Search PubMed⌕ Search

Biomedical subjects

E Braunwald

Publications and source records attributed to E Braunwald.

At least 235 records · Page 13Linked to original sources
PubMed1988

Factors leading to shorter survival after acute myocardial infarction in patients ages 65 to 75 years compared with younger patients.

Although the number of elderly patients with acute myocardial infarction (AMI) has steadily increased and these patients are known to have a higher early subsequent mortality than younger patients, the reasons for this adverse prognosis are poorly understood. We compared the clinical courses of 217 patients, ages 65 to 75 years, with 631 patients younger than 65 years of age enrolled in the Multicenter Investigation of the Limitation of Infarct Size (MILIS). The older group had a higher prevalence of adverse baseline risk factors, including history of congestive heart failure (14 vs 7%, p less than 0.001), previous AMI (28 vs 22%, p less than 0.05), angina pectoris (42 vs 34%, p less than 0.05), systemic hypertension (64 vs 52%, p less than 0.01), diabetes mellitus (24 vs 17%, p less than 0.05) and female gender (37 vs 24%, p less than 0.001). Despite having a smaller infarct size index than younger patients (15 +/- 1 vs 18 +/- 1 CK-MB g-Eq/m2, p less than 0.002), the elderly patients had a lower admission left ventricular ejection fraction (43 +/- 1 vs 47 +/- 1%, p less than 0.01) and a higher frequency of clinical congestive heart failure (44 vs 28%, p less than 0.001) and in-hospital death (14 vs 7%, p less than 0.01). The 1-year mortality for elderly hospital survivors was also markedly greater (19 vs 5%, p less than 0.001) as was the 4-year mortality (35 vs 13%, p less than 0.001). Adjustment for 7 adverse baseline characteristics in the elderly could account for their increased in-hospital mortality. However, these and 12 additional in-hospital characteristics did not account for the increased 1- and 4-year mortalities of the elderly hospital survivors, which are presumably affected by variables not included in the present age-associated study.

Age Factors↗
PubMed1988

Six- and twelve-month follow-up of the phase I Thrombolysis in Myocardial Infarction (TIMI) trial.

The Thrombolysis in Myocardial Infarction (TIMI) trial Phase I was designed to compare the efficacy and side effects of intravenous recombinant tissue-type plasminogen activator (rt-PA) and intravenous streptokinase (SK) in patients with acute myocardial infarction (AMI). As previously reported, rt-PA led to a reperfusion rate of 62% of totally occluded coronary arteries compared with 31% for SK (p less than 0.001). This study was not designed to determine if intravenous thrombolytic therapy decreases the mortality of AMI; however, the findings in these patients after 1 year of follow-up do permit certain insights into the impact of early reperfusion and reocclusion on the clinical course of patients with AMI. The mortality rate at 6 and 12 months was not significantly different in patients treated with rt-PA compared with SK (7.7% and 10.5% rt-PA vs 9.5% and 11.6% for SK). The frequency of recurrent AMI, coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) was similar in the 2 treatment groups. There was no significant difference in 6- and 12-month mortality or in the rate of recurrent AMI in patients who received thrombolytic therapy before compared with after 4 hours of the onset of AMI symptoms. When the results were analyzed on the basis of the patency of the infarct-related artery, irrespective of thrombolytic agent used, for those patients with patent arteries 90 minutes after the initiation of therapy, there was a trend toward a lower 6-month (5.6% vs 12.5%) and 12-month mortality (8.1% vs 14.8%) (p = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
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

Electrocardiographic diagnosis of myocardial infarction in the presence of complete left bundle branch block.

Whether myocardial infarction (MI) can be diagnosed electrocardiographically in the presence of left bundle branch block (LBBB) is controversial. Our study sought to test the reliability of ECG criteria for diagnosing MI in patients with LBBB. Among 985 patients presenting within 18 hours of the onset of ischemic chest pain, 35 had complete LBBB. Acute MI was identified by serial MB-creatine kinase (CK) elevations and prior MI was determined by previously documented ECG and/or enzyme changes. Among those with LBBB, 24 patients had acute and/or prior MI, while 11 had neither. Eleven ECG criteria previously proposed for detecting MI in the presence of LBBB were evaluated. In patients presenting with ischemic chest pain and complete LBBB, presence of any one of the following ECG criteria was highly specific (90% to 100%) and predictive (85% to 100%) for acute or prior MI: Q waves in at least two of leads I, aVL, V5, or V6; R wave regression from V1 to V4; notching of the upstroke of the S wave in at least two of leads V3, V4, or V5, and primary ST-T wave changes in two or more adjacent leads.

Bundle-Branch Block↗
PubMed1988

Rate of disappearance of creatine kinase-MB after acute myocardial infarction: clinical determinants of variability.

The apparent rate of disappearance (Kd) of creatine kinase (CK)-MB is used in the calculation of the size of acute myocardial infarction (AMI), but little is known about the determinants of variability of this parameter. We therefore evaluated the relationship between clinical characteristics and apparent Kd in 328 patients with AMI without evidence of recurrent infarction. Patients with a history of cigarette smoking within 6 months had higher rates of disappearance of CK-MB, but no relationship was found between renal function and apparent Kd. Slower rates of disappearance of CK-MB were correlated with longer times from the onset of symptoms to peak CK-MB value (p less than 0.001), while higher peak CK-MB levels were not correlated with apparent rates of enzyme clearance. Decreased rates of disappearance of CK-MB were found in patients who had congestive heart failure during or after the hospitalization (both p less than 0.05), and who died during the hospitalization or during study follow-up (both p less than 0.05). Slower rates of disappearance were also significantly correlated with lower ejection fractions on radionuclide ventriculography at 10 days (p less than 0.001) and at 3 months (p less than 0.05) after AMI. These data suggest that patients with slower rates of disappearance of CK-MB may have poorer prognoses, perhaps reflecting continuing necrosis and enzyme release from jeopardized myocardium.

Creatine Kinase↗
PubMed1988

Thrombolytic reperfusion of acute myocardial infarction: resolved and unresolved issues.

Intensive clinical investigation has led to the acceptance of many fundamental aspects of reperfusion therapy, especially its salutary effects on improved survival, left ventricular function and reduced infarct size. However, many unresolved issues are currently being addressed or will be the focus of future clinical trials. These include patient selection with respect to risk profile and time of presentation, the choice of a thrombolytic agent, the role of adjunctive therapies and the optimal use and timing of follow-up coronary revascularization procedures. The rapidly evolving status of myocardial reperfusion therapy is reviewed, with specific attention to these important yet unresolved aspects.

Anticoagulants↗
PubMed1988

Effect of hyaluronidase on mortality and morbidity in patients with early peaking of plasma creatine kinase MB and non-transmural ischaemia. Multicentre investigation for the limitation of infarct size (MILIS).

A multicentred, randomised, blind study was started in 1978 to compare propranolol or hyaluronidase with placebo in patients with acute myocardial infarction admitted within 18 hours of onset of symptoms. Patients were randomised to group A and received hyaluronidase, propranolol, or placebo, or, if propranolol was contraindicated, to group B and received hyaluronidase or placebo. Hyaluronidase (500 U/kg given every six hours for 48 hours) had no effect on mortality or infarct size in the overall population. Because spontaneous reperfusion was more common in patients with early peaking of plasma creatine kinase MB or non-transmural electrocardiographic changes or both, the results were reanalysed for two subgroups: those in whom plasma creatine kinase peaked less than 15 hours after the onset of symptoms (early peak, n = 184) and those with a peak greater than 15 h after the onset of symptoms (late peak, n = 546). The distribution of time to peak activity of creatine kinase MB was similar in the hyaluronidase and placebo groups. In the early peak patients who were given hyaluronidase (groups A and B) total mortality and cardiac-specific four year mortality were significantly lower. This was most pronounced in group B in which the total mortality was 45% and cardiovascular mortality was 47% less than in the placebo group. Similarly, mortality from cardiovascular disease in patients (groups A and B) with nontransmural ischaemia (ST-T changes) given hyaluronidase was significantly lower, with group B showing a 50% reduction. In the subsets of patients with late peaking of creatine kinase MB or those presenting with transmural electrocardiographic changes there was no difference in total mortality or deaths from cardiac disease between those given hyaluronidase and those given placebo. Hyaluronidase was associated with improved survival in patients with early peaking of plasma creatine kinase MB, suggesting the possibility of salvage of myocardium in patients who have early spontaneous reperfusion and possibly after therapeutic reperfusion.

Clinical Trials as Topic↗
PubMed1988

Myocardial infarct extension: occurrence, outcome, and risk factors in the Multicenter Investigation of Limitation of Infarct Size.

The occurrence, outcome, and predictors of myocardial infarct extension were determined in 848 patients with acute myocardial infarction. An increase in the level of plasma MB creatine kinase activity was used to detect extension, which occurred in 71 of 848 patients (8.4%). For these patients, hospital mortality was more than four times higher than for those without extension (30% versus 7%, P less than 0.01). However, for patients surviving the initial hospitalization, there was no significant difference in mortality during the following year (12% compared with 9%). Multivariable analyses indicated that extension was more likely to occur in patients with recurrent ischemic pain during the second hospital day, a history of previous myocardial infarction, and ST segment depression on the admission electrocardiogram. The occurrence of extension in patients with two of these risk factors was more than twice that of patients without any of the risk factors (15.1% compared with 5.8%). Patients with these risk factors should be considered for early coronary angiography and possible intervention to prevent infarct extension and its sequellae.

Analysis of Variance↗
PubMed1987

Effects of calcium antagonists on infarcting myocardium.

Numerous studies have been conducted over the past 10 years on the effects of calcium antagonists on regional myocardial ischemia and infarct size. Verapamil, for example, reduced the degree of adenosine triphosphate degradation during 15 minutes of coronary occlusion followed by reperfusion in an anesthetized canine preparation. It also preserved the ultrastructural appearance of mitochondria in myocardium subjected to 1 hour of ischemia. Using an 8-hour permanent coronary artery occlusion model in which risk zone was assessed with radioactive microspheres and infarct size determined by tetrazolium staining, verapamil, administered 1 hour after occlusion, resulted in a modest decrease in infarct size. In a reperfusion model in which anesthetized dogs were subjected to 3 hours of coronary artery occlusion followed by 3 hours of reperfusion, verapamil decreased infarct size when it was administered during the period of ischemia, but failed to decrease infarct size when administered only during the reperfusion phase, i.e., after 3 hours of ischemia. Although verapamil is known to have negative inotropic effects, the newer calcium antagonist agent nisoldipine is less negatively inotropic, and might therefore be preferable in the situation of compromised hemodynamics. In a 6-hour permanent coronary artery occlusion model, nisoldipine decreased infarct size without decreasing left ventricular contractility. Most published reports support the concept that calcium antagonists decrease infarct size in models of experimental infarction. Of 4 major clinical studies, only 1 has shown that calcium antagonists are capable of reducing infarct size in man. However, in most of these studies, drug therapy commenced relatively late--4 or more hours after symptoms. In order for these drugs to demonstrate beneficial effects, the risk zone may have to be small and the degree of collateral flow adequate, the drug may have to be given very early or even before coronary occlusion (in a prophylactic fashion) and administration of the drug may have to be coupled to early coronary reperfusion.

Adenosine Triphosphate↗
PubMed1987

Differential effects of reperfusion on incidence of ventricular arrhythmias and recovery of ventricular function at 4 days following coronary occlusion.

To determine the influence of coronary reperfusion on ventricular arrhythmias and ventricular function at 4 days post occlusion, anesthetized dogs randomly received no occlusion (sham), permanent occlusion, or 1-, 2-, 3-, 4-, or 6-hour occlusions of the left anterior descending coronary artery, followed by reperfusion. An ambulatory ECG was recorded between 78 and 96 hours. The total runs of ventricular tachycardia were 1 +/- 0 (sham), 155 +/- 101 (1 hour), 66 +/- 32 (2 hours), 56 +/- 35 (3 hours), 167 +/- 68 (4 hours), 942 +/- 618 (6 hours), and 1422 +/- 486 (permanent occlusion); the runs of ventricular tachycardia were significantly less in the combined 1- to 4-hour groups (93 +/- 24) compared to the 6-hour and permanent occlusion groups (1282 +/- 384; p less than 0.006). Similar results were obtained for the number of hours in which ventricular tachycardia or frequent ventricular premature beats occurred. At 96 hours, improvement in percent systolic wall thickening of the ischemic myocardium assessed by two-dimensional echocardiography was seen in the group reperfused at 1 hour (p less than 0.01). Similar results were obtained for the reduction in degrees of wall circumference showing systolic thinning. In summary, at 4 days post occlusion in a dog model, spontaneous ventricular arrhythmias are reduced by reperfusion within 4 hours, while return of ventricular function is only improved by reperfusion within approximately 1 hour of coronary occlusion.

Animals↗
PubMed1987

Early reversal of right ventricular dysfunction in patients with acute pulmonary embolism after treatment with intravenous tissue plasminogen activator.

To assess abnormalities of right heart function and their reversal with thrombolysis in pulmonary embolism, serial imaging and Doppler echocardiographic studies were performed before and after a 6 hour intravenous infusion of 80 to 90 mg of recombinant tissue-type plasminogen activator (rt-PA) in seven patients with segmental or lobar acute pulmonary embolism. None of the five men and two women had known prior pulmonary hypertension. Substantial clot lysis and improvement in pulmonary blood flow, as determined by serial pulmonary angiography and perfusion lung scanning, were achieved in all. Coincident with clot lysis, pulmonary artery systolic pressure decreased (from 42 +/- 11 to 26 +/- 7 mm Hg, p less than 0.005), right ventricular diameter decreased (from 3.9 +/- 1.0 to 2.0 +/- 0.5 cm, p less than 0.005) and left ventricular diameter increased (from 3.7 +/- 0.9 to 4.4 +/- 0.6 cm, p less than 0.01). Right ventricular wall movement, initially mildly, moderately or severely hypokinetic in one, two and four patients, respectively, normalized in five and improved to mild hypokinesia in two. Tricuspid regurgitation was present before lytic therapy in six patients. In five, flow velocity in the tricuspid regurgitant jets indicated a peak systolic right ventricular minus right atrial pressure gradient of 25 to 52 mm Hg. Tricuspid regurgitation was detected early after lytic therapy in only two patients. Systolic septal flattening was noted before but not after lysis. These findings confirm that pulmonary emboli may result in appreciable right ventricular dysfunction and dilation, resultant tricuspid regurgitation, abnormal septal position and decreased left ventricular size.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗