Sinoatrial node (SAN) automaticity is jointly regulated by a voltage (cyclic activation and deactivation of membrane ion channels) and Ca2+ clocks (rhythmic spontaneous sarcoplasmic reticulum Ca2+ release). Using optical mapping in Langendorff-perfused canine right atrium, we previously demonstrated that the beta-adrenergic stimulation pushes the leading pacemaker to the superior SAN, which has the fastest activation rate and the most robust late diastolic intracellular calcium (Cai) elevation. Dysfunction of the superior SAN is commonly observed in animal models of heart failure and atrial fibrillation (AF), which are known to be associated with abnormal SAN automaticity. Using the 3D electroanatomic mapping techniques, we demonstrated that superior SAN served as the earliest atrial activation site (EAS) during sympathetic stimulation in healthy humans. In contrast, unresponsiveness of superior SAN to sympathetic stimulation was a characteristic finding in patients with AF and SAN dysfunction, and the 3D electroanatomic mapping technique had better diagnostic sensitivity than corrected SAN recovery time testing. However, both tests have significant limitations in detecting patients with symptomatic sick sinus syndrome. Recently, we reported that the location of the EAS can be predicted by the amplitudes of P-wave in the inferior leads. The inferior P-wave amplitudes can also be used to assess the superior SAN responsiveness to sympathetic stimulation. Inverted or isoelectric P-waves at baseline that fail to normalize during isoproterenol infusion suggest SAN dysfunction. P-wave morphology analyses may be helpful in determining the SAN function in patients at risk of symptomatic sick sinus syndrome.
Adrenergic beta-Agonists ; Atrial Fibrillation ; Biological Clocks ; Calcium ; Heart Atria ; Heart Failure ; Humans ; Isoproterenol ; Membranes ; Models, Animal ; Sarcoplasmic Reticulum ; Sick Sinus Syndrome ; Sinoatrial Node*

No abstract available.
Defibrillators, Implantable* ; Humans ; Magnetic Resonance Imaging*

Atrial fibrillation (AF) remains the most common adult rhythm disorder, and it associated with a substantial rate of morbidity and economic burden. AF involves a wide spectrum of arrhythmias from lone AF to paroxysmal to chronic AF. It is likely that AF comprises a spectrum of disease with no single mechanism adequate enough to comprehensively explain AF and its variability. Mechanism of fibrillation is explained by multiple wavelets and focal activation theories. Electrical, contractile and mechanical remodeling is involved in AF progression. Atrial remodeling may also increase in atrial fibrosis which can slow conduction velocity and can shorten the refractory period in atria ith long-standing AF. Mechanical remodeling manifests as decreased atrial contractility and increased atrial compliance which leads to a stretch of the atrial myocardium. Abnormal intracellular calcium dynamics is observed in AF. Modulating factors such as genetic factors, age, obesity, sleep apnea, inflammation, autonomic factors and atrial and pulmonary vein stretch only partially account for the increase in AF. It is still unclear whether initiation of AF activates direct inflammatory effects or whether the presence of a pre-existing systemic inflammatory state promotes further persistence of AF. Although significant progress in understanding the mechanism of this arrhythmia has been accomplished, the pathophysiology of AF is complex and likely has many possible mechanisms which may be interrelated.
Adult ; Age Factors ; Arrhythmias, Cardiac ; Atrial Fibrillation ; Calcium ; Compliance ; Fibrosis ; Humans ; Inflammation ; Myocardium ; Obesity ; Pulmonary Veins ; Risk Factors ; Sleep Apnea Syndromes

Cardiac rhythm management devices (pacemakers) are being increasingly implanted worldwide for the management of not only bradycardia but also arrhythmia and heart failure. This increase in the frequency of device therapy is paralleled with an increase in the requirement for systemic extraction. Safe lead extraction is central to the management of several complications related to pacemakers. The most common indication for lead extraction is systemic infection. Adhesions in chronically implanted leads can become major obstacles to safe lead extraction, leading to life-threatening bleeding and cardiac perforations. Currently, several extraction tools enable safe and successful transvenous lead extraction (TLE) of pacemaker and implantable cardioverter–defibrillator leads. This article provides a comprehensive review of the indications, tools, techniques, and outcomes for TLE. Operator experience is vital in determining success, as familiarity with a wide array of techniques will increase the likelihood of uncomplicated extraction. Lead extraction should, therefore, ideally be performed in high-volume centers with experienced staff and on-site support from a cardiothoracic surgical team that is able to deal with bleeding complications from cardiovascular perforation.
Arrhythmias, Cardiac ; Bradycardia ; Heart Failure ; Hemorrhage ; Recognition (Psychology)

No abstract available.
Catheter Ablation* ; Catheters*

No abstract available.
Atrial Fibrillation ; Socioeconomic Factors

Regulatory approvals of non-vitamin K antagonist oral anticoagulants (NOACs) have been based on large randomized phase III trials evaluating dabigatran, rivaroxaban, apixaban, or edoxaban relative to warfarin for atrial fibrillation (AF). The results of the trials showed that all NOACs were at least non-inferior to warfarin in the prevention of stroke/thromboembolism and showed lower rates of intracranial bleeding than those associated with warfarin. However, the trials were designed differently, varied in the inclusion/exclusion criteria, and used either one dose or a low/high dose of the NOAC drug. Some of these differences have challenged the ability to directly compare various NOACs, and comparative data on effectiveness and intracranial bleeding are sparse in “real-world” patients. Real-world data complement data from large randomized phase III trials by providing new aspects of the “real-world” absolute risks of ischemic and hemorrhagic stroke associated with NOACs vs. warfarin. Moreover, “real-world” fragile patients might have been included (e.g., patients with increased risk of bleeding, liver disease, and chronic kidney disease), although these patients would be less represented in trials. This paper introduces recently published real-world data of NOACs and further suggests the recommended dosage of NOACs for Korean patients.
Anticoagulants* ; Atrial Fibrillation ; Complement System Proteins ; Dabigatran ; Factor Xa Inhibitors ; Hemorrhage ; Humans ; Kidney ; Liver Diseases ; Rivaroxaban ; Stroke ; Warfarin

Recent evidence indicates that the voltage clock (cyclic activation and deactivation of membrane ion channels) and Ca2+ clocks (rhythmic spontaneous sarcoplasmic reticulum Ca2+ release) jointly regulate sinoatrial node (SAN) automaticity. However, the relative importance of the voltage clock and Ca2+ clock for pacemaking was not revealed in sick sinus syndrome. Previously, we mapped the intracellular calcium (Cai) and membrane potentials of the normal intact SAN simultaneously using optical mapping in Langendorff-perfused canine right atrium. We demonstrated that the sinus rate increased and the leading pacemaker shifted to the superior SAN with robust late diastolic Cai elevation (LDCAE) during beta-adrenergic stimulation. We also showed that the LDCAE was caused by spontaneous diastolic sarcoplasmic reticulum (SR) Ca2+ release and was closely related to heart rate changes. In contrast, in pacing induced canine atrial fibrillation and SAN dysfunction models, Ca2+ clock of SAN was unresponsiveness to beta-adrenergic stimulation and caffeine. Ryanodine receptor 2 (RyR2) in SAN was down-regulated. Using the prolonged low dose isoproterenol together with funny current block, we produced a tachybradycardia model. In this model, chronically elevated sympathetic tone results in abnormal pacemaking hierarchy in the right atrium, including suppression of the superior SAN and enhanced pacemaking from ectopic sites. Finally, if the LDCAE was too small to trigger an action potential, then it induced only delayed afterdepolarization (DAD)-like diastolic depolarization (DD). The failure of DAD-like DD to consistently trigger a sinus beat is a novel mechanism of atrial arrhythmogenesis. We conclude that dysfunction of both the Ca2+ clock and the voltage clock are important in sick sinus syndrome.
Animals ; Arrhythmia, Sinus/physiopathology ; Atrial Fibrillation/physiopathology ; Bradycardia/physiopathology ; Calcium/*physiology ; Calcium Channels/*physiology ; Dogs ; Humans ; Sick Sinus Syndrome/physiopathology ; Sinoatrial Node/physiology/*physiopathology

Atrial fibrillation (AF) is a strong risk factor for ischemic stroke and systemic embolism. To prevent thromboembolic events in patients with AF, anticoagulation therapy is essential. The anticoagulant strategy is determined after stroke and bleeding risk assessments using the CHA2DS2-VASc and HAS-BLED scores, respectively; both consider clinical risk factors. Vitamin K antagonists (VKAs) are the sole anticoagulant option in AF patients with a prosthetic mechanical valve or moderate-severe mitral stenosis; in all other AF patients VKA or non-vitamin K antagonist oral anticoagulants are therapeutic options. However, antiplatelet therapy should not be used for stroke prevention in AF patients. Anticoagulation is not needed in AF patients with low stroke risk but strongly recommended in those with a with low bleeding risk. Left atrial appendage (LAA) occlusion offers an alternative in AF patients in whom long-term anticoagulation is contraindicated. Surgical occlusion or the exclusion of LAA can be considered for stroke prevention in AF patients undergoing cardiac surgery. In this article, we review existing data for stroke prevention and suggest optimal strategies to prevent stroke in AF patients.