Effects of Hormonal Anabolic Deficiency and Neurovascular Alterations on Mortality in Male Patients With Heart Failure (TestoHF)

Hormonal Anabolic Deficiency Associated With Neurovascular Alterations Predict Poor Prognosis in Male Patients With Heart Failure

Heart failure (HF) has been associated with chronic deleterious effects on skeletal muscle, endocrine system, vasculature and sympathetic nervous system. These alterations have a significant impact on quality of life, leading to a reduction in functional capacity and limited symptoms, which involve dyspnea and fatigue. The investigators tested the hypothesis that hormonal anabolic deficiency associated with neurovascular alterations may worsen the prognosis of patients with heart failure.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Diagnostic test: Cardiopulmonary exercise test; Diagnostic test: Muscle Sympathetic Nerve Activity; Diagnostic test: Dual-energy X-ray absorptiometry; Diagnostic test: Venous occlusion plethysmography; Diagnostic test: Blood sample collection; Diagnostic test: Dynamometers for Handgrip Strength

Detailed Description

One hundred and fifty six patients have been enrolled so far. Methods were as described below:

• Muscle sympathetic nerve activity (MSNA) was directly recorded from the peroneal nerve using the microneurography technique ;
• All patients underwent symptom-limited cardiopulmonary exercise test performed on a cycle ergometer, using a ramp protocol with workload increments of 5 or 10 Watts per minute;
• Body composition measurements were performed using dual-energy X-ray absorptiometry (DXA);
• Muscle strength was assessed by handgrip dynamometer using the mean value of three attempts;
• Blood samples were drawn in the morning after 12h overnight fasting. The laboratory tests included B-type natriuretic peptide (BNP; pg/mL) plasma level, serum sodium (mEq/L), serum potassium (mEq/L), creatinine (mg/dL), haemoglobin level (g/dL), high-sensitivity C-reactive protein (CRP; mg/L), lipid profile (triglyceride, total cholesterol, high-density lipoprotein, and low-density lipoprotein; mg/dL), and fasting glucose (mg/dL). Blood sample to assess hormone plasma levels were also drawn at the same time: total testosterone (TT), free testosterone (FT), sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid stimulating hormone (TSH) and insulin-like growth factor 1 (IGF1).

• Study Type: Observational
• Enrollment (Actual): 169

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 05403-900
      • Instituto do Coração do Hospital da Clínicas da Universidade de Sao Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Probability Sample

Study Population

Patients with heart failure recruited at Clinical Unit of Myocardiopathy at General Hospital of the University of São Paulo Medical School (UNCAR/HC-FMUSP).

Description

Inclusion Criteria:

• age between 18 and 65 years old;
• at least1 year of diagnosed HF;
• left ventricular ejection fraction (LVEF) lower than 40% measured by echocardiography;
• non-ischaemic and ischaemic aetiologies;
• compensated HF with optimal medication for at least 3 months prior the study;
• New York Heart Association (NYHA) class of I to IV.

Exclusion Criteria:

• patients with autonomic diabetic neuropathy;
• patients with chronic renal failure with haemodialysis;
• heart transplantation;
• presence of pacemaker;
• patients with muscular dystrophy (i.e. Duchenne muscular dystrophy);
• patients submitted to any hormonal treatment;
• history of cancer;
• ongoing infection;
• myocardial infarction with percutaneous coronary intervention or revascularization 6 months prior to the study entry.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Low testosterone; Patients with HF and testosterone deficiency.; Cardiopulmonary exercise test; Muscle Sympathetic Nerve Activity; Dual-energy X-ray absorptiometry; Venous occlusion plethysmography; Blood sample collection; Dynamometers for Handgrip Strength	Diagnostic test: Cardiopulmonary exercise test; Oxygen consumption (VO2) and carbon dioxide output (VCO2) were measured by means of gas exchange on a breath-by-breath basis. The patients were initially monitored for 2 minutes at rest when seated on the ergometer, after that they were instructed to pedal at a pace of 60-70 rpm and the completion of the test occurred when, in spite of verbal encouragement, the patient reached maximal volitional fatigue.; Diagnostic test: Muscle Sympathetic Nerve Activity; Multiunit post-ganglionic muscle sympathetic nerve recordings were made using a tungsten microelectrode placed in the peroneal nerve near the fibular head. Nerve signals were amplified by a factor of 50,000 to 100,000 and band-pass filtered (700 to 2000 Hz). For recording and analysis, nerve activity was rectified and integrated (time constant 0.1 seconds) to obtain a mean voltage display of sympathetic nerve activity.; Diagnostic test: Dual-energy X-ray absorptiometry; Dual-energy X-ray absorptiometry (DXA) scan was used to measure total lean mass, body fat and bone mineral content.; Diagnostic test: Venous occlusion plethysmography; Venous occlusion plethysmography was used to assess non-invasively blood flow.; Diagnostic test: Blood sample collection; Blood samples were drawn in the morning after 12h overnight fasting.; Diagnostic test: Dynamometers for Handgrip Strength; Muscle strength was assessed by handgrip dynamometer using the mean value of three attempts.
Normal testosterone; Patients with HF and normal plasma levels of testosterone.; Cardiopulmonary exercise test; Muscle Sympathetic Nerve Activity; Dual-energy X-ray absorptiometry; Venous occlusion plethysmography; Blood sample collection; Dynamometers for Handgrip Strength	Diagnostic test: Cardiopulmonary exercise test; Oxygen consumption (VO2) and carbon dioxide output (VCO2) were measured by means of gas exchange on a breath-by-breath basis. The patients were initially monitored for 2 minutes at rest when seated on the ergometer, after that they were instructed to pedal at a pace of 60-70 rpm and the completion of the test occurred when, in spite of verbal encouragement, the patient reached maximal volitional fatigue.; Diagnostic test: Muscle Sympathetic Nerve Activity; Multiunit post-ganglionic muscle sympathetic nerve recordings were made using a tungsten microelectrode placed in the peroneal nerve near the fibular head. Nerve signals were amplified by a factor of 50,000 to 100,000 and band-pass filtered (700 to 2000 Hz). For recording and analysis, nerve activity was rectified and integrated (time constant 0.1 seconds) to obtain a mean voltage display of sympathetic nerve activity.; Diagnostic test: Dual-energy X-ray absorptiometry; Dual-energy X-ray absorptiometry (DXA) scan was used to measure total lean mass, body fat and bone mineral content.; Diagnostic test: Venous occlusion plethysmography; Venous occlusion plethysmography was used to assess non-invasively blood flow.; Diagnostic test: Blood sample collection; Blood samples were drawn in the morning after 12h overnight fasting.; Diagnostic test: Dynamometers for Handgrip Strength; Muscle strength was assessed by handgrip dynamometer using the mean value of three attempts.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of testosterone deficiency on mortality	Blood sample was collected in the morning (between 8:00-10:00 a.m.) after 12 hours fasting.	2 years
Impact of muscle sympathetic nerve activity on mortality	Microneurography was used to assess the sympathetic nervous system.	2 years
Impact of neurovascular alterations on mortality	Venous occlusion pletysmography was used to evaluate vasodilation.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of testosterone deficiency on body composition	Body composition measurements were performed using dual-energy X-ray absorptiometry.	2 years
Impact of testosterone deficiency on functional capacity	All patients underwent symptom-limited cardiopulmonary exercise test to measure functional capacity.	2 years
Impact of testosterone deficiency on strength	Muscle strength was assessed by handgrip dynamometer using the mean value of three attempts.	2 years

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Investigators: Principal Investigator: Maria Janieire de Nazaré Nunes Alves, PhD, InCor Heart Institute

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2016
• Primary Completion (Actual): March 23, 2020
• Study Completion (Actual): December 30, 2020

Study Registration Dates

• First Submitted: March 1, 2018
• First Submitted That Met QC Criteria: March 9, 2018
• First Posted (Actual): March 13, 2018

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 29, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Testosterone Deficiency; Sympathetic overactivity; Exercise Intolerance
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: AnabolicHormonesPrognosis

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