Hypertrophic Cardiomyopathy Management

Beta-Blockers

Example drugs: Metoprolol, Propranolol

Non-vasodilating beta-blockers are preferred first-line agents for patients with obstructive disease and heart failure or hypertension. These may also be given to patients with non-obstructive disease with preserved ejection fraction and symptoms of exertional angina or dyspnea. These are negative inotropic agents that act by increasing diastolic filling and reducing contractility and provocable gradient; but likelihood of peripheral vasodilation is low. These control rate in patients with atrial fibrillation; combination with Amiodarone may suppress ventricular extrasystoles and non-sustained ventricular tachycardia. Treatment with beta-blockers decreases heart rates both at rest and with exertion and improves chest pain and dyspnea. Use with caution in patients with severe conduction disease or sinus bradycardia. These are used to control symptoms during pregnancy, though increased monitoring is needed for the development of fetal bradycardia or other complications.

Calcium Channel Blockers (CCBs)







Non-dihydropyridine CCBs (eg Verapamil, Diltiazem) may be used as monotherapy (when beta-blockers are ineffective, not tolerated, or contraindicated) or in combination with a beta-blocker in patients with significant heart failure and LV outflow tract obstruction (LVOTO) despite treatment with a beta-blocker. These may also be given to patients with hypertrophic cardiomyopathy and hypertension or patients with non-obstructive disease with preserved ejection fraction and symptoms of exertional angina or dyspnea. CCBs decrease symptoms of angina by improving myocardial perfusion and control rate in patients with atrial fibrillation. Practice caution with use if with significant LVOT gradient or advanced heart failure. Combination therapy with a beta-blocker may lead to symptomatic bradycardia or atrioventricular (AV) block. Dihydropyridine CCBs are vasodilators that can lead to hypotension and/or worsening symptoms of heart failure resulting from the decrease in peripheral resistance and increase in LVOTO and thus should be avoided in patients with resting or provocable LVOTO.

Disopyramide

Disopyramide is used in combination with AV nodal blocking agents (eg a beta-blocker or a non-dihydropyridine CCB) in patients with persistent heart failure and LVOTO symptoms despite treatment with a beta-blocker or a non-dihydropyridine CCB. This is an antiarrhythmic agent with negative inotropic properties, and reduces LV contractility, subaortic gradient, afterload, and resting and provocable gradient. This slows LV ejection acceleration and may cause prolongation of the QT interval and acceleration of the ventricular rate in the presence of atrial fibrillation or flutter. Avoid in patients with prostatic hypertrophy and those receiving class I antiarrhythmic drugs.

Mavacamten

Mavacamten is indicated for the treatment of adults with symptomatic NYHA class II-III obstructive hypertrophic cardiomyopathy. This is a reversible inhibitor of cardiac myosin ATPase, which prevents sarcomere hypercontractility and excessive myosin-actin cross-bridging. This reduces LVOT obstruction, LV mass, left atrial volume, and NT-proBNP levels, which results in improvement of functional capacity and symptoms. This may be used in addition to a beta-blocker or a non-dihydropyridine CCB to improve persistent symptoms of patients with LVOTO. Mavacamten may be used as monotherapy in symptomatic patients with LVOTO and known sensitivity or contraindications to beta-blockers, non-dihydropyridine CCBs or Disopyramide. This is not recommended to initiate in patients with left ventricular ejection fraction (LVEF) <55%. Avoid concomitant use with Disopyramide in combination with Verapamil or Diltiazem due to association with LV systolic dysfunction and heart failure symptoms. Avoid the concomitant use of Disopyramide, Ranolazine, Diltiazem with a beta-blocker or Verapamil with a beta-blocker, as these were not included in the EXPLORER-HCM clinical study.

Other Therapeutic Agents

Diuretics

Low-dose diuretics used cautiously may be considered to improve exertional dyspnea in symptomatic patients with LVOTO and can help patients with non-obstructive disease with preserved ejection fraction and persistent exertional dyspnea despite treatment with beta-blockers or CCBs. To improve heart failure in NYHA class II-IV patients without LVOTO, consider low-dose loop and thiazide diuretics in those with preserved LVEF and low-dose loop diuretics in those with reduced LVEF.

Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers

ACE inhibitors and angiotensin receptor blockers are considered as alternative agents in the treatment of hypertrophic cardiomyopathy patients with heart failure associated with decreased LVEF. Use with caution in patients with LVOTO at rest or with provocation, as these agents can worsen dynamic outflow tract obstruction symptoms. Valsartan may be considered to slow adverse cardiac remodeling in patients ≤45 years old with non-obstructive hypertrophic cardiomyopathy from a pathogenic or likely pathogenic cardiac sarcomere genetic variant and a mild phenotype.

Antibiotic Prophylaxis

Infective endocarditis is a complication of hypertrophic cardiomyopathy resulting from bacterial seeding in damaged cardiac valves or endocardium caused by turbulent blood flow. Though routine antibiotic prophylaxis is no longer recommended, benefits should be weighed against the risks of treatment, particularly with high-risk procedures in patients with congenital heart disease, prior endocarditis, or those with prosthetic cardiac valves.

Thromboprophylaxis

Patients with hypertrophic cardiomyopathy and chronic, paroxysmal, or persistent atrial fibrillation are at increased risk of stroke and should be anticoagulated with first-line agents direct-acting oral anticoagulants (DOACs) (direct thrombin inhibitors [eg Dabigatran] or factor Xa inhibitors [eg Apixaban, Rivaroxaban]) and second-line agents vitamin K antagonists (VKA) (eg Warfarin), independent of CHA₂DS₂-VASc score. Therapy is lifelong, even with restoration of sinus rhythm. Oral anticoagulation also reduces the risk of thromboembolism in patients with hypertrophic cardiomyopathy and LV apical aneurysm. In patients who cannot or do not want to take oral anticoagulants, combination therapy with Aspirin and Clopidogrel should be considered. Low-molecular-weight Heparin or VKA is recommended for stroke prevention in pregnant patients with hypertrophic cardiomyopathy and atrial fibrillation.

Antiarrhythmic Agents

Example drugs: Amiodarone, Dofetilide, Mexiletine, Sotalol

Antiarrhythmic agents are recommended in patients with hypertrophic cardiomyopathy and ventricular arrhythmias unresponsive to beta-blocker therapy. The choice of agent is guided by the patient's age, comorbidities, severity of disease, preferences, and balance of therapeutic efficacy and safety.

Phenylephrine

Phenylephrine may be given alone or in combination with beta-blockers to patients with obstructive hypertrophic cardiomyopathy and acute hypotension unresponsive to fluid administration. 

Lifestyle Modification

Advise patients to avoid alcohol and caffeine. Adequate hydration in patients with no evidence of fluid overload. Patients with LVOTO should avoid excess consumption of alcohol and dehydration. Advise patients regarding smoking and its health risks. Maintain a healthy BMI with appropriate diet and exercise. In patients with LVOTO, large meals can cause chest pain; thus, small, frequent meals may be of help.

Mild- to moderate-intensity exercise is advised. Low-intensity sports and activities are reasonable (eg brisk walking, bowling, golf, skating, and snorkeling). Vigorous physical activities and competitive sports may be considered after an annual thorough assessment and shared decision-making that considers potential risks and benefits. Competitive sports (any intensity) are reasonable in patients with genotype-positive, phenotype-negative hypertrophic cardiomyopathy. Occupations requiring manual labor, heavy lifting, or a high level of physical performance may be considered after a comprehensive clinical evaluation and shared decision-making. A sleep medicine specialist referral is recommended for the evaluation and treatment of sleep-disordered breathing.

Family Counseling 







Family counseling helps in checking the extent of the condition in a family and in protecting other family members through further counseling and genetic testing, as hypertrophic cardiomyopathy has a 50% risk of transmission of the same disease-causing genetic variant to offspring. It is recommended that all of the clinically affected patient’s first-degree relatives be screened for hypertrophic cardiomyopathy with individually tailored time intervals, typically every 5 years in adults and 12-18 months in children and adolescents. Clinical screening is long-term but becomes less frequent in older age groups. Evaluation will include genetic testing, ECG, and echocardiography. 

Invasive Therapies

Indications for septal reduction therapy include the following: Systolic anterior motion of the mitral valve resulting in obstructive disease; ≥50 mmHg LVOTO gradient at rest or on provocation; anterior septal thickness >16 mm; moderate to severe symptoms resistant to maximum medication treatment (eg recurrent pre-syncope or syncope or NYHA class III or IV); and in the asymptomatic patient, septal reduction therapy with either septal myectomy or alcohol septal ablation should not be carried out regardless of the severity of obstruction and without contraindications to specific procedures.

Several meta-analyses have demonstrated that both surgical myectomy and alcohol septal ablation improve patients' functional status with similar procedural mortality. However, choice of intervention will be based on assessment of the septal anatomy and mitral valve, concomitant cardiac problems and medical comorbidities, and patient preference, in consultation with an experienced multidisciplinary team.

Surgical Myectomy (Ventricular Septal Myectomy)

Surgical myectomy is considered first in patients with LVOTO and symptoms resistant to treatment. This is recommended over alcohol septal ablation in patients with an indication for septal reduction therapy and other lesions or cardiac disease needing surgical intervention (eg mitral valve abnormalities, anomalous papillary muscle, markedly elongated anterior mitral leaflet, multivessel coronary artery disease, or valvular aortic stenosis). Consider mitral valve repair or replacement in patients with an LVOTO gradient of ≥50 mmHg when there is moderate to severe mitral regurgitation after isolated myectomy.

Surgical candidates include patients with absent to minimal comorbidities who are young; baseline left bundle branch block; diffuse or massive septal hypertrophy with several touch points to the papillary muscle or mitral valve leaflet; significant intrinsic abnormality of the aortic or mitral valve; and coronary disease necessitating a surgical bypass or other lesions needing surgical intervention.

A concomitant surgical atrial fibrillation ablation procedure may be performed for rhythm control in patients with hypertrophic cardiomyopathy and atrial fibrillation. Intraoperative TEE is recommended to assess the anatomy and function of the mitral valve and adequacy of septal myectomy. Studies have shown a slightly better reduction in gradient compared with ablation; improvements in functional class and long-term outcomes are comparable. The disadvantages of surgical myectomy are the surgical risk involved and the longer hospital stay and recovery period, including rehabilitation.

Alcohol Septal Ablation

Alcohol septal ablation is an echocardiography-guided (TTE or intraoperative TEE) direct injection of alcohol into a septal perforator artery, creating a limited septal infarct or scar. This requires an acceptable anatomy of the coronary, septum, and mitral valve. This is an alternative when surgical myectomy is contraindicated. This may be performed in patients with multiple or significant comorbidities who are older, ie >65 years old; have a baseline right bundle branch block; and have a desire to avoid open heart surgery after an informed discussion. Successful ablation during the procedure shows at least a decrease of 50% in peak gradient or <20 mmHg residual gradient. Because of the risk of a complete heart block, patients are inserted with a pacemaker and monitored in the ICU for 48 hours.

Dual Chamber (DDD) Pacing

Dual chamber pacing is the second-line invasive therapeutic option when other procedures have been declined, are contraindicated, or considered high risk. Randomized controlled trials had suggested a modest benefit when performed in patients >65 years old. This may also be performed in patients with previously implanted dual chamber pacing devices for non-hypertrophic cardiomyopathy indications.

Permanent Pacemaker Implantation

Permanent pacemaker implantation is performed in patients in whom conduction disease or bradycardia limits optimal medication treatment, symptomatic patients with obstructive hypertrophic cardiomyopathy refractory to medication treatment, and patients with relative or absolute contraindications to septal reduction therapies.

Heart Transplantation 







Patients considered for heart transplantation are those with non-obstructive hypertrophic cardiomyopathy, LVEF <50% and advanced heart failure not manageable with other treatment interventions (NYHA class III-IV), or intractable ventricular arrhythmia refractory to maximal antiarrhythmic drug therapy and ablation.