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Background Cardiometabolic disease is a clinical syndrome characterized by multiple metabolic disorders, with atherosclerosis as the core and cardiovascular and cerebrovascular events as the outcome. Drug research and development (R&D) in cardiometabolic diseases has grown rapidly worldwide. However, the development of cardiometabolic drug clinical trials in China remains unclear. This study aims to depict the changing landscape of drug clinical trials for cardiometabolic diseases in China during 2009–2021. Methods The detailed information of drug trials on cardiometabolic diseases registered in the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform was collected between January 1, 2009, and July 1, 2021. The landscape of cardiometabolic drug clinical trials was analyzed by the characteristics, time trends, indications, pharmacological mechanisms, and geographical distribution. Results A total of 2466 drug clinical trials on cardiometabolic diseases were extracted and analyzed. The annual number of drug trials increased rapidly in the past twelve years. Among all the trials, the bioequivalence trials (1428; 58.3%) accounted for the largest proportion, followed by phase I (555; 22.5%), phase III (278; 11.3%), phase II (169; 6.9%), and phase IV (26; 1.1%). Of 2466 trials, 2133 (86.5%) trials were monomer drugs, only 236 (9.6%) trials were polypills and 97 (3.9%) were traditional Chinese medicine (TCM) compounds. In terms of pharmacological mechanisms, the number of trials in dihydropyridine (DHP) calcium antagonists 321 (11.9%) ranked first, while trials in angiotensin receptor blocker (ARB) 289 (10.7%) and dipeptidyl peptidase-4 (DPP-4) inhibitor 205 (7.6%) ranked second and third place respectively. Of 236 chemical polypills trials, 23 (9.7%) polypills were the combination of DHP calcium antagonists and statins, while others were the combination of two same pharmacological effect agents. As for the geographical distribution of leading units, 36 trials were led by principal investigators (PI) units from Beijing, followed by Jiangsu (n = 29), Shanghai (n = 19), Guangdong (n = 19), and Hunan (n = 19), showing an uneven regional distribution. Conclusions Great progress has been made in drug clinical trials on cardiometabolic diseases, especially in antihypertensive agents, hypoglycemic agents, and hypolipidemic agents. However, the insufficient innovation of first-in-class drugs and polypills should be carefully considered by all stakeholders in drug trials.

Background Familial hypercholesterolemia (FH) is an inherited metabolic disorder with a high level of low-density lipoprotein cholesterol and the worse prognosis. The triglyceride-glucose (TyG) index, an emerging tool to reflect insulin resistance (IR), is positively associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD) in healthy individuals, but the value of TyG index has never been evaluated in FH patients. This study aimed to determine the association between the TyG index and glucose metabolic indicators, insulin resistance (IR) status, the risk of ASCVD and mortality among FH patients. Methods Data from National Health and Nutrition Examination Survey (NHANES) 1999–2018 were utilized. 941 FH individuals with TyG index information were included and categorized into three groups: 9.0. Spearman correlation analysis was used to test the association of TyG index and various established glucose metabolism-related indicators. Logistic and Cox regression analysis were used to assess the association of TyG index with ASCVD and mortality. The possible nonlinear relationships between TyG index and the all-cause or cardiovascular death were further evaluated on a continuous scale with restricted cubic spline (RCS) curves. Results TyG index was positively associated with fasting glucose, HbA1c, fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) index (all p p = 0.01). During the median 114-month follow-up, 151 all-cause death and 57 cardiovascular death were recorded. Strong U/J-shaped relations were observed according to the RCS results (p = 0.0083 and 0.0046 for all-cause and cardiovascular death). A higher TyG index was independently associated with both all-cause death and cardiovascular death. Results remained similar among FH patients with IR (HOMA-IR ≥ 2.69). Moreover, addition of TyG index showed helpful discrimination of both survival from all-cause death and cardiovascular death (p Conclusion TyG index was applicable to reflect glucose metabolism status in FH adults, and a high TyG index was an independent risk factor of both ASCVD and mortality.

Context Limited studies have focused on the impact of subclinical hyperthyroidism (SHyper) on poor prognosis in patients with known coronary artery disease (CAD). Objective We implemented the present study to explore the association between SHyper and adverse cardiovascular events in CAD patients who underwent drug-eluting stent implantation. Methods We consecutively recruited 8283 CAD patients undergoing percutaneous coronary intervention (PCI). All subjects were divided into 2 groups according to their thyroid function: group 1 (euthyroidism group, n = 7942) and group 2 (SHyper group, n = 341). After 1:4 propensity score (PS) matching, 1603 patients (332 SHyper group and 1271 euthyroidism group) were selected. The primary endpoint was major adverse cardiovascular events (MACEs), a composite of cardiac mortality, nonfatal myocardial infarction (MI), and target vessel revascularization (TVR). Results Kaplan–Meier (K-M) survival analyses suggested that there was no significant difference in the primary endpoint and secondary endpoints (MACE: 11.4% vs 8.8%, log-rank P = .124; cardiac death: 1.2% vs 0.9%, log-rank P = .540; nonfatal MI: 5.7% vs 4%, log-rank P = .177; and TVR: 6% vs 4.7%, log-rank P = .303) in the PS-matched population. Cox regression analysis indicated that SHyper was not an independent risk factor for MACEs (HR 1.33, 95% CI 0.92-1.92, P = .127). Conclusion SHyper is not independently associated with adverse cardiovascular events in CAD patients undergoing PCI. More studies should be implemented in the future to assess the long-term predictive value of SHyper with thyrotropin levels

This study aimed to evaluate predictors for adverse cardiovascular outcomes in patients with atrial fibrillation (AF) undergoing coronary stenting.We retrospectively recruited consecutive patients with previously documented non-valvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. Major adverse cardiac/cerebrovascular events (MACCE) were a composite of all-cause death, non-fatal myocardial infarction, repeat revascularization, and ischaemic stroke/systemic thromboembolism (IS/STE). Major bleeding referred to grade 2 or higher of Bleeding Academic Research Consortium criteria.A total of 2394 patients (men: 72.3%Chinese patients with AF and coronary stenting had high mortality and incidence of MACCE. We compiled separate predictive models for all-cause death, IS/STE, MACCE, and major bleeding.

Aim: The efficacy and safety of ticagrelor and clopidogrel in patients with stable coronary artery disease (SCAD) undergoing percutaneous coronary intervention (PCI) remain uncertain. Thus, this study aimed to compare the efficacy and safety of ticagrelor and clopidogrel in patients with SCAD treated with PCI. Methods: A total of 9,379 patients with SCAD undergoing PCI who received dual antiplatelet therapy (DAPT) were consecutively enrolled in two groups, namely, ticagrelor ( n =1,081) and clopidogrel ( n =8,298) groups. Major adverse cardiovascular and cerebrovascular events (MACCEs) and bleeding events according to ticagrelor or clopidogrel use were compared. Results: After propensity matching ( n =1,081 in each group), ticagrelor was associated with fewer MACCEs compared with clopidogrel (3.6% vs. 5.7%, hazard ratio [HR]=0.62, 95% confidence interval [CI] 0.41–0.93, p =0.019), and the difference between ticagrelor and clopidogrel for bleeding events was nonsignificant (4.0% vs. 3.2%, HR=1.24, 95% CI 0.79-1.93, p =0.356). On the other hand, the difference between ticagrelor and clopidogrel for net adverse clinical events was significant (4.1% vs. 6.0%, HR=0.67, 95% CI 0.46–0.98, p =0.039). In a multivariate analysis, the use of ticagrelor, number of stents, previous history of diabetes, previous history of smoking, and ACC/AHA type B2 or C lesions were considered independent predictors of MACCEs, while radial artery access, previous history of stroke, and weight ＜60kg were independent predictors of bleeding events. Conclusions Ticagrelor was associated with a lower incidence of MACCEs without an increased risk of bleeding events in patients with SCAD receiving PCI.

We aim to analyze the effect of liver fibrosis, assessed by the Fibrosis-4 (FIB-4) index, on cardiovascular events in acute coronary syndrome (ACS) patients with and without type 2 diabetes mellitus (T2DM).6563 ACS patients undergoing PCI were analyzed in this study. Patients were divided into three groups according to literature-based FIB-4 cut-offs:1.45, 1.45-3.25, and ≥ 3.25.During the median 2.4-year follow-up, 270 major adverse cardiac and cerebrovascular events (MACCE) and 194 major bleeding were recorded. Intermediate or high FIB-4 scores were significantly associated with an elevated risk of MACCE, mortality, and MI but not associated with ischemic stroke and major bleeding. Further restricted cubic spline analysis showed that FIB-4 as a continuous variable was positively associated with an increased adjusted risk of MACCE. The results were consistent in subgroups with and without T2DM.Liver fibrosis staged by FIB-4 was correlated with an increased risk of MACCE, mortality, and MI in ACS patients who underwent PCI with and without T2DM. FIB-4 index may help risk stratification of ACS patients independent of T2DM status.

Thyroid dysfunction contributes to adverse events in several types of cardiovascular diseases. The aim of the present study is to determine whether thyroid status is associated with the prognosis of patients with acute myocardial infarction (AMI). The present cohort arose from the China PEACE‑Prospective AMI study. Based on the evaluation of thyroid status, participants were divided into euthyroid, hypothyroid, and hyperthyroid groups. A total of 2569 AMI patients met the inclusion criteria of our present study. The primary outcomes were the 12-month composite cardiovascular endpoint (CCVE, a composite of all-cause death, myocardial infarction, revascularization, and heart failure) and the composite cardio-cerebral vascular endpoint (CCCVE, comprising CCVE and stroke). Of the entire cohort, 431 patients (16.8%) confirmed hypothyroid status and 102 (4.0%) were at hyperthyroid status. There were total 594 CCVEs (23.1%) and 687 CCCVEs (26.7%) in the general population. After adjusting conventional risk factors, AMI patients from the hypothyroid status group were at increased risk of the two composite endpoints, compared with euthyroid individuals (CCVE, HR:1.337, 95%CI: 1.097–1.630; CCCVE, HR:1.336, 95%CI: 1.111–1.607). However, no significant increased trends of the two composite endpoints could be observed in hyperthyroid group. Furthermore, hypothyroid status was also independently associated with a higher risk of revascularization (HR: 1.648, 95%CI: 1.047–2.595) and heart failure (HR: 1.382, 95%CI: 1.066–1.792). Compared with euthyroid status, hypothyroid status has an independent predicting value for adverse cardiovascular events in AMI patients. Further investigations are required to illustrate whether treatment of thyroid dysfunction could improve the prognosis of AMI patients.

Debate exists on the prognostic significance of spontaneous myocardial infarction (SMI) and periprocedural myocardial infarction (PMI), which could be diagnosed by various definitions.A total of 10,724 patients undergoing percutaneous coronary intervention (PCI) were consecutively enrolled and followed up for a median of 2.4 years. We evaluated outcomes of all-cause death, cardiac death, and major adverse cardiovascular events (MACE). Patients were stratified into three groups, including the No MI group, PMI group, and SMI group. PMI was defined based on different diagnostic criteria, including the third and fourth universal myocardial infarction (MI) definitions, the society for cardiovascular angiography and interventions (SCAI) definition, and the independent biomarker definition. Regardless of these definitions, the PMI groups were all associated with a significantly increased MACE risk at one year or 1000 days (all P0.05), but not all-cause or cardiac death. The SMI group was associated with a markedly elevated risk of death and MACE, but it showed no significant different risk of MACE to PMI using varying definitions.According to various PMI definitions, PMI and SMI were associated with an increased risk of MACE, but not death for PMI. No significantly different risk of MACE was observed between PMI and SMI.

Background:. Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR). Methods:. The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism. Results:. The results demonstrated that increased TSH levels were significantly associated with higher TC (β = 0.052, P = 0.002) and LDL (β = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (β = 0.240, P = 0.033) and LDL (β = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids. Conclusion:. Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.

Background Acute respiratory infections have been associated with a transient increase in cardiovascular risk. However, whether such an association persists beyond 1 month and the potential modifying effect of cardiovascular risk factors on such an association are less well established. Methods The China Kadoorie Biobank enrolled 512 726 participants aged 30–79 years from 10 areas across China during 2004–2008. By the end of 2017, a total of 5444 participants with new-onset ischaemic heart disease (IHD) and 4846 with ischaemic stroke (IS) who also had at least a record of hospitalization for pneumonia during follow-up were included. We used a self-controlled case-series method and calculated the age- and season-adjusted relative incidences (RIs) and 95% confidence intervals (CIs) for ischaemic cardiovascular disease (CVD) after pneumonia. Results The risk of ischaemic CVD increased during days 1–3 after pneumonia hospitalization, with an RI (95% CI) of 4.24 (2.92–6.15) for IHD and 1.85 (1.02–3.35) for IS. The risk gradually reduced with longer duration since pneumonia hospitalization but remained elevated until days 92–365 for IHD (1.23, 1.12–1.35) and days 29–91 for IS (1.25, 1.05–1.48). Pre-existing cardiovascular risk factors amplified the associations between pneumonia and ischaemic CVD risks, such as chronic obstructive pulmonary disease for both IHD and IS, and diabetes and smoking for IHD (all Pinteraction Conclusion Among middle-aged and older Chinese adults, pneumonia hospitalization was associated with both short- and long-term increases in ischaemic CVD risk for ≤1 year.

Aims. This study sought to report the 10-year clinical outcomes of patients who underwent unprotected left main (LM) percutaneous coronary intervention (PCI) in a large centre. Methods and Results. A total of 913 consecutive patients who underwent unprotected LM PCI from January 2004 to December 2008 at Fu Wai Hospital were retrospectively analysed; the mean age was 60.0 ± 10.9 years, females accounted for 22% of patients, diabetes was present in 27.7% of patients, and an LM bifurcation lesion occurred in 82.9% of patients. During the median follow-up of 9.7 years, major adverse cardiac or cerebrovascular events (MACCEs) occurred in 25.6% (234) of patients, and the rates of all-cause death, myocardial infarction, and stroke were 14.9%, 11.0%, and 7.1%, respectively. Cardiac death occurred in only 7.9% of patients. The estimated event rate was 41.9% for death/myocardial infarction/any revascularization and 45.9% for death/MI/stroke/any revascularization. Definite/probable stent thrombosis occurred in 4.3% (39) of patients. According to the subgroup analysis, IVUS-guided PCI was associated with less long-term MACCEs. Further multivariate analysis identified that age and LVEF

The efficacy and safety of ticagrelor and clopidogrel in East Asian patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains uncertain. The purpose of this study was to compare the efficacy and safety of ticagrelor and clopidogrel in East Asian patients with CAD treated with PCI.A total of 12383 patients with CAD undergoing PCI who received dual antiplatelet therapy (DAPT) were consecutively enrolled in the ticagrelor group (After propensity matching (Ticagrelor was associated with a lower incidence of MACCEs and an increased risk of TIMI bleeding events in East Asian patients with CAD receiving PCI.

Background: Cardiac ryanodine receptor 2 (RyR2) dysfunction and elevated diastolic Ca2+ leak have been linked to arrhythmogenesis not only in inherited arrhythmia syndromes but also in acquired forms of heart disease including heart failure (HF) and atrial fibrillation (AF). Thus, stabilizing RyR2 may exert therapeutic effects in these conditions. Objective: The purpose of this study was to investigate the effects of stabilizing RyR2 with chronic dantrolene treatment on HF development and AF inducibility in a myocardial infarction (MI)–induced HF model in rats. Methods: MI was induced in adult Sprague-Dawley rats by ligation of the left anterior descending coronary artery. Two weeks after MI surgery, rats with large MI (≥40%) were randomly assigned to MI-vehicle (n = 14) or MI-dantrolene (10 mg/kg/d; n = 13) groups. Sham-surgery rats (n = 7) served as controls. Results: Compared to the MI-vehicle group, 4-week dantrolene treatment significantly improved cardiac function, with increased left ventricular (LV) fractional shortening (19.48% ± 3.61% vs 15.43% ± 2.65%; P

Background:. Imprecise interpretation of coronary angiograms was reported and resulted in inappropriate revascularization. Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score is a comprehensive system to evaluate the complexity of the overall lesions. We hypothesized that a real-time SYNTAX score feedback from image analysts may rectify the mis-estimation and improve revascularization appropriateness in patients with stable coronary artery disease (CAD). Methods:. In this single-center, historical control study, patients with stable CAD with coronary lesion stenosis ≥50% were consecutively recruited. During the control period, SYNTAX scores were calculated by treating cardiologists. During the intervention period, SYNTAX scores were calculated by image analysts immediately after coronary angiography and were provided to cardiologists in real-time to aid decision-making. The primary outcome was revascularization deemed inappropriate by Chinese appropriate use criteria for coronary revascularization. Results:. A total of 3245 patients were enrolled and assigned to the control group (08/2016–03/2017, n = 1525) or the intervention group (03/2017–09/2017, n = 1720). For SYNTAX score tertiles, 17.9% patients were overestimated and 4.3% were underestimated by cardiologists in the control group. After adjustment, inappropriate revascularization significantly decreased in the intervention group compared with the control group (adjusted odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.73–0.95; P = 0.007). Both inappropriate percutaneous coronary intervention (adjusted OR: 0.82; 95% CI: 0.74–0.92; P

OBJECTIVE In recent years, some studies have indicated that a novel marker described as the stress hyperglycemia ratio (SHR) can reflect true acute hyperglycemic status and is associated with the short-term poor prognosis in patients with acute myocardial infarction. In the current study we evaluated the association of SHR with adverse cardiovascular events among patients with acute coronary syndrome (ACS). RESEARCH DESIGN AND METHODS We consecutively enrolled 5,562 ACS patients who underwent drug-eluting stent (DES) implantation. All subjects were divided into five groups according to SHR, which was determined by the following formula: ABG / [(28.7 × HbA1c %) − 46.7], where ABG is admission blood glucose level. The primary end point was major adverse cardiovascular and cerebrovascular events (MACCE) at the 2-year follow-up, and the secondary end point included major adverse cardiovascular events (MACE) at 2-year follow-up, cardiac death, and nonfatal myocardial infarction (MI) at 2-year follow-up and in-hospital cardiac death and nonfatal MI. RESULTS A total of 643 MACCE were recorded during a median follow-up of 28.3 months. Kaplan-Meier survival analysis showed the lowest MACCE incidence in quintile 3 (P < 0.001). Moreover, the outcomes of restricted cubic spline analysis suggested that there was a U-shaped or J-shaped association between the SHR and early and late cardiovascular outcomes even after adjustment for other confounding factors. CONCLUSIONS There were U-shaped associations of SHR with MACCE rate and MACE rate at 2-year follow-ups and J-shaped associations of SHR with in-hospital cardiac death and MI and that at 2-year follow-up in ACS patients who underwent DES implantation, and the inflection point of SHR for poor prognosis was 0.78.

OBJECTIVE: Presently, an effective model to predict long-term cardiac mortality in patients with hypertrophic obstructive cardiomyopathy (HOCM) is lacking. Therefore, the objective of this study was to evaluate the predictive value of the modified Age, Creatinine clearance, and Ejection Fraction (mACEF) score for long-term cardiac mortality in patients with HOCM. METHODS: Two hundred and ninety two patients with HOCM treated non-invasively were enrolled in this study, all of whom had intact medical information. RESULTS: Over a median follow-up period of 41.9 months, 28 cardiac deaths occurred. In univariate Cox regression analysis, the mACEF score was associated with long-term cardiac death [hazard ratio (HR)=1.795, 95% confidence interval (CI) 1.518–2.124, p

BackgroundThe triglyceride-glucose index (TyG index) is a valuable marker for predicting adverse cardiovascular events in diabetic patients. However, for nondiabetic patients, whether the TyG index is independently related to poor prognosis remains unclear. This cohort study assessed the association of the TyG index with future cardiovascular risk in nondiabetic subjects who received percutaneous coronary intervention (PCI).MethodsWe consecutively enrolled 5,489 nondiabetic patients who underwent PCI. All experimental subjects were divided into three groups based on their TyG index, which was determined by the equation ln (fasting triglyceride (mg/dl) × fasting blood glucose (mg/dl)/2). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, and target vessel revascularization (TVR).ResultsA total of 386 MACCE were documented during a median 29-month follow-up. The Kaplan–Meier survival results indicated that among the three groups, there was no obvious difference in any endpoints. Further Cox regression analyses suggested that the TyG index was not independently related to adverse cardiovascular outcomes for nondiabetic patients who underwent PCI (HR: 0.77, 95% CI 0.56–1.16, P = 0.210 for MACCE). Subgroup analysis suggested that the TyG index was independently relevant to MACCE for patients with low-density lipoprotein cholesterol (LDL-C) lower than 1.8 mmol/L.ConclusionThe TyG index is not an effective predictive factor for adverse cardiovascular prognosis in nondiabetic patients who underwent PCI. However, in subjects with LDL-C lower than 1.8mmol/L, it may predict future cardiovascular risk.

Background: The Chinese appropriate use criteria (AUC) for coronary revascularization was released in 2016 to improve the use of coronary revascularization. This study aimed to evaluate the association between the appropriateness of coronary revascularization based on the Chinese AUC and 1-year outcomes in stable coronary artery disease (CAD) patients. Methods: We conducted a prospective, multi-center cohort study of stable CAD patients with coronary lesion stenosis ≥50%. After the classification of appropriateness based on Chinese AUC, patients were categorized into the coronary revascularization group or the medical therapy group based on treatment received. The primary outcome was a composite of death, myocardial infarction, stroke, repeated revascularization, and ischemic symptoms with hospital admission. Results: From August 2016 to August 2017, 6085 patients were consecutively enrolled. Coronary revascularization was associated with a lower adjusted hazard of 1-year major adverse cardiovascular and cerebrovascular events (MACCEs; hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.45–0.86; P = 0.004) than medical therapy in patients with appropriate indications (n = 1617). No significant benefit in 1-year MACCEs was found after revascularization compared to after medical therapy in patients with uncertain indications (n = 2658, HR: 0.81; 95% CI: 0.52–1.25; P = 0.338) and inappropriate indications (n = 1810, HR: 0.80; 95% CI: 0.51–1.23; P = 0.308). Conclusions: In patients with appropriate indications according to Chinese AUC, coronary revascularization was associated with significantly lower risk of MACCEs at 1 year. No benefit was found in coronary revascularization in patients with inappropriate indications. Our findings provide evidence for using Chinese AUC to guide clinical decision-making. Clinical trial registration: NCT02880605. https://www.clinicaltrials.gov. Key words: Stable coronary artery disease; Appropriate use criteria; Coronary revascularization

Objective To investigate what is the most appropriate strategy for patients with ST-segment elevation myocardial infarction (STEMI) aged ≥80 years in China. Methods This cohort study retrospectively enrolled patients with STEMI aged ≥80 years old and grouped them according to the treatment strategy that was used: a conservative treatment strategy or an invasive treatment strategy. Factors associated with whether to perform an invasive intervention, in-hospital death and a good prognosis were investigated using logistic regression analyses. Results A total of 232 patients were enrolled: conservative treatment group ( n = 93) and invasive treatment group ( n = 139). Patients in the invasive treatment group had a better prognosis and lower incidence of adverse events compared with the conservative treatment group. Advanced age, creatinine level and a higher Killip class were inversely correlated with whether to perform an invasive intervention, while the use of beta-receptor-blocking agents was a favourable factor for invasive treatment. Hypertension and a higher Killip class were risk factors for in-hospital death, while the use of beta-receptor-blocking agents and diuretics decreased the risk of in-hospital death. Conclusions An invasive treatment strategy was superior to a conservative treatment strategy in patients with STEMI aged ≥80 years.

Background Coronary artery-to-pulmonary artery fistula is a rare disorder characterized by abnormal vascular communication between the coronary artery and pulmonary artery. While most patients remain asymptomatic, some might exhibit symptoms of myocardial ischemia, congestive heart failure, or even sudden cardiac death if coronary aneurysm, thrombosis, infective carditis, or other congenital cardiac defects coexist. Case presentation We present a 66-year-old male complaining of angina pectoris with a history of hypertension and active smoking. He was diagnosed with a coronary aneurysm based on coronary computed tomography angiography. We subsequently identified a coronary artery-to-pulmonary artery fistula with giant aneurysmal dilation on coronary angiography. Ultimately we conducted surgery ligation and aneurysmorrhaphy. During surgery, we discovered newly formed thrombus within the aneurysmal cavity. Histological analysis of the aneurysmal wall supported the diagnosis of the congenital disorder. Our patient was successfully discharged and remained asymptomatic at two months of follow-up. Conclusion We presented a rare and complex combination of congenital coronary artery-to pulmonary artery fistula, giant coronary aneurysmal dilatation, and thrombosis through multi-modality evaluations.

PURPOSE/OBJECTIVE(S) To compare the prognostic value of neoadjuvant rectal (NAR) score and MRI-based nomogram model for locally advanced rectal cancer (LARC) treated with neoadjuvant therapy. MATERIALS/METHODS Retrospective analysis was performed for 233 patients with LARC (T3-4 and/or N1-2, M0), who were initially treated in our institution from Mar.2015 to Mar.2018. All patients had baseline MRI assessments and received neoadjuvant therapy and TME surgery. The neoadjuvant rectal (NAR) score was calculated according to the baseline MRI factor (cT) and pathological stage (pT, pN). NAR = [5pN-3(cT-pT)+12]2/9.61. The patients were sequentially allocated to two cohorts (training cohort and validation cohort) in a ratio of 4:3 based on the date of image examination. The nomogram model was constructed based on the results of univariate logistic regression analysis and multivariable cox regression analysis of the training cohort for disease-free survival (DFS). The nomogram and NAR score were evaluated by Harrell's concordance index (C-index), calibration plots, receiver operating characteristic curve (ROC) analysis, and decision curve analysis (DCA) in both training and validation cohort. RESULTS With a median follow-up of 43.2 months (13.3-61.3months) in the training cohort and 32.0 months (12.3-39.5 months) in the validation cohort. Multivariate cox regression analysis identified the MRI-detected extramural vascular invasion (mrEMV), pathological T stage (ypT) and perineural invasion (PNI) as independent predictors. According to previous studies, lymph vascular invasion (LVI) (which was founded to be significant after univariate regression analysis) and three other independent predictors are included in the nomogram model. The univariate survival analysis showed that the nomogram model and NAR score were correlated with 3-year DFS (P < 0.05). For comparison, the nomogram performed better over the NAR score (C-index 0.76 (95% CI 0.70-0.84) versus 0.66 (95% CI 0.60-0.71) for the training cohort, and 0.77 (95% CI 0.70-0.85) versus 0.69(0.60-0.78) for the validation cohort).The nomogram model achieved a better 3-year DFS predictive capacity (AUC = 0.84 in the training cohort; AUC = 0.77 in the validation cohort) than NAR score (AUC = 0.70 in the training cohort; AUC = 0.73 in the validation cohort). DCA revealed that the use of the nomogram model was associated with better benefit gains relative to the prediction of 3-year DFS compared to NAR score in training cohort (threshold probability range between 0.06 and 0.54) and validation cohort (threshold probability range between 0.08 and 0.50). CONCLUSION We developed and validated a novel nomogram model based on MRI factor and pathological factors for predicting DFS in LARC treated with neoadjuvant therapy. Compared with NAR score, nomogram model shows the better potential predictive value of prognosis, which could improve the risk stratification and individual treatment for LARC patients.

BACKGROUND: Altered thyroid function and increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) are prognostic factors in acute myocardial infarction (AMI). The study aims to investigate whether free triiodothyronine (fT3) and NT-proBNP are prognostic factors for long-term outcomes in patients with AMI undergoing percutaneous coronary intervention (PCI). METHODS: This was an observational, prospective, single-center study of consecutive patients enrolled at Fuwai Hospital between January, 2013 and December, 2013. The patients were divided into two groups according to fT3 levels: low fT3 (2 years of follow-up, patients with low fT3 levels had higher rates of MACEs than those with normal fT3 (27.0% vs. 7.8%, P802.7 pg/mL [hazard ratio (HR) =5.063, 95% confidence interval (CI): 3.176–8.071, P802.7 pg/mL and fT3

BackgroundThis study aims to investigate the role of free triiodothyronine (fT3) in predicting poor prognosis of adult patients with acute myocarditis.MethodsA total of 173 consecutive adult patients with acute myocarditis completed thyroid function evaluations. They were divided into two groups according to fT3 levels: low fT3 group (n = 54, fT3 < 3.54 pmol/liter) and normal fT3 group (n = 119, fT3 ≥ 3.54 pmol/liter). The primary endpoint was major adverse cardiac events (MACE).ResultsDuring the 3.5 ± 2.8 years follow-up, the rate of MACE was 29.6% versus 3.5% in low fT3 group versus normal fT3 group, respectively (P < 0.0001). Long-term at 8 years MACE-free survival were lower in low fT3 group versus normal fT3 group (52.9% versus 92.3%, log-rank P < 0.0001), respectively. Univariate Cox analysis showed that left ventricular ejection fraction (LVEF) < 50% [hazard ratio (HR) 10.231, 95% confidence interval (CI): 3.418–30.624, P < 0.0001) and low fT3 level (HR 0.360, 95% CI: 0.223–0.582, P < 0.0001) were strongest two predictors of MACE. After adjustment for traditional risk predictors, the prognostic value of fT3 status was still significant (HR 0.540, 95% CI: 0.316–0.922, P = 0.024). Compared with normal fT3 group, those in low fT3 group were at a much higher risk of MACE (HR 5.074, 95% CI: 1.518–16.964, P = 0.008).ConclusionsLow T3 syndrome was a strong predictor of poor prognosis in adult patients with acute myocarditis. These findings suggest that fT3 level could serve as a biomarker for risk stratification in acute myocarditis patients.

BackgroundHigh lipoprotein(a) (Lp[a]) levels are associated with increased risks of cardiovascular events in Percutaneous Coronary Intervention (PCI) patients with diabetes mellitus (DM). Peri-procedural myocardial infarction (PMI) occurs commonly during the PCI, whereas the relationship between Lp(a) and PMI remains unclear. Our study aimed to evaluate the association between Lp(a) value and the incidence of PMI in a larger-scale diabetic cohort undergoing PCI throughout 2013.MethodsA total of 2,190 consecutive patients with DM were divided into two groups according to the median Lp(a) level of 175 mg/L: Low Lp(a) group (N = 1095) and high Lp(a) group (N = 1095). PMI was defined based on the 2018 universal definition of myocardial infarction.ResultsPatients with high Lp(a) levels exhibited higher rates of PMI compared to those with low Lp(a) levels (2.3% versus 0.8%, P = 0.006). The multivariable logistic analysis showed that PMI was independently predicted by Lp(a) as a dichotomous variable (OR 2.64, 95%CI 1.22–5.70) and as a continuous variable (OR 1.57, 95% CI 1.12–2.20). However, further investigation found that this association was only maintained in men, whose Lp(a) levels were significantly associated with the frequency of PMI, both as a dichotomous variable (OR 3.66, 95%CI 1.34–10.01) and as a continuous variable (OR 1.81, 95%CI 1.18–2.78). Lp(a) wasn’t a risk factor of PMI in women.ConclusionsHigh Lp(a) levels had forceful correlations with the increased frequency of PMI in male diabetic patients undergoing PCI. Lp(a) might act as a marker of risk stratification and a therapeutic target to reduce PCI-related ischemic events.

Objective: Sex differences in the clinical outcomes of patients with atrial fibrillation (AF) and coronary stenting should be assessed according to age. Methods: We analyzed the clinical data of all patients with nonvalvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. Results: A total of 2,146 patients (71.8% men and 28.2% women) were included in the study. The mean age of the patients was 66.6±9.4 years. Women in this study were older and had higher prevalence of hypertension, diabetes, chronic kidney disease (CKD), and anemia. Smoking history was found to be higher in men, and women were less likely to be current smokers. The mean follow-up duration was 39.7 months. Women younger than 65 years had a remarkably higher mortality (11.2% vs. 5.3%, p=0.012) and a significantly lower rate of repeat revascularization (1.6% vs. 6.3%, p=0.034) than men. Female gender remained an independent predictor for all-cause mortality [hazard ratio (HR)=2.03, 95% confidence interval (CI): 1.09–3.79, p=0.025], along with heart failure (HR=3.64, 95% CI: 2.02–6.57, p

BACKGROUND: The prognostic value of the CYP2C19 genotype in post-percutaneous coronary intervention (PCI) patients remains controversial. The recently-published, limited-sample PHARMCLO trial indicates a personalized pharmacogenomic approach may reduce adverse events. This study aimed to determine the prognostic value of CYP2C19 genotypes. METHODS: The original cohort consisted of 10,724 PCI patients in 2013. 756 patients with genotyped CYP2C19 were included in our analysis. The CYP2C19 genotype prognostic value was tested based on different clinical factors. The primary endpoint was major adverse cardio- and cerebro-vascular event (MACCE). RESULTS: MACCE 2-years post-PCI occurred in 19 patients (17.4%) in poor metabolizers (PM, CYP2C19 *2/*2, *2/*3, *3/*3), 43 patients (12.2%) in intermediate metabolizers (IM, CYP2C19 *1/*2 or *1/*3) and 27 patients (9.2%) in extensive metabolizers (EM, CYP2C19 *1/*1). PM was an independent MACCE predictor compared with EM (HR: 1.960, 95% CI: 1.139–3.372), but the difference between IM and PM was not significant (HR: 1.314, 95% CI: 0.843–2.048). Major bleeding (BARC grade ≥3) was not significantly different between the three groups (2.5% vs. 2.1% vs. 0.8%, P=0.133). Subgroup analysis showed that the CYP2C19 genotype prognostic value was present in the following subgroups: male, age >60 years, body mass index (BMI) >24 kg/m(2), SYNTAX score >15, current smokers, and patients without chronic kidney disease. CONCLUSIONS: Utilizing CYP2C19 genotype to guide post-PCI antiplatelet therapy might be appropriate in patients with the following characteristics: male, age >60 years, BMI >24 kg/m(2), SYNTAX score >15, current smokers, and non-chronic kidney disease (CKD) patients.

Subclinical hypothyroidism and low T3 syndrome are commonly associated with an increased risk of cardiovascular disease (CVD) and mortality. We examined effects of T3 on T-tubule (TT) structures, Ca2+ mobilization and contractility, and clustering of dyadic proteins. Thyroid hormone (TH) deficiency was induced in adult female rats by propyl-thiouracil (PTU; 0.025%) treatment for 8 weeks. Rats were then randomized to continued PTU or triiodo-L-thyronine (T3; 10 μg/kg/d) treatment for 2 weeks (PTU + T3). After in vivo echocardiographic and hemodynamic recordings, cardiomyocytes (CM) were isolated to record Ca2+ transients and contractility. TT organization was assessed by confocal microscopy, and STORM images were captured to measure ryanodine receptor (RyR2) cluster number and size, and L-type Ca2+ channel (LTCC, Cav1.2) co-localization. Expressed genes including two integral TT proteins, junctophilin-2 (Jph-2) and bridging integrator-1 (BIN1), were analyzed in left ventricular (LV) tissues and cultured CM using qPCR and RNA sequencing. The T3 dosage used normalized serum T3, and reversed adverse effects of TH deficiency on in vivo measures of cardiac function. Recordings of isolated CM indicated that T3 increased rates of Ca2+ release and re-uptake, resulting in increased velocities of sarcomere shortening and re-lengthening. TT periodicity was significantly decreased, with reduced transverse tubules but increased longitudinal tubules in TH-deficient CMs and LV tissue, and these structures were normalized by T3 treatment. Analysis of STORM data of PTU myocytes showed decreased RyR2 cluster numbers and RyR localizations within each cluster without significant changes in Cav1.2 localizations within RyR clusters. T3 treatment normalized RyR2 cluster size and number. qPCR and RNAseq analyses of LV and cultured CM showed that Jph2 expression was T3-responsive, and its increase with treatment may explain improved TT organization and RyR-LTCC coupling.

The present study aimed to explore the clinical characteristics and management of retroperitoneal hematoma (RPH) after invasive intervention during a 12-year period in China. A retrospective review of patients with RPH after various invasive interventions was conducted at the China National Center for Cardiovascular Diseases. A total of 42 patients with a mean age of 63.1±2.5 years were continuously recruited in the study between January 2007 and September 2018. The incidence, manifestations and management of RPH were analyzed. A total of 20 patients had punctures in the femoral arterial access under the inguinal ligament and 5 patients had punctures above the inguinal ligament. The majority of RPH occurred within 24 h after intervention, while some occurred after postoperative 24 h. Pain was the most common symptom in patients with RPH. All patients who underwent intervention presented a reduction in hemoglobin (HB) concentration. The overall incidence of nosocomial infection was 38.1% and mortality was 7.1%. The findings demonstrated that RPH is a rare complication after invasive intervention of cardiovascular diseases with non-specific clinical manifestations. The reduction of HB concentration was a vital manifestation for RPH. Most RPH cases could be treated by conservative treatment and blood transfusion. A puncture in the femoral arterial access under the inguinal ligament may result in RPH.

Background: The prevalence of familial hypercholesterolemia (FH) in the patients with acute myocardial infarction (AMI) in China is unclear. Materials and Methods: In China Acute Myocardial Infarction (CAMI) Registry, 13,002 patients with age 18–80 were consecutively enrolled with first-onset AMI who were naïve to statin before admission from January 1st, 2013 to October 31st, 2014. According to Dutch Lipid Clinical Network Criteria (DLCNC), the patients were divided to heterozygous familial hypercholesterolemia (HeFH) (definite/probable HeFH, possible HeFH) or non-HeFH group. Results: The number of the patients in the three groups was as following, 62 in definite/probable HeFH group, 484 in possible HeFH group, 12,456 in non-HeFH group. The prevalence of HeFH is 4.2% (including 0.47% of definite/probable HeFH, 3.73% of possible FH). The average age of onset of first-time AMI was 54 ± 12, 56 ± 12, 63 ± 12 years old (p < 0.0001) in definite/probable HeFH group, possible HeFH group and non-HeFH group, respectively. The percentage of Killip III or above (8.1 vs. 4.3 vs. 6.3%, p = 0.1629), cardiac arrest (1.6 vs. 0.6 vs. 0.9%, p = 0.6990), and TIMI 0–2 grade after primary percutaneous cardiac intervention (PCI) (0 vs. 6.8 vs. 4.3%, p = 0.5866) was not significantly different in definite/probable HeFH group, possible HeFH group and non-HeFH group, respectively. Conclusions: The prevalence of HeFH in Chinese patients with AMI is 4.2%. The patients were significantly younger in HeFH group, when compared with those with non-HeFH. However, no significant differences were found in the severity of clinical manifestations in both HeFH and non-HeFH group.

BACKGROUND It is ill-defined which factors affect the prognosis of patients with recanalized chronic total occlusion (CTO). This study sought to investigate predictors for adverse outcome in such a cohort with long-time follow-up. METHODS From 2010 to 2013, patients with successfully recanalized CTO were included. The primary endpoint was a composite of all-cause death, myocardial infarction or target vessel revascularization (TVR). The secondary endpoints were TVR and target lesion revascularization (TLR). RESULTS A total of 1987 patients were enrolled and 1806 (90.6%) subjects completed 5-year follow-up. Multivariate Cox analysis revealed that age ≥ 75 years (HR,1.70; 95% CI, 1.09-2.64; P = .02), left ventricular ejection fraction

There are controversies on optimal stenting strategy regarding true left main (LM) bifurcation lesions. The present study compared 1- and 2-stenting strategy for patients with true LM bifurcation lesions as differentiated by DEFINITION criteria. 928 patients with true LM bifurcation lesions (Medina 1,1,1 or 0,1,1) treated with DES were enrolled consecutively. 297 (32.0%) patients were identified as complex LM bifurcation, and 631 (68.0%) patients into simple LM bifurcation group according to DEFINTION criteria. Patients in complex vs. simple LM bifurcation group had significantly higher major adverse cardiac event (MACE, including cardiac death, myocardial infarction [MI] and ischemia-driven target vessel revascularization) rate at 30 days (7.8% vs. 4.0%, p = 0.01), 1 year (10.3% vs. 6.4%, p = 0.04), and numerically at 3 years (14.2% vs. 10.1%, p = 0.07), which was mainly driven by increased MI. Moreover, patients in the 2-stent strategy group had strong trend towards lower incidence of cardiac death in both complex LM bifurcation group (2.0% vs. 5.9%, p = 0.08) and simple LM bifurcation group (1.9% vs. 4.5%, p = 0.07). In conclusion, the complex bifurcation lesion criteria established in DEFINITION study was able to risk-stratify LM bifurcation patients. Two-stent technique yielded numerically lower 3-year cardiac mortality regardless of LM bifurcation complexity.

Xiangbin Meng,1,* Wenyao Wang,2,* Kuo Zhang,2,* Yu Qi,2 Shimin An,2 Siyuan Wang,2 Jilin Zheng,2 Joyce Kong,3 Henghui Liu,4 Jing Wu,4 Yong Zhou,5 Chuanyu Gao,1 Yi-Da Tang2 1Department of Cardiology, Zhengzhou University People’s Hospital, Zhengzhou, Henan, China; 2Department of Cardiology Medicine, Coronary Heart Disease Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 3New York Institute of Technology-College of Osteopathic Medicine, Old Westbury, NY, USA; 4Beijing Recdata Technology Co., Ltd., Beijing, China; 5Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vascular Diseases, Beijing, China *These authors contributed equally to this work Background: Epicardial adipose tissue (EAT) is considered an important source of bioactive molecules that can influence coronary arteries directly and is related to the concurrent presence of both obstructive coronary stenosis and myocardial ischemia independently. Non-alcoholic fatty liver disease (NAFLD) has become an emergent health problem worldwide. Aim: This cross-sectional study aimed to address the relationship between the volume of EAT and NAFLD and other cardiovascular risk factors in the general population. Materials and methods: In this study, we selected a total of 2,238 participants aged at least 40 years from the Jidong community in Tangshan, China. The 64-slice CT was used to survey the volume of EAT and liver ultrasonography was used for the diagnosis of NAFLD. The study cohorts were compared according to EAT volume. Results: Cardiovascular risk factors, such as coronary artery calcium score, carotid intima-media thickness, NAFLD, and ideal cardiovascular health metrics were also found to be related to EAT. In multivariate logistic regression analysis, NAFLD groups showed significant association with higher EAT volume, after correcting for main cardiovascular disease risk factors (OR [95% CI], 1.407 [1.117, 1.773]). Conclusion: Our findings in a general community population provide evidence that EAT is strongly associated with NAFLD and other cardiovascular risk factors. Keywords: epicardial adipose tissue, EAT, coronary artery calcium, CAC, carotid intima-media thickness, CIMT, ideal cardiovascular health metrics, CVH

Background: Beta blockers are standard therapy for myocardial infarction (MI). Preclinical studies have shown efficacy and safety of thyroid hormone (TH) treatment of cardiovascular disorders. Since THs interact with the sympathoadrenergic system, this study aimed to compare triiodothyronine (T3) and metoprolol (Met) in the treatment of rats with MI on pathophysiology and TH-adrenergic signaling. Methods: Female Sprague–Dawley rats aged 12 weeks underwent left anterior descending coronary artery ligation (MI) or sham surgeries. T3 (5 μg/kg/day) or Met (100 mg/kg/day) was given in drinking water immediately after surgery for eight weeks. At the terminal of the experiments, the rats were subjected to morphological, functional, and molecular examination. Results: T3 and Met significantly enhanced left ventricular contractility (left ventricular fractional shortening 21.37 ± 2.58% and 21.14 ± 3.71%, respectively) compared to untreated MI (17.88 ± 1.23%), and decreased the incidence of inducible atrial tachyarrhythmia by 87.5% and 62.5%, respectively. Although both treatments showed efficacy, T3 but not Met showed statistically significant improvements compared to MI in arrhythmia duration, left atrial diameter (T3 vs. MI 4.33 ± 0.63 vs. 5.65 ± 1.32 mm; p

Background: Patients undergoing percutaneous coronary intervention react differently to antiplatelet drugs. Those with low responsiveness to clopidogrel have a higher risk of cardiac ischemic events. The goal of this study is to conduct a head-to-head comparison of the safety and effectiveness of intensified antiplatelet therapies (either double-dose clopidogrel [DOUBLE] or adjunctive cilostazol [TRIPLE]) and conventional strategy (STANDARD) in patients after percutaneous coronary intervention. Methods: In this single-center, randomized, controlled trial, we used thromboelastography, a platelet function test, to select 1078 patients undergoing percutaneous coronary intervention at high thrombotic risk and compared the intensified antiplatelet therapies with standard antiplatelet therapy. The primary outcome was the incidence of major adverse cardiac and cerebrovascular events at 18 months after percutaneous coronary intervention, defined as a composite of all-cause death, myocardial infarction, target vessel revascularization, or stroke. Bleeding Academic Research Consortium defined bleeding complications (types 1, 2, 3, or 5) were the safety end points. Results: The primary end point occurred in 52 patients (14.4%) in the STANDARD group, 38 patients (10.6%) in the DOUBLE group, and 30 patients (8.5%) in the TRIPLE group (hazard ratio, 0.720; 95% confidence interval, 0.474–1.094, DOUBLE versus STANDARD; hazard ratio, 0.550; 95% confidence interval, 0.349–0.866, TRIPLE versus STANDARD). No significant difference in the rates of major bleeding (Bleeding Academic Research Consortium grade≥3) was found in the DOUBLE group (3.34% versus 1.93% in STANDARD, P =0.133) and the TRIPLE group (2.53% versus 1.93% in STANDARD, P =0.240). The rate of Bleeding Academic Research Consortium–defined minor bleeding increased in the DOUBLE group (27.4% versus 20.3% in STANDARD, P =0.031), but not in the TRIPLE group (23.6% versus 20.3% in STANDARD, P =0.146). Conclusions: In patients with low responsiveness to clopidogrel, as measured by thromboelastography, the intensified antiplatelet strategies with adjunctive use of cilostazol significantly improved the clinical outcomes without increasing the risk of major bleeding. Decreased trend of negative outcomes could be observed in patients with double dosage of clopidogrel, but the difference was not significant. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01779401.

With the development of coronary angiography for the diagnosis of coronary artery disease, its clinical significance in detecting coronary artery anomalies and evaluating the seriousness is attracting more attention. In the study we aimed to assess the prevalence of anomalous origin of coronary arteries in a Chinese population who underwent coronary angiography for coronary artery disease, and explore any patterns in the common variants and typical anomalies, especially the potentially serious ones. Patients who underwent coronary angiography from January 2013 to December 2016 in Fuwai Hospital were included. Baseline characteristics and angiographic data were collected, the incidence of anomalous origin of coronary arteries was calculated, and the typical patterns were analyzed. Comparisons between the present results and those of existing reports were also conducted. A total of 110,158 patients were included in the study, among which 0.76% (835 cases) had anomalous origin of coronary arteries. Among the anomalies, the incidences of anomalous origin of the right coronary artery (RCA), the left coronary artery (LCA), both the RCA and LCA, single coronary artery (SCA) and dextrocardia were 76.76% (641 cases), 14.61% (122 cases), 1.80% (15 cases), 4.67% (39 cases) and 2.16% (18 cases), respectively. Moreover, 47.54% (397 cases) of the anomalies were shown to be potentially serious, and an RCA arising from the left sinus of Valsalva (LSV) was the most common subtype (39.28%, 328 cases). Although anomalous origin of coronary arteries is not quite common, more clinical attention should be paid to this condition due to the potential risk of serious sequelae.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent and complex disease that confers a high risk of severe liver disorders. Despite such public and clinical health importance, very few effective therapies are currently available for NAFLD. We report a protective function and the underlying mechanism of dual-specificity phosphatase 14 (DUSP14) in NAFLD and related metabolic disorders. Insulin resistance, hepatic lipid accumulation, and concomitant inflammatory responses, key pathological processes involved in NAFLD development, were significantly ameliorated by hepatocyte-specific DUSP14 overexpression (DUSP14-HTG) in high-fat diet (HFD)-induced or genetically obese mouse models. By contrast, specific DUSP14 deficiency in hepatocytes (DUSP14-HKO) aggravated these pathological alterations. We provided mechanistic evidence that DUSP14 directly binds to and dephosphorylates transforming growth factor β-activated kinase 1 (TAK1), resulting in the reduced activation of TAK1 and its downstream signaling molecules c-Jun N-terminal kinase 1 (JNK), p38, and nuclear factor kappa B NF-κB. This effect was further evidenced by the finding that inhibiting TAK1 activity effectively attenuated the deterioration of glucolipid metabolic phenotype in DUSP14-HKO mice challenged by HFD administration. Furthermore, we identified that both the binding domain and the phosphatase activity of DUSP14 are required for its protective role against hepatic steatosis, because interruption of the DUSP14-TAK1 interaction abolished the mitigative effects of DUSP14. CONCLUSION Hepatocyte DUSP14 is required for maintaining hepatic metabolic homeostasis and for suppressing inflammation, a novel function that relies on constraining TAK1 hyperactivation. (Hepatology 2018;67:1320-1338).

Purpose/Objective(s) Portal vein or hepatic vein tumor thrombosis is a leading predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). We conduct this phase II clinical trial to investigate the efficacy and safety of concurrent sorafenib and radiotherapy for advanced HCC with portal vein and/or hepatic vein tumor thrombosis. Materials/Methods We designed a single-arm, prospective phase II trial to evaluate median survival time (MST), overall response rate (ORR), time to progression (TTP) and toxicities in patients of HCC with portal vein and/or hepatic vein tumor thrombosis receiving concurrent sorafenib and radiotherapy. Eligibility criteria included the following: clinical or histologic diagnosis of HCC with portal vein or hepatic vein tumor thrombosis; liver-GTV > 700ml; and ECOG performance status score of 0 or 1 etc. Eligibility patients would receive radiotherapy to hepatic primary tumor and vein tumor thrombosis with concurrently sorafenib with a dose of 400mg twice daily. Prescription of radiotherapy would be a conventional fraction dose of 2-2.6Gy to a total dose of 40 to 65Gy to tumor. Sorafenib will be maintained with a dose of 400mg twice daily after radiotherapy until disease progression, or unacceptable adverse events. Results Between April 2018 and January 2020, a total of 86 eligible patients were enrolled. Seventy patients were with portal vein thrombosis, 5 patients were with hepatic vein tumor thrombosis, and 11 patients were with portal vein and hepatic vein tumor thrombosis. For portal vein thrombosis, 87.5% patients involved main trunk or first branches of portal vein. For hepatic vein tumor thrombosis, 43.8% patients involved inferior vena cava, and 2 patients involved right atrium. The median dose of radiotherapy was 54Gy (40-65Gy). ORR was 53.4% and disease control rate (DCR) was 76.6%. With a median follow-up of 24 months for living patients, MST and TTP was 16.8 months and 7.1 months, respectively. The 2-year local control rate for hepatic primary tumor and tumor thrombosis were 83.0% and 90.7%, respectively. Out-field recurrence in liver and distance metastasis were the main failure pattern. The 2-year out-field recurrence rate in liver and distance metastasis rate were 43.6% and 45.7%. Concurrent sorafenib and radiotherapy was well tolerated by patients. All patients were able to complete radiotherapy as planned. And 87.2% patients could complete concurrent sorafenib as a dose of 400mg twice daily. The most common grade 3 toxicities were thrombocytopenia (23.3%), leukopenia (14.0%), dermatitis (4.7%), anemia (3.5%), hand-foot syndrome (2.3%) and elevated alanine aminotransferase (2.3%). Classical or non-classical radiation-induced liver disease was not noted. Conclusion Concurrent sorafenib and radiotherapy is an effective, well tolerated and promising treatment in HCC patients with portal vein and/or hepatic vein tumor thrombosis. This trial was registered at ClinicalTrials.gov (number NCT03535259).

Purpose/Objective(s) Anti-programmed death-1 (PD-1) is an emerging paradigm for treating metastatic malignancies. However, limited response rate and unsatisfactory results of PD-1 inhibitor as monotherapy in advanced liver cancer prompted the exploration of combination strategies. Preclinical studies demonstrated that combination of radiation and PD-1 inhibitors can synergistically augment the anti-tumor efficacy induced by both agents. This study addressed the hypothesis that the application of radiation combined with Toripalimab, an anti-PD-1 agent, may foster immune efficacy in metastatic and recurrent liver cancer. Materials/Methods We did this study in patients with stage IV (defined by the American Joint Committee on Cancer 8th edition staging system) or recurrent liver cancer in 2nd-line or 3rd-line treatment, with an Eastern Cooperative Oncology Group performance score of 0-2, child-Pugh grade of A-B. All enrolled patients received radiation at doses of 40-60Gy. Toripalimab (240mg per day, 21 days per cycle) was delivered during and/or after radiation until progression or severe toxicities. The primary endpoint was progression-free survival and the secondary endpoints were objective response, overall survival and toxicities. Survivals were calculated from the beginning of immunotherapy. Results From April 2017 to September 2020, 17 patients were enrolled and evaluable. Sixteen patients (94.1%) were male and 1(5.9%) was female. The median age was 56 years old (range 36-74 years old). Ten patients (58.8%) had hepatocellular carcinoma. Sixteen patients (94.1%) were with Child-Pugh grade A. Fifty-two lesions, including 15 venous tumor emboli, 13 metastatic bones, 12 lymph nodes, 11 liver malignancies and 2 other sites, received radiation. The median radiation dose is 53Gy (40-60Gy, 2-4Gy per fraction). Sixteen patients received targeted therapy (9 patients with sorafenib, 3 patients with lenvatinib, 3 patients with regorafenib and 1 patient with apatinib) during the treatment of immunotherapy and radiotherapy. The objective response rate and disease control rate were 64.7% (the complete response was 5.9% and partial response was 58.8%) and 88.2%. Grade≥3 adverse events were observed in 5 patients (29.4%), including 3 with thrombocytopenia (2 with grade 4, 1 with grade 3),1 with gastrointestinal event and 1 with infection. All the adverse events were cured after treatment. The median follow-up time was 15.9 months. At the last follow up, 6 patients died. No in-field relapse was recorded. Progression-free survival was 43.3% at 1 year and 21.6% at 2 years, overall survival was 60% at 1 year and 24% at 2 years. The median survival time and progression free survival time were 12.1 months and 11.1 months, respectively. Conclusion For patients with advanced or recurrent liver cancer, toripalimab in combination with concurrent or previous radiotherapy is an effective treatment with tolerable toxicities. A prospective trial with large number of patients is warranted.

BACKGROUND: Thyroid dysfunction and myocardial fibrosis are both associated with cardiovascular events in patients with dilated cardiomyopathy (DCM). HYPOTHESIS: The combination of thyroid hormone (TH) and myocardial fibrosis (detected by late gadolinium enhancement [LGE]) is an independent and incremental predictor of adverse events in DCM. METHODS: We consecutively enrolled 220 idiopathic DCM patients with thyroid function and LGE assessment at Fuwai Hospital (China) from January 2010 to October 2011 and followed up through December 2015. Patients were divided into 4 groups according to the presence or absence of LGE and FT3 value (median level of 2.79 pg/mL): LGE‐positive + FT3

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, impaired insulin sensitivity, and chronic low-grade inflammation. However, the pathogenic mechanism of NAFLD is poorly understood, which hinders the exploration of possible treatments. Here, we report that ubiquitin-specific protease 18 (USP18), a member of the deubiquitinating enzyme family, plays regulatory roles in NAFLD progression. Expression of USP18 was down-regulated in the livers of nonalcoholic steatohepatitis patients and high-fat diet (HFD)-induced or genetically obese mice. When challenged with HFD, hepatocyte-specific USP18 transgenic mice exhibited improved lipid metabolism and insulin sensitivity, whereas mice knocked out of USP18 expression showed adverse trends regarding hepatic steatosis and glucose metabolic disorders. Furthermore, the concomitant inflammatory response was suppressed in USP18-hepatocyte-specific transgenic mice and promoted in USP18-hepatocyte-specific knockout mice treated with HFD. Mechanistically, hepatocyte USP18 ameliorates hepatic steatosis by interacting with and deubiquitinating transforming growth factorβ-activated kinase 1 (TAK1), which inhibits TAK1 activation and subsequently suppresses the downstream c-Jun N-terminal kinase and nuclear factor kappa B signaling pathways. This is further validated by alleviated steatotic phenotypes and highly activated insulin signaling in HFD-fed USP18-hepatocyte-specific knockout mice administered a TAK1 inhibitor. The therapeutic effect of USP18 on NAFLD relies on its deubiquitinating activity because HFD-fed mice injected with active-site mutant USP18 failed to inhibit hepatic steatosis. Conclusion USP18 associates with and deubiquitinates TAK1 to protect against hepatic steatosis, insulin resistance, and the inflammatory response. (Hepatology 2017;66:1866-1884).

In most developed countries, coronary artery disease (CAD), mostly caused by atherosclerosis of coronary arteries, is one of the primary causes of death. From 1990s to 2000s, mortality caused by acute MI declined up to 50%. The incidence of CAD is related with age, gender, economic, etc. Atherosclerosis contains some highly correlative processes such as lipid disturbances, thrombosis, inflammation, vascular smooth cell activation, remodeling, platelet activation, endothelial dysfunction, oxidative stress, altered matrix metabolism, and genetic factors. Risk factors of CAD exist among many individuals of the general population, which includes hypertension, lipids and lipoproteins metabolism disturbances, diabetes mellitus, chronic kidney disease, age, genders, lifestyle, cigarette smoking, diet, obesity, and family history. Angina pectoris is caused by myocardial ischemia in the main expression of pain in the chest or adjoining area, which is usually a result of exertion and related to myocardial function disorder. Typical angina pectoris would last for minutes with gradual exacerbation. Rest, sit, or stop walking are the usual preference for patients with angina, and reaching the maximum intensity in seconds is uncommon. Rest or nitroglycerin usage can relieve typical angina pectoris within minutes. So far, a widely accepted angina pectoris severity grading system included CCS (Canadian Cardiovascular Society) classification, Califf score, and Goldman scale. Patients with ST-segment elevated myocardial infarction (STEMI) may have different symptoms and signs of both severe angina pectoris and various complications. The combination of rising usage of sensitive MI biomarkers and precise imaging techniques, including electrocardiograph (ECG), computed tomography, and cardiac magnetic resonance imaging, made the new MI criteria necessary. Complications of acute myocardial infarction include left ventricular dysfunction, cardiogenic shock, structural complications, arrhythmia, recurrent chest discomfort, recurrent ischemia and infarction, pericardial effusion, pericarditis, post-myocardial infarction syndrome, venous thrombosis pulmonary embolism, left ventricular aneurysm, left ventricular thrombus, and arterial embolism.

Thyroid hormone (TH) has strong positive chronotropic and inotropic action on cardiac myocyte during systolic period and also enhances the duration of diastolic relaxation. Systolic and diastolic changes of the heart made by triiodothyronine (T3) is not only caused by its direct action on cardiac myocyte but also indirectly mediated by its effects on peripheral vessels and renin-angiotensin-aldosterone system (RAAS). In hyperthyroid heart, the number of β-adrenergic receptors is upregulated, causing an imbalanced sympathovagal tone. In hyperthyroidism, thyroid hormones promote the breakdown of collagen by increasing matrix metalloproteinase-1 activity, leading to hypertrophy without increased fibrosis, at least in the earlier stage. Hypothyroidism-mediated characteristic changes in the expression of cardiac genes, such as reduced levels of the sarcoplasmic reticulum Ca2+-ATPase (SERCA2), and increased expression of phospholamban, which play a significant role in regulating intracellular calcium cycling, can partly account for the decreased cardiac contractility and the abnormalities in diastolic function. Thyroid dysfunction also alters blood pressure, and hypertension combined with hypothyroidism appears to be characterized by a low-renin state. Animal models showed that administration of low-dose T3 after myocardial infarction improved cardiac structure and function, decreased the incidence of tachyarrhythmia, and reduced adverse left ventricular remodeling. The beneficial effects of thyroid hormone make it potentially attractive for the usage in the management of cardiac diastolic and systolic dysfunction.

BACKGROUND: This study aims to investigate the gender differences in treatment strategies among non-ST-segment elevation myocardial infarction (NSTEMI) patients ≥80 years old in China. METHODS: A total of 190 consecutive NSTEMI patients ≥80 years old in Fuwai Hospital were included from 2014 to 2017. These patients were grouped by gender, and sub-grouped by conservative treatment or invasive treatment. The clinical characteristics, medical history, discharge drug used, and prognosis were collected and compared between these two treatment strategies. RESULTS: There were significant differences between these two treatment strategies in terms of GRACE grade, history of myocardial infarction (MI), after coronary artery bypass grafting (CABG), III grade, renal dysfunction, anemia, and use of diuretic (P

Background Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) prevents ischemic events while increasing bleeding risk. Real-world-based metrics to accurately predict postdischarge bleeding (PDB) occurrence and its potential impact on postdischarge major cardiovascular event (MACE) remain undefined. This study sought to evaluate the impact of PDB on MACE occurrence, and to develop a score to predict PDB risk among Chinese acute coronary syndrome (ACS) patients after PCI. Methods and results From May 2014 to January 2016, 2496 ACS patients who underwent PCI were recruited consecutively from 29 nationally representative Chinese tertiary hospitals. Among 2,381 patients (95.4%, 2,381/2,496) who completed 1-year follow-up, the cumulative incidence of PDB (bleeding academic research consortium type [BARC] ≥2) and postdischarge MACE (a composite of all-cause death, nonfatal myocardial infarction, ischemic stroke, or urgent revascularization) was 4.9% (n = 117) and 3.3% (n = 79), respectively. The association between PDB and MACE during 1-year follow-up, as well as the impact of DAPT with ticagrelor or clopidogrel on PDB were evaluated. PDB was associated with higher risk of postdischarge MACE (7.7 vs. 3.1%; adjusted hazard ratio: 2.59 [95% confidence interval: 1.17-5.74]; p = .02). For ticagrelor versus clopidogrel, PDB risk was higher (8.0 vs. 4.4%; 2.05 [1.17-3.60]; p = .01), while MACE risk was similar (2.0 vs. 3.4%; 0.70 [0.25-1.93]; p = .49). Based on identified PDB predictors, the constructed bleeding risk in real world Chinese acute coronary syndrome patients (BRIC-ACS) score for PDB was established. C-statistic for the score for PDB was 0.67 (95% CI: 0.62-0.73) in the overall cohort, and >0.70 in subgroups with non-ST- and ST-segment elevation myocardial infarction, diabetes and receiving more than two drug eluting stents. Conclusions In Chinese ACS patients, PDB with BARC ≥2 was associated with higher risk for MACE after PCI. The constructed BRIC-ACS risk score provides a useful tool for PDB discrimination, particularly among high ischemic and bleeding risk patients.

Background Subclinical hypothyroidism is a common condition in patients with heart failure and is defined as elevated serum thyroid hormone (TSH) with normal circulating free thyroxine (FT4). Evidence on the effect of thyroid hormone treatment is lacking. We designed a randomized controlled trial to compare the efficacy and safety of thyroid hormone supplementation in patients with chronic heart failure complicated with subclinical hypothyroidism. Methods/design Eligible participants were identified from the cardiology units of five study centers based on the following criteria: 18 years or older, systolic heart failure with NewYork Heart Association (NYHA) class II–III, left ventricular ejection fraction ≤ 40%, and subclinical hypothyroidism (TSH > 4.78μIU/ml

ObjectivesThis study sought to investigate the relationship between occlusion length and long-term outcomes of patients with recanalised chronic total occlusion (CTO) lesion.DesignA retrospective cohort study.SettingFuwai Hospital, National Center for Cardiovascular Disease, Beijing, ChinaParticipantsConsecutive patients with successfully recanalised CTO were included from January 2010 to December 2013.Primary and secondary outcome measuresThe primary endpoint of the present study was a composite event of all-cause death and myocardial infarction (MI). The secondary endpoints included target lesion revascularisation (TLR) and target vessel revascularisation (TVR).ResultsA total of 1987 patients were included and 1801 (90.6%) subjects completed 5-year follow-up in this study. Based on occlusion length, the patients were divided equally into two groups: short (length ConclusionPatients with long CTO lesion did not show a higher risk of death and MI after recanalisation, but had higher risks of TLR and TVR. Lesion with occlusion length ≥15 mm should be under close surveillance for restenosis after recanalisation.