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Biomedical subjects

S Yusuf

Publications and source records attributed to S Yusuf.

At least 235 records · Page 13Linked to original sources

Effect of drug therapy on survival in chronic congestive heart failure.

A review of the current evidence on the effects of various agents on survival among patients with congestive heart failure (CHF) suggests that angiotensin-converting enzyme inhibitors probably offer the greatest potential for benefit. Trials undertaken before the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) revealed favorable trends among patients in New York Heart Association functional classes II to IV who received angiotensin-converting enzyme inhibitors. Data from CONSENSUS clearly demonstrate that enalapril reduces mortality rates among patients in New York Heart Association class IV, but conclusions regarding effects in patients with mild or moderate CHF must await the results of future studies. In contrast, the large data base on alpha-adrenergic blockers suggests that these drugs are not likely to improve survival. Information on inotropic agents is sparse, but it is possible that these drugs may not improve survival and, in fact, may have a harmful effect. Mortality data on CHF patients treated with beta blockers and calcium channel blockers are likewise limited; conclusions concerning effects on survival must be postponed until further studies are conducted. Many of the investigations undertaken thus far to examine survival in patients with CHF have been small and of short duration, so any comparisons of the effects of various drugs must be interpreted with caution.

Adrenergic beta-Antagonists↗

Effect of intravenous nitrates on mortality in acute myocardial infarction: an overview of the randomised trials.

About 2000 patients have been randomised in ten trials of intravenous nitroglycerin or nitroprusside in acute myocardial infarction. Taken separately, the individual trials have all been too small to provide a reliable estimate of the effects of treatment on mortality, but collectively they provide strong evidence of benefit. In total there have been 136 nitrate and 193 control deaths, and an appropriate overview of the separate trial results indicated a "typical" reduction of 35% (SD 10) in the odds of death (2p less than 0.001, with 95% confidence limits of about one-sixth to one-half). Both nitroglycerin and nitroprusside reduced mortality, the reduction being non-significantly greater with nitroglycerin than with nitroprusside. The greatest reduction in mortality occurred during the first week or so of follow-up, with a non-significant further reduction after this early period. This suggests that the early benefit is not rapidly lost.

Clinical Trials as Topic↗

The 24-hour heart rate behavior in long-term survivors of cardiac transplantation.

A detailed computerized analysis of heart rate (HR) behavior during ambulatory monitoring was performed in 19 long-term survivors of cardiac transplantation (12 orthotopic, 7 heterotopic) and in 10 normal volunteers. Compared with normal hearts, the transplanted denervated and the recipient innervated hearts in the heterotopic group showed higher average HRs over the whole 24 hours, the waking and sleeping periods. The rates of the denervated and the recipient hearts did not differ significantly. The maximal HR was similar in all 3 groups, but the minimal HR was lower in the normal hearts than in denervated and recipient hearts. The 24-hour RR interval variability was greatly reduced in the denervated hearts (60 +/- 22 ms) compared with the recipient (89 +/- 26 ms) and normal (151 +/- 38 ms) hearts. During arousal from sleep, the magnitude, time and rate of the HR change were significantly reduced in the denervated hearts compared with the innervated hearts and in the recipient compared with the normal hearts. These findings demonstrate that denervated hearts can show significant variations in HR during the 24-hour period, but to a lesser extent than normal hearts. The widest deviation from normal occurs during sleep, when the denervated heart shows minimal slowing probably due to lack of parasympathetic innervation. In heterotopic transplant recipients, the patients' own HR responses also are significantly blunted.

Adult↗

Early intravenous beta blockade in acute myocardial infarction.

In the critical period during which ischemia progresses to infarction, beta-blocking drugs are known to reduce oxygen demand and prevalence of arrhythmia. To investigate whether this treatment confers clinical benefits, 28 trials have been conducted involving some 27,500 patients during the early hours after onset of symptoms suggesting acute myocardial infarction (MI). Patients were randomized to receive either initial intravenous beta blocker plus oral maintenance or standard therapy. In toto, these trials indicated that early-intervention short-term beta-blocker treatment reduces: (1) the risk for early death, reinfarction, and ventricular fibrillation by about 15%; (2) enzymatic indices of infarct size; (3) the number of patients with threatened MI in whom a confirmed MI develops; and (4) the frequency of repetitive and nonrepetitive ventricular arrhythmias. Overall, the treated group had few major side effects other than a small excess of reversible and nonfatal heart block and hypotension. Retrospective analyses suggest (but do not prove) that the reduction in mortality is greatest for those treated within two hours of pain and during the first two days. These results indicate that early initial administration of intravenous beta blocker plus one week's oral beta-blocker treatment produces modest benefits that would presumably be of major public health importance if such treatment were widely used.

Acute Disease↗

An overview of the clinical trials of agents (other than beta-blockers) that potentially limit myocardial infarct size.

In this article, data on mortality have been systematically reviewed from the randomized trials of intracoronary and intravenous (i.v.) thrombolytic therapy, hyaluronidase, i.v. nitrates, and calcium channel blockers in acute myocardial infarction (AMI). Such analyses confirm that i.v. streptokinase (SK) reduces short-term mortality by about 20%. Despite a higher incidence of reinfarction in the treated group, this early benefit is maintained long term. The excess reinfarction was observed whether or not SK was followed by anticoagulants or aspirin. The roles of pharmacologic interventions and percutaneous transluminal coronary angioplasty (PTCA) in preventing reinfarction and improving survival further are currently being evaluated. The pooled data from the existing trials of hyaluronidase and i.v. nitrates are consistent with a 20-30% reduction in mortality; ideally, these interventions should also be studied in future large randomized trials. Currently, there is no evidence either from individual studies or the aggregate of all the trials that calcium channel blockers reduce mortality. The collective experience from these trials conducted over the last two decades suggests that most interventions in AMI can at best have only moderate effects (10%, 20%, or at best 30%) on mortality. However, such modest effects produced by the widespread use of these agents could prevent several thousand premature deaths each years. Therefore, current and future trials that assess the effects of new or existing cardiovascular treatments on mortality should aim to randomize at least 10,000 average risk patients or a few thousand high risk patients.

Cardiovascular Agents↗

Ventricular arrhythmias in long term survivors of orthotopic and heterotopic cardiac transplantation.

Fourteen long term survivors with orthotopic (recipient heart replaced by donor heart) and nine with heterotopic cardiac transplants (recipient heart retained) had 24 hour ambulatory electrocardiographic monitoring to detect ventricular arrhythmias. Arrhythmia was uncommon in the patients with orthotopic transplants; none of them had more than one extrasystole per hour. In the patients with heterotopic cardiac transplants the recipient's own heart showed significantly more frequent ventricular arrhythmias than the corresponding donor heart: abnormal complexes (mean/24 h) 4583 vs 42.7; extrasystoles 1772 vs 17.8; pairs 121 vs 0.8. There was no relation between the abnormal ventricular activity of the two hearts in the patients with heterotopic transplants on a beat by beat, hourly, or 24 hour basis. There was no consistent diurnal variation in the frequency of the abnormal ventricular beats after cardiac transplantation. The occurrence of ventricular arrhythmia was unrelated to the interval from operation to the study. In long term survivors of cardiac transplantation the denervated heart shows a little ventricular ectopic activity even when compared with normal hearts. In patients with heterotopic transplants ventricular arrhythmias commonly occur in the recipient's own heart; these are probably related to the underlying severity of the original disease.

Adult↗

Interventions that potentially limit myocardial infarct size: overview of clinical trials.

Theoretically, interventions that restore the balance between oxygen supply and demand when given during the early hours of a heart attack may reduce infarct size and prevent fatal arrhythmias and thereby prolong survival. Data on mortality from the available randomized trials of thrombolytic therapy, intravenous beta blockers, hyaluronidase, intravenous nitrates and calcium channel blockers in acute myocardial infarction, are systematically reviewed. Analyses confirm that intravenous streptokinase reduces mortality by about 25% but suggests that measures to prevent reinfarction may be required after thrombolytic therapy. beta blockers reduced mortality by approximately 15%. The pooled data from the existing trials of hyaluronidase and intravenous nitrates are consistent with a 15% to 20% decrease in mortality; ideally this should be confirmed in future large randomized trials. Currently, there is no evidence either from individual studies or the aggregate of all the trials that calcium channel blockers reduce mortality. The collective experience from the trials carried out over the last 2 decades suggests that most interventions in acute myocardial infarction have, at best, only moderate effects with a 10% to 20% reduction in mortality. Current and future trials that assess the effects of cardiovascular treatments on mortality should therefore aim to randomize 10,000 to 20,000 average risk patients or a few thousand high risk patients.

Adrenergic beta-Antagonists↗

Significance of elevated MB isoenzyme with normal creatine kinase in acute myocardial infarction.

The significance of elevated levels of the MB isomer of creatine kinase (CK-MB) when creatine kinase (CK) level is normal was studied in 400 patients with suspected acute myocardial infarction (AMI). In 350 patients both CK and CK-MB were elevated (group 1), in 21 only CK-MB was elevated (group 2), in 24 neither enzyme was elevated (group 3) and in 5 only CK was elevated (group 4). In 57% of patients in group 2 the CK level was doubled, with a characteristic enzyme curve, within the normal range, suggesting that an increase in CK had been missed because arbitrary definitions of "normal" were used. The median CK increase (60 IU/liter) in group 2 was greater than that in group 3 (23 IU/liter) (p less than 0.001). Patients in group 1 with small AMIs had a relative increase in CK similar to that in group 2. However, patients in group 2 had a lower baseline CK level so that peak CK did not become abnormally high despite a 5-fold increase in some patients. In patients in group 1 with small AMIs, CK was elevated in fewer samples than CK-MB. If only 2 samples were obtained in all patients, elevation of CK levels would have been missed in 63 group 1 patients, erroneously increasing the number of patients in group 2 fourfold (to 84 of 400, or 21%, instead of 21 of 400, or only 5%). Conversely, if patients in group 2 with a doubling of CK are excluded, the prevalence of elevated CK-MB with normal CK would be only 9 of 400 (2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Increased sensitivity of the denervated transplanted human heart to isoprenaline both before and after beta-adrenergic blockade.

It is not known whether surgical denervation leads to increased beta-receptor sensitivity after human cardiac transplantation. We assessed cardiac beta-receptor sensitivity by studying the heart rate response to isoprenaline of the denervated donor heart as compared with the innervated recipient heart in eight patients who underwent heterotopic cardiac transplantation and in six patients with orthotopic transplantation. Changes in the donor and recipient hearts seen in these 14 patients were further compared with those seen in 10 normal volunteers. Incremental intravenous infusion of isoprenaline (5, 10, and 15 ng/kg/min) raised heart rate to a greater extent in the donor compared with the recipient hearts in the eight patients who had heterotopic grafts (slopes [beats/min/ng/kg]: donor = +2.26, recipient = +1.59; p less than .01). In addition, the donor hearts of the transplant patients were more sensitive than hearts of the normal volunteers (slopes: donor = +2.26, normal = +0.94; p less than .01). The changes in the two groups of donor hearts were similar (slopes: orthotopic = +2.24, heterotopic = +2.27; NS). The recipient hearts in the patients with heterotopic transplants were more sensitive than the hearts of the normal volunteers (p less than .05), suggesting that the observed differences in isoprenaline sensitivity in the patients with heterotopic grafts were not caused by a decreased sensitivity of the recipient heart. After beta-blockade, the heart rate responses to isoprenaline were attenuated to the same extent in denervated and innervated hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗