Phosphodiesterase-5 (PDE5) Inhibition and Pulmonary Hypertension in Diastolic Heart Failure
Phosphodiesterase-5 (PDE5) Inhibition and Pulmonary Hypertension in Diastolic Heart Failure
Prevalence of heart failure (HF) with left ventricular (LV) diastolic dysfunction and
 preserved ejection fraction (EF) (HFpEF) is increasing. Prognosis worsens with development of
 pulmonary vasoconstriction and hypertension (PH) and right ventricular (RV) failure. The
 investigators aimed at modulating pulmonary vascular tone and RV burden in HFpEF due to high
 blood pressure (HBP), by using the phosphodiesterase-5 (PDE5) inhibitor sildenafil.
Heart failure (HF) with preserved left ventricular (LV) ejection fraction (EF) (HFpEF) is a
 public health problem and a major topic in clinical cardiology. Its prevalence, in fact, is
 increasing and the outcome seems to be similar to that of HF with LV systolic dysfunction
 (LVSD). Pulmonary hypertension (PH) in HFpEF is highly prevalent and often severe and, like
 in LVSD (3), is a predictor of morbidity and mortality (4). Because of the thin wall and the
 distensibility, the right ventricle (RV) is much more vulnerable by an excessive afterload
 than by preload. The pulmonary circulation is a central determinant of RV afterload, and an
 increase in impendance to RV ejection, like occurring in LV dysfunction, can easily result in
 RV failure, tricuspid regurgitation, central venous pressure (CVP) rise. Development of RV
 failure is unanimously viewed as a predictor of poor prognosis but the underlying mechanisms
 have not been extensively investigated.

 Because of the prevalence and clinical significance of PH secondary to HF, attenuation of the
 pulmonary vascular tone and of the RV hemodynamic burden has been suggested as a goal to be
 achieved with HF therapy. Attempts with endothelin receptor antagonists, or prostacyclin
 analogues, were basically unsuccessful. Experimental models and human studies, showing that
 in HF nitric oxide (NO) - dependent pulmonary vasodilatation is impaired and pulmonary
 vascular resistance elevation is at least in part due to pulmonary endothelial dysfunction,
 have suggested therapeutic strategies with agents that increase NO activity, like nitrates or
 phosphodiesterase - 5 (PDE5) inhibitors (12-14). The latter agents offer the double advantage
 of selectively dilating the pulmonary vessels and not producing tachyphylaxis.

 In this 1-year duration study, the primary end-point was to probe whether pulmonary
 hemodynamics and RV performance in HFpEF with PH may be targets of PDE5 inhibition with
 sildenafil.
Inclusion Criteria:

 -  LVEF >50%

 -  sinus rhythm and stable clinical condition defined as no changes in therapeutic
 regimen, or hospitalization in the 6 months preceding recruitment.

 -  pulmonary artery systolic pressure > 40 mm Hg,

 Exclusion Criteria:

 -  Patients receiving nitrates

 -  A history of pulmonary disease

 -  Alternative causes of PH other than cardiac-related

 -  Renal failure (creatinine > 2mg/dL)

 -  Anemia

 -  Pericardial disease

 -  Cardiac amyloidosis