Effect of optimisation to contemporary HFrEF medical therapy with sacubitril/valsartan (Entresto) and dapaglifloziN on left Ventricular reverse remodelling as demonstrated by cardiac magnetic resonance (CMR) Imaging: the ENVI study.

INTRODUCTION: Heart failure with reduced ejection fraction (HFrEF) guidelines recommend 'four pillars' of medical therapy and device therapy if left ventricular ejection fraction (LVEF) remains ≤35% after 3 months optimum medical therapy.We conducted the first study to examine the effects of optimisation to contemporary medical therapy on cardiac reverse remodelling, as demonstrated by cardiac magnetic resonance imaging (CMR).We hypothesised a proportion of patients would undergo beneficial remodelling and LVEF improvement above the threshold for complex device prescription after 6 months.

METHODS: HFrEF patients with symptomatic LVEF≤35% despite ACE inhibitor/beta blocker/mineralocorticoid receptor antagonist therapy, and qualified for sacubitril/valsartan switchover were recruited to this single centre prospective study.CMR was performed at baseline and at follow-up. Clinical, volumetric and outcome data were collected and compared.

RESULTS: Between June 2021 and August 2022, 49 patients were recruited. The majority (80%) were male, mean age 63±14 years. 35 (71%) had non-ischaemic cardiomyopathy. 2 (4%) patients died and 47 were followed up for a median of 7.4 months. There were no heart failure hospitalisations.Significant reductions were seen in median indexed left atrial volume: 54 mL/m2 (41-72) to 39 mL/m2 (30-60) (p<0.001); indexed left ventricular end-diastolic volume: 109 mL/m2 (74-125) to 76 mL/m2 (58-102) (p<0.001); indexed left ventricular end-systolic volume: 74mL/m2 (50-92) to 43 mL/m2 (27-58) (p<0.001) and mean indexed left ventricular mass: 72±13 g/m2 to 62±13 g/m2 (p<0.001).Median LVEF increased by 12 points from 31% to 43% (p<0.001). 29 (59%) patients improved to LVEF>35%. 13 (27%) patients improved to LVEF≥50%.Median N-terminal pro B type natriuretic peptide (NTproBNP) reduced from 883 ng/L (293-2043) to 429 ng/L (171-1421) (p<0.001).

CONCLUSIONS: Optimisation to contemporary HFrEF medical therapy results in beneficial cardiac reverse remodelling and significant improvements in LVEF and NTproBNP at 6 months as demonstrated by CMR. 59% of our cohort no longer met complex device indications. Guidelines suggest re-assessment of LVEF at 3 months, but our data suggests a longer period is required.

TRIAL REGISTRATION NUMBER: NCT05348226.