What is the management of moderate septal hypertrophy, a form of Hypertrophic Cardiomyopathy (HCM)?

Management of Moderate Septal Hypertrophy in Hypertrophic Cardiomyopathy

The management of moderate septal hypertrophy in hypertrophic cardiomyopathy (HCM) should focus on symptom control with beta-blockers as first-line therapy, followed by calcium channel blockers if beta-blockers are ineffective, with septal reduction therapies reserved for patients with severe symptoms refractory to medical management. 1

Diagnosis and Classification

Hypertrophic cardiomyopathy is defined as a disease state characterized predominantly by left ventricular hypertrophy (LVH) in the absence of another cardiac, systemic, or metabolic disease capable of producing the magnitude of hypertrophy evident in a given patient. According to the 2024 AHA/ACC guidelines, the clinical diagnosis of HCM in adults is established by imaging showing a maximal end-diastolic wall thickness of ≥15 mm anywhere in the left ventricle. More limited hypertrophy (13-14 mm) can be diagnostic when present in family members of a patient with HCM or with a positive genetic test 1.

Key diagnostic features of HCM include:

• Unexplained LVH with non-dilated ventricles
• Preserved or increased ejection fraction
• Myocyte hypertrophy, disarray, and interstitial fibrosis on histopathology
• Primarily sarcomeric mutations (MYBPC3, MYH7 most common) 2

Pathophysiology Considerations

Several pathophysiologic mechanisms contribute to symptoms in HCM:

1. Left ventricular outflow tract obstruction (LVOTO): Common in HCM, often due to systolic anterior motion (SAM) of the mitral valve 1
2. Diastolic dysfunction: Results from altered ventricular load, impaired LV compliance from hypertrophy and fibrosis, altered energetics, and microvascular ischemia 1
3. Mitral regurgitation: Can occur secondarily from SAM or primarily from leaflet abnormalities 1
4. Myocardial ischemia: Due to mismatch between oxygen supply and demand, microvascular dysfunction, and impaired coronary flow reserve 1

Management Approach

Medical Management

1. Beta-blockers:

   • First-line therapy for symptom control
   • Should be titrated to resting heart rate <60-65 bpm
   • Effective for reducing symptoms related to obstruction and diastolic dysfunction 2

2. Calcium channel blockers (Verapamil):

   • Second-line therapy if beta-blockers are ineffective or contraindicated
   • Can be used at doses up to 480 mg/day
   • Caution: Verapamil should be avoided in patients with severe LV outflow obstruction due to risk of hypotension and pulmonary edema 3
   • In patients with hypertrophic cardiomyopathy, verapamil has been associated with serious adverse effects including pulmonary edema and severe hypotension, particularly in those with marked left ventricular outflow obstruction 3

3. ACE inhibitors or ARBs:

   • May be considered, though a 12-month trial of losartan showed no benefit on LV mass or fibrosis 2

4. Cardiac myosin inhibitors:

   • Newer class of medications developed specifically for HCM
   • Target the cellular pathophysiologic mechanism of HCM 4

Invasive Management for Refractory Symptoms

For patients with significant LVOTO and symptoms refractory to medical therapy, septal reduction therapies should be considered:

1. Surgical myectomy:

   • Gold standard for patients with severe symptoms unresponsive to medical therapy
   • Involves transaortic resection of the hypertrophied septum
   • Very effective in reducing LVOTO and improving symptoms
   • Operative mortality approximately 1% in experienced centers 1
   • Should be performed in centers with extensive experience 1

2. Alcohol septal ablation:

   • Alternative to surgery for selected patients
   • Success depends on septal artery anatomy
   • Higher rate of permanent pacemaker requirement (10-20% of patients) 1
   • Slightly higher mortality (0-4%) compared to myectomy 1

Risk Stratification for Sudden Cardiac Death

Risk factors for sudden cardiac death in HCM include:

• Family history of sudden cardiac death at a young age
• LV hypertrophy >3 cm
• Unexplained syncope
• Non-sustained ventricular tachycardia on Holter monitoring
• Abnormal blood pressure response during exercise 5

Patients with two or more risk factors are considered high risk and may benefit from implantable cardioverter-defibrillator (ICD) placement 5.

Monitoring and Follow-up

• Regular clinical assessment for heart failure symptoms
• Periodic echocardiography every 1-2 years to monitor cardiac structure and function
• ECG monitoring for development of arrhythmias
• Assessment of functional capacity with standardized tools 2
• Special attention to development of atrial fibrillation, which is more common with greater extent of septal hypertrophy 6

Special Considerations

1. Children with HCM:

   • Diagnostic criteria differ: z-score >2.5 for those without family history; z-score >2 for those with family history or positive genetic test 1
   • Medical treatment principles similar to adults, with beta-blockers showing prognostic benefit 5
   • Technical limitations of invasive therapies must be carefully considered 5

2. Pregnancy:

   • Most women with HCM tolerate pregnancy well
   • Beta-blockers can generally be continued during pregnancy
   • Close monitoring required, especially during labor and delivery

Pitfalls to Avoid

1. Misdiagnosis: Ensure other causes of LVH are excluded (hypertension, aortic stenosis, athlete's heart)
2. Inappropriate use of vasodilators: Can worsen LVOTO
3. Verapamil use in severe obstruction: Can precipitate pulmonary edema and hypotension 3
4. Dehydration: Can worsen obstruction; adequate hydration is important
5. Failure to recognize progression: Regular monitoring is essential as the disease can progress over time

By following this management approach, most patients with moderate septal hypertrophy can achieve good symptom control and quality of life with appropriate medical therapy, with invasive options reserved for those with refractory symptoms.