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Biomedical subjects

M A Pfeffer

Publications and source records attributed to M A Pfeffer.

At least 127 records · Page 7Linked to original sources
PubMed1991

Rationale, design and baseline characteristics of the survival and ventricular enlargement trial. SAVE Investigators.

Heart failure, often associated with ventricular enlargement and recurrent myocardial infarction, is one of the major causes of postinfarction mortality. This observation suggests that measures used to prevent ventricular enlargement may improve postinfarction survival. The Survival and Ventricular Enlargement (SAVE) trial is a randomized, double-blind, placebo-controlled clinical trial with the purpose of evaluating the effect of angiotensin-converting enzyme (ACE) inhibition on postinfarction death and ventricular dilation. This multicenter trial had a sample size goal of 2,220 patients between 21 and 79 years of age who had recently sustained a myocardial infarction and who have an ejection fraction determined by radionuclide ventriculogram (RVG-EF) of less than or equal to 40%. In addition to conventional therapy, patients were randomly assigned to captopril or placebo therapy commencing within 3-16 days following their myocardial infarction. A second RVG-EF is performed on all surviving participants at the end of the average 3.5-year treatment and follow-up period. The study has 90% power to detect a 25% improvement in postinfarction mortality or prevention of greater than or equal to 9 unit absolute reduction in radionuclide ejection fraction. Additional end points, design features, and the administrative organization of the trial are described.

Adult↗
PubMed1991

Ventricular enlargement following infarction is a modifiable process.

The dilation and distortion of the left ventricle that may occur as a consequence of myocardial infarction are associated with a heightened risk for adverse cardiovascular events. Infarcts that are extensive, transmural, and involve the apex as well as persistently occluded, infarct-related coronary arteries are predisposing factors for ventricular enlargement. Infarct expansion is an early component of the overall process of volume enlargement, which later continues as a volume overload hypertrophy of the remaining myocardium. Therapy to limit myocardial necrosis has been associated with the preservation of a more normal ventricular architecture. The late phase of ventricular remodeling has also been shown to be amendable to therapy, as chronic administration of angiotensin-converting enzyme (ACE) inhibitors has been associated with a reduction in the extent of ventricular dilation. There is currently a great deal of clinical investigative interest not only in whether ACE inhibition therapy following acute myocardial infarction will result in preservation of ventricular volume and topography, but, more importantly, whether it will lead to an improvement in clinical outcome.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Left ventricular remodeling after acute myocardial infarction: clinical course and beneficial effects of angiotensin-converting enzyme inhibition.

LV enlargement is an important determinant of survival after AMI. Pathophysiologic mechanisms leading to LV dilatation after an AMI include early thinning and stretching of the infarcted segment (e.g., infarct expansion) and hypertrophy of the noninfarcted myocardium. Such LV dilatation may adversely affect subsequent cardiac function, leading to heart failure and death. Experimental data in animals and preliminary studies in humans have demonstrated that early administration of captopril, an angiotensin-converting enzyme inhibitor, may limit infarct expansion and will attenuate progressive LV dilatation. This article discussed the clinical importance of the dilated left ventricle and reviewed advances and ongoing research in the use of angiotensin-converting enzyme inhibitors in the chronic phase after AMI.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Progressive ventricular remodeling in rat with myocardial infarction.

Ventricular dilatation may have important prognostic implications for the survival of patients with left ventricular (LV) dysfunction. To determine the manner and extent to which the left ventricle of the rat remodels and dilates after myocardial infarction, we obtained the passive pressure-volume relationships, chamber stiffness constants, and mass during both the early and late phases. In moderate and large infarcts as inflammation and edema developed, LV weight increased then progressively decreased as a thin scar formed, returning to normal values as a result of compensatory hypertrophy of the residual myocardium. LV dilatation occurred in all rats with infarcts but to different extents depending on infarct size and duration. In the early postinfarction phase, pressure-volume relationship was relatively unchanged in all infarct-size groups, except for significant rightward shift in low pressure range for rats with moderate and large infarcts and significant leftward shift in high pressure range for rats with small infarcts. During resolution of the inflammatory response, LV dilatation occurred in all infarct groups in relation to infarct size. As scar formation became complete, LV enlargement did not progress in rats with small infarcts but did so in rats with moderate and large infarcts. LV chamber stiffness remained within the range of normal values during the early phase in all rats with infarcts but decreased significantly during the late phase in rats with moderate and large infarcts in association with the extent of ventricular enlargement. Alterations in the volume-to-mass ratio (V/Vwt) were most marked in the late postinfarction phase, wherein both volume (increased) and mass (decreased, then increased) changed dramatically and V/Vwt progressively increased in rats with large infarcts.

Animals↗
PubMed1991

Angiotensin converting enzyme inhibition therapy following myocardial infarction. Rationale for clinical trials.

Progressive enlargement following myocardial infarction can be anticipated to adversely effect outcome since prognosis is intimately related to the degree of left ventricular dysfunction and resultant ventricular cavity size. Recent experimental and clinical data have indicated that chronic angiotensin converting enzyme inhibitor therapy can be effective in attenuating the ventricular enlargement which occurs following infarction. These observations have provided a rationale for ongoing large multicenter clinical trials designed to determine whether angiotensin converting enzyme inhibition will be of clinical benefit following infarction. This article reviews the rationale for studies of angiotensin converting enzyme inhibition in post-infarct patients and summarizes the ongoing international research effort to fully define the role of angiotensin converting enzyme inhibition following infarction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Role of left ventricular dysfunction in selective neurohumoral activation in the recovery phase of anterior wall acute myocardial infarction.

Neurohumoral activation is readily apparent in patients with symptomatic congestive heart failure (CHF) and in the acute phase after acute myocardial infarction. In this study, the neurohumoral profiles of 36 asymptomatic patients in the early convalescent phase after acute myocardial infarction were examined. All patients in the study had a radionuclide ejection fraction less than or equal to 45% and underwent cardiac catheterization 11 to 30 days after infarction. Venous blood samples were obtained in the supine state for the measurement of norepinephrine, angiotensin II, plasma renin activity and aldosterone in all patients. Despite the reduced ejection fraction and extensive wall motion abnormalities, plasma norepinephrine was not elevated and did not correlate with any measured hemodynamic, angiographic or clinical variables. The renin-angiotensin II aldosterone system was activated, as expected, in the 9 study patients receiving loop diuretics. However, even in the 27 patients not taking diuretics, plasma angiotensin II and renin activity levels were increased in relation to Killip classification, the presence of a left ventricular (LV) aneurysm and LV ejection fraction. Activation of the renin-angiotensin-aldosterone system can be identified in hemodynamically compensated postinfarction patients not taking diuretics and appears to be related to the extent of LV dysfunction.

Aged↗
PubMed1990

Systemic hemodynamic effects of endothelin in rats.

Endothelin type 1 (ET-1) is an endothelial cell-derived 21-amino acid peptide with potent contractile effects on isolated vascular smooth muscle. The systemic hemodynamic effects of bolus intravenous injections of ET-1 and angiotensin II (ANG II, 300 pmol) were examined in anesthetized male Munich-Wistar rats by measurements of mean arterial (AP) and right atrial (RAP) blood pressures and cardiac index (CI, electromagnetic flowmetry) over a 60-min period. ET-1 induced a biphasic pressure response: transient hypotension occurred in the early phase with all doses, followed by a more prolonged dose-dependent elevation of blood pressure in the late phase. Because CI was unchanged during the early phase, the hypotension resulted from systemic vasodilation. On the other hand, the marked rise in AP produced by 300 pmol of ET-1 in the late phase was associated with a significant fall in CI, and thus total peripheral resistance index (TPRI) increased profoundly. A fall in right atrial pressure and significant hemoconcentration were associated with this pronounced vasoconstrictor effect, suggesting that a contraction of plasma volume contributed to the reduction of CI. Additionally, stroke and minute work indexes and peak flow velocity became significantly reduced in the late phase for the 300-pmol dose of ET-1. When compared with an equimolar dose of ET-1, 300 pmol of ANG II produced a prompt, more marked, but shorter-lived rise in AP with minimal changes in CI, TPRI, RAP, and hematocrit. These results raise the intriguing possibility that endothelin may play a role in both the control of normal vascular smooth muscle tone and in the pathogenesis of vasospastic disorders.

Angiotensin II↗
PubMed1990

Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications.

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.

Adaptation, Physiological↗
PubMed1989

Effects of left ventricular shape and captopril therapy on exercise capacity after anterior wall acute myocardial infarction.

The importance of left ventricular (LV) shape in determining exercise capacity was assessed in 40 male patients with LV dysfunction after anterior acute myocardial infarction (AMI). Because captopril therapy is known to improve exercise capacity in this patient population, the potential interaction between LV shape and captopril therapy was also evaluated. Patients underwent cardiac catheterization 2 to 4 weeks after AMI followed by randomization to receive placebo or captopril. LV shape was defined from biplane ventriculography by a sphericity index (volume observed/volume of sphere using long axis as diameter). Quarterly clinical assessments and maximal exercise testing were performed. A cumulative heart failure score, specific activity scale and average exercise time for the year were calculated. A greater shape distortion (increasing sphericity index) was associated with increased LV volumes, decreased ejection fraction and a larger abnormally contracting segment. Sphericity index was the only independent predictor of average exercise duration in the placebo group. Placebo-treated patients in the tercile with the most spherical ventricles had not only the lowest exercise capacity (p less than 0.01), but also accumulated the highest heart failure (p less than 0.05) and specific activity scale (p less than 0.05) scores. Captopril-treated patients with the same baseline distortion of LV shape did not manifest these shape-dependent objective and subjective measures of reduced functional capacity.

Adult↗
PubMed1988

Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction.

We conducted a double-blind, placebo-controlled trial to determine whether ventricular dilatation continues during the late convalescent phase after myocardial infarction and whether therapy with captopril alters this process. Fifty-nine patients with a first anterior myocardial infarction and a radionuclide ejection fraction of 45 percent or less underwent cardiac catheterization 11 to 31 days after infarction, when they were not in overt congestive heart failure. They were randomly assigned to placebo or captopril and were followed for one year. A repeat catheterization was performed to evaluate interval changes in hemodynamic function and left ventricular volume. Thirty-eight male patients were evaluated with maximal-exercise treadmill tests every three months. No differences were detected at base line in clinical, hemodynamic, or quantitative ventriculographic variables. During one year of follow-up, the end-diastolic volume of the left ventricle increased by a mean [+/- SEM] of 21 +/- 8 ml (P less than 0.02) in the placebo group, but by only 10 +/- 6 ml (P not significant) in the captopril group. The left ventricular filling pressure remained elevated with placebo but decreased (P less than 0.01) with captopril. In a subset of 36 patients who were at high risk for ventricular enlargement because they had persistent occlusion of the left anterior descending coronary artery, captopril prevented further ventricular dilatation (P less than 0.05). Patients given captopril also had increased exercise capacity (P less than 0.05). This preliminary study indicates that after anterior myocardial infarction, ventricular enlargement is progressive and that captopril may attenuate this process, reduce filling pressures, and improve exercise tolerance.

Captopril↗
PubMed1988

Left ventricular thrombus formation after first anterior wall acute myocardial infarction.

The characteristics of the left ventricle and coronary arteries associated with left ventricular (LV) thrombus in patients with recent anterior acute myocardial infarction were defined. Of 77 patients studied, 35 (46%) had LV thrombi. The presence of LV thrombus was not correlated to the extent of coronary artery disease. The frequency of LV thrombus progressively increased with groups of increasing wall motion abnormality as determined by the extent of akinesia and dyskinesia (%AD) (%AD 0 to 14, thrombus present in 3 of 16 [19%], %AD 15 to 29, thrombus in 8 of 27 [30%]; %AD greater than or equal to 30%, thrombus in 24 of 34 [71%]; p less than 0.001) and with increasingly severe degrees of early ventricular shape change (normal or mildly abnormal contour, 16% with thrombus; moderately abnormal contour, 36% with thrombus; severely abnormal contour, 70% with thrombus; p less than 0.001). Patients with thrombi had higher diastolic (249 +/- 55 vs 225 +/- 48 ml; p less than 0.05) and systolic (158 +/- 48 vs 120 +/- 45 ml; p less than 0.001) volumes than patients without thrombi, respectively. A stepwise discriminant analysis identified ejection fraction, extent of early shape change and LV end-diastolic pressure as independent correlates of LV thrombus after acute myocardial infarction.

Adult↗
PubMed1988

Angiotensin converting enzyme inhibition and ventricular remodeling in heart failure.

The prevention or attenuation of the development of heart failure by the angiotensin converting enzyme inhibitor captopril was examined in two animal models, spontaneously hypertensive rats and rats with myocardial infarction produced by coronary artery ligation. In 24-month-old female spontaneously hypertensive rats with marked left ventricular hypertrophy, cardiac output was reduced despite an increase in ventricular volume, resulting in a greatly reduced ejection fraction. Treatment with captopril from 14 to 24 months of age maintained forward output and prevented ventricular dilatation so that ejection fraction remained normal; left ventricular hypertrophy regressed to levels observed in six-month-old spontaneously hypertensive rats. In rats with moderate and large infarcts three months after ligation, left ventricular filling pressures were elevated, forward output was reduced, and ventricular volumes were greatly increased. Long-term therapy with captopril maintained filling pressures within normal limits and maintained forward output from a lesser dilated left ventricle to yield an ejection fraction that was elevated compared with that in untreated rats. Thus, the potentially deleterious remodeling of the left ventricle in heart failure, an extensive increase in mass and chamber volume, can be favorably altered by long-term angiotensin converting enzyme inhibition (captopril) with salutary effects on hemodynamics.

Animals↗