Cardiac amyloidosis and coronary artery disease: an overlooked clinical intersection

Cardiac amyloidosis has emerged as an important and underrecognized cause of heart failure with preserved ejection fraction, particularly in elderly patients who commonly carry concomitant coronary artery disease. The coexistence of these two conditions creates a layered diagnostic and therapeutic problem. Epicardial atherosclerosis is present in roughly 30-40% of patients with cardiac amyloidosis, yet the dominant ischemic mechanism in the amyloidotic heart is rarely flow-limiting epicardial obstruction. Instead, ischemia is driven by coronary microvascular dysfunction arising from amyloid infiltration of the arteriolar wall, capillary rarefaction, extravascular compression by the hypertrophied myocardium, and in light-chain disease direct endothelial toxicity. This distinction has immediate clinical consequences. Chronic troponin elevation from subendocardial ischemia and wall stress frequently mimics acute coronary syndromes, prompting invasive procedures that carry disproportionate risk in this population, while pressure-derived indices such as fractional flow reserve are unreliable because the infiltrated microvasculature cannot mount a normal hyperemic response. This review synthesizes the pathophysiological interplay between amyloid infiltration and coronary disease, defines the diagnostic pitfalls of the dual pathology, and proposes a multimodality imaging strategy, integrating advanced echocardiography, cardiac magnetic resonance, nuclear perfusion imaging, and cardiac computed tomography that distinguishes microvascular from epicardial ischemia and supports more rational clinical decisions. Critical evidence gaps, foremost the absence of randomized data comparing revascularization with medical therapy in this population, are discussed alongside emerging tools for refining ischemic assessment in the amyloidotic heart.