BACKGROUND:Aortic stenosis (AS) is a common progressive valvular disease with no approved medical therapy to slow progression. Insulin resistance may contribute to valvular degeneration, but the prognostic value of non-insulin-based insulin resistance (IR) indices remains uncertain. METHODS:We retrospectively analyzed 2,220 patients with mild-to-moderate AS from the WenZhou Valve Heart Disease registry. Four IR surrogates were assessed: triglyceride-glucose (TyG) index, TyG-BMI, atherogenic index of plasma (AIP), and metabolic score for insulin resistance (METS-IR). AS progression was defined as an annual increase in peak aortic jet velocity (ΔVmax/year) ≥0.3 m/s/year. Associations and predictive performance were evaluated using multivariable Cox regression, Kaplan-Meier analysis, restricted cubic splines, ROC curves, and sensitivity analyses. RESULTS:During a median follow-up of 3.03 years, 414 patients (18.6%) developed AS progression. After multivariable adjustment, the highest tertiles of TyG, AIP, and TyG-BMI were independently associated with higher progression risk, with HRs of 1.58 (95% CI: 1.20-2.07), 1.43 (95% CI: 1.10-1.85), and 1.52 (95% CI: 1.18-1.95), respectively. TyG showed the strongest standalone discrimination (AUC 0.638), outperforming AIP and METS-IR. Associations were stronger in hypertensive patients. Adding IR indices modestly improved discrimination and reclassification, especially for TyG-BMI. Sensitivity analyses confirmed robustness. CONCLUSION:TyG and AIP were independently associated with non-severe AS progression, while TyG-BMI improved risk classification. These routine metabolic markers may help guide closer echocardiographic surveillance and metabolic risk management.

Background Patients with both acute myocardial infarction (AMI) and chronic kidney disease (CKD) face a markedly poor prognosis, a key driver of which is insulin resistance (IR). This study aims to systematically evaluate and compare the predictive performance of four commonly used IR indices for major adverse cardiovascular events (MACE), and to assess their incremental value over the GRACE score in this patient group.Methods This retrospective cohort study analyzed 1,803 patients with AMI and CKD. Multivariable Cox regression determined associations between IR indices and MACE. Predictive performance was evaluated using C-statistics, continuous net reclassification improvement (cNRI), and integrated discrimination improvement (IDI).Results During a median follow-up of 28.2 months, 462 MACE occurred. Patients with MACE were older, had higher female proportion, elevated GRACE score, and increased diabetes prevalence (all p < 0.05). the triglyceride-glucose (TyG) index and the atherogenic index of plasma (AIP) demonstrated linear associations with MACE risk, whereas TyG-body mass index (TyG-BMI) and metabolic score for insulin resistance (METS-IR) exhibited U-shaped nonlinear relationships (p < 0.001). The Area Under the Curve (AUCs) for MACE prediction were: TyG index 0.62, AIP 0.57, TyG-BMI 0.58, and METS-IR 0.56. Incorporating IR indices significantly enhanced the GRACE score’s predictive capacity, with TyG index providing the greatest incremental improvement (cNRI = 0.137, IDI = 0.03).Conclusion IR indices predict outcomes in patients with AMI and CKD and enhance GRACE score prediction, with TyG index demonstrating superior performance.

Background Ventricular free wall rupture (VFWR) and acute mitral regurgitation (MR) are life-threatening complications of acute myocardial infarction (AMI). Although surgical intervention is standard, alternatives are needed for those unfit for immediate operation. Case Summary An 81-year-old woman developed a VFWR with tamponade and severe MR after inferior AMI. Conservative management with pericardiocentesis and extracorporeal membrane oxygenation (ECMO) stabilized her hemodynamics, allowing spontaneous VFWR sealing. After ECMO weaning, refractory heart failure due to severe MR prompted transcatheter edge-to-edge repair (TEER). TEER successfully reduced MR from 4+ to 1+, enabling recovery to NYHA functional class I. Discussion This case demonstrates that a small VFWR may heal conservatively under ECMO support, challenging the dogma of mandatory emergency surgery. TEER after stabilization is feasible for post-AMI MR in high-risk patients. Take-Home Messages Conservative management with ECMO support can be a viable option for small VFWR in selected high-risk patients. TEER is a valuable therapeutic alternative for severe MR in patients with concomitant VFWR or those at prohibitive surgical risk.

Transcatheter aortic valve replacement (TAVR), also known as transcatheter aortic valve implantation (TAVI), is an interventional technology in which an artificial aortic valve is compressed and assembled outside the body, then delivered through a catheter and implanted at the site of the diseased aortic valve, thereby functionally replacing the native valve. Two versions of the Chinese expert consensus on TAVR were issued in China in 2015 and 2020, respectively. To promptly update the field's understanding of TAVR and to promote its broader, more standardized, and higher-quality application in China, an expert panel has developed this new version of the consensus. This consensus includes substantial updates compared with the previous version, covering topics such as the epidemiology of aortic valve disease, recent advances in TAVR research, indications, procedural standards, post-procedural antithrombotic therapy, prevention and management of complications, management of special cases, and future development trends. This consensus integrates international research evidence and references international guidelines to ensure rigor and evidence-based recommendations, while also incorporating domestic research findings and clinical practice in China, thereby enhancing both its forward-looking perspective and practical applicability.

Background Conventional local infiltration anesthesia (LIA) may not consistently provide adequate analgesia during cardiac device implantation. Objective To compare the analgesic efficacy of ultrasound-guided peripheral regional anesthesia (PRA) with LIA during cardiac device implantation. Methods We conducted a single-center prospective observational cohort study including patients undergoing first-time cardiac device implantation. Data were collected in real time during routine clinical care. Patients received PRA or LIA according to routine clinical practice, as determined by the treating clinicians. Propensity score-matching (PSM) was performed to reduce selection bias, resulting in 48 matched patients per group. Pain intensity was assessed using a numerical rating scale (NRS) at predefined intraoperative procedural steps and postoperative time points, as part of standardized peri-procedural care. Additional anesthetic supplementation, pain-related movement, and adverse events were recorded. Results Among the matched patients (n = 96), pain scores at all seven procedural steps were significantly lower in the PRA group than in the LIA group (all P < 0.01). In the LIA group, pain intensity peaked during pocket creation (all P < 0.05), whereas pain scores remained relatively consistent across procedural steps in the PRA group. Postoperative NRS scores at 2–24 hours were significantly lower in the PRA group (all P < 0.05). Pain-related movement and additional anesthetic supplementation were less frequent in the PRA group. Adverse events were infrequent and comparable between groups. Conclusion In this PSM prospective observational cohort study, ultrasound-guided PRA was associated with improved peri-procedural analgesia without an observed increase in adverse events.

Myocardial infarction (MI) is a leading global cause of mortality and morbidity, with current therapies failing to achieve effective cardiac regeneration. Exercise-derived exosomes (Exos) hold great promise for cardioprotection, yet their clinical translation is severely hindered by rapid in vivo clearance and poor retention in infarcted myocardial tissue. Herein, we engineered an injectable polyethylene glycol-based hydrogel (Gel-PEG) as a localized and sustained delivery platform for exercise-derived exosomes (Exos@Gel-PEG), and systematically characterized the hydrogel’s physicochemical, mechanical and biocompatibility properties, as well as exosome encapsulation efficiency and release kinetics. The association between exercise exosomes and ferroptosis of cardiomyocytes and vascular biology was determined through multi-omics analysis (metabolomics and proteomics).The therapeutic efficacy and underlying mechanisms of Exos@Gel-PEG were evaluated in a murine MI model, and the results demonstrated that Exos@Gel-PEG exhibited excellent injectability, biocompatibility and a sustained exosome release profile for up to 28 days in vitro, with significantly improved exosome retention in the infarcted heart for 15 days in vivo compared to free exosomes. In vivo, Exos@Gel-PEG treatment markedly improved cardiac systolic function, reduced myocardial interstitial fibrosis, and attenuated adverse ventricular remodeling in MI mice. Mechanistically, Exos@Gel-PEG activated the AKT/eNOS signaling pathway to promote endothelial cell proliferation, migration and post-infarction angiogenesis, and modulated myocardial iron homeostasis and oxidative stress to upregulate the expression of anti-ferroptotic proteins (xCT, GPX4, FTH1), thereby effectively suppressing cardiomyocyte ferroptosis. Furthermore, Exos@Gel-PEG showed no systemic toxicity and good in vivo biosafety. Collectively, our findings highlight that the Exos@Gel-PEG system integrates the cardioprotective merits of exercise-derived exosomes with the sustained delivery advantages of Gel-PEG, and exerts myocardial repair effects via dual mechanisms of angiogenesis promotion and ferroptosis inhibition, representing a novel and promising biomaterial-based therapeutic strategy for MI with potential clinical translation value.

Background:Transcatheter edge-to-edge repair (TEER) poses significant technical challenges in patients with a massive left atrium (LA), where conventional anatomical criteria often deem the procedure unsuitable. Case summary:A 77-year-old man, at prohibitive surgical risk, presented with a giant LA (113 × 129 × 133 mm) and severe mitral regurgitation (MR). After pacemaker implantation, TEER was performed. Despite suboptimal echocardiographic windows and challenging leaflet capture, a tailored posteroinferior transseptal puncture 4.67 cm above the mitral annular plane provided a stable trajectory, enabling successful navigation and deployment of three MitraClip devices (Abbott, Santa Clara, CA, USA). The procedure achieved an excellent outcome with a mean gradient of 5 mmHg and only mild residual MR. Marked left atrial reverse remodelling and symptomatic improvement were observed at 1-month follow-up. Discussion:This case demonstrates that TEER is a viable and effective intervention for patients with extreme LA enlargement, challenging conventional anatomical selection criteria. Success hinges on technical precision-particularly an optimized transseptal puncture-and prioritizing favourable haemodynamic outcomes over rigid anatomic thresholds.

BACKGROUND:Angiography-derived index of microcirculatory resistance (angio-IMR) is a reliable measure for assessing coronary microvascular function. However, the prognostic significance of changes in angio-IMR (Δangio-IMR) remains unclear. OBJECTIVES:The aim of this study was to assess the long-term prognostic utility of Δangio-IMR following percutaneous coronary intervention (PCI) in patients with intermediate coronary stenosis. METHODS:A total of 814 vessels with intermediate coronary stenosis that underwent PCI were enrolled from the FLAVOUR (Fractional Flow Reserve and Intravascular Ultrasound for Clinical Outcomes in Patients with Intermediate Stenosis) trial. The primary endpoint was target vessel failure (TVF) during long-term follow-up, defined as a composite of cardiac death, target vessel-related myocardial reinfarction, and target vessel revascularization. RESULTS:The median Δangio-IMR was 2.02 (Q1-Q3: 0.50-5.00). Using the 75th percentile (Δangio-IMR >5) as the cutoff, 203 vessels were assigned to the high Δangio-IMR group. Vessels with high Δangio-IMR demonstrated a significantly elevated risk for TVF compared with those with low Δangio-IMR (15.62% vs 9.47%; HR: 1.82; 95% CI: 1.15-2.88; P = 0.011). High Δangio-IMR independently predicted TVF (HR: 1.72; 95% CI: 1.04-2.83; P = 0.034). There was a notable interaction effect between Δangio-IMR and post-PCI angio-IMR (P = 0.028). A stratified analysis by post-PCI angio-IMR revealed that vessels with high Δangio-IMR showed a markedly increased TVF risk compared with vessels with low Δangio-IMR in those with post-PCI angio-IMR >25 (26.2% vs 11.9%; HR: 5.18; 95% CI: 1.28-20.94; P = 0.021), whereas no such association was observed in those with post-PCI angio-IMR ≤25 (12.6% vs 9.3%; HR: 1.33; 95% CI: 0.77-2.29; P = 0.305). CONCLUSIONS:An elevated Δangio-IMR correlates with a heightened risk of TVF in vessels with intermediate coronary stenosis underwent PCI. ΔAngio-IMR could be used as a valuable risk stratification indicator, particularly in patients with high post-PCI angio-IMR.

BACKGROUND:While angiography-derived fractional flow reserve (AngioFFR)- and intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) yield similar outcomes, with AngioFFR associated with lower PCI rates, the relative clinical effectiveness of AngioFFR versus IVUS-guided PCI according to angiographic lesion characteristics remains unclear. METHODS:This post hoc analysis of the FLAVOUR II trial (Comparison of Angiography-Derived Fractional Flow Reserve- and Intravascular Ultrasound-Guided Intervention Strategy for Clinical Outcomes in Patients with Coronary Artery Disease) included patients with ≥50% stenosis randomized to AngioFFR- or IVUS-guided PCI. A composite lesion risk score was derived using a marginal Cox model-based linear predictor incorporating % diameter stenosis, lesion length, true bifurcation, ostial lesion, and heavy calcification. The primary end point was target vessel failure (TVF: cardiac death, target vessel myocardial infarction, and target vessel revascularization). RESULTS:Among 1726 patients, 884 (51.2%) underwent AngioFFR-guided PCI and 842 (48.8%) underwent IVUS-guided PCI. During a median 12-month follow-up, TVF occurred in 2.4% of AngioFFR-treated vessels and 1.9% of IVUS-treated vessels (P=0.50). TVF risk increased progressively with a higher composite lesion risk score (adjusted hazard ratio, 2.76 [95% CI, 1.35-5.65]). This association was more pronounced in the AngioFFR group (adjusted hazard ratio, 3.93 [95% CI, 1.79-8.63]) than in the IVUS group (adjusted hazard ratio, 1.62 [95% CI, 0.42-6.22]). Compared with IVUS guidance, AngioFFR-guided vessels with high-risk lesions (score >0.32) had a higher TVF rate (5.1% versus 1.9%; P=0.010), whereas outcomes were comparable in those with low-risk lesions (1.5% versus 1.9%; P=0.531). AngioFFR guidance was associated with lower target vessel PCI rates in low-risk lesions (60.1% versus 76.5%; P<0.001), whereas PCI rates were uniformly high and similar between groups in high-risk lesions (96.4% versus 97.4%; P=0.675). CONCLUSIONS:A higher composite lesion risk score was associated with increased PCI rates and TVF risk after AngioFFR- or IVUS-guided treatment. AngioFFR guidance was associated with lower PCI rates in low-risk lesions, whereas IVUS guidance may yield more favorable outcomes in high-risk lesions. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04397211.

Background Conduction system pacing (CSP) combined with atrioventricular node ablation (AVNA) is a feasible option for symptomatic atrial fibrillation (AF), but comparative studies with pulmonary vein isolation (PVI) are limited. Objectives The aim of this study was to compare the clinical outcomes of CSP+AVNA and PVI in patients with persistent AF and a left atrial size. Methods This observational study included patients with persistent AF and a left atrial size >50 mm received PVI or CSP+AVNA (ablate and pace [AP]) from 2016 to 2022. Clinical outcomes, AF recurrence, and the composite endpoint of heart failure hospitalization and cardiac death were assessed. Results Out of 718 screened patients, 473 received PVI and 245 received AP. The AP strategy was associated with higher composite risk in univariate analysis (HR: 2.84; 95% CI: 1.79-4.50; P < 0.001) but not after multivariate adjustment (HR: 1.10; 95% CI: 0.54-2.23; P = 0.795). After 1:1 matching (n = 174), left ventricular ejection fraction improved similarly in both groups. Over an average 40 months’ follow-up, the composite endpoint was similar between groups (propensity score matching [PSM]-AP: 14.9% vs PSM-PVI: 16.1%; P = 0.864). AF recurred in 54.0% in the PSM-PVI group and atrioventricular conduction recurred in 1.2% in the PSM-AP group. Conclusions In this observational study, outcomes were numerically similar between PVI and AP in patients with persistent AF and enlarged left atria. Given the limited sample size and residual confounding, these results should be considered hypothesis-generating pending confirmation from randomized trials.

BACKGROUND: Conduction system pacing (CSP) combined with atrioventricular node ablation (AVNA) is a feasible option for symptomatic atrial fibrillation (AF), but comparative studies with pulmonary vein isolation (PVI) are limited. OBJECTIVES: The aim of this study was to compare the clinical outcomes of CSP+AVNA and PVI in patients with persistent AF and a left atrial size. METHODS: This observational study included patients with persistent AF and a left atrial size >50 mm received PVI or CSP+AVNA (ablate and pace [AP]) from 2016 to 2022. Clinical outcomes, AF recurrence, and the composite endpoint of heart failure hospitalization and cardiac death were assessed. RESULTS: Out of 718 screened patients, 473 received PVI and 245 received AP. The AP strategy was associated with higher composite risk in univariate analysis (HR: 2.84; 95% CI: 1.79-4.50; P < 0.001) but not after multivariate adjustment (HR: 1.10; 95% CI: 0.54-2.23; P = 0.795). After 1:1 matching (n = 174), left ventricular ejection fraction improved similarly in both groups. Over an average 40 months' follow-up, the composite endpoint was similar between groups (propensity score matching [PSM]-AP: 14.9% vs PSM-PVI: 16.1%; P = 0.864). AF recurred in 54.0% in the PSM-PVI group and atrioventricular conduction recurred in 1.2% in the PSM-AP group. CONCLUSIONS: In this observational study, outcomes were numerically similar between PVI and AP in patients with persistent AF and enlarged left atria. Given the limited sample size and residual confounding, these results should be considered hypothesis-generating pending confirmation from randomized trials.

BACKGROUND:The constant resistance ratio (cRR) is a novel nonhyperemic pressure ratio based on piezoresistive pressure microcatheter (PMC) measurements. With repeated measurements in randomized order of PMC and pressure wire techniques, this study aimed primarily to validate the diagnostic performance of cRR compared with fractional flow reserve (FFR) in coronary lesions of 30% to 90% diameter stenosis. METHODS:SUPREME II (Sensor-Equipped Ultrathin Pressure Microcatheter Versus Pressure Wire for Physiological Measurements) was a multicenter, prospective study that included 466 patients (483 vessels) from 11 centers. All target vessels were assessed using both pressure wire and PMC separately in randomized order under resting and hyperemic conditions. The primary end point was the diagnostic accuracy of the cRR using a PMC-based FFR of ≤0.80 as the reference standard. Secondary end points included the cRR "gray zone" of the cRR-FFR hybrid strategy and the proportion of patients in whom diagnosed was achieved without vasodilator use. RESULTS:The optimal cRR cutoff was 0.89, which correctly classified 82.8% of the patients, with a sensitivity and specificity of 87.0% and 80.1%, respectively, and achieved an area under the curve of 0.92 with FFRPMC as reference (area under the curve 0.90 with FFRpressure wire as reference). If FFR was added for decision-making in cases of cRR values between 0.85 and 0.91, a cRR--FFR hybrid strategy achieved a 95.3% agreement with the FFR-only strategy and allowed 68.5% of the patients to not require using vasodilator. CONCLUSIONS:In coronary stenosis of 30% to 90% diameter stenosis, cRR measurements were highly feasible. The diagnostic accuracy of cRR with FFRPMC as reference was excellent. Further, a cRR-FFR hybrid strategy may reduce vasodilator use without compromising diagnostic accuracy. REGISTRATION:URL: https://clinicaltrials.gov/study/NCT05417763; Unique Identifier: NCT05417763.

BACKGROUND:Cardiovascular-kidney-metabolic (CKM) syndrome encompasses the complex interplay among the cardiovascular, kidney, and metabolic systems. The influence of frailty and its progression on future cardiovascular disease (CVD) risk within CKM stages 1 to 3 remains unclear. OBJECTIVES:The purpose of this study was to investigate the association between frailty progression and CVD risk in individuals with CKM stages 1 to 3, clarifying the prognostic significance of frailty dynamics in this population. METHODS:Data were obtained from the CHARLS (China Health and Retirement Longitudinal Study). Frailty status was evaluated by the Rockwood frailty index and classified as robust, prefrail, or frail. Changes in frailty status were divided into sustained robust state, frailty progression, frailty improvement, and sustained nonrobust state. CVD was identified by self-reported physician-diagnosed heart disease or stroke. Cox proportional hazard models and subgroups analysis were used to analyze the effect of frailty and its progression on the risk of CVD. RESULTS:Among 3,616 participants, prefrail (HR: 1.63; 95% CI: 1.45-1.84) and frail groups (HR: 1.89; 95% CI: 1.57-2.28) exhibited higher CVD risk than the robust group. Participants transitioning to a nonrobust state showed increased CVD risk (HR: 1.70; 95% CI: 1.38-2.09), with the highest risk in those with sustained nonrobust status (HR: 2.35; 95% CI: 1.99-2.78). Frailty improvement did not significantly affect CVD risk (HR: 1.21; 95% CI: 0.92-1.57). CONCLUSIONS:Frailty progression and sustained nonrobust state increased CVD risk in CKM stages 1 to 3, while frailty improvement had no significant effect. Our findings highlight frailty as a key CVD risk factor, emphasizing the need for early identification and intervention.

Background:Right atrial appendage pacing (RAAp) may increase the risk of atrial fibrillation (AF), compared to right atrial septal pacing (RASp). However, the implantation of atrial septal stylet-driven leads (SDLs) for RASp can present procedural challenges and limit its clinical application. We evaluated the long-term safety and feasibility of using lumenless leads (LLLs) with the delivery sheath for RASp and SDLs for RAAp, and compared AF events between the RASp and RAAp in patients with sick sinus syndrome. Methods:A total of 329 patients with sick sinus syndrome who underwent pacemaker implantation were divided into 2 groups, based on the site of atrial lead placement: the RASp group (n = 162) with LLLs, and the RAAp group (n = 167) with SDLs. Implantation success rate, procedural time, P-wave characteristics, pacing parameters, complications, and AF episodes were compared between the 2 groups. Results:The success rates were similar for the RASp and RAAp groups (98.8% vs 97.6%, P > 0.05). The lead implantation time was significantly shorter in the RASp group (2.5 ± 1.9 minutes vs 10.3 ± 2.9 minutes, P < 0.05). During a mean follow-up of 36.4 ± 20.5 months, the pacing parameters remained stable without serious complications. Additionally, the RASp group had a significantly reduced incidence of AF episodes (6.7% vs 14.0%, P < 0.05) and new-onset AF (1.8% vs 4.6%, P < 0.05). Conclusions:The long-term safety and feasibility of RASp with LLLs were comparable to those of RAAp patients with SDLs. The RASp reduced the incidence of postoperative AF episodes and new-onset AF. The RASp by delivery sheath implantation is a safe and effective method.

BACKGROUND:The association between coronary microcirculation and clinical outcomes in patients with intermediate stenosis remains unclear. OBJECTIVES:The aim of this study was to assess the prognostic significance of angiography-derived index of microcirculatory resistance (angio-IMR) in patients with intermediate coronary stenosis. METHODS:This post hoc analysis included 1,658 patients from the FLAVOUR (Fractional Flow Reserve and Intravascular Ultrasound for Clinical Outcomes in Patients with Intermediate Stenosis) trial, with angio-IMR measured in each vessel exhibiting intermediate stenosis. The primary endpoint was a patient-oriented composite outcome (POCO), a composite of all-cause death, myocardial infarction, or revascularization over a 2-year period. RESULTS:The median follow-up period was 24.8 months (Q1-Q3: 24.4-26.4 months). Over the 2-year follow-up period, patients with angio-IMR >25 exhibited a significantly higher POCO rate in both the percutaneous coronary intervention (PCI) group (35.06% [27 of 77] vs 7.2% [51 of 708]; P < 0.001) and the non-PCI group (17.95% [21 of 117] vs 4.23% [32 of 756]; P < 0.001). After adjusting for potentially related risk factors, angio-IMR >25 remained an independent predictor of the POCO in the PCI group (HR: 6.235; 95% CI: 3.811-10.203; P < 0.001) and the non-PCI group (HR: 5.282; 95% CI: 2.948-9.462; P < 0.001). The addition of angio-IMR demonstrated incremental prognostic value in both an angiographic risk factor model (C-index 0.710 [95% CI: 0.663-0.756] vs 0.615 [95% CI: 0.563-0.664] [P < 0.001]; net reclassification index 0.268 [95% CI: 0.191-0.362; P < 0.001]; integrated discrimination improvement 0.055 [95% CI: 0.030-0.108; P < 0.001]) and a clinical risk factor model (C-index 0.705 [95% CI: 0.658-0.751] vs 0.594 [95% CI: 0.544-0.644] [P < 0.001]; net reclassification index 0.268 [95% CI: 0.171-0.350; P < 0.001]; integrated discrimination improvement 0.057 [95% CI: 0.027-0.102; P < 0.001]). CONCLUSIONS:In individuals with intermediate coronary stenosis, elevated angio-IMR is linked to an adverse prognosis. Using angio-IMR significantly enhanced the capability to reclassify patients and accurately estimate the risk for the POCO.