Worsening HFpEF Linked With Low T3/T4 Ratio

Marlene Busko, for Medscape

October 06, 2022

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key Takeaways

  • In the study, 79 patients with heart failure with preserved ejection fraction (HFpEF) were seen at a heart failure clinic in Portugal and were followed for a median of 2.8 years. Among those whose ratio of free triiodothyronine (FT3) to free thyroxine (FT4) was in the lowest tertile, there was a significantly increased rate of a composite of urgent heart failure (HF) visits involving diuretic intensification, HF hospitalization, or cardiovascular death compared with those whose ratios were in the higher tertiles.

  • Patients whose T3/T4 ratio was in the lowest tertile were more likely to have obesity, type 2 diabetes, atrial fibrillation, higher body fat, higher pulmonary arterial systolic pressure, and lower left ventricular ejection fraction (LVEF).

Why This Matters

  • Up to 30% of patients with HF have some form of thyroid dysfunction that may contribute to the onset and progression of HF. Results from this study suggest a potential mechanism that could in part explain this relationship.

  • The results suggest that decreased T4 to T3 conversion may help explain HFpEF progression and decompensation.

  • Persistently low T3 levels negatively influence myocardial function and structure and impair cardiac remodeling.

Study Design

  • The researchers identified 79 patients with stable HFpEF who had no history of thyroid disease or of taking medication and were seen at an HF outpatient clinic in Porto, Portugal. The patients participated in the prospective New Targets in Diastolic Heart Failure: From Comorbidities to Personalized Medicine (NETDiamond) study, which focuses on finding novel disease mechanisms and therapeutic targets for people with HFpEF.

  • All participants underwent blood testing to measure thyroid-stimulating hormone, T3, and T4, and they all had undergone echocardiography.

Key Results

  • The average age of the patients was 74 years, and 53% were women. The mean T3/T4 ratio was 2.63.

  • Those in the lowest tertile for FT3/FT4 ratio were older and were more likely to be women and to have orthopnea, obesity, type 2 diabetes, and atrial fibrillation. They also had a higher body mass index, and levels of high-sensitivity troponin-I were increased.

  • Increased T3/T4 ratios were positively associated with LVEF and negatively associated with pulmonary arterial systolic pressure.

  • During a median follow-up of 2.8 years, participants had 32 first events for the composite HF endpoint.

  • The highest rate of the composite HF outcome was found among people in the lowest tertile for T3/T4 ratio. The fully adjusted hazard ratio for the primary outcome increased by a significant 2.5-fold for each 1-unit decrease in FT3/FT4 ratio.


  • This was an observational study; as such, it cannot establish causality, and the generalizability of the findings is limited.

  • Because of its small size, the study had limited statistical power.

  • The analysis may be affected by residual confounding.

  • Participants' thyroid hormone levels were measured once, and potential variations within individuals could have been missed.


  • The study did not receive commercial funding.

  • One author has been a consultant to Boehringer Ingelheim and AstraZeneca and has received research support from AstraZeneca, Bayer, Boehringer Ingelheim, and Novartis through his institution. Another author has received consulting or speaker fees from AstraZeneca, BIAL, Boehringer Ingelheim, Lilly, Merck, and Novo Nordisk. A third author has received speaker fees from AstraZeneca.

This is a summary of a preprint article, "Clinical and Pathophysiologic Insights of FT3/FT4 Ratio in Patients With Heart Failure With Preserved Ejection Fraction: Data From the NETDiamond Cohort," written by researchers from the University of Porto, Spain, published on Research Square, and provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on researchsquare.com.

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