Background-The transmembrane sodium/hydrogen exchanger maintains myocardial cell pH integrity during myocardial ischemia but paradoxically may precipitate cell necrosis. The development of cariporide, a potent and specific inhibitor of the exchanger, prompted this investigation of the potential of the drug to prevent myocardial cell necrosis. Methods and Results-A total of 11 590 patients with unstable angina or non-ST-elevation myocardial infarction (MI) or undergoing high-risk percutaneous or surgical revascularization were randomized to receive placebo or 1 of 3 doses of cariporide for the period of risk. The trial failed to document benefit of cariporide over placebo on the primary end point of death or MI assessed after 36 days. Doses of 20 and 80 mg every 8 hours had no effect, whereas a dose of 120 mg was associated with a 10% risk reduction (98% CI 5.5% to 23.4%, Pϭ0.12). With this dose, benefit was limited to patients undergoing bypass surgery (risk reduction 25%, 95% CI 3.1% to 41.5%, Pϭ0.03) and was maintained after 6 months. No effect was seen on mortality. The rate of Q-wave MI was reduced by 32% across all entry diagnostic groups (2.6% versus 1.8%, Pϭ0.03), but the rate of non-Q-wave MI was reduced only in patients undergoing surgery (7.1% versus 3.8%, Pϭ0.005). There were no increases in clinically serious adverse events. Conclusions-No significant benefit of cariporide could be demonstrated across a wide range of clinical situations of risk.The trial documented safety of the drug and suggested that a high degree of inhibition of the exchanger could prevent cell necrosis in settings of ischemia-reperfusion. (Circulation. 2000;102:3032-3038.)

clinicaltrials.gov Identifier: NCT00091637.

Forty-one patients undergoing coronary artery bypass grafting were randomly assigned to receive prophylactic timolol or placebo, given in a double-blind fashion. /3-Adrenoceptor-blocking therapy was stopped at least one half-life before surgery. Three to 7 hr after surgery (304 + 56 min), 0.5 mg of timolol or placebo was given intravenously twice daily in a double-blind manner. When oral medications were resumed postoperatively, 10 mg of timolol twice daily or placebo was continued orally. Continuous electrocardiograms were recorded for 24 hr before and for 7 days after surgery with a standard cassette recorder. No patient received digoxin. Both groups were comparable for frequency of preoperative supraventricular arrhythmias, left ventricular ejection fraction, duration of cardiopulmonary bypass, aortic cross-clamp time, number of bypass grafts, and total duration of monitoring. Analysis of arrhythmias was done by hand counts, and supraventricular arrhythmias were divided into supraventricular tachycardia and atrial fibrillation and/or flutter. Timolol decreased the frequency of supraventricular tachycardia (581 episodes placebo vs 84 timolol; p < .05) and of atrial fibrillation and/ or flutter (291 episodes placebo vs five timolol; p < .05). Timolol decreased the number of patients with severe (heart rate > 200 beats/min, duration > 50 beats) episodes of supraventricular tachycardia (four placebo vs 0 timolol; p < .05) and also decreased the number of episodes of severe (heart rate > 200 beats/min, duration > 5 min) atrial fibrillation and/or flutter (16 placebo vs one timolol; p < .005). There were no differences in the durations of supraventricular arrhythmias. All 1 1 episodes of supraventricular tachycardia and 11 episodes of atrial fibrillation and/or flutter with heart rates over 200 beats/min occurred in the placebo group (p < .005). Four patients on placebo and one patient on timolol required treatment for symptomatic supraventricular arrhythmias. Two patients in the timolol group were nauseated and one patient developed wheezing while on placebo. The results of this study demonstrate that prophylactic use of timolol after coronary bypass surgery is effective and safe therapy for decreasing the frequency and severity of supraventricular arrhythmias. Circulation 70, No. 3, 479-484, 1984. SUPRAVENTRICULAR arrhythmias are common after coronary artery bypass surgery, occurring in 20% to 54% of patients. -110 These arrhythmias may be associated with excessively rapid ventricular rates that jeopardize hemodynamic stability; in such cases urgent treatment is required to slow the heart rate or restore sinus rhythm. On occasion, when antiarrhythmic drug therapy is ineffective, it is even necessary to

No abstract

Mixed-exponential survival modelling describes timing of post-infarction complications and supports discharge 4 days after uncomplicated infarction. Such time-based risk assessment could guide decision-making in other settings in which randomized studies are impractical.

When ST depression is present in STEMI patients undergoing primary PCI, STD-R<50% provides independent prognostic value that is incremental to STE-R.

In order to further define clinical and angiocardiographic predictors of long-term survival after myocardial infarction we followed 616 consecutive male patients under 60 years of age, survivors of a first (N = 455) or recurrent (N = 161) myocardial infarction, for 8.8 +/- 2.9 years. Patients had angiocardiography at 4-8 weeks after infarction; none had thrombolysis, but 33% had cardiac surgery, 14% on a clinical trial basis. Left ventricular end-systolic volume was the most powerful predictor of cardiac mortality; ejection fraction and end-diastolic volume added no further information. Myocardial score, a measure of the severity of coronary stenoses in relation to the amount of myocardium supplied, was of only borderline predictive value on multivariate analysis, possibly because any effect had been negated by coronary surgery. Administration of beta-blocker drugs had an independent effect of improving prognosis, while continued cigarette smoking worsened it. Age, status of index infarction (first or recurrent) and serum cholesterol did not affect survival. A trial of surgery, carried out in a subset of 200 of these patients who were relatively asymptomatic but had severe coronary disease, showed no survival advantage for intended surgical over non-surgical management. We conclude that a high left ventricular end-systolic volume remains the most important adverse prognostic factor after recovery from myocardial infarction.

Thrombolytic treatment for acute myocardial infarction increases the risk of subsequent reocclusion of the infarct related artery. The efficacy and safety of repeat thrombolytic treatment was assessed in 31 patients treated with streptokinase (n = 13) or tissue plasminogen activator (n = 18) a median of five days (1-716) after the first infusion. The The benefits of repeat thrombolytic treatment for threatened reinfarction may resemble those of the initial administration, but the risks and benefits have not been well described. We report the results of repeat thrombolytic treatment in 31 patients with threatened reinfarction. Patients and methodsWe studied 31 patients (22 men and nine women, mean (SD) age 58 (9) years) who had all been treated with intravenous thrombolysis for acute myocardial infarction. Indications for initial thrombolysis included ischaemic chest pain lasting more than 30 minutes with onset less than six hours before thrombolytic treatment and associated ST segment elevation of > 1 mm in two limb leads or V4-V6 or >2 mm in leads V1-V3. The initial thrombolytic treatment was an infusion of streptokinase 1-5 million units intravenously over 30 minutes in 23 patients and of recombinant tissue plasminogen activator 100 mg intravenously over three hours in eight patients. In all patients treatment with aspirin (50-300 mg per day) was started on admission to the coronary care unit and 12 patients were also given dipyridamole (400 mg daily