Heart Failure Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction A Target of Phosphodiesterase-5 Inhibition in a 1-Year Study

Background—The prevalence of heart failure with preserved ejection fraction is increasing. The prognosis worsens with pulmonary hypertension and right ventricular (RV) failure development. We targeted pulmonary hypertension and RV burden with the phosphodiesterase-5 inhibitor sildenafil. Methods and Results—Forty-four patients with heart failure with preserved ejection fraction (heart failure signs and symptoms, diastolic dysfunction, ejection fraction Ն50%, and pulmonary artery systolic pressure Ͼ40 mm Hg) were randomly assigned to placebo or sildenafil (50 mg thrice per day). At 6 months, there was no improvement with placebo, but sildenafil mediated significant improvements in mean pulmonary artery pressure (Ϫ42.0Ϯ13.0%) and RV function, as suggested by leftward shift of the RV Frank-Starling relationship, increased tricuspid annular systolic excursion (ϩ69.0Ϯ19.0%) and ejection rate (ϩ17.0Ϯ8.3%), and reduced right atrial pressure (Ϫ54.0Ϯ7.2%). These effects may have resulted from changes within the lung (reduced lung water content and improved alveolar-capillary gas conductance, ϩ15.8Ϯ4. Conclusions—The multifaceted response to phosphodiesterase-5 inhibition in heart failure with preserved ejection fraction includes improvement in pulmonary pressure and vasomotility, RV function and dimension, left ventricular relaxation and distensibility (structural changes and/or ventricular interdependence), and lung interstitial water metabolism (wedge pulmonary pressure decrease improving hydrostatic balance and right atrial pressure reduction facilitating lung lymphatic drainage). These results enhance our understanding of heart failure with preserved ejection fraction and offer new directions for therapy.