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

NCT ID: NCT03463226

Last Updated: 2021-05-03

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 169 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2020-12-30

Brief Summary

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.

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).

Conditions

Heart Failure

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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

Cardiopulmonary exercise test

Intervention Type: DIAGNOSTIC_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.

Muscle Sympathetic Nerve Activity

Intervention Type: DIAGNOSTIC_TEST

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.

Dual-energy X-ray absorptiometry

Intervention Type: DIAGNOSTIC_TEST

Dual-energy X-ray absorptiometry (DXA) scan was used to measure total lean mass, body fat and bone mineral content.

Venous occlusion plethysmography

Intervention Type: DIAGNOSTIC_TEST

Venous occlusion plethysmography was used to assess non-invasively blood flow.

Blood sample collection

Intervention Type: DIAGNOSTIC_TEST

Blood samples were drawn in the morning after 12h overnight fasting.

Dynamometers for Handgrip Strength

Intervention Type: DIAGNOSTIC_TEST

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

Cardiopulmonary exercise test

Intervention Type: DIAGNOSTIC_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.

Muscle Sympathetic Nerve Activity

Intervention Type: DIAGNOSTIC_TEST

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.

Dual-energy X-ray absorptiometry

Intervention Type: DIAGNOSTIC_TEST

Dual-energy X-ray absorptiometry (DXA) scan was used to measure total lean mass, body fat and bone mineral content.

Venous occlusion plethysmography

Intervention Type: DIAGNOSTIC_TEST

Venous occlusion plethysmography was used to assess non-invasively blood flow.

Blood sample collection

Intervention Type: DIAGNOSTIC_TEST

Blood samples were drawn in the morning after 12h overnight fasting.

Dynamometers for Handgrip Strength

Intervention Type: DIAGNOSTIC_TEST

Muscle strength was assessed by handgrip dynamometer using the mean value of three attempts.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DIAGNOSTIC_TEST

Venous occlusion plethysmography

Venous occlusion plethysmography was used to assess non-invasively blood flow.

Intervention Type: DIAGNOSTIC_TEST

Blood sample collection

Blood samples were drawn in the morning after 12h overnight fasting.

Intervention Type: DIAGNOSTIC_TEST

Dynamometers for Handgrip Strength

Muscle strength was assessed by handgrip dynamometer using the mean value of three attempts.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Fundação de Amparo à Pesquisa do Estado de São Paulo

OTHER_GOV

Sponsor Role: collaborator

University of Sao Paulo General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Maria Janieire de Nazaré Nunes Alves

PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Maria Janieire de Nazaré Nunes Alves, PhD

Role: PRINCIPAL_INVESTIGATOR

InCor Heart Institute

Locations

Instituto do Coração do Hospital da Clínicas da Universidade de Sao Paulo

São Paulo, São Paulo, Brazil

Countries

Brazil

Other Identifiers

AnabolicHormonesPrognosis

Identifier Type: -

Identifier Source: org_study_id