Abstract 4371524: The Right Ventricle as a Hidden Culprit: How Sympathetic Overdrive Fuels Pulmonary Congestion in Heart Failure with Preserved Ejection Fraction

Background: In the era of heart failure (HF) pandemics, prevention of acute HF is an urgent issue to be overcome. However, the mechanisms underlying the development of acute HF are not fully understood. Sympathetic activation is exceptionally high at the onset of acute HF, suggesting a link. The aim of this study is to elucidate the role of right ventricular (RV) sympathetic innervation as a mechanism for the development of pulmonary congestion by sympathetic activation in left ventricular diastolic HF. Hypothesis: The presence of right ventricular sympathetic nerves contributes to pulmonary congestion through sympathetic activation. Methods: Hemodynamic simulation was performed using commercially available simulator (Harvi). The change in diastolic property was calculated using α, the stiffness constant. Our previous reports have shown that sympathetic activation determines hemodynamics by changing ventricular properties (contractility and heart rate) and vascular properties (vascular resistance and stressed blood volume), with each element increasing by approximately 50% at maximal sympathetic activation. We tested whether sympathetic activation in various LV diastolic properties produces an increase in left atrial pressure, a marker of pulmonary congestion. We also assessed the increase in left atrial pressure when only RV contractility remained unchanged, and tested the effect of increased RV contractility on the increase in left atrial pressure (LAP). Results: When α=0.3, sympathetic activation increased right atrial pressure (RAP) 5 to 7 mmHg, LAP 11 to 21 mmHg and cardiac output (CO) 5.59 to 6.41 L/min, whereas in the absence of RV contractility enhancement, RAP 9 mmHg, LAP 16 mmHg and CO 6.13 mmHg, an increase in LAP of 5 mmHg was suppressed. At α=0.5, sympathetic activation resulted in RAP 4 to 5 mmHg, LAP 22 to 40 mmHg and CO 3.86 to 4.29 L/min, whereas in the absence of enhancement of RV contractility, RAP 7 mmHg, LAP 32 mmHg and CO 4.1 mmHg, an increase in LAP of 8 mmHg was suppressed. Conclusions: Sympathetic activation caused a marked increase in left atrial pressure, i.e. pulmonary congestion, in left ventricular diastolic dysfunction. RV contractility enhanced by RV sympathetic innervation may result in exacerbation of pulmonary congestion. These results also suggest that selective right ventricular sympathetic denervation may be an effective strategy to prevent acute exacerbations of heart failure.