Electrophysiology and Heart Modeling Institute

BACKGROUND: A leadless intracardiac transcatheter pacing system has been designed to avoid the need for a pacemaker pocket and transvenous lead. METHODS: In a prospective multicenter study without controls, a transcatheter pacemaker was implanted in patients who had guideline-based indications for ventricular pacing. The analysis of the primary end points began when 300 patients reached 6 months of follow-up. The primary safety end point was freedom from system-related or procedure-related major complications. The primary efficacy end point was the percentage of patients with low and stable pacing capture thresholds at 6 months (≤2.0 V at a pulse width of 0.24 msec and an increase of ≤1.5 V from the time of implantation). The safety and efficacy end points were evaluated against performance goals (based on historical data) of 83% and 80%, respectively. We also performed a post hoc analysis in which the rates of major complications were compared with those in a control cohort of 2667 patients with transvenous pacemakers from six previously published studies. RESULTS: The device was successfully implanted in 719 of 725 patients (99.2%). The Kaplan-Meier estimate of the rate of the primary safety end point was 96.0% (95% confidence interval [CI], 93.9 to 97.3; P<0.001 for the comparison with the safety performance goal of 83%); there were 28 major complications in 25 of 725 patients, and no dislodgements. The rate of the primary efficacy end point was 98.3% (95% CI, 96.1 to 99.5; P<0.001 for the comparison with the efficacy performance goal of 80%) among 292 of 297 patients with paired 6-month data. Although there were 28 major complications in 25 patients, patients with transcatheter pacemakers had significantly fewer major complications than did the control patients (hazard ratio, 0.49; 95% CI, 0.33 to 0.75; P=0.001). CONCLUSIONS: In this historical comparison study, the transcatheter pacemaker met the prespecified safety and efficacy goals; it had a safety profile similar to that of a transvenous system while providing low and stable pacing thresholds. (Funded by Medtronic; Micra Transcatheter Pacing Study ClinicalTrials.gov number, NCT02004873.).

Providing therapies tailored to each patient is the vision of precision medicine, enabled by the increasing ability to capture extensive data about individual patients. In this position paper, we argue that the second enabling pillar towards this vision is the increasing power of computers and algorithms to learn, reason, and build the 'digital twin' of a patient. Computational models are boosting the capacity to draw diagnosis and prognosis, and future treatments will be tailored not only to current health status and data, but also to an accurate projection of the pathways to restore health by model predictions. The early steps of the digital twin in the area of cardiovascular medicine are reviewed in this article, together with a discussion of the challenges and opportunities ahead. We emphasize the synergies between mechanistic and statistical models in accelerating cardiovascular research and enabling the vision of precision medicine.

Empagliflozin (EMPA), an inhibitor of the renal sodium–glucose cotransporter (SGLT) 2, reduces the risk of cardiovascular death in patients with type 2 diabetes. The underlying mechanism of this effect is unknown. Elevated cardiac cytoplasmic Na+ ([Na+]c) and Ca2+ ([Ca2+]c) concentrations and decreased mitochondrial Ca2+ concentration ([Ca2+]m) are drivers of heart failure and cardiac death. We therefore hypothesised that EMPA would directly modify [Na+]c, [Ca2+]c and [Ca2+]m in cardiomyocytes. [Na+]c, [Ca2+]c, [Ca 2+]m and Na+/H+ exchanger (NHE) activity were measured fluorometrically in isolated ventricular myocytes from rabbits and rats. An increase in extracellular glucose, from 5.5 mmol/l to 11 mmol/l, resulted in increased [Na+]c and [Ca2+]c levels. EMPA treatment directly inhibited NHE flux, caused a reduction in [Na+]c and [Ca2+]c and increased [Ca2+]m. After pretreatment with the NHE inhibitor, Cariporide, these effects of EMPA were strongly reduced. EMPA also affected [Na+]c and NHE flux in the absence of extracellular glucose. The glucose lowering kidney-targeted agent, EMPA, demonstrates direct cardiac effects by lowering myocardial [Na+]c and [Ca2+]c and enhancing [Ca2+]m, through impairment of myocardial NHE flux, independent of SGLT2 activity.

BACKGROUND: Catheter ablation of atrial fibrillation using thermal energies such as radiofrequency or cryothermy is associated with indiscriminate tissue destruction. During pulsed field ablation (PFA), subsecond electric fields create microscopic pores in cell membranes-a process called electroporation. Among cell types, cardiomyocytes have among the lowest thresholds to these fields, potentially permitting preferential myocardial ablation. OBJECTIVES: The purpose of these 2 trials was to determine whether PFA allows durable pulmonary vein (PV) isolation without damage to collateral structures. METHODS: Two trials were conducted to assess the safety and effectiveness of catheter-based PFA in paroxysmal atrial fibrillation. Ablation was performed using proprietary bipolar PFA waveforms: either monophasic with general anesthesia and paralytics to minimize muscle contraction, or biphasic with sedation because there was minimal muscular stimulation. No esophageal protection strategy was used. Invasive electrophysiological mapping was repeated after 3 months to assess the durability of PV isolation. RESULTS: In 81 patients, all PVs were acutely isolated by monophasic (n = 15) or biphasic (n = 66) PFA with ≤3 min elapsed delivery/patient, skin-to-skin procedure time of 92.2 ± 27.4 min, and fluoroscopy time of 13.1 ± 7.6 min. With successive waveform refinement, durability at 3 months improved from 18% to 100% of patients with all PVs isolated. Beyond 1 procedure-related pericardial tamponade, there were no additional primary adverse events over the 120-day median follow-up, including: stroke, phrenic nerve injury, PV stenosis, and esophageal injury. The 12-month Kaplan-Meier estimate of freedom from arrhythmia was 87.4 ± 5.6%. CONCLUSIONS: In first-in-human trials, PFA preferentially affected myocardial tissue, allowing facile ultra-rapid PV isolation with excellent durability and chronic safety. (IMPULSE: A Safety and Feasibility Study of the IOWA Approach Endocardial Ablation System to Treat Atrial Fibrillation; NCT03700385; and PEFCAT: A Safety and Feasibility Study of the FARAPULSE Endocardial Ablation System to Treat Paroxysmal Atrial Fibrillation; NCT03714178).

The function of the right ventricle determines the fate of patients with pulmonary hypertension. Since right heart failure is the consequence of increased afterload, a full physiological description of the cardiopulmonary unit consisting of both the right ventricle and pulmonary vascular system is required to interpret clinical data correctly. Here, we provide such a description of the unit and its components, including the functional interactions between the right ventricle and its load. This physiological description is used to provide a framework for the interpretation of right heart catheterisation data as well as imaging data of the right ventricle obtained by echocardiography or magnetic resonance imaging. Finally, an update is provided on the latest insights in the pathobiology of right ventricular failure, including key pathways of molecular adaptation of the pressure overloaded right ventricle. Based on these outcomes, future directions for research are proposed.

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society, the Asia Pacific Heart Rhythm Society, and the Latin American Heart Rhythm Society .

OBJECTIVES: This study sought to determine whether durable pulmonary vein isolation (PVI) using pulsed field ablation (PFA) translates to freedom from atrial fibrillation recurrence without an increase in adverse events. BACKGROUND: PFA is a nonthermal ablative modality that, in preclinical studies, is able to preferentially ablate myocardial tissue with minimal effect on surrounding tissues. Herein, we present 1-year clinical outcomes of PFA. METHODS: In 3 multicenter studies (IMPULSE [A Safety and Feasibility Study of the IOWA Approach Endocardial Ablation System to Treat Atrial Fibrillation], PEFCAT [A Safety and Feasibility Study of the FARAPULSE Endocardial Ablation System to Treat Paroxysmal Atrial Fibrillation], and PEFCAT II [Expanded Safety and Feasibility Study of the FARAPULSE Endocardial Multi Ablation System to Treat Paroxysmal Atrial Fibrillation]), paroxysmal atrial fibrillation patients underwent PVI using a basket or flower PFA catheter. Invasive remapping was performed at ∼2 to 3 months, and reconnected PVs were reisolated with PFA or radiofrequency ablation. After a 90-day blanking period, arrhythmia recurrence was assessed over 1-year follow-up. RESULTS: In 121 patients, acute PVI was achieved in 100% of PVs with PFA alone. PV remapping, performed in 110 patients at 93.0 ± 30.1 days, demonstrated durable PVI in 84.8% of PVs (64.5% of patients), and 96.0% of PVs (84.1% of patients) treated with the optimized biphasic energy PFA waveform. Primary adverse events occurred in 2.5% of patients (2 pericardial effusions or tamponade, 1 hematoma); in addition, there was 1 transient ischemic attack. The 1-year Kaplan-Meier estimates for freedom from any atrial arrhythmia for the entire cohort and for the optimized biphasic energy PFA waveform cohort were 78.5 ± 3.8% and 84.5 ± 5.4%, respectively. CONCLUSIONS: PVI with a "single-shot" PFA catheter results in excellent PVI durability and acceptable safety with a low 1-year rate of atrial arrhythmia recurrence. These data mitigate concern that the nonthermal ablative mechanism of PFA might mask undiscovered compromises to clinical success. (IMPULSE: A Safety and Feasibility Study of the IOWA Approach Endocardial Ablation System to Treat Atrial Fibrillation, NCT03700385; A Safety and Feasibility Study of the FARAPULSE Endocardial Ablation System to Treat Paroxysmal Atrial Fibrillation, NCT03714178; PEFCAT II Expanded Safety and Feasibility Study of the FARAPULSE Endocardial Multi Ablation System to Treat Paroxysmal Atrial Fibrillation [PEFCAT II], NCT04170608).

Atrial fibrillation (AF) is a highly prevalent arrhythmia, with substantial associated morbidity and mortality. There have been significant management advances over the past 2 decades, but the burden of the disease continues to increase and there is certainly plenty of room for improvement in treatment options. A potential key to therapeutic innovation is a better understanding of underlying fundamental mechanisms. This article reviews recent advances in understanding the molecular basis for AF, with a particular emphasis on relating these new insights to opportunities for clinical translation. We first review the evidence relating basic electrophysiological mechanisms to the characteristics of clinical AF. We then discuss the molecular control of factors leading to some of the principal determinants, including abnormalities in impulse conduction (such as tissue fibrosis and other extra-cardiomyocyte alterations, connexin dysregulation and Na + -channel dysfunction), electrical refractoriness, and impulse generation. We then consider the molecular drivers of AF progression, including a range of Ca 2+ -dependent intracellular processes, microRNA changes, and inflammatory signaling. The concept of key interactome-related nodal points is then evaluated, dealing with systems like those associated with CaMKII (Ca 2+ /calmodulin-dependent protein kinase-II), NLRP3 (NACHT, LRR, and PYD domains-containing protein-3), and transcription-factors like TBX5 and PitX2c. We conclude with a critical discussion of therapeutic implications, knowledge gaps and future directions, dealing with such aspects as drug repurposing, biologicals, multispecific drugs, the targeting of cardiomyocyte inflammatory signaling and potential considerations in intervening at the level of interactomes and gene-regulation. The area of molecular intervention for AF management presents exciting new opportunities, along with substantial challenges.

Pulsed field ablation (PFA) is an emerging technology for the treatment of atrial fibrillation (AF), for which pre-clinical and early-stage clinical data are suggestive of some degree of preferentiality to myocardial tissue ablation without damage to adjacent structures. Here in the MANIFEST-17K study we assessed the safety of PFA by studying the post-approval use of this treatment modality. Of the 116 centers performing post-approval PFA with a pentaspline catheter, data were received from 106 centers (91.4% participation) regarding 17,642 patients undergoing PFA (mean age 64, 34.7% female, 57.8% paroxysmal AF and 35.2% persistent AF). No esophageal complications, pulmonary vein stenosis or persistent phrenic palsy was reported (transient palsy was reported in 0.06% of patients; 11 of 17,642). Major complications, reported for ~1% of patients (173 of 17,642), were pericardial tamponade (0.36%; 63 of 17,642) and vascular events (0.30%; 53 of 17,642). Stroke was rare (0.12%; 22 of 17,642) and death was even rarer (0.03%; 5 of 17,642). Unexpected complications of PFA were coronary arterial spasm in 0.14% of patients (25 of 17,642) and hemolysis-related acute renal failure necessitating hemodialysis in 0.03% of patients (5 of 17,642). Taken together, these data indicate that PFA demonstrates a favorable safety profile by avoiding much of the collateral damage seen with conventional thermal ablation. PFA has the potential to be transformative for the management of patients with AF.

Background: Pulsed field ablation is a novel nonthermal cardiac ablation modality using ultra-rapid electrical pulses to cause cell death by a mechanism of irreversible electroporation. Unlike the traditional ablation energy sources, pulsed field ablation has demonstrated significant preferentiality to myocardial tissue ablation, and thus avoids certain thermally mediated complications. However, its safety and effectiveness remain unknown in usual clinical care. Methods: MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-Approval Clinical Use of Pulsed Field Ablation) is a retrospective, multinational, patient-level registry wherein patients at each center were prospectively included in their respective center registries. The registry included all patients undergoing postapproval treatment with a multielectrode 5-spline pulsed field ablation catheter to treat atrial fibrillation (AF) between March 1, 2021, and May 30, 2022. The primary effectiveness outcome was freedom from clinical documented atrial arrhythmia (AF/atrial flutter/atrial tachycardia) of ≥30 seconds on the basis of electrocardiographic data after a 3-month blanking period (on or off antiarrhythmic drugs). Safety outcomes included the composite of acute (&lt;7 days postprocedure) and latent (&gt;7 days) major adverse events. Results: At 24 European centers (77 operators) pulsed field ablation was performed in 1568 patients with AF: age 64.5±11.5 years, female 35%, paroxysmal/persistent AF 65%/32%, CHA 2 DS 2 -VASc 2.2±1.6, median left ventricular ejection fraction 60%, and left atrial diameter 42 mm. Pulmonary vein isolation was achieved in 99.2% of patients. After a median (interquartile range) follow-up of 367 (289–421) days, the 1-year Kaplan-Meier estimate for freedom from atrial arrhythmia was 78.1% (95% CI, 76.0%–80.0%); clinical effectiveness was more common in patients with paroxysmal AF versus persistent AF (81.6% versus 71.5%; P =0.001). Acute major adverse events occurred in 1.9% of patients. Conclusions: In this large observational registry of the postapproval clinical use of pulsed field technology to treat AF, catheter ablation using pulsed field energy was clinically effective in 78% of patients with AF.

AIMS: Pulsed field ablation (PFA) is a novel atrial fibrillation (AF) ablation modality that has demonstrated preferential tissue ablation, including no oesophageal damage, in first-in-human clinical trials. In the MANIFEST-PF survey, we investigated the 'real world' performance of the only approved PFA catheter, including acute effectiveness and safety-in particular, rare oesophageal effects and other unforeseen PFA-related complications. METHODS AND RESULTS: This retrospective survey included all 24 clinical centres using the pentaspline PFA catheter after regulatory approval. Institution-level data were obtained on patient characteristics, procedure parameters, acute efficacy, and adverse events. With an average of 73 patients treated per centre (range 7-291), full cohort included 1758 patients: mean age 61.6 years (range 19-92), female 34%, first-time ablation 94%, paroxysmal/persistent AF 58/35%. Most procedures employed deep sedation without intubation (82.1%), and 15.1% were discharged same day. Pulmonary vein isolation (PVI) was successful in 99.9% (range 98.9-100%). Procedure time was 65 min (38-215). There were no oesophageal complications or phrenic nerve injuries persisting past hospital discharge. Major complications (1.6%) were pericardial tamponade (0.97%) and stroke (0.4%); one stroke resulted in death (0.06%). Minor complications (3.9%) were primarily vascular (3.3%), but also included transient phrenic nerve paresis (0.46%), and TIA (0.11%). Rare complications included coronary artery spasm, haemoptysis, and dry cough persistent for 6 weeks (0.06% each). CONCLUSION: In a large cohort of unselected patients, PFA was efficacious for PVI, and expressed a safety profile consistent with preferential tissue ablation. However, the frequency of 'generic' catheter complications (tamponade, stroke) underscores the need for improvement.

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AIMS: The mechanisms underlying persistent atrial fibrillation (AF) in patients with atrial fibrosis are poorly understood. The goal of this study was to use patient-derived atrial models to test the hypothesis that AF re-entrant drivers (RDs) persist only in regions with specific fibrosis patterns. METHODS AND RESULTS: Twenty patients with persistent AF (PsAF) underwent late gadolinium-enhanced MRI to detect the presence of atrial fibrosis. Segmented images were used to construct personalized 3D models of the fibrotic atria with biophysically realistic atrial electrophysiology. In each model, rapid pacing was applied to induce AF. AF dynamics were analysed and RDs were identified using phase mapping. Fibrosis patterns in RD regions were characterized by computing maps of fibrosis density (FD) and entropy (FE). AF was inducible in 13/20 models and perpetuated by few RDs (2.7 ± 1.5) that were spatially confined (trajectory of phase singularities: 7.6 ± 2.3 mm). Compared with the remaining atrial tissue, regions where RDs persisted had higher FE (IQR: 0.42-0.60 vs. 0.00-0.40, P < 0.05) and FD (IQR: 0.59-0.77 vs. 0.00-0.33, P < 0.05). Machine learning classified RD and non-RD regions based on FD and FE and identified a subset of fibrotic boundary zones present in 13.8 ± 4.9% of atrial tissue where 83.5 ± 2.4% of all RD phase singularities were located. CONCLUSION: Patient-derived models demonstrate that AF in fibrotic substrates is perpetuated by RDs persisting in fibrosis boundary zones characterized by specific regional fibrosis metrics (high FE and FD). These results provide new insights into the mechanisms that sustain PsAF and could pave the way for personalized, MRI-based management of PsAF.

Rationale: Postoperative atrial fibrillation (POAF) is a common and troublesome complication of cardiac surgery. POAF is generally believed to occur when postoperative triggers act on a preexisting vulnerable substrate, but the underlying cellular and molecular mechanisms are largely unknown. Objective: To identify cellular POAF mechanisms in right atrial samples from patients without a history of atrial fibrillation undergoing open-heart surgery. Methods and Results: Multicellular action potentials, membrane ion-currents (perforated patch-clamp), or simultaneous membrane-current (ruptured patch-clamp) and [Ca 2+ ] i -recordings in atrial cardiomyocytes, along with protein-expression levels in tissue homogenates or cardiomyocytes, were assessed in 265 atrial samples from patients without or with POAF. No indices of electrical, profibrotic, or connexin remodeling were noted in POAF, but Ca 2+ -transient amplitude was smaller, although spontaneous sarcoplasmic reticulum (SR) Ca 2+ -release events and L-type Ca 2+ -current alternans occurred more frequently. CaMKII (Ca 2+ /calmodulin-dependent protein kinase-II) protein-expression, CaMKII-dependent phosphorylation of the cardiac RyR2 (ryanodine-receptor channel type-2), and RyR2 single-channel open-probability were significantly increased in POAF. SR Ca 2+ -content was unchanged in POAF despite greater SR Ca 2+ -leak, with a trend towards increased SR Ca 2+ -ATPase activity. Patients with POAF also showed stronger expression of activated components of the NLRP3 (NACHT, LRR, and PYD domains-containing protein-3)-inflammasome system in atrial whole-tissue homogenates and cardiomyocytes. Acute application of interleukin-1β caused NLRP3-signaling activation and CaMKII-dependent RyR2/phospholamban hyperphosphorylation in an immortalized mouse atrial cardiomyocyte cell-line (HL-1-cardiomyocytes) and enhanced spontaneous SR Ca 2+ -release events in both POAF cardiomyocytes and HL-1-cardiomyocytes. Computational modeling showed that RyR2 dysfunction and increased SR Ca 2+ -uptake are sufficient to reproduce the Ca 2+ -handling phenotype and indicated an increased risk of proarrhythmic delayed afterdepolarizations in POAF subjects in response to interleukin-1β. Conclusions: Preexisting Ca 2+ -handling abnormalities and activation of NLRP3-inflammasome/CaMKII signaling are evident in atrial cardiomyocytes from patients who subsequently develop POAF. These molecular substrates sensitize cardiomyocytes to spontaneous Ca 2+ -releases and arrhythmogenic afterdepolarizations, particularly upon exposure to inflammatory mediators. Our data reveal a potential cellular and molecular substrate for this important clinical problem.

BACKGROUND: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. METHODS: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator-treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. RESULTS: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0-7.2] and 5.1 [2.0-9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711-0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642-0.959), and the calibration slope was 1.082 (95% CI, 0.643-1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. CONCLUSIONS: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03058185.

In the originally published version of this manuscript, the names of authors Marcio Jansen de Oliveira Figueiredo and Manlio F. Márquez were incorrectly given. Both names have now been corrected online. In addition, the following affiliation was inadvertently omitted for author Manlio F. Márquez: Cardiology, Electrophysiology Service, American British Cowdray Medical Center, Mexico City, México This affiliation has now been added to the online version of the manuscript as affiliation 27 and all subsequent affiliations in this manuscript affected by this change have been updated accordingly.

INTRODUCTION: Radiofrequency (RF) lesion metrics are influenced by underlying parameters like RF power, duration, and contact force (CF), and utilization of lesion metric indices (ablation index [AI]) is a proposed strategy to predict lesion quality. The aim of this study was to analyze the influence of underlying parameters on lesion metrics of high-power short-duration (HPSD) and standard RF applications using an in silico and ex vivo model. METHODS AND RESULTS: An in silico simulation study was designed to simulate HPSD and standard ablations, in which ablation parameters could systematically be varied. For each simulated ablation process (n = 5732), the corresponding AI value was calculated. HPSD and standard RF settings were then applied in a porcine ex vivo model ( n = 120 lesions). The resulting lesion metrics were compared and analyzed regarding underlying parameters. RF applications of 50 W/13 seconds, 60 W/10 seconds, 70 W/7 seconds, and 80 W/6 seconds resulted in lesion volumes not significantly different from standard RF applications (30 W/30 seconds, P > 0.05). HPSD lesion diameters were significantly larger and lesion depths were significantly smaller ( P < 0.01) when compared with standard settings. Prolonging RF duration from 5 to 10 seconds resulted in a +27.5% increase, whereas a prolongation of RF duration from 35 to 40 seconds resulted in a +4.8% increase of AI value only. An increase of CF from 1 to 10 g resulted in a +73.0%, an increase of CF from 20 to 30 g resulted in a +10.1% increase of AI value. CONCLUSION: HPSD RF applications resulted in similar lesion volumes but significantly different lesion geometries when compared with standard setting RF applications.

AIMS: Permanent cardiac pacing is the only effective treatment for symptomatic bradycardia, but complications associated with conventional transvenous pacing systems are commonly related to the pacing lead and pocket. We describe the early performance of a novel self-contained miniaturized pacemaker. METHODS AND RESULTS: Patients having Class I or II indication for VVI pacing underwent implantation of a Micra transcatheter pacing system, from the femoral vein and fixated in the right ventricle using four protractible nitinol tines. Prespecified objectives were >85% freedom from unanticipated serious adverse device events (safety) and <2 V 3-month mean pacing capture threshold at 0.24 ms pulse width (efficacy). Patients were implanted (n = 140) from 23 centres in 11 countries (61% male, age 77.0 ± 10.2 years) for atrioventricular block (66%) or sinus node dysfunction (29%) indications. During mean follow-up of 1.9 ± 1.8 months, the safety endpoint was met with no unanticipated serious adverse device events. Thirty adverse events related to the system or procedure occurred, mostly due to transient dysrhythmias or femoral access complications. One pericardial effusion without tamponade occurred after 18 device deployments. In 60 patients followed to 3 months, mean pacing threshold was 0.51 ± 0.22 V, and no threshold was ≥2 V, meeting the efficacy endpoint (P < 0.001). Average R-wave was 16.1 ± 5.2 mV and impedance was 650.7 ± 130 ohms. CONCLUSION: Early assessment shows the transcatheter pacemaker can safely and effectively be applied. Long-term safety and benefit of the pacemaker will further be evaluated in the trial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02004873.

The J-wave syndromes (JWSs), consisting of the Brugada syndrome (BrS) and early repolarization syndrome (ERS), have captured the interest of the cardiology community over the past 2 decades following the identification of BrS as a new clinical entity by Pedro and Josep Brugada in 1992. A great deal of new information has emerged since. The present forum was organized to evaluate new information and highlight emerging concepts with respect to differential diagnosis, prognosis, cellular and ionic mechanisms, and approaches to therapy of the JWSs. Leading experts, including members of the Heart Rhythm Society (HRS), the European Heart Rhythm Association (EHRA), and the Asian-Pacific Heart Rhythm Society (APHRS), met in Shanghai, China, in April 2015. The Task Force was charged with a review of emerging concepts and assessment of new evidence for or against particular diagnostic procedures and treatments. Every effort was made to avoid any actual, potential, or perceived conflict of interest that might arise as a result of outside relationships or personal interest. This consensus report is intended to assist health care providers in clinical decision-making. The ultimate judgment regarding care of a particular patient, however, must be made by the health care provider based on all of the facts and circumstances presented by the patient.

AIMS: Extra-atrial injury can cause complications after catheter ablation for atrial fibrillation (AF). Pulsed field ablation (PFA) has generated preclinical data suggesting that it selectively targets the myocardium. We sought to characterize extra-atrial injuries after pulmonary vein isolation (PVI) between PFA and thermal ablation methods. METHODS AND RESULTS: Cardiac magnetic resonance (CMR) imaging was performed before, acutely (<3 h) and 3 months post-ablation in 41 paroxysmal AF patients undergoing PVI with PFA (N = 18, Farapulse) or thermal methods (N = 23, 16 radiofrequency, 7 cryoballoon). Oesophageal and aortic injuries were assessed by using late gadolinium-enhanced (LGE) imaging. Phrenic nerve injuries were assessed from diaphragmatic motion on intra-procedural fluoroscopy. Baseline CMR showed no abnormality on the oesophagus or aorta. During ablation procedures, no patient showed phrenic palsy. Acutely, thermal methods induced high rates of oesophageal lesions (43%), all observed in patients showing direct contact between the oesophagus and the ablation sites. In contrast, oesophageal lesions were observed in no patient ablated with PFA (0%, P < 0.001 vs. thermal methods), despite similar rates of direct contact between the oesophagus and the ablation sites (P = 0.41). Acute lesions were detected on CMR on the descending aorta in 10/23 (43%) after thermal ablation, and in 6/18 (33%) after PFA (P = 0.52). CMR at 3 months showed a complete resolution of oesophageal and aortic LGE in all patients. No patient showed clinical complications. CONCLUSION: PFA does not induce any signs of oesophageal injury on CMR after PVI. Due to its tissue selectivity, PFA may improve safety for catheter ablation of AF.