Triiodothyronine induces a proinflammatory monocyte/macrophage profile and impedes cardiac regeneration.

Neonatal mouse hearts can regenerate post-injury, unlike adult hearts that form fibrotic scars. The mechanism of thyroid hormone signaling in cardiac regeneration warrants further study. We found that triiodothyronine impairs cardiomyocyte proliferation and heart regeneration in neonatal mice after apical resection. Single-cell RNA-Sequencing on cardiac CD45-positive leukocytes revealed a pro-inflammatory phenotype in monocytes/macrophages after triiodothyronine treatment. Furthermore, we observed that cardiomyocyte proliferation was inhibited by medium from triiodothyronine-treated macrophages, while triiodothyronine itself had no direct effect on the cardiomyocytes in vitro. Our study unveils a novel role of triiodothyronine in mediating the inflammatory response that hinders heart regeneration.

Triglyceride-glucose index as a suitable non-insulin-based insulin resistance marker to predict cardiovascular events in patients undergoing complex coronary artery intervention: a large-scale cohort study.

BACKGROUND: Insulin resistance (IR), a hallmark of proceeding diabetes and cardiovascular (CV) disease, has been shown to predict prognosis in patients undergoing percutaneous coronary intervention (PCI). The triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and metabolic score for insulin resistance (METS-IR) have been shown to be simple and reliable non-insulin-based surrogates for IR. However, limited studies have determined the associations between distinct non-insulin-based IR markers and CV outcomes in patients undergoing complex PCI who are at higher risk of CV events after PCI. Therefore, this study aimed to investigate and compare the prognostic value of these markers in patients undergoing complex PCI. METHODS: This was a descriptive cohort study. From January 2017 to December 2018, a total of 9514 patients undergoing complex PCI at Fuwai Hospital were consecutively enrolled in this study. The 3 IR indices were estimated from the included patients. The primary study endpoint was CV events, defined as a composite of CV death, nonfatal myocardial infarction and nonfatal stroke. RESULTS: During a median follow-up of 3.1 years, 324 (3.5%) CV events occurred. Multivariable Cox regression models showed per-unit increase in the TyG index (hazard ratio [HR], 1.42; 95% confidence interval [CI] 1.13-1.77), rather than per-unit elevation in either Ln(TG/HDL-C ratio) (HR, 1.18; 95%CI 0.96-1.45) or METS-IR (HR, 1.00; 95%CI 0.98-1.02), was associated with increased risk of CV events. Meanwhile, adding the TyG index to the original model led to a significant improvement in C-statistics (0.618 vs. 0.627, P < 0.001), NRI (0.12, P = 0.031) and IDI (0.14%, P = 0.003), whereas no significant improvements were observed when adding Ln (TG/HDL-C ratio) or METS-IR (both P > 0.05) to the original model. CONCLUSIONS: The TyG index, not TG/HDL-C ratio and METS-IR, was positively associated with worse CV outcomes in patients undergoing complex PCI. Our study, for the first time, demonstrated that the TyG index can serve as the suitable non-insulin-based IR marker to help in risk stratification and prognosis in this population.

Glycemic control and cardiovascular outcomes in patients with diabetes and coronary artery disease according to triglyceride-glucose index: a large-scale cohort study.

BACKGROUND: The role of triglyceride-glucose (TyG) index, an insulin resistance indicator, in glycemic management for diabetic patients with coronary artery disease (CAD) was still unknown. Therefore, we aimed to explore the association between glycemic control and cardiovascular (CV) outcomes in patients with diabetes and CAD according to different TyG index levels. METHODS: A total of 9996 diabetic patients with angiograph-proven CAD were consecutively recruited from 2017 to 2018 at Fuwai Hospital. Patients were assigned into 3 groups according to TyG index tertiles (T) (T1: <8.895; T2: 8.895-9.400; T3: ≥9.400). According to American Diabetes Association guidelines, controlled glycemia was defined as targeting glycosylated hemoglobin Alc (HbA1c) < 7%. The primary endpoint was CV events including CV death, nonfatal myocardial infarction, and nonfatal stroke. RESULTS: During a median 3-year follow-up, 381 (3.8%) CV events occurred. Overall, high TyG index (T3) was associated with increased risk of CV events (hazard ratio [HR]: 1.40; 95% confidence interval [CI]: 1.02-1.94) compared with the lowest TyG index (T1) after multivariable adjustment. Upon stratification by the TyG index, in fully adjusted models, controlled glycemia was associated with reduced risk of CV events in the high TyG index (T3) subgroup (HR: 0.64; 95%CI: 0.42-0.96) but not in the low (T1; HR: 0.79; 95%CI: 0.53-1.16) and moderate (T2; HR: 0.84; 95%CI: 0.56-1.25) TyG index subgroups. CONCLUSIONS: Controlled glycemia was associated with improved CV outcomes in patients with diabetes and established CAD, especially in those with high TyG index levels. Our study, for the first time, provided valuable information that TyG index could help making risk stratification on the glycemic management in diabetic patients with CAD.

High stress hyperglycemia ratio predicts adverse clinical outcome in patients with coronary three-vessel disease: a large-scale cohort study.

BACKGROUND: Coronary three-vessel disease (CTVD) accounts for one-third of the overall incidence of coronary artery disease, with heightened mortality rates compared to single-vessel lesions, including common trunk lesions. Dysregulated glucose metabolism exacerbates atherosclerosis and increases cardiovascular risk. The stress hyperglycemia ratio (SHR) is proposed as an indicator of glucose metabolism status but its association with cardiovascular outcomes in CTVD patients undergoing percutaneous coronary intervention (PCI) remains unclear. METHODS: 10,532 CTVD patients undergoing PCI were consecutively enrolled. SHR was calculated using the formula: admission blood glucose (mmol/L)/[1.59×HbA1c (%)-2.59]. Patients were divided into two groups (SHR Low and SHR High) according to the optimal cutoff value of SHR. Multivariable Cox regression models were used to assess the relationship between SHR and long-term prognosis. The primary endpoint was cardiovascular (CV) events, composing of cardiac death and non-fatal myocardial infarction (MI). RESULTS: During the median follow-up time of 3 years, a total of 279 cases (2.6%) of CV events were recorded. Multivariable Cox analyses showed that high SHR was associated with a significantly higher risk of CV events [Hazard Ratio (HR) 1.99, 95% Confidence interval (CI) 1.58-2.52, P < 0.001). This association remained consistent in patients with (HR 1.50, 95% CI 1.08-2.10, P = 0.016) and without diabetes (HR 1.97, 95% CI 1.42-2.72, P < 0.001). Additionally, adding SHR to the base model of traditional risk factors led to a significant improvement in the C-index, net reclassification and integrated discrimination. CONCLUSIONS: SHR was a significant predictor for adverse CV outcomes in CTVD patients with or without diabetes, which suggested that it could aid in the risk stratification in this particular population regardless of glucose metabolism status.

Impact of Relative Improvement in Quantitative Flow Ratio on Clinical Outcomes After Percutaneous Coronary Intervention　- A Subanalysis of the PANDA III Trial.

BACKGROUND: The clinical impact of relative improvements in coronary physiology in patients receiving percutaneous coronary intervention (PCI) for coronary artery disease (CAD) remains undetermined. METHODS AND RESULTS: The quantitative flow ratio (QFR) recovery ratio (QRR) was calculated in 1,424 vessels in the PANDA III trial as (post-PCI QFR-pre-PCI QFR)/(1-pre-PCI QFR). The primary endpoint was the 2-year vessel-oriented composite endpoint (VOCE; a composite of vessel-related cardiac death, vessel-related non-procedural myocardial infarction, and ischemia-driven target vessel revascularization). Study vessels were dichotomously stratified according to the optimal QRR cut-off value. During the 2-year follow-up, 41 (2.9%) VOCEs occurred. Low (<0.86) QRR was associated with significantly higher rates of 2-year VOCEs than high (≥0.86) QRR (6.6% vs. 1.4%; adjusted hazard ratio [aHR] 5.05; 95% confidence interval [CI] 2.53-10.08; P<0.001). Notably, among vessels with satisfactory post-procedural physiological results (post-PCI QFR >0.89), low QRR also conferred an increased risk of 2-year VOCEs (3.7% vs. 1.4%; aHR 3.01; 95% CI 1.30-6.94; P=0.010). Significantly better discriminant and reclassification performance was observed after integrating risk stratification by QRR and post-PCI QFR to clinical risk factors (area under the curve 0.80 vs. 0.71 [P=0.010]; integrated discrimination improvement 0.05 [P<0.001]; net reclassification index 0.64 [P<0.001]). CONCLUSIONS: Relative improvement of coronary physiology assessed by QRR showed applicability in prognostication. Categorical classification of coronary physiology could provide information for risk stratification of CAD patients.

Association of triglyceride-glucose index with adverse cardiovascular events in patients with established coronary artery disease according to different inflammatory status.

BACKGROUND AND AIMS: This study aimed to investigate the association of the triglyceride-glucose (TyG) index, a simple-but-reliable indicator of insulin resistance, with risk of cardiovascular (CV) events in coronary artery disease (CAD) patients with different inflammation status. METHODS AND RESULTS: We consecutively recruited 20,518 patients with angiograph-proven-CAD from 2017 to 2018 at Fuwai Hospital. Patients were categorized according to baseline TyG index tertiles (T) (tertile 1: ≤8.624; T2: 8.624-9.902 and T3: >9.902) and further assigned into 6 groups by high-sensitivity C-reactive protein (hsCRP) medians. The primary endpoint was CV events including CV death, nonfatal myocardial infarction and nonfatal stroke. During the 3.1-year-follow-up, 618 (3.0%) CV events were recorded. Overall, patients with high TyG index levels (T2 or T3) showed significantly increased risk of CV events (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.01-1.53; HR: 1.33; 95%CI: 1.05-1.68, respectively) compared with those with lowest Tyg index (T1) after adjusting for confounding factors. Upon stratification by hsCRP levels, elevated TyG index was associated with increased risk of CV events only in patients with hsCRP levels > median (per-1-unit-increase HR: 1.39; 95%CI: 1.11-1.74), rather than in those with hsCRP levels ≤ median. Furthermore, adding the TyG index to the predicting model led to a significant improvement in patients with hsCRP > median rather than in those with hsCRP ≤ median. CONCLUSIONS: We firstly found that elevated TyG index levels were associated with increased risk of CV events in CAD patients, especially in those with increased inflammatory status, suggesting that it could help in risk stratification and prognosis in this population.

The effect of lipid-lowering therapy on lipid-related residual risk factors: a prospective study.

BACKGROUND: Remnant cholesterol (RC) and nonhigh-density lipoprotein cholesterol (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] also contributing to its residual risk. However, real-world population-based evidence regarding the impact of current clinical LDL-C-centric lipid-lowering therapy (LLT) on achieving RC and nonHDL-C goals, as well as on modifying residual CVD risk factors is limited. METHODS: This prospective observational study enrolled 897 CVD patients from September, 2020 to July, 2021. All participants had previously received low-/moderate-intensity LLT and were discharged with either low-/moderate-intensity LLT or high-intensity LLT. After a median follow-up of 3 months, changes in RC, nonHDL-C, and other biomarkers were assessed. Multivariate logistic regression was performed to analyze the impact of the LLT on goal attainment. RESULTS: Among all patients, 83.50% transitioned to high-intensity LLT from low or moderate. After follow-up, the high-intensity group saw significantly greater reductions in RC (-20.51% vs. -3.90%, P = 0.025), nonHDL-C (-25.12% vs. 0.00%, P < 0.001), apoB (-19.35% vs. -3.17%, P < 0.001), triglycerides (-17.82% vs. -6.62%, P < 0.001), and LDL-C and total cholesterol. Spearman correlation analysis revealed that LDL-C reduction from current LLT was strongly correlated with nonHDL-C reduction (r = 0.87, P < 0.001). Patients who received high-intensity LLT had significant improvements in attainment of RC (from 44.2% to 60.7%, χ² = 39.23, P < 0.001) and nonHDL-C (from 19.4% to 56.9%, χ² = 226.06, P < 0.001) goals. Furthermore, multivariate logistic regression showed that high-intensity LLT was a protective factor for RC [odds ratio (OR) = 0.66; 95% confidence intervals (CI), 0.45-0.97; P = 0.033] and nonHDL-C goal attainment (OR = 0.51; 95% CI, 0.34-0.75; P < 0.001), without a significant increase of adverse reactions. CONCLUSION: Current levels of clinically prescribed LDL-C-centric treatment can reduce RC and other lipid-related residual risk factors, but high-intensity LLT is better at achieving nonHDL-C and RC goals than low-/moderate-intensity LLT, with a good safety profile. More targeted RC treatments are still needed to reduce residual lipid risk further.

Impacts of Diabetes Mellitus on Cardiovascular Outcomes and Differential Effects of Direct Oral Anticoagulants in Patients with Left Ventricular Thrombus.

Background: The focus of this investigation into the impact of type 2 diabetes mellitus (T2DM) on left ventricular thrombus (LVT) is (a) the differences in LVT characteristics, (b) long-term clinical outcomes, and (c) differential effects of direct oral anticoagulants (DOAC) among patients with T2DM and without diabetes. Methods: Patients with confirmed LVT from 2009 to 2021 were included. The primary endpoints were major adverse cardiac and cerebrovascular events (MACCE), composite of cardiovascular death, ischemic stroke, and acute myocardial infarction (AMI). The secondary endpoints were all-cause death and cardiovascular death. Multivariable competing-risk regression and cumulative incidence functions (CIF) were used to evaluate the adverse consequences. Results: In total, 1675 patients were assessed initially. Follow-up data were available for 91.1% of the participants. Median follow-up was 3.8 years. This retrospective study ultimately comprised 1068 participants, of which 429 had T2DM. Significantly higher proportions of comorbidities were observed in the T2DM group. The location, morphology, and size of LVT were similar in the two groups. Multivariable analysis suggested a higher risk of MACCE among patients with T2DM. The difference in risk between the two groups after matching and weighting was not statistically significant. Among the whole sample (n = 638) or the just the non-diabetic patients with LVT and anticoagulation (n = 382), the incidence of MACCE did not differ between DOAC treatment and warfarin treatment. In the diabetic LVT population with anticoagulation (n = 256), DOAC treatment was associated with a significantly higher risk of MACCE than was warfarin treatment. Conclusions: The location and morphology of LVT are similar in T2DM and non-diabetic patients. A higher risk of MACCE was found among patients with diabetes.

Prognostic Value of Temporary Pacemaker Insertion in Patients with Acute Myocardial Infarction in the Era of Percutaneous Coronary Revascularization.

Background: Patients with acute myocardial infarction (AMI) complicated with arrhythmia are not uncommon. Insertion of temporary pacemakers (tPMs) in patients with arrythmia during acute myocardial infarction (AMI) is imperative support therapy. Arrhythmias include high-degree atrioventricular block (AVB), sinus arrest/bradycardia, and ventricular arrythmia storm. To date, no study has evaluated the prognosis of tPMs in patients with AMI complicated with arrhythmia. Especially in the era of thrombolysis or emergency percutaneous coronary intervention (PCI) for coronary artery revascularization, our study was designed to investigate the value of tPMs implantation in cases of AMI complicated with various arrhythmias. Methods: From January 2009 to January 2019, 35,394 patients with AMI, including 62.0% (21,935) with ST-segment elevation myocardial infarction (STEMI) and 38.0% (13,459) with non-ST-segment elevation myocardial infarction (NSTEMI) in four hospitals, were reviewed. A total of 552 patients with AMI associated with arrythmia were included in the cohort. Among the 552 patients, there were 139 patients with tPM insertions. The incidence trend of myocardial infarction complicated with various arrhythmias in the past 10 years was analysed, and the clinical characteristics, in-hospital mortality, postdischarge mortality, composite endpoints of modality, and independent risk factors were compared in patients with and without tPM in the era of coronary artery revascularization. Results: In patients with AMI-associated arrythmia, high-degree AVB was the major cause of tPM insertion (p = 0.045). In the past 10 years, the number of patients with high-degree AVB, tPM implantation, ventricular arrythmia storm, and in-hospital mortality has decreased year by year in the era of coronary artery revascularization. In the tPM group, the culprit vessel was the left main artery, and cardiogenic shock, acute renal injury and high brain natriuretic peptide (BNP) levels were independent risk factors for patients with AMI complicated with arrhythmia. The in-hospital mortality in the tPM group was higher than that in the non-tPM group. The patients with tPM insertion showed better postdischarge survival than patients without tPM insertion. Conclusions: In the era of emergency thrombolysis or PCI, coronary revascularization can ameliorate the prognosis of patients with AMI complicated with various arrhythmias. Temporary pacemaker insertion in patients with AMI complicated with arrhythmia can reduce the postdischarge mortality of these patients.

Feasibility and Safety of Drug-Coated Balloon for Treatment of De Novo Coronary Artery Lesions in Large Vessel Disease: A Large-Scale Multicenter Prospective Study.

Background: Drug-coated balloons (DCB) have been evaluated to be safe and practical in treating coronary small vessel disease (SVD). However, evidence about the practicality and safety of DCB in treating coronary lesions with diameters greater than 3.0 mm is limited. Methods: 1166 patients who received DCB angioplasty were enrolled and divided into groups of SVD or large vessel disease (LVD) according to the target vessel diameters ( < 3.0 mm for SVD; ≥ 3.0 mm for LVD). All participants received a 2-year follow-up. The two main outcomes were patient-oriented composite endpoint (patient-oriented composite endpoint (POCE), all-cause mortality, all myocardial infarctions [MI], or any revascularization), and target lesion failure (target lesion failure (TLF), cardiac death, target vessel MI, or ischemia-driven target lesion revascularization). Results: In these patients, a total of 30 (2.6%) TLF and 82 (7.0%) POCE were recorded. Patients in the LVD group showed statistically greater rates of lesion success compared to the SVD group (752 [96.0%] vs. 380 [99.2%], p = 0.004) and procedural success (751 [95.9%] vs. 380 [99.2%], p = 0.003). No significant difference was found in the 2-year risk of TLF (hazard ratio (HR) 1.41, 95% CI 0.58-3.44; p = 0.455), POCE (HR 1.29, 95% CI 0.76-2.20; p = 0.354), MI (HR 0.88, 95% CI 0.24-3.13; p = 0.837), revascularization (HR 1.22, 95% CI 0.68-2.21; p = 0.506), and stroke (HR 0.78, 95% CI 0.03-15.26; p = 0.784) between the SVD and LVD groups. Conclusions: There was no discernible inferiority of the DCB intervention in the LVD group as compared to the SVD group. The DCB intervention is practical for coronary lesions with diameters higher than 3.0 mm.

Time Trends of Etiology, Treatment, and Long-Term Outcomes Among Patients with Left Ventricular Thrombus.

Background: Recommendations for drug treatment of left ventricular thrombus (LVT) are based on the ST-segment elevation myocardial infarction (STEMI) guidelines; however, the etiology of LVT has changed. Due to the lack of evidence regarding LVT treatment in the heart failure population, current heart failure guidelines do not cover LVT treatment. We sought to review the etiology of LVT and changes in antithrombotic therapy over the previous 12 years and explore the impact of anticoagulation treatment from a single center's experience. Methods: From January 2009 to June 2021, we studied 1675 patients with a discharge diagnosis of LVT at a single center to investigate the clinical characteristics, incidence of all-cause death, cardiovascular death, ischemic stroke, major adverse cardiac and cerebrovascular events (MACCE), systemic embolism (SE), and major bleeding events. Patients were divided into an anticoagulant group and a non-anticoagulant group according to whether they received oral anticoagulant therapy at discharge. Results: The study included 909 patients (anticoagulation, 510; no anticoagulation, 399). While overall antiplatelet therapy dramatically decreased, more patients with LVT received oral anticoagulation in 2021 (74.0%) than in 2009 (29.6%). In addition, more than half of the patients had heart failure with reduced ejection fraction (HFrEF) each year. The all-cause mortality was 17.3% during 3.8 years of follow-up. The incidences of cardiovascular death, stroke, MACCE, SE, and major bleeding were 16.0%, 3.3%, 19.8%, 5.1%, and 1.7%, respectively. The anticoagulation group had a significantly higher proportion of dilated cardiomyopathy than the non-anticoagulation group (24.7% vs. 5.5%, p < 0.001), and a lower LVEF (34.0 vs. 41.0, p < 0.001). The anticoagulation group also had a higher probability of adverse events on long-term follow-up (p > 0.05). A multivariable competing risk regression model found no significant difference in all six endpoints between the groups (all p > 0.05). Similar results were found by matched and weighted data analysis. Diabetes mellitus (hazard ratio (HR), 1.42; 95% confidence interval (CI), 1.04-1.93; p = 0.027), renal insufficiency (HR, 2.36; 95% CI, 1.60-3.50; p < 0.001), history of previous stroke (HR, 1.60; 95% CI, 1.13-2.29; p = 0.009), and HFrEF (HR, 2.54; 95% CI, 1.78-3.64; p < 0.001) were predictors of increased risk of MACCE. Conclusions: Heart failure, rather than acute myocardial infarction, is currently the primary cause of LVT. A trend towards better prognosis in the no anticoagulation group was noted. Multivariable, matching and weighting analysis showed no improvement in prognosis with anticoagulant therapy. Our study does not negate the efficacy of anticoagulation but suggests the need to strengthen the management of anticoagulation in order to achieve better efficacy.

Effect of Thin-Walled Radial Sheath for Large-Bore Access On Reducing Periprocedural Radial Artery Occlusion Following Complex PCI: The REDUCE-RAO Randomized Trial.

Background: Transradial artery (TRA) access for percutaneous coronary intervention (PCI) was associated with lower risks of major bleeding and vascular complications compared to transfemoral artery access. Use of large-bore ( ≥ 7-Fr) guiding catheters through TRA approach increased the likelihood of radial artery occlusion (RAO). This study aimed to investigate whether use of the thin-walled 7-Fr Glidesheath Slender, allowing PCI with large-caliber guiding catheters, is superior to standard 7-Fr Cordis sheath with respect to periprocedural RAO within 24 hours after transradial coronary intervention (TRI) in complex lesions. Methods: A prospective randomized, controlled, single-blinded (patient-blinded) trial was conducted, randomizing 504 patients with TRI for complex lesions to either 7-Fr Glidesheath Slender or conventional 7-Fr Cordis sheath. The primary outcome was defined as the incidence of periprocedural RAO with Doppler ultrasound during the first 24 hours after TRI. Results: The incidence of early RAO was 10.3% for 7-Fr Glidesheath Slender and 13.5% for conventional 7-Fr sheath (p = 0.271). The procedural success rate for Glidesheath Slender was 92.9% and for Cordis sheath was 93.7% (p = 0.722). There was no signficiant difference between treatment arms in terms of local hematoma and radial spasm, whereas use of the Glidesheath Slender was associated with significantly less pain during the procedure (numeric rating scale [NRS], 2.27 ± 0.75 vs. 2.45 ± 0.95, p = 0.017). The assessment of radial artery in ultrasound parameters after complex TRI was improved with Glidesheath Slender. Conclusions: Among patients with complex coronary lesions undergoing TRI, 7-Fr Glidesheath Slender was not superior to conventional 7-Fr in the prevention of periprocedural RAO within 24 hours following complex PCI, without reducing RAO occurrence. Clinical Trial Registration: NCT04748068.

The Neutrophil to Lymphocyte Ratio Modifies Lipoprotein (a)-Related Poor Prognosis in Patients After Percutaneous Coronary Intervention.

Lipoprotein (a) [Lp(a)] could contribute to coronary artery disease (CAD) through proinflammatory effects. The neutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker. We consecutively enrolled 7,922 CAD patients to investigate the synergistic association of Lp(a) and NLR with prognosis in patients undergoing percutaneous coronary intervention (PCI). NLR was calculated as the neutrophil count divided by the lymphocyte count. Cutoff for NLR was a median of 2.07. The threshold value was set at 30 mg/dL for Lp(a). The primary endpoint was major adverse cardiac events (MACEs), including all-cause mortality and myocardial infarction. During 2 years follow-up, 111 (1.40%) MACEs occurred. Lp(a) > 30 mg/dL was associated with an increased MACE risk in participants with NLR ≥2.07 [adjusted hazard ratio (HR), 1.84; 95% CI, 1.12-3.03], but not in participants with NLR <2.07 (adjusted HR, 0.74; 95% CI, 0.38-1.45) (Pinteraction = 0.021). Subgroup analysis demonstrated that the synergistic association of Lp(a) and NLR with prognosis was more pronounced in female patients (Pinteraction = 0.028). This study suggested that combining Lp(a) and NLR may be useful for risk stratification in CAD population.

Insulin-based or non-insulin-based insulin resistance indicators and risk of long-term cardiovascular and all-cause mortality in the general population: A 25-year cohort study.

OBJECTIVE: Although insulin resistance (IR) has been recognized to be a causal component in various diseases, current information on the relationship between IR and long-term mortality in the general population is limited and conclusions varied among different IR indicators and different populations. We aimed to assess associations between different measurements of IR with long-term all-cause mortality and cardiovascular mortality risk for the general population. RESEARCH DESIGN AND METHODS: We included 13,909 individuals from the Third National Health and Nutrition Examination Survey. Mortality was identified via National Death Index information until December 31, 2019. IR was measured using fasting insulin, homeostasis model assessment of IR (HOMA-IR), homeostasis model assessment of ß-cell function, quantitative insulin sensitivity check index (QUICKI), insulin-to-glucose ratio (IGR), triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), and hypertriglyceridemic-waist phenotype. RESULTS: During median 25-year follow-up, 5,306 all-cause mortality events occurred. After multivariate adjustment, variables significantly associated with elevated all-cause mortality risk were (hazard ratio [95 % confidence interval]): higher insulin (1.07 [1.02;1.13]); HOMA-IR (1.08 [1.03;1.13]); IGR (1.05 [1.00;1.11]); TyG (1.07 [1.00;1.14]); TyG-BMI (1.24 [1.02;1.51]); lower QUICKI (0.91 [0.86-0.96]). After stratification by diabetes status, higher insulin, HOMA-IR, TyG-BMI and lower QUICKI were significantly associated with increased risk of all-cause mortality in both diabetes and non-diabetes populations (all P for interaction > 0.05). Higher TyG (adjusted HR 1.17 [1.09;1.26], P for interaction = 0.018) and hypertriglyceridemic-waist phenotype (adjusted HR 1.26 [1.08;1.46], P for interaction = 0.047) were significantly associated with increased risk of all-cause mortality in patients with diabetes, however, these associations could not be seen in people without diabetes. Similar results were observed between the above-mentioned IR indicators and cardiovascular death. CONCLUSIONS: Fasting insulin, HOMA-IR, TyG-BMI, and QUICKI may indicate mortality risk in diabetes and non-diabetes populations, with TyG and the hypertriglyceridemic-waist phenotype showing particular relevance for individuals with diabetes. Further studies are needed to validate these findings and determine their broader applicability.

A New Scoring System Predicting Side-Branch Occlusion in Patients Undergoing Left Main Bifurcation Intervention: The LM V-RESOLVE Score.

BACKGROUND: The risk of side-branch (SB) occlusion is pivotal for decision making of stenting strategies during unprotected left main (LM) bifurcation percutaneous coronary intervention (PCI). Accordingly, this study aimed to develop a scoring system for predicting SB occlusion during unprotected LM bifurcation PCI. METHODS: A total of 855 consecutive patients undergoing unprotected LM bifurcation PCI with provisional strategy at Fuwai Hospital from January 2014 to December 2016 were recruited. A prediction model was selected by means of all-subsets logistic regression, and a multivariable risk score (Left Main Visual Estimation for Risk Prediction of Side Branch Occlusion in Coronary Bifurcation Intervention [LM V-RESOLVE]) was then established with incremental weights attributed to each component variable based on its estimate coefficients. SB occlusion was defined as any decrease in Thrombolysis in Myocardial Infarction (TIMI) flow grade or absence of flow in SB after main vessel (MV) stenting. RESULTS: SB occlusion occurred in 19 LM bifurcation lesions (2.22%). In multivariable model, 3 variables, including MV/SB diameter ratio, MV plaque ipsilateral to SB, and baseline diameter stenosis of SB, were independent predictors for SB occlusion (model C-statistic 0.829, 95% confidence interval [CI] 0.735-0.923, with good calibration). The risk score had a C-statistics of 0.830 (95% CI 0.738-0.923) with good calibration. Satisfactory discriminative ability of the risk score was also preserved in external validation (C-statistic 0.794, 95% CI 0.691-0.896). CONCLUSIONS: The LM bifurcation-specific novel scoring system, LM V-RESOLVE, based on 3 simple baseline angiographic findings, could help to rapidly discriminate lesions at risk of SB occlusion during LM bifurcation PCI.

Development and validation of a model integrating clinical and coronary lesion-based functional assessment for long-term risk prediction in PCI patients.

OBJECTIVES: To establish a scoring system combining the ACEF score and the quantitative blood flow ratio (QFR) to improve the long-term risk prediction of patients undergoing percutaneous coronary intervention (PCI). METHODS: In this population-based cohort study, a total of 46 features, including patient clinical and coronary lesion characteristics, were assessed for analysis through machine learning models. The ACEF-QFR scoring system was developed using 1263 consecutive cases of CAD patients after PCI in PANDA III trial database. The newly developed score was then validated on the other remaining 542 patients in the cohort. RESULTS: In both the Random Forest Model and the DeepSurv Model, age, renal function (creatinine), cardiac function (LVEF) and post-PCI coronary physiological index (QFR) were identified and confirmed to be significant predictive factors for 2-year adverse cardiac events. The ACEF-QFR score was constructed based on the developmental dataset and computed as age (years)/EF (%) + 1 (if creatinine ≥ 2.0 mg/dL) + 1 (if post-PCI QFR ≤ 0.92). The performance of the ACEF-QFR scoring system was preliminarily evaluated in the developmental dataset, and then further explored in the validation dataset. The ACEF-QFR score showed superior discrimination (C-statistic = 0.651; 95% CI: 0.611-0.691, P < 0.05 versus post-PCI physiological index and other commonly used risk scores) and excellent calibration (Hosmer-Lemeshow χ2 = 7.070; P = 0.529) for predicting 2-year patient-oriented composite endpoint (POCE). The good prognostic value of the ACEF-QFR score was further validated by multivariable Cox regression and Kaplan-Meier analysis (adjusted HR = 1.89; 95% CI: 1.18-3.04; log-rank P < 0.01) after stratified the patients into high-risk group and low-risk group. CONCLUSIONS: An improved scoring system combining clinical and coronary lesion-based functional variables (ACEF-QFR) was developed, and its ability for prognostic prediction in patients with PCI was further validated to be significantly better than the post-PCI physiological index and other commonly used risk scores.

Association of platelet-to-lymphocyte ratio levels with the risk of cardiac adverse events in people with type 2 diabetes undergoing percutaneous coronary intervention: A large-scale prospective cohort study.

BACKGROUND: The platelet-to-lymphocyte ratio (PLR), a promising inflammatory biomarker, contributes to the development of atherosclerosis and type 2 diabetes (T2D). Therefore, this study aimed to elucidate the importance of PLR in predicting adverse events in people undergoing percutaneous coronary intervention (PCI) with T2D. METHODS: We consecutively enrolled 8831 people who underwent PCI and divided them into four groups according to PLR and glycemic metabolic status (PLR-Low/High without T2D, PLR-Low/High with T2D). The endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and stent thrombosis. A multivariate Cox regression analysis was performed to determine this association. RESULTS: During the 2.4-year follow-up, 663 (7.5%) MACCE and 75 (0.85%) stent thromboses were recorded. The risk of MACCE (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.10-1.53, P = 0.002) and stent thrombosis (HR: 2.32, 95% CI: 1.38-3.90, P = 0.002) was significantly higher in people with high PLR levels than in those with low PLR. Among people with T2D, the PLR-High group showed a significantly higher risk of MACCE (HR: 1.59, 95% CI: 1.21-2.09, P = 0.001) and stent thrombosis (HR: 3.15, 95% CI: 1.32-7.52, P = 0.010). However, these associations were not significant in people without T2D. CONCLUSIONS: PLR has been originally documented as a significant predictor of poor prognosis and a high incidence of stent thrombosis in people undergoing PCI, especially in those with T2D.

Molecular Imaging of Fibroblast Activation in Rabbit Atherosclerotic Plaques: a Preclinical PET/CT Study.

AIM: Atherosclerosis remains the pathological basis of myocardial infarction and ischemic stroke. Early and accurate identification of plauqes is crucial to improve clinical outcomes of atherosclerosis patients. Our study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-04 PET/CT in identifying plaques via a preclinical rabbit model of atherosclerosis. METHODS: New Zealand white rabbits were fed high-fat diet (HFD), and randomly divided into the model group injured by the balloon, and the sham group only with incisions. Ultrasound was performed to detect plaques, and FAPI-avid was determined through Al18F-NOTA-FAPI-04 PET/CT. Mean standardized uptake values (SUVmean) in lesions were compared, and biodistribution of Al18F-NOTA-FAPI-04 and target-to-background ratios (TBRs) were calculated. Histological staining was performed to display arterial plaques, and autoradiography (ARG) was employed to measure the in vitro intensity of Al18F-NOTA-FAPI-04. At last, the correlation among FAP levels, plaque area, SUVmean values and fibrous cap thickness was assessed. RESULTS: The rabbit carotid and abdominal atherosclerosis model was established. Al18F-NOTA-FAPI-04 showed a higher uptake in carotid plaques (SUVmean 1.32 ± 0.11) and abdominal plaques (SUVmean 0.73 ± 0.13) compared to corresponding controls (SUVmean 1.07 ± 0.06; 0.46 ± 0.03) (P < 0.05). Biodistribution analysis of Al18F-NOTA-FAPI-04 revealed that the bigger plaques were delineated with higher TBRs. Pathological staining showed the formation of arterial plaques, and ARG staining exhibited a higher intensity of Al18F-NOTA-FAPI-04 in the bigger plaques. Lastly, plaque area was found to be positively correlated to FAP expression and SUVmean, while FAP expression was negatively correlated to fibrous cap thickness of plaques. CONCLUSIONS: We successfully achieve molecular imaging of fibroblast activation in atherosclerotic lesions of rabbits, suggesting Al18F-NOTA-FAPI-04 PET/CT may be a potentially valuable tool to identify plaques.

Association of ß-blocker use at discharge and prognosis of oldest old with acute myocardial infarction: a prospective cohort study.

PURPOSE: It is uncertain whether ß-blockers are beneficial for long-term prognosis in older patients following acute myocardial infarction (AMI). Thus, this study sought to examine the effect of ß-blockers on long-term cardiovascular mortality (CVM) in the oldest old (≥ 80 years) with AMI. METHODS: In this prospective, consecutive, non-randomized study, a total of 1156 patients with AMI admitted within 24 h after onset of symptoms were enrolled from January 2012 to February 2020. Univariate and multivariate Cox regression analyses were performed to examine the impact of ß-blocker use on prognosis. Furthermore, one-to-one propensity score matching (PSM) and inverse probability treatment weighting (IPTW) analyses were used to control for systemic differences between groups. The primary outcome was long-term CVM. RESULTS: Among the enrolled subjects, 972 (85.9%) were prescribed with ß-blockers at discharge. Over a mean follow-up of 26.3 months, 224 cardiovascular deaths were recorded. Both univariate [hazard ratio (HR), 1.41, 95% confidence interval (CI) 0.93-2.13] and multivariate (HR, 1.29, 95% CI 0.79-2.10) Cox regression analyses showed that ß-blocker use had no significant association with the long-term CVM, which was further demonstrated by PSM (HR, 1.31, 95% CI 0.75-2.28) and IPTW (HR, 1.41, 95% CI 0.73-2.69) analyses. Subgroup analyses according to sex, heart rate, hypertension, diabetes, revascularization, left ventricular ejection fraction, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers use showed consistent results as well. CONCLUSION: Our findings first suggested that the use of ß-blockers at discharge in oldest old with AMI was not useful for reducing post-discharge CVM, which need to be further verified by randomized controlled trials.