Circulation Journal最新文献

Cardiac conduction is a central determinant of normal rhythm and arrhythmia susceptibility. Although arrhythmias have traditionally been attributed to abnormal automaticity, triggered activity, and re-entry, emerging evidence indicates that conduction abnormalities integrate structural, electrical, and immune-derived signals into a common arrhythmogenic substrate. This review summarizes multiscale mechanisms of impulse propagation, with an emphasis on gap junction-mediated coupling. Connexin 43 (Cx43), the principal ventricular connexin, maintains intercellular current flow through phosphorylation-dependent localization at intercalated discs; its remodeling leads to conduction slowing, heterogeneous propagation, and reentrant vulnerability. Recent studies have revealed that cardiac resident macrophages preserve ventricular conduction by promoting Cx43 phosphorylation via amphiregulin-epidermal growth factor receptor signaling. Loss of this macrophage-derived pathway causes Cx43 disorganization, atrioventricular block, ventricular fibrillation, and sudden death during cardiac stress, establishing an immune-electrical interface essential for conduction stability. This review further highlights conduction abnormalities in human disease, differences between mice and humans, and insights derived from electrocardiography and advanced computational modeling. Simulations linking molecular alterations to organ-level activation patterns provide a mechanistic bridge between cellular coupling, Purkinje network integrity, fibrosis distribution, and clinical electrophysiology. Together, these findings position conduction as a dynamic, regulated property of the ventricular myocardium and suggest that targeting gap junction and immune pathways may enable future conduction-based precision cardiology.

Background: Ischemic heart disease remains the leading cause of death worldwide, and although early coronary revascularization is essential, it can paradoxically induce additional myocardial damage known as ischemia-reperfusion (I/R) injury, driven in part by excessive generation of reactive oxygen species (ROS). This study evaluated the cardioprotective potential of resorcimoline (RML), a newly developed free radical scavenger, in mitigating ROS-mediated myocardial injury in a preclinical setting.

Methods and results: ROS production was induced in primary cardiomyocytes through hypoxia, angiotensin II, or hydrogen peroxide treatment. The antioxidant effects of RML were assessed by cytosolic and mitochondrial ROS assays. Cell viability and cytotoxicity were evaluated by metabolic activity and lactate dehydrogenase release assays. In vivo, myocardial I/R injury was induced in rats by transient coronary artery ligation followed by reperfusion. RML significantly reduced intracellular and mitochondrial ROS levels and improved cardiomyocyte viability in vitro. Consistently, in vivo DHE staining demonstrated that RML suppressed myocardial ROS accumulation, decreased infarct size, lowered serum troponin I, reduced apoptosis, and preserved left ventricular function, whereas these protective effects were not observed without reperfusion.

Conclusions: RML exerts cardioprotective effects by scavenging ROS and mitigating downstream oxidative damage in both in vitro and in vivo models of myocardial I/R injury, suggesting promise as a therapeutic agent against reperfusion-induced myocardial injury.

Catheter ablation has become the cornerstone therapy for cardiac arrhythmias, supported by continuous technological innovation. Since the introduction of radiofrequency (RF) ablation in the 1980s, remarkable progress, such as open irrigation, contact force sensing, local impedance monitoring, and index-guided ablation, has significantly improved procedural safety, reproducibility, and efficacy. In atrial fibrillation ablation, pulmonary vein isolation remains the fundamental strategy, and advances in RF technology have contributed to durable lesion formation and reduced complications. Although new non-thermal energy sources such as pulsed-field ablation (PFA) have recently emerged, RF ablation continues to play a central role in clinical practice. Its ability to provide precise lesion control and adaptability across a wide range of arrhythmia substrates, including supraventricular and ventricular tachycardias, remains unmatched. Furthermore, recent developments such as dual-energy catheters capable of delivering both RFA and PFA suggest a complementary future for both modalities. RF ablation has evolved in pursuit of greater safety and efficiency through sustained technological advancement. These innovations have improved lesion predictability and procedural outcomes, and RF ablation will remain an indispensable component of arrhythmia management in the coming era of energy diversification.

Renal denervation is a catheter-based therapy that interrupts renal sympathetic traffic and lowers blood pressure through durable neuromodulation. Contemporary catheter-based systems deliver energy to the periadventitial space with an acceptable safety profile. Across blinded placebo-controlled trials in off-medication and on-medication settings, renal denervation achieves greater reductions in ambulatory and office blood pressure than placebo, with a uniform 24-h effect that includes night-time and early-morning periods. Long-term follow-up data from randomized programs and large registries show sustained separation in blood pressure between renal denervation and control groups, preserved renal function, and low re-intervention rates over several years, with select cohorts approaching a decade. This review summarizes the mechanism and target anatomy of renal denervation, key features and results of placebo-controlled trials, and practical considerations for integrating the procedure with contemporary pharmacologic therapy in patients with uncontrolled hypertension.

Background: Congenital heart disease involving outflow tract (OFT) malformations remains a major clinical challenge, particularly in 22q11.2 deletion syndrome. Although folic acid (FA) reduces the incidence of neural tube defects, its mechanistic role in cardiac OFT development is not fully understood.

Methods and results: Using Tbx1^neo/neo hypomorphic mice as a model of 22q11.2 deletion syndrome, we investigated the effects of maternal FA supplementation on cardiac development. Pregnant dams received FA through diet or intraperitoneal injection and embryonic cardiac morphology was assessed at E15.5 and E18.5. Maternal FA administration significantly improved the persistent truncus arteriosus (PTA) phenotype, with 60% of Tbx1^neo/neo embryos exhibiting a partially septated PTA (Van Praagh type A1) vs. complete PTA (type A2) in controls. Neural crest cell (NCC) migration from the neural tube into the OFT was enhanced. GFP lineage tracing confirmed the presence of increased NCCs in the OFT and reduced ectopic neuronal differentiation. Single-cell RNA-sequencing and immunohistochemistry revealed activation of the Notch and Midkine signaling pathways in NCCs following FA treatment.

Conclusions: Maternal FA supplementation improved cardiac OFT malformations in Tbx1^neo/neo embryos by enhancing NCC migration and fate specification, possibly mediated by Notch and Midkine signaling activation. Our findings provide mechanistic insights into the observed reduction in congenital heart defects with FA and suggest its potential as a minimally invasive prenatal intervention.