What is the initial medical management for hypertrophic cardiomyopathy (HCM)?

Medical Management of Hypertrophic Cardiomyopathy

For patients with hypertrophic cardiomyopathy (HCM), nonvasodilating beta-blockers are the first-line pharmacological therapy, followed by nondihydropyridine calcium channel blockers if beta-blockers are ineffective or not tolerated. 1

Initial Medical Management Algorithm

For Obstructive HCM (with LVOT gradient ≥50 mmHg):

1. First-line therapy: Nonvasodilating beta-blockers

   • Titrate to effectiveness or maximally tolerated doses
   • Target heart rate between 50-60 beats per minute
   • Aim: Reduce early LV ejection acceleration and systolic pushing force on mitral leaflet
   • Examples: Metoprolol, propranolol, atenolol

2. Second-line therapy (if beta-blockers ineffective or not tolerated):

   • Nondihydropyridine calcium channel blockers
     • Verapamil (use with caution in patients with high resting gradients >100 mmHg)
     • Diltiazem
   • Particularly effective for chest pain and improving exercise capacity 1, 2
   • Caution: Verapamil is potentially harmful in patients with severe dyspnea at rest, hypotension, very high resting gradients (>100 mmHg), and in children <6 weeks of age 1, 3

3. For persistent symptoms despite above therapies:

   • Add one of the following:
     • Myosin inhibitors (adult patients only) 1
     • Disopyramide (in combination with beta-blockers or calcium channel blockers) 1, 2
       • Requires monitoring of QTc interval during dose titration
       • Side effects: constipation, dry mouth, urinary retention
     • Consider septal reduction therapy at experienced centers 1

4. For acute hypotension:

   • Intravenous phenylephrine or other vasoconstrictors without inotropic activity 1

For Nonobstructive HCM:

1. For symptomatic patients:

   • Beta-blockers or calcium channel blockers may be used, though benefit is not well established 1

2. For younger patients (≤45 years) with nonobstructive HCM due to pathogenic cardiac sarcomere genetic variant and mild phenotype:

   • Valsartan may be beneficial to slow adverse cardiac remodeling 1

3. For volume overload:

   • Cautious use of low-dose oral diuretics 1
   • Usually as intermittent dosing or chronic low-dose therapy
   • Monitor for symptomatic hypotension and hypovolemia

Important Considerations and Pitfalls

Medications to Avoid or Use with Caution:

• Avoid vasodilators in obstructive HCM (can worsen LVOT gradient):

  • Angiotensin-converting enzyme inhibitors
  • Angiotensin receptor blockers (except valsartan in specific cases)
  • Dihydropyridine calcium channel blockers
  • Digoxin 1

• Discontinue myosin inhibitors if systolic dysfunction develops (LVEF <50%) 1

• Contraindicated in pregnancy: Myosin inhibitors (potential teratogenic effects) 1

Monitoring Requirements:

• Regular assessment of symptom status
• Periodic echocardiography (every 1-2 years) to evaluate:
  • LVOT gradient
  • Myocardial hypertrophy
  • Mitral regurgitation
  • Myocardial function 2
• ECG monitoring for arrhythmias
• Extended ambulatory monitoring for high-risk patients with atrial fibrillation 1, 2

Comorbidity Management:

• Weight loss in overweight/obese patients (may lower risk of LVOTO, HF, and AF) 2
• Appropriate treatment of hypertension (preferably with beta-blockers or nondihydropyridine calcium channel blockers) 2
• Assessment and treatment of sleep-disordered breathing 2

Special Populations

Pediatric Patients:

• Beta-blockers should be the primary medical therapy in neonates and children 1
• Verapamil can be used safely as an alternative to beta-blockers in patients >6 months of age 1

Elderly Patients:

• May have better response to verapamil therapy 4
• Consider comorbidities that may influence medication choice

Evidence Quality and Controversies

The evidence for medical management of HCM is largely based on small trials and clinical experience rather than large randomized controlled trials 5, 6. Recent studies suggest that verapamil therapy is not associated with a higher incidence of adverse events compared to beta-blocker therapy in low-risk HCM patients 4, despite historical concerns about potential adverse effects.

In a head-to-head comparison of intravenous drug administration, the relative efficacy for lowering gradient was: disopyramide > beta-blockade > verapamil 6. However, the 2024 AHA/ACC guidelines now include myosin inhibitors as a recommended option for adult patients with persistent symptoms despite beta-blockers or calcium channel blockers 1.

The medical management of HCM should focus on symptom relief, reduction of LVOT obstruction, and prevention of complications, with the ultimate goal of improving quality of life and reducing mortality.