Coronary Physiology Beyond Coronary Flow Reserve: A Giant Leap in the Understanding of Coronary Microvascular Disease A JACC State-of-the-Art Review

In a JACC State-of-the-Art Review by Dr. Lance Gould and his colleagues at UTHealth, Houston, Texas, the pathophysiology of Coronary microvascular disease (CMD) was summarized and an update was provided of diagnostic testing strategies, and classification of CMD into phenotypes according to severity and coexistence with atherosclerosis. Moreover, emerging data highlighting the significance of CMD in specific populations, including obesity and insulin resistance, myocardial injury and heart failure with preserved ejection fraction, and nonobstructive and obstructive coronary artery disease were analyzed. Lastly, the role of CMD as a potential target for novel interventions beyond conventional approaches, representing a new frontier in cardiovascular disease reduction was explored. 

Angina with no angiographic stenosis is commonly labeled microvascular angina, assumed due to impaired microvascular function and reduced CFR, but with widely conflicted published reports. However, comprehensive quantitative myocardial perfusion offers new insights beyond overly simplistic coronary flow reserve. Integrating regional absolute stress flow, relative stress flow, coronary flow reserve, and qualitative subendocardial perfusion gradient on tomograms of relative images, provides correct diagnosis, quantitative physiological classification, and potential treatment. Angina without angiographic stenosis is associated with abnormal quantitative perfusion with rare, but instructive, exceptions. However, microvascular dysfunction without angina is common, particularly associated with risk factors.

Reduced subendocardial/epicardial relative activity is common with diffuse coronary artery disease without focal stenosis with or without angina depending on the severity of reduced subendocardial perfusion. Precision quantitative myocardial perfusion in 5,900 cases objectively classifies angina with no angiographic stenosis into 4 categories: subendocardial ischemia due to diffuse coronary artery disease (most common), overlooked stenosis, diffuse microvascular dysfunction due to risk factors or specific microvasculopathies, and nonischemic cardiac pain mechanisms (rare), or some mix of these prototypes, of which 95% are associated with risk factors, or subclinical or clinically manifest coronary atherosclerosis needing vigorous risk factor treatment. Clinical application of these concepts requires ongoing research within the objective, quantitative, evidence-based, physiological framework reviewed here wherein coronary physiology trumps coronary anatomy.

In an accompanying article also published in JACC, Viviany R. Taqueti and Marcelo F. Di Carli illustrate the link between CMD and poor prognosis in patients. Coronary microvascular disease (CMD) refers to the subset of disorders affecting the structure and function of the coronary microcirculation, is prevalent in patients across a broad spectrum of cardiovascular risk factors, and is associated with an increased risk of adverse events. Contemporary evidence supports that most patients with CMD also have macro vessel atherosclerosis, which has important implications for their prognosis and management.

The authors state that CMD represents a combination of structural and functional abnormalities in the coronary microcirculation, is prevalent across a broad spectrum of cardiovascular risk factors and diseases, and is associated with increased risk of MACE. Contemporary evidence already supports that most patients with CMD have coexisting obstructive or nonobstructive atherosclerosis, with important implications for their prognosis. Most importantly, the interaction of CMD, CAD, and adverse outcomes, including heart failure, likely holds a key to novel therapeutic strategies for cardiovascular health promotion.