Evaluation of early left-sided cardiac reverse remodeling under combined therapy of sacubitril-valsartan and spironolactone compared with angiotensin-converting enzyme inhibitors and spironolactone.

Unlabelled: We aimed to compare therapies of sacubitril/valsartan + spironolactone (S/V + S) with angiotensin-converting enzyme inhibitors + spironolactone (ACEI + S) on the left-sided cardiac reverse remodeling (L-CRR). The second objective was to analyze the usefulness of GLS and LVEF in response to therapy.

Methods: 78 patients (mean age 63.4 years, 20 females) with symptomatic heart failure with reduced ejection fraction were randomized to groups of equal numbers, i.e., 39 patients, and started on therapy of S/V + S or ACEI + S. Second evaluations were made after 6-8 weeks of therapy.

Results: GLS changed from -7.4% to -9.4% (18% improvement) in both arms equally. More than 50% of patients, initially with very severe systolic dysfunction (GLS > -8%), were reclassified to severe (GLS -8% to -12%). LVEF did not improve in any of the groups. The quality of life measured by MLHFQ and walking distance by 6-MWT increased. Positive correlations between GLS and 6MWT ( = 0.41,  = 0.02) and GLS and MHFLQ ( = 0.42,  = 0.03) were found. The S/V + S subgroup demonstrated improvements in LVEDV (Δ16.7 vs. 4.5 ml), E/e ratio (Δ 2.8 vs. 1.4), and LAVI (Δ 9.4 vs. 8.4 ml/m) as compared to ACEI + S.

Conclusion: GLS, unlike LVEF, detects early changes in LV systolic function after 6-8 weeks of combined therapy, i.e., SV + S and ACE + S. GLS is more useful than LVEF in assessing early response to treatment. The effect of S/V + S and ACEI + S on LV systolic function was comparable, but the improvement in diastolic function as expressed by E/e', LAVI, and LVEDV was more pronounced with S/V + S.