Thyroxine in Acute Myocardial Infarction (ThyrAMI)

Ph. D. ThesisImportance: Thyroid hormones play a key role in modulating myocardial contractility and vascular function. Subclinical hypothyroidism is associated with worse cardiovascular outcomes, in those without cardiovascular disease, and a poor prognosis in patients with acute myocardial infarction. Objective: To evaluate the effect of levothyroxine treatment on left ventricular function, markers of vascular function and patient reported outcomes in patients with acute myocardial infarction and subclinical hypothyroidism. Hypotheses: Levothyroxine treatment will improve left ventricular function as a primary outcome measure. Furthermore, levothyroxine treatment will decrease thrombus burden, improve clot kinetics, platelet reactivity and endothelial function as well as patient reported outcomes. Design, Setting, and Participants: A double blind, randomized clinical trial conducted in six hospitals in the United Kingdom. Patients with acute myocardial infarction including STsegment 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 mcg 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 outcomes were surrogate markers of vascular function and patient reported outcome measures of health status, health-related quality of life, and depression. ii Results: Among the 95 participants randomized, the primary outcome measurements at 52 weeks were available in 85 (89.5%) patients. The mean left ventricular ejection fraction at baseline and at 52 weeks was 51.3% and 53.8% in the levothyroxine group compared to 54.0% and 56.1% in the placebo group; adjusted difference in groups (95% confidence interval) of 0.76% (-0.93% to 2.46%), p=0.37. Levothyroxine treatment did not significantly decrease thrombus burden, improve clot kinetics, decrease platelet reactivity or improve endothelial function. Furthermore, patient reported outcomes were not significantly different between both groups at the study end. 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 low dose levothyroxine, compared to placebo, did not significantly improve left ventricular ejection fraction, markers of vascular function and patient reported outcomes after 52 weeks. These findings do not support treatment of subclinical hypothyroidism in patients with acute myocardial infarction

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 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 (±SD) age of 64.2 (±12.1) years] analysed, 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 00:01-06:00hrs and lowest between 12:01-18:00hrs, p for trend <0.001, and risk of SHyper was highest between 12:01-18:00hrs and lowest between 00:01-06:00hrs. 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 utilised. However, when time-period-specific TSH reference ranges were utilised, the mortality risk was significantly higher in SCH patients with HR (95% CI) of 2.26 (1.01-5.19), p=0.04. 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

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