How should diuretics be used in patients with Hypertrophic Cardiomyopathy (HCM)?

Diuretics in Hypertrophic Cardiomyopathy

Diuretics should be added cautiously at low doses only when congestive symptoms (dyspnea, orthopnea, edema) persist despite optimal beta-blocker or verapamil therapy in HCM patients, but they must never be used as first-line or monotherapy. 1

Treatment Algorithm for Symptomatic HCM

First-Line Therapy: Beta-Blockers

• Beta-blockers are the mandatory first-line treatment for all symptomatic HCM patients (both obstructive and non-obstructive). 1, 2
• Titrate beta-blockers aggressively to achieve a resting heart rate of 50-60 beats per minute before declaring treatment failure. 2, 3, 4
• Beta-blockers improve diastolic filling time, reduce myocardial oxygen demand, and decrease exercise-induced gradient increases (though they do not significantly reduce resting gradients). 3, 4

Second-Line Therapy: Calcium Channel Blockers

• If beta-blockers are ineffective, not tolerated, or contraindicated, add verapamil (or diltiazem as an alternative). 1, 2
• Verapamil provides symptom relief through negative inotropic effects and improved diastolic function. 1, 2
• Critical warning: Verapamil must be used with extreme caution in patients with high resting gradients (>50 mmHg), advanced heart failure, or systemic hypotension, as it can precipitate hemodynamic collapse. 1, 2, 5

Third-Line Therapy: Diuretics (When and How)

• Diuretics receive a Class IIb recommendation ("may be reasonable") from ACC/AHA guidelines—meaning they are optional and should be used sparingly. 1
• Add oral diuretics only when congestive symptoms (pulmonary congestion, peripheral edema, elevated jugular venous pressure) persist despite optimized beta-blocker or verapamil therapy. 1, 2
• Start with the lowest effective dose and titrate cautiously. 1, 2
• The rationale for caution: HCM patients depend on adequate preload to fill their stiff, hypertrophied, small left ventricular cavity—excessive diuresis can precipitate hypotension, worsen symptoms, and reduce cardiac output. 2, 6

Critical Pitfalls to Avoid

Never Use Diuretics as Monotherapy

• Diuretics should never be used alone in HCM—they do not address the underlying pathophysiology (diastolic dysfunction, outflow obstruction) and can worsen hemodynamics. 1
• Unlike heart failure with reduced ejection fraction (where diuretics are Class I), diuretics in HCM are adjunctive only. 1

Avoid Aggressive Diuresis

• Aggressive diuresis is harmful in HCM because it reduces preload excessively, worsening the small cavity size and diastolic dysfunction. 2, 6
• If hypotension or azotemia develops during diuresis, slow the rate but continue cautiously until fluid retention resolves, as long as the patient remains asymptomatic. 1

Monitor for Volume Depletion

• Volume depletion from excessive diuretics increases the risk of hypotension when combined with beta-blockers or verapamil, and can worsen outflow tract obstruction in obstructive HCM. 1
• Assess volume status carefully—both hypovolemia and hypervolemia worsen HCM symptoms. 7

Medications to Absolutely Avoid in HCM

Vasodilators Are Contraindicated

• ACE inhibitors, ARBs, and dihydropyridine calcium channel blockers (nifedipine, amlodipine) are Class III: HARM in obstructive HCM—they worsen outflow tract obstruction by reducing afterload and can precipitate hemodynamic collapse. 1, 2, 5, 7
• These agents decrease systemic vascular resistance, allowing more vigorous ejection and worsening the LVOT gradient. 5, 7

Positive Inotropes Are Harmful

• Dopamine, dobutamine, norepinephrine, and other positive inotropic drugs are Class III: HARM in obstructive HCM—they worsen outflow obstruction and can cause hemodynamic collapse. 1, 2

Digitalis Should Be Avoided

• Digitalis is potentially harmful in HCM patients without atrial fibrillation, as it increases contractility and worsens obstruction. 1

Special Considerations

Obstructive vs. Non-Obstructive HCM

• Both obstructive and non-obstructive HCM patients may benefit from cautious diuretic use when congestive symptoms persist despite rate-controlling agents. 1, 2
• In obstructive HCM with high resting gradients (>50 mmHg), diuretics carry higher risk and require even more cautious dosing. 1, 2

HCM with Atrial Fibrillation

• If atrial fibrillation develops, anticoagulation is mandatory regardless of CHA₂DS₂-VASc score. 2
• Disopyramide should never be used alone in HCM patients with atrial fibrillation, as it enhances AV conduction and increases ventricular rate—it must be combined with beta-blockers or verapamil. 1

End-Stage HCM with Systolic Dysfunction

• In the rare scenario where HCM progresses to systolic dysfunction (LVEF <50%) with loss of obstruction, transition to guideline-directed medical therapy for heart failure with reduced ejection fraction, which includes ACE inhibitors/ARBs and diuretics as Class I recommendations. 1, 5

Practical Clinical Approach

1. Start with beta-blockers, titrate to heart rate 50-60 bpm. 2, 3, 4
2. If symptoms persist, add verapamil (or diltiazem), monitoring for bradycardia and hypotension. 1, 2
3. If congestive symptoms (dyspnea, edema) persist despite steps 1-2, add low-dose loop diuretics (furosemide 20-40 mg daily or torsemide 10-20 mg daily). 1, 2
4. Monitor closely for signs of volume depletion (hypotension, dizziness, worsening fatigue) and adjust diuretic dose accordingly. 1
5. If symptoms remain refractory despite optimal medical therapy, consider disopyramide (combined with beta-blocker or verapamil) or refer for septal reduction therapy (surgical myectomy or alcohol septal ablation). 1, 8, 3, 4