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 macrovessel atherosclerosis, which has important implications for their prognosis and management. In this state-of-the-art review, the authors summarize the pathophysiology of CMD, provide an update of diagnostic testing strategies, and classify CMD into phenotypes according to severity and coexistence with atherosclerosis. They examine 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. Finally, they discuss the role of CMD as a potential target for novel interventions beyond conventional approaches, representing a new frontier in cardiovascular disease reduction.
Graphical Abstract
Graphical Abstract
(A) Coronary flow reserve (CFR) is a quantitative measure of myocardial ischaemia that integrates the haemodynamic contribution of the large and small coronary ...vessels to myocardial tissue perfusion. CFR is a sensitive marker of cardiac ischaemia beyond inducible regional wall motion abnormalities or visible perfusion defects. (B) The value proposition of coronary blood flow measurement for personalized imaging of patients with coronary heart disease. CAD, coronary artery disease.
Coronary microvascular dysfunction (CMD) is a prevalent and prognostically important finding in patients with symptoms suggestive of coronary artery disease. The relative extent to which CMD affects ...both sexes is largely unknown.
We investigated 405 men and 813 women who were referred for evaluation of suspected coronary artery disease with no previous history of coronary artery disease and no visual evidence of coronary artery disease on rest/stress positron emission tomography myocardial perfusion imaging. Coronary flow reserve was quantified, and coronary flow reserve <2.0 was used to define the presence of CMD. Major adverse cardiac events, including cardiac death, nonfatal myocardial infarction, late revascularization, and hospitalization for heart failure, were assessed in a blinded fashion over a median follow-up of 1.3 years (interquartile range, 0.5-2.3 years). CMD was highly prevalent both in men and women (51% and 54%, respectively; Fisher exact test =0.39; equivalence P=0.0002). Regardless of sex, coronary flow reserve was a powerful incremental predictor of major adverse cardiac events (hazard ratio, 0.80 95% confidence interval, 0.75-086 per 10% increase in coronary flow reserve; P<0.0001) and resulted in favorable net reclassification improvement (0.280 95% confidence interval, 0.049-0.512), after adjustment for clinical risk and ventricular function. In a subgroup (n=404; 307 women/97 men) without evidence of coronary artery calcification on gated computed tomography imaging, CMD was common in both sexes, despite normal stress perfusion imaging and no coronary artery calcification (44% of men versus 48% of women; Fisher exact test P=0.56; equivalence P=0.041).
CMD is highly prevalent among at-risk individuals and is associated with adverse outcomes regardless of sex. The high prevalence of CMD in both sexes suggests that it may be a useful target for future therapeutic interventions.
Myocardial perfusion imaging has limited sensitivity for the detection of high-risk coronary artery disease (CAD). We tested the hypothesis that a normal coronary flow reserve (CFR) would be helpful ...for excluding the presence of high-risk CAD on angiography.
We studied 290 consecutive patients undergoing (82)Rb PET within 180 d of invasive coronary angiography. High-risk CAD on angiography was defined as 2-vessel disease (≥ 70% stenosis), including the proximal left anterior descending artery; 3-vessel disease; or left main CAD (≥ 50% stenosis). Patients with prior Q wave myocardial infarction, elevated troponin levels between studies, prior coronary artery bypass grafting, a left ventricular ejection fraction of less than 40%, or severe valvular heart disease were excluded.
Fifty-five patients (19%) had high-risk CAD on angiography. As expected, the trade-off between the sensitivity and the specificity of the CFR for identifying high-risk CAD varied substantially depending on the cutoff selected. In multivariable analysis, a binary CFR of less than or equal to 1.93 provided incremental diagnostic information for the identification of high-risk CAD beyond the model with the Duke clinical risk score (>25%), percentage of left ventricular ischemia (>10%), transient ischemic dilation index (>1.07), and change in the left ventricular ejection fraction during stress (<2) (P = 0.0009). In patients with normal or slightly to moderately abnormal results on perfusion scans (<10% of left ventricular mass) during stress (n = 136), a preserved CFR (>1.93) excluded high-risk CAD with a high sensitivity (86%) and a high negative predictive value (97%).
A normal CFR has a high negative predictive value for excluding high-risk CAD on angiography. Although an abnormal CFR increases the probability of significant obstructive CAD, it cannot reliably distinguish significant epicardial stenosis from nonobstructive, diffuse atherosclerosis or microvascular dysfunction.
PDF
