Evaluation of the Entresto Effect on Sympathic Nervous System in Patient With Heart Failure

Evaluation of the Effect of Double Inhibition of Angiotensin II AT1 Receptor and Neprilysin Activity on Sympathic Nervous System Activity in Patient With Heart Failure

The hyperactivation of the sympathetic nervous system is a feature of the heart failure and the determinants of disease progression and risk of sudden cardiac death. This research project aims to study, in the drug use conditions provided in the summary of product characteristics based on European marketing authorization (indications and dosage), the effect of the Entresto® on the activity of sympathic nervous system using the reference method, the microneurographic recording of sympathetic activity in muscle destiny (MSNA). This study will try to determine if the double inhibition of AT1 receptor and neprilysin activity result in lower sympathic nervous system burst rate versus single AT1 receptor inhibition using angiotensin-converting-enzyme inhibitor or AT1 receptor of angiotensin II inhibitor.

Inclusion Criteria:

• Men or women with heart failure with symptomatic left ventricular systolic dysfunction (left ventricular ejection fraction ≤ 40 %) with :

  • Functional class New York Heart Association II and at least 2 hospitalizations for cardiac decompensation in the year with N terminal pro brain-type natriuretic peptide ≥300 pg/ml (or brain-type natriuretic peptide ≥100 pg/ml) or usage of intravenous diuretics,
  • Functional class New York Heart Association III-IV,
  • Insufficiently controlled by alternative drug-free therapies (surgery, cardiac resynchronization ...) or well managed drug therapies: angiotensin-converting-enzyme inhibitor, AT1 receptor of angiotensin II inhibitor diuretics or beta blockers.
  • Treated by maximum dosage of AT1 receptor of angiotensin II inhibitor or angiotensin-converting-enzyme inhibitor for New York Heart Association II patient or 50% of the recommended dose for New York Heart Association III-IV patients or New York Heart Association II patients with clinical manifestation restricting the use of maximum dosage, like orthostatic hypotension.

• Patient member of his home social security scheme

Exclusion Criteria:

• Patient who are receiving direct renin inhibitor like aliskiren
• Patient who are receiving phosphodiesterase V inhibitors
• Patient who are receiving a potassium-sparing drug
• Patient with medical history of angioedema with previous treatment by angiotensin-converting-enzyme inhibitor or AT1 receptor of angiotensin II inhibitor
• Hypersensitivity to any component of Entresto®
• Adult protected by the law
• Severe renal impairment (DFGe <30 ml/min/1,73 m2)
• Severe hepatic impairment, cirrhosis or cholestasis (Child-Pugh C class)
• Patient with are receiving anticoagulant therapies or suffering from known hemostatic trouble
• Patient participating in another biomedical research or with an active exclusion period
• Pregnancy
• Breast-feeding