Sex differences among ATTR-CM patients in real-world setting

A retrospective single-center cohort study showed sex-specific differences in diagnostic delay, clinical presentation, and disease progression among patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM).

This summary is based on the publication of Vogel J, Jura S, Settelmeier S, et al. - Sex-specific differences in cardiac transthyretin amyloidosis: addressing the diagnostic gap in women. Eur Heart J Open. 2026;6(1):oeaf175. doi: 10.1093/ehjopen/oeaf175

Introduction and methods

Background

Transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal disease characterized by the deposition of amyloid fibrils, which consist of misfolded transthyretin (TTR) aggregates, in the myocardium. The male:female ratio is approximately 10:1. However, women appear to be underrepresented in ATTR-CM diagnoses [1], possibly because most large studies have primarily included male patients [2,3]. To enhance early detection of ATTR-CM in women, sex-specific diagnostic criteria could be useful.

Aim of the study

The study aim was to investigate whether there are sex-specific differences in the clinical presentation, diagnosis, and clinical outcomes among ATTR-CM patients.

Methods

In a retrospective cohort study, 240 patients diagnosed with ATTR-CM at the West German Amyloidosis Center in Essen, Germany in the period 2018–2024 were included, of whom 34 (14.2%) were women. Clinical, laboratory, and echocardiographic parameters as well as outcomes under TTR stabilizer therapy at 6 and 12 months were collected.

Outcome

The primary endpoint was diagnostic delay, defined as the time from the first documented symptom or identifiable abnormal finding (e.g., on echocardiography, MRI, or scintigraphy) to confirmation of the ATTR-CM diagnosis.

Main results

Laboratory and echocardiographic parameters

• At the time of diagnosis, women had lower a median hs-cTnI level than men (30 ng/L; IQR: 14–81 vs. 45 ng/L; IQR: 27–72; P=0.042) and worse renal function as indicated by a lower mean ± SD eGFR (53.2 ± 18.8 mL/min/1.73 m² vs. 60.1 ± 18.6 mL/min/1.73 m²; P=0.046).
• There was no difference in median NT-proBNP level between women and men (3046 pg/mL; IQR: 907–4800 vs. 3216 pg/mL; IQR: 1686–6065; P=0.136), nor in NYHA functional class (P=0.855).
• Echocardiography showed women had a higher median LVEF compared with men (55%; IQR: 50%–60% vs. 53%; IQR: 43%–55%; P<0.001), a lower mean ± SD interventricular septum diameter (16.2 ± 4.5 mm vs. 18.1 ± 4.5 mm; P=0.026), and a decreased median stroke volume (49 mL; IQR: 42–49 vs. 56 mL; IQR: 46–69; P=0.020).

Time to diagnosis

• Diagnostic delay was longer in women than women (median time: 750 vs. 86 days; P=0.022).
• In the subgroup of patients with complete symptom-onset data (n=185), the median time to diagnosis was similar for men and women (273 days; IQR: 73–744 vs. 312 days; IQR: 121–1050; P=0.421).

Clinical outcomes

• At baseline, 94% of the patients received tafamidis (i.e., the only TTR stabilizer used in this cohort), with comparable treatment rates between men and women (P=0.74). During follow-up, tafamidis was discontinued in 16.2% of the treated patients.
• At 6 and 12 months, women had a higher LVEF, lower interventricular septum diameter, and lower LV myocardial mass indexed to body surface area than men (all P<0.05).
• At 6 months, eGFR was decreased in women compared with men (P=0.047), but there was no difference between the sexes at 12 months (P>0.05).
• There were no sex differences in hs-cTnI and NT-proBNP levels, stroke volume, or NYHA functional class during follow-up (all P>0.05).

Conclusion

This retrospective single-center cohort study among ATTR-CM patients showed sex-specific differences in diagnostic delay, clinical presentation—particular echocardiographic findings—and disease progression during the first year following diagnosis. The authors note that “the overall number of female patients included was notably low, making comparisons with the substantially larger male cohort difficult and limiting sex-specific conclusions. This raises the question of whether the observed differences truly reflect sex-specific disease manifestations or are at least partly due to underdiagnosis of cardiac amyloidosis in women.”

Still, they conclude that “[c]urrent diagnostic thresholds may not adequately reflect female disease patterns, underscoring the need for sex-adapted diagnostic criteria to improve early detection and management.”

Find this article online at Eur Heart J Open.

References

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2. Gillmore JD, Judge DP, Cappelli F, Fontana M, Garcia-Pavia P, Gibbs S, Grogan M, Hanna M, Hoffman J, Masri A, Maurer MS, Nativi-Nicolau J, Obici L, Poulsen SH, Rockhold F, Shah KB, Soman P, Garg J, Chiswell K, Xu H, Cao X, Lystig T, Sinha U, Fox JC. Efficacy and safety of acoramidis in transthyretin amyloid cardiomyopathy. N Engl J Med 2024;390:132–142.
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