Pulmonary Artery Pressure Reduction With ENTresto (Sacubitril/Valsartan)
Condition: Congestive Heart Failure
MeSH terms: Heart Failure
Intervention: Implantable Hemodynamic Monitor; Angiotensin-Converting Enzyme Inhibitor; Angiotensin II Type 1 Receptor Blocker; sacubitril/valsartan
Intervention description: The CardioMEMS device is an implantable pulmonary artery pressure monitor that is FDA-approved for use in patients with symptomatic heart failure and previous heart failure hospitalization. Patients eligible for this study are those with an already implanted CardioMEMS device.; Conventional, guideline-directed therapy for heart failure and reduced ejection fraction; Conventional, guideline-directed therapy for heart failure and reduced ejection fraction in ACE-inhibitor intolerant patients; Angiotensin-neprilysin inhibitor that is now FDA-approved and guideline-directed therapy for patients with symptomatic heart failure and reduced ejection fraction despite treatment with an ACE-inhibitor/Angiotensin-Receptor Blocker
Intervention MeSH terms: Valsartan; Angiotensin II; Giapreza; Angiotensin II Type 1 Receptor Blockers; Sacubitril and valsartan sodium hydrate drug combination; Angiotensin Receptor Antagonists; Enzyme Inhibitors; Angiotensinogen; Angiotensin-Converting Enzyme Inhibitors
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: heart failure; neprilysin; implantable hemodynamic monitor; angiotensin-receptor blocker; angiotensin-converting enzyme inhibitor

Summary:

      This pilot study will assess the impact of sacubitril/valsartan (trade name Entresto) on the
      elevated pulmonary artery pressures in patients with heart failure with reduced ejection
      fraction, measured using a previously implanted hemodynamic monitoring device (CardioMEMS).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients able to provide written informed consent

          2. 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%.

          3. Systolic BP > 95 mm Hg at most recent clinical assessment.

          4. 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

          5. CardioMEMS HF System implanted for NYHA Class III HF. Patient transmitting information
             regularly and system functioning appropriately.

          6. NT-proBNP > 500 pg/ml within 90 days of CardioMEMS implantation.

          7. Average PAPm >20mm Hg during the 7 days prior to enrollment, including at least 4
             daily measurements.

          8. Women of childbearing age must be on highly effective method of contraception

        Exclusion Criteria:

          1. Treatment with vasodilators (other than nitrates, hydralazine) and/or IV inotropic
             drugs.

          2. Entresto taken within the past 30 days.

          3. History of hypersensitivity, intolerance or angioedema to previous renin-angiotensin
             system (RAS) blocker, ACE inhibitor, ARB, or Entresto.

          4. eGFR < 30 ml/min/1.73 m2 as measured by the simplified MDRD formula.

          5. Serum potassium > 5.5 mmol/L.

          6. Acute coronary syndrome, stroke, transient ischemic attack, cardiovascular surgery,
             PCI, or carotid angioplasty within the preceding 3 months.

          7. Coronary or carotid artery disease likely to require surgical or percutaneous
             intervention within 3 months after trial entry.

          8. Non-cardiac condition(s) as the primary cause of dyspnea.

          9. 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.

         10. 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.

         11. Documented untreated ventricular arrhythmia with syncopal episodes within the prior 3
             months.

         12. Symptomatic bradycardia or second or third degree heart block without a pacemaker.

         13. Hepatic dysfunction, as evidenced by total bilirubin > 3 mg/dl.

         14. Pregnancy

         15. Women who are breastfeeding

         16. Chronic lithium use