Microcirculatory Dysfunction
More than 20 % of patients referred for coronary angiography because of chest pain have no angiographic evidence of coronary artery stenosis. According to a recent study, however, more than 75 % of these patients have occult coronary abnormalities, mostly endothelial dysfunction and microvascular impairment.34
Microvascular dysfunction could develop before the occurrence of atherosclerotic epicardial artery involvement and it could also coexist with angiographically significant coronary artery disease. Coronary microvasculature cannot be visualised directly and CFVR represents a useful tool to assess microcirculatory function. Many risk factors and clinical conditions have been proved to be associated with microcirculatory impairment. Patients with type 2 diabetes, for example, have reduced CFVR compared with healthy controls, and diabetics with CFVR ≤2 have worse prognosis compared with those with CFVR >2, despite the fact that both groups have preserved left ventricular ejection fraction, normal wall motion score analysis during dipyridamole stress test and absence of angiographically significant coronary stenoses.35
In patients with chronic kidney disease in the absence of obstructive coronary artery disease, the presence of microvascular dysfunction, defined as CFVR <2, was associated with worse cardiovascular outcomes, independent of traditional cardiovascular risk factors.36
Stress Echocardiography
According to the European Association of Cardiovascular Imaging Expert consensus statement for performing stress echocardiography from 2008 wall motion analysis should be combined with perfusion assessment (CFVR) in order to provide dual imaging vasodilator stress echocardiography.37 Wall motion abnormalities are more specific for inducible ischaemia while perfusion changes are more sensitive and may occur in the absence of ischaemia. CFVR and wall motion analysis offer complementary information during stress echo, combining flow and function together. Wall motion abnormality is more efficient to include coronary artery disease, while a normal CFVR is more efficient to exclude it (CFVR has higher negative predictive value).
In a study of 1,660 patients with chest pain and no wall motion abnormalities at rest and during dipyridamole stress echocardiography, decreased CFVR on LAD was associated with significantly increased 4-year event rate both in women and men.38
Although some authors have reported successful application of three-vessel CFVR assessment during vasodilator stress test,28 dual imaging vasodilator stress echocardiography at present utilises LAD- only CFVR evaluation. A three-coronary approach would probably be more fruitful but it remains too technically challenging. Moreover, microvascular dysfunction, which is the mainstay of perfusion abnormalities detected with LAD CFVR measurement during stress echocardiography, is a global phenomenon and could be adequately assessed with Doppler interrogation of the distal LAD segment.
Athletes’ Heart
CFVR could be used to differentiate between physiological left ventricular hypertrophy (typical for endurance athletes) and pathological hypertrophy in the setting of hypertrophic cardiomyopathy (CMP) and hypertensive heart disease. In a group of 29 male endurance athletes CFVR has been found to be supranormal (mean value 5.9) and significantly higher compared with healthy controls despite the presence of left ventricular hypertrophy in the former group.39
Aortic Stenosis
Aortic stenosis induces a pressure overload of the left ventricle, leading eventually to concentric left ventricular remodelling and hypertrophy, and increase in left ventricular mass. In order to provide an adequate blood supply to an increased muscle mass at rest coronary arteries dilate. This baseline vasodilation leads in turn to a reduced capacity to increase coronary flow during exercise (or after pharmacological challenge with adenosine or dipyridamole) and therefore to a reduction in CFVR.
Decreased CFVR in patients with haemodynamically significant aortic stenosis in the absence of epicardial coronary artery stenosis has been repeatedly demonstrated and also the prognostic value of CFVR has been shown in this population. In the SummariZation of long-tErm prognostic siGnificance of coronary flow rEserve in special Disorders (SZEGED) study 49 aortic stenosis patients were followed-up for nearly 9 years after baseline CFVR assessment. Univariate and multivariate regression analysis showed that CFVR was an independent predictor of cardiovascular morbidity and mortality. The authors found that CFVR cut-off value of 2.13 had the highest accuracy in predicting cardiovascular outcome.40
In a larger study of 127 asymptomatic patients with moderate and severe aortic stenosis with preserved ejection fraction and without obstructive epicardial coronary disease followed-up for nearly 3 years, CFVR was shown to bear an independent prognostic significance of total mortality. A CFVR cut-off value of 1.85 had the highest accuracy in predicting death.41
After aortic valve replacement, CFVR increases together with a decrease in left ventricular mass. This has been demonstrated in a study with 39 aortic stenosis patients evaluated before and 6 months after aortic valve replacement: CFVR increased from 1.76±0.5 to 2.61±0.7, which paralleled a decrease in left ventricular mass index from 154±21 to 134±21g/m2.42