Stroke volume augmentation improves with PH-targeted therapy in patients with exercise-induced pulmonary hypertension

Abstract

Exercise-induced pulmonary arterial hypertension (EiPH) is often treated with off-label use of pulmonary arterial hypertension-targeted therapy (PH-targeted therapy). Most measures of PAH severity are normal in patients with EiPH, posing challenges in evaluating for physiological improvement in patients treated for EiPH. In this study, we used non-invasive cardiopulmonary exercise testing (CPET) to assess for objective improvement in patients treated for EiPH. Fourteen patients were included in the study, diagnosed with EiPH by invasive CPET with simultaneous right heart catheterization and subsequently treated with PH-targeted therapy. Follow-up non-invasive CPET was performed to evaluate oxygen consumption (VO₂, L/min) and oxygen pulse (O₂ pulse, ml/beat), which was defined by the ratio of VO₂ to heart rate (beats/min).). Adequate stroke volume augmentation was a ratio of O₂ pulse at anaerobic threshold (O₂ pulse_AT) to O₂ pulse at rest (O₂ pulse_R) of >2.6. The results showed a significant improvement in O₂ pulse and VO₂ at anaerobic threshold after treatment with PH-targeted therapy. In addition, O₂ Pulse_AT:O2 Pulse_R significantly improved. Patients treated for EiPH demonstrated improvement in both stroke volume augmentation and VO₂ measured on non-invasive CPET, supporting the use of this test to assess for objective improvement in exercise capacity for patients treated for EiPH. Structured Abstract.

Rationale: Exercise-induced pulmonary arterial hypertension (EiPH) is a clinical entity characterized by exertional dyspnea. Cardiopulmonary exercise testing (CPET) can evaluate exertional limitations in EiPH patients and assess response to therapy. We describe a series of patients treated for EiPH and monitored with non-invasive CPET.

Methods: case series of 14 patients with EiPH treated with PH-targeted therapy. EiPH was defined by a slope of the mean pulmonary artery pressure (mPAP) vs cardiac output of >3 mmHg/L/min with a resting mPAP of <20 mmHg and pulmonary vascular resistance <3 Woods units. Oxygen pulse (O₂ pulse, ml/beat), a surrogate of stroke volume (SV), was measured by the ratio of oxygen consumption (VO₂, L/min) to heart rate (beats/min). Adequate SV augmentation was a ratio of O₂ pulse at anaerobic threshold (O₂ pulse_AT) to O₂ pulse at rest (O₂ pulse_R) of >2.6.

Results: Patients were majority female (86 %) with a mean age of 59.1.±12.2 years, and 57 % had connective tissue diseases. Patients took PH-targeted therapy (endothelin receptor antagonist (n = 7), phosphodiesterase-5 inhibitor (n = 5) or both (n = 2)) for a median exposure of 150 days. There was no change in O₂ pulse_R after treatment. However, there was a significant increase in the O₂ pulse_AT (9.7 ± 3.1 vs 7.4 ± 3.2 ml/beat, p = 0.003), O₂ pulse_AT/O₂ pulse_R ratio (2.8 ± 0.9 vs. 2.0 ± 0.6, p = 0.006) and VO₂ at anaerobic threshold (0.9 ± 0.3 vs 0.7 ± 0.4 ml/kg/min, p = 0.04).

Conclusions: Patients with EiPH treated with PH-targeted therapy demonstrate improvement in SV augmentation and VO₂ at anaerobic threshold on non-invasive CPET. CPET can serve an objective measure of improvement in exercise capacity in patients treated for EiPH.

Keywords: CPET; EiPH; Oxygen pulse; Stroke volume augmentation.