Single-cell RNA sequencing reveals the altered innate immunity in immune checkpoint inhibitor-related myocarditis.

Myocarditis has emerged as a rare but lethal immune checkpoint inhibitor (ICI)-associated toxicity. However, the exact mechanism and the specific therapeutic targets remain underexplored. In this study, we aim to characterise the transcriptomic profiles based on single-cell RNA sequencing from ICI-related myocarditis. Peripheral blood mononuclear cell (PBMC) samples were collected from four groups for single-cell RNA sequencing: (1) patients with newly diagnosed lung squamous cell carcinoma before treatment (Control Group); (2) patients with lung squamous cell carcinoma with PD-1 inhibitor therapy who did not develop myocarditis (PD-1 Group); (3) patients during fulminant ICI-related myocarditis onset (Myocarditis Group); and (4) Patients with fulminant ICI-related myocarditis during disease remission (Recovery Group). Subcluster determination, functional analysis, single-cell trajectory and cell-cell interaction analysis were performed after scRNA-seq. Bulk-RNA sequencing was performed for further validation. Our results revealed the diversity of cellular populations in ICI-related myocarditis, marked by their distinct transcriptional profiles and biological functions. Monocytes, NKs as well as B cells contribute to the regulation of innate immunity and inflammation in ICI-related myocarditis. With integrated analysis of scRNA-seq and bulk sequencing, we identified S100A protein family as a potential serum marker for ICI-related myocarditis. Our study has created a cell atlas of PBMC during ICI-related myocarditis, which would shed light on the pathophysiological mechanism and potential therapeutic targets of ICI-related myocarditis in continuous exploration.

MED1 Regulates BMP/TGF-ß in Endothelium: Implication for Pulmonary Hypertension.

BACKGROUND: Dysregulated BMP (bone morphogenetic protein) or TGF-ß (transforming growth factor beta) signaling pathways are imperative in idiopathic and familial pulmonary arterial hypertension (PAH) as well as experimental pulmonary hypertension (PH) in rodent models. MED1 (mediator complex subunit 1) is a key transcriptional co-activator and KLF4 (Krüppel-like factor 4) is a master transcription factor in endothelium. However, MED1 and KLF4 epigenetic and transcriptional regulations of the BMP/TGF-ß axes in pulmonary endothelium and their dysregulations leading to PAH remain elusive. We investigate the MED1/KLF4 co-regulation of the BMP/TGF-ß axes in endothelium by studying the epigenetic regulation of BMPR2 (BMP receptor type II), ETS-related gene (ERG), and TGFBR2 (TGF-ß receptor 2) and their involvement in the PH. METHODS: High-throughput screening involving data from RNA-seq, MED1 ChIP-seq, H3K27ac ChIP-seq, ATAC-seq, and high-throughput chromosome conformation capture together with in silico computations were used to explore the epigenetic and transcriptional regulation of BMPR2, ERG, and TGFBR2 by MED1 and KLF4. In vitro experiments with cultured pulmonary arterial endothelial cells (ECs) and bulk assays were used to validate results from these in silico analyses. Lung tissue from patients with idiopathic PAH, animals with experimental PH, and mice with endothelial ablation of MED1 (EC-MED1-/-) were used to study the PH-protective effect of MED1. RESULTS: Levels of MED1 were decreased in lung tissue or pulmonary arterial endothelial cells from idiopathic PAH patients and rodent PH models. Mechanistically, MED1 acted synergistically with KLF4 to transactivate BMPR2, ERG, and TGFBR2 via chromatin remodeling and enhancer-promoter interactions. EC-MED1-/- mice showed PH susceptibility. In contrast, MED1 overexpression mitigated the PH phenotype in rodents. CONCLUSIONS: A homeostatic regulation of BMPR2, ERG, and TGFBR2 in ECs by MED1 synergistic with KLF4 is essential for the normal function of the pulmonary endothelium. Dysregulation of MED1 and the resulting impairment of the BMP/TGF-ß signaling is implicated in the disease progression of PAH in humans and PH in rodent models.

Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism.

BACKGROUND: Increased circulating uric acid (UA) concentration may disrupt cardiac function in heart failure patients, but the specific mechanism remains unclear. Here, we postulate that hyperuremia induces sterol regulatory element binding protein 1 (SREBP1), which in turn activate hepatic fatty acid biosynthesis response, leading to cardiac dysfunction. METHODS AND RESULTS: Increased circulating uric acid was observed in heart failure patients and inversely correlated to cardiac function. Besides, uric acid correlated to circulating lipids profile based on metabolomics in heart failure patients. Using cultured human hepatoellular carcinomas (HepG2) and Tg(myl7:egfp) zebrafish, we demonstrated that UA regulated fatty acid synthase (FASN) via SREBP1 signaling pathway, leading to FFA accumulation and impaired energy metabolism, which could be rescued via SREBP1 knockdown. In ISO treated zebrafish, UA aggravated heart failure via increased cardiovascular cavity size, decreased heart beats, pericardial edema and long-stretched heart deformation. CONCLUSIONS: Our findings suggest that UA-SREBP1-FASN signaling exacerbates cardiac dysfunction during FFA accumulation. Identification of this mechanism may help in treatment and prevention of heart failure.

Exosomal microRNA-16-5p from macrophage exacerbates atherosclerosis via modulating mothers against decapentaplegic homolog 7.

OBJECTIVE: Studies have probed the function of microRNA (miR)-16-5p in the progression of atherosclerosis (AS), while the regulatory function of exosomal miR-16-5p from macrophage on AS remains largely unknown. This study commits to exploring the efficiency of exosomal miR-16-5p from macrophage on AS via modulating mothers against decapentaplegic homolog 7 (SMAD7). METHODS: Macrophages were cultured and transfected with miR-16-5p antagomir, then, the exosomes from macrophages were extracted. The AS mouse model was established, and miR-16-5p or SMAD7 expression in AS mice was detected. Thereafter, the effects of macrophage-derived exosomes, miR-16-5p or SMAD7 on serum inflammatory response, oxidative stress response, pathological changes and apoptosis in AS mice were observed by immunohistochemical and biochemical analysis. Finally, the binding relation between miR-16-5p and SMAD7 was examined. RESULTS: MiR-16-5p was elevated while SMAD7 was depleted in AS mice. Macrophage-derived exosomes aggravated AS progression via facilitating inflammatory response and oxidative stress, exacerbating pathological changes and increasing cell apoptosis in AS mice; while downregulation of miR-16-5p reversed the exacerbation of AS progression by macrophage-derived exosomes in AS mice. MiR-16-5p targeted SMAD7, and the down-regulated SMAD7 reversed the impacts of depleted miR-16-5p on AS progression. CONCLUSION: Exosomal miR-16-5p from macrophages aggravates AS progression via downregulating SMAD7 expression. This study provides novel therapeutic targets for AS treatment from the animal level.

In-hospital initiation of PCSK9 inhibitor and short-term lipid control in patients with acute myocardial infarction.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes when added to conventional statin therapy. This study aims to investigate the efficacy and safety of in-hospital initiation of PCSK9 inhibitors among patients with acute myocardial infarction (AMI) based on real-world experience. METHODS AND RESULTS: Data were collected from the Biobank of the First Affiliated Hospital of Xi'an Jiaotong University between January 2016 and December 2020. A total of 7556 AMI patients were screened for eligibility. Propensity Score Match (PSM) was employed, and covariates were age, sex, admission blood pressure and lipid profiles. Eligible participants were (1) propensity-matched 1:2:2 of statin plus evolocumab (dual therapy) vs. statin vs. statin plus ezetimibe. Ninety-five statin plus evolocumab users achieved significantly decreased low density lipoprotein (LDL) levels (0.92 ± 0.62 mmol/L in the 1st month and 1.17 ± 0.73 in the 3rd month) and a promising attainment rate of LDL (79.5% in the 1st month and 80.0% in the 3rd month) compared to the other two groups. (2) Propensity-matched 1:2:2 of statin plus ezetimibe evolocumab (triple therapy) vs. statin vs. statin plus ezetimibe. Similarly, 75 triple medication users achieved significantly decreased LDL levels and a promising attainment rate of LDL compared to the other two groups. In-hospital mortality and readmission rates within 3 months were then analyzed, and a decreased readmission rate was observed with PCSK9i therapy. CONCLUSIONS: Based on the present single-center real-world PSM-adjusted study, PCSK9i has been effective in short-term lipid control among AMI patients. The long-term effectiveness for reducing major cardiovascular events among AMI patients based on real-world experience remains to be explored. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov, ClinicalTrials.gov ID: NCT05184530.

Glycoursodeoxycholic acid ameliorates diet-induced metabolic disorders with inhibiting endoplasmic reticulum stress.

Recent studies reveal that bile acid metabolite composition and its metabolism are changed in metabolic disorders, such as obesity, type 2 diabetes and metabolic associated fatty liver disease (MAFLD), yet its role and the mechanism remain largely unknown. In the present study, metabolomic analysis of 163 serum and stool samples of our metabolic disease cohort was performed, and we identified glycoursodeoxycholic acid (GUDCA), glycine-conjugated bile acid produced from intestinal bacteria, was decreased in both serum and stool samples from patients with hyperglycemia. RNA-sequencing and quantitative PCR results indicated that GUDCA alleviated endoplasmic reticulum (ER) stress in livers of high fat diet (HFD)-fed mice without alteration of liver metabolism. In vitro, GUDCA reduced palmitic acid induced-ER stress and -apoptosis, as well as stabilized calcium homeostasis. In vivo, GUDCA exerted effects on amelioration of HFD-induced insulin resistance and hepatic steatosis. In parallel, ER stress and apoptosis were decreased in GUDCA-treated mice as compared with vehicle-treated mice in liver. These findings demonstrate that reduced GUDCA is an indicator of hyperglycemia. Supplementation of GUDCA could be an option for the treatment of diet-induced metabolic disorders, including insulin resistance and hepatic steatosis, with inhibiting ER stress.

Targeted metabolomic analysis of plasma fatty acids in acute myocardial infarction in young adults.

BACKGROUND AND AIMS: Acute myocardial infarction (AMI) in young adults has distinct clinical features and risk profile as compared with that in elder adults. The pathophysiologic mechanism of AMI in young adults remains unclear. In this study, we used targeted metabolomics to measure metabolic profile and analyzed plasma fatty acids levels in young adults with AMI, seeking to determine whether circulating fatty acid metabolism was correlated with the occurrence of AMI in young adults. METHODS AND RESULTS: Consecutive young and elder patients admitted to hospital for AMI were enrolled. Plasma samples of all participants were obtained after overnight fast and then measured using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) based targeted metabolomic platform. A total of 201 plasma metabolites were measured using UPLC-MS/MS. Several plasma fatty acids were significantly altered in young AMI patients compared with control or elder AMI patients, which also showed significant prediction value for AMI in young adults. Percentage of short chain fatty acids (SCFAs) was decreased and long chain increased in AMI as compared with control. Moreover, alpha-linolenic acid and linoleic acid metabolism (ALALAM) pathway metabolites were gradually increased in control, young, and elder AMI patients. Altered fatty acid correlation network further identified fatty acid metabolism disorder in AMI in young adults. CONCLUSION: By utilizing targeted metabolomic technique, we have found several altered fatty acids and respective pathways that show diagnostic value for AMI in young adults. SCFA and long-chain fatty acid (LCFA) were differentially altered in AMI patients.

Duration of Viral Shedding of Discharged Patients With Severe COVID-19.

COVID-19 has drawn global intensive attention. We analyzed the duration of viral shedding and the total time from illness onset to discharge in groups. This has important implications for making decisions for isolation of discharged patients and to provide guidance for the duration of hospitalization of patients with severe COVID-19.

Venous thrombosis and arteriosclerosis obliterans of lower extremities in a very severe patient with 2019 novel coronavirus disease: a case report.

The outbreak of 2019 novel coronavirus disease (COVID-19) began since early December 2019, and has been declared as a public health emergency by the World Health Organization. Due to the hypercoagulable state, blood stasis and endothelial injury, severe patients with COVID-19 are at high risk for thrombosis. We report a case of very severe COVID-19 complicated with venous thrombosis and arteriosclerosis obliterans of lower extremities. Risk stratification for deep vein thrombosis and peripheral arterial disease are of vital importance for the prognosis of COVID-19.

Dysregulated serum lipid profile and its correlation to disease activity in young female adults diagnosed with systemic lupus erythematosus: a cross-sectional study.

BACKGROUND: Recent studies showed that dyslipidemia could be a critical factor in the progression of cardiovascular disease in systemic lupus erythematosus (SLE). The aim of the present study was to describe the relationship between serum lipid profile and SLE disease activity in young female adults with SLE. METHODS: Seventy-one female subjects diagnosed with SLE aged 20~30 years were enrolled. Serum lipid profile including TC, TG, HDL-C, LDL-C, VLDL-C, Apo A, Apo B, and Apo E were evaluated between control and young female SLE patients. Univariate correlation analyses were performed to explore the correlation between serum lipid levels and SLE disease activity. RESULTS: Our results showed that TG and VLDL-C levels were significantly increased in young female SLE as compared to control, with TC, HDL-C, LDL-C, Apo A, and Apo B significantly reduced. Meanwhile, univariate correlation analyses showed negative correlations between SLE disease activity index and HDL-C, LDL-C, Apo A, and Apo B; with positive correlations between SLE disease activity index and TG and VLDL-C. CONCLUSION: Serum lipid profile was significantly dysregulated in young female SLE patients. Moreover, SLE disease activity was correlated to the serum lipid levels, supporting the notion that the young patients with SLE might also have a higher risk of cardiovascular disease.

Serum lipids profiling perturbances in patients with ischemic heart disease and ischemic cardiomyopathy.

BACKGROUND: Ischemic heart disease (IHD) is a common cardiovascular disorder associated with inadequate blood supply to the myocardium. Chronic coronary ischemia leads to ischemic cardiomyopathy (ICM). Despite their rising prevalence and morbidity, few studies have discussed the lipids alterations in these patients. METHODS: In this cross-sectional study, we analyzed serum lipids profile in IHD and ICM patients using a lipidomics approach. Consecutive consenting patients admitted to the hospital for IHD and ICM were enrolled. Serum samples were obtained after overnight fasting. Non-targeted metabolomics was applied to demonstrate lipids metabolic profile in control, IHD and ICM patients. RESULTS: A total of 63 and 62 lipids were detected in negative and positive ion mode respectively. Among them, 16:0 Lyso PI, 18:1 Lyso PI in negative ion mode, and 19:0 Lyso PC, 12:0 SM d18:1/12:0, 15:0 Lyso PC, 17:0 PC, 18:1-18:0 PC in positive ion mode were significantly altered both in IHD and ICM as compared to control. 13:0 Lyso PI, 18:0 Lyso PI, 16:0 PE, 14:0 PC DMPC, 16:0 ceramide, 18:0 ceramide in negative ion mode, and 17:0 PE, 19:0 PC, 14:0 Lyso PC, 20:0 Lyso PC, 18:0 PC DSPC, 18:0-22:6 PC in positive ion mode were significantly altered only in ICM as compared to IHD and control. CONCLUSION: Using non-targeted lipidomics profiling, we have successfully identified a group of circulating lipids that were significantly altered in IHD and ICM. The lipids metabolic signatures shed light on potential new biomarkers and therapeutics for preventing and treating ICM.

Targeting amino acids metabolic profile to identify novel metabolic characteristics in atrial fibrillation.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia whose incidence is on the rise globally. However, the pathophysiologic mechanism of AF remains poorly understood and there has been a lack of circulatory markers to diagnose and predict prognosis of AF. In the present study, by measuring metabolic profile and analyzing plasma amino acid levels in AF patients, we sought to determine whether amino acid metabolism was correlated to the occurrence of AF. Methods: Consecutive patients admitted to hospital for AF were enrolled. Plasma samples were obtained after overnight fast and a profile of 61 amino acids was then measured using gas chromatography/mass spectrometry (GC/MS). Results: Twenty-three AF and thirty-seven control patients were enrolled in the study. A number of plasma amino acids were altered in AF, which showed significant prediction value for AF. Intriguingly, circulating 4-hydroxypyrrolidine-2-carboxylic was gradually lowered with the persistence of AF. Plasma amino acid levels were more strongly correlated with each other in AF as compared with control. Conclusion: By utilizing non-target metabolic profile surveys, we have found a number of altered amino acids, which exhibit diagnostic value for AF. Enhanced amino acids correlation network further identified AF as a metabolism disorder.

Hemoglobin A1c is associated with severity of coronary artery stenosis but not with long term clinical outcomes in diabetic and nondiabetic patients with acute myocardial infarction undergoing primary angioplasty.

BACKGROUND: Acute myocardial infarction (AMI) patients with type 2 diabetes mellitus are known to present with multiple vessel lesions during coronary angiography. The underlying mechanism remains elusive and there is a shortage of serum prediction markers. In this study, we investigate the relationship between admission HbA1c and severity of coronary artery stenosis and subsequent prognosis in AMI patients with or without diabetes. RESEARCH DESIGN AND METHODS: We measured admission HbA1c, and vessel scores based on the number of diseased coronary vessels with significant stenosis in 628 patients diagnosed with AMI. Simple and multi-regression analysis were performed to investigate the correlation between HbA1c and the severity of coronary artery stenosis. Major adverse cardiovascular events (MACE), including new-onset myocardial infarction, acute heart failure and cardiac death, were documented during the follow-up. 272 non-DM participants and 137 DM participants were separated into two groups based on HbA1c levels for survival analysis during a 2-year follow up. RESULTS: 448 non-DM patients and 180 DM patients were included in the initial observational analysis. 272 non-DM patients and 137 DM patients were included in the follow-up survival analysis. The admission HbA1c level was found to be significantly positively correlated to the number of affected vessels suffering from significant coronary artery stenosis both in DM (R square = 0.012; 95% CI 0.002 to 0.623, P = 0.049) and non DM patients (R square = 0.025; 95% CI 0.009 to 0.289, P = 0.037). Kaplan-Meier survival analysis revealed no significant difference with regard to different HbA1c levels either in DM or non-DM patients at the end of follow-up. CONCLUSIONS: In patients with AMI, admission HbA1c is an important predictor for the severity of coronary artery stenosis in non-DM and DM patients. Further studies are needed to determine whether longer term follow-up could further identify the prognosis effect of HbA1c on MACE.

Chest Pain after Aortic Valve Replacement: Rupture of Right Sinus of Valsalva Presenting as Myocardial Infarction.

BACKGROUND: A 47-year-old male presented with retrosternal chest pain, which had started 4 days previously and had become excruciating for the past 6 h. He had undergone mechanical aortic valve replacement surgery 4 months previously. INVESTIGATION: Electrocardiography, echocardiography, computed tomography-angiography of the aorta. DIAGNOSIS: Rupture of the right sinus of Valsalva and right coronary artery dissection. MANAGEMENT: The defect in the right coronary sinus was closed, and the dissection at the root of the right coronary artery was resected and the right coronary artery bypassed to the root of the aorta.

Predictive value of serum TBA for 2-year MACEs in ACS patients undergoing PCI: a prospective cohort study.

Bile acids play important roles in lipid metabolism and glucose homeostasis. Limited research exist on the association between serum total bile acid (TBA) levels and major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS), particularly those with comorbid type 2 diabetes mellitus (T2DM). This study was conducted to examine the relationship between baseline serum TBA level and T2DM status in patients with ACS after percutaneous coronary intervention (PCI) and to identify the predictive value of TBA levels for a 2-year risk of MACEs. 425 ACS patients underwent PCI were recruited and divided into three groups based on baseline serum TBA concentration. An analysis of the association between the T2DM status and baseline serum TBA levels was conducted using univariate linear regression and multivariate linear regression. The predictive relevance of serum TBA levels was evaluated using the receiver operating characteristic (ROC) curve and Cox regression. Kaplan-Meier curves were employed to analyze the differences among groups in predicting MACEs over a 2-year follow-up period. Baseline serum TBA levels were higher in ACS patients who were diagnosed with T2DM (the median 3.6 µmol/L) than those without T2DM (the median 3.0 µmol/L). T2DM status in ACS patients was positively correlated with baseline serum TBA concentrations (ß: 1.7, 95% confidence interval [CI] 0.3-3.0), particularly in the male (ß: 2.0, 95% CI 0.3-3.6) and 50-69-year-old (ß: 2.5, 95% CI 0.6-4.4) populations. The areas under the ROC curve of baseline serum TBA levels predicted MACEs in ACS and ACS-T2DM patients following PCI were 0.649 (95% CI 0.595-0.703) and 0.783 (95% CI 0.685-0.881), respectively. Furthermore, Cox regression analysis showed that baseline serum TBA level was associated with the occurrence of MACEs in patients with ACS after PCI over a 2-year follow-up period, especially in those diagnosed with T2DM, whose baseline TBA concentration was lower than 10.0 µmol/L. ACS Patients with T2DM had higher serum TBA levels. TBA level at baseline was an independent predictor of MACEs in ACS patients who underwent PCI, especially with comorbid T2DM.

Statins aggravate insulin resistance through reduced blood glucagon-like peptide-1 levels in a microbiota-dependent manner.

Statins are currently the most common cholesterol-lowering drug, but the underlying mechanism of statin-induced hyperglycemia is unclear. To investigate whether the gut microbiome and its metabolites contribute to statin-associated glucose intolerance, we recruited 30 patients with atorvastatin and 10 controls, followed up for 16 weeks, and found a decreased abundance of the genus Clostridium in feces and altered serum and fecal bile acid profiles among patients with atorvastatin therapy. Animal experiments validated that statin could induce glucose intolerance, and transplantation of Clostridium sp. and supplementation of ursodeoxycholic acid (UDCA) could ameliorate statin-induced glucose intolerance. Furthermore, oral UDCA administration in humans alleviated the glucose intolerance without impairing the lipid-lowering effect. Our study demonstrated that the statin-induced hyperglycemic effect was attributed to the Clostridium sp.-bile acids axis and provided important insights into adjuvant therapy of UDCA to lower the adverse risk of statin therapy.

The Predictive Values of White Blood Cell Indices (Lymphocyte and Eosinophilic Granulocyte) for Heart Failure in Acute Coronary Syndrome Patients Following Percutaneous Coronary Intervention: A Prospective Cohort Study.

Background: White blood cell (WBC) indices are strongly associated with cardiovascular disease, but data on the prognostic values of these parameters in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI) are sparse. The current study aimed to investigate the relationship between baseline WBC indices levels and the incidence of heart failure (HF) in ACS patients after PCI and explore the predictive values over a 2-year follow-up period. Methods: A total of 416 consecutive ACS patients treated with PCI were enrolled and received a median of 27.7 months follow-up. Univariate and multivariate Cox regression analyses and the receiver operating characteristic (ROC) curves were performed. Results: Baseline lymphocyte (LYMPH) count, eosinophil (EO) count and eosinophil percentage (EO %) were higher in patients who experienced HF over a 2-year follow-up. In multivariate Cox proportional hazards analysis, LYMPH count, EO count and EO % were independently associated with the occurrence of HF (hazard ratio [HR] = 12.876, P = 0.025; HR = 16.625, P = 0.004; HR = 1.196, P = 0.031, respectively). The area under the ROC curve of baseline EO count predicting the occurrence of HF in ACS patients following PCI was 0.625 (P = 0.037). For patients aged 60 years and above, who had PCI or history of coronary artery bypass grafting, the higher EO count, the higher the risk of HF. Conclusion: Elevated baseline LYMPH count, EO count and EO % were independently associated with the incidence of HF in ACS patients following PCI, suggesting that WBC indices might be available, simple, and cost-efficient biomarkers with predictive value, especially for patients aged more than 60 years.

Higher serum triglyceride can predict recurrent coronary revascularization events in patients undergoing percutaneous coronary intervention with baseline LDL-C <55 mg/dL.

Patients with low baseline low-density lipoprotein cholesterol (LDL-C) but experiencing recurrent coronary revascularization events have been rarely investigated. In this retrospective cohort study, we enrolled patients undergoing percutaneous coronary intervention (PCI) with baseline LDL-C <55 mg/dL at the First Affiliated Hospital of Xi'an Jiaotong University between January and December 2017. Subsequent ischemia-driven coronary revascularization events and all-cause death were documented during a 4-year follow-up. Cox analysis was used to evaluate the association between baseline clinical characteristics and long-term events. As a result, among 388 patients (mean age 63 years; 79.1% male) enrolled, 32 patients underwent recurrent revascularization events, and 38 patients occurred all-cause death. After adjustment for age, diabetes mellitus, multi-vessel disease, and lipoprotein(a), multivariate Cox analysis showed that baseline serum triglyceride (TG) (HR 1.691, 95% CI 1.178 to 2.428, p=0.004) was an independent predictor of recurrent coronary revascularization events. Kaplan-Meier analysis revealed that a higher TG level (≥1.17 mmol/L, determined by receiver operating characteristic curve) was associated with increased risk of recurrent revascularization events than lower TG level (<1.17 mmol/L) (p=0.021). Female (HR 2.647, 95% CI 1.350 to 5.190, p=0.005) and previous atrial fibrillation (HR 3.163, 95% CI 1.403 to 7.132, p=0.006) were associated with increased risk of all-cause death. In conclusion, for patients undergoing PCI with baseline LDL-C <55 mg/dL, higher baseline TG can predict recurrent coronary revascularization events.

Case Report: Acute Myocarditis Due to PD-L1 Inhibitor Durvalumab Monotherapy in a Patient With Lung Squamous Cell Carcinoma.

Background: Durvalumab, as a PD-L1 inhibitor, is commonly used for the treatment of various cancers. Adverse events associated with the therapy include hepatitis, nephritis, dermatitis, and myocarditis. Especially, myocarditis as an adverse event after PD-L1 inhibitor therapy is characterized for its low incidence and high mortality. Case Summary: Here we present a rare case of a 67-year-old male with lung squamous cell carcinoma complicated with empyema who experienced myocarditis after only PD-L1 inhibitor durvalumab monotherapy. He presented with markedly decrease left ventricular ejection fraction, elevated Natriuretic peptide BNP, Troponin T, Troponin I, ESR, CRP and interleukin-6. The electrocardiogram showed sinus tachycardia, low voltage of limb leads, T wave inversion in anterior waves and V1-V3 QS type. Myocardial injury occurred in a short period and quickly returned to normal after glucocorticoids therapy. Conclusion: This case report is of clinical value for the treatment of PD-L1 related myocarditis.

Cardiotoxicity Related to Immune Checkpoint Inhibitors: A Real-World Retrospective Analysis.

Background: Cardiotoxicity related to immune checkpoint inhibitors (ICIs) is a rare but potentially lethal. In ICI-associated adverse events, evidence of cardiotoxicity and clinical predictive factors related to ICI is lacking. Here, we aim to assess the incidence and predictive factors of cardiotoxicity related to ICIs in real-world practice. Objective: We retrospectively analyzed consecutive patients who received PD-1 or PD-L1 at the First Affiliated Hospital of Xi'an Jiaotong University. Clinical characteristics and cardiac lesion markers were collected both at baseline and during longitudinal follow-up from the Biobank database. Follow-up CKMB and NT-proBNP levels and ratios were then evaluated. Results: A total of 2,304 patients with either PD-1 or PDL-1 utilization between August 2018 and April 2021 were collected. The average age was 59.44 ± 11.45 among PD-1 inhibitor utilizer and 58.97 ± 12.16 among PDL-1 inhibitor utilizer. The baseline creatine kinase isoenzyme MB (CKMB) levels were 17 ± 19 U/L in PD-1 inhibitor users and 17 ± 23 U/L in PDL-1 inhibitor users. Majority of patients were male, with advanced stage cancer, and received ICIs as second-line therapy. The longitudinal change of cardiac enzymes and NT-pro BNP were collected. Cardiac lesion as defined by three times increase of CKMB happens in only minority of patients receiving ICIs therapy. It is also identified that increased CKMB happened in PD-1 inhibitor groups, but not PDL-1 inhibitor groups. Conclusion: We evaluated the profile of cardiotoxicities caused by ICIs based on real-world experience. The cardiac lesion markers are generally unaltered, but it appears that the increased CKMB happened in PD-1 inhibitor groups, but not PDL-1 inhibitor groups.