[Effect of combined captopril-spironolactone therapy of cardiac insufficiency on kidney function and serum electrolyte values]. / A captopril-spironolacton kombinált kezelés hatása szívelégtelenségben a vesefunkcióra és a szérum elektrolit értékekre.

Author investigated the safety of combined ACE inhibitor (captopril) and spironolacton therapy on 237 pts with severe heart failure (NYHA III-IV.) treated with digitalis and loop diuretic during on average 65.4 months follow-up period. Incidence of clinically significant increase in serum urea, creatinine and potassium level was evaluated and compared with those of in group treated 47 pts with the same standard therapy captopril, digitalis, furosemide, without spironolacton. There was no significant difference between the incidence of azotemia and hyperkalemia in the two groups. The author emphasizes on the base of their results the safety of combined captopril and low dose spironolactone therapy in heart failure.

Randomised study of effect of ibopamine on survival in patients with advanced severe heart failure. Second Prospective Randomised Study of Ibopamine on Mortality and Efficacy (PRIME II) Investigators.

BACKGROUND: Drugs that improve symptoms in patients with heart failure must also be assessed for their effects on survival. Ibopamine stimulates DA-1 and DA-2 receptors and causes peripheral and renal vasodilatation; the drug improves symptoms of heart failure. We assessed the effect of ibopamine on survival in patients with advanced heart failure in a multicentre, randomised placebo-controlled study. METHODS: Patients with advanced severe heart failure (New York Heart Association classes III and IV) and evidence of severe left-ventricular disease, who were already receiving optimum treatment for heart failure, were randomly allocated oral ibopamine 100 mg three times daily or placebo. The primary endpoint was all-cause mortality. The study was designed to recruit 2200 patients, and the minimum duration of treatment would be 6 months. We did intention-to-treat and on-treatment analyses; a post-hoc subgroup analysis was also done. FINDINGS: After we had recruited 1906 patients the trial was stopped early, because of an excess of deaths among patients in the ibopamine group. 232 (25%) of 953 patients in the ibopamine group died, compared with 193 (20%) of 953 patients in the placebo group (relative risk 1.26 [95% CI 1.04-1.53], p = 0.017). The average length of follow-up was 347 days in the ibopamine group and 363 days in the placebo group. In multivariate analysis, only the use of antiarrhythmic drugs at baseline was a significant independent predictor of increased fatality in ibopamine-treated patients. INTERPRETATION: Ibopamine seems to increase the risk of death among patients with advanced heart failure who are already receiving optimum therapy, but the reasons for this increase are not clear. Our finding that antiarrhythmic treatment was a significant predictor of increased mortality in ibopamine-treated patients may be important, but exploratory analyses must be interpreted with caution.

[Clinical course, prognosis in patients treated for dilated cardiomyopathy]. / A dilatitiv cardiomyopathia kórlefolyása, prognózisa gondozott betegeken.

Studies on heart failure treatment established the rationale of polypharmacy: it means combined diuretics, digoxin and vasodilators first of all ACE inhibitor therapy. The aim of the study was to evaluate the effect of this therapy on the clinical course of 209 pts with dilatative cardiomyopathy and consecutive moderate--severe heart failure followed by and regularly controlled through 2.5-4 on the average 3 years at specialised out-patient clinic. Analysis of pts history showed the different frequency in occurrence of previous longlasting physical stress, alcohol consumption and viral infection respectively, which might have been the conditioning factors of heart failure. Cardiomegaly was evaluated on the basis of quantitative data of X-ray, and haemodynamic data from radionuclide measurements, that of the clinical course by a score system. The improvement of cardiomegaly and haemodynamic data, were observed in 6 months of treatment. The evaluation of clinical course showed improvement in 61%, and stable condition in 26% of pts in half a year. The rate of pts with improved and stable condition proved the beneficial effect of regular care and combined drug therapy. A similar longterm follow-up study on same large pts population with heart failure has not been published yet in Hungary.

[Current management of heart failure]. / A szívelégtelenség korszerü kezelése.

Heart failure has emerged as a major cardiovascular public health syndrome with increasing incidence, reduced quality life, risk of progression, and high mortality. It's therapy still continues to pose a major clinical problem. The main goals of therapy are: improving the quality life and prolonging the survival. For many years digitalis and diuretics have been the cornerstones of pharmacologic treatment recently completed with vasodilators. Regarding the results of experimental and clinical investigations efforts to refine therapy have focused on choosing a combination of drugs particularly those that effectively inhibit the renin-angiotensin-aldosterone (RAA) system. The ACE inhibitors proved to be effective in managing heart failure of all degrees of severity including left ventricular dysfunction and end-stage of syndrome and in prolonging survival in patients. Spironolactone which inhibits the activity of aldosterone may exert an independent and additive effect to that of ACE inhibitors. The standard therapy of heart failure became: digitalis, diuretics--including spironolactone--and ACE inhibitors. In end-stage of heart failure refractory to therapy the only choice is heart transplantation.

Noninvasive follow-up study in hypertrophic obstructive cardiomyopathy.

The clinical course of hypertrophic cardiomyopathy with left ventricular outflow obstruction showed a symptomatic progression in 25% of patients, independent of the of degree of left ventricular obstruction. Echocardiographic and mechanocardiographic examinations showed a close relationship between severity of asymmetric ventricular hypertrophy and diastolic failure. During the follow-up septal hypertrophy became more severe without left ventricular dilatation. Global diastolic function deteriorated and the left atrium dilated. The probability of survival was 67.2%. Our data suggest that septum hypertrophy and diastolic dysfunction are progressive in HOCM. The mortality is independent of the severity of hypertrophy and diastolic dysfunction, and shows a close correlation with arrhythmias.

Left ventricular diastolic function in diabetics.

Left ventricular diastolic function was studied in 29 young diabetic patients (aged from 14 to 44 years) without any clinical sign of heart disease. The metabolic state, the presence and the degree of microvascular and neuropathic complications have been established. Age and sex matched 32 healthy subjects served as controls. The parameters of left ventricular diastolic function were determined by means of phonomechanocardiography. By this method in diabetic patients impaired diastolic function of the left ventricle was found. This alteration could be best characterized by the values of normalized relaxation index referring to the isovolumetric relaxation of the left ventricle. A close correlation was found between the microvascular and neuropathic complications and the left ventricular diastolic dysfunction, while no correlation could be demonstrated between the metabolic state and the diastolic cardiac disorder.

Study of the effect of Tensiomin (captopril) in chronic heart failure.

Tensiomin (captopril) was tested in 23 patients with chronic heart failure for 7.5 months on the average. In 9 outpatients suffering from congestive cardiomyopathy the effect of Tensiomin as an adjuvant to digitalis, diuretic, vasodilator etc. was evaluated by non-invasive methods. During the 3-month follow-up period the heart rate was decreased and the PEP/LVET ratio was improved. The parameters calculated from the X-ray examination (cardiothoracic index, cardiac volume index) indicated the regression of cardiomegaly. Radioisotopic circulatory examinations (systolic volume index, cardiac output index) indicated an increase in cardiac performance. In addition to the significant changes of these parameters the patients' clinical state was also improved in all cases as assessed according to the NYHA classification. Significant side effects were not observed during the treatment.

Skeletal muscle biopsy studies of cardiac patients.

Eleven patients diagnosed and treated for congestive cardiomyopathy (COCM) of unknown aetiology, and another 10 patients, with congestive alcoholic heart muscle disease (ACOCM) were studied. Muscle biopsy samples were obtained from the vastus lateralis (VL) and the gastrocnemius (G) muscles. In part of the sample muscle the fibre pattern was classified by means of ATPase activity staining, a technique based on the pH lability of the fibres concerned. Fibre typing and area measurements were carried out by light microscope. The other part of the sample was used as muscle homogenate of which the Ca2+-activated ATPase activity as well as citrate synthetase (CS) and aldolase activities were measured. No significant difference was found in these enzyme activities between the two groups of patients. The proportion of the slow twitch (ST) fibres in the VL, mainly in the patients with ACOCM, was lower as compared to data for healthy subjects. A similar tendency was revealed for G. In both muscles tested, the area of ST fibres was smaller in the ACOCM group. The fast twitch (FT) fibre area proved to be slightly different in the two groups of subjects tested. Occurrence of degenerative signs in the histological tests was higher in the ACOCM than in the COCM group. It was concluded that differences in the skeletal muscles of patients with ACOCM and COCM may primarily account for the alcoholism. The disease of the heart muscle has little effect on the function of skeletal muscle. Even so, a low amount or lack of physical activity may have an unfavourable influence on the skeletal muscles of patients with heart muscle disease.

Combined echo-apexcardiographic assessment of left ventricular function in cardiomyopathy.

Eleven patients with hypertrophic obstructive cardiomyopathy (HOCM) and 9 patients with congestive cardiomyopathy (COCM) were studied to determine the usefulness of mean normalized velocity of circumferential fiber shortening (VCFS), mean normalized velocity of circumferential fiber lengthening (VCFL) and left ventricular diastolic distensibility obtained noninvasively from combined recordings of simultaneously calibrated left apex cardiogram and M-mode echogram. Twenty-two normal subjects were similarly investigated and served as a control. In HOCM VCFS were increased (1.83 +/- 0.2 s-1 versus 1.22 +/- 0.1 s-1 for controls, p less than 0.02) and both VCFL and diastolic distensibility were decreased (VCFL: 0.50 +/- 0.1 s-1 versus 1.32 s-1 in controls, p less than 0.001; diastolic distensibility: 0.03 +/- 0.004 cm/mmHg-1 compared with 0.18 +/- 0.003 cm/mmHg-1 for controls, p less than 0.001). In COCM all investigated indexes were diminished (VCFS: 0.49 +/- 0.1 s-1 versus 1.22 +/- 0.1 s-1 for controls, p less than 0.001; VCFL: 0.70 +/- 0.1 s-1 versus 1.32 +/- 0.1 s-1 in controls, p less than 0.01 and diastolic distensibility: 0.05 +/- 0.003 cm/mmHg-1 compared with 0.18 +/- 0.003 cm/mmHg-1 for controls, p less than 0.01). The echo-apexcardiographic indexes were significantly correlated with many analogous invasive indexes. It is concluded that the value of both M-mode echocardiography and calibrated apex cardiography is enchanced by a combination of the two methods which opens the possibility of a fresh approach to the noninvasive study of cardiac performance in cardiomyopathy.

[Long-term therapy of hypertrophic obstructive and non-obstructive cardiomyopathy with nifedipine in comparison to propranolol]. / Langzeittherapie der hypertrophischen obstruktiven und nichtobstruktiven Kardiomyopathie mit Nifedipin im Vergleich zu Propranolol.

On 24 patients with ascertained hypertrophic obstructive cardiomyopathy and hypertrophic non-obstructive cardiomyopathy in a long-term experiment over 6 months the effect of 30 mg Nifedipin per day on subjective and objective parameters was investigated and compared with Propranolol. The subjective symptoms were in a larger extent improved by Propranolol than by Nifedipin. In contrast to Propranolol Nifedipin had no influence on the systolic function on the basis of the systolic time intervals. The diastolic heart function, assessed by means of the cardiographic criteria of the apex, was improved by Nifedipin in circa the same extent as by Propranolol. The results altogether allow the conclusion that the application of Nifedipin seems to be reasonable in patients with contraindication to beta-receptor-blockers or Verapamil or when there is no reaction to these preparations. When there is no satisfying result, a combination with beta-blockers should also be attempted.

Myocardial systolic alterations of insulin-dependent diabetics in rest.

Left ventricular systolic function was tested in 27 insulin-dependent diabetic patients by measuring the systolic time intervals. In diabetics longer pre-ejection period, and higher PEP/LVET quotient were found showing a good correlation with the values of glycosylated haemoglobin. These findings emphasize the importance of metabolic control in the development of cardiac dysfunction.