SAT-391 - A Silent Modifier of Heart Failure Risk: Subclinical Hypothyroidism and Adverse Outcomes in HFrEF-A Large Real-World Analysis

Background
Subclinical hypothyroidism (SCH) is common in patients with cardiovascular disease, yet its prognostic significance in heart failure with reduced ejection fraction (HFrEF) remains incompletely defined. While overt thyroid dysfunction is known to influence myocardial contractility, vascular resistance, and arrhythmogenesis, the clinical impact of SCH in HFrEF is underrecognized and under-studied in large contemporary populations.

Methods
We conducted a retrospective cohort study using the TriNetX U.S. Collaborative Network, including adults with HFrEF (LVEF ≤40%). SCH was defined by elevated serum TSH (≥4.5 mIU/L) with normal free thyroxine (0.8–1.8 ng/dL). Patients with HFrEF and SCH were compared with HFrEF patients without SCH. Propensity score matching (1:1) was performed across demographic, clinical, medication, and laboratory variables to minimize confounding. Outcomes were assessed over 1 year following index diagnosis and included all-cause mortality, major adverse cardiovascular events (MACE), heart failure exacerbation, new-onset atrial fibrillation, acute kidney injury (AKI), all-cause hospitalization, ICU admission, and cardiogenic shock.

Results
After 1:1 propensity score matching, 15,708 patients were included in each cohort. Over 1 year of follow-up, patients with subclinical hypothyroidism (SCH) experienced significantly higher rates of adverse outcomes compared with those without SCH. All-cause mortality was higher among patients with SCH (22.8% vs 16.5%; hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.38–1.53; p< 0.001). Major adverse cardiovascular events (MACE) occurred more frequently in the SCH group (41.1% vs 34.7%; HR 1.25, 95% CI 1.21–1.30; p< 0.001).
Heart failure exacerbation was more common and occurred earlier among patients with SCH (63.4% vs 58.5%; HR 1.19, 95% CI 1.16–1.22; p< 0.001). SCH was also associated with higher rates of new-onset atrial fibrillation (10.5% vs 8.2%; HR 1.38; p< 0.001), acute kidney injury (34.2% vs 24.6%; HR 1.53; p< 0.001), ICU admission (26.2% vs 18.4%; HR 1.52; p< 0.001), and cardiogenic shock (9.9% vs 4.5%; HR 2.34; p< 0.001). Stroke rates did not differ significantly between groups.

Conclusion
In this large real-world cohort of patients with HFrEF, subclinical hypothyroidism was independently associated with increased mortality, adverse cardiovascular events, heart failure decompensation, and greater critical care utilization. These findings suggest that SCH represents a clinically meaningful modifier of risk rather than a benign biochemical abnormality in HFrEF.

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