Ole Storstein

Studies on digitalis: XIII. A prospective study of 649 patients on maintenance treatment with digitoxin

Summary In a prospective study of digitalis intoxication in 649 patients on maintenance treatment with digitoxin a low incidence of digitalis toxicity was found, namely, 5.8 per cent. This is mainly due to a more careful use of digitalis glycosides. It is especially important to reduce the dose of digitoxin in elderly and thin individuals. Digitoxin is metabolized in the liver and partly excreted through the kidneys as metabolites. Serum half-time of digitoxin is shortened in patients with impaired renal function. Patients with reduced renal function may be treated with digitoxin in the same doses as individuals with normal renal function. This is in contrast to patients treated with digoxin. Digitoxin should therefore be the cardiac glycoside of choice in treatment of patients with renal failure. Digitoxin is further rapidly eliminated in patients with reduced liver function in spite of its extensive hepatic metabolism. In this study extracardiac symptoms were found equally often as cardiac signs of toxicity. Patients intoxicated usually had several symptoms and signs of toxicity at the same time. The specificity of commonly used symptoms and signs of digitalis intoxication is very low. In this study atrial tachycardia with block, which has been considered to be an important cardiotoxic arrhythmia, very seldom was found in digitalis intoxication. There is an overlap in digitalis serum concentration between toxic and nontoxic patients. The diagnosis of toxicity was made on clinical ground. Most of the intoxicated patients had high serum concentrations, but some had concentrations in the normal or low range. Apart from being a guide to the diagnosis of digitalis intoxication, serum digitalis levels may further be a guide to underdigitalization of cardiac patients, especially patients in sinus rhythm.

False positive diagnostic tests and coronary angiographic findings in 105 presumably healthy males.

SUMMARY Among 2014 presumably healthy males aged 40-59 years coronary heart disease (CHD) was suggested in 115 in the presence of one or more of the following criteria: 1) a WHOquestionnaire on angina pectoris positive on interview, 2) typical angina during a near maximal bicycle exercise test, 3) a positive exercise ECG during and/or post exercise, 4) a Minnesota Code 1.1 on a resting ECG. Diagnostic coronary angiography was offered to all 115 CHD-suspect cases. Six refused angiography and four others were excluded. Of the remaining 105, thirty-six had less than 50% obstruction of any major coronary artery (34.3%). Eighteen (17.1%) had single, 25 (23.8%) had double and 26 (24.8%) had triple vessel disease. In 62 of the 69 with pathologic angiograms at least one obstruction ≥75% was found. Eighty percent of the cases with proven CHD were ≥50 years. All CHD-suggestive criteria had approximately the same diagnostic performance regardless of age, i.e., approximately one false positive/two true positives. Except for one retroperitoneal hematoma no complications to angiography occurred.

Prevention of arterial thromboembolism with acetylsalicylic acid: A controlled clinical study in patients with aortic ball valves

Prevention of arterial thromboembolism with acetylsalicylic acid (ASA) was studied in 148 patients with single Starr-Edwards aortic ball-valve prostheses. These patients are suitable for such a study because they have a high incidence of arterial emboli derived mainly from thrombi formed on the valves. They were given either 1 Gm. of ASA daily or placebo in combination with anticoagulants, and were observed for 2 years. Only two emboli occurred in patients receiving ASA, none of them severe. In the placebo group 12 thromboembolic episodes were diagnosed in 10 patients, and three with cerebral emboli died; in one a subdural hematoma unrelated to the embolus was found. In addition, one fatal and the one nonfatal intracranial bleeding occurred in each group, whereas gastrointestinal complications were seen more frequently in patients taking ASA. It is concluded that ASA combined with anticoagulants offered a significantly better protection against arterial thromboembolism than did anticoagulant therapy alone.

Quinidine in maintenance of sinus rhythm after electroconversion of chronic atrial fibrillation. A controlled clinical study.

One hundred patients were subjected to a controlled study of the effectiveness of quinidine treatment upon the maintenance of sinus rhythm after electroconversion. The quinidine series was treated with a long-acting preparation of quinidine sulphate, which was given in a dosage to achieve serum levels between 4 and 6 mg/l. The control series received no quinidine. The maintenance rate did not differ significantly in the two series during the first three months, but for the remaining observation time until I2 months a sigmficant difference in favour of quinidine was present. Identical results were found in a cross-over experiment, in which 24 patients served as their own controls. Further analysis broughtforward that quinidine was effective only if the atrial fibrillation had lasted for less than one year before electroconversion. Complications due to the

Circulatory Failure in Metastatic Carcinoma of the Lung A Physiologic and Pathologic Study of Its Pathogenesis

Four cases of extensive metastatic pulmonary carcinomatosis have been studied from the point of view of hemodynamics (cardiac catheterization) and pathology in order to evaluate the various factors in the pathogenesis of the subacute form of cor pulmonale. The author stresses the importance of distinguishing between the extensive destruction of lung tissue, leading to anoxemia, and the invasion of lung vessels by cancer cells, leading to pulmonary arterial hypertension and later to failure of the right ventricle.

The circulation in hyperthyroidism: a cardiac catheterization study before and after treatment.

Abstract The influence of increased body metabolism on the circulation has been studied by means of cardiac catheterization in 32 patients with thyrotoxicosis. In 15 patients recatheterization was performed after treatment with antithyroid drugs. The average cardiac index before treatment was 6.1 ± 1.63 L. per minute per square meter of body surface, with an average increase in basal metabolic rate of 55 per cent. After treatment the cardiac index showed a significant decrease to an average of 4.67. The pulse rate decreased significantly during treatment; the arteriovenous oxygen difference and the stroke volume showed only a slight fall. Only in the patients with the highest cardiac outputs before treatment and the greatest fall during treatment was a marked reduction in stroke volume observed. The increased cardiac output in hyperthyroidism is accompanied by an elevation of systolic pressure in the pulmonary artery and the right ventricle. Effective treatment leads to a decrease in systolic pressure and pulse pressure in the pulmonary, as well as in the systemic, circulation.

The effect of theophylline ethylenediamine on the pulmonary circulation

Abstract 1. 1. In a group of patients with various heart and lung diseases, exclusive of hypertensive heart disease, a study of the ventilatory and circulatory effect of theophylline ethylenediamine has been carried out. 2. 2. TED gave a distinct increase in maximal breathing capacity, indicating a bronchodilating effect. This improved ventilation lowered the arterial pCO 2 , while the arterial O 2 saturation was unchanged. 3. 3. TED increased the heart rate and decreased the blood pressure, both in the systemic and in the pulmonary circulations (more pronounced in the latter). The cardiac output and the pulmonary capillary venous pressure was unchanged, and there was a pronounced fall both in peripheral arterial and in pulmonary arteriolar resistance. 4. 4. It is concluded that this pressure fall was mediated through a direct dilating effect of TED on the arterioles, both of the pulmonary and systemic circulations. 5. 5. The work of the right ventricle showed a fall. This indicated that TED in this group of patients lessened the burden of the load placed on the right ventricle by pulmonary hypertension. 6. 6. Compared to earlier investigations there seems to be a different reaction to TED in this group of patients and in patients with hypertensive cardiovascular disease. In the latter group the most pronounced effect was the increase in the cardiac output, while the vasodilating action on the pulmonary circulation was insignificant.

Quinidine before direct current countershock. A controlled study.

One hundred and twenty-four patients with chronic atrial fibrillation were subjected to a controlled study on the effect of quinidine treatment upon the incidence ofpostconversion arrhythmias. Digitalis medication was stopped 2 to 4 days before the electroconversion. For the same period the quinidine series was treated with a long-acting quinidine sulphate. The mean serum level of quinidine on the day of electroconversion was 3y6 mEqll. Arrhythmias related to the DC shock occurred at an equal rate in the quinidine and in the control series. Of 3 cases with ventricular fibrillation, 2 were observed in the control series. No deaths were recorded. The study shows that quinidine treatment before direct current countershock does not affect the incidence ofpostconversion arrhythmias.