The effects of adding torasemide to standard therapy on peak oxygen consumption, natriuretic peptides, and quality of life in patients with compensated left ventricular systolic dysfunction.

AIMS: Diuretics, when used to treat congestion in patients with chronic heart failure, improve symptoms and, perhaps, prognosis but little information is available to guide their use in patients with left ventricular systolic dysfunction (LVSD) who are not congested. Chronic diuretic therapy causes persistent and potentially harmful neuroendocrine activation. Alternatively, in patients in whom neuroendocrine activation is blocked with angiotensin-converting enzyme (ACE)-inhibitors and beta-blockers, diuretics may be beneficial by decreasing preload and afterload and preventing congestion. We aimed to assess the effect of the loop diuretic, torasemide on quality of life, and surrogate markers of prognosis when given to patients with LVSD who were not clinically congested and who were optimally treated with ACE-inhibitors (or angiotensin receptor antagonists) and beta-blockers. METHODS AND RESULTS: Thirty patients with stable LVSD who had no clinically detectable fluid overload were randomized to receive either torasemide 5 mg daily or placebo for 3 months (Phase A), and after a washout phase of 2 months, cross-over was performed for 3 months (Phase B). Diuretic therapy did not cause significant change in peak VO(2), mean N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) levels, or measures of quality of life compared with placebo. Diuretic therapy did however lead to significant fall in systolic and diastolic blood pressures and increase in plasma renin levels compared with placebo. CONCLUSION: Diuretic therapy with torasemide is not superior to placebo in improving peak VO(2) or reducing NT-proBNP levels in patients with left ventricular dysfunction who are not clinically congested.

The effect of beta-blockers on the adaptive immune system in chronic heart failure.

It remains possible that the benefit from beta-blockers (BBs) in chronic heart failure (CHF) may not entirely be derived from a class-specific effect. Several experimental reports have alluded to the capability of immunomodulation by individual BBs. Given the increasingly recognized importance of the immune system in the pathogenesis of CHF, we studied the effects of BBs on the circulating immune system of these patients. Blood samples from CHF outpatients were prospectively analyzed using flow cytometry and gating software. Results were analyzed against comprehensive clinical details that were recorded during sample donation, including the type of BB administered. 273 blood samples were analyzed from 141 CHF patients, with an average ejection fraction of 31.9% and a mean age of 69.1 years. Patients taking carvedilol had a significantly lower expression of CD107a on cytotoxic T cells compared to bisoprolol (P= 0.001) and nebivolol (P= 0.008). They also had a significantly lower expression of HLA-DR on lymphocytes (P < 0.001 and P= 0.009 for bisoprolol and nebivolol, respectively). Cytotoxic T cells and lymphocytes expressing HLA-DR have been implicated in the pathogenesis of CHF. The fact that carvedilol, but not other commonly used beta-blockers, appears to modulate these important parameters, supports the concept that important differences exist between these agents, which may affect outcomes in CHF.