Knud H. Olesen

THE NATURAL HISTORY OF 271 PATIENTS WITH MITRAL STENOSIS UNDER MEDICAL TREATMENT

This report is a follow-up of 271 patients with isolated mitral stenosis under medical treatment. The material comprises patients who came under medical care for cardiac symptoms during the years 1933-49. A first report of this series has already been published (Olesen, 1955). By 1959, 83 per cent of the patients had died, and the majority of survivors showed symptoms and signs of progression of the disease. On this background an analysis of the last follow-up data is presented as a contribution to the description of the natural history of mitral stenosis.

The supra-additive natriuretic effect addition of bendroflumethiazide and bumetanide in congestive heart failure: Permutation trial tests in patients in long-term treatment with bumetanide

The additive natriuretic effect of a single dose of bendroflumethiazide, 5 mg., has been studied in patients with advanced congestive heart failure in long-term treatment with bumetanide, 4 mg., daily. Three permutation trial tests were performed including six patients each. In the first trial, the response to supplementary bendroflumethiazide, 5 mg., was definitely superior to that of additional bumetanide, 4 mg., in terms of renal output of sodium, chloride, potassium, water, and osmolar clearance. In the second trial, a similar pattern was found in patients receiving a combination of bumetanide, 4 mg., and spironolactone, 100 mg., daily. The third trial compared the effects of bendroflumethiazide, 5 mg., plus bumetanide, 4 mg.; of bendroflumethiazide, 5 mg.; and of bumetanide, 4 mg. In terms of natriuresis and chloruresis, the response to the combination of two drugs was significantly larger than the sum of the effects of other treatments. It is concluded that the combined effects of the drugs represent a supra-additive effect addition for sodium and chloride. A tentative explanation of the mechanism of interaction in terms of inhibition of renal tubular supplementary spironolactone, involve a tendency to development of hypokalemia, hypochloremia, and alkalosis, it is recommended that supplementary use of bendroflumethiazide in this setting is combined with the administration of potassium chloride or potassium-saving diuretics.

Pulmonic valvular regurgitation during twenty-seven years after gonorrheal endocarditis: Report of a case with catheterization data

Abstract We report the case of a 45-year-old woman, presenting pulmonic valvular regurgitation developed after a gonorrheal endocarditis at the age of 18. The value of heart catheterization as an aid in the diagnosis of pulmonic valvular regurgitation is stressed.

DC-Conversion of Atrial Fibrillation after Mitral Valve Operation. An Analysis of the Long-term Results

In a prospective study comprising 43 patients with atrial fibrillation after mitral valve surgery, an evaluation was made of the prognostic significance of clinical, radiological, haemodynamic and operative factors for the maintenance of sinus rhythm after DC-conversion. Atrial fibrillation with a duration of less than 12 months proved to be the only single factor of significance for sustained sinus rhythm after 12 months and it is suggested as a simple clinical criterion for selection of patients for DC-conversion after mitral valve operation.

The supra-additive natriuretic effect addition of theophylline ethylenediamine and bumetanide in congestive heart failure

Summary The additive natriuretic effect of oral theophylline ethylenediamine, 400 mg., and the potent diuretic bumetanide has been studied in patients with advanced congestive heart failure. Two permutation trial tests including six patients each were performed in subjects receiving long-term therapy with digoxin and bumetanide, 4 mg. daily. In the first trial, the response to supplementary theophylline ethylenediamine, 400 mg., was definitely superior to that of additional bumetanide, 2 mg., in terms of renal output of sodium, chloride, potassium, water and osmolal clearance. In the second trial the comparison was made of the effects of theophylline ethylenediamine, 400 mg. plus bumetanide, 4 mg., of theophylline ethylenediamine, 400 mg., and of bumetanide, 4 mg. In terms of natriuresis and chloruresis, the response to the combination of two drugs was significantly larger than the sum of the effects of other treatments. The third permutation trial test comprised six patients, who had not previously received bumetanide. In this group no additive natriuretic or diuretic effect could be demonstrated after administration of theophylline ethylenediamine. It is concluded that in patients receiving longterm treatment with the potent diuretic bumetanide the combined effects of oral theophylline ethylenediamine and bumetanide represent a supra-additive natriuretic and chloruretic effect addition. A tentative explanation for the mechanism of interaction of drugs in terms of inhibition of renal tubular sodium transport is given. Since the combined effects of the two drugs involve a tendency to development of increased kaliuresis, it is recommended that supplementary use of theophylline ethylenediamine in this setting is combined with the administration of potassium chloride. Apparently oral theophylline ethylenediamine represents an alternative possibility to thiazide diuretics when additional natriuresis and diuresis are required in patients with advanced heart failure on long-term treatment with potent diuretics like bumetanide.

Dynamic aspects of volume and osmoregulation in congestive heart failure during furosemide diuresis.

* From Medical Department B, Rigshospitalet, University of Copenhagen Medical School, Copenhagen, Denmark. It is convenient to consider the regulation of extracellular fluid solute concentration and the control of extracellular fluid volume as relatively independent processes. Extracellular fluid solute concentration is regulated by alterations in the renal excretion of free water, and this in turn depends primarily upon changes in the secretion of antidiuretic hormone. Control of extracellular fluid volume depends upon the regulation of total extracellular solutes. Because of the great preponderance of sodium and its anions the problem resolves itself essentially to the control of body sodium which is regulated by adrenal, renal and other mechanisms not thus far elucidated. The distribution of extracellular water between plasma and interstitial fluid volume is determined by the balance between colloid osmotic and hydrostatic pressures in the intraand extravascular phases. Control of intracellular solute concentration depends upon extracellular solute concentration as no osmotic gradient exists for most cells, and the control of intracellular fluid volume is closely related to the regulation of intracellular potassium content. These considerations are unified in the concept that the sum of osmotically active sodium and potassium is the major determinant of body water.1-5 In patients with congestive heart failure a disturbance in volume regulation exists as indicated by the increase of intravascular and extracellular volumes, of total exchangeable sodium, total exchangeable chloride and body water.6, 7 Apparently, a retention of sodium is the primary event, and because the osmoregulation tends to adapt itself to the rise in solute content, a retention of water ensues.

Interrelations Between Total Exchangeable Sodium, Potassium, Body Water, and Serum Sodium and Potassium Concentrations in Hyponatremic and Normonatremic Heart Disease

Interrelations between total body water, total exchangeable cation (sodium + potassium), and cation (sodium + potassium) concentration of serum water were examined in 20 normonatremic and 11 hyponatremic edematous cardiac patients. The total exchangeable cation and total body water were highly significantly correlated in the normonatremic and hyponatremic groups. However, for the combined groups the correlation coefficient was lower than that found in the individual populations, and in covariance analysis the cation content in relation to total body water was significantly lower in the hyponatremic than in the normonatremic group. When it is assumed that the total exchangeable cation differs little from the total osmotically active cation, and that the cation concentrations of the extracellular and intracellular water are approximately equal, the ratio: total exchangeable cation ÷ cation concentration in serum water, that is, the cation space, should reflect the total body water. The cation space and total body water were highly significantly correlated in the normonatremic and hyponatremic groups, and the correlation coefficient remained at the same high level for the combined groups. The relationship between cation space and body water was very close to unity, and in covariance analysis no significant difference was found in cation space in relation to total body water. These results were confirmed in 10 sequential studies. It is concluded that the cation space in hyponatremic and normonatremic cardiac patients has proved to reflect the total body water very closely, and the implications of this finding are discussed.

Total Exchangeable Potassium, Sodium and Chloride in Patients with Severe Valvular Heart Disease During Preparation for Cardiac Surgery

Exchangeable potassium, sodium and chloride were measured in 41 patients with severe valvular heart disease subjected to optimal medical treatment during preparation for intracardiac surgery. The results obtained were evaluated with the aid of two references for normal body composition: (1) ideal body weight, based upon body height, and (2) population weight taking into account body height and body weight increasing with age. According to both references, total exchangeable potassium was below normal, while exchangeable sodium and chloride were slightly elevated or normal. The decrement of exchangeable potassium, which was most pronounced in patients receiving diuretics, was interpreted as being due to a decrease of body cell mass in response to chronic wasting illness. No correlation was found between the incidence of postoperative ventricular arrhythmias and the decrease of exchangeable potassium or previous use of diuretics.

Systemic Arterial Embolism After Mitral Valvulotomy

During an average period of follow-up of 6 years, 255 patients subjected to closed mitral valvulotomy had an incidence of late arterial emboli of 1.0% per patient-year. In an unoperated series of 271 patients with mitral stenosis the incidence was 3.7% per patient-year. The significant protective value of mitral valvulotomy against late systemic embolism was particularly evident in patients with pre-operative atrial fibrillation. In subjects with pre-operative arterial emboli the rate of late embolism was 3.0% per patient-year, and it is suggested that long-term anticoagulant therapy is considered in this group of patients.

Mitral Stenosis: Factors Influencing Long-term Survival Rates after Closed Valvulotomy

The 10-year survival rates of 165 consecutive patients with mitral stenosis subjected to closed valvulotomy are reviewed. While patients operated on for mitral stenosis appear to live longer than medically treated patients, their survival rates are less than those of the general population. Factors with significantly adverse influence upon postoperative survival are pre-operative heart failure, severe disability, atrial fibrillation, mitral regurgitation, mitral valvular calcification, and severe mitral stenosis with marked changes of the valves. The prognostic significance of operative restoration of normal valvular function, as indicated by postoperative catheteri-zation studies, is clearly demonstrated in the present material.