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

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), = 0.0003), fibrinogen (OR= 1.019 (1.005-1.033), = 0.085), creatinine (OR =1.025 (1.004-1.047), = 0.0223) and right ventricular end-diastolic dimension (RVEDd) (OR = 1.279 (1.074-1.525), = 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.