Imaging Chest Pain in Women Across the Lifespan: A Multimodality Framework for Sex-Specific Diagnosis

Women with suspected ischemic heart disease remain underrecognized, underdiagnosed, and undertreated, in part because conventional diagnostic pathways emphasize obstructive epicardial coronary disease and insufficiently account for life-stage-dependent vascular and myocardial biology. Reproductive and hormonal transitions do not create a single “female phenotype”; rather, they may modify arterial-wall integrity, vascular tone, endothelial and microvascular function, inflammation and myocardial remodeling. Cardiovascular imaging does not measure hormonal exposure directly, but it can identify these downstream phenotypes through assessment of coronary anatomy and plaque, myocardial blood flow, vasomotor function, tissue injury, fibrosis, and hemodynamics. This review proposes a practical, question-driven multimodality framework for evaluating chest pain and related ischemic presentations across four life stages: young and premenopausal women, pregnancy and postpartum, midlife and the menopause transition, and older age. The dominant differential and imaging priority evolve from spontaneous coronary artery dissection, myocardial injury with non-obstructive coronary arteries, and congenital coronary anomalies; to pregnancy-associated vascular and myocardial emergencies; to non-obstructive plaque, coronary microvascular and vasomotor dysfunction; and finally to calcific coronary disease, heart failure phenotypes, and multimorbidity. Matching echocardiography, coronary computed tomography angiography, cardiac magnetic resonance, nuclear perfusion imaging, and invasive physiology to the unresolved clinical question may reduce premature diagnostic closure. Future priorities include integrating reproductive history into imaging algorithms, establishing life-stage-specific reference standards, and validating quantitative plaque, perfusion, and artificial intelligence biomarkers in women.