Biomedical subjects
Publications and source records attributed to J Leor.
In conclusion, considering the results from our model, magnesium infusion is effective as adjunct therapy to enhance myocardial salvage in the setting of acute myocardial infarction. However, its effectiveness may be limited to a subset of patients whose magnesium therapy can be started early and combined with early reperfusion therapy.
Controversy surrounds the safety of digoxin use in patients recovering from acute myocardial infarction. Previous observations yielded contradictory conclusions. To determine whether digoxin therapy is associated with increased mortality in patients recovering from acute myocardial infarction, we analyzed data from 1731 survivors of acute myocardial infarction enrolled in the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT), from which patients with severe heart failure were excluded. At the time of hospital discharge, 175 patients (10%) were taking digoxin. Mortality over 1 year after infarction was significantly higher in patients treated with digoxin than in patients who were not receiving digoxin [27 of 175 (15%) vs. 60 of 1556 (4%); p < 0.0001]. Digoxin administration was associated with increased mortality in several subsets of patients. Since patients treated with digoxin had baseline characteristics predictive of mortality more frequently than their counterparts, we adjusted for these differences. Multivariate analysis performed by the Cox proportional hazards model identified treatment with digoxin as an independent determinant associated with increased death during the first year after myocardial infarction [relative risk (RR) 2.8; 90% confidence interval (CI) 1.8-4.2]. Subgroup multivariate analysis indicated digoxin as an independent predictor of first year death in 464 patients who developed heart failure during their hospital stay (RR 2.3; 90% CI 1.3-4.0), as well as among 1267 patients who did not (RR 3.4; 90% CI 1.7-6.9). The present study suggests a significant excess mortality associated with digoxin therapy after myocardial infarction. The increased mortality risk may be related to unidentified variables associated with the severity of disease in patients treated with digoxin. However, our findings raise concern that the administration of digoxin may contribute to increased mortality in survivors of acute myocardial infarction.
Digoxin therapy has been suggested to increase mortality risk in survivors of acute myocardial infarction. Since digoxin is a drug with a narrow therapeutic/toxic ratio, we raised the hypothesis that the association between digoxin and post myocardial infarction mortality may have a dose-dependent relationship. The purpose of this study was to evaluate this hypothesis. We retrospectively analyzed data from 1731 survivors of acute myocardial infarction. At the time of hospital discharge, 175 patients (10%) were taking digoxin. The exact dosage of digoxin was ascertained in 153 (87%) patients. Patients were divided into two groups based on the weekly dosage of digoxin at hospital discharge: The first group included 41 patients who were treated with a low dose (< or = 1.5 mg per week, usually 0.125 mg daily). The second group included 112 patients treated with a full dose (> 1.5 mg per week, usually 0.25 mg daily). Both groups were comparable with regard to mean age, gender, history of prior myocardial infarction, diabetes mellitus, hypertension, and prior angina. There were no significant differences in the incidence of in-hospital complications, such as heart failure, atrial fibrillation, ventricular tachycardia, ventricular fibrillation, and postinfarction angina. One year mortality was significantly higher among patients treated with a full dose [19 of 112 (17%)] than patients treated with a low dose of digoxin [1 of 41 (2%); p < 0.02] Multivariate analysis performed by the Cox proportional hazards model identified treatment with a full dose of digoxin as an independent determinant associated with increased death during the first year after myocardial infarction (hazard ratio 10.7; 95% confidence interval 1.4-80.5). Thus, mortality among myocardial infarction survivors treated with digoxin was related to a full-dose therapy. Patients treated with a low dose experienced a low mortality rate. Our findings raise concern that digoxin may exert a dose-dependent deleterious effect upon the survival of patients recovering from acute myocardial infarction.
Reperfusion injury refers to cellular death or dysfunction caused by restoration of blood flow to previously ischemic tissue. This should be differentiated from the normal reparative processes that follow an ischemic insult. Four types of reperfusion injury have been described in the literature: (1) lethal reperfusion injury, (2) nonlethal reperfusion injury (myocardial stunning), (3) reperfusion arrhythmias, and (4) vascular injury (including the "no-reflow" phenomenon). There is continued debate whether reperfusion itself is capable of killing viable myocytes, which otherwise would have survived the ischemic insult. However, there is firm evidence for the existence of myocardial stunning following various ischemic syndromes, including reperfusion therapy for acute myocardial infarction, unstable angina pectoris, vasospastic angina, effort-induced ischemia, coronary artery bypass surgery, and cardiac transplantation. Reperfusion arrhythmia is more common after short ischemic episodes than after long ischemic periods. Thus, while reperfusion arrhythmias in the setting of acute myocardial infarction are relatively rare, reperfusion arrhythmias may be an important cause of sudden death. The "no-reflow" phenomenon has been described following reperfusion in patients with acute myocardial infarction. Three major components have been proposed as mediators of reperfusion injury: (1) oxygen free radicals, (2) the complement system, and (3) neutrophils. Numerous experimental studies have shown short-term benefit by blocking various stages of the postischemic inflammatory response. Oxygen free radicals scavangers, complement inhibition, leukocyte depletion, and the use of antibodies against various adhesion molecules have shown a reduction of infarct size in many ischemic/reperfusion experimental models. However, many of these agents failed to show a benefit in the clinical setting. Moreover, the long-term benefit of such intervention is still unknown.
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OBJECTIVES: This study was designed to investigate the association between wall motion abnormalities and the occurrence of ischemic mitral regurgitation in patients with a first inferior or posterior myocardial infarction and to reassess the role of thrombolytic treatment in these patients. BACKGROUND: We previously demonstrated that thrombolytic therapy reduces the incidence of significant mitral regurgitation in patients with a first inferior myocardial infarction, but the mechanisms responsible for this decrease were not clear. METHODS: Wall motion score on two-dimensional echocardiography (16 segments) and mitral regurgitation grade (0 to 3) on Doppler color flow imaging were assessed in 95 patients (in 47 after thrombolysis) at 24 h, 7 to 10 days and 1 month after myocardial infarction. Significant mitral regurgitation was defined as moderate or severe (grade 2 or 3). RESULTS: Multivariate analysis revealed that the presence of an advanced wall motion abnormality of the posterobasal segment of the left ventricle was the most significant independent variable associated with significant mitral regurgitation: odds ratio (OR) 15.0, 90% confidence interval (CI) 1.4 to 165.6 at 24 h; OR 2.8, CI 0.9 to 9.3 at 7 to 10 days; OR 4.2, CI 1.2 to 11.4 at 1 month. Thrombolysis reduced the prevalence of advanced wall motion abnormalities in the posterobasal segment at 24 h (55% vs. 75%, OR 0.5, CI 0.2 to 0.99), 7 to 10 days (44% vs. 73%, OR 0.3, CI 0.1 to 0.7) and 1 month (36% vs. 56%, OR 0.4, CI 0.2 to 0.9). CONCLUSIONS: There is a strong association between advanced wall motion abnormalities in the posterobasal segment and significant mitral regurgitation. In this study group, thrombolysis reduced the prevalence of advanced wall motion abnormalities in the posterobasal segment and thereby reduced the incidence of significant mitral regurgitation.
PTCA is not only an effective therapeutic tool but a unique opportunity to study the pathobiology of the human myocardium during ischemia and reperfusion. In addition, it is a good model to assess potential therapeutic interventions. Studies performed during PTCA contributed significantly to the understanding of the metabolic, electrophysiologic, hemodynamic, and coronary perfusion changes in the human heart following coronary occlusion. Combining the data from experimental models and human patients may lead to better techniques for myocardial protection during PTCA and consequently reduce the risk of patients undergoing mechanical revascularization.
Not all patients with neurocardiogenic syncope respond to beta-blockers. To determine whether differences in heart rate response to head-up tilt test with and without isoproterenol may predict drug efficacy, we evaluated 32 consecutive patients with a history of syncope, who were treated with beta-blockers after a positive tilt test. During the tilt test 21 patients (group A) with a baseline heart rate of 72 +/- 15 beats/min had tachycardia (mean 131 +/- 15) during tilt, before syncope, whereas 11 patients (group B) with a baseline heart rate of 68 +/- 13 beats/min did not (mean 86 +/- 13; p < 0.001). There were no significant differences between groups with regard to demographic and clinical characteristics or mean heart rate and mean arterial pressure in the supine position and during syncope. However, the proportion of patients requiring isoproterenol for provocation of syncope was significantly higher in group A compared with group B (15 of 21 vs 1 of 11; p < 0.001). All patients were treated with beta-blockers (propranolol or metoprolol). During a follow-up period of 18 +/- 6 months only one patient in group A had syncope and a positive tilt test compared with six patients in group B (9% vs 54%; p < 0.01). Development of tachycardia was a better predictor of drug efficacy than an isoproterenol-induced positive tilt test. The six nonresponders from group B were subsequently treated with disopyramide. During a mean follow-up period of 9 +/- 3 months, only one patient had syncope and another had a positive response to tilt test.(ABSTRACT TRUNCATED AT 250 WORDS)
Captopril, a sulfhydryl-containing angiotensin-converting enzyme inhibitor, has been suggested as possessing antiischemic and antiinflammatory properties. To test the hypothesis that captopril may prevent neutrophil-induced myocardial injury during acute myocardial infarction (AMI), the authors subjected rats to coronary occlusion for thirty minutes and reperfusion for twenty-four hours (MI) or to sham operation (sham MI). Oral captopril (100 mg/kg) or vehicle was administered thirty minutes before coronary occlusion. The effect of captopril on mean arterial blood pressure was assessed in separate group of animals (n = 8). Infarct size and neutrophil accumulation in myocardium were determined by measuring creatine phosphokinase depletion and myeloperoxidase (MPO) activity, respectively, in the left ventricular free wall (LVFW). Animals treated with 100 mg/kg of captopril exhibited significant reduction in mean arterial blood pressure compared with vehicle-treated animals (P < 0.01). Compared with vehicle-treated animals, administration of 100 mg/kg of captopril to MI animals attenuated neither twenty-four-hour mortality (56% vs 52%, respectively), nor infarct size (36 +/- 7% vs 34% +/- 7% respectively), nor MPO activity (1.0 +/- 0.17 vs 1.26 +/- 0.19). Thus, in the present experiment captopril did not reduce neutrophil-induced myocardial damage following coronary occlusion and reperfusion. These findings may be partly explained by the negative effect of captopril on arterial blood pressure during AMI.
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PURPOSE: Patients with large myocardial infarction (MI) presenting with clinical signs of heart failure are at increased risk for subsequent development of cardiogenic shock and death. Little is known, however, about the development of cardiogenic shock among patients with acute MI presenting without clinical signs of heart failure. The aim of the present study was to examine the incidence, predictors for occurrence, and outcome of in-hospital development of cardiogenic shock among patients with acute MI without heart failure on admission. PATIENTS AND METHODS: Clinical data of 5,839 consecutive patients hospitalized with acute MI were analyzed. RESULTS: Of 3,465 (59%) patients without heart failure on admission (Killip class I), 89 (2.6%) developed cardiogenic shock during their hospital stay. This represented 24% of all cases of in-hospital cardiogenic shock in the entire group. Cardiogenic shock developed more than 24 hours after admission in 66% of cases. All but three patients with cardiogenic shock died whereas a 5% in-hospital mortality was found among patients without cardiogenic shock. Independent predictors for in-hospital shock were age (for a 10-year increment, adjusted relative odds [RO] = 2.45, 90% confidence interval [CI] = 1.50 to 4.02); female gender (RO = 1.51, 90% CI = 0.91 to 2.50); history of angina (RO = 2.64, 90% CI = 1.36 to 3.76); history of stroke (RO = 2.12, 90% CI = 1.26 to 6.35); peripheral vascular disease (RO = 1.99, 90% CI = 0.95 to 4.18); peak lactate dehydrogenase (LDH) greater than four times the normal (RO = 3.16, 90% CI = 1.79 to 5.57); and hyperglycemia on admission (RO = 3.52, 90% CI = 2.13 to 5.84). Patients with six risk factors (excluding LDH values) had an estimated probability of 35% for developing in-hospital cardiogenic shock. CONCLUSIONS: (1) A significant proportion of MI patients who developed cardiogenic shock during hospitalization were free of heart failure on admission. (2) Our study identified several risk factors facilitating early identification of subgroups at risk for cardiogenic shock within otherwise low-risk patients.
OBJECTIVES: This study was designed to test the hypothesis that reperfusion therapy with thrombolysis will prevent the development of significant mitral regurgitation in patients with inferior myocardial infarction. BACKGROUND: The value of thrombolytic therapy in patients with inferior or posterior wall myocardial infarction has been controversial. We hypothesized that successful reperfusion therapy with intravenous thrombolysis may reduce the incidence and severity of postinfarction mitral regurgitation in this patient group. METHODS: We prospectively studied 104 patients with a first inferior myocardial infarction. Thrombolytic therapy was administered to 55 patients (treatment group) 3.2 +/- 2.1 h after the onset of symptoms. The other 49 patients formed the control group. Doppler echocardiographic color flow imaging was performed in all patients within 24 h, at 7 to 10 days and at 28 to 30 days after myocardial infarction. Significant mitral regurgitation was defined as moderate or severe (grade 2 or 3). RESULTS: No significant differences in baseline clinical characteristics were observed between the treatment and control groups. The overall incidence rates of significant mitral regurgitation at 24 h, 7 to 10 days and at 28 to 30 days were 10 (10%) of 104 patients, 18 (17%) of 104 patients and 11 (11%) of 100 patients, respectively. Multivariate analysis reveals the following independent predictors of the occurrence of significant mitral regurgitation: female gender (at 7 to 10 days, odds ratio 5.3, 90% confidence interval [CI] 1.8 to 15.5; at 28 to 30 days, odds ratio 3.7, 90% CI 1.1 to 12.7), heart failure (at 7 to 10 days, odds ratio 7.7, 90% CI 2.2 to 26.9) and transient complete atrioventricular block (at 24 h of myocardial infarction, odds ratio 5.8, 90% CI 1.2 to 27). Compared with the control group, the treatment group exhibited marked reduction in the incidence of significant mitral regurgitation at 24 h (16% vs. 4%; odds ratio 0.1, 90% CI 0.0 to 0.7); at 7 to 10 days (24% vs. 11%; odds ratio 0.3, 90% CI 0.1 to 0.9) and at 28 to 30 days (15% vs. 7%; odds ratio 0.4, 90% CI 0.1 to 1.6). Severe (grade 3) mitral regurgitation developed in five patients in the control group but in no patient in the treatment group. CONCLUSIONS: Thrombolytic therapy in the patients with a first inferior myocardial infarction was associated with a reduced incidence of significant mitral regurgitation. These results support the use of such therapy in patients with inferior myocardial infarction.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.