Risk factors for thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study.

As previously reported, 1007 patients with chronic atrial fibrillation participated in the Copenhagen AFASAK study. Before inclusion to trial, they all had a physical examination, chest roentgenogram, and echocardiogram with determination of left atrial size. This study evaluated the importance of cardiovascular risk factors for development of thromboembolic complications. To exclude any treatment effects on occurrence of thromboembolic complications, we included only the 336 patients from the placebo group. Using Cox's regression model, previous myocardial infarction was a significant risk factor for development of thromboembolic complications. Age, gender, heart failure, chest pain, hypertensive heart disease, diabetes, systolic and diastolic blood pressure, smoking, relative heart volume, and left atrial size were all without statistical importance.

Central hemodynamic changes after ingestion of a meal in patients with coronary artery disease.

Thirty-six patients with coronary artery disease participated in a controlled trial of the influence of food intake on central hemodynamic parameters determined noninvasively by radionuclide cardiography. Stroke volume increased considerably (23%) and heart rate was slightly higher (8%) half an hour after the meal, whereas the elevated cardiac output two hours postprandially could be ascribed entirely to relative tachycardia. No significant hemodynamic changes occurred in the patients who fasted. That the left ventricular ejection fraction was increased postprandially (3% to 4%) indicated that food intake had positive inotropic as well as chronotropic effects on the ischemic heart, even in heart failure. Afterload reduction and increased sympathetic nervous activity contribute to the changes, but the primary mechanism may be a change in resistance and blood flow in the intestinal vascular bed involved in digestion.

Fixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study.

BACKGROUND: Despite the efficacy of warfarin sodium therapy for stroke prevention in atrial fibrillation, many physicians hesitate to prescribe it to elderly patients because of the risk for bleeding complications and because of inconvenience for the patients. METHODS: The Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study was a randomized, controlled trial examining the following therapies: warfarin sodium, 1.25 mg/d; warfarin sodium, 1.25 mg/d, plus aspirin, 300 mg/d; and aspirin, 300 mg/d. These were compared with adjusted-dose warfarin therapy (international normalized ratio of prothrombin time [INR], 2.0-3.0). Stroke or a systemic thromboembolic event was the primary outcome event. Transient ischemic attack, acute myocardial infarction, and death were secondary events. Data were handled as survival data, and risk factors were identified using the Cox proportional hazards model. The trial was scheduled for 6 years from May 1, 1993, but due to scientific evidence of inefficiency of low-intensity warfarin plus aspirin therapy from another study, our trial was prematurely terminated on October 2, 1996. RESULTS: We included 677 patients (median age, 74 years). The cumulative primary event rate after 1 year was 5.8% in patients receiving minidose warfarin; 7.2%, warfarin plus aspirin; 3.6%, aspirin; and 2.8%, adjusted-dose warfarin (P = .67). After 3 years, no difference among the groups was seen. Major bleeding events were rare. CONCLUSIONS: Although the difference was insignificant, adjusted-dose warfarin seemed superior to minidose warfarin and to warfarin plus aspirin after 1 year of treatment. The results do not justify a change in the current recommendation of adjusted-dose warfarin (INR, 2.0-3.0) for stroke prevention in atrial fibrillation.

Cerebral blood flow in patients with congestive heart failure treated with captopril.

The effect of captopril on cerebral blood flow was studied in five patients with severe congestive heart failure and in five control subjects. Cerebral blood flow was measured by inhalation of 133xenon and registration of its uptake and washout from the brain by single photon emission computer tomography. In addition, cerebral (internal jugular) venous oxygen tension was determined in the controls. The measurements were made before and 15, 60, and 180 minutes after a single oral dose of captopril (6.25 mg in patients with congestive heart failure and 25 mg in controls). Despite a marked decrease in blood pressure, cerebral blood flow increased slightly in the patients with severe congestive heart failure. When a correction was applied to take account of a change in arterial carbon dioxide tension, however, cerebral blood flow was unchanged after captopril administration even in patients with the greatest decrease in blood pressure, in whom a decrease in cerebral blood flow might have been expected. In the controls, blood pressure was little affected by captopril, whereas a slight, but not statistically significant, decrease in cerebral blood flow was observed. The cerebral venous oxygen tension decreased concomitantly.

First-pass radionuclide determination of cardiac output: an improved gamma camera method.

A technique for noninvasive determination of cardiac output by aid of first-pass radionuclide cardiography is described. After intravenous injection of 10-15 mCi technetium-99m-(99mTc) labeled red blood cells the method requires acquisition of a first passage time-activity curve recorded with a gamma camera over the left ventricle, the background corrected left ventricular count rate recorded after complete mixing of the tracer in the circulation, and determination of the distribution volume of the tracer. The method was applied in 14 patients with heart disease of various origins and evaluated against the conventional tracer dilution technique with arterial sampling of blood activity. Cardiac output determinations by external counting ranged from 2.30 to 8.56 l/min, mean +/- s.d. 4.50 +/- 1.66 l/min and by arterial blood sampling from 1.88 to 8.96 l/min, mean +/- s.d. 4.52 +/- 1.71 l/min. An excellent correlation was demonstrated between the two techniques, r = 0.978 (p less than 0.001). When no background subtraction was applied to the left ventricular counts at equilibrium, radionuclide cardiac output values were approximately 40% higher than those obtained by arterial sampling. The new first-pass radionuclide cardiographic technique may prove a useful tool in the noninvasive evaluation of cardiac function, especially in patients with arrhythmias and/or valvular incompetence.

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.

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.

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.

Cardiac performance in patients with asymptomatic alcoholic cirrhosis of the liver.

Twenty patients with biopsy-proved alcoholic cirrhosis of the liver and no cardiac symptoms entered a noninvasive investigation program in which cardiac performance was evaluated. One patient was excluded from the study because of a significant ethanol content in the serum at the time of investigation and 4 patients were excluded because of significant electrocardiographic ST-segment changes during exercise testing. Fifteen patients (12 men, 3 women, median age 47 years) who had abstained from alcohol drinking for at least 2 months were studied by exercise testing, echocardiography, measurement of systolic time intervals and left ventricular (LV) radionuclide ejection fraction (EF) at rest and during submaximal exercise. Twelve healthy persons of the same age served as control subjects. Heart rate at rest was significantly elevated in the patient group, median 90 beats/min (range 62 to 128) vs 73 beats/min (range 61 to 89) (p less than 0.02). No significant differences were found in physical work capacity and systolic time intervals, and echocardiographic parameters did not differ with the exception of left atrial dimension (median 36 mm [range 22 to 47] in the patient group and 31 mm [range 17 to 38] in the control subjects, p less than 0.05). No significant difference was found in LVEF at rest. During exercise, however, the median LVEF increased only 6% in the patients versus 14% in the control subjects (p less than 0.05). The results of this study suggest that patients with alcoholic liver cirrhosis, although free of cardiac symptoms, may have a latent or preclinical cardiomyopathy that is manifest during physical stress.

Pulmonary hypertension secondary to minor pulmonary embolism.

The response of pulmonary arterial pressure to minor degrees of pulmonary embolism was examined in 18 patients with embolic occlusion of less than 25% of the pulmonary vascular bed. Patients with pulmonary embolism were compared to normal controls matched for age and sex and to patients with a variety of acute pulmonary disorders without pulmonary embolism. Patients with pulmonary embolism and patients with other acute pulmonary diseases had significantly higher pulmonary arterial pressures and significantly lower values for arterial oxygen tension (PaO2) than did normal subjects. The degree of pulmonary hypertension correlated with the PaO2. Pulmonary hypertension occurring after minor degrees of pulmonary embolism may be a response to mild arterial hypoxemia.

Autonomic nervous control of postprandial hemodynamic changes at rest and upright exercise.

Postprandial hemodynamic changes were studied in healthy subjects at rest and during exercise in the upright position with and without autonomic blockade of the heart. At rest cardiac output increased 61% mostly because of a stroke volume increase accomplished by left ventricular end-diastolic dilation. These changes seemed to be dependent on the autonomic nervous system, whereas the postprandial heart rate increase did not. During exercise cardiac output was 23% higher after food intake due to a rise in both stroke volume and heart rate. These changes were apparently under influence of the autonomic nervous system, whereas left ventricular dilation was not. The present findings indicate that most of the postprandial changes in the central circulation are under control of the autonomic nervous system.

Effects of autonomic blockade on cardiac function at rest and during upright exercise in humans.

The cardiac function was studied by radionuclide cardiography in eight healthy subjects at rest and during submaximal upright exercise before and after autonomic blockade with metoprolol and atropine. At rest the median stroke volume was reduced by 21% during autonomic blockade (P less than 0.01), but cardiac output was maintained by a concomitant increase in heart rate. The systolic blood pressure was reduced from 120 to 105 mmHg (P less than 0.01), and left ventricular ejection fraction was reduced from 61 to 56% (P less than 0.05). After autonomic blockade the heart rate reached during exercise was the same. Stroke volume and cardiac output were maintained through cardiac dilation. The increase in left ventricular end-diastolic volume was 31 vs. 10% during control conditions (P less than 0.01). The systolic blood pressure was reduced from 174 to 135 mmHg (P less than 0.01). Left ventricular ejection fraction was reduced from 75 to 67% (P less than 0.05), but the increase from rest to exercise was preserved. Total peripheral resistance was reduced by 17% (P less than 0.05). These findings suggest that the heart possesses intrinsic mechanisms to maintain cardiac output during submaximal upright exercise. End-diastolic dilation results in a preserved stroke volume despite a reduced contractility.

Prospective evaluation of chronic cardiotoxicity due to high-dose epirubicin or combination chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil.

In a prospective study the left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), systolic blood pressure, ECG, and heart rate were recorded at rest and during submaximal work to compare the cardiotoxic effect of epirubicin with a combination chemotherapy without known cardiotoxicity. A total of 14 females with advanced breast cancer were treated with epirubicin at a median cumulative dose of 827 mg/m2 (range, 550-1244). These patients had previously received cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or cyclophosphamide alone as adjuvant treatment, or CMF for advanced disease. The control group consisted of 11 females with advanced breast cancer given CMF only. The systolic blood pressure at rest as well as during submaximal work was significantly lower (P less than 0.05) after treatment in the epirubicin group than in the CMF controls. With regard to LVEF, the median value of 54% at rest was significantly lower after treatment in the epirubicin group than in the controls (59%). There was a significant fall in LVEF at rest and during exercise in the epirubicin group, whereas no such changes were found in the CMF controls after treatment. The RVEF was unaffected. In the epirubicin-treated group one patient developed fatal congestive heart failure, and in the remaining 13 patients treatment was discontinued due to progression of the cancer and not to cardiotoxicity. Thus, the cardiotoxicity of epirubicin changed the clinical outcome in only 1 of 14 patients with advanced breast cancer.

First passage radionuclide cardiography for determination of cardiac output: evaluation of an improved method.

A noninvasive method for determination of cardiac output by aid of first passage radionuclide cardiography is presented. As opposed to most other scintigraphic methods, a forward blood flow is measured, even in patients with valvar incompetence. In addition, the technique allows measurement of cardiac output in the presence of cardiac arrhythmias. No geometrical assumptions, corrections for radiation attenuation, loss of tracer, or empirical correction factors due to extracardiac radioactivity are required. We have evaluated the method in 19 patients with various heart diseases by comparison of the radionuclide cardiac outputs with those derived from the thermodilution technique performed simultaneously. Eight patients had valvar incompetence and 2 had cardiac arrhythmias. The mean radionuclide and thermodilution cardiac output values were 5.03 l/min (SD 1.21) and 5.18 l/min (SD 1.09), respectively. The 95% confidence interval for the bias was -0.40 to 0.10 l/min, and correlation analysis demonstrated an excellent correlation between results obtained with the two methods, r = 0.91 (P less than 0.001). This study shows that the improved gamma camera method represents a valid noninvasive technique for determination of cardiac output.

Cardiac function and plasma catecholamines during upright exercise in healthy young subjects.

Radionuclide left ventricular ejection fraction, left ventricular volume changes and plasma catecholamines were recorded in six healthy untrained male subjects at rest and during upright exercise at increasing work loads. During mild submaximal exercise mean left ventricular ejection fraction increased 10% because of end-diastolic dilation, while a further 4% increase of left ventricular ejection fraction was recorded at heavy submaximal exercise mainly due to increased end-systolic contraction. Great individual changes were recorded during maximal exercise. Alterations in plasma catecholamines were most pronounced at the high exercise levels indicating that changes in cardiac contractility are not linearly correlated with changes in sympathetic nervous activity. Repeat studies showed only minor variations of mean left ventricular ejection fraction and plasma catecholamines indicating an acceptable reproducibility of the measurements. Variations of both left ventricular ejection fraction and catecholamines were smaller during exercise than at rest.

The value of the left ventricular ejection fraction in the treatment of angina pectoris following acute myocardial infarction: a randomized double blind study.

Radionuclide determination of left ventricular ejection fraction was performed at hospital discharge and one month later in 60 patients who had suffered acute myocardial infarction. At the first determination, the patients were randomized into two groups. In the first group, the cardiologist who cared for the patients was provided with the result of the determination of the ejection fraction whereas, in the second group, the result was withheld. At a 'blinded' evaluation two months after hospital discharge, 7 of those patients (24%) from the group where the cardiologist knew the ejection fraction and 11 of the patients (38%) in whom this result was withheld complained of angina pectoris on exertion (ns). The medication of the patients did not differ in the two groups. No significant difference was found in the values of the ejection fraction in patients with and without angina pectoris. In this controlled study, we were not able to document a clinical effect by routinely determinating left ventricular ejection fraction in patients with acute myocardial infarction in the treatment of angina pectoris.

Spontaneous and/or training-induced haemodynamic changes after myocardial infarction.

Maximal oxygen uptake (VO2max) determinations and haemodynamic studies at rest and during two submaximal exercise levels (60 and 85% of the maximal) were performed in 30 male patients under 60 yr of age, 2, 5 and 8 mth after an uncomplicated myocardial infarction. Fourteen patients participated in a physical training programme during the first 3 mth of the study, while 16 patients attended the training during the second 3-mth period. An increase in VO2max occurred at 5 mth in both groups, 16 and 11%, respectively. Corresponding to this improvement cardiac index (CI) at the same relative submaximal work load increased similarly in the two groups. During the second period of the study only slight increments in VO2max and no salient alterations of the haemodynamics were recorded within or between the two groups. The linear relationship between oxygen uptake and CI was not affected throughout the study. As the work load was augmented from 60 to 85% of the maximal during the exercise test, the stroke volume index did not tend to fall. Our data suggest that allowing all patients to resume work in the very early rehabilitation period after an uncomplicated myocardial infarction, the improvement in physical work capacity and cardiac function is not significantly affected by a training programme of low intensity and short weekly duration.

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.

[Atrial fibrillation--thromboembolism and prevention]. / Atrieflimren--tromboemboli og profylakse.

Chronic non-rheumatic atrial fibrillation is associated with a risk of thromboembolic complications of about 5% per year. Previous myocardial infarction seems to be a significant risk factor for development of thromboembolic complications in chronic atrial fibrillation, whereas paroxysmal atrial fibrillation and isolated atrial fibrillation in younger patients may be associated with a lower risk of emboli. Silent cerebral infarction occurs more often in chronic atrial fibrillation than among controls in sinus rhythm. Three prospective trials of patients with atrial fibrillation found effect of warfarin on the occurrence of thromboembolic complications. In one study aspirin 325 mg daily was effective in patients below 75 years of age, but not in patients above this age. The other trials revealed no effect of aspirin.

[A quantitative assessment of the impact of diet on the mortality of heart disease in Denmark. Estimation of etiologic fraction]. / En kvantitativ vurdering af kostens betydning for dødeligheden af hjertesygdomme i Danmark. Beregning af aetiologisk fraktion.

INTRODUCTION: The aim of the present study was to quantify the impact of different dietary factors on the mortality from ischaemic heart disease in Denmark. METHODS: Relative risks and knowledge on the distribution of different dietary factors were used to estimate etiological fractions. RESULTS: It is estimated that an intake of fruit and vegetables and saturated fat as recommended would prevent 12 and 22%, respectively, of deaths from ischaemic heart disease in Denmark. An intake of fish among those at high risk for ischaemic heart disease, would lead to a 26% lower mortality, while alcohol intake among abstainers would have no significant quantitative effect. DISCUSSION: These results suggest that changes in dietary habits according to current recommendations would have an impact on public health in Denmark.