A new deep learning algorithm of 12-lead electrocardiogram for identifying atrial fibrillation during sinus rhythm.

Atrial fibrillation (AF) is the most prevalent arrhythmia and is associated with increased morbidity and mortality. Its early detection is challenging because of the low detection yield of conventional methods. We aimed to develop a deep learning-based algorithm to identify AF during normal sinus rhythm (NSR) using 12-lead electrocardiogram (ECG) findings. We developed a new deep neural network to detect subtle differences in paroxysmal AF (PAF) during NSR using digital data from standard 12-lead ECGs. Raw digital data of 2,412 12-lead ECGs were analyzed. The artificial intelligence (AI) model showed that the optimal interval to detect subtle changes in PAF was within 0.24 s before the QRS complex in the 12-lead ECG. We allocated the enrolled ECGs to the training, internal validation, and testing datasets in a 7:1:2 ratio. Regarding AF identification, the AI-based algorithm showed the following values in the internal and external validation datasets: area under the receiver operating characteristic curve, 0.79 and 0.75; recall, 82% and 77%; specificity, 78% and 72%; F1 score, 75% and 74%; and overall accuracy, 72.8% and 71.2%, respectively. The deep learning-based algorithm using 12-lead ECG demonstrated high accuracy for detecting AF during NSR.

Atrial arrhythmogenesis in a rabbit model of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) increases the risk of atrial fibrillation (AF), however, its arrhythmogenic mechanisms are unclear. This study investigated the effects of COPD on AF triggers (pulmonary veins, PVs) and substrates (atria), and their potential underlying mechanisms. Electrocardiographic, echocardiographic, and biochemical studies were conducted in control rabbits and rabbits with human leukocyte elastase (0.3 unit/kg)-induced COPD. Conventional microelectrode, Western blotting, and histological examinations were performed on PV, left atrium (LA), right atrium, and sinoatrial node (SAN) preparations from control rabbits and those with COPD. The rabbits with COPD had a higher incidence of atrial premature complexes, PV burst firing and delayed afterdepolarizations, higher sympathetic activity, larger LA, and faster PV spontaneous activity than did the control rabbits; but they exhibited a slower SAN beating rate. The LA of the rabbits with COPD had a shorter action potential duration and longer tachyarrhythmia induced by tachypacing (20 Hz) and isoproterenol (1 µM). Additionally, the rabbits with COPD had higher fibrosis in the PVs, LA, and SAN. H89 (10 µM), KN93 (1 µM), and KB-R7943 (10 µM) significantly suppressed burst firing and delayed afterdepolarizations in the PVs of the rabbits with COPD. Moreover, compared with the control rabbits, those with COPD had lower expression levels of the ß1 adrenergic receptor, Cav 1.2, and Na+/Ca2+ exchanger in the PVs; Cav 1.2 in the LA; and hyperpolarization-activated cyclic nucleotide-gated K+ channel 4 in the SAN. COPD increases atrial arrhythmogenesis by modulating the distinctive electrophysiological characteristics of the PVs, LA, and SAN.

Whole-Mount Immunofluorescence Staining, Confocal Imaging and 3D Reconstruction of the Sinoatrial and Atrioventricular Node in the Mouse.

The electrical signal physiologically generated by pacemaker cells in the sinoatrial node (SAN) is conducted through the conduction system, which includes the atrioventricular node (AVN), to allow excitation and contraction of the whole heart. Any dysfunction of either SAN or AVN results in arrhythmias, indicating their fundamental role in electrophysiology and arrhythmogenesis. Mouse models are widely used in arrhythmia research, but the specific investigation of SAN and AVN remains challenging. The SAN is located at the junction of the crista terminalis with the superior vena cava and AVN is located at the apex of the triangle of Koch, formed by the orifice of the coronary sinus, the tricuspid annulus, and the tendon of Todaro. However, due to the small size, visualization by conventional histology remains challenging and it does not allow the study of SAN and AVN within their 3D environment. Here we describe a whole-mount immunofluorescence approach that allows the local visualization of labelled mouse SAN and AVN. Whole-mount immunofluorescence staining is intended for smaller sections of tissue without the need for manual sectioning. To this purpose, the mouse heart is dissected, with unwanted tissue removed, followed by fixation, permeabilization and blocking. Cells of the conduction system within SAN and AVN are then stained with an anti-HCN4 antibody. Confocal laser scanning microscopy and image processing allow differentiation between nodal cells and working cardiomyocytes, and to clearly localize SAN and AVN. Furthermore, additional antibodies can be combined to label other cell types as well, such as nerve fibers. Compared to conventional immunohistology, whole-mount immunofluorescence staining preserves the anatomical integrity of the cardiac conduction system, thus allowing the investigation of AVN; especially so into their anatomy and interactions with the surrounding working myocardium and non-myocyte cells.

Assessment of left ventricle magnetic resonance temperature stability in patients in the presence of arrhythmias.

BACKGROUND: Magnetic resonance (MR) thermometry allows visualization of lesion formation in real-time during cardiac radiofrequency (RF) ablation. The present study was performed to evaluate the precision of MR thermometry without RF heating in patients exhibiting cardiac arrhythmia in a clinical setting. The evaluation relied on quantification of changes in temperature measurements caused by noise and physiological motion. METHODS: Fourteen patients referred for cardiovascular magnetic resonance imaging underwent an extra sequence to test the temperature mapping stability during free-breathing acquisition. Phase images were acquired using a multi-slice, cardiac-triggered, single-shot echo planar imaging sequence. Temperature maps were calculated and displayed in real-time while the electrocardiogram (ECG) was recorded. The precision of temperature measurement was assessed by measuring the temporal standard deviation and temporal mean of consecutive temperature maps over a period of three minutes. The cardiac cycle was analyzed from ECG recordings to quantify the impact of arrhythmia events on the precision of temperature measurement. Finally, two retrospective strategies were tested to remove acquisition dynamics related either to arrhythmia events or sudden breathing motion. RESULTS: ECG synchronization allowed categorization of inter-beat intervals (RR) into distinct beat morphologies. Five patients were in stable sinus rhythm, while nine patients showed irregular RR intervals due to ectopic beats. An average temporal standard deviation of temperature of 1.6°C was observed in patients under sinus rhythm with a frame rate corresponding to the heart rate of the patient. The temporal standard deviation rose to 2.5°C in patients with arrhythmia. The retrospective rejection strategies increased the temperature precision measurement while maintaining a sufficient frame rate. CONCLUSIONS: Our results indicated that real-time cardiac MR thermometry shows good precision in patients under clinical conditions, even in the presence of arrhythmia. By providing real-time visualization of temperature distribution within the myocardium during RF delivery, MR thermometry could prevent insufficient or excessive heating and thus improve safety and efficacy.

Pseudoaneurysm of thoracic aorta presenting as inappropriate sinus tachycardia: a case report.

BACKGROUND: Pseudoaneurysm of thoracic aorta as a complication of blunt trauma to the chest, can present with a variety of symptoms due to mass compression effect. Here we report the first pseudoaneurysm of thoracic aorta presenting with chronic cough and inappropriate sinus tachycardia. The purpose of this case report is to highlight pseudoaneurysm of thoracic aorta as a rare differential diagnosis for inappropriate sinus tachycardia. CASE PRESENTATION: Here we report a case of 29-year-old white woman, a nurse, with history of a motor vehicle accident. She initially presented to medical attention with inappropriate sinus tachycardia 2 years following the motor vehicle accident during her pregnancy. Six years later she underwent sinoatrial node modification after failing a number of medications. Days prior to the ablation she developed a mild cough which became constant within a week following ablation. A computed tomography scan of her chest performed as part of a workup revealed an outpouching of the inferomedial aspect of the aortic arch, which was compressing her left main bronchus. She underwent arch repair surgery and recovered without complications. Four years later she presented with significant symptomatic sinus bradycardia requiring pacemaker placement. CONCLUSIONS: This is the first reported case of thoracic pseudoaneurysm of aorta presenting with inappropriate sinus tachycardia due to compression of the vagal nerve and cough as a result of the left main bronchus compressive effect; it highlights the importance of considering structural abnormalities in a differential diagnosis of inappropriate sinus tachycardia before any interventions.

High resolution 3-Dimensional imaging of the human cardiac conduction system from microanatomy to mathematical modeling.

Cardiac arrhythmias and conduction disturbances are accompanied by structural remodelling of the specialised cardiomyocytes known collectively as the cardiac conduction system. Here, using contrast enhanced micro-computed tomography, we present, in attitudinally appropriate fashion, the first 3-dimensional representations of the cardiac conduction system within the intact human heart. We show that cardiomyocyte orientation can be extracted from these datasets at spatial resolutions approaching the single cell. These data show that commonly accepted anatomical representations are oversimplified. We have incorporated the high-resolution anatomical data into mathematical simulations of cardiac electrical depolarisation. The data presented should have multidisciplinary impact. Since the rate of depolarisation is dictated by cardiac microstructure, and the precise orientation of the cardiomyocytes, our data should improve the fidelity of mathematical models. By showing the precise 3-dimensional relationships between the cardiac conduction system and surrounding structures, we provide new insights relevant to valvar replacement surgery and ablation therapies. We also offer a practical method for investigation of remodelling in disease, and thus, virtual pathology and archiving. Such data presented as 3D images or 3D printed models, will inform discussions between medical teams and their patients, and aid the education of medical and surgical trainees.

Ionic mechanisms of the action of anaesthetics on sinoatrial node automaticity.

Although various general anaesthetics affect the heart rate in clinical settings, their precise mechanisms remain to be fully elucidated. Because the heart rate is determined by automaticity of the cardiac pacemaker sinoatrial node and its regulation by autonomic nervous system, it is important to clarify the effect of anaesthetics on sinoatrial node automaticity. The spontaneous electrical activity of sinoatrial node is generated by a complex but coordinated interaction of multiple ionic currents, such as the hyperpolarisation-activated cation current (If), T-type and L-type Ca2+ currents (ICa,T and ICa,L), Na+/Ca2+ exchange current (INCX), and rapidly and slowly activating delayed rectifier K+ currents (IKr and IKs). Patch-clamp studies have revealed the direct inhibitory effects of various anaesthetics on sinoatrial node automaticity and its underlying ionic mechanisms. Sevoflurane, desflurane and propofol directly suppress the sinoatrial node automaticity by inhibiting multiple ionic channels and transporter, such as If, ICa,T, ICa,L, IKs and INCX. By incorporating these inhibitory effects of anaesthetics on multiple ion channels and transporter into sinoatrial node model, suppression of sinoatrial node activity is well reproduced in computer simulation. The inhibitory effect of anaesthetics on sinoatrial node automaticity can be exaggerated under some pathophysiological conditions, such as aging, heart failure and arrhythmias, where the function and/or expression of ion channels involved in sinoatrial node automaticity are modulated. This review focuses on molecular, ionic and cellular mechanisms underlying the regulation of sinoatrial node automaticity by anaesthetics, which will provide an electrophysiological and molecular basis for understanding the changes in heart rate during perioperative period.

Novel application of 3D contrast-enhanced CMR to define fibrotic structure of the human sinoatrial node in vivo.

AIMS: The adult human sinoatrial node (SAN) has a specialized fibrotic intramural structure (35-55% fibrotic tissue) that provides mechanical and electrical protection from the surrounding atria. We hypothesize that late gadolinium-enhanced cardiovascular magnetic resonance (LGE-CMR) can be applied to define the fibrotic human SAN structure in vivo. METHODS AND RESULTS: LGE-CMR atrial scans of healthy volunteers (n olu, 23-52 y.o.) using a 3 Tesla magnetic resonance imaging system with a spatial resolution of 1.0 mm3 or 0.625 × 0.625 × 1.25 mm3 were obtained and analysed. Percent fibrosis of total connective and cardiomyocyte tissue area in segmented atrial regions were measured based on signal intensity differences of fibrotic vs. non-fibrotic cardiomyocyte tissue. A distinct ellipsoidal fibrotic region (length: 23.6 ± 1.9 mm; width: 7.2 ± 0.9 mm; depth: 2.9 ± 0.4 mm) in all hearts was observed along the posterior junction of the crista terminalis and superior vena cava extending towards the interatrial septum, corresponding to the anatomical location of the human SAN. The SAN fibrotic region consisted of 41.9 ± 5.4% of LGE voxels above an average threshold of 2.7 SD (range 2-3 SD) from the non-fibrotic right atrial free wall tissue. Fibrosis quantification and SAN identification by in vivo LGE-CMR were validated in optically mapped explanted donor hearts ex vivo (n ivo, 19-65 y.o.) by contrast-enhanced CMR (9.4 Tesla; up to 90 µm3 resolution) correlated with serial histological sections of the SAN. CONCLUSION: This is the first study to visualize the 3D human SAN fibrotic structure in vivo using LGE-CMR. Identification of the 3D SAN location and its high fibrotic content by LGE-CMR may provide a new tool to avoid or target SAN structure during ablation.

Acute Sinus Node Dysfunction after Atrial Ablation: Incidence, Risk Factors, and Management.

BACKGROUND: Many patients with atrial fibrillation (AF) or atrial flutter (Aflutter) have concomitant sinus node dysfunction (SND). Ablation may result in injury to the sinus node complex or its blood supply resulting in sinus arrest and need for temporary pacing. We sought to characterize patients who develop acute SND (ASND) during/immediately after AF/Aflutter ablation. METHODS: We performed a retrospective analysis of AF/Aflutter ablation patients between January 1, 2010 and February 28, 2015 to characterize those who required temporary pacemaker (TPM) implantation due to ASND (sinus arrest, sinus bradycardia <40 beats/min, or junctional rhythm with hemodynamic compromise) following atrial ablation. RESULTS: Of 2,151 patients, eight patients (<0.5%) with ASND manifesting as sinus arrest (n = 2), severe sinus bradycardia (n = 2), and junctional rhythm with hemodynamic compromise (n = 4) were identified (all male, age 66 ± 9.9 years, 4/8 [50%] persistent AF). AF ablation was performed in four, atypical Aflutter in one, and AF/Aflutter in three patients. The ablation set consisted of: pulmonary vein (PV) isolation (n = 6), roof line ablation (n = 6), mitral annulus-left inferior PV line ablation (n = 5), left atrial appendage-mitral annulus ablation (n = 1), cavotricuspid isthmus ablation (n = 5), and isolation or ablation near the superior vena cava (SVC, n = 4). Patients with peri-SVC ablation were more likely to develop ASND (P = 0.03). All patients received TPM; six received permanent pacemaker before discharge, performed 3.5 days postablation (range 2-6 days). At 3-month device interrogation, all patients were atrially paced >50%. CONCLUSION: ASND is a rare complication of atrial ablation. It may be more common when peri-SVC ablation is performed and may necessitate permanent pacemaker implantation.

Three-dimensional mapping and intracardiac echocardiography in the treatment of sinoatrial nodal tachycardias.

Three-dimensional mapping and intracardiac echocardiography are important tools for the study of the site of origin of an arrhythmia and its substrate. This review examines the application of these techniques in the diagnosis and treatment of sinoatrial tachycardias with a special focus on the syndrome of inappropriate sinus tachycardia. The use of these techniques in electrophysiologic mapping and interventions such as catheter ablation is discussed. Three-dimensional mapping provides unique insights into the generation of normal and abnormal sinus impulses in man and their propagation in the atrium. It permits precise placement of ablation lesions and assessment of real-time electrophysiologic impact of these interventions. Intracardiac echocardiography provides delineation of important anatomic structures in the vicinity of the sinoatrial node complex and monitors the safety of interventions such as catheter ablation.

High-resolution Optical Mapping of the Mouse Sino-atrial Node.

Sino-atrial node (SAN) dysfunctions and associated complications constitute important causes of morbidity in patients with cardiac diseases. The development of novel pharmacological therapies to cure these patients relies on the thorough understanding of both normal physiology and pathophysiology of the SAN. Among the studies of cardiac pacemaking, the mouse SAN is widely used due to its feasibility for modifications in the expression of different genes that encode SAN ion channels or calcium handling proteins. Emerging evidence from electrophysiological and histological studies has also proved the representativeness and similarity of the mouse SAN structure and functions to larger mammals, including the presence of specialized conduction pathways from the SAN to the atrium and a complex pacemakers' hierarchy within the SAN. Recently, the technique of optical mapping has greatly facilitated the exploration and investigation of the origin of excitation and conduction within and from the mouse SAN, which in turn has extended the understanding of the SAN and benefited clinical treatments of SAN dysfunction associated diseases. In this manuscript, we have described in detail how to perform the optical mapping of the mouse SAN from the intact, Langendorff-perfused heart and from the isolated atrial preparation. This protocol is a useful tool to enhance the understanding of mouse SAN physiology and pathophysiology.

Catheter ablation of inappropriate sinus tachycardia.

Catheter ablation for inappropriate sinus tachycardia (IST) is recommended for patients symptomatic for palpitations and refractory to other treatments. The current approach consists in sinus node modification (SNM), achieved by ablation of the cranial part of the sinus node to eliminate faster sinus rates while trying to preserve chronotropic competence. This approach has a limited efficacy, with a very modest long-term clinical success. To overcome this, proper patient selection is crucial and an epicardial approach should always be considered. This brief review will discuss the current role and limitations of catheter ablation in the management of patients with IST.

Sinoatrial node dysfunction induces cardiac arrhythmias in diabetic mice.

BACKGROUND: The aim of this study was to probe cardiac complications, including heart-rate control, in a mouse model of type-2 diabetes. Heart-rate development in diabetic patients is not straight forward: In general, patients with diabetes have faster heart rates compared to non-diabetic individuals, yet diabetic patients are frequently found among patients treated for slow heart rates. Hence, we hypothesized that sinoatrial node (SAN) dysfunction could contribute to our understanding of the mechanism behind this conundrum and the consequences thereof. METHODS: Cardiac hemodynamic and electrophysiological characteristics were investigated in diabetic db/db and control db/+ mice. RESULTS: We found improved contractile function and impaired filling dynamics of the heart in db/db mice, relative to db/+ controls. Electrophysiologically, we observed comparable heart rates in the two mouse groups, but SAN recovery time was prolonged in diabetic mice. Adrenoreceptor stimulation increased heart rate in all mice and elicited cardiac arrhythmias in db/db mice only. The arrhythmias emanated from the SAN and were characterized by large RR fluctuations. Moreover, nerve density was reduced in the SAN region. CONCLUSIONS: Enhanced systolic function and reduced diastolic function indicates early ventricular remodeling in obese and diabetic mice. They have SAN dysfunction, and adrenoreceptor stimulation triggers cardiac arrhythmia originating in the SAN. Thus, dysfunction of the intrinsic cardiac pacemaker and remodeling of the autonomic nervous system may conspire to increase cardiac mortality in diabetic patients.

Right coronary artery aneurysm with aneurysmal dilation and thrombosis of the sinoatrial nodal branch mimicking a right atrial mass.

Aneurysms of the branches of the coronary arteries are rare. We report a case of a right coronary artery aneurysm with aneurysmal dilation and thrombosis of the sinoatrial nodal branch presenting as a right atrial mass. The patient underwent multiple imaging evaluations before coronary CT angiography diagnosed aneurysm and thrombosis of the sinoatrial nodal branch.