[Genetic testing and clinical analysis of a patient with Dilated cardiomyopathy due to variant of FLNC gene].

OBJECTIVE: To explore the genetic basis for a patient with Dilated cardiomyopathy. METHODS: A patient admitted to Beijing Anzhen Hospital Affiliated to Capital Medical University in April 2022 was selected as the study subject. Clinical data and family history of the patient was collected. Targeted exome sequencing was carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of the American College of Medical Genetics and Genomics (ACMG). RESULTS: DNA sequencing revealed that the patient has harbored a heterozygous c.5044dupG frameshift variant of the FLNC gene. Based on the ACMG guidelines, the variant was predicted to be likely pathogenic (PVS1+PM2_Supporting+PP4). CONCLUSION: The heterozygous c.5044dupG variant of the FLNC gene probably underlay the pathogenesis in this patient, which has provided a basis for the genetic counseling for his family.

Fufang Xueshuantong Improves Diabetic Cardiomyopathy by Regulating the Wnt/ß-Catenin Pathway.

Diabetic cardiomyopathy (DCM) is one of the main complications of diabetic patients and the major reason for the high prevalence of heart failure in diabetic patients. Fufang Xueshuantong (FXST) is a traditional Chinese medicine formula commonly used in the treatment of diabetic retinopathy and stable angina pectoris. However, the role of FXST in DCM has not yet been clarified. This study was conducted to investigate the effects of FXST on diabetic myocardial lesions and reveal its molecular mechanism. The rats were intraperitoneally injected with 65 mg/kg streptozotocin (STZ) to induce diabetes mellitus (DM). DM rats were given saline or FXST. The rats in the control group were intraperitoneally injected with an equal amount of sodium citrate buffer and gavaged with saline. After 12 weeks, echocardiography, heart weight index (HWI), and myocardial pathological changes were determined. The expression of transforming growth factor-beta1 (TGF-ß1), collagen I, and collagen III was examined using immunofluorescence staining and western blot. The expressions of Wnt/ß-catenin signaling pathway-related proteins and mRNA were detected by western blot and real-time PCR. The results showed that FXST significantly improved cardiac function, ameliorated histopathological changes, and decreased HWI in the DM rats. FXST significantly inhibited the expression of myocardial TGF-ß1, collagen I, and collagen III in DM rats. Furthermore, FXST significantly inhibited the Wnt/ß-catenin pathway. Taken together, FXST has a protective effect on DCM, which might be mediated by suppressing the Wnt/ß-catenin pathway.

Association of Prolonged Disease Duration and TG/HDL-C Ratio in Accelerating Atherosclerosis in Patients with Takayasu's Arteritis.

Background and aim: Takayasu's arteritis (TA) is a chronic inflammation that frequently involves the aorta and its major branches. It has been known that atherosclerosis can occur in some TA patients. Objectives: This study aimed to identify the risk factors associated with the development of atherosclerosis in TA. Methods: This retrospective study enrolled a total of 101 TA patients. All patients were divided into two groups according to the absence or presence of atherosclerosis. Baseline demographic features and clinical characteristics were compared between two groups. A logistic model was applied to determine the risk factors associated with the development of atherosclerosis. Results: Our data suggested that the disease duration of patients in the atherosclerosis group was significantly longer than that of patients in the non-atherosclerosis group [96(18.00, 180.00) versus 48.00(12.00, 111.00) months] (P = .015). In addition, the average age of patients with atherosclerosis was significantly older compared to patients without atherosclerosis [44.00(38.00, 48.00)versus 28.50(24.00，37.00)years] (P < .001). Logistic regression analysis showed that the risk of developing atherosclerosis increased by 9.2% per 1 year increase in the disease duration (P = .005, OR 1.092, 95%CI: 1.027-1.162). Patients with TG/HDL-C ratio more than 0.8875 were associated with a 5.861fold increase of risk developing atherosclerosis (P < .001, OR 5.861, 95%CI: 2.299-14.939). Conclusion: Our study indicated that prolonged disease duration and elevated TG/HDL-C ratio are associated with the development of atherosclerosis in TA patients.

Underlying mechanisms of saphenous vein graft stenosis after coronary artery bypass caused by clipping of the side branches: an experimental study.

Background: Saphenous veins are regular bypass conduits selected in non-left anterior descending artery (LAD) coronary artery bypass graft (CABG) surgery. Despite the technical errors, acute thrombosis, intimal hyperplasia and arteriosclerosis which could lead to saphenous vein graft (SVG) failure, the metal-clipping-related SVG failure is unique and rare. This study was conducted to investigate the clinical and underlying mechanisms of the metal-clipping-related SVG failure. Methods: We collected 6 typical cases of the metal-clipping-related SVG failure in 41 patients who were diagnosed graft stenosis by coronary angiograph after CABG in the Department of Cardiology, Beijing Anzhen Hospital, from January 2020 to September 2021. Furthermore, we built an in vitro model to verify the identical intravascular ultrasound (IVUS) pattern of metal clip. Results: There were 6 in 41 cases of SVG stenosis caused by clipping of the side branches. We found that the stenosis of SVG caused by metal clipping mostly occurred at the corner and multipole clipping points. In this situation, great resistance could be felt when pushing the instruments through the stenosis and crystallized cholesterol was rarely caught by the distal protection device. We verified the similar IVUS pattern of metal clip at the side-branches of SVG in vitro. Conclusions: The metal-clipping-related stenosis may lead to SVG failure. The stenosis of SVG caused by metal clipping mostly occurred at the corner and multipole clipping points. IVUS showed great modality for clarification.

Risk factors for adverse cardiac events in adults with fulminant myocarditis during hospitalization.

BACKGROUND: Fulminant myocarditis is the critical form of myocarditis that is often associated with heart failure, malignant arrhythmia, and circulatory failure. Patients with fulminant myocarditis who end up with severe multiple organic failure and death are not rare. AIM: To analyze the predictors of in-hospital major adverse cardiovascular events (MACE) in patients diagnosed with fulminant myocarditis. METHODS: We included a cohort of adult patients diagnosed with fulminant myocarditis who were admitted to Beijing Anzhen Hospital from January 2007 to December 2017. The primary endpoint was defined as in-hospital MACE, including death, cardiac arrest, cardiac shock, and ventricular fibrillation. Baseline demographics, clinical history, characteristics of electrocardiograph and ultrasonic cardiogram, laboratory examination, and treatment were recorded. Multivariable logistic regression was used to examine risk factors for in-hospital MACE, and the variables were subsequently assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: The rate of in-hospital MACE was 40%. Multivariable logistic regression analysis revealed that baseline QRS duration > 120 ms was the independent risk factor for in-hospital MACE (odds ratio = 4.57, 95%CI: 1.23-16.94, P = 0.023). The AUC of QRS duration > 120 ms for predicting in-hospital MACE was 0.683 (95%CI: 0.532-0.833, P = 0.03). CONCLUSION: Patients with fulminant myocarditis has a poor outcome. Baseline QRS duration is the independent risk factor for poor outcome in those patients.

A randomized controlled trial to assess the efficacy and safety of doubling dose clopidogrel versus ticagrelor for the treatment of acute coronary syndrome in patients with CYP2C19*2 homozygotes.

BACKGROUND: Compared with non-reversible, indirect P2Y12 inhibitor clopidogrel, ticagrelor is a reversible, direct acting inhibitor. The CYP2C19*2 allele is a common genetic variant in individuals that need given higher clopidogrel in acute coronary syndrome patients. OBJECTIVE: We aimed to assess a pharmacogenetic approach of doubling dose clopidogrel compare with standard dose of ticagrelor among carriers with the CYP2C19*2 homozygotes. MATERIALS AND METHODS: We compared ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) with clopidogrel (600 mg loading dose, 150 mg daily thereafter) for the prevention of cardiovascular events in CYP2C19*2 homozygotes patients admitted to the hospital with an acute coronary syndrome, with or without ST-segment elevation. RESULTS: After genetic test to identify carriers of the CYP2C19*2 allele from 2295 patients, 224 cases with CYP2C19*2 homozygotes were enrolled into our prospective, randomized trial. Patients were random assignment with colpidogrel group (n = 112) and ticagrelor group (n = 112). The two groups were similar in terms of baseline characteristics. After the first 600 mg loading dose of clopidogrel, patients carrying two CYP2C19*2 allele had weaker PRU inhibition (39.8±37.4 vs 27.9±12.4; P = 0.001) and more bleeding adverse events (20.5% vs. 7.1%; hazard ratio = 2.88; 95% [CI], 1.34-6.15; P = 0.001) compared to those taking standard dose of ticagrelor. CONCLUSIONS: In CYP2C19*2 carriers with ACS, ticagrlor is as effective as high clopidogrel in reducing platelet reactivity, particularly in first days. This study suggests that ticagrelor may be much better than doubling dose clopidogrel in patients with CYP2C19*2 in according to platelet reactivity monitoring. Use of ticagrelor instead of clopidogrel may eliminate the need for genetic testing and lead to less mild bleeding adverse.

Prevalence and management of hypertension in patients with acute coronary syndrome vary with gender: Observations from the Chinese registry of acute coronary events (CRACE).

Hypertension affects one billion people worldwide and is an independent risk factor for death after acute coronary syndrome (ACS). The aim of this study was to examine the prevalence and medical treatment of hypertension among 1,301 ACS patients enrolled into the Chinese registry of acute coronary events (CRACE) trial. Analyses were performed by gender, with both genders combined and according to international practice. Multivariable models identified factors associated with use of different classes of antihypertensive medication, and examined the correlation between hypertension and gender with mortality. The use of angiotensin­converting enzyme inhibitors (ACEI), ß-blockers, calcium channel blockers (CCBs) and diuretics increased in both genders during management of presenting ACS. Hypertensive men were more likely to have been receiving ß-blockers when they were discharged (77.2%) than women (69.2%). Hypertensive women were more likely to have received diuretics when they were discharged (28.4%) than men (22%). ACEI use increased by ~60% (absolute increase) in both women and men as a result of ACS treatment, but remained similar between the genders, and the same phenomenon was observed in the use of CCBs. Moreover, hypertensive women were less likely to receive evidence­based medication to treat their acute coronary event than men (for women and men, respectively: ß-blocker, 69.2 vs. 77.2%; ACEI, 85.8 vs. 87.5%). Hypertension is more prevalent in women than in men with ACS, and its medical management varies with gender, but it has a similar association with mortality in both genders. Opportunities exist to improve medical therapy and outcomes for women with hypertension.

Clinical outcomes and cost-utility after sirolimus-eluting versus bare metal stent implantation.

BACKGROUND: Randomized studies have shown beneficial effects of drug-eluting stent (DES) in reducing the risk of repeated revascularization. Other studies have shown higher proportion of death, myocardial infarction (MI) and increased cost concerning DES. However the long term safety and effectiveness of DES have been questioned recently. METHODS: To compare long term clinical outcomes, health-related quality of life (HRQOL) and cost-utility after sirolimus-eluting stent (SES) and bare metal stent (BMS) implantation in angina patients in China, 1241 patients undergoing percutaneous coronary revascularization (PCI) with either SES (n = 632) or BMS (n = 609) were enrolled continuously in this prospective, nonrandomized, multi-center registry study. RESULTS: Totally 1570 stents were implanted for 1334 lesions. Follow-up was completed in 1205 (97.1%) patients at 12 months. Rates of MI, all causes of death were similar between the two groups. Significant differences were found at rate of cardiovascular re-hospitalization (136 (22.4%) in BMS group vs. 68 (10.8%) in SES group, P = 0.001) and recurrent angina (149 (24.5%) vs. 71 (11.3%), P = 0.001). Dramatic difference was observed when compared the baseline and 9-month HRQOL scores intra-group (P < 0.001). However no significant difference was found inter-group either in baseline or follow-up HRQOL. Compared with SES, the total cost in BMS was significantly lower on discharge (62 546.0 vs. 78 245.0 Yuan, P = 0.001). And follow-up expenditure was remarkably higher in the BMS group than that in the SES group (13 412.0 vs. 8 812.0 Yuan, P = 0.0001). CONCLUSIONS: There were no significant differences on death, in-stent thrombosis, MI irrespective of stent type. SES was superior to BMS on improvement of life quality. SES was with higher cost-utility compared to BMS.