Abstract
Background. We sought to evaluate the long-term effects of angiotensin receptor blocker–neprilysin inhibitor (ARNI) therapy on reverse remodeling of the failing myocardium in HFrEF patients. Methods. We performed a prospective non-randomized longitudinal study on 228 HFrEF patients treated with ARNI at our center. Prior to ARNI introduction all patients received stable doses of ACEI/ARB for at least six months. Clinical, biochemical and echocardiography data were obtained at ARNI introduction and 12-month follow-up. Results At follow-up, we found significant improvements in LVEF (29.7% ± 8% vs. 36.5% ± 9%; p < 0.001), LVOT-VTI (14.8 ± 4.2 cm vs. 17.2 ± 4.2 cm; p < 0.001), TAPSE (1.7 ± 0.5 cm vs. 2.1 ± 0.6 cm; p < 0.001) and LV-EDD (6.5 ± 0.8 cm vs. 6.3 ± 0.9 cm; p = 0.001). NT-proBNP serum levels also decreased significantly (1324 (605, 3281) pg/mL vs. 792 (329, 2022) pg/mL; p = 0.001). A total of 102 (45%) of patients responded favorably to ARNI (ΔLVEF < +5%; Group A) and 126 (55%) patients achieved ΔLVEF ≥ +5% (Group B). The two groups differed significantly in age, heart failure etiology, baseline LVEF and baseline NT-proBNP. On multivariable analysis, nonischemic heart failure, LVEF < 30% and NT-proBNP < 1500 pg/mL emerged as independent correlates of favorable response to ARNI therapy. Conclusion. ARNI therapy appears to improve echocardiographic parameters of left and right ventricular function in HFrEF patients above the effect of pre-existing optimal medical management. These effects may be particularly pronounced in patients with nonischemic heart failure, LVEF < 30% and lower degree of neurohumoral activation.
Highlights
With the publication of paradigm-HF trial in 2014 [1] angiotensin receptor blocker–neprilysin inhibitors (ARNI) became a new promising class of drugs for the treatment of patients with heart failure with reduced ejection fraction (HFrEF)
ARNI therapy appears to improve echocardiographic parameters of left and right ventricular function in HFrEF patients above the effect of pre-existing optimal medical management. These effects may be pronounced in patients with nonischemic heart failure, left ventricular systolic dysfunction (LVEF) < 30% and lower degree of neurohumoral activation
Studies of guidelines-based optimal heart failure medical therapy using angiotensin converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), beta receptor blocking agents (β-blockers) and mineralocorticoid receptor antagonists (MRA) have demonstrated that improved clinical outcomes of HFrEF patients were associated with the reverse remodeling of the failing myocardium [4] which largely predicated on the inhibition of renin–angiotensin–aldosterone axis
Summary
With the publication of paradigm-HF trial (prospective comparison of ARNI with ACEI to determine impact on global mortality in heart failure) in 2014 [1] angiotensin receptor blocker–neprilysin inhibitors (ARNI) became a new promising class of drugs for the treatment of patients with heart failure with reduced ejection fraction (HFrEF). Diagnostics 2020, 10, 522 establishing ARNI as an evolving first-line treatment approach in this patient population [2,3]. Despite these encouraging findings, the underlying mechanisms still remain incompletely understood. Studies of guidelines-based optimal heart failure medical therapy using angiotensin converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), beta receptor blocking agents (β-blockers) and mineralocorticoid receptor antagonists (MRA) have demonstrated that improved clinical outcomes of HFrEF patients were associated with the reverse remodeling of the failing myocardium [4] which largely predicated on the inhibition of renin–angiotensin–aldosterone axis. We sought to evaluate the long-term effects of angiotensin receptor blocker–neprilysin inhibitor (ARNI) therapy on reverse remodeling of the failing myocardium in HFrEF patients.
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