The CardioMEMS Vericiguat Heart Failure Trial

Prior treatment

• Concurrent or anticipated use of: o Long-acting nitrates or nitric oxide (NO) doners including isosorbide dinitrate, isosorbide 5-mononitrate, pentaerythritol tetranitrate, nicorandil or transdermal nitroglycerin (NTG) patch, and molsidomine. o sGC stimulators such as riociguat. o PDE5 inhibitors such as vardenafil, tadalafil, and sildenafil. o Intravenous inotropes.
• Previous or planned LVAD or HTx implantation.
• Implantation of CRT device within the previous 90 days.

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.

Lab values

• Tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia 15. 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.
  • 16\. Symptomatic carotid stenosis, transient ischemic attack (TIA) or stroke within 60 days 17. Complex congenital heart disease 18. Active endocarditis or constrictive pericarditis 19. eGFR \<15 mL/min/1.73 m2 or chronic dialysis. 20. Severe hepatic insufficiency such as with hepatic encephalopathy 21. Malignancy or other non-cardiac condition limiting life expectancy to \<1 years.
  • 22\. Require continuous home oxygen for severe pulmonary disease. 23. Current alcohol and/or drug abuse. 24. Participating in another interventional clinical study or plans to participate in any other trial/investigation during the duration of this study.
  • 25\. Mental or legal incapacitation and is unable to provide informed consent. 26. Immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is involved with this study.
  • 27\. Interstitial Lung Disease. 28. Is pregnant or breastfeeding (or lactating) or plans to become pregnant or to breastfeed during the course of the study.
  • 29\. Females 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.
• Recent (within 14 days) hospitalization for decompensated HF.
• 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).
• Diagnosed with hypertrophic obstructive cardiomyopathy, acute myocarditis, amyloidosis, sarcoidosis, or takotsubo cardiomyopathy.

• ≥18 years
• Ability to provide informed consent.
• CardioMEMS implanted for clinical indication (≥ 2 weeks prior to first visit).
• Known CHF with 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)
• SBP ≥100 mmHg
• dPAP \>15 mmHg more than 8 days in the last 14 days on the CardioMEMS system.