Pulmonary vascular disease in pulmonary hypertension due to left heart disease: pathophysiologic implications

Abstract

Aims Pulmonary hypertension (PH) and pulmonary vascular disease (PVD) are common and associated with adverse outcomes in left heart disease (LHD). This study sought to characterize the pathophysiology of PVD across the spectrum of PH in LHD. Methods and results Patients with PH-LHD [mean pulmonary artery (PA) pressure >20 mmHg and PA wedge pressure (PAWP) ≥15 mmHg] and controls free of PH or LHD underwent invasive haemodynamic exercise testing with simultaneous echocardiography, expired air and blood gas analysis, and lung ultrasound in a prospective study. Patients with PH-LHD were divided into isolated post-capillary PH (IpcPH) and PVD [combined post- and pre-capillary PH (CpcPH)] based upon pulmonary vascular resistance (PVR <3.0 or ≥3.0 WU). As compared with controls (n = 69) and IpcPH-LHD (n = 55), participants with CpcPH-LHD (n = 40) displayed poorer left atrial function and more severe right ventricular (RV) dysfunction at rest. With exercise, patients with CpcPH-LHD displayed similar PAWP to IpcPH-LHD, but more severe RV–PA uncoupling, greater ventricular interaction, and more severe impairments in cardiac output, O2 delivery, and peak O2 consumption. Despite higher PVR, participants with CpcPH developed more severe lung congestion compared with both IpcPH-LHD and controls, which was associated lower arterial O2 tension, reduced alveolar ventilation, decreased pulmonary O2 diffusion, and greater ventilation-perfusion mismatch. Conclusions Pulmonary vascular disease in LHD is associated with a distinct pathophysiologic signature marked by greater exercise-induced lung congestion, arterial hypoxaemia, RV–PA uncoupling, ventricular interdependence, and impairment in O2 delivery, impairing aerobic capacity. Further study is required to identify novel treatments targeting the pulmonary vasculature in PH-LHD.

Response by Borlaug and Shah Regarding Article, “Latent Pulmonary Vascular Disease and Therapeutic Atrial Shunt”

“…Impairments in dynamic RV-pulmonary artery coupling are more likely here given the observed hemodynamics and what is known from the literature. 2,3 Systemic vascular resistance with exercise was ≈30% higher in patients with PVD as Jha notes, but pulmonary vascular resistance with exercise was almost 300% higher, a difference of even greater importance given the heightened afterload sensitivity of the RV in HF with preserved ejection fraction. 4 Although exercise echocardiography was not performed in our study, others have shown dramatic limitations in RV-pulmonary artery coupling during exercise in patients with HF and PVD, 2,3 suggesting that the circulatory bottleneck existed in the pulmonary rather than systemic vasculature.…”

Exercise testing in heart failure with preserved ejection fraction: an appraisal through diagnosis, pathophysiology and therapy – A clinical consensus statement of the Heart Failure Association and European Association of Preventive Cardiology of the European Society of Cardiology

“…membrane diffusion (Dm) and capillary volume (Vc) in parallel with CO changes, is explanatory of the altered pulmonary perfusion pattern occurring in HFpEF, 24 definitively resulting in an increased dead space to tidal volume (VD/VT) ratio and inefficient VE 55 . Exercise‐induced dynamic congestion often overlaps as an additive reason for impaired gas exchange and vascular distensibility 56,57 . The elevated afterload and RV dysfunction sustains further impairment in lung perfusion and challenges cardiac dynamics through an unfavourable RV to LV diastolic interaction.…”

“…55 Exercise-induced dynamic congestion often overlaps as an additive reason for impaired gas exchange and vascular distensibility. 56,57 The elevated afterload and RV dysfunction sustains further impairment in lung perfusion and challenges cardiac dynamics through an unfavourable RV to LV diastolic interaction. This may be observed under maximal exercise quite early and even in HFpEF patients who are otherwise asymptomatic at rest.…”

Diagnosing heart failure with preserved ejection fraction with pulmonary vascular disease

“…1 8 Studies concurred that independent of the underlying left heart pathology (HFpEF, aortic stenosis), patients with CpcPH have substantially worse symptoms and prognosis than those with IpcPH or no PH. Combined noninvasive and invasive studies (eg, the recent study by Omote et al 1 ) have improved our understanding of the mechanisms underlying the symptoms of patients with . Importantly, the studies compiling this evidence used the 2015 CpcPH definition as inclusion criterion (most often by using only the PVR ≥3 WU criterion).…”