RIGHT VENTRICULAR - PULMONARY ARTERIAL UNCOUPLING PREDICTS MORTALITY IN CANDIDATES FOR ADVANCED HEART FAILURE THERAPIES

Abstract

Advanced therapies for heart failure with reduced ejection fraction (HFrEF) include cardiac transplantation and mechanical circulatory support. For both therapies, right ventricular (RV) dysfunction and/or pulmonary hypertension portend adverse outcomes, particularly when systolic PA pressure (sPAP) ≥50 mmHg. End-systolic elastance (Ees) quantifies load-independent systolic RV performance, which can be related to the effective PA load (Ea) by their coupling ratio (Ees:Ea). Elastance may be more sensitive than pressures to detect elevated RV afterload and assess RV-PA coupling. We tested the hypothesis that elevated Ea and Ees:Ea uncoupling are associated with worse prognosis in this population. We prospectively enrolled consecutive patients with HFrEF who underwent right heart catheterization as part of their evaluation for advanced therapies into a registry. A sodium nitroprusside challenge was initiated if sPAP ≥50mmHg and either transpulmonary gradient ≥15 mmHg or pulmonary vascular resistance >3 WU. RV and PA pressures were analyzed offline, and Ees and Ea were determined using a single-beat approach. PA Ea >0.5 mmHg/mL was defined as ‘elevated’, and an Ees:Ea ratio < 0.8 was defined as ‘uncoupled’. We retrospectively collected all-cause mortality from electronic patient records, and examined its association with Ees, Ea, and Ees:Ea using Kaplan-Meier analysis and Cox regression adjusted for age and sex. Data are reported as n (%), median [interquartile range], or hazard ratio (HR). We included 175 patients (57 [50-63] years, 77% male) (Table 1). Ea was normal in 65 patients (37%); of these, 14 (22%) demonstrated uncoupled Ees:Ea. Of the 110 (63%) with elevated Ea, 47 had a sPAP ≥50mmHg and 36 (21% overall) met criteria for a vasodilator challenge. For these cases, sodium nitroprusside (0.75 [0.25-1.00] mcg/kg/min) reduced Ea, (0.63 [0.52-0.82] vs. 0.93 [0.83-1.32] mmHg/mL, p < 0.001). Among patients with an elevated Ea, Ees:Ea was uncoupled in 68 (62%) and coupled in 42. Follow-up was available for 164/175 patients. Fifty patients (29%) died over a median follow-up of 2.2 [0.7-4.4] years. Ea (HR = 2.04 (95%CI 1.20-3.48), p = 0.009, χ2 = 6.5) and Ees:Ea (HR = 0.42 (95%CI 0.23-0.76), p = 0.005, χ2 = 13.8) were each associated with mortality, but isolated Ees was not. Mortality was greater in all subgroups compared to patients with normal Ea and coupled Ees:Ea (Figure 1). Elastance measurements identify RV-PA uncoupling, as well as elevated RV afterload in patients with HFrEF even with acceptable PA pressures. Elevated Ea and uncoupled Ees:Ea identify patients with worse prognosis.View Large Image Figure ViewerDownload Hi-res image Download (PPT)