I. Origin of the “gold standard” At present, clinically, regardless of diagnosis or treatment, we strictly follow the “gold standard” – the results of coronary arteriography. Coronary artery angiography shows that the patient has ≥ 50% diameter stenosis, which means the diagnosis of coronary heart disease. Even if other diagnostic techniques, including electrocardiogram, echocardiogram and MRI, are positive, as long as the angiogram shows <50% stenosis, the other results are considered false positive; conversely, if other tests are negative, as long as the angiogram shows positive, the other results are considered false negative. In contrast, the treatment criteria were: ≥70% of stenosis was treated with intervention, and <70% was not treated with intervention. In short, all opinions always revolve around the degree of lumen diameter stenosis shown by coronary angiography. The "gold standard" originated from a trial of dogs published in the American Journal of Cardiology in 1974. This is where the concept of coronary flow reserve fraction (FFR) originated. In this study, the researchers ligated the coronary arteries of resting dogs, causing them to narrow gradually to complete occlusion. Because coronary blood volume is automatically regulated, the flow in the resting state is altered only when the coronary artery is narrowed by >80% of its diameter. In contrast, if the coronary artery is enlarged to the maximum and then ligated, its blood volume is 4 to 5 times higher than the resting state; the blood flow starts to change significantly when the coronary artery reaches a stenosis of 50%. After several years, in clinical practice, this test was realized in translational medicine from dogs to humans. Current cardiology considers: a stenosis of ≥ 50% of the vessel diameter as a hemodynamic stenosis and ≥ 85% as a critical stenosis. And these are derived from the above mentioned studies. After clinical practice, the critical stenosis of coronary arteries in turn quickly turns into ischemic stenosis. Second, studies related to coronary artery disease Clinical trials in recent years have shown (both in animal tests and in studies on patients) that there is no direct relationship between chronic coronary stenosis and myocardial ischemia. Equating coronary artery stenosis with ischemic heart disease and treating the two as a correspondence oversimplifies the problem. This is because many patients have evidence of myocardial ischemia but no coronary stenosis lesion on imaging; conversely, a patient may have severe stenosis without symptoms of myocardial ischemia such as chest pain. Experienced interventionalists should be aware that many patients with chronic occlusive lesions often have no ischemic symptoms, and many patients who have undergone coronary intervention continue to have persistent ischemic symptoms or have to undergo another intervention within a short period of time. In general, the prognosis of patients does not improve much if their stenosis is not reduced. 1. Diagnostic aspects In a study published in Atherosclerosis in 2008, coronary angiography was performed in 163 patients with ischemic symptoms. 105 of them had coronary stenosis but to a lesser extent without obstructive stenosis, 39 patients had significant coronary stenosis, but only 15 had flow-limiting lesions and had normal loading test results. This suggests a serious paradoxical phenomenon between lesions and ischemia. It was found that the majority of patients who died from acute coronary syndromes died from plaque rupture rather than progressive stenosis of the vessel lumen. Most patients with STEMI died from plaque rupture combined with thrombus that obstructed the lumen, whereas patients with NSTEMI or unstable angina did not have obstructive thrombus and the cause of acute coronary syndrome was rupture and erosion of the plaque. A study of autopsies performed on patients who died of non-coronary heart disease (suicide, car accident, etc.) after 2000 showed that 60% of young men with coronary plaque of grade II or higher did not have ischemic heart disease; 90% of patients with acute or chronic ischemic heart disease had critical stenosis, while 50% of controls, i.e., those without ischemic heart disease, had critical stenosis, so critical stenosis does not necessarily lead to ischemia; 1/3 of the 212 patients with acute coronary syndrome had normal cardiovascular In the GUSTO IIb trial published in 1999, 7% to 10% of STEMI patients did not have coronary heart disease; among NTSTEMI patients, 4% to 9% of young patients had myocardial infarction but no coronary heart disease; in addition, the proportion of unstable angina was greater, 14% of men and 30% of women had angina but no coronary heart disease. 2. Treatment For the treatment of coronary artery disease, should we target stenosis or ischemia? In the COURAGE trial, 1/3 of highly selected patients were still symptomatic one year after PCI, and there was no statistically significant difference in the incidence of angina and the endpoint events (myocardial infarction, death, stroke) between the medical drug treatment and intervention groups. The study suggests that even when coronary stenosis is relieved, PCI does not result in more symptomatic improvement compared to drug therapy in the long run. The FAME study randomized 1005 patients with coronary artery disease with multiple vascular lesions into two groups: one group was treated with pharmacologic stenting PCI for >70% of stenotic lesions under the guidance of coronary angiography; the other group was treated with PCI for patients with FFR ≤0.8 by coronary angiography and FFR to see if the myocardium was ischemic (i.e., the first group only looked at the anatomy, the second group also looked at (i.e., the first group only looked at the anatomy, while the second group also looked at functional myocardial ischemia). After one year of follow-up, a difference in MACE events was found between the two groups, with patients whose FFR showed ischemia and thus underwent PCI having a better prognosis than those who had stents implanted regardless of ischemia. This clearly indicates that treatment for ischemia improves patient prognosis more than treatment for stenosis under modern treatment conditions. Another trial, published in the New England Journal of Medicine, looked at 1,000 patients with severe coronary stenosis with heart failure to compare the effects of bypass therapy with those of medical drug therapy. The results found no significant differences between the two groups (mortality, improvement in angina, etc.), meaning that bypass therapy for patients with coronary artery disease combined with heart failure did not significantly improve patient prognosis. A study published in 2010 in the American Journal of Cardiology divided 532 patients with angina equally into two groups: one group was treated with medication and one group was treated with PCI. After six years of follow-up, no significant differences were found between the two groups in terms of mortality and myocardial infarction. Instead, there were significant differences in (1) recanalization therapy within one year, more in the PCI-treated group, (2) angina symptoms, more in the drug-treated group, and (3) nitrate use, more in the drug-treated group. The overall conclusion is that PCI therapy is not significantly better than drug therapy in modern conditions. The BARI study, published in JACC in 2004, evaluated damaged myocardium and angina symptoms and did revascularization in 407 patients without coronary artery disease after five years. The study found that these patients had rapidly progressive lesions over the five-year period that eventually led to myocardial ischemia and angina, not because complete revascularization was not performed at that time. Many of the milder lesions had progressed substantially in the pre-follow-up period, and the myocardial ischemia resulting from failed revascularization therapy was secondary. The PROSPECT trial, published in the New England Journal of Medicine in 2011, was designed to look at plaque progression. It was also the first multicenter clinical trial to evaluate vulnerable plaques (n = 697). The study found that plaques that were not treated at the beginning of the intervention because they were small could become “criminal vessels” three years later. Of the events caused, 12.9% were caused by the original “offender vessel” and 11.6% were caused by non-offender vessels. In addition, we should consider other factors, including spontaneous thrombosis, coronary artery spasm, inflammation, microvascular abnormalities, endothelial abnormalities, and vascular neovascularization in the plaque. An autopsy study of 132 patients found that the presence of spontaneously formed thrombus on the surface of the plaque was not related to the type of plaque and its severity. Therefore, the idea that larger plaques are more prone to thrombus formation is not valid. A group of 308 patients undergoing transcatheter examination found that abnormal coronary artery endothelial function in microvessels or epicardial vessels predicted acute cardiovascular events. Angiography showed that cardiovascular events were predicted on the basis of abnormal endothelial function regardless of coronary stenosis, suggesting that abnormal endothelial function itself can cause cardiovascular events. In addition, plaques secrete a variety of inflammatory factors during growth, and their mediation at different times can also cause acute cardiovascular events. In response to these, a new concept of the pathogenesis of ischemic heart disease has been proposed in recent international conferences – a “solar system”, which centers on myocardial ischemia The pathogenesis of coronary heart disease has to change from a “plaque” to a “myocardial cell” center. In addition to critical stenosis, there are many other causes that can cause myocardial ischemia and myocardial infarction. Therefore, experts recommend that clinical practice should focus on “myocardial ischemia” in both diagnosis and treatment, and that interventions should be performed only when ischemic lesions are present. In past doctrine and practice, everything revolves around stenosis, which is not correct. In conclusion, how to evaluate myocardial ischemia is the next issue that we need to consider urgently. Besides imaging, what guiding significance does FFR possess? Performing loading test to observe the time, degree, and extent of ST-segment depression as well as the severity and extent during myocardial perfusion imaging can provide us with some non-invasive evaluation information. The “gold standard” of false positives or false negatives, which used to be determined by whether stenosis was 50% on imaging, has been challenged. This means that in clinical practice, we need to explore other mechanisms of myocardial ischemia besides stenosis. In addition, the need for individualized treatment of patients and the possibility of myocardial protection by pharmacological treatment in addition to interventions also needs to be further investigated. The available evidence suggests that severe coronary artery stenosis is only one of the factors leading to ischemic heart disease, and that the combined etiology is so complex that we need to invent additional methodologies and reduce mortality and disability through preventive medicine. This shift in value reminds us that we cannot focus only on the coronary arteries, but that the myocardial cells also deserve our attention. The new doctrine of the “solar system”, which brings together many leading experts in coronary artery disease and the international discussions of guideline chairs, suggests that stable ischemic heart disease should be reconsidered, which means the beginning of a new era. We hope that these debates will lead to a reflection among the interventional cardiology community in China, which will inspire our future research.