In PARADIGM-HF, Valsartan/Sacubitril (ARNI) therapy was shown to reduce morbidity and mortality compared to ace-inhibitor (ACE-I) therapy in Heart Failure with Reduced Ejection Fraction (HFrEF). However, PARADIGM-HF did not report echocardiographic findings which may provide a mechanism for the observed improvement in clinical outcomes. ACE-I, mineralocorticoid receptor antagonist (MRA) and beta-blockers have previously demonstrated favorable left ventricular (LV) remodeling. We sought to analyze echocardiographic markers of cardiac remodeling before and after ARNI therapy.
Methods and Results
We conducted a blinded retrospective cohort study at a regional cardiovascular center. All HFrEF patients who had 3 months of stable disease on optimal background therapy with ACE-I, Beta-blocker and MRA (where tolerated) who were newly switched to maximal dose ARNI therapy were screened for inclusion. Only patients who previously had an echocardiogram within 6 months prior to ARNI initiation and a second echocardiogram within 3 to 12 months after initiation were included. Patients who had adjustments to other HFrEF therapies (such as beta-blockers or MRA) between follow-up echocardiograms were excluded from the study. Following inclusion, all echocardiograms (pre and post ARNI initiation) were re-evaluated by a single cardiologist reviewer in a blinded fashion under the same protocol in order to decrease the variability and reviewer bias. LV end systolic volume index (LVESVi) was the pre-specified primary outcome. We screened 252 HFrEF patient charts. 21 patients met inclusion criteria and their echocardiograms were re-evaluated in a blinded manner. The primary reason for exclusion was lack of available pre and post echocardiograms. Mean age was 67 and 81% were male. Prior to ARNI initiation, the mean LVEF was 34%, 67% of patients had ischemic cardiomyopathy and 81% of patients had New York Heart Association class II symptoms. Mean LVESVi was significantly reduced from 49.4 ml/m2 at baseline to 37.4 ml/m2 post-ARNI initiation (mean reduction 11.9 ml/m2, 95% CI -22.2, -1.7). Among secondary outcomes, LVEF was significantly increased by a mean 10.9% (95% CI 5.0, 16.8) and right ventricular systolic pressure was significantly reduced by a mean 6.7 mmHg (95% CI -11.5, -1.9). There was no significant reduction in LV end diastolic volume index (mean reduction -7.1 ml/m2, 95% CI -17.0, 2.8) or significant increase in stroke volume (mean increase 4.6 mL, 95% CI -4.5, 13.7).
This study demonstrates significant improvements in multiple echocardiographic parameters following ARNI optimization in HFrEF patients, suggesting favorable LV remodeling. This may provide a mechanistic explanation for the benefits of ARNI therapy in HFrEF.
© 2022 Published by Elsevier Inc.