Hypertrophic Cardiomyopathy and New Guidelines for Electrophysiologists

“Hard to treat and harder to diagnose” is how many clinicians have often thought of hypertrophic cardiomyopathy (HCM). As electrophysiologists, it hasn’t always been on the radar since it’s often viewed as a rare, somewhat obscure disease. However, according to Dr. Barry J. Maron, one of the world’s experts on HCM and an investigator at the Minneapolis Heart Institute, HCM is the most common cause of sudden death in young people.¹ As such, new developments on HCM are critical for EPs to understand and integrate into their practice. This article outlines the newly published recommendations for treating HCM patients.

Practice Guidelines and HCM Background

Led by Dr. Maron and Dr. Bernard Gersh from the Mayo Clinic, new practice guidelines were just released on HCM from the American College of Cardiology Foundation (ACCF) and the American Heart Foundation (AHA). These recommendations were co-published online by these international societies in the Journal of the American College of Cardiology, the Journal of Thoracic and Cardiovascular Surgery, and Circulation.²

HCM is a very common genetically-based disease. It is estimated that 1 in 500 people (or at least 600,000 people in the US alone) suffer from the condition.³ This far dwarfs other genetic conditions such as long QT syndrome (LQTS) or Brugada syndrome, which often get more attention in the literature. Braunwald et al’s early report of the condition in 1964 launched full-scale investigations into the entity.⁴ Although originally given the term of idiopathic hypertrophic subaortic stenosis (IHSS) or hypertrophic obstructive cardiomyopathy (HOCM), at least one-third of affected patients do not have any discernible obstruction.²

The new HCM guidelines clearly outline accepted definitions of HCM as “a disease state characterized by unexplained LV hypertrophy… in the absence of another cardiac or systemic disease...”.² One can recognize HCM in a patient if their maximal LV wall thickness is >15 mm by echocardiography.

Clinical Symptoms for HCM Patients

The HCM guidelines emphasize the heterogeneous nature of the clinical symptoms in HCM patients. In a small number of afflicted patients, they can experience sudden death or life-threatening arrhythmias, yet most have no symptoms and achieve a normal lifespan. Below we will attempt to outline some of the prominent clinical symptoms seen in HCM patients:

Mitral Regurgitation (MR). MR is common in HCM patients who have LVOT (left ventricular outflow obstruction). MR is often produced by disturbance of the mitral valve due to the LVOT obstruction.² MR can lead to dyspnea or contribute to the development of atrial fibrillation (AF).

LVOT Obstruction. Up to one-third of HCM patients can have an intracardiac obstruction of over 30 mmHg at rest, and another one-third can develop this obstruction with provocative maneuvers.² Obstruction may cause no symptoms or could lead to chest pains, syncope, and shortness of breath.

AF and Ischemia. AF is fairly common in HCM patients and can trigger a stroke. HCM can cause major myocardial ischemia or even a myocardial infarction, leading to sudden death.²

Genetic Testing Strategies and HCM Guideline Recommendations

HCM is an autosomal dominant, genetic disease. More than 1,400 mutations have been described in HCM patients, mostly in sarcomere proteins.^2,5 Unfortunately, despite much research in this area, there is not a lot of concrete genotype-phenotype correlation to guide clinicians.⁶

The guidelines give a Class I recommendation to performing genetic testing in first-degree relatives of HCM patients.² They report that experienced clinical labs may identify a pathogenic HCM mutation in 60–70% of such patients.² In genotype-positive/phenotype-negative patients (those with no symptoms), the guidelines suggest performing a stress test or Holter monitor as a means of determining if any high-risk features for sudden death may be present.²

They also recommend that gene-positive HCM subjects without symptoms undergo serial ECGs, echos, and clinical evaluations every 12–18 months in children or every 5 years in adults.

Imaging Modalities and Testing for HCM

A transthoracic echo remains the gold standard diagnostic tool for HCM, and should be performed as the initial test in all patients suspected of having HCM; Class I recommendation.² First-degree relatives of HCM subjects should also be screened with an echo.

Cardiac MRI can be done as an imaging modality if HCM is suspected by echo but the echo is inconclusive for the diagnosis (Class I).² Stress testing can be done to look for hypotension with exercise or to determine functional capacity (Class IIa recommendation).²

Management of HCM

As with all cardiac diseases, the new guidelines recommend that comorbid illnesses also be aggressively treated in HCM patients (Class I).² Hyperlipidemia, diabetes, smoking cessation, and hypertension should all be addressed in HCM patients. Interestingly, the use of beta-blockers or calcium channel blockers, long a mainstay of such subjects, is given only a IIb recommendation if they have no symptoms, even in those with obstruction.² However, if subjects do have symptoms, beta-blockers are the first-line agent that should be used.^2,7 Verapamil at high doses can be used as a second-line agent.² Nifedipine should not be used in those with a gradient (Class III).

One of the biggest surprises for the updated guidelines is with the use of septal ablation. The authors suggest that septal reduction therapy be performed “only by experienced operators” at centers that have an HCM program.^2,8 This Class I recommendation is also only for those patients with severe symptoms despite aggressive medical management and severe LVOT obstruction. If septal ablation must be done, surgical myomectomy is in general preferable to alcohol ablation (Class IIa). The authors note the long-term usage of surgical myomectomy (over 50 years), which is partly why this procedure is preferable to the more non-invasive alcohol ablation approach.

Primary pacemaker therapy for HCM is relegated largely to a Class IIb recommendation.^2,9 It should be used for those patients who have medically refractory symptoms or can’t have some type of ablation procedure. It should not be used as a first-line therapy to relieve obstruction (Class III). Several randomized crossover trials showed that there was quite a bit of individual variability among LVOT obstruction reduction among patients given pacemakers.

Risk Stratification for HCM

It is difficult to accurately risk stratify these patients. A personal history of ventricular fibrillation or ventricular tachycardia, unexplained syncope, or massive LV hypertrophy (>30 mm) can be considered higher risk features for sudden cardiac death (SCD).² Family history of SCD may (or may not) be a high-risk feature.

One interesting caveat to this discussion is the recognition that HCM patients could face SCD during certain types of exercise. The guidelines break down in some detail what kinds of exercise are higher versus lower risk for SCD.^2,10 For example, playing basketball, skiing, or engaging in ice hockey are “intense, competitive sports” and should be avoided by all HCM patients. However, brisk walking, playing golf, or bowling are low risk for SCD in such subjects and can be safely done.

Summary

HCM is the most common genetic cause of sudden cardiac death. There have been new developments in the diagnosis, genetic evaluation, and treatment of this fascinating disease, which have important implications in how we care for these patients. The new 2011 ACCF/AHA guidelines for HCM make for stimulating reading.

References

1. Stiles S, Lie D. “Landmark Hypertrophic Cardiomyopathy Recommendations Issued.” Medscape. 14 Nov. 2011. <https://www.medscape.org/viewarticle/753490?src=emailthis>.
2. Gersh BJ, Maron BJ, Bonow RO, et al. 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. J Thorac Cardiovasc Surg 2011;142:e153-e203.
3. Maron BJ. Hypertrophic cardiomyopathy: An important global disease. Am J Med 2004;116:63-65.
4. Braunwald E, Lambert CT, Rockoff SD, et al. Idiopathic hypertrophic subaortic stenosis. Circulation 1964:30(suppl 4):199.
5. Alcalai R, Seidman JG, Seidman CE. Genetic basis of hypertrophic cardiomyopathy: From bench to the clinics. J Cardiovasc Electrophysiol 2008;19:104-110.
6. Bos JM, Towbin JA, Ackerman MJ. Diagnostic, prognostic, and therapeutic implications of genetic testing for hypertrophic cardiomyopathy. J Am Coll Cardiol 2009;54:201-211. 
7. Swanton RH, Brooksby IA, Jenkins BS, Webb-Peploe MM. Hemodynamic studies of beta blockade in hypertrophic obstructive cardiomyopathy. Eur J Cardiol 1977;5:327-341.
8. Nagueh SF, Ommen SR, Lakkis NM, et al. Comparison of ethanol septal reduction therapy with surgical myectomy for the treatment of hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 2001;38:1701-1706.
9. Linde C, Gadler F, Kappenberger L, et al. Placebo effect of pacemaker implantation in obstructive hypertrophic cardiomyopathy. PIC Study Group. Pacing in Cardiomyopathy. Am J Cardiol 1999;83:903-907.
10. Corrado D, Basso C, Rizzoli G, et al. Does sports activity enhance the risk of sudden death in adolescents and young adults? J Am Coll Cardiol 2003;42:1959-1963.