Thyroid function in heart failure and impact on mortality. JACC. Heart failure OBJECTIVES:The aim of this study was to investigate whether patients with systolic heart failure (HF) and abnormal thyroid function are at increased risk for death. BACKGROUND:Thyroid hormone homeostasis is vital to the optimal functioning of the cardiovascular system, but an independent prognostic effect of thyroid abnormalities in patients with HF has not been established. METHODS:In SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial), which randomized patients with ischemic or nonischemic HF to placebo or amiodarone or implantable cardioverter-defibrillator therapy, thyroid-stimulating hormone (TSH) was measured at baseline and at 6-month intervals throughout the 5-year study. RESULTS:Of 2,225 patients, the majority (87%) had normal TSH levels (0.3 to 5.0 μU/ml) at baseline, 12% had values suggestive of hypothyroidism, and 1% had values consistent with hyperthyroidism. Compared with euthyroid patients, those hypothyroid at baseline were older and included more women and Caucasians (all p values <0.05). Over the median follow-up period of 45.5 months, among patients euthyroid at baseline, 89 developed abnormally low TSH levels, and 341 developed abnormally high values. Patients randomized to amiodarone (median dose 300 mg) had an elevated risk for developing abnormal TSH levels compared with implantable cardioverter-defibrillator therapy or placebo (p < 0.0001). Patients with baseline or new-onset abnormal thyroid function had a higher mortality than those with normal thyroid function, even after controlling for other known mortality predictors (hazard ratio: 1.58; 95% confidence interval: 1.29 to 1.94; p < 0.0001 for hypothyroid; hazard ratio: 1.85; 95% confidence interval: 1.21 to 2.83; p = 0.0048 for hyperthyroid). Implantable cardioverter-defibrillator benefit did not vary with thyroid function. CONCLUSIONS:Abnormal thyroid function in patients with symptomatic HF and ejection fractions ≤35% is associated with significantly increased risk for death, even after controlling for known mortality predictors. 10.1016/j.jchf.2012.10.004

Repeated heart rate measurement and cardiovascular outcomes in left ventricular systolic dysfunction. Hamill Victoria,Ford Ian,Fox Kim,Böhm Michael,Borer Jeffrey S,Ferrari Roberto,Komajda Michel,Steg Philippe Gabriel,Tavazzi Luigi,Tendera Michal,Swedberg Karl The American journal of medicine BACKGROUND:Elevated resting heart rate is associated with increased cardiovascular risk, particularly in patients with left ventricular systolic dysfunction. Heart rate is not monitored routinely in these patients. We hypothesized that routine monitoring of heart rate would increase its prognostic value in patients with left ventricular systolic dysfunction. METHODS:We analyzed the relationship between heart rate measurements and a range of adverse cardiovascular outcomes, including hospitalization for worsening heart failure, in the pooled placebo-treated patients from the morBidity-mortality EvAlUaTion of the If inhibitor ivabradine in patients with coronary disease and left ventricULar dysfunction (BEAUTIFUL) trial and Systolic Heart failure treatment with the If inhibitor ivabradine (SHIFT) Trial, using standard and time-varying covariate Cox proportional hazards models. By adjusting for other prognostic factors, models were fitted for baseline heart rate alone or for time-updated heart rate (latest heart rate) alone or corrected for baseline heart rate or for immediate previous time-updated heart rate. RESULTS:Baseline heart rate was strongly associated with all outcomes apart from hospitalization for myocardial infarction. Time-updated heart rate increased the strengths of associations for all outcomes. Adjustment for baseline heart rate or immediate previous time-updated heart rate modestly reduced the prognostic importance of time-updated heart rate. For hospitalization for worsening heart failure, each 5 beats/min increase in baseline heart rate and time-updated heart rate was associated with a 15% (95% confidence interval, 12-18) and 22% (confidence interval, 19-40) increase in risk, respectively. Even after correction, the prognostic value of time-updated heart rate remained greater. CONCLUSIONS:In patients with left ventricular systolic dysfunction, time-updated heart rate is more strongly related with adverse cardiovascular outcomes than baseline heart rate. Heart rate should be measured to assess cardiovascular risk at all assessments of patients with left ventricular systolic dysfunction. 10.1016/j.amjmed.2015.04.042

Thyroid Dysfunction in Heart Failure and Cardiovascular Outcomes. Kannan Lakshmi,Shaw Pamela A,Morley Michael P,Brandimarto Jeffrey,Fang James C,Sweitzer Nancy K,Cappola Thomas P,Cappola Anne R Circulation. Heart failure BACKGROUND:The effects of thyroid dysfunction in patients with preexisting heart failure have not been adequately studied. We examined the prevalence of thyroid dysfunction and associations with cardiovascular outcomes in a large, prospective cohort of outpatients with preexisting heart failure. METHODS AND RESULTS:We examined associations between thyroid dysfunction and New York Heart Association class, atrial fibrillation, and a composite end point of ventricular assist device placement, heart transplantation, or death in 1365 participants with heart failure enrolled in the Penn Heart Failure Study. Mean age was 57 years, 35% were women, and the majority had New York Heart Association class II (45%) or III (32%) symptoms. More severe heart failure was associated with higher thyroid-stimulating hormone (TSH), higher free thyroxine (FT4), and lower total triiodothyronine (TT3) concentrations ( P<0.001 all models). Atrial fibrillation was positively associated with higher levels of FT4 alone ( P≤0.01 all models). There were 462 composite end points over a median 4.2 years of follow-up. In adjusted models, compared with euthyroidism, subclinical hypothyroidism (TSH 4.51-19.99 mIU/L with normal FT4) was associated with an increased risk of the composite end point overall (hazard ratio, 1.82; 95% CI, 1.27-2.61; P=0.001) and in the subgroup with TSH ≥7.00 mIU/L (hazard ratio, 3.25; 95% CI, 1.96-5.39; P<0.001), but not in the subgroup with TSH 4.51-6.99 mIU/L (hazard ratio, 1.26; 95% CI, 0.78-2.06; P=0.34). Isolated low T3 was also associated with the composite end point (hazard ratio, 2.12; 95% CI, 1.65-2.72; P<0.001). CONCLUSIONS:In patients with preexisting heart failure, subclinical hypothyroidism with TSH ≥7 mIU/L and isolated low T3 levels are associated with poor prognosis. Clinical trials are needed to explore therapeutic effects of T4 and T3 administration in heart failure. 10.1161/CIRCHEARTFAILURE.118.005266