Variation in the reference range limits of thyroid function tests and association with the prevalence of levothyroxine treatment.

Many individuals with marginally abnormal thyroid function test (TFT) results may be treated and it is unknown if the limits of the thyrotropin (TSH) and free thyroxine (FT4) reference intervals reported alongside the laboratory results are associated with the prevalence of levothyroxine treatment. We obtained information regarding reported TFT reference intervals from UK National Health Service (NHS) laboratories and evaluated its relationship with the prevalence of levothyroxine treatment for corresponding health areas for 2014. The upper limit of serum TSH was significantly, linearly, independently, and negatively associated with prevalent levothyroxine treatment: -0.54% (95% CI, -0.68% to -0.40%). The lower limit of serum FT4 was significantly and independently associated with the prevalence of levothyroxine treatment in a non-linear (J-shaped) manner with an increase being noted from a FT4 level of ≈9.5 pmol/L onwards. We conclude that minor changes in the reference range limits for serum TSH and FT4 are associated with levothyroxine treatment.

Triiodothyronine (T3), inflammation and mortality risk in patients with acute myocardial infarction.

Objectives: To study the relationship between serum-free T3 (FT3), C-reactive protein (CRP) and all-cause mortality in patients with acute myocardial infarction (AMI). Design: Prospective multicentre longitudinal cohort study. Methods: Between December 2014 and December 2016, thyroid function and CRP were analysed in AMI (both ST-elevation (STEMI) and non-ST-elevation) patients from the Thyroxine in Acute Myocardial Infarction study. The relationship of FT3 and CRP at baseline with all-cause mortality up to June 2020 was assessed. Mediation analysis was performed to evaluate if CRP mediated the relationship between FT3 and mortality. Results: In 1919 AMI patients (29.2% women, mean (s.d.) age: 64.2 (12.1) years and 48.7% STEMI) followed over a median (interquartile range) period of 51 (46-58) months, there were 277 (14.4%) deaths. Overall, lower serum FT3 and higher CRP levels were associated with higher risk of mortality. When divided the patients into tertiles based on the levels of FT3 and CRP; the group with the lowest FT3 and highest CRP levels had a 2.5-fold increase in mortality risk (adjusted hazard ratio (95% CI) of 2.48 (1.82-3.16)) compared to the group with the highest FT3 and lowest CRP values. CRP mediated 9.8% (95% CI: 6.1-15.0%) of the relationship between FT3 and mortality. Conclusions: In AMI patients, lower serum FT3 levels on admission are associated with a higher mortality risk, which is partly mediated by inflammation. Adequately designed trials to explore the potential benefits of T3 in AMI patients are required.

Effect of Levothyroxine on Left Ventricular Ejection Fraction in Patients With Subclinical Hypothyroidism and Acute Myocardial Infarction: A Randomized Clinical Trial.

Importance: Thyroid hormones play a key role in modulating myocardial contractility. Subclinical hypothyroidism in patients with acute myocardial infarction is associated with poor prognosis. Objective: To evaluate the effect of levothyroxine treatment on left ventricular function in patients with acute myocardial infarction and subclinical hypothyroidism. Design, Setting, and Participants: A double-blind, randomized clinical trial conducted in 6 hospitals in the United Kingdom. Patients with acute myocardial infarction including ST-segment elevation and non-ST-segment elevation were recruited between February 2015 and December 2016, with the last participant being followed up in December 2017. Interventions: Levothyroxine treatment (n = 46) commencing at 25 µg titrated to aim for serum thyrotropin levels between 0.4 and 2.5 mU/L or identical placebo (n = 49), both provided in capsule form, once daily for 52 weeks. Main Outcomes and Measures: The primary outcome measure was left ventricular ejection fraction at 52 weeks, assessed by magnetic resonance imaging, adjusted for age, sex, type of acute myocardial infarction, affected coronary artery territory, and baseline left ventricular ejection fraction. Secondary measures were left ventricular volumes, infarct size (assessed in a subgroup [n = 60]), adverse events, and patient-reported outcome measures of health status, health-related quality of life, and depression. Results: Among the 95 participants randomized, the mean (SD) age was 63.5 (9.5) years, 72 (76.6%) were men, and 65 (69.1%) had ST-segment elevation myocardial infarction. The median serum thyrotropin level was 5.7 mU/L (interquartile range, 4.8-7.3 mU/L) and the mean (SD) free thyroxine level was 1.14 (0.16) ng/dL. The primary outcome measurements at 52 weeks were available in 85 patients (89.5%). The mean left ventricular ejection fraction at baseline and at 52 weeks was 51.3% and 53.8%, respectively, in the levothyroxine group compared with 54.0% and 56.1%, respectively, in the placebo group (adjusted difference in groups, 0.76% [95% CI, -0.93% to 2.46%]; P = .37). None of the 6 secondary outcomes showed a significant difference between the levothyroxine and placebo treatment groups. There were 15 (33.3%) and 18 (36.7%) cardiovascular adverse events in the levothyroxine and placebo groups, respectively. Conclusions and Relevance: In this preliminary study involving patients with subclinical hypothyroidism and acute myocardial infarction, treatment with levothyroxine, compared with placebo, did not significantly improve left ventricular ejection fraction after 52 weeks. These findings do not support treatment of subclinical hypothyroidism in patients with acute myocardial infarction. Trial Registration: isrctn.org Identifier: http://www.isrctn.com/ISRCTN52505169.

Sample Timing, Diagnosis of Subclinical Thyroid Dysfunction and Mortality in Acute Myocardial Infarction: ThyrAMI1 Study.

OBJECTIVE: The objective of this study was to determine the impact of blood sample timing on the diagnosis of subclinical thyroid dysfunction (SCTD) and mortality in patients with acute myocardial infarction (AMI). PATIENTS, DESIGN, AND MAIN OUTCOME MEASURES: Patients with AMI had thyroid function evaluated on admission between December 2014 and December 2016 and those with abnormal serum thyrotropin (TSH) had repeat thyroid function assessed at least a week later. The association between sample timing and SCTD was evaluated by logistic regression analysis. Secondary outcomes were confirmation of SCTD on repeat testing and all-cause mortality up to June 2018. RESULTS: Of the 1806 patients [29.2% women, mean (± standard deviation) age of 64.2 (±12.1) years] analyzed, the prevalence of subclinical hypothyroidism (SCH) was 17.2% (n = 311) and subclinical hyperthyroidism (SHyper) was 1.2% (n = 22) using a uniform TSH reference interval. The risk of being diagnosed with SCTD varied by sample timing in fully-adjusted models. The risk of SCH was highest between 00.01 and 06.00 hours and lowest between 12.01 and 18.00 hours, P for trend <.001, and risk of SHyper was highest between 12.01 hours and 18.00 hours and lowest between 00.01 hours and 06.00 hours. Furthermore, time of the initial sample was associated with the risk of remaining in a SCH state subsequently. Mortality in SCH patients was not elevated when a uniform TSH reference interval was utilized. However, when time period-specific TSH reference ranges were utilized, the mortality risk was significantly higher in SCH patients with HR (95% CI) of 2.26 (1.01-5.19), P = .04. CONCLUSIONS: Sample timing impacts on the diagnosis and prognosis of SCH in AMI patients. If sample timing is not accounted for, SCH is systemically misclassified, and its measurable influence on mortality is lost.

Thyroid Hormones and Cardiovascular Function and Diseases.

Thyroid hormone (TH) receptors are present in the myocardium and vascular tissue, and minor alterations in TH concentration can affect cardiovascular (CV) physiology. The potential mechanisms that link CV disease with thyroid dysfunction are endothelial dysfunction, changes in blood pressure, myocardial systolic and diastolic dysfunction, and dyslipidemia. In addition, cardiac disease itself may lead to alterations in TH concentrations (notably, low triiodothyronine syndrome) that are associated with higher morbidity and mortality. Experimental data and small clinical trials have suggested a beneficial role of TH in ameliorating CV disease. The aim of this review is to provide clinicians dealing with CV conditions with an overview of the current knowledge of TH perturbations in CV disease.

Excimer Laser With and Without Contrast for the Management of Under-Expanded Stents.

Under-expanded and under-deployed stents carry a high risk of restenosis and thrombosis, with inherent serious clinical complications. The management of under-expanded stents is a difficult clinical entity. METHOD: A retrospective analysis of prospectively collected data on all under-expanded, under-deployed stents that were managed by excimer laser, with and without contrast, performed at the Freeman Hospital, a large tertiary cardiac center, in the northeast of England. RESULTS: Between November 2014 and September 2016, a total of 19 cases were treated with excimer laser with or without contrast, with the initial approach done without contrast. All cases were successful with a stepwise energy-level approach. There were no clinical, procedural, or in-hospital complications, with full expansion of the stents after laser application. CONCLUSION: The use of excimer laser with or without contrast offers a safe and effective method for managing under-expanded and under-deployed stents and potentially avoiding long-term complications of under-expansion.

Effect of weekend admission on process of care and clinical outcomes for the management of acute coronary syndromes: a retrospective analysis of three UK centres.

OBJECTIVES: The effect of weekend versus weekday admission following acute coronary syndrome (ACS) on process of care and mortality remains controversial. This study aimed to investigate the 'weekend-effect' on outcomes using a multicentre dataset of patients with ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction/unstable angina (NSTEMI/UA). DESIGN: This retrospective observational study used propensity score (PS) stratification to adjust estimates of weekend effect for observed confounding. Logistic regression was used to estimate odds ratios (ORs) for binary outcomes and time-to-event endpoints were modelled using Cox proportional hazards to estimate hazard ratios (HRs). SETTING: Three tertiary cardiac centres in England and Wales that contribute to the Myocardial Ischaemia National Audit Project. PARTICIPANTS: Between January 2010 and March 2016, 17 705 admissions met the study inclusion criteria, 4327 of which were at a weekend. PRIMARY AND SECONDARY OUTCOMES: Associations were studied between weekend admissions and the following primary outcome measures: in-hospital mortality, 30-day mortality and long-term survival; secondary outcomes included several processes of care indicators, such as time to coronary angiography. RESULTS: After PS stratification adjustment, mortality outcomes were similar between weekend and weekday admission across patients with STEMI and NSTEMI/UA. Weekend admissions were less likely to be discharged within 1 day (HR 0.72, 95% CI 0.66 to 0.78), but after 4 days the length of stay was similar (HR 0.97, 95% CI 0.90 to 1.04). Fewer patients with NSTEMI/UA received angiography between 0 and 24 hours at a weekend (HR 0.71, 95% CI 0.65 to 0.77). Weekend patients with STEMI were less likely to undergo an angiogram within 1 hour, but there was no significant difference after this time point. CONCLUSION: Patients with ACS had similar mortality and processes of care when admitted on a weekend compared with a weekday. There was evidence of a delay to angiography for patients with NSTEMI/UA admitted at the weekend.

Thyroid hormones and cardiovascular disease.

Myocardial and vascular endothelial tissues have receptors for thyroid hormones and are sensitive to changes in the concentrations of circulating thyroid hormones. The importance of thyroid hormones in maintaining cardiovascular homeostasis can be deduced from clinical and experimental data showing that even subtle changes in thyroid hormone concentrations - such as those observed in subclinical hypothyroidism or hyperthyroidism, and low triiodothyronine syndrome - adversely influence the cardiovascular system. Some potential mechanisms linking the two conditions are dyslipidaemia, endothelial dysfunction, blood pressure changes, and direct effects of thyroid hormones on the myocardium. Several interventional trials showed that treatment of subclinical thyroid diseases improves cardiovascular risk factors, which implies potential benefits for reducing cardiovascular events. Over the past 2 decades, accumulating evidence supports the association between abnormal thyroid function at the time of an acute myocardial infarction (MI) and subsequent adverse cardiovascular outcomes. Furthermore, experimental studies showed that thyroid hormones can have an important therapeutic role in reducing infarct size and improving myocardial function after acute MI. In this Review, we summarize the literature on thyroid function in cardiovascular diseases, both as a risk factor as well as in the setting of cardiovascular diseases such as heart failure or acute MI, and outline the effect of thyroid hormone replacement therapy for reducing the risk of cardiovascular disease.

Local Versus General Anesthesia in Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) is conventionally performed under general anesthesia (GA) allowing intraoperative transoesophageal echocardiogram imaging. We present our experience in patients having the procedure under local anesthesia (LA), who were subsequently transferred to a low dependency unit postprocedure, to assess safety and length of hospital stay. We retrospectively assessed all the transfemoral TAVR procedures conducted at our center from January 03, 2011. Of 216 patients, 145 had the procedure under GA and 71 under LA. Both groups were similar with respect to age, co-morbidities, Euro Score, and the severity of the aortic stenosis. The procedure time was significantly shorter in the LA group measured from time in room to skin closure (108 vs 143 minutes, p <0.001). Skin open to skin closure time were the same in both groups (78 vs 79.4 minutes, p = 0.57). There was no difference in 30 days: aortic regurgitation > mild (2.1% in GA and 2.8% in LA, p = 0.67), need for permanent pacing (3.4% in GA and 1.4% in LA, p = 0.32), and disabling cerebrovascular accidents (1.4% and 1.4%, p = 1.0). The 30-day survival was not significantly different (95.9% in GA and 100% in LA, p = 0.17), whereas the median number of days in hospital was shorter in the LA group (4 in GA and 2 in LA, p <0.001). No emergency conversions to GA were performed in the LA group and only 1 patient needed admission to a high dependency (HD) unit. In conclusion, performing a TAVR under LA is at least as safe as GA. In addition, there is a reduced procedural time and length of hospital stay. LA is a safe and cost-effective alternative to GA and patients can be safely transferred to a low dependency unit.

Thyroxine in acute myocardial infarction (ThyrAMI) - levothyroxine in subclinical hypothyroidism post-acute myocardial infarction: study protocol for a randomised controlled trial.

BACKGROUND: Cardiac disease is the most common cause of morbidity and mortality in the United Kingdom. Even minor changes in thyroid hormone concentration may impact adversely on the cardiovascular system. Subclinical hypothyroidism (SCH) after admission for an acute cardiac problem has been associated with an increase in cardiac mortality and overall death. We have designed protocols for a prospective observational study to assess the association of thyroid function at the time of acute myocardial infarction (AMI) with cardiovascular outcomes, and a double-blinded randomised placebo-controlled trial of levothyroxine to evaluate its effect on LV function and vascular health. METHODS/DESIGN: ThyrAMI 1: This will be a prospective longitudinal observational study of patients with AMI that will be followed for 24 months to study the association between thyroid status at the time of AMI (within 24 hours of diagnosis) with vascular outcomes. ThyrAMI 2: This will be a prospective double-blinded randomised placebo-controlled trial of levothyroxine of 12 months duration in patients with AMI and SCH. SETTING: Patients will be recruited from five hospitals in the North East of England. PARTICIPANTS: One hundred patients with thyroid function tests within the subclinical hypothyroid range upon admission with an AMI and no previous history of thyroid disease. INTERVENTION: Levothyroxine will be administered at a starting dose of 25 mcg once daily, which will be increased at intervals if needed to maintain a TSH level between 0.4 to 2.5 mU/L, versus a placebo. RANDOMISATION: Participants will be randomized with a computerised randomisation algorithm, stratified by type of MI (NSTEMI versus STEMI), in a 1:1 ratio to levothyroxine therapy or placebo (as container or bottle numbers), starting within 21 (+/- 7) days of AMI. BLINDING: Assignment to either the LT4 or placebo arm will be double-blinded. OUTCOMES: The outcome will be the effect of levothyroxine on ventricular function, endothelial function and blood coagulability and rheology. DISCUSSION: There is evidence to suggest that treatment of SCH can improve cardiovascular parameters. Therefore, ThyrAMI 1 and ThyrAMI 2 will be the first trials investigating SCH in AMI to give a better insight into whether thyroid hormone levels are a key target for improving cardiovascular outcomes. TRIAL REGISTRATION: ISRCTN number: ISRCTN52505169 . Date of registration: 09/01/2015.

Thyroid disease and vascular risk.

Subclinical hypothyroidism (SCH) is a common condition seen in up to 10% of adults, mainly women and the elderly. Several prospective longitudinal cohort studies have shown a higher risk of cardiovascular disease in people with SCH but mainly in younger individuals. There are also a number of interventional trials that have shown that treatment of SCH with levo-thyroxine improves cardiovascular risk factors, but there is a dearth of level 1 evidence regarding cardiovascular events. In addition, there is increasing proof concerning the association of abnormal thyroid function at the time of an acute myocardial infarction with adverse cardiovascular outcomes. This review describes the literature dealing with thyroid function in relation to cardiovascular disease and also outlines the effect of treatment in addressing cardiovascular risk.

'A one-sided affair': unilateral pulmonary oedema and the role of cardiac MRI in diagnosing premature coronary artery disease in a patient with Prader-Willi syndrome.

There is no formal association between premature coronary artery disease (CAD) and Prader-Willi syndrome despite its association with hyperlipidaemia, diabetes mellitus and hypertension. A 36-year-old man with Prader-Willi syndrome presented with acute breathlessness. Inflammatory markers were borderline elevated and chest radiography demonstrated unilateral diffuse alveolar shadowing. Bronchopneumonia was diagnosed and despite treatment with multiple courses of antimicrobial therapy, there was minimal symptomatic and radiographical improvement. A diagnosis of unilateral pulmonary oedema was suspected. Echocardiography was non-diagnostic due to body habitus and coronary angiography was deemed inappropriate due to uncertainty in diagnosis, invasiveness and pre-existing chronic kidney disease. Therefore, cardiac magnetic resonance was performed, confirming severe triple-vessel CAD. This case demonstrates a presentation of heart failure with unilateral chest radiograph changes in a young patient with Prader-Willi syndrome and severe premature CAD detected by multiparametric cardiac magnetic resonance imaging.