BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*

Objective:To evaluate the long-term outcomes and predictors of coronary atherosclerotic lesions deemed functionally non-ischemic (quantitative flow ratio(QFR)>0.80) and deferred from intervention.Methods:This study is a post-hoc analysis of the FAVOR Ⅲ China trial, which enrolled 3 825 patients with stable or unstable angina pectoris or with myocardial infarction occurring at least 72 hours prior to screening, between December 5, 2018 and January 9, 2020 from 26 research centers in China. Coronary vessels with QFR>0.80 and without interventional treatment were analyzed in this study. The primary endpoint was 3-year target vessel revascularization. Vessels with revascularization (revascularized group) during follow-up were matched 1∶1 using propensity score matching to comparable vessels without revascularization (non-revascularized group). Multivariate Cox regression analysis was used to identify the risk factors for target vessel revascularization (TVR).Results:A total of 6 212 functionally negative vessels with deferred intervention were included in the final analysis, among which 153 vessels (2.5%) underwent TVR during a 3-year follow-up. Prior to propensity score matching, 6 059 vessels comprised the non-revascularized group. At the vessel level, compared to the non-revascularized group, the revascularized group exhibited a significantly higher proportion of males (79.1% (121/153) vs. 70.2% (4 253/6 059), P=0.018), higher body mass index ((25.6±4.0) kg/m2 vs. (24.3±5.2) kg/m2, P=0.003), and a higher prevalence of hypertension (73.9% (113/153) vs. 65.1% (3 944/6 059), P=0.025). And 152 pairs of vessels were successfully matched. Multivariate Cox regression analysis identified in-stent restenosis lesions ( HR=2.59, 95% CI 1.28-5.23, P=0.008) as an independent risk factor for target vessel revascularization. Conclusions:Coronary lesions classified as functionally non-ischemic at baseline are not entirely stable and may progress to lesions that requiring revascularization over time. In-stent restenosis emerges as a critical independent predictor of revascularization.

Objectives:To explore the feasibility of a coronary angiography-based method developed with artificial intelligence which was able to automatically and quickly calculate coronary volumetric blood flow and coronary flow reserve (CFR), and explore the differences in CFR after injection of different vasodilators.Methods:This was a observational study screening patients with suspected coronary artery disease who underwent coronary angiography From June to September 2022 in Fuwai Hospital, Chinese Academy of Medical Sciences. Patients without obstructive coronary artery disease in the left anterior descending artery (<50% diameter stenosis by visual) and accompanied by coronary slow flow phenomenon (Thrombolysis in Myocardial Infarction flow grade ≤2) were enrolled. According to pre-specified coronary angiography acquisition protocol, one angiographic image in optimal projection was acquired for each of the following five states: baseline when none of the vasodilators was injected (resting state), intracoronary injection of 200 μg nitroglycerin (nitroglycerin-induced hyperemia), intracoronary injection of 100 μg adenosine (adenosine-induced hyperemia), 5 minutes after cessation of adenosine injection (resting state 2), and intracoronary injection of 4 mg nicorandil (nicorandil-induced hyperemia). Coronary volumetric blood flow and CFR were assessed in a fully automatic manner at an independent core laboratory. One-way repeated measures ANOVA was used to detect the differences in coronary volumetric blood flow at five states and the differences in CFR after injection of different vasodilators.Results:A total of 21 eligible patients were included. The age was (62±9) years, and 5 (24%) were female. Coronary volumetric blood flow at five states and CFR after injection of different vasodilators were successfully calculated in all patients, with a feasibility of 100% (21/21) for CFR. Resting coronary volumetric blood flow was (80.6±12.4) ml/min. Using this as a reference, the volumetric blood flow increased to (167.7±30.5) ml/min under nitroglycerin-induced hyperemia (adjusted P<0.001), and remained at (171.5±23.1) ml/min under adenosine-induced hyperemia (adjusted P<0.001). The volumetric blood flow under resting state 2 was (83.8±15.6) ml/min, returning to baseline level (adjusted P=0.94). Under nicorandil-induced hyperemia, the coronary volumetric blood flow increased again to (182.9±28.3) ml/min (adjusted P<0.001). CFR was 2.09±0.29, 2.15±0.27, and 2.29±0.29 after injection of nitroglycerin, adenosine, and nicorandil, respectively( P=0.034). Using CFR after adenosine injection as a reference, CFR after nicorandil injection was higher (adjusted P=0.044). Using the coronary volumetric blood flow under resting state 2 as the baseline flow for CFR calculation, there was no statistically significant difference compared to the CFR calculated using the volumetric blood flow under resting state (all P>0.05). Conclusions:Preliminary findings confirm the high feasibility of rapid, automated assessment of coronary volumetric blood flow and CFR from a single angiographic projection, as well as good reproducibility in calculating baseline volumetric blood flow. In patients with coronary slow flow, the CFR after nicorandil injection is significantly higher than that after adenosine injection.

Objectives:To explore the predictive value of residual Murray's law-based quantitative flow ratio(μQFR)on long-term vessel-oriented composite endpoints(VoCE).Methods:This retrospective study included 3 510 patients from the FAVOR Ⅲ China trial.Offline residual μQFR analysis was performed on all vessels(diameter≥2.5 mm)with 50%-90%stenotic lesions.Patients were stratified into high-,intermediate-,and low-risk groups based on residual μQFR tertiles.The primary endpoint was 3-year VoCE,defined as a composite of cardiac death related to the target vessel,target vessel-related spontaneous myocardial infarction,and ischemia-driven target vessel revascularization.Results:Offline analysis was performed on 5 256 vessels from 3 510 patients.The mean residual μQFR was 0.92±0.75.The high-risk group(residual μQFR≤0.91)with 1 554 patients(1 958 vessels);the intermediate-risk group(residual μQFR 0.92-0.96)with 1 211 patients(1 906 vessels);and the low-risk group(residual μQFR>0.96)with 745 patients(1 392 vessels).Over 3-year follow-up,VoCE occurred in 227 vessels(4.3%).The 3-year VoCE incidence was significantly higher in the high-risk group compared to the intermediate-and low-risk groups(6.2%vs.4.1%vs.2.5%,log-rank P<0.001),primarily driven by ischemia-driven target vessel revascularization(5.0%vs.3.0%vs.1.6%,log-rank P<0.001).Hypertension(OR=0.83,95%CI:0.72-0.96),hypercholesterolemia(OR=0.84,95%CI:0.73-0.97),bifurcation lesions(OR=0.72,95%CI:0.63-0.83),moderate/severe calcification(OR=0.70,95%CI:0.57-0.84),and tandem lesions(OR=0.59,95%CI:0.47-0.75)were independent predictors of lower residual μQFR values.Conclusions:Lower residual μQFR is significantly associated with increased VoCE risk during the 3-year follow up period.

Objectives:To explore the predictive value of residual Murray's law-based quantitative flow ratio(μQFR)on long-term vessel-oriented composite endpoints(VoCE).Methods:This retrospective study included 3 510 patients from the FAVOR Ⅲ China trial.Offline residual μQFR analysis was performed on all vessels(diameter≥2.5 mm)with 50%-90%stenotic lesions.Patients were stratified into high-,intermediate-,and low-risk groups based on residual μQFR tertiles.The primary endpoint was 3-year VoCE,defined as a composite of cardiac death related to the target vessel,target vessel-related spontaneous myocardial infarction,and ischemia-driven target vessel revascularization.Results:Offline analysis was performed on 5 256 vessels from 3 510 patients.The mean residual μQFR was 0.92±0.75.The high-risk group(residual μQFR≤0.91)with 1 554 patients(1 958 vessels);the intermediate-risk group(residual μQFR 0.92-0.96)with 1 211 patients(1 906 vessels);and the low-risk group(residual μQFR>0.96)with 745 patients(1 392 vessels).Over 3-year follow-up,VoCE occurred in 227 vessels(4.3%).The 3-year VoCE incidence was significantly higher in the high-risk group compared to the intermediate-and low-risk groups(6.2%vs.4.1%vs.2.5%,log-rank P<0.001),primarily driven by ischemia-driven target vessel revascularization(5.0%vs.3.0%vs.1.6%,log-rank P<0.001).Hypertension(OR=0.83,95%CI:0.72-0.96),hypercholesterolemia(OR=0.84,95%CI:0.73-0.97),bifurcation lesions(OR=0.72,95%CI:0.63-0.83),moderate/severe calcification(OR=0.70,95%CI:0.57-0.84),and tandem lesions(OR=0.59,95%CI:0.47-0.75)were independent predictors of lower residual μQFR values.Conclusions:Lower residual μQFR is significantly associated with increased VoCE risk during the 3-year follow up period.

Objective:To evaluate the long-term outcomes and predictors of coronary atherosclerotic lesions deemed functionally non-ischemic (quantitative flow ratio(QFR)>0.80) and deferred from intervention.Methods:This study is a post-hoc analysis of the FAVOR Ⅲ China trial, which enrolled 3 825 patients with stable or unstable angina pectoris or with myocardial infarction occurring at least 72 hours prior to screening, between December 5, 2018 and January 9, 2020 from 26 research centers in China. Coronary vessels with QFR>0.80 and without interventional treatment were analyzed in this study. The primary endpoint was 3-year target vessel revascularization. Vessels with revascularization (revascularized group) during follow-up were matched 1∶1 using propensity score matching to comparable vessels without revascularization (non-revascularized group). Multivariate Cox regression analysis was used to identify the risk factors for target vessel revascularization (TVR).Results:A total of 6 212 functionally negative vessels with deferred intervention were included in the final analysis, among which 153 vessels (2.5%) underwent TVR during a 3-year follow-up. Prior to propensity score matching, 6 059 vessels comprised the non-revascularized group. At the vessel level, compared to the non-revascularized group, the revascularized group exhibited a significantly higher proportion of males (79.1% (121/153) vs. 70.2% (4 253/6 059), P=0.018), higher body mass index ((25.6±4.0) kg/m2 vs. (24.3±5.2) kg/m2, P=0.003), and a higher prevalence of hypertension (73.9% (113/153) vs. 65.1% (3 944/6 059), P=0.025). And 152 pairs of vessels were successfully matched. Multivariate Cox regression analysis identified in-stent restenosis lesions ( HR=2.59, 95% CI 1.28-5.23, P=0.008) as an independent risk factor for target vessel revascularization. Conclusions:Coronary lesions classified as functionally non-ischemic at baseline are not entirely stable and may progress to lesions that requiring revascularization over time. In-stent restenosis emerges as a critical independent predictor of revascularization.

Objectives:To explore the feasibility of a coronary angiography-based method developed with artificial intelligence which was able to automatically and quickly calculate coronary volumetric blood flow and coronary flow reserve (CFR), and explore the differences in CFR after injection of different vasodilators.Methods:This was a observational study screening patients with suspected coronary artery disease who underwent coronary angiography From June to September 2022 in Fuwai Hospital, Chinese Academy of Medical Sciences. Patients without obstructive coronary artery disease in the left anterior descending artery (<50% diameter stenosis by visual) and accompanied by coronary slow flow phenomenon (Thrombolysis in Myocardial Infarction flow grade ≤2) were enrolled. According to pre-specified coronary angiography acquisition protocol, one angiographic image in optimal projection was acquired for each of the following five states: baseline when none of the vasodilators was injected (resting state), intracoronary injection of 200 μg nitroglycerin (nitroglycerin-induced hyperemia), intracoronary injection of 100 μg adenosine (adenosine-induced hyperemia), 5 minutes after cessation of adenosine injection (resting state 2), and intracoronary injection of 4 mg nicorandil (nicorandil-induced hyperemia). Coronary volumetric blood flow and CFR were assessed in a fully automatic manner at an independent core laboratory. One-way repeated measures ANOVA was used to detect the differences in coronary volumetric blood flow at five states and the differences in CFR after injection of different vasodilators.Results:A total of 21 eligible patients were included. The age was (62±9) years, and 5 (24%) were female. Coronary volumetric blood flow at five states and CFR after injection of different vasodilators were successfully calculated in all patients, with a feasibility of 100% (21/21) for CFR. Resting coronary volumetric blood flow was (80.6±12.4) ml/min. Using this as a reference, the volumetric blood flow increased to (167.7±30.5) ml/min under nitroglycerin-induced hyperemia (adjusted P<0.001), and remained at (171.5±23.1) ml/min under adenosine-induced hyperemia (adjusted P<0.001). The volumetric blood flow under resting state 2 was (83.8±15.6) ml/min, returning to baseline level (adjusted P=0.94). Under nicorandil-induced hyperemia, the coronary volumetric blood flow increased again to (182.9±28.3) ml/min (adjusted P<0.001). CFR was 2.09±0.29, 2.15±0.27, and 2.29±0.29 after injection of nitroglycerin, adenosine, and nicorandil, respectively( P=0.034). Using CFR after adenosine injection as a reference, CFR after nicorandil injection was higher (adjusted P=0.044). Using the coronary volumetric blood flow under resting state 2 as the baseline flow for CFR calculation, there was no statistically significant difference compared to the CFR calculated using the volumetric blood flow under resting state (all P>0.05). Conclusions:Preliminary findings confirm the high feasibility of rapid, automated assessment of coronary volumetric blood flow and CFR from a single angiographic projection, as well as good reproducibility in calculating baseline volumetric blood flow. In patients with coronary slow flow, the CFR after nicorandil injection is significantly higher than that after adenosine injection.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

The mild-natured and bitter-flavored traditional Chinese medicines (MB-TCMs) are an important class of TCMs that have been widely used in clinical practice and recognized as safe long-term treatments for chronic diseases. However, as an important class of TCMs, the panorama of pharmacological effects and the mechanisms of MB-TCMs have not been systemically reviewed. Compelling studies have shown that gut microbiota can mediate the therapeutic activity of TCMs and help to elucidate the core principles of TCM medicinal theory. In this systematic review, we found that MB-TCMs commonly participated in the modulation of metabolic syndrome, intestinal inflammation, nervous system disease and cardiovascular system disease in association with promoting the growth of beneficial bacteria Bacteroides, Akkermansia, Lactobacillus, Bifidobacterium, Roseburia as well as inhibiting the proliferation of harmful bacteria Helicobacter, Enterococcus, Desulfovibrio and Escherichia-Shigella. These alterations, correspondingly, enhance the generation of protective metabolites, mainly including short-chain fatty acids (SCFAs), bile acid (BAs), 5-hydroxytryptamine (5-HT), indole and gamma-aminobutyric acid (GABA), and inhibit the generation of harmful metabolites, such as proinflammatory factors trimethylamine oxide (TAMO) and lipopolysaccharide (LPS), to further exert multiplicative effects for the maintenance of human health through several different signaling pathways. Altogether, this present review has attempted to comprehensively summarize the relationship between MB-TCMs and gut microbiota by establishing the TCMs-gut microbiota-metabolite-signaling pathway-diseases axis, which may provide new insight into the study of TCM medicinal theories and their clinical applications.

Atherosclerosis is classified as"vessel bi"in traditional Chinese medicine,and cold evil is one of its important causes.Cold,having the properties of coagulation,stagnation,and contraction,tends to narrow the diameter of blood vessels and slow down blood flow,which can promote the pathophysiological process of atherosclerosis.At present,the etiological theory of vessel bi caused by cold evil has not been fully elaborated.Based on the explanations of"evening"in"pathogenic cold affecting in the evening",such as"ying","end of year","end of day",and"time of yang decline and yin exuberance",this paper proposes the viewpoint that the cold evil tends to affect ying-blood and cause vessel bi,and discusses its pathogenesis.From the perspective of the external environment,cold evil affecting the vessel is conditional,often occurring in winter and in the middle of the night.From the perspective of internal environment,the cold evil affects the vessel in a process which can be manifested in three stages:cold injury,cold stagnation,and cold congelation.The strength of yang qi is the factor that determine whether the cold evil can cause disease.Exploring the etiology and pathogenesis of atherosclerosis from the perspective of"pathogenic cold affecting in the evening"provides a new idea for further elucidating the pathogenesis of the disease and expanding its clinical treatment.