Chronic ischemic heart disease: A nonuniform syndrome

Ischemic heart disease (IHD) is a leading cause of morbidity and mortality worldwide. Decades of progress have focused on identification of obstructive coronary plaque (“stenosis” >50–70% diameter narrowing) as a threshold for diagnosis and target for therapy. Emerging evidence underscores the significance of a myriad of relevant isolated or coexisting biologic, physiologic, and radiologic mechanisms and features, beyond stenosis, as causes of ischemia and hence predictors of ischemia-related clinical outcomes. In the context of the chronic ischemic syndrome, a persistent challenge lies in the disconnect between obstructive plagues and symptoms, clinical outcomes, and responses to revascularization and guideline-based medical therapy. For instance, a study elucidating some mechanisms observed a 2.6- fold increase in identification of a nonobstructive cause for myocardial ischemia among symptomatic patients referred for invasive coronary angiography. This review aims at highlighting emerging impactful elements and mechanisms and proposes a broad spectrum of phenotypes, which better capture the heterogeneous characteristics of chronic coronary artery disease (CAD). We examine nontraditional factors, radiometric features, polygenic and genetic signatures, and biomechanical plaque characteristics, which underpin numerous coexisting and overlapping pathologic and clinical manifestations. The focus shifts from quantifying mechanical obstruction to identifying biologically active plaques, which may not be confined to Acute Coronary Syndromes but are present across the spectrum of chronic CAD. Recognizing these features carries important prognostic and therapeutic implications.