Pulmonary Vascular Distensibility Predicts Pulmonary Hypertension Severity, Exercise Capacity, and Survival in Heart Failure

Abstract

Background Pulmonary vascular (PV) distensibility, defined as the percent increase in pulmonary vessel diameter per mmHg increase in pressure, permits the pulmonary arteries to increase in size to accommodate increased blood flow. We hypothesized that PV distensibility is abnormally low in patients with heart failure (HF) and serves as an important determinant of right ventricular performance and exercise capacity. Methods and Results Patients with HF and preserved ejection fraction (HFpEF, n=48), HF and reduced ejection fraction (HFrEF, n=55), pulmonary hypertension without left-heart failure (PAH, n=18), and control subjects (n=30) underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring and first-pass radionuclide ventriculography. PV distensibility was derived from 1257 matched measurements (mean±SD, 8±2 per subject) of PA pressure, PA wedge pressure and cardiac output. PV distensibility was lowest in the PAH group (0.40±0.24% per mmHg) and intermediate in the HFpEF and HFrEF groups (0.92±0.39 and 0.84±0.33% per mmHg, respectively) compared to the control group (1.39±0.32% per mmHg, P<0.0001 for all three). PV distensibility was associated with change in RVEF (ρ=0.39, P<0.0001) with exercise and was an independent predictor of peak VO2. PV distensibility also predicted cardiovascular mortality independent of peak VO2 in HF patients (n=103, Cox HR 0.30, 95% CI 0.10–0.93, P=0.036). In a subset of HFrEF patients (n=26), 12 weeks of treatment with the pulmonary vasodilator sildenafil or placebo led to a 24.6% increase in PV distensibility (P=0.015) in the sildenafil group only. Conclusions PV distensibility is reduced in patients with HF and PAH and is closely related to RV systolic function during exercise, maximal exercise capacity, and survival. Furthermore, PV distensibility is modifiable with selective pulmonary vasodilator therapy and may represent an important target for therapy in selected HF patients with pulmonary hypertension. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00309790.

Role of Diastolic Stress Testing in the Evaluation for Heart Failure With Preserved Ejection Fraction

“…While some might consider this finding as being sufficient to abandon maximal invasive exercise testing, it is important to consider that other valuable information can be obtained with peak testing, including insight on the roles of cardiac vs peripheral factors in limiting exercise capacity 19, 24–28 and more detailed understanding of pulmonary vascular physiology. 29, 30 …”

Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology

“…Elevation in left atrial pressure and impaired left atrial strain response during exercise (despite preserved LV ejection fraction) is pathognomonic for HFpEF, and this acutely shifts the PA resistance–compliance relationship leftward, causing an increase in pulsatile RV load . Assessment of PA pressure–flow relationships with exercise has been proposed as a useful and prognostically relevant metric to evaluate vascular reserve in HFpEF, and some HFpEF phenotypes, such as those with obesity‐related HFpEF, may display greater abnormalities in RV–PA coupling during exercise that potentially move forward towards therapeutic implications …”

Hemodynamic Phenotyping of Pulmonary Hypertension in Left Heart Failure

“…[15][16][17][18] This may be explained by the fact that decreased C PA increases RV afterload and may, thus, determine a predominantly right HF phenotype of poor prognosis. The exquisite sensitivity of C PA to increased PAWP 12,13 makes it also a marker of the severity of left ventricular (LV) failure, which in itself is an additional risk factor of decreased survival.…”