Thyroid dysfunction had virtually no independent impact on survival in a retrospective study of nearly 5,000 English patients with chronic heart failure, adding to evidence that subclinical thyroid disorders in these patients requires no special management beyond ongoing monitoring.
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“Although thyroid dysfunction is related to outcome in patients with chronic heart failure, the association disappears when adjustment is made for established prognostic variables, such as age, NT-proBNP [N-terminal of the prohormone brain natriuretic peptide], and [New York Heart Association] class,” wrote Nathan A. Samuel, MBChB, and coauthors in the American Journal of Cardiology.
Results from several earlier studies had shown evidence for reduced survival in heart failure patients with thyroid dysfunction, but in analyses that did not adjust for heart failure severity, such as a 2013 report that used data from the Sudden Cardiac Death in Heart Failure Trial SCD-HeFT. Other studies that adjusted for heart failure severity based on serum level of natriuretic peptides did not show significant associations between thyroid function and mortality, and when those results couple with the new report they together minimize the immediate risk from subclinical thyroid dysfunction faced by heart failure patients, wrote the authors of the new report.
Don’t treat subclinical thyroid dysfunction
“Our results suggest that subclinical thyroid disease has little impact on outcomes, and that we should not treat subclinical hypothyroidism in the expectation of improving outlook,” said Andrew L. Clark, MD, senior author on the new report and professor and head of the department of academic cardiology at Hull (England) York Medical School.
“Both hyper-and hypothyroidism can cause heart failure, so thyroid function should always be checked in patients when they present with heart failure. A small proportion of patients have heart failure that is potentially reversible” with thyroid-directed treatment, Dr. Clark said in an interview.
But “subclinical disease should probably not be treated, although we have not conducted a clinical trial that proves this assertion. We speculate, based on our findings, that such a trial is unlikely to be positive.”
Patients with subclinical thyroid disorders, particularly subclinical hypothyroidism, “need to be followed and treated should they develop clinical disease,” he maintained. “Except in extreme circumstances, such as the handful of patients who might have gross myxedema and may be near coma, thyroid replacement therapy for those [with heart failure] who have clinical hypothyroidism should follow standard lines.”
It is important to monitor thyroid function,” agreed Dr. Samuel, a researcher in the department of academic cardiology at Hull York Medical School. “We found that thyroxine use was most common among patients with hyperthyroidism, suggesting that they were previously hypothyroid and had received inappropriate treatment.”
Confounder adjustment mitigates the thyroid link
The new analysis used data collected from 6,782 consecutive heart failure patients enrolled during 2000-2018 at a community heart failure clinic that serves patients in the region of Hull, England. The researchers identified 4,992 of these patients with confirmed heart failure and adequate data for their analyses, including 2,997 (60%) with heart failure with reduced ejection fraction (HFrEF) and 1,995 (40%) with heart failure with normal ejection fraction (HFnEF, the term used by the authors but often called heart failure with preserved ejection fraction).
Thyroid hormone levels showed that 90% of these patients were euthyroid, 6% were hyperthyroid, and 4% were hypothyroid, rates consistent with prior reports for both the general population and heart failure patients. Only 12 patients (0.2%) had overt hypothyroidism, and fewer that 1% (about 45 patients) had overt hyperthyroidism. Patients averaged about 73 years of age, and during a median 4.6 years of follow-up 58% died.
Both the hypo- and hyperthyroid patients showed significantly higher mortality rates than euthyroid patients in a univariate analysis. But the patients with thyroid dysfunction also had more comorbidities, more severe heart failure symptoms measured by NYHA functional class, and more severe heart failure measured as higher serum levels of NT-proBNP.
Levothyroxine: No LV benefit in subclinical hypothyroidism with MI
In a multivariate analysis that adjusted for these factors, the significant differences disappeared among the entire group of heart failure patients for the outcomes of all-cause mortality, and mortality or hospitalization with heart failure. The multivariate analysis also showed no significant association between higher levels of thyroid-stimulating hormone (TSH) and all-cause death or death plus heart failure hospitalization among the patients with HFrEF.
Among patients with HFnEF, the multivariate adjusted analysis showed a small increase in both mortality and mortality plus hospitalization for heart failure, a 2% rise for each of these two endpoints for each 1 mIU/L increase in TSH, the authors reported. Although the P value for each of these two significant differences among patients with HFnEF was .02, the 95% confidence interval included 1.00 and ranged from 1.00 to 1.04.
The multivariate analysis identified three variables with the strongest associations with all-cause mortality: older age, higher levels of NT-proBNP, and higher NYHA class indicating greater functional impairment.
The results support the hypothesis that “worsening heart failure can lead to down-regulation of thyroid hormone signaling,” the authors suggested. Their study is also “the first to examine the prognostic significance of thyroid dysfunction in a large population of patients with HFnEF.” This analysis showed a “weak but significant association between increasing TSH and both mortality and the composite endpoint in patients with HFnEF.”
“HFnEF is a heterogeneous group of conditions that are difficult to diagnose in many cases. Therefore, future studies are needed to provide further clarity on the effect of thyroid dysfunction in these patients,” Dr. Samuel said.
The study received no commercial funding. Dr. Samuel and Dr. Clark had no disclosures.
SOURCE: Samuel NA et al. Am J Cardiol. 2020 Oct 24. doi: 10.1016/j.amjcard.2020.10.034.
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