Objective To determine the effect of remote ischemic postconditioning (RIPC) on patients with acute ischemic stroke (AIS) undergoing IV thrombolysis (IVT). Methods A single-center randomized controlled trial was performed with patients with AIS receiving IVT. Patients in the RIPC group were administered RIPC treatment (after IVT) during hospitalization. The primary endpoint was a score of 0 or 1 on the modified Rankin scale (mRS) at day 90. The safety, tolerability, and neuroprotection biomarkers associated with RIPC were also evaluated. Results We collected data from both the RIPC group (n = 34) and the control group (n = 34). The average duration of hospitalization was 11.2 days. There was no significant difference between 2 groups at admission for the NIH Stroke Scale score (p = 0.364) or occur-to-treatment time (p = 0.889). Favorable recovery (mRS score 0–1) at 3 months was obtained in 71.9% of patients in the RIPC group vs 50.0% in the control group (adjusted odds ratio 9.85, 95% confidence interval 1.54–63.16; p = 0.016). We further found significantly lower plasma S100-β (p = 0.007) and higher vascular endothelial growth factor (p = 0.003) levels in the RIPC group than in the control group. Conclusions Repeated RIPC combined with IVT can significantly facilitate recovery of nerve function and improve clinical prognosis of patients with AIS. ClinicalTrials.gov identifier NCT03218293. Classification of evidence This study provides Class IV evidence that RIPC after tissue plasminogen activator treatment of AIS significantly increases the proportion of patients with an MRS score of 0 or 1 at 90 days.

The voltage-gated sodium channel 1.5 (Nav1.5), encoded by the SCN5A gene, is responsible for the rising phase of the action potential of cardiomyocytes. The sodium current mediated by Nav1.5 consists of peak and late components (I_Na-Pand I_Na-L). Mutant Nav1.5 causes alterations in the peak and late sodium current and is associated with an increasingly wide range of congenital arrhythmias. More than 400 mutations have been identified in the SCN5A gene. Although the mechanisms of SCN5A mutations leading to a variety of arrhythmias can be classified according to the alteration of I_Na-Pand I_Na-Las gain-of-function, loss-of-function and both, few researchers have summarized the mechanisms in this way before. In this review article, we aim to review the mechanisms underlying dysfunctional Nav1.5 due to SCN5A mutations and to provide some new insights into further approaches in the treatment of arrhythmias.Impact statement: The field of ion channelopathy caused by dysfunctional Nav1.5 due to SCN5A mutations is rapidly evolving as novel technologies of electrophysiology are introduced and our understanding of the mechanisms of various arrhythmias develops. In this review, we focus on the dysfunctional Nav1.5 related to arrhythmias and the underlying mechanisms. We update SCN5A mutations in a precise way since 2013 and presents novel classifications of SCN5A mutations responsible for the dysfunction of the peak (I_Na-P) and late (I_Na-L) sodium channels based on their phenotypes, including loss-, gain-, and coexistence of gain- and loss-of function mutations in I_Na-P, I_Na-L, respectively. We hope this review will provide a new comprehensive way to better understand the electrophysiological mechanisms underlying arrhythmias from cell to bedside, promoting the management of various arrhythmias in practice.

Atrial cardiomyopathy refers to structural and electrical remodelling of the atria, which can lead to impaired mechanical function. While historical studies have implicated atrial fibrillation as the leading cause of cardioembolic stroke, atrial cardiomyopathy may be an important, underestimated contributor. To date, the relationship between atrial cardiomyopathy, atrial fibrillation, and cardioembolic stroke remains obscure. This review summarizes the pathogenesis of atrial cardiomyopathy, with a special focus on neurohormonal and inflammatory mechanisms, as well as the role of adipose tissue, especially epicardial fat in atrial remodelling. It reviews the current evidence implicating atrial cardiomyopathy as a cause of embolic stroke, with atrial fibrillation as a lagging marker of an increased thrombogenic atrial substrate. Finally, it discusses the potential of antithrombotic therapy in embolic stroke with undetermined source and appraises the available diagnostic techniques for atrial cardiomyopathy, including imaging techniques such as echocardiography, computed tomography, and magnetic resonance imaging as well as electroanatomic mapping, electrocardiogram, biomarkers, and genetic testing. More prospective studies are needed to define the relationship between atrial cardiomyopathy, atrial fibrillation, and embolic stroke and to establish a prompt diagnosis and specific treatment strategies in these patients with atrial cardiomyopathy for the secondary and even primary prevention of embolic stroke.

Nearly 30% of ischemic strokes have an unknown cause, which are referred to as cryptogenic strokes (CS). Imaging studies suggest that a large proportion of these patients show features that are consistent with embolism, and thus the term embolic stroke of undetermined source (ESUS) was proposed to describe these CS patients. Atrial cardiomyopathy predisposes to thrombus formation and thus embolic stroke even in the absence of atrial fibrillation (AF). This may provide a mechanistic link with ESUS, suggesting that anticoagulant therapy may be more beneficial than antiplatelet therapy in ESUS patients with atrial cardiomyopathy. The present review discusses the concept of atrial cardiomyopathy and ESUS and the relationship between them based on the mechanisms and clinical evidence, suggests that atrial cardiomyopathy may be a potential mechanism of ESUS, and highlights a theoretical basis that supports that anticoagulant therapy may be more applicable to ESUS patients with atrial cardiomyopathy and aims to help us better understand and identify the risk of ESUS, thereby improving the management of these patients in clinical practice.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in chronic kidney disease (CKD) patients. QT interval prolongation is a congenital or acquired condition that is associated with an increased risk of torsade de pointes (TdP), sudden cardiac death (SCD), and all-cause mortality in the general population. The prevalence of acquired long QT syndrome (aLQTS) is high, and various acquired conditions contribute to the prolonged QT interval in patients with CKD. More notably, the prolonged QT interval in CKD is an independent risk factor for SCD and all-cause mortality. In this review, we focus on the epidemiological characteristics, risk factors, underlying mechanisms and treatments of aLQTS in CKD, promoting the management of aLQTS in CKD patients.