Why are Angiotensin-Converting Enzyme (ACE) inhibitors contraindicated in patients with valvular heart disease?

ACE Inhibitors Are NOT Contraindicated in Valvular Heart Disease—With One Critical Exception

ACE inhibitors are contraindicated specifically in pregnant patients with valvular heart disease due to severe fetal toxicity, but they are not contraindicated in non-pregnant patients with most forms of valvular disease. 1

The Pregnancy Exception (Class III: Harm)

ACE inhibitors and ARBs must not be given to pregnant patients with valve stenosis or any valvular heart disease. 1 The contraindication is absolute and based on documented fetal toxicity including:

• Renal or tubular dysplasia 1
• Oligohydramnios and growth retardation 1
• Ossification disorders of the skull 1
• Lung hypoplasia 1
• Intrauterine fetal death 1

If a patient with valvular heart disease is taking ACE inhibitors or ARBs for any reason, these medications must be discontinued or replaced with alternative agents before conception. 1

ACE Inhibitors Are Actually Recommended in Many Valvular Conditions

Aortic Regurgitation (Class IIa)

Medical therapy with ACE inhibitors is reasonable in patients with severe aortic regurgitation who have symptoms and/or left ventricular dysfunction when surgery is not performed due to comorbidities. 1

• In a cohort study of 2,266 patients with chronic aortic regurgitation, treatment with ACE inhibitors or ARBs was associated with reduced composite endpoint of valve replacement, heart failure hospitalization, and death from heart failure (HR: 0.68; 95% CI: 0.54 to 0.87; P<0.01). 1
• ACE inhibitors improve hemodynamic abnormalities and forward cardiac output in aortic regurgitation. 1
• Vasodilators that do not slow heart rate, such as ACE inhibitors or dihydropyridine calcium channel blockers, should be used for blood pressure control in moderate aortic regurgitation. 2

Aortic Stenosis

Hypertension in patients with aortic stenosis should be treated according to standard guidelines, and ACE inhibitors may be advantageous due to potential beneficial effects on left ventricular fibrosis in addition to blood pressure control. 1

• ACE inhibitors should be started at low doses and gradually titrated upward with frequent clinical monitoring. 1
• Recent research demonstrates that ACE inhibitors are well tolerated in severe aortic stenosis and may provide hemodynamic improvement with left ventricular unloading. 3
• In a randomized controlled trial of 44 patients with severe aortic stenosis, trandolapril caused decreased left ventricular end-systolic volume and NT-proBNP without symptomatic hypotension. 3
• Another randomized trial showed enalapril significantly improved effort tolerance and reduced dyspnea in symptomatic aortic stenosis patients. 4

Dilated Ascending Aorta

In patients with hypertension and dilated ascending aorta, ACE inhibitors are warranted for blood pressure control. 5

Important Clinical Caveats

When to Exercise Caution (Not Contraindication)

In patients with severe aortic stenosis and left ventricular dysfunction with congestive heart failure and low-normal blood pressure, ACE inhibitors should be used cautiously as these patients are prone to hypotension. 4

• In one study, 3 of 5 patients with left ventricular dysfunction and congestive heart failure developed hypotension requiring withdrawal. 4
• However, when left ventricular systolic function is preserved, ACE inhibitors are tolerated without hypotension or syncope. 4

Avoid in Specific Aortic Regurgitation Scenarios

Beta blockers should be avoided in aortic regurgitation as they prolong diastole and increase regurgitant volume, but ACE inhibitors do not have this limitation. 2

The Historical Misconception

The traditional teaching that ACE inhibitors are contraindicated in valvular heart disease, particularly aortic stenosis, has been challenged by contemporary evidence. 6, 7 This outdated belief stemmed from theoretical concerns about inducing hypotension in patients with fixed outflow obstruction, but clinical studies have not confirmed these fears in most patients. 8, 3

In fact, a study reviewing echocardiography logs found that 30% of patients with aortic stenosis were already receiving ACE inhibitors despite the presumed contraindication, suggesting widespread real-world use. 8

Summary Algorithm

Use ACE inhibitors in valvular heart disease EXCEPT:

1. Absolute contraindication: Pregnancy (any valvular disease) 1
2. Relative caution: Severe aortic stenosis with left ventricular dysfunction, congestive heart failure, and baseline low-normal blood pressure 4

Appropriate indications include:

• Symptomatic severe aortic regurgitation with left ventricular dysfunction (when surgery deferred) 1
• Hypertension in aortic stenosis (start low, titrate slowly) 1
• Hypertension in dilated ascending aorta 5
• Blood pressure control in moderate aortic regurgitation 2