Pulmonary Artery Pressure Reduction With ENTresto (Sacubitril/Valsartan) (PARENT)
Congestive Heart Failure
About this trial
This is an interventional treatment trial for Congestive Heart Failure focused on measuring heart failure, neprilysin, implantable hemodynamic monitor, angiotensin-receptor blocker, angiotensin-converting enzyme inhibitor
Eligibility Criteria
Inclusion Criteria:
- Patients able to provide written informed consent
- Patients ≥18 years of age, male or female, in NYHA Class II- III HF, previously hospitalized for HFrEF with LVEF < 35% (measured within the past year), and who have no subsequent LVEF>35%.
- Systolic BP > 95 mm Hg at most recent clinical assessment.
- Stable, ambulatory patients without the need for change in diuretics and other HF drugs (RAS blockers, beta blockers or mineralocorticoid receptor blockers) during the past 5 days
- CardioMEMS HF System implanted for NYHA Class III HF. Patient transmitting information regularly and system functioning appropriately.
- NT-proBNP > 500 pg/ml within 90 days of CardioMEMS implantation.
- Average PAPm >20mm Hg during the 7 days prior to enrollment, including at least 4 daily measurements.
- Women of childbearing age must be on highly effective method of contraception
Exclusion Criteria:
- Treatment with vasodilators (other than nitrates, hydralazine) and/or IV inotropic drugs.
- Entresto taken within the past 30 days.
- History of hypersensitivity, intolerance or angioedema to previous renin-angiotensin system (RAS) blocker, ACE inhibitor, ARB, or Entresto.
- eGFR < 30 ml/min/1.73 m2 as measured by the simplified MDRD formula.
- Serum potassium > 5.5 mmol/L.
- Acute coronary syndrome, stroke, transient ischemic attack, cardiovascular surgery, PCI, or carotid angioplasty within the preceding 3 months.
- Coronary or carotid artery disease likely to require surgical or percutaneous intervention within 3 months after trial entry.
- Non-cardiac condition(s) as the primary cause of dyspnea.
- Implantation of a cardiac resynchronization therapy device (CRT/D) within the pr preceding 3 months or intent to implant a CRT/D, which may alter the pressures during the course of the study.
- History of heart transplantation, placement of an LVAD, listing for Status IA for cardiac transplantation or planned placement of an LVAD within 3 months following randomization.
- Documented untreated ventricular arrhythmia with syncopal episodes within the prior 3 months.
- Symptomatic bradycardia or second or third degree heart block without a pacemaker.
- Hepatic dysfunction, as evidenced by total bilirubin > 3 mg/dl.
- Pregnancy
- Women who are breastfeeding
- Chronic lithium use
Sites / Locations
- Brigham and Women's Hospita
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Group A
Group B
Group A will receive sacubitril/valsartan + placebo for weeks 1-12. and then sacubitril/valsartan only for weeks 13-32. All subjects in Group A will also receive longitudinal pulmonary artery pressure monitoring using a previously placed implantable hemodynamic monitor (CardioMEMS device).
Group B will receive an Angiotensin-Converting Enzyme Inhibitor (ACEi) or Angiotensin II Type 1 Receptor Blocker (ARB) + placebo for weeks 1-6 (depending on previous background therapy) and then switch to sacubitril/valsartan + placebo for weeks 7-12. Group B will then receive sacubitril/valsartan only for weeks 13-32. All subjects in Group B will also receive longitudinal pulmonary artery pressure monitoring using a previously placed implantable hemodynamic monitor (CardioMEMS device).