Versican Promotes Cardiomyocyte Proliferation and Cardiac Repair.

BACKGROUND: The adult mammalian heart is incapable of regeneration, whereas a transient regenerative capacity is maintained in the neonatal heart, primarily through the proliferation of preexisting cardiomyocytes. Neonatal heart regeneration after myocardial injury is accompanied by an expansion of cardiac fibroblasts and compositional changes in the extracellular matrix. Whether and how these changes influence cardiomyocyte proliferation and heart regeneration remains to be investigated. METHODS: We used apical resection and myocardial infarction surgical models in neonatal and adult mice to investigate extracellular matrix components involved in heart regeneration after injury. Single-cell RNA sequencing and liquid chromatography-mass spectrometry analyses were used for versican identification. Cardiac fibroblast-specific Vcan deletion was achieved using the mouse strains Col1a2-2A-CreER and Vcanfl/fl. Molecular signaling pathways related to the effects of versican were assessed through Western blot, immunostaining, and quantitative reverse transcription polymerase chain reaction. Cardiac fibrosis and heart function were evaluated by Masson trichrome staining and echocardiography, respectively. RESULTS: Versican, a cardiac fibroblast-derived extracellular matrix component, was upregulated after neonatal myocardial injury and promoted cardiomyocyte proliferation. Conditional knockout of Vcan in cardiac fibroblasts decreased cardiomyocyte proliferation and impaired neonatal heart regeneration. In adult mice, intramyocardial injection of versican after myocardial infarction enhanced cardiomyocyte proliferation, reduced fibrosis, and improved cardiac function. Furthermore, versican augmented the proliferation of human induced pluripotent stem cell-derived cardiomyocytes. Mechanistically, versican activated integrin ß1 and downstream signaling molecules, including ERK1/2 and Akt, thereby promoting cardiomyocyte proliferation and cardiac repair. CONCLUSIONS: Our study identifies versican as a cardiac fibroblast-derived pro-proliferative proteoglycan and clarifies the role of versican in promoting adult cardiac repair. These findings highlight its potential as a therapeutic factor for ischemic heart diseases.

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.

Novel insights on dual antiplatelet therapy duration following stenting for angiography-detected moderate-to-severe calcified coronary lesions.

Dual antiplatelet therapy (DAPT), comprising both aspirin and the P2Y12 receptor inhibitor, is crucial in managing patients with coronary artery disease following percutaneous coronary intervention (PCI). The optimal duration for DAPT in patients with angiography-detected moderate-to-severe calcified coronary (MSCC) lesions who underwent PCI with drug-eluting stents (DES) implantation remains uncertain. We recruited patients with angiography-detected MSCC lesions who received DES implantation from the prospective Fuwai Percutaneous Coronary Intervention Registry. Patients were classified into two groups according to the duration of DAPT: those with a DAPT duration of one year or less, and those with a DAPT duration of more than one year. The primary endpoint was the major adverse cardiovascular and cerebrovascular event, which was defined as composed of all-cause death, nonfatal myocardial infarction, or nonfatal stroke. The key-safety endpoint was bleeding type 2, 3, or 5 according to the Bleeding Academic Research Consortium criteria. There were 1730 patients included in the study, and 470 (27.17 %) continued DAPT for more than one year after undergoing MSCC-PCI with DES implantation. The median follow-up time was 2.5 years. DAPT>1-year versus ≤1-year DAPT was significantly associated with a reduced risk of the primary outcome (1.59 % versus 3.19 %; adjusted hazard ratio=0.44; 95 % CI: 0.22-0.88). Similar trends were observed for all-cause death (0.16 % versus 1.91 %; P<0.001) and cardiovascular death (0.08 % versus 1.06 %; P=0.001). There was no significant difference in the key-safety endpoint between 2 regimens (1.75 % versus 0.85 %; adjusted hazard ratio=1.95; 95 % CI: 0.65-5.84). In conclusion, long-term DAPT after DES implantation in patients with MSCC lesions resulted in improved clinical outcomes at 2.5 years. This was achieved by reducing the risk of ischemia without increasing clinically significant bleeding.

Prognostic value of the stress-hyperglycaemia ratio in patients with moderate-to-severe coronary artery calcification: Insights from a large cohort study.

AIM: To evaluate the relationship between the stress-hyperglycaemia ratio (SHR) and the clinical prognosis of patients with moderate-to-severe coronary artery calcification (MSCAC). METHODS: We consecutively enrolled 3841 patients with angiography-detected MSCAC. The individuals were categorized into three groups based on SHR tertiles: T1 (SHR ≤ 0.77), T2 (0.77 < SHR ≤ 0.89) and T3 (SHR > 0.89). The SHR value was calculated using the formula SHR = [admission glucose (mmol/L)]/[1.59 × HbA1c (%) - 2.59]. The primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCEs), including all-cause death, non-fatal myocardial infarction and non-fatal stroke. RESULTS: During a median follow-up of 3.11 years, 241 MACCEs were recorded. Kaplan-Meier survival analysis showed that the SHR T3 group had the highest incidence of MACCEs (P < .001). Moreover, findings from the restricted cubic spline analysis showed a significant and positive association between the SHR and MACCEs. This correlation remained consistent even after considering other variables that could potentially impact the results (Pnon-linear = .794). When comparing SHR T1 with SHR T3, it was found that SHR T3 was significantly associated with an increased risk of the primary outcome (adjusted hazard ratio = 1.50; 95% confidence interval: 1.10-2.03). CONCLUSIONS: Patients with MSCAC showed a positive correlation between the SHR and MACCE rate over a 3-year follow-up period. The study showed that an SHR value of 0.83 is the key threshold, indicating a poor prognosis. Future large-scale multicentre investigations should be conducted to determine the predictive value of the SHR in patients with MSCAC.

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.

Left main bifurcation stenting: impact of residual ischaemia on cardiovascular mortality.

AIMS: The present study sought to determine the rate and prognostic implications of post-procedural physiologically significant residual ischemia according to Murray law-based quantitative flow ratio (µQFR) after left main (LM) bifurcation percutaneous coronary intervention (PCI). METHODS AND RESULTS: Consecutive patients undergoing LM bifurcation stenting at a large tertiary care center between January 2014 and December 2016 with available post-PCI µQFR were included. Physiologically significant residual ischemia was defined by post-PCI µQFR values ≤0.80 in the left anterior descending (LAD) or left circumflex artery (LCX). The primary outcome was 3-year cardiovascular death. The major secondary outcome was 3-year bifurcation-oriented composite endpoint (BOCE). Among 1170 included patients with analyzable post-PCI µQFR, 155 (13.2%) had residual ischemia in either LAD or LCX. Patients with vs. those without residual ischemia had a higher risk of 3-year cardiovascular mortality [5.4% vs. 1.3%; adjusted hazard ratio (HR) 3.20, 95% confidence interval (CI): 1.16-8.80]. The 3-year risk of BOCE was significantly higher in the residual ischemia group (17.8% vs. 5.8%; adjusted HR 2.79, 95% CI: 1.68-4.64), driven by higher incidence of the composite of cardiovascular death and target bifurcation-related myocardial infarction (14.0% vs. 3.3%; adjusted HR 4.06, 95% CI: 2.22-7.42). A significant, inverse association was observed between continuous post-PCI µQFR and the risk of clinical outcomes (per 0.1 µQFR decrease, HR of cardiovascular death 1.27, 95% CI: 1.00-1.62; HR of BOCE 1.29, 95% CI: 1.14-1.47). CONCLUSION: After angiographically successful LM bifurcation PCI, residual ischemia assessed by µQFR was identified in 13.2% of patients and was associated with higher risk of 3-year cardiovascular death, indicating the superior prognostic value of post-PCI physiological assessment.

Intensified glycemic control by HbA1c for patients with coronary heart disease and Type 2 diabetes: a review of findings and conclusions.

The occurrence and development of coronary heart disease (CHD) are closely linked to fluctuations in blood glucose levels. While the efficacy of intensified treatment guided by HbA1c levels remains uncertain for individuals with diabetes and CHD, this review summarizes the findings and conclusions regarding HbA1c in the context of CHD. Our review showed a curvilinear correlation between regulated level of HbA1c and therapeutic effectiveness of intensified glycemic control among patients with type 2 diabetes and coronary heart disease. It is necessary to optimize the dynamic monitoring indicators of HbA1c, combine genetic profiles, haptoglobin phenotypes for example and select more suitable hypoglycemic drugs to establish more appropriate glucose-controlling guideline for patients with CHD at different stage of diabetes.

High triglyceride-glucose index and stress hyperglycemia ratio as predictors of adverse cardiac events in patients with coronary chronic total occlusion: a large-scale prospective cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index and the stress hyperglycaemia ratio (SHR) are both positively associated with cardiovascular (CV) risk in patients with coronary heart disease. However, the prognostic value of these two biomarkers has not been well elucidated in patients with chronic total occlusion (CTO). Therefore, this study aims to evaluate the association of the TyG index and the SHR with long-term prognosis in patients with CTO. METHODS: This prospective cohort study consecutively included 2740 angina patients with CTO from January 2017 to December 2018 at Fuwai Hospital. The outcomes are a composite of CV death and target vessel myocardial infarction (TVMI) and major CV cerebrovascular adverse events (MACCEs, including all-cause death, nonfatal MI, ischaemia-driven target vessel revascularization, and stroke). The association between biomarkers and prognosis was analysed by multivariable Cox proportional hazard models, and the predictive value was determined by a receiver-operating characteristic (ROC) curve. RESULTS: During the follow-up with a median time of 3 years, 179 (6.5%) cases of MACCEs and 47 (1.7%) cases of CV death or TVMI were recorded. Patients with a high TyG index (> 9.10) and a high SHR (> 0.87) showed a significantly increased risk of CV death/TVMI (TyG index: HR 4.23, 95% CI 1.58-11.37; SHR: HR 5.14, 95% CI 1.89-13.98) and MACCEs (TyG index: HR 2.47, 95% CI 1.54-3.97; SHR: HR 2.91, 95% CI 1.84-4.60) compared with those with a low Tyg index and a low SHR (TyG < 8.56, SHR < 0.76). The area under the curve (AUC) values were 0.623 (TyG index) and 0.589 (SHR) for CV death/TVMI and 0.659 (TyG index) and 0.624 (SHR) for MACCEs. Furthermore, patients with both a high TyG index and a high SHR showed the highest risk of clinical outcomes among patients with different levels of these two biomarkers, and the AUC for the TyG-SHR combination was larger than the TyG index alone in predicting MACCE risk. CONCLUSIONS: The study revealed that a high TyG index and a high SHR were significantly correlated with poor prognosis in patients with CTO and suggested that these two biomarkers are reliable in predicting long-term prognosis in CTO patients.

High triglyceride-glucose index predicts cardiovascular events in patients with coronary bifurcation lesions: a large-scale cohort study.

BACKGROUND: Coronary bifurcation lesion, as a complex coronary lesion, is associated with higher risk of long-term poor prognosis than non-bifurcation lesions. The triglyceride-glucose (TyG) index has been shown to predict cardiovascular (CV) events in patients with coronary artery disease (CAD). However, the prognostic value of the TyG index in patients with bifurcation lesions who are at high risk of CV events remains undetermined. Therefore, this study aimed to investigate the association between the TyG index and CV events in patients with bifurcation lesions. METHODS: A total of 4530 consecutive patients with angiography-proven CAD and bifurcation lesions were included in this study from January 2017 to December 2018. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2]. Patients were assigned into 3 groups according to TyG tertiles (T) (T1: <8.633; T2: 8.633-9.096 and T3: ≥9.096). The primary endpoint was CV events, including CV death, nonfatal myocardial infarction and nonfatal stroke at 3-year follow-up. Restricted cubic spline (RCS) analysis, Kaplan-Meier curves and Cox proportional hazard models were used to investigate the associations between the TyG index and study endpoints. RESULTS: During a median follow-up of 3.1 years, 141 (3.1%) CV events occurred. RCS analysis demonstrated a linear relationship between the TyG index and events after adjusting for age and male sex (non-linear P = 0.262). After multivariable adjustments, elevated TyG index (both T2 and T3) was significantly associated with the risk of CV events (hazard ratio [HR], 1.68; 95% confidence interval [CI],1.06-2.65; HR, 2.10; 95%CI, 1.28-3.47, respectively). When study patients were further stratified according to glycemic status, higher TyG index was associated with significantly higher risk of CV events in diabetic patients after adjusting for confounding factors (T3 vs. T1; HR, 2.68; 95%CI, 1.17-6.11). In addition, subgroup analysis revealed consistent associations of the TyG index with 3-year CV events across various subgroups. Furthermore, adding the TyG index to the original model significantly improved the predictive performance. CONCLUSIONS: High TyG index was associated with CV events in patients with bifurcation lesions, suggesting the TyG index could help in risk stratification and prognosis in this population.

The impact of fasting stress hyperglycemia ratio, fasting plasma glucose and hemoglobin A1c on in-hospital mortality in patients with and without diabetes: findings from the China acute myocardial infarction registry.

BACKGROUND: Stress hyperglycemia was positively associated with poor prognosis in individuals with acute myocardial infarction (AMI). However, admission glucose and stress hyperglycemia ratio (SHR) may not be the best indicator of stress hyperglycemia. We performed this study to evaluate the comparative prognostic value of different measures of hyperglycemia (fasting SHR, fasting plasma glucose [FPG], and hemoglobin A1c [HbA1c]) for in-hospital mortality in AMI patients with or without diabetes. METHODS: In this prospective, nationwide, multicenter China Acute Myocardial Infarction (CAMI) registry, 5,308 AMI patients including 2081 with diabetes and 3227 without diabetes were evaluated. Fasting SHR was calculated using the formula [(first FPG (mmol/l))/(1.59×HbA1c (%)-2.59)]. According to the quartiles of fasting SHR, FPG and HbA1c, diabetic and non-diabetic patients were divided into four groups, respectively. The primary endpoint was in-hospital mortality. RESULTS: Overall, 225 (4.2%) patients died during hospitalization. Individuals in quartile 4 had a significantly higher rate of in-hospital mortality compared with those in quartile 1 in diabetic cohort (9.7% vs. 2.0%; adjusted odds ratio [OR] 4.070, 95% CI 2.014-8.228) and nondiabetic cohort (8.8% vs. 2.2%; adjusted OR 2.976, 95% CI 1.695-5.224). Fasting SHR was also correlated with higher in-hospital mortality when treated as a continuous variable in diabetic and nondiabetic patients. Similar results were observed for FPG either as a continuous variable or a categorical variable. In addition, fasting SHR and FPG, rather than HbA1c, had a moderate predictive value for in-hospital mortality in patients with diabetes (areas under the curve [AUC] for fasting SHR: 0.702; FPG: 0.689) and without diabetes (AUC for fasting SHR: 0.690; FPG: 0.693). The AUC for fasting SHR was not significantly different from that of FPG in diabetic and nondiabetic patients. Moreover, adding fasting SHR or FPG to the original model led to a significant improvement in C-statistic regardless of diabetic status. CONCLUSIONS: This study indicated that, in individuals with AMI, fasting SHR as well as FPG was strongly associated with in-hospital mortality regardless of glucose metabolism status. Fasting SHR and FPG might be considered as a useful marker for risk stratification in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT01874691.

HbA1c-based rather than fasting plasma glucose-based definitions of prediabetes identifies high-risk patients with angiographic coronary intermediate lesions: a prospective cohort study.

BACKGROUND: Prediabetes is common and associated with poor prognosis in patients with acute coronary syndrome and those undergoing revascularization. However, the impact of prediabetes on prognosis in patients with coronary intermediate lesions remains unclear. The objective of the current study is to explore the impact of prediabetes and compare the prognostic value of the different definitions of prediabetes in patients with coronary intermediate lesions. METHODS: A total of 1532 patients attending Fuwai hospital (Beijing, China), with intermediate angiographic coronary lesions, not undergoing revascularization, were followed-up from 2013 to 2021. Patients were classified as normal glucose tolerance (NGT), prediabetes and diabetes according to various definitions based on HbA1c or admission fasting plasma glucose (FPG). The primary endpoint was defined as major adverse cardiovascular events (MACE), the composite endpoint of all-cause death, non-fatal myocardial infarction and repeated revascularization therapy. Multivariate cox regression model was used to explore the association between categories of abnormal glucose category and MACE risk. RESULTS: The proportion of patients defined as prediabetes ranged from 3.92% to 47.06% depending on the definition used. A total of 197 MACE occurred during a median follow-up time of 6.1 years. Multivariate cox analysis showed that prediabetes according to the International Expert Committee (IEC) guideline (6.0 ≤ HbA1c < 6.5%) was associated with increased risk of MACE compared with NGT (hazard ratio [HR]: 1.705, 95% confidence interval [CI] 1.143-2.543) and after confounding adjustment (HR: 1.513, 95%CI 1.005-2.277). Consistently, the best cut-off point of glycated haemoglobin (HbA1c) identified based on the Youden's index was also 6%. Restricted cubic spline analysis delineated a linear positive relationship between baseline HbA1c and MACE risk. Globally, FPG or FPG-based definition of prediabetes was not associated with patients' outcome. CONCLUSIONS: In this cohort of patients with intermediate coronary lesions not undergoing revascularization therapy, prediabetes based on the IEC-HbA1c definition was associated with increased MACE risk compared with NGT, and may assist in identifying high-risk patients who can benefit from early lifestyle intervention.

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.