Abstract 14195: The Effects of Pulmonary Capillary Wedge Pressure (PCWP) Reduction on Starling Mechanisms in Heart Failure With Preserved Ejection Fraction (HFpEF): Potential for Harm?

Abstract

Introduction: Elevated left ventricular (LV) filling pressure during exercise is a pathognomonic characteristic of HFpEF. Multiple therapies aiming to reduce filling pressures in HFpEF patients have failed to improve exercise capacity and in some studies, decreased activity levels. The Dynamic Starling Mechanism (DSM) quantifies beat-by-beat modulation of stroke volume (SV) by respiratory-mediated changes in LV filling and provides insight into the efficiency with which changes in LV filling pressure are converted to SV. Low DSM gain reflects inefficient conversion of LV pressures (input) into stroke volume (output). In this study, we examined the effect of sublingual nitroglycerin (NTG; 400μg given q15 minutes) to lower PCWP compared to placebo on DSM. Methods: HFpEF patients (n=11, 7 women; age 73 ± 7 years) were studied seated upright at rest following sublingual administration of placebo or NTG. DSM was quantified by transfer function analyses of beat-by-beat changes in pulmonary artery diastolic pressure (PAD, right heart catheterization as index for PCWP) and SV (Modelflow from radial arterial line waveform, normalized to direct Fick-derived SV) at the prevailing respiratory frequency. Direct Fick SV was calculated as VO2/a-vO2 difference divided by heart rate. Results: Compared to placebo, NTG decreased both SV (Placebo: 53 ml vs NTG: 43 ml, p=0.004) and PAD (Placebo: 15.0 mmHg vs NTG: 13.9 mmHg, p=0.026). The DSM gain was decreased with NTG compared to placebo (0.57 vs 0.82 ml/mmHg, p<0.0001) suggesting a smaller change in SV for a change in filling pressure. Conclusions: Lowering cardiac filling pressures in the seated upright position decreased efficiency of the beat-by-beat Starling mechanism. The results may provide insight into how reducing LV filling pressures impacts stroke volume regulation, potentially leading to decreased exercise tolerance in HFpEF patients.