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Showing papers by "Marc A. Pfeffer published in 1994"


Journal ArticleDOI
TL;DR: This study demonstrates the linkage between attenuation of left ventricular enlargement by captopril after infarction and improved clinical outcome and two-dimensional echocardiography provides important and independent prognostic information in patients afterinfarction.
Abstract: BACKGROUNDLeft 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 RESULTSTwo-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 hospitaliz...

819 citations


Journal ArticleDOI
TL;DR: The finding that the recurrence of MI was independent ofLeft ventricular ejection fraction suggests that captopril could be useful in preventing recurrent MI in patients with more preserved left ventricular function and either an anti-ischemic effect or the ability to modify the atherosclerotic process in survivors of MI.
Abstract: BACKGROUNDIn 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 RESULTSThe 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 (...

336 citations



Journal ArticleDOI
TL;DR: It is demonstrated 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.
Abstract: 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.

201 citations


Journal ArticleDOI
TL;DR: The SAVE study as discussed by the authors showed 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.
Abstract: 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.

84 citations


Journal ArticleDOI
TL;DR: 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.
Abstract: 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.

54 citations


Journal ArticleDOI
TL;DR: Although a component ofleft 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.
Abstract: 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.

43 citations


Journal ArticleDOI
TL;DR: 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 globalleft ventricular function and on clinical prognosis.
Abstract: 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.

31 citations


Journal ArticleDOI
TL;DR: In view of high intra-and inter-subject variability in buspirone concentrations, definitive dosing recommendations for patients with compromised renal or hepatic function could not be made, but such patients should initially be dosed cautiously with buspir one.
Abstract: The single dose and steady-state pharmacokinetics of buspirone and its metabolite 1-pyrimidinyl piperazine (1-PP) have been evaluated in normal volunteers and patients with renal or hepatic impairment, using a parallel group design, with assignment of patients to study group on the basis of the degree of renal (mild, moderate, severe) or hepatic (compensated or decompensated) impairment. Each healthy volunteer or patient received a single dose of 10 mg buspirone on Day 1 of the study, and starting 36 h after the first dose, healthy volunteers and patients received 10 mg doses of buspirone every 12 hours for 9 days. On the morning of Day 10 they received the last dose. Serial blood samples were collected on Days 1, 5 and 10 and plasma was analysed for buspirone and 1-PP. The plasma concentrations of buspirone and 1-PP were highly variable regardless of the renal or hepatic function. The peak concentrations (Cmax) and area under the curves (AUC) of buspirone and 1-PP on Days D 5 and 10 were higher than on Day D 1. The trough levels (Cmin) and AUCs (D 5 and 10) of buspirone and 1-PP indicated, that, regardless of renal or hepatic function, steady state was reached after 3 to 5 days of dosing. At steady-state, patients with renal or hepatic impairment had significantly higher Cmax and AUC values of buspirone than in normal volunteers. However, the intensity and frequency of adverse experiences in patients with renal or hepatic impairment were not significantly different from those observed in normal volunteers. There was no correlation between the average plasma concentrations of buspirone (\(\bar C\)) and the degree of renal impairment judged by creatinine clearance. An excellent correlation was observed between \(\bar C\) of buspirone and serum albumin (r=0.862, and P<0.0001) as well as between \(\bar C\) and bromsulphalein clearance (r=0.678, P<0.0003).

31 citations


01 Dec 1994
TL;DR: Dipyridamole infusion determined a significant increase in heart rate and rate pressure-product in all patients (both in positive and in negative), whereas calcium induced a slight, not significant decrease of these parameters.
Abstract: In the first part of the study 5 control subjects were submitted to iv infusion of 0.2 mM/kg of calcium gluconate in 20 min. Total calcium (atomic absorbtion method), ionized calcium (ion-selective electrode method) and adenosine (HPLC technique) were measured at the following times: 0 (baseline), 5, 10, 15, 20 (end of infusion), 25, 30, 35, and 50 min. The increase of total and ionized calcium serum levels was associated with a significant increase of adenosine plasma levels (from 207 +/- 41 to 362 +/- 63 nM, p < 0.001). Since the increase of adenosine plasma levels, obtained either with adenosine or dipyridamole (an adenosine reuptake inhibitor), has been used to test the coronary reserve in patients with coronary artery disease (CAD), in the second part of the study we compared the effects of calcium infusion with dipyridamole in 15 CAD subjects. Pharmacological stress tests were evaluated by monitoring two-dimensional echocardiography, ECG, heart rate, blood pressure and rate-pressure product. Ten patients were positive both to dipyridamole stress test and to calcium infusion, ad demonstrated by the onset of new areas of transient asynergy in the same myocardial regions. Dipyridamole infusion determined a significant increase in heart rate and rate pressure-product in all patients (both in positive and in negative), whereas calcium induced a slight, not significant decrease of these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

21 citations



Journal ArticleDOI
TL;DR: Clinical observations point to an important potentially modifiable interface between the renin-angiotensin system and the risk of experiencing a coronary atherosclerotic event, supported by observation from the Studies of Left Ventricular Dysfunction studies.

01 Dec 1994
TL;DR: 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.
Abstract: 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.