• To screen and treat silent ischemia: A tough dilemma

    Atherosclerosis is a progressive disease that can cause clinical manifestations in middle and late adulthood. Coronary artery atherosclerosis can result in stable angina pectoris complaints, but also in acute onset or worsening of complaints, captured under the name of acute coronary syndrome. Frequently, and specifically in the elderly and diabetic patients, severe coronary atherosclerosis can be asymptomatic or present with complaints of exertional dyspnea and fatigue instead of the typical chest discomfort complaints. Although severe coronary artery narrowing causes myocardial ischemia, it is not always felt by the patient nor recognized as a symptom of the heart. When myocardial ischemia is objectified without complaints, we tend to call this silent ischemia.

    In the paper by Balouch et al. in this issue of Cardiovascular Revascularization Medicine, two tough issues concerning silent ischemia are brought up: A) the mismatch between ischemia and complaints and B) the mismatch between visual and functional severity of a coronary artery lesion. In this mini review, the evolution of diagnosis and management of silent ischemia in the last 10 years is nicely discussed and, although current guidelines and appropriate use criteria have been updated to reflect the current technology of identifying ischemia causing coronary artery lesions, the authors and I feel that current clinical practice is not keeping pace with this knowledge. In my years of cardiology training, I was taught that no exercise stress testing on myocardial ischemia should be done for screening purposes in asymptomatic persons, except for men over 40 years old with multiple risk factors for atherosclerosis or with special occupations, such as pilots, firefighters, etc. To put men without risk factors on a treadmill or bicycle test for screening purposes was a no-go area, let alone asymptomatic women. Nowadays, we have multiple more sensitive and specific tests to detect myocardial ischemia and in particular better knowledge of what to treat and not to treat for prognosis purposes. Applying these new diagnostic tests in asymptomatic persons for screening purposes is opening a Pandora’s box and will introduce difficult dilemmas concerning what to do next if significant coronary artery disease or extensive ischemia is observed, apart from the economic and logistic impact on healthcare this is going to have. Unfortunately, the relationship with symptoms and ischemia due to coronary artery disease is not well-defined, nor is the relationship between ischemia and prognosis. According to the COURAGE trial, prognosis and occurrence of cardiac events are not so much related to the extent of ischemia, but more to the coronary anatomy factors and left ventricular ejection fraction.

    In the article, Balouch et al. describe a case example of an asymptomatic 40-year-old man with some risk factors who is visiting his primary care physician because he is about to start an exercise program. Based on his Framingham and Atherosclerosis Cardiovascular Disease (ASCVD) Risk Estimator borderline high-risk profile, he is put through a treadmill test, which was positive for myocardial ischemia at peak exercise, showing significant diffuse ST depression that slowly recovered at rest, but without complaints or blood pressure drop. As a consequence of the abnormal treadmill test result, a coronary angiography was performed together with instantaneous wave-free ratio (iFR), fractional flow reserve (FFR) and optical computed tomography (OCT) measurements of the left main and left anterior descending (LAD) arteries. Angiography revealed an intermediate stenosis of the left main and intermediate three-vessel disease. Based on functional data derived from FFR/iFR and anatomical OCT data of the left main, this asymptomatic person was referred for coronary artery bypass grafting. First, I think many of us would not expose this asymptomatic man to an exercise stress test from the start. Second, after the stress test, I think many of us would give medication first in this medication-free asymptomatic patient with signs of silent ischemia at peak exercise, probably a beta-blocker in combination with a statin and perhaps aspirin. Silent ischemia without previous manifestations of coronary artery disease has similar prognosis as stable angina, and optimal medical treatment is an acceptable first approach to these patients. But in this specific case, the balance is tipped in favor of bypass surgery because of the significant left main disease, I believe with good reason, considering the better outcome of revascularization compared to medical treatment in case of an important anatomical burden.

    This brings is us to the second issue of the paper, the mismatch between visual (angiography) and functional data. The FFR and iFR data of the left main is compelling in that we are dealing with an obscure but important left main disease. However, we should know that an FFR or iFR measurement of an isolated left main stenosis is not so simple and straightforward as described in this paper. It is known that distal disease from the left main in the LAD and/or right circumflex artery influences the FFR and iFR measurement over the left main stenosis. In case of important distal disease from the left main, the FFR and iFR value over the left main stenosis is higher compared to the similar stenosis without the distal disease. In other words, distal disease attenuates the FFR/iFR value over the proximal lesion. Nevertheless, OCT measurements of the left main were significant and concordant with FFR/iFR measurements, and this asymptomatic person was referred for bypass surgery for prognosis purposes. However, we should also bear in mind that this minimal lumen area cutoff value of 6.0 mm for a sufficient left main lumen should also be carefully applied. This cutoff value is generally applicable for Western males. Ethnicity and gender, but not weight, of the patient has impact on the size of normal coronary arteries. In case of Asian or Indian and female persons, the cutoff value for a flow-limiting left main stenosis could be well around 4.5 mm .

    We are about to enter a new era of a combined non-invasive anatomical and functional assessment of coronary artery disease by CT angiography (CTA). One-dimensional computational analysis technique (Siemens cFFR) and three-dimensional analysis technique (Heartflow FFR ct ) have shown to increase specificity while keeping the sensitivity in detecting flow-limiting lesions compared to conventional coronary CTA. Whether these new techniques can and will be used for screening asymptomatic high-risk persons has yet to be determined. In the meantime, how to screen and treat silent ischemia in asymptomatic persons remains a tough dilemma.


    Cardiovascular Revascularization Medicine, 2018-10-01, Volume 19, Issue 7, Pages 738-739, Copyright © 2018


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