Pulmonary Vascular Load Impairs Dynamic Right Ventricular-pulmonary Artery Coupling And Increases Lung Congestion During Exercise In Left Heart Disease

Abstract

Background Pulmonary hypertension (PH) is common complication of left heart disease (LHD) and associated with poor outcomes. Exertional dyspnea and fatigue are frequently reported symptoms among patients with PH due to LHD, and these symptoms are more severely observed in patients with combined post- and pre-capillary PH (CpcPH) as compared with isolated post-capillary PH (IpcPH). However, the pathophysiologic mechanisms underlying exercise intolerance in this setting remain poorly understood. Methods Subjects with elevated both mean pulmonary artery pressure (>20 mmHg) and pulmonary capillary wedge pressure (PCWP) (>15 mmHg) at rest were classified into two groups: CpcPH (pulmonary vascular resistance [PVR]≥3.0 WU, n=32), IpcPH (PVR<3.0 WU, n=54), and controls (n=52) underwent cardiopulmonary exercise testing with invasive hemodynamics and simultaneous echocardiography and lung ultrasound in a prospective study. Results As compared with controls and IpcPH-LHD, subjects with CpcPH-LHD displayed poorer LV diastolic function, lower left atrial (LA) reservoir and booster strain with greater LA volume and more severe right ventricular systolic dysfunction at rest. With exercise, subjects with CpcPH-LHD displayed more severe exercise-induced pulmonary hypertension, higher right atrial pressure (RAP) and more pronounced right ventricular-pulmonary vascular uncoupling. Peak oxygen consumption was lowest in patients with CpcPH-LHD, coupled with greater limitations in cardiac output reserve and more severe increases in lung congestion, arterial hypoxia and pulmonary vascular resistance (Figure 1). Dynamic ventricular interaction was greatest in CpcPH-LHD, evidenced by greater LV eccentricity index and RAP/PCWP and less increase in LV transmural pressure compared with IpcPH-LHD (Figure 2). Conclusions : Patients with CpcPH-LHD display more severe abnormalities in pulmonary vascular reserve with exercise leading to greater lung congestion and enhanced exertional ventricular interdependence compared to patients with IpcPH-LHD. Further study is required to identify therapies targeting pulmonary vascular disease or ventricular interdependence to improve outcomes in people with CpcPH-LHD. Pulmonary hypertension (PH) is common complication of left heart disease (LHD) and associated with poor outcomes. Exertional dyspnea and fatigue are frequently reported symptoms among patients with PH due to LHD, and these symptoms are more severely observed in patients with combined post- and pre-capillary PH (CpcPH) as compared with isolated post-capillary PH (IpcPH). However, the pathophysiologic mechanisms underlying exercise intolerance in this setting remain poorly understood. Subjects with elevated both mean pulmonary artery pressure (>20 mmHg) and pulmonary capillary wedge pressure (PCWP) (>15 mmHg) at rest were classified into two groups: CpcPH (pulmonary vascular resistance [PVR]≥3.0 WU, n=32), IpcPH (PVR<3.0 WU, n=54), and controls (n=52) underwent cardiopulmonary exercise testing with invasive hemodynamics and simultaneous echocardiography and lung ultrasound in a prospective study. As compared with controls and IpcPH-LHD, subjects with CpcPH-LHD displayed poorer LV diastolic function, lower left atrial (LA) reservoir and booster strain with greater LA volume and more severe right ventricular systolic dysfunction at rest. With exercise, subjects with CpcPH-LHD displayed more severe exercise-induced pulmonary hypertension, higher right atrial pressure (RAP) and more pronounced right ventricular-pulmonary vascular uncoupling. Peak oxygen consumption was lowest in patients with CpcPH-LHD, coupled with greater limitations in cardiac output reserve and more severe increases in lung congestion, arterial hypoxia and pulmonary vascular resistance (Figure 1). Dynamic ventricular interaction was greatest in CpcPH-LHD, evidenced by greater LV eccentricity index and RAP/PCWP and less increase in LV transmural pressure compared with IpcPH-LHD (Figure 2). : Patients with CpcPH-LHD display more severe abnormalities in pulmonary vascular reserve with exercise leading to greater lung congestion and enhanced exertional ventricular interdependence compared to patients with IpcPH-LHD. Further study is required to identify therapies targeting pulmonary vascular disease or ventricular interdependence to improve outcomes in people with CpcPH-LHD.