ARETHA: cARdiomems vEriciguaT Heart fAilure (A double-blind randomized placebo-controlled trial of vericiguat in heart failure patients with CardioMEMS™ HF System)

Prior treatment

• Implantation of CRT device within the previous 90 days
• Current alcohol and/or drug abuse
• Concurrent or anticipated use of (1) long-acting nitrates or nitric oxide (NO) doners including isosorbide dinitrate, isosorbide 5-mononitrate, pentaerythritol tetranitrate, nicorandil or transdermal nitroglycerin (NTG) patch, and molsidomine, (2) sGC stimulators such as riociguat, (3) PDE5 inhibitors such as vardenafil, tadalafil, and sildenafil or (4) intravenous inotropes
• Previous or planned LVAD or HTx implantation

Other illness

• Known allergy or sensitivity to any sGC stimulator
• Primary valvular heart disease requiring surgery or intervention or is within 3 months after valvular surgery or intervention
• Acute coronary syndrome (unstable angina, non-ST elevation myocardial infarction [NSTEMI], or ST elevation myocardial infarction [STEMI] or coronary revascularization (coronary artery bypass grafting [CABG] or percutaneous coronary intervention [PCI]) within 60 days, or indication for coronary revascularization at first study visit
• Symptomatic carotid stenosis, transient ischemic attack (TIA) or stroke within 60 days
• Complex congenital heart disease
• Severe hepatic insufficiency such as with hepatic encephalopathy
• Require continuous home oxygen for severe pulmonary disease
• Interstitial Lung Disease

Lab values

• eGFR <15 mL/min/1.73 m2 or chronic dialysis

Age

• Malignancy or other non-cardiac condition limiting life expectancy to <1 years
• Women of reproductive age and childbearing potential not using at least one safe form of contraception

Other

• Patients in optimization phase in the CardioMEMS system or implantation of the CardioMEMs device within the past 2 weeks
• Diagnosed with hypertrophic obstructive cardiomyopathy, acute myocarditis, amyloidosis, sarcoidosis, or takotsubo cardiomyopathy
• Tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia
• Active endocarditis or constrictive pericarditis
• Recent (within 14 days) hospitalization for decompensated HF
• Participating in another interventional clinical study or plans to participate in any other trial/investigation during the duration of this study
• Mental or legal incapacitation and is unable to provide informed consent
• Immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is involved with this study
• Pregnant or breastfeeding (or lactating) or plans to become pregnant or to breastfeed during the course of the study
• Average supine SBP <100 mmHg at the screening or randomization visit
• Current symptomatic hypotension
• Recent changes (within 48 hours) in diuretic dose, recent (within 4 weeks) initiation of hydralazine, long-acting nitrates, β-blockers, ACEi/ARB or ARNi.
• Marked variability in PA diastolic pressure during screening period
• Low CardioMEMS reading compliance (<75% 30 days reading compliance)

• 18 years or older
• Ability to provide informed consent
• CardioMEMS implanted for clinical indication (≥ 2 weeks prior to first visit)
• Known chronic heart failure (HF) with left ventricular ejection fraction (LVEF) <45% (documented within the past 24 months by an imaging modality: echocardiography, nuclear imaging, LV angiography, or magnetic resonance imaging)
• NYHA functional class II-IV symptoms.
• Optimal and stable medical therapy for HF (as indicated under point 5 of exclusion criteria)
• Systolic blood pressure (SBP) ≥100 mmHg
• Diastolic pulmonary artery pressure (dPAP) >15 mmHg more than 8 days in the last 14 days on the CardioMEMS system.