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Sick sinus syndrome (SSS) encompasses a group of conduction disorders characterized by the inability of sinoatrial node to perform its pacemaker function. Our aim was to identify genetic predictors of SSS in a prospective cohort of patients admitted to the clinic for pacemaker implantation using single-locus and multilocus approaches. We performed genotyping for polymorphic markers of CLCNKA (rs10927887), SCN10A (rs6795970), FNDC3B (rs9647379), MIR146A (rs2910164), SYT10 (rs7980799), MYH6 (rs365990), and KCNE1 (rs1805127) genes in the group of 284 patients with SSS and 243 healthy individuals. Associations between the studied loci and SSS were tested using logistic regression under recessive genetic model using sex and age as covariates. Multilocus analysis was performed using Markov chain Monte Carlo method implemented in the APSampler program. Correction for multiple testing was performed using Benjamini–Hochberg procedure. We detected an individual association between KCNE1 rs1805127*A allele and SSS in the total study group (OR 0.43, PFDR = 0.028) and in the subgroup of patients with 2nd or 3rd degree sinoatrial block (OR 0.17, PFDR = 0.033), and identified seven allelic patterns associated with the disease. SCN10A rs6795970*T and MIR146A rs2910164*C alleles were present in all seven combinations associated with SSS. The highest risk of SSS was conferred by the combination SCN10A rs6795970*T+FNDC3B rs9647379*C+MIR146A rs2910164*C+SYT10 rs7980799*C+KCNE1 rs1805127*G (OR 2.98, CI 1.77–5.00, P = 1.27 × 10–5, PFDR = 0.022). Our findings suggest that KCNE1 rs1805127 polymorphism may play a role in susceptibility to sinoatrial node dysfunction, particularly presenting as 2nd or 3rd degree sinoatrial block, and the risk-modifying effect of other studied loci is better detected using multilocus approach.

Introduction It has been claimed that patients with systemic sclerosis (SSc) have an increased risk of developing cardiac arrhythmias and atrioventricular conduction disorders, but it is unknown whether SSc may be a cause of sinoatrial conduction abnormalities. Aim To establish the incidence of sinoatrial conduction abnormalities in patients with SSc and verify the relationship of these disorders with various clinical descriptors of SSc. Material and methods Forty women with systemic sclerosis of varying duration and severity underwent 24-hour ambulatory ECG monitoring. The occurrence of type I second-degree sinoatrial block (SA-block) and calculation of sinoatrial conduction time (SACT) were evaluated to establish the incidence of sinoatrial conduction abnormalities. The measurements of SACT were obtained using spontaneous atrial premature beats. The effect of various clinical descriptors on sinoatrial conduction abnormalities was assessed. Results The mean ± SD SACT for the 40 patients was 150 ±15 ms. Prolonged (> 150 ms) SACT was found in 20 patients. In 14 (35%) patients SA-block occurred during ambulatory ECG monitoring. The discriminant analysis identified the severity of SSc cutaneous manifestation as an independent marker for developing SA-block (p < 0.005) and SACT prolongation (p < 0.0002). Conclusions Patients with SSc are at an increased risk of developing type I second-degree sinoatrial block and prolonged sinoatrial conduction time. The occurrence of these abnormalities is related to the severity of skin involvement. Therefore, cardiological diagnosis using 24-hour ambulatory ECG in this group of patients should be focused also on this type of disorders. Prospective, controlled studies are needed to assess their prognostic role.

Background Psychological adaptation after cardiac pacemaker implantation is a challenge for patients with mental illness. Case presentation Here we report a self-harming patient with a psychiatric disorder. A 73-year-old female patient with 16-year coronary heart disease and a 4-year depression was admitted to our hospital for a coma. Two months earlier, the local hospital confirmed that the patient had a second-degree sinoatrial (SA) block (type 2) as well as basal septal hypertrophy with the left ventricular outflow obstruction. Therefore, metoprolol sustained-release tablets 95 mg QD and diltiazem sustained-release tablets 90 mg QD was given as treatment after a pacemaker was implanted. However, the patient had continued complaining about discomfort due to the pacemaker implanted after being discharged from the hospital. Two months later, she attempted to commit suicide by removing her pacemaker and taking 80 sleeping pills. After a series of treatments, the patient improved and was discharged without a pacemaker re-implantation. With continued anti-depression treatment and strengthen family supervision, the patient’s condition is stable now. Conclusions A suicide attempt by intentionally removing the permanent pacemaker system was rarely reported. In bradycardia patients with a history of psychological or psychiatric disease, careful evaluation should be done before and after implantation of the pacemaker.

Background Atrial fibrillation with symptomatic bradycardia, higher grade atrioventricular block, and sinus node disease are all common indications for permanent pacemaker implantation. The most frequent causes of sinus node disease treated with pacemaker implantation involve degenerative structural changes of the sinus node; less often, extrinsic causes (such as damage due to myocardial infarction or heightened parasympathetic nervous system activity) lead to pacemaker implantation. Case presentation A 50-year-old patient with syncope and documented sinoatrial arrest was referred. Neurologic exams (including CT and EEG) revealed no pathologies, so a pacemaker was implanted. Postoperatively, syncope occurred again due to a focal seizure during which sinus rhythm transitioned to atrial pacing by the device. Further neurologic testing revealed focal epilepsy. Six months later, stage IV glioblastoma was diagnosed and the patient was treated surgically. Conclusion Intracerebral tumors should be considered in the differential diagnosis for patients with unexplained sinoatrial block, as well as in patients with repeat syncope after pacemaker implantation. Cranial MRI could aid the diagnostic workup of such cases.

Summary The hearts of 28 dogs, clinically diagnosed as having symptomatic sick sinus syndrome (SSS), were examined post mortem, with a particular focus on the sinus node (SN) region. The affected dogs were divided into two groups according to the findings of ambulatory electrocardiography: 16 dogs with severe sinoatrial (SA) block and/or sinus arrest (group A) and 12 dogs with long sinus or atrial pauses due to SA block and/or sinus arrest accompanied by atrial tachyarrhythmias (group B). The most significant histopathological changes found in both SSS groups were extensive destruction of the SN characterized by depletion of nodal cells with fatty or fibrofatty replacement and interruption of contiguity between the SN and the surrounding atrial myocardium. Furthermore, in group B, the SN lesions were combined with fibrosis of the atrial myocardium. The results of this investigation improve our understanding of the close relationship between the electrocardiogram findings and pathological alterations in each group. Because most human cases of SSS are due to degenerative fibrosis of the SN, the loss and disappearance of nodal cells with a corresponding increase in fatty or fibrofatty tissue, may be specific to canine cases of SSS.

Funding Acknowledgements Type of funding sources: None. Background An early and comprehensive rhythm-control therapy emerges as a need to treat AF in an effective way and to improve the ablation outcomes, in terms of arrhythmia-free survival. Purpose We aimed to investigate the importance of timing of ablation in preventing AF recurrences. Methods 153 consecutive patients (pts) undergoing AF ablation from the CHARISMA registry at 8 Italian centres were included. Ablations were guided by a novel radiofrequency ablation catheter with local impedance (LI)-sensing capability through a dedicated algorithm (DirectSense, Boston Scientific). Pts were grouped as early treated (ET) if the procedure was performed within 1 year after the first AF episode and as delayed treated (DT) if admitted for ablation after more than 1 year. The ablation endpoint was PVI as assessed by entrance and exit block. Post-ablation follow-up was scheduled at 3, 6 and 12 months. AF and atrial tachycardia (AT) recurrences were considered as long-term endpoint. Results Of the 153 pts enrolled (69.9% male, 59 ± 10 years, 61.4% paroxysmal AF, 38.6% persistent AF), 123 (80.4%) met Class I indications, 23 (15%) Class IIa indications and 7 (4.6%) Class IIb indications according to current ESC AF guidelines. The mean time to ablation procedure from the first AF episode was 1034 ± 1483 days. Eighty pts (52.3%) were included in ET group, whereas 73 pts (47.7%) in DT group. No differences were found between AF type in terms of ablation strategy (53.3% of the cases -52 out 94- were classified as ET for paroxysmal AF vs 47.5% of the cases -28 out 59- were ET for persistent AF, p = 0.4346). At the end of the procedures, all PVs had been successfully isolated in all study pts. During a mean follow-up of 366 ± 130 days, 18 pts (11.8%) suffered an AF/AT recurrence after the 90-day blanking period. Recurrences occurred mostly in the DT group compared to the ET one (13 out 73 -17.8%- vs 5 out 80 -6.3%-, p = 0.042) and the time to AT/AF recurrence was longer in the ET group (HR = 0.2876, 95%CI: 0.1029 to 0.8038; p = 0.0181). On multivariate logistic analysis adjusted for baseline confounders, only hypertension (HR = 4.66, 95%CI: 1.5 to 14.48, p = 0.0081) was independently associated with recurrences. An early rhythm-control therapy was associated with a low risk of recurrences beyond the hypertension risk factor, ranging from 2% (no hypertension and an ET ablation therapy) to 30.3% (with hypertension and a DT procedure) (Figure 1). Conclusion A LI-guided ablation strategy for PVI proved to be safe and effective and resulted in a very high recurrence-free rate. An early rhythm-control therapy in the absence of common risk factors was associated with the lowest rate of recurrences. Abstract Figure. AT/AF Recurrence

Funding Acknowledgements Type of funding sources: None. Background Many tools and techniques are utilized to assess pulmonary vein isolation (PVI), such as evaluation of entrance and exit block, voltage mapping, and use of drugs such as adenosine. It is unclear which tools and techniques may provide greater sensitivity in the identification and elimination of pulmonary vein (PV) gaps, leading to better long-term outcomes. The HD Grid simultaneously records orthogonal bipolar EGMs to reduce directional sensitivity. Previously published data suggest that the use of HD Grid may improve sensitivity for gap identification. Purpose To determine, in a large cohort of procedures, the rate of gap detection when using HD Grid to check for PVI as compared to circular mapping catheters (CMC). Methods Anonymized, acute procedural data was prospectively collected in de novo AF ablation procedures in which either a 10- or 20-pole CMC or HD Grid catheter was used to assess PVI. Procedural data including gap detection and PVI assessment method were analyzed using chi-squared test. Results 559 cases from over 60 institutions in 8 countries were analyzed. Of the 559 cases, 47.4% (265/599) used HD Grid, and 52.6% (294/599) used a CMC. PV gaps were found in 52.5% (139/265) of HD Grid procedures and in 36.7% (108/294) of CMC procedures (p < 0.001). The most common PVI assessment method in both HD Grid and CMC groups was entrance/exit block (90.9%, 92.5%, respectively). Mapping as a post-ablation assessment method was used in 69.1% (183/265) of HD Grid procedures whereas it was only used in 42.8% (126/294) of CMC procedures (p < 0.001). Of the 183 HD Grid procedures that utilized mapping for PV assessment, 57.9% (106/183) used both voltage and activation mapping, 41.0% (75/183) used voltage only and 1.1% (2/183) used activation mapping only. Significantly more gaps were found in the HD Grid group that used both activation and voltage mapping (83.0%, 88/106) as compared to voltage mapping only (49.3%, 37/75, p < 0.001). At the end of the procedure, 95.8% of patients in the HD Grid group were in sinus rhythm, as compared to 84.7% of the CMC group. Conclusions While this analysis does not represent a direct comparison of the sensitivity of the two different technologies, HD Grid detected significantly more PV gaps compared to CMC in AF procedures. Previous publications have attributed similar findings to HD Grid’s ability to reduce voltage amplitude dependence on wavefront directionality. The significantly larger number of HD Grid cases that utilized mapping as a method of determining PVI could be explained by the need to maneuver the HD Grid around the circumference of the vein, which may naturally lead to map collection. This data also suggests that using both voltage and activation mapping identifies significantly more gaps as compared to only voltage mapping, however, further analysis could be warranted to better understand how these maps were collected and what map settings were used.

Funding Acknowledgements Type of funding sources: None. Background Despite advances in cardiac ablation technologies and the introduction of single-shot ablation devices such as the cryoballoon, the ability to consistently achieve complete and durable PVI remains elusive. While this is often attributed to PV reconnections that develop after the index procedure, recent data has suggested that traditional diagnostic techniques and technologies may in fact fail to identify gaps that remain upon completion of the index ablation. Initial observations in a small cohort of patients suggested that these residual gaps could be detected by a high-density, grid-style mapping catheter (HD Grid) post-cryoballoon ablation (CBA). The true incidence of these residual gaps as identified in a large patient population has not been previously reported. Purpose To quantify in a large cohort of CBA procedures, the presence of residual gaps identified by HD Grid which are missed by standard techniques of PVI confirmation using a 3.3F circular mapping catheter (CMC). Methods Self-reported data was prospectively collected in CBA procedures in which PVI was first confirmed using CMC followed by assessment using the HD Grid. Procedural characteristics and acute outcomes, including the incidence and location of residual gaps were analyzed. Results Data was collected in 150 CBA procedures performed in 24 centers across the US, Europe and Japan. De novo and repeat ablations represented 78.7% and 12.0% of cases, respectively (9.3% NR). A left common PV was present and ablated in 5.3%; right common in 0.7%. The CMC was used to confirm isolation in all cases using a variety of techniques including voltage mapping (73.3%), exit block (54.7%), and entrance block (29.3%); note: total exceeds 100% as >1 technique may be used in a single case. PVI was then reassessed with HD Grid, enabling a direct comparison of the two technologies. The HD Wave configuration, measuring simultaneous orthogonal bipoles, was used in 94.0% of cases. HD Grid identified a total of 119 gaps in 41 (27.3%) patients, which were missed by the CMC (Figure 1). Conclusions Assessment of PVI using the HD Grid identified residual PV conduction gaps that were missed by the CMC and standard diagnostic techniques in over a quarter of the patients evaluated. One limitation of this analysis is that the technique(s) used for confirmation of PVI were left to the discretion of the operator. Additionally, this analysis includes only workflows in which PVI was confirmed with HD Grid after confirmation using the CMC. Considering the prevalence of residual gaps observed, it is reasonable to interpret that new diagnostic catheter technologies could be critical in the pursuit of more complete and durable PVI, potentially impacting long-term clinical outcomes. Further study on other high-density mapping catheter configurations would be warranted before extrapolating these results to different technologies. Abstract Figure.

Funding Acknowledgements Type of funding sources: None. Background Complete electrical pulmonary vein isolation (PVI) by cryo-balloon approach is a well-established ablation strategy of atrial fibrillation (AF). Recently, a new cryoablation system (POLARx) with unique features has been made available for clinical use. To date, no data exist on procedural characteristics of this system in a multicentric clinical practice. Purpose We aimed to characterize the initial experience of this technology in the Italian clinical practice. Methods Consecutive patients (pts) undergoing AF ablation from the CHARISMA registry at 5 Italian centres were included. Protocol-directed cryoablation was delivered for 180 sec or 240 sec according to operator’s preference for isolation achieved in ≤60 sec, or 240 sec if isolation occurred >60 sec or when time to isolation (TTI) was not available. The ablation endpoint was PV isolation as assessed by entrance and exit block. Results Two-hundred sixty-two cryoapplications from 49 pts (194 PVs) were analyzed. PVI was achieved with cryoablation only in all pts. The mean number of freeze applications per pt was 5.3 ± 1.5 (1.3 ± 0.6 for LIPV, LSPV and RSPV, 1.6 ± 1.3 for RIPV), with 143 (73.7%) PVs treated in a single-shot fashion (38, 19.6% with 2 shots; 13, 6.7% with more than 2 shots). Sixteen (33%) pts were treated with a single freeze to each of the PVs. The mean nadir temperature was -55.5 ± 6.9 °C and was colder than -50°C in 83% of the PVs. TTI information was evaluable in 120 (46%) cryoapplications with a median TTI of 47 [32-75] sec (median temperature at TTI = -49 [-53 to -42] °C). The mean time to target -40 °C (TTT) was 30.1 ± 6.9 sec with a TTT < 60 sec achieved in 99.2% of the cryoapplications; the mean thaw time to 0 °C was 18.6 ± 5.8 sec (thaw time >15 sec in 70.3% of the cryoapplications). The mean PV occlusion grade (rank 1-4) was 3.6 ± 0.6 (grade 2 in 5.2% of the cases, grade 3 in 25.6% and grade 4 in 69.2%). No complications were observed at 30 days post-procedure. Conclusion In this first multicentric experience in a clinical practice setting, the novel cryo-balloon system proved to be safe and effective and resulted in a high proportion of successful single-freeze isolation. Cooling parameters seem to be slightly different from reference cryo-balloon technology.

Funding Acknowledgements Type of funding sources: None. Background A high incidence of pulmonary vein (PV) reconnection has been reported in patients with clinical recurrences of AF. Detailed characterization of PV gaps in terms of local impedance (LI) is still lacking. Purpose to characterize PV gaps with a novel local impedance algorithm during redo PV ablation in AF patients (pts). Methods Consecutive pts undergoing repeated AF ablation from the CHARISMA registry with complete characterization of PV gaps through local impedance at 6 Italian centers were included. A complete map of the left atrium and PVs was performed prior and after ablation through the Rhythmia mapping system. A novel RF ablation catheter with dedicated algorithm (DirectSense) was used to measure LI at the distal electrode of this catheter. Each gap was characterized in terms of LI and its variations during ablation procedure according to different ablation sites around the PVs. 7 sites around the left and right pair of PV for LI evaluation during ablation were defined: 2 for posterior sites (PS) (posterior inferior and posterior superior), 2 for anterior sites (AN) (anterior inferior and anterior superior), 1 for interior site (INF), 1 for superior site (SUP) and 1 for the carina (CAR). Ablation endpoint was PVI as assessed by entrance and exit block. Results Eighteen cases of redo AF ablation were analyzed (9 after prior RF ablation, 9 after prior cryoablation). A total of 41 PV gaps were detected (20 after RF ablation, 21 after cryoablation; mean number of gaps per pt = 2.3 ± 1.1): one gap was identified In five (27.8%) pts, 2 gaps were present in 7 (38.9%) pts, 3 gaps were detected in 2 (11.1%) pts and 4 gaps were identified in the remaining 4 (22.2%) pts. PV gaps were most common at AN sites (17, 41.5%), followed by PS sites (12, 29.3%) and CAR sites (11, 28.6%). The mean LI at gap sites was 113.9 ± 15Ω prior to ablation: it was significantly higher than LI at scar tissue closer to gap (99.7 ± 8Ω, p Conclusion In our preliminary experience, PV gaps after failed PVI were most common at anterior, followed by posterior and carina sites. LI characteristics at PV gaps significantly differ from both scar and healthy tissue and could be used to target ablation deliveries.

Funding Acknowledgements Type of funding sources: None. Background It has been demonstrated that an ablation strategy based on local impedance (LI) algorithm is helpful in guiding successful ablation of atrial fibrillation (AF) cases. How the magnitude and the course of LI drop could impact the effectiveness of ablation has to be proved. Purpose We aimed to evaluate LI drop characteristics in predicting effective radiofrequency (RF) ablation of consecutive AF cases. Methods Consecutive patients undergoing AF ablation at 8 Italian centers were included in the CHARISMA registry. A RF ablation catheter equipped with mini-electrodes technology and a dedicated algorithm was used to measure LI and to guide ablation. For our purpose, we defined the time to drop (τ) as the time for the first deflection of LI drop to the plateau. RF applications were targeted to a LI drop of 10 Ω and were stopped when a maximum cut-off LI drop of Results 153 consecutive patients (61% paroxysmal AF, 39% persistent AF) were enrolled in the study. 3556 point-by-point first-pass RF applications of >10 s duration were performed around PVs. The mean LI drop was 13 ± 8Ω, the mean τ was 18.7 ± 13s and the median LI drop/τ was 0.67 [QI-QIII, 0.37 – 1.17] Ω/s. Both absolute drops in LI and LI drop/τ were greater at successful ablation sites (n = 3122, 88%) than at ineffective ablation sites (n = 434, 12%) (14 ± 8Ω vs 6 ± 4Ω, p Conclusions The magnitude and time-course of the LI drop during RF delivery were associated with effective lesion formation. This ablation strategy for PVI guided by LI technology proved safe and effective, and resulted in a very low rate of AF recurrence over 1-year follow-up.

Background Accurate delivery of transmural lesion is associated with improved durability of pulmonary vein isolation and reduced reconduction. Lesion quality depends on multiple parameters such as radiofrequency power, tissue-catheter contact, duration of energy application, and catheter tip temperature. Consequently, energy delivery parameters vary based on individual operators’ preferences and procedural needs. Purpose To characterize and compare the utilization of automated lesion marking feature and lesion delivery parameters used during paroxysmal atrial fibrillation ablation performed with a magnetic sensor enabled contact force-sensing catheter across European and U.S. centers. Methods Procedural data were prospectively collected in clinical cases performed with a new magnetic sensor enabled, contact force ablation catheter within the first 6 months of use at participating centers in Europe and the U.S. Use of bidirectional CF catheters, steerable sheaths, automated lesion marking software and associated lesion delivery parameters during paroxysmal atrial fibrillation ablation were evaluated. Results A total of 149 cases across 37 centers in 11 European countries, and 112 cases across 31 U.S. centers were analyzed. A bidirectional contact force catheter (56.4% and 90.2%), a steerable sheath (65.8% and 69.6%), and the automated lesion marking module (77.9% and 90.2%) were used in most European and U.S. cases, respectively. The most commonly reported energy delivery parameters were: lesion index (LSI), Force-Time Integral (FTI), and time from European cases; LSI, average force, and FTI for U.S. cases (Table). Target LSI values were recorded for 126 cases in Europe and 34 in the U.S, ranging from 3 to 6. In anterior/roof segments, most common LSI target values for anterior/roof and posterior/inferior segments were 6 (42.9%) and 5 (51.2%) in Europe, and 5.5 (44.1%) and 5 (54.5%) in the U.S. PVI was confirmed with an average of 20.3 minutes waiting period (69.1%) for European cases and exit block (57.1%) in U.S. cases. First pass PVI were 67.1% and 74.4% for European and U.S. cases, respectively. Conclusion Energy delivery parameters and PVI confirmation method varied considerably by geography during paroxysmal atrial fibrillation ablation using the magnetic sensor enabled, contact force ablation catheter. Further study on efficacy implication on these differences in practice should be examined. Energy delivery parameters used Paroxysmal AF N LSI FTI Time Imp Drop Avg Force Other N/A Europe 149 44.0 % 13.4 % 7.0 % 6.0 % 2.4 % 1.0 % 26.2 % U.S. 112 31.2% 17.9 % 6.2 % 8.0 % 23.2 % 11.7 % 1.8 % Energy delivery parameters used in paroxysmal AF ablation in Europe and U.S.

Background Successful delivery of continuous and durable pulmonary vein isolation (PVI) lesion sets is recognized as being critical to long-term clinical outcomes following ablation for atrial fibrillation (AF). Confirmation of PVI following cryoballoon ablation is commonly achieved using a 3.3F circular mapping catheter (CMC) which can be delivered through the central lumen of the cryoballoon, but other diagnostic tools may be used alone or in conjunction with the 3.3F CMC. A high-density, grid-style mapping catheter is now available in multiple geographies; use in cryoballoon ablation procedures and associated outcomes has not been previously reported. Purpose To evaluate diagnostic catheter usage patterns in cryoablation procedures and identify associated trends in procedural characteristics and acute outcomes. Methods Self-reported procedural data was prospectively collected in AF cryoablation cases utilizing various diagnostic catheter tools, including the 3.3F CMC and high-density, grid-style mapping catheter (HD Grid). Procedural characteristics and acute outcomes, including the incidence and location of gaps post-ablation, were recorded and analyzed. Results Data was collected in 23 cryoablation procedures performed in 7 centers across the United States and Europe. De novo and repeat ablations represented 65.2% and 21.7% of cases, respectively (13.0% not reported). 3D mapping was employed in 95.7% of cases. A left common pulmonary vein was present and ablated in 8.7% (2/23). The 28mm cryoballoon was utilized in all cases, with a single case using both a 23mm and 28mm cryoballoon. The 3.3F CMC was used to confirm isolation in all cases using a variety of techniques: voltage mapping (60.9%), exit block (56.5%), entrance block (30.4%), propagation mapping (4.3%), and activation mapping (4.3%); note: total exceeds 100% as more than one technique may be employed in a single case. In 18 cases, PVI was confirmed using a 3.3F CMC followed by secondary confirmation with HD Grid, enabling a direct comparison of the two technologies. The HD Grid identified a total of 12 gaps in 4 (22.2%) patients, which were missed by the 3.3F CMC (Figure 1). No adenosine or isoproterenol use was documented in any case. Conclusion(s): The 3.3F CMC is routinely used to confirm PVI following cryoballoon ablation for atrial fibrillation, but it may fail to identify gaps in some patients. Subsequent assessment of PVI using the HD Grid identified residual gaps in nearly a quarter of patients, suggesting that sensitivity for gap detection may be improved with this tool. Limitations of this analysis include the small sample size and workflows which consistently assessed PVI with the high-density mapping catheter after confirming isolation with the 3.3F CMC. Despite these limitations, the incidence of residual gaps observed is noteworthy and may warrant additional study. Abstract Figure.

Simple Summary In sport horses, cardiovascular problems, such as arrhythmias, can cause poor performance. However, only the role of atrial fibrillation and severe bradyarrhythmias on athletic performance has been well established. On the other hand, the significance of other arrhythmias, such as supraventricular and ventricular premature complexes, is still not well defined. The present study reports on the prevalence of cardiac arrhythmias during maximal treadmill exercise in poorly performing Standardbreds, and investigates the possible relationship of demographic, cardiac, and performance indices on premature complexes. The results showed weak evidence of the dependence of premature complexes on minimum heart rate, and a tendency for the occurrence of premature complexes to increase with aging and increasing maximum lactate concentration. Our results suggest that premature complexes are frequent in poorly performing Standardbred racehorses, but further studies are necessary to clarify their role and clinical significance. Abstract The incidence of significant arrhythmias in sport horses and knowledge about their exact influence on athletic performance need to be clarified. The aims of the present study are to report the prevalence of cardiac arrhythmias during maximal treadmill exercise in poorly performing Standardbreds, and to investigate the possible relationship of demographic, cardiac and performance indices on premature complexes (PCs). Electrocardiographic Holter recordings before, during and after treadmill exercise testing of 158 poorly performing Standardbreds were analyzed retrospectively. Fifty horses did not have any type of arrhythmia. One hundred and eight horses had at least one type of arrhythmia, such as sinus arrhythmia (8.2%), sinoatrial block (3.2%), second-degree atrioventricular block (33.5%), supraventricular PCs (7.6%), and ventricular PCs (48.1%). A multiple regression analysis showed weak evidence that the occurrence of premature complexes decreases as the minimum heart rate increases, and a tendency for these arrhythmias to increase with increasing age and maximum lactate concentration. Our results suggest that PCs are frequent in poorly performing Standardbred racehorses, but further studies are necessary to clarify their role and clinical significance.

The sinoatrial block is a new side effect of meglumine antimoniate. Prompt interruption of the drug results in the normalization of electrographic changes and prevents sudden cardiac arrest.

Introduction Swallow syncope is a neurally mediated syncope. Multiple causes have been described in literature. A rare cause is arrhythmias. Only a limited amount of cases present the association of swallow syncope and third degree AV-block. Case presentation A 39-year-old man presented with episodes of presyncope while eating. Further medical history, physical examination, resting 12-lead ECG, cyclo-ergometry, transthoracic echocardiography and MRI of the heart were normal. 24 h Holter monitoring demonstrated high-grade third-degree atrioventricular (AV) block. The patient was scheduled for pacemaker implantation. Discussion Arrhythmia is a rare cause of swallow syncope. Reported arrhythmic causes are sinus bradycardia, sinoatrial block, atrioventricular block and complete atrial and ventricular asystole. Essential to the diagnosis is that (pre)syncope is preceded by swallowing and documentation of AV block on 24 h Holter monitoring. Treatment is guided by ESC guidelines which state that reflex syncope has a grade IIa recommendation for pacing, while current evidence suggests that asymptomatic vagally mediated AV block should not be treated until symptomatic.

In 1899, Karel Frederik Wenckebach described a cardiac arrhythmia with periodic dropped beats now referred to as a Wenckebach sequence. This was later shown to be due to a block in the atrioventricular node, but today, we identify Wenckebach sequences throughout the heart with most being recognised on the surface electrocardiograph as characteristic footprints. This manuscript will revisit Wenckebach atrioventricular block, the typical features of which only occur in about 15% of cases, with the remainder atypical. Earlier reports regarded Wenckebach atrioventricular sequences as rare as they are only occasionally seen on the surface 12-lead electrocardiograph. Today, however, with the increased use of ambulatory Holter monitoring, Wenckebach atrioventricular sequences occur in 4-6% of all traces and are particularly common at night in the young. Most, but not all cases are benign and the clinical spectrum will be reviewed. Atypical Wenckebach atrioventricular sequences are a complex group which will be analysed in detail with a broad range of illustrations. Outside the atrioventricular conducting system, such as in the sinus node, Wenckebach sequences may not be obvious as they are partially hidden from the electrocardiographic tracing. However, by understanding the sequence footprints, clues are available in interpreting tracing with periodic pauses. Dual chamber paced rhythms may show Wenckebach sequences due to electronic control of the atrioventricular delay. Rarely exit blocks at the cellular level in the atrium, ventricle or at the pacing electrode-tissue interface can demonstrate Wenckebach sequences recognised on the surface electrocardiograph.

The relationship among cardiac pacemakers is characterized by the fact that one pacemaker is usually dominant and all the others are subsidiary. The sinoatrial node acts as the dominant pacemaker, and all other potential pacemaker tissues are discharged by a conducted impulse before their respective diastolic depolarizations attain threshold. These pacemakers are called subsidiary to emphasize the fact that, under normal circumstances, they are engaged in conducting impulses, but, under abnormal circumstances, they may become actual pacemakers.

An 82-year-old female patient was admitted for catheter ablation of drug-refractory atrial tachycardia (AT). Initially, during right atrial mapping, only a small portion (100 ms) of the tachycardia cycle length (TCL) (200 ms) could be mapped. Mapping of the left atrium (LA) revealed the critical

Background Arrhythmias are frequent in Takotsubo cardiomyopathy (TTC) and a major determinant of outcome. Objective The purpose of this study was to provide a rationale for management strategies, particularly for permanent device implantation given the reversible nature of TTC. Methods Treatment strategies of arrhythmias including ventricular fibrillation (VF), ventricular tachycardia (VT), asystole, pulseless electrical activity, and complete atrioventricular (AV) or sinoatrial block were assessed in a bicentric cohort of consecutive patients with TTC (n = 286) with a mean follow-up period of 3.3 ± 2.4 years. Results The prevalence of arrhythmias during the acute phase of TTC was 12.2% (n = 35), consisting predominantly of VT (n = 16 [5.6%]), VF (n = 7 [2.4%]), and complete AV block (n = 8 [2.8%]). Seven patients received a permanent pacemaker because of complete AV (n = 6) or sinoatrial (n = 1) block. Regular device checkups were available in 2 patients and demonstrated ongoing high-degree AV block despite recovery of left ventricular function. Three patients with transient bradyarrhythmias who did not receive devices died shortly after hospital discharge from unknown causes. One patient received an implantable cardioverter-defibrillator after resuscitation for VF and did not require device interventions during 2-year follow-up. Patients with polymorphic VT (n = 7), monomorphic VT (n = 6), or VF (n = 2) who were discharged from hospital survived or died of noncardiac reasons, with the cause of death remaining unclear in 1 patient with monomorphic sustained VT. Conclusion Our data suggest that bradyarrhythmias in the acute setting of TTC may require permanent pacemaker implantation. In contrast, polymorphic ventricular arrhythmias might be managed with a temporary approach (eg, wearable cardioverter-defibrillators) until recovery of repolarization time and left ventricular function.

The paper describes a clinical case of a female patient with severe obstructive sleep apnea syndrome in the presence of congenital hemangioma of the face, soft palate, and tongue concurrent with paroxysmal atrial fibrillation and atrial flutter, paroxysmal supraventricular tachycardia, and sinoatrial block (maximally up to 3.9 sec). Continuous positive airway pressure therapy could reduce the number of paroxysms of atrial fibrillation and atrial flutter, supraventricular tachycardia and eliminate sinoatrial block.Представлен клинический случай пациентки с синдромом обструктивного апноэ во сне тяжелой степени тяжести на фоне врожденной гемангиомы лица, мягкого неба и языка в сочетании с пароксизмальной формой фибрилляции и трепетания предсердий, пароксизмальной формой наджелудочковой тахикардии, синоатриальной блокадой (максимально до 3,9 с). Использование CPAP-терапии (от англ. continuous positive airway pressure) позволило уменьшить количество пароксизмов фибрилляции и трепетания предсердий, наджелудочковой тахикардии, устранить синоатриальную блокаду.

Although drug-induced short QT syndrome (SQTS) has been recognized, we currently report the first acquired SQTS case induced by bufotalinin (toad, an antineoplastic drug), which is a traditional Chinese folk prescription. It has cross reaction with digoxin and affects the Na+ -K+ -ATPase, the SR Ca2+ release from ryanodine receptor-2 (RyR2), the reactive oxygen species (ROS) production from the mitochondria. The case presented with bradycardia, extreme QT shortening, and sinoatrial block that were resolved after gastric lavage, rehydration, electrolyte (hyperkalemia, hyponatremia, hypocalcemia) correction, and atropine injection. Clinicians should recognize a potential association between toad poisoning and SQTS from this case.

Cardiac arrhythmias are commonly reported in freedivers during maximal voluntary breath-holds, but their influence on the cardiological status and their long-term effects on the cardiac health of these athletes have not been investigated. Here we present the results of a study on 32 healthy young men (mean age 32.6 ± 1.3 years) who were divided into two groups of 16 subjects. One group included 16 continuously training freedivers at the "high achievers in sports" level (DIVERS group). The CONTROL group included 16 healthy young men not involved in sports. The subjects were monitored using 24-h electrocardiogram (ECG), and echocardiological study (EchoCG) for all the subjects was performed. The mean heart rate in the DIVERS group was 69.5 ± 1.7 bpm compared with 70.9 ± 1.5 bpm in the CONTROL group. The minimal heart rate was 42.3 ± 1.0 bpm in the DIVERS group and 48.8 ± 1.7 bpm in the CONTROL group (P

Aim. To evaluate the clinical and electrophysiological picture of binodal disease in children, as well as studying the clinical course of this disease. Methods. To study the clinical and electrophysiological picture of autonomic binodal disease, 426 patients under 18 years old were examined; the average age was 15.35±2.43 years (3-17.9). Patient’s complaints, medical history were examined, ECG, 24-hour ECG, stress ECG (treadmill or bicycle test), echocardiography, transesophageal electrophysiologic study were performed. In the case of a combination with pathological signs of sinus node dysfunction and atrioventricular node conduction disorders with the normalization of all parameters after the atropine administration, hypervagotonic binodal dysfunction was diagnosed. To assess the clinical course of the disease, a group of 72 children was selected, who were monitored repeatedly. Mean follow-up duration was 33 months. Results. During the study period, sinus node dysfunction and atrioventricular blocks completely resolved in 14 (19.44%), seen as normal clinical picture with no complaints, normal heart rate, no signs of sinoatrial block or atrioventricular block, normalization of Wenckebach point position. Another 35 (48.62%) had only one node dysfunction resolved (either sinoatrial or atrioventricular - Wenckebach point position within the age normal values and/or atrioventricular block resolved). In 23 (31.94%) - deterioration of the sinus node and atrioventricular node dysfunction was observed. Conclusion. There are significant differences in the frequency characteristics of heart rhythm and electrophysiological parameters of sinus node function in children with a favorable clinical course of binodal disease and progressive course of the disease.

Although it has been reported that endotoxin-induced expression of Nox1 in the heart contributes to apoptosis in cardiomyocytes, functional role of Nox1 at the physiological expression level has not been elucidated. The aim of this study was to clarify the role of Nox1 under a hypoxic condition using wild-type (WT, Nox1(+/Y)) and Nox1-deficient (Nox1(-/Y)) mice. ECG recordings from anesthetized mice revealed that Nox1(-/Y) mice were more sensitive to hypoxia, resulting in bradycardia, compared to WT mice. Atrial and ventricular electrocardiograms recorded from Langendorff-perfused hearts revealed that hypoxic perfusion more rapidly decreased heart rate in Nox1(-/Y) hearts compared with WT hearts. Sinus node recovery times measured under a hypoxic condition were prolonged more markedly in the Nox1(-/Y) hearts. Sinoatrial node dysfunction of Nox1(-/Y) hearts during hypoxia was ameriolated by the pre-treatment with the Ca(2+) channel blocker nifedipine or the K(+) channel opener pinacidil. Spontaneous action potentials were recorded from enzymatically-isolated sinoatrial node (SAN) cells under a hypoxic condition. There was no significant difference in the elapsed times from the commencement of hypoxia to asystole between WT and Nox1(-/Y) SAN cells. These findings suggest that Nox1 may have a protective effect against hypoxia-induced SAN dysfunction.

Adenosine stress testing in conjunction with radionuclide myocardial perfusion imaging has become a common approach for the detection of coronary artery diseases in patients who are unable to perform adequate levels of exercise. However, specific electrocardiographic alterations during the test have been rarely described. Using a Chinese population, the aim of the present study was to provide a detailed electrocardiographic profile of adenosine stress testing. The study population included 1,168 consecutive outpatients who had undergone adenosine-induced stress myocardial perfusion imaging. Electrocardiographic data during and immediately following the adenosine infusion were collected, and the corresponding myocardial perfusion images were assessed. During adenosine infusion, 174 transient and 47 persistent arrhythmic events occurred in 110 patients (9.42%). Furthermore, frequent premature atrial contractions occurred in 65 individuals and frequent premature ventricular contractions were observed in 73 individuals. Atrioventricular block (AVB) occurred in 75 patients [first degree (I°) AVB, 16; second degree (II°) AVB, 58; third degree AVB, 1), while sinoatrial block occurred in eight patients. ST depression emerged in 69 patients. Patients with a baseline I° AVB had an increased risk of a II° AVB, and patients exhibiting baseline ST depression were more likely to have a further depressed ST segment during the stress test (odds ratio, 28.68 and 5.01, respectively; both P

Narrow complex bigeminy is a common electrocardraphic finding that can be caused by second degree sinoatrial exit block or ectopic atrial bigeminy. These rhythms can be very challenging to distinguish on a 12-lead electrocardiogram. In this case of an elderly woman who presented with narrow complex bigeminy, we review the differentiating features of second degree sinoatrial exit block and ectopic atrial bigeminy.

The sick sinus syndrome includes symptoms and signs related to sinus node dysfunction. This can be caused by intrinsic abnormal impulse formation and/or propagation from the sinus node or, in some cases, by extrinsic reversible causes. Careful evaluation of symptoms and of the electrocardiogram is of crucial importance, because diagnosis is mainly based on these 2 elements. In some cases, the pathophysiologic mechanism that induces sinus node dysfunction also favors the onset of atrial arrhythmias, which results in a more complex clinical condition, known as "bradycardia-tachycardia syndrome."

There are 120 years since the myocarditis was described for the first time in children and infants. At that time, Emmet Holt said “Myocarditis may...occur at any age, even in foetal life”. We describe two cases of Coxsackie B4 neonatal myocarditis. Both appeared almost in the same period of time, at 3 and 4 week-old, female and male newborns and had a similar course. The onset was with rhythm and conduction disturbances: ventricular ectopies, nonsustained ventricular tachicardia, supraventricular tachicardia, sinoatrial block, atrioventricular block, blocked extrasystoles. From the beginning both had the myocardial enzymes persistently elevated: CK-MB and troponin T, which maintained elevated levels even at distance from the onset. No inflammatory response and no kinetics disturbancies were noted neighter at admission nor at 2 months distance from the onset. Serology for Coxsackie B4 was first in progressively increasing, then decreasing titers. MRI confirmed a small degree of myocardial oedema for both of them, compatible with focal myocarditis. They received IV immunoglobulin, 2 g/kg/one dose in the second day from admission and the rhythm and conduction problems were treated with Propafenone, 10 mg/kg/day. They did not tolerate beta blockers (aggravated cardiac blocks). After 2 weeks, the rythm disturbancies almost disapeared. They remained on maintenance treatment with propafenone for a three months period. Conclusion: Neonatal myocarditis must be taken into consideration at any paediatric age, even in asymptomatic patients. Rhythm problems could aggravate the progression towards dilated cardiomyopathy and early treatment could interrupt a possible deterioration.

摘出した家兎の右心房版本を用い、洞房ブロックにおけるアセチルコリン(Ach)の作用を検討した。標本は洞結節および分界稜、心房中隔、房室結節を合む輪状構造を保持する型で作製した。微小電極法により洞結節および分界稜の膜電位を双極電極により心房中隔の表面電位をそれぞれ記録した。洞房伝導の最も速く行なわれる洞結節と分界稜右枝との問(洞稜領域)を切断することにより、伝導様式から2つのType AとBの第1度洞房ブロックがみられた。19例中13例に生じたType Aは洞結節からの伝導が分界稜右枝を先行し、残りの6例に生じたType Bは心房中隔への伝導が先行した。正常条件下でAch10^-7g/mlを投与すると、20例全例に洞房伝導時間の遅延すなわち第I度の洞房ブロックのみがみられ、その伝導様式は投与前後で変化はみられなかった。また、洞周期はAch投与前後で有意に延長した。Type Aの第I度洞房ブロックにAchを投与すると、8例中4例は洞房伝導がさらに有意に遅延し、残る4例はWenckebach型の第II度洞房ブロックがみられた。Type Bの第I度洞房ブロックを呈した10例にAchを投与すると、全例に第III度洞房ブロックがみられた。洞稜領域にある優位伝導路はAchに対し抵抗性が強いが、心房中隔への伝導経路は抵抗性が低いことが判った。Ach投与により発生した第I度から第III度洞房ブロック は、正常液やAch＋アトロピン混合液投与により1:1 伝導に回復したことから、これらのブロックはAchによる作用であることが判明した。以上のことから、優位伝導路が健常の場合、アセチルコリン投与は第I度洞房ブロックのみを発生させるが、優位伝導路が傷害され、さらにアセチルコリンが加わると容易に第II度あるいは第III度洞房ブロックに移行することが判明した。

In China, it is a routine procedure to inject 250 μg of hemabate (sterile solution, an oxytocic, contains the tromethamine salt of the (I5S)-15 methyl analogue of naturally occurring prostaglandin F2α in a solution suitable for intramuscular injection) into the myometrium of patients experiencing uterine inertia after delivery, with an additional dose given in the event that the efficacy is not obvious. Although hemabate is prohibited from being used in patients with active liver disease, there are no restrictions regarding the application of hemabate in positive hepatitis B surface antigen (HbsAg)-positive subjects with normal liver function. Here we report adverse effects of hemabate in 1 HbsAg-positive subject with normal liver function. This subject experienced increased blood pressure, chest tightness, and type II second degree sinoatrial block 25 minutes after an additional injection of hemabate. Thus, special attention should be paid when applying hemabate in HbsAgpositive subjects with normal liver function.

Objectives This study sought to test the hypothesis that inducing an autoimmune response against the cardiac sodium channel (NaV1.5) induces arrhythmias. Background Sporadic evidence supports the concept that autoantibodies may cause cardiac arrhythmias but substantial experimental investigations using in vivo models have been lacking to date. The NaV1.5 is essential for cardiac impulse propagation and its dysfunction has been linked to conduction disease. Methods Rats were immunized with a peptide sequence derived from the third extracellular loop of the first domain of NaV1.5. After 28 days, we evaluated in vivo both the electrical and mechanical parameters of cardiac function. Histopathology, myocardial gene and protein expression were assessed. Whole-cell patch-clamp was used to measure sodium current (INa) density in isolated cardiomyocytes. Results NaV1.5-immunized rats had high titers of autoantibodies against NaV1.5. On ECG recording, NaV1.5-immunized animals showed significantly prolonged PR-intervals. During Holter ECG-monitoring we observed repeated prolonged episodes of third-degree atrioventricular and sinoatrial block in every NaV1.5-immunized animal, but not in controls. Immunization had no effect on cardiac function. In comparison to controls, myocardial NaV1.5 mRNA and protein levels were decreased in immunized rats. INa density was reduced in cardiomyocytes incubated with sera from NaV1.5-immunized rats and from patients with idiopathic atrioventricular block (AVB) in comparison to sera from respective controls. In patients with idiopathic AVB, we observed autoantibodies against NaV1.5 that were absent in sera from healthy controls. Conclusions Provocation of an autoimmune response against NaV1.5 induces conductance defects probably caused by a reduced expression level and an inhibition of NaV1.5 by autoantibodies, resulting in decreased INa.

Aims Prior reports using pacing manoeuvres, demonstrated an up to 42% prevalence of residual pulmonary vein to left atrium (PV–LA) exit conduction after apparent LA–PV entry block. We aimed to determine in a two-centre study the prevalence of residual PV–LA exit conduction in the presence of unambiguously proven entry block and without pacing manoeuvres. Methods and results Of 378 patients, 132 (35%) exhibited spontaneous pulmonary vein (PV) potentials following circumferential PV isolation guided by three-dimensional mapping and a circular mapping catheter. Pulmonary vein automaticity was regarded as unambiguous proof of LA–PV entry block. We determined the prevalence of spontaneous exit conduction of the spontaneous PV potentials toward the LA. Pulmonary vein automaticity was observed in 171 PVs: 61 right superior PV, 33 right inferior PV, 47 left superior PV, and 30 left inferior PV. Cycle length of the PV automaticity was >1000 ms in all cases. Spontaneous PV–LA exit conduction was observed in one of 171 PVs (0.6%). In a subset of 69 PVs, pacing from within the PV invariably confirmed PVLA exit block. Conclusion Unidirectional block at the LA–PV junction is unusual (0.6%). This observation is supportive of LA–PV entry block as a sufficient electrophysiological endpoint for PV isolation.

Background: Ozone (O3) is a well-documented respiratory oxidant, but increasing epidemiological evidence points to extrapulmonary effects, including positive associations between ambient O3 concentrations and cardiovascular morbidity and mortality. Objective: With preliminary reports linking O3 exposure with changes in heart rate (HR), we investigated the hypothesis that a single inhalation exposure to O3 will cause concentration-dependent autonomic modulation of cardiac function in rats. Methods: Rats implanted with telemeters to monitor HR and cardiac electrophysiology [electrocardiography (ECG)] were exposed once by whole-body inhalation for 4 hr to 0.2 or 0.8 ppm O3 or filtered air. A separate cohort was tested for vulnerability to aconitine-induced arrhythmia 24 hr after exposure. Results: Exposure to 0.8 ppm O3 caused bradycardia, PR prolongation, ST depression, and substantial increases in atrial premature beats, sinoatrial block, and atrioventricular block, accompanied by concurrent increases in several HR variability parameters that were suggestive of increased parasympathetic tone. Low-O3 exposure failed to elicit any overt changes in autonomic tone, heart rhythm, or ECG. However, both 0.2 and 0.8 ppm O3 increased sensitivity to aconitine-induced arrhythmia formation, suggesting a latent O3-induced alteration in myocardial excitability. Conclusions: O3 exposure causes several alterations in cardiac electrophysiology that are likely mediated by modulation of autonomic input to the heart. Moreover, exposure to low O3 concentrations may cause subclinical effects that manifest only when triggered by a stressor, suggesting that the adverse health effects of ambient levels of air pollutants may be insidious and potentially underestimated.