Clinical studies in severe heart failure : neurohormonal, electrolyte and metabolic aspects

Congestive heart failure is a common and complex syndrome with a poor prognosis. Although heart disease is usually the primary event, the clinical syndrome is characterised by several extra-cardiac manifestations. Neurohormonal activation seems to play a crucial role for these manifestations and the progression of the disease. Twenty-seven consecutive patients with acute left ventricular heart failure were found to have increased plasma concentrations of atrial natriuretic peptide, arginine vasopressin and catecholamines, while the renin-angiotensin system was not activated until diuretic therapy was introduced. To counteract this activation it seems suitable to combine the diuretics with an angiotensin-converting enzyme inhibitor. Skeletal muscle biopsies were performed in 22 patients participating in the CONSENSUS trial, which was a randomised, double-blind, placebo-controlled study of the effects of the angiotensin-converting enzyme inhibitor enalapril on mortality in patients with severe congestive heart failure. The biopsies revealed decreased content of magnesium andpotassium while sodium and water were retained in skeletal muscle. Ventricular arrhythmias occurred frequently. The ventricular arrhythmias seemed to be related to lower serum levels of potassium, but no significant correlations were found to muscle electrolyte content. This may indicate that the ratio of electrolytes across the cell membrane is moreimportant for the development of arrhythmias than changes in the absolute amount of electrolytes are. The muscle biopsies also revealed metabolic derangement with decreased content of energy-rich compunds, such as adenosine triphosphate (ATP), phosphocreatine and glycogen,Treatment with enalapril did not seem to influence these peripheral abnormalities, but some beneficial effect was found regarding the prevalence of ventricular arrhythmias. In another 22 patients with severe congestive heart failure, similar signs of energy depletion were found in skel
Papers, included in the Ph.D. thesis, are not registered and included in the posts from 1999 and backwards.