PubMed Health⌕ Search

Biomedical subjects

M A Pfeffer

Publications and source records attributed to M A Pfeffer.

At least 91 records · Page 5Linked to original sources
PubMed1995

Effect of infarct artery patency on prognosis after acute myocardial infarction. The Survival and Ventricular Enlargement Investigators.

BACKGROUND: In patients with acute myocardial infarction (MI), early restoration of patency of the infarct-related artery (IRA) leads to preservation of left ventricular function and improved clinical outcome. However, there is evidence that the benefits associated with a patent IRA are out of proportion to the observed improvement in ventricular function and may result not only from salvage of ischemic myocardium but also from the opening of the IRA beyond a narrow postinfarct time window. The objectives of this study were (1) to assess the effect of IRA patency on outcome of patients after acute MI with left ventricular dysfunction while controlling for differences in left ventricular ejection fraction and the extent of coronary disease and (2) to determine the effect of angiotensin-converting enzyme (ACE) inhibitor therapy on patients with patent as well as occluded infarct arteries. METHODS AND RESULTS: The Survival and Ventricular Enlargement (SAVE) study consisted of 2231 patients with a documented MI and a left ventricular ejection fraction < or = 40%. They were randomized to the ACE inhibitor captopril (50 mg TID) or placebo 3 to 16 days after MI and were followed for an average of 3.5 years. Left ventricular ejection fraction, measured with radionuclide left ventriculography, was repeated at the end of the follow-up period. The 946 patients in whom the patency of the IRA was established before randomization form the basis of this study. At cardiac catheterization averaging 4.2 days after infarction, 30.7% of patients had an initially occluded IRA. After revascularization, 162 of the 946 patients (17.1%) were left with an occluded IRA at the time of randomization. The 162 patients with persistently occluded IRAs and 784 with patent IRAs had similar clinical baseline characteristics, but those with occluded arteries had a slightly lower ejection fraction than the 784 patients with patent infarct arteries (30% versus 32%, P = .01). Cox proportional-hazards analyses showed that the independent predictors of all-cause mortality were hypertension (relative risk [RR] 1.94, P < .001), number of diseased coronary arteries (RR 1.68, P < .001), occluded IRA (RR 1.49, P = .039), ejection fraction (RR 1.36, P < .001), age (RR 1.10, P = .030), and use of beta-adrenergic receptor blocking agents (RR 0.60, P = .007). Independent predictors of a composite end point consisting of cardiovascular mortality, morbidity, or reduction of ejection fraction of > or = 9 units were occluded IRA (odds ratio [OR] 1.73, P = .002), hypertension (OR 1.71, P < .001), number of diseased vessels (OR 1.38, P < .001), ejection fraction (OR 1.18, P = .003), use of beta-adrenergic receptor blocking agents (OR 0.67, P = .007), and randomization to captopril (OR 0.70, P = .009). CONCLUSIONS: IRA patency within 16 days after MI predicts a favorable clinical outcome, independent of the number of obstructed coronary arteries or of left ventricular function. The beneficial effect of ACE inhibition is independent of patency status of the IRA. These findings support the need for additional, prospective clinical trials of late reperfusion in MI patients.

Adrenergic beta-Antagonists↗
PubMed1995

Arrhythmias and death after coronary artery occlusion in the rat. Continuous telemetric ECG monitoring in conscious, untethered rats.

BACKGROUND: The onset of acute myocardial infarction (MI) is accompanied by a rapid increase in electrical instability and often fatal ventricular arrhythmias. The aim of this study was to assess the continuous arrhythmia profile during the initial 48 hours after coronary artery ligation in the rat in relation to time course, mortality, and infarct size. METHODS AND RESULTS: Continuous ECG recording were obtained in 26 conscious, untethered rats for 24 hours before and 48 hours after coronary ligation by use of an implantable telemetry system. All episodes of ventricular tachycardia and fibrillation were counted and their durations summed. Infarct size was measured at 48 hours after MI or after spontaneous death. After ligation, two distinctly active arrhythmogenic periods developed (A1, 0 to 0.5 hours; A2, 1.5 to 9 hours), each followed by a quiescent phase of low ectopy (Q1, 0.5 to 1.5 hours; Q2, 10 to 48 hours). The total mortality rate of 65% was found within the two active periods, with 13 of 15 deaths occurring in A2. Rats with larger infarcts (> or = 50%) and nonsurvivors tended to have increased arrhythmia frequency and duration compared with both animals with smaller MIs (< 50%) and survivors. CONCLUSIONS: Two distinct arrhythmogenic periods occur in rats with acute MI that may be caused by different mechanisms and correspond to the bimodal arrhythmia time course seen in dogs and humans after acute MI. Telemetric monitoring of the ECG in the conscious rat after infarction will be useful in assessment of the differential effects of therapeutic interventions on these two arrhythmogenic periods and in the study of potential mechanisms for the spontaneous resolution of ventricular ectopy and risk of sudden death.

Animals↗
PubMed1995

A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease.

BACKGROUND: In a previous study, men with a history of myocardial infarction were found to have an increased prevalence of homozygosity for the deletional allele (D) of the angiotensin-converting-enzyme (ACE) gene. The D allele is associated with higher levels of ACE, which may predispose a person to ischemic heart disease. We investigated the association between the ACE genotype and the incidence of myocardial infarction, as well as other manifestations of ischemic heart disease, in a large, prospective cohort of U.S. male physicians. METHODS: In the Physicians' Health Study, ischemic heart disease as defined by angina, coronary revascularization, or myocardial infarction developed in 1250 men by 1992. They were matched with 2340 controls according to age and smoking history. Zygosity for the deletion-insertion (D-I) polymorphism of the ACE gene was determined by an assay based on the polymerase chain reaction. Data were analyzed for both matched pairs and unmatched samples, with adjustment for the effects of known or suspected risk factors by conditional and nonconditional logistic regression, respectively. RESULTS: The ACE genotype was not associated with the occurrence of either ischemic heart disease or myocardial infarction. The adjusted relative risk associated with the D allele was 1.07 (95 percent confidence interval, 0.96 to 1.19; P = 0.24) for ischemic heart disease and 1.05 (95 percent confidence interval, 0.89 to 1.25; P = 0.56) for myocardial infarction, if an additive mode of inheritance is assumed. Additional analyses assuming dominant and recessive effects of the D allele also failed to show any association, as did the examination of low-risk subgroups. CONCLUSIONS: In a large, prospectively followed population of U.S. male physicians, the presence of the D allele of the ACE gene conferred no appreciable increase in the risk of ischemic heart disease or myocardial infarction.

Alleles↗
PubMed1995

Cost-effectiveness of captopril therapy after myocardial infarction.

OBJECTIVES: This study sought to assess the cost-effectiveness of captopril therapy for survivors of myocardial infarction. BACKGROUND: The recent randomized, controlled Survival and Ventricular Enlargement (SAVE) trial showed that captopril therapy improves survival in survivors of myocardial infarction with an ejection fraction < or = 40%. The present ancillary study was designed to determine how the costs required to achieve this increase in survival compared with those of other medical interventions. METHODS: We developed a decision-analytic model to assess the cost-effectiveness of captopril therapy in 50- to 80-year old survivors of myocardial infarction with an ejection fraction < or = 40%. Data on costs, utilities (health-related quality of life weights) and 4-year survival were obtained directly from the SAVE trial, and long-term survival was estimated using a Markov model. In one set of analyses, we assumed that the survival benefit associated with captopril therapy would persist beyond 4 years (persistent-benefit analyses), whereas in another set we assumed that captopril therapy incurred costs but no survival benefit beyond 4 years (limited-benefit analyses). RESULTS: In the limited-benefit analyses, the incremental cost-effectiveness of captopril therapy ranged from $3,600/quality-adjusted life-year for 80-year old patients to $60,800/quality-adjusted life-year for 50-year old patients. In the persistent-benefit analyses, incremental cost-effectiveness ratios ranged from $3,700 to $10,400/quality-adjusted life-year, depending on age. The outcome was generally not sensitive to changes in estimates of variables when they were varied individually over wide ranges. In a "worst-case" analysis, incremental cost-effectiveness ratios for captopril therapy remained favorable ($8,700 to $29,200/quality-adjusted life-year) for 60- to 80-year old patients but were higher ($217,600/quality-adjusted life-year) for 50-year old patients. CONCLUSIONS: We conclude that the cost-effectiveness of captopril therapy for 50- to 80-year old survivors of myocardial infarction with a low ejection fraction compares favorably with other interventions for survivors of myocardial infarction.

Aged↗
PubMed1995

Role of the fibrinolytic system in preventing myocardial infarction.

Activation of the renin-angiotensin system (RAS) has been implicated in the pathogenesis of acute myocardial infarction (AMI). Similarly, reduced fibrinolytic activity has been associated with an increased risk of AMI. Evidence is now accumulating that the RAS plays an important role in the regulation of fibrinolysis and that pharmacological interruption of the RAS exerts a positive effect on endogenous fibrinolytic balance. This relationship appears to provide a partial explanation for the newly recognized effect of angiotensin converting enzyme inhibitors in preventing AMI.

Angiotensin II↗
PubMed1995

Left ventricular remodeling after acute myocardial infarction.

The loss of myocytes as a consequence of myocardial infarction results in a prompt reduction in regional wall motion and often leads to more protracted and progressive changes in ventricular architecture. The recognition that the process of ventricular enlargement following myocardial infarction is modifiable provided the initial rationale for the use of angiotensin-converting enzyme (ACE) inhibitors as therapy to prevent deterioration in ventricular size and function following infarction. Experimental and clinical studies have documented the effectiveness of this therapy in preventing this late enlargement following infarction. Increasing clinical evidence indicates that this new use of ACE inhibitor therapy in survivors of acute myocardial infarction will lead to an improvement in clinical outcome.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Post-myocardial infarction ventricular remodeling: animal and human studies.

Segmental alterations in left ventricular function are generally present in patients who suffer an acute myocardial infarction. Regional wall motion abnormalities in left ventricular systolic function can be identified in the hyperacute period and generally persist in patients who complete a myocardial infarction. Through the process of infarct expansion, the infarcted territory may thin and lengthen in the short term following a myocardial infarction. Some infarct survivors are also prone to further progressive alterations in the shape and size of the left ventricle, a process that has been termed postinfarction ventricular remodeling. Although left ventricular remodeling appears to represent an adaptive process serving to preserve stroke volume (and cardiac output) following myocardial injury, the enlargement process may have undesirable long-term effects on global left ventricular function and on clinical prognosis. Fortunately, recent experimental and clinical evidence demonstrates that ventricular remodeling and its deleterious consequences may be preventable.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Mechanistic lessons from the SAVE Study. Survival and Ventricular Enlargement.

The Survival and Ventricular Enlargement (SAVE) study was designed to test the hypothesis that chronic use of the angiotensin-converting enzyme (ACE) inhibitor captopril in survivors of myocardial infarction with left ventricular dysfunction would prevent a further deterioration of ventricular function and thereby improve clinical outcome. The study did demonstrate that randomization to the ACE inhibitor resulted in improved survival and, specifically, lessened cardiovascular deaths. The prestudy rationale that less ventricular enlargement would be observed in ACE inhibitor treated patients was validated by an echocardiographic substudy. As anticipated, fewer patients treated with the ACE inhibitor went on to manifest the prespecified definitions of more overt congestive heart failure. Importantly, not only were the manifestations of congestive heart failure reduced, there were fewer fatal events subsequent to development of failure. Although this concept of attenuation of progressive remodeling leading to benefits was upheld, the study also yielded other observations to support the generation of new hypotheses to explain a component of the overall benefit of ACE inhibitor therapy. Particularly attractive, and supported by observation from the Studies of Left Ventricular Dysfunction (SOLVD) studies, is the reduction in myocardial infarction and subsequent death following myocardial infarction with chronic ACE inhibitor therapy. These clinical observations point to an important potentially modifiable interface between the renin-angiotensin system and the risk of experiencing a coronary atherosclerotic event.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Angiotensin converting enzyme inhibitors and cardiovascular remodelling.

Regional alterations in left ventricular function are generally present in patients who sustain an acute myocardial infarction. Segmental wall motion abnormalities in left ventricular systolic function can be identified in the hyperacute period and generally persist in patients with myocardial infarction. Through the process of infarct expansion, the infarcted territory may thin and lengthen in the short term following a myocardial infarction. Some infarct survivors are also prone to further progressive alterations in the shape and size of the left ventricle, a process that has been termed "postinfarction ventricular remodelling". Although a component of left ventricular remodelling appears to represent an adaptive process serving to preserve stroke volume and cardiac output following myocardial injury, the enlargement process may have undesirable long term effects on global left ventricular function and on clinical prognosis. Fortunately, recent experimental and clinical evidence shows that ventricular remodelling and its deleterious consequences may be preventable.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Uniformity of captopril benefit in the SAVE Study: subgroup analysis. Survival and Ventricular Enlargement Study.

The Survival and Ventricular Enlargement (SAVE) Study demonstrated that long-term administration of the angiotensin-converting enzyme inhibitor captopril to recent survivors of myocardial infarction with left ventricular dysfunction resulted in a reduction in cardiovascular mortality and morbidity. Analysis of multiple subgroups demonstrated that baseline demographics (older age) and clinical characteristics (such as prior MI, history of diabetes or hypertension), that have previously been associated with a higher risk of cardiovascular events, were associated with greater end point event rates in SAVE regardless of therapy assignment at the time of randomization. The effectiveness of captopril therapy in reducing cardiovascular mortality and morbidity was examined in multiple subgroups. Although not all subgroups provided adequate statistical power, the benefits of captopril therapy were relatively uniform in the SAVE study. This indicates that the benefits were not confined to one particular subgroup and conversely that targeting of captopril therapy should be to the broadest group, as defined by SAVE entry criteria, to result in a reduction in cardiovascular mortality and morbidity.

Captopril↗
PubMed1994

Measurement of aortic input impedance in rats.

Measurement of aortic input impedance in the rat is complicated by a high basal heart rate but is possible if appropriate compensation is made for frequency-dependent errors in modulus and phase resulting from analog filters in the equipment and from nonalignment of pressure and flow sensors. Because input impedance is a complex quantity, accurate values for both phase and modulus are required before meaningful interpretation of the data can be made. We measured aortic pressure and electromagnetic ascending aortic blood flow in mature, ether-anesthetized, open-chest male Wistar rats. Pressure and flow waveforms were averaged in the time domain and converted to Fourier series. Flow moduli were corrected for the measured frequency response of the flowmeter. Phase spectra were corrected by the classic frequency-domain and two new time-domain methods. Compensation for instrumentation errors was assessed at two different flowmeter filter settings in five animals. Reproducibility, variability, and the effects of vasoconstriction were assessed in 43 animals. Three methods of estimating characteristic impedance from the impedance spectra were evaluated and found to produce comparable results at baseline and following pharmacological elevation of blood pressure with graded methoxamine infusion. Physiologically equivalent values for phase, as assessed by comparing oscillatory power calculated from the impedance spectra, were obtained with each of the phase-correction techniques. The new time-domain methods facilitate the assessment of aortic input impedance in this small animal model because they do not require measurement of the spatial separation between pressure and flow transducers and pulse wave velocity in the proximal aorta.

Analysis of Variance↗
PubMed1994

Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. The protective effects of captopril.

BACKGROUND: Left ventricular enlargement after myocardial infarction increases the likelihood of an adverse outcome. In an echocardiographic substudy of the Survival and Ventricular Enlargement (SAVE) Trial, we assessed whether captopril would attenuate progressive left ventricular enlargement in patients with left ventricular dysfunction after acute myocardial infarction and, if so, whether this would be associated with improved clinical outcome. METHODS AND RESULTS: Two-dimensional transthoracic echocardiograms were obtained in 512 patients at a mean of 11.1 +/- 3.2 days after infarction and were repeated at 1 year in 420 survivors. Left ventricular size was assessed as left ventricular cavity areas at end diastole and end systole and left ventricular function as percent change in cavity area from end diastole to end systole. Patients were randomly assigned to placebo or captopril, and the incidence of adverse cardiovascular events consisting of cardiovascular death, heart failure requiring either hospitalization or open-label angiotensin-converting enzyme inhibitor therapy, and recurrent infarction were determined over a follow-up period averaging 3.0 +/- 0.6 years. Irrespective of treatment assignment, baseline left ventricular systolic area and percent change in area were strong predictors of cardiovascular mortality and adverse cardiovascular events. At 1 year, left ventricular end-diastolic and end-systolic areas were larger in the placebo than in the captopril group (P = .038, P = .015, respectively), and percent change in cavity area was greater in the captopril group (P = .005). One hundred eleven of the 420 1-year survivors with 1-year echo measurements (26.4%) experienced a major adverse cardiovascular event, and these patients had more than a threefold greater increase in left ventricular cavity areas than those with an uncomplicated course. Sixty-nine patients with adverse cardiovascular events were in the placebo group compared with 42 patients in the captopril-treated group (a risk reduction of 35%, P = .010). CONCLUSIONS: Two-dimensional echocardiography provides important and independent prognostic information in patients after infarction. Left ventricular enlargement and function after infarction are associated with the development of adverse cardiac events. Attenuation of ventricular enlargement with captopril in these patients was associated with a reduction in adverse events. This study demonstrates the linkage between attenuation of left ventricular enlargement by captopril after infarction and improved clinical outcome.

Captopril↗