Transcutaneous Electrical Nerve Stimulation and Cardiac Sympathetic Overdrive in Heart Failure

Cervicothoracic Transcutaneous Electrical Nerve Stimulation Attenuates Cardiac Sympathetic Overdrive in Heart Failure: A 123l-MIBG Myocardial Scintigraphy, Randomized Double-Blind Crossover Trial

Introduction: Cardiac sympathetic drive provides inotropic support to the failing heart and preserves cardiovascular homeostasis. Nonetheless, as myocardial insult evolves, this compensatory response leads to a progressive decline in contractile function, increases the vulnerability to arrhythmias and constitutes an independent mortality predictor. Despite advanced pharmacological therapies, side effects and persistent cardiac sympathetic overdrive highlights the modulation of the adrenergic system as a primary target for non-pharmacological strategies in the heart failure (HF) treatment. In this scenario, we will propose cervicothoracic transcutaneous electrical nerve stimulation (TENS) as a non-pharmacological therapy to attenuate cardiac sympathetic overdrive in patients with heart failure. Methods: In this prospective, randomized, sham-controlled, double-blind crossover trial, ten (10) HF patients under optimal pharmacological treatment will be randomly assigned to either an in-home cervicothoracic transcutaneous electrical nerve stimulation therapy (TENS: 30 min twice a day with 80 Hz frequency and pulse duration of 150 μs) or a sham control intervention (SHCI) for two weeks. Following a two-month washout phase from TENS/SHCI, patients crossed over and started the opposite condition. Washout rate and heart-to-mediastinum ratio (planar 123l-metaiodobenzylguanidine myocardial scintigraphy images), indexes of cardiac sympathetic activity and innervation density, muscle sympathetic nerve activity (microneurography) and brachial artery blood flow (Doppler ultrasound) during dynamic handgrip exercise will be obtained at the beginning and end of each condition.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Abnormalities
• Intervention / Treatment: Radiation: Scintigraphy

Detailed Description

Introduction: Cardiac sympathetic drive provides inotropic support to the failing heart and preserves cardiovascular homeostasis. Nonetheless, as myocardial insult evolves, this compensatory response leads to a progressive decline in contractile function, increases the vulnerability to arrhythmias and constitutes an independent mortality predictor. Despite advanced pharmacological therapies, side effects and persistent cardiac sympathetic overdrive highlights the modulation of the adrenergic system as a primary target for non-pharmacological strategies in the heart failure (HF) treatment. In this scenario, we will propose cervicothoracic transcutaneous electrical nerve stimulation (TENS) as a non-pharmacological therapy to attenuate cardiac sympathetic overdrive in patients with heart failure. Methods: In this prospective, randomized, sham-controlled, double-blind crossover trial, ten (10) HF patients under optimal pharmacological treatment will be randomly assigned to either an in-home cervicothoracic transcutaneous electrical nerve stimulation therapy (TENS: 30 min twice a day with 80 Hz frequency and pulse duration of 150 μs) or a sham control intervention (SHCI) for two weeks. Following a two-month washout phase from TENS/SHCI, patients crossed over and started the opposite condition. Washout rate and heart-to-mediastinum ratio (planar 123l-metaiodobenzylguanidine myocardial scintigraphy images), indexes of cardiac sympathetic activity and innervation density, muscle sympathetic nerve activity (microneurography) and brachial artery blood flow (Doppler ultrasound) during dynamic handgrip exercise will be obtained at the beginning and end of each condition.

• Study Type: Observational
• Enrollment (Actual): 17

Contacts and Locations

Study Locations

• Brazil
  • CA
    • Niteroi, CA, Brazil, 94706
      • Fabio A Alves

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with heart failure

Description

Inclusion Criteria:

Patients with a diagnosis of heart failure, New York Heart Association (NYHA) functional classification between II to III and left ventricular ejection fraction ≤ 50%

Exclusion Criteria:

• Regular physical activity, pregnancy, unstable angina, acute myocardial infarction in the last 6 months, pacemaker, history of chronic kidney disease (on dialysis) and cardiac surgery.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
123-MIBG Washout rate	This measurement provides a highly reproducible index of cardiac sympathetic activity	12 months
123-MIBG heart-to-mediastinum ratio	This measurement provides a highly reproducible index of cardiac sympathetic innervation	12 months
Muscle Sympathetic nerve activity	This measurement provides a highly reproducible index of muscle sympathetic activity	12 months

Collaborators and Investigators

• Sponsor: Universidade Federal Fluminense

Publications and helpful links

General Publications

• Campos MO, Nobrega ACL, Miranda SM, Ribeiro ML, Guerra TRB, Braghirolli AMS, Mesquita CT, Fernandes IA. Transcutaneous electrical nerve stimulation attenuates cardiac sympathetic drive in heart failure: a 123MIBG myocardial scintigraphy randomized controlled trial. Am J Physiol Heart Circ Physiol. 2019 Aug 1;317(2):H226-H233. doi: 10.1152/ajpheart.00091.2019. Epub 2019 May 31.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 20, 2017
• Primary Completion (ACTUAL): September 19, 2018
• Study Completion (ACTUAL): October 20, 2018

Study Registration Dates

• First Submitted: November 21, 2017
• First Submitted That Met QC Criteria: November 26, 2017
• First Posted (ACTUAL): November 28, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 27, 2021
• Last Update Submitted That Met QC Criteria: April 26, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Heart Failure; Cardiovascular Abnormalities
• Other Study ID Numbers: 39141414.5.0000.5243

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No