Clinical trial NCT02099903: Renal Denervation in Patients With Heart Failure Secondary to Chagas Disease
Official title: Transcatheter Renal Denervation in Patients With Systolic Heart Failure Due to Chagas' Disease - a Safety and Efficacy Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Heart Failure
Heart Failure, Systolic
Chagas Disease
Chagas Cardiomyopathy
Keywords: Heart Failure
Heart Failure, Systolic
Chagas Disease
Chagas Cardiomyopathy
Renal Denervation
Irrigated Radiofrequency Catheter
Lead sponsor: InCor Heart Institute
Sponsor class: OTHER
Collaborators: name: Johnson & Johnson
First posted: 2014-03-31
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: It is a randomized prospective controlled study of transcatheter renal denervation in patients with systolic heart failure secondary to Chagas' disease. The purpose of the study is to evaluate the safety and effectiveness of renal denervation in patients with Chagas heart disease, due to reduction in renal and systemic sympathetic activity.

Detailed description: The activation of the sympathetic nervous system is one of the main mechanisms involved in heart failure pathophysiology, as well as activation of the renin-angiotensin-aldosterone system. These compensatory mechanisms are initially beneficial, in order to restore adequate cardiac output. Their long-term activation, nevertheless, leads to several deleterious effects on cardiovascular system, such as direct myocite lesion, cardiac hypertrophy, myocardial ischemia, oxidative stress, cardiac arrhythmias and myocite apoptosis, among others.

It has been widely demonstrated that modulation of sympathetic nervous system is an important therapeutic target for the treatment of systolic heart failure. Beta-blocker and ACE inhibitors therapies are the main stem of heart failure treatment and have demonstrated reduction in morbidity and mortality of this condition. Despite optimized medical treatment, heart failure carries a poor prognosis.

Surgical sympathectomy has been used decades ago for the treatment of malignant hypertension and showed marked reduction in arterial pressure. However, these procedures were very aggressive and lead to long hospitalization and recovery periods, as well as several limiting adverse effects. Recently, transcatheter renal denervation has evolved as a promising and less invasive technique, which allows destruction of renal nerves located on the adventitia of the renal arteries. The ablation procedure is performed by delivery of radiofrequency energy from the tip of a catheter positioned into the renal arteries, through standard femoral artery catheterization, a less morbid and safer approach.

Renal denervation has been tested mainly in patients with resistant hypertension, among other indications, with promising results. The pathophysiological basis for this treatment in hypertension, as well as heart failure, stands on the participation of renal afferent and efferent nerves on the maintenance of elevated systemic vascular resistance. Activation of efferent nerves leads to excretion o renin, aldosterone, angiotensin II, elevated norepinephrine levels and consequent retention of salt and water and reduction of renal blood flow. This mechanism and also afferent renal nerves activation contributes to the elevation of sympathetic tonus on the central nervous system.

In animal models of heart failure, renal denervation demonstrated improvement on renal and cardiac function. Initial clinical studies suggest that this intervention is safe and potentially effective on the treatment of heart failure in humans. Chagas heart disease is a prevalent cause of heart failure in Brazil and shares several pathophysiological aspects described for other causes of heart failure. Our aim is to evaluate the safety and effectiveness of renal denervation in systolic heart failure due to Chagas Heart disease.

Eligibility criteria: Inclusion Criteria:

1. Patients ≥ 18 to ≤ 70 years of age with chronic systolic heart failure, Chagas disease etiology.
2. Two positive serology results for Chagas by two distinct methods.
3. NYHA (New York Heart Association) class II or III.
4. Patients treated with maximum tolerated doses of standard pharmacotherapy for heart failure.
5. LVEF (Left Ventricular Ejection Fraction) ≤ 40% (Simpson Method).

Exclusion Criteria:

1. Patients with NYHA class I or IV.
2. Sustained ventricular tachycardia (\>30 sec) or with hemodynamic compromise.
3. Presence of permanent pacemaker or implantable defibrillator.
4. Systolic blood pressure \< 90 mmHg.
5. Heart beat \< 60 bpm at rest.
6. Advanced renal insufficiency (estimated glomerular filtration rate (GFR) \< 30 ml/min/1.73 square meters).
7. Patients with planned cardiac surgery or percutaneous revascularization.
8. Other reasons which would preclude the patient from participating in the study (comorbidities, life expectancy less than 1 year).
9. Unsuitable anatomy of renal arteries, renal stenosis or previous treatment with balloon or stent.
10. Refusal of the patient.

Primary outcomes:
measure: Composite: death, myocardial infarction, cerebrovascular event, need of intervention on renal arteries and renal function impairment (decrease in estimated GFR > 30% from baseline).
timeFrame: 30 days.
Secondary outcomes:
measure: Left Ventricular Ejection Fraction (LVEF) by echocardiography.
timeFrame: 9 months.
measure: New York Heart Association (NYHA) functional class.
timeFrame: 9 months.
measure: 6-minute walk test
timeFrame: 9 months.
measure: Peak Oxygen consumption (VO2) by ergoespirometry.
timeFrame: 9 months.
Other outcomes:
measure: Change in serum B-type natriuretic peptide (BNP).
timeFrame: 9 months.
measure: Quality of life assessed by Minnesota and EuroQOL five dimensions (EQ-5D)questionnaires.
timeFrame: 9 months.
measure: Peripheral sympathetic activity measured by microneurography.
timeFrame: 9 months.
Locations:
city: Sao Paulo
country: Brazil
facility: Heart Institute - InCor. University of Sao Paulo Medical School
Study officials:
References: