What is the role of spironolactone in managing hypertrophic cardiomyopathy (HCM)?

Spironolactone Has No Role in Standard HCM Management

Spironolactone is not recommended for routine use in hypertrophic cardiomyopathy, as high-quality randomized controlled trial data demonstrate no benefit on myocardial fibrosis, cardiac remodeling, symptoms, or functional capacity. 1, 2

Evidence Against Spironolactone in HCM with Preserved EF

The most definitive evidence comes from a prospective, double-blind randomized controlled trial that directly tested spironolactone 50 mg daily versus placebo over 12 months in HCM patients 2:

• No reduction in myocardial fibrosis by late gadolinium enhancement on cardiac MRI 2
• No improvement in serum markers of collagen synthesis or degradation 2
• No functional benefit measured by peak VO2 or NYHA functional class 2
• No favorable cardiac remodeling with respect to left ventricular wall thickness, mass, volume, left atrial size, or diastolic function 2

This negative trial is explicitly cited in the most recent 2020 and 2024 AHA/ACC guidelines, which state that when tested in RCTs in patients with HCM and normal ejection fraction, spironolactone had no effect on markers of fibrosis, LV dimensions, EF, or symptoms 1

Limited Role: End-Stage HCM with Systolic Dysfunction Only

Spironolactone has a narrow, specific indication only in the small subset (~5%) of HCM patients who develop end-stage disease with systolic dysfunction (LVEF <50%) 1:

• When HCM evolves to the "end-stage," "burnt-out," or "dilated" phase with LV remodeling, wall thinning, and chamber enlargement, treatment strategies shift to standard heart failure with reduced ejection fraction (HFrEF) therapies 1
• In this context, spironolactone is part of guideline-directed medical therapy (GDMT) for HFrEF, along with ACE inhibitors/ARBs, beta-blockers, and diuretics 1
• This represents a complete paradigm shift from typical HCM management, as these patients now have systolic failure rather than the characteristic preserved systolic function with diastolic dysfunction 1

Why the Theoretical Promise Failed

Despite mechanistic rationale and animal model data suggesting mineralocorticoid receptor blockade might reduce cardiac hypertrophy and fibrosis 3, 4, human trials failed to demonstrate benefit:

• Animal studies showed potential for spironolactone (especially combined with ACE inhibitors) to reduce cardiac hypertrophy and fibrosis in genetic HCM models 3, 4
• However, translational failure from animal models to human patients is common in HCM pharmacotherapy 5
• The pathophysiology of human HCM is more complex than can be replicated in animal models 5

Critical Management Pitfall to Avoid

Do not use diuretics (including spironolactone) in typical HCM patients with preserved EF and diastolic dysfunction 1:

• Most HCM patients have diastolic dysfunction requiring relatively high filling pressures to achieve adequate ventricular filling 1
• Diuretics should be administered cautiously, preferably in the absence of marked outflow obstruction 1
• For obstructive HCM patients with persistent dyspnea and clinical evidence of volume overload despite other GDMT, only low-dose oral diuretics may be considered cautiously 1

Current Evidence-Based Treatment Algorithm for Symptomatic HCM

Instead of spironolactone, the 2024 guidelines recommend 1, 6, 7:

For obstructive HCM:

1. First-line: Beta-blockers (titrated to resting HR <60-65 bpm) or non-dihydropyridine calcium channel blockers (verapamil/diltiazem) 7
2. Second-line: Mavacamten (cardiac myosin inhibitor) or disopyramide for persistent NYHA class II-III symptoms 6, 7
3. Third-line: Septal reduction therapy at experienced centers 6

For nonobstructive HCM with preserved EF:

• Valsartan may be beneficial in younger patients (≤45 years) with pathogenic sarcomere variants and mild phenotype to slow adverse remodeling 1
• This represents a Class 2b recommendation (may be beneficial) 1