Background: Bivalirudin is a direct thrombin inhibitor (DTI) that can be an alternative to unfractionated heparin (UFH). The efficacy and safety of bivalirudin in anticoagulation therapy in extracorporeal membrane oxygenation (ECMO) remain unknown.Methods: This study followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A systematic literature search was performed in PubMed, EMBASE, and The Cochrane Library databases to identify all relevant original studies estimating bivalirudin’s efficacy and safety versus UFH as anticoagulation therapy in ECMO. The time limit for searching is from the search beginning to June 2021. Two researchers independently screened the literature, extracted data and evaluated the risk of bias of the included studies. The meta-analysis (CRD42020214713) was performed via the RevMan version 5.3.5 Software and STATA version 15.1 Software.Results: Ten articles with 847 patients were included for the quantitative analysis. Bivalirudin can significantly reduce the incidence of major bleeding in children (I2 = 48%, p = 0.01, odd ratio (OR) = 0.17, 95% confidence interval (CI): 0.04–0.66), patient thrombosis (I2 = 0%, p = 0.02, OR = 0.58, 95% CI: 0.37–0.93), in-circuit thrombosis/interventions (I2 = 0%, p = 0.0005, OR = 0.40, 95% CI: 0.24–0.68), and in-hospital mortality (I2 = 0%, p = 0.007, OR = 0.64, 95% CI: 0.46–0.88). Also, comparable clinical outcomes were observed in the incidence of major bleeding in adults (I2 = 48%, p = 0.65, OR = 0.87, 95% CI: 0.46–1.62), 30-day mortality (I2 = 0%, p = 0.61, OR = 0.83, 95% CI: 0.41–1.68), and ECMO duration in adults (I2 = 41%, p = 0.75, mean difference (MD) = −3.19, 95% CI: −23.01–16.63) and children (I2 = 76%, p = 0.65, MD = 40.33, 95% CI:−135.45–216.12).Conclusions: Compared with UFH, bivalirudin can be a safe and feasible alternative anticoagulant option to UFH as anticoagulation therapy in ECMO, especially for heparin resistance (HR) and heparin-induced thrombocytopenia (HIT) cases.

Background Cancer therapy‐related cardiovascular toxicity (CTR‐CVT) is a major contributor to poor prognosis in breast cancer (BC) patients undergoing chemotherapy. Left ventricular global longitudinal strain (LV GLS) has predictive value for CTR‐CVT, while few researchers take into account late‐onset CTR‐CVT. This study sought to provide a guide for the prediction of late‐onset CTR‐CVT in primary BC over the 2 years follow‐up via strain and contrast‐enhanced echocardiography. Methods Anthracycline and anthracycline + targeted medication groups were created from 111 patients with stage I–III primary BC who were prospectively included. The left ventricular diastolic function, LV global long‐axis strain (GLS); left ventricular ejection fraction by contrast‐enhanced echocardiography (c‐LVEF), and electrocardiograms were collected at baseline, 3, 6, 12, and 24 months after the start of cancer treatment. The high‐sensitivity troponin‐T and NT‐pro BNP at baseline and 3 months after chemotherapy were measured. Results (1) LV GLS decreased in BC patients over time. (2) After 12 months' follow‐up, the LV GLS in the anthracycline+ targeted group was lower than in the anthracycline group. After 24 months' follow‐up, the GLS and c‐LVEF in the anthracycline + targeted group declined while the E/e’ increased. (3) Decreased LVEF (56%) and arrhythmia (38%) are the common causes of CTR‐CVT. Lower LVEF was a major factor in late‐onset CTR‐CVT. (4) Combination of LV GLS and c‐LVEF at 3 months were used as predictors for CTR‐CVT and exhibited a higher AUC than either one alone (AUC = 0.929, 95% CI: 0.863–0.970). LV GLS at 3 months can predict the late‐onset CTR‐CVT (AUC = 0.745, p < 0.001), and the cut‐off is 20.32%. Conclusions As time went on, the systolic and diastolic dysfunction of BC patients get worsened. The combination of LV GLS and c‐LVEF is better in the prediction of CTR‐CVT. Only the LV GLS at 3 months can predict the late‐onset CTR‐CVT.

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Background PRKAG2 cardiac syndrome is a rare autosomal dominant genetic disorder caused by a PRKAG2 gene variant. There are several major adverse cardiac presentations, including hypertrophic cardiomyopathy (HCM) and life‐threatening arrhythmia. Two cases with pathogenic variants in the PRKAG2 gene are reported here who presents different cardiac phenotypes. Methods Exome sequencing and variant analysis of PRKAG2 were performed to obtain genetic data, and clinical characteristics were determined. Results The first proband was a 9‐month‐old female infant (Case 1), and was identified with severe DCM and resistant heart failure. The second proband was a 10‐year‐old female infant (Case 2), and presented with HCM and ventricular preexcitation. Exome sequencing identified a de novo c.425C > T (p.T142I) heterozygous variant in the PRKAG2 gene for Case 1, and a c.869A > T (p.K290I) for Case 2. The mutated sites in the protein were labeled and identified as p.K290 in the CBS domain and p.T142 in the non‐CBS domain. Differences in the molecular functions of CBS and non‐CBS domains have not been resolved, and variants might lead to the different cardiomyopathy phenotypes. Single‐cell RNA analysis demonstrated similar expression levels of PRKAG2 in cardiomyocytes and conductive tissues. These results suggest that the arrhythmia induced by the PRKAG2 variant was the primary change, and not secondary to cardiomyopathy. Conclusion In summary, this is the first case report to describe a DCM phenotype with early onset in patients possessing a PRKAG2 c.425C > T (p.T142I) pathogenic variant. Our results aid in understanding the molecular function of non‐CBS variants in terms of the disordered sequence of transcripts. Moreover, we used scRNA‐seq to show that electrically conductive cells express a higher level of PRKAG2 than do cardiomyocytes. Therefore, variants in PRKAG2 are expected to also alter the biological function of the conduction system.

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