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Heart Rhythm

Elsevier BV

All preprints, ranked by how well they match Heart Rhythm's content profile, based on 22 papers previously published here. The average preprint has a 0.04% match score for this journal, so anything above that is already an above-average fit. Older preprints may already have been published elsewhere.

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Effects of Right and Left Ventricular Pacing for Substrate Mapping Using Decrement-Evoked Potential Mapping in Patients with Scar-Related Ventricular Tachycardia

Uhm, J.-S.; Park, J.; Song, H.; In, J.-K.; Lee, J.; Hwang, T.; Cho, S.; Park, H.; Kim, D.; Yu, H. T.; Kim, T.-H.; Lee, C. J.; Oh, J.; Joung, B.; Pak, H.-N.; Kang, S.-M.; Lee, M.-H.

2025-08-12 cardiovascular medicine 10.1101/2025.08.09.25332991 medRxiv
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BackgroundThe ventricular tachycardia (VT) substrate map is influenced by the rhythm during mapping. This study aimed to elucidate the effects of different pacing sites on substrate mapping using decrement-evoked potential (DEEP) mapping in patients with scar-related VT. MethodsPatients with ischemic cardiomyopathy (ICM) or nonischemic cardiomyopathy (NICM) who underwent substrate mapping and ablation for scar-related VT were included. DEEP mapping was performed during right ventricular apex (RVA) and left ventricular outflow tract (LVOT) pacing. We analyzed the number, location, shape, and timing of lines of conduction block (LOB) using substrate maps obtained during RVA and LVOT pacing. ResultsA total of 19 patients (mean age, 62.7 {+/-} 16.6 years; 17 males; 10 with ICM and 9 with NICM) were studied. DEEP mapping during RVA and LVOT pacing was performed in 16 patients. The number of pacemap-matching LOBs identified from the RVA S1, RVA S2, LVOT S1, and LVOT S2 maps were 0.61 {+/-} 0.70, 1.24 {+/-} 1.09, 1.00 {+/-} 0.85, and 1.50 {+/-} 1.17, respectively. The number of final pacemap-matching LOBs was 1.58 {+/-} 1.07. Two LOBs were visible only during RVA pacing because they were parallel to the conduction direction. Six LOBs were visible only during LVOT pacing--five LOBs were parallel to the conduction direction, and one LOB was located at the wavefront collision area. During a mean follow-up of 7.6 {+/-} 3.9, VT recurred in 26.3% of patients. ConclusionA high number of LOBs on critical substrates can be identified using two-site pacing DEEP mapping.

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Safety and long-term performance of the Medtronic 3830 lead in His-bundle vs. Left bundle branch area pacing: A single-center 5-year experience.

Sarkar, A.; Sanchez-Nadales, A.; Sleiman, J.; Alonso, M.; seijo, y.; bibawy, j.; helguera, m.; pinski, s.; lewis, a.

2024-04-24 cardiovascular medicine 10.1101/2024.04.23.24306255 medRxiv
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BACKGROUNDThe short-term safety, feasibility, and performance of the Medtronic SelectSecure 3830-69 cm pacing lead for conduction system pacing (CSP) has been reported; however, its longer-term performance is not well established. OBJECTIVEThe purpose of this study is to examine the long-term performance of the 3830 lead for His Bundle Pacing (HBP) and Left Bundle Branch Area Pacing (LBBAP). METHODSWe retrospectively reviewed all cases of CSP performed with the Medtronic SelectSecure 3830-69 cm pacing lead at Cleveland Clinic Florida between May 2016 and October 2021. RESULTSOf 515 attempts, HBP achieved an 85% success rate (340 cases), while LBBAP demonstrated a higher success rate of 97.4% (150 cases). The mean follow-up was 28 months for HBP and 14 months for LBBAP, with patient ages averaging 75 and 77 years, respectively. Only 7% of the cohort had an ejection fraction below 50%. The primary indications for HBP were sick sinus syndrome (35.5%), atrioventricular block (35.2%), cardiac resynchronization therapy (10%), and refractory atrial fibrillation (18.8%), with similar distributions for LBBAP. The HBP groups capture threshold at implant was 1.3 {+/-} 0.8 V at 0.8 {+/-} 0.2 ms, which significantly increased at chronic follow-up to 1.68 {+/-} 1.3 V at 0.7 {+/-} 0.3 ms (p <0.001), whereas the LBBAP groups capture threshold remained stable from 0.8 {+/-} 0.5 V at 0.5 {+/-} 0.3 ms to to 0.9 {+/-} 0.5 V at 0.5 {+/-} 0.3 ms, (p= 0.35). Lead revisions were more common in the HBP group (50 cases) than in the LBBAP group (5 cases), with exit block rates of 11.7% and 3%, respectively. CONCLUSIONUsing the 3830 lead for HBP can result in significantly elevated thresholds, loss of His-bundle capture, and frequent lead revision rates at long-term follow-up. These issues are less commonly seen when the lead is used for LBBAP.

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A Multicenter Study of the Electrical Characteristics and Short-Term Outcomes of the Aveir VR Leadless Pacemaker

Yang, J.; Li, R.; Liu, X.; Xue, X.; Zhang, J.-H.; Hu, Y.-m.; Zhang, B.; Tong, L.; Luo, H.; Shen, M.; Chen, Z.; Aiyasiding, X.; Cai, M.; Chi, X.; Dai, Y.; Tang, B.; Chen, K.

2026-03-09 cardiovascular medicine 10.64898/2026.03.06.26347827 medRxiv
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BackgroundThe Aveir leadless pacemaker employs an active fixation method, enabling real-time monitoring of electrical parameters during implantation. However, comprehensive studies regarding the electrical parameters during this procedure are rare. ObjectiveThis study aims to analyze the electrical characteristics to further guide the implantation strategy and improve device stability and safety. MethodsThis multi-center retrospective study enrolled 119 patients (mean age 70.18 years; 59.58% female) who received the Aveir VR leadless pacemaker from November 2024 to May 2025 across ten centers in China. Intraprocedural variations in commanded electrogram (CEGM), current of injury (COI), impedance, pacing threshold, and sensing parameters were meticulously documented. ResultsCEGM mapping demonstrated various morphologies (R, RS, QR, QRS, and QS) aiding localization. During fixation, 58.82% of patients exhibited an increased COI from mapping to 0.5 turns, which was associated with reduced short-term pacing thresholds. From 0.5 to 1 turn, 52.94% showed further COI increases. ROC analysis revealed that an impedance increase has predictive value for short-term pacing thresholds, with an AUC of 0.634 and a cut-off value of 230 {Omega} (sensitivity 0.622, specificity 0.41). Lead stability showed a moderate correlation with impedance increase ({rho}=0.44, P<0.001), while the correlation with COI was weak. ConclusionDuring Aveir implantation, CEGM variations guide site localization. Initial COI increases (0-0.5 turns) are linked to optimal short-term thresholds. Monitoring impedance increase is vital, as a threshold of 230 {Omega} serves as a key indicator of device stability and fixation quality.

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Conventional electrode catheter placement can miss crucial atypical atrioventricular nodal reentrant tachycardia circuit details. -New insights into the retrograde slow pathways-

Kawabata, M.; Maeda, S.; Okishige, K.; Shirai, Y.; Kamata, T.; Kawashima, T.; Yonai, R.; Atarashi, H.; Hirao, K.

2024-01-17 cardiovascular medicine 10.1101/2024.01.16.24301387 medRxiv
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BackgroundDuring atypical atrioventricular nodal reentrant tachycardia (AVNRT), the earliest atrial activation site following retrograde slow pathway (SP) conduction is at the atrial exit of the left inferior extension of the compact node (LIE) in the coronary sinus (CS) or the right inferior extension (RIE) on the tricuspid annulus (TA). We tested the validity of conventional electrode placement-based mapping of the atrial ends of these extensions. MethodsWe retrospectively evaluated the efficiency of the two catheter (His bundle and CS) mapping method for localization of LIE and RIE in atypical AVNRT patient using electroanatomical 3D mapping validation. ResultsAmong 19 atypical AVNRTs (15 fast/slow and 4 slow/slow) in 14 patients (9 females, age 59{+/-}17), 8 AVNRTs had LIE involvement and 11 had RIE. The 8 LIE exits were inside the CS, and localization by 3D mapping and CS electrode catheter matched in all. In contrast, RIE exits were on the posterior TA where electrode catheters are conventionally not placed. All RIE exits required 3D mapping for accurate localization. During retrograde RIE conduction, comparison of the activation time of the CS ostium and HBE showed that the CS ostium was earlier in 7 RIEs, HBE was earlier in 1, and they were simultaneous in 3, resulting in the presence of RIE being missed in 4/11 (36%) AVNRTs using current diagnostic criteria. Activation time of the CS ostium and His bundle were determined by their relative closeness to the RIE exit. ConclusionsConventionally placed electrode catheter mapping in atypical AVNRT was able to identify 100% of LIE, but only 64% of RIE. It is critical to place a catheter on or use a 3D mapping system for the posterior TA in cases of suspected atypical AVNRT, so that all inferior extensions of the AV node can be identified and targeted for treatment.

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Management of Engraftment Arrhythmias Associated with Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Transplantation

Zhang, A.; Jing, R.; Liu, X.-C.; Zhang, Y.; Chen, Y.; Wang, Y.; Wang, J.; Guo, Z.; Zhang, J.; Yang, Q.; Liu, Y.; Wei, Y.; Fu, Y.

2026-01-12 cardiovascular medicine 10.64898/2026.01.09.26343817 medRxiv
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BackgroundHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a highly promising approach for cell-based replacement therapy in heart failure. However, the development of graft-related ventricular arrhythmias immediately following transplantation impedes its clinical translation. To date, there have been no reports worldwide characterizing the features of engraftment arrhythmias after hiPSC-CMs transplantation in human. Consequently, this study aims to analyze the characteristics of ventricular arrhythmias and the efficacy of antiarrhythmic drugs following hiPSC-CMs transplantation, and to identify risk factors associated with the occurrence of ventricular arrhythmias. MethodsThis study enrolled patients who underwent coronary artery bypass grafting (CABG) combined with hiPSC-CMs implantation under general anesthesia with cardiopulmonary bypass at our hospital between November 2023 and November 2025. Patients were assigned to low- and medium-dose groups based on the injected cardiomyocyte dose: 0.5x10 cells and 1.5x10 cells, respectively. Eleven patients were enrolled in each dose group. Ventricular tachycardia-related parameters were compared between the two groups after hiPSC-CMs implantation, and the characteristics of ventricular tachycardia episodes as well as the effectiveness of antiarrhythmic drugs were analyzed. A multivariate logistic regression model was applied to analyze risk factors influencing the occurrence of ventricular arrhythmias. ResultsNo statistically significant differences were observed between the two groups in terms of gender, age, LVEF, LVEDD, myocardial infarction percentage, intraoperative CPB time, mean heart rate, QRS duration, QTc interval, PVC burden, or daily dose of beta-blocker or cell viability (P > 0.05). The incidence of VT was significantly higher in the medium-dose group compared to the low-dose group (P < 0.05). No statistically significant differences were observed between the groups regarding the time interval from hiPSC-CMs implantation to initial VT onset, the slowest frequency at initial VT onset, the fastest VT frequency, or VT duration (P > 0.05). Further analysis of VT in both groups at different time points after implantation revealed that the incidence of VT in the medium-dose group was significantly higher than that in the low-dose group on days 14, 21, and 28. However, comparisons of the fastest VT frequency at various time points and the incidence of VT at day 7 between the two groups showed no statistically significant differences (P > 0.05). Among all enrolled patients, VT occurred in 12 patients (54.5%). Based on ECG localization, the origin of VT in all cases was identified at the cell injection site. The time from hiPSC-CMs injection to initial VT onset ranged from 5 to 20 days (median 8.5 days). VT persisted for 9 to 411 days (median 59 days) before spontaneous termination, with 9 patients (75% of those with VT) experiencing VT lasting more than 1 month. The slowest frequency at initial VT onset ranged from 55 to 96 bpm (72.58 {+/-} 9.86 bpm), while the fastest recorded frequency reached 111 to 185 bpm (146.33 {+/-} 21.44 bpm). Hemodynamics remained stable in all patients during increases in VT frequency. Throughout the observed VT episodes, QRS morphology was consistently monomorphic, although cycle length varied. During VT episodes, overdrive pacing via the temporary epicardial atrial lead successfully suppressed but did not terminate VT. While overdrive pacing failed to reduce the frequency of VT, it provided a critical window for optimizing antiarrhythmic drug therapy to control VT. Cardioversion also failed to terminate VT. Administration of beta-blockers, ivabradine, or amiodarone controlled the VT frequency to a range of 55-95 bpm (79.67 {+/-} 12.51 bpm) but likewise did not terminate the arrhythmia. VT terminated spontaneously in patients, after which it either did not recur, recurred intermittently, or reoccurred as sustained VT after a period of time. Multivariate logistic regression analysis indicated that the dose of hiPSC-CMs injection was an independent influencing factor for the risk of VT onset (P < 0.05). ConclusionThe ectopic arrhythmia (EA) is primarily driven by an automaticity mechanism. It is characterized by early onset (median 8.5 days) and prolonged duration (median 59 days), with the cell injection dose identified as an independent risk factor (OR=9.00). Within the controlled dose range (0.5-1.5x10 cells) and under strict clinical management, this type of arrhythmia can be effectively monitored and managed.

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Accurate Detection of Lead Malfunction From ECG-derived Bipolar Pacing Stimulus Amplitude

Lloyd, M.; Pelling, M.; Ibrahim, R.; El-Chami, M. F.; Iravanian, S.

2024-01-13 cardiovascular medicine 10.1101/2024.01.12.24301251 medRxiv
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BackgroundOne of the most common modes of lead failure is outer insulation breach which may result in myopotential noise and device malfunction. "Pseudo-unipolarization" of bipolar pacing stimuli, as observed from a routine 12-lead ECG has been observed with insulation breaches. We sought to characterize this ECG finding to detect lead this type of lead malfunction. Methods138 transvenous leads were analyzed (88 with known malfunction and 50 normal leads). The highest amplitude (any of 12-leads on standard ECG, 10mm/mV, GE Marquette) of a bipolar pacing stimulus on ECG was recorded and compared to a control dataset of newly implanted leads. An ROC curve for maximum ECG bipolar pacing stimulus amplitude was generated for prediction of lead functional status (normal vs malfunction). ResultsThe cohort (49% females, 34% non-white) had an average age of 67 {+/-} 16 years at implant. The malfunction group consisted of 61% RA and 39% RV leads with mean pacing output 2.74V at 0.5ms. There was a significant difference in ECG bipolar stimulus amplitudes at time of identification of failure (15.06 {+/-} 13.533mm or 7.89 {+/-} 7.56mm per V, p<0.001) compared to those of normal leads (2.54 {+/-} 1.265mm or 0.86 {+/-} 0.41mm per V). An EKG stimulus amplitude cut-off at 3.5mm for the prediction of this type of lead malfunction demonstrated a sensitivity of 86.4% and a specificity of 76%. When normalized for programmed stimulus output, a cutoff of 5mm/V demonstrated a sensitivity of 91% and a specificity of 92% (AUC 0.967 95% CI 0.938-0.996). ConclusionFor a given output, the maximum amplitude of a bipolar pacing stimulus on ECG is significantly lower in normal functioning leads compared to those with known malfunction due to insulation breach. This simply-derived variable demonstrated good accuracy at identifying this lead failure due to insulation breach and exposed electrodes.

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Characterization of ventricular tachycardia ablation in end-stage heart failure patients with left ventricular assist device (CHANNELED registry).

van den Bruck, J.-H.; Hohendanner, F.; Heil, E.; Albert, K.; Duncker, D.; Estner, H. L.; Deneke, T.; Parwani, A. S.; Potapov, E.; Seuthe, K.; Woermann, J.; Sultan, A.; Schipper, J.-H.; Eckardt, L.; Doldi, F.; Lugenbiel, P.; Servatius, H.; Thalmann, G.; Reichlin, T.; Khalaph, M.; Guckel, D.; Sommer, P.; Steven, D.; Lüker, J.

2024-11-26 cardiovascular medicine 10.1101/2024.10.30.24316462 medRxiv
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AbstractO_ST_ABSBackgroundC_ST_ABSPatients with left-ventricular-assist-devices (LVAD) are at high risk for ventricular tachycardia (VT), and data on VT ablation in LVAD patients is scarce. This multicenter registry assessed the mechanism of VT, procedural parameters, and outcome of VT ablation in LVAD patients (NCT06063811). MethodsData of LVAD patients referred for VT ablation at 9 tertiary care centers were collected retrospectively. Parameters included VT mechanisms, procedural data, VT recurrence, and mortality. ResultsOverall, 69 patients (90% male, mean age 60.7{+/-}8.4 years) undergoing 72 catheter ablation procedures were included. Most procedures were conducted after intensification of antiarrhythmic drug (AAD) treatment (18/72; 25%) or after prior combination of [&ge;] 2 AADs (31/72; 43%). Endocardial low voltage areas were detected in all patients. 96 different VTs were targeted. The predominant mechanism was scar-related re-entry (76/96 VTs; 79%) and 19/96 VTs (20%) were related to the LVAD cannula. Non-inducibility of any VT was achieved in 28/72 procedures (39%). No LVAD related complication was observed. The extent of endocardial scar was associated with VT recurrence. Over a median follow-up of 283 days (IQR 70-587 days), 3/69 were lost to follow-up, 10/69 (14%) patients were transplanted, 26/69 (38%) died, and 16/69 (23%) patients were free from VT. ConclusionAlthough often a last resort, VT ablation in LVAD patients is feasible and safe when performed in experienced centers. These patients suffer from a high scar burden, and cardiomyopathy-associated rather than cannula-related scar seems to be the dominant substrate. VT recurrence after ablation is high, despite extensive treatment, and the overall prognosis of these patients is limited. What is knownVT ablation in LVAD patients is one of the most complex procedures in interventional electrophysiology dealing with critically ill patients. These procedures are highly prone to technical difficulties and complications, potentially limiting procedural success and outcome. What the study addsO_LIMost LVAD patients requiring VT ablation have a history of ventricular arrhythmia prior to LVAD implantation, and scar-related re-entry is the predominant arrhythmogenic mechanism. C_LIO_LILVAD related technical challenges are present but seem to have little impact on procedural efficacy. No association of electromagnetic interference and LVAD model was observed. C_LIO_LIExtensive low voltage areas were detected in most patients. Unlike in non-LVAD patients, LVAD patients showed no difference in endocardial scar between ICM and NICM. C_LIO_LINeither the type of cardiomyopathy nor the endpoint of non-inducibility but the extent of myocardial scar seems to predict VT recurrence in patients with LVAD. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/24316462v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@db2aa1org.highwire.dtl.DTLVardef@cbd358org.highwire.dtl.DTLVardef@1a03f05org.highwire.dtl.DTLVardef@1897cc4_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Left atrial substrate characterization based on bipolar voltage electrograms acquired with multipolar, focal and mini-electrode catheters- the CHAZE-Substrate study

Knecht, S.; Schlageter, V.; Badertscher, P.; Krisai, P.; Jousset, F.; Spies, F.; Kueffer, T.; Madaffari, A.; Schaer, B.; Osswald, S.; Sticherling, C.; Kühne, M.

2023-01-28 cardiovascular medicine 10.1101/2023.01.24.23284964 medRxiv
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BackgroundBipolar voltage (BV) electrograms for left atrial (LA) substrate characterization depend on catheter design and electrode configuration. The aim of the study was to investigate the relationship between the BV amplitude (BVA) using four different catheters and to identify their specific LA cutoffs for scar and healthy tissue. MethodsConsecutive high-resolution electroanatomic mapping was performed using a multipolar Orion catheter (Orion-map), a duo-decapolar variable circular mapping catheter (Lasso-Map) and an irrigated focal ablation catheter with minielectrodes (Mifi-map). Virtual remapping using the Mifi-map was performed with a 4.5 mm tip-size electrode configuration (Nav-map). BVAs were compared in voxels of 3x3x3 mm3. The equivalent BVA cutoff for every catheter was calculated for established reference cutoff values of 0.1 mV, 0.2 mV, 0.5 mV, 1.0 mV, and 1.5 mV. ResultsWe analyzed 25 patients (72% men, age 68{+/-}15 years). For scar tissue, a 0.5 mV cutoff using the Nav corresponds to a lower cutoff of 0.35 mV for the Orion and of 0.48 mV for the Lasso. Accordingly, a 0.2 mV cutoff corresponds to a cutoff of 0.09 mV for the Orion and of 0.14 mV for the Lasso. For a healthy tissue cutoff at 1.5 mV, a larger BVA cutoff for the small electrodes of the Orion and the Lasso was determined of 1.68 mV and 2.21 mV, respectively. ConclusionsWhen measuring LA BVA in scar and healthy tissue, relevant differences were seen between focal, multielectrode and mini-electrode catheters. Adapted cutoffs for scar and healthy tissue are required.

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A rare gain of function HCN4 gene mutation is responsible for inappropriate sinus tachycardia in a Spanish family

Camara-Checa, A.; Perin, F.; Rubio-Alarcon, M.; Dago, M.; Crespo-Garcia, T.; Rapun, J.; Marin, M.; Cebrian, J.; Bermudez-Jimenez, F.; Monserrat, L.; Tamargo, J.; Caballero, R.; Jimenez-Jaimez, J.; Delpon, E.

2023-01-20 cardiovascular medicine 10.1101/2023.01.20.23284606 medRxiv
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BackgroundIn a family with inappropriate sinus tachycardia (IST) we identified a novel mutation (p.V240M) of the hyperpolarization-activated cyclic nucleotide-gated type 4 (HCN4) channel, which contributes to the pacemaker current (If) in human sinoatrial node cells. Here we clinically study the family and functionally analyze the p.V240M variant. MethodsMacroscopic (IHCN4) and single-channel currents were recorded using patch-clamp in cells expressing human native (WT) and/or p.V240M HCN4 channels. ResultsAll p.V240M mutation carriers exhibited IST (mean heart rate 113[7] bpm, n=9), that in adults, was accompanied by cardiomyopathy. IHCN4 generated by p.V240M channels either alone or in combination with WT was significantly greater than that generated by WT channels. The variant, which lies in the N-terminal HCN domain, increased single-channel conductance and opening frequency and probability of HCN4 channels. Conversely, it did not modify channel sensitivity for cAMP and ivabradine or the level of expression at the membrane. Treatment with ivabradine based on functional data reversed the IST and the cardiomyopathy of the carriers. ConclusionsThe p.V240M gain-of-function variant increases If during diastole, which explains the IST of the carriers. The results demonstrate the importance of the unique HCN domain in HCN4 which stabilizes the channels in the closed state. FundingMinisterio de Ciencia e Innovacion (PID2020-118694RB-I00); Comunidad Autonoma de Madrid (P2022/BMD-7229), European Structural and Investment Funds); and Instituto de Salud Carlos III (CIBERCV; CB16/11/00303).

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Electrophysiological Features and Catheter Ablation for Supraventricular Tachyarrhythmias in Patients with Fontan Circulation: A Multicenter Study

Uhm, J.-S.; Song, M. K.; Ban, J.-E.; Baek, S. M.; Hwang, T.; Cho, S.; Park, H.; Kim, D.; Yu, H. T.; Kim, T.-H.; Joung, B.; Pak, H.-N.; Tchah, N.; Lee, N. H.; Kim, C. S.; Park, S. J.; Jung, J. W.; Choi, J. Y.; Bae, E.-J.

2026-03-25 cardiovascular medicine 10.64898/2026.03.23.26349127 medRxiv
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Background: Patients with Fontan circulation experience significant morbidity from supraventricular tachyarrhythmias (SVTs). However, the electrophysiological features of SVT and the efficacy and safety of catheter ablation in patients with Fontan circulation are poorly understood. This study aimed to elucidate the electrophysiological features of SVT and evaluate the efficacy and safety of catheter ablation in patients with Fontan circulation. Methods: Forty-nine patients (age, 29.2{+/-}10.0 years; 27 males) with functional single ventricle and Fontan circulation who had undergone electrophysiological study for SVT were retrospectively enrolled. Parameters analyzed included underlying congenital heart disease, Fontan type, conduit puncture technique, tachycardia mechanisms, tachycardia origin site, acute success rate, procedure-related complications, and recurrence. Results: Fifty-nine SVTs were induced, and 69 catheter ablations were performed. The Fontan types included atriopulmonary connection (APC, 18.4%), lateral tunnel (LT, 38.8%), and extracardiac conduit (ECC, 42.9%). Inducible tachycardias included intra-atrial reentrant tachycardia (IART, 39.0%), focal atrial tachycardia (AT, 28.8%), atrioventricular reentrant tachycardia (11.9%), atrioventricular nodal reentrant tachycardia (10.2%), and atrioventricular reciprocating tachycardia involving the twin atrioventricular nodes (10.2%). The right atrial (RA) lateral wall was the most common location of IART and focal AT. The acute success and complication rates were 73.5% and 4.1%, respectively. Recurrence rate was 34.7% during follow-up of 78.0{+/-}71.9 months. The cumulative recurrence rate was significantly lower in patients who underwent LT or ECC Fontan procedures than in those who underwent the APC Fontan procedure (P<0.001). Conclusions: Catheter ablation for SVT is effective and safe in patients who have undergone LT and ECC Fontan procedures.

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Long-term Serial Exercise Stress Testing in RyR2-Positive Genotype Patients with Catecholaminergic Polymorphic Ventricular Tachycardia on Beta-Blocker and Flecainide Therapy.

Wangüemert-Perez, F.; Ostos-Canero, G.; Wangüemert-Guerra, M.; Acosta-Materan, C.; Cardenes-Leon, A.; Caballero Dorta, E.; Perez-Rodriguez, K.; Brugada, R.; Brugada, J.; Martinez-Quintana, E.

2025-04-11 cardiovascular medicine 10.1101/2025.04.08.25325493 medRxiv
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IntroductionCatecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a potentially life-threatening arrhythmic disorder typically treated with beta-blockers and, occasionally, with flecainide. MethodsAll patients underwent genetic testing, ECG, echocardiogram, and exercise tests. Ventricular arrhythmias were assessed using qualitative and quantitative scoring. Flecainide dosing was gradually increased, and follow-up extended from 2007 to 2024. Results235 patients were genetically positive for the RyR2 p.Gly357Ser mutation, of whom 32 required beta-blockers and flecainide (age at diagnosis 18 (1-55) years old, start of flecainide at 32 (15-66) years old, 16 (50%) male patients). 47% had an implantable cardioverter defibrillator (ICD). Flecainide was indicated for ventricular arrhythmia (97%) during the exercise test despite beta-blocker therapy and median treatment duration with flecainide was of 7.3 years. All patients were on propranolol (median dose 65 mg/day). Flecainide (median dose 100 mg/day) was well tolerated, with no syncope or stress-induced dizziness. Before flecainide, 5 patients (16%) had ventricular arrhythmic events in the ICD, with 2 requiring appropriate shocks. After flecainide, no events occurred. Both qualitative (2.07{+/-}0.77 vs. 1.22{+/-}1.08, p<0.001) and quantitative (69.78{+/-}83.17 vs. 15.29{+/-}5.53, p<0.001) arrhythmic scores improved significantly after adding flecainide. Additionally, there was a significant increase in METs (Z=-2.564, p=0.010) and a reduction in the maximum heart rate (Z=-2.870, p=0.004) and the percentage of the age-predicted maximum heart rate (Z=-3.403, p=0.001) during the exercise test with the combined therapy. ConclusionFlecainide and beta-blocker therapy in CPVT patients resulted in significant improvements in exercise capacity and a reduction in arrhythmic burden in the long-term follow-up.

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Fractionated Potential-Guided Cryoablation Targeting Termination of Atrioventricular Nodal Reentrant Tachycardia While Avoiding the Compact Node Electrogram

Hirata, S.; Nagashima, K.; Watanabe, R.; Wakamatsu, Y.; Hirata, M.; Kurokawa, S.; Otsuka, N.; Sawada, M.; Okumura, Y.

2024-11-19 cardiovascular medicine 10.1101/2024.11.18.24317515 medRxiv
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BackgroundFractionated potential (FP) ablation during atrioventricular nodal reentrant tachycardia (AVNRT), is an effective strategy that minimizes redundant radiofrequency (RF) applications. This study aimed to evaluate the utility of cryoablation targeting FPs to effectively terminate AVNRT while further minimizing redundant cryoapplications. Moreover, we observed what appeared to be compact AVN (cAVN) or proximal His potentials--tiny, dull potentials (TDPs) with continuity to the His potential during sinus rhythm (SR) and AVNRT--in the anteroseptal area. The second aim of this study was to explore the significance of those potentials. MethodsAnalyzed were 53 slow-fast AVNRT patients who underwent ablation procedures. Ultra-high resolution activation maps in the triangle of Koch were obtained during SR (n=34) and AVNRT (n=46). TDPs during SR and AVNRT in the anteroseptal area were identified and annotated using the LUMIPOINT Activation Search tool. ResultsFP areas were observed in 19 patients (56%) during SR and in 46 (100%) during AVNRT. This area corresponded to the AVNRT termination and/or successful ablation site in all, with peak numbers of 8.8{+/-}1.4 during AVNRT and 5.3{+/-}1.3 during SR. The number of ablation points was 3.6{+/-}1.5 for the FP-guided cryoablation (n=32) (Bonferroni corrected P<0.05 vs. anatomical RF; and P<0.05 vs. FP-guided RF), 5.4{+/-}2.1 for the FP-guided RF ablation (n=11) (P=0.0825 vs. anatomical RF), and 8.2{+/-}3.2 for the conventional RF ablation (n=10). Transient AV block occurred in 11 patients (21%). All AV block sites overlapped with the TDP area in the phase just before the His potential during AVNRT and SR, with a confidence setting of [&ge;]24% (35[24-60]%). Conversely, in 42 patients without AV block, no ablation was performed in this area. ConclusionThe FP-guided cryoablation strategy targeting AVNRT termination required fewer cryoapplications than RF ablation. The RF/cryo application in the TDP area during SR and AVNRT posed a risk of AV block.

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Comparison of LA and PVC mapping using OCTARAY and OPTRELL catheters

Saito, J.; Kato, D.; Sato, H.; Matsuda, T.; Koyanagi, Y.; Yoshihiro, K.; Gibo, Y.; Usumoto, S.; Kimura, T.; Shimazu, S.; Igawa, W.; Ebara, S.; Okabe, T.; ISOMURA, N.; Ochiai, M.

2025-03-04 cardiovascular medicine 10.1101/2025.03.03.25323279 medRxiv
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BackgroundMultielectrode mapping catheters, such as the OCTARAY and OPTRELL, are essential in creating myocardial electroanatomical mapping in arrhythmias. The OCTARAY is a multi-spline mapping catheter with 48 closely spaced multielectrodes that enables high-resolution electroanatomical mapping, while the OPTRELL is a multi-electrode catheter with 36 electrodes arranged on eight radiating splines. However, only a few studies have compared their performance. In this study, we aimed to compare the OCTARAY and OPTRELL catheters in two areas: left atrial (LA) mapping during atrial fibrillation (AF) ablation; and premature ventricular contraction (PVC) mapping. MethodsTwenty patients (Ten patients for LA mapping and ten for PVC mapping) were enrolled. LA voltage mapping was performed twice, alternating between catheters post-AF ablation. Parameters compared included mapping time, mapping points, catheter-induced premature atrial contraction (PACs), tissue proximity indication, low voltage area, and fluoroscopy time. For PVC mapping, comparisons included mapping time, catheter-induced PVCs, earliest activation time measured from the onset of PVC QRS, earliest activation point, and fluoroscopy time. ResultsCompared with THE OCTARAY, mean voltage using the OPTRELL was higher (0.192 mV[0.072, 0.48] vs. 0.126 mV[0.042, 0.378]; P = .001) and the percentage of tissue proximity indication positive was also higher (14.97% vs. 11.45%; P < .001). However, there were no significant differences in low voltage area between the two groups (39.5 m2[16.5, 66.8] vs. 40[23.6, 61]; P = .861), and in other LA parameters. In PVC mapping, catheter-induced PVCs using OPTRELL were significantly fewer than the OCTARAY (100 [32, 337] vs. 247 [110, 745], P = .039), with fewer catheter induced PVCs per minute (15 [6, 23] vs. 35 [20, 71], P = .039). However, no significant differences were observed in other PVCs mapping parameters. ConclusionThe OPTRELL catheter demonstrated higher voltage recordings in LA mapping and fewer catheter-induced PVCs compared with the OCTARAY catheter. However, no significant difference was observed in other mapping parameters.

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Programmed deep septal pacing for the diagnosis of left bundle branch capture.

Jastrzebski, M.; Moskal, P.; Kusiak, A.; Bednarek, A.; Sondej, T.; Kielbasa, G.; Bednarski, A.; Vijayaraman, P.; Czarnecka, D.

2019-09-30 physiology 10.1101/786665 medRxiv
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BackgroundDuring permanent deep septal pacing, it is important to confirm left bundle branch (LBB) capture.\n\nObjectiveThe effective refractory period (ERP) of the working myocardium is different than the ERP of the LBB; we hypothesized that it should be possible to differentiate LBB capture from septal myocardial capture using programmed extra-stimulus technique.\n\nMethodsIn consecutive patients undergoing pacemaker implantation who received pacing lead in a deep septal position programmed pacing was delivered from this lead. Responses to programmed pacing were categorized on the basis of QRS morphology of the extrastimuli as: myocardial (broader QRS, often slurred), selective (narrower QRS, preceded by an isoelectric interval) or non-diagnostic (unequivocal change).\n\nResultsProgrammed deep septal pacing was performed 269 times in 143 patients; in every patient with the use of an 8-beat basic drive train of 600 ms and when possible also during supraventricular rhythm. Responses diagnostic for LBB capture were observed in 114 (79.7%) of patients. Selective LBB paced QRS was more often seen when premature beats were introduced during the intrinsic rhythm rather than after the basic drive train. The average septal-myocardial refractory period was significantly shorter than the LBB refractory period: 263.0{+/-}34.4 ms vs. 318.0{+/-}37.4 ms.\n\nConclusionsA novel maneuver for the diagnosis of LBB capture during deep septal pacing, was formulated, assessed and found as diagnostically valuable. This method, based on the differences in refractoriness between LBB and the septal myocardium is unique in enabling the visualization of components of the usually fused, non-selective LBB paced QRS complex.\n\nGraphical abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

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Clinical significance and possible mechanism of different ventricular electrogram morphology in selective left bundle branch pacing

Wang, D.; Jiang, L.; Shen, J.; Li, H.

2024-12-03 cardiovascular medicine 10.1101/2024.12.02.24318355 medRxiv
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BackgroundCurrently, splitting of electrogram (EGM) or electrocardiogram (ECG) under threshold test are used as the gold standard to assess Left bundle branch (LBB) capture in LBB area pacing. However, discrete intracardiac ventricular EGM has not been reported until now. This study aims to explore the clinical significance and possible mechanism of different pacing ventricular EGM morphologies in selective LBB pacing. MethodsOnly patients with evidence of selective LBB pacing (splitting of EGM under threshold test) were included. According to the differences between intrinsic and paced ventricular EGM morphologies, the participants were further divided into three groups: concordant EGM (CE) group, similar EGM (SE) group and discordant EGM (DE) group. Baseline characteristics, indications for pacing, pacing parameters, and V6 R-wave peak time were analyzed. Results274 patients (85.6%) achieved successful selective LBB pacing. After excluding 34 LBBB patients, LBB potential was recorded in 192 (80%) of 240 patients. In patients with LBB potential, the correlation between V-V6(P) RWPT and V-V6(S) RWPT in CE group (r=0.083, P<0.0001) and SE group (r=0.766, P<0.0001) were strong. V-V6(S) RWPT was significantly shorter than V-V6(P) RWPT (38.14{+/-}9.42 vs. 43.68{+/-}6.72, P<0.01) in DE group. In patients without LBB potential, V-V6(S) RWPT was significantly shorter than V-V6 RWPT (38.14{+/-}11.60 vs. 46.15{+/-}11.81, P<0.05) in DE group. There was a strong correlation (r=0.943, P<0.0001) between V-V6 RWPT and V-V6(S) RWPT in CE group, a possible correlation (r=0.564, P=0.07) in SE group, while poor correlation (r=0.259, P=0.27) in DE group. ConclusionThe continuous recording technique combined with High Pass-200 Hz filter setting was feasible and effective for confirming selective LBB pacing by discrete EGM. Concordant or similar intrinsic and pacing ventricular EGM indicated that the electric conduction shared the same pathway, while discordant intrinsic and pacing ventricular EGM indicated that the electrical stimulation is conducted through different pathway. WHAT IS KNOWN?1. Left bundle branch (LBB) pacing is a novel physiological pacing strategy. 2. Double transition in QRS morphology during threshold testing was considered as the criteria for LBB capture, and splitting of EGM under threshold test was used as the gold standard to assess selective LBB pacing. 3. Identifying discrete local ventricular EGM is still a challenging task. WHAT THE STUDY ADDS1. The continuous recording technique combined with High Pass-200 Hz filter setting was feasible and effective for confirming selective LBB pacing by discrete EGM. 2. Different pacing ventricular EGM morphologies compared with intrinsic EGM accounted for clinical significance and possible mechanism: concordant or similar intrinsic and pacing ventricular EGM indicated that the electric conduction shared the same pathway, while discordant intrinsic and pacing ventricular EGM indicated that the electrical stimulation is conducted through different pathway. 3. The anatomical structure of LBB and its fascicular branch was complex, which could not be adequately recorded by 12-lead ECG and EGM.

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Cryoballoon Ablation of RooF line combined with pulmonary vein Isolation for persistent atrial fibrillation (The CARFI-PerAF Randomized Clinical Trial)

Huang, S.; Zhao, Y.; Ju, R.; Liu, C.; Dong, S.; Qin, A.; Cao, J.; Yu, M.; Guo, Z.-F.; Huang, X.

2023-09-08 cardiovascular medicine 10.1101/2023.09.06.23295158 medRxiv
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BackgroundThe limited effectiveness of pulmonary vein isolation (PVI) alone using cryoballoon ablation (CBA) led to addictive ablation in procedures of persistent atrial fibrillation (AF) ablation. Roof line (RL) ablation in addition to PVI hold great promise for reduction of AF recurrence after CBA. The randomized controlled CARFI-PerAF trial aimed to prospectively investigate the efficacy of a novel CBA strategy for block of RL and reduction of AF recurrence. MethodsOne hundred and ten patients who were diagnosed with persistent AF were randomized into PVI group and PVI+RL group. Quarter balloon ablation technique and roof distortion technique were used to improve quality of RL ablation. Conduction block of RL was confirmed by both voltage mapping and upper right atrial septum pacing. Primary effectiveness was freedom from AF or atrial tachycardia absent class I/III antiarrhythmic drugs through 12-month follow-up according to ECGs collected by portable device and 24-hour Holter. ResultsThere was no significant difference in AF recurrence between PVI group and PVI+RL group (63.5% vs 76.2%, P = 0.296) after 532.7 {+/-} 171.0 days of follow-up. However, blocked RL was associated with a significant reduction in risk of AF recurrence in the PVI+RL group (84.0% vs 45.5%, P = 0.025). The shape of RL was the only factor affecting the success rate of RL block. Patients with Regular shape of RL predicted a higher rate of RL block than other types (89.7% vs 56.3%, P = 0.014). ConclusionsBlocked roof line ablation was associated with a significant reduction in risk of atrial fibrillation recurrence after cryoballoon ablation. Patients with Regular shape of roof line may benefit more from roof line ablation.

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Stereotactic arrhythmia radioablation (STAR) in patients with ventricular tachycardia: a meta-analysis of efficacy and safety outcomes.

Viani, G. A.; Pavoni, J. F.; de Fendi, L. I.

2020-05-13 cardiovascular medicine 10.1101/2020.05.09.20094763 medRxiv
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ObjectivesThe effectiveness and safety of STAR in patients with refractory ventricular tachycardia (VT) to catheter ablation are limited to small series. We performed a meta-analysis of observational studies to summarize existing data about efficacy and toxicity following START for VT. Methods: Eligible studies were identified on Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through March 2020. We followed the PRISMA and MOOSE guidelines. An estimative of % VT burden reduction at 6 months higher than 85% was considered effective. A rate of any grade 3 or higher toxicity lower than 10% and no grade 4 or 5 were considered safe. Results: Four observational studies with a total of 39 patients treated were included. The % of VT burden reduction at 6 months was 91% (CI95% 83 - 10%). The consumption of lower than 2 anti-arrhythmia drugs (AAD) at 6 months was 81%. The ejection fraction improved in 12.8%, unchanged 82%, and decreased by 5.2%. The overall survival (OS) was 92% and 82 % in 6 and 12 months. The cardiac death and disease-specific survival at 12 months were 12% and 88.5%. Late grade 3 toxicity 5% with no grade 4-5. Conclusion: STAR produced satisfactory % of VT burden reduction, with a significant reduction in the consumption of AAD at 6 months, and no severe toxicity. These findings support the continued work to develop new trials and to adopt STAR as a treatment option for medical practice.

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Electrophysiological characteristics of lead-position-dependent EGM uninterrupted transition during left bundle branch pacing

Shen, J.; Jiang, L.; Wu, H.; Zhang, L.; Li, H.; Pan, L.

2024-06-18 cardiovascular medicine 10.1101/2024.06.16.24308988 medRxiv
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Background and AimsLeft bundle branch pacing (LBBP) is a novel pacing strategy that improves ventricular synchrony by utilizing the native conduction system. However, the current standard practices limit continuous monitoring of paced electrocardiogram (ECG) and intracardiac electrogram (EGM) transition, which may result in overlooked or misinterpreted subtle transitions. This study aimed to explore the electrophysiological characteristics of the lead-position-dependent EGM continuous transition and evaluate their clinical significance. MethodsThis observational study included patients referred for LBBP due to symptomatic bradyarrhythmia. A continuous pacing and recording technique was employed, allowing real-time monitoring of progressive alterations in the paced QRS complex as the lead penetrates deeper into the ventricular septum. EGM and ECG parameters were continuously monitored and analyzed. ResultsThe study encompassed 105 patients, with selective LBBP achieved in 88 patients (83.8%). The amplitude of ventricular EGM predictably changed with radial interventricular septum depth and peaked in the mid-septum. As the lead was inserted into the left ventricular subendocardium, the ventricular current of injury (COI) declined to a level approximating that of the right septum. Continuous recording technique enabled real-time monitoring of the entire perforation process and the subtle variations that exist among different perforation modalities. The discernment of discrete was feasible through the examination of unfiltered EGM, suggesting that selective LBB capture can also be confirmed by observing the subtle morphological transitions within the ventricular COI. ConclusionsThe continuous recording technique provides a more detailed understanding of the radial depth of the pacing lead throughout the implantation process. It simplifies the implantation procedures and facilitates the prevention or early detection of perforations. Future studies are needed to validate these findings and explore their clinical implications. Whats new?O_LIUtilization of Ventricular Electrogram (EGM) for Lead Positioning: The amplitude of ventricular EGM changes predictably with radial interventricular septum depth, peaking in the mid-septum. This provides a useful way to determine whether the lead is located on the left, right, or middle of the ventricular septum. C_LIO_LIReal-time Monitoring of Perforation Process: The continuous recording technique enables real-time monitoring of the entire perforation process. This feature helps to distinguish the subtle variations that exist among different perforation modalities, facilitating early detection and prevention of perforations. C_LIO_LIConfirmation of Selective Left Bundle Branch Pacing (SLBBP): The emergence of a discrete ventricular current of injury (COI) may serve as a novel characteristic of SLBBP. This suggests that SLBBP can be confirmed by observing the subtle morphological transitions within the ventricular COI. C_LI

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A Pilot Study of an Esophageal Cooling Device During Radiofrequency Ablation for Atrial Fibrillation

Clark, B.; Alvi, N.; Hanks, J.; Suprenant, B.

2020-01-28 cardiovascular medicine 10.1101/2020.01.27.20019026 medRxiv
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BackgroundEsophageal thermal injury is a risk of ablation of the posterior left atrium despite various devices utilized to date. ObjectiveEvaluate the potential of a commercially-available esophageal cooling device to provide esophageal protection during left atrial catheter ablation. MethodsIn this pilot study, we randomized 6 patients undergoing catheter ablation for atrial fibrillation. Three patients received standard of care for our site (use of a single-sensor temperature probe, with adjunct iced-water instillation for any temperature increases >1{degrees}C). Three patients received standard ablation after placement of the esophageal cooling device using a circulating water temperature of 4{degrees}C. All patients underwent transesophageal echocardiogram (TEE) and esophagogastroduodenoscopy (EGD) on the day prior to ablation followed by EGD on the day after. ResultsIn the 3 control patients, one had no evidence of esophageal mucosal damage, one had diffuse sloughing of the esophageal mucosa and multiple ulcerations, and one had a superficial ulcer with large clot. Both patients with lesions were classified as Zargar 2a. In the 3 patients treated with the cooling device, one had no evidence of esophageal mucosal damage, one had esophageal erythema (Zargar 1), and one had a solitary Zargar 2a lesion. At 3-month follow-up, 1 patient in each group had recurrence of atrial fibrillation. ConclusionsThe extent of esophageal injury was less severe with a commercially available esophageal cooling device than with reactive instillation of ice-cold water. This pilot study supports further evaluation with a larger clinical trial.

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The Calcium Transient Coupled to the L-Type Calcium Current Attenuates Action Potential Alternans

Warren, M. D.; Poelzing, S.

2023-04-28 physiology 10.1101/2023.04.25.538350 medRxiv
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BackgroundAction potential (AP) alternans are linked to increased arrhythmogenesis. It is suggested that calcium (Ca2+) transient (CaT) alternans cause AP alternans through bi-directional coupling feedback mechanisms because CaT alternans can precede AP alternans and develop in AP alternans free conditions. However, the CaT is an emergent response to intracellular Ca2+ handling, and the mechanisms linking AP and CaT alternans are still a topic of investigation. This study investigated the development of AP alternans in the absence of CaT. MethodsAP (patch clamp) and intracellular Ca2+ (Fluo-4 epifluorescence) were recorded simultaneously from isolated rabbit ventricle myocytes perfused with the intracellular Ca2+ buffer BAPTA (10-20 mM) to abolish CaT and/or the L-type Ca2+ channel activator Bay K 8644 (25 nM). ResultsAfter a rate change, alternans were critically damped and stable, overdamped and ceased over seconds, underdamped with longer scale harmonics, or unstably underdamped progressing to 2:1 capture. Alternans in control cells were predominantly critically damped, but after CaT ablation with 10 or 20 mM BAPTA, exhibited respectively increased overdamping or increased underdamping. Alternans were easier to induce in CaT free cells as evidenced by a higher alternans threshold (ALT-TH: at least 7 pairs of alternating beats) relative to control cells. Alternans in Bay K 8644 treated cells were often underdamped, but the ALT-TH was similar to control. In CaT ablated cells, Bay K 8644 prolonged AP duration (APD) leading predominantly to unstably underdamped alternans. ConclusionsAP alternans occur more readily in the absence of CaT suggesting that the CaT dampens the development of AP alternans. The data further demonstrate that agonizing the L-type calcium current without the negative feedback of the CaT leads to unstable alternans. This negative feedback mechanism may be important for understanding treatments aimed at reducing CaT or its dynamic response to prevent arrhythmias.