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Right Ventriclo-Arterial Coupling in Patients with Pulmonary Arterial Hypertension Undergoing Rapid Dose Escalation of Treprostinil

Franz Rischard


Hunter Champion


Marc Simon


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Conference: 2014 International PHA Conference and Scientific Sessions

Release Date: 06.21.2014

Presentation Type: Abstracts

File Download: 2014 Conference Abstract - Franz Rischard

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The mechanism of vasoactive therapy in pulmonary arterial hypertension (PAH) on ventriculo-arterial interaction is not well established. Therefore, we prospectively investigated the effect of treprostinil on pulmonary vascular elastance (Ea), right ventricular (RV) systolic (Ees) and coupling in PAH patients.

Background: The mechanism of vasoactive therapy in pulmonary arterial hypertension (PAH) on ventriculo-arterial interaction is not well established. Therefore, we prospectively investigated the effect of treprostinil on pulmonary vascular elastance (Ea), right ventricular (RV) systolic (Ees) and coupling in PAH patients.

Methods and Results: Single-beat RV pressure-volume analysis was performed in 9 functional class IV PAH patients before and after rapid inpatient dose escalation, and after gradual outpatient dose increase of treprostinil. Data are presented as mean+SEM. Treprostinil dose was 12.8+0.46 ng/kg/min at discharge and 44.2+4.34 ng/kg/min by 3 months (mo.). Treprostinil was most consistently associated with a decrease in Ea (2.44+0.26 mmHg/ml baseline, 1.95+0.49 mmHg/ml discharge, and 1.38+0.28 mmHg/ml 3 mo. Ees was decreased slightly at discharge (1.62+0.35 mmHg/ml baseline vs. 1.49+0.3 mmHg/ml) and then reduced further by 3 mo. (0.85+0.18 mmHg/ml). The decrease in Ea, compared to Ees, was more pronounced at discharge, but relatively the same at 3 mo. leading to a coupling ratio of 0.68+0.15 baseline, 0.98+0.23 discharge, and 0.68+0.16 at 3 mo. Most patients demonstrate similar changes in Ea and Ees (both direction and magnitude) at discharge and 3 mo. Although Ees decreased at 3 mo., there was 906+530 mmHg*ml stroke work reserve with exercise and a 139+45 M increase in 6 minute walk distance vs. discharge. Both RV stroke work (RVSW) increased and work efficiency maintained at discharge and 3 mo. RV end-diastolic volumes (RV EDV) however remained elevated 241+28.2 ml baseline, 225+30.4 ml discharge,  and 218+24.5 ml 3 mo.

Conclusions: Treprostinil primarily exerts its effects by lowering RV afterload (Ea) both acutely and at 3 mo. This effect governs the improvement in RV systolic pump failure and contractile reserve.  Increases in RVSW are likely related to significant lowering of afterload and persistently high baseline preload dependent (heterometric) autoregulation. 

Type: Clinical Science