John Godtfredsen

PLACEBO-CONTROLLED, RANDOMISED TRIAL OF WARFARIN AND ASPIRIN FOR PREVENTION OF THROMBOEMBOLIC COMPLICATIONS IN CHRONIC ATRIAL FIBRILLATION: The Copenhagen AFASAK Study

From November, 1985, to June, 1988, 1007 outpatients with chronic non-rheumatic atrial fibrillation (AF) entered a randomised trial; 335 received anticoagulation with warfarin openly, and in a double-blind study 336 received aspirin 75 mg once daily and 336 placebo. Each patient was followed up for 2 years or until termination of the trial. The primary endpoint was a thromboembolic complication (stroke, transient cerebral ischaemic attack, or embolic complications to the viscera and extremities). The secondary endpoint was death. The incidence of thromboembolic complications and vascular mortality were significantly lower in the warfarin group than in the aspirin and placebo groups, which did not differ significantly. 5 patients on warfarin had thromboembolic complications compared with 20 patients on aspirin and 21 on placebo. 21 patients on warfarin were withdrawn because of non-fatal bleeding complications compared with 2 on aspirin and none on placebo. Thus, anticoagulation therapy with warfarin can be recommended to prevent thromboembolic complications in patients with chronic non-rheumatic AF.

Relation between left atrial dimension and duration of atrial fibrillation

Abstract Atrial fibrillation (AF) is a common finding, especially in elderly patients. 1 It is widely accepted that the left atrium is dilated in AF, but whether left atrial (LA] enlargement is a cause or a consequence of the arrhythmia is still debated. 2–4 The present study determines the LA dimension in patients with AF of short and of long duration.

Acute effects of alcohol on left ventricular function in healthy subjects at rest and during upright exercise

Six healthy men, aged 23 to 30 years, were studied by radionuclide angiocardiography at rest and at 2 submaximal exercise levels in the upright position during increasing alcohol intoxication. At light intoxication (serum ethanol 23 mmol/liter), the median value of left ventricular (LV) ejection fraction (EF) at rest decreased by 5%. At heavy intoxication (serum ethanol 45 mmol/liter), the median LVEF decreased at rest by 11% and during 75% submaximal exercise by 6%, heart rate at rest increased (median 81 vs 62 beats/min), and systolic blood pressure decreased during 50% submaximal exercise (median 145 vs 163 mm Hg). No significant changes of plasma epinephrine concentrations were recorded, whereas plasma norepinephrine concentrations were increased by 24% at rest during light intoxication and by 30 to 38% during heavy intoxication. No changes of LVEF and plasma catecholamine levels were recorded after ingestion of isovolumic, isocaloric drinks as compared with values obtained before intake. Thus, influences of ingestion per se and repeated investigations of LV function were excluded. These findings suggest that in healthy subjects alcohol intoxication causes a dose-dependent impairment of cardiac contractility. Compensatory mechanisms may account for a reduced influence during exercise.

Interpretation of the electrocardiogram in suspected myocardial infarction: a randomized controlled study of the effect of a training programme to reduce interobserver variation

Abstract. We examined the effect of a training programme to reduce interobserver variation in interpretation of electrocardiography in suspected myocardial infarction. Sixteen doctors with 6–24 months of clinical training in internal medicine read serial electro‐cardiographic recordings in 107 patients and assessed whether signs indicative of acute myocardial infarction were present. There was disagreement in approximately 70% of cases. Eight of the doctors were randomly allocated to attend an 8‐h intensive course on interpretation of electrocardiography in myocardial infarction. The remaining eight participants were allocated to a control group, received no training, and were not told about the subject of the study. All the doctors then reviewed another series of electrocardiographic recordings. No difference was found in the level of agreement within the two groups before and after the training programme, or between the two groups before and after the training. The raters ability to discriminate between electrocardiograms with a high and low indication of infarction remained unaffected. We conclude that the training programme did not increase agreement regarding the interpretation of electrocardiographic data in suspected myocardial infarction. Our results suggest that the diagnostic approach of physicians is established at a very early stage in their clinical training. The effect of training programmes should be evaluated by the use of randomized clinical studies.

Left ventricular function during alcohol intoxication and autonomic nervous blockade

Eight healthy young subjects (6 men, 2 women) entered a controlled investigation of left ventricular (LV) function during alcohol intoxication and autonomic nervous blockade. Radionuclide cardiography was performed at rest and during upright 50% submaximal bicycle exercise. During alcohol intoxication alone (serum ethanol 30 mmol/liter), heart rate at rest increased by 11% (p less than 0.05) and LV ejection fraction (EF) decreased by 6% because of end-systolic dilation. No significant alcohol-induced hemodynamic changes were observed during exercise. Plasma norepinephrine concentration increased by 29% (p less than 0.05), whereas plasma epinephrine concentration did not change. During subsequent autonomic nervous blockade with intravenous metoprolol and atropine infusion, heart rate at rest further increased and systolic blood pressure decreased. These changes were not, however, significantly different from those of a control experiment in which a nonalcoholic isocaloric drink was substituted for alcohol. Plasma norepinephrine levels at rest and during exercise were 25% and 32% higher (both p less than 0.05), respectively, than those during control conditions. Plasma epinephrine concentrations did not change. These findings suggest that alcohol intoxication has a depressant effect on LV function at rest that stimulates autonomic nervous blockade. The increased sympathetic nervous activity during exercise appears to be a toxic rather than a compensatory effect of alcohol.

Hemodynamic effects of alcohol at rest and during upright exercise in coronary artery disease

The hemodynamic effects of acute alcohol intoxication were studied at rest and during upright exercise in 28 patients with coronary artery disease by right-sided heart catheterization and radionuclide cardiography. The mean arterial blood pressure at rest was reduced by 5% and the left ventricular ejection fraction at rest decreased 2% because of end-systolic dilation during intoxication (serum ethanol 21 mmol/liter). No changes were observed in heart rate, stroke volume, pulmonary artery pressure, pulmonary artery wedge pressure or total peripheral resistance. No significant changes occurred in plasma catecholamines, and no changes occurred in any variable during mild exercise corresponding to a 30 to 40% heart rate increase. Thus, alcohol ingested in moderate doses causes slight impairment of left ventricular emptying and a reduction in the arterial blood pressure at rest in patients with coronary artery disease. A mild exercise load can be tolerated during alcohol intoxication without hemodynamic changes.

PROSPECTIVE, RANDOMISED, DOUBLE-BLIND STUDY OF RADIONUCLIDE DETERMINATION OF LEFT-VENTRICULAR EJECTION FRACTION IN ACUTE MYOCARDIAL INFARCTION

In a controlled, randomised, double-blind study to see whether knowledge of left-ventricular ejection fraction (LVEF) could reduce the frequency of left-sided heart failure after acute myocardial infarction, LVEF was determined a few days before hospital discharge in a consecutive series of 60 patients. Subsequently, the patients were randomly assigned to two groups. The cardiologist responsible for their treatment was aware of the LVEF result in group I but not in group II. A month after hospital discharge there was no significant difference in the LVEF between the groups. 2 months after discharge there were no significant differences between the groups in clinical and radiological signs of left-ventricular heart failure or the use of drugs. The cardiologists clinical estimate of the LVEF and the result of the radionuclide determination were significantly correlated. Thus, the use of LVEF did not change the clinical outcome. The need for randomised controlled studies in the evaluation of diagnostic methods is emphasised.

Cardiac function at rest and during exercise in early and late alcohol intoxication

Seven healthy men, aged 21 to 30 years, were investigated by radionuclide cardiography at rest and during submaximal exercise at heavy (early) and during declining (late) alcohol intoxication. Control studies, in which alcohol was substituted by an isocaloric, isovolumic drink, were performed on a different day. The left ventricular ejection fraction at rest decreased from 59 to 56% during early intoxication (serum ethanol 35 +/- 6 mmol/l), whereas no change was observed in the ejection fraction during exercise. No significant change was recorded in stroke volume after alcohol consumption as opposed to a small increase after ingestion of the caloric drink. Plasma noradrenaline concentrations were elevated during exercise and early intoxication. During late intoxication (serum ethanol 21 +/- 5 mmol/l) the left ventricular ejection fraction at rest was increased by 7% compared with the baseline value. At rest the heart rate was increased from 68 +/- 7 to 84 +/- 15 beats/min, whereas cardiac output had reverted to the baseline value. Plasma noradrenaline at late intoxication was increased both at rest and during exercise compared with the baseline values. Apart from tachycardia and a reduction in left ventricular volumes during late intoxication no alcohol induced hemodynamic changes occurred during exercise.

Determination of cardiac output by first passage radiocardiography: theoretical considerations and phantom studies.

Non-invasive determination of cardiac output by aid of precordial first passage radiocardiography may prove a useful tool in the management of cardiac disorders. The basic concepts of a method together with theoretical assumptions necessary for the clinical application of the method are described. The principle of the technique was tested in a cardiac phantom model with adjustable stroke volume and heart rate, in which background problems were avoided. First passage radiocardiography gave highly accurate cardiac output determinations compared with the true phantom values, r = 0.998 (p less than 0.001).

Electrocardiographic changes in patients with upper abdominal pain admitted to a surgical ward

Abstract Several reports of abnormalities on the electrocardiogram in patients with abdominal disease have been published. 1–4 In only 1 study of patients with acute pancreatitis, however, have the electrocardiographic changes been recorded systematically. 5 We have evaluated the frequency of transient electrocardiographic changes in an unselected patient population with upper abdominal pain.