A worldwide survey on incidence, management, and prognosis of oesophageal fistula formation following atrial fibrillation catheter ablation: the POTTER-AF study.

AIMS: Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management, and outcome are sparse. METHODS AND RESULTS: This international multicentre registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation. A total of 553 729 catheter ablation procedures (radiofrequency: 62.9%, cryoballoon: 36.2%, other modalities: 0.9%) were performed, at 214 centres in 35 countries. In 78 centres 138 patients [0.025%, radiofrequency: 0.038%, cryoballoon: 0.0015% (P < 0.0001)] were diagnosed with an oesophageal fistula. Peri-procedural data were available for 118 patients (85.5%). Following catheter ablation, the median time to symptoms and the median time to diagnosis were 18 (7.75, 25; range: 0-60) days and 21 (15, 29.5; range: 2-63) days, respectively. The median time from symptom onset to oesophageal fistula diagnosis was 3 (1, 9; range: 0-42) days. The most common initial symptom was fever (59.3%). The diagnosis was established by chest computed tomography in 80.2% of patients. Oesophageal surgery was performed in 47.4% and direct endoscopic treatment in 19.8% and conservative treatment in 32.8% of patients. The overall mortality was 65.8%. Mortality following surgical (51.9%) or endoscopic treatment (56.5%) was significantly lower as compared to conservative management (89.5%) [odds ratio 7.463 (2.414, 23.072) P < 0.001]. CONCLUSION: Oesophageal fistula after catheter ablation of atrial fibrillation is rare and occurs mostly with the use of radiofrequency energy rather than cryoenergy. Mortality without surgical or endoscopic intervention is exceedingly high.

Age differences of patients treated with wearable cardioverter defibrillator: Data from a multicentre registry.

BACKGROUND: Wearable cardioverter defibrillators (WCD) are used as a 'bridging' technology in patients, who are temporarily at high risk for sudden cardiac death (SCD). Several factors should be taken into consideration, for example patient selection, compliance and optimal drug treatment, when WCD is prescribed. We aimed to present real-world data from seven centres from Germany and Switzerland according to age differences regarding the outcome, prognosis, WCD data and compliance. MATERIALS AND METHODS: Between 04/2012 and 03/2021, 1105 patients were included in this registry. Outcome data according to age differences (old ≥45 years compared to young <45 years) were analysed. At young age, WCDs were more often prescribed due to congenital heart disease and myocarditis. On the other hand, ischaemic cardiomyopathy (ICM) was more present in older patients. Wear days of WCD were similar between both groups (p = .115). In addition, during the WCD use, documented arrhythmic life-threatening events were comparable [sustained ventricular tachycardia: 5.8% vs. 7.7%, ventricular fibrillation (VF) .5% vs. .6%] and consequently the rate of appropriate shocks was similar between both groups. Left ventricular ejection fraction improvement was documented over follow-up with a better improvement in younger patients as compared to older patients (77% vs. 63%, p = .002). In addition, at baseline, the rate of atrial fibrillation was significantly higher in the older age group (23% vs. 8%; p = .001). The rate of permanent cardiac implantable electronic device implantation (CiED) was lower in the younger group (25% vs. 36%, p = .05). The compliance rate defined as wearing WCD at least 20 h per day was significantly lower in young patients compared to old patients (68.9% vs. 80.9%, p < .001). During the follow-up, no significant difference regarding all-cause mortality or arrhythmic death was documented in both groups. A low compliance rate of wearing WCD is predicted by young patients and patients suffering from non-ischaemic cardiomyopathies. CONCLUSION: Although the compliance rate in different age groups is high, the average wear hours tended to be lower in young patients compared to older patients. The clinical events were similar in younger patients compared to older patients.

Cardiac autonomic dysfunction in adult congenital heart disease.

PURPOSE: Due to recent advances in diagnosis and treatment, the number of adults with congenital heart disease (ACHD) has substantially increased. This achievement is mitigated by rhythm disorders. Here, we sought to determine alterations in heart rate variability (HRV) and their prognostic value in ACHD. METHODS: Ninety seven ACHD patients (39.2 ± 14.1 years, 51.5% female) and 19 controls (39.7 ± 15.0 years, 47.4% female) underwent 24-h Holter monitoring. RESULTS: As compared to controls, ACHD patients offered a significantly higher burden of premature ventricular contractions (p = 0.02) and decreased HRV indices (natural logarithmic transformation of very low frequency (lnVLF): 7.46 ± 0.76 ms2 vs. 7.91 ± 0.92ms2, p = 0.03; natural logarithmic transformation of low frequency (lnLF): 6.39 ± 0.95ms2 vs. 7.01 ± 1.07ms2, p = 0.01; natural logarithmic transformation of the ratio of low to high frequency spectra (lnLF/HF): 0.81 ± 0.74 vs. 1.17 ± 0.51, p = 0.04). No differences in HRV measures were observed across ACHD lesion groups. NT-proBNP levels were significantly related to both time and frequency domain indices (natural logarithmic transformation of the standard deviation of NN intervals (lnSDNN): Spearman´s rho = -0.32, p = 0.001; natural logarithmic transformation of the standard deviation of the average NN intervals for each 5-min segment of a 24-h Holter monitoring (lnSDANN): Spearman´s rho: -0.33, p = 0.001; natural logarithmic transformation of the total power (lnTP): Spearman´s rho: -0.25, p = 0.01; lnVLF: Spearman´s rho: -0.33, p = 0.001; lnLF: Spearman´s rho: -0.35, p < 0.001; lnLF/HF: Spearman´s rho: -0.34, p = 0.001). After a mean follow-up of 3.9 ± 0.7 years, 8 patients died and 3 patients survived sudden cardiac death (SCD). Several HRV parameters were significantly higher in event-free ACHD patients than in those who died or survived SCD (natural logarithmic transformation of the average of the standard deviations of NN intervals for each 5-min segment of a 24-h Holter monitoring (lnASDNN): p = 0.04; lnPNN30: p = 0.04; lnVFL: p = 0.03; lnLF: p < 0.01). On univariate Cox regression analysis, the time domain indices lnSDNN, lnASDNN and lnPNN30, as well as the frequency domain parameters lnTP, lnVLF and lnLF were associated with death and survived cardiac arrest. CONCLUSION: ACHD is accompanied by HRV impairment that carries prognostic implications on ACHD mortality and survived SCD.

The CT derived angle between the transseptal puncture site and the left atrial appendage as a predictor for complex interventional occlusion procedures.

OBJECTIVE: To evaluate the role of the CT-derived angle between the intra-atrial septum (IAS) and the left atrial appendage (LAA) on procedural complexity and clinical outcomes in left atrial appendage occlusion (LAAO) procedures. BACKGROUND: Given the broad variations in anatomy, LAAO remains one of the most challenging interventional procedures in structural heart disease. In recent years, preprocedural cardiac tomography (CT) has evolved as a valuable tool; however, prediction of procedural complexity remains cumbersome. METHODS: We retrospectively analyzed 47 patients that underwent LAAO at our center in whom pre-procedural cardiac CT-scans were available. Among other baseline parameters, we measured the angle between the LAA ostium and the preferred transseptal puncture site at the IAS. We compared patients with an angle above and below the median regarding procedural characteristics and procedural outcome. RESULTS: The median angle between the LAA and the IAS was 127.3° (IQR: 120.9-141.3). LAAO took longer in patients with a measured angle below the median (55.0 ± 22.7 min vs. 41.3 ± 17.5 min; p = .04), resulting in longer radiation times (13.0 ± 5.3 min vs. 9.8 ± 5.7 min; p = .04) and more contrast use (61.1 ± 47.5 mL vs. 33.6 ± 24.7 mL; p = .05). Moreover, the necessity for a sheath exchange was significantly higher (30.4% vs. 4.2%, p = .02) and device repositioning or device resizing trended to be more frequent (26.1% vs. 8.3%; p = .1 and 21.7% vs. 8.3%; p = .2). There were no differences in procedural outcome, device-position and peri-device leak (PDL). CONCLUSIONS: The angle between the transseptal puncture site and the LAA ostium may serve as a predictor for more demanding LAAO interventions. In our study a steeper angle led to a prolonged procedure resulting in higher doses of contrast and radiation, but was not associated with a worse procedural outcome.

Incidence, persistence, and clinical relevance of iatrogenic atrial septal defects after percutaneous left atrial appendage occlusion.

OBJECTIVE: To investigate the rate and clinical impact of a persisting iatrogenic atrial septal defect (iASD) after percutaneous left atrial appendage occlusion (LAAO). BACKGROUND: Percutaneous LAAO is an alternative to oral anticoagulation (OAC) for the prevention of ischemic stroke and systemic embolism in patients with atrial fibrillation (AF). Data regarding incidence and persistence of iASD after LAAO procedures and its clinical relevance is scarce. METHODS: We retrospectively analyzed 144 patients that underwent LAAO at our center between 2009 and 2020 who had at least one follow-up including transesophageal echocardiography (TEE). Baseline clinical, procedural data and echocardiographic characteristics in patients with and without evidence of an iASD were compared. We furthermore determined the rate of iASD persistence over time and evaluated outcomes of patients with and without spontaneous iASD closure. RESULTS: After a median of 92 days (IQR 75-108 days) after LAAO, 50 patients (50/144, 34.7%) showed evidence of an iASD. Patients with iASD had higher CHADS-VASc-scores (4.9±1.5 vs 4.2±1.2, p = 0.03), larger left atrial volumes (80.5±30.5 ml vs 67.1±19.7 ml, p = 0.01) and were more likely to have relevant mitral regurgitation (≥° II) (46.0% vs 12.3%, p = 0.001). LAAO procedures took longer (50.1±24.3 vs 41.1±17.8 min, p = 0.06) in patients with a persisting iASD. Furthermore, larger device sizes were implanted (24.3±3.4 mm vs 22.1±2.8 mm, p = 0.03). The presence of an iASD had no impact on RV dysfunction, thromboembolism or mortality. Spontaneous closure of an iASD was documented in 52.0% (26/50). Hereby, similar risk factors were identified for the persistence of an iASD in follow-up.

Low-voltage shock impedance measurements: A false sense of security.

BACKGROUND: Implantable cardioverter defibrillators use low-voltage shock impedance measurements to monitor the lead integrity. However, previous case reports suggest that low-voltage shock impedance measurements may fail to detect insulation breaches that can cause life-threatening electrical short circuits. METHODS AND RESULTS: We report six cases of insulation breaches in transvenous defibrillation leads that were not obvious during standard interrogations and testing of the lead beforehand. In two cases, an electrical short circuit during commanded shock delivery for internal electrical cardioversion resulted in a total damage of the ICD generator. In one of these cases, commanded shock delivery induced ventricular fibrillation, which required external defibrillation. In two cases, a shock due to ventricular tachycardia was aborted as the shock impedance was less than 20 Ω. However, in both cases the tiny residual shock energy terminated the ventricular tachycardia. In contrast, in one case the residual energy of the aborted shock did not end ventricular fibrillation induced at defibrillator threshold testing. In one case, the ICD indicated an error code for a short circuit condition detected during an adequate shock delivery. CONCLUSIONS: This case series illustrates that low-voltage shock impedance measurements can fail to detect insulation breaches. These data suggest that in patients without a contraindication, traditional defibrillator threshold testing or high voltage synchronized shock at the time of device replacement should be considered.

Outcome in patients with left common pulmonary vein after cryoablation with second-generation cryoballoon.

BACKGROUND: Pulmonary vein isolation (PVI) has become a widely accepted therapy in patients suffering from symptomatic atrial fibrillation (AF). HYPOTHESIS: AF-free survival differs in patients with left common pulmonary vein (LCPV) after PVI with second-generation cryoballoon. METHODS: We included patients scheduled for first PVI for paroxysmal or persistent AF. Symptomatic and/or documented arrhythmia episodes (>30 seconds) were defined as AF recurrence, excluding a 3-month blanking period. RESULTS: We observed a LCPV in 37 of 270 consecutive patients (13.7%). Analyses were performed in a 1:1 propensity score matched cohort of 68 patients. During a median follow-up of 77.0 weeks, 37 patients (54.4%) had recurrent AF. The prevalence of LCPV was numerically higher in patients with AF recurrence (62.2% vs 35.5%, P  =  0.051) and Kaplan-Meier analysis showed lower AF-free survival in patients with existence of a LCPV (P  =  0.028). At 1-year follow-up, 70.6% of patients without versus 55.1% of patients with LCPV were free of AF. Multivariate Cox regression analysis revealed presence of a LCPV (hazard ratio [HR]: 2.996), chronic heart failure (HR: 3.423), and mitral regurgitation > I° (HR: 2.571) as predictors of AF recurrence. CONCLUSION: Patients with LCPV had significantly reduced AF-free survival after ablation with the second-generation cryoballoon, despite similar acutely successful PVIs.

Aging-related mitochondrial dysfunction facilitates the occurrence of serious arrhythmia after myocardial infarction.

BACKGROUND: During aging a mosaic of normal cells and cells with mitochondrial deficiency develops in various tissues including the heart. Whether this contributes to higher susceptibility for arrhythmia following myocardial infarction (MI) is unknown. METHODS AND RESULTS: Myocardial cryoinfarction was performed in 12-month-old transgenic mice with accelerated accumulation of deletions in mitochondrial DNA. Occurrence and pathogenesis of arrhythmia was investigated after two weeks. Holter-ECG recordings revealed higher rates of premature ventricular complexes (incidence > 10/24 h: 100% vs. 20%; p = 0.048) and more severe spontaneous arrhythmia during stress test in mutant mice with MI as compared to control mice with MI. Mice with mitochondrial dysfunction exhibited longer spontaneous AV-blocks (467 ± 26 ms vs. 377 ± 24 ms; p = 0.013), an increased probability for induction of ventricular tachycardia during in vivo electrophysiological investigation (22% vs. 9%; p = 0.044), and a reduced conduction velocity in the infarct borderzone (38.5 ± 0.5 cm/s vs. 55.3 ± 0.9 cm/s; p = 0.001). Furthermore, mutant mice exhibited a significant reduction of the phospho-Cx43/Cx43 ratio in right (0.59 ± 0.04 vs. 0.85 ± 0.01; p = 0.027) and left ventricular myocardium (0.72 ± 0.01 vs. 0.86 ± 0.02; p = 0.023). CONCLUSIONS: Aging-related cardiac mosaic respiratory chain dysfunction facilitates the occurrence of spontaneous and inducible cardiac arrhythmia after myocardial infarction and is associated with slowing of electrical impulse propagation in the infarct borderzone.

Relaxin reduces susceptibility to post-infarct atrial fibrillation in mice due to anti-fibrotic and anti-inflammatory properties.

BACKGROUND: Relaxin-2 (RLX) is a peptide hormone that exerts beneficial anti-fibrotic and anti-inflammatory effects in diverse models of cardiovascular disease. The goal of this study was to determine the effects of RLX treatment on the susceptibility to atrial fibrillation (AF) after myocardial infarction (MI). METHODS: Mice with cryoinfarction of the left anterior ventricular wall were treated for two weeks with either RLX (75 µg/kg/d) or vehicle (sodium acetate) delivered via subcutaneously implanted osmotic minipumps. RESULTS: RLX treatment significantly attenuated the increase in AF-inducibility following cryoinfarction and reduced the mean duration of AF episodes. Furthermore, epicardial mapping of both atria revealed an increase in conduction velocity. In addition to an attenuation of atrial hypertrophy, chronic application of RLX reduced atrial fibrosis, which was linked to a significant reduction in atrial mRNA expression of connective tissue growth factor. Transcript levels of the pro-inflammatory cytokines interleukin-6 and interleukin-1ß were reduced in RLX treated mice, but macrophage infiltration into atrial myocardium was similar in the vehicle and RLX treated groups. CONCLUSION: Treatment with RLX in mice after MI reduces susceptibility to AF due to anti-inflammatory and anti-fibrotic properties. Because to these favorable actions, RLX may become a new therapeutic option in the treatment of AF, even when complicating MI.

A real world wearable cardioverter defibrillator experience - Very high appropriate shock rate in ischemic cardiomyopathy patients at a European single-center.

BACKGROUND: The wearable cardioverter defibrillator (WCD) has emerged as a valuable tool to protect patients with increased risk of sudden cardiac death (SCD). We sought to characterize WCD patients and to analyze predictors of ventricular arrhythmia (VA) occurrence and WCD shock delivery. METHODS AND RESULTS: One hundred fourteen patients with WCD use were included in the study. Indications were mainly ischemic cardiomyopathy (ICM; 31.6%), non-ICM (45.6%) and explantation of implantable cardioverter defibrillator due to device infection (11.4%). We observed sustained VA in 9.6% of the study population and 6.1% received an appropriate shock. VA occurred in 16.7% of ICM, 3.8% of non-ICM and 15.4% of patients with device infection. CONCLUSIONS: Our data demonstrate a very high rate of sustained VA in patients at risk for SCD during WCD use. ICM patients, including those with recent MI, bore the highest risk.

Atrial flutter presenting as broad complex tachycardia in a patient with right sided pneumonectomy.

A 71-year-old man with no history of coronary artery disease presented with palpitations to the emergency department. The 12-lead ECG showed a regular tachycardia with wide QRS complexes (220 bpm) suggestive of ventricular tachycardia. Instead invasive electrophysiological investigation revealed typical atrial flutter as underlying arrhythmia. The altered QRS morphology resulted from displacement of the heart into the right hemithorax due to right-sided pneumonectomy in combination with bundle branch block.

Laserballoon and Cryoballoon Pulmonary Vein Isolation in Persistent and Longstanding Persistent Atrial Fibrillation.

BACKGROUND: Visually guided laserballoon (LB) ablation has recently been introduced for pulmonary vein (PV) isolation (PVI). We analyzed efficacy and safety results of the newly introduced LB ablation technique in patients with persistent and longstanding persistent atrial fibrillation (AF), and compared this with an established standard method using the cryoballoon (CB). METHODS: A total of 35 patients with symptomatic persistent AF underwent LB ablation and were followed-up for 1 year. Results were compared to 35 patients who underwent CB ablation at the same institution and case matched for age, sex, CHA2 DS2 -VASc score, and left atrial volume. RESULTS: Complete isolation of all PVs was achieved in 68.6% in the LB and 97.1% in the CB group (P < 0.01). No significant differences were found for AF-free survival after 12 months in the complete cohort of all patients (LB: 53.3% vs CB: 70.4%; P = n.s.) and after excluding patients without complete PVI (LB: 57.8% vs CB: 72.5%; P = n.s.). LB ablation resulted in longer procedure (158.5 ± 37.9 minutes vs 110.9 ± 26.5 minutes; P < 0.01) and fluoroscopy durations (28.4 ± 11.1 minutes vs 23.5 ± 9.4 minutes; P = 0.04.), and a trend toward more major complications (14.3% vs 2.9%; P = n.s.). Procedure durations and complications declined over time and were level with CB-treated patients when reaching the last quartile of the LB patients. CONCLUSION: PVI in patients with persistent AF using the LB or the CB resulted in comparable success rates. Initial prolongations in procedure and safety parameters as a result of a learning curve effect for the LB have to be considered before starting to use this technique.

Association of Heart Rate Turbulence With Arrhythmia Susceptibility and Heart Disease in Mice.

INTRODUCTION: Recent studies have demonstrated the feasibility of measuring heart rate turbulence (HRT) as a marker of baroreflex function in healthy mice. The aim of this investigation was to measure HRT in a mouse model with induced structural heart defects and to determine if there were threshold values of HRT for inducible ventricular tachycardias (VTs). METHODS AND RESULTS: HRT was measured during electrophysiological investigations 2 weeks after transverse aortic constriction (TAC, n = 13) or myocardial cryoinfarction (MCI, n = 14). Sham-operated mice served as controls (n = 8 for TAC controls and n = 9 for MCI controls). Mice with heart disease lacked an early acceleration (turbulence onset [TO]) in heart rate after extrastimulus pacing (heart disease: 0.39% [0.19%-0.59%] vs. all controls: -0.04% [-0.25-0.19%]; P < 0.01). At a cutoff value of >0.25%, TO could be used to classify mice with induced heart disease with a sensitivity of 64.0% and specificity of 88.2% (P < 0.01) but did not identify mice at higher risk of induced VTs. Animals that were susceptible to VTs (n = 8) had lower values for turbulence slope (TS) compared with noninducible mice (6.2 milliseconds/beat [3.1-9.5 milliseconds/beat] vs. 10.1 milliseconds/beat [7.2-14.2 milliseconds/beat]; P = 0.03). TS <7.8 milliseconds/beat identified mice with inducible VTs with a sensitivity of 75.0% and specificity of 75.8% (P = 0.02). CONCLUSION: Measurement of HRT is feasible in mouse models with induced structural heart disease. More abnormal values for TO were found in the presence of structural heart disease but did not predict susceptibility to VTs. Decreased TS was associated with VTs induced by programmed stimulation.

Comparison of Arctic Front Advance Pro and POLARx cryoballoons for ablation therapy of atrial fibrillation: an intraprocedural analysis.

INTRODUCTION: Cryoballoon (CB) ablation has become a popular method for pulmonary vein isolation (PVI) in atrial fibrillation (AF) treatment. This study aimed to compare the intraprocedural ablation characteristics of two cryoballoons, Arctic Front Advance Pro™ (AFA-Pro, Medtronic) and POLARx™ (Boston Scientific). METHODS AND RESULTS: In this retrospective single-center study, 230 symptomatic paroxysmal or persistent AF patients underwent CB ablation with either AFA-Pro or POLARx. Propensity-score matching resulted in two cohorts of 114 patients each. Baseline and procedural characteristics were comparable between both CBs. POLARx achieved lower minimal temperatures (e.g., left superior pulmonary vein, LSPV: AFA-Pro - 49.0 °C vs. POLARx - 59.5 °C) and lower temperatures at time-to-isolation (TTI). Additionally, POLARx reached lower temperatures faster, as evidenced by lower temperatures after 40 and 60 s, and a larger mean temperature change between 20 and 40 s. POLARx also had a greater area under the curve below 0 °C and a longer thawing phase. Both CBs achieved comparable high rates of final PV-isolation. TTI, minimal esophagus temperature, and first-pass isolation rates were similar between groups. Periprocedural complications, including phrenic nerve injuries, were comparable. Troponin levels in the left atrium were elevated with both systems. Values and change in troponin were numerically higher in the POLARx group (delta troponin: AFA-Pro 36.3 (26.4, 125.4) ng/L vs. POLARx 104.9 (49.5, 122.2) ng/L), p = 0.077). CONCLUSION: AFA-Pro and POLARx are both highly effective and safe CB systems for PVI. POLARx exhibited significant faster and lower freezing characteristics, and numerically higher troponin levels might indicate greater myocardial injury. However, these differences did not translate into improved performance, procedural efficiency, or safety.

Loss of ceramide synthase 5 inhibits the development of experimentally induced aortic valve stenosis.

AIM: Inflammation and calcification are hallmarks in the development of aortic valve stenosis (AVS). Ceramides mediate inflammation and calcification in the vascular tissue. The highly abundant d18:1,16:0 ceramide (C16) has been linked to increased cardiovascular mortality and obesity. In this study, we investigate the role of ceramide synthase 5 (CerS5), a critical enzyme for C16 ceramide synthesis, in the development of AVS, particularly in conjunction with a high-fat/high-cholesterol diet (Western diet, WD). METHODS: We used wild-type (WT) and CerS5-/- mice on WD or normal chow in a wire injury model. We measured the peak velocity to determine AVS development and performed histological analysis of the aortic valve area, immune cell infiltration (CD68 staining), and calcification (von Kossa). In vitro experiments involved measuring the calcification of human aortic valvular interstitial cells (VICs) and evaluating cytokine release from THP-1 cells, a human leukemia monocytic-like cell line, following CerS5 knockdown. RESULTS: CerS5-/- mice showed a reduced peak velocity compared to WT only in the experiment with WD. Likewise, we observed reduced immune cell infiltration and calcification in the aortic valve of CerS5-/- mice, but only on WD. In vitro, calcification was reduced after knockdown of CerS5 in VICs, while THP-1 cells exhibited a decreased inflammatory response following CerS5 knockdown. CONCLUSION: We conclude that CerS5 is an important mediator for the development of AVS in mice on WD and regulates critical pathophysiological hallmarks of AVS formation. CerS5 is therefore an interesting target for pharmacological therapy and merits further investigation.

Contrast-free left atrial appendage occlusion in patients using the LAMBRE™ device.

BACKGROUND: Advances in imaging have led to procedural optimization of left atrial appendage closure (LAAC). Contrast-free approaches, guided merely by echocardiography, have been established, however data on this topic remains scarce. In this analysis, we assessed contrast-free procedural results with the LAMBRE LAAC device. METHODS: The multicenter retrospective BoBoMa (Bonn/Bordeaux/Mainz)-Registry included a total of 118 patients that underwent LAAC with LAMBRE devices omitting contrast-dye. Baseline and echocardiographic characteristics as well as intra- and postprocedural complications and outcomes were assessed. RESULTS: Patients were at a mean age of 77.5 ± 7.5 years with high thromboembolic and bleeding risk (CHADS-VASc-score 4.6 ± 1.4, HAS-BLED-score 3.7 ± 1.0, respectively). Renal function was impaired with a mean glomerular filtration rate (GFR) of 50 ± 22 ml/min. Mean procedural time was 47.2 ± 37.5  minutes with a mean radiation dose of 4.75 ± 5.25 Gy*cm2. Device success, defined as proper deployment in a correct position, was achieved in 97.5% (115/118) of cases with repositioning of the occluder in 7.6% (9/118) and resizing in 3.4% (4/118) of cases. No relevant peri-device leakage (>3 mm) was observed with 42% of occluders being implanted in an ostial position. Periprocedural complications occurred in 6.8% (8/118) of cases, including two cases of device embolization and one case of clinically-relevant pericardial effusion requiring surgical intervention. Other complications included pericardial effusion (2.5%, 3/118) and vascular access site complications (1.7%, 2/118). CONCLUSION: Echocardiography-guided contrast-free LAAC using the LAMBRE device is safe and feasible. Further prospective studies including the direct comparison of devices as well as imaging techniques are warranted in contrast-free LAAC.

Optogenetic control of heart muscle in vitro and in vivo.

Electrical stimulation is the standard technique for exploring electrical behavior of heart muscle, but this approach has considerable technical limitations. Here we report expression of the light-activated cation channel channelrhodopsin-2 for light-induced stimulation of heart muscle in vitro and in mice. This method enabled precise localized stimulation and constant prolonged depolarization of cardiomyocytes and cardiac tissue resulting in alterations of pacemaking, Ca(2+) homeostasis, electrical coupling and arrhythmogenic spontaneous extrabeats.

Increased in vivo perpetuation of whole-heart ventricular arrhythmia in heterozygous Na+/Ca2+ exchanger knockout mice.

Aims: Na+/Ca2+ exchanger (NCX) upregulation in cardiac diseases like heart failure promotes as an independent proarrhythmic factor early and delayed afterdepolarizations (EADs/DADs) on the single cell level. Consequently, NCX inhibition protects against EADs and DADs in isolated cardiomyocytes. We here investigate, whether these promising cellular in vitro findings likewise apply to an in vivo setup. Methods/Results: Programmed ventricular stimulation (PVS) and isoproterenol were applied to a murine heterozygous NCX-knockout model (KO) to investigate ventricular arrhythmia initiation and perpetuation compared to wild-type (WT). KO displayed a reduced susceptibility towards isoproterenol-induced premature ventricular complexes. During PVS, initiation of single or double ectopic beats was similar between KO and WT. But strikingly, perpetuation of ventricular tachycardia (VT) was significantly increased in KO (animals with VT - KO: 82 %; WT: 47 %; p = 0.0122 / median number of VTs - KO: 4.5 (1.0, 6.25); WT: 0.0 (0.0, 4.0); p = 0.0039). The median VT duration was prolonged in KO (in s; KO: 0.38 (0.19, 0.96); WT: 0.0 (0.0, 0.60); p = 0.0239). The ventricular refractory period (VRP) was shortened in KO (in ms; KO: 15.1 ± 0.7; WT: 18.7 ± 0.7; p = 0.0013). Conclusions: Not the initiation, but the perpetuation of provoked whole-heart in vivo ventricular arrhythmia was increased in KO. As a potential mechanism, we found a significantly reduced VRP, which may promote perpetuation of reentrant ventricular arrhythmia. On a translational perspective, the antiarrhythmic concept of therapeutic NCX inhibition seems to be ambivalent by protecting from initiating afterdepolarizations but favoring arrhythmia perpetuation in vivo at least in a murine model.

Use of the Wearable Cardioverter-Defibrillator Among Patients With Myocarditis and Reduced Ejection Fraction or Ventricular Tachyarrhythmia: Data From a Multicenter Registry.

Background Data on the use of the wearable cardioverter-defibrillator (WCD) among patients with myocarditis remain sparse. Consequently, evidence for guideline recommendations in this patient population is lacking. Methods and Results In total, 1596 consecutive patients were included in a multicenter registry from 8 European centers, with 124 patients (8%) having received the WCD due to myocarditis and reduced left ventricular ejection fraction or prior ventricular tachyarrhythmia. The mean age was 51.6±16.3 years, with 74% being male. Patients were discharged after index hospitalization on heart failure medication: Angiotensin-converting enzyme inhibitors (62.5%), angiotensin-receptor-neprilysin inhibitor (22.9%), aldosterone-antagonists (51%), or beta blockers (91.4%). The initial median left ventricular ejection fraction was 30% (22%-45%) and increased to 48% (39%-55%) over long-term follow-up (P<0.001). The median BNP (brain natriuretic peptide) level at baseline was 1702 pg/mL (565-3748) and decreased to 188 pg/mL (26-348) over long-term follow-up (P=0.022). The mean wear time was 79.7±52.1 days and 21.0±4.9 hours per day. Arrhythmic event rates documented by the WCD were 9.7% for nonsustained ventricular tachycardia, 6.5% for sustained ventricular tachycardia, and 0% for ventricular fibrillation. Subsequently, 2.4% of patients experienced an appropriate WCD shock. The rate of inappropriate WCD shocks was 0.8%. All 3 patients with appropriate WCD shock had experienced ventricular tachycardia/ventricular fibrillation before WCD prescription, with only 1 patient showing a left ventricular ejection fraction <35%. Conclusions Patients with myocarditis and risk for occurrence of ventricular tachyarrhythmia may benefit from WCD use. Prior ventricular arrhythmia might appear as a better risk predictor than a reduced left ventricular ejection fraction <35% in this population.