What is the role of hydralazine in treating acute decompensated heart failure (ADHF)?

Hydralazine for Acute Decompensated Heart Failure

Hydralazine is NOT recommended as a primary treatment for acute decompensated heart failure (ADHF), as it lacks evidence for use in the acute setting and is specifically indicated only for chronic heart failure with reduced ejection fraction (HFrEF) in combination with isosorbide dinitrate. 1

Evidence Base and Clinical Context

The available guidelines address hydralazine exclusively in the context of chronic HFrEF management, not acute decompensation:

Guideline-Directed Use (Chronic HFrEF Only)

For African American patients with chronic HFrEF:

• Hydralazine combined with isosorbide dinitrate is appropriate for African Americans who remain symptomatic despite optimal therapy with ACE inhibitors (or ARBs), beta-blockers, and mineralocorticoid receptor antagonists 1
• This combination demonstrated mortality reduction and reduced healthcare costs in the A-HeFT trial 1
• The benefit is presumed related to enhanced nitric oxide bioavailability 1

For patients intolerant to first-line agents:

• Hydralazine-isosorbide dinitrate combination might be considered in patients unable to tolerate ACE inhibitors, ARNIs, or ARBs due to hypotension or renal insufficiency 1
• However, recent observational datasets have not confirmed benefit in this population 1
• Referral to a heart failure specialist is recommended before initiating this therapy 1

Why Hydralazine Is Problematic in ADHF

Hemodynamic concerns:

• Hydralazine causes reflex tachycardia and increased cardiac output through arterial vasodilation, which increases myocardial oxygen demand 2, 3
• The American Heart Association notes hydralazine has unpredictable response and prolonged duration of action (2-4 hours), making it less desirable for acute treatment 4
• It preferentially dilates arterioles over veins, providing minimal benefit for pulmonary congestion—the primary target in ADHF 2

Lack of acute evidence:

• All major trials (V-HeFT I, A-HeFT) studied chronic oral therapy, not acute intravenous administration for decompensation 1
• Guidelines emphasize vasodilators like nitroglycerin or nitroprusside for ADHF, not hydralazine 5, 6

Appropriate ADHF Management Instead

For normotensive/hypertensive ADHF:

• Intravenous nitroglycerin is preferred for venous vasodilation and preload reduction 5
• Nitroprusside may be used in patients with congestion and low cardiac output (with caution in hypotension) 5

For hypotensive ADHF:

• Inotropes (dobutamine, milrinone) are indicated only with evidence of poor tissue perfusion 5, 6
• Mechanical circulatory support should be considered early if medical therapy fails 5

Diuretics remain the mainstay:

• Intravenous loop diuretics are essential for decongestion in ADHF 5, 6

Critical Pitfalls to Avoid

• Do not use hydralazine monotherapy in any heart failure setting—it should only be combined with isosorbide dinitrate for chronic HFrEF 1
• Do not substitute hydralazine-isosorbide dinitrate for ACE inhibitors in patients tolerating them well 1
• Expect poor compliance—the combination requires multiple daily doses and causes frequent headaches and gastrointestinal complaints 1
• Avoid in acute MI or active ischemia—reflex tachycardia can provoke myocardial ischemia 7