What is the best course of action for a patient with worsening hypertrophy due to Hypertrophic Cardiomyopathy (HCM)?

Management of Worsening Hypertrophy in HCM

For a patient with worsening hypertrophy in HCM, immediately reassess symptom burden, optimize medical therapy with beta-blockers or non-dihydropyridine calcium channel blockers, evaluate for left ventricular outflow tract obstruction, and perform comprehensive risk stratification for sudden cardiac death. 1

Immediate Assessment and Imaging

• Obtain a transthoracic echocardiogram immediately to quantify the degree of hypertrophy progression, assess for development or worsening of LVOT obstruction (gradient ≥50 mmHg), evaluate mitral regurgitation severity, and measure left ventricular ejection fraction 1
• If resting LVOT gradient is <50 mmHg but symptoms are present, perform provocative maneuvers (Valsalva, exercise) during echocardiography to unmask dynamic obstruction 1
• Consider cardiac MRI with gadolinium enhancement to assess maximum LV wall thickness, detect apical aneurysm formation, quantify extent of myocardial fibrosis, and evaluate for alternative diagnoses if diagnostic uncertainty exists 1
• Repeat cardiac MRI every 3-5 years may be considered for ongoing SCD risk stratification as hypertrophy progresses 1

Optimize Medical Therapy Based on Obstruction Status

For Obstructive HCM (LVOT gradient ≥50 mmHg):

• Start or uptitrate nonvasodilating beta-blockers (metoprolol, atenolol, propranolol) to achieve resting heart rate of 60-65 bpm as first-line therapy 1, 2
• If beta-blockers are ineffective at maximally tolerated doses or contraindicated, switch to verapamil (up to 480 mg/day) or diltiazem as second-line monotherapy 1, 2
• For persistent NYHA class II-III symptoms despite optimal beta-blocker or calcium channel blocker therapy, add mavacamten (cardiac myosin inhibitor) with mandatory echocardiographic monitoring of LVEF every 4 weeks 1, 3
• Disopyramide (combined with AV nodal blocking agent) is a third-line alternative when other therapies fail 1, 2

Critical Medications to AVOID:

• Immediately discontinue all vasodilators: ACE inhibitors, ARBs, dihydropyridine calcium channel blockers (amlodipine, nifedipine), nitrates, hydralazine, and alpha-blockers 2, 4
• These agents worsen LVOT obstruction by decreasing afterload and can precipitate hemodynamic collapse 2
• Avoid aggressive diuresis as this decreases preload and worsens obstruction; use low-dose diuretics cautiously only for volume overload 2

Sudden Cardiac Death Risk Stratification

Worsening hypertrophy mandates immediate reassessment of SCD risk using the following markers:

• Maximum LV wall thickness (particularly ≥30 mm) 1
• Family history of premature SCD in first-degree relatives 1
• Unexplained syncope within the past 6 months 1
• Non-sustained ventricular tachycardia on ambulatory monitoring 1
• Abnormal blood pressure response to exercise 1
• New high-risk features: apical aneurysm, LVEF <50%, extensive late gadolinium enhancement on CMR 1

If multiple risk markers are present or estimated 5-year SCD risk is elevated, discuss ICD placement through shared decision-making that incorporates the patient's risk tolerance and treatment goals 1

Consider Septal Reduction Therapy

For patients with severe symptoms (NYHA class III-IV) despite maximally tolerated medical therapy, septal reduction therapy is recommended 1, 2:

• Surgical myectomy is preferred when performed at experienced HCM centers (>90% relief of obstruction, <1% perioperative mortality) 1, 2
• Alcohol septal ablation is an alternative for older patients or those with prohibitive surgical risk due to comorbidities 1, 2
• Eligibility requires LVOT gradient ≥50 mmHg at rest or with provocation and symptoms interfering with daily activities despite optimal medical therapy 2

Address Comorbidities That Accelerate Hypertrophy

• Aggressively manage hypertension using beta-blockers or non-dihydropyridine calcium channel blockers as preferred agents 2
• Implement weight loss interventions if obese (present in >70% of HCM patients), as obesity independently worsens LV hypertrophy burden and outcomes 2
• Screen for and treat sleep-disordered breathing (affects 55-70% of HCM patients), which is associated with greater symptom burden and atrial fibrillation 2

Monitoring Strategy

• Repeat echocardiography every 1-2 years if clinically stable, or immediately with any change in symptoms 1
• Perform 24-48 hour ambulatory ECG monitoring annually to detect non-sustained VT 1
• Exercise stress testing to assess functional capacity and detect latent LVOT obstruction 2
• If on mavacamten, mandatory echocardiography every 4 weeks to monitor for LVEF reduction <50% 3

Referral to Specialized HCM Center

Refer to a multidisciplinary HCM center when worsening hypertrophy is accompanied by:

• Refractory symptoms despite optimal medical therapy requiring consideration of septal reduction therapy 1
• Uncertainty regarding ICD placement decisions 1
• Development of high-risk features (apical aneurysm, systolic dysfunction, extensive fibrosis) 1
• Need for invasive procedures specific to HCM 1

Common Pitfalls to Avoid

• Do not declare beta-blocker failure until maximally tolerated doses with documented heart rate <60-65 bpm are achieved 2
• Never use dihydropyridine calcium channel blockers or other vasodilators in obstructive HCM—this is a Class III: Harm recommendation 2, 4
• Do not restrict all physical activity universally; individualized exercise recommendations after comprehensive evaluation are reasonable 1
• Pharmacologic therapy alone does not prevent sudden cardiac death in high-risk patients—ICD is the primary prevention strategy 5