ARNI Versus plAcebo in Patients With Congenital sYStemic Right Ventricle Heart Failure

Exclusion Criteria

• •Participation in a clinical trial of an investigational drug, concurrently, or within the last 30 days prior enrolment
• •Planned cardiac surgery (e.g., severe tricuspid regurgitation with planned tricuspid valve replacement or repair)
• •Previous cardiac transplantation, or on heart transplant wait list
• •Myocardial infarction, stroke, or open-heart surgery in the previous 4 weeks
• •NYHA Functional class I or IV symptoms
• •Symptomatic hypotension (fainting, dizziness, lightheadedness, blurred vision, weakness, fatigue, nausea, palpitations, and headache) with a systolic blood pressure \<100 mmHg at screening, or asymptomatic \<90 mmHg at screening
• •eGFR \<30 mL/min/1.73 m2
• •Reduction in eGFR \>35% from screening to randomization
• •Potassium \>5.2 mmol/L at screening or \>5.4 mmol/L at randomization
• •Known history of angioedema related to previous ACEI or ARB therapy or patients with a history of hereditary or idiopathic angioedema.
• •Patients who require concomitant treatment with an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) or a renin inhibitor for other indication than heart failure
• •Evidence of hepatic disease as determined by any one of the following: serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) values exceeding 3x upper limit of normal, bilirubin \>1.5 mg/dl at screening.
• •Unacceptable side effects with ACE-inhibitors or ARBs
• •Patient known with bilateral renal artery stenosis
• •Cyanosis; substantial left-to-right shunting (Qp/Qs \>1.5); severe mitral, aortic, or pulmonary regurgitation; systemic or pulmonary inflow obstruction with a peak velocity \>1.5 m/s by transthoracic echocardiography; and severe outflow tract obstruction with a peak systolic gradient \>80 mm Hg.
• •Inability to provide informed consent
• •Unable to exercice
• •Pregnant or planned pregnancy during the study
• •Breastfeeding
• •Severe pulmonary hypertension defined as pulmonary pressure egal or superior to systemic pressure