Initial Treatment for Hypertrophic Cardiomyopathy
Beta-blockers are the first-line treatment for all symptomatic patients with hypertrophic cardiomyopathy, whether obstructive or non-obstructive, titrated to achieve a resting heart rate below 60-65 bpm. 1, 2
First-Line Therapy: Beta-Blockers
Start with non-vasodilating beta-blockers (metoprolol, propranolol, or atenolol) and titrate aggressively to maximum tolerated doses until physiologic beta-blockade is achieved, demonstrated by resting heart rate suppression below 60-65 bpm. 2, 3
Beta-blockers work through multiple mechanisms: they slow heart rate to improve diastolic filling time, reduce myocardial oxygen demand, decrease dynamic outflow tract gradients through negative inotropic effects, and reduce left ventricular filling pressures. 2, 3
Do not declare beta-blocker failure until adequate dosing achieves resting heart rate suppression—this is the physiologic evidence that true beta-blockade has been reached. 3
Use caution in patients with sinus bradycardia or severe conduction disease, but beta-blockers remain the primary medical therapy even in neonates and children with HCM. 2
Second-Line Therapy: Non-Dihydropyridine Calcium Channel Blockers
If beta-blockers are ineffective, not tolerated, or contraindicated, switch to verapamil or diltiazem—never combine them with beta-blockers due to risk of high-grade atrioventricular block. 1, 2, 3
Verapamil should be started at low doses and titrated up to 480 mg/day, providing symptom relief through negative inotropic and chronotropic effects that improve diastolic function and reduce chest pain. 2, 3
Exercise extreme caution with verapamil in patients with high outflow gradients (especially resting gradients), advanced heart failure symptoms, or severe left ventricular outflow obstruction—pulmonary edema and severe hypotension have occurred in these high-risk patients. 4
The FDA label warns that in 120 HCM patients treated with verapamil, three died in pulmonary edema (all had severe outflow obstruction and prior left ventricular dysfunction), and eight others developed pulmonary edema and/or severe hypotension. 4
Recent real-world data from 600 French HCM patients showed no significant difference in cardiovascular death, heart failure hospitalization, or atrial fibrillation hospitalization between beta-blockers and verapamil over median 3.9 years follow-up, though this was a low-risk cohort. 5
Medications to Eliminate Immediately
Discontinue all vasodilators including dihydropyridine calcium channel blockers (nifedipine, amlodipine), ACE inhibitors, and ARBs—these worsen outflow tract obstruction by reducing preload and afterload. 2, 3
Avoid high-dose diuretics that promote obstruction through volume depletion; low-dose diuretics may be cautiously added only if congestive symptoms persist despite first-line therapy. 2, 3
Digitalis is potentially harmful in HCM patients without atrial fibrillation and should not be used for dyspnea. 1, 2
Adjunctive Therapy for Persistent Symptoms
If symptoms persist despite optimal beta-blocker or verapamil therapy, add low-dose oral diuretics (loop or thiazide) cautiously to improve dyspnea and volume overload. 1, 2
For obstructive HCM with refractory symptoms, add disopyramide (400-600 mg/day) combined with beta-blocker or verapamil—never as monotherapy due to risk of enhanced AV conduction in atrial fibrillation. 2, 3
Aldosterone antagonists may be considered in some patients with refractory symptoms, with diuretics used intermittently or at chronic low doses to prevent symptomatic hypotension and hypovolemia. 2
Special Clinical Scenarios
In patients who develop systolic dysfunction with LVEF <50%, transition to guideline-directed therapy for heart failure with reduced ejection fraction. 2
For patients with nonobstructive HCM who have a pathogenic cardiac sarcomere genetic variant and mild phenotype, valsartan may be beneficial to slow adverse cardiac remodeling. 2
In patients with atrial fibrillation, initiate anticoagulation immediately with direct-acting oral anticoagulants (first-line) or vitamin K antagonists (second-line), independent of CHA₂DS₂-VASc score—all HCM patients with AF require anticoagulation. 1, 3
For rate control in atrial fibrillation, use beta-blockers, verapamil, or diltiazem according to patient preferences and comorbid conditions. 1
Critical Pitfalls to Avoid
Never combine beta-blockers with verapamil or diltiazem for HCM treatment due to high-grade AV block risk. 2, 3
Do not treat HCM patients like typical heart failure patients—standard heart failure therapies (vasodilators, aggressive diuresis) can be harmful. 6
Success is determined by symptom response, not measured gradient, as outflow tract obstruction varies remarkably throughout daily life. 3
Avoid septal reduction therapy in asymptomatic patients regardless of gradient severity, as there is no benefit and potential harm. 3