What medications are used to treat cardiomyopathy?

Medications for Cardiomyopathy

First-Line Pharmacologic Management by Cardiomyopathy Type

Beta-blockers are the cornerstone of medical therapy for most cardiomyopathies, with specific agents and dosing strategies varying by underlying etiology. 1, 2

Hypertrophic Cardiomyopathy (HCM)

Non-vasodilating beta-blockers are the first-line treatment for symptomatic obstructive HCM, titrated to maximally tolerated doses targeting a resting heart rate <60-65 bpm. 1, 2, 3

• Metoprolol is preferred, starting at 25-50 mg twice daily and titrating up to 100 mg twice daily or metoprolol XL 50-400 mg once daily 1, 2
• Atenolol 25-100 mg once daily is an alternative 1
• Bisoprolol 2.5-10 mg once daily can be used 1
• Propranolol 10-40 mg three to four times daily is another option 1

If beta-blockers are ineffective or not tolerated, non-dihydropyridine calcium channel blockers (verapamil or diltiazem) should be substituted as second-line therapy. 1, 2

• Verapamil can be titrated up to 180-480 mg once daily (extended-release formulation) 1, 2
• Diltiazem 120-360 mg once daily (extended-release) is an alternative 1, 2
• Critical warning: Verapamil is potentially harmful in patients with severe dyspnea at rest, hypotension, very high resting gradients (>100 mmHg), and all children <6 weeks of age 1

For patients with persistent severe symptoms despite beta-blockers or calcium channel blockers, adding disopyramide in combination with one of these agents is recommended. 1, 2

• Disopyramide is particularly effective in patients with left ventricular outflow tract (LVOT) obstruction 2
• This represents third-line pharmacologic therapy before considering septal reduction therapy 1, 2

Mavacamten (cardiac myosin inhibitor) is recommended for adults with persistent NYHA class II-III symptoms despite beta-blockers or calcium channel blockers. 2

Dilated Cardiomyopathy (DCM)

Beta-blockers are the primary pharmacologic therapy for DCM, with metoprolol, bisoprolol, and carvedilol all demonstrating mortality benefit. 4, 5, 6

• Metoprolol should be initiated at very low doses (12.5-25 mg once daily for metoprolol CR/XL) and gradually titrated at 2-week intervals to a target of 200 mg once daily or maximally tolerated dose 5, 6
• Carvedilol 3.125-25 mg twice daily, starting at the lowest dose and up-titrating slowly 1, 4
• Bisoprolol 2.5-10 mg once daily 1, 4

The rationale for beta-blockade in DCM is that chronic sympathetic nervous system activation, while initially compensatory, becomes detrimental long-term. 7 Treatment with metoprolol CR/XL in the MERIT-HF trial demonstrated a 34% reduction in all-cause mortality at 12 months in patients with chronic heart failure due to ischemic or dilated cardiomyopathy. 5, 6

Standard heart failure therapy should be added to beta-blockers, including ACE inhibitors or ARBs, aldosterone antagonists, and diuretics as needed for volume management. 1

• Diuretics should be used cautiously at low doses for congestive symptoms 2
• ACE inhibitors and ARBs are appropriate in DCM without significant LVOT obstruction 2

For patients with DCM and atrial fibrillation, oral anticoagulation is recommended when CHA2DS2-VASc score ≥2 in men or ≥3 in women. 1

• Direct oral anticoagulants (DOACs) are preferred over warfarin 1
• Rate control with beta-blockers targeting heart rate <110 bpm (lenient control) is acceptable initially 1

Alcoholic Cardiomyopathy

Total abstinence from alcohol is the most critical intervention, combined with standard heart failure therapy including beta-blockers. 1

• Thiamine supplementation should be provided because chronic alcoholism predisposes to thiamine deficiency, which can contribute to cardiomyopathy 1
• Standard beta-blocker therapy as used in DCM should be initiated 1
• Survival is significantly better in patients who abstain compared to those who continue drinking, with mortality rates of 40-50% within 3-6 years in non-abstinent patients 1

Cocaine-Related Cardiomyopathy

For patients demonstrating abstinence for >6 months, standard therapy for left ventricular dysfunction including beta-blockers is reasonable. 1

In patients at risk for relapse, non-selective beta-blockers with α-, β1-, or β2-receptor antagonism are preferred to prevent unopposed α-agonism effects of cocaine. 1

• Carvedilol is preferred over selective β1-blockers like metoprolol in this population 1
• Selective β1-blockers alone may worsen cocaine-induced vasoconstriction through unopposed α-receptor stimulation 1

Restrictive Cardiomyopathy (RCM)

Beta-blockers may not be well tolerated in RCM due to fixed stroke volume and dependence on heart rate for cardiac output. 1

• Cardiac output is crucially dependent on heart rate, making negative chronotropic agents problematic 1
• Reverse remodeling is not a therapeutic goal in RCM 1
• Rate control for atrial fibrillation (present in 45-51% of RCM patients) should be approached cautiously, as aggressive rate reduction can worsen cardiac output 1

Chemotherapy-Related Cardiomyopathy

Standard heart failure therapy including beta-blockers should be initiated once cardiotoxicity is detected. 1

• Early detection is critical, as anthracycline cardiotoxicity can occur at cumulative doses as low as 200 mg/m² 1
• There is no safe cutoff dose for anthracycline cardiotoxicity 1
• Cardiac troponin monitoring can detect myocardial damage even after a single treatment 1

Critical Medications to Avoid

In Hypertrophic Cardiomyopathy with LVOT Obstruction

Dihydropyridine calcium channel blockers (nifedipine, amlodipine, felodipine) are potentially harmful and should never be used in patients with resting or provocable LVOT obstruction. 1, 2

All vasodilators should be avoided, including:

• ACE inhibitors and ARBs (uncertain benefit and potentially harmful) 2
• Alpha-blockers (terazosin, doxazosin) - contraindicated as they cause vasodilation worsening LVOT obstruction 2
• Nitrates and hydralazine 2
• Digoxin should not be used for dyspnea in HCM patients without atrial fibrillation 3

Drug Interactions Requiring Caution

Never combine beta-blockers with verapamil or diltiazem due to risk of high-grade atrioventricular block. 2, 8

• Concomitant therapy may result in additive negative effects on heart rate, AV conduction, and cardiac contractility 8
• Excessive bradycardia and complete heart block have been reported with this combination 8

Verapamil increases digoxin levels by 50-75% during the first week of therapy, requiring dose adjustment to avoid digitalis toxicity. 8

Acute Management Considerations

Acute Hypotension in Obstructive HCM

Phenylephrine (pure α-agonist vasoconstrictor) is the preferred agent to reverse acute hypotension in obstructive HCM. 1, 2, 3

• Intravenous phenylephrine should be administered alone or in combination with beta-blockers 1
• Never use inotropes (dopamine, dobutamine) or vasodilators, as these worsen LVOT obstruction 2, 8
• Beta-blockade can be combined with vasoconstrictors to dampen contractility and improve preload by prolonging diastolic filling 2

Cautious IV fluid boluses of 250-500 mL normal saline over 30-60 minutes should be given if hypotension develops. 3

Atrial Fibrillation in HCM

Immediate anticoagulation is indicated in HCM patients with atrial fibrillation regardless of CHA2DS2-VASc score. 1, 3

• HCM patients have inherently high thromboembolic risk 1, 3
• Direct current cardioversion is recommended for new-onset AF with hemodynamic compromise 1

For rhythm control, amiodarone or sotalol are preferred antiarrhythmic drugs in HCM. 1

• Amiodarone 100-200 mg once daily for long-term therapy 1
• Sotalol has a better side-effect profile but amiodarone is often the only effective option 1
• Disopyramide combined with a beta-blocker is reasonable for patients with LVOT obstruction 1

Tachycardia-Induced Cardiomyopathy

A rhythm-control strategy with pharmacological therapy is useful for treating tachycardia-induced cardiomyopathy in patients with atrial fibrillation. 1

• Flecainide, dofetilide, propafenone, and intravenous ibutilide are effective for pharmacological cardioversion 1
• Rate control should target heart rate <110 bpm initially 1

Common Pitfalls and Caveats

Starting beta-blockers at standard doses in cardiomyopathy patients frequently causes decompensation. 4, 5, 6

• Always initiate at very low doses (one-tenth to one-twentieth of doses used for hypertension or angina) 4
• Gradual up-titration at 1-2 week intervals is essential for tolerability 4, 5, 6
• Approximately 80% of patients tolerate long-term beta-blockade when properly initiated 9

Aggressive diuresis in HCM worsens LVOT obstruction by decreasing preload. 2

• Use diuretics cautiously at low doses only for volume overload 1, 2
• Maintaining euvolemia is critical 3

Treating HCM patients like typical heart failure patients with standard vasodilator therapy can be harmful. 2, 3

• The pathophysiology differs fundamentally from systolic heart failure 2
• Vasodilators reduce preload and afterload, worsening dynamic outflow obstruction 3

In patients with RCM, beta-blockers may worsen symptoms due to fixed stroke volume and heart rate-dependent cardiac output. 1

• Carefully assess tolerability before continuing beta-blocker therapy 1
• Negative chronotropic effects can be particularly problematic 1