Study of Renal Denervation in Patients With Heart Failure
Condition: Heart Failure
MeSH terms: Heart Failure
Intervention: Symplicity Renal Denervation
Intervention description: Renal denervation
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 21 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      Congestive heart failure is a common disorder in which the heart cannot pump enough blood to
      meet the needs of the rest of the body. Poor sodium handling by the kidneys is a damaging
      effect of heart failure, and it leads to symptoms of congestion such as shortness of breath
      or ankle swelling. Recent studies suggest that reducing the nerve activity to a kidney could
      reduce sodium retention and blood pressure. An improvement in the way the kidneys handle
      sodium may reduce disease progression and decrease symptoms for heart failure patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, aged 21-80 years old.

          -  History of chronic HF (>6 months) with current NYHA II-III symptoms.

          -  Left Ventricular Ejection Fraction ≤40% on a clinically indicated echocardiogram
             obtained within 6 months prior to informed consent.

          -  Requires daily loop diuretic (≥40mg furosemide per day, or equivalent) to maintain
             euvolemia (absence of congestive signs including jugular venous distension with
             Jugular Venous Pressure > 7cm H20, ≥ moderate (2+) peripheral edema, S3).

          -  Optimized medical therapy for HF. Patients will be receiving guideline-recommended
             therapy (per the 2013 ACCF/AHA HF Guidelines) including angiotensin-converting enzyme
             (ACE) inhibitors and/or angiotensin receptor blocker, beta-blockers, and aldosterone
             antagonists without changes in heart failure medication regimen (including diuretics)
             for previous 14 days.

          -  Systolic blood pressure (BP) ≥110 mmHg at time of informed consent.

          -  Able to maintain stable medications for 52 weeks.

          -  Suitable renal artery anatomy for Renal Sympathetic Denervation (RSD) procedure. All
             of the following criteria must be met, based on the screening renal Doppler
             ultrasound:

          -  ≥ 20mm treatable length in each renal artery,

          -  Diameter in treatable segments must be ≥4mm,

          -  Lone main renal vessel feeding each kidney.

        Exclusion Criteria:

          -  Unable to comply with protocol or procedures.

          -  Evidence of orthostatic hypotension or known dysautonomia. Orthostatic hypotension is
             defined by ≥1 of the following feature(s) within 2-5 minutes of quiet standing:

          -  ≥ 20 mmHg fall in systolic pressure

          -  ≥ 10 mmHg fall in diastolic pressure

          -  Symptoms of cerebral hypoperfusion (e.g. dizziness or lightheadedness, visual blurring
             or darkening of the visual fields, syncope).

          -  Evidence of or history of renal artery stenosis, nephrectomy, or renal transplant.

          -  Significant renal impairment as defined by estimated glomerular filtration rate (eGFR)
             < 45 ml/min/1.73m2 determined by Modification of Diet in Renal Disease (MDRD)
             equation.

          -  Significant proteinuria (>2g protein/daily protein excretion).

          -  Body mass index (BMI) >35 kg/m2.

          -  Acute coronary syndrome within last 4 weeks as defined by ECG changes and biomarkers
             of myocardial necrosis (e.g. troponin) in an appropriate clinical setting (chest
             discomfort or angina equivalent).

          -  Coronary revascularization procedures (percutaneous coronary intervention or cardiac
             artery bypass graft) and or valve surgery within 30 days of screening or expected
             procedures within the next 6 months.

          -  Cardiac resynchronization therapy, with or without implantable cardiac defibrillator
             within 90 days of screening or expected procedures within the next 6 months.

          -  Hypertrophic or restrictive cardiomyopathy, constrictive pericarditis, active
             myocarditis, active endocarditis, or complex congenital heart disease.

          -  Severe advanced HF, with ANY of the following features:

          -  Current or anticipated use of ventricular assist device within the next 6 months.

          -  Current or anticipated IV vasoactive drug therapy for HF management within the next 6
             months.

          -  Listed cardiac transplant candidate, with transplantation likely within the next 6
             months.

          -  Known allergic reactions to iodinated radiological contrast media or iodinated
             antiseptics.

          -  Greater than moderate mitral or aortic stenosis, and/or severe tricuspid
             regurgitation.

          -  Terminal illness (other than HF) with expected survival of less than 1 year.

          -  Female who is pregnant, nursing, or of childbearing potential not practicing effective
             birth control.

          -  Enrollment or planned enrollment in another clinical trial within the next 12 months.

          -  History of urinary outflow tract obstruction, bladder retention and/ or moderate to
             severe prostate hypertrophy.

          -  History of adrenal insufficiency

          -  History of untreated hypothyroidism

          -  Patients with non-cardiac dyspnea or fatigue due to frailty, motivational factors,
             pulmonary disease or orthopedic problems that precludes them from performing 6MWT
             (Six-Minute WalkTest).