Factors Associated with Ineffectiveness of Sildenafil Treatment in Patients with End-Stage Heart Failure and Elevated Pulmonary Vascular Resistance

Abstract

Introduction: Elevated pulmonary vascular resistance (PVR) unresponsive to vasodilator treatment is a marker of heart failure (HF) severity, and an important predictor of poor results of heart transplantation (HT). Objective: We sought to analyze factors associated with ineffectiveness of sildenafil treatment in end-stage HF patients with elevated PVR with particular emphasis placed on tenascin-C (TNC) serum concentrations. Patients and Methods: The study is an analysis of 132 end-stage HF patients referred for HT evaluation in the Cardiology Department between 2015 and 2018. TNC was measured by sandwich enzyme-linked immunosorbent assay (Human TNC, SunRedBio Technology, Shanghai, China). The endpoint was PVR > 3 Wood units after the six-month sildenafil therapy. Results: The median age was 58 years, and 90.2% were men. PVR >3 Wood units after 6 months of sildenafil treatment were found in 36.6% patients. The multivariable logistic regression analysis confirmed that TNC (OR = 1.004 (1.002–1.006), p = 0.0003), fibrinogen (OR= 1.019 (1.005–1.033), p = 0.085), creatinine (OR =1.025 (1.004–1.047), p = 0.0223) and right ventricular end-diastolic dimension (RVEDd) (OR = 1.279 (1.074–1.525), p = 0.0059) were independently associated with resistance to sildenafil treatment. Area under the ROC curves indicated an acceptable power of TNC (0.9680 (0.9444–0.9916)), fibrinogen (0.8187 (0.7456–0.8917)) and RVEDd (0.7577 (0.6723–0.8431)), as well as poor strength of creatinine (0.6025 (0.4981–0.7070)) for ineffectiveness of sildenafil treatment. Conclusions: Higher concentrations of TNC, fibrinogen and creatinine, as well as a larger RVEDd are independently associated with the ineffectiveness of sildenafil treatment. TNC has the strongest predictive power, sensitivity and specificity for evaluation of resistance to sildenafil treatment.