Effect of sacubitril/valsartan on cardiac filling pressures in patients with left ventricular systolic dysfunction

Abstract

Background: Sacubitril/valsartan is the newest neurohormonal agent approved for therapy in patients with heart failure with reduced ejection fraction (HFrEF). Little is known about its acute and incremental hemodynamic effects. We aimed to evaluate the change in hemodynamic profiles measured using an implanted monitoring device in HFrEF patients initiated on sacubitril/valsartan therapy.

Methods: We prospectively enrolled 13 subjects with HFrEF and pre-implanted CardioMEMS™ device on maximally tolerated guideline-directed medical therapy and no contraindications to sacubitril/valsartan therapy. Transmitted pulmonary artery diastolic pressures (PAdP) from CardioMEMS™ were averaged and compared for one week before and after initiation of sacubitril/valsartan, as well as after change in medication strength and finally at three months.

Results: Sacubitril/valsartan dose increase was tolerated in 7/13 subjects with drug discontinuation in one subject after a week due to renal dysfunction. There was a significant reduction in mean PAdP after sacubitril/valsartan initiation compared to standard therapy (20.8 vs 18.3 mm Hg, p = 0.020). No further PAdP reduction was noted after sacubitril/valsartan dose increase (19.7 vs 20 mm Hg, p = 0.673) and at 3-month follow-up compared to baseline (20.8 vs 19.2 mm Hg, p = 0.352).

Conclusions: Sacubitril/valsartan causes an acute reduction mean pulmonary artery pressures after initiation. However, no incremental reduction in PAdP was noted after dose increase and short-term follow-up. The current study demonstrates the utility of CardioMems™ device to study the drug's impact on hemodynamic profile in both short- and long-term follow-up.

Keywords: Cardiac filling pressure; CardioMems; Congestive heart failure; Sacubitril/valsartan.