Sumit Basu

Beneficial Effects of Intravenous and Oral Carvedilol Treatment in Acute Myocardial Infarction A Placebo-Controlled, Randomized Trial

BACKGROUND Evidence of efficacy and safety of beta-blockers after thrombolysis for acute myocardial infarction (AMI) is equivocal. Newer beta-blockers such as carvedilol have not been tested in this setting. METHODS AND RESULTS This study investigated the effects of acute (intravenous) and long-term (6 months, oral) treatment with carvedilol versus placebo in 151 consecutive patients with AMI. Exercise ECG, ambulatory monitoring, and two-dimensional echocardiography were performed before hospital discharge and at 3 and 6 months. All patients were followed up and cardiovascular events recorded. The Cox proportional hazards model was used to compare time from randomization with the occurrence of a cardiovascular event, and Kaplan-Meier survival curves were calculated. Carvedilol was found to be safe, and it significantly reduced cardiac events compared with placebo (18 on carvedilol and 31 on placebo, P < .02). Fifty-four patients had heart failure at study entry; 34 received carvedilol. There were no adverse effects of carvedilol therapy and no excess events in this subgroup. Carvedilol produced significant reductions in heart rate (P < .0001), blood pressure (P < .005) at rest, and rate-pressure product at peak exercise (P < .003), but exercise capacity was unchanged. Left ventricular ejection fraction was not altered significantly by carvedilol, but stroke volume was higher at pre-hospital discharge examination (63 versus 53 mL; P < .01). Diastolic filling of the left ventricle (E/A ratio) was also improved (1.2 versus 0.9; P < .001). In a subgroup with left ventricular ejection fraction < 45% (n = 49 patients; 24 on carvedilol and 25 on placebo), carvedilol showed attenuation of remodeling. CONCLUSIONS Carvedilol was well tolerated and safe to use in patients immediately after AMI, including those with heart failure, and significantly improved outcome.

Value of thallium-201 imaging in detecting adverse cardiac events after myocardial infarction and thrombolysis: A follow up of 100 consecutive patients

Abstract Objective: To determine the prognostic role of thallium-201 imaging compared with that of exercise electrocardiography in patients with acute myocardial infarction treated by thrombolysis. Design: Patients who remained free of adverse cardiac events six weeks after myocardial infarction had stress and rest 201Tl imaging and exercise electrocardiography and were followed up for 8–32 months. Adverse cardiac events (death, reinfarction, unstable angina, and congestive heart failure) were documented. Setting: Large district general hospital, Middlesex. Subjects: 100 consecutive male and female patients who were stable six weeks after thrombolysis for myocardial infarction. Main outcome measures: Prediction of occurrence of adverse cardiac events after myocardial infarction by exercise cardiography and 201Tl myocardial perfusion imaging. Results: Reversible ischaemia on 201Tl imaging predicted adverse cardiac events in 33 out of 37 patients with such events during follow up (hazard ratio 8.1 (95% confidence interval 2.7 to 23.8), P<0.001). Exercise electrocardiography showed reversible ischaemia in 33 patients, of whom 13 had subsequent events, and failed to predict events in 24 patients (hazard ratio 1.1 (0.56 to 2.2), P = 0.8). Conclusion: 201Tl imaging is a sensitive predictor of subsequent adverse cardiac events in patients who have received thrombolysis after acute myocardial infarction, whereas exercise electrocardiography fails to predict outcome. Key messages Exercise electrocardiography is a poor predictor of such events Presence of reversible ischaemia on 201Tl imaging identifies 89% of patients who subsequently have such events

Prognostic value of predischarge exercise testing, ejection fraction, and ventricular ectopic activity in acute myocardial infarction treated with streptokinase☆

The relative importance of prognostic parameters that delineate left ventricular function, myocardial ischemia, and arrhythmogenic potential after thrombolytic therapy is not clear. This study investigated 112 patients with acute myocardial infarction who were treated with thrombolysis to determine the relative prognostic value of predischarge treadmill exercise testing, radionuclide ventriculography, and ambulatory electrocardiographic monitoring for ventricular ectopic activity. During a mean follow-up period of 18 months (range 6 to 30), 42 first cardiac events were recorded, consisting of 3 deaths, 6 reinfarctions, 16 bouts of unstable angina, 16 episodes of heart failure, and 1 arrhythmic event. Univariate analysis revealed ejection fraction, exercise time, and ventricular ectopic count of > or = 10/hour to be predictive of future cardiac events. Subsequent multivariate analysis showed ejection fraction (p <0.001) and exercise time (p=0.002 to have independent prognostic value, but ventricular ectopic activity did not provide additional information. Ventricular ectopic count > or = 10/hour was additionally predictive only when combined with either ejection fraction (R2=5.4%) or exercise time (R2=2.9%). Event-free survival analysis revealed hazard ratios for ejection fraction <40% and exercise time <7 minutes of 3.63 (p=0.001) and 2.16 (p=0.01), respectively. Although ejection fraction and exercise time were able to predict future episodes of heart failure, neither could adequately identify patients at risk of recurrent ischemic events.

Independent prognostic value of the extent and severity of systolic wall thickening abnormality at infarct site after thrombolytic therapy

BACKGROUND The prognostic value of systolic wall thickening abnormality after acute myocardial infarction in the thrombolytic era is not clearly known. METHODS AND RESULTS Accordingly, 119 consecutive patients with acute myocardial infarction who underwent thrombolysis were investigated with exercise electrocardiography and rest echocardiography at predischarge evaluation and were followed up for cardiac events. During a mean follow-up period of 19 months, 43 patients had cardiac events. Multivariate analysis with clinical, exercise electrocardiographic, and rest echocardiographic parameters showed that the independent predictors of cardiac events were systolic wall thickening score at the site of infarct (p = 0.02), end-systolic volume (p = 0.03), and exercise time (p = 0.02). The only independent predictor for both recurrent ischemic (death, unstable angina, and reinfarction) and nonischemic events (congestive heart failure and ventricular tachycardia) was systolic wall thickening score at the site of infarct (p = 0.02 and p = 0.007, respectively). CONCLUSIONS Systolic wall thickening abnormality at rest is an important independent predictor of cardiac events in patients who have undergone thrombolysis after acute myocardial infarction.

Reverse redistribution of thallium-201 represents a low-risk finding in thrombolysed patients following myocardial infarction

The aim of the study was to evaluate the prevalence and clinical significance of reverse redistribution on thallium-201 imaging in post-myocardial infarction patients who have undergone thrombolytic therapy. Sixty-two patients aged 35–79 (mean 60) years with proven myocardial infarction who had undergone thrombolysis were studied 6 weeks post infarction. Standard stress and 4-h redistribution imaging was performed with 201Tl following treadmill exercise. Separate day rest injection of 201T1 was given after sublingual nitroglycerine; imaging was performed at 1 h. Planar images were acquired in three standard views and semiquantitative segmental analysis of the images was performed from the unprocessed images. All patients had radionuclide ventriculography for the assessment of left ventricular ejection fraction and wall motion abnormality. Thirty-three patients also had coronary angiography. 201T1 scintigraphy revealed fixed defects in 19 patients, reversible defects in 22, and reverse redistribution in 21. Those with reverse redistribution had a significantly higher exercise capacity (P < 0.01). Mean (SD) left ventricular ejection fraction was 46 (12)% for those with fixed defects, 47 (9)% for those with reversible defects and 45 (15)% for patients with reverse redistribution (P = NS). The regional wall motion abnormality score was 8 (5), 11.8 (2.2) and 14.2 (6) respectively in patients with reverse redistribution, redistribution alone and fixed defects. Regions with reverse redistribution revealed less regional wall motion abnormality compared to the other two groups (P < 0.01). Fifteen patients demonstrated significant 201Tl uptake in the region showing reverse redistribution, with rest injection of 201Tl following sublingual nitroglycerine, suggesting viable myocardium in that region. Patients with reverse redistribution had less residual stenosis of the infarct-related artery than those with fixed or reversible defects. Reverse redistribution on 201T1 scintigraphy is a common phenomenon, even at 6 weeks, in patients with myocardial infarction who have received thrombolytic therapy. Areas with reverse redistribution demonstrate 201T1 uptake following rest injection, less regional wall motion abnormality and a more patent infarct-related artery. Thus, reverse redistribution in these patients represents a “low risk” finding which suggests retained myocardial viability and successful thrombolytic therapy.

Improved efficacy and safety of controlled-release diltiazem compared to nifedipine may be related to its negative chronotropic effect.

&NA; The objective of this study was to assess the safety and efficacy of long-acting preparations of two commonly used calcium antagonists with particular reference to their effects on heart rate. Twenty patients with chronic stable angina were recruited to a double-blind, double-dummy crossover study of controlled-release diltiazem (diltiazem CR) versus sustained-release nifedipine (nifedipine SR) and underwent clinical assessment, symptom and adverse event reporting, and repeated treadmill exercise tests over a 10- to 11-week period. The main outcome measures were heart rate at rest and exercise, incidence of angina and nitroglycerin use, treadmill exercise performance (duration, time to angina, time to 1-mm ST-segment depression, heart rate at equivalent maximal exercise, and maximal ST-segment depression), and adverse events. Diltiazem CR significantly reduced heart rate at rest and equivalent exercise and incidence of angina and nitroglycerin use compared with nifedipine SR. Exercise duration time to angina and time to 1-mm ST-segment depression (but not maximal ST-segment depression) were all significantly improved by diltiazem CR. Diltiazem CR also caused significantly fewer adverse events than nifedipine SR. Calcium antagonists with negative chronotropic effects (eg, diltiazem CR) are safer and more efficacious as monotherapy in chronic stable angina than dihydropyridines (eg, nifedipine SR) even when a long-acting formulation of the latter is used.