Clinical trial NCT03354689: Transcutaneous Electrical Nerve Stimulation and Cardiac Sympathetic Overdrive in Heart Failure
Official title: Cervicothoracic Transcutaneous Electrical Nerve Stimulation Attenuates Cardiac Sympathetic Overdrive in Heart Failure: A 123l-MIBG Myocardial Scintigraphy, Randomized Double-Blind Crossover Trial
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiovascular Abnormalities
Lead sponsor: Universidade Federal Fluminense
Sponsor class: OTHER
First posted: 2017-11-28
Enrollment: 17
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with heart failure

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 123-MIBG Washout rate
timeFrame: 12 months
measure: 123-MIBG heart-to-mediastinum ratio
timeFrame: 12 months
measure: Muscle Sympathetic nerve activity
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Niteroi
country: Brazil
facility: Fabio A Alves
state: CA
Study officials:
References:
citation: 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.