Acute Effects Of Triiodothyronine T. (T3) Replacement Therapy in Patients with Chronic Heart Failure and Low-T3 Syndrome: A Randomized, Placebo-Controlled Study

Context: Low-T3 syndrome is a predictor of poor outcome in patients with cardiac dysfunction. The study aimed to assess the short-term effects of synthetic L-T3 replacement therapy in patients with low-T3 syndrome and ischemic or nonischemic dilated cardiomyopathy (DC). Design:Atotal of 20 clinically stable patients with ischemic (n12) or nonischemic (n8) DC were enrolled. There were 10 patients (average age 72 yr, range 66–77; median, 25–75th percentile) who underwent 3-d synthetic L-T3 infusion (study group); the other 10 patients (average age 68 yr, range 64–71) underwent placebo infusion (control group). Clinical examination, electrocardiography, cardiac magnetic resonance, and bio-humoral profile (free thyroid hormones, TSH, plasma renin activity, aldosterone, noradrenaline, N-terminal-pro-B-Type natriuretic peptide, and IL-6) were assessed at baseline and after 3-d synthetic L-T3 (initial dose: 20 g/m2 body surfaced) or placebo infusion. Results: After T3 administration, free T3 concentrations increased until reaching a plateau at 24–48 h (3.43, 3.20–3.84 vs. 1.74, 1.62–1.93 pg/ml; P 0.03) without side effects. Heart rate decreased significantly after T3 infusion (63, 60–66 vs. 69, 60–76 beats per minute; P 0.008). Plasma noradrenaline (347; 270–740 vs. 717, 413–808 pg/ml; P 0.009), N-terminal pro-B-Type natriuretic peptide (3000, 438-4005 vs. 3940, 528-5628 pg/ml; P0.02), and aldosterone (175, 152–229 vs. 231, 154–324 pg/ml; P 0.047) significantly decreased after T3 administration. Neurohormonal profile did not change after placebo infusion in the control group. After synthetic L-T3 administration, left-ventricular end-diastolic volume (142, 132–161 vs. 133, 114–158 ml/m2 body surface; P 0.02) and stroke volume (40, 34–44 vs. 35, 28–39 ml/m2 body surface; P 0.01) increased, whereas external and intracardiac workload did not change. Conclusions: In DC patients, short-term synthetic L-T3 replacement therapy significantly improved neuroendocrine profile and ventricular performance. These data encourage further controlled trials with more patients and longer periods of synthetic L-T3 administration

Altered tissue degradation and distribution of Atrial Natriuretic Peptide in patients with idiopathic dilated cardiomyopathy and its relationship with clinical severity of the disease and sodium handling

Background Atrial natriuretic peptide (ANP) has been suggested to play an important role in heart failure, preserving cardiorenal homeostasis through maintenance of the sodium balance and inhibition of the detrimental effects of the neurohormonal vasoconstrictor system. The current study was designed to investigate whether there is a disturbed renewal and distribution of ANP in patients with idiopathic dilated cardiomyopathy (IDC) with differing clinical severity of disease. Methods and Results We used a tracer method to perform a cross-sectional study of 15 IDC patients with differing clinical severity (New York Heart Association functional class I to III), prospectively divided into two groups according to their functional class (group 1, classes I and II; group 2, classes II-III and III). Eleven normotensive, nonobese male volunteers also were studied as a control group. Main ANP kinetic parameters were derived from the disappearance curve of the labeled hormone after the bolus injection of [ 125 I]-labeled ANP. A high-performance liquid chromatography technique was used to separate the radiolabeled hormone in each plasma sample. Patients in group 1 showed higher ANP metabolic clearance rate (MCR) (2731.9±726.2 mL · min −1 · m −2 ) than patients of group 2 (1718.4±621.2 mL · min −1 · m −2 ) and control subjects (1873.1±551.2 mL · min −1 · m −2 ). ANP disposal (MCR) positively correlated with biological hormonal effect (urinary sodium excretion) both in control subjects and in patients. In IDC patients of both groups, however, MCR values were always higher (approximately doubled) than the values found in control subjects at the corresponding sodium excretion. This finding indicates that a reduced ANP biological activity is associated with hormone degradation in patients. Moreover, patients of group 2 showed significantly higher ANP production rates (395.6±183.8 ng · min −1 · m −2 ) than group 1 (166.0±139.0 ng · min −1 · m −2 ) and control subjects (130.7±105.4 ng · min −1 · m −2 ) despite a marked reduction in sodium excretion. Patients with IDC showed a progressive reduction in the total distribution volume (group 1, 19.8±5.8 L/m 2 ; group 2, 12.7±6.9 L/m 2 ; control subjects, 27.0±11.6 L/m 2 ) of the hormone; this probably was due to a reduction in exchanges of ANP with peripheral tissues. Conclusions Our study demonstrates a markedly altered degradation and distribution of ANP in patients with IDC, even in those at the early stage of clinical disease (classes I and II, group 1) who have ANP plasma levels in the normal range. </jats:p

Association Between Increased Mortality and Mild Thyroid Dysfunction in Cardiac Patients

BACKGROUND: The effects of subclinical thyroid dysfunction on cardiac outcome are not well defined. METHODS: To assess the relationship between mild thyroid dysfunction and the incidence of death in cardiac patients, we evaluated 3121 cardiac patients. Cardiac and overall deaths were considered. Four groups were defined: euthyroidism, subclinical hypothyroidism (SCH), subclinical hyperthyroidism (SCT), and low triiodothyronine syndrome (low T3). RESULTS: After mean follow-up of 32 months, there were 65 and 140 cardiac and overall deaths (3.4% and 7.3%), respectively, in euthyroidism, 15 and 27 (7.2% and 13.0%) in SCH, 8 and 9 (8.2% and 9.2%) in SCT, and 59 and 119 (6.5% and 13.1%) in low T3. Survival rates for cardiac death were lower in SCH, SCT, and low T3 than in euthyroidism (log-rank test; chi2 = 19.46; P < .001). Survival rates for overall death were lower in SCH and low T3 than in euthyroidism (log-rank test; chi2 = 26.67; P < .001). After adjustment for several risk factors, hazard ratios (HRs) for cardiac death were higher in SCH (HR, 2.40; 95% confidence interval [CI], 1.36-4.21; P = .02), SCT (HR, 2.32; 95% CI, 1.11-4.85; P = .02), and low T(3) (HR, 1.63; 95% CI, 1.14-2.33; P = .007) than in euthyroidism; HRs for overall death were higher in SCH (HR, 2.01; 95% CI, 1.33-3.04; P < .001) and low T3 (HR, 1.57; 95% CI, 1.22-2.01; P < .001) but not in SCT. CONCLUSION: A mildly altered thyroid status is associated with an increased risk of mortality in patients with cardiac disease

Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis.

OBJECTIVE: The objective was to determine the risk of stroke associated with subclinical hypothyroidism. DATA SOURCES AND STUDY SELECTION: Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data on thyroid function and stroke outcome. Euthyroidism was defined as TSH levels of 0.45-4.49 mIU/L, and subclinical hypothyroidism was defined as TSH levels of 4.5-19.9 mIU/L with normal T4 levels. DATA EXTRACTION AND SYNTHESIS: We collected individual participant data on 47 573 adults (3451 subclinical hypothyroidism) from 17 cohorts and followed up from 1972-2014 (489 192 person-years). Age- and sex-adjusted pooled hazard ratios (HRs) for participants with subclinical hypothyroidism compared to euthyroidism were 1.05 (95% confidence interval [CI], 0.91-1.21) for stroke events (combined fatal and nonfatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years, with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years old (HR, 1.00; 95% CI, 0.86-1.18) or ≥ 80 years old (HR, 1.31; 95% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations. CONCLUSIONS: Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed

Increased risk of bone fractures in hemodialysis patients treated with proton pump inhibitors in real world: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS)

Long-term treatment with Proton Pump Inhibitors (PPIs) is associated with an increased risk of fractures in the general population. PPIs are widely prescribed to dialysis patients but to date no study specifically tested, by state-of-art statistical methods, the relationship between PPIs use and fractures in this patient-population. This study aimed to assess whether PPIs use is associated with bone fractures (i.e. hip fractures and fractures other than hip fractures) in a large international cohort of hemodialysis patients. We considered an observational prospective cohort of 27097 hemodialysis patients from the DOPPS study. Data analysis was performed by the Fine &amp; Gray method, considering the competitive risk of mortality, as well as by a cause-specific hazards Cox model dealing death as a censoring event and matching patients according to the prescription time. Out of 27,097 hemodialysis patients, 13,283 patients (49%) were on PPI treatment. Across the follow-up (median:19\u2009months), 3.8 bone fractures x 100 person-years and 1.2 hip fractures x 100 person-years occurred. In multiple Cox models, considering the competitive risk of mortality, the incidence rate of bone (SHR: 1.22, 95% CI: 1.10-1.36, P\u2009&lt;\u20090.001) and hip fractures (SHR: 1.35, 95% CI: 1.13-1.62, P&nbsp;=&nbsp;0.001) was significantly higher in PPI treated than in PPI untreated patients. These findings held true also in multiple, cause-specific, hazards Cox models matching patients according to the prescription time (bone fractures, HR: 1.47, 95% CI: 1.23-1.76, P\u2009&lt;\u20090.001, hip fractures (HR: 1.85, 95% CI: 1.37-2.50, P\u2009&lt;\u20090.001). The use of PPIs requires caution and a careful evaluation of risks/benefits ratio in hemodialysis patients