Letter by Jamous Regarding Article, “Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction: A Target of Phosphodiesterase-5 Inhibition in a 1-Year Study” To the Editor: We read with great interest the article by Guazzi et al1 that, despite its limited sample size, demonstrated a significant change in hemodynamic parameters of sildenafil-treated, uncontrolled hypertensive patients with diastolic heart failure–associated pulmonary hypertension. According to Hoper et al,2 the right heart catheterization algorithm for wedge pulmonary pressure (WPP) 15 and pulmonary vascular resistance 3 (the current study population) is to challenge with Nipride or nitroglycerin, after which a WPP 15 is expected. The patients will fall into 2 groups of pulmonary vascular resistance more or less than 3 Woods Units, with the former indicative of persistent pulmonary arterial hypertension that may respond to vasodilator treatment. Knowing the hemodynamics of the current study population would add more weight to the results and clarify further a subgroup that may benefit from sildenafil. A vasoreactivity test with nitric oxide, epoprostenol, or adenosine is commonly performed during a right heart catheterization for pulmonary arterial hypertension with ensuing prognostic and therapeutic implications. We would have expected the current study patients to have an improvement in the mean pulmonary artery pressure with vasodilators and also a concomitant increase in WPP. Did the follow-up hemodynamics improve with sildenafil despite such findings on the vasoreactivity test, or did the vasoreactivity test actually predict the 6and 12-month findings? As discussed in the article, the drop in mean pulmonary artery with sildenafil was impressive (from 39 at baseline to 20.8 at 12 months). It seems that pulmonary artery dilation alone may not be at play here as in the original study of sildenafil in pulmonary arterial hypertension patients3; the drop in mean pulmonary artery was by 2.6 with 40 mg TID and 4.7 with 80 mg TID. One wonders if other factors caused the change in hemodynamics and the reduction in WPP. If, as postulated, the increase in transpulmonary gradient in diastolic heart failure is a pulmonary capillary response to a chronically elevated WPP increase rather than a primary pulmonary arteriopathy, then one could expect a resolution of the transpulmonary gradient with a reduction in WPP (even if not back to normal). Finally, a vasodilator, epoprostenol, was studied in New York Heart Association III/IV heart failure. That study4 was terminated early secondary to increased mortality that occurred despite an increase in cardiac index and a decrease in WPP. Thus, the results of the current study, especially when confirmed with a large clinical trial, will cause a paradigm shift in the use of vasodilators in the setting of pulmonary hypertension associated with elevated WPP and preserved ejection fraction.