What other side effects are seen with ACE inhibitors?

Other less common side effects of ACE inhibitors, most often seen with captopril, include rash, dysgeusia, angioedema, and reversible neutropenia.

In asymptomatic patients with severe chronic left ventricular volume overload lesions, aortic insufficiency, and mitral regurgitation, ACE inhibitors and other vasodilators have been utilized to attempt to slow or reverse left ventricular dilation and systolic dysfunction. However, some cardiologists have voiced concerns over the routine use of these agents for these conditions. Why?

Chronic left ventricular volume overload lesions are typically well tolerated for many years, though about one-fourth of patients will develop left ventricular dysfunction prior to onset of symptoms. Once the ventricle begins to fail, 20-30% of patients continue to deteriorate despite valve repair. Left ventricular function is an important marker used to time valve repair. Vasodilators improve left ventricular function, but there are few clinical data on how vasodilators might affect the timing of valve surgery. For example, if an asymptomatic patient with severe chronic aortic insufficiency would normally undergo valve replacement when the left ventricular ejection fraction fell to 50%, at what ejection fraction should the valve be replaced in the same patient being managed with hydralazine? Conversely, aggressive vasodilation may improve the failing heart enough to allow valve repair in patients once thought to be inoperable. Vasodilators may be used in other nonsurgical candidates to relieve symptoms and postpone surgery indefinitely.

What are some cardiovascular diseases in which arterial vasodilators may be contraindicated?

Most contraindications to the use of arterial vasodilators are relative. For example, in severe aortic stenosis, blood pressure may be dependent on arterial vasoconstriction due to a relatively fixed stroke volume; thus, arterial vasodilators should be used cautiously. However, in patients with severe aortic stenosis and congestive heart failure who were not considered candidates for aortic valve replacement, careful use of arterial vasodilators has provided symptomatic improvement. Similar concerns apply in hypertrophic cardiomyopathy and severe pulmonary hypertension. Many patients with left ventricular dysfunction are relatively hypotensive (systolic blood pressure 100 mmHg); however, because this group of patients derives symptomatic and survival benefits from ACE inhibition, cautious use of ACE inhibitors is still indicated in such circumstances.

In what acute conditions can the prompt initiation of vasodilator therapy be life-saving?

Vasodilators can be life-saving in several situations that require acute afterload reduction and/or systemic blood pressure reduction.

Severe acute mitral regurgitation from any cause results in a sudden rise in left atrial and pulmonary venous pressure, leading to pulmonary edema. Emergent use of sodium nitroprusside lowers systemic blood pressure and afterload, which favors forward ejection of the left ventricular volume, lowers the regurgitant volume, and reduces pulmonary venous pressure. Severe acute aortic insufficiency causes a sudden elevation in left ventricular diastolic pressure, leading to pulmonary congestion and systemic hypoperfusion. As in acute mitral regurgitation, the regurgitant volume can be reduced by lowering the systemic blood pressure by acute vasodilation with nitroprusside. Aggressive vasodilation in these instances can stabilize a significant number of patients and allow valve replacement under less emergent circumstances. Hypertensive emergency and aortic dissection are two other examples.

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