Hypertrophic Cardiomyopathy

March 3, 2021|Elizabeth Moxley

The recently updated clinical practice guideline for hypertrophic cardiomyopathy (HCM) entitled, 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients with Hypertrophic Cardiomyopathy: Executive Summary1 provides recommendations for the diagnosis and management of adult and pediatric populations, with Class of Recommendation (COR) and Level of Evidence (LOE).

HCM is an inherited cardiovascular disease in 1 of 500 in the general population,2 although the prevalence may be closer to 1 out of every 200 adults (0.5 percent), 3 and many cases are under-recognized in clinical practice.4 Laboratory tests confirm diagnosis, but contemporary understanding differs from the initial description more than five decades ago.5 HCM is the most frequent cause of sudden cardiac death (SCD) in youth, as well as trained athletes under 35 years of age.2, 6 HCM is a genetic disorder characterized by left ventricular (LV) hypertrophy unexplained by secondary causes, and the LV remains non-dilated with preserved or increased ejection fraction(EF).7

Genetic Transmission

HCM is the most common monogenic cardiovascular disorder;4 caused by a variation in a single gene, usually inherited in an autosomal dominant pattern.8-9 Genotype-phenotype correlations are inconsistent in predicting prognosis, thus, management is often clinically based.4, Genetic testing is confined to next-generation (cascade) family screening to identify affected family members without LV hypertrophy who may transmit mutations to subsequent generations.10-12

Pathophysiology: Nonobstructive and Obstructive

The pathogenesis involves a diverse array of mechanisms, consistent with the causal genes and mutations7. LV wall stiffness increases, reducing diastolic filling and ejection. There are four sets of connected mechanisms in which the primary defect is the mutation7 and phenotypes result from effects of the mutations on sarcomeres. In[BM1]  nonobstructive HCM, which occurs in one-third of cases, the LV becomes stiff, limiting diastolic filling and systole; ejection is not blocked. Whereas, in obstructive HCM, which occurs in two-thirds of cases, an estimated 70% experience LV outflow impedance during rest or exercise due to septum thickening and wall stiffness.13

Identification of Hypertrophic Cardiomyopathy

Symptoms

Patients may present as asymptomatic or be asymptomatic in early stages with a gradual progression of severity.2, Abnormal ECG findings and a systolic ejection murmur are suggestive of diagnosis, but no pattern is pathognomonic.9 Treatment coincides with early symptom recognition to include:

  • Chest pain, shortness of breath with physical exertion
  • Fatigue
  • Arrhythmias
  • Dizziness
  • Syncope
  • Lower extremity or abdominal edema

Diagnosis and Screening

Cardiac hypertrophy is the keystone to clinical diagnosis.8 If suspected, a physical exam,  medical history, 3-generation history, and diagnostics are recommended. Family member screening hinges on pathogenicity of detected variants which should be reconfirmed every 2 to 3 years.1 SCD risk assessment is recommended initially and every 1 to 2 years.

Testing may include; transthoracic echocardiogram, cardiovascular magnetic resonance imaging, CT, heart rhythm, angiography and hemodynamic assessment, exercise stress testing, genetics and family screening for genotype-positive, and phenotype-Negative.

Hypertrophic Cardiomyopathy in Clinical Practice

Management

Management and treatment depend on signs and symptoms. For symptomatic patients, management emphasizes medications and procedures, although no specific medications exist for HCM.

Symptomatic Obstructive Hypertrophic Cardiomyopathy

Pharmacologic management for symptomatic obstructive HCM involves effort-related dyspnea or chest pain and other exertional symptoms (syncope, attributed to left ventricular outflow tract obstruction [LVOTO], interferes with activity). If symptoms are attributable to LVOTO and beta-blockers are ineffective, substitution with calcium channel blockers (e.g., verapamil) is recommended.  

Nonobstructive Hypertrophic Cardiomyopathy with Preserved EF

Treatment with beta blockers or calcium channel blockers is recommended if exertional angina or dyspnea exists, and oral diuretics if exertional dyspnea persists. ACEI and ARB use is not well established. With symptoms consistent with NYHA class III or IV heart failure (HF), despite maximal therapy and preserved EF and small LV size, apical myectomy may be considered. Beta-blockers or calcium channel blockers are not well established in asymptomatic patients with non-obstructive HCM.

Atrial Fibrillation

As HCM progresses, the risk for atrial fibrillation, ventricular arrhythmias and advanced HF may increase. Oral anticoagulants, vitamin K antagonists and rate control strategies may be recommended for clinical or subclinical atrial fibrillation.

Ventricular Arrhythmias

A heart transplant is recommended in the presence of life-threatening ventricular tachyarrhythmias. Anti-arrhythmic drugs are recommended in adults, and symptomatic ventricular arrhythmias or ICD shocks despite beta-blocker use, according to age, comorbidities, disease severity, efficacy, and safety.

Advanced Heart Failure

HF symptoms in the absence of LVOTO involves similar treatment to HF symptom management. An EF <50% connotes poor prognosis and increased SCD risk. In NYHA class III to IV, a cardio-pulmonary exercise test quantifies degree of functional limitation, heart transplantation selection and mechanical circulatory support.

Lifestyle Considerations

Lifestyle recommendations for asymptomatic individuals include:

  • Sports and Physical Activity. Mild-to-moderate-intensity exercise consistent with physical activity guidelines. High-intensity participation requires a more thorough evaluation.
  • Occupational recommendations of driving, pilot or aircrew, lifting, and manual labor.
  • Pregnancy recommendations for management, family care, type of delivery, arrhythmia, and fetal monitoring treatment.
  • Comorbidities specifying differences between children and adults with consideration to growth and ICD implantation

Recent Trial Data

Longitudinal studies in HCM cohorts demonstrate a strong relationship between the amount of late gadolinium enhancement and SCD risk.14 Research also indicates that the benefits of exercise, depending on the individual and intensity, may outweigh the risks of inactivity.15

Working Collaboratively: Take-Home Messages

  • A team approach including shared decision-making17 is recommended to optimize care.
  • HCM centers include multidisciplinary care, including a cardiology team for evaluation, treatment, and longitudinal care.
  • Counseling is a cornerstone of care to discuss genetic transmission, screening for first-degree family, and genetic testing (any age) according to family history and preference.
  • SCD risk assessment and magnitude of risk should involve patients in decisions regarding ICD placement and treatment goals.
  • Risk factors for SCD in children with HCM are different than those observed in adults as they vary with age and must account for different body sizes.
  • Septal reduction therapies continue to improve in safety and efficacy at comprehensive HCM centers. These decisions represent an optimal referral opportunity.
  • Default treatment includes oral anticoagulation or warfarin, independent of paroxysmal atrial fibrillation for rhythm and rate control.
  • In those with an EF <50% with SCD risk, treatment is similar to symptomatic HF, with or without LVOTO.
  • Recommend moderate-intensity exercise or tailor exercise to the individual

Hypertrophic Cardiomyopathy Tool for Providers

You can help improve awareness of HCM with our tool for providers, Hypertrophic Cardiomyopathy: What healthcare providers need to know. This electronic or hard copy fact sheet covers HCM’s underlying pathophysiology, common signs, symptoms, and complications, as well as the common steps toward diagnosis, treatment, and surveillance. A list of resources for patients and professionals is included for those looking for additional information about HCM.

References

  1. Ommen S, Mital S, Burke M, et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2020;142: e558–e631.
  2. Maron BJ, Maron MS. Hypertrophic cardiomyopathy. Lancet. 2013;381(9862):242-255. doi:10.1016/S0140-6736(12)60397-3
  3. Semsarian C, Ingles J, Maron MS, Maron BJ. New perspectives on the prevalence of hypertrophic cardiomyopathy. J Am Coll Cardiol. 2015;65(12):1249-1254. doi:10.1016/j.jacc.2015.01.019
  4. Maron BJ, Rowin EJ, Casey SA, Maron MS. How hypertrophic cardiomyopathy became a contemporary treatable genetic disease with low mortality: shaped by 50 years of clinical research and practice. JAMA Cardiol. 2016; 1: 98-105.
  5. Braunwald E, Lambrew CT, Rockoff SD, Ross J Jr, Morrow AG. Idiopathic hypertrophic subaortic stenosis. I. A description of the disease based on an analysis of 64 patients. Circulation. 1964; 30: Suppl 4:3-119.
  6. Maron BJ, Udelson JE, Bonow RO, et al. Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task Force 3: hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and other cardiomyopathies, and myocarditis: a scientific statement from the American Heart Association and American College of Cardiology. J Am Coll Cardiol. 2015;66: 2362-71
  7. Marian AJ, Braunwald E. Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy. Circ Res. 2017;121(7):749-770. doi:10.1161/CIRCRESAHA.117.311059
  8. Maron BJ. Clinical course and management of hypertrophic cardiomyopathy. N Engl J Med. 2018;379(7):655-668. doi:10.1056/NEJMra1710575
  9. Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, Naidu SS, Nishimura RA, Ommen SR, Rakowski H, Seidman CE Towbin JA, Udelson JE, Yancy CW; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines; 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; Society of Thoracic Surgeons. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011; 124:2761–2796. doi: 10.1161/CIR.0b013e318223e230.
  10. Maron BJ, Maron MS. A discussion of contemporary nomenclature, diagnosis, imaging, and management of patients with hypertrophic cardiomyopathy. Am J Cardiol. 2016; 118:1897–1907. doi: 10.1016/j.amjcard.2016.08.086.
  11. Jensen MK, Havndrup O, Christiansen M, et al. Penetrance of hypertrophic cardiomyopathy in children and adolescents: a 12-year follow-up study of clinical screening and predictive genetic testing. Circulation.2013; 127: 48-54.
  12. Valente AM, Lakdawala NK, Powell AJ, Evans SP, Cirino AL, Orav EJ, MacRae CA, Colan SD, Ho CY. Comparison of echocardiographic and cardiac magnetic resonance imaging in hypertrophic cardiomyopathy sarcomere mutation carriers without left ventricular hypertrophy. Circ Cardiovasc Genet. 2013; 6:230–237. doi: 10.1161/CIRCGENETICS.113.000037.
  13. Maron MS, Olivotto I, Zenovich AG, et al. Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction. Circulation.2006; 114: 2232-9.
  14. Weng Z, Yao J, Chan RH, et al. Prognostic value of LGE-CMR in HCM: a meta-analysis. J Am Coll Cardiol Img. 2016;9:1392–402.
  15. Dias KA, Link MS, Levine BD. Exercise Training for Patients With Hypertrophic Cardiomyopathy: JACC Review Topic of the Week. J Am Coll Cardiol. 2018;72(10):1157-1165. doi:10.1016/j.jacc.2018.06.054
  16. Legare F, Adekpedjou R, Stacey D, et al.. Interventions for increasing the use of shared decision making by healthcare professionals. Cochrane Database Syst Rev. 2018; 7:CD006732.
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