RIGHT VENTRICULAR - PULMONARY ARTERIAL UNCOUPLING PREDICTS MORTALITY IN CANDIDATES FOR ADVANCED HEART FAILURE THERAPIES
CCC ePoster Library. Wright S. 10/26/19; 280527; 292
Dr. Stephen Wright
Dr. Stephen Wright
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Abstract
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BACKGROUND: 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.

METHODS AND RESULTS: 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).

CONCLUSION: 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.
BACKGROUND: 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.

METHODS AND RESULTS: 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).

CONCLUSION: 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.
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