Challenges in Diagnosis and Functional Assessment of Coronary Artery Disease in Patients With Severe Aortic Stenosis

Abstract

More than half of patients with severe aortic stenosis (AS) over 70 years old have coronary artery disease (CAD). Exertional angina is often present in AS-patients, even in the absence of significant CAD, as a result of oxygen supply/demand mismatch and exercise-induced myocardial ischemia. Moreover, persistent myocardial ischemia leads to extensive myocardial fibrosis and subsequent coronary microvascular dysfunction (CMD) which is defined as reduced coronary vasodilatory capacity below ischemic threshold. Therefore, angina, as well as noninvasive stress tests, have a low specificity and positive predictive value (PPV) for the assessment of epicardial coronary stenosis severity in AS-patients. Moreover, in symptomatic patients with severe AS exercise testing is even contraindicated. Given the limitations of noninvasive stress tests, coronary angiography remains the standard examination for determining the presence and severity of CAD in AS-patients, although angiography alone has poor accuracy in the evaluation of its functional severity. To overcome this limitation, the well-established invasive indices for the assessment of coronary stenosis severity, such as fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR), are now in focus, especially in the contemporary era with the rapid increment of transcatheter aortic valve replacement (TAVR) for the treatment of AS-patients. TAVR induces an immediate decrease in hyperemic microcirculatory resistance and a concomitant increase in hyperemic flow velocity, whereas resting coronary hemodynamics remain unaltered. These findings suggest that FFR may underestimate coronary stenosis severity in AS-patients, whereas iFR as the non-hyperemic index is independent of the AS severity. However, because resting coronary hemodynamics do not improve immediately after TAVR, the coronary vasodilatory capacity in AS-patients treated by TAVR remain impaired, and thus the iFR may overestimate coronary stenosis severity in these patients. The optimal method for evaluating myocardial ischemia in patients with AS and co-existing CAD has not yet been fully established, and this important issue is under further investigation. This review is focused on challenges, limitations, and future perspectives in the functional assessment of coronary stenosis severity in these patients, bearing in mind the complexity of coronary physiology in the presence of this valvular heart disease.

Unmasking of a significant left main stenosis in a patient with high left ventricular pressures

“…Furthermore, the vasodilatory capacity of coronary arterioles in patients with increased LVEDP, in our case being related to persisting, large myocardial ischemia and LV dysfunction, is reduced or exhausted at rest; thus, the vasodilatory effect of adenosine on microcirculatory resistance is limited. A similar condition has been described in patients with severe aortic stenosis, where LVEDP reduction by transcatheter aortic valve replacement leads to immediate recovery of coronary microcirculatory resistance and increased hyperemic flow velocity 4 . In our patient, LV unloading and LVEDP decreasing by Impella, coupled with the device‐related increase of aortic pressures and reduction of coronary pressures, restored the coronary autoregulation pathways, in particular improving the physiological diastolic “suction wave” and increasing coronary flow.…”

“…A similar condition has been described in patients with aortic stenosis, where LVEDP reduction by transcatheter aortic valve replacement leads to immediate recovery of coronary microcirculatory resistance and increased hyperemic flow velocity. 4 In our patient, LV unloading and LVEDP decreasing by Impella, coupled with the device-related increase of aortic pressures and reduction of coronary pressures, restored the coronary autoregulation pathways, in particular improving the physiological diastolic "suction wave" and increasing coronary flow. This "unmasked" the functional severity of LM stenosis.…”

Invasive Functional Assessment of Coronary Artery Disease in Patients with Severe Aortic Stenosis in the TAVI Era

“…In addition, diastolic filling time and the severity of the aortic valve area have been positively correlated to reduced CFR [ 34 ]. Thus, even in the absence of epicardial CAD, ischemia can occur, further triggering fibrotic changes in the myocardium and inducing angina [ 35 ]. Due to these factors, the presence of angina has a low positive predictive value for CAD in patients with aortic stenosis [ 2 ].…”

“…From a pathophysiological perspective, because LV hypertrophy leads to external compression of the microvasculature and relative capillary rarefication, the resting vasodilatory capacity to maintain stable coronary flow is already exhausted in AS patients [ 38 , 47 ]. Thus, the vasodilatory response to adenosine is attenuated during FFR measurement, which may lead to false negative (too high) FFR values in intermediate epicardial stenoses and subsequent underestimation of stenosis severity [ 35 ]. Structural and functional alterations of the microvasculature further contribute to this finding, including perivascular fibrosis, arteriolar remodeling, endothelial dysfunction, and a higher sympathetic tone, all of which lead to a higher hyperemic microvascular resistance with subsequent attenuation of the vasodilatory effect of adenosine [ 34 , 38 , 47 , 48 ].…”

Management of coronary artery disease in patients with aortic stenosis

“…The FFR is measured over the entire cardiac cycle during maximal hyperaemia using adenosine and is expressed as the ratio of the mean coronary pressure distal to stenosis relative to the mean proximal aortic pressure. Adenosine is a potent vasodilator of coronary arterioles and can be safe, but has also been associated with haemodynamic instability in the presence of severe AS with coexisting CAD 27. Some small observational studies have suggested that percutaneous coronary intervention (PCI) under FFR guidance in TAVI recipients with CAD may lead to improved clinical outcomes in comparison with angiography-guided PCI, but this is yet to be established in a randomised controlled trial (RCT) 28…”