What is the management plan for a patient with asymmetric septal hypertrophic cardiomyopathy (HCM), left ventricular outflow tract (LVOT) obstruction, and patchy midwall fibrosis?

Management of Asymmetric Septal HCM with LVOT Obstruction and 10% Midwall Fibrosis

This patient requires immediate initiation of non-vasodilating beta-blockers as first-line therapy, titrated to a resting heart rate of 60-65 bpm, with consideration for septal reduction therapy if symptoms persist despite optimal medical management. 1, 2

Initial Pharmacologic Management

First-Line Therapy: Beta-Blockers

• Start non-vasodilating beta-blockers (propranolol, nadolol, or bisoprolol) and titrate to maximum tolerated dose 1, 2
• Target resting heart rate of 60-65 bpm to optimize diastolic filling and reduce LVOT gradient 2, 3
• Beta-blockers reduce contractility, prolong diastolic filling time, and can prevent exercise-induced LVOT obstruction in 52% of patients 3
• Continue beta-blockers without interruption in the perioperative period if surgery is needed 1

Second-Line Therapy: Non-Dihydropyridine Calcium Channel Blockers

• If beta-blockers are ineffective, contraindicated, or not tolerated, switch to verapamil (starting 40 mg three times daily, maximum 480 mg daily) or diltiazem 1, 2
• Critical warning: Use verapamil cautiously in patients with severe obstruction (≥100 mm Hg) or elevated pulmonary pressures, as it can precipitate pulmonary edema 1
• Monitor closely during initiation in patients with high gradients 1

Third-Line Therapy: Disopyramide

• Add disopyramide (400-600 mg/day) if beta-blockers alone are ineffective 1, 2
• This Class IA antiarrhythmic can abolish basal LVOT gradients and improve exercise tolerance 1
• Monitor QTc interval during dose titration; reduce dose if QTc exceeds 480 ms 1
• Avoid in patients with glaucoma, prostatism, or those taking other QT-prolonging drugs (amiodarone, sotalol) 1

Fourth-Line Therapy: Mavacamten

• Consider mavacamten (cardiac myosin inhibitor) for persistent NYHA class II-III symptoms despite beta-blockers or calcium channel blockers 2
• This represents a novel mechanism targeting the underlying pathophysiology of HCM 4
• Monitor for reversible reduction in left ventricular ejection fraction to <50% (occurs in 7-10% of patients) 5

Critical Medications to AVOID

Absolute Contraindications in Obstructive HCM

• Dihydropyridine calcium channel blockers (amlodipine, nifedipine, felodipine) - can worsen LVOT obstruction and precipitate hemodynamic collapse 2
• Arterial and venous dilators including nitrates and phosphodiesterase-5 inhibitors - exacerbate LVOT obstruction 1, 6
• Digoxin - positive inotropic effects worsen obstruction 1
• Alpha-blockers (terazosin, doxazosin) - cause vasodilation leading to hemodynamic compromise 2
• ACE inhibitors and ARBs - uncertain benefit and potentially harmful in patients with resting or provocable LVOT obstruction 2

Diuretic Use Requires Caution

• Use diuretics cautiously at low doses for congestive symptoms only 2
• Aggressive diuresis worsens LVOT obstruction by decreasing preload and reducing ventricular cavity size 6

General Measures and Lifestyle Modifications

Preload Management

• Avoid dehydration and maintain adequate fluid intake, especially during exercise or hot weather 6
• Avoid excess alcohol consumption 1, 6
• Encourage weight loss if obese (present in >70% of adult HCM patients and independently associated with increased symptom burden) 2

Arrhythmia Management

• New-onset or poorly controlled atrial fibrillation exacerbates symptoms due to loss of atrial contribution to ventricular filling 1, 6
• Promptly restore sinus rhythm or achieve appropriate rate control before considering invasive therapies 1
• Patients with HCM are highly dependent on atrial systole for adequate ventricular filling due to impaired ventricular relaxation 6

Septal Reduction Therapy (SRT) Indications

When to Consider SRT

SRT is indicated when patients remain severely symptomatic despite guideline-directed medical therapy with:

• Dynamic LVOT gradient at rest or with physiologic provocation ≥50 mm Hg 2
• Severe dyspnea or chest pain attributable to LVOTO that interferes with everyday activity 2

Surgical Myectomy (Preferred Option)

• Surgical myectomy is the preferred SRT when performed by experienced operators at comprehensive HCM centers 2
• Achieves >90% relief of obstruction with perioperative mortality <1% in most centers 2
• Mandatory for patients requiring concomitant cardiac surgery 2

Consider Earlier Myectomy in Specific Scenarios:

• Severe progressive pulmonary hypertension attributable to LVOTO or associated mitral regurgitation 2
• Left atrial enlargement with ≥1 episodes of symptomatic atrial fibrillation 2
• Poor functional capacity attributable to LVOTO on treadmill testing 2
• Children and young adults with very high resting LVOT gradients (>100 mm Hg) 2

Alcohol Septal Ablation (Alternative Option)

• Reserved for adult patients who remain severely symptomatic despite GDMT when surgery is contraindicated or risk is unacceptable due to serious comorbidities or advanced age 1, 2
• Should not be performed in patients <21 years of age and is discouraged in adults <40 years if myectomy is viable 1
• Uncertain effectiveness in patients with marked septal hypertrophy (>30 mm) 1

SRT Contraindications

• Do not perform SRT in asymptomatic patients with normal exercise tolerance 1, 2
• Do not perform SRT in patients whose symptoms are controlled or minimized on optimal medical therapy 1

Management of Acute Hypotension in HOCM

Emergency Protocol

• Acute hypotension in obstructive HCM is a medical urgency requiring immediate intervention 2
• Prioritize intravenous fluid administration to maximize preload 1, 2
• Use phenylephrine (pure alpha-agonist) as the preferred vasopressor to increase afterload without increasing contractility 1, 2
• Consider vasopressin as an alternative alpha-agonist 1
• Avoid beta-agonists (dopamine, dobutamine) which worsen LVOT obstruction by increasing contractility 2
• Consider intravenous beta-blockade in combination with vasoconstrictors to dampen contractility and improve preload by prolonging diastolic filling 1, 2
• Use intraoperative echocardiography to evaluate LVOT obstruction in the setting of hypotension 1

Special Consideration: The 10% Midwall Fibrosis Finding

Prognostic Implications

• Myocardial fibrosis plays an important role in the progression to advanced heart failure in patients with HCM 7
• Late gadolinium enhancement on cardiac MRI provides better risk evaluation for management strategies 7
• This finding warrants closer monitoring for heart failure progression and arrhythmia risk 7

Does Not Change Initial Management

• The presence of 10% fibrosis does not alter the initial pharmacologic approach 1, 2
• Continue with standard stepwise medical therapy as outlined above 1, 2
• Monitor for development of systolic dysfunction (EF ≤50%) which would require transition to heart failure-directed medical therapy 1

Common Pitfalls to Avoid

• Never abruptly discontinue beta-blockers - can precipitate rebound tachycardia and worsening symptoms 2
• Never combine beta-blockers with non-dihydropyridine calcium channel blockers - increased risk of bradycardia and heart block 2
• Never use vasodilators for blood pressure control in patients with obstructive physiology 2, 6
• Never perform dobutamine stress testing to identify latent LVOTO - lacks specificity 6
• Never refer for SRT without first optimizing medical therapy - SRT should only be performed as part of a program dedicated to longitudinal and multidisciplinary care of HCM patients 1