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

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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Heart Failure

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Low testosterone<br>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<br>* 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.<br>Diagnostic Test: Muscle Sympathetic Nerve Activity<br>* 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.<br>Diagnostic Test: Dual-energy X-ray absorptiometry<br>* Dual-energy X-ray absorptiometry (DXA) scan was used to measure total lean mass, body fat and bone mineral content.<br>Diagnostic Test: Venous occlusion plethysmography<br>* Venous occlusion plethysmography was used to assess non-invasively blood flow.<br>Diagnostic Test: Blood sample collection<br>* Blood samples were drawn in the morning after 12h overnight fasting.<br>Diagnostic Test: Dynamometers for Handgrip Strength<br>* Muscle strength was assessed by handgrip dynamometer using the mean value of three attempts.<br>|
| Normal testosterone<br>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<br>* 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.<br>Diagnostic Test: Muscle Sympathetic Nerve Activity<br>* 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.<br>Diagnostic Test: Dual-energy X-ray absorptiometry<br>* Dual-energy X-ray absorptiometry (DXA) scan was used to measure total lean mass, body fat and bone mineral content.<br>Diagnostic Test: Venous occlusion plethysmography<br>* Venous occlusion plethysmography was used to assess non-invasively blood flow.<br>Diagnostic Test: Blood sample collection<br>* Blood samples were drawn in the morning after 12h overnight fasting.<br>Diagnostic Test: Dynamometers for Handgrip Strength<br>* Muscle strength was assessed by handgrip dynamometer using the mean value of three attempts.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Testosterone Deficiency, Sympathetic overactivity, Exercise Intolerance