options, treatment options, interventions, and lifestyle modifications.
To begin with, patients and families should understand the terminology and their level in the class of the recommendation. Level A indicates multiple populations have been evaluated and the data is collected from multiple randomized clinical trials or meta-analysis -- it is important to understand that there is very little Level A evidence in hypertrophic cardiomyopathy. In Level B limited populations have been evaluated and the data is derived from single randomized trials or non-randomized studies. There is some information on HCM that meets the Level B classification. Level C is a very limited population of valuation. Consensus opinions of experts’ case studies for the standard of care are used to validate Level C recommendations. Level C is the most common level of evidence noted in this document. Class I recommendations are those that should be performed and administered. In Class IIa it is reasonable to perform this procedure or administer this treatment and generally advised - meaning the benefits outweigh the risk. Class IIb procedures may be considered, while additional studies may still need to be collected and registry data would be helpful to decide whether it is more beneficial than the risk benefit ratio does seem to favor benefit and thereby may be considered as a treatment or procedural option. Class III is broken down into two classifications - no benefit or harm. Any indication that is a Class III should be avoided and, if a physician is recommending a treatment that falls into Class III recommendation, patients are advised to seek a second opinion prior to moving forward.
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1. Introduction |
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1.1. Methodology and Evidence Review |
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The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted through January 2011. Searches were limited to studies, reviews, and other evidence conducted in human subjects and published in English. Key search words included, but were not limited to, hypertrophic cardiomyopathy (HCM), surgical myectomy, ablation, exercise, sudden cardiac death (SCD), athletes, dual-chamber pacing, left ventricular outflow tract (LVOT) obstruction, alcohol septal ablation, automobile driving and implantable cardioverterdefibrillators (ICDs), catheter ablation, defibrillators, genetics, genotype, medical management, magnetic resonance imaging, pacing, permanent pacing, phenotype, pregnancy, risk stratification, sudden death in athletes, surgical septal myectomy, and septal reduction. Additionally, the committee reviewed documents related to the subject matter previously published by the ACCF and AHA. References selected and published in this document are representative and not all-inclusive.
To provide clinicians with a comprehensive set of data, whenever deemed appropriate or when published, the absolute risk difference and number needed to treat or harm will be provided in the guideline, along with confidence intervals and data related to the relative treatment effects, such as odds ratio, relative risk, hazard ratio, or incidence rate ratio |
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1.2. Organization of the Writing Committee |
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The committee was composed of physicians and cardiac surgeons with expertise in HCM, invasive cardiology, noninvasive testing and imaging, pediatric cardiology, electrophysiology, and genetics. The committee included representatives from the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons.
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1.3. Document Review and Approval |
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This document was reviewed by 2 outside reviewers nominated by both the ACCF and AHA, as well as 2 reviewers each from the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. Other content reviewers included members from the ACCF Adult Congenital and Pediatric Cardiology Council, ACCF Surgeons’ Scientific Council, and ACCF Interventional Scientific Council. All information on reviewers’ RWI was distributed to the writing committee and is published in this document (Appendix 2). This document was approved for publication by the governing bodies of the ACCF and the AHA and endorsed by the AQ: 6 [INSERT ENDORSERS]. |
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1.4. Scope of the Guideline |
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HCM is characterized by left ventricular (LV) hypertrophy without dilatation in the absence of another cardiac or systemic condition that could be responsible for the extent of hypertrophy that is present. Mutations involving the gene encoding proteins in the sarcomere are responsible for the majority of genetically mediated cases.
Although there are reports of this disease dating back to the 1800s, the first modern pathologic description was provided over 50 years ago by Teare2 and the most important early clinical report by Braunwald et al in 1964.3 Since then, there has been a growing understanding of the complexity and diversity of the underlying genetic substrate, the clinical phenotype, natural history, and approaches to treatment. The impetus for the guidelines is based on an appreciation of the frequency of this clinical entity and a realization that many aspects of clinical management, including the use of diagnostic modalities and genetic testing, lack consensus. Moreover, the emergence of 2 different approaches to septal
AQ: 7 reduction therapy, for example, septal myectomy and alcohol septal ablation, in addition to the ICD have created considerable controversy about the relative indications for these procedures. The discussion and recommendations about the various diagnostic modalities apply to patients with established HCM and to a variable extent to patients with a high index of suspicion of the disease. Although the Task Force was aware of the lack of high levels of evidence regarding HCM provided by clinical trials, it was believed that a guideline document based on expert consensus that outlines the most important diagnostic and management strategies would be helpful. To facilitate ease of use, it was decided that recommendations in the pediatric and adolescent age groups would not appear as a separate section but instead would be integrated into the overall content of the guideline where relevant.
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2. Prevalence/Nomenclature/Differential Diagnosis |
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2.1. Prevalence |
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HCM is a common genetic cardiovascular disease. In addition, HCM is a global disease,4 with epidemiological studies from several parts of the world5 reporting a similar prevalence of LV hypertrophy, the quintessential phenotype of HCM, to be about 0.2% (ie, 1:500) in the general population, which is equivalent to at least 600 000 people affected in the United States.6 This estimated frequency in the general population appears to exceed the relatively uncommon occurrence of HCM in cardiology practices, implying that most without symptoms or shortened life expectancy.
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2.2. Nomenclature |
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2.2.1. Historical Context |
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Although HCM is the preferred nomenclature to describe this disease, confusion over the names used to describe, define,and characterize the entity of HCM has arisen over the years. At last count, _80 individual names, terms, and acronyms have been used (most by early investigators) to describe HCM.7 Furthermore, nomenclature that was popular in the 1960s and 1970s, such as IHSS (idiopathic hypertrophic subaortic stenosis) or HOCM (hypertrophic obstructive cardiomyopathy), is potentially confusing by virtue of the inference that LVOT is an invariable and obligatory component of the disease. In fact, fully one third of patients have noobstruction either at rest or with physiologic provocation.8
Although terms such as IHSS and HOCM persist occasionally in informal usage, they now rarely appear in the literature, whereas HCM, initially used in 1979, allows for both the obstructive and nonobstructive hemodynamic forms and has become the predominant formal term used to designate this disease.7 |
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2.2.2. Clinical Definition and Differential Diagnosis |
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The generally accepted definition of HCM, the clinical entity that is the subject of this guideline, is a disease state characterized by unexplained LV hypertrophy associated with non-dilated ventricular chambers in the absence of another cardiac or systemic disease that itself would be capable of producing the magnitude of hypertrophy evident in a given patient,6,7,9–12 with the caveat that patients who are genotype positive may be phenotypically negative without overt hypertrophy.13,14 Clinically, HCM is usually recognized by maximal LV wall thickness _15 mm, with wall thickness of 13 to 14 mm considered borderline, particularly in the presence of other compelling information (eg, family history of HCM), based on echocardiography. In terms of LV wall-thickness measurements, the literature at this time has been largely focused on echocardiography, although cardiovascular magnetic resonance (CMR) is now used with increasing frequency in HCM,15 and we presume that data with this latter modality will increasingly emerge. In the case of children, increased LV wall thickness is defined as wall thickness _2 standard deviations above the mean (z score _2) for age, sex, or body size. However, it should be underscored that in principle, any degree of wall thickness is compatible with the presence of the HCM genetic substrate and that an emerging subgroup within the broad clinical spectrum is composed of family members with disease causing sarcomere mutations but without evidence of the disease phenotype (ie, LV hypertrophy).16–19 These individuals are usually referred to as being “genotype positive/phenotype negative” or as having “subclinical HCM.” Furthermore, although a myriad of patterns and distribution of LV hypertrophy (including diffuse and marked) have been reported in HCM,15,20,21 about one third of patients have largely segmental wall thickening involving only a small portion of the left ventricle, and indeed such patients with HCM usually have normal calculated LV mass.15 The clinical diagnosis of HCM may also be buttressed by other typical features, such as family history of the disease, cardiac symptoms, tachyarrhythmias, or electrocardiographic abnormalities.9,10
Differential diagnosis of HCM and other cardiac conditions (with LV hypertrophy) may arise, most commonly, hypertensive heart disease and the physiologic remodeling associated with athletic training (“athlete’s heart”).22–25 These are not uncommon clinical scenarios, and confusion between mild morphologic expressions of HCM and other conditions with LV hypertrophy usually arises when maximum wall thickness is in the modest range of 13 mm to 15 mm. In older patients with LV hypertrophy and a history of systemic hypertension, coexistence of HCM is often a consideration. The likelihood of HCM can be determined by identification of a diagnostic sarcomere mutation or inferred by marked LV thickness _25 mm and/or LVOT obstruction with systolic anterior motion (SAM) and mitral-septal contact.
The important distinction between pathologic LV hypertrophy (ie, HCM) and physiologic LV hypertrophy (ie, athlete’s heart) is impacted by the recognition that athletic conditioning can produce LV, right ventricular, and left atrial (LA) chamber enlargement, ventricular septal thickening, and even aortic enlargement26 but is often resolved by noninvasive markers,including sarcomeric mutations or family history of HCM, LV cavity dimension (if enlarged, favoring athlete’s heart), pattern of LV hypertrophy (if unusual location or noncontiguous, favoring HCM), or short deconditioning periods in which a decrease in wall thickness would favor athlete’s heart.
Notably, it is evident that metabolic or infiltrative storage disorders with LV hypertrophy in babies, older children, and young adults can mimic clinically diagnosed HCM (attributable to sarcomeric protein mutations), for example, conditions such as mitochondrial disease,27,28 Fabry disease,29 or storage diseases caused by mutations in the genes encoding the _-2-regulatory subunit of the adenosine monophosphate (AMP)-activated protein kinase (PRKAG2) or the X-linked lysosome-associated membrane protein gene (LAMP2; Danon disease).30–33 Use of the term HCM is not appropriate to describe these and other patients with LV hypertrophy that occurs in the context of a multisystem disorder such as Noonan syndrome (with craniofacial and congenital heart malformations as well as LV hypertrophy from mutations in genes of the RAS [RAt Sarcoma] pathway 14, 15), or distinct cardiomyopathies such as Pompe disease (also a glycogen storage disease II, with skeletal muscle weakness and cardiomyopathy because of deficiency of _1,4 glycosidase [acid maltase])34–38 (Figure 1). In addition, differential diagnosis of HCM may require distinction from systemic hypertension or physiologic athlete’s heart23 or from dilated cardiomyopathy when HCM presents in the end stage.39 |
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2.2.3. Impact of Genetics |
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On the basis of the genotype-phenotype data available at this time, HCM is regarded here as a disease entity caused by autosomal dominant mutations in genes encoding protein components of the sarcomere and its constituent myofilament elements. 30,40–42 Intergenetic diversity is compounded by considerable intragene heterogeneity, with >1000 mutations identified among at least 8 genes. The current weight of evidence supports the view that the vast majority of genes and mutations responsible for clinically diagnosed HCM encode proteins within and associated with the sarcomere, accounting in large measure for those patients described in the voluminous amount of HCM literature published over 50 years.30,40–42
In conclusion, the writing committee believes that the most prudent recommendation for nomenclature is that hypertrophic cardiomyopathy and the acronym HCM remain a clinical diagnosis limited to those patients in whom (1) overt disease expression (with LV hypertrophy) appears to be confined to the heart and (2) the definitive mutation is either one of a gene encoding proteins of the cardiac sarcomere or alternatively when the genotype is unresolved using current genetic testing. Therefore, nomenclature that describes patients as “Noonan hypertrophic cardiomyopathy” is discouraged, whereas “Noonan syndrome with LV hypertrophy” or “Noonan syndrome with cardiomyopathy” is preferred. |
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2.2.4. Hypertrophic Cardiomyopathy Centers |
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The writing committee considers it important to emphasize that HCM is a complex disease entity with a broad (and increasing) clinical and genetic spectrum.9 Although HCM is one of the most common forms of genetic heart disease and relatively common in the general population,6 this disease entity is infrequent in general clinical practice, with most cardiologists responsible for the care of only a few patients with HCM.43 This principle has led to an impetus for establishing clinical programs of excellence— usually within established centers—in which cardiovascular care is focused on the management of HCM (ie, “HCM centers”).43,44 Such programs are staffed by cardiologists and cardiac surgeons familiar with the contemporary management of HCM and offer all diagnostic and treatment options, including genetic testing and counseling, comprehensive transthoracic echocardiogram (TTE), CMR imaging, both surgical septal myectomy and alcohol ablation, and the management of atrial fibrillation (AF)/atrial flutter, and ICDs. Another advantage is the potential to perform outcomes research on large groups of patients. Although the writing committee does not necessarily recommend that all patients with HCM should be evaluated in such centers, nevertheless, it is the strong view that patients with this disease may well benefit from a clinical environment with specific expertise in HCM. The selection of patients for referral to an HCM center should be based largely on the judgment of the managing cardiologist and the degree to which he or she is comfortable advising and evaluating patients with HCM with a particular clinical profile. |
Comment from HCMA: In 1996 when the HCMA was created there were 3-4 programs actively serving the HCM community in an organized and comprehensive manner. In the past 16 years the HCMA has worked with nearly 30 programs in the USA to develop them into fully-functional HCM programs able to serve the needs of this patient/family population.
In addition to the services and expertise listed to the left, the HCMA has found that, while all programs must start somewhere, those with high volumes have the most constant outcomes that benefit patients.
HCM Centers of Excellence-COE’s and HCM Programs (which have slightly lower patient volumes than COE’s) provide the best overall care of patients with HCM. It is, however, important to state that the hometown cardiologist is an important partner to both the patient and COE/HCM program as collaboratively we will all improve our knowledge and understanding of HCM and improve patient outcomes. |
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3. Clinical Course and Natural History, Including Absence of Complications |
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HCM is a heterogeneous cardiac disease with a diverse clinical presentation and course, presenting in all age groups from infancy to the very elderly.9,10,39,45 Most affected individuals probably achieve a normal life expectancy without disability or the necessity for major therapeutic interventions. 46–49 On the other hand, in some patients, HCM is associated with disease complications that may be profound, with the potential to result in disease progression or premature death.9,10,39,45,50,51 When the disease does result in significant complications, there are 3 relatively discrete but not mutually exclusive pathways of clinical progression (Figure 2):
1. SCD due to unpredictable ventricular tachyarrhythmias, most commonly in young asymptomatic patients _35 years of age50–59 (including competitive athletes).58,59
2. Heart failure characterized by exertional dyspnea (with or without chest discomfort) that may be progressive despite preserved systolic function and sinus rhythm, or in a small end stage with LV remodeling and systolic dysfunction caused by extensive myocardial scarring.39
3. AF, either paroxysmal or chronic, also associated with various degrees of heart failure60 and an increased risk of systemic thromboembolism and both fatal and nonfatal stroke.
The natural history of HCM can be altered by a number of therapeutic interventions: ICDs for secondary or primary prevention of sudden death in patients with risk factors54–56; drugs appropriate to control heart failure symptoms (principally those of exertional dyspnea and chest discomfort),9,10 surgical septal myectomy61 or alcohol septal ablation62 for progressive and drug-refractory heart failure caused by LVOT obstruction; heart transplantation for systolic (or less frequently intractable diastolic) dysfunction associated with severe unrelenting symptoms39; and drug therapy or possibly radiofrequency ablation or surgical maze procedure for AF.63–65 |
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4. Pathophysiology |
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The pathophysiology of HCM is complex and consists of multiple interrelated abnormalities, including LVOT obstruction, diastolic dysfunction, mitral regurgitation, myocardial ischemia, and arrhythmias.9,66,67 It is clinically important to distinguish between the obstructive and nonobstructive forms of HCM because management strategies are largely dependent on the presence or absence of symptoms caused by obstruction. |
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4.1. LVOT Obstruction |
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The original observations by Brock68 and Braunwald et al3 emphasized the functional subvalvular LVOT gradient, which was highly influenced by alterations in the load and contractility of the left ventricle. The clinical significance of the outflow tract gradient has periodically been controversial, 69–72 but careful studies have shown definitively that true mechanical obstruction to outflow does occur.66,67 For HCM, it is the peak instantaneous LV outflow gradient rather than the mean gradient that influences treatment decisions. Throughout the remainder of this document the term gradient will be used to denote peak instantaneous gradient. Up to one third of patients with HCM will have obstruction under basal (resting) conditions (defined as gradients _30 mm Hg). Another one third or more of patients will have labile, physiologically provoked gradients (_30 mm Hg at rest and _30 mm Hg with physiologic provocation).8 The final one third of patients will have the nonobstructive form of HCM (gradients _30 mm Hg at rest and with provocation) (Table 2). Marked gradients _50 mm Hg, either at rest or with provocation, represent the conventional threshold for surgical or percutaneous intervention if symptoms cannot be controlled with medications.
Obstruction causes an increase in LV systolic pressure, which leads to a complex interplay of abnormalities including prolongation of ventricular relaxation, elevation of LV diastolic pressure, mitral regurgitation, myocardial ischemia, and a decrease in forward cardiac output.9,66,67 Outflow obstruction usually occurs in HCM by virtue of mitral valve SAM and mitral-septal contact. Although the mechanism of the outflow tract gradient in HCM was initially thought to be caused by systolic contraction of the hypertrophied basal ventricular septum encroaching on the LVOT, most recent studies emphasize that during ventricular systole, flow against the abnormally positioned mitral valve apparatus results in drag force on a portion of the mitral valve leaflets, which pushes the leaflets into the outflow tract.66,67,75–78 Muscular obstruction can also be present in the midcavitary region, occasionally because of hypertrophied papillary muscles abutting the septum79 or anomalous papillary muscle insertion into the anterior mitral leaflet.80
Obstruction to LV outflow is dynamic, varying with loading conditions and contractility of the ventricle.3 Increased myocardial contractility, decreased ventricular volume, or decreased afterload increases the degree of subaortic obstruction. Patients may have little or no obstruction of the LVOT at rest but can generate large LVOT gradients under conditions such as exercise, the strain phase of the Valsalva maneuver, or during pharmacologic provocation.66,67 There is often large spontaneous variation in the severity of the gradient during day-to-day activities or even with food or alcohol intake81; exacerbation of symptoms during the postprandial period is common. Importantly, it has been well established that LVOT obstruction contributes to the debilitating heart failure–related symptoms that may occur in HCM66,67 and is also a major determinant of outcome.45
The presence and magnitude of outflow obstruction is usually assessed with 2-dimensional echocardiography and continuous wave Doppler. It is a late-peaking systolic velocity that reflects the occurrence of subaortic obstruction late in systole, and the peak instantaneous gradient derived from the peak velocity should be reported. If the resting outflow gradient is _50 mm Hg, provocative measures may be used to ascertain if higher gradients can be elicited, preferably with physiologic exercise (stress echocardiography) but alternatively with the Valsalva maneuver or selectively with amyl nitrite.3,10 Provocation with dobutamine infusion during Doppler echocardiography is no longer recommended as a strategy to induce outflow gradients in HCM. However in equivocal cases, cardiac catheterization with isoproterenol infusion may further aid in eliciting a provocable gradient.82 Otherwise, routine invasive cardiac catheterization to document outflow gradients is necessary only when there is discordant data from Doppler echocardiography and the physical examination.10 The peak-to-peak gradient obtained with catheterization most closely approximates the peak instantaneous gradient by continuous wave Doppler echocardiography.73,74 |
Left ventricular outflow tract obstruction, hereafter in this document referred to LVOT, was originally believed to explain all cases of hypertrophic cardiomyopathy. We have since learned that many patients will not have obstruction at all and as many as one-third of patients may have obstruction that is best described as transient in nature, meaning it can come and go at any time with activity or provocation.
The best explanation for a layperson to understand obstruction must come from a complete understanding of how blood moves through the heart. In a normal heart ,blood enters the atria, moves through the mitral valve to the left ventricle and exits the heart through the aortic valve - the area under the aortic valve is referred to as the left ventricular outflow tract. Patients with HCM may develop a “pressure gradient”. This term refers to abnormal pressures within the left ventricle that are created because the blood attempting to leave the left ventricle is impeded by a temporary blockage. This is NOT the same type of a blockage that causes a “heart attack”. This temporary blockage of blood flow may occur high up in the outflow tract, in the mid-cavity or in the lower part of the left ventricular cavity. The degree of obstruction is measured in millimeters of mercury with a normal gradient being zero in an unobstructed heart - gradient measured over 30 mmHg at rest or with provocation are present in approximately 2/3 of all patients with HCM. Gradients measuring 50 mmHg or greater at rest or provocation are those patients who are viewed as candidates for surgical or non-surgical septal reduction therapies. Obstruction causes a complex process to occur within the left ventricle - it raises left ventricular systolic pressures which can lead to prolongation of relaxation, elevation and diastolic pressure, mitral regurgitation, myocardial ischemia and a decrease in cardiac output. Obstruction has several contributing mechanisms including the mitral valve inappropriately making contact with the septal wall. This is, most likely, the most common form of obstruction, but not the only method in which obstruction can occur. Obstruction can occur in the mid-cavity region. This is most commonly caused by thickened papillary muscles making contact with the septum or being inserted directly into the mitral valve apparatus. Obstruction can vary with loading conditions and functioning of the ventricle; therefore, patients, on exam, may have a very small gradient in resting situations but when stressed, with exercise Valsalva maneuver (bearing down) or pharmaceutical provocation, this gradient can grow severely. Daily activities including exercise, food consumption, alcohol consumption or mild dehydration can also provoke large gradients. It is well-established in the literature that LVOT contributes to debilitating heart-failure related symptoms and those with HCM obstruction should be measured using two-dimensional echocardiography and continuous wave Doppler. If the resting gradient is under 50 mmHg provocable measures should be used to ascertain if a higher gradient might exist. The preferred method of provocation is physiologic exercise or a stress echocardiogram but, alternatively, a Valsalva maneuver, or in selected patients, the use of amyl nitrate can be helpful. Provocation with dobutamine during echocardiography is no longer recommended as a strategy to induce outflow tract obstruction in HCM, as it has proven unreliable and misleading. However, in rare cases, the use of cardiac catheterization with isoproterenol may aid in identifying provocable gradients. Otherwise routine invasive cardiac catheterization is necessary only when there is an unresolved question from the Doppler echo and physical exam. |
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4.2. Diastolic Dysfunction |
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Diastolic dysfunction arising from multiple factors is a major pathophysiologic abnormality in HCM that ultimately affects both ventricular relaxation and chamber stiffness.66,67,83 Impairment of ventricular relaxation results from the systolic contraction load caused by outflow tract obstruction, nonuniformity of ventricular contraction and relaxation, and delayed inactivation caused by abnormal intracellular calcium reuptake. Severe hypertrophy of the myocardium results in an increase in chamber stiffness. Diffuse myocardial ischemia may further affect both relaxation and chamber stiffness. A compensatory increase in the contribution of late diastolic filling during atrial systole is associated with these alterations. 84 With exercise or any other type of catecholamine stimulation, the decrease in diastolic filling period as well as myocardial ischemia will further lead to severe abnormalities of diastolic filling of the heart, with chest pain and/or an increase in pulmonary venous pressure causing dyspnea. |
Diastole refers to the relaxation phase of the heartbeat. HCM will normally include some degree of diastolic dysfunction. This dysfunction includes a stiffening of the chamber and a failure for the chamber to relax. The thicker the walls become the more likely they are to become stiff and may also create something called myocardial ischemia ,which will be discussed in the next section. Diastolic dysfunction can lead to chest pain and/or increased pulmonary venous pressures causing shortness of breath. |
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4.3. Myocardial Ischemia |
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Severe myocardial ischemia and even infarction may occur in HCM.85,86 The myocardial ischemia is frequently unrelated to the atherosclerotic epicardial coronary artery disease (CAD) but is caused by supply–demand mismatch. Patients with HCM of any age have increased oxygen demand caused by the hypertrophy and adverse loading conditions. They also have compromised coronary blood flow to the LV myocardium because of intramural arterioles with thickened walls attributable to medial hypertrophy associated with luminal narrowing.87 |
Myocardial ischemia is frequently described as being related to coronary artery disease and the mismatch of supply and demand of oxygen within the heart walls. Myocardial ischemia and HCM is rarely associated with coronary artery disease. Those with HCM have an increased oxygen demand in the heart muscle caused by the thickening and abnormal conditions within the ventricle. Some may also have compromised coronary artery flow in the left ventricle because the walls have become thickened and narrow the blood vessels within the wall of the heart.
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4.4. Autonomic Dysfunction |
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During exercise, approximately 25% of patients with HCM have an abnormal blood pressure response defined by either a failure of systolic blood pressure to rise _20 mm Hg or a fall in systolic blood pressure.88,89 The presence of this finding is associated with a poorer prognosis.89,90 This inability to augment and sustain systolic blood pressure during exercise is caused by either the dynamic LVOT obstruction or systemic vasodilatation during exercise. It is speculated that autonomic dysregulation88 is present in patients with HCM and that the fall in blood pressure associated with bradycardia may be an abnormal reflex response to obstruction. |
Patients with HCM may have an abnormal blood pressure response when exercising. This means the blood pressure fails to increase as the body's demand for blood and oxygen increases. The presence of this finding is associated with a poorer prognosis. The inability to maintain or increase systolic blood pressure during exercise is the core problem. Why this happens has yet to be determined. It is either because of left ventricular outflow tract obstruction or systemic vasodilation. During exercise it is speculated that there is a phenomenon that occurs causing autonomic dysregulation The autonomic nervous system controls most of the involuntary reflexive activities of the human body. The system is constantly working to regulate the glands and many of the muscles of the body through the release or uptake of the neurotransmitters acetylcholine and norepinephrine. The autonomic nervous system is made up of two primary parts: the sympathetic and parasympathetic systems. The sympathetic nervous system prepares the body for emergencies or times of stress and is responsible for the body's "fight or flight" response when faced with a dangerous situation. During this response, the heart rate and blood pressure increase, the pupils of the eye dilate, and the digestive system slows down. The parasympathetic system helps the body's functions return to normal after they have been stimulated by the sympathetic nervous system and also has some responsibility for keeping the body's immune system properly functioning. Autonomic dysregulation involves malfunctioning of the autonomic nervous system, the portion of the nervous system that conveys impulses between the blood vessels, heart, and all the organs in the chest, abdomen, and pelvis and the brain (mainly the medulla, pons and hypothalamus).
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4.5. Mitral Regurgitation |
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Mitral regurgitation is common in patients with LVOT obstruction and may play a primary role in producing symptoms of dyspnea. The temporal sequence of events of eject-obstruct-leak supports the concept that the mitral regurgitation in most patients is a secondary phenomenon.66,67,91 The mitral regurgitation is usually caused by the distortion of the mitral valve apparatus from the SAM secondary to the LVOT obstruction. The jet of mitral regurgitation is directed laterally and posteriorly and predominates during mid andlate systole. An anteriorly directed jet should suggest an intrinsic abnormality of the mitral valve. If the mitral regurgitation is caused by distortion of leaflet motion by SAM of the mitral valve, the severity of the mitral regurgitation may be proportional to the LVOT obstruction in some patients. Changes in ventricular load and contractility that affect the severity of outflow tract obstruction similarly affect the degree of mitral regurgitation. It is important to identify patients with additional intrinsic disease of the mitral valve apparatus (prolapse or flail), because this finding influences subsequent treatment options.92 |
Mitral regurgitation is common in patients with outflow tract obstruction and may produce symptoms of shortness of breath. In HCM mitral regurgitation is usually caused by the mitral valve apparatus creating systolic anterior motion – SAM - secondary to obstruction. Careful evaluation of the exact type of mitral regurgitation is important, and like many other aspects of HCM, should be evaluated by an HCM center, who can help to identify the very unique and specific types of mitral valve abnormalities present in HCM patients.
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5. Diagnosis |
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The clinical diagnosis of HCM is conventionally made with cardiac imaging, at present most commonly with 2-dimensional echocardiography and increasingly with CMR. Morphologic diagnosis is based on the presence of a hypertrophied and nondilated left ventricle in the absence of another cardiac or systemic disease capable of producing the magnitude of hypertrophy evident in a patient (usually_15 mm in adults or the equivalent relative to body surface area in children). Genetic testing, which is now commercially available, is a powerful strategy for definitive diagnosis of affected genetic status and is currently used most effectively in the identification of affected relatives in families known to have HCM. |
Intentionally left blank as the guidelines document is self explanatory. |
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5.1. Genetic Testing Strategies/Family Screening—Recommendations |
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Class I 1. Evaluation of familial inheritance and genetic counseling is recommended as part of the assessment of patients with HCM.17,31,93–96 (Level of Evidence: B) 2. Patients who undergo genetic testing should also undergo counseling by someone knowledgeable in the genetics of cardiovascular disease so that results and their clinical significance can be appropriately reviewed with the patient.97–101 (Level of Evidence: B) 3. Screening (clinical, with or without genetic testing) is recommended in first-degree relatives of patients with HCM.17,31,93,94,96,102,103 (Level of Evidence: B) 4. Genetic testing for HCM and other genetic causes of unexplained cardiac hypertrophy is recommended in patients with an atypical clinical presentation of HCM or when another genetic condition is suspected to be the cause.104–106 (Level of Evidence: B)
Class IIa 1. Genetic testing is reasonable in the index patient to facilitate the identification of first-degree family members at risk for developing HCM.17,95,102 (Level of Evidence: B)
Class IIb 1. The usefulness of genetic testing in the assessment of risk of SCD in HCM is uncertain.107,108 (Level of Evidence: B)
Class III: No Benefit 1. Genetic testing is not indicated in relatives when the index patient does not have a definitive pathogenic mutation.17,31,93–96,109 (Level of Evidence: B) 2. Ongoing clinical screening is not indicated in genotype- negative relatives in families with HCM.109–112 (Level of Evidence: B) See Data Supplement 1: Genetics Table for further information on data supporting the recommendations for genetic testing strategies/family screening.
HCM is caused by an autosomal dominant mutation in genes that encode sarcomere proteins or sarcomer eassociated proteins. The most vigorous evidence indicates that 8 genes are known to definitively cause HCM: beta myosin heavy chain, myosin binding protein C, troponin T, troponin I, alpha tropomyosin, actin, regulatory light chain, and essential light chain.11,12,30,40–42 In addition, actinin and myozenin are associated with less definitive evidence for causing HCM. At this time there is inconclusive evidence to support other genes causing HCM,94,96,113,114 but research is ongoing and other genetic causes may be identified.93,115 A single mutation in 1 of the 2 alleles (or copies) of a gene is sufficient to cause HCM; however, 5% of patients with HCM have _2 mutations in the same gene or different genes.110,116
Genetic and/or clinical screening of all first-degree family members of patients with HCM is important to identify those with unrecognized disease. On the basis of family history, clinical screening, and pedigree analyses, the pattern of inheritance is ascertained to identify and counsel relatives at risk.101 Because familial HCM is a dominant disorder, the risk that an affected patient will transmit disease to each offspring is 50%. When a pathogenic mutation is identified in an index patient, the genetic status of each family member can be readily ascertained. Because HCM mutations are highly penetrant, a mutation conveys substantial (_95%) risk over a lifetime for developing clinical and/or phenotypic evidence of HCM.94,96,113,114
Genetic counseling before genetic testing will increase understanding of the medical and familial implications of test results, enabling informed decision making about potential risks and benefits.98,99 Genetic counseling can also reduce potential psychologic responses to learning one’s mutation status.4,101 Even when genetic testing is not undertaken, genetic counseling about the potential for familial transmission of HCM is medically important.
The occurrence of HCM can be isolated or sporadic, but the frequency of sporadic HCM is unresolved. Sporadic HCM can reflect an inaccurate family history, incomplete penetrance (absence of clinical expression despite the presence of a mutation) in family members, or a de novo (new) mutation that can initiate new familial disease.93,115
Because unrelated patients with HCM will have different mutations, a comprehensive sequence-based analysis of all HCM genes is necessary to define the pathogenic (eg, disease-causing) mutation in an index patient. Experienced clinical laboratories identify the pathogenic HCM mutation in approximately 60% to 70% of patients with a positive family history and approximately 10% to 50% of patients without a family history.93,102 Genetic testing may identify a pathogenic mutation (eg, analysis defines a sequence variant known to cause HCM) or a “likely pathogenic” mutation, a DNA variant that was previously unknown as a cause of HCM but has molecular characteristics that are similar to recognized HCM mutations. Genetic testing may also identify “variants of uncertain significance.” This term indicates that the nucleotide change is not commonly recognized to be variable (or polymorphic) in the general population and that some molecular characteristics of the variant suggest deleterious consequences (similar to all pathogenic mutations). Genetic analyses of family members can help establish or refute the causality of “likely pathogenic” and “variants of uncertain significance.” When a variant occurs in multiple clinically affected family members but is absent from clinically unaffected adult family members, the likelihood for pathogenicity increases. In contrast, when a variant occurs in multiple clinically unaffected adult family members, the likelihood for pathogenicity is low.
Adult patients with HCM and an established pathogenic mutation have increased risk for the combined endpoints of cardiovascular death, nonfatal stroke, or progression to New York Heart Association (NYHA) functional class III or IV compared with patients with HCM in whom no mutation is identified.103 Studies suggest that the presence of _1 HCMassociated sarcomere mutation is associated with greater severity of disease.110,111,117,118
When genetic testing reveals a mutation in the index patient, ascertainment of genetic status in first-degree relatives can be predictive of risk for developing HCM.105 Genetic counseling should precede genetic testing of family members.101 Relatives with overt HCM will have the same pathogenic HCM mutation as the index patient. Pathogenic mutations may also be identified in other relatives with unknown clinical status. These mutation carriers should be evaluated by physical examination, electrocardiography, and 2-dimensional echocardiography, and if HCM is identified, these individuals should undergo risk stratification (Section 6.3.1). Mutation carriers without evidence of HCM (genotype positive/phenotype negative) are at considerable risk for future development of HCM and guidelines to evaluate these individuals are discussed below.13,14 Mutation-negative family members and their descendents have no risk for developing HCM and do not need further evaluation. Information from genotyping may help define clinical manifestations and outcomes in specific families with HCM.94–96,105,107–109,119
When genetic testing is not performed or a mutation is not identified in the index patient, clinical screening of all first-degree family members is important to identify those with unrecognized HCM. Offspring of unaffected individuals do not warrant clinical screening unless prompted by unexpected signs or symptoms. For more information on screening intervals, see Section 5.4.1.
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Class I 1. Recommendations: It is recommended that the affected individual seek genetic counseling, if possible. If the affected person is no longer living, their family members should seek genetic counseling. The term genetic counseling refers to a consultation with a trained genetics counselor or a physician with extensive genetics knowledge and experience.
2. Those who undergo genetic testing should have their results reviewed by a specialist, who not only understands genetics, but also understands hypertrophic cardiomyopathy, as the results can be very complicated and confusing to physicians with limited experience in cardiovascular genetics to fully appreciate.
3. Screening family members for HCM is recommended in first-degree relatives of patients with HCM. First degree is described as 1° away from the affected individual, which would include parents, siblings and children of the affected individual.
4. Genetic testing for other genetic causes or unexplained cardiac hypertrophy or a thickened heart muscle is recommended for those with a questionable diagnosis of true HCM or when another genetic condition is suspected. This can occur with such conditions as Fabry’s Disease, Danon’s disease or Pompei’s disease, most commonly, but may include athlete’s heart.
Class II A 1. Genetic testing is reasonable to identify first-degree family members who may develop HCM. Therefore, once Index, also known as clinically-diagnosed, patient with HCM, has had genetic testing, their parents, siblings and children can have a much more limited and inexpensive test performed to determine whether or not they carry the same genetic mutation as this individual. It is important to note that since 2008 the Genetic Information Non-discrimination Act (GINA) provides protection to individuals who seek genetic testing to identify their status. This protection includes freedom from discrimination in employment and access to health insurance. It does not cover life insurance or long-term disability insurance; therefore, it is recommended that before anybody undergoes genetic testing for HCM that they secure basic life insurance coverage and inquire about long-term disability coverage in advance of screening. We make this recommendation, not because we fear that someone will die suddenly or unexpectedly, simply because they are genetically positive, but for the financial reality that life insurance provides protection for your dependents and it becomes financially unobtainable for the majority of people to access life insurance post diagnosis, either genetically or clinically.
Class IIB 1. The usefulness of genetic testing has not been effective to determine one's risk of sudden death. This is due in part to the variability of HCM within any family. While early literature suggested there were some mutations which could be identified specifically as high risk of sudden death, over time this did not prove to be true. Therefore, one should not base their decision to implant an ICD upon the results of genetic testing.
Class III 1. Genetic testing should not be done on the relatives of those who have received the results of their genetic testing and those results indicate that a mutation of unknown significance was identified; unless, of course, one is engaged in a research protocol or linkage analysis to help identify the potential value of a mutation.
2. Should the genetic mutation be identified in the index patient and the relatives are screened for the same mutation and found not to carry the same mutation, the need for ongoing clinical surveillance with annual echo, EKG and evaluation with a cardiologist for those ages 12 to 22 and every three to five years within the adult population is not necessary.
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5.1.1. Genotype Positive/Phenotype Negative Patients—Recommendation |
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Class I 1. In individuals with pathogenic mutations who do not express the HCM phenotype, it is recommended to perform serial ECG, TTE, and clinical assessment at periodic intervals (12 to 18 months in children and adolescents and about every 5 years in adults), based on the patient’s age and change in clinical status. 16,120–122 (Level of Evidence: B)
Genetic screening of first-degree relatives of an index patient with HCM can reveal typically young family members with a mutation (genotype positive) but without cardiac hypertrophy (phenotype negative) (Table 3).13,14,17,105,123,124 As the clinical expression of HCM usually increases with age, clinical screening (by physical examination, electrocardiography, and 2-dimensional echocardiography or CMR) of genotype positive/phenotype negative individuals is also recommended at the intervals indicated below. Electrocardiographic abnormalities, increased ejection fraction (EF), and delayed myocardial relaxation can precede the onset of hypertrophy.17,124 When abnormal, these parameters can indicate early emergence of clinical disease. Information about risk of SCD is limited.13,14,121,122
Information about risk for SCD is limited in genotype positive/phenotype negative individuals. However, when family history indicates a high risk for SCD, periodic assessment of arrhythmias (by exercise stress testing or Holter monitoring) in genotype positive/phenotype negative individuals may be appropriate. Decisions about participation in competitive athletics must be resolved on a case-by-case basis with the patient and family fully informed about the potential risks13 (Section 6.3.3). |
Class I It is to be stressed to HCM family members, who are tested gene positive, that they would benefit from evaluations annually between the onset of puberty through the age of 21+ and every 5 years thereafter throughout life. This evaluation should include ECG, echocardiogram and evaluation by a cardiac professional (cardiologist). In both children and adults any onset of symptoms should be investigated by a cardiologist.
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5.2. Electrocardiography—Recommendations |
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Class I 1. A 12-lead ECG is recommended in the initial evaluation of patients with HCM. (Level of Evidence: C) 2. Twenty-four–hour ambulatory (Holter) electrocardiographic monitoring is recommended in the initial evaluation of patients with HCM to detect ventricular tachycardia (VT) and identify patients who may be candidates for ICD therapy.10,127–129 (Level of Evidence: B) 3. Twenty-four–hour ambulatory (Holter) electrocardiographic monitoring or event recording is recommended in patients with HCM who develop palpitations or lightheadedness.10,127,128 (Level of Evidence: B) 4. A repeat ECG is recommended for patients with HCM when there is worsening of symptoms. (Level of Evidence: C) 5. A 12-lead ECG is recommended every 12 to 18 months as a component of the screening algorithm for adolescent first-degree relatives of patients with HCM who have no evidence of hypertrophy on echocardiography. (Level of Evidence: C) 6. A 12-lead ECG is recommended as a component of the screening algorithm for first-degree relatives of patients with HCM. (Level of Evidence: C)
Class IIa 1. Twenty-four–hour ambulatory (Holter) electrocardiographic monitoring, repeated every 1 to 2 years, is reasonable in patients with HCM who have no previous evidence of VT to identify patients who may be candidates for ICD therapy.129 (Level of Evidence: C) 2. Annual 12-lead ECGs are reasonable in patients with known HCM who are clinically stable to evaluate for asymptomatic changes in conduction or rhythm (ie, AF). (Level of Evidence: C)
Class IIb 1. Twenty-four–hour ambulatory (Holter) electrocardiographic monitoring might be considered in adults with HCM to assess for paroxysmal AF/atrial flutter. (Level of Evidence: C)
The 12-lead ECG is useful largely for raising the suspicion of HCM in family members without LV hypertrophy and in identifying patterns such as Wolff-Parkinson-White syndrome, which may suggest certain phenocopies of HCM.9,130–132 In addition, patterns mimicking myocardial infarction may provide evidence of the diagnosis and may be present in young individuals before there is manifest evidence of wall thickening on echocardiography.10,132,133 The 12-lead ECG is abnormal in 75% to 95% of patients with HCM.9,131,132 These abnormalities do not correlate with severity or pattern of hypertrophy as determined by echocardiography.
Ambulatory electrocardiographic monitoring for detection of ventricular tachyarrhythmias plays an important role in risk stratification of asymptomatic or symptomatic patients with HCM because episodes of nonsustained ventricular tachycardia (NSVT) identify patients at significantly higher risk of subsequent SCD.9,10,132–134 It is reasonable to perform serial ambulatory electrocardiographic monitoring on an annual basis or every 2 years in patients who are stable and do not manifest arrhythmias on baseline 12-lead ECG and Holter monitoring and who do not have ICDs.
The yield of ambulatory electrocardiographic monitoring for detection of AF or atrial flutter in patients who were previously asymptomatic without arrhythmias is unknown.
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Class I 1. ECG is recommended in the initial evaluation of all patients with HCM. In addition, it is recommended that patients carry a copy of their ECG with them for the purpose of maintaining a baseline in the event of an emergency.
2. 24-hour ambulatory or Holter monitoring is recommended at the initial evaluation of patients with HCM for the purpose of identifying abnormal heart rhythms. Some patients may not feel abnormal rhythms; therefore, testing can uncover hidden dangers.
3. 24-hour ambulatory or Holter monitoring is also recommended when symptoms of palpitations or lightheadedness is reported by the patient. This could mean the use of longer-term monitoring as well. Some monitors are now able to be used for up to three weeks to help identify those heart rhythms which are very sporadic.
4. A repeat ECG is recommended in those with HCM when there is a worsening of symptoms.
5. A 12-lead ECG is recommended every 12 to 18 months as a component of the screening algorithm for all adolescent first-degree relatives of patients with HCM who have no evidence of hypertrophy or thickened heart muscle on their echocardiogram. It is important to note, however, that some patients may maintain a normal ECG even in the presence of echo positive HCM.
6. 12-lead ECG is recommended as a component of the screening algorithm for first-degree adult relatives of those with HCM.
Class IIa 1. 24-hour ambulatory or Holter monitoring should be repeated every one to two years in patients with HCM with no previous evidence of abnormal heart rhythms including ventricular tachycardia as part of risk stratification for sudden cardiac arrest.
2. 12-lead ECG is used on patients with HCM to evaluate changes in their conduction or heart rhythm. It is a well appreciated fact that many patients with HCM develop changes in their heart over time that may not create symptoms that they are cognitively aware of. This simple task can help in management decisions the doctor may make.
Class IIb 1. 24-hour ambulatory Holter monitoring may be considered for those with HCM experiencing atrial fibrillation or atrial rhythms that are abnormal.
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5.3. Imaging |
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5.3.1. Echocardiography—Recommendations |
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Class I 1. A TTE is recommended in the initial evaluation of all patients with suspected HCM.9,20,66,67,135–138 (Level of Evidence: B) 2. A TTE is recommended as a component of the screening algorithm for family members of patients with HCM unless the family member is genotype negative in a family with known definitive mutations. 41,126,139,140 (Level of Evidence: B) 3. Periodic (12 to 18 months) TTE screening is recommended for children of patients with HCM, starting by age 12 or earlier if a growth spurt or signs of puberty are evident and/or when there are plans for engaging in intense competitive sports or there is a family history of SCD.126,141 (Level of Evidence: C) 4. Repeat TTE is recommended for the evaluation of patients with HCM with a change in clinical status or new cardiovascular event.39,45,57,142–145 (Level of Evidence: B) 5. A transesophageal echocardiogram (TEE) is recommended for the intraoperative guidance of surgical myectomy.146–148 (Level of Evidence: B) 6. TTE or TEE with intracoronary contrast injection of the candidate’s septal perforator(s) is recommended for the intraprocedural guidance of alcohol septal ablation.62,149–151 (Level of Evidence: B) 7. TTE should be used to evaluate the effects of surgical myectomy or alcohol septal ablation for obstructive HCM.61,62,152–156 (Level of Evidence: C)
Class IIa 1. TTE studies performed every 1 to 2 years can be useful in the serial evaluation of symptomatically stable patients with HCM to assess the degree of myocardial hypertrophy, dynamic obstruction, and myocardial function.20,67,136 (Level of Evidence: C) 2. Exercise TTE can be useful in the detection and quantification of dynamic LVOT obstruction in the absence of resting outflow tract obstruction in patients with HCM.8,45,143,145,157 (Level of Evidence: B) 3. TEE can be useful if TTE is inconclusive for clinical decision making about medical therapy and in situations such as planning for myectomy, exclusion of subaortic membrane or mitral regurgitation secondary to structural abnormalities of the mitral valve apparatus, or in assessment for the feasibility of alcohol septal ablation.146–148 (Level of Evidence: C) 4. TTE combined with the injection of an intravenous contrast agent is reasonable if the diagnosis of apical HCM or apical infarction or severity of hypertrophy is in doubt and other imaging modalities such as CMR are not readily available or contraindicated. (Level of Evidence: C) 5. Serial TTE studies are reasonable for clinically unaffected patients who have a first-degree relative with HCM when genetic status is unknown. Such follow-up may be considered every 12 to 18 months for children or adolescents from high-risk families and every 5 years for adult family members. 41,126,140,141 (Level of Evidence: C)
Class III: No Benefit 1. TTE studies should not be performed more frequently than every 12 months in patients with HCM when it is unlikely that any changes have occurred that would have an impact on clinical decision making. (Level of Evidence: C) 2. Routine TEE and/or contrast echocardiography is not recommended when TTE images are diagnostic of HCM and/or there is no suspicion of fixed obstruction or intrinsic mitral valve pathology. (Level of Evidence: C)
Comprehensive TTE and Doppler studies should be performed in the initial evaluation of all patients with suspected HCM, as well as during follow-up, particularly when there is a change in cardiovascular symptoms or an event. Echocardiographic studies are essential for establishing the diagnosis and the nature and extent of hypertrophy, defining prognosis, and guiding management.9,20,66,67,135–138 Although septal thickness _15 mm is commonly used to identify HCM, one must be aware of the potential confusion with secondary hypertrophy attributable to aortic valve or discrete subaortic stenosis, systemic hypertension, amyloidosis, and other genetic phenocopies such as Fabry disease.158 In affected family members with HCM, the degree of hypertrophy may be below the usual diagnostic threshold of _15 mm LV wall thickness, and indeed some patients carry an HCM definitive mutation without hypertrophy.
It has been suggested that identification of morphologic subtypes of LV hypertrophy, namely apical hypertrophy159 or septal hypertrophy with reverse or neutral curvature, or sigmoid shape,160 have implications for the likelihood of detection of myofilament mutations and prognosis.139 However, there is no recognized relationship between the pattern or distribution of LV hypertrophy and clinical course or outcome. Nevertheless, documentation of the extent of hypertrophy is important because there is a relatively linear association between maximal wall thickness and sudden death, with highest risk in patients with wall thickness _30 mm.161
The presence of dynamic LVOT obstruction is related to symptomatic status as well as development of AF, embolic complications, and death.45,57,142–145 Continuous wave Doppler studies can accurately quantitate the LVOT gradient and determine the response to pharmacologic157 and interventional therapy. Amyl nitrite can be used to provoke echocardiographically documented gradients when available and in laboratories with expertise and has the advantage of being capable of being integrated into a single examination. The correlation between pharmacologic and physiologic exercise provocation of outflow gradients is unresolved. Care must be taken to correctly identify the site of obstruction, distinguish the Doppler spectral profile from cavity obliteration, and avoid contamination of the signal by mitral regurgitation. Although many patients have dynamic LVOT obstruction at rest, a significant number will have new or higher gradients after the Valsalva maneuver, inhalation of amyl nitrite, or during provocative exercise.8 In HCM, it is the peak instantaneous LVOT velocity, usually caused by SAM, that should be used to determine the maximum gradient, using the modified Bernoulli formula (Table 2).
Systolic function, as assessed by wall motion and EF, is usually normal in patients with HCM; however, the development of systolic dysfunction heralds the risk of progressive and irreversible heart failure, which may result in heart transplantation or death.39 The importance of diastolic dysfunction in HCM has led to an extensive search for noninvasive methods to quantify its severity. With the complex interplay of factors causing diastolic dysfunction in HCM, no single noninvasive measure has been demonstrated as superior. 162,163 LA volume may provide a long-term indication of the effects of chronically elevated filling pressures in patients with HCM.164–166 Patients with HCM and a maximal LA volume index _34 mL/m2 have a higher incidence of abnormal diastolic filling, a higher mitral inflow/annular velocity (E/e_) ratio, a higher calculated LA pressure, and less favorable outcome.164,166 Moreover, LA volumetric remodeling predicts exercise capacity in nonobstructive HCM and thus may reflect chronic LV diastolic burden independent of LVOT obstruction. The more recent use of myocardial deformation measurements to quantify strain parameters, torsion, and dyssynchrony has detected abnormalities in systolic performance, especially longitudinal strain and twist.167–171 These methods have also shown promise in better quantifying abnormalities in early relaxation and elevation of filling pressures.172 They may also be useful in distinguishing HCM from other forms of hypertrophy173 as well as detecting preclinical disease.17,19,174
Echocardiographic studies are useful in patients with LVOT obstruction who fail to respond to medical therapy and who undergo invasive intervention.61,146 –148,155,175,176 TEE studies, performed before arrival in the operating suite for surgical septal myectomy (and intraoperative TEE), can determine the length and extent of myectomy required, evaluate the presence and severity of mitral regurgitation independent of obstruction, and identify the presence of abnormal papillary muscle architecture.146–148,155,176 Following myectomy, postbypass intraoperative TEE studies can confirm the adequacy of myectomy and quantitate residual gradients, severity of mitral and aortic regurgitation, ventricular function, and development of a ventricular septal defect. 146–148,155,176 When the myectomy is inadequate based on TEE study, surgical revision can be considered.
Intraprocedural echocardiographic studies should be routinely performed during alcohol septal ablation procedures. 62,149 –152,156,177 Contrast-enhanced echocardiographic studies with intracoronary injection of the candidate coronary septal perforator(s) are important in determining the perfusion bed supplied by the septal perforator so that only an appropriate site and degree of myocardium is infarcted and complications avoided.149–151 After alcohol septal ablation there may be an early recurrence in the LVOT gradient a few days after the procedure, with subsequent reduction over 6 to 12 months.152,156 It should be recognized that in some patients TTE studies may be limited by image quality, and other investigations, including CMR, should be performed. In addition, TEE may detect the presence of subaortic membrane causing fixed obstruction with or without coexisting dynamic obstruction. In patients with the apical variant of HCM, the diagnosis is missed by echocardiographic studies in about 10% of patients, 159 and the use of peripheral injection of an echocardiographic contrast agent, as well as CMR, may be useful in establishing the diagnosis. Similarly, a subset of patients with HCM may have an apical LV aneurysm associated with normal epicardial coronary arteries,159 which is usually best visualized with CMR. TEE studies may be helpful in some patients, particularly when the cause and severity of mitral regurgitation is uncertain.147,148 |
Class I 1 .A transthoracic echocardiogram, or TTE, better known as a standard echocardiogram, is recommended at the initial evaluation for all patients suspected of having hypertrophic cardiomyopathy.
2. An echocardiogram is recommended as a component of screening for all family members of those with diagnosed HCM. If, however, a family member has tested genetically negative, it is not necessary to continue screening with ECG for the presence of hypertrophic cardiomyopathy.
3. Periodic echo screening is recommended at intervals of no greater than 12 to 18 months for children of patients with HCM. The age in which to begin screening should not exceed 12 years and may be earlier under the following circumstances: a family history of sudden death, a child's wish to compete in high level competitive athletics, and for those children entering puberty prior to the age of 12 years. Once screening has begun in a child, it is wise to maintain the 12 to 18 month interval until full maturity is reached, which can be up to the age of 25.
4. Repeat echocardiograms are recommended for those diagnosed with HCM who experience a change in their symptoms or has experienced a cardiovascular event, including nearly passing out, passing out, increased chest discomfort, increased palpitations, increased fatigue or other similar situations.
5. Transesophageal echocardiography, or TEE, can be useful if the TTE is inconclusive to identify the appropriate treatment plan. This could be used in cases where the quality of the standard echo is substandard due to many variables. It is advised that if one were to consider a transesophageal echocardiogram that they do so in the care of an HCM center of excellence to avoid unnecessary testing. The use of TEE can be very helpful in planning for therapeutic options to reduce obstruction including myectomy or alcohol septal ablation.
6. TTE/standard echocardiography can be enhanced with the use of contrast agents. These agents are delivered through an IV and are used for patients who cannot undergo cardiac magnetic resonating or CMR. The use of a contrast agent helps to create clearer pictures and identify such anomalies as apical hypertrophic cardiomyopathy or aneurysms.
Serial TTE/standard echocardiographic evaluations are reasonable for clinically unaffected patients who have a first-degree relative with HCM and for whom the genetic status is unknown. Again, the frequency in which family member should be evaluated with this technology is from the onset of puberty, or younger, as discussed above, every 12 to 18 months until the age of maturity and every five years for adults.
7. TTE should be used to evaluate the outcome following surgical myectomy or alcohol septal ablation.
Class IIa 1. TTE studies performed every 1 to 2 years can be useful in the serial evaluation of symptomatically stable patients with HCM to assess the degree of myocardial hypertrophy, dynamic obstruction, and myocardial function.
2. Exercise TTE can be useful in the detection and quantification of dynamic LVOT obstruction in the absence of resting outflow tract obstruction in patients with HCM.
3. TEE can be useful if TTE is inconclusive for clinical decision making about medical therapy and in situations such as planning for myectomy, exclusion of subaortic membrane or mitral regurgitation secondary to structural abnormalities of the mitral valve apparatus, or in assessment for the feasibility of alcohol septal ablation.
4. TTE combined with the injection of an intravenous contrast agent is reasonable if the diagnosis of apical HCM or apical infarction or severity of hypertrophy is in doubt and other imaging modalities such as CMR are not readily available or contraindicated.
5. Serial TTE studies are reasonable for clinically unaffected patients who have a first-degree relative with HCM when genetic status is unknown. Such follow-up may be considered every 12 to 18 months for children or adolescents from high-risk families and every 5 years for adult family members.
Class III no benefit 1. Transthoracic echocardiography/standard echo should not be performed more frequently than every 12 months in patients with HCM when it is unlikely that changes have occurred that could impact clinical decision-making. It is unlikely that significant change will occur in that short amount of time in a person that has reached full maturity. The occurrence of a symptom does not necessarily indicate something structurally has changed. Patients and families should be reassured that the frequency of an echocardiogram is not paramount to dealing with minor changes in symptoms and, therefore, unnecessary to require an echocardiogram more often than every 12 months.
2. Routine transesophageal echocardiograms and/or contrast echoes are not recommended when the transthoracic echocardiogram/standard echo images are diagnostic and there is no suspicion of a fixed obstruction, intrinsic or abnormal mitral valve anatomy or other factors. Simply because the test is more invasive TEE and/or contrast echo does not necessarily mean that it is better for a patient or will shed light on more anatomic findings than the standard transthoracic echocardiogram.
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5.3.2. Stress Testing—Recommendations |
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Class IIa 1. Treadmill exercise testing is reasonable to determine functional capacity and response to therapy in patients with HCM. (Level of Evidence: C) 2. Treadmill testing with monitoring of an ECG and blood pressure is reasonable for SCD risk stratification in patients with HCM.89,90,178 (Level of Evidence: B) 3. In patients with HCM who do not have a resting peak instantaneous gradient of greater than or equal to 50 mm Hg, exercise echocardiography is reasonable for the detection and quantification of exerciseinduced dynamic LVOT obstruction.8,88–90 (Level of Evidence: B)
Exercise testing with monitoring of ECG and cuff blood pressure is helpful in risk assessment of patients with HCM, because abnormal blood pressure responses to exercise (defined as either a failure to increase by at least 20 mm Hg or a drop of at least 20 mm Hg during effort) has been demonstrated to be 1 factor associated with risk of SCD.9,10,89,90,134,178 A hypotensive blood pressure response was defined as either an initial increase in systolic blood pressure with a subsequent fall by peak exercise of _20 mm Hg compared with peak blood pressure value or8,90 a continuous decrease in systolic blood pressure of _20 mm Hg throughout the exercise test when compared with baseline. A flat response was defined by a change in systolic blood pressure during the whole exercise period of _20 mm Hg compared with the resting systolic blood pressure. Most published studies examining exercise blood pressure response use symptom-limited treadmill exercise testing with a Bruce protocol,89,178 whereas others use symptom-limited bicycle ergometry, with 25-W increments in 3-minute stages.90
Combining exercise testing with Doppler echocardiography is also useful for determining the presence of physiologically provocable LVOT obstruction and is particularly helpful in patients with symptoms during routine physical activities who do not manifest outflow obstruction at rest.8 Stress testing modalities include either bicycle, treadmill using the Bruce protocol, or cardiopulmonary (metabolic) testing, with measurement of gradient either during or immediately after exercise.8 In symptomatic patients with a peak resting gradient of _50 mm Hg, it is helpful to perform exercise echocardiography to determine if a significant exercise-induced gradient (or increase in mitral regurgitation) or augmentation thereof is present.
The role of metabolic stress testing (ie, determination of maximum oxygen consumption) in the routine evaluation of patients with HCM remains to be decided, particularly with regard to clinical outcome, but in individual patients this test may be helpful in providing a more precise assessment of functional capacity.179 |
Class IIa 1. Treadmill exercise testing is reasonable to determine functional capacity and response to therapy in patients with HCM.
2. Treadmill testing with monitored ECG and blood pressure is reasonable for sudden death risk stratification in patients with HCM. While the guidelines document does not address this particular issue the HCMA felt it important to bring up this additional item. It is further cautioned that this test may need to be repeated on a regular basis, annually or semi-annually as a risk profile changes over time and the results of stress testing are not to be expected to be consistent over long periods of time.
3. In patients who do not have a resting peak gradient of 50mmHg or greater, also known as obstruction of 50mmHg or more, exercise echocardiography is reasonable for the detection and qualification of stress or exercise-induced left ventricular outflow tract obstruction. It is reported in the literature that up to 75% of those with hypertrophic cardiomyopathy will obstruct on exercise or with provocation. It is important to know if someone does have a provocable obstruction to ensure that proper management strategies are utilized.
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5.3.3. Cardiac Magnetic Resonance—Recommendations |
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Class I 1. CMR imaging is indicated in patients with suspected HCM when echocardiography is inconclusive for diagnosis.180,181 (Level of Evidence: B) 2. CMR imaging is indicated in patients with known HCM when additional information that may have an impact on management or decision making regarding invasive management, such as magnitude and distribution of hypertrophy or anatomy of the mitral valve apparatus or papillary muscles, is not adequately defined with echocardiography.15,180–183 (Level of Evidence: B)
Class IIa 1. CMR imaging is reasonable in patients with HCM to define apical hypertrophy and/or aneurysm if echocardiography is inconclusive.180,182 (Level of Evidence: B)
Class IIb 1. In selected patients with known HCM, when SCD risk stratification is inconclusive after documentation of the conventional risk factors (Section 6.3.1), CMR imaging with assessment of late gadolinium enhancement (LGE) may be considered in resolving clinical decision making.184–188 (Level of Evidence: C) 2. CMR imaging may be considered in patients with LV hypertrophy and the suspicion of alternative diagnoses to HCM, including cardiac amyloidosis, Fabry disease, and genetic phenocopies such as LAMP2 cardiomyopathy. 189–191 (Level of Evidence: C)
There have been significant advances in CMR in recent years, and most centers now have access to this advanced imaging technique. Compared with other noninvasive cardiac imaging modalities, CMR provides superior spatial resolution with sharp contrast between blood and myocardium, as well as complete tomographic imaging of the entire LV myocardium and therefore the opportunity to more accurately characterize the presence, distribution, and extent of LV hypertrophy in HCM. Because of the technical complexity of CMR imaging, data from the published literature are only generalizable if imaging is performed with high technical quality by experienced operators and interpreted by well-trained and experienced readers.
The primary role for CMR in patients with HCM is clarification of diagnosis and phenotype. Advances in 2-dimensional echocardiography have demonstrated the heterogeneity of the hypertrophic phenotype in patients with HCM, particularly with regard to distribution of LV hypertrophy and mechanisms of outflow obstruction.8–10,15,21,72,192 However, there remain patients in whom the diagnosis of HCM is suspected but the echocardiogram is inconclusive, mostly because of suboptimal imaging from poor acoustic windows or when hypertrophy is localized to regions of the LV myocardium not well visualized by echocardiography.15 In 1 study, 6% of patients with suspected HCM were identified with increased LV wall thickness (predominantly in the anterolateral wall) by CMR but not by echocardiography. 15,181,183 In addition, in patients with HCM in whom hypertrophy is predominantly confined to the apex (ie, apical HCM), increased wall thickness in this region of the LV myocardium may be difficult to visualize clearly with echocardiography but can be well seen with CMR.180,182 Similarly, in the subgroup of patients with HCM who develop apical aneurysms, CMR can more readily detect the presence of an aneurysm (particularly when small) compared with noncontrast echocardiography.182 Identification of the end-stage phenotype and particularly an apical aneurysm has implications for management in that an ICD may be indicated and anticoagulation could be considered, based on the morphologic appearance of the aneurysm. In addition to diagnosis, the extent of maximal LV wall thickening may be underestimated by echocardiography compared with CMR, particularly when this region involves the anterolateral wall.15,183 This observation is related to the limitation of 2-dimensional echocardiography in differentiating the epicardial border of the lateral LV free wall from thoracic parenchyma, allowing significant underestimation of wall thickness compared with CMR, which provides more reliable definition of the epicardial border. Accurate characterization of the HCM phenotype by CMR may also be useful in management decisions for invasive therapies (septal myectomy or alcohol septal ablation) by more precisely defining the location and magnitude of hypertrophy as well as characterizing the mitral and submitral apparatus and papillary muscles.193,194 The opportunity for contrast-enhanced CMR with LGE to identify areas of myocardial fibrosis in patients with HCM has been the subject of a growing area of the literature.185–187,195,196 The extent and transmural distribution of areas of infarction can be quantitatively defined in patients with CAD.197 Many studies have now documented that approximately half of patients with HCM have LGE suggestive of areas of fibrosis and in some patients may occupy a substantial volume of LV myocardium (ie, on average, 10% of the LV wall).185,195 Although patients with the end-stage phenotype almost universally demonstrate such findings,39 patients with HCM with preserved systolic function may also have areas of LGE.185–187 Importantly, patients with HCM with evidence of LGE on CMR imaging tend to have more markers of risk of SCD, such as NSVT on Holter monitoring, than patients without LGE.184,186
It is a plausible and attractive concept that areas of LGE (ie, probably largely replacement myocardial fibrosis) could represent a substrate for the generation of malignant ventricular tachyarrhythmias in HCM and thus a marker for risk of SCD. Several studies have addressed this issue and have reported either trends in such a direction or significant associations between the presence of LGE (not extent) and cardiac outcome events.187,198 However, there is insufficient evidence at this time to support a significant association between the extent of LGE and outcome. Larger studies with longer follow-up and more events with greater statistical power are needed to fully characterize whether the finding of LGE can be considered a specific risk marker for SCD to the same degree as currently accepted markers such as family history of SCD or extreme LV wall thickness. Nonetheless, the present cross-sectional and short-term follow-up data would support a potential role of contrast-enhanced CMR (with evidence of LGE) as an arbitrator to consider in clinical decision making for primary prevention ICDs in patients in whom high-risk status for SCD remains uncertain after assessment of conventional risk factors.186
In some patients with LV hypertrophy, CMR imaging can depict patterns of LGE that may suggest an alternative diagnosis. In patients with Anderson-Fabry disease, it has been reported that approximately half have LGE localized to the mid-myocardial portion of the basal inferolateral wall, sparing the subendocardium,191 a location and distribution of LGE that may help distinguish this disease from other forms of nonischemic cardiomyopathies such as HCM.189 Patterns of LGE in HCM are heterogeneous, may occur commonly in either the ventricular septum or LV free wall, and usually involve segments of the chamber that are most hypertrophied and do not conform to particular coronary arterial distributions.185
Among patients with LV hypertrophy caused by cardiac amyloidosis, it has been reported that approximately 70% demonstrate a pattern of global subendocardial gadolinium enhancement, a pattern of enhancement not usually seen in patients with HCM.190 These data suggest that gadolinium-enhanced CMR imaging may be useful in select cases to assist a clinician in the differential diagnosis of a patient with LV hypertrophy. |
Class I 1. CMR, cardiac magnetic resonating imaging, also known as cardiac MRI, is indicated in patients with suspected HCM when echocardiography is inconclusive for diagnosis.
2. CMR is indicated in patients with HCM when additional information, such as magnitude and distribution of hypertrophy or the anatomy of the mitral valve or papillary muscles, when not adequately defined in echocardiograms, may impact management or decision-making regarding invasive treatments. Simply put, CMR provides a much clearer picture of the cardiac anatomy and allows for more definitive decision making as to where the borders of the heart wall muscle exist and where smaller parts of the cardiac anatomy, such as papillary muscles and valve apparatus, are situated.
Class I Ia 1. CMR imaging is reasonable in HCM to define apical hypertrophy and/or aneurysms if echo is inconclusive.
Class IIb 1. In some patients with HCM, when sudden cardiac arrest risk stratification is inconclusive or borderline, CMR images can assess whether there is scar present, and to what magnitude, within the left ventricle. While some scar is expected, the greater amount of scar, also known as late gadolinium enhancement, is believed to be associated with more significant clinical meaning.
2. CMR may also be considered if the diagnosis of HCM is inconclusive and may be suspected to actually be cardiac hypertrophy caused by amyloidosis, Fabry’s disease, and genetic phenocopies such as Danon’s disease or LAMP2.
CMR with large amounts of late gadolinium enhancement maybe considered in select populations for whom the risk of sudden cardiac death is not completely resolved. For lack of better terms, it may add enough weight to the argument to either encourage someone to choose an implantable defibrillator or to wait for the next full risk stratification to be completed and see if there are changes a year down the road.
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5.4. Detection of Concomitant Coronary Disease—Recommendations |
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Class I 1. Coronary arteriography (invasive or computed tomographic imaging) is indicated in patients with HCM with chest discomfort who have an intermediate to high likelihood of CAD when the identification of concomitant CAD will change management strategies. (Level of Evidence: C)
Class IIa 1. Assessment of coronary anatomy with computed tomographic angiography (CTA) is reasonable for patients with HCM with chest discomfort and a low likelihood of CAD to assess for possible concomitant CAD. (Level of Evidence: C) 2. Assessment of ischemia or perfusion abnormalities suggestive of CAD, with single photon emission computed tomography myocardial perfusion imaging (SPECT MPI) (because of excellent negative predictive value) is reasonable in patients with HCM with chest discomfort and a low likelihood of CAD to rule out possible concomitant CAD. (Level of Evidence: C)
Class III: No Benefit 1. Routine SPECT MPI or stress echocardiography is not indicated for detection of “silent” CAD-related ischemia in patients with HCM who are asymptomatic. 8 (Level of Evidence: C) 2. Assessment for the presence of blunted flow reserve (microvascular ischemia) using quantitative myocardial blood flow measurements by positron emission tomography (PET) is not indicated for the assessment of prognosis in patients with HCM. (Level of Evidence: C)
Chest discomfort is a common symptom in patients with HCM. A key management issue revolves around whether the discomfort may be caused by concomitant epicardial obstructive CAD with inducible ischemia, a consequence of microvascular dysfunction, or a combination of these factors.9 The concomitant presence of CAD, particularly if severe, in patients with HCM identifies a higher risk for adverse outcomes, as well as patients who are potential candidates for revascularization.199,200 Moreover, in considering management options such as alcohol septal ablation or septal myectomy for patients with highly symptomatic HCM, knowledge of coronary anatomy is an important factor informing the decision.
Myocardial bridging (ie, tunneling) is a clinical feature in patients with HCM that may be associated with myocardial ischemia in the absence of epicardial coronary stenosis. In myocardial bridging, a segment of the left anterior descending coronary artery courses within the myocardium. The prevalence of myocardial bridging varies based on the type of investigation. In a recent autopsy-based study in patients with HCM, bridging was evident in 40% of hearts,201 whereas angiographic prevalence in HCM is reported to be 15%.202 Myocardial bridges are a frequent component of phenotypically expressed HCM and more common than in other disorders with or without LV hypertrophy. Although it has been suggested that ischemia secondary to bridging could be a potential mechanism for sudden death in patients with HCM,203 there is no consistent evidence to support this hypothesis in either adults or children.202,204 However, the possibility that coronary arterial bridges could contribute to increased risk in some individual patients cannot be excluded, potentially impacting management decisions on a case-by-case basis.
In patients with HCM who have chest pain and who undergo coronary angiography, the finding of a myocardial bridge raises the question of whether myocardial ischemia associated with the bridge is the cause of symptoms. There are no data assessing stress MPI in patients with HCM with myocardial bridges; however, reports of patients with myocardial bridges who do not have HCM suggest that stress perfusion abnormalities may be commonly detected in the vascular territory distal to the bridge.205 Although it has been suggested that systolic compression of a bridged coronary artery may not be responsible for ischemia because most coronary blood flow takes place in diastole, angiographic studies have demonstrated arterial compression in diastole as well.206,207
If chest pain symptoms in a patient with HCM are suspected to be related to abnormal coronary blood flow (as a result of bridging), beta blockers may be effective in controlling the symptoms. Intravenous beta blockade in patients with myocardial bridges and non-HCM disease has been shown to have favorable effects on coronary dimensions and myocardial blood flow and diminished ischemia induced by pacing tachycardia.207 If medical therapy is ineffective, consideration can be given to surgery with supra-arterial myotomy (“unroofing”),206,208 which may be technically challenging depending on the depth of the tunneled segment. CTA can define the course and depth of a bridged segment and may be useful in planning surgical strategy.209
In patients with HCM who are undergoing surgical myectomy and in whom preoperative angiography has demonstrated a myocardial bridge, there are no data to guide the decision on whether to “unroof” the bridged segment during the surgical myectomy. In patients with chest pain in whom perfusion imaging demonstrates blunted flow reserve distal to the myocardial bridge, supra-arterial myotomy has been suggested to reduce anginal symptoms. |
Class I 1. Coronary arteriography (either with catheterization or computer topographic imaging) is indicated in HCM patients with chest discomfort who have an intermediate or high likelihood of also having coronary artery disease. Identifying the presence of coronary artery disease will change management strategies.
Class IIa 1. Assessment of coronary anatomy with CTA is reasonable for patients with chest discomfort and a low likelihood of coronary artery disease to assess the possible presence of coronary artery disease.
2. The assessment of ischemia or perfusion abnormalities, suggestive of coronary artery disease, with single photon emission computer topography myocardial perfusion imaging, also known as SPECT MPI, is reasonable in HCM with chest discomfort and a low likelihood of coronary artery disease, to help rule out the presence of coronary artery disease, as this particular test has an excellent negative predictive value.
Class III 1. Routine SPECT MPI or stress echocardiography is not indicated for detection of “silent” coronary artery disease-related ischemia in patients with HCM who are not experiencing any symptoms of chest discomfort and are believed to be asymptomatic.
2. Assessment for the presence of blunted flow reserve or microvascular ischemia using quantitative myocardial blood flow measurements with PET scan is not indicated for the assessment of diagnosis in patients with HCM.
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5.4.1. Choice of Imaging Modality |
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5.4.1.1. Invasive Coronary Arteriography
Invasive coronary arteriography is the gold standard for defining the presence, extent, severity, and location of epicardial coronary stenoses. Performance of invasive coronary arteriography is indicated in patients with HCM when knowledge of these features will importantly influence management strategies as discussed above. Invasive coronary arteriography should be a routine accompaniment to an invasive catheterization performed in a patient with HCM for assessment of hemodynamic status and in such cases should generally be performed after documentation of hemodynamics so as not to influence important measurements such as the magnitude of the LVOT gradient. When catheterization is performed, invasive coronary arteriography should be undertaken before alcohol septal ablation in order to define the anatomy of the septal perforators in detail and exclude obstructive coronary stenoses. Furthermore, if alcohol septal ablation is being considered, the decision may be influenced by the location and extent of coronary disease as defined by coronary arteriography. |
Intentionally left blank as the guidelines document is self explanatory. |
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5.4.1.2. Noninvasive CTA |
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Although there are no published data specifically assessing the performance characteristics of CTA for documenting the presence or absence of epicardial CAD in HCM, there is no reason to believe that performance of the test should differ in patients with HCM compared with those with suspected or known CAD. Many studies have reported very good capability of contemporary CTA technology to distinguish the presence from absence of a _50% epicardial stenosis.210 A high negative predictive value to exclude CAD is particularly consistent in the literature. In this regard, for patients with HCM with chest discomfort, CTA would be a reasonable strategy to assess for possible concomitant CAD. Anatomical demonstration of an epicardial stenosis does not necessarily indicate that the symptoms of chest discomfort are attributable to ischemia but are suggestive and outlines a potential management strategy as well as indicates the need for specific preventive strategies. |
Intentionally left blank as the guidelines document is self explanatory. |
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5.4.1.3. Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging |
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Stress SPECT MPI in patients with HCM will often demonstrate reversible or fixed perfusion defects consistent with ischemia or infarction, respectively, even in the absence of epicardial CAD.211,212 In 1 study, approximately 50% of young patients with HCM (unlikely to have CAD attributable to age) had reversible perfusion defects on exercise stress SPECT MPI that were prevented when exercise imaging was repeated on verapamil.213 Several lines of evidence support that these defects, even in the absence of symptoms, represent true flow abnormalities and possibly “silent” ischemia. Studies of autopsy specimens or myectomy specimens in patients with HCM have shown that patients with HCM may have structural abnormalities of the myocardial microvasculature.87 During pacing-induced tachycardia, patients with HCM with reversible SPECT MPI defects demonstrate production of lactate consistent with ischemia,214 and following relief of outflow tract obstruction with myectomy, patients with HCM with reversible defects often have normal perfusion.215
Fixed defects may also be seen with SPECT MPI, a finding consistent with infarction. These patients will often have the “end-stage” clinical phenotype with reduced EF211 and likely correspond to patients who demonstrate LGE in CMR studies.39
The concept that true abnormalities of perfusion at the tissue level may be demonstrated by SPECT MPI in patients with HCM in the absence of epicardial CAD, however, does make the interpretation of SPECT MPI to detect CAD challenging. Moreover, myocardial ischemia in patients with HCM, in the absence of epicardial coronary artery stenosis, may be attributable to intramural small-vessel abnormalities or massive hypertrophy.216 Given the above discussion, the positive predictive value of an abnormal SPECT MPI study for epicardial obstructive CAD in a patient with HCM with chest discomfort will be relatively low, but the negative predictive value will be high. The demonstration of a reversible defect, even in the absence of CAD, does suggest that the symptoms of chest discomfort may be caused by ischemia, although not necessarily related to the presence of obstructive CAD. Although the true performance characteristics of SPECT MPI for detection of CAD have not been rigorously studied in patients with HCM, it would be expected that the negative predictive value should be high.
In considering any imaging procedure that involves exposure to radiation such as SPECT or PET imaging (Section 5.4.1.4) or invasive or CTA (5.4.1.2), contemporary recommendations suggest that the potential risks of radiation exposure be taken into account and that the benefits of the information gained sufficiently balance those risks.217 This concept may be particularly important in patients with HCM, who in general will be younger compared with other subgroups of patients being evaluated for heart disease.
Interpretation of SPECT perfusion imaging studies in patients with HCM should be mindful that areas with substantial wall thickening may appear inordinately “hot,” making other areas without hypertrophy appear to have a relatively mild reduction in tracer activity. Quantitative analysis programs may falsely interpret this as a perfusion defect. Moreover, gated SPECT analysis of EF with use of contouring programs may underestimate EF, because the assumptions driving the contouring algorithms searching for the endocardial borders may not be reliable in some patients with HCM because of the relative brightness of the hypertrophied wall. |
Intentionally left blank as the guidelines document is self explanatory. |
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5.4.1.4. Positron Emission Tomography
PET imaging has been used in patients with HCM to study myocardial blood flow as well as myocardial metabolism. In patients with HCM with normal coronary arteries, myocardial perfusion PET studies have shown that although resting myocardial blood flow may be similar to that of normal control subjects, the augmentation of blood flow with vasodilation, for example, dipyridamole, may be significantly blunted.218–221 In addition, such abnormal myocardial blood flow reserve was shown to be more pronounced in the subendocardial regions, consistent with so-called “apparent” transient ischemic cavity dilatation.212,218,219 In 1 study using techniques to quantify myocardial blood flow reserve with PET perfusion tracers, patients with HCM who had blunted flow reserve in response to hyperemic stress had more unfavorable event-free survival compared with patients with preserved hyperemic flow reserve.220 A follow-up study suggested that 1 mechanism for the unfavorable outcomes associated with the flow reserve abnormalities included progression to a remodeled, end-stage phenotype.221 These findings are consistent with the concept that repetitive episodes of myocardial ischemia may influence long-term outcome of patients with HCM. However, the quantitative PET techniques used in these studies are not part of routine clinical practice, and the management implications of identifying abnormalities in flow reserve are unresolved. |
Intentionally left blank as the guidelines document is self explanatory. |
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5.4.1.5. Stress Echocardiography
There are no published studies addressing the performance characteristics of stress echocardiography to detect or exclude CAD in patients with HCM. Although performance of this modality has been well studied in patients who do not have HCM and criteria about appropriate use of the test222 exist, aspects of the HCM phenotype would in theory undermine performance. Patients with HCM have heterogeneous wall-thickness patterns, and wall motion at rest may appear abnormal in regions of hypertrophied myocardium. A wall-motion response to stress therefore would be complex to interpret and may be particularly so in the presence of the enhanced loading that occurs in the setting of outflow tract obstruction, which may be seen in up to 75% of patients during exercise. For these reasons, stress echocardiography to detect or rule out CAD may be unreliable in HCM but may be useful to document the presence or magnitude of outflow tract obstruction generated by exercise8 (Section 4.1). |
Intentionally left blank as the guidelines document is self explanatory. |
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6. Management of HCM |
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Treatment of patients with HCM requires a thorough understanding of the complex, diverse pathophysiology and natural history and must be individualized to the patient. The general approach of the writing committee is outlined in Figure 3. |
Intentionally left blank as the guidelines document is self explanatory. |
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6.1. Asymptomatic Patients—Recommendations |
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Class I 1. For patients with HCM, it is recommended that comorbidities that may contribute to cardiovascular disease (eg, hypertension, diabetes, hyperlipidemia, obesity) be treated in compliance with relevant existing guidelines.223 (Level of Evidence: C)
Class IIa 1. Low-intensity aerobic exercise is reasonable as part of a healthy lifestyle for patients with HCM.10,224 (Level of Evidence: C)
Class IIb 1. The usefulness of beta blockade and calcium channel blockers to alter clinical outcome is not well established for the management of asymptomatic patients with HCM with or without obstruction.10 (Level of Evidence: C)
Class III: Harm 1. Septal reduction therapy should not be performed for asymptomatic adult and pediatric patients with HCM with normal effort tolerance regardless of the severity of obstruction.9,10 (Level of Evidence: C) 2. In patients with HCM with resting or provocable outflow tract obstruction, regardless of symptom status, pure vasodilators and high-dose diuretics are potentially harmful.3,9 (Level of Evidence: C)
A large proportion of patients presenting with HCM are asymptomatic, and most will achieve a normal life expectancy. 48,131,225 It is essential to educate these patients and their families about the disease process, including screening of first-degree relatives and avoiding particularly strenuous activity or competitive athletics.134,224 Risk stratification for SCD should also be performed in all patients, irrespective of whether symptoms are present.9,10
Because concomitant CAD has a significant impact on survival in patients with HCM,199 it is recommended that other risk factors that may contribute to atherosclerotic cardiovascular disease be treated aggressively in concordance with existing guidelines (Figure 3).10,223 This includes aggressive modification of risk factors such as hypertension, diabetes, obesity, and hyperlipidemia.223 A low-intensity aerobic exercise program is also reasonable to achieve cardiovascular fitness.224
Hydration and avoidance of environmental situations where vasodilatation may occur is important in the asymptomatic patient with resting or provocable LVOT obstruction. High-dose diuretics and vasodilators (for treatment of other diseases such as hypertension) should be avoided, because these may exacerbate the degree of obstruction.3,9 However, the lack of symptoms attributable to HCM should not detract from the use of negative inotropic agents such as beta blockers or calcium channel blockers as treatment for relevant comorbidities such as hypertension.10 Although data support the use of verapamil to relieve symptoms in HCM, other calcium antagonists such as diltiazem, even though widely used, have not been studied systematically.
Preliminary data in the animal model suggest that inhibitors of the renin-angiotensin pathway or statins or the calcium channel inhibitor diltiazem226 may prevent progression of hypertrophy in animal models of HCM.227,228 However, there is no completed randomized trial to indicate that these drugs are effective in reducing hypertrophy in humans with HCM. Thus, these drugs should not be given with the intent of altering HCM-related clinical outcome but only for the control of heart failure–related symptoms. Finally, the indication for septal reduction therapy is to improve symptoms that are not relieved by medical therapy and that impair the patient’s quality of life, usually consistent with NYHA functional classes III or IV.9,10 Thus, septal reduction therapy with either septal myectomy or alcohol septal ablation should not be performed in the asymptomatic patient, regardless of the severity of obstruction.9,10
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Class I 1 .It is recommended for all patients with HCM that co-morbidities that normally contribute to cardiovascular disease, including hypertension, diabetes, obesity and hyperlipidemia, be treated in compliance with relevant existing guidelines.
The HCMA also wishes to address the importance of maintaining an active lifestyle and wise eating plan to avoid adding to the burden on HCM hearts. It is a well established fact that lifestyle, diet and exercise can make meaningful impact upon overall fitness and health, including hypertension, obesity, and diabetes.
Class IIa 1. Low intensity aerobic activity is reasonable as a healthy part of lifestyle for those with HCM. In other words, it's okay to get off the couch and move, in fact, it is preferred.
Class IIb 1. The usefulness of beta-blockers and calcium channel blockers to alter clinical outcomes is not well established for the management of asymptomatic HCM patients with or without obstruction. The HCMA feels that a note of caution be given here as some patients and families may not completely appreciate the choice of words of the guideline committee. There is no perceivable harm in taking beta-blockers or calcium channel blockers for those with HCM. The potential for benefit for those who are not exhibiting overt or outward symptoms has yet to be identified.
Class III Harm 1. Septal reduction therapy should not be performed in asymptomatic adults or in pediatric HCM patients who have a normal exercise tolerance regardless of the severity of obstruction. Simply because a gradient is a number that is perceived as high by either a physician or a patient, is not ample information to choose an invasive therapeutic option that frankly is not reversible.
2. Among HCM patients with resting or provocable outflow tract obstruction, regardless of symptomatic status, pure vasodilators and high-dose diuretics are potentially harmful and should be avoided.
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6.2. Symptomatic Patients |
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6.2.1. Pharmacologic Management—Recommendations |
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Class I 1. Beta-blocking drugs are recommended for the treatment of symptoms (angina or dyspnea) in adult patients with obstructive or nonobstructive HCM but should be used with caution in patients with sinus bradycardia or severe conduction disease. 3,9,10,134,137,229 –236 (Level of Evidence: B) 2. If low doses of beta-blocking drugs are ineffective for controlling symptoms (angina or dyspnea) in patients with HCM, it is useful to titrate the dose to a resting heart rate of less than 60 to 65 bpm (up to generally accepted and recommended maximum doses of these drugs).3,10,137,229–236 (Level of Evidence: B) 3. Verapamil therapy (starting in low doses and titrating up to 480 mg/d) is recommended for the treatment of symptoms (angina or dyspnea) in patients with obstructive or nonobstructive HCM who do not respond to beta-blocking drugs or who have side effects or contraindications to beta-blocking drugs. However, verapamil should be used with caution in patients with high gradients, advanced heart failure, or sinus bradycardia.10,134,137,237–241 (Level of Evidence: B) 4. Intravenous phenylephrine (or other pure vasoconstricting agents) is recommended for the treatment of acute hypotension in patients with obstructive HCM who do not respond to fluid administration.137,242–244 (Level of Evidence: B
Class IIa 1. It is reasonable to combine disopyramide with a beta-blocking drug or verapamil in the treatment of symptoms (angina or dyspnea) in patients with obstructive HCM who do not respond to betablocking drugs or verapamil alone.10,134,137,245–248 (Level of Evidence: B) 2. It is reasonable to add oral diuretics in patients with nonobstructive HCM when dyspnea persists despite the use of beta blockers or verapamil or their combination.67,134 (Level of Evidence: C)
Class IIb 1. Beta-blocking drugs might be useful in the treatment of symptoms (angina or dyspnea) in children or adolescents with HCM, but patients treated with these drugs should be monitored for side effects, 2. It may be reasonable to add oral diuretics with caution to patients with obstructive HCM when congestive symptoms persist despite the use of beta blockers or verapamil or their combination.10,134,137 (Level of Evidence: C) 3. The usefulness of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in the treatment of symptoms (angina or dyspnea) in patients with HCM with preserved systolic function is not well established, and these drugs should be used cautiously (if at all) in patients with resting or provocable LVOT obstruction. (Level of Evidence: C) 4. In patients with HCM who do not tolerate verapamil or verapamil is contraindicated, diltiazem may be considered. (Level of Evidence: C)
Class III: Harm 1. Nifedipine or other dihydropyridine calcium channel-blocking drugs are potentially harmful for treatment of symptoms (angina or dyspnea) in patients with HCM who have resting or provocable LVOT obstruction. (Level of Evidence: C) 2. Verapamil is potentially harmful in patients with obstructive HCM in the setting of systemic hypotension or severe dyspnea at rest. (Level of Evidence: C) 3. Digitalis is potentially harmful in the treatment of dyspnea in patients with HCM and in the absence of AF.3,10,137,249–251 (Level of Evidence: B) 4. The use of disopyramide alone without beta blockers or verapamil is potentially harmful in the treatment of symptoms (angina or dyspnea) in patients with HCM with AF because disopyramide may enhance atrioventricular conduction and increase the ventricular rate during episodes of AF.10,66,134,252–257 (Level of Evidence: B) 5. Dopamine, dobutamine, norepinephrine, and other intravenous positive inotropic drugs are potentially harmful for the treatment of acute hypotension in patients with obstructive HCM.3,82,242–244,258–260 (Level of Evidence: B)
The major goal of pharmacologic therapy in symptomatic patients with HCM is to alleviate symptoms of exertional dyspnea, palpitations, and chest discomfort, which may reflect pathophysiologic mechanisms such as LVOT obstruction, reduced supply of myocardial oxygen, mitral regurgitation, and impaired LV diastolic relaxation and compliance.9,10,134
Beta blockers are the mainstay of pharmacologic therapy and the first-line agents because of their negative inotropic effects261 and their ability to attenuate adrenergic-induced tachycardia (Figure 3). These effects improve myocardial oxygen supply-demand relationships and hence reduce myocardial ischemia. The reduction in heart rate also prolongs the diastolic filling period, which may allow for more efficient inactivation of myocardial contractile proteins, thereby improving diastolic filling.262,263
In those patients unable to tolerate beta blockers or those with symptoms unresponsive to beta blockers, calcium channel blockers may provide effective symptomatic relief. Verapamil has been the most intensively studied such agent (Figure 3).239,264 Possible mechanisms for symptomatic improvement include negative inotropic and rate-lowering effects similar to those of beta blockers. However, the effect of verapamil on diastolic dysfunction is controversial.84,265–268 Whether improvement in indices of diastolic performance is a direct effect of verapamil or the result of reduction in ischemia is uncertain.213 Diltiazem has also been shown to improve measures of diastolic performance269 and to prevent or diminish myocardial ischemia.270 Both verapamil and diltiazem should be used cautiously in patients with severe outflow tract obstruction, elevated pulmonary artery wedge pressure, and low systemic blood pressure, because a decrease in blood pressure with treatment may trigger an increase in outflow obstruction and precipitate pulmonary edema. Administration of beta-blocking drugs with either verapamil or diltiazem should also be performed with caution because of the potential for high-grade atrioventricular block. In addition, because of the bradycardic effects when both classes of agents are used concomitantly, the addition of verapamil or diltiazem to a beta blocker may prevent titration of the beta blocker to optimal dosage. Dihydropyridine class calcium channel blockers (eg, nifedipine) should not be used in patients with obstructive physiology because their vasodilatory effects may aggravate outflow obstruction.
In patients with obstructive HCM who remain symptomatic despite the use of beta blockers and calcium channel blockers, alone or in combination, disopyramide may be effective in ameliorating symptoms in many patients (Figure 3).157,271 Anticholinergic side effects may occur and can be managed if necessary by dose reduction. Symptomatic benefit with disopyramide appears to represent a pure negative inotropic effect. The initiation of disopyramide should be performed in-hospital with cardiac monitoring for potential arrhythmias and lengthening of the QT. Diuretics may be effective for symptomatic relief in patients with pulmonary congestion but should be used judiciously in those with outflow tract obstruction. |
Class I 1. Beta-blockers are recommended for treatment of symptoms in adult patients with both obstructive and non- obstructive HCM, but should be used with caution in patients with bradycardia (low heart rates) or severe conduction disease.
2. If low dose beta-blockers are ineffective at controlling the symptoms of angina, or shortness of breath, in HCM patients, it is useful to slowly increase the dose to a resting heart rate of less than 60 to 65 beats per minute. Doses can reach up to an equivalent of Metropolol 200 mg per day or higher, for those who can tolerate it.
3. Verapamil therapy starting at low doses, slowly increasing upward to 480 mg per day is recommended for symptoms when obstructive and non-obstructive HCM do not respond to beta-blockers or have side effects or contraindication to beta -blocking agents. Verapamil is to be used with caution in patients with high gradients, advanced heart failure, or sinus bradycardia also known as slow heart rate.
4. Intravenous phenylephrine or other pure constricting agents is recommended in the treatment of acute hypotension in patients with obstruction who do not respond to fluid administration. Patients are cautioned to ensure anesthesiologists are well aware of their diagnostic status prior to any surgical intervention.
Class IIa 1. It is reasonable to combine disopyrimide, also known as Norpace, with a beta-blocking drug, or verapamil in the treatment of symptoms of angina, or shortness of breath, in patients with obstructive HCM who do not respond to beta- blocking drugs or verapamil alone.
2. It is reasonable to add oral diuretics to patients with non-obstructive HCM when shortness of breath persists despite the use of beta-blockers, verapamil or a combination of both.
Class IIb 1. Beta-blockers might be useful in the treatment of symptoms including chest pain or shortness of breath in children or adolescents with HCM. It is important to know that patients being treated with these drugs should be monitored for side effects including depression, fatigue or impaired scholastic performance. In addition, the HCMA wishes to remind parents that children who are taking medication for their HCM may benefit from having a 504 plan in place should the child develop side effects, from the medication, that alter their cognitive ability.
2. It may be reasonable to add oral diuretics, with caution, to patients with obstructive HCM when congestive symptoms persist despite the use of beta-blockers, calcium channel blockers or a combination of both.
3. The usefulness of ACE inhibitors or ARB’s in the treatment of symptoms, including chest pain or shortness of breath, in patients with preserved systolic function is not well established and these drugs should be used with caution if, in fact, used at all in patients with resting or provocable obstruction.
4. In patients with HCM who do not tolerate verapamil or verapamil is contraindicated, diltiazem may be considered
Class III Harmful 1. Nifedipine or other dyhydropyrodyidrine calcium channel blocking drugs are potentially harmful for treatment of symptoms, including shortness of breath and chest pain, in HCM patients who have resting or provocable left ventricular outflow tract obstruction. 2. Verapamil is potentially harmful in patients with obstructive HCM in the setting of static hypotension or severe shortness of breath at rest.
3. Digitalis is potentially harmful in the treatment of shortness of breath in patients with HCM in the absence of atrial fibrillation.
4. The use of disopyrimide alone, without a beta blocker or Verapamil,is potentially harmful in the treatment of symptoms, including chest pain or shortness of breath in HCM patients with atrial fibrillation, as the agent may enhance conduction delays that increase the heart rate from the ventricle during episodes of atrial fibrillation.
5. Dopamine, dobutamine, norepinephrine and other intravenous positive inotropic drugs are potentially harmful for the treatment of acute hypotension in patients with obstructive HCM.
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6.2.2. Invasive Therapies—Recommendations |
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Class I 1. Septal reduction therapy should be performed only by experienced operators* in the context of a comprehensive HCM clinical program and only for the treatment of eligible patients with severe drug refractory symptoms and LVOT obstruction.†272 (Level of Evidence: C) *Experienced operators are defined as an individual operator with a cumulative case volume of at least 20 procedures or an individual operator who is working in a dedicated HCM program with a cumulative total of at least 50 procedures (Section 6.2.2.3). †Eligible patients are defined by all of the following: a. Clinical: Severe dyspnea or chest pain (usually NYHA functional classes III or IV) or occasionally other exertional symptoms (such as syncope or near syncope) that interfere with everyday activity or quality of life despite optimal medical therapy. b. Hemodynamic: Dynamic LVOT gradient at rest or with physiologic provocation greater than or equal to 50 mm Hg associated with septal hypertrophy and SAM of the mitral valve. c. Anatomic: Targeted anterior septal thickness sufficient to perform the procedure safely and effectively in the judgment of the individual operator.
Class IIa 1. Consultation with centers experienced in performing both surgical septal myectomy and alcohol septal ablation is reasonable when discussing treatment options for eligible patients with HCM with severe drug-refractory symptoms and LVOT obstruction. (Level of Evidence: C) 2. Surgical septal myectomy, when performed in experienced centers, can be beneficial and is the first consideration for the majority of eligible patients with HCM with severe drug-refractory symptoms and LVOT obstruction.61,62,155,273–275 (Level of Evidence: B) 3. Surgical septal myectomy, when performed at experienced centers, can be beneficial in symptomatic children with HCM and severe resting obstruction (greater than 50 mm Hg) for whom standard medical therapy has failed.276 (Level of Evidence: C) 4. When surgery is contraindicated or the risk is considered unacceptable because of serious comorbidities or advanced age, alcohol septal ablation, when performed in experienced centers, can be beneficial in eligible adult patients with HCM with LVOT obstruction and severe drug refractory symptoms (usually NYHA functional classes III or IV).62,153,277–281 (Level of Evidence: B)
Class IIb 1. Alcohol septal ablation, when performed in experienced centers, may be considered as an alternative to surgical myectomy for eligible adult patients with HCM with severe drug-refractory symptoms and LVOT obstruction when, after a balanced and thorough discussion, the patient expresses a preference for septal ablation.153,273,278,280,281 (Level of Evidence: B) 2. The effectiveness of alcohol septal ablation is uncertain in patients with HCM with marked (eg, greater than 30 mm) septal hypertrophy, and therefore the procedure is generally discouraged in such patients. (Level of Evidence: C)
Class III: Harm 1. Septal reduction therapy should not be done for adult patients with HCM who are asymptomatic with normal exercise tolerance or whose symptoms are controlled or minimized on optimal medical therapy. (Level of Evidence: C) 2. Septal reduction therapy should not be done unless performed as part of a program dedicated to the longitudinal and multidisciplinary care of patients with HCM. (Level of Evidence: C) 3. Mitral valve replacement for relief of LVOT obstruction should not be performed in patients with HCM in whom septal reduction therapy is an option. (Level of Evidence: C) 4. Alcohol septal ablation should not be done in patients with HCM with concomitant disease that independently warrants surgical correction (eg, coronary artery bypass grafting for CAD, mitral valve repair for ruptured chordae) in whom surgical myectomy can be performed as part of the operation. (Level of Evidence: C) 5. Alcohol septal ablation should not be done in patients with HCM who are less than 21 years of age and is discouraged in adults less than 40 years of age if myectomy is a viable option. (Level of Evidence: C)
See Data Supplement 2 for further information on data supporting the recommendations for invasive therapies. Although the writing committee recognizes that surgical myectomy and ablation are methodologically very different approaches and interventions, in this section they are discussed together because they are the 2 generally accepted methods for relief of symptoms in patients with LVOT obstruction. Most patients with HCM lead active lifestyles with minimal or no symptoms, but some patients incur significant symptoms that interfere with everyday activity or quality of life.48 For symptoms that are attributable to LVOT obstruction, invasive therapies can be used to improve quality of life (Figure 3). Surgical approaches have been used for 5 decades72,144 so that relief of outflow tract obstruction and symptoms can be achieved with minimal perioperative morbidity or mortality in experienced centers.61,155 However, some patients are not optimal surgical candidates (eg, because of comorbidities or advanced age) or have such a strong desire to avoid surgery that alternative therapeutic interventions have been implemented. Alcohol septal ablation, which has been in use for the past 17 years, has become the leading strategy in these circumstances.282 This procedure causes a regional infarction of the basal septum, thereby initially decreasing contractility and eventually causing thinning (because of scarring) of the basal septum and consequent widening of the outflow tract.
Dual-chamber pacing has also been used and studied for the relief of outflow tract obstruction. The proposed mechanism relates to a change in the activation sequence of the septum and possibly long-term remodeling. Randomized controlled trials suggested a modest benefit of pacing therapy, primarily in those _65 years of age.283,284 In the current era, application of dual-chamber pacing for the relief of symptoms attributable to outflow tract obstruction is primarily used in patients with significant comorbidities for whom both surgical septal myectomy and alcohol septal ablation are considered to have unacceptable risk or in patients who already have an implanted dual-chamber pacing device (often implanted for nonhemodynamic indications). |
Class I 1. Septal reduction therapy should be performed only by experienced operators. The definition of experience, while open for interpretation and elsewhere is defined for purposes of this document, are those operators with a cumulative case volume of the least 20 procedures and working in a dedicated HCM program with a cumulative total volume of at least 50 procedures.
The HCMA wants you to know that our experience clearly indicates that those programs with high volume have the lowest complication rates and best outcomes.
Patients who are eligible for septal reduction therapy fit the following three characteristics:
Clinical severe shortness of breath or chest pain usually described as New York Heart Association functional Classes III or IV or those with occasional or exceptional symptoms, such as syncope or near syncope, also known as passing out or nearly passing out, that interferes with everyday activity or quality of life despite optimal medical therapy.
Hemodynamic status of dynamic left ventricular outflow tract gradient at rest or with provocation (either with Valsalva maneuver or on stress test) of 50 mmHg of mercury or greater is associated with septal hypertrophy and systolic anterior motion of the mitral valve.
Anatomic anterior septal thickness sufficient to perform the procedure safely and effectively in the judgment of the operator.
Class IIa 1. Consultation with centers experienced in performing surgical septal myectomy and alcohol septal ablation, meeting the criteria set forth in this document as a high volume operator, is reasonable when discussing treatment options for eligible HCM patients with refractory symptoms and left ventricular outflow tract obstruction.
2. Surgical septal myectomy, when performed in a high-volume center as described previously in this document, can be beneficial and is the first consideration for the majority of eligible HCM patients with severe drug refractory symptoms and left ventricular outflow tract obstruction.
3. Surgical septal myectomy, when performed in a high-volume center as described previously in this document, can be beneficial to symptomatic children with HCM and severe resting obstruction – with gradients over 50 mmHg who have failed standard medical therapy.
4. When surgical myectomy is contraindicated, or the risk is considered unacceptable due to serious co-morbidities or advanced age, and anatomy is appropriate for a successful intervention, then alcohol septal ablation, when performed in experienced centers as described earlier in this document, can be a beneficial therapy for adults with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction which is severe and not responsive to medical management. This therapy is usually reserved for patients with New York Heart Association class III or IV symptoms.
Class IIb 1. Alcohol septal ablation when performed in experienced centers, as previously defined in this document, may be considered as an alternative to surgical myectomy for eligible adult HCM patients with severe drug refractory symptoms and left ventricular outflow tract obstruction when a balanced and thorough discussion has been performed.
Additional language entered here by the Hypertrophic Cardiomyopathy Association - expert opinion has concluded that if the anatomy is appropriate for this intervention, and the patient expresses a preference for alcohol septal ablation and age is appropriate, the procedure can be conducted safely and effectively.
2. The effectiveness of alcohol septal ablation is uncertain in HCM patients with severe hypertrophy defined as 3.0 or greater and is, therefore, discouraged in such patients. Patients with septal wall measurements approaching 3.0 cm may wish to have very balanced discussions with high-level, experienced operators in both myectomy and alcohol septal ablation before proceeding onward with either treatment option.
Class III harm 1. Septal reduction therapy should not be done for adult patients with HCM who are asymptomatic with normal exercise tolerance or whose symptoms are controlled or minimized efficiently on optimal medical therapy.
2. Septal reduction therapy should not be done at centers without longitudinal and multidisciplinary care of patients with HCM.
Comment by the Hypertrophic Cardiomyopathy Association - It is strongly discouraged for patients to proceed with low volume operators in medical programs that are not centers of excellence with a focused program on the treatment and management of hypertrophic cardiomyopathy and appropriate staff with extensive training in this sub-specialty care. Patients are cautioned that these programs may not be geographically convenient at all times and while it is potentially burdensome to travel to these large scale programs, to experience the benefit far outweighs the burden. These observations come from 16 years of experience with over 5000 families heeding this advice and benefiting from the advanced knowledge and care of HCM specialty programs throughout the world.
3. Mitral valve replacement for the purpose of relief of left ventricular outflow tract obstruction should not be performed in patients with hypertrophic cardiomyopathy in whom septal reduction therapy is an option. Please refer to the comments in the previous recommendation regarding centers of excellence. It is far more common to see patients undergo unnecessary mitral valve replacement in programs and medical centers with little experience in the treatment and management of hypertrophic cardiomyopathy. Again high volume HCM programs should be sought after for any major intervention in the care or management of HCM patients.
4. Alcohol septal ablation should not be done in HCM patients with co-existing disease that independently warrants surgical correction. For example, coronary artery bypass, grafting for coronary artery disease, or mitral valve repair for ruptured Corday or, in those who would benefit from any of these procedures, in whom surgical myectomy can be performed as part of the operation.
5. Alcohol septal ablation should not be done in HCM patients under the age of 21 years, and is discouraged in adults less than 50 years of age, in the experience of the Hypertrophic Cardiomyopathy Association; yet, for some reason, we suspect due to the lobbying of interventional cardiologists in the production of this document, the age of 40 is cited. Myectomy remains the gold standard treatment and should be considered as the primary method for the relief of left ventricular outflow tract obstruction in refractory patients.
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6.2.2.1. Selection of Patients
It is well recognized that the appropriate selection of patients for individual procedures is an important predictor of outcome. Because the majority of patients with HCM can achieve control of their symptoms with optimal pharmacologic therapy, and in light of the complications inherent with invasive therapies, a core set of clinical, anatomic, and hemodynamic criteria are required before patients are considered candidates for invasive therapies. Specifically, patients must have symptoms attributable to LVOT obstruction that are refractory to optimal pharmacologic therapy. Similarly, it must be demonstrated that the obstruction is caused by apposition of the mitral valve with the hypertrophied septum (and not attributable to systolic cavity obliteration). 72,144 It has been generally accepted that maximal instantaneous gradients of at least 50 mm Hg at rest or with physiologic provocation are necessary to produce symptoms amenable to invasive therapies.10
Given the duration of experience, documented long-term results, and safety data, surgical septal myectomy is considered the preferred treatment for most patients who meet these criteria (Figure 3). Considerations that would favor surgical intervention include younger age, greater septal thickness, and concomitant cardiac disease independently requiring surgical correction (eg, intrinsic mitral valve disease or coronary artery bypass grafting). Additionally, specific abnormalities of the mitral valve and its support apparatus can contribute significantly to the generation of outflow tract obstruction, suggesting the potential value of additional surgical approaches (eg, plication, valvuloplasty, and papillary muscle relocation) and making myectomy more appropriate than alcohol septal ablation in some patients.16,80,285–290 Among patients who meet the core selection criteria, factors that influence a decision to proceed with alcohol septal ablation include older or advanced age, significant comorbidity that selectively increases surgical risk, (eg, significant concerns about lung or airway management) and the patient’s strong desire to avoid open-heart surgery after a thorough discussion of both options. |
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6.2.2.2. Results of Invasive Therapy for the Relief of LVOT Obstruction
More detailed discussions specific to each type of procedure follow in subsequent sections of this document. Overall, reports suggest that technical success, variably defined, is achieved in 90% to 95% of patients who undergo surgical myectomy,291 less in septal ablation, and only in the minority of patients studied in trials of pacemaker therapy.292–295 Patients undergoing septal ablation may have hemodynamic and symptomatic improvement comparable to septal myectomy if the area of the SAM-septal contact can be accessed by the first septal perforator and ablated. However, compared with septal myectomy in which the hypertrophied muscle is directly visualized and resected, successful septal ablation is dependent on the variable septal artery anatomy, which may not supply the targeted area of the septum in up to 20% to 25% of patients.62,296 In a nonrandomized retrospective evaluation of patients _65 years of age in whom relief of outflow tract obstruction was initially achieved, survival free from recurrent symptoms favored myectomy over ablation (89% versus 71%, P_0.01).62 Longer comparative follow-up data are unavailable at this time. These procedural successes are balanced by very low procedural mortality (_1% for myectomy, 61,155,297 ranging from 0% to 4% for ablation),298–300 and low nonfatal complication rates (2% to 3% in experienced centers), with the exception of high-grade atrioventricular block following septal ablation. The latter is an inherent aspect of the septal infarction and based on the available data that can result in the need for permanent pacemakers in 10% to 20% of ablation patients.301–303 The data from trials of dual-chamber pacing suggest that there was a significant placebo effect and inconsistent symptomatic benefit.283,284,29 |
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6.2.2.3. Operator Experience |
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Operator and institutional experience, including procedural volume, is a key determinant of successful outcomes and lower complication rates for any procedure. For HCM, a disease of substantial heterogeneity that is relatively uncommon in general cardiology practice, this is an important issue. As with the recommendations made in the “ACCF/AHA Guidelines for the Management of Patients With Valvular Heart Disease” about expected outcomes for surgeons offering mitral valve repair,304 it would be prudent and appropriate for individual centers, surgeons, and interventional cardiologists to demonstrate sufficient success and safety to justify ongoing use of these procedures. Although it is difficult to define a precise case volume or cumulative experience required to perform these procedures, at least 1 study suggests that the learning curve relative to invasive therapy in HCM may require the performance of at least 40 procedures.272 As a consensus opinion, the writing committee recommends an operator volume of at least 20 procedures or that the operator work within the context of an HCM program with a cumulative procedural volume of at least 50 procedures. In addition, given the data available from experienced centers, operators and institutions should aim to achieve mortality rates of _1% and major complication rates of _3%, with documented success in both hemodynamic and symptom benefit for their patients. This is best achieved in the context of a systematic program dedicated to the multidisciplinary and longitudinal care of patients with HCM. |
The HCMA’s experience of over 5000 families with HCM completely aligns with the recommendation that high volume operators are key – however the number that defines “high” is by its nature arbitrary.
Patients are advised to ask for the experience level of the operator for septal reduction (surgical or ASA), atrial fibrillation therapies, ICD implants or any invasive procedure in two ways – what is the individual operators experience and what is the centers experience? Patients are cautioned to ask for the time frame of this experience – for example. How many did you perform last year, in the last 3 years and in the last 5 years? How many did your center perform in the past year, last 3 and last 5 years? Patients will want to ensure that that number is at or in excess of the recommended 50 procedures in the recent past.
Based on the experience of the HCMA this number currently limits the number of surgical and ASA programs to under 10 in the USA in 2011 – this number is expected to grow in coming years. |
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6.2.2.4. Surgical Therapy |
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Transaortic septal myectomy is currently considered the most appropriate treatment for the majority of patients with obstructive HCM and severe symptoms unresponsive to medical therapy (Figure 3).276,291,305–313 Surgical results, although vastly improved in recent years, are nevertheless limited to relatively few centers with extensive experience and particular interest in the management of HCM.288,314 Both the traditional myectomy (Morrow procedure) with about a 3-cm long resection309 and extended myectomy (a resection of about 7 cm) are currently used.288,314
The transaortic approach remains the primary method of exposure. Virtual abolition of the LV outflow gradient and mitral regurgitation is usually accomplished by muscular resection resulting in physical enlargement of the outflow tract and by interruption of the mitral valve SAM, which is usually responsible for the outflow gradient.315 Septal myectomy in the current era is commonly referred to as an “extended myectomy.” This refers to the fact that the muscular resection becomes progressively wider as the resection proceeds into the ventricle (ie, toward the apex), effectively making the trough wider at the mid-ventricular level. As a result, the myectomy resection is opposite the lateral portion of the anterior leaflet (to avoid conduction tissue), the chordae, and both papillary muscles. In addition, muscular resection is also performed along the left lateral free wall (also part of the LVOT), resulting in a much more extensive myectomy than that originally described by Morrow et al about 50 years ago.309 In selected circumstances, some surgeons have also used concomitant mitral valve repair, particularly when the anterior leaflet is elongated. This valve repair maneuver usually involves shortening the height of the anterior leaflet. However, residual mitral valve regurgitation after adequate septal myectomy is almost always caused by intrinsic mitral valve abnormalities such as ruptured chordate, myxomatous degeneration with prolapse, or annular dilatation, and can be corrected by direct valve repair. Finally, enlarged or malpositioned papillary muscles can also contribute to residual obstruction. This can be effectively treated by shaving the hypertrophied papillary muscles, incising papillary muscles off the ventricular free wall, and in selected circumstances repositioning one papillary muscle by suture approximation to the adjacent papillary muscle.
The surgical specimen obtained at the time of myectomy should be submitted for pathologic examination, not only to confirm the histopathology of HCM, but also for special stains to rule out storage diseases that can mimic HCM.31 |
The original surgery for those with obstructive HCM was created and first performed by Morrow at NIH in the 1960’s. Since that time, it has been refined and enhanced by modern programs to include a more complete and extended re-sectioning of the left ventricle.
This procedure allows the surgeon to remove not only the bulk of muscle contributing to obstruction, but to also repair the mitral valve and/or papillary muscles lower in the chamber or those inserted into the mitral valve itself, as well as, other abnormalities which may be present in the HCM heart (including ruptured chordae, myxomatous degeneration with prolapse, or annular dilatation).
The procedure is performed through a traditional “open heart” procedure requiring the patient be placed on cardiac bypass.
Patients with a pre-existing right bundle branch block are at a higher likelihood of needed pacing for heart block after surgery as the procedure will create a left bundle branch block.
After surgery is complete the specimen obtained should be submitted for pathological examination to evaluate the cellular structure of the heart. This can help to determine if the patient has HCM or an HCM mimicker. |
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6.2.2.4.1. Selection of Patients. |
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It is important to underscore that the subjective assessment of operative risk by clinicians frequently results in an overestimate of risk, resulting in the denial of proven therapies for eligible patients in favor of less effective or less proven options.316 In patients perceived to be at prohibitively high risk because of major comorbidities, including age, the use of objective risk tools in the context of individual institutional experience could lead to a reassessment of operative risk to be lower than initially thought |
Patients should receive information on risk in a balanced and factual manner. Patient should appreciate the risk of the procedure balanced with the potential benefits. Each patient must be evaluated based on their condition at the time of surgery and all factors including other medical conditions, age, weight and lifestyle habits should be discussed in a candid manner.
Operative risks at high volume programs are very low – and the list of potential side effects and risks are very low, normally very treatable and should be thought about and discussed well in advance. |
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6.2.2.4.2. Outcomes
Early Results. Based on the experience and data assembled from multiple centers worldwide over the last 4 decades, 276,291,305,307,308,310,311 septal myectomy is established as the most effective and proven approach for reversing the consequences of heart failure by providing amelioration of obstruction (and relief of mitral regurgitation) at rest, with restoration of functional capacity and acceptable quality of life at any age, exceeding that achievable with long-term administration of cardioactive drugs.10,175 These salutary benefits have been demonstrated subjectively by patient history and objectively by increased treadmill time, maximum workload, peak oxygen consumption, and improved myocardial oxygen demand, metabolism, and coronary flow.10,273,294
LV outflow gradient reduction with myectomy results from basal septal thinning with resultant enlargement of the LVOT area (and redirection of forward flow with loss of the drag and Venturi effects on the mitral valve)317 and consequently abolition of SAM and mitral-septal contact.314,318,319 Mitral regurgitation is also usually eliminated without the need for additional mitral valve surgery.148 With myectomy, LA size (and possibly long-term risk for AF) is reduced155 and LV pressures (and wall stress) are normalized 10,61,148,317,320 Thus, obstructive HCM is a surgically and mechanically reversible form of heart failure. In experienced centers, operative risk is now particularly low, in the range of _1%.175
Late Results. Relief of outflow obstruction by septal myectomy may also extend the longevity of patients with HCM.61 Although randomized trials involving myectomy surgery have not been performed, in a nonrandomized study, myectomy resulted in excellent long-term survival similar to that in the general population. After septal myectomy, long-term actuarial survival was 99%, 98%, and 95% at 1, 5, and 10 years, respectively (when considering HCM-related mortality). This survival rate did not differ from that expected in a matched general US population and was superior to that achieved by patients with obstructed HCM who did not undergo surgical myectomy.61 Similarly, the rate of SCD or appropriate ICD discharge after myectomy is very low (_0.9%).61,321,322 Nonetheless, surgical myectomy does not eliminate the need to assess each patient’s risk for SCD and to consider placement of an ICD in those with a significant risk burden. |
Intentionally left blank as the guidelines document is self explanatory.
HCMA will add this note: The muscle does not grow back in adults. Those patients requiring second surgeries normally fall into two groups – those who had surgery under the age of 25 and for whom growth was still a factor and those who did not have an adequate myectomy the first time because they did not take out ample amounts of muscle.
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6.2.2.4.3. Complications.
Complications following myectomy are rare when myectomy is performed in experienced centers.315 The risk of complete heart block is 2% with myectomy (higher in patients with preexisting right bundlebranch block), but in patients who have had previous alcohol septal ablation, risk is much higher (50% to 85%).323 Iatrogenic ventricular septal defect occurs in _1% of patients. Finally, the risk of aortic valve or mitral valve injury is also low (_1%), particularly when myectomy is performed by an experienced operator. |
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6.2.2.4.4. Mitral Valve Abnormalities and Other Anatomic Issues.
Abnormalities of the mitral valve and subvalvar apparatus (including anomalous direct anterolateral papillary muscle insertion into anterior mitral leaflet and elongated mitral leaflets)80,324 can be identified preoperatively with TTE or intraoperative TEE and can be corrected with modified mitral valve repair or extended myectomy techniques without the need for mitral valve replacement. Indeed, the excellent early and late outcome of extended myectomy for treatment of obstructive HCM has made mitral valve replacement exceedingly rare.315 Associated degenerative mitral valve disease (ie, prolapse, ruptured chordae) can be treated by concomitant mitral valve repair at the time of myectomy. Mitral valve repair techniques may need to be modified in HCM to avoid subsequent development of SAM.325
Mitral valve replacement in patients with obstruction has been performed rarely when septal reduction therapy was judged unsafe or likely to be ineffective. When the basal septum is only mildly hypertrophied (_16 mm), the risk for either iatrogenic ventricular septal defect from excessive muscular resection or residual postoperative outflow obstruction from inadequate resection increase. Mitral valve replacement may be an option in rare patients.326,327 |
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6.2.2.5. Alcohol Septal Ablation |
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First reported in 1995,282 alcohol septal ablation uses transcoronary administration of absolute ethanol via a percu-taneous approach to induce a localized infarction of the basal septum at the point of contact of the anterior mitral valve leaflet, thereby reducing outflow tract gradient and associated mitral regurgitation and simulating the results of surgical myectomy. Developed as an alternative to surgical septal myectomy, the technique is particularly useful when surgery is contraindicated and in patients who are considered poor surgical candidates.279 Since its development, alcohol septal ablation has been performed successfully in a large number of patients.153
After measurement of resting or provoked outflow tract gradients, a temporary pacemaker is placed in the right ventricle because of the risk of procedural complete heart block.328–330 With the use of standard angioplasty equipment and anticoagulation, a guidewire and coronary angioplasty balloon are placed in the septal perforator that appears to perfuse the target myocardium. Contrast angiography of the perforator through the balloon central lumen with simultaneous echocardiographic guidance331,332 confirms delivery to only the target myocardium. About 1 to 3 mL of alcohol is infused in controlled fashion.151,333–335 Incorporation of myocardial contrast echocardiography reduces the number of septal branches into which ethanol is injected and may both improve the success rate and lower cardiac biomarker release and the need for pacing.331–333,336 It is important that the balloon be inflated and that a contrast injection also show that there is no extravasation of dye into the distal left anterior descending coronary artery. Contrast enhancement of other regions (papillary muscles, free wall) indicates collateral circulation from the septal perforator artery, and alcohol should not be infused. A decrease in resting and provocable gradients usually occurs immediately after the procedure (because of stunning), and remodeling can result in continued or variable gradient reduction over the first 3 months after the procedure. Patients are monitored for arrhythmias and conduction disturbances in the intensive care unit for 24 to 48 hours; implantation of a permanent pacemaker may be necessary for complete or high-grade atrioventricular block and through discharge at 3 to 4 days. |
This procedure was first reported in 1995 as an alternative to surgical myectomy. It has proven very successful in patients who are not viewed as appropriate surgical candidates. The procedure has been preformed safely in large numbers of patients.
The procedure is performed through a cardiac catheter. An appropriate vein in the heart called a septal perforator is located and isolated. A small amount of alcohol is injected into this area which causes a small infarct. The desired result is to remove the area in which the mitral valve and the septum make contact thus causing the obstruction.
Patients with a pre-existing left bundle branch block are at a higher likelihood of needed pacing for heart block after the procedure as it will create a right bundle branch block.
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6.2.2.5.1. Selection of Patients. |
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Alcohol septal ablation has the potential for greater patient satisfaction because of the absence of a surgical incision and general anesthesia, less overall discomfort, and a much shorter recovery time. The benefit of alcohol septal ablation in patients of advanced age is similar to that in other patients.277,337 Because the postoperative risks and complications of cardiac surgery increase with age, ablation may offer a selective advantage in older patients, in whom operative risk may be increased because of comorbidities. Alcohol septal ablation is not indicated in children.
On the other hand, longer-term follow-up data are available for septal myectomy than for septal ablation, a consideration relevant to the selection of patients for either septal reduction therapy. The likelihood of implantation of a permanent pacemaker is 4- to 5-fold higher after septal ablation than after septal myectomy. Clinical and hemodynamic benefit is achieved immediately after recovery from septal myectomy but may be delayed for up to 3 months after septal ablation, although many patients achieve a notable symptomatic benefit after the procedure. Furthermore, patients with massive septal thickness approaching or exceeding 30 mm may experience little or no benefit from septal ablation. The surgeon can tailor the myectomy under direct visualization to address specific anatomic abnormalities of the LVOT or mitral valve apparatus, whereas alcohol septal ablation indirectly (and is restricted to) targets the distribution of the septal perforator artery.
Septal myectomy is the preferred treatment option for most severely symptomatic patients with obstructive HCM, especially in younger, healthy adults, whereas septal ablation is preferred in patients for whom surgery is contraindicated or considered high risk (particularly the elderly) (Figure 3). Data comparing alcohol septal ablation with septal myectomy are inadequate to fully inform clinical decision making in certain cases. For such patients, the principle of patient autonomy dictates that it is appropriate for the informed patient to choose between the 2 procedures. |
While ablation may appear less invasive it has a limited utility in that patient selection is far less about what a patient may “want” but rather what the patient’s anatomy dictates is “needed”.
Most people would prefer not to have open heart surgery ,that is rather obvious; however, the option of alcohol septal ablation is not equally compared to myectomy when patients are reviewing options.
Those with: Very thick septums, abnormal papillary muscles, mid cavity obstruction, walls that are too thin (under 1.7), in need of procedures for atrial fibrillation or coronary artery disease and those under the age of 40-50 are generally not candidates for the procedure.
On the other hand those who are: Over 60, have basal septal hypertrophy, a septal wall measurement of 1.8 to 2.5, and anatomy of the heart that does not include significant mitral valve disease or abnormalities in the papillary muscles and whom have other medical issues including obesity, diabetes, kidney disease or other conditions are potential candidates for alcohol septal ablation. |
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6.2.2.5.2. Results |
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Necrosis of the basal ventricular septum338 produces an immediate fall in gradient from decreased septal contraction in _90% of patients.156,300,339–341 This effect is followed by LV remodeling over 6 to 12 months, a process that includes scar retraction and resultant widening of the outflow tract, associated with further reduction in gradient and degree of mitral regurgitation, regression of hypertrophy, and improvement in diastolic function.154,300,342–344 LA pressure is reduced, which may promote a decreased incidence of AF and amelioration of pulmonary hypertension.345 Two studies have demonstrated that, as with septal myectomy, the benefit of septal ablation in patients with provocable gradients is similar to that in patients with resting gradients.346,347 The beneficial results of alcohol septal ablation have been reported to almost 5 years after the procedure with improved functional and angina classes, exercise capacity, and quality of life.153,300,348–351 However, hemodynamic and symptomatic success is dependent on the ability to cannulate and ablate a septal perforator artery that supplies the area of the SAM-septal contact.
Although randomized controlled trials comparing surgical myectomy with alcohol septal ablation have not been conducted and are highly unlikely in the future, meta-analyses have noted similar hemodynamic and functional improvement over 3 to 5 years when examining the cumulative average of outcomes.352–354 What the meta-analyses do not report are a subset of patients in whom alcohol septal ablation is unreliable because of the inability to ablate the area of the SAM-septal contact.355 Older patients, especially those considered to be at high surgical risk, may be well served by alcohol septal ablation, whereas younger patients may benefit most from surgical myectomy.62,279 Despite age differences in treatment allocation, with septal ablation patients on average approximately 10 years older in clinical practice,352,353 the 4-year survival rate is similar for the 2 procedures.62,278 Most studies that have compared surgical myectomy and alcohol septal ablation have involved a large single-center experience in which treatment assignment was not randomized. |
It may take a while for the area that has been injected with alcohol to completely die off – on average remolding will occur in 6-12 months.
Long term survival is good. Older patients do very well and younger patients are encouraged to seek myectomy. |
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6.2.2.5.3. Complications.
In approximately half of patients undergoing alcohol septal ablation, temporary complete atrio-ventricular block occurs during the procedure.328–330 Persistent complete heart block prompting implantation of a permanent pacemaker occurs in 10% to 20% of patients based on the available data.36 Approximately 5% of patients have sustained ventricular tachyarrhythmias during hospitalization. The in-hospital mortality rate is up to 2%.62,153,279,353 Because of the potential for creating a ventricular septal defect, septal ablation should not be performed if the target septal thickness is _15 mm.
Alcohol septal ablation is a therapeutic alternative to surgical myectomy for selected patients and produces a transmural infarction of ventricular septum occupying on average 10% of the overall LV wall.53,296,356 There has been concern that the potential ventricular arrhythmogenicity of the scar created by septal ablation might augment risk in the HCM population. Several studies have documented the occurrence of sustained ventricular arrhythmias332,349,357–363 and SCD following septal ablation322 in about 3% to 10% of patients both with or without risk factors for SCD. In a single-center experience (N_91), 21% of patients experienced sudden or other cardiac death, aborted sudden death, and/or appropriate ICD discharge resulting in an annualized event rate of 4.4% per year after ablation.322 In a second single-center experience (n_89), no mortality was attributable to SCD in 5.0_2.3 years of follow-up. However, in a selected subset of 42 patients with an ICD or permanent pacemaker that enabled detection of device-stored electrograms, the annualized event rate (VT, ventricular fibrillation, and/or appropriate ICD discharge, including periprocedural arrhythmias) was 4.9% per year.362 Data from another center suggest appropriate ICD intervention rates after ablation of 2.8% per year364; similarly, the multicenter HCM ICD registry (N_506) demonstrated that the rate of appropriate ICD therapy among ablation patients with primary prevention ICDs was 3 to 4 times more frequent than in other patients in that registry (10.3% per year compared with 2.6% per year).55 Patients with HCM considered to carry sufficient risk to warrant ICD placement have an annual incidence of appropriate interventions for VT/ventricular fibrillation of 3% to 10%.55,360,364 It is uncertain how common such events are attributable to the procedure or alternatively to the underlying disease, but the incidence of sustained ventricular arrhythmias after myectomy is extremely low (0.2% to 0.9% per year).61,321,322
Meta-analyses have indicated no difference between septal ablation and myectomy in the medium-term incidence of SCD or all-cause mortality.352,365 Although no definitive evidence is available that the ablation scar as such increases (or does not increase) long-term risk for sudden death in absolute terms in this patient population, resolution will require greatly extended follow-up studies in larger patient cohorts.53,357 |
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6.2.2.6. Pacing—Recommendations |
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Class IIa 1. In patients with HCM who have had a dual-chamber device implanted for non-HCM indications, it is reasonable to consider a trial of dual-chamber atrial-ventricular pacing (from the right ventricular apex) for the relief of symptoms attributable to LVOT obstruction.292,294,295,366 (Level of Evidence: B)
Class IIb 1. Permanent pacing may be considered in medically refractory symptomatic patients with obstructive HCM who are suboptimal candidates for septal reduction therapy.283,292,294,295,366 (Level of Evidence: B)
Class III: No Benefit 1. Permanent pacemaker implantation for the purpose of reducing gradient should not be performed in patients with HCM who are asymptomatic or whose symptoms are medically controlled.283,284,367 (Level of Evidence: C) 2. Permanent pacemaker implantation should not be performed as a first-line therapy to relieve symptoms in medically refractory symptomatic patients with HCM and LVOT obstruction in patients who are candidates for septal reduction.283,284,367 (Level of Evidence: B)
See Data Supplement 3 for further information on data supporting the recommendations for pacing.
Implantation of a dual-chamber pacemaker has been proposed as an alternative treatment for patients with severe symptomatic obstructive HCM.368–371 Pacing the right ventricular apex with maintenance of atrioventricular synchrony results in a decrease in the LVOT gradient and improvement of symptoms in a subset of patients. Although the exact mechanism of improvement with pacing remains unknown, the decrease in gradient may be caused by timing of septal contraction but may also reflect long-term remodeling.369 Although there was an initial enthusiasm for dual-chamber pacing as a primary treatment for patients with obstructive HCM, subsequent randomized trials demonstrated long lasting beneficial results in only a small minority of patients, whereas most perceived improvement was judged to be a placebo effect.283,284,367 A trial of dual-chamber pacing may be considered for symptomatic patients with obstruction in whom an ICD has already been implanted for high-risk status. |
Class I Ia In HCM patients who have a dual chamber device implanted for non-HCM indications, it is reasonable to consider a trial of dual chamber ventricular pacing -- from the right apex -- for the relief of symptoms due to outflow tract obstruction. It is important for patients to understand that one should not receive the device with the intent to try to pace the heart out of obstruction; but rather with the philosophy that if the device is already implanted for another purpose, there would be no harm potentially in an attempt to alter the settings to accomplish this task.
Class IIb Permanent pacing may be considered medically refractory for symptomatic patients with obstruction who are not an optimal candidate for septal reduction. There are an incredibly small subsection of patients and, like most of the other recommendations for patients with HCM, it is advised that one seek the advice of a center of excellence before committing themselves to a lifetime of pacemaker dependency.
Class III No Benefit Permanent pacemaker implantation for the purpose of reducing gradient should not be performed in patients who are asymptomatic or whose symptoms are medically controlled.
Permanent pacemaker implantation should not be performed as a first-line therapy to relieve symptoms in medically refractory symptomatic patients with HCM and LV outflow tract, who are candidates for septal reduction therapy.
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6.2.2.6.1. Results of DDD Pacing.
Initial cohort studies of the results of dual-chamber pacing in patients with obstructive HCM and limiting symptoms showed symptomatic improvement in almost 90% of patients, accompanied by an improvement in exercise time and a reduction in gradient.368– 371 However, there have been 3 randomized crossover trials in which patients received 2 to 3 months of continuous DDD pacing but also underwent a back-up AAI mode (no pacing) as a control arm.283,284,367 DDD pacing consists of continuously sensing or pacing the atrium and pacing the right ventricular apex. The overall reduction in outflow tract gradient was modest (25% to 40%) with substantial variation among individual patients. Objective measurements of exercise capacity were improved during DDD pacing versus baseline, but there was no significant difference comparing the AAI back-up mode with continuous DDD pacing. Al-though symptomatic improvement was reported by the majority of patients following continuous DDD pacing, a similar frequency of improvement was reported by patients during the AAI mode (control mode without pacing). These findings suggest a placebo effect as well as a “training effect” contributing to the initial symptomatic improvement of patients undergoing dual-chamber pacing.283,284,372
Overall, the percent of patients with sustained symptomatic improvement from continuous dual-chamber pacing varies from 30% to 80%.292,294,295,366 A consistent improvement in symptoms with a decrease in gradient and objective improvement in exercise duration is seen in _50% of patients. The overall success rate in terms of symptom relief and gradient reduction is significantly lower than that seen in patients who undergo septal myectomy. The mean residual gradient after septal myectomy is _10 mm Hg compared with a 40 to 50 mm Hg gradient after dual-chamber pacing. 283,284,295,369 There is no reliable predictor of success for dual-chamber pacing, including the results of acute hemodynamic studies or morphologic echocardiographic features. 295,367,373 Patients _65 years of age may be a subgroup who achieve the greatest benefit.283 There are no data that indicate dual-chamber pacing either reduces the risk of sudden death in patients with HCM or alters the underlying progression of disease.283,369 Dual-chamber pacing has not been shown to be beneficial for patients with nonobstructive HCM.374 |
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6.2.2.6.2. DDD Pacing: Caveats.
A thorough understanding of the complex interplay between pacemaker programming and the hemodynamics of HCM is necessary to achieve possible beneficial results from this therapy. It is necessary to optimize the atrioventricular delay because too short an interval results in hemodynamic deterioration and too long an atrioventricular interval without complete preexcitation of the ventricle results in an inadequate response.375 The position of the pacemaker lead is important, requiring distal apical capture for optimal hemodynamic results.376 Programming of rate-adaptive pacing is also necessary so that full preexcitation of the ventricle is obtained during exercise. |
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6.2.2.6.3. Pacing and ICDs.
Patients with HCM are at increased risk for ventricular tachyarrhythmias and SCD. Comprehensive SCD risk stratification should be performed in all patients with HCM (Section 6.3.1). However, current SCD risk stratification does not identify all patients at risk for ventricular arrhythmias and SCD.377 An ICD has been shown to be effective at aborting SCD in patients with HCM.55 Consideration of an ICD if a pacing device is indicated for either rhythm or hemodynamic indications is controversial in contrast to the situation in patients with established risk factors for SCD. |
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6.2.3. Patients With LV Systolic Dysfunction—Recommendations |
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Class I 1. Patients with nonobstructive HCM who develop systolic dysfunction with an EF less than or equal to 50% should be treated according to evidence-based medical therapy for adults with other forms of heart failure with reduced EF, including ACE inhibitors, ARBs, beta blockers, and other indicated drugs.39,378 (Level of Evidence: B) 2. Other concomitant causes of systolic dysfunction (such as CAD) should be considered as potential contributors to systolic dysfunction in patients with HCM. (Level of Evidence: C)
Class IIb 1. ICD therapy may be considered in adult patients with advanced (as defined by NYHA functional class III or IV heart failure) nonobstructive HCM, on maximal medical therapy, and EF less than or equal to 50%, who do not otherwise have an indication for an ICD.39 (Level of Evidence: C) 2. For patients with HCM who develop systolic dysfunction, it may be reasonable to reassess the use of negative inotropic agents previously indicated, for example, verapamil, diltiazem, or disopyramide, and consideration given to discontinuing those therapies. (Level of Evidence: C)
Although HCM has typically been excluded from randomized clinical trials in heart failure, there is no compelling reason to believe that the etiology of reduced EF heart failure differs sufficiently to disqualify many highly effective, evidence-based, guideline-directed therapies for heart failure with reduced EF.379,380 Standard heart failure therapies should be implemented when EF is _50% rather than the 40% normally recommended in the ACCF/AHA heart failure guidelines.39
The discovery of reduced EF in the setting of HCM is not inconsistent with the known natural history of HCM but is uncommon (approximately 3%) and should prompt an appropriate search for other potential contributing causes of LV dysfunction. 39 Those causes should include, but are not limited to, CAD, valvular heart disease, and metabolic disorders.
Although patients with HCM were not included in the primary prevention trials for heart failure with reduced EF, nevertheless, implantation of an ICD has been the generally accepted clinical practice for primary prevention in patients with HCM with systolic dysfunction. Furthermore, despite the absence of clinical trials or observational data, the use of negative inotropic drugs that would otherwise be discouraged in the setting of conventional heart failure with reduced EF can be considered in patients with HCM. |
Class I 1. Patients with non-obstructive HCM, who develop systolic dysfunction with an ejection fraction less than or equal to 50%, should be treated according to evidence-based medical therapy for adults with other forms of heart failure with reduced ejection fractions including ACE inhibitors ARB’s, beta-blockers and other indicated drugs. What patients need to understand about this recommendation is the ejection fraction; the amount of blood pumped out for each contraction of the heart decreases is what should be closely monitored to help guide therapy. HCM treatments become more in line with other forms of heart disease and the fact that the condition began as hypertrophic cardiomyopathy is no longer as critical in the decision-making aspect of medical management.
2. Other concomitant causes of systolic dysfunction, including coronary artery disease, should be considered as a potential contributor to systolic dysfunction in HCM patients.
Class IIb 1. ICD therapy may be considered in adult patients with advanced , defined as class III or IV heart failure by the New York Heart Association scale, non-obstructive HCM on maximal medical therapy and who have an ejection fraction less than or equal to 50% who don't otherwise have indications for ICD. This means that the traditional risk stratifiers used to determine who should have an implantable defibrillator need not be met if the ejection fraction is 50% or less. Thus, making this an independent risk factor, and should therefore allow patients to consider whether they wish to have the protection of an implantable defibrillator.
2. For HCM patients who develop systolic dysfunction it may be reasonable to use negative inotropics previously indicated including verapamil, diltiazem or disopyramide and consideration given to discontinue those therapies. Patients should understand that there is a time when therapy may shift from traditional HCM therapies to traditional heart failure therapies. As with most other recommendations made herein, these considerations should be made with the input and guidance of HCM specialists practicing in HCM centers of excellence with a large practice in the field.
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6.2.4. Selection of Patients for Heart Transplantation—Recommendations |
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Class I 1. Patients with advanced heart failure (end-stage*) and nonobstructive HCM not otherwise amenable to other treatment interventions, with EF less than 50% (or occasionally with preserved EF), should be considered for heart transplantation.39,381 (Level of Evidence: B) 2. Symptomatic children with HCM with restrictive physiology who are not responsive or appropriate for other therapeutic interventions should be considered for heart transplantation.382,383 (Level of Evidence: C)
Class III: Harm 1. Heart transplantation should not be performed in mildly symptomatic patients with HCM of any age. (Level of Evidence: C)
In general, the indications for heart transplantation include advanced heart disease, typically with NYHA functional class III or IV symptoms that are refractory to all other reasonable interventions. Transplant referral for refractory symptoms does not absolutely require reduced EF, although this treatment strategy is rarely recommended and performed in the presence of preserved EF. For patients with HCM, outcome after heart transplantation is not different from that of patients with other heart diseases.39,384,385 |
Class I Patients with advanced heart failure, referred to as end-stage or burnt-out, and non-obstructive HCM, not otherwise amenable to other treatment interventions, with ejection fractions of 50% or less and, in rare cases, with preserved ejection fractions, should be considered for heart transplantation. It is important for patients to understand that the number itself, meaning the ejection fraction, does not determine whether someone should be considered for transplantation or not; however, a balanced assessment of heart function, symptoms and management strategies should be discussed and closely followed by an HCM center of excellence. Patients are cautioned not to panic or become despondent if they notice their ejection fraction has dropped and understand that it may persist at this level for many years to come.
Symptomatic children with HCM restrictive physiology, which is basically described as a stiffening of the heart -- who are not responsive or appropriate for other therapeutic interventions, should be considered for heart transplantation. Again, this is a very small minority of patients who fall into this description. Parents should be reassured that this is not commonplace but, in fact, very rare.
Special note: The terminology end-stage or burnt-out hypertrophic cardiomyopathy is characterized by systolic dysfunction, meaning an impairment in the heart's ability to contract represented with an ejection fraction of 50% or less, it is often also associated with a left ventricular remodeling including cavity enlargement and wall thinning and believed to be due to myocardial scarring.
Class III Harm
Heart transplantation should not be performed in mildly symptomatic HCM patients of any age.
Special note by Hypertrophic Cardiomyopathy Association -- throughout this document the term hypertrophic cardiomyopathy center of excellence or high-volume HCM program has been mentioned. It is cautioned that any young person with a new diagnosis of hypertrophic cardiomyopathy who is recommended for heart transplantation be evaluated by one of these programs prior to being listed. In the experience of the HCMA we have definitely identified regional biases and have seen patients listed for transplant that would not necessarily meet these qualifications when being evaluated by an HCM center of excellence. Patients and families are cautioned that a heart transplant is not a cure, in the purest sense of the word, it is simply exchanging one set of concerns and problems for others. While heart transplantation is a tremendous option for those with no other alternatives, it is most assuredly not the answer for the majority.
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6.3. Prevention of SCD |
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6.3.1. SCD Risk Stratification—Recommendations |
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Class I 1. All patients with HCM should undergo comprehensive SCD risk stratification at initial evaluation to determine the presence of the following:50,53,55,127,128,386 –392 (Level of Evidence: B) a. A personal history for ventricular fibrillation, sustained VT, or SCD events, including appropriate ICD therapy for ventricular tachyarrhythmias.† b. A family history for SCD events, including appropriate ICD therapy for ventricular tachyarrhythmias.† c. Unexplained syncope. d. Documented NSVT defined as 3 or more beats at greater than or equal to 120 bpm on ambulatory (Holter) ECG. e. Maximal LV wall thickness greater than or equal to 30 mm.
Class IIa 1. It is reasonable to assess blood pressure response during exercise as part of SCD risk stratification in patients with HCM.89,127,390 (Level of Evidence: B) 2. SCD risk stratification is reasonable on a periodic basis (every 12 to 24 months) for patients with HCM who have not undergone ICD implantation but would otherwise be eligible in the event that risk factors are identified (12 to 24 months). (Level of Evidence: C)
Class IIb 1. The usefulness of the following potential SCD risk modifiers is unclear but might be considered in selected patients with HCM for whom risk remains borderline after documentation of conventional risk factors: a. CMR imaging with LGE.184,188 (Level of Evidence: C) b. Double and compound mutations (ie, more than 1). (Level of Evidence: C) c. Marked LVOT obstruction.45,127,143,390 (Level of Evidence: B)
Class III: Harm 1. Invasive electrophysiologic testing as routine SCD risk stratification for patients with HCM should not be performed. (Level of Evidence: C)
See Data Supplement 4 for further information on data supporting the recommendations for SCD risk stratification.
A minority of clinically recognized patients with HCM are judged to be at increased risk for SCD with a rate of about 1% per year.53,55,386–389 ICDs offer the only effective means of preventing SCD and prolonging life in patients with HCM.55 Selection of patients who are appropriate for implantation for primary as opposed to secondary prevention can be a difficult clinical decision, owing to the individuality of each patient and family, variable definitions for risk markers, sparse clinical data, the relative infrequency of both HCM and SCD in most clinical practices, and the cumulative morbidity of living with an ICD. |
Class I Patients with HCM should undergo comprehensive sudden cardiac arrest/death risk stratification upon an initial evaluation to determine the presence of the following: a. Personal history of ventricular fibrillation, sustained ventricular tachycardia or sudden cardiac arrest events including appropriate ICD therapy for ventricular tachyarrhythmias. b. Family history for sudden cardiac arrest or death events including appropriate ICD therapy for ventricular tachyarrhythmias c. Unexplained syncope or passing out d. Documented non-sustained ventricular tachycardia and SVT, defined as three or more beats at rest, or equal to 120 beats per minute, on ambulatory Holter ECG e. Maximal wall thickness greater than or equal to 30 mm -- special note by HCMA: Consideration should be given to body mass index and age of patient for calculations and evaluation of children.
Special note: Appropriate ICD discharge is defined as an ICD therapy triggered by ventricular tachycardia or ventricular fibrillation, documented rise toward intracardiac electrocardiogram or cycle length data in conjunction with patient's symptoms immediately before and after the device has discharged.
Class IIa 1. It is reasonable to assess blood pressure response during exercise as part of sudden cardiac arrest risk stratification in HCM patients. This is achieved by monitoring blood pressure response as part of a stress test to determine whether the blood pressure rises appropriately with stress.
2. Sudden cardiac arrest risk stratification is reasonable on a periodic basis -- every 12 to 24 months -- for HCM patients who have not undergone ICD implantation but would otherwise be eligible in the event that a risk factor were to be identified. But of significant importance to patients and families is the understanding that sudden cardiac arrest/death risk stratification is not made for a lifetime, but for a period of time, as the body is ever-changing. Thus, the importance of revisiting risk assessment not only gives us the ability to re-evaluate the parameters stated in the previous section but to also include our expanded knowledge as the body of information grows and the addition of new risk factors may alter our appreciation of the disease and an individual's risk. It is critically important that patients revisit risk stratification every one to two years.
Class IIb The usefulness of the following potential sudden cardiac arrest/death risk modifiers is unclear what might be considered in select HCM patients for whom the risk remains borderline after conventional risk factors have been evaluated: a. CMR images with LGE -- use of cardiac MRI with gadolinium enhancement can help to identify areas of scar within the heart. It is currently believed that the greater degree of scarring be associated to a higher degree of risk. For those who are “on the fence”, the availability of this data may assist in making a decision. b. Genetic testing that indicates a double or compound mutation, meaning more than one mutation, may be associated with greater risk hence genetic testing may prove helpful in stratification. c. Significant left ventricular outflow tract obstruction. While the document does not define, the HCMA would suggest consultation with a high-volume program to help ascertain one's individual risk would be advised. Class III Harm Invasive electrophysiologic testing routine for sudden cardiac arrest/death risk stratification in HCM patients should not be performed.
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6.3.1.1. Established Risk Markers
6.3.1.1.1. Prior Personal History of Ventricular Fibrillation,SCD or Sustained VT. As expected, patients with HCM who have experienced SCD or sustained VT represent the highest risk for subsequent arrhythmogenic events. The annualized rate of subsequent events is approximately 10% per year, although it has been shown that individuals may have no recurrent events or may have decades-long arrhythmia-free intervals between episodes.55,387–389,393
6.3.1.1.2. Family History of SCD. It has been recognized that SCD events can cluster in families. Notably, some studies have not demonstrated an independent link between family history of SCD and risk for individual patients on multivariate analysis,50,390,394 whereas others have suggested that family history is an independent predictor.127,391 These differences may be explained in part by the relative infrequency of events but also likely reflect variability in the definition of a family history of SCD. Some studies have used a definition of SCD in _2 first-degree relatives,50 whereas others have counted a single event.127,390 None of these studies have rigorously accounted for the total number of clinically apparent patients with HCM in each family, nor have they included SCD in more remote relations (eg, cousins, uncles, aunts, grandparents).
6.3.1.1.3. Syncope. Syncope represents a complex symptom with a multifactorial etiology that requires a careful clinical history before it can be considered a potential marker for SCD. In a recent analysis, syncope that was unexplained or thought to be consistent with arrhythmia (ie, not neurally mediated) showed a significant independent association with SCD only when the events occurred in the recent past (_6months) but not if the syncopal episodes occurred _5 years before the clinical visit.392 One other large study reports a similar independent association between recent unexplained syncope and SCD.127 Another study showed that it was the interaction between syncope and family history that was an important prognostic marker.50
6.3.1.1.4. Nonsustained Ventricular Tachycardia. Although sustained ventricular arrhythmia is clearly associated with SCD, the data for NSVT are less robust. Only 1 of 5 studies showed a univariate association between NSVT on 24-hour ambulatory monitors and SCD,50,128,389,395–397 whereas 1 more contemporary and larger study showed that NSVT is independently associated with SCD on multivariate analysis127 but may be more important in younger patients (_30 years of age).129 Furthermore, exercise-induced NSVT has also been found to have an independent association with SCD.398 NSVT probably should not be considered in a simply binary manner (ie, as either positive or negative), and there may be some value in long-term ambulatory monitoring when NSVT is discovered on the screening 24-hour assessment. Intuitively, it would seem appropriate to place more weight on frequent, longer, and/or faster episodes of NSVT; however, there have been no systematic investigations of whether number of episodes and duration or ventricular rate of episodes of NSVT definitely have an impact on SCD risk.
6.3.1.1.5. Maximum LV Wall Thickness. The relationship between severity of LV hypertrophy and SCD has been investigated in several studies predicated on the concept that the more severe the disease expression, the more likely the individual patient is to experience adverse events. Most, but not all,51,399 studies have shown at least a univariate association between maximum wall thickness and SCD,389,396,399 whereas other large studies have shown that when magnitude of hypertrophy is _30 mm, there is an independent association with SCD.50,161,392 Notably, 3 reports derive from overlapping samples of patients50,127,391 have shown different strengths in the relationship between wall thickness and SCD that may reflect a slight variance in exclusion criteria, definition of other risk markers, and the number of risk markers included in multivariate analysis. It is crucial to recognize that the risk estimate does not abruptly increase for patients with _30 mm wall thickness but rather increases in a linear fashion161 and appears to carry more prognostic significance in younger patients.400 With this in mind, a young adult with hypertrophy that approaches 30 mm may have similar or greater SCD risk than older patients with maximum wall thickness _30 mm.
6.3.1.1.6. Abnormal Blood Pressure Response During Exercise. For up to a third of patients with HCM, there is an inappropriate systemic systolic blood pressure response during exercise testing (defined as either a failure to increase by at least 20 mm Hg or a drop of at least 20 mm Hg during effort).89,90 It has been postulated that this finding is a risk factor for SCD. Two studies have shown a univariate association between this finding and subsequent SCD.50,89,127,390 It is also unclear how this finding is related to the well-recognized increase in dynamic LVOT obstruction that occurs with effort, a hemodynamic condition that is readily modifiable with medication or mechanical procedures. It would be appropriate to reassess this particular SCD risk marker following invasive therapies to relieve outflow tract obstruction, although there are no data in such patients. |
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6.3.1.2. Other Potential SCD Risk Modifiers
6.3.1.2.1. LVOT Obstruction. Although some studies have not found a significant association between LVOT obstruction and SCD,47,161 more recent studies involving larger sample sizes have found higher rates of SCD among patients with resting gradients _30 mm Hg45,390 and that the risk is positively correlated with severity of LVOT obstruction.127 Conversely, relief of outflow tract obstruction through surgical myectomy is associated with very low rates of SCD.61,321 A limitation to using LVOT obstruction as an independent risk marker is that the obstruction in HCM is dynamic and highly variable from hour to hour to the extent that no gradient may be detectable during one evaluation, whereas the next day (or even a short time later during the same day), a moderate to severe gradient may be apparent.81,401 This variability makes it not only difficult to assess risk in the individual patient, but it also likely explains the difficulty in demonstrating statistical significance in smaller studies. Whether exercise-induced augmentation of the gradient is one of the mechanisms that results in syncope and/or abnormal blood pressure response during exercise has not been completely addressed.
6.3.1.2.2. LGE on CMR Imaging. There has been considerable interest in promoting LGE on CMR imaging as a potential SCD risk marker in HCM. Because LGE is believed to represent myocardial fibrosis or scarring, it has been hypothesized that LGE may represent myocardium prone to ventricular tachyarrhythmia.188 Indeed, LGE has been associated with NSVT and ventricular ectopy but has not been associated with clinical SCD events or ICD discharge in published studies.184,185,188 More recent studies have shown a relationship between LGE and SCD and heart failure but with low positive predictive accuracy.186,187 LGE is a common feature observed in patients with HCM, and there is no consensus on the appropriate imaging protocols or threshold for detection of LGE. Both of these features currently limit the role of LGE as an independent risk marker.
6.3.1.2.3. LV Apical Aneurysm. A subset of patients with HCM (prevalence about 2%) develop a thin-walled LV apical aneurysm associated with regional scarring182 and more adverse clinical events during follow-up, including progressive heart failure and evolution into the end-stage phase as well as SCD. Although data on LV aneurysms in HCM are limited, this abnormality may warrant consideration in SCD risk-assessment strategies.
6.3.1.2.4. Genetic Mutations. SCD may cluster in certain families with HCM, and the possibility that specific sarcomere mutations may confer SCD risk has been hypothesized. Indeed, several early studies of HCM pedigrees implicated certain mutations as “malignant.”107,114,402,403 However, subsequent studies of less selected consecutive patients with HCM found that it was problematic to infer likelihood of SCD events on the basis of the proposed mutations, because in some instances the rate of adverse events (and prevalence of associated SCD risk markers) was lower in patients with “malignant” mutations than it was in those with mutations believed to be “benign.”95,404–406 The data from unselected consecutive outpatients suggest that most mutations are “novel” and limited to particular families (“private” mutations). Therefore, routine mutational screening would appear to be of little prognostic value in HCM. |
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6.3.1.3. Utility of SCD Risk Markers in Clinical Practice
Other than cardiac arrest, each of the HCM risk factors has low positive predictive value (_10% to 20%) and modestly high negative predictive value (85% to 95%). Multiple risk markers in individual patients would intuitively suggest greater risk for SCD; however, the vast majority of patients with _1 risk markers will not experience SCD, and simple arithmetic summing of risk markers is not precise because of the uncertainty implicit in assigning a relative weight to any individual risk factor.50,51,407 Notably, in the international HCM-ICD registry,55 the number of risk factors did not correlate with the rate of subsequent appropriate ICD discharges among presumably high-risk patients selected for ICD placement. These data suggest that the presence of a single risk marker may be sufficient to warrant ICD placement in many patients, but these decisions need to be individualized with regard to age, the strength of the risk factor, and the risk-benefit of lifelong ICD therapy.55,408 The potential for SCD needs to be discussed with each patient with HCM and family members in the context of their concerns and anxieties and should be balanced against the risks and benefits of proposed prophylactic ICD strategy. Consideration for the patient’s age is warranted, particularly because device complications are more likely in children and young adults over the long period of follow-up.55,408 |
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6.3.2. Selection of Patients for ICDs—Recommendations |
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Class I 1. The decision to place an ICD in patients with HCM should include application of individual clinical judgment, as well as a thorough discussion of the strength of evidence, benefits, and risks to allow the informed patient’s active participation in decision making (Figure 4).53–56 (Level of Evidence: C) 2. ICD placement is recommended for patients with HCM with prior documented cardiac arrest, ventricular fibrillation, or hemodynamically significant VT.55,387–389 (Level of Evidence: B)
Class IIa 1. It is reasonable to recommend an ICD for patients with HCM with: a. Sudden death presumably caused by HCM in 1 or more first-degree relatives.394 (Level of Evidence: C) b. A maximum LV wall thickness greater than or equal to 30 mm.50,51,161,400 (Level of Evidence: C) c. One or more recent, unexplained syncopal episodes.392 (Level of Evidence: C) 2. An ICD can be useful in select patients with NSVT (particularly those less than 30 years of age) in the presence of other SCD risk factors or modifiers.‡53,129 (Level of Evidence: C) 3. An ICD can be useful in select patients with HCM with an abnormal blood pressure response with exercise in the presence of other SCD risk factors or modifiers.‡89,90,390 (Level of Evidence: C) 4. It is reasonable to recommend an ICD for high-risk children with HCM, based on unexplained syncope, massive LV hypertrophy, or family history of SCD, after taking into account the relatively high complication rate of longterm ICD implantation. (Level of Evidence: C)
Class IIb 1. The usefulness of an ICD is uncertain in patients with HCM with isolated bursts of NSVT when in the absence of any other SCD risk factors or modifiers.‡ 53 (Level of Evidence: C) 2. The usefulness of an ICD is uncertain in patients with HCM with an abnormal blood pressure response with exercise when in the absence of any other SCD risk factors or modifiers,‡ particularly in the presence of significant outflow obstruction. 89,90,390 (Level of Evidence: C)
Class III: Harm 1. ICD placement as a routine strategy in patients with HCM without an indication of increased risk is potentially harmful. (Level of Evidence: C) 2. ICD placement as a strategy to permit patients with HCM to participate in competitive athletics is potentially harmful. (Level of Evidence: C) 3. ICD placement in patients who have an identified HCM genotype in the absence of clinical manifestations ofHCM is potentially harmful. (Level of Evidence: C)
Although the overall rate of SCD in HCM is _1% per year, clearly there are individuals at higher risk for whom prophylactic therapy may be indicated. To date, however, no pharmacologic therapy has been demonstrated to provide protection from SCD. Conversely, the ICD has been used in patients with HCM since its introduction and has proved to be effective in terminating life-threatening ventricular arrhythmia in HCM. However, the decision for placement of an ICD must involve the application of individual clinical judgment, as well as a thorough discussion of the strength of evidence regarding risk assessment, benefits, and risks of the ICD to allow the fully informed patient to actively participate in ultimate decision making. |
Class I 1. The decision for placement of an ICD in HCM patients should include application of clinical judgment -- Comment from HCMA: Clinical judgment, if possible, should include input from a high-volume HCM program in the event there is any gray area at all -- as well as a thorough discussion of the strength of evidence, benefits and risks to allow the patient to be informed at all levels of decision-making.
2. ICD placement is recommended for HCM patients with prior documented cardiac arrest, ventricular fibrillation or hemodynamically significant ventricular tachycardia. Note to patients: The occurrence of a cardiac arrest is significant and, in itself, enough to require ICD implantation. While some SCA victims, weak from their event or hospital stay, with a device implanted may be feeling as if they had no real opportunity to evaluate alternative options, it is advised to give this new data some time to soak in along with the gravity of your recent situation and work toward developing a positive relationship with this life-saving technology.
Class IIa 1. It is reasonable to recommend an ICD for HCM patients with:
a. Sudden death or sudden cardiac arrest presumably due to hypertrophic cardiomyopathy in one or more first degree relatives. b. A maximum left ventricular wall thickness in any region greater than or equal to 30 mm. c. One or more recent unexplained episodes of syncope or loss of consciousness. The term of unexplained in this area refers to eliminating obstruction as the causes of the syncope/loss of consciousness. Also should be noted that events that occurred many years ago should not carry the same weight as recent events.
2. An ICD can be useful in select patients with non-sustained ventricular tachycardia -- particularly younger patients, less than 30 years of age, in the presence of other sudden cardiac arrest death risk factor or modifiers.
3. An ICD can be useful in select patients with abnormal blood pressure response with exercise in the presence of other sudden cardiac death/arrest risk factors or modifiers.
4. It is reasonable to recommend ICD's for high-risk children with HCM based on the same criteria for adults including unexplained syncope, massive left ventricular hypertrophy, and family history of sudden cardiac arrest or death after taking into account the relatively higher complication rate of long-term ICD implantation. The HCMA cautions parents and physicians and interested parties to take under consideration the relatively short period of time in the modern generation of ICD implantation that children were considered primary users of such technology. Devices have become smaller and our knowledge of how young hearts respond over time has grown, therefore, data that is greater than seven to 10 years of age should be viewed with an eye toward our advanced understanding of technology and phenotype. Complication rates are dropping in this unique population.
Class IIb 1. The usefulness of an ICD is uncertain in HCM patients with isolated episodes of non-sustained ventricular tachycardia in the absence of any other sudden cardiac arrest risk factor or modifiers. HCMA wishes to note that patients with this one item as an indication for their ICD implant may benefit from thorough evaluation with a high-volume HCM program to help them determine whether the ICD implantation is appropriate.
2. The usefulness of an ICD is uncertain in patients with HCM with an abnormal blood pressure response with exercise when in the absence of any other SCD risk factors or modifiers, particularly in the presence of significant outflow obstruction. Therefore, careful evaluation by an HCM expert is encouraged to help arrive at an appropriate decision.
Class III: Harm 1. ICD placement as a routine strategy in patients with HCM without an indication of increased risk is potentially harmful. The diagnosis of HCM alone does not mean a defibrillator should be implanted.
2. ICD placement as a strategy to permit patients with HCM to participate in competitive athletics is potentially harmful.
3. ICD placement in patients who have an identified HCM genotype in the absence of clinical manifestations of HCM is potentially harmful. |
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6.3.2.1. Results of ICD Therapy in HCM
There have been 2 reports from an international, multicenter registry of patients with HCM who have undergone ICD placement on the basis of the clinical perception of SCD sufficient to justify device therapy.54,55 Among patients who received a device as a result of a prior personal history of SCD or sustained ventricular arrhythmia (secondary prevention ICD), the annualized rate of subsequent appropriate ICD discharge was approximately 10% to 11% per year. Patients with primary prevention ICDs placed on the basis of 1 or more of the conventional risk markers experienced appropriate ICD therapy at a rate of 4% to 5% per year. Among these patients, who were selected for ICD placement based on clinical risk perceptions, the number of risk markers present did not predict subsequent device discharge. Whether this is related to the highly selected population involved or possibly because an appropriate ICD discharge may not necessarily be synonymous with SCD prevention is uncertain. The relative weight of the individual risk markers in predicting device discharge rate has not been reported.55,408
6.3.2.2. Complications of ICD Therapy in HCM
It is important to recognize and discuss with patients potential ICD-related complications (both procedural and long term) that occur at a rate of 4% per year in patients with HCM.408 Potential early problems may include pneumothorax, pericardial effusion, pocket hematoma, acute pocket infection, and/or lead dislodgment. Late complications include upper extremity deep venous thrombosis, lead dislodgment, infection, high defibrillation threshold necessitating lead revision, and inappropriate shocks, that is, shocks triggered by supraventricular arrhythmias, sinus tachycardia, lead fractures or dislodgment, oversensing, double counting, and programming malfunctions. Reported rates of complications include _25% of patients with HCM who experienced inappropriate ICD discharge; 6% to 13% who experienced lead complications (fracture, dislodgment, oversensing); 4% to 5% who developed device-related infection; and _2% to 3% who experienced bleeding or thrombosis complications.55,408 The rate of inappropriate shocks and lead fractures appears to be higher in children than in adults, largely because their activity level and body growth places continual strain on the leads, which are the weakest link in the system.386 This issue is of particular concern, given the long periods that young patients will have prophylactically implanted devices. Industry-related ICD problems have affected patients with HCM. Prominent recalls have included defective generators leading to several deaths409 and small-diameter high-voltage leads prone to fracture.410,411 The implant procedure has been largely free of significant risk, without reported deaths, although selected patients with extreme hypertrophy or who have received amiodarone may require high-energy output generators or epicardial lead systems.412
6.3.2.3. Overall Risk Assessment and Selection of Patients for ICD Therapy
The decision to recommend and pursue ICD placement is a complex process that can be oversimplified. The individuality of each patient and family circumstance, including level of anxiety, life situation, and views on death, and individual assessment of the relative weight of potential benefits compared with potential risks must be processed for each patient. The low positive predictive value of any of the SCD risk factors and the variability in the strength of data also introduce a degree of ambiguity to the SCD risk assessment and dramatically limit the applicability of counting the number of risk factors as the primary risk assessment methodology. Based on the weight of evidence, plausibility, and consensus judgment reflecting clinical experience, it is recognized that patients with massive hypertrophy, a family history of HCM-related SCD, or recent unexplained syncope would probably benefit from ICD placement. Apart from these, it was believed that a combination of conventional risk factors and other risk modifiers provided the optimal identification of the subset of patients with HCM with sufficient risk of SCD to warrant strong consideration of ICD placement (Figure 4).
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6.3.2.4. Selection of ICD Device Type—Recommendations |
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Class IIa 1. In patients with HCM who meet indications for ICD implantation, single-chamber devices are reasonable in younger patients without a need for atrial or ventricular pacing.410,413–415 (Level of Evidence: B) 2. In patients with HCM who meet indications for ICD implantation, dual-chamber ICDs are reasonable for patients with sinus bradycardia and/or paroxysmal AF.413 (Level of Evidence: C) 3. In patients with HCM who meet indications for ICD implantation, dual-chamber ICDs are reasonable for patients with elevated resting outflow gradients greater than 50 mm Hg and significant heart failure symptoms who may benefit from right ventricular pacing (most commonly, but not limited to, patients greater than 65 years of age).283,284,367,413 (Level of Evidence: B)
All ICDs incorporate a right ventricular lead that has both pacing and defibrillation capabilities. ICDs are available as single-chamber, dual-chamber, or 3-chamber (ie, cardiac resynchronization therapy) devices. Whether a patient receives a dual-chamber or cardiac resynchronization therapy system depends on other considerations, including the need for atrial pacing, enhanced supraventricular tachycardia (SVT) discrimination, right ventricular pacing, and importantly, consideration of the patient’s age and the subsequent longevity of the lead and ICD system.416 In patients with LVOT obstruction, particularly the elderly, in whom ICDs are indicated, dual-chamber pacing may have the potential to reduce gradient and symptoms in some patients (Section 6.2.2.6).
ICD leads fail at a rate of 0.5% to 1% per year, although there are concerning data that failure rates are increased in a younger, healthier population.410 When a lead fails, a new lead is needed; the old lead can remain in, which over time places the patient at risk for venous obstruction, or the old lead may be removed, which carries a significant risk of morbidity and mortality. In young patients with HCM, an ICD may be needed for up to 70 years. There is no expectation that a single lead will remain functional for that amount of time. Thus, in general, the younger the patient, the more single-chamber devices should be used to decrease the amount of hardware in the venous system.
Dual-chamber devices have been advocated to increase the ability of the ICD to differentiate between SVT and ventricular arrhythmias. Data to support this hypothesis are mixed with some studies showing no difference between inappropriate therapy for SVT417,418 and others showing a benefit.419,420 Currently, discrimination of SVT is inadequate as a sole justification for a dual-chamber device in patients with HCM.
Whether cardiac resynchronization therapy devices are useful for patients with HCM is unclear. There is a paucity of published data on the use of cardiac resynchronization therapy devices in patients with HCM and end-stage heart failure.421
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Class IIa 1. In patients with HCM who meet indications for ICD implantation, single-chamber devices are reasonable in younger patients without a need for atrial or ventricular pacing. Single chamber devices have only one lead.
2. In patients with HCM who meet indications for ICD implantation, dual-chamber ICDs are reasonable for patients with sinus bradycardia and/or paroxysmal AF. These devices have two leads.
3. In patients with HCM who meet indications for ICD implantation, dual-chamber ICDs are reasonable for patients with elevated resting outflow gradients greater than 50 mm Hg and significant heart failure symptoms who may benefit from right ventricular pacing (most commonly, but not limited to, patients greater than 65 years of age). |
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6.3.3. Participation in Competitive or Recreational Sports and Physical Activity—Recommendations |
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Class IIa 1. It is reasonable for patients with HCM to participate in low-intensity competitive sports (eg, golf and bowling). 422,423 (Level of Evidence: C) 2. It is reasonable for patients with HCM to participate in a range of recreational sporting activities as outlined in Table 4.224 (Level of Evidence: C)
Class III: Harm 1. Patients with HCM should not participate in intense competitive sports regardless of age, sex, race, presence or absence of LVOT obstruction, prior septal reduction therapy, or implantation of a cardioverter-defibrillator for high-risk status.58,59,422–426 (Level of Evidence: C)
A number of large cohort studies from the United States indicate that HCM is the most common cardiovascular cause of sudden death in young athletes, accounting for about one third of these events.58,59,425,427 The American College of Cardiology Bethesda Conference No. 36428 as well as the European Society of Cardiology guidelines423 indicate that risk for sudden death is increased during intense competitive sports and also suggest that the removal of these individuals from the athletic arena can diminish their risk. This principle is also the basis for the Bethesda Conference No. 36 and the European Society of Cardiology consensus recommendations governing sports disqualification of athletes with HCM from sanctioned high school and college sports.428,429 It should be underscored that these recommendations for competitive athletes are independent of recommendations for noncompetitive, informal recreational sporting activities.224
General recommendations for recreational exercise in patients with HCM should be tailored to the individual’s desires and abilities; however, certain guidelines prevail. For example, aerobic exercise as opposed to isometric exercise is preferable. Patients with HCM should avoid recreational sports in which participation is intense and simulates competitive organized athletics. Also, burst exertion, in which an abrupt increase in heart rate is triggered (eg, sprinting in half-court basketball), is less desirable than swimming laps or cycling. Finally, it is prudent for such patients to avoid physical activity in extreme environmental conditions of heat, cold, or high humidity, with attention paid to maintaining volume status. Detailed recommendations for individual sports appear in Table 4. |
Class IIa 1. It is reasonable for patients with HCM to participate in low-intensity competitive sports (eg, golf and bowling).
2. It is reasonable for patients with HCM to participate in a range of recreational sporting activities as outlined in Table 4
Class III: Harm 1. Patients with HCM should not participate in intense competitive sports regardless of age, sex, race, presence or absence of LVOT obstruction, prior septal reduction therapy, or implantation of a cardioverter-defibrillator for high-risk status.
HCMA Comments: Competitive athletics is defined as participation in an organized team that has regularly scheduled practices and competitions. It is important to recognize that the term athlete has many definitions depending upon one's point of view. To some people, a seven-year-old child playing T-ball may be defined as an athlete, to others it may be someone participating in NCAA athletics. For purposes of understanding who should be participating in competitive athletics with hypertrophic cardiomyopathy, it is a reasonable idea for parents to think about the longevity of the child's potential career in a particular sport when choosing what activities to engage the child and if they know HCM is in the family tree.
Competitive athletics has been associated with additional risk for those with HCM. Therefore, competitive sports are discouraged and, in fact, upon diagnosis many sports teams will ban participation of those with hypertrophic cardiomyopathy, rightfully so.
The guidelines state that based upon scientific data, including the Bethesda Conference No. 36 and the European Society of Cardiology guidelines, that there is a direct increase in risk associated with competitive sports and those with HCM. A diagnosis of HCM is a disqualifying event for athletes from sanctioned high school and collegiate sports. The exceptions to the rules for competitive athletics include participation in low-intensity competitive sports, which could include such items as golf, bowling, archery, riflery and equestrian.
Recreational activity: There is an important differentiation between competitive athletics and recreational athletics. Simply put, recreational sports do not have the same level of intensity and physical demand as their competitive counterparts. Those participating in recreational sports do not have the same training regiment or high level intensity competition. Participation in recreational style sports for those with HCM should also be entered into with some caution and an appreciation and respect for HCM itself. To say that all recreational sports are appropriate for those with HCM can be a bit naïve, as we know things can get pretty heated between friends and the intensity level can quickly ramp up. This should be considered when participating in any athletic endeavor.
It is critical that patients with HCM enjoy recreational activities and sports, as long as it is beneficial and not detrimental. Participating in typical fitness center activities such as a treadmill or stationary bike or elliptical, the use of non-free weights for sculpting and toning and the participation in such activities as tai chi, yoga, and general fitness programs are to be encouraged for all of those with HCM. Participating in a pickup game of softball, baseball, basketball, or similar type sport, needs to be done so with caution and consultation with one's physician.
Having a diagnosis of HCM does not suggest that patients should become sedentary and not participate in activities they find enjoyable; however, it is critical that environmental conditions such as heat and cold and other factors be taken under consideration prior to participating in any activity. The HCMA often reminds patients that proper hydration is incredibly important prior to and during exercise for all those with HCM. |
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6.4. Management of AF—Recommendations |
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Class I 1. Anticoagulation with vitamin K antagonists (ie, warfarin, to an international normalized ratio [INR] of 2.0 to 3.0) is indicated in patients with paroxysmal, persistent, or chronic AF and HCM.60,430,431 (Anticoagulation with direct thrombin inhibitors [ie, dabigatran§] may represent another option to reduce the risk of thromboembolic events, but data for patients with HCM are not available. 432) (Level of Evidence: C) 2. Ventricular rate control in patients with HCM with AF is indicated for rapid ventricular rates and can require high doses of beta antagonists and nondihydropyridine calcium channel blockers.60,430 (Level of Evidence: C)
Class IIa 1. Disopyramide (with ventricular rate– controlling agents) and amiodarone are reasonable antiarrhythmic agents for AF in patients with HCM.430,433 (Levelof Evidence: B) 2. Radiofrequency ablation for AF can be beneficial in patients with HCM who have refractory symptoms or who are unable to take antiarrhythmic drugs.63– 65,434,435 (Level of Evidence: B) 3. Maze procedure with closure of LA appendage is reasonable in patients with HCM with a history of AF, either during septal myectomy or as an isolated procedure in selected patients. (Level of Evidence: C)
Class IIb 1. Sotalol, dofetilide, and dronedarone might be considered alternative antiarrhythmic agents in patients with HCM, especially in those with an ICD, but clinical experience is limited. (Level of Evidence: C)
AF is an important cause of symptoms, morbidity, and even mortality in patients with HCM.57,60 Diagnosis may be made by an ECG during an AF episode or occasionally on ambulatory Holter monitoring; use of an event recorder may be helpful in some patients. Patients with HCM are at increased risk of AF compared with age-matched cohorts, but AF is seldom seen in young patients with HCM who are _30 years of age and becomes more prevalent with age. Risk factors for AF in HCM include age, congestive heart failure, and LA function, diameter, and volume.60,436 A family history of AF is a risk factor in the Framingham Heart Study, but there are no data in patients with HCM. AF occurring in HCM may not be associated with symptoms or hemodynamic compromise in one third of patients but is poorly tolerated in many others. There is evidence that AF is an indicator of unfavorable prognosis, including increased risk of HCMrelated heart failure, death, and stroke.60,437
Therapy for AF includes prevention of thromboembolic stroke and controlling symptoms (Figure 5). The risk of systemic embolization is high in patients with HCM with AF but is not related to the severity of symptoms.57,60 Occurrence of paroxysmal, persistent, or chronic AF is a strong indication for anticoagulation with a vitamin K antagonist.430 Whether there is a threshold for AF that warrants anticoagulation is unresolved; however, given the high risk of thromboembolism in HCM, even patients with short episodes of AF should be strongly considered for anticoagulation. Even a single episode of AF should be cause to consider anticoagulation because the likelihood of recurrent AF is high. Aspirin should be reserved for those who cannot or will not take warfarin or other oral anticoagulants, but its efficacy in HCM is unestablished. The role of LA occlusion devices in HCM is untested but could possibly be a future option in patients who cannot tolerate anticoagulant therapy.438
Symptom control may be attained with adequate rate control, although many patients will require rhythm control. Rate control is best maintained by beta blockers and calcium channel blockers. High doses of these agents may be required. Digoxin may modestly reduce ventricular rate at rest and to a lesser extent with exertion. Because there is a paucity of data on rhythm control in patients with HCM, evidence from other patient populations is extrapolated to HCM. However, whether patients with HCM respond similarly to antiarrhythmic agents is not clear. The “2006 ACCF/AHA Guidelines for the Management of Patients With Atrial Fibrillation” state that disopyramide and amiodarone are potential agents for rhythm control.430 The limited published data on amiodarone suggest that it is safe and effective for patients with HCM.439–442 Disopyramide has been shown to be safe when prescribed for reduction of LVOT obstruction, but its safety and efficacy in AF are not well established.157,443 Dronedarone, an antiarrhythmic agent similar to amiodarone but lacking the iodine moiety and much of the long-term toxicity, has been approved for use in the United States. There are no data regarding the efficacy of dronedarone or the use of flecainide and propafenone in patients with HCM. In the CAST (Cardiac Arrhythmia Suppression Trial) trial, Class IC agents were associated with an increased mortality in patients with CAD.444 Thus, caution is advised when these agents are prescribed for patients with HCM and their use should probably be limited to individuals with an ICD. The management of atrial flutter in HCM is similar to that in other disease states, including the role of radiofrequency ablation.
The long-term benefits of radiofrequency ablation versus antiarrhythmic drugs in patients with HCM remain to be established. It does appear that early success and complication rates are similar between HCM and other forms of heart disease or absence of heart disease.63–65,445 Thus, radiofrequency ablation may play a role in the management of AF, but further investigation is necessary. The surgical maze procedure for AF has shown some limited success446; however, whether a prophylactic or therapeutic surgical maze procedure is indicated for patients undergoing other open chest surgical procedures (ie, septal myectomy) is unresolved. |
Class I 1. Anticoagulation with vitamin K antagonists (ie, warfarin, to an international normalized ratio [INR] of 2.0 to 3.0) is indicated in patients with paroxysmal, persistent, or chronic AF and HCM.
2. Ventricular rate control in patients with HCM with AF is indicated for rapid ventricular rates and can require high doses of beta antagonists and nondihydropyridine calcium channel blockers.
Class IIa 1. Disopyramide (with ventricular rate– controlling agents) and amiodarone are reasonable antiarrhythmic agents for AF in patients with HCM.
2. Radiofrequency ablation for AF can be beneficial in patients with HCM who have refractory symptoms or who are unable to take antiarrhythmic drugs.
3. Maze procedure with closure of LA appendage is reasonable in patients with HCM with a history of AF, either during septal myectomy or as an isolated procedure in selected patients.
Class IIb 1. Sotalol, dofetilide, and dronedarone might be considered alternative antiarrhythmic agents in patients with HCM, especially in those with an ICD, but clinical experience is limited. (Level of Evidence: C)
Atrial fibrillation is a difficult problem for those with HCM, as those with HCM do not always respond in a highly predictable manner and often, unlike their non-HCM atrial fibrillation counterparts, identifying episodes of atrial fibrillation can be challenging. Use of Holter monitoring or event monitoring may be useful in identifying patients who are having atrial fibrillation and not experiencing significant symptoms. Atrial fibrillation is uncommon in those under 30 years of age and becomes more prevalent as age increases. It is estimated that up to 20 to 25% of those with HCM may experience atrial fibrillation and those with atrial fibrillation and HCM do not tolerate this abnormal rhythm very well.
Atrial fibrillation increases risk in those with HCM for heart failure, stroke, and death and should be taken very seriously. Patients with HCM and atrial fibrillation should be managed with anti-coagulation therapy, also known as blood thinners or vitamin K antagonists. The use of aspirin as an anticoagulant in those with HCM is not well established and should not be used as a primary source to achieve anticoagulation but should be reserved for those who are not able to tolerate warfarin or other anti-coagulation medications.
Medications are used to maintain rate control and may include the use of beta blockers or calcium channel blockers. It is not clear whether HCM patients respond to other antiarrhythmic agents at the general public however the use of dysopyramide and amiodarone may be considered. Newer agents such as dronedarone have yet to be used in great numbers in those with HCM, therefore, its effectiveness is not well-established.
Procedures to eradicate atrial fibrillation structure have very sporadic results in HCM and, therefore, should be entered into after extensive consultation with an HCM specialist, as well as an electrophysiologist with an HCM specialty. Procedures such as radio frequency ablation, pulmonary vein isolation, and surgical MAZE have all been attempted in those with HCM with varying degrees of success. There does not appear to be any additional risk to these procedures when performed on somebody with HCM and the outcomes are not as predictable.
Patients undergoing septal myectomy who have encountered even minimal issues with atrial fibrillation should consult with their surgeon prior to surgery for the potential of including a surgical MAZE while the myectomy is being performed.
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7. Other Issues |
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7.1. Pregnancy/Delivery—Recommendations |
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Class I 1. In women with HCM who are asymptomatic or whose symptoms are controlled with beta-blocking drugs, the drugs should be continued during pregnancy, but increased surveillance for fetal bradycardia or other complications is warranted.41,140,447,448 (Level of Evidence: C) 2. For patients (mother or father) with HCM, genetic counseling is indicated before planned conception. (Level of Evidence: C) 3. In women with HCM and resting or provocable LVOT obstruction greater than or equal to 50 mm Hg and/or cardiac symptoms not controlled by medical therapy alone, pregnancy is associated with increased risk, and these patients should be referred to a high-risk obstetrician. (Level of Evidence: C) 4. The diagnosis of HCM among asymptomatic women is not considered a contraindication for pregnancy, but patients should be carefully evaluated in regard to the risk of pregnancy. (Level of Evidence: C)
Class IIa 1. For women with HCM whose symptoms are controlled (mild to moderate), pregnancy is reasonable, but expert maternal/fetal medical specialist care, including cardiovascular and prenatal monitoring, is advised. (Level of Evidence: C)
Class III: Harm 1. For women with advanced heart failure symptoms and HCM, pregnancy is associated with excess morbidity/mortality. (Level of Evidence: C)
Women with HCM safely experience pregnancy and labor with minimal documented risks. The maternal mortality rate is extraordinarily low and limited to those patients with particularly advanced disease.449 Nevertheless, careful evaluation of the mother and functional assessment is paramount during and just prior to pregnancy. Usually, special medical precautions are unnecessary, and cesarean delivery is not obligatory. However, women with advanced disease, including progressive heart failure, severe diastolic dysfunction, VT, SVT, or marked LVOT obstruction, will require the care of a high-risk maternal/fetal medical team with close involvement of a cardiologist. For the woman whose disease is well controlled with medical therapy (beta blockers, verapamil, or disopyramide), there should be no interruption of therapy, but careful maternal and fetal monitoring is advised.157 For any woman of childbearing age with HCM, it is paramount that genetic counseling be advised before conception. Such patients should be counseled prospectively about the risks of pregnancy and discouraged if deemed necessary. Careful monitoring is advisable in the first 24 hours after delivery, when large fluid shifts can lead to acute pulmonary edema in the setting of a noncompliant and hypertrophied left ventricle. |
Class I 1. In women with HCM who are asymptomatic or whose symptoms are controlled with beta-blocking drugs, the drugs should be continued during pregnancy, but increased surveillance for fetal bradycardia or other complications is warranted. It is a wise idea to have a high risk pregnancy specialist for HCM mothers.
2. For patients (mother or father) with HCM, genetic counseling is indicated before planned conception.
3. In women with HCM and resting or provocable LVOT obstruction greater than or equal to 50 mm Hg and/or cardiac symptoms not controlled by medical therapy alone, pregnancy is associated with increased risk, and these patients should be referred to a high-risk obstetrician.
4. The diagnosis of HCM among asymptomatic women is not considered a contraindication for pregnancy, but patients should be carefully evaluated in regard to the risk of pregnancy.
Class IIa 1. For women with HCM whose symptoms are controlled (mild to moderate), pregnancy is reasonable, but expert maternal/fetal medical specialist care, including cardiovascular and prenatal monitoring, is advised.
Class III: Harm 1. For women with advanced heart failure symptoms and HCM, pregnancy is associated with excess morbidity/mortality.
Planning a pregnancy in HCM families requires input from both the father and the mother regardless of who is the genetic carrier or the affected individual. It is advised to seek out the input from a genetic counselor prior to planning a pregnancy to review all available options for family planning.
Women with HCM can carry a successful pregnancy and experience labor with minimal additional risk. However, individual cases must be evaluated to ensure that mother and child will encounter the experience successfully. Women with significant obstruction, heart failure symptoms or symptoms that are not well managed are encouraged to address these issues prior to becoming pregnant. Women can remain on medical therapy while pregnant and at the time of delivery. Discussion with anesthesiology and labor and delivery professionals, in advance, helps to ensure appropriate hydration, pain management and fetal monitoring. Careful monitoring is advised for the first 24 hours after delivery when large fluid shifts can lead to pulmonary edema.
Some patients may be discouraged from becoming or continuing a pregnancy based on their individual status. The majority of patients will, however, be able to maintain a healthy pregnancy and delivery. |
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7.2. Occupational Considerations |
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In 2002, the US Department of Transportation Federal Motor Carrier Safety Administration published its “Cardiovascular Advisory Panel Guidelines for the Medical Examination of Commercial Motor Vehicle Drivers.” The guidelines state that “irrespective of symptoms, a person should not be certified as a [commercial motor vehicle] driver if a firm diagnosis of [HCM] is made…”.[450(p83)]_ Although consideration has subsequently been given to liberalizing this restriction, the guidelines have not yet been revised.
The criteria for the disqualification of aircraft pilots with cardiovascular disease are set by the Federal Aviation Administration. Currently, HCM is regarded as generally incompatible with the highest grade aviation license for commercial pilots, based on the unpredictable risk for impairment in the cockpit attributable to HCM.452 |
There are only a few occupations that are not advised or are restricted based upon the diagnosis of hypertrophic cardiomyopathy. US Department of Transportation published guidelines on cardiovascular risks for commercial motor vehicle drivers. The guidelines state that irrespective of symptoms a person should not be certified as a commercial motor vehicle driver with a firm diagnosis of hypertrophic cardiomyopathy. This language, therefore, restricts issuing a CDL or commercial drivers’ license to any person with a diagnosis of hypertrophic cardiomyopathy, and any person seeking work in this particular area should be counseled against this line of work. Additionally, the criteria for disqualification of aircraft pilots with cardiovascular disease are set by the Federal Aviation Administration. Currently HCM is regarded as generally incompatible with the highest grade of aviation license for commercial pilots. Therefore, this line of work should also be avoided.
Generally speaking, and in the experience of the Hypertrophic Cardiomyopathy Association, most occupations are compatible with the diagnosis of hypertrophic cardiomyopathy. Patients may, however, wish to consider not embarking upon career paths that require a great degree of physical labor or which require one to be on their feet for the majority of their workday.
Careers that include such skills as welding or being on high platforms or ladders for extended periods of time may become problematic in the event the patient receives an implantable cardioverter defibrillator, ICD. Therefore, if you are a younger person starting out in your career path, you may wish to avoid careers that would require these skills or requirements.
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8. Future Research Needs |
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Despite progress in the understanding of the etiology and pathophysiology of HCM and in certain aspects of management, more substantial insights into the fundamental and clinical components of HCM provide considerable opportunities to improve patient outcomes. The research priorities in HCM were detailed in 2010 by a National Heart, Lung, and Blood Institute working group.453 |
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8.1. Establishing the Cause of HCM |
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Over the past 20 years there have been major advances in identification of genetic mutations that cause HCM. Contemporary data sets include _1000 mutations that primarily occur in at least 8 genes that encode protein components of the sarcomere. Nonetheless, the genetic cause remains unknown for a substantial proportion of patients with clinical manifestations of HCM. Mutation-negative patients may have LV hypertrophy attributable to another genetic (or nongenetic) cause, with morphologic features that mimic HCM but with distinctive pathophysiology and clinical outcomes. Definition of the cause(s) of HCM morphology in mutationnegative patients is important for the basic understanding of mechanisms that remodel the heart and for determining whether or not the clinical practice guidelines established for HCM are relevant in these patients. The ability to pool data from multiple registries is encouraged. |
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8.2. Defining the Link Between Genotype and Phenotype |
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The emergence of newer sequencing methodologies provides unparalleled opportunities for defining the precise mutation in most patients with HCM. Such information can expand our understanding of the relationship between genotype and phenotype in HCM, a link that remains incompletely understood. Directing future efforts to identify genetic modifiers (ie, genes that influence clinical expression) and environmental influences may expand understanding of the signaling pathways that are responsible for phenotypic expression of HCM and related disease states. These strategies also hold the potential to define novel therapeutic targets that may attenuate the consequences of sarcomere gene mutations, so that disease expression may be delayed or conceivably prevented. |
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8.3. Management and Evaluation of HCM Genotype Positive/Phenotype Negative Relatives |
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Gene-based diagnosis of HCM families has increased the identification of genotype positive/phenotype negative individuals. There are many unanswered questions about the natural history of these patients, including the identity of factors that influence duration of the preclinical phase, the likelihood of clinical identification by screening with echocardiography (or CMR), the risk of SCD, and decisions about the periodicity of clinical screening, the use of ICDs for primary prevention, and participation in competitive sports. Longitudinal data are needed to develop appropriate management recommendations for this growing subset of patients. In addition, as more information is accrued regarding the signaling pathways that account for clinical manifestation associated with sarcomere protein gene mutations, the study of therapeutic interventions aimed at preventing the emergence of disease in preclinical patients can be expected. |
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8.4. Clinical Significance of Myocardial Fibrosis |
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Myocardial fibrosis of the heart is increased in HCM because of an expansion of the interstitial matrix and also myocardial replacement scarring (caused by microvascular ischemia and other factors). Consistent with histopathologic findings, serum biomarkers of collagen turnover are elevated in patients with clinically overt HCM. Recent studies in HCM models indicate that extracellular matrix remodeling predates the emergence of hypertrophy and may contribute to diastolic dysfunction.18 Studies are needed to ascertain whether prevention of interstitial (matrix) expansion or replacement scarring can improve HCM pathophysiology and reduce late outcomes such as progressive heart failure. Replacement fibrosis and scarring can be visualized (in vivo) by CMR gadolinium contrast enhancement. Clearer understanding of the relationship between LGE, fibrosis, and clinical outcomes (including ventricular tachyarrhythmias and sudden death) is needed. |
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8.5. Therapies to Directly Modify the HCM Pathophysiology |
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The most widely used medical therapies for patients with HCM (beta-adrenergic blockers, calcium channel blockers, disopyramide) nonspecifically address aspects of the hemodynamic abnormalities in patients with HCM, such as reducing contractility to diminish the magnitude of outflow tract obstruction. As noted above, a more sophisticated understanding of the links between the molecular pathophysiology and outcome is necessary in HCM to promote the development of more relevant and targeted treatment strategies.453 For example, characterization of the fundamental biophysical defects produced by different mutations in sarcomere proteins, assessment of energy requirements of the heart in HCM, and assessment of the role of myocardial ischemia may lead to interventions that alter the natural history of disease expression. |
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8.6. Refining Risk Stratification for SCD |
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As noted in this document, identifiable clinical markers are being used successfully in risk stratification for SCD in HCM, assisting in recommendations about prophylactic ICDs. Nonetheless, much ambiguity is often encountered in using the current SCD risk stratification algorithm in individual patients, and there is a need to identify additional and more sensitive/specific risk factors. Moreover, sudden death may occasionally occur in “low-risk” patients without conventional risk factors. The assembly of larger cohorts from multiple centers with detailed clinical, genetic, and lifestyle information may improve SCD risk stratification and enable more efficient use of ICDs. |
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8.7. Comparative Assessment of Septal Reduction Strategies |
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The opportunity for percutaneous strategies to reduce outflow tract obstruction in HCM was realized through the development of alcohol septal ablation. The potential of this approach to provide clinical benefit in reducing symptoms with lower patient morbidity and reduced healthcare expenditures has been somewhat undermined by a concern for increased ventricular arrhythmias following the procedure. Robust information about the types and frequency of adverse outcomes following alcohol septal ablation are needed in addition to rigorous assessment of whether these events are intrinsic to the procedure or related to underlying hypertrophic substrate, concomitant coronary or other comorbid disease, or the advanced age at which patients receive this therapy versus myectomy. In addition, observational registries might be useful to compare rates of HCM-related death. Such comparisons of short- and long-term outcomes of patients treated with alcohol septal ablation or myectomy surgery would foster appropriate use of these strategies and improve patient symptoms and outcomes. |
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8.8. Therapies to Treat and Prevent AF and Its Associated Risks |
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AF is a common cause of morbidity and mortality in patients with HCM. Anticoagulation is well established in other causes of AF and almost certainly extends to the HCM patient with paroxysmal, chronic, or persistent AF. However, whether anticoagulation should extend to those patients with HCM who are at high risk of development of AF is unclear. In addition, the relative role of antiarrhythmic agents, radiofrequency ablation, and surgical maze procedure need improved definition. |
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