Phosphodiesterase-5 (PDE5) Inhibition and Pulmonary Hypertension in Diastolic Heart Failure

Brief Title

Phosphodiesterase-5 (PDE5) Inhibition and Pulmonary Hypertension in Diastolic Heart Failure

Official Title

Pulmonary Hypertension Secondary to Heart Failure With Preserved Systolic Function: a Target of Phosphodiesterase - 5 Inhibition in a 1- Year Duration Study

Brief Summary

      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.
    

Detailed Description

      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.
    

Study Phase

Phase 2/Phase 3

Study Type

Interventional


Primary Outcome

Pulmonary hemodynamics


Condition

Pulmonary Hypertension

Intervention

Sildenafil

Study Arms / Comparison Groups

 Sildenafil
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

44

Start Date

January 2006

Completion Date

December 2009

Primary Completion Date

September 2009

Eligibility Criteria

        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
      

Gender

Male

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

, , 



Administrative Informations


NCT ID

NCT01156636

Organization ID

444-10



Study Sponsor

University of Milan


Study Sponsor

, , 


Verification Date

June 2009