Hypertrophic Cardiomyopathy

Background

• Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease characterized by hypertrophy of a nondilated left ventricle in the absence of any other cardiac or systemic disease (such as hypertension) that could account for observed hypertrophy, microvascular dysfunction and myocardial fibrosis.
• Histopathological features include myofiber disarray and myocardial fibrosis resulting from microvascular ischemia and cell death.
• HCM is caused largely by mutations in genes encoding thick and thin contractile myofilament proteins of the cardiac sarcomere.
• Phenotypically, HCM can be obstructive (70% of patients), with presence of left ventricular outflow tract obstruction, or nonobstructive (30% of patients).
• Complications include syncope, heart failure, and sudden death.

Evaluation

• Suspect hypertrophic cardiomyopathy (HCM) in a patient with a family history of HCM or sudden cardiac death. Often asymptomatic but presenting symptoms may include chest pain, dyspnea, syncope, or palpitations.
• Signs may include systolic murmur

Initial testing in patients suspected of having HCM

• Obtain a 12-lead electrocardiogram (ECG) and transthoracic echocardiography (TTE) (Strong recommendation).
• Consider TTE in combination with IV contrast agent if the severity of hypertrophy is in doubt (Weak recommendation).
• Left ventricular hypertrophy in adults with HCM is commonly defined as a maximal left ventricular free wall thickness ≥ 15 mm, with 13-14 mm considered borderline.
• Use cardiac magnetic resonance imaging (MRI) when TTE is inconclusive (Strong recommendation).
• Consider exercise TTE to detect and quantifying dynamic outflow obstruction in the absence of resting outflow obstruction (Weak recommendation).
• Obtain a 24- to 48-hour ambulatory (Holter) monitor to detect ventricular tachycardia and identify candidates for implantable cardioverter defibrillators (Strong recommendation).

Genetic testing in patients with suspected HCM

• Use genetic testing for patients with atypical clinical presentation of HCM or if another genetic condition is suspected (Strong recommendation).
• Offer genetic testing for family members and appropriate relatives after disease-causing mutation has been identified in index patient (Strong recommendation).
• Offer counseling to patients having genetic testing for HCM by someone knowledgeable in cardiovascular disease genetics to appropriately review the results and their clinical significance (Strong recommendation).
• Consider genetic testing in index patient to facilitate identification of first-degree relatives at risk for developing HCM (Weak recommendation).

Management

Management considerations for all patients with hypertrophic cardiomyopathy

• Level of activity recommendations:
  • do not participate in intense competitive sports (Strong recommendation)
  • consider low intensity noncompetitive aerobic exercise as a component of a healthy lifestyle if asymptomatic (Weak recommendation)
  • consider low intensity competitive sports such as golf and bowling or a range of recreational sporting activities such swimming laps, modest hiking, and skating (Weak recommendation)
• Medications for treating symptomatic patients:
  • Use beta blockers to treat angina or dyspnea in adults, but with caution in patients with sinus bradycardia or severe conduction disease (Strong recommendation).
  • Titrate dose of beta blockers to achieve resting heart rate < 60-65 beats per minute in patients who do not respond to low doses of beta blockers for angina or dyspnea (Strong recommendation).
  • Use verapamil to treat angina or dyspnea in patients who do not respond to beta blockers, have side effects, or contraindications, using caution in patients with high outflow gradients, heart failure, sinus bradycardia (Strong recommendation).
  • Consider diltiazem for patients who do not tolerate verapamil or in whom verapamil is contraindicated (Weak recommendation).
• Use implantable cardioverter devices for patients with a history of cardiac arrest, ventricular fibrillation, hemodynamically significant ventricular tachycardia, or spontaneous sustained ventricular tachycardia causing syncope (Strong recommendation).
• Consider implantable cardioverter devices for patients with (Weak recommendation):
  • maximum left ventricle wall thickness ≥ 30 mm
  • recent unexplained syncope
  • family history of sudden death due to hypertrophic cardiomyopathy (such as sudden death in a first-degree relative)
  • select patients with abnormal blood pressure response to exercise or nonsustained ventricular tachycardia on monitoring if additional sudden cardiac death risk modifiers or high-risk features
• For patients with atrial fibrillation:
  • anticoagulate with a vitamin K antagonist (VKA) to an INR of 2-3 (Strong recommendation)
  • consider a direct oral anticoagulant (DOAC) (apixaban, rivaroxaban, edoxaban, or dabigatran) as an alternative to VKA
  • use beta blockers and nondihydropyridine calcium channel blockers to control ventricular rate (Weak recommendation)
  • amiodarone is considered the most effective treatment for preventing recurrences of atrial fibrillation
  • consider disopyramide (plus ventricular rate controlling agents) for rhythm control, but do not use alone without beta blockers or verapamil due to potential for enhancing atrioventricular conduction and increasing ventricular rate during episodes of atrial fibrillation (Weak recommendation)
  • consider radiofrequency ablation for refractory symptoms of atrial fibrillation despite maximal medical management (Weak recommendation)

Additional management for obstructive disease

• Additional medications for treating patients with symptomatic HCM:
  • Consider adding disopyramide to beta blocker or verapamil therapy to treat angina or dyspnea if there is no response to beta blockers or verapamil alone (avoid in patients with reduced systolic function) (Weak recommendation).
  • Consider adding oral diuretics (with caution) if persistent dyspnea or symptoms of congestion are present despite beta blocker and/or verapamil (Weak recommendation).
• Avoid vasodilation due to potential to exacerbate degree of obstruction, regardless of symptom status or obstruction status (resting or provocable)
• For acute hypotension
  • use IV phenylephrine (or other pure vasoconstricting agents) if no response to fluid administration (Strong recommendation).
  • Do not use positive inotropic drugs in patients with HCM for treatment of acute hypotension (Strong recommendation).
• Consider septal reduction therapies to treat medication-refractory symptoms of obstructive HCM (for example, severe dyspnea, chest pain, or syncope).
  • Consider surgical septal myectomy first for severe drug-refractory symptoms and outflow obstruction (Weak recommendation).
  • Offer surgical septal myectomy instead of alcohol septal ablation in patients with indications for septal reduction therapy plus other lesions requiring surgical intervention (such as mitral valve repair/replacement or papillary muscle intervention) (Strong recommendation).
  • Consider alcohol septal ablation as an alternative to surgical septal myectomy in adults when surgery is contraindicated due to comorbidities or advanced age (Weak recommendation).
• Consider using permanent pacemaker implantation in patients with obstructive HCM:
  • to alleviate symptoms of outflow obstruction who are having a dual-chamber pacemaker implanted for other indications (Weak recommendation)
  • that have symptoms refractory to medication therapy and are suboptimal candidates for septal reduction therapy (Weak recommendation)
• Consider heart transplantation for obstructive HCM with advanced heart disease and/or class III/IV heart failure (Weak recommendation).

Additional management for nonobstructive disease

• A variety of medications may be tried to alleviate symptoms in patients with nonobstructive HCM.
• Use heart transplantation to treat refractory nonobstructive HCM despite optimal medical therapy and in patients who have either an ejection fraction > 50% (or occasional ejection fraction > 50%), or end-stage heart failure (Strong recommendation).