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

Department of Cardiology, Antwerp University Hospital, Edegem, Belgium, University of Antwerp, Antwerp, Belgium.
European Journal of Heart Failure (Impact Factor: 6.53). 12/2011; 14(2):219-25. DOI: 10.1093/eurjhf/hfr161
Source: PubMed


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.

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    • "In the Swedish Doppler-echocardiographic study (SWEDIC), carvedilol showed echocardiographic improvement in diastolic function [64]. Nevertheless, exercise capacity [65] and mortality within beta-blockers-treated HFPEF patients remain unchanged in other RCTs [66–68]. Recently, the results of Japanese Diastolic Heart Failure (J-DHF) study were published [67]. "
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    ABSTRACT: ACCORDING TO THE EJECTION FRACTION, PATIENTS WITH HEART FAILURE MAY BE DIVIDED INTO TWO DIFFERENT GROUPS: heart failure with preserved or reduced ejection fraction. In recent years, accumulating studies showed that increased mortality and morbidity rates of these two groups are nearly equal. More importantly, despite decline in mortality after treatment in regard to current guideline in patients with heart failure with reduced ejection fraction, there are still no trials resulting in improved outcome in patients with heart failure with preserved ejection fraction so far. Thus, novel pathophysiological mechanisms are under development, and other new viewpoints, such as multiple comorbidities resulting in increased non-cardiac deaths in patients with heart failure and preserved ejection fraction, were presented recently. In this review, we will focus on the tested as well as the promising therapeutic options that are currently studied in patients with heart failure with preserved ejection fraction, along with a brief discussion of pathophysiological mechanisms and diagnostic options that are helpful to increase our understanding of novel therapeutic strategies.
    Full-text · Article · Oct 2013
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    • "In patients with systolic HF, systolic [5] and diastolic [6,7] LV velocity parameters, as well as right ventricular [8] function have been shown to correlate with functional capacity. However, detailed assessment of cardiac function timing [9] has shown that similar clinical limitation could be seen in patients with isolated diastolic myocardial abnormalities in the presence of preserved LV ejection fraction (EF) (HFpEF) [10]. Irrespective of EF, the morbidity and mortality of patients with HF remain high, despite advances in pharmacological and non-pharmacological treatments [11,12], suggesting a need for identifying other functional parameters that guide towards optimum management and better clinical outcome. "
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    ABSTRACT: Background The aim of this study was to prospectively examine echocardiographic parameters that correlate and predict functional capacity assessed by 6 min walk test (6-MWT) in patients with heart failure (HF), irrespective of ejection fraction (EF). Methods In 147 HF patients (mean age 61 ± 11 years, 50.3% male), a 6-MWT and an echo-Doppler study were performed in the same day. Global LV dyssynchrony was indirectly assessed by total isovolumic time - t-IVT [in s/min; calculated as: 60 – (total ejection time + total filling time)], and Tei index (t-IVT/ejection time). Patients were divided into two groups based on the 6-MWT distance (Group I: ≤300 m and Group II: >300 m), and also in two groups according to EF (Group A: LVEF ≥ 45% and Group B: LVEF < 45%). Results In the cohort of patients as a whole, the 6-MWT correlated with t-IVT (r = −0.49, p < 0.001) and Tei index (r = −0.43, p < 0.001) but not with any of the other clinical or echocardiographic parameters. Group I had lower hemoglobin level (p = 0.02), lower EF (p = 0.003), larger left atrium (p = 0.02), thicker interventricular septum (p = 0.02), lower A wave (p = 0.01) and lateral wall late diastolic myocardial velocity a’ (p = 0.047), longer isovolumic relaxation time (r = 0.003) and longer t-IVT (p = 0.03), compared with Group II. In the patients cohort as a whole, only t-IVT ratio [1.257 (1.071-1.476), p = 0.005], LV EF [0.947 (0.903-0.993), p = 0.02], and E/A ratio [0.553 (0.315-0.972), p = 0.04] independently predicted poor 6-MWT performance (<300 m) in multivariate analysis. None of the echocardiographic measurements predicted exercise tolerance in HFpEF. Conclusion In patients with HF, the limited exercise capacity, assessed by 6-MWT, is related mostly to severity of global LV dyssynchrony, more than EF or raised filling pressures. The lack of exercise predictors in HFpEF reflects its multifactorial pathophysiology.
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