Safety and Effectiveness of Pulsed Field Ablation to Treat Atrial Fibrillation: One-Year Outcomes From the MANIFEST-PF Registry.

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 (<7 days postprocedure) and latent (>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%, CHA2DS2-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.

Damage to the left descending coronary artery due to radiofrequency ablation in the right ventricular outflow tract: Clinical case series and anatomical considerations.

The purpose of this paper was to highlight the importance of the anatomy of the right ventricular outflow tract (RVOT) and the proximity of the mid segment of the left anterior descending coronary artery (LAD) to the RVOT in the setting of ablation of ventricular arrhythmias in the RVOT. During the period from 2014 till 2017, five patients with injury to the LAD during ablation within RVOT were identified in three centers, in Belgium, Germany and Israel. The clinical characteristics, procedural data and follow up data, where available, are reported. The literature review over coronary artery damage during radiofrequency ablation procedures is provided and the anatomy of the RVOT and the neighboring vascular structures is discussed. We present five patients who underwent radiofrequency ablation of ventricular arrhythmias mapped to the inferior and anterior part of the RVOT, at the insertion of the right ventricular wall to the septum, whereby ablation resulted in occlusion in four and severe stenosis in one, of the mid segment of the LAD coronary artery. All patients underwent percutaneous coronary intervention and stenting, four of them immediately during the same procedure and one 3 days later because of lack of signs and symptoms of acute coronary occlusion. In conclusion, the mid segment of the LAD at the level of the second septal perforator/second diagonal branch runs in very close proximity to the endocardial aspect of the lower part of the RVOT and care should be taken during ablation of ventricular arrhythmias in this region. Additional imaging such as intracardiac echocardiography and coronary angiography may be helpful in avoiding complications.

Visualization of fibroblast activation using 68Ga-FAPI PET/CT after pulmonary vein isolation with pulsed field compared with cryoballoon ablation.

BACKGROUND: Pulsed-field ablation (PFA) is a novel ablation modality for atrial fibrillation (AF) ablating myocardium by electroporation without tissue-heating. With its different mechanism of tissue ablation, it is assumed that lesion creation is divergent to thermal energy sources. 68Ga-fibroblast-activation protein inhibitor (FAPI) PET/CT targets FAP-alpha expressed by activated fibroblasts. We aimed to assess 68Ga-FAPI uptake in pulmonary veins as surrogate for ablation damage after PFA and cryoballoon ablation (CBA). METHODS: 26 patients (15 PFA, 11 CBA) underwent 68Ga-FAPI-PET/CT after ablation. Standardized uptake values (SUV) and fibroblast-activation volumes of localized tracer uptake were assessed. RESULTS: Patient characteristics were comparable between groups. In PFA, focal FAPI uptake was only observed in 3/15 (20%) patients, whereas in the CBA cohort, 10/11 (90.9%) patients showed atrial visual uptake. We observed lower values of SUVmax (2.85 ± 0.56 vs 4.71 ± 2.06, P = 0.025) and FAV (1.13 ± 0.84 cm3 vs 3.91 ± 2.74 cm3, P = 0.014) along with a trend towards lower SUVpeak and SUVmean in PFA vs CBA patients, respectively. CONCLUSION: Tissue response with respect to fibroblast activation seems to be less pronounced in PFA compared to established thermal ablation systems. This functional assessment might contribute to a better understanding of lesion formation in thermal and PFA ablation potentially contributing to better safety outcomes.

Visualization of thermal damage using 68 Ga-FAPI-PET/CT after pulmonary vein isolation.

PURPOSE: 68 Ga-fibroblast-activation protein inhibitor (FAPI) positron emission tomography (PET) is a novel technique targeting FAP-alpha. This protein is expressed by activated fibroblasts which are the main contributors to tissue remodeling. The aim of this proof-of-concept study was to assess 68 Ga-FAPI uptake in the pulmonary vein (PV) region of the left atrium after pulmonary vein isolation (PVI) with cryoballoon ablation (CBA) and radiofrequency (RFA) as a surrogate for thermal damage. METHODS: Twelve PVI patients (5 RFA, 7 CBA) underwent 68 Ga-FAPI-PET 20.5 ± 12.8 days after PVI. Five patients without atrial fibrillation or previous ablation served as controls. Standardized uptake values of localized tracer uptake were calculated. RESULTS: Focal FAPI uptake around the PVs was observed in 10/12 (83.3%) PVI patients, no uptake was observed in 2 PVI patients and all controls. Patients after PVI had higher FAPI uptake in PVs compared to controls (SUVmax: 4.3 ± 2.2 vs. 1.6 ± 0.2, p < 0.01; SUVpeak: 2.9 ± 1.4 vs. 1.3 ± 0.2, p < 0.01). All CBA patients had an intense uptake, while in the RFA, group 2 (40%), 1 (20%), and 2 (40%) patients had an intense, moderate, and no uptake, respectively. We observed higher uptake values (SUVpeak) in CBA compared to RFA patients (4.4 ± 1.5 vs. 2.5 ± 0.8, p = 0.02). CONCLUSION: We demonstrate in-vivo visualization of 68 Ga-FAPI uptake as a surrogate for fibroblast activation after PVI. CBA seems to cause more pronounced fibroblast activation following tissue injury than RFA. Future studies are warranted to assess if this modality can contribute to a better understanding of the mechanisms of AF recurrence after PVI by lesion creation and gap assessment.

Novel cryoballoon ablation system for pulmonary vein isolation: multicenter assessment of efficacy and safety-ANTARCTICA study.

AIMS: Pulmonary vein isolation (PVI) either by balloon devices or radiofrequency forms the cornerstone of invasive atrial fibrillation (AF) treatment. Although equally effective cryoballoon (CB)-based PVI offers shorter procedure duration and a better safety profile. Beside the worldwide established Arctic Front Advance system, a novel CB device, POLARx, was recently introduced. This CB incorporates unique features, which may translate into improved efficacy and safety. However, multicentre assessment of periprocedural efficacy and safety is lacking up to date. METHODS AND RESULTS: A total of 317 patients with paroxysmal or persistent AF were included and underwent POLARx CB-based PVI in 6 centres from Germany and Italy. Acute efficacy and safety were assessed in this prospective multicenter observational study. In 317 patients [mean age: 64 ± 12 years, 209 of 317 (66%) paroxysmal AF], a total of 1256 pulmonary veins (PVs) were identified and 1252 (99,7%) PVs were successfully isolated utilizing mainly the short tip POLARx CB (82%). The mean minimal CB temperature was -57.9 ± 7°C. Real-time PVI was registered in 72% of PVs. The rate of serious adverse events was 6.0% which was significantly reduced after a learning curve of 25 cases (9.3% vs. 3.0%, P = 0.018). The rate of recurrence-free survival after mean follow-up of 226 ± 115 days including a 90-day blanking period was 86.1%. CONCLUSION: In this large multicentre assessment, the novel POLARx CB shows a promising efficacy and safety profile after a short learning curve.

Multi-national survey on the methods, efficacy, and safety on the post-approval clinical use of pulsed field ablation (MANIFEST-PF).

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.

Early Pacemaker Implantation after Transcatheter Aortic Valve Replacement: Impact of PlasmaBlade™ for Prevention of Device-Associated Bleeding Complications.

Background and Objectives: Permanent pacemaker implantation (PPI) is frequently required following transcatheter aortic valve replacement (TAVR). Dual antiplatelet therapy (DAPT) or oral anticoagulation therapy (OAK) is often necessary in these patients since they are at higher risk of thromboembolic events due to TAVR implantation, high incidence of coronary artery diseases (CAD) with the necessity of coronary intervention, and high rate of atrial fibrillation with the need of stroke prevention. We sought to evaluate the safety, efficiency, and clinical outcomes of early PPI following TAVR using the PlasmaBlade™ (Medtronic Inc., Minneapolis, MN, USA) pulsed electron avalanche knife (PEAK) for bleeding control in patients under DAPT or OAK. Materials and Methods: This retrospective single-center study included patients who underwent PPI after transfemoral TAVR (TF) at our center between December 2015 and May 2020. All PPI were performed using the PlasmaBlade™ Device. Results: The overall PPI rate was 14.1% (83 of 587 patients; 82.5 ± 4.6 years; 45.8% male). The PPI procedures were used to treat high-grade atrioventricular block (81.9%), severe sinus node dysfunction (13.3%), and alternating bundle branch block (4.8%). At the time of the procedure, 35 (42.2%) patients received DAPT, and 48 (57.8%) patients received OAK (50% with vitamin K antagonist (VKA) and 50% with novel oral anticoagulants (NOAK)). One device-pocket hematoma treated conservatively occurred in a patient (1.2%) receiving NOAK. Two re-operations were necessary in patients due to immediate lead dislocation (2.4%). Conclusions: The results of this study illustrate that the use of PlasmaBlade™ for PPI in patients after a TAVR who require antithrombotic treatment is feasible and might result into lower rates of severe bleeding complications compared to rates reported in the literature. Use of the PlasmaBlade device may be considered in this specific group of patients because of their high risk of bleeding.

Proximity to COVID-19 on Mental Health Symptoms among Hospital Medical Staff.

BACKGROUND: Exposure to patients with COVID-19 can have a significant impact on mental health of hospital medical staff. The aim of this study was to examine the influence of proximity to patients with COVID-19 considering occupational position and gender on the mental health of hospital staff. SUBJECTS AND METHODS: N=78 participants were included in the study, with n=40 of them with direct contact to patients with COVID-19 (51%); eight had contact with patients suspected of having COVID-19 (10%), and n=30 with no direct contact to people with COVID-19 (39%). RESULTS: Multinomial regression analyses showed that proximity had a negative (inverse) influence on avoidance behaviour as part of PTSD, physical symptoms, somatization, compulsiveness and anger expression-in as tendency to suppress anger. In addition, there was a significant impact of the female gender on increased physical symptoms, while age, work experience and occupation had no further influence. CONCLUSIONS: These results that hospital medical staff is less psychologically stressed when closer to COVID-19 patients are inconsistent with previous studies. Self-efficacy and locus of control in these situations are relevant for processing the trauma. In summary, perception of personal risk is essential. Proximity is believed to be a proxy variable for personal risk perception. As a synopsis of these results, regular briefings of the hospital staff are recommended to prevent psychological impairment. They should contain specific information about conditions in the affected wards and the risk of infection, which could help reduce risk perception of medical personnel.

Impact of previous left atrial ablation procedures on the mechanism of left atrial flutter: A single-centre experience.

INTRODUCTION: Left atrial flutter predominantly occurs after surgical or ablation procedures but this entity has also been recently reported in individuals without previous interventions. The use of high-density electroanatomical mapping-systems (HDM) has improved the understanding of underlying mechanisms beyond entrainment maneuvers and substrate analyses. We aimed to evaluate the mechanism of left atrial (LA) flutters in preablated vs ablation-naïve individuals and sought to assess the efficacy of empiric ablations sets in these groups. METHODS AND RESULTS: We included 55 patients admitted for ablation of LA flutter between July 2017 and August 2019. On the basis of HDM analyses the arrhythmia mechanism was determined with consecutive ablation targeting the suspected critical isthmus. Mean age was 69.8 ± 10.7 years, with 26 of 55 (47.3%) male patients. Thirty-nine (71%) patients had previously undergone LA ablation. Arrhythmia mechanisms differed between preablated and ablation-naïve patients as anatomical structure-related LA flutters (perimitral, roof-dependent, within-pulmonary veins) were more frequent in the preablated cohort compared to ablation-naïve individuals (74.4% vs 43.8%; P = .03). In ablation-naïve patients, most flutters (9 of 16, 56.3%) were related to low-voltage areas at the anterior/posterior wall. Acute termination rates were high (>90%) in both groups. Empirical mitral isthmus or roof lines showed a potential higher success rate in preablated patients. CONCLUSION: We identified different mechanisms of LA flutters in preablated vs ablation-naïve patients. In ablation-naïve patients, most tachycardias involved low-voltage areas rather than anatomical structures. Using HDM, acute success rates were high. Hypothetical linear ablations were less successful in ablation-naïve individuals, further highlighting the need to identify the specific individual tachycardia mechanism in these patients.

Assessment of right ventricular sympathetic dysfunction in patients with arrhythmogenic right ventricular cardiomyopathy: An 123I-metaiodobenzylguanidine SPECT/CT study.

PURPOSE: The purpose of the study was to evaluate a novel approach for the quantification of right ventricular sympathetic dysfunction in patients diagnosed with ARVC/D through state-of-the-art functional SPECT/CT hybrid imaging. METHODS: Sympathetic innervation of the heart was assessed using 123I-MIBG-SPECT/CT in 17 patients diagnosed with ARVC according to the modified task force criteria, and in 10 patients diagnosed with idiopathic ventricular fibrillation (IVF). The 123I-MIBG-uptake in the left (LV) and right ventricle (RV) was evaluated separately based on anatomic information derived from the CT scan, and compared to the uptake in the mediastinum (M). RESULTS: There was a significant difference in the LV/M ratio between the ARVC/D and the IVF groups (3.2 ± 0.5 vs. 3.9 ± 0.8, P = 0.014), with a cut-off value of 3.41 (77% sensitivity, 80% specificity, AUC 0.78). There was a highly significant difference in the mean RV/M ratios between both groups (1.6 ± 0.3 vs. 2.0 ± 0.2, P = 0.001), with optimal cut-off for discrimination at 1.86 (88% sensitivity, 90% specificity, AUC 0.93). CONCLUSION: Employing state-of-the-art functional SPECT/CT hybrid imaging, we could reliably assess and quantify right and left ventricular sympathetic innervation. The RV/M ratio was significantly lower in patients diagnosed with ARVC/D and provided sensitive and specific discrimination between patients with ARVC/D and IVF patients.

One-Year Course of Periprocedural Anticoagulation in Atrial Fibrillation Ablation: Results of a German Nationwide Survey.

INTRODUCTION: Periprocedural oral anticoagulation (OAC) strategies for atrial fibrillation (AF) ablation procedures are changing rapidly. OBJECTIVE: To assess the management and course of periprocedural OAC for AF ablation procedures in experienced electrophysiology (EP) centers in Germany over the last 12 months. METHODS: The data are based on an electronic questionnaire, which was sent to 35 experienced EP centers in September 2018 and then exactly 1 year later. Participants provided information on their periprocedural OAC management, the handling with dual therapy (OAC plus single antiplatelet therapy), the availability of specific antidotes, the transseptal puncture approach, and noteworthy complications. RESULTS: Responses were received from all 35 centers and represent 10,010 AF ablation procedures annually. In 2018, the administration of vitamin K antagonist (VKA) was continued throughout the procedure at all centers (100%). In contrast, the majority of centers used minimally interrupted periprocedural non-vitamin K antagonist oral anticoagulants (NOAC) (54.3%), 13 centers (37.2%) completely interrupted NOAC, and only 3 centers (8.5%) continued NOAC throughout the procedure. At the 1-year follow-up survey, 32 centers were found to have continued their previous strategy of periprocedural OAC and 3 changed from a minimally interrupted to a continued NOAC strategy. Of note, 30 centers (85.7%) performed transseptal puncture fluoroscopically without additional cardiac imaging. In the setting of uninterrupted periprocedural OAC management, no relevant complications were noted. CONCLUSION: Our survey shows marked heterogeneous periprocedural OAC management at experienced EP centers in Germany. Whereas continuation of VKA has already been integrated into clinical practice, the majority of centers still use a minimally interrupted NOAC strategy.

Atrial fibrosis in non-atrial fibrillation individuals and prediction of atrial fibrillation by use of late gadolinium enhancement magnetic resonance imaging.

INTRODUCTION: Besides the traditional concept of atrial fibrillation (AF) perpetuating atrial structural remodeling, there is increasing evidence that atrial fibrosis might precede AF, highlighting the need for better characterization of the fibrotic substrate. We aimed to assess atrial fibrosis by use of late gadolinium enhancement magnetic resonance imaging (LGE-MRI) in non-AF individuals and to identify predisposing risk factors. A second aim was to establish a risk score for the prevalence of AF using atrial fibrosis in addition to established clinical variables. METHODS AND RESULTS: Non-AF individuals without structural heart disease (n = 91) and matched AF controls (n = 91) underwent MRI for assessment of LGE. According to the established UTAH classification, atrial LGE ≥20% was considered extensive. Mean left atrial (LA) fibrosis in non-AF and AF individuals were 8.8 ± 6.5% and 12.5 ± 5.8%, respectively. Body mass index (BMI) >30 kg/m 2 and LA volume were predictors of atrial fibrosis. Diastolic function was not significantly different with respect to atrial fibrosis. A novel scoring system for the prevalence of AF (2 points for arterial hypertension and/or left ventricular ejection fraction <55%; 3 points for atrial fibrosis >6%) was derived demonstrating that patients in the intermediate/high-risk group had a significantly increased risk of AF. CONCLUSION: This study reports unexpectedly high atrial fibrosis in non-AF patients without apparent heart disease, highlighting the concept that structural fibrotic alterations may precede AF onset in a significant proportion of individuals. BMI as a predictor of atrial fibrosis suggests that lifestyle and drug intervention, that is, weight reduction, could positively influence fibrosis development. The derived risk score for AF prevalence provides the basis for prospective studies on AF incidence.

Straight to the heart: Pleiotropic antiarrhythmic actions of oral anticoagulants.

Mechanistic understanding of atrial fibrillation (AF) pathophysiology and the complex bidirectional relationship with thromboembolic risk remains limited. Oral anticoagulation is a mainstay of AF management. An emerging concept is that anticoagulants may themselves have potential pleiotropic disease-modifying effects. We here review the available evidence for hemostasis-independent actions of the oral anticoagulants on electrical and structural remodeling, and the inflammatory component of the vulnerable substrate.

Coding and non-coding variants in the SHOX2 gene in patients with early-onset atrial fibrillation.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia with a strong genetic component. Molecular pathways involving the homeodomain transcription factor Shox2 control the development and function of the cardiac conduction system in mouse and zebrafish. Here we report the analysis of human SHOX2 as a potential susceptibility gene for early-onset AF. To identify causal variants and define the underlying mechanisms, results from 378 patients with early-onset AF before the age of 60 years were analyzed and compared to 1870 controls or reference datasets. We identified two missense mutations (p.G81E, p.H283Q), that were predicted as damaging. Transactivation studies using SHOX2 targets and phenotypic rescue experiments in zebrafish demonstrated that the p.H283Q mutation severely affects SHOX2 pacemaker function. We also demonstrate an association between a 3'UTR variant c.*28T>C of SHOX2 and AF (p = 0.00515). Patients carrying this variant present significantly longer PR intervals. Mechanistically, this variant creates a functional binding site for hsa-miR-92b-5p. Circulating hsa-miR-92b-5p plasma levels were significantly altered in AF patients carrying the 3'UTR variant (p = 0.0095). Finally, we demonstrate significantly reduced SHOX2 expression levels in right atrial appendages of AF patients compared to patients with sinus rhythm. Together, these results suggest a genetic contribution of SHOX2 in early-onset AF.

Early repolarization pattern is the strongest predictor of arrhythmia recurrence in patients with idiopathic ventricular fibrillation: results from a single centre long-term follow-up over 20 years.

AIMS: Idiopathic ventricular fibrillation (iVF) accounts for up to 14% of VF incidence. Data regarding long-term outcome and clinical risk markers of arrhythmia recurrence are scarce. The objective of our study was to describe a long-term follow-up (FU) of a cohort of iVF survivors in our centre during the past 20 years, and to investigate the influence of clinical parameters, e.g. presence of an early repolarization pattern (ERP), on recurrence rate of arrhythmias. METHODS AND RESULTS: Thirty-five iVF survivors were identified and retrospectively analysed regarding recurrent implantable cardioverter-defibrillator (ICD) interventions and covariates potentially influencing arrhythmia recurrence. Appropriate ICD interventions occurred in 15 patients (43%) after a median of 6.6 years during a median FU period of 8.8 years. Two patients (13%) received the first appropriate therapy after an assumed average ICD battery longevity of 7 years, while in all other patients, the first therapy occurred within the first ICD period. Appropriate interventions were observed more often and earlier in patients with ERP (HR 3.9; 1.4-11.0; P = 0.01), whereas all other covariates failed to predict subsequent events. A high incidence of inappropriate ICD therapies (67 interventions in 14 patients) could be attributed to the occurrence of atrial fibrillation (66% of all inappropriate therapies). CONCLUSION: The recurrence rate of ventricular arrhythmias in iVF survivors is high and recurrence might occur delayed (>7 years after the initial event). ERP seems to be highly predictive with respect to early arrhythmia recurrence. Our results highlight that better pathophysiologic understanding of ERP might facilitate a better risk stratification before and an optimal treatment after an iVF event. The high rate of AF and ERP in iVF survivors might indicate an underlying heart disease or myocardial electrical disorder not apparent at the index event.

One-year clinical outcome after ablation with a novel multipolar irrigated ablation catheter for treatment of atrial fibrillation: potential implications for clinical use.

AIMS: Pulmonary vein isolation (PVI) is an established therapy for atrial fibrillation (AF). However, PVI remains a time-consuming procedure. A novel multipolar irrigated radiofrequency (RF) ablation catheter (nMARQ™) is aiming to improve PVI. We investigated the influence on procedural parameters and assessed clinical outcomes after PVI using this novel catheter. METHODS AND RESULTS: Fifty-eight consecutive patients with paroxysmal AF were equally allocated (n = 29/group) to PVI treatment with (i) the novel multipolar ablation catheter (nMARQ™) and (ii) a standard single-tip ablation catheter (SAC). Study endpoints included procedure time, fluoroscopy time, radiation dose, RF time, number of energy applications, and clinical outcome defined as freedom from AF after a single procedure. Successful PVI was confirmed by a separate circular, multipolar mapping catheter in all patients treated with the nMARQ™. Pulmonary vein isolation was achieved in 100% in the SAC group. In the nMARQ™ group, PVI was suggested in all patients. However, confirmatory mapping revealed persistent pulmonary vein (PV) conduction in 19 out of 29 nMARQ™ patients. These patients underwent further ablation, which still failed to achieve PVI in 5 of the 29 nMARQ™ patients, mainly due to significant temperature rise in the oesophagus and device-related limitations reaching the right inferior PV. Mean fluoroscopy time (31 ± 12 vs. 23 ± 10 min, P < 0.05) and (132 ± 37 vs. 109 ± 30 min, P < 0.05) were longer in nMARQ™ vs. SAC patients. Radiofrequency time was shorter in nMARQ™ vs. SAC group (21 ± 9 vs. 35 ± 12 min, P < 0.001). Radiation dose and the number of energy applications did not differ between both groups. Clinical outcome analysis revealed no significant differences (nMARQ™: 72 vs. SAC: 72%) after a mean follow-up of 373 ± 278 days. CONCLUSION: The use of the nMARQ™ catheter is associated with important device-related limitations to achieve successful PVI. However, clinical outcomes were equivalent in nMARQ™- and SAC-treated patients.

The Effect of Increasing Intracranial Pressure on Ocular Vestibular-Evoked Myogenic Potential Frequency Tuning.

OBJECTIVE: Ocular vestibular-evoked myogenic potentials (oVEMPs) represent extraocular muscle activity in response to vestibular stimulation. The authors sought to investigate whether posture-induced increase of the intracranial pressure (ICP) modulated oVEMP frequency tuning, that is, the amplitude ratio between 500-Hz and 1000-Hz stimuli. DESIGN: Ten healthy subjects were enrolled in this study. The subjects were positioned in the horizontal plane (0 degree) and in a 30-degree head-downwards position to elevate the ICP. In both positions, oVEMPs were recorded using 500-Hz and 1000-Hz air-conducted tone bursts. RESULTS: When tilting the subject from the horizontal plane to the 30-degree head-down position, oVEMP amplitudes in response to 500-Hz tone bursts distinctly decreased (3.40 µV versus 2.06 µV; p < 0.001), whereas amplitudes to 1000 Hz were only slightly diminished (2.74 µV versus 2.48 µV; p = 0.251). Correspondingly, the 500/1000-Hz amplitude ratio significantly decreased when tilting the subjects from 0- to 30-degree inclination (1.59 versus 1.05; p = 0.029). Latencies were not modulated by head-down position. CONCLUSIONS: Increasing ICP systematically alters oVEMPs in terms of absolute amplitudes and frequency tuning characteristics. oVEMPs are therefore in principle suited for noninvasive ICP monitoring.

Detailed characterization of microRNA changes in a canine heart failure model: Relationship to arrhythmogenic structural remodeling.

Heart failure (HF) causes left-atrial (LA) and left-ventricular (LV) remodeling, with particularly-prominent changes in LA that create a substrate for atrial fibrillation (AF). MicroRNAs (miRs) are potential regulators in cardiac remodeling. This study evaluated time-dependent miR expression-changes in LA and LV tissue, fibroblasts and cardiomyocytes in experimental HF. HF was induced in dogs by ventricular tachypacing (varying periods, up to 2weeks). Following screening-microarray, 15 miRs were selected for detailed real-time qPCR assay. Extracellular matrix mRNA-expression was assessed by qPCR. Tachypacing time-dependently reduced LV ejection-fraction, increased LV-volume and AF-duration, and caused tissue-fibrosis with LA changes greater than LV. Tissue miR-expression significantly changed in LA for 10 miRs; in LV for none. Cell-selective analysis showed significant time-dependent changes in LA-fibroblasts for 10/15 miRs, LV-fibroblasts 8/15, LA-cardiomyocytes in 6/15 and LV-cardiomyocytes 3/15. Cell-expression specificity did not predict cell-specificity of VTP-induced expression-changes, e.g. 4/6 cardiomyocyte-selective miRs changed almost exclusively in fibroblasts (miR-1, miR-208b, miR133a/b). Thirteen miRs directly implicated in fibrosis/extracellular-matrix regulation were prominently changed: 9/13 showed fibroblast-selective alterations and 5/13 LA-selective. Multiple miRs changed in relation to associated extracellular-matrix targets. Experimental HF causes tissue and cell-type selective, time-dependent changes in cardiac miR-expression. Expression-changes are greater in LA versus LV, and greater in fibroblasts than cardiomyocytes, even for most cardiomyocyte-enriched miRs. This study, the first to examine time, chamber and cell-type selective changes in an experimental model of HF, suggests that multiple miR-changes underlie the atrial-selective fibrotic response and emphasize the importance of considering cell-specificity of miR expression-changes in cardiac remodeling paradigms.

MicroRNA29: a mechanistic contributor and potential biomarker in atrial fibrillation.

BACKGROUND: Congestive heart failure (CHF) causes atrial fibrotic remodeling, a substrate for atrial fibrillation (AF) maintenance. MicroRNA29 (miR29) targets extracellular matrix proteins. In the present study, we examined miR29b changes in patients with AF and/or CHF and in a CHF-related AF animal model and assessed its potential role in controlling atrial fibrous tissue production. METHODS AND RESULTS: Control dogs were compared with dogs subjected to ventricular tachypacing for 24 hours, 1 week, or 2 weeks to induce CHF. Atrial miR29b expression decreased within 24 hours in both whole atrial tissue and atrial fibroblasts (-87% and -92% versus control, respectively; p<0.001 for both) and remained decreased throughout the time course. Expression of miR29b extracellular matrix target genes collagen-1A1 (COL1A1), collagen-3A1 (COL3A1), and fibrillin increased significantly in CHF fibroblasts. Lentivirus-mediated miR29b knockdown in canine atrial fibroblasts (-68%; p<0.01) enhanced COL1A1, COL3A1, and fibrillin mRNA expression by 28% (p<0.01), 19% (p<0.05), and 20% (p<0.05), respectively, versus empty virus-infected fibroblasts and increased COL1A1 protein expression by 90% (p<0.05). In contrast, 3-fold overexpression of miR29b decreased COL1A1, COL3A1, and fibrillin mRNA by 65%, 62%, and 61% (all p<0.001), respectively, versus scrambled control and decreased COL1A1 protein by 60% (p<0.05). MiR29b plasma levels were decreased in patients with CHF or AF (by 53% and 54%, respectively; both p<0.001) and were further decreased in patients with both AF and CHF (by 84%; p<0.001). MiR29b expression was also reduced in the atria of chronic AF patients (by 54% versus sinus rhythm; p<0.05). Adenoassociated viral-mediated knockdown of miR29b in mice significantly increased atrial COL1A1 mRNA expression and cardiac tissue collagen content. CONCLUSIONS: MiR29 likely plays a role in atrial fibrotic remodeling and may have value as a biomarker and/or therapeutic target.

Immediate and 12 months follow up of function and lead integrity after cranial MRI in 356 patients with conventional cardiac pacemakers.

BACKGROUND: Conventional cardiac pacemakers are still often regarded as a contraindication to magnetic resonance imaging (MRI). We conducted this study to support the hypothesis that it is safe to scan patients with cardiac pacemakers in a 1.5 Tesla MRI, if close supervision and monitoring as well as adequate pre- and postscan programming is provided. METHODS: We followed up 356 patients (age 61.3 ± 9.1 yrs., 229 men) with single (n = 132) or dual chamber (n = 224) cardiac pacemakers and urgent indication for a cranial MRI for 12 months. The scans were performed at 1.5T. During the scan patients were monitored with a 3-lead ECG and pulse oximetry. Prior to the scan pacemakers were programmed according to our own protocol. RESULTS: All 356 scans were completed without complications. No arrhythmias were induced, programmed parameters remained unchanged. No pacemaker dysfunction was identified. Follow-up examinations were performed immediately, 2 weeks, 2, 6, and 12 months after the scan. There was no significant change of pacing capture threshold (ventricular 0.9 ± 0.4 V@0.4 ms, atrial 0.9 ± 0.3 V@0.4 ms) immediately (ventricular 1.0 ± 0.3 V@0.4 ms, atrial 0.9 ± 0.4 V@0.4 ms) or at 12 months follow-up examinations (ventricular 0.9 ± 0.2 V@0.4 ms, atrial 0.9 ± 0.3 V@0.4 ms). There was no significant change in sensing threshold (8.0 ± 4.0 mV vs. 8.1 ± 4.2 mV ventricular lead, 2.0 ± 0.9 mV vs. 2.1 ± 1.0 mV atrial lead) or lead impedance (ventricular 584 ± 179 Ω vs. 578 ± 188 Ω, atrial 534 ± 176 Ω vs. 532 ± 169 Ω) after 12 months. CONCLUSIONS: This supports the evidence that patients with conventional pacemakers can safely undergo cranial MRI in a 1.5T system with suitable preparation, supervision and precautions. Long term follow-up did not reveal significant changes in pacing capture nor sensing threshold.