HCM Summit notes; Part 3

            Part 3

                                   

Mutations do not predict risk for sudden death

Michael J. Ackerman, MD

 

Research and increased use of genetic testing in HCM has greatly increased knowledge of mutations.  A focus has been to identify “malignant mutations..  This shows no mutations are “common”.  Most patients have “benign” mutations yet a number of these had significant HCM.  Key variable is a gene test positive, but not the specific mutation.  Best functional test is the echo.  Specific HCM-causitive mutations are rate, do not predict the future, but positive results do indicate possible complications and are the “gold standard”.

Are there more malignant genes?  Historically there were a couple of BAD mutations.  In a study of unrelated patients, only 4 of 389 had previously thought malignant mutations so most HCM patients who die suddenly will not have one of the BAD mutations.  None of these mutations are common so we cannot make a prediction based on a mutation.  They then looked for a “benign” mutation, they were infrequent, and were not really found to have been benign.  So there is really no such thing as a malignant mutation.  Is there a positive or negative genetic test..  If a positive test, they are more likely to have earlier interventions.  When you look at these patients in time, those with a positive test have a more severe progressive history toward end stage HCM more than any traditional testing variable.   So, prognostic information may not be with regard to sudden death but whole clinical course.               

The number of first degree relatives that are not even being echoed is way too high.      Family history can, in an extreme case, and in certain instances, justify an ICD in a gene positive individual.           

 

In Europe gene positive status is an automatic disqualifier from competitive sports.  This is not the case in the US where we need phenotypic evidence.                         In the next 10 years, everyone will have their entire genome mapped out . 

Lisa:   Can genes predict SCA – NO…

What about in an individual family?… yes   - after sister and brothers death a second brother had 3 vf with NO hypertrophy……. But gene +

Genetic testing is the gold standard diagnostic predictor for the rest of the family

HCM without H…. 3 deaths associated

Game changer….??? Uff da

                                                                                                                                   

Take Home Message: 

 “HCM is unpredictable and we have much to learn”   “non-hypertrophic” HCM

Key points: 

When an individual is gene test positive for HCM, “genetic testing is the gold standard for the rest of the family.”   “The disease in unpredictable and we have a lot to learn.”                                                                                                                         

 

Prevention of sudden death with the implantable cardioverter-defibrillator

Barry J. Maron, MD

 

Prevention of sudden cardiac death (SCD) was initially approached using drug therapy—beta blockers, anti-arrhythmia meds, etc.  Drugs do not protect absolutely from SCD.  As HCM is unpredictable, ICD therapy offers proven results.  A joint international registry of ICD use in HCM of 500+ patients has identified appropriate shocks in 20% and a life-saving role in prevention.  The registry indicates possible problems including long time use when ICD’s are implanted in children.  33% of appropriate shocks were in persons with one risk factor with syncope (fainting) the largest factor.

Drugs do not protect absolutely against HCM.  ICDs are the only choice.    HCM is unpredictable.  Patients with the most risk are often kids, and you have to weigh the risk of them having devices over a lifetime.  Not all one risk factor patients should get an ICD.  In looking at retrospective data, if one factor has more weight, it is syncope.  After being saved by sudden death prevention, in 90% of patients it did not trade with heart failure. Patients lived for a long time often with no symptoms.          

Take Home Message: 

Unpredictability of the course of HCM means years can pass before an ICD is “triggered”.  Continued data collection and longer follow-up analysis will assist future decision-making by physicians and patients.  Top risk factor – “syncope”  

Key points: 

Dick:  Complete transparency, informed consent and full disclosure must guide ICD decisions.  One risk factor can be enough for ICD implantation in a particular patient but not all “one risk factor” patients should receive ICD.                                                            

An electrophysiologist’s perspective on mechanisms and decision-making for sudden death prevention.

N.A. Mark Estes, III, MD

 

 We lack an animal or biological model for sudden cardiac death (SCD) prevention.  HCM SCD is the “perfect storm” of multiple risk factors.  Available data is limited.  Registry (1500+ patients) shows unexplained syncope related to SCD.  Research methods and analysis are developing for events such as ICD shocks.  Although randomized clinical trials have not studied ICD SCD use, registry data are being used in building consensus on recommendations for ICD use.  Inappropriate shocks remain greatest in complication.  New ICD features are developing and will be included in registry reports.

Your risk is higher for unexplained syncope within 6 months of being implanted-about a five time increase of risk of sudden death.  Exercise related syncope is also dangerous.     There may be arrhythmia caused by ICD implantation.  Most complications with ICDs in HCM patients are in those patients who are younger or who have problems with A-fib.       There is a much lower rate of infection when an ICD is implanted at an experienced center.    There seems to be a much worse outcome at inexperienced centers.     

Take Home Message: 

Training and experience matter for limiting ICD problems and enhancing prevention, especially with young patients.  We need improved research on ICD use in HCM.

Key points: 

Over 85% of ICD patients are in the National Registry which is helping us to understand many dimensions of ICD use.  Recent syncope & exertional syncope = high risk  “Training & experience really matters” in preventing ICD complications.  Complications can be minimized in experienced centers.  Complications increase 2 fold in less experienced centers. 

 

The defibrillator industry and HCM:  The good with the bad:  progress in device quality with optimism for the future

Robert G. Hauser, MD

 

ICD therapy has evolved since 1980 with technological innovation, improvements in medical implants, and expanded diagnostic information.  Yet, uniform collection of product information and reliability of devices have lagged.  Problems include lead failures and pulse generator issues.  Malfunctions have been linked to faulty materials.  Problems also occurred in other devices such as pacemakers.  Meaningful post-market studies, however, did not occur.  Failure rates are very low, however, for proven devices.  Extraction of problem devices remains a problem.

Choice of device is key.  No clinical testing was done before implantation of the ICD that failed due to moisture in cans.  That was the genesis of the ICD registry so that failure rates of devices could be tracked.  Then they figured out how to seal the can so moisture didn’t get in.  Drs. were unhappy with silicone leads so they came up with polyurethane which became popular and were rapidly adopted without clinical information to demonstrate safety.  Then, they were found likely to fail and 21% would fail within 6 years.                               Reliability of leads can only be assessed after a time.  Silicone leads are lasting much better than polyurethane which disintegrated.  Sprint Fidelis was not clinically tested and was approved quickly and rapidly adopted.  Over 250K implanted and there was no meaningful post market study required or done by FDA.  They began fracturing in early 2006.  It was much worse when compared to Sprint Quattro.      Important differences in lead models.  Since HCM patients are young, Doctors should choose leads with proven outcomes.   Single chamber devices last longer than dual chamber...                                                                                                                            

 

Take Home Message: 

Improved methods are needed to identify problems and certify success in ICD’s and their leads.  Care and expertise are crucial for problem resolution/extraction.

Key points: 

ICDs and leads are safe and effective for HCM patients yet continued vigilance is required.  Pre-clinical & short time clinical studies may fail to identify real risks & outcomes in the real world (actual implant in human body over time & stress).  Hazards/failures can accelerate over time.  There is optimism from hard lessons learned.     

                                                                                                                       

 

The HCMA after 10 years:  Evolution of HCM centers of excellence in the U.S.

Lisa Salberg

 

 The HCMA has over ten years experience providing support, advocacy and education to patients, the medical community and the public about HCM.  Current initiatives include review of CDC data on HCM deaths, designation of HCM Centers of Excellence using specific knowledge and experience criteria and surveys of HCM patients showing the value of HCM specialty care.  Case studies of HCM patients show the wide range of problems brought to the HCMA and successful outcomes from the assistance provided.

Take Home Message: 

Increasing use of HCMA resources has been documented from calls to the HCMA and visits to the HCMA website, records of referrals to HCM centers, and increasing number of regional meetings for patients and HCM specialists.  Amazing growth of organization with profound results for patients                  

Key points: 

For HCM patients, “a little information goes a long way” and the HCMA is a vital resource for all.  Collaborative effort – patients benefit greatly from advocacy & HCM centers.  Advocacy, education benefits patients but also helps medical world.  Education (knowledge) is key.                

 

Cardiovascular pathology is “alive and well” in Italy:  Evidence for the unstable myocardial substrate and significance (or lack thereof) of myocardial bridging as a risk factor

Cristina Basso, MD

 

Clinical and pathological studies in Italy have addressed myocardial bridging (MB is where the artery-usually the left anterior descending coronary artery—has “tunneled” through a part of the heart muscle) in HCM.  Usually in younger patients, MB has been linked with myocardial ischemia (heart attack) and sudden death – with or without HCM.  The association of MB with HCM remains controversial, difficult to identify and distinguished from MI and complex to study.  Distinctions should be made from available data – imaging and pathological – of the depth and orientation of the MB.  Case-by-case decisions are required in treatment.

Take Home Message: 

There is need for improved recognition and treatment in MB in HCM.  Additional studies and case reports will help in clinical diagnosis and distinctions in management of MB associated with HCM.  Myocardial bridging is defined as a segment of a major epicardial coronary artery that goes intramurally through the myocardium beneath the muscle; it is a mechanism for myocardial schemia in HCM.  Cannot be regarded as a marker for ↑ risk, precise patho/physiological significance in individual patients is uncertain – must evaluate by case.                

Key points: 

 Myocardial bridging or a “muscle tunneled” artery, while rare in HCM, has great significance and calls for improved care and research.

 

From “Down Under”:  Insights on establishing a national HCM center in a “small” country

Christopher Semsarian, MD, PhD

 

 Australia has a population of 22 million but a land area nearly as large as the USA.  Since 2002 the national center for HCM has linked Royal Prince Alfred Hospital, University of Sydney and the Centenary Institute.  A multidisciplinary approach includes cardiology, genetics, pathology, and patient support.  Innovative studies include multiple mutations in HCM, ensuring HCM data is included in the Australian National Genetic Heart Disease Registry, and a population-based study of sudden cardiac death in young Australians.

Australia is made up of 22 million people.but a large land mass as big as U,S. which presents challenges in creating an HCM center.  Clinic established in1991 and has been a center since 2002 and sees over 600 families.  Most patients seeno n a regular basis but also some who are referred by their own cardiologist. General cardiologists encourage referral.      Multidisciplinary clinic help patients better adjust and worry less.                 

Take Home Message: 

The Australian HCM center is leading the way for improving HCM services and research in Australia while also participating actively in HCM international research and treatment.

 Key points: 

In seven years Australia has made major progress to define excellence in HCM treatment and research.:             HCM clinic established 1991 became a Centre in 2002 – truly national now with referrals from all Australian states.  Multidisciplinary approach – over 600 families – provide on going, & “one –off” referrals.  Provide assessment, education & counseling/genetic testing, appropriate clinical management & research.                      

 

Prevalence and clinical/genetic spectrum of HCM in China

Rutai Hui, MD

 

An estimated one million persons have HCM in China.  New studies may show up to two million.  Genetic studies are underway, MYH7 mutations in China have been linked to sudden cardiac death while MYBPC3 mutations led to low rates of SCE and near normal life spans.  Additional studies are examining hypertension, diabetes and increased body fat as associated HCM gene factors in animal models.

Take Home Message: 

China is addressing novel studies in the genetics of HCM with access to a very large population base.  Efforts have been modest in numbers to date but methods and reports are being shared internationally.

Key points: 

China is an important and growing partner in HCM research and treatment.

Gene studies ongoing in China.                                                                                                                         

 

Athlete’s heart and its distinction from HCM:  Consensus guidelines for eligibility/disqualification from sports competition to reduce risk

Antonio Pelliccia, MD

 

Unresolved issues confront diagnosis and management of HCM in athletes.  These include interpretation of ECG and Echo testing.  Cardiology associations in the US and Europe have reached different conclusions on recommendations for participation in athletics for athletes who are genotype positive without HCM symptoms.  US=no compelling evidence to preclude participation; Europe=limit participation to recreational, low intensity sports.  Both US and Europe recommend limits for athletes with HCM diagnosis/symptoms.  ICD use by athletes enhances risk of inappropriate shocks and displacement of leads.

 What is clinical significance of abnormal EKG if normal echo?  Majority of abnormal EKG in atheletes appear to be ot causing of problems.

Summary – hard to detect HCM in black athletes.  Cost of the evaluation is $50.00 in Italy.

Take Home Message: 

Athlete screening presents many issues and complex factors impacting participation decisions.  Development of multiple medical resources based on specific expertise and repeated evaluations informs decisions and reduces risk.

Key points: 

Consensus building for HCM athletic participation is an international topic where many points of agreement exist but key differences remain.:  Current recommendations are intended to support the physicians decision and protect patients from the avoidable hazards of competitive sports (sport induced cardiac arrest, inappropriate shocks, lead fracture or displacement).  Recommendations exclude HCM patients from competitive sports with exception of law intensity sports in selected cases.  In Italy the current knowledge of the diagnostic power of 12-lead ECG is limited to Caucasian athletes, more studies are needed in Africans & Asians.  The vast majority of abnormal EG patterns in trained athletes seem to be deprived of long term clinical consequences, evidence of cardiovascular events, or late development of hypertrophy.       

                                                                                                                                               

Debate:  What is the most effective strategy for preparticipation screening to detect cardiovascular abnormalities in trained athletes?

Point:  The Italian model saves lives and is best

Domenico Corrado, MD

 

 Annual incidence rates of sudden cardiac death in screened competitive athletes has declined significantly.  Trends in decreased rates are significant for athletes with HCM.  Italy uses a 12-lead ECG for screening plus family and personal history.

EKG screening is cost effective due to long lives of people identified, Family members, relatively low cost,

Take Home Message: 

The Italian model is appropriate for Italy’s governmental, legal, athletic and medical system.   Pre-participation screening with ECG is mandated by law in Italy.  Italian pre-participation screening essentially based on 12-lead ECG has resulted in a sharp decline of sudden death during sports.  Italian ECG screening meets the criteria to be a valid public health concern.

Key points: 

 Data and procedures from Italy in screening show positive impact of screening to prevent sudden cardiac death.

Add to:   del.icio.us |   AskJeeves |   Yahoo MyWeb |   reddit |   Digg |   Facebook |   Google |   Myspace |   Windows Live Favorites