Effects of Sacubitril/Valsartan on Exercise Capacity, Natriuretic Peptides and Ventricular Remodeling in Heart Failure
Condition: Heart Failure
MeSH terms: Heart Failure; Ventricular Remodeling
Study type: Observational

Summary: 
      Background: Sacubitril/valsartan, a novel therapy in the treatment of heart failure with
      reduced ejection fraction (HFrEF), has recently proved efficacy in improving exercise
      tolerance and cardiac performance. Cardiopulmonary exercise test (CPET) provides functional
      prognostic parameters for patient with HFrEF (i.e. peakVO2 and ventilation/CO2 production
      [VE/VCO2] slope) and it is a well-recognized, valuable, accurate tool for risk
      stratification.

      Aim of the study and methods: The aim of the study is to prospectively enroll a cohort of 100
      HFrEF outpatients eligible for sacubitril/valsartan and perform serial CPET, laboratory and
      echocardiographic assessments before and during the gradual titration of the treatment, in
      order to evaluate its effects on cardiopulmonary function and left ventricular remodeling.
      The procedures will be repeated along the follow-up at 1, 2 and 3 months after the enrollment
      (titration period) and at 6 months after the reach of the maximum tolerated dose.
    

Detailed description: 
      Given the recent introduction of the drug into the clinical routine, the evaluation of the
      experience "on the field" is important to refine the clinical management of patients treated
      with sacubitril / valsartan. Furthermore, at the moment sacubitril / valsartan has proven
      effective in some small preliminary studies in improving the ejection fraction and some
      echocardiographic parameters of ventricular remodeling on top of the concomitant optimal
      medical therapy, although further data are needed in this regard.

      In particular, the potential benefits on exercise capacity, respiratory function parameters
      and left ventricular remodeling in heart failure patients treated with sacubitril / valsartan
      has not been studied extensively at the moment. In this regard, the cardiopulmonary exercise
      test (CPET) allows to obtain prognostic functional parameters in patients with chronic heart
      failure such as peak V02 (peak V02) and the ventilation / production of C02 slope (VE / VC02
      slope). CPET is a valid, recognized and accurate tool for risk stratification in heart
      failure patients.

      Furthermore, few data are available on lung diffusion (DLCO) and on specific markers of the
      alveolar-capillary membrane, such as type B surfactant proteins (SPB) in patients treated
      with sacubtril / valsartan. Our team has already shown how these biomarkers and DLCO are
      influenced by drug treatments such as Levosimendan and Ace inhibitors.

      The aim of the study is to evaluate the exercise capacity, spirometry, echocardiographic
      parameters of left ventricular sistolic and diastolic function, Nt-proBNP dosage and quality
      of life and the related dose-effect correlation in a multicenter cohort of 100 patients with
      stable heart failure (class functional NYHA II e lII) and reduced left ventricular ejection
      fraction in patients eligible for sacubitril / valsartan treatment.

      A subgroup of patients will be also analyzed for data relating to the effect of sacubitril /
      valsartan on DLCO and blood levels of Surfactant Bindig protein (SPB).

      Sacubitril / Valsartan will be prescribed according to guidelines, initially at the lowest
      dosage of 24/26 mg b.i.d. to verify its tolerability with the prospect of gradually
      increasing the dosage during subsequent follow-up visits. The re-evaluation of the treatment
      and the titration of the sacubitril / valsartan dose will take place every 4 weeks until the
      maximum tolerated dose is reached. The dose under study will be the maximum tolerated by the
      patient (however not higher than 97 mg / 103mg bd).

      Cardiological examination with ECG, spirometry, CPET, the Kansas City Cardiomyopathy
      Questionnaire, blood count, creatinine, nitrogen, sodium, potassium, chlorine and NTproBNP
      will be performed at each visit (from Baseline to 6 months). The colordoppler echocardiogram
      will instead be performed only at the baseline and after 6 months.

      A subset of patients will also be subjected to analysis of the blood levels of SPB and DLCO
      at baseline and 6 months after reaching the maximum tolerated dose.
    

Intervention name(s): Sacubitril-Valsartan
Intervention type(s): Drug
Intervention description(s): outpatients who start treatment with sacubitril/valsartan according to guidelines will andergo cardiopulmonary exercise testing evaluation
Intervention MeSH terms: Valsartan; Sacubitril and valsartan sodium hydrate drug combination
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        HFrEF outpatients eligible for sacubitril/valsartan according to guidelines and perform
        serial CPET, laboratory and echocardiographic assessments before and during the gradual
        titration of the treatment
      
Keywords: sacubitril/valsartan; exercise; cardiopulmonary exercise test; left ventricular remodeling