UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Medline ® Abstracts for References 5-8

of 'Angiotensin converting enzyme inhibitors in acute myocardial infarction: Mechanisms of action'

5
TI
Progressive left ventricular dysfunction and remodeling after myocardial infarction. Potential mechanisms and early predictors.
AU
Gaudron P, Eilles C, Kugler I, Ertl G
SO
Circulation. 1993;87(3):755.
 
BACKGROUND: Left ventricular enlargement and the development of chronic heart failure are potent predictors of survival in patients after myocardial infarction. Prospective studies relating progressive ventricular enlargement in individual patients to global and regional cardiac dysfunction and the onset of late chronic heart failure are not available. It was the aim of this study to define the relation between left ventricular dilatation and global and regional cardiac dysfunction and to identify early predictors of enlargement and chronic heart failure in patients after myocardial infarction.
METHODS AND RESULTS: Left ventricular volumes, regional area shrinkage fraction in 18 predefined sectors (gated single photon emission computed tomography), global ejection fraction, and hemodynamics at rest and during exercise (supine bicycle, 50 W, 4 minutes, Swan-Ganz catheter) were assessed prospectively 4 days, 4 weeks, 6 months, and 1.5 and 3 years after first myocardial infarction. Seventy patients were assigned to groups with progressive, limited, or no dilatation. Patients without dilatation (n = 38) maintained normal volumes and hemodynamics until 3 years. With limited dilatation (n = 18), left ventricular volume increased up to 4 weeks after infarction and stabilized thereafter; depressed stroke volume was restored 4 weeks after infarction and then remained stable at rest. Wedge pressure during exercise, however, progressively increased. With progressive dilatation (n = 14), depressed cardiac and stroke indexes were also restored by 4 weeks but progressively deteriorated thereafter. Area shrinkage fraction as an estimate of regional left ventricular function in normokinetic sectors at 4 days gradually deteriorated during 3 years, but hypokinetic and dyskinetic sectors remained unchanged. Global ejection fraction fell after 1.5 years, whereas right atrial pressure, wedge pressure, and systemic vascular resistance increased. By multivariate analysis, ejection fraction and stroke index at 4 days, ventriculographic infarct size, infarct location, and Thrombolysis in Myocardial Infarction trial grade of infarct artery perfusion were significant predictors of progressive ventricular enlargement and chronic dysfunction.
CONCLUSIONS: Almost 26% of patients may develop limited left ventricular dilatation within 4 weeks after first infarction, which helps to restore cardiac index and stroke index at rest and to preserve exercise performance and therefore remains compensatory. A somewhat smaller group (20%) develops progressive structural left ventricular dilatation, which is compensatory at first, then progresses to noncompensatory dilatation, and finally results in severe global left ventricular dysfunction. In these patients, depression of global ejection fraction probably results from impairment of function of initially normally contracting myocardium. Early predictors from multivariate analysis allow identification of patients at high risk for progressive left ventricular dilatation and chronic ventricular dysfunction within 4 weeks after acute infarction.
AD
Department of Medicine, Julius-Maximilians-University, Würzburg, FRG.
PMID
6
TI
Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications.
AU
Pfeffer MA, Braunwald E
SO
Circulation. 1990;81(4):1161.
 
An acute myocardial infarction, particularly one that is large and transmural, can produce alterations in the topography of both the infarcted and noninfarcted regions of the ventricle. This remodeling can importantly affect the function of the ventricle and the prognosis for survival. In the early period, infarct expansion has been recognized by echocardiography as a lengthening of the noncontractile region. The noninfarcted region also undergoes an important lengthening that is consistent with a secondary volume-overload hypertrophy and that can be progressive. The extent of ventricular enlargement after infarction is related to the magnitude of the initial damage to the myocardium and, although an increase in cavity size tends to restore stroke volume despite a persistently depressed ejection fraction, ventricular dilation has been associated with a reduction in survival. The process of ventricular enlargement can be influenced by three interdependent factors, that is, infarct size, infarct healing, and ventricular wall stresses. A most effective way to prevent or minimize the increase in ventricular size after infarction and the consequent adverse effect on prognosis is to limit the initial insult. Acute reperfusion therapy has been consistently shown to result in a reduction in ventricular volume. The reestablishment of blood flow to the infarcted region, even beyond the time frame for myocyte salvage, has beneficial effects in attenuating ventricular enlargement. The process of scarification can be interfered with during the acute infarct period by the administration of glucocorticosteroids and nonsteroidal antiinflammatory agents, which result in thinner infarcts and greater degrees of infarct expansion. Modification of distending or deforming forces can importantly influence ventricular enlargement. Even short-term augmentations in afterload have deleterious long-term effects on ventricular topography. Conversely, judicious use of nitroglycerin seems to be associated with an attenuation of infarct expansion and long-term improvement in clinical outcome. Long-term therapy with an angiotensin converting enzyme inhibitor can favorably alter the loading conditions on the left ventricle and reduce progressive ventricular enlargement as demonstrated in both experimental and clinical studies. With the former therapy, this attenuation of ventricular enlargement was associated with a prolongation in survival. The long-term clinical consequences of long-term angiotensin converting enzyme inhibitor therapy after myocardial infarction is currently being evaluated. Although studies directed at attenuating left ventricular remodeling after infarction are in the early stages, it does seem that this will be an important area in which future research might improve long-term outcome after infarction.
AD
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115.
PMID
7
TI
Development and prevention of congestive heart failure following myocardial infarction.
AU
Pfeffer MA, Pfeffer JM, Lamas GA
SO
Circulation. 1993;87(5 Suppl):IV120.
 
Ischemic heart disease is the major etiology for the development of congestive heart failure. Patients with acute myocardial infarction have a greatly increased risk for mortality and for manifesting symptomatic heart failure. This risk is not a uniform one but is greatly augmented in patients with a more extensive infarction and, consequently, a more depressed global ventricular function. An important concept that was derived from studies in rats with myocardial infarction and has been confirmed in patients is that ventricular enlargement, which has been shown to be a marker for an adverse outcome, can be a progressive process that leads to further deterioration of ventricular performance. Both experimental and early clinical studies have indicated that chronic therapy with an angiotensin converting enzyme inhibitor may attenuate this progressive ventricular enlargement. More definitive clinical trials are currently under way to determine whether this form of therapy, which may diminish the extent of ventricular enlargement over time, will result in an improvement in survival and in the prevention of the development of congestive heart failure. The addition of this pharmacological therapy to that of the primary prevention of atherosclerosis and that of the limitation of infarct size should make a substantial impact on the reduction of the incidence of congestive heart failure.
AD
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02115.
PMID
8
TI
Left ventricular remodeling after myocardial infarction: pathophysiology and therapy.
AU
Sutton MG, Sharpe N
SO
Circulation. 2000;101(25):2981.
 
AD
University of Pennsylvania Medical Center, Philadelphia, PA, USA.
PMID