Renal Denervation in Patients With Heart Failure Secondary to Chagas Disease
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.
Heart Failure, Systolic
Device: transcatheter renal denervation
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Transcatheter Renal Denervation in Patients With Systolic Heart Failure Due to Chagas' Disease - a Safety and Efficacy Study.|
- Composite: death, myocardial infarction, cerebrovascular event, need of intervention on renal arteries and renal function impairment (decrease in estimated GFR > 30% from baseline). [ Time Frame: 30 days. ] [ Designated as safety issue: Yes ]
- Left Ventricular Ejection Fraction (LVEF) by echocardiography. [ Time Frame: 9 months. ] [ Designated as safety issue: No ]
- New York Heart Association (NYHA) functional class. [ Time Frame: 9 months. ] [ Designated as safety issue: No ]
- 6-minute walk test [ Time Frame: 9 months. ] [ Designated as safety issue: No ]
- Peak Oxygen consumption (VO2) by ergoespirometry. [ Time Frame: 9 months. ] [ Designated as safety issue: No ]
- Change in serum B-type natriuretic peptide (BNP). [ Time Frame: 9 months. ] [ Designated as safety issue: No ]
- Quality of life assessed by Minnesota and EuroQOL five dimensions (EQ-5D)questionnaires. [ Time Frame: 9 months. ] [ Designated as safety issue: No ]
- Peripheral sympathetic activity measured by microneurography. [ Time Frame: 9 months. ] [ Designated as safety issue: No ]
|Study Start Date:||March 2014|
|Estimated Study Completion Date:||August 2015|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
No Intervention: Medical therapy for heart failure
Standard optimized medical therapy for heart failure.
Experimental: Renal denervation + medical therapy.
Transcatheter Renal Denervation with irrigated radiofrequency catheter + standard medical therapy.
Device: transcatheter renal denervation
Renal sympathetic denervation with an irrigated radiofrequency catheter.
Other Name: Celsius Thermocool (Biosense Webster, California, USA)
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02099903
|Heart Institute - InCor. University of Sao Paulo Medical School||Recruiting|
|Sao Paulo, Brazil, 05403-000|
|Contact: Patricia Pereira +55 11 2661-5368 email@example.com|
|Principal Investigator: Pedro Lemos, MD PhD|