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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.

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.

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 β1 adrenergic receptor, Cav 1.2, and Na + /Ca 2+ 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., Competing Interests: Declaration of Competing Interest All authors have read the journal's policy on disclosure of potential conflicts of interest and none declared., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (© 2019 John Wiley & Sons, Ltd.)

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.

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 (I f ), T-type and L-type Ca 2+ currents (I Ca,T and I Ca,L ), Na + /Ca 2+ exchange current (I NCX ), and rapidly and slowly activating delayed rectifier K + currents (I Kr and I Ks ). 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 I f , I Ca,T , I Ca,L , I Ks and I NCX . 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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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.

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

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.

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., (© 2016 Wiley Periodicals, Inc.)

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.

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.

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.

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., (Copyright © 2014 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate, on a retrospective basis, the anatomic characteristics of the arterial supply to the sinoatrial node (SAN) in the Korean population using an ECG-gated multi-detector CT (MDCT)., Materials and Methods: The electrocardiographic-gated MDCTs of 500 patients (258 men and 242 women; age range, 17-83 years; mean age, 58.6 ± 12.04 years) were analyzed retrospectively. In each case, the SAN artery (arteries) was named according to a special nomenclature with regard to origin, course, and termination., Results: A total of 516 SAN arteries were visualized in 496 patients. The SAN was supplied by a single artery in 476 (96.4%) cases and by 2 arteries in 18 (3.6%) cases. The SAN originated from the right coronary artery in 265 (53.4%) cases and from the left circumflex in 213 (43%) cases., Conclusion: This study can provide basic data on variations of the SAN artery in the Korean population.

Purpose: The aim of this study is to depict anatomic characteristics of sinuatrial nodal artery (SANA) and atrioventricular nodal artery (AVNA) of the heart with multidetector computed tomography., Methods: In our study, 400 patients referred to radiology departments of two institutions for coronary CT angiography were retrospectively evaluated. 350 patients had been examined by dual-source 64-slice CT, and 50 patients by 64-section multidetector CT. Transverse sections with a thickness of 0.6 mm were used in dual-source 64-slice CT studies, and 0.8 mm were used in 64-section multidetector CT examinations for the evaluation of coronary arteries and conduction system branches. Anatomic origin, localization of the origin, diameter, number, course, and variants of the SANA and AVNA were examined with coronary multidetector CT angiography., Results: SANA and AVNA could be imaged by multidetector CT in all patients. There was a single SANA in 383 (95.7%) patients, and two SANAs in 17 (4.2%) patients. Two hundred thirty-three (58.2%) patients had one SANA originating from right coronary artery (RCA), 149 (37.2%) patients had one SANA originating from left circumflex (LCX) artery, and one patient had a SANA originating from the aorta. AVNA originated from distal RCA in 351 patients (87.7% of all patients), and from distal LCX artery in 49 patients (12.3% of all patients)., Conclusions: The arteries that supply the sinuatrial node and atrioventricular node can be imaged with multidetector CT. These arteries have variations in number, origin and course., (© Springer-Verlag 2011)

The general anatomy of the cardiac conduction system (CCS) has been known for 100 years, but its complex and irregular three-dimensional (3D) geometry is not so well understood. This is largely because the conducting tissue is not distinct from the surrounding tissue by dissection. The best descriptions of its anatomy come from studies based on serial sectioning of samples taken from the appropriate areas of the heart. Low X-ray attenuation has formerly ruled out micro-computed tomography (micro-CT) as a modality to resolve internal structures of soft tissue, but incorporation of iodine, which has a high molecular weight, into those tissues enhances the differential attenuation of X-rays and allows visualisation of fine detail in embryos and skeletal muscle. Here, with the use of a iodine based contrast agent (I(2)KI), we present contrast enhanced micro-CT images of cardiac tissue from rat and rabbit in which the three major subdivisions of the CCS can be differentiated from the surrounding contractile myocardium and visualised in 3D. Structures identified include the sinoatrial node (SAN) and the atrioventricular conduction axis: the penetrating bundle, His bundle, the bundle branches and the Purkinje network. Although the current findings are consistent with existing anatomical representations, the representations shown here offer superior resolution and are the first 3D representations of the CCS within a single intact mammalian heart.

The presented case and discussion illustrate the use of CT coronary angiography to depict coronary artery fistulae. A 41-year-old man presented with an acute myocardial infarction. Invasive angiography revealed an incidental coronary artery fistula but was unable to depict its course. CT coronary angiography was undertaken to define the course and termination of the fistula. This confirmed a fistulous connection between the left circumflex artery and the superior vena cava that followed the typical course of an S-shaped sinoatrial nodal artery. Even in such an unusual anomaly this case highlights the ability of CT coronary angiography to accurately depict the coronary artery anatomy.

We aimed to investigate the variances in especially the origin, course and termination of the sinoatrial node (SAN) artery in this study, using coronary CT angiography. The coronary CT angiography images of 251 patients (190 men and 61 women; age range, 20-82 years; mean age, 54.4 ± 13.6 years) were retrospectively analyzed. The SAN artery (arteries) in each case was named according to a special nomenclature with regard to their origin, course and termination. The sinoatrial node was being vascularized by a single artery in 241 (96%) cases and by two arteries in 10 (4%) cases. It was arising from RCA in 139 (55.4%) cases, from LCX in 99 (39.4%) cases, from the aorta in 2 (0.8%) cases, and from the bronchial artery in 1 (0.4%) case. The mean diameter of the SAN arteries was 2.3 mm. The mean distance between the origin of the SAN artery from RCA and the RCA ostium was 16.2 mm, from LCX and the origin of LCX was 19.3 mm. Frequency of the atrial branch was 35.9%. S-shaped SAN artery is determined in 51 (20.3%) cases. Coronary CT angiography is considerably effective in depicting the various vascularization types of SAN.

Disturbance of cardiac rhythm is one of the consequences of myocardial ischemia/reperfusion injury. Many researchers have prompted considerable interests in developing therapeutic approaches for its control. In present study, we want to determine whether that adenosine pre- and postconditioning have protective effects on sinoatrial node ischemia/reperfusion injury on morphology, arrhythmia score, serological markers (CK-MB and cTnT), SOD activities, MDA levels and expression of HCN4 channels in SA node cells. According to the arrhythmia score recorded, whether adenosine used in terms of ischemia or reperfusion, the total number of arrhythmia was significantly reduced, as well as the number of its episodes was also markedly decreased. We have also shown a clear correlation between HCN4 channels expression and the dysfunction of SA node cells. HCN4 immunoreactivity decreased after adenosine pre- and postconditioning, but changes were significantly smaller in the cells of the SA node compared with cells of I/R group. The content of cTnT, CK-MB and MDA in adenosine pre- and postconditioning group reduced significantly; but the level of SOD increased significantly. Histological examination and electron microscopy observations found in adenosine pre- and postconditioning group sinoatrial node injury also mitigated. These findings suggested that adenosine pre- or postconditioning were to reduce the incidence of ischemia/reperfusion arrhythmias, reduce myocardial ischemia reperfusion injury. The mechanism was to stabilize the SA node cells membrane and one possible mechanism involves modulation of HCN4 channels in pacemaker cells of the sinoatrial node.

Introduction: The area of the functional sinus node complex exceeds that of the anatomical sinus node; however, reasons for this discrepancy are unknown. We aimed to characterize the functional sinus node complex in health and disease with high-density simultaneous mapping., Methods and Results: Sinus node activity was characterized in 15 reference patients after ablation for supraventricular tachycardia. A further 16 patients were studied following ablation of chronic atrial flutter to determine effects of atrial remodeling. High-density simultaneous mapping of the sinus node complex was performed using a multi-electrode array. In reference patients, distance from superior vena cava-right atrial (SVC-RA) junction to earliest activation (EA) was 4 +/- 4 mm and sinus break-out (SBO) 9 +/- 6 mm. Preferential pathways of conduction were observed between EA and SBO. For patients with flutter, these distances were greater (EA: 15 +/- 12 mm, P = 0.003; SBO: 23 +/- 11 mm, P < 0.001). Conduction time along preferential pathways was 15 +/- 5 ms for reference patients and 23 +/- 8 ms for patients with flutter (P = 0.005). Following pacing, distance from SVC-RA junction to EA and SBO lengthened to 13 +/- 8 mm (P = 0.006) and 16 +/- 10 mm (P = 0.02), respectively, in reference patients, and 19 +/- 12 mm (P = 0.045), 28 +/- 9 mm (P = 0.02) in patients with flutter. This resulted in caudal shifts in EA and SBO of 10 +/- 9 mm and 7 +/- 8 mm in reference patients but diminished shifts in patients with flutter; 4 +/- 7 mm and 4 +/- 6 mm., Conclusion: The functional sinus node complex demonstrates dynamic changes in activation. There are preferential pathways of conduction from sinus node to atrial myocardium. The remodeled atria demonstrate longer conduction times along preferential pathways and a restricted functional sinus node complex.

Sinus node artery originates from the proximal segment of the right coronary artery, left circumflex artery, or from both. We present a 55-year-old man who underwent coronary angiography for exercise-induced chest pain localized in the epigastric region that resolved within several minutes of resting. He had an anomalous sinus node artery originating from the left anterior descending artery and right coronary artery agenesis. To our knowledge, this is the first reported case of coexistence of these two rare coronary anomalies.

Recent studies demonstrated a role of sphingosine-1-phosphate (S1P) in the protection against the stress of ischemia/reperfusion (I/R) injury. In experiments reported here, we have investigated the signaling through the S1P cascade by FTY720, a sphingolipid drug candidate displaying structural similarity to S1P, underlying the S1P cardioprotective effect. In ex vivo rat heart and isolated sinoatrial node models, FTY720 significantly prevented arrhythmic events associated with I/R injury including premature ventricular beats, VT, and sinus bradycardia as well as A-V conduction block. Real-time PCR and Western blot analysis demonstrated the expression of the S1P receptor transcript pools and corresponding proteins including S1P1, S1P2, and S1P3 in tissues dissected from sinoatrial node, atrium and ventricle. FTY720 (25 nM) significantly blunted the depression of the levels of phospho-Pak1 and phospho-Akt with ischemia and with reperfusion. There was a significant increase in phospho-Pak1 levels by 35%, 199%, and 205% after 5, 10, and 15 min of treatment with 25 nM FTY720 compared with control nontreated myocytes. However, there was no significant difference in the levels of total Pak1 expression between nontreated and FTY720 treated. Phospho-Akt levels were increased by 44%, 63%, and 61% after 5, 10, and 15 min of treatment with 25 nM FTY720, respectively. Our data provide the first evidence that FTY720 prevents I/R injury-associated arrhythmias and indicate its potential significance as an important and new agent protecting against I/R injury. Our data also indicate, for the first time, that the cardioprotective effect of FTY720 is likely to involve activation of signaling through the Pak1., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Objective: Sinoatrial node (SAN) artery originates from proximal segment of right coronary artery (RCA) or from left circumflex artery. Sinoatrial node artery artery originating from posterolateral (PL) branch of RCA is very rare. Only several cases have been reported. The study was performed to seek the frequency of this variation, evaluate clinical relevance, and describe electrocardiographic, angiographic characteristics of patients., Methods: Consecutive 1500 coronary angiography were screened to detect specifically SAN artery originating from PL branch of RCA. Patients with this variation were followed-up for one year regarding the arrhythmic events., Results: The origin of SAN artery was proximal RCA in 1280 (85%), circumflex artery in 208 (14%), and PL branch of RCA in 12 (0.8%) patients (8 male, 4 female, mean age 64+/- 9 years). There was no history of arrhythmia in all patients. One patient presented with atrioventricular block. Indications of angiography were stable angina in 5, unstable angina in 5, and acute myocardial infarction in 2 patients. The patient with inferior myocardial infarction due to RCA total occlusion did not develop bradycardia or conduction defect. In four patients (33%) there was another artery originating from proximal RCA, ending at same territory with the variant artery suggesting dual blood supply. During one-year follow-up none of the patients experienced arrhythmic event., Conclusions: Sinoatrial node artery originating from distal RCA is very rare. This variation, even in patients with severe RCA disease is not associated with severe arrhythmia. Dual blood supply may be a protective factor in this subgroup of patients from arrhythmic events. To be aware of the origin and course of variant SAN artery may provide safe approach to interventional cardiologist and cardiac surgeon during percutaneous and surgical coronary and atrial interventions.

Background: To study the arterial supply of the conducting system and its correlation with the dominance of the coronary arteries in the South Indian population., Objective: To determine angiographically the origins of the sinoatrial nodal artery (SAna) and atrioventricular nodal artery (AVna) in Indians., Methods: The study included 300 consecutive patients (114 females, 186 males; mean age, 55 years) living in the southern coastal region of India, who underwent coronary angiography either for the symptoms of chest pain, angina pectoris or positive Treadmill Test. The angiograms contained both coronary arteries (right and left) in the right and left anterior oblique position. The origin of SAna and AVna from the coronary arteries was observed and correlated with the arterial dominance., Results: The SA (sinoatrial) node was supplied by the right coronary artery (RCA) in 53% of the cases, by the circumflex (Cx) branch of left coronary artery (LCA) in 42.66%, and by both coronary arteries in 4.33% of cases. The AV (atrioventricular) node was also more often supplied by the RCA (72.33% of cases) than by the Cx branch of the LCA (27.66%), and surprisingly in none of the cases was this node supplied by both coronary arteries., Conclusion: The results of the present study may help cardiac surgeons, particularly in surgeries related to certain valvular disorders, due to the proximity of the nodal branches to the valve complex.

Objective: The purpose of this study was to use 64-MDCT to investigate the anatomic characteristics of the S-shaped variant of the sinoatrial node (SAN) artery and to describe the clinical implications of the findings in ablative procedures involving the left atrium., Materials and Methods: Coronary CT angiograms of 250 patients (152 men, 98 women; mean age, 60 +/- 12 [SD] years) were retrospectively analyzed for identification of the origin, number, anatomic course, mode of termination, and S-shaped variant of the SAN artery., Results: At least one SAN artery was detected in 244 patients. The S-shaped variant was seen in 35 (14.3%) of these patients. Thirty-four of the variants (30.6% of all left SAN arteries) arose from the proximal to middle portion of the left circumflex artery (mean distance between the ostium of the left circumflex artery and the origin of S-shaped variant, 28.7 +/- 13.1 mm). The other variant (0.7% of all right SAN arteries) originated from the distal right coronary artery. The S-shaped variant was the only artery supplying the SAN in 28 (11.4%) of the patients. In patients with two arteries supplying the SAN, the right SAN artery and the S-shaped variant of the left SAN artery were seen together in seven patients. The S-shaped SAN artery (mean distance from atrial wall, 2.43 +/- 0.992 mm) had a predictable proximal course, lying in the posterior aspect in a groove between the orifices of the left superior pulmonary vein and the left atrial appendage close to the left atrial wall. The terminal segment of the artery approached the nodal tissue posterior to the superior vena cava in 22 patients, anterior to the vena cava in 10 patients, and through branches surrounding the vena cava in two patients., Conclusion: The S-shaped variation of the SAN artery is common and has a characteristic anatomic course. MDCT can be used to plan surgical and catheter-based left atrial interventions in which this artery is at risk of injury.

Purpose: To retrospectively evaluate the depiction of anatomic characteristics of the arterial supply to the sinuatrial node (SAN) and the atrioventricular node (AVN) with 64-section computed tomography (CT)., Materials and Methods: The institutional review board approved this HIPAA-compliant study; informed consent was not required. Anatomic origin, number, course, and variants of the arteries to the SAN and AVN were examined with coronary multidetector CT in 102 patients (55 men, 47 women; mean age, 57 years +/- 13 [standard deviation]). Known accessory blood supplies to the AVN, including left and right Kugel anastomotic arteries, were investigated. Possible extension of the first septal perforating artery to the AVN was evaluated. Univariate and bivariate statistical data were reported. Means +/- standard deviations, 95% confidence intervals, and percentages were calculated., Results: A single sinuatrial nodal artery originated from the proximal 40 mm of the right coronary artery (RCA) in 67 and from the proximal 35 mm of the left circumflex (LCX) artery in 28 patients. A dual blood supply to the SAN was seen in six patients. The sinuatrial nodal artery was not visualized in one patient. An S-shaped variant was seen in 18% of left sinuatrial nodal arteries and invariably traveled posteriorly in the sulcus between the left superior pulmonary vein and left atrial appendage. The sinuatrial nodal artery approached the nodal tissue by one of three routes-retrocaval (47.5%), precaval (42.6%), or pericaval (9.9%). The AVN was supplied by the RCA in 89 patients, the LCX artery in 11 patients, and by both arteries in two patients. Two left and six right Kugel anastomotic arteries were detected as supplying the AVN area. The first septal perforating artery had no detectable connection to the AVN., Conclusion: The arterial blood supply to the SAN and the AVN is variable and can be imaged with multidectector CT., Supplemental Material: http://radiology.rsnajnls.org/cgi/content/full/2461070030/DC1., (RSNA, 2007)

Objective: To present a technical proposal based on the experience of 130 implantations using a simplified technique for coronary sinus catheterization, based on the atrial component of the intracavitary electrogram and radiological anatomy., Methods: From October, 2001 to October, 2004, 130 biventricular pacemaker implantations were performed, using radiological anatomy and observation of the intracavitary electrogram, focusing on the atrial component., Results: The implantation of the system using left ventricular pacing via coronary sinus was not possible in 8 patients. Difficulties on the cannulation of the coronary ostium were felt in 12 patients and difficulties of lead advancement through the coronary sinus were felt in 15 patients. The mean time of radioscopy utilization was 18.69 min., Conclusion: The implantation technique, using the atrial component morphology of the intracavitary electrogram and radiological anatomy showed to be workless, safe and effective for the cannulation of the coronary sinus ostium requesting reduced time of radioscopy.

Objective: We sought to investigate whether left atrial (LA) appendage (LAA) function was impaired in patients with systemic embolism in sinus rhythm., Methods: Transesophageal echocardiography was performed in 7 patients within 5 days after embolism (early group) and in 32 patients, more than 5 days after embolism (late group). We searched intracardiac thrombus and determined LAA area and LAA flow velocity, and the grade of spontaneous echocontrast., Results: LA thrombus could be detected in 2 of the 39 patients only in early group (P = .028). The patients of early group, as compared with late group, had lower LAA flow velocity (28 +/- 16 vs 60 +/- 26 cm/s, P = .007) and higher grade of spontaneous echocontrast score (1.14 +/- 1.46 vs 0.25 +/- 0.62, P = .013). LA dimension and LAA area were not statistically different., Conclusion: LAA function may be impaired early after embolism even in sinus rhythm.

A method has been developed to quantitatively analyze sinoatrial nodes (SAN) using Doppler tissue images (DTI). Doppler tissue images of SAN are acquired using an intracardiac catheter via the superior vena cava in an in vivo experiment. A sequence of DTI images of a SAN is obtained, and a complete cycle of the SAN excitation is observed. The tissue acceleration of the SAN is extracted and quantitatively analyzed. The estimated time-acceleration curve of the SAN exhibits remarkable similarity to the electrocardiogram curve. This is the first report on such finding. The experimental results show that the tissue movement of the SAN correlates with electrical cardiac activities and closely associates with the different phases of the cardiac cycle. This method has great potential in characterizing the local cardiac activities through the study of the conduct pathway.

Objective: To precisely visualize cardiac anatomic structures and simultaneously depict electro-mechanical events for the purpose of precise underblood intervention., Methods: Intracardiac high-resolution tissue Doppler imaging was used to map real time myocardial contractions in response to electrical activation within the anatomic structure of the cardiac conductive system using a canine open-chest model., Results: The detailed inner anatomic structure of the cardiac conductive system at different sites (i.e., sino-atrial, atrial wall, atrial-ventricular node and ventricular wall) with the inside onset and propagation of myocardial velocity and acceleration induced by electrical activation was clearly visualized and quantitatively evaluated., Conclusion: The simultaneous single modality visualization of the anatomy, function and electrical events of the cardiac conductive system will foster target pacing and precision ablation.

Dilation of the coronary sinus is mostly a congenital lesion. As acquired lesion it was found to be associated with poor left ventricular function. In the present case an angiographic diagnosed posterior left ventricular aneurysm was during surgery found to be a dilated coronary sinus. Preoperative left ventricular function was normal.

Study Objective: To measure coronary sinus blood flow during coronary artery bypass graft (CABG) with transesophageal echocardiography (TEE)., Design: Prospective study., Setting: Elective cardiac surgery at a university hospital., Patients: Thirty-one ASA physical status III and IV adult patients free of significant coexisting disease and undergoing CABG., Intervention: We measured coronary sinus blood flow velocity by using TEE and hemodynamic variables, before and after cardiopulmonary bypass (CPB) and after CPB., Measurements and Main Results: We obtained a complete set of control measurements for 29 subjects (94%) and a complete set of post-CPB measurements in 28 patients (90%). In the normal group, peak velocity, and velocity time integral (VTI) of coronary sinus blood flow in the post-CPB period increased significantly compared with the pre-CPB period with CABG (n = 23). In the group of new regional wall motion abnormalities in the post-CPB period, peak velocity and VTI of coronary sinus blood flow in the post-CPB period did not increase significantly compared with the pre-CPB period by CABG (n = 5)., Conclusions: We were able to measure the coronary sinus flow velocity by pulse-Doppler TEE during CABG. The peak velocity and VTI of coronary sinus blood flow in the post-CPB period increased significantly compared with in the pre-CPB period by CABG. The results of this preliminary study show the feasibility of clinical evaluation of CABG intraoperatively.

Background: Orthotopic heart transplantation (HTx) results in complete cardiac denervation. Reestablished partial sympathetic nerve function has been found in patients some years after HTx. However, the atrial and ventricular regional patterns of reinnervation have not been established., Methods: Two parallel methods were used to evaluate the regional restoration of sympathetic nerves in the myocardium. Patients were investigated with respect to ventricular reinnervation (VI) using positron emission tomography (PET) and the norepinephrine analogue C-11-hydroxyephedrine (HED). Tracer uptake was quantified using dynamic imaging protocols, yielding regional HED retention fraction. A regional value above 7%/minute ( +/- 2.5 SD above the mean value of denervated hearts) was considered evidence of sympathetic reinnervation. Spectral analysis of heart rate variability (HRV) served as a quantitative marker for reinnervation at the sinus node (SI). Spectra of HRV during positive head-up tilt were calculated. The low frequency (LF) power spectral density (0.05 to 0.18 Hz) was evaluated., Results: After HTx (4. 6 +/- 3.9 years; range, 0.2 to 13.6 years), 38 patients (aged 50.9 +/- 7.6 years; range, 37 to 65 years) were investigated by PET imaging and HRV. Twenty-two patients with a mean HED retention of 10. 7 +/- 2.6%/minute were classified as left ventricular reinnervated. Sixteen patients with a mean HED retention of 4.8 +/- 0.8%/minute did not reach the threshold. The time difference after HTx was significant for these 2 groups, 5.3 +/- 3.0 years vs 3.8 +/- 4.7 years ( p < 0.05 ). The LF power spectral density of the ventricular reinnervated patients was 5.9 +/- 8.6 ms(2), and 1.8 +/- 4.4 ms(2) (p <0.005 ) for those not reinnervated. Low frequency showed small values and narrow distribution for the patients not reinnervated, assuming sinus node denervation, and showed extended distribution for the reinnervated, suggesting a heterogeneous reinnervation pattern., Conclusions: Two non-invasive parallel methods were used to investigate regional reestablishment of cardiac nerves in the myocardium in HTx patients. Left VI assessed by PET imaging and SI by HRV was congruent in 60% of HTx patients. Lack of SI paralleled absence of VI. Our results suggest that partial VI occurs prior to SI.

The aim of this study was to compare AAIR and DDDR pacing at rest and during exercise. We studied 15 patients (10 men, age 65 +/- 6 years) who had been paced for at least 3 months with activity sensor rate modulated dual chamber pacemakers. All had sick sinus syndrome (SSS) with impaired sinus node chronotropy. The patients underwent a resting echocardiographic evaluation of systolic and diastolic LV function at 60 beats/min during AAIR and DDDR pacing with an AV delay, which ensured complete ventricular activation capture. Cardiac output (CO) was also measured during pacing at 100 beats/min in both pacing modes. Subsequently, the oxygen consumption (VO2AT) and VO2AT pulse at the anaerobic threshold were measured during exercise in AAIR mode and in DDDR mode with an AV delay of 120 ms. The indices of diastolic function showed no significant differences between the two pacing modes, except for patients with a stimulus-R interval > 220 ms, for whom the time velocity integral of LV filling and LV inflow time were significantly lower under AAI than under DDD pacing. At 60 beats/min, CO was higher under AAI than under DDD mode only when the stimulus-R interval was below 220 ms. For stimulus-R intervals longer than 220 ms, and also during pacing at 100 beats/min, the CO was higher in DDD mode. The stimulus-R interval decreased in all patients during exercise. The time to anaerobic threshold, VO2AT, and VO2AT pulse showed no significant differences between the two pacing modes. Our results indicate that, at rest, although AAIR pacing does not improve diastolic function in patients with SSS, it maintains a higher CO than does DDDR pacing in cases where the stimulus-R interval is not excessively prolonged. On exertion, the two pacing modes appear to be equally effective, at least in cases where the stimulus-R interval decreases in AAIR mode.

Background: The sinus P wave arises from a pacemaker complex distributed along the crista terminalis. We investigated the feasibility of modification of sinus pacemaker function using graded applications of radiofrequency energy along the crista terminalis in dogs to achieve sinus rate control., Methods and Results: Modification of sinus pacemaker function (30 +/- 5% reduction in intrinsic heart rate with retention of a normal P-wave axis) was performed in 11 dogs (group 1). Total sinus pacemaker ablation (> 50% reduction in intrinsic heart rate with development of a low ectopic atrial or a junctional rhythm) was performed in 4 dogs (group 2). Intracardiac echocardiography was used to identify the crista terminalis as an anatomic marker of sinus node location. Sinus pacemaker modification caused a significant decrease in intrinsic heart rate (31% reduction, P < .001), heart rate responsiveness to isoproterenol (30% reduction, P < .0001), and average (20% reduction, P = .0002) and maximal (22% reduction, P = .0007) heart rates during 24-hour Holter monitoring. In 6 of the 11 animals, the targeted rate reduction of 30 +/- 5% was accurately achieved (mean, 31.6 +/- 4.3%; P < .001), and in the other 5, significant reduction of intrinsic heart rate was achieved but with greater variation (28.0 +/- 17.3%, P < .005). Corrected sinus node recovery time was not prolonged. After modification, earliest activation was mapped to the crista terminalis inferior to the lesion in all animals. In long-term follow-up (3.7 +/- 1.0 months), effects were maintained. After total sinus pacemaker ablation, junctional and low atrial escape pacemakers were unstable., Conclusions: This study demonstrates the feasibility of modification of sinus pacemaker function for sinus rate control using catheter-based radiofrequency ablation guided by intracardiac echocardiography. This can be done while pacemaker stability and attenuated responsiveness to autonomic influences are preserved. Intracardiac echocardiography accurately defined the crista terminalis and provided a reliable means to anatomically localize catheter position in relation to the sinus node.

Coronary angiograms of 309 consecutive patients undergoing coronary angiography were reviewed to investigate the blood supply to the sinus node area. Blood was supplied from the right coronary artery in 59% of cases, from the left coronary artery in 38%, and from both coronary arteries in 3%. The posterior sinus node artery was demonstrated in 32 patients (27% of the 119 patients with the sinus node artery originating from the left circumflex and 10.5% of all patients).

Postmortem angiography was used to examine the blood vessels supplying the sinoatrial node in 25 subjects with chronic sinoatrial disorder (group 1). The results were compared with similar studies in 54 subjects who died of heart block and in whom sinus node function was normal (group 2). Although no significant lesion obstructing the blood flow to the sinus node was seen in the majority of those in group 1, there were abnormalities in seven cases, with reduced filling of the sinus node artery in five. In group 2 the sinus node artery filled normally in all cases despite major disease of the parent vessel in three. The combination of contralateral coronary artery disease with extensive atrial anastomoses was actively sought because this arrangement might predispose to a steal phenomenon. Such conditions were fully met in three cases in group 1 and two cases in group 2, and were found to a lesser extent in a further two cases in group 1 and three in group 2. Although coronary artery disease was unlikely to be the principal cause of sinus node dysfunction in most of the cases studied it was relatively common and may have been a factor in about one third. Improved survival after myocardial infarction may increase the number of patients with chronic sinoatrial disorder of ischaemic origin.