Background Sacubitril/valsartan (S/V) improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Data about the immediate, short-, and intermediate-term hemodynamic effects of S/V are limited. Methods In this prospective observational study, 37 outpatients with chronic HFrEF were treated with S/V according to current guideline recommendations. Next to clinical, laboratory and echocardiographic parameters, haemodynamic variables were assessed non-invasively by use of inert gas rebreathing and bioimpedance cardiography at baseline and at 2-week, 3-month and 6-month follow-up. The course of variables throughout the study and the relationship between variables were analysed using fractional polynomials. Results S/V treatment resulted in short- and intermediate-term improvements in NYHA functional class (2.3 ± 0.6 at baseline vs. 1.9 ± 0.5 at 6-month follow-up, p = 0.14), 6-min walk test (453 ± 110 vs. 528 ± 98 m, p = 0.02), ejection fraction (31 ± 9 vs. 36 ± 12%, p = 0.13), pulmonary artery pressure (39 ± 10 vs. 31 ± 10 mmHg, p = 0.02), and NT-proBNP values (1702 (782–2897 vs. 1004 (599–1627) ng/L, p = 0.03). In addition, S/V caused immediate decreases in systemic vascular resistance index (SVRI) and systolic blood pressure (SBP), which were associated with a simultaneous drop in stroke volume (SV) and cardiac index (CI). However, while SVRI and SBP remained at low levels during further treatment, SV and CI restored rapidly and increased to slightly higher levels thereafter. Conclusion The vasodilative effects of S/V result in immediate reductions in SVRI, SBP, SV and CI. However, S/V induces reverse cardiac remodelling, which is apparent shortly after treatment initiation and leads to improvements of clinical, functional, echocardiographic, laboratory and haemodynamic variables. Supplementary Information The online version contains supplementary material available at 10.1007/s40256-022-00549-2.
Introduction: The long-term evolution of clinical, echocardiographic and laboratory parameters of cardiac function in patients with chronic heart failure (HF) with either reduced (HFrEF) or mildly reduced (HFmrEF) left ventricular ejection fraction (LVEF) is incompletely characterized. Methods: We identified patients with chronic stable HF who presented at least twice to a university HF outpatient clinic between 1995 and 2021. Trajectories of NYHA functional class, LVEF, left ventricular internal enddiastolic diameter (LVIDD), NT-proBNP concentrations and HF treatment over ten years follow-up were analysed using fractional polynomials. Analyses were repeated after stratifying patients according to aetiology (ischemic vs. dilated) or HF category (HFrEF vs. HFmrEF). Results: A total of 2,132 patients were included, of whom 51% had ischemic and 49% had dilated HF. 86% and 14% were classified as HFrEF and HFmrEF, respectively. Mean LVEF was 28±10%, and median NT-proBNP and eGFR values were 1,170 (385-3,176) pmol/L and 81 (62-100) ml/min/1.73m², respectively. Median follow-up was 5.2 (2.6-9.2) years. Overall, NYHA functional class and LVIDD trajectories were U-shaped, whereas LVEF and NT-proBNP concentrations markedly improved during the first year and remained stable thereafter. However, the evolution of HF parameters significantly differed with respect to HF category and aetiology, with greater improvements seen in patients with HFrEF of non-ischemic origin. Improvements in HF variables were associated with optimization of HF therapy, notably with initiation and up-titration of renin-angiotensin-system blockers. Discussion/Conclusion: This study provides insights into the natural history of HF in a large cohort of well-treated chronic HF outpatients with respect to subgroups of HF and different etiologist.
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