Atrial fibrillation (AF) represents the most common sustained cardiac arrhythmia and confers an elevated risk of major adverse cardiovascular events (MACEs). Emerging evidence indicates that metabolic dysregulation substantially influences the AF prognosis. The cardiometabolic index (CMI) and triglyceride–glucose (TyG) index are non-insulin-dependent surrogate markers of metabolic dysfunction that are readily obtainable in clinical practice. However, their comparative prognostic value for predicting MACEs in patients with AF has not been previously evaluated within the same cohort. This retrospective single-center cohort study enrolled 380 AF patients who received treatment at the Shanghai Jinyang Community Health Center between January 2022 and June 2025, with a maximum follow-up duration of 3 years. CMI and TyG were calculated from routinely collected baseline clinical and laboratory data. MACEs served as the primary endpoint. Predictive performance was examined using adjusted Cox regression with restricted cubic spline (RCS) to assess potential nonlinearity, along with Kaplan–Meier survival curves, receiver operating characteristic (ROC) curve–based discrimination analysis, machine learning approaches, and subgroup interaction testing. Incremental predictive benefit over the CHA2DS2-VASc score was further evaluated. A total of 53 patients (13.9

BACKGROUND:Accurate prognostic models for ST-segment elevation myocardial infarction (STEMI) are essential to guide clinical practice. OBJECTIVES:This study sought to construct predictive models integrating demographic, clinical, and cardiac magnetic resonance (CMR) imaging variables to forecast long-term major adverse cardiac and cerebrovascular events (MACCEs). METHODS:Patients with STEMI underwent CMR imaging within 1 week and 1 month after primary percutaneous coronary intervention. Twenty-four demographic, clinical, and CMR variables were used to construct 4 predictive models (naive Bayes, logistic regression, k-nearest neighbors, and XGBoost) for forecasting MACCEs during long-term follow-up. Model interpretability was assessed using Shapley values. RESULTS:A total of 483 patients were included (median age: 59.6 years, IQR: 54.0-65.0 years; median follow-up: 89.3 months; IQR: 60.3-115.4 months). During follow-up, 98 of 483 patients (20.3%) experienced MACCEs. The XGBoost model demonstrated superior predictive performance compared with the other approaches. Key CMR predictors included microvascular obstruction, left ventricular ejection fraction recovery, infarct size, intramyocardial hemorrhage, infarct core T1, and remote myocardium T1. Among clinical features, Killip class, body mass index, and age were most influential. Remote myocardium T1 was inversely correlated with left ventricular ejection fraction recovery at 1 month after percutaneous coronary intervention (R = -0.34; 95% CI: -0.43 to -0.27; P < 0.01). CONCLUSIONS:An XGBoost model integrating clinical and CMR features effectively predicted long-term MACCEs in patients with STEMI. Microvascular obstruction emerged as the most important CMR-based prognostic factor.

Early diagnosis of acute diseases is fundamentally constrained by the lack of chemically tractable methods for biomarker discovery directly from a complex plasma. Here, we report PSABD (plasma-SELEX-enriched aptamer-based biomarker discovery and diagnosis), a chemical platform that integrates carboxylate magnetic-bead-mediated plasma protein capture within situ aptamer SELEX, enabling molecular-recognition-driven identification of disease-associated biomarkers. With this strategy, enriched aptamers not only serve as affinity probes but also function as structurally programmable molecular handles to pull down their targets, thereby linking selection chemistry with proteomic discovery. With acute myocardial infarction (AMI) as a model, PSABD identified malate dehydrogenase 2 (MDH2) as an unexpected AMI-associated plasma protein, which was significantly elevated in AMI patient samples and exhibited a high binding affinity to selected aptamers. On the basis of this interaction, we developed an aptamer-based analytical platform capable of distinguishing AMI patients from healthy individuals. Collectively, PSABD establishes a general chemical strategy that bridges molecular recognition, biomarker discovery, and diagnostic development, highlighting aptamers as programmable chemical probes for the acute disease diagnosis and clinical translation.

Obesity is a major modifiable risk factor for early-onset ischemic heart disease (IHD), yet its contribution to the global burden across regions and demographics is not fully quantified. This study assesses global trends in obesity-related early-onset IHD, focusing on young adults (aged 25–39 years). We utilized Global Burden of Disease Study 2021 data to track 30-year trends in obesity and early-onset IHD via average annual percentage changes (AAPCs) and socio-demographic index (SDI)-stratified disability-adjusted life year (DALY) counts. Pearson correlation was then applied to evaluate the associations between these variables. Further multi-factor adjustment analysis was conducted using a multivariable linear regression model on 5-year age-stratified data. A significant positive correlation was found between the AAPC in obesity age-standardized prevalence rate (ASPR) and the AAPC in early-onset IHD age-standardized mortality rate (ASMR) (ρ = 0.36, P < 0.001) and ASPR (ρ = 0.29, P < 0.001) among young males, with stronger associations than in females. The impact of obesity on early-onset IHD prevalence and mortality strengthened with age, peaking at 35–39 years old for both male and female. Even after having adjusted for dietary, environmental, and metabolic risk factors, obesity remains the top IHD risk factor in almost all subgroups. Clearly, obesity is strongly linked to higher morbidity and mortality in early-onset IHD.

BACKGROUND:The multicenter, randomized, sham-controlled FAVOR III China trial (Comparison of Quantitative Flow Ratio-Guided and Angiography-Guided Percutaneous Intervention in Patients with Coronary Artery Disease) demonstrated that quantitative flow ratio (QFR)-guided percutaneous coronary intervention (PCI) resulted in better outcomes compared with angiographic guidance at 1-year and 2-year follow-up. Whether these benefits are sustained over long-term follow-up remains uncertain. OBJECTIVES:The purpose of this study was to evaluate the long-term effectiveness and safety of a QFR-guided PCI strategy compared with angiography-guided PCI at 5 years. METHODS:Patients with at least 1 angiographically intermediate coronary lesion (50%-90% diameter stenosis) in a vessel ≥2.5 mm diameter were randomized to a QFR-guided (PCI performed only if QFR ≤0.80) or angiography-guided strategy. The primary endpoint was major adverse cardiac events (a composite of all-cause death, myocardial infarction, or ischemia-driven revascularization) at 1 year; 5-year outcomes data are reported herein. RESULTS:At 5 years, major adverse cardiac events composite was lower with QFR guidance than with angiography guidance (17.5% vs 21.1%; HR: 0.80; 95% CI: 0.69-0.92; P = 0.002), driven by fewer myocardial infarctions (5.8% vs 9.0%; HR: 0.63; 95% CI: 0.49-0.80; P < 0.0001) and ischemia-driven revascularizations (9.6% vs 12.0%; HR: 0.78; 95% CI: 0.64-0.95; P = 0.02) in the QFR-guided group. All-cause death did not differ between groups. Landmark analysis showed that the benefit of QFR guidance accrued predominantly within the first 2 years (8.5% vs 12.5%; HR: 0.66; 95% CI: 0.54-0.81; P < 0.0001), with similar outcomes between 2 and 5 years (10.2% vs 11.2%; HR: 0.90; 95% CI: 0.73-1.11; P = 0.32; P for interaction = 0.001). CONCLUSIONS:Compared with angiography guidance, QFR-guided strategy improved 5-year clinical outcomes, with benefits primarily achieved within the first 2 years. (The FAVOR III China Study; NCT03656848).

Background Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) is associated with fewer clinical events than angiography-guided PCI. Whether the use of IVUS guidance improves the outcomes as compared with angiography guidance in patients with complex coronary bifurcation lesion undergoing double kissing (DK) crush is uncertain. Objectives This study aimed to investigate the treatment effect of IVUS-guided PCI, as compared with angiography-guided PCI, in patients with complex bifurcation lesions. Methods We conducted a multicenter, randomized, open-label trial at 24 centers in China. Patients with clinical indications for PCI and a complex bifurcation lesion based on DEFINITION (Definitions and Impact of Complex Bifurcation Lesions on Clinical Outcomes After Percutaneous Coronary Intervention Using Drug-Eluting Stents) criteria (particularly side branch lesion length ≥10 mm) from coronary angiography were randomly assigned in a 1:1 ratio to IVUS-guided PCI or angiography-guided PCI. The primary endpoint was a composite of target vessel failure, defined as cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 1 year after randomization. Results We assigned 555 patients to IVUS-guided PCI (n = 277) or angiography-guided PCI (n = 278). A total of 124 patients (44.8%) in the IVUS-guided PCI group and 122 (43.9%) in the angiography-guided PCI group had a bifurcation lesion involving the left main coronary artery. DK crush was used in 96.8% of patients. At 1 year, a primary endpoint event occurred in 17 patients (6.1%) in the IVUS-guided PCI group and in 41 patients (14.7%) in the angiography-guided PCI group (HR: 0.40; 95% CI: 0.23-0.71; P = 0.002), driven mainly by reductions in target vessel myocardial infarction or target vessel revascularization. Conclusions In the present randomized trial comparing IVUS-guided vs angiography-guided PCI for complex coronary bifurcation lesions treated with the 2-stent DK crush technique, the benefits of IVUS-guided PCI at 1 year was achieved largely through achievement of IVUS-defined optimization targets rather than IVUS use alone. (IVUS-guided DK Crush Stenting Technique for Patients With Complex Bifurcation Lesions [DKCRUSH VIII]; NCT03770650)

Background: Cardiovascular disease (CVD) is a leading cause of mortality among cancer survivors, yet the contributions of socioeconomic, lifestyle, and clinical factors to CVD remain unexplored. Objective: This study was aimed at examining associations between these factors and prevalent CVD in adults with prior cancer and comparing them with those in a matched non-cancer cohort. Methods: We analyzed 97,648 adults from the National Health and Nutrition Examination Survey. Associations of socioeconomic, lifestyle, and clinical factors with a composite endpoint of five self-reported cardiovascular events were assessed with multivariable logistic regression. Interaction analyses assessed differences by cancer status, and sensitivity analyses examined individual cardiovascular outcomes. Results: We included 5584 cancer survivors and 9933 matched participants without cancer. Age, sex, unemployment, low income, current smoking, obesity, diabetes, hypertension, and hypercholesterolemia were associated with elevated odds of CVD prevalence in both groups. Among only cancer survivors, an absence of private insurance, or the presence of food insecurity or low educational attainment, was also independently associated with CVD prevalence. Sensitivity analyses indicated broadly consistent results across individual outcomes. Conclusions: Socioeconomic, lifestyle, and clinical factors were associated with prevalent CVD among cancer survivors, with socioeconomic disadvantage contributing to disparities in CVD burden. Because the outcomes were self-reported, and the study was cross-sectional, the findings should be interpreted as associative rather than causal or predictive.

Percutaneous coronary intervention (PCI) relieves epicardial coronary stenosis, but anatomical treatment does not necessarily indicate recovery of integrated exercise function. We examined whether patients during stable recovery after PCI had lower measured cardiorespiratory fitness (CRF) than a contemporaneous angiographic reference group and how much body composition and common clinical and metabolic factors accounted for the difference. This single-center retrospective cross-sectional study included 682 patients who underwent coronary angiography, cardiopulmonary exercise testing (CPET), and bioelectrical-impedance assessment: 209 in the reference group and 473 in the PCI group. Both groups completed the study assessments 4–6 weeks after the corresponding coronary angiography or planned PCI. Propensity score overlap weighting was used to compare absolute peak oxygen uptake (VO₂peak), body weight-normalized VO₂peak, and percent-predicted VO₂peak (pVO₂). Skeletal muscle mass and body fat mass or their height-indexed measures were aligned with the scale of each outcome. Robustness was assessed using an extended clinical model, cross-fitted reference-group mapping, and sensitivity analyses. The six propensity-score covariates were balanced after overlap weighting. In the primary extended model, the PCI group had lower absolute VO₂peak (difference, − 59.69 mL/min; 95

Research on the association between atherosclerosis cardiovascular diseases (ASCVDs) and hearing loss (HL) in older people has yielded mixed findings in recent years. Understanding this relationship is crucial for developing early strategies that address both cardiovascular health and auditory function in older adults. To examine the potential association between common ASCVDs (heart attack, coronary heart disease, and stroke) and HL, assessing the mediating effect of the frailty index (FI) and Life’s essential 8 (LE8) metrics. The degree of HL was measured by pure tone average (PTA). This cross-sectional analysis utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 2003 to 2018, including 4,441 adults aged 60 or older with comprehensive cardiovascular and hearing measurement data. Statistical analysis was conducted from February 16, 2024, to July 7, 2024. The study identified significant correlations between all three ASCVDs and HL in older participants aged 60 or older, particularly noting that heart attacks were notably associated with HL at higher frequencies (2 and 4 kHz). Older participants, especially those aged 75 and above, were more susceptible to stroke-related HL, with a delayed impact observed in females. FI and LE8 mediated the heart attack-HL association in adults aged 75 and above, with FI demonstrating a stronger role than LE8. The findings elucidate a complex interplay between cardiovascular health and auditory function, emphasizing that heart attacks may exacerbate HL through the frailty pathway in certain older populations. These results highlight the need for tailored cardiovascular interventions and proactive measures to mitigate HL risks. Future research should focus on defining these pathophysiological associations more clearly to develop targeted interventions for vulnerable older people.

Exercise is widely prescribed to prevent cardiovascular disease, which encompasses a heterogeneous spectrum of disorders involving vascular dysfunction, myocardial injury and remodeling, inflammation, and electrophysiological disturbances; however, its benefits are not uniformly dose-dependent. While aerobic and resistance training generally elicit sustained cardioprotective adaptations, evidence from ultra-endurance exercise suggests a distinct physiological regime in which repeated extreme load, prolonged duration and individual susceptibility may precipitate maladaptive remodeling. Here we synthesize an epigenetic remodeling framework to reconcile these divergent outcomes and to explain how exercise modality, intensity and exposure duration may influence the balance between cardiovascular adaptation and vulnerability. We systematically examine epigenetic pathways, including DNA methylation, histone modifications and non-coding RNA-mediated regulation, through which aerobic exercise and resistance training may modulate vascular function, myocardial metabolism, inflammation and fibrosis. We then contrast these signatures with those reported in ultra-endurance settings, highlighting mechanistic patterns associated with transient myocardial damage markers, arrhythmogenic substrates and adverse structural remodeling in susceptible individuals. We further discuss emerging sex-specific epigenetic mechanisms that may contribute to differential cardiovascular disease trajectories under ultra-high-intensity endurance stress. Finally, we outline key limitations in current evidence, including incomplete causal epigenetic chains, heavy reliance on experimental models, peripheral tissues and elite athlete cohorts, limited tissue-specific evidence and a paucity of longitudinal population studies. Addressing these gaps will be essential for translating epigenetic insights into risk-stratified and individualized exercise prescriptions that maximize cardioprotection while minimizing potential risk.

BACKGROUND:Premature atrial contractions (PACs) are independently associated with atrial fibrillation, stroke, and heart failure, yet no pharmacological therapy is approved for PAC suppression. Experimental studies have identified a functional cardiac glutamatergic system in which N-methyl-D-aspartate receptors regulate atrial electrophysiology. Preclinical studies show that pharmacological antagonism of N-methyl-D-aspartate receptors with memantine suppresses atrial arrhythmias. METHODS:We conducted an investigator-initiated, phase 2, multicenter, randomized, double-blind, placebo-controlled trial. Symptomatic adults with frequent PACs (≥1000/24 h) were randomly assigned to receive memantine or placebo for 6 weeks. The primary end point was the percentage change in mean 24-hour PAC count from baseline to the end of treatment. The primary analysis was performed in the intention-to-treat population. Prespecified secondary end points included the responder rate (≥50% PAC reduction), percentage change in nonsustained atrial tachycardia burden, and cumulative incidence of new-onset atrial fibrillation. RESULTS:Among 241 patients included in the efficacy analysis, memantine resulted in a greater reduction in PAC count than placebo (between-group difference, 47.1 percentage points; P=0.0045). The responder rate was higher with memantine than with placebo (52.4% versus 23.1%; P<0.0001). Memantine also reduced nonsustained atrial tachycardia burden (between-group difference, 30.98 percentage points; P=0.0043) and was associated with a lower cumulative incidence of new-onset atrial fibrillation (4.8% versus 23.9%; P<0.0001). No clinically meaningful differences were observed in electrocardiographic intervals or left ventricular function, and no drug-related serious adverse events occurred. CONCLUSIONS:In patients with frequent symptomatic PACs, memantine reduced atrial ectopy and atrial tachyarrhythmia burden and demonstrated a favorable safety profile. These findings provide proof of concept for a novel, non-ion channel-based therapeutic strategy targeting the cardiac glutamatergic system. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06501638.

This study aims to compare the prognostic value of the extent of microvascular obstruction (MVO) combined with intramyocardial hemorrhage (IMH) for major adverse cardiovascular events (MACE) in patients with STEMI. We analyzed 568 STEMI patients in this retrospective multicenter study. Microvascular injury was visualized using late gadolinium enhancement for MVO, and T2* mapping and T2-weighted cardiovascular magnetic resonance imaging for IMH. The Youden index was used as the cutoff value to divide the study population into four groups. The Eitel CMR risk score, Glasgow CMR risk score, and GRACE (Global Registry of Acute Coronary Events) score were used as references to form Scores 1 and 2. Score 3 included LVEF ≤ 45

BACKGROUND:AccuIMR is a novel angiography-based method for assessing microvascular dysfunction (MVD) by simulating the index of microcirculatory resistance (IMR). In a prior study, AccuIMR showed a strong correlation with wire-based IMR. OBJECTIVES:This study aimed to evaluate the clinical significance of the angiography-derived index of microcirculatory resistance (AccuIMR) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS:This was a retrospective analysis of a prospective multicenter registry of STEMI patients who underwent cardiac magnetic resonance (CMR). This investigation included 482 STEMI patients. AccuIMR was obtained using angiographic images after percutaneous coronary intervention. The patients were categorized into the MVD group (AccuIMR >40) and the non-MVD group (AccuIMR ≤40). CMR results at 5 ± 2 days after percutaneous coronary intervention served as the reference standard for assessing CMR-derived microvascular obstruction (CMR-MVO) and infarct size. RESULTS:Compared with the non-MVD group, the MVD group exhibited a larger CMR-MVO area, a larger infarct size area, and a lower left ventricular ejection fraction. Multivariate logistic regression analysis indicated that AccuIMR >40 was an independent predictive factor for CMR-MVO (OR: 4.730, 95% CI: 2.868-7.799, P < 0.001) and larger infarct size (OR: 2.101, 95% CI: 1.323-3.337, P = 0.002). DeLong's test, net reclassification index/integrated discrimination improvement, and likelihood ratio test demonstrated that incorporating AccuIMR into conventional predictive factors significantly improved the predictive accuracy for CMR-MVO and larger infarct size. CONCLUSIONS:AccuIMR is an efficient and dependable method for evaluating MVD in STEMI patients after percutaneous coronary intervention. When combined with conventional predictive factors, it provides supplementary information regarding cardiac function.

BACKGROUND:The prognostic utility of residual pressure wire-based physiological assessment after percutaneous coronary intervention (PCI) has been demonstrated. OBJECTIVES:The aim of this study was to investigate the prognostic value of the residual global Murray law-based angiographic quantitative flow ratio (μQFR) in an acute coronary syndrome (ACS) population. METHODS:In this post hoc analysis from the FAVOR III China (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients With Coronary Artery Disease) trial, off-line μQFR was computed for 3 major coronary arteries. Residual global μQFR was calculated as the sum of postprocedural μQFR values for treated vessels and preprocedural values for nontreated vessels. ACS patients (including those with ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina) were categorized into high-risk (less than or equal to the cutoff value) and low-risk (greater than the cutoff value) groups according to residual global μQFR. The primary endpoint was 3-year major adverse cardiac events (MACE), the composite of all-cause death, myocardial infarction, or ischemia-driven revascularization. RESULTS:Among 2,428 ACS patients, 2,241 (92.3%) had analyzable μQFR, with a cutoff value of 2.71. High-risk patients (n = 407 [18.2%]) had a greater incidence of 3-year MACE (21.2% vs 10.4%; adjusted HR [aHR]: 1.53; 95% CI: 1.10-2.13; P = 0.01) and MACE excluding periprocedural myocardial infarction (16.2% vs 7.8%; aHR: 1.72; 95% CI: 1.17-2.53; P = 0.006) compared with the low-risk group. The prognostic effect of residual global μQFR was consistent across QFR- and angiography-guided subgroups (P for interaction = 0.35). Patients with low residual ischemia derived the best outcomes after QFR-guided PCI (MACE 8.8% vs 11.9% for angiography-guided PCI; HR: 0.73; 95% CI: 0.55-0.97). CONCLUSIONS:Residual global μQFR is a robust angiographic index for post-PCI ischemia burden and long-term risk stratification. In patients with ACS, QFR-guided PCI achieving low residual global ischemia was associated with the most favorable 3-year prognosis.

BACKGROUND:Atrial fibrillation (AF) and ovarian cancer are leading causes of morbidity, with emerging evidence suggesting potential interplay. However, their temporal and genetic relationships remain unclear. METHODS:We analyzed 265,248 women from the UK Biobank using bidirectional Cox models to examine associations between AF and ovarian cancer. Two-sample Mendelian randomization (MR) assessed genetically proxied AF liability on ovarian cancer risk, complemented by summary data-based MR and functional genomic analyses to identify shared genes. Loss-of-function assays in SKOV3 ovarian cancer cells evaluated biological plausibility. RESULTS:During a median 17.8-year follow-up, both directions showed significant associations: AF increased ovarian cancer risk [HR, 1.30; 95% confidence interval (CI), 1.05-1.61], and ovarian cancer increased AF risk (HR, 1.75; 95% CI, 1.43-2.14), particularly for serous histotypes. MR analyses indicated a modest genetic association between AF liability and ovarian cancer (OR, 1.05; 95% CI, 1.00-1.11), with directionality confirmed by MR-Steiger tests. Summary data-based MR and integrative analyses identified nucleoporin 50 and synaptotagmin-like 2 as shared susceptibility genes, in which knockdown inhibited the proliferation of ovarian cancer cells. CONCLUSIONS:This study provides complementary observational and genetic evidence linking AF and ovarian cancer. Although bidirectional associations were observed in the UK Biobank cohort, MR analyses supported a genetic contribution of AF liability to ovarian cancer risk but not the reverse. Integrative genomic analyses further nominated nucleoporin 50 and synaptotagmin-like 2 as potential mediators of the AF-ovarian cancer connection. IMPACT:Women with AF may represent a high-risk group for ovarian cancer, highlighting the need for cardio-oncology surveillance and biomarker-guided screening strategies.

Acute myocardial infarction is a leading cause of morbidity and mortality, with ischaemia–reperfusion (I/R) injury exacerbating myocardial damage. Vagus nerve stimulation (VNS) has been reported to exert cardioprotective effects, but its efficacy in preconditioning against I/R injury requires further investigation. We evaluated the cardioprotective effects of VNS preconditioning in a rat model of acute myocardial infarction with induced I/R injury. Sixty rats were randomized into Pre‐VNS, Control and Sham groups. The Pre‐VNS group received 1 week of low‐level cervical VNS before induction of I/R injury; stimulation was deactivated 30 min before ischaemia. Survival, echocardiographic function, reperfusion arrhythmias, arrhythmia inducibility, infarct size, apoptosis and inflammatory cytokines were assessed. Survival did not differ significantly between Pre‐VNS and Control groups (75.0% vs. 65.0%, p = 0.497). However, Pre‐VNS animals exhibited preserved cardiac function, with higher ejection fraction and fractional shortening ( p < 0.001). VNS preconditioning reduced the incidence of reperfusion arrhythmia during left anterior descending coronary artery ligature release ( p = 0.006) and decreased the arrhythmia index on programmed stimulation ( p = 0.003). Infarct size and cardiomyocyte apoptosis were significantly attenuated ( p < 0.001), accompanied by markedly lower serum interleukin‐1β, interleukin‐6 and tumour necrosis factor‐alpha levels ( p < 0.001). VNS preconditioning effectively mitigates I/R injury by improving cardiac function, reducing infarct size and arrhythmias, and attenuating inflammatory and apoptotic responses.

The prognostic value of the American College of Cardiology/American Heart Association (ACC/AHA) lesion classification in NSTEMI remains insufficiently investigated, especially regarding its interaction with coronary microvascular disease (CMD). In 2212 NSTEMI patients, we evaluated lesion complexity by applying the modified ACC/AHA classification system and then measured post-PCI angio-IMR. The primary endpoint was major adverse cardiovascular events (MACE) at 2 years. Patients with complex lesions demonstrated substantially elevated 2-year MACE rates compared to those with simple lesions (13.5

BACKGROUND:The optimization of a treatment plan developed on the basis of coronary angiography alone is recognized as one of the underlying rationales for the clinical benefits of physiology-guided percutaneous coronary intervention (PCI). OBJECTIVES:The aim of this study was to investigate the diagnostic impact of quantitative flow ratio (QFR) through a post hoc analysis of the multicenter randomized FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients With Coronary Artery Disease) III China trial. METHODS:In FAVOR III China, operators were required to declare all target vessels intended for PCI before randomization (prerandomization declared treatment plan). After randomization, the actual treatment strategy was performed with online QFR or angiographic guidance (randomized allocation). In this study, prerandomization treatment plan and postrandomization treatment strategy were adjudicated using off-line QFR by independent core laboratory to determine physiological concordance. The primary outcome of interest for the present study was major adverse cardiac events. RESULTS:Among 3,768 pooled patients with available off-line QFR, 2,601 (69.0%) had prerandomization physiology-concordant plans, proportions of which were comparable between the online QFR-guided and angiography-guided groups (70.9% [1,340 of 1,891] vs 67.2% [1,261 of 1,877], standardized mean difference = 0.087). Physiological concordance was reclassified in 447 (23.6%) and 87 (4.6%) patients with online QFR and angiographic guidance, respectively, and a significant between-group difference was identified in terms of achieving postrandomization physiological concordance (92.3% vs 67.2%, standardized mean difference = 0.665). A significant interaction was identified between prerandomization physiological concordance and randomized allocation for 2-year major adverse cardiac events (P for interaction = 0.002). Patients with older age, multivessel disease, left circumflex or right coronary artery involved, and lower SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores were found more likely to have prerandomization physiological nonconcordance. CONCLUSIONS:In the FAVOR III China trial, approximately 30% of patients showed discrepancies between angiography-based treatment plans and physiological ischemia. The mechanistic insight underlying the benefits of QFR-guided PCI is reclassification following online QFR guidance, which leads to a shift from initially flawed plans toward physiology-concordant decisions. (The FAVOR III China Study [FAVORIII]; NCT03656848).