HCM Summit notes :Part 2

Part 2

The spectrum of progressive heart failure in HCM:  Clinical-pathologic correlations

Christina Basso, MD, PhD

Pathology is of increasing importance in understanding HCM.  Heart transplants have allowed detailed pathological study of HCM diseased hearts.  Pathological study has linked obstructive features to function.  Time lines and charts have been used to show relationships of pathological features and HCM.  Clinical profiles of heart failure in Italy document AF, end-stage systolic dysfunction, LV outflow obstruction and diastolic dysfunction.  These diverse dysfunctions reflect the heterogeneity of HCM and confirm that a range of treatment/management strategies are required.

HCM converts to End stage in young patients… those with low EF and young should move to transplant.

End stage is quick – from onset to death 2.7 years

 Take Home Message: 

HCM requires inter-disciplinary approaches for discovery, analysis, and development of treatment.  Pathology is a key tool and discipline for improving the understanding of HCM.  Collection of significant numbers of HCM pathology samples is key to improved knowledge.

Key points: 

News from Italy documents the value of pathology data—a priority area for the HCMA.  Profile outcome of advanced heart failure in HCM are due to diverse pathophysiologic mechanism; including LV outflow obstruction, atrial fibrillation, and diastolic or global systolic ventricular dysfunction.  AF is the most common disease variable associated with heart failure.  Targeted management strategies are required.

Franco Cecchi, MD

Myocardial ischemia (MI) can be seen as a neglected area in HCM studies.  The Italian Registry found 5% - but frequently is undetected.  MI in HCM patients may be detected by PET studies and Cardiac MRI.  PET or Positron Emission Tomography measures bloodflow.  MI is a key factor for some with HCM leading to disease progression, LV remodeling and premature death.  New studies are examining genetic mutations and myofibril mechanisms.

5% of patients have atherosclerosis.  Most time coronary arteries look normal.    Angina is reported in 1.2 of partients, but up to ¾ have it.  No correlation with severity of hypetrophy.  Microvascular dysfunction is to blame.  Triggers of ischemia are when oxygen demand increases.  Exercise or tachyarrythmias.  Increasing wall stress = LVOT obstruction. 

The HCM “heart consumes fuel like a Ferrari, but performs as a very old   car.”                                                                                                                                                  

Take Home Message: 

Blood flow may be a key cause of specific cardiac functions and long-term consequences relevant for patients with HCM.  MI can be detected by PET, sarcomeric gene mutations help explain pathogensis of heart failure in HCM

Key points:

Microvascular dysfunction leads to myocardial ischemia & hypoperfusion causing angina.  Mycardial hypoperfusion & severe microvascular dysfunction are predictors of left ventricular remodeling & dysfunction, disease progression and premature death.                                            

Clinical spectrum of the “end-stage”

Iacopo Olivotto, MD

Most HCM patients have a stable course over many years.  A minority have progressive symptoms leading to end-stage HCM, marked by systolic dysfunction, LV dysfunction and poor outcomes.  Mortality has been measured at 11% per year for end-stage HCM.  Increasingly genetic findings have been linked with end-stage HCM.

            Right ventricle thinning is bad news for patients.  Epidemiology of end stage varies in age, with mean 45.  3.5 – 5/year progression to end stage.     Very advanced and progressive.  Annual mortality of 11%/year and high risk of sudden death/ICD inerevention.  MYBPC3 has almost 50% in end stage.  9% of MYH7 go into end stage.  Is a good rationale for doing genotyping in patients so prognosis and possible progression to end stage can be assessed.       Cases with triple mutations have bad, bad prognosis.                                    

End stage progression begins when?  When does it go from hypercontractile to end stage?  MRI can allow precise quantization of LV volume in HCM.  patients, 15% with low EFs, there is probably a movement to end stage.  50 – 65% should be considered suspicious when it is combined with fibrosis.  Treatment options:       switch to standard HF treatments; ICD; CRT; LVAD; Transplant.                    CRT has had good preliminary results but very early…    Once entered end stage can progress quickly.  Sometimes with LVAD can reverse heart failure with rest.  Women tend to do better with CRT.

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Is END stage really that bad? Yes but treatments make a difference.  End stage average age is 45 but can occur at any age (14-74) Patients get to end stage very slowly… then fall of a cliff quickly – prompt transplant is critical.

Take Home Message: 

As research methods and analysis progress, and as data on cohorts of patients over long time periods grows, understanding of key factors in the progression of HCM to end-stage increases.   “End Stage” doesn’t necessarily mean terminal.”  Typical triad of symptoms seen: systolic dysfunction, left ventricular thinning, cavity dilatation.  CMR allows precise quantification of systolic function & myocardial fibrosis providing clues for timely switch to classic HCM treatment.  End stage HCM behaves as DCM.  Don’t wait for overt dystolic dysfunction.                              

Key points: 

End-stage HCM, while rate, is a fast-growing area of research and treatment 

Brief introduction to risk stratification strategies and selection of high risk patients in HCM

Barry J. Maron, MD

 Bethesda Conference No. 36  recommendation is that a person diagnosed with HCM should not participate in most competitive sports.  Intensive competitive sports  equals “modifiable risk” of sudden cardiac arrest.                                                                      

Key points: 

Bethesda Conference #36 Recommedation – those with unequal diagnosis of HCM should not participate in most competitive sports – sports is a “modifiable” risk factor in SLP.  ASA may increase the risk of sudden cardiac death due to septal scarring as studies show this places them at greater risk for ventricular tachyarrhythmias.  LVOT obstruction greater than 30 mm at rest increases risk for sudden cardiac death.                      

Three Primary Prevention Risk Markers:  Prognostic significance of syncope, LVH and the ambulatory Holter.  Sudden death risk without risk factors?

Paolo Spirito, MD

  Risk factors for primary prevention of sudden death may be analyzed, rated, and related to outcomes based on data collected in 1511 patients with HCM.  Unexplained and recurrent unexplained syncope show patterns of higher risk for sudden death.

Five risk factors have to be integrated by clinical experience..  Extreme LVH increases oxygen requirements, turns into ischemia and then sudden death.  Thickest hearts have the highest risk.  Extreme hypertrophy is an important risk factor and for these patients the issue of sudden death should be considered.                                                          Non-sustained VT arrhythmias are important and should not be dismissed, particularly in the young patient.  A second event might degenerate into VF.

Syncope is one of the most challenging symptoms.  Unexplained syncope believed to be an aborted SCA… but this may be incorrect…

Sudden death in the absence of risk factors occurs most often in young patients under 40.  Absence of risk factors does not guarantee no sudden death.                                  

Take Home Message: 

Recent unexplained syncope (fainting) is associated with increased sudden death risk, particularly in young patients.                                                                                          
                                                                                               

Two Primary Prevention Risk Markers: Prognostic significance of family history of sudden death and blood pressure response to exercise

Steve Ommen, MD

Limited studies have examined family history of sudden cardiac death in HCM.  Risk estimate for SCD in HCM is low (.5 to 1.5% per year).  Identifying and analyzing additional variables increases risk but research methods and data remain incomplete.  Abnormal blood pressure response to exercise requires more study.  Defining risks in ABPR is complicated by possible drug effects, reporting challenges and need for improved methods.  Combing risk factors analysis to determine ICD need is complicated.

How important is family history with no other considerations.  This is the most overwhelming consideration for the patient personally due to emotional factor.  The results were inconsistent within studies.  When an ICD was placed for a single risk factor the discharge rates were 2 to 3 times higher than expected.  Not statically higher when there is more than one risk factor.  Family history data suggests risk 2 times higher with a family member.     Abnormal blood pressure response – blood pressure should increase.  It is considered abnormal if it stays the same or drops.    This occurs in ½ of patients.  This can be bad when a patient is obstructed.   Is the risk higher when they are medicated which affects that data.  What does it mean?  Myectomy may impact need for ICD as risk of sudden death goes down after myectomy..  Rate of events goes up dramatically after alcohol ablation.  Each patient has to evaluate the risk factors and the need for the ICD with all of their unique circumstances.

Take Home Message:

Analysis of family history and risk factors is complicated.  Decision-making by patients and physicians should be informed by frequently used decision aids—checklists of risk—but comprehensive analysis requires specialized expertise, communication skills, and constant awareness of changing factors. 

Key points:

The challenges and interactions of identification of risks in HCM of sudden cardiac death reinforce need for patients to seek highly expert treatment at a center of excellence.   Family history of sudden cardiac death approximately doubles risk of SCD in affected members.         

New potential risk markers:  Status of CMR post-contrast delayed enhancement

Martin S. Maron, MD

Cardiac Magnetic Resonance Imaging (CMRI) may be enhanced by late or delayed gadolinium enhancement (GE) for identification of risk and treatment in HCM.  Extent and progression of HCM heart failure may be measured.  Studies are new with small number of participants, but indicate late GE is valuable for identification of risk of sudden cardiac death, progression of HF, and treatment needs.  Clinical use of late GE may provide decision data for some patients but additional analysis/studies are needed to discern patterns/recommendations for use.

Fibrosis may be the genesis for arrhythmias…..theory….HCM patients with late enhancement were much more likely to have arrhythmias and also more adverse events.  Presence of late enhancement alone is not enough to use to put ICDs in everyone.  It is too common.  The amount of fibrosis may instead be where the answer is but this is unclear.  Late enhancement means different things for different people.  You see more in older patients, so it is not incompatible with long lifespan.  It can possibly be used clinically, maybe as a tiebreaker for risk in assessing ICD need.  No ICD decision for primary prevention should be based on MRI.

Is DE a risk factor and up and coming marker for risk in HCM.

Prevelance of pts with DE – 55%  DE location important – LV wall and septum most common area while RV insertion point and apex are more rare

Those with normal to low EF have more DE, Holter has more NSVT in DE.

Meta analysis of large and adverse cardio events  - tevents total 21 in those with DE 17  predictive value .04 statistically significant but weak 

Take Home Message:

Diagnostic techniques in HCM are rapidly evolving and present challenges for researchers, clinicians, patients and health care providers.                                                                                                                               

Key points: 

Best uses of new CMR techniques are developing rapidly in HCM Centers of Excellence with positive findings for some patients.  Can we use LGE clinically?  “Yes, maybe” “Should not be the sole decision factor”  Late Gadalinium Enhancement (LGE) shows fibrosis in the HCM heart.  The presence of LGE is not enough to guide/manage HCM as it is too common.  The extent of the LGE shows promise for use as risk tool for evaluation for ICD implant.  But LGE may have different significance for different patients. – Inconclusive.