What is the management plan for severe asymmetric hypertrophy?

Management of Severe Asymmetric Hypertrophy

For patients with severe asymmetric hypertrophic cardiomyopathy (HCM), the management should focus on a stepwise pharmacological approach starting with beta-blockers, followed by non-dihydropyridine calcium channel blockers, and then adding myosin inhibitors, disopyramide, or proceeding to septal reduction therapy for persistent symptoms. 1

Initial Pharmacological Management

First-Line Therapy

• Beta-blockers are the cornerstone of initial pharmacological management:
  • Target heart rate between 50-60 beats per minute 2
  • Titrate to maximally tolerated doses
  • Mechanism: Reduce systolic overcontraction and early LV ejection acceleration 3
  • Particularly effective for exercise-induced LVOT obstruction 4
  • In a prospective study, beta-blockers prevented exercise-induced LVOT obstruction in 85% of patients 4

Second-Line Therapy

• Non-dihydropyridine calcium channel blockers (verapamil, diltiazem) if beta-blockers are ineffective or not tolerated:
  • Verapamil dosing: 320-720 mg/day (average 530 mg) 5
  • Particularly effective for chest pain and improving exercise capacity
  • Mechanism: Primarily improve diastolic filling characteristics 5
  • Caution: Avoid in patients with severe dyspnea at rest, hypotension, very high resting gradients (>100 mmHg), and in children <6 weeks of age 2

Management of Persistent Symptoms

For patients with obstructive HCM who have persistent symptoms attributable to LVOT obstruction despite beta-blockers or calcium channel blockers, the following options are recommended (Class 1 recommendation) 1:

Additional Pharmacological Options

1. Myosin inhibitors (adult patients only)

   • Contraindicated during pregnancy due to potential teratogenic effects 1, 2
   • Should be discontinued if systolic dysfunction develops (LVEF <50%) 1, 2

2. Disopyramide (in combination with an atrioventricular nodal blocking agent)

   • Requires monitoring of QTc interval during dose titration 2
   • In head-to-head comparisons, disopyramide showed greater efficacy for lowering gradient compared to beta-blockers and verapamil 3

Invasive Management

• Septal reduction therapy (SRT) performed at experienced centers when medical therapy fails 1
  • Surgical myectomy
  • Alcohol septal ablation
  • Dual-chamber permanent pacing has shown efficacy in reducing LVOT gradients and improving symptoms in patients refractory to medical therapy 6

Special Considerations

Non-obstructive HCM

• For younger patients (≤45 years) with non-obstructive HCM due to pathogenic cardiac sarcomere genetic variants and mild phenotype, valsartan may be beneficial to slow adverse cardiac remodeling (Class 2b recommendation) 1, 2

Comorbidity Management

• Hypertension: Treat with lifestyle modifications and medical therapy, preferring beta-blockers and non-dihydropyridine calcium channel blockers in obstructive HCM 1
• Obesity: Comprehensive lifestyle interventions for weight loss to potentially lower risk of LVOT obstruction, heart failure, and atrial fibrillation 1
• Sleep-disordered breathing: Assessment and referral to sleep medicine specialist if present 1

Monitoring and Follow-up

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

Contraindications and Precautions

• Nitrates are contraindicated in HCM due to potential worsening of LVOT obstruction 2
• Vasodilators (ACE inhibitors, ARBs) should be avoided in obstructive HCM 2
• Myosin inhibitors are contraindicated in pregnancy and should be discontinued if systolic dysfunction develops 1, 2

Physical Activity Recommendations

• Participation in vigorous recreational activities is reasonable after comprehensive evaluation and shared decision-making 1
• Universal restriction from vigorous physical activity is not indicated for most patients with HCM 1

By following this management approach, patients with severe asymmetric hypertrophy can experience significant symptom improvement and reduced risk of complications.