Effects Of Angiotensin Receptor Neprilysin Inhibition On Blood Pressure Response To Exercise In Heart Failure

Abstract

Angiotensin Receptor Neprilysin inhibitors (ARNi) is a new class of drug approved for heart failure patients with reduced ejection fraction (HFrEF). ARNi reduces resting blood pressure (BP) in HFrEF. However, the effect of ARNi on BP response to exercise in HFrEF has not been established. PURPOSE: We hypothesized that BP response to isometric handgrip exercise (IHG) would be attenuated in HFrEF after 12 weeks of ARNi therapy. METHODS: HFrEF participants were recruited from local cardiology clinics and completed a baseline experimental visit and follow up visit 12 weeks later: 6 patients were prescribed ARNi by their cardiologist [64±10 years, Men: 5, BMI: 30±6 kg/m2, EF: 26±7%; 4 with Non-ischemic cardiomyopathy (NICM)], and 5 participants continued on conventional treatment [CON: 57±6 years, Men: 2, BMI: 27±5 kg/m2, EF: 30±4% and NICM: 3; all P = NS]. During each experimental visit, BP was measured at rest and during 2-minutes IHG at 30% maximal voluntary contraction followed by post-HG exercise ischemia (PEI) to isolate the metaboreflex. The change in mean arterial pressure (∆ MAP) from baseline to exercise and PEI was assessed; statistical comparisons were performed using 2x2 repeated-measures ANOVA. RESULTS: At baseline, resting MAP was similar between ARNi (96±14 mmHg) and CON (86±12 mmHg; P=0.17) and MAP increased similarly during IHG (ARNi: ∆ 10±12 vs. CON: 8±10 mmHg) and PEI (ARNi: ∆ 6±4 vs. CON: 5±10 mmHg; ANOVA P>0.90). Resting MAP was reduced after 12 weeks of ARNi (87±7 mmHg) and was unchanged in CON (91±20 mmHg; ANOVA interaction P=0.048). However, the increase in MAP during IHG (ARNi: ∆ 11±8 vs. CON: 13±6 mmHg; P>0.60) and PEI (ARNi: ∆ 8±6 vs. CON: 12±3 mmHg; P>0.60) after 12 weeks was not impacted by ARNi (ANOVA time P=0.24) or different between groups. Maximal raw force and RPE ratings during IHG were similar between groups and not different following 12 weeks of ARNi (ANOVA P>0.70). CONCLUSION: These preliminary data suggest that although 12 weeks of ARNi therapy reduces resting MAP in HFrEF, there are no significant reductions on MAP response to exercise. Additional data are needed to fully understand the impact of ARNi on cardiovascular responses to exercise in HFrEF. Supported by ACSM grant 19-00934 and P20 GM 113125.