Conference Coverage

Sex Differences Found in Cardiac Wall Thickness but Not Adjusted Mortality in AL Cardiomyopathy

Edited by:
Ashton L. Stahl

Key Highlights

  • Women with AL-CM had significantly lower interventricular septal and posterior wall thickness than men (P < .001 for both comparisons).
  • NT-proBNP levels, Mayo disease stage, and New York Heart Association (NYHA) functional class were similar between sexes.
  • Men had higher all-cause mortality in unadjusted analyses (HR, 1.48; 95% CI, 1.04-2.10), but the association was no longer present after multivariable adjustment.

Women with immunoglobulin light-chain amyloid cardiomyopathy (AL-CM) demonstrated lower cardiac wall thickness than men despite comparable disease stage, biomarker burden, and functional status, according to findings from a multicenter retrospective study scheduled for presentation at the 2026 American Heart Association's (AHA) Scientific Sessions.

The analysis also found that although men experienced higher all-cause mortality in unadjusted analyses, sex was not independently associated with mortality after accounting for clinical covariates. Researchers examined sex-related differences in cardiac characteristics, disease severity, and survival among patients with AL-CM.

Investigators conducted a retrospective analysis of 536 patients diagnosed with AL-CM between 1997 and 2023 across 22 US sites participating in the multicenter Cardiac Amyloidosis Registry Study (CARS). Women represented 38.8% of the study population.

Researchers compared demographic characteristics, clinical presentation, cardiac biomarkers, echocardiographic measurements, Mayo disease stage, diagnostic trends, and survival between men and women. Multivariable survival analyses adjusted for age, race, and Mayo stage.

Study Findings

Age at diagnosis was similar between men and women (63.9 ± 10.1 vs 62.3 ± 10.4 years; P = .08). NYHA functional class (P = .82) and Mayo disease stage distribution (P = .58) were also comparable between sexes.

Cardiac biomarker analyses showed similar NT-proBNP z-scores in men and women (0.03 ± 0.99 vs 0.03 ± 0.97; P = .92). However, men demonstrated modestly higher troponin z-scores than women (0.02 ± 1.05 vs 0.01 ± 1.05; P = .037).

Echocardiographic measurements revealed significant sex-related differences in cardiac wall thickness. Women had lower interventricular septal thickness than men (13.8 ± 3.4 vs 15.4 ± 3.7 mm; P < .001). Posterior wall thickness was also lower among women (13.7 ± 3.0 vs 15.0 ± 3.3 mm; P < .001).

AL-CM diagnoses increased over time in both sexes, with no marked differences in the diagnostic distribution between men and women.

In unadjusted survival analyses, male sex was associated with higher all-cause mortality (hazard ratio [HR], 1.48; 95% CI, 1.04-2.10; P = .03). However, after multivariable adjustment for age, race, and Mayo stage, sex was no longer associated with mortality.

Clinical Implications

According to the study authors, the findings suggest that sex influences the cardiac expression of AL-CM, particularly cardiac wall thickness, without substantial differences in disease severity or long-term prognosis.

Although women demonstrated lower interventricular and posterior wall thickness, similar biomarker burden, functional status, and disease stage indicate that these structural differences did not correspond to marked differences in disease severity at presentation.

Expert Commentary

“In this multicenter cohort of AL cardiac amyloidosis, females with AL-CM had lower interventricular wall thickness despite similar biomarker burden, disease stage, and functional status at presentation. Although males exhibited worse unadjusted survival, sex was not independently associated with mortality after adjustment for clinical covariates,” the researchers concluded.

Reference

Guhan M, Jefferson A, Ayers C, et al. Sex differences in immunoglobulin light chain amyloidosis with cardiomyopathy: insights from the CARS Registry. Abstract Sa4017. Presented at: American Heart Association Scientific Sessions 2026; November 7, 2026.