Search PubMed⌕ Search

Biomedical subjects

M A Pfeffer

Publications and source records attributed to M A Pfeffer.

At least 109 records · Page 6Linked to original sources
PubMed1994

Effects of captopril on ischemic events after myocardial infarction. Results of the Survival and Ventricular Enlargement trial. SAVE Investigators.

BACKGROUND: In the Survival and Ventricular Enlargement (SAVE) trial, recurrent myocardial infarction (MI) was the most important predictor of a poor outcome and conferred a sevenfold increase in risk of death. The purpose of this study was to determine the predictors of recurrent MI in study participants and to examine the influence of the angiotensin-converting enzyme inhibitor captopril on this and other myocardial ischemic events. METHODS AND RESULTS: The 2231 patients had survived the acute phase of MI (3 to 16 days) and had a radionuclide ventricular ejection fraction < or = 40%. Patients were randomly assigned to receive double-blind treatment with either placebo or captopril and were followed for an average of 42 months. The influence of captopril on recurrent MI, cardiac revascularization procedures, and hospitalization with unstable angina was examined. The likelihood of recurrent MI was greater in patients with an MI or functional disability before the index infarction and higher systolic pressure (all P < .001) but was not influenced by baseline left ventricular ejection fraction. Therapy with captopril reduced the risk of development of recurrent MI by 25% (95% confidence intervals, 5% to 40%; P = .015) and the risk of death after recurrent MI by 32% (95% confidence intervals, 4% to 51%; P = .029). Captopril-assigned patients were also less likely to require cardiac revascularization procedures (P = .010), but hospitalization for unstable angina was unaltered. When all three of these major coronary ischemic events were considered together, captopril therapy reduced the risk (14% risk reduction; 95% confidence intervals, 0% to 26%; P = .047). CONCLUSIONS: In post-MI patients with asymptomatic left ventricular dysfunction, long-term administration of captopril reduced recurrence of MI and the need for cardiac revascularization but had no influence on the rate of hospitalization with a discharge diagnosis of unstable angina. The finding that the recurrence of MI was independent of left ventricular ejection fraction suggests that captopril could be useful in preventing recurrent MI in patients with more preserved left ventricular function. The need for cardiac revascularization was reduced in patients receiving long-term captopril therapy, suggesting either an anti-ischemic effect or the ability of the angiotensin-converting enzyme inhibitor to modify the atherosclerotic process in survivors of MI.

Angina, Unstable↗
PubMed1994

Progressive ventricular remodeling in response to diffuse isoproterenol-induced myocardial necrosis in rats.

The purpose of the present study was to gain a better understanding of the relation between ventricular remodeling and heart failure by assessing the adaptation of the heart through time to graded myocardial injury in the presence of a patent coronary circulation. Left ventricular (LV) remodeling is a dynamic response of the heart to injury and a critical component in the development of heart failure. However, most previous studies have been in the presence of an occluded coronary vessel, which may in itself effect remodeling. Male Wistar rats received two subcutaneous injections of either 0, 85, 170, or 340 mg isoproterenol per kilogram of body weight. At 2, 6, and 16 weeks after injection, LV pressure, the pressure-volume relation, and histology were assessed. The graded myocardial necrosis produced in isoproterenol-treated rats was associated with dose-dependent increases in LV end-diastolic pressure, volume indexes, and global diastolic wall stress. In the higher dose groups, the LV continued to enlarge after 2 weeks, resulting in a further reduction in the ratio of LV mass to volume and a persistent rise in diastolic wall stress. These progressive changes in LV structure were associated with an increase in long-term mortality in rats from the intermediate- and high-isoproterenol dose groups. The present study in rats demonstrates that diffuse isoproterenol-induced myocardial necrosis results in a progressive enlargement of the LV cavity that is out of proportion to mass, a finding similar to that observed in discrete myocardial infarction.

Animals↗
PubMed1994

Prevention of post-infarction left ventricular remodeling by ACE-inhibitors.

Left ventricular remodeling post-infarction occurs in at least a third of patients post-infarction and is associated with diminished survival and an increased incidence of adverse cardiovascular events. This process, which has been well described in recent years, can be largely attenuated with the use of ACE-inhibitors and with it survival improved and adverse events minimized. Since it is currently not possible to identify people at risk from left ventricular remodeling, ACE-inhibitors should be administered to all patients within the first 48 hours of infarction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

A comparison of management patterns after acute myocardial infarction in Canada and the United States. The SAVE investigators.

BACKGROUND: There are major differences in the organization of the health care systems in Canada and the United States. We hypothesized that these differences may be accompanied by differences in patient care. METHODS: To test our hypothesis, we compared the treatment patterns for patients with acute myocardial infarction in 19 Canadian and 93 United States hospitals participating in the Survival and Ventricular Enlargement (SAVE) study, which tested the effectiveness of captopril in this population of patients after a myocardial infarction. RESULTS: In Canada, 51 percent of the patients admitted to a participating coronary care unit had acute myocardial infarctions, as compared with only 35 percent in the United States (P < 0.001). Despite the similar clinical characteristics of the 1573 U.S. patients and 658 Canadian patients participating in the study, coronary arteriography was more commonly performed in the United States than in Canada (in 68 percent vs. 35 percent, P < 0.001), as were revascularization procedures before randomization (31 percent vs. 12 percent, P < 0.001). During an average follow-up of 42 months, these procedures were also performed more commonly in the United States than in Canada. These differences were not associated with any apparent difference in mortality (22 percent in Canada and 23 percent in the United States) or rate of reinfarction (14 percent in Canada and 13 percent in the United States), but there was a higher incidence of activity-limiting angina in Canada than in the United States (33 percent vs. 27 percent, P < 0.007). CONCLUSIONS: The threshold for the admission of patients to a coronary care unit or for the use of invasive diagnostic and therapeutic interventions in the early and late periods after an infarction is higher in Canada than in the United States. This is not associated with any apparent difference in the rate of reinfarction or survival, but is associated with a higher frequency of activity-limiting angina.

Angina Pectoris↗
PubMed1993

Phosphonate-modified Gd-DTPA complexes. III: The detection of myocardial infarction by MRI.

The potential of a phosphonate-modified-Gd-DTPA for MR image enhancement of myocardial infarction has been demonstrated in imaging experiments on rats. The agent, 1-hydroxy-3-aminopropane-1,1-diphosphonate-modified-Gd-DTPA (Gd-DTPA-HPDP) accumulates in two models of myocardial infarction, (i.e., drug-induced diffusely infarcted whole hearts and in focal acute myocardial infarction from a left coronary artery ligation). The time course of the accumulation of the agent in the focal model of infarction and subsequent washout has also been followed in vitro. Results of this kinetics demonstrate that the agent first perfuses all normal fluid spaces and then slowly diffuses into the occluded zone where it is retained for a prolonged period, in sufficient quantities to be useful as an MRI contrast agent. Wash-out of the agent from normal myocardium is fast and complete with MR signal returning to background in minutes. The specificity of Gd-DTPA-HPDP for soft-tissue calcification and its retention within the infarcts permitted imaging at 1 to 2 h postinjection, (after unbound material has cleared the normal tissues). Infarcted tissue appeared as regions of increased signal intensity in T1-weighted images (> 200% enhancement), and correlated with histopathology. Unmodified Gd-DTPA was not retained under identical conditions. Gd-DTPA-HPDP permits a more accurate infarct delineation than is possible with the unmodified agent.

Animals↗
PubMed1993

Ventricular remodeling after myocardial infarction.

Acute transmural myocardial infarction initiates a series of changes in left ventricular (LV) volume, regional function and geometry. This process, known as post-infarction LV remodeling, may continue for months or years following the initial ischemic event. To characterize the components of late ventricular remodeling, biplane left ventriculography was performed in 52 patients at 3 weeks and repeated at 1 year after first anterior myocardial infarction. Biplane circumference and contractile and noncontractile segment lengths were measured. Global geometry was evaluated by calculating a sphericity index and regional geometry was assessed by measurement of endocardial curvature. End-diastolic (ED) volume was increased at 3 weeks and enlarged further at one year. This late enlargement was accompanied by an increase in the length of the contractile segment and an increase in sphericity, whereas the length of the noncontractile segment decreased. Curvature analysis revealed that this late increase in sphericity resulted from flattening of regions of presumably high tension negative curvature at the infarct border zone and from less bulging of the infarcted anterior wall. Even in patients selected for late ventricular enlargement (change in ED volume > 20 ml, n = 19), this increase in volume resulted from both lengthening of the contractile segment and an increase in sphericity without a change in the noncontractile segment length. Thus, late ventricular enlargement after anterior myocardial infarction results from an increase in contractile segment length and a change in ventricular geometry and is not a result of progressive infarct expansion.

Adult↗
PubMed1993

Angiotensin-converting enzyme inhibition in congestive heart failure: benefit and perspective.

Therapy with angiotensin-converting enzyme (ACE) inhibitors was developed approximately 15 years ago as a novel therapeutic approach to hypertension. Although ACE inhibitor therapy was initially reserved for patients with severe hypertension, extensive clinical experience has broadened its use. These agents should now be considered as cornerstone therapy for patients with symptomatic heart failure and are of proved value in preventing the development of this syndrome. This article reviews the key studies that have documented the efficacy of ACE inhibitors in improving clinical outcome for patients with overt congestive heart failure, as well as for those with asymptomatic left ventricular dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

[Effect of captopril on mortality and morbidity in patients with dysfunction of the left ventricle after myocardial infarction. Results on survival and hypertrophic studies].

Left ventricular dilation and dysfunction after myocardial infarction are major predictors of death. In experimental and clinical studies, long-term therapy with captopril, an angiotension-converting enzyme inhibitor, decreased ventricular dilation and rearrangement. This study was undertaken to examine whether captopril may reduce morbidity and mortality in patients with left ventricular dysfunction following myocardial infarction. On days 3 to 16 after myocardial infarction, 2231 patients with <40% ejection fraction, but without signs of obvious heart failure ot symptoms of myocardial ischemia were studied in a double-blind study, of them 1116 took placebo and 1115 had captopril. The follow-up averaged 42 months. The mortabity due to any causes was significantly lower in the captopril group (228 deaths or 20% than in the placebo group (275 deaths or 25%). The decrease in the risk was 19 percent (95 percent confidence interval, 3 to 32 percent; p = 0.019). The incidence of fatal and grave nonfatal cardiovascular events significantly decreased in captopril-treated patients. The risk decrease was 21 percent (95 percent confidence interval, 5 to 35 percent; p = 0.014) for cardiovascular mortality; 37 percent (95 percent confidence interval, 20 to 50 percent; p < 0.001) for the development of severe heart failure; 22 percent (95 percent confidence, 4 to 37 percent, p = 0.019) for congestive heart failure requiring hospitalization; 25 percent (95 percent confidence interval, 5 to 40 percent; p = 0.015) for recurrent myocardial infarction. Thus, long-term captopril use in patients with asymptomatic left ventricular dysfunction following prior myocardial infarction resulted in survival improvement and decreased morbidity and mortality due to severe cardiovascular events. There were positive results both in patients treated with thrombolytics, aspirin or <$Ebeta>-blockers and in those untreated with the above drugs. This suggests that the use of captopril additionally improved the therapeutic outcomes in patients with prior myocardial infection.

Adrenergic beta-Antagonists↗
PubMed1993

The Survival and Ventricular Enlargement (SAVE) study: rationale and perspective.

Myocardial infarction increases the risk of subsequent cardiovascular events (e.g., heart failure or another myocardial infarction) among survivors as compared with the general population. Left ventricular dysfunction is among the major risk factors for such adverse events. Although reductions in cardiovascular risk have been achieved by use of aspirin, beta-blockers (and sometimes revascularization and/or serum lipid-lowering agents), the potential of angiotensin-converting enzyme (ACE) inhibitors to improve the outcome for survivors of myocardial infarction has only recently been examined. The concept that ACE inhibition might be of benefit for these patients originated from animal studies demonstrating that long-term ACE inhibition therapy attenuated left-ventricular enlargement. After clinical confirmation of this initial finding, the Survival and Ventricular Enlargement (SAVE) trial was designed to determine whether long-term ACE inhibition therapy would reduce morbidity and mortality among survivors of myocardial infarction. The SAVE study found the following risk reductions among captopril vs placebo recipients: death (all causes) 19% (95% confidence interval, 3 to 35%; p = 0.019); cardiovascular death 21% (95% confidence interval, 5 to 35%; p = 0.014); myocardial infarction 25% (95% confidence interval, 5 to 40%; p = 0.012). To the list of proved therapies that extend survival following myocardial infarction, the physician can now add ACE inhibition with captopril for patients with left ventricular dysfunction. Survivors of myocardial infarction are at heightened risk for subsequent adverse cardiovascular events.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Development and prevention of congestive heart failure following myocardial infarction.

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.

Animals↗
PubMed1992

Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators.

BACKGROUND: Left ventricular dilatation and dysfunction after myocardial infarction are major predictors of death. In experimental and clinical studies, longterm therapy with the angiotensin-converting--enzyme inhibitor captopril attenuated ventricular dilatation and remodeling. We investigated whether captopril could reduce morbidity and mortality in patients with left ventricular dysfunction after a myocardial infarction. METHODS: Within 3 to 16 days after myocardial infarction, 2231 patients with ejection fractions of 40 percent or less but without overt heart failure or symptoms of myocardial ischemia were randomly assigned to receive doubleblind treatment with either placebo (1116 patients) or captopril (1115 patients) and were followed for an average of 42 months. RESULTS: Mortality from all causes was significantly reduced in the captopril group (228 deaths, or 20 percent) as compared with the placebo group (275 deaths, or 25 percent); the reduction in risk was 19 percent (95 percent confidence interval, 3 to 32 percent; P = 0.019). In addition, the incidence of both fatal and nonfatal major cardiovascular events was consistently reduced in the captopril group. The reduction in risk was 21 percent (95 percent confidence interval, 5 to 35 percent; P = 0.014) for death from cardiovascular causes, 37 percent (95 percent confidence interval, 20 to 50 percent; P less than 0.001) for the development of severe heart failure, 22 percent (95 percent confidence interval, 4 to 37 percent; P = 0.019) for congestive heart failure requiring hospitalization, and 25 percent (95 percent confidence interval, 5 to 40 percent; P = 0.015) for recurrent myocardial infarction. CONCLUSIONS: In patients with asymptomatic left ventricular dysfunction after myocardial infarction, long-term administration of captopril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events. These benefits were observed in patients who received thrombolytic therapy, aspirin, or beta-blockers, as well as those who did not, suggesting that treatment with captopril leads to additional improvement in outcome among selected survivors of myocardial infarction.

Adult↗
PubMed1992

Do the results of randomized clinical trials of cardiovascular drugs influence medical practice? The SAVE Investigators.

BACKGROUND: Medical practice patterns change in response to a variety of stimuli, one of which may be the publication of the results of randomized clinical trials. We assessed the temporal association between the publication of clinical trials on myocardial infarction and changes in treatment practices for this disorder. METHODS: We analyzed the use of aspirin before and after myocardial infarction and that of calcium antagonists after myocardial infarction in 2231 survivors of myocardial infarction enrolled in the Survival and Ventricular Enlargement (SAVE) study over a three-year period (from January 1987 through January 1990). The proportion of patients using these treatments was analyzed before and after the publication dates of three clinical trials: the Physicians' Health Study, published in January 1988, which supported the use of aspirin to prevent a first myocardial infarction; the Second International Study of Infarct Survival (ISIS-2), published in August 1988, which supported the use of aspirin after myocardial infarction; and the Multicenter Diltiazem Postinfarction Trial, published in August 1988, which reported a deleterious effect of diltiazem in some patients after myocardial infarction. RESULTS: The use of aspirin before myocardial infarction increased from 16.2 percent to 23.9 percent between January 1987 and January 1990 (P less than 0.001). Enrollment in the study after the publication of the Physicians' Health Study independently predicted aspirin use before myocardial infarction (odds ratio, 1.43; 95 percent confidence interval, 1.11 to 1.85). The use of aspirin after myocardial infarction increased from 38.8 percent to 71.9 percent (P less than 0.001) during the three-year study period. Enrollment in the study after the publication of ISIS-2 independently predicted the use of aspirin after myocardial infarction (odds ratio, 2.28; 95 percent confidence interval, 1.89 to 2.76). The use of calcium antagonists after myocardial infarction decreased from 57.1 percent to 33.1 percent (P less than 0.001) during the study period. Enrollment in the study after the publication of the Multicenter Diltiazem Postinfarction Trial independently predicted the use of calcium antagonists after myocardial infarction (odds ratio, 0.47; 95 percent confidence interval, 0.39 to 0.57). CONCLUSIONS: These observations suggest that randomized clinical trials have a measurable influence on medical practice patterns.

Adult↗
PubMed1992

The effect of treatment on survival in congestive heart failure.

Congestive heart failure (CHF) is a disorder characterized by a variety of clinical, biochemical, electrophysiological, and hemodynamic abnormalities. During the past two decades, numerous drugs have been employed in the treatment of this complex syndrome, and many agents have been shown to improve symptoms and ventricular function in patients with CHF. Because CHF is associated with a high risk of death, treatment should be directed not only toward the relief of symptoms, but also toward a reduction in mortality. Many variables have been shown to be related to survival; taken individually, however, each is limited in its utility in predicting prognosis. In recent years, large-scale studies with large sample sizes have directly assessed the effects of treatment on mortality in CHF. Results from these trials indicate that vasodilators and angiotensin-converting enzyme (ACE) inhibitors may improve mortality in patients with symptoms of heart failure. Additional trials are now in progress to evaluate the effect of treatment on patients with asymptomatic left ventricular dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Left ventricular remodeling in the year after first anterior myocardial infarction: a quantitative analysis of contractile segment lengths and ventricular shape.

Infarct expansion after myocardial infarction results in early ventricular enlargement and distortion of ventricular geometry. To characterize the components of late volume enlargement, biplane left ventriculography was performed in 52 patients 3 weeks and 1 year after a first anterior myocardial infarction. Biplane diastolic circumference and contractile and noncontractile segment lengths were measured. Global geometry was evaluated by using a sphericity index (angiographic volume of the ventricle divided by the volume of a sphere with the same circumference). Regional geometry was assessed by measurement of endocardial curvature, an important determinant of wall tension. End-diastolic volume was enlarged at baseline and increased at 1 year (230 +/- 42 to 244 +/- 55 ml, p = 0.01) as a result of increases in contractile segment length (34 +/- 5 to 37 +/- 5 cm, p less than 0.001) and sphericity index (0.74 +/- 0.07 to 0.76 +/- 0.08, p less than 0.001), whereas the noncontractile segment length decreased (15 +/- 6 to 12 +/- 6 cm, p less than 0.005). Curvature analysis revealed a flattening of presumably high tension concavity at the anterobasal (-6.0 +/- 4.0 to -4.5 +/- 3.7, p less than 0.01) and inferior (-4.5 +/- 2.0 to -3.6 +/- 2.1, p less than 0.005) margins of the infarct and less bulging of the anterior wall (9.4 +/- 2.5 to 8.2 +/- 2.3, p less than 0.001). Patients selected for late enlargement (diastolic volume increase greater than 20 ml, n = 19) had an increase in sphericity (0.75 +/- 0.05 to 0.80 +/- 0.08, p less than 0.005) and in diastolic circumference (54 +/- 3 to 56 +/- 4 cm, p less than 0.001) secondary to elongation of the contractile segment (32 +/- 4 to 36 +/- 4 cm, p = 0.001) at 1 year. Thus, late ventricular enlargement after anterior infarction results from an increase in contractile segment length and a change in ventricular geometry and is not a result of progressive infarct expansion. In the group of patients at high risk for late ventricular enlargement because of persistent occlusion of the infarct-related vessel, captopril therapy attenuated late volume enlargement by preventing these changes in contractile segment length and chamber geometry.

Adult↗
PubMed1991

Rationale and design of a secondary prevention trial of lowering normal plasma cholesterol levels after acute myocardial infarction: the Cholesterol and Recurrent Events trial (CARE)

Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol decreases the incidence of coronary heart disease in patients with elevated plasma cholesterol. However, it is not known whether patients with established coronary artery disease and normal plasma cholesterol can be benefited. Several previous prevention trials reviewed in this report found that patients who had plasma cholesterol levels at baseline in the upper portion of the eligibility range (e.g., greater than 240 mg/dl) received greater benefit from hypolipidemic diet or drug therapy than patients who had lower plasma cholesterol levels at baseline. The recent availability of drugs that are more potent and less prone to cause adverse reactions than previous regimens permits this important question to be addressed. The Cholesterol and Recurrent Events trial is testing whether pravastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, will decrease the sum of fatal coronary heart disease and nonfatal myocardial infarction (MI) in patients who have recovered from a MI and who have normal total cholesterol levels. Fatal cardiovascular disease and total mortality are important secondary end points. The trial is enrolling 4,000 men and women from 80 centers throughout North America, age 21 to 75 years, who have survived MI for 3 to 20 months, who have plasma total cholesterol less than 240 mg/dl (6.2 mmol/liter) and low-density cholesterol of 115 to 174 mg/dl (3.0 to 4.5 mmol/liter), and who are representative of the general population of patients with MI. Patients are randomized to either active or inactive drug therapy. Active therapy consists of pravastatin, 40 mg/day, designed to achieve an average decrease in low-density lipoprotein cholesterol of approximately 30%, and an increase in high-density lipoprotein of 5%. The average duration of follow-up will be greater than or equal to 5 years. To protect against a lower than expected rate of recurrent events, the trial will be continued until a predetermined fixed number of coronary heart disease events occurs in the entire cohort so that the original sensitivity of the trial will be maintained.

Adult↗
PubMed1991

Ventricular enlargement and remodeling following acute myocardial infarction: mechanisms and management.

Severe myocardial ischemia, when sustained, leads to a predictable sequence of events, including myocardial necrosis, expansion of the infarct, and later its replacement by scar tissue. The nonischemic tissue sustains ventricular function, but it frequently adapts to the extra load placed on it by dilating. The enlargement and remodeling of the left ventricle may lead to ventricular failure and arrhythmias. Rational management to prevent these complications includes restoration of the patency of the occluded vessel and ventricular unloading. These two interventions may be useful both early and late in the course of infarction.

Cardiomegaly↗
PubMed1991

Patency of the infarct-related coronary artery and ventricular geometry.

The pathogenesis of acute myocardial infarction (AMI) involves a sudden thrombotic occlusion of a coronary artery. Spontaneous or pharmacologic thrombolysis may lead to myocardial salvage if patency is achieved within a narrow time window. However, patients in whom thrombolysis occurs late seem to demonstrate improved left ventricular (LV) function and prognosis, which may be independent of myocardial salvage. Preservation of normal LV geometry by reducing expansion of the infarcted segment is a likely mechanism for this benefit. Infarct expansion is most pronounced in patients with anterior wall AMI who have a persistently occluded infarct-related vessel. This process of expansion leads to early increases in LV volume and distortions of LV contour (abnormal LV geometry). Patients whose infarct segment is largest, patients who have manifested infarct expansion, and patients with a persistently occluded infarct-related artery are at highest risk for progressive LV dilation. Experimental data support the concept that reperfusion of occluded vessels that occurs too late for myocardial salvage will preserve LV geometry by limiting infarct expansion. Prospective clinical trials should address whether there is a late, "second time window" during which infarct expansion and distortions of LV geometry may be reduced by (1) therapy with thrombolytic agents applied late after infarction, (2) late mechanical reperfusion with percutaneous transluminal coronary angioplasty (PTCA) or related methods, and (3) load-reducing agents to decrease remodeling, such as angiotensin-converting enzyme inhibitors or nitroglycerin.

Animals↗