A 56-year-old man comes to the hospital due to 24 hours of burning substernal chest pain. The most intense pain occurred approximately 6 hours ago, and it has started to subside. The patient has a history of diabetes mellitus. ECG shows sinus rhythm with ST-segment elevation in leads V3 to V5. In the cardiac catheterization laboratory, he is found to have total occlusion of the left anterior descending artery. Successful intervention is performed to restore blood flow in the artery. The next day, the patient's echocardiogram shows a normal-sized left ventricle with no evidence of hypertrophy; there is apical and anterior akinesia with a reduced left ventricular ejection fraction of 38%. Which of the following is the most likely long-term effect of ACE inhibitor therapy in this patient?
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This patient has a reduced left ventricular (LV) ejection fraction (<45%) due to acute myocardial infarction; echocardiography shows akinesia of the anterior and apical segments, findings consistent with infarction in those locations. In the months following infarction, the affected myocardium undergoes fibroblastic proliferation and fibrosis to repair the necrotic region (ie, initial remodeling phase); disproportionate thinning of the infarcted area can lead to ballooning of affected segments and marked LV cavity enlargement. Although LV cavity enlargement is initially beneficial as it acts as a compensatory mechanism for LV volume overload, progressive cavity enlargement (eg, eccentric hypertrophy) leads to overwhelming wall stress and further worsening of LV contractile dysfunction. With progressive dilation, the LV begins to assume a spherical, rather than its normal elliptical, shape.
Much of the deleterious remodeling that occurs following myocardial infarction is likely driven by neurohormonal signaling via angiotensin II. Accordingly, ACE inhibitors (eg, lisinopril) reduce the deleterious remodeling that takes place following myocardial infarction, minimizing LV dilation and helping preserve LV function.
(Choices B and C) Angiotensin II enhances post–myocardial infarction collagen deposition to contribute to deleterious cardiac remodeling. This effect is especially prominent in peri-infarct cardiomyocytes (cardiomyocytes at the edge of an infarction), which have high angiotensin II levels. ACE inhibitors reduce deleterious cardiac remodeling at least in part via inhibition of myocardial collagen deposition and fibrosis.
(Choice D) Noninfarcted cardiac segments (eg, the basal segments in this patient) are subject to postinfarction remodeling caused by LV hemodynamic influences (eg, pressure and volume changes). ACE inhibitors also reduce remodeling of these segments, further contributing to maintenance of the normal LV elliptical shape and preservation of LV contractile function.
(Choice E) Stroke work is the work done by the left ventricle with each contraction and is estimated by the product of stroke volume and LV systolic pressure (ie, stroke volume × LV systolic pressure). ACE inhibitors reduce stroke work by causing peripheral vasodilation and reducing systemic blood pressure (ie, reducing the pressure the left ventricle must overcome during each contraction).
Educational objective:
Following myocardial infarction, collagen deposition and fibrosis within the infarct region and eccentric hypertrophy of surviving myocytes can lead to progressive left ventricular (LV) dilation and worsening contractile dysfunction. Because much of this remodeling is driven by neurohormonal signaling via angiotensin II, ACE inhibitors (eg, lisinopril) reduce deleterious cardiac remodeling following myocardial infarction, minimizing LV dilation and helping preserve contractile function.