Chronic Sildenafil Treatment in Heart Failure
Condition: Heart Failure
MeSH terms: Heart Failure
Study type: Interventional
Phase: Phase 3

Summary: 
      In heart failure (HF), a defective nitric oxide (NO) signaling may be involved in left
      ventricular (LV) diastolic abnormalities and LV remodelling progression. PDE5-inhibition, by
      blocking NO degradation and overexpressing cellular cyclic guanosine monophosphate (cGMP)
      pathways might be beneficial. Several short term studies have demonstrated safety and
      clinical improvement in stable heart failure (HF) patients.

      The purpose of this study is to test the effects on LV diastolic function, cardiac geometry
      and clinical status in a cohort of HF patients.
    

Detailed description: 
      Heart failure (HF) is a significant health care concern that is evolving to epidemic
      proportions. Development of new forms of interventions remains a challenging task. An
      abnormal nitric oxide (NO) pathway is involved in several basic pathophysiological
      abnormalities encountered in HF syndrome and NO overexpression may represent a desirable
      therapeutic target in the cure of the disease.

      PDE5-inhibition is an intriguing pharmacological strategy to enhance in vivo nitric oxide
      (NO) signaling by increasing the cyclic guanosine monophosphate (cGMP). availability. A
      number of theoretical backgrounds support the use of PDE5-inhibitors in HF and an increasing
      number of clinical studies have been testing PDE5-inhibition as a potential valid adjunct in
      the management of HF patients.

      In failing hearts of animal models, PDE5-inhibition has also provided the attractive
      therapeutic properties to reverse left ventricular chamber remodelling by preventing and
      reversing LV cardiac hypertrophy and fibrosis and by protecting the myocardium from
      ischemia-reperfusion injury and apoptosis. There is also evidence that a defective NO
      activity plays an important role in the excitation-relaxation process of the failing heart,
      an effect explained by a defective cGMP-induced phosphorylation of troponin I, which
      facilitates calcium-independent diastolic cross-bridge cycling and concomitant myocardium
      diastolic stiffening.

      No report has so far investigated whether cardiac function and, primarily, diastolic LV
      function may be a target of chronic PDE5-inhibition and whether any improvement in diastolic
      function is related to a reverse effect in cardiac geometry in patients with HF. Furthermore,
      it is undefined whether a favourable effect on left ventricular function may be involved in
      the reported changes in important clinical correlates such as functional status and quality
      of life. We tested these hypotheses, by addressing the effects of chronic sildenafil
      administration (50 mg three times/day) on diastolic function and clinical status by Tissue
      Doppler imaging, cardiopulmonary exercise testing and quality of life score.
    

Intervention name(s): Sildenafil; Placebo
Intervention type(s): Drug; Drug
Intervention MeSH terms: Sildenafil Citrate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: pde5-inhibition; sildenafil; LV diastolic function; heart failure patients