What is the initial management for patients with hypertrophic cardiomyopathy?

Initial Management of Hypertrophic Cardiomyopathy

For symptomatic patients with hypertrophic cardiomyopathy, initiate treatment with nonvasodilating beta-blockers as first-line therapy, titrated to a resting heart rate of 60-65 bpm, with the goal of reducing symptoms and improving quality of life. 1, 2

First-Line Pharmacological Management

Beta-Blockers (Primary First-Line)

• Nonvasodilating beta-blockers are the Class I recommended initial treatment for all symptomatic HCM patients, regardless of whether obstruction is present. 1, 2
• Titrate to achieve resting heart rate <60-65 bpm or to maximally tolerated doses. 2
• Beta-blockers reduce left ventricular outflow tract (LVOT) gradients, alleviate dyspnea, and improve quality of life. 1, 3
• Common side effects include bradycardia, hypotension, and risk of AV nodal blockade. 3

Non-Dihydropyridine Calcium Channel Blockers (Alternative First-Line)

• If beta-blockers are ineffective, not tolerated, or contraindicated, substitute with verapamil or diltiazem. 1, 2
• Verapamil can be titrated up to 480 mg/day for symptom control in both obstructive and nonobstructive HCM. 2
• Verapamil improves diastolic filling characteristics and can increase physical resilience. 4, 3
• Critical warning: Verapamil is potentially harmful in patients with severe LVOT obstruction (gradients >100 mmHg), severe dyspnea at rest, hypotension, or children <6 weeks of age. 1, 5
• In 120 HCM patients treated with verapamil, three deaths occurred in pulmonary edema—all had severe LVOT obstruction and prior left ventricular dysfunction. 5

Second-Line Pharmacological Options

For Persistent Symptoms Despite First-Line Therapy

If symptoms persist despite optimal beta-blocker or calcium channel blocker therapy, add one of the following: 1

• Mavacamten (cardiac myosin inhibitor) - Class I recommendation for adults with persistent NYHA class II-III symptoms. 1, 6

  • Improves LVOT gradients, functional capacity, and quality of life in 30-60% of patients. 6
  • Mandatory REMS program monitoring required: LVEF reduction <50% occurs in 5.7-10% of patients. 6
  • Must discontinue if persistent systolic dysfunction (LVEF <50%) develops. 1, 6
  • Contraindicated in pregnancy due to teratogenic effects. 1, 6

• Disopyramide (in combination with AV nodal blocking agent) - Alternative third-line agent when beta-blockers and calcium channel blockers fail. 1, 2

• Septal reduction therapy (SRT) at experienced centers for patients with severe symptoms refractory to medical therapy. 1, 2

Critical Management Pitfalls to Avoid

Medications That Are Harmful in Obstructive HCM

• Discontinue all vasodilators: ACE inhibitors, ARBs, dihydropyridine calcium channel blockers (amlodipine, nifedipine), digoxin, alpha-blockers (terazosin), nitrates, and hydralazine can worsen LVOT obstruction. 1, 2
• Dihydropyridine calcium channel blockers (nifedipine, amlodipine) are Class III: Harm recommendations for patients with resting or provocable LVOT obstruction. 2

Diuretic Use Requires Caution

• Use diuretics cautiously at low doses only for congestive symptoms with clinical evidence of volume overload. 1, 2
• Aggressive diuresis can worsen LVOT obstruction by decreasing preload. 2
• For nonobstructive HCM with preserved ejection fraction, adding oral diuretics is reasonable when exertional dyspnea persists despite beta-blockers or calcium channel blockers. 1

Management of Acute Hypotension in Obstructive HCM

Acute hypotension in obstructive HCM is a medical urgency requiring immediate intervention. 2

• Phenylephrine (pure vasoconstrictor) is the preferred agent to reverse acute hypotension. 2
• Maximize preload with intravenous fluids. 1
• Beta-blockade can be useful in combination with vasoconstrictors to dampen contractility and improve preload by prolonging diastolic filling. 2
• Never use vasodilators or inotropes like dopamine or dobutamine in acute hypotension with obstructive HCM. 2

Special Populations and Considerations

Nonobstructive HCM with Preserved Ejection Fraction

• Beta-blockers or non-dihydropyridine calcium channel blockers are recommended for symptoms of exertional angina or dyspnea. 1
• For younger patients (≤45 years) with pathogenic sarcomere variants and mild phenotype, valsartan may be beneficial to slow adverse cardiac remodeling (Class 2b recommendation). 1, 7

End-Stage HCM with Systolic Dysfunction (LVEF <50%)

• Cardiac myosin inhibitors must be discontinued if persistent systolic dysfunction develops. 1
• Shift to standard heart failure with reduced ejection fraction therapies: ACE inhibitors/ARBs, beta-blockers, spironolactone, and diuretics. 7

Comprehensive Risk Factor Modification

Intensive management of cardiometabolic risk factors is essential, as these are highly prevalent in HCM and associated with poorer prognosis. 1

• Obesity management: Present in >70% of adult HCM patients and independently associated with increased left ventricular hypertrophy burden, more symptoms, and worse outcomes. 2
• Hypertension control: Beta-blockers and non-dihydropyridine calcium channel blockers are preferred antihypertensive agents in obstructive HCM. 2
• Sleep-disordered breathing assessment: Affects 55-70% of HCM patients and is associated with greater symptom burden, reduced exercise capacity, and higher prevalence of atrial fibrillation. 2

Atrial Fibrillation Management

In patients with HCM and clinical atrial fibrillation, anticoagulation is recommended with direct-acting oral anticoagulants as first-line option, independent of CHA₂DS₂-VASc score. 1

• For rate control strategy, beta-blockers, verapamil, or diltiazem are recommended, with choice based on patient comorbidities. 1

Sudden Cardiac Death Risk Stratification

All patients require sudden cardiac death risk stratification using major noninvasive risk markers to identify candidates for implantable cardioverter-defibrillator placement. 1

• For patients ≥16 years with ≥1 major sudden cardiac death risk factor, discuss estimated 5-year sudden death risk during shared decision-making for ICD placement. 1

Referral to Specialized Centers

Referral to multidisciplinary HCM centers with appropriate expertise is important for optimizing care, particularly for challenging treatment decisions. 1