The silent scar: remote myocardial fibrosis underlies diastolic dysfunction in women after STEMI-multimodality imaging phenotyping

Abstract

Despite equivalent reperfusion, women experience higher rates of heart failure and mortality after STEMI. Conventional imaging alone cannot explain this disparity. Whether multimodality imaging reveals sex-specific differences in LV remodelling, diastolic function, and tissue characteristics — independent of age — remains unknown. To evaluate age-adjusted sex differences in LV morphology, diastolic function, and myocardial tissue characteristics using multimodality imaging within a prospective STEMI registry. We analysed 251 consecutive STEMI patients treated with primary percutaneous coronary intervention (196 men [78%], 55 women [22%]), who underwent echocardiography (end-diastolic and end-systolic volumes, global longitudinal strain (GLS), myocardial work indices, and systolic and diastolic parameters) and CMR (indexed LV volumes, myocardial mass, late gadolinium enhancement (LGE), native T1 mapping, extracellular volume fraction (ECV), microvascular obstruction (MVO), and intramyocardial haemorrhage (IMH)). Sex differences were assessed by ANCOVA with age as a continuous covariate; sex-by-age interaction terms were tested to evaluate effect modification. Women were significantly older than men (p<0.001). After age adjustment, men demonstrated significantly larger LV volumes (EDV: p<0.001; ESV: p<0.001), left atrial volume (LAV: p=0.003), CMR-derived indexed LV volumes (EDVI: p<0.001; ESVI: p=0.010), and LV myocardial mass (p<0.001). Despite comparable LGE-defined infarct size (p>0.05), women exhibited higher LV filling pressures (E/e′: p=0.015) and elevated remote zone native T1 (p=0.049). Although MVO was more frequent in men on unadjusted analysis (p=0.016), this difference was no longer significant after age adjustment (p=0.116); age was the primary determinant of MVO (p=0.008; sex×age interaction p=0.825). Remote zone native T1 correlated positively with E/e′ average (r=0.297, p=0.036). Male sex is associated with larger LV volumes and mass after age adjustment, while excess MVO in men is primarily age-driven rather than sex-specific. Women exhibit elevated remote zone native T1, reflecting diffuse interstitial fibrosis, and higher LV filling pressures independent of age. The positive correlation between remote zone native T1 and E/e′ provides mechanistic evidence of fibrosis-mediated diastolic dysfunction in women after STEMI. These findings support sex-specific myocardial tissue characterisation and early cardioprotective therapy in women after STEMI.