In chronic heart failure diuretic drugs improve central hemodynamic variables and cardiac pumping secondary to altered plasma and extracellular volumes; humoral markers of these changes include increased plasma renin and aldosterone levels. The latter increases are maximal over the first week but decline with chronic therapy. The plasma alpha-ANP levels show a reciprocal effect; these data are compatible with a rapid contraction of the plasma volume which is sustained during chronic therapy. The acute hemodynamic actions of diuretic agents reflect both immediate and direct vascular actions and also effects secondary to diuresis (volume redistribution). At rest substantial reductions in pulmonary "wedge" pressure (-29%), with a consequent fall in cardiac output (-10%), are described. Total systemic vascular resistance initially increases but "reverse autoregulation" over subsequent weeks returns this elevation gradually towards control values. Tolerance to these initial hemodynamic effects does not occur with maintained therapy; moreover, echocardiographic markers of contractility and exercise capacity may increase. The early venodilator effects of diuretic drugs can be attributed to prostaglandin release and the initial pressor actions to activation of the renin angiotensin system; these vascular actions may have limited relevance to long-term beneficial effects on hemodynamics. Direct pulmonary vasodilation and improved pulmonary compliance remain an interesting finding. Although most patients are both symptomatically and hemodynamically improved at rest, the actions during exercise are more varied. Some individuals with severely impaired left ventricular function show little hemodynamic improvement, whereas those with milder dysfunction usually benefit; in the main this is probably related to the latter being on a steeper cardiac function curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Central hemodynamic effects of diuretic therapy in chronic heart failure.

Quality of life (QOL) analysis provides a unique insight into the global impact of drug therapy as seen from the patient’s perspective. Because of their relative novelty, these measurements have been preferentially applied to more recently developed drugs. There are little data of this type available for most of the more established heart failure agents.

The Effect of Drug Therapy on Quality of Life in Heart Failure

Magnesium deficit must be prevented and treated with particular zeast in chronic congestive heart failure. Besides its usual general consequences, in the case of chronic congestive heart failure under chronic therapy with loop or thiazide-type diuretics magnesium deficit predisposes to (digitalis-induced or not) cardiac arrhythmias, causes resistance to potassium replenishment in patients with hypokalemia, could impair cardiac pump function directly at the cardiac level, and could facilitate (exaggerate) vasoconstriction.

The Diuretic-Magnesium Question in Heart Failure

The efficacy of muzolimine (BAY g 2821) in doses of 30 or 60 mg/day was studied over an observation period of 4 weeks in 48 patients with mild to moderate heart failure (NYHA stage 2 or 3) in a biometrically planned, multicentre study. Eleven of these patients were excluded from the evaluation of efficacy for various reasons. All 37 patients who remained (23 men and 14 women; mean age 59.6 years, mean body weight 73.8 kg) were treated throughout with one tablet per day (30 mg). A marked improvement of the symptoms of cardiac insufficiency was observed in these 37 evaluated cases in the course of the treatment period. At the end of the study body weight was reduced by 1.8 kg, heart rate fell from 84 to 75 beats/min and blood pressure decreased from 154/88 to 145/85 mm Hg on average. The laboratory parameters tested failed to show any clinically abnormal alterations. Twelve of 48 patients complained of side effects (dizziness, headaches, vomiting, nausea), these developing largely in the first 2 weeks and being transient in character. To summarize, it can be stated that patients with chronic heart failure (NYHA 2 and 3) can be effectively treated by muzolimine monotherapy.

Hanisch M

Papers

Muzolimine as monotherapy in the treatment of patients with congestive cardiac failure.