Treatment of exercise pulmonary hypertension improves pulmonary vascular distensibility

Abstract

Exercise pulmonary hypertension (ePH) is an underappreciated form of exertional limitation. Despite normal resting pulmonary artery pressures, patients with ePH demonstrate early pulmonary vascular changes with reduced pulmonary arterial compliance (PAC) and vascular distensibility (α). Recent data suggest that targeted vasodilator therapy may improve hemodynamics in ePH, but it is not well-known whether such medications alter pulmonary vascular distensibility. Thus, we sought to evaluate if vasodilator therapy improved α a marker of early pulmonary vascular disease in ePH. Ten patients performed supine exercise right heart catheterization (exRHC) with bicycle ergometer to peak exercise. Patients diagnosed with ePH were treated with pulmonary vasodilators. A repeat symptom-limited exercise RHC was performed at least six months after therapy. Patients with ePH had evidence of early pulmonary vascular disease, as baseline PAC and α were reduced. After pulmonary vasodilator therapy, a number of peak exercise hemodynamics statistically improved, including a decrease of total pulmonary resistance and pulmonary vascular resistance, while cardiac output increased. Importantly, vasodilator therapy partially reversed the pathogenic decreases of α at the time of repeat exRHC. Pulmonary vascular distensibility, α, a marker of early pulmonary vascular disease, improves in ePH after therapy with pulmonary vasodilators.

Keywords: early pulmonary vascular disease; exercise hemodynamics; exercise pulmonary hypertension; pulmonary hypertension; vascular distensibility.

Fig. 1.

Peak pulmonary artery compliance vs. pulmonary vascular resistance pre-treatment (blue line) and post-treatment (red line). Plotted values are mean values for PAC and PVR.

Fig. 2.

Peak exercise hemodynamics measured before and after therapy. (a) Alpha; (b) PAC; (c) PVR; (d) cardiac output; (e) mPAP; (f) TPR. Box plots show median, IQR, and minimum and maximum values.

Fig. 3.

Relationship of α with peak exercise hemodynamics. (a) Pre-therapy Spearman correlation demonstrated a non-significant correlation with PAC and strongly significant inverse correlations with TPG and PA pulse pressure. (b) Post-therapy Spearman correlation demonstrated a significant correlation with PAC and strongly significant inverse correlations with TPG and PA pulse pressure.

Fig. 4.

Correlation of resting DLco% with peak exercise PAC and PVR. Resting DLco% strongly correlated with (a) PAC and (b) PVR at peak exercise.

Fig. 5.

Hemodynamics at submaximal stages of exercise. Each stage of exercise represents approximately 10–25 W of workload representing < 4 METS effort consistent with activities of daily living. TPR, PVR, and mPAP are reduced with increased CO during post-treatment measures, indicating that at lower workloads there are improved flows, pressure, and resistance.