Distinct cardiovascular phenotypes in CAR-T candidates by sex
L Moreno De Redrojo Cortes, B Aumente Rodriguez, A C Martin-Garcia, S Rodriguez Diego, E Iglesias Colino, E Perez Lopez, A A Martin Lopez, R Eiros Bachiller, M Garcia Lopez, J Calle Perez, P Urbiola Saez, D Clavo Martin, P L Sanchez Fernandez, L Lopez Corral, A Martin-GarciaAbstract
Introduction
Differences in cardiovascular involvement between men and women undergoing CAR-T therapy are not well characterized. We aimed to prospectively describe the sex-specific baseline cardiovascular phenotype using a comprehensive multimodal approach.
Methods
A total of 236 consecutive candidates underwent systematic screening before CAR-T infusion, including - clinical stratification, biomarkers (NT-proBNP, high sensitivity troponin I/T), electrocardiogram (ECG), echocardiography and cardiovascular magnetic resonance (CMR).
Results
The cohort (mean age 59.3±11.4 years, 61.4% male) presented a non-negligible cardiovascular disease and risk burden: 86.4% had at least one CV risk factor, yet 44.5% had suboptimal control. Men showed a higher estimated cardiovascular risk (SCORE2 5.6 [3.7–8.6] vs 3.7 [2.2–5.5]; p<0.001) and suboptimal risk factor control (50.3% vs 35.2%; p=0.022) compared to women, driven largely by a higher prevalence of overweight/obesity (60.7% vs 41.8%; p=0.005). Additionally, men presented with longer QRS duration (93 [87–102] vs 89 [81–94] ms; p<0.001) and women experienced more frequent NT-proBNP elevation (6.9% vs 16.7%; p=0.019). Regarding imaging, left ventricular ejection fraction was comparable between sexes (60.8±6.5% vs 61.9±6.6%; p=0.207). Similarly, new-onset left ventricular systolic dysfunction was observed in 9.7% and myocardial edema in 14.2%, without differences between sexes (8.3% vs 12.1%, p 0.337; and 11.2% vs 18.9%, p 0.101, respectively). However, CMR unveiled divergent phenotypes:
• Men exhibited a significantly higher presence of myocardial scar (late gadolinium enhancement) compared to women (20.2% vs 4.2%; p=0.002) and larger indexed right ventricular volumes (RVEDVi 74 [64–86] vs 65 [55–79] ml/m²; p<0.001).
• Women, in contrast, showed higher native mapping values (T1 Z-score 0.32 [−0.44–1.41] vs 0.00 [−0.89–0.99], p=0.010; and T2 Z-score 0.71±1.99 vs −0.04±1.87, p=0.010), indicating a distinct tissue profile compared to the male cohort. Women showed higher proportions of pathological Z-scores than men (T1: 14.7% vs 6.8%, p=0.120; T2: 23.2% vs 13.8%, p=0.112), although differences did not reach statistical significance.
Conclusion
Significant sex-related differences exist in the baseline cardiovascular profile of CAR-T candidates. While men show a higher prevalence of structural heart disease and fibrosis, women present with distinct myocardial tissue alterations despite a lower traditional risk profile. These findings highlight the importance of interpreting cardiovascular screening results within a sex-specific context.Table. Figure.