Testosterone deficiency increases hospital readmission and mortality rates in male patients with heart failure.

BackgroundTestosterone deficiency in patients with heart failure (HF) is associated with decreased exercise capacity and mortality; however, its impact on hospital readmission rate is uncertain. Furthermore, the relationship between testosterone deficiency and sympathetic activation is unknown.ObjectiveWe investigated the role of testosterone level on hospital readmission and mortality rates as well as sympathetic nerve activity in patients with HF.MethodsTotal testosterone (TT) and free testosterone (FT) were measured in 110 hospitalized male patients with a left ventricular ejection fraction < 45% and New York Heart Association classification IV. The patients were placed into low testosterone (LT; n = 66) and normal testosterone (NT; n = 44) groups. Hypogonadism was defined as TT < 300 ng/dL and FT < 131 pmol/L. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography in a subpopulation of 27 patients.ResultsLength of hospital stay was longer in the LT group compared to in the NT group (37 ± 4 vs. 25 ± 4 days; p = 0.008). Similarly, the cumulative hazard of readmission within 1 year was greater in the LT group compared to in the NT group (44% vs. 22%, p = 0.001). In the single-predictor analysis, TT (hazard ratio [HR], 2.77; 95% confidence interval [CI], 1.58-4.85; p = 0.02) predicted hospital readmission within 90 days. In addition, TT (HR, 4.65; 95% CI, 2.67-8.10; p = 0.009) and readmission within 90 days (HR, 3.27; 95% CI, 1.23-8.69; p = 0.02) predicted increased mortality. Neurohumoral activation, as estimated by MSNA, was significantly higher in the LT group compared to in the NT group (65 ± 3 vs. 51 ± 4 bursts/100 heart beats; p < 0.001).ConclusionThese results support the concept that LT is an independent risk factor for hospital readmission within 90 days and increased mortality in patients with HF. Furthermore, increased MSNA was observed in patients with LT

Exercise training prevents the deterioration in the arterial baroreflex control of sympathetic nerve activity in chronic heart failure patients

Arterial baroreflex control of muscle sympathetic nerve activity (ABRMSNA) is impaired in chronic systolic heart failure (CHF). the purpose of the study was to test the hypothesis that exercise training would improve the gain and reduce the time delay of ABRMSNA in CHF patients. Twenty-six CHF patients, New York Heart Association Functional Class II-III, EF <= 40%, peak (V) over dot O-2 <= 20 ml.kg(-1).min(-1) were divided into two groups: untrained (UT, n = 13, 57 +/- 3 years) and exercise trained (ET, n = 13, 49 +/- 3 years). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique. Arterial pressure was measured on a beat-to-beat basis. Time series of MSNA and systolic arterial pressure were analyzed by autoregressive spectral analysis. the gain and time delay of ABRMSNA was obtained by bivariate autoregressive analysis. Exercise training was performed on a cycle ergometer at moderate intensity, three 60-min sessions per week for 16 wk. Baseline MSNA, gain and time delay of ABRMSNA, and low frequency of MSNA (LFMSNA) to high-frequency ratio (HFMSNA) (LFMSNA/HFMSNA) were similar between groups. ET significantly decreased MSNA. MSNA was unchanged in the UT patients. the gain and time delay of ABRMSNA were unchanged in the ET patients. in contrast, the gain of ABRMSNA was significantly reduced [3.5 +/- 0.7 vs. 1.8 +/- 0.2, arbitrary units (au)/mmHg, P = 0.04] and the time delay of ABRMSNA was significantly increased (4.6 +/- 0.8 vs. 7.9 +/- 1.0 s, P = 0.05) in the UT patients. LFMSNA-to-HFMSNA ratio tended to be lower in the ET patients (P < 0.08). Exercise training prevents the deterioration of ABRMSNA in CHF patients.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao ZerbiniCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)National Heart, Lung, and Blood InstituteUniv São Paulo, Sch Med, Heart Inst InCor, São Paulo, BrazilUniv São Paulo, Sch Phys Educ & Sport, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Cardiol, São Paulo, BrazilUniv Calif Los Angeles, David Geffen Sch Med, Dept Med Cardiol & Physiol, Los Angeles, CA 90095 USAUniversidade Federal de São Paulo, Dept Med, Div Cardiol, São Paulo, BrazilFAPESP: 2010/50048-1FAPESP: 140643/2009-5FAPESP: 2013/07651-7CNPq: 142366/2009-9CNPq: 301867/2010-0CNPq: 308068/2011-4FAPESP: 2013/15651-7National Heart, Lung, and Blood Institute: RO1-HL084525Web of Scienc

Screening for organic acidurias and aminoacidopathies in high-risk Brazilian patients: Eleven-year experience of a reference center

Abstract Organic acidurias and aminoacidopathies are groups of frequent inborn errors of metabolism (IEMs), which are caused by mutations in specific genes that lead to loss of protein/enzyme or transport function with important deleterious effects to cell metabolism. Since a considerable number of such disorders are potentially treatable when diagnosed at an early stage of life, diagnosis is crucial for the patients. In the present report, we describe symptomatic individuals referred to our service that were diagnosed with these disorders from 2006 to 2016. We used blood and urine samples from 21,800 patients suspected of aminoacidopathies or organic acidemias that were processed by the analytical techniques reverse phase high-performance liquid chromatography for amino acid quantification and gas chromatography coupled to mass spectrometry for organic acid detection. Analysis of dried blood spots by liquid chromatography-tandem mass spectrometry was used in some cases. We detected 258 cases of organic acidurias, and 117 patients with aminoacidopathies were diagnosed. Once diagnosis was performed, patients were promptly submitted to the available treatments with clear reduction of mortality and morbidity. The obtained data may help pediatricians and metabolic geneticists to become aware of these diseases and possibly expand newborn screening programs in the future

Testosterone Deficiency Increases Hospital Readmission and Mortality Rates in Male Patients with Heart Failure

Background: Testosterone deficiency in patients with heart failure (HF) is associated with decreased exercise capacity and mortality; however, its impact on hospital readmission rate is uncertain. Furthermore, the relationship between testosterone deficiency and sympathetic activation is unknown. Objective: We investigated the role of testosterone level on hospital readmission and mortality rates as well as sympathetic nerve activity in patients with HF. Methods: Total testosterone (TT) and free testosterone (FT) were measured in 110 hospitalized male patients with a left ventricular ejection fraction < 45% and New York Heart Association classification IV. The patients were placed into low testosterone (LT; n = 66) and normal testosterone (NT; n = 44) groups. Hypogonadism was defined as TT < 300 ng/dL and FT < 131 pmol/L. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography in a subpopulation of 27 patients. Results: Length of hospital stay was longer in the LT group compared to in the NT group (37 ± 4 vs. 25 ± 4 days; p = 0.008). Similarly, the cumulative hazard of readmission within 1 year was greater in the LT group compared to in the NT group (44% vs. 22%, p = 0.001). In the single-predictor analysis, TT (hazard ratio [HR], 2.77; 95% confidence interval [CI], 1.58–4.85; p = 0.02) predicted hospital readmission within 90 days. In addition, TT (HR, 4.65; 95% CI, 2.67–8.10; p = 0.009) and readmission within 90 days (HR, 3.27; 95% CI, 1.23–8.69; p = 0.02) predicted increased mortality. Neurohumoral activation, as estimated by MSNA, was significantly higher in the LT group compared to in the NT group (65 ± 3 vs. 51 ± 4 bursts/100 heart beats; p < 0.001). Conclusion: These results support the concept that LT is an independent risk factor for hospital readmission within 90 days and increased mortality in patients with HF. Furthermore, increased MSNA was observed in patients with LT

Testosterone Deficiency Increases Hospital Readmission and Mortality Rates in Male Patients with Heart Failure

Background: Testosterone deficiency in patients with heart failure (HF) is associated with decreased exercise capacity and mortality; however, its impact on hospital readmission rate is uncertain. Furthermore, the relationship between testosterone deficiency and sympathetic activation is unknown. Objective: We investigated the role of testosterone level on hospital readmission and mortality rates as well as sympathetic nerve activity in patients with HF. Methods: Total testosterone (TT) and free testosterone (FT) were measured in 110 hospitalized male patients with a left ventricular ejection fraction < 45% and New York Heart Association classification IV. The patients were placed into low testosterone (LT; n = 66) and normal testosterone (NT; n = 44) groups. Hypogonadism was defined as TT < 300 ng/dL and FT < 131 pmol/L. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography in a subpopulation of 27 patients. Results: Length of hospital stay was longer in the LT group compared to in the NT group (37 ± 4 vs. 25 ± 4 days; p = 0.008). Similarly, the cumulative hazard of readmission within 1 year was greater in the LT group compared to in the NT group (44% vs. 22%, p = 0.001). In the single-predictor analysis, TT (hazard ratio [HR], 2.77; 95% confidence interval [CI], 1.58–4.85; p = 0.02) predicted hospital readmission within 90 days. In addition, TT (HR, 4.65; 95% CI, 2.67–8.10; p = 0.009) and readmission within 90 days (HR, 3.27; 95% CI, 1.23–8.69; p = 0.02) predicted increased mortality. Neurohumoral activation, as estimated by MSNA, was significantly higher in the LT group compared to in the NT group (65 ± 3 vs. 51 ± 4 bursts/100 heart beats; p < 0.001). Conclusion: These results support the concept that LT is an independent risk factor for hospital readmission within 90 days and increased mortality in patients with HF. Furthermore, increased MSNA was observed in patients with LT

Molecular basis for the improvement in muscle metaboreflex and mechanoreflex control in exercise-trained humans with chronic heart failure

Previous studies have demonstrated that muscle mechanoreflex and metaboreflex controls are altered in heart failure (HF), which seems to be due to changes in cyclooxygenase (COX) pathway and changes in receptors on afferent neurons, including transient receptor potential vanilloid type-1 (TRPV1) and cannabinoid receptor type-1 (CB1). the purpose of the present study was to test the hypotheses: 1) exercise training (ET) alters the muscle metaboreflex and mechanoreflex control of muscle sympathetic nerve activity (MSNA) in HF patients. 2) the alteration in metaboreflex control is accompanied by increased expression of TRPV1 and CB1 receptors in skeletal muscle. 3) the alteration in mechanoreflex control is accompanied by COX-2 pathway in skeletal muscle. Thirty-four consecutive HF patients with ejection fractions <40% were randomized to untrained (n = 17; 54 +/- 2 yr) or exercise-trained (n = 17; 56 +/- 2 yr) groups. MSNA was recorded by microneurography. Mechanoreceptors were activated by passive exercise and metaboreceptors by postexercise circulatory arrest (PECA). COX-2 pathway, TRPV1, and CB1 receptors were measured in muscle biopsies. Following ET, resting MSNA was decreased compared with untrained group. During PECA (metaboreflex), MSNA responses were increased, which was accompanied by the expression of TRPV1 and CB1 receptors. During passive exercise (mechanoreflex), MSNA responses were decreased, which was accompanied by decreased expression of COX-2, prostaglandin-E-2 receptor-4, and thromboxane-A(2) receptor and by decreased in muscle inflammation, as indicated by increased miRNA-146 levels and the stable NF-kappa B/I kappa B-alpha ratio. in conclusion, ET alters muscle metaboreflex and mechanoreflex control of MSNA in HF patients. This alteration with ET is accompanied by alteration in TRPV1 and CB1 expression and COX-2 pathway and inflammation in skeletal muscle