Sinus Node Research Articles

The electrophysiological effects of Tongyang Huoxue granules on the ignition phase during hypoxia/reoxygenation injury in sinoatrial node cells.

This study was undertaken to explore the potential therapeutic effects of Tongyang Huoxue Granules (TYHX) on sinoatrial node (SAN) dysfunction, a cardiac disorder characterized by impaired impulse generation or conduction. The research question addressed whether TYHX could positively influence SAN ion channel function, specifically targeting the sodium-calcium exchanger (I NCX) and L-type calcium channel (I CaL) of the SAN. Sinoatrial node cells (SANCs) were isolated and cultured from neonatal Japanese big-eared white rabbits within 24h of birth. The study encompassed five groups: Control, H/R (hypoxia/reoxygenation), H/R+100μg/mL TYHX, H/R+200μg/mL TYHX, and H/R+400μg/mL TYHX. The H/R model, simulating hypoxia/reoxygenation stress, was induced within 5days of culture. Whole-cell patch clamp technique was employed to record currents following a 3-min perfusion and stabilization period with TYHX. TYHX administration demonstrated improvements in the ignition phase of impaired SANCs. The half-maximal effective dose of TYHX, as determined by SANC beating frequency, was found to be 323.63μg/mL. Inward current density of I NCX increased in response to TYHX (200 and 400μg/mL), while TYHX enhanced I CaL current density in H/R SANCs, with 400μg/mL exhibiting greater efficacy. Additionally, TYHX regulated the gating mechanisms of I CaL by right-shifting the steady-state inactivation curve and accelerating recovery from inactivation. Notably, TYHX increased the activation time constant under 200 and 400μg/mL, prolonged the fast inactivation time constant τ1 with 400μg/mL, and extended the slow inactivation time constant τ2 with 100 and 400μg/mL. The findings suggest that TYHX may hold promise as a therapeutic intervention for sinus node dysfunction, offering potential avenues for drug development aimed at safeguarding SAN function.

Intraoperative characterization of cardiac tissue: the potential of light scattering spectroscopy.

Damage to the cardiac conduction system remains one of the most significant risks associated with surgical interventions to correct congenital heart disease. This work demonstrates how light-scattering spectroscopy (LSS) can be used to non-destructively characterize cardiac tissue regions. To present an approach for associating tissue composition information with location-specific LSS data and further evaluate an LSS and machine learning system as a method for non-destructive tissue characterization. A custom LSS probe was used to gather spectral data from locations across 14 excised human pediatric nodal tissue samples (8 sinus nodes, 6 atrioventricular nodes). The LSS spectra were used to train linear and neural-network-based regressor models to predict tissue composition characteristics derived from the 3D models. Nodal tissue region nuclear densities were reported. A linear model trained to regress nuclear density from spectra achieved a prediction r-squared of 0.64 and a concordance correlation coefficient of 0.78. These methods build on previous studies suggesting that LSS measurements combined with machine learning signal processing can provide clinically relevant cardiac tissue composition.

Glucagon-like peptide-1 increases heart rate by a direct action on the sinus node.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used to treat type 2 diabetes and obesity. Albeit cardiovascular outcomes generally improve, treatment with GLP-1 RAs is associated with increased heart rate, the mechanism of which is unclear. We employed a large animal model, the female landrace pig, and used multiple in vivo and ex vivo approaches including pharmacological challenges, electrophysiology, and high-resolution mass spectrometry to explore how GLP-1 elicits an increase in heart rate. In anaesthetized pigs, neither cervical vagotomy, adrenergic blockers (alpha, beta, or combined alpha-beta blockade), ganglionic blockade (hexamethonium), nor inhibition of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (ivabradine) abolished the marked chronotropic effect of GLP-1. GLP-1 administration to isolated perfused pig hearts also increased heart rate, which was abolished by GLP-1 receptor blockade. Electrophysiological characterization of GLP-1 effects in vivo and in isolated perfused hearts localized electrical modulation to the atria and conduction system. In isolated sinus nodes, GLP-1 administration shortened the action potential cycle length of pacemaker cells and shifted the site of earliest activation. The effect was independent of HCN blockade. Collectively, these data support a direct effect of GLP-1 on GLP-1 receptors within the heart. Consistently, single nucleus RNA sequencing showed GLP-1 receptor expression in porcine pacemaker cells. Quantitative phosphoproteomics analyses of sinus node samples revealed that GLP-1 administration leads to phosphorylation changes of calcium cycling proteins of the sarcoplasmic reticulum, known to regulate heart rate. GLP-1 has direct chronotropic effects on the heart mediated by GLP-1 receptors in pacemaker cells of the sinus node, inducing changes in action potential morphology and the leading pacemaker site through a calcium signalling response characterized by PKA-dependent phosphorylation of Ca2+ cycling proteins involved in pacemaking. Targeting the pacemaker calcium clock may be a strategy to lower heart rate in people treated with GLP-1 RAs.

Peri-mortem arrhythmias in the non-cardiac intensive care unit.

Cardiovascular failure is recognized as a common final pathway at the end of life but there is a paucity of data describing terminal arrhythmias. We aimed to describe arrhythmias recorded peri-mortem in critically ill patients. We enrolled intensive care unit patients admitted to two tertiary Canadian medico-surgical centres. Participants wore a continuous electrocardiogram (ECG) monitor for 14 days, until discharge, removal or death. We recorded all significant occurrences of arrhythmias in the final hour of life. Among 39 patients wearing an ECG monitor at the time of death, 22 (56%) developed at least 1 terminal arrhythmia as adjudicated by an arrhythmia physician: 23% (n = 9) had ventricular fibrillation/polymorphic ventricular tachycardia, 18% (n = 7) had sinoatrial pauses, 15% (n = 6) had atrial fibrillation and 13% (n = 5) had high-degree atrioventricular block. Five participants (13%) developed multiple arrythmias. Arrhythmias are common in dying critically ill patients. There is a roughly even distribution between ventricular arrhythmias, atrial fibrillation, sinus node dysfunction and atrioventricular block. The results of this study may be most useful for critically ill patients who are organ donation candidates. The appearance of arrhythmias may serve as a marker of change in clinical status for organ donation teams to plan mobilization efforts. In participants who are sedated or intubated, arrhythmias could be a surrogate marker for respiratory or neurologic changes.

Transcutaneous vagal nerve stimulation during lower body negative pressure

BackgroundPara-sympathetic vagal activation has profound influence on heart rate and other cardiovascular parameters. We tested the hypothesis that transcutaneous Vagal Nerve Stimulation (tVNS) through the auricular branch of the vagus nerve would attenuate the normal sympathetic response to central blood volume reduction by lower body negative pressure (LBNP). Method10 healthy volunteers (6 female; age 21 ± 2 years; weight 62 ± 13 kg; height 167 ± 12 cm) were included in this cross-over design trial. After 15 min rest in supine position, subjects underwent three 15-min periods of 30 mmHg LBNP intervention with and without cyclic tVNS stimulation. Continuous cardiovascular parameters (Nexfin) were recorded. ResultsOverall tVNS did not convincingly attenuate sympathetic response to central hypovolemia. Deactivation of the tVNS during LBNP resulted in increased MAP at 2.3 ± 0.5 mmHg (P < 0.001). Comparing the cyclic actual active stimulation periods to periods with pause during tVNS intervention showed a decrease in HR by 72.9 ± 11.2 to 70.2 ± 11.6 bpm (mean ± SD; P < 0.05), and concomitant increases in SV (86.0 ± 12.1 to 87.2 ± 12.6 mL; P < 0.05), MAP (82.9 ± 6.3 to 84.0 ± 6.2 mmHg; P < 0.05) and TPR (1116.0 ± 111.1 to 1153 ± 104.8 dyn*s/cm5; P < 0.05). ConclusiontVNS in 30 s cycles during LBNP can selectively attenuate HR, prompting a compensatory augmented sympathetic response. It would appear the method used in this study at least, has an isolated cardiac inhibitory effect probably mediated by augmented vagal activity on the sinoatrial or atrio-ventricular node, possibly in combination with reduced activity in the sympathetic cardiac nerve.

NOD-1 activation increases the spontaneous activity and the I(f) current of murine sinoatrial node cells

NOD-1 activation increases the spontaneous activity and the I(f) current of murine sinoatrial node cells

The role of sinoatrial node heterogeneity in atrial driving and arrhythmia

The role of sinoatrial node heterogeneity in atrial driving and arrhythmia

Genetic ablation of G protein-gated K+ channels (GIRK4) rescues cardiac conduction defects and reduces fibrosis in mouse model of Sinus Node Dysfunction

Genetic ablation of G protein-gated K+ channels (GIRK4) rescues cardiac conduction defects and reduces fibrosis in mouse model of Sinus Node Dysfunction

Wide Spectrum of Bradyarrhythmias and Supraventricular Tachyarrhythmias in Sportsmen: Run Forrest, Run?!

The intricate relationship between sports participation and cardiac arrhythmias is a key focus of cardiovascular research. Physical activity, integral to preventing atherosclerotic cardiovascular disease, induces structural, functional, and electrical changes in the heart, potentially triggering arrhythmias, particularly atrial fibrillation (AF). Despite the cardiovascular benefits, the optimal exercise amount remains unclear, revealing a J-shaped association between AF and exercise. Endurance athletes, particularly males, face elevated AF risks, influenced by age. Risk factors vary among sports modalities, with unique physiological responses in swim training potentially elevating AF risk. Clinical management of AF in athletes necessitates a delicate balance between rhythm control, rate control, and anticoagulation therapy. Sport-induced bradyarrhythmias, including sinus bradycardia and conduction disturbances, are prevalent among athletes. Managing bradycardia in athletes proves challenging due to its complex and not fully understood pathophysiology. Careful consideration is required, particularly in symptomatic cases, where pacemaker implantation may be necessary for sinus node dysfunction. Although pacing is recommended for specific atrioventricular (AV) blocks, milder forms often prevail without restricting sports participation. This review explores the nuanced relationship between exercise and tachy- and bradyarrhythmia in athletes, addressing the challenges clinicians face when optimizing patient care in this distinctive population.

High initial heart rate score is an independent predictor of new atrial high-rate episodes in pacemaker patients with sinus node dysfunction

BackgroundHeart Rate Score (HRSc), the percent of atrial depolarizations in the largest paced/sensed 10-bpm histogram bin recorded in cardiac devices, is associated with several adverse outcomes but it remains uncertain if HRSc independently predicts atrial high-rate episodes (AHREs) in patients with sinus node dysfunction (SND) undergoing pacemaker (PM) implantation. ObjectiveTo determine if initial HRSc post-PM implant predicts new-onset AHREs in patients with SND. MethodsPatients had Boston Scientific PMs implanted for SND from 2012-2021 at Cleveland Clinic, University of Occupational and Environmental Health, Japan, Kyushu Rosai Hospital, and JCHO Kyushu Hospital. Patients were excluded if they had atrial fibrillation before PM implant or AHREs within 3-months post-implant. Subsequent AHREs post-implant were evaluated and correlated with HRSc. ResultsOver 48.9 (IQR 25.7-50.4) months, 130 consecutive PM patients (76±10 years, 40% male) had a median initial HRSc of 74(57-86)%. AHREs defined by >1%, >6h/day burden, and ATR events>24h developed in 27/130(21%), 15/130(12%), and 9/130(7%), respectively. For each definition, patients with HRSc≥80% had higher occurrence of AHREs than those with HRSc<80% (both p=0.008, log-rank test). After adjusting for age, race, comorbidities, left ventricular ejection fraction, left atrial diameter, and cumulative %RA/RV pacing, initial HRSc ≥80% (HR:3.33, 95% CI:1.35-8.18; P=0.009) and male sex (HR:2.59, 95% CI:1.06-6.33; P=0.04) independently predicted AHREs. ConclusionHRSc≥80% is associated with new-onset, device-determined AHREs for patients undergoing PM implant for SND. HRSc may have prognostic and therapeutic implications.

Ectopic Pitx2 expression and sinoatrial node dysfunction in mice recapitulating a novel cardiac syndrome identified in unrelated families with deletions in a gene desert on chromosome 4q25

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Research Councin/NWO Introduction Several unrelated families presenting with a complex, heterogeneous cardiac syndrome including sinoatrial node dysfunction and atrial fibrillation were found to share overlapping deletions in a 1.5 Megabase pair gene desert on chromosome 4q25. These overlapping regions contain evolutionarily conserved CTCF binding sites that modulate the separation of topologically associating domains containing the transcription factor-encoding gene PITX2 and noncoding RNA genes. Aim To understand mechanistically how the deletion in the gene desert causes sinoatrial node dysfunction and atrial arrhythmias. Methods Mice lacking the orthologue of the minimally overlapping genomic region deleted in affected patients were generated. Electrophysiology, morphology, tissue composition, and transcriptomes were analysed in this mouse model. Results These mice recapitulated major morpho-functional features of the syndrome, including sinoatrial node dysfunction and atrial arrhythmogenesis . Out of the 15 genes flanking the gene desert, only Pitx2 expression was deregulated in the sinoatrial node. During development, cardiac Pitx2c expression is normally restricted to the left side where it drives left sinus venosus and left atrial morphogenesis and prevents the formation of a left-sided sinoatrial node. The PITX2 locus has also been associated with atrial fibrillation in GWAS. Immunohistochemistry together with 3D volume analysis showed that Pitx2c was ectopically expressed in half of the pacemaker cardiomyocytes of the developing and postnatal sinoatrial node while its expression in the left atrium was maintained. Key transcription factors that drive pacemaker cell differentiation, Tbx3, Isl1 and Shox2, were lost where Pitx2c was ectopically expressed. Moreover, a conserved long non-coding RNA (Playrr) previously linked to Pitx2 regulation in the developing dorsal mesentery, was downregulated in the sinoatrial node of homozygous mutants. The downregulation of the pacemaker gene program additionally coincided with the activation of the atrial myocardial gene program in half of the pacemaker cardiomyocytes. Conclusion We generated a mouse model of a novel human cardiac syndrome including sinoatrial node dysfunction associated with the deletion of critical CTCF binding sites in a gene desert on chromosome 4q25. This deletion induced ectopic Pitx2c expression in the sinoatrial node alongside a substantial loss of pacemaker cardiomyocyte identity and a gain in a working atrial myocardium-like phenotype in the sinoatrial node of affected mice.Loss of pacemaker cardiomyocyte identitySinoatrial node dysfunction in mutants

AAV-mediated gene delivery to the cardiac conduction system

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NWO open technology program Biopace #18485 Background Gene therapy for cardiac arrhythmias has so far mostly focused on modifying the arrhythmogenic substrate in working myocardium or on creating biological pacemakers with viral vectors that did not selectively target the cardiac conduction system (CCS). As a result, CCS targeting by viral vectors is a relatively unexplored area. Aim In the current project, we explored the basic requirements for CCS targeting using adeno-associated virus (AAV) vectors. Methods Regular AAV9 and AAV-Myo4A capsid-pseudotyped AAV2 vectors (hereafter called AAV2/9 and AAV2/Myo4A vectors, respectively) expressing enhanced green fluorescent protein (eGFP) from a CMV or TNNT2 promoter, respectively, and an AAV2/9 vector expressing eGFP from a human GJA5 regulatory element were systemically injected in mice. After 4 weeks, hearts were harvested, fixed with paraformaldehyde and stained for TNNT2, eGFP, HCN4 and DNA to determine CCS transduction. Results Transduction of the sinoatrial and atrioventricular (AV) node using AAV2/9 vectors was very poor, while transduction was visible in the atrioventricular (i.e. His) bundle and working myocardium. In contrast, the transduction rate of the AV node and bundle using AAV2/Myo4A vectors were similar to that of the working myocardium. The human GJA5 regulatory element was able to restrict eGFP expression by AAV2/9 vectors to the AV bundle in 2/3 animals but the transduction efficiency was low. A third animal showed no transduction of any tissue, either indicative of the low transduction efficiency or of a failed injection. Conclusion This study not only provides proof-of-principle for CCS-targeted gene therapy but also shows that CCS transduction can be improved through AAV capsid engineering and be restricted to (parts of) the CCS by using specific transcriptional control elements.

Altered firing activity of intracardiac neurons isolated from mice carrying the Scn5a-1798insD mutation

Abstract Funding Acknowledgements None. Background Dysfunction of the cardiac sodium channel Nav1.5 (encoded by SCN5A) is associated with arrhythmias and sudden cardiac death, the mechanisms of which have been extensively studied in cardiomyocytes. However, patients carrying an SCN5A mutation often display clinical symptoms which are not readily explained solely by alterations in cardiomyocyte electrophysiology. For instance, carriers of the SCN5A-1795insD mutation, which is associated with features of Brugada syndrome and Long QT syndrome type 3 (LQT3), display severe bradycardia leading to excessive QT-prolongation and sudden death especially occurring at rest or during the night, suggesting autonomic triggers. Interestingly, SCN5A is not only present in cardiomyocytes, but also in intracardiac neurons (ICN). ICN modulate cardiac electrophysiological properties and their dysregulation may contribute to arrhythmogenesis. Purpose To explore whether ICN from mice carrying the Scn5a-1798insD mutation (the murine equivalent of SCN5A-1795insD) display electrophysiological alterations that may (in part) contribute to the arrhythmogenic phenotype. Methods and Results ICN were isolated by enzymatic dissociation from fat pads located in the pulmonary veins and sinoatrial node regions of the hearts of wild-type (WT) and Scn5a-1798insD mice. Immunodetection of the cholinergic marker ChAT confirmed the prominent cholinergic phenotype of ICN. In agreement with previous reports in other species, we also detected the presence of Nav1.5 in murine ICN. Nav1.5 expression was mainly observed in ChAT positive cells. To evoke repetitive action potential (AP) firing in single ICN, 500 ms-sustained depolarizing current pulses were applied of increasing amplitude (from 0 pA to 150 pA). Two types of neurons were identified on the basis of firing pattern characteristics: accommodating (neurons that discharged multiple APs decrementing in frequency during the pulse) and tonic (neurons that discharged multiple APs at a high frequency). APs firing frequency did not differ between WT and Scn5a-1798insD accommodating ICN, while it was significantly increased in Scn5a-1798insD tonic ICN as compared to WT (at 100 pA, AP count/500ms in WT CMs: 29.5±1.7, n=24; at 100 pA, AP count/500ms in Scn5a-1798insD: 36.2±2.0, n=18, p=0.02). Conclusions The impact of SCN5A mutations on ICN function are unexplored, but may play an essential role in arrhythmogenesis. The increased AP firing frequency observed in Scn5a-1798insD ICN may lead to increased release of neurotransmitters, such as acetylcholine, that in turn may contribute to the bradycardia observed in patients. Overall, further elucidation of the electrophysiological consequences of inherited Nav1.5 dysfunction in ICN might provide novel therapeutic targets to prevent lethal arrhythmias.

Bradycardia in a long QT type 2 family: coinciding KCNH2 and HCN4 variants

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): the Dutch Research Council: NWO Talent Scheme Background A large multigenerational family harboring a pathogenic KCNH2 variant (L69P) was identified. This gene encodes the hERG channel, responsible for the cardiac rapid delayed rectifier K+ current (IKr). Pathogenic variants in KCNH2 can cause Long QT syndrome type 2 (LQTS2). Interestingly, in addition to LQTS2 we observed a high incidence of bradycardia in this family. Bradycardia is a known feature of some types of LQTS. However, evidence of bradycardia in LQTS2 is limited to a few sporadic cases. Purpose This study aims to identify the genetic variants and biophysiological changes in ion channel function, explanatory of the phenotypes LQTS2 and bradycardia. Methods An overview of the phenotype and genetic information of the index and family members was generated , including symptoms and electrocardiogram (ECG) parameters. QTc was calculated using Bazetts’ correction. Segregation of the identified genetic variants with LQTS and bradycardia were determined by LOD score. Biophysiological properties of the encoded ion channels was measured by manual whole-cell patch-clamp experiments. Results On the basis of linkage analysis, the pathogenic variant KCNH2-p.L69P was found to be unrelated to the bradycardia. Therefore, Sanger sequencing of HCN4, encoding the channel responsible for the hyperpolarization-activated current (If), an important current for sinoatrial node automaticity, was performed. We identified the HCN4-p.R666W variant in multiple family members, which co-segregated with bradycardia (LOD-score 3.2). Patients carrying both variants had more severe phenotypes than carriers of a single variant. Patch-clamp experiments in HEK293A-cells expressing wild type, or KCNH2-p.L69P show a reduced current density, and an altered time component of the fast deactivation, explaining the observed LQTS2. Functional assays of HCN4-p.R666W will elucidate the biophysiological changes possibly underlying the bradycardia. Conclusion we present a large multigenerational family that harbors a likely pathogenic variant in HCN4 in conjunction with a pathogenic variant of KCNH2. Double carriers were more affected than single carriers, arguing for continued alertness and deep phenotyping even in families with known pathogenic variants. Furthermore, we identified functional changes in the kinetics of the hERG channel encoded by KCNH2-p.L69P, elucidating the molecular mechanism underlying LQTS2 in this family.

Arrhythmias in Cardiac Sarcoidosis: Management and Prognostic Implications.

Cardiac sarcoidosis (CS) is characterized by various arrhythmic manifestations ranging from catastrophic sudden cardiac death secondary to ventricular arrhythmia, severe conduction disease, sinus node dysfunction, and atrial fibrillation. The management of CS is complex and includes not only addressing the arrhythmia but also controlling the myocardial inflammation resultant from the autoimmune reaction. Arrhythmic manifestations of CS carry significant prognostic implications and invariably affect long-term survival in these patients. In this review, we focus on management of arrhythmic manifestation of cardiac sarcoidosis as well as risk stratification for sudden cardiac death in these patients.

Differential and synergistic effects of left and right atrial ablation of paraseptal ganglionated plexuses in a cohort of consecutive patients undergoing cardioneuroablation

Abstract Background Cardioneuroablation (CNA) treats reflex syncope by ablating the main epicardial ganglionated plexuses (GPs) conveying vagal outputs to the sino-atrial (SA) and atrio-ventricular (AV) nodes. The two main GPs, superior paraseptal (SPSGP) and inferior paraseptal (IPSGP), regulate vagal tone to SA and AV nodes, respectively. Both GPs can be targeted with radiofrequency energy (RF) from the right (RA) and left atrium (LA). It is unclear if bi-atrial ablation yields more effective GP ablation or if the ablation sequence affects GP response. Purpose We aimed to assess the added efficacy of ablating the SPSGP and IPSGP in the LA after initial RA ablation, and vice versa, in a separate group of patients. Methods In a consecutive patient population undergoing CNA we evaluated the acute efficacy of RF delivery on the SPSGP and the IPSGP. The population was divided into two consecutive groups: one receiving RF initially in the RA and then in the LA (group 1), and the other in the reverse order (group 2). The acute effect of RF applications was measured as percentage increase in heart rate (HR) for the SPSGP and as reduction of PR interval for the IPSGP. Results Sixty-one patients (50±15 years; 61% males) underwent CNA. Of these, 17 underwent ablation of the SPSGP and IPSGP starting from the RA and completing the procedure in the LA (group 1), while in 44 patients, the procedure was performed in the opposite order (group 2). In group 1, RF delivery on the SPSGP from the RA prompted an increase in HR (54.1±11.1 vs 60.6±14.7 bpm; p=0.03; median HR increment 3.8%, IQR 0-38.3) that was further enhanced after LA ablation (from 57.5±11.9 to 64.5±13.5 bpm; p&amp;lt;0.001; median HR increment: 8.0%, IQR: 2.0-13.5). In group 1, RA ablation of the IPSGP reduced PR interval in a single patient (from 224 to 184 ms), without further shortening after LA ablation. Final CNA success was 82% in group 1. In group 2, RF delivery on the SPSGP from the LA induced a marked increase in HR (58.4±13.1 vs 76.8±16.1 bpm; p&amp;lt;0.001; median HR increase 30.0%, IQR 14.0-43.0). In the same patients, additional ablation from the RA prompted further but lower incremental effect (from 70.0±17.3 to 76.9±17.9 bpm; p&amp;lt;0.001; median HR increment 8.3%, IQR: 0-16.4). In group 2, 4 (9%) patients had PR shortening after LA ablation of the IPSGP (241±93 vs 172±14 ms; p value). Of these, a single patient had further PR reduction after IPSGP RA ablation (from 189 to 161 bpm). Final CNA success was 93% in group 2. Symptoms-free survival was 88% at 16±5 months in group 1 and 89% at 19±7 months in group 2 (p= ns). Conclusions Bi-atrial ablation of the SPSGP and IPSGP provides incremental acute efficacy compared to ablation from either the RA or the LA alone. LA ablation of the main GPs seems an essential component of CNA. The physiological significance of these findings requires further investigationGanglionated Plexuses Segmentation

Rare origin of the sinoatrial node artery: an anatomic report and a brief review of the literature.

Several studies reported anatomical variations in the sinoatrial node artery (SANa). Here, we report a rare variation in the origin of the SANa on a human adult male cadaver. During dissection, we identified the SANa originating from a large atrial branch of the right coronary artery (RCA). This branch originates at the level of the inferior border of the heart and courses upwards. The initial part of this vessel is tortuous, and then it follows a straight path parallel to the RCA along the anterior surface of the right atrium. After this part, the artery curves posteriorly and to the left until it reaches the lower border of the right auricle, where it closely approaches the RCA. Finally, the artery runs posteriorly and to the right to follow a course along the medial wall of the right auricle and right atrium to reach a location close to the region of the junction of the superior vena cava and right atrium, where it follows its path buried in the myocardium. After perforating the myocardium, this vessel gives rise to branches that are distributed to both atria in addition to the SANa. The SANa runs to the sinoatrial node in a precaval (anterior to the superior vena cava) course. We also tried to characterize the vessels radiologically. The knowledge of the anatomical variations of the SANa is of the utmost importance for cardiologists and heart surgeons to better understand cardiac disease and accurately plan and execute cardiac interventions and surgical procedures.

Cardioneuroablation guided by extracardiac vagal stimulation for cardioinhibitory vasovagal syncope

Abstract Introduction Vasovagal Syncope (VVS) is often linked to abnormal autonomic reflexes, with hypervagotonia identified as a key mechanism, especially in cases with pronounced cardioinhibition. Cardioneuroablation (CNA), which involves radiofrequency ablation of cardiac vagal ganglia, targets parasympathetic hyperactivity, offering a promising treatment for recurrent VVS. This study evaluates the effectiveness and safety of anatomically guided CNA, which may provide an alternative treatment option to pacemaker implantation for younger patients with severe cardioinhibitory VVS. Methods Consecutive patients between January 2019 and October 2023 who underwent CNA at two cardiology centers were enrolled. All patients had a history of recurrent syncope, predominantly cardioinhibitory and unresponsive to conventional treatments. Patients showed no signs of conduction system disease, evidenced by normal rate responses in treadmill stress tests and 24-hour Holter monitoring. Electroanatomic mapping of the left atrium and pulmonary veins was performed. Extracardiac vagal stimulation (ECVS) through the right internal jugular vein, with or without atrial pacing, was utilized to assess baseline responses of the sinus and atrioventricular (AV) nodes. The ablation strategy was tailored based on rhythm disturbances triggered by ECVS, using sequential and anatomically guided ablation of ganglionated parasympathetic plexuses. Radiofrequency ablation, conducted with an irrigated catheter, was guided by the ablation index. Acute success was defined as the absence or significant reduction of cardiac parasympathetic response to ECVS, indicated by the elimination of asystole, severe bradycardia, or AV block. The primary endpoint was syncope recurrence during follow-up. Results The study included 25 patients (16 males; mean age 36 ± 12 years). All had documented cardioinhibition, identified through ECG monitoring (N=12), implantable loop recorders (N=5), or head-up tilt tests (N=8). The average number of syncopal episodes per patient in the year preceding ablation was 2.7, ranging from 1 to 10. Ablation was acutely successful in all cases. Post-ablation, there were no immediate complications related to the procedure, except for one convulsion deemed unrelated. Over a mean follow-up of 17 ± 14 months, 23 patients remained syncope-free. Two patients experienced syncope recurrence; despite undergoing a repeat ablation, they eventually required pacemaker implantation. Conclusion The results of this study suggest that CNA guided by ECVS, may offer a promising treatment for patients with refractory cardioinhibitory VVS. While the procedure showed a high rate of acute success and a notable reduction in syncope recurrence, further research is warranted to fully establish its role as an alternative to pacemaker implantation.

Reduction in pacemaker rates post-heart transplantation with use of organ preservation systems

Abstract Background Approximately 10% of heart transplant recipients require permanent pacemaker (PPM) implantation. (1) Prolonged graft ischaemic time may contribute to conduction system injury and PPM requirement. (2) Ex-vivo preservation of heart allografts at the time of organ retrieval, using either normothermic or hypothermic organ preservation systems (OPS), allows for the reduction of graft ischaemic time which can facilitate long-distance procurements and use of marginal donors including donation after circulatory death (DCD) donors. (3) Purpose We sought to determine if the use of organ preservation systems reduced PPM implantation in heart transplant recipients. Methods This was a single-centre retrospective study of 405 consecutive heart transplant recipients between July 2014 and March 2023. Baseline demographics, utilisation of organ preservation systems, donor ischaemic times, history of graft dysfunction, rejection and chronic allograft vasculopathy were obtained from the medical records. The primary outcome was PPM implantation. Results Of 405 heart transplants performed, an organ preservation system (OPS) was utilised in 118 (29.1%) patients. Normothermic OPS was used in 93/405 (23%) transplants, 90 of which were DCD transplants. Twenty-five of 405 (6.2%) transplants were performed using a hypothermic OPS to facilitate donation after brain death (DBD). The remaining 287 (70.9%) organs underwent cold ischaemic storage (CIS) from retrieval until transplant. Apart from male sex (81% in OPS group versus 69% in the CIS group), there were no significant differences in baseline demographics between the two groups (table 1). Two of 118 (1.7%) patients in the OPS group required PPM implantation, compared to 27/287 (9.4%) in the cold ischaemic storage group (Chi-Square 7.5, p = 0.006). Kaplan-Meier analysis (figure 1) demonstrates a significantly lower rate of PPM implantation in the OPS arm (Log Rank 6.975, p = 0.008). Of the 29 patients who required pacing, 12/29 (41.4%) had AV block and 17/29 (58.6%) had sinus node dysfunction. Thirteen of 29 patients (44.8%) required PPM implantation within 30 days of transplant. Six of 29 patients (20.7%) were pacing dependent at last follow up. Conclusion Heart transplants performed utilising an organ preservation system were associated with lower PPM rates.Table 1.Figure 1.

Superior vena cava isolation in paroxysmal atrial fibrillation - mind the phrenic

Abstract Background Pulmonary vein isolation (PVI) is the standard of care for patients with atrial fibrillation (AF), but medium-term success rates are far from ideal. Therefore, new methods are being developed, with emphasis on ectopic foci outside the pulmonary veins. Superior vena cava (SVC) is one of the most important non-pulmonary origins of AF and some studies suggested that empiric SVC isolation could improve outcomes in ablation of paroxysmal atrial fibrillation (PAF). Although complications have been reported in SVC ablation, most studies found complication rates of SVC ablation similar to conventional cryoballoon PVI. Aim This prospective, single-center study aimed to assess the complication rate and success rate of PVI followed by SVC isolation by cryoballoon application in comparison with conventional cryoballoon PVI. Methods We designed an unblinded, randomized clinical trial and recruited consecutive patients with PAF who were randomized to a conventional cryoballoon PVI or PVI and additional SVC cryoballoon isolation using single 180 s freeze. Results A total of 140 patients (61.4% male, mean age 62.1 years) with PAF were included and 67 (47.9%) were randomized to SVC isolation in addition to conventional ablation. Planned 180-s freeze in the SVC could be completed in 15 (22.4%) patients, while 27 (40.3%) patients received at least 120-s freeze. The mean time to SVC isolation was 40.2 ± 37.9 s. Real-time recording of SVC isolation was observed in 39 (58.2%) patients. Right phrenic nerve palsy (PNP), impending or transient, occurred in 6 (8.2%) patients in the PVI-only group and in 25 (37.3%) patients in the SVC-group (Chi-square test p &amp;lt; 0.001). There were no persistent PNP cases. Bradycardia or junctional rhythm was observed during a procedure in 15 (22.4%) patients who received SVC isolation. One patient eventually received a permanent AAI pacemaker due to a sinus node injury. Conclusion Our data suggest that SVC isolation can be successfully achieved in the majority of PAF patients using conventional cryoballoon. However, this significantly increases the rate of transient or impending PNP and sinus node injury in comparison to conventional cryoballoon PVI. Therefore, careful phrenic nerve function monitoring and attention to sinus bradycardia or junctional rhythm are important to mitigate this risk. Follow-up data are being collected to determine whether this risk could be outweighed by a lower rate of PAF recurrence.