Effects of the long-term administration of nebivolol on the clinical symptoms, exercise capacity, and left ventricular function of patients with diastolic dysfunction: Results of the ELANDD study
ABSTRACT We hypothesized that nebivolol, a beta-blocker with nitric oxide-releasing properties, could favourably affect exercise capacity in patients with heart failure and preserved left ventricular ejection fraction (HFPEF).
A total of 116 subjects with HFPEF, in New York Heart Association (NYHA) functional class II-III, with left ventricular ejection fraction (LVEF) >45%, and with echo-Doppler signs of LV diastolic dysfunction, were randomized to 6 months treatment with nebivolol or placebo, following a double-blind, parallel group design. The primary endpoint of the study was the change in 6 min walk test distance (6MWTD) after 6 months. Nebivolol did not improve 6MWTD (from 420 ± 143 to 428 ± 141 m with nebivolol vs. from 412 ± 123 to 446 ± 119 m with placebo, P = 0.004 for interaction) compared with placebo, and the peak oxygen uptake also remained unchanged (peakVO(2); from 17.02 ± 4.79 to 16.32 ± 3.76 mL/kg/min with nebivolol vs. from 17.79 ± 5.96 to 18.59 ± 5.64 mL/kg/min with placebo, P = 0.63 for interaction). Resting and peak blood pressure and heart rate decreased with nebivolol. A significant correlation was found between the change in peak exercise heart rate and that in peakVO(2) (r = 0.391; P = 0.003) for the nebivolol group. Quality of life, assessed using the Minnesota Living with Heart Failure Questionnaire, and NYHA classification improved to a similar extent in both groups, whereas N-terminal pro brain natriuretic peptide (NT-pro BNP) plasma levels remained unchanged.
Compared with placebo, 6 months treatment with nebivolol did not improve exercise capacity in patients with HFPEF. Its negative chronotropic effect may have contributed to this result.
Article: Diastolische Herzinsuffizienz[Show abstract] [Hide abstract]
ABSTRACT: Die Prognose von Patienten mit diastolischer Herzinsuffizienz – Herzinsuffizienz mit erhaltener Linksventrikelfunktion – blieb in den letzten Dekaden gleich schlecht, obwohl die Prognose bei der Gesamtheit der Patienten mit Herzinsuffizienz besser wurde. Eine diastolische Dysfunktion wird bei älteren Patienten mit Herzinsuffizienz häufig diagnostiziert. Die Diagnostik stellt für die Kliniker aufgrund der Begleiterkrankungen wie chronische Atemwegserkrankung, Polyarthrosen, Sarkopenie oder Diabetes eine Herausforderung dar. Klassische Behandlungsempfehlungen versagen bei der diastolischen Herzinsuffizienz, ein umfassender und spezifischer Behandlungsplan ist daher nötig.Zeitschrift für Gerontologie + Geriatrie 01/2013; 46(1). DOI:10.1007/s00391-012-0345-z · 1.02 Impact Factor
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ABSTRACT: Beneficial effects of beta-blockade remain unclear in heart failure patients who have atrial fibrillation (AF), especially in the elderly. We evaluated the effect of nebivolol on cardiovascular outcomes in elderly patients with heart failure and AF. The SENIORS trial showed an overall benefit of nebivolol compared with placebo in 2128 heart failure patients >70 years of age. At baseline, AF was present in 738 (34.7%) patients. The primary outcome was all-cause mortality or cardiovascular hospitalizations. After 21 months, the cumulative incidence of the primary outcome was significantly more common in patients with AF compared with those with sinus rhythm (38.5% vs. 30.4%, respectively, P < 0.001). In patients with AF, nebivolol had no beneficial effect on the primary outcome [nebivolol vs. placebo, 37.1% vs. 39.8%, hazard ratio (HR) 0.92, 95% confidence interval (CI), 0.73-1.17, P = 0.46], in contrast to patients with sinus rhythm (28.1% vs. 32.9%, in the nebivolol vs. placebo group, respectively, HR 0.82, 95% CI 0.67-0.99, P = 0.049). In patients with AF, the primary outcome was similar in the impaired and preserved left ventricular ejection fraction (LVEF) groups (39.0% with LVEF ≤35% vs. 37.3% in patients with LVEF > 35%). There was also no evidence of benefit of nebivolol in AF patients stratified by LVEF. Nebivolol failed to improve outcomes in elderly patients with stable heart failure and co-existing AF, irrespective of LVEF. Furthermore, in patients with AF, outcome was comparable between patients with preserved and impaired LVEF.European Journal of Heart Failure 07/2012; 14(10):1171-8. DOI:10.1093/eurjhf/hfs100 · 6.58 Impact Factor
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ABSTRACT: AimsIn diabetes mellitus, heart failure with preserved ejection fraction (HFPEF) is a significant comorbidity. No therapy is available that improves cardiovascular outcomes. The aim of this study was to characterize myocardial function and ventricular-arterial coupling in a mouse model of diabetes and to analyse the effect of selective heart rate (HR) reduction by I(f)-inhibition in this HFPEF-model.Methods and resultsControl mice, diabetic mice (db/db), and db/db mice treated for 4 weeks with the I(f)-inhibitor ivabradine (db/db-Iva) were compared. Aortic distensibility was measured by magnetic resonance imaging. Left ventricular (LV) pressure-volume analysis was performed in isolated working hearts, with biochemical and histological characterization of the cardiac and aortic phenotype. In db/db aortic stiffness and fibrosis were significantly enhanced compared with controls and were prevented by HR reduction in db/db-Iva. Left ventricular end-systolic elastance (E(es)) was increased in db/db compared with controls (6.0 ± 1.3 vs. 3.4 ± 1.2 mmHg/µL, P < 0.01), whereas other contractility markers were reduced. Heart rate reduction in db/db-Iva lowered E(es) (4.0 ± 1.1 mmHg/µL, P < 0.01), and improved the other contractility parameters. In db/db active relaxation was prolonged and end-diastolic capacitance was lower compared with controls (28 ± 3 vs. 48 ± 8 μL, P < 0.01). These parameters were ameliorated by HR reduction. Neither myocardial fibrosis nor hypertrophy were detected in db/db, whereas titin N2B expression was increased and phosphorylation of phospholamban was reduced both being prevented by HR reduction in db/db-Iva.Conclusion In db/db, a model of HFPEF, selective HR reduction by I(f)-inhibition improved vascular stiffness, LV contractility, and diastolic function. Therefore, I(f)-inhibition might be a therapeutic concept for HFPEF, if confirmed in humans.European Heart Journal 07/2012; 34(36). DOI:10.1093/eurheartj/ehs218 · 14.72 Impact Factor