Aldosterone receptor antagonism induces reverse remodeling when added to angiotensin receptor blockade in chronic heart failure.

OBJECTIVES: The objective of this study was to determine if adding spironolactone to an angiotensin II receptor blocker improves left ventricular (LV) function, mass, and volumes in chronic heart failure. BACKGROUND: Add-on spironolactone therapy substantially improves clinical outcomes among patients with severe heart failure (HF) on standard therapy. However, the value of combining spironolactone with an angiotensin II receptor blocker on LV reverse remodeling in mild-to-moderate systolic HF is unclear. METHODS: Fifty-one systolic HF patients with left ventricular ejection fraction (LVEF) <40% were randomly assigned to receive 1-year treatment of candesartan and spironolactone (combination group) or candesartan and placebo (control group). Reverse remodeling was assessed by serial cardiac magnetic resonance imaging and echocardiographic tissue Doppler imaging (TDI). RESULTS: There were significant improvements in LVEF (35 +/- 3% vs. 26 +/- 2%, p < 0.01) and reduction of LV end-diastolic volume index (121 +/- 16 ml/m2 vs. 155 +/- 14 ml/m2, p = 0.001), end-systolic volume index (88 +/- 17 ml/m2 vs. 120 +/- 15 ml/m2, p < 0.0005), and LV mass index (81 +/- 6 g/m2 vs. 93 +/- 6 g/m2, p = 0.002) in the combination group at 1 year. In addition, there was significant increase in peak basal systolic velocity and strain by TDI, decrease in index of filling pressure, and increase in cyclic variation integrated backscatter. In the control group, there were no significant changes in all these parameters after 1 year. CONCLUSIONS: The addition of spironolactone to candesartan has significant beneficial effects on LV reverse remodeling in patients with mild-to-moderate chronic systolic HF.

Is beta-blockade useful in heart failure patients with atrial fibrillation? An analysis of data from two previously completed prospective trials.

BACKGROUND: Beta-adrenergic blockade is of proven value in chronic heart failure. It is uncertain, however, if beta-blockade provides a similar degree of clinical benefit for heart failure patients with atrial fibrillation (AF) as those in sinus rhythm (SR). AIMS: To compare the effectiveness of beta blockade in patients with heart failure and AF. METHODS: Patients with chronic heart failure were randomized to treatment (double blind) with metoprolol 50 mg twice daily or carvedilol 25 mg twice daily in addition to standard therapy. Response was assessed after 12 weeks by a quality of life questionnaire, New York Heart Association class, exercise capacity (6-min walk test), radionucleotide ventriculography for LVEF, 2-D echocardiography measurement of left ventricular (LV) dimensions and diastolic filling and 24-h electrocardiograph monitoring to assess heart rate changes. RESULTS: Both beta-blockers produced significant improvements in LVEF in both the SR group: (+6+/-10% at 12-week, P<0.001) and the AF group: (+11+/-9% at 12-week, P<0.05). However, significant improvement in symptoms (P<0.001) and exercise capacity (P<0.001) were observed only in the SR group but not in the AF group despite a significant improvement in LVEF. CONCLUSION: Beta-blockers were effective in improving LV ejection fraction in chronic heart failure patients in either SR or AF but had less effect on symptoms and exercise capacity in those with AF.

Slow breathing increases arterial baroreflex sensitivity in patients with chronic heart failure.

BACKGROUND: It is well established that a depressed baroreflex sensitivity may adversely influence the prognosis in patients with chronic heart failure (CHF) and in those with previous myocardial infarction. METHODS AND RESULTS: We tested whether a slow breathing rate (6 breaths/min) could modify the baroreflex sensitivity in 81 patients with stable (2 weeks) CHF (age, 58+/-1 years; NYHA classes I [6 patients], II [33], III [27], and IV [15]) and in 21 controls. Slow breathing induced highly significant increases in baroreflex sensitivity, both in controls (from 9.4+/-0.7 to 13.8+/-1.0 ms/mm Hg, P<0.0025) and in CHF patients (from 5.0+/-0.3 to 6.1+/-0.5 ms/mm Hg, P<0.0025), which correlated with the value obtained during spontaneous breathing (r=+0.202, P=0.047). In addition, systolic and diastolic blood pressure decreased in CHF patients (systolic, from 117+/-3 to 110+/-4 mm Hg, P=0.009; diastolic, from 62+/-1 to 59+/-1 mm Hg, P=0.02). CONCLUSIONS: These data suggest that in patients with CHF, slow breathing, in addition to improving oxygen saturation and exercise tolerance as has been previously shown, may be beneficial by increasing baroreflex sensitivity.