Renal Denervation in Patients With Heart Failure Secondary to Chagas Disease

Transcatheter Renal Denervation in Patients With Systolic Heart Failure Due to Chagas' Disease - a Safety and Efficacy Study.

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.

Study Overview

• Status: Unknown
• Conditions: Heart Failure; Chagas Cardiomyopathy; Chagas Disease; Heart Failure, Systolic
• Intervention / Treatment: Device: transcatheter renal denervation

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 05403-000
    • Recruiting
    • Heart Institute - InCor. University of Sao Paulo Medical School
    • Contact: Patricia Pereira; Phone Number: +55 11 2661-5368; Email: patricia.pereira@incor.usp.br
    • Principal Investigator: Pedro Lemos, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Celsius Thermocool (Biosense Webster, California, USA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite: death, myocardial infarction, cerebrovascular event, need of intervention on renal arteries and renal function impairment (decrease in estimated GFR > 30% from baseline).	30 days.

Secondary Outcome Measures

Outcome Measure	Time Frame
Left Ventricular Ejection Fraction (LVEF) by echocardiography.	9 months.
New York Heart Association (NYHA) functional class.	9 months.
6-minute walk test	9 months.
Peak Oxygen consumption (VO2) by ergoespirometry.	9 months.

Other Outcome Measures

Outcome Measure	Time Frame
Change in serum B-type natriuretic peptide (BNP).	9 months.
Quality of life assessed by Minnesota and EuroQOL five dimensions (EQ-5D)questionnaires.	9 months.
Peripheral sympathetic activity measured by microneurography.	9 months.

Collaborators and Investigators

• Sponsor: InCor Heart Institute
• Collaborators: Johnson & Johnson

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): August 1, 2015

Study Registration Dates

• First Submitted: March 19, 2014
• First Submitted That Met QC Criteria: March 26, 2014
• First Posted (Estimate): March 31, 2014

Study Record Updates

• Last Update Posted (Estimate): March 31, 2014
• Last Update Submitted That Met QC Criteria: March 26, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Heart Failure; Chagas Cardiomyopathy; Renal Denervation; Heart Failure, Systolic; Chagas Disease; Irrigated Radiofrequency Catheter
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Trypanosomiasis; Euglenozoa Infections; Heart Murmurs; Heart Failure; Cardiomyopathies; Chagas Cardiomyopathy; Systolic Murmurs; Heart Failure, Systolic; Chagas Disease
• Other Study ID Numbers: 18400613.1.0000.0068