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

Wioletta Szczurek,Bożena Szyguła-Jurkiewicz,Ewa Romuk,Michał Skrzypek,Mariusz Gąsior

doi:10.3390/jcm9113539

Wioletta Szczurek, Bożena Szyguła-Jurkiewicz + Show 3 more

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https://doi.org/10.3390/jcm9113539

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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.

Highlights

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)
All the included patients were classified as New York Heart Association (NYHA) classes III (32.6%) and IV (67.4%)
All the patients were subjected to an optimal medical therapy and were on the same drug regimen that included: angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) (2.3% of patients), beta-blockers, loop diuretics and mineralocorticoid receptor antagonist (MRA)

Summary

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). Structural remodeling and endothelial dysfunction in the pulmonary vascular tree result in an increase of pulmonary vascular resistance (PVR) in some heart failure (HF) patients, leading to severe PH [2,3]. The elevation of left-sided filling pressures that results from left ventricular dysfunction leads to a passive increase in pulmonary venous pressure [3] This passive component affects an endothelium-dependent reactive component and causes deficiency in nitric oxide-mediated vasodilation in the pulmonary arterial bed, as well as increased transpulmonary gradient and PVR [3]. Reactive pulmonary vasoconstriction may be reversed, if treated early enough and over a long period [5,6]

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