Prognostic impact of LV contractility in patients treated with sacubitril/valsartan for heart failure with reduced ejection fraction
T Stegmann, M Niedermeier, L Parentin, S H Schirmer, A Hagendorff, U Laufs, D LavallAbstract
Background
Sacubitril/valsartan (S/V) reduces heart failure (HF) hospitalizations and all-cause mortality in patients with HF and reduced ejection fraction (HFrEF). We recently demonstrated improvements in the pressure-volume relationship after 6 months of S/V treatment. The long-term hemodynamic trajectories and prognostic impact of pressure-volume parameters during S/V administration are unknown.
Purpose
Primary objectives of this study were 1) to evaluate long-term LV hemodynamic alterations (LV end-systolic elastance [Ees], representing LV contractility; effective arterial elastance [Ea], representing LV afterload; and ventricular-arterial coupling [Ea/Ees]), and 2) to investigate the association between pressure-volume-parameters Ees and Ea/Ees and all-cause mortality.
Methods
Between April 2020 and November 2021, we prospectively enrolled patients with symptomatic HF, NYHA class II–IV and reduced left ventricular ejection fraction (LVEF) ≤40% in this registry. Patients were followed for 24 months. Transthoracic echocardiography with simultaneous blood pressure measurements at baseline, 3, 6, and 12 months was used for non-invasive pressure–volume loop analyses. Multivariable Cox regression analyses were performed to assess the association with all-cause mortality at 24 months.
Results
117 patients were included in this analysis. At baseline, mean age was 65 (SD±13) years, 35 (30%) were female, 30 (26%) were in NYHA class III, median LV ejection fraction (LVEF) was 33% (IQR 27;38), and median NT-proBNP was 2096 pg/ml (IQR 927;5611). 64 (55%) had ischemic and 53 (45%) had a non-ischemic cardiomyopathy. After 12 months, 6 (5%) patients were in NYHA class III, NT-proBNP decreased (655 pg/ml; IQR 260;1524), and LVEF improved (44%, IQR 40;49). There was a sustained leftward shift of LV pressure-volume relationship with improved Ees (0.66 [IQR 0.45;0.96] vs. 0.97 [IQR 0.67;1.29], p<0.001), Ea (1.75 [IQR 1.48;2.15] vs.1.55 [IQR 1.32;1.98], p<0.001), and, a better ventricular-arterial coupling ratio Ea/Ees (2.52 [IQR 1.84;4.03] vs. 1.69 [IQR 1.27;2.35], p<0.001), Fig. 1. At 24 months, 16 (13.7%) patients died and 47 (40.2%) had at least one HF event. Ees at baseline was independently associated with all-cause mortality (adjusted HR 0.25, 95% CI 0.07-0.95, p=0.041). Patients with lower baseline values, reflecting poorer LV contractility function, had an approximately 4-fold increased risk of mortality. Changes in pressure-volume-parameters from baseline to 3 months were not associated with outcome.
Conclusion
There were sustained improvements in LV contractility, LV afterload, and LV arterial-ventricular coupling after 12 months of treatment with sacubitril/valsartan therapy in HF and reduced ejection fraction. LV contractility at baseline was an independent predictor of mortality in long-term follow-up. These data indicate an incremental value of LV pressure-volume-analysis for the evaluation of cardiac hemodynamics in HF.Figure 1