TRI-SCORE is superior to EuroSCORE II and STS-Score in mortality prediction following transcatheter edge-to-edge tricuspid valve repair.

BACKGROUND: The development of transcatheter tricuspid edge-to-edge repair for tricuspid regurgitation is a therapeutic milestone but a specific periprocedural risk assessment tool is lacking. TRI-SCORE has recently been introduced as a dedicated risk score for tricuspid valve surgery. AIMS: This study analyzes the predictive performance of TRI-SCORE following transcatheter edge-to-edge tricuspid valve repair. METHODS: 180 patients who underwent transcatheter tricuspid valve repair at Ulm University Hospital were consecutively included and stratified into three TRI-SCORE risk groups. The predictive performance of TRI-SCORE was assessed throughout a follow-up period of 30 days and up to 1 year. RESULTS: All patients had severe tricuspid regurgitation. Median EuroSCORE II was 6.4% (IQR 3.8-10.1%), median STS-Score 8.1% (IQR 4.6-13.4%) and median TRI-SCORE 6.0 (IQR 4.0-7.0). 64 patients (35.6%) were in the low TRI-SCORE group, 91 (50.6%) in the intermediate and 25 (13.9%) in the high-risk groups. The procedural success rate was 97.8%. 30-day mortality was 0% in the low-risk group, 1.3% in the intermediate-risk and 17.4% in the high-risk groups (p < 0.001). During a median follow-up of 168 days mortality was 0%, 3.8% and 52.2%, respectively (p < 0.001). The predictive performance of TRI-SCORE was excellent (AUC for 30-day mortality: 90.3%, for one-year mortality: 93.1%) and superior to EuroSCORE II (AUC 56.6% and 64.4%, respectively) and STS-Score (AUC 61.0% and 59.0%, respectively). CONCLUSION: TRI-SCORE is a valuable tool for prediction of mortality after transcatheter edge-to-edge tricuspid valve repair and its performance is superior to EuroSCORE II and STS-Score. In a monocentric cohort of 180 patients undergoing edge-to-edge tricuspid valve repair TRI-SCORE predicted 30-day and up to one-year mortality more reliably than EuroSCORE II and STS-Score. AUC area under the curve, 95% CI 95% confidence interval.

MRI-based training model for left atrial appendage closure.

PURPOSE: Percutaneous closure of the left atrial appendage (LAA) reduces the risk of embolic stroke in patients with atrial fibrillation. Thereby, the optimal transseptal puncture (TSP) site differs due to the highly variable anatomical shape of the LAA, which is rarely considered in existing training models. Based on non-contrast-enhanced magnetic resonance imaging (MRI) volumes, we propose a training model for LAA closure with interchangeable and patient-specific LAA enabling LAA-specific identification of the TSP site best suited. METHODS: Based on patient-specific MRI data, silicone models of the LAAs were produced using a 3D-printed cast model. In addition, an MRI-derived 3D-printed base model was set up, including the right and left atrium with predefined passages in the septum, mimicking multiple TSP sites. The various silicone models and a tube mimicking venous access were connected to the base model. Empirical use of the model allowed the demonstration of its usability. RESULTS: Patient-specific silicone models of the LAA could be generated from all LAA patient MRI datasets. The influence of various combinations regarding TSP sites and LAA shapes could be demonstrated as well as the technical functionality of the occluder system. Via the attached tube mimicking the venous access, the correct handling of the deployment catheter even in case of not optimal puncture site could be practiced. CONCLUSION: The proposed contrast-agent and radiation-free MRI-based training model for percutaneous LAA closure enables the pre-interventional assessment of the influence of the TSP site on the access of patient-specific LAA shapes. A straightforward replication of this work is measured by using clinically available imaging protocols and a widespread 3D printer technique to build the model.

Impact of cryoballoon application abortion due to phrenic nerve injury on reconnection rates: a YETI subgroup analysis.

AIMS: Cryoballoon (CB)-based pulmonary vein isolation (PVI) is an effective treatment for atrial fibrillation (AF). The most frequent complication during CB-based PVI is right-sided phrenic nerve injury (PNI) which is leading to premature abortion of the freeze cycle. Here, we analysed reconnection rates after CB-based PVI and PNI in a large-scale population during repeat procedures. METHODS AND RESULTS: In the YETI registry, a total of 17 356 patients underwent CB-based PVI in 33 centres, and 731 (4.2%) patients experienced PNI. A total of 111/731 (15.2%) patients received a repeat procedure for treatment of recurrent AF. In 94/111 (84.7%) patients data on repeat procedures were available. A total of 89/94 (94.7%) index pulmonary veins (PVs) have been isolated during the initial PVI. During repeat procedures, 22 (24.7%) of initially isolated index PVs showed reconnection. The use of a double stop technique did non influence the PV reconnection rate (P = 0.464). The time to PNI was 140.5 ± 45.1 s in patients with persistent PVI and 133.5 ± 53.8 s in patients with reconnection (P = 0.559). No differences were noted between the two populations in terms of CB temperature at the time of PNI (P = 0.362). The only parameter associated with isolation durability was CB temperature after 30 s of freezing. The PV reconnection did not influence the time to AF recurrence. CONCLUSION: In patients with cryoballon application abortion due to PNI, a high rate of persistent PVI rate was found at repeat procedures. Our data may help to identify the optimal dosing protocol in CB-based PVI procedures. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03645577?term=YETI&cntry=DE&draw=2&rank=1 ClinicalTrials.gov Identifier: NCT03645577.

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.

Phrenic Nerve Injury During Cryoballoon-Based Pulmonary Vein Isolation: Results of the Worldwide YETI Registry.

BACKGROUND: Cryoballoon-based pulmonary vein isolation (PVI) has emerged as an effective treatment for atrial fibrillation. The most frequent complication during cryoballoon-based PVI is phrenic nerve injury (PNI). However, data on PNI are scarce. METHODS: The YETI registry is a retrospective, multicenter, and multinational registry evaluating the incidence, characteristics, prognostic factors for PNI recovery and follow-up data of patients with PNI during cryoballoon-based PVI. Experienced electrophysiological centers were invited to participate. All patients with PNI during CB2 or third (CB3) and fourth-generation cryoballoon (CB4)-based PVI were eligible. RESULTS: A total of 17 356 patients underwent cryoballoon-based PVI in 33 centers from 10 countries. A total of 731 (4.2%) patients experienced PNI. The mean time to PNI was 127.7±50.4 seconds, and the mean temperature at the time of PNI was -49±8°C. At the end of the procedure, PNI recovered in 394/731 patients (53.9%). Recovery of PNI at 12 months of follow-up was found in 97.0% of patients (682/703, with 28 patients lost to follow-up). A total of 16/703 (2.3%) reported symptomatic PNI. Only 0.06% of the overall population showed symptomatic and permanent PNI. Prognostic factors improving PNI recovery are immediate stop at PNI by double-stop technique and utilization of a bonus-freeze protocol. Age, cryoballoon temperature at PNI, and compound motor action potential amplitude loss >30% were identified as factors decreasing PNI recovery. Based on these parameters, a score was calculated. The YETI score has a numerical value that will directly represent the probability of a specific patient of recovering from PNI within 12 months. CONCLUSIONS: The incidence of PNI during cryoballoon-based PVI was 4.2%. Overall 97% of PNI recovered within 12 months. Symptomatic and permanent PNI is exceedingly rare in patients after cryoballoon-based PVI. The YETI score estimates the prognosis after iatrogenic cryoballoon-derived PNI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03645577. Graphic Abstract: A graphic abstract is available for this article.

Feasibility of digital atrial fibrillation screening in an elderly population : The Ulm heart rhythm weeks.

AIMS: Atrial fibrillation (AF) screening in risk populations has the potential to prevent strokes. The authors tested the feasibility of a digital program with initial photoplethysmographic (PPG) self-screening and cardiologist-attended electrocardiographic (ECG) confirmation of screen-positive cases. METHODS: Inhabitants of the city of Ulm aged ≥ 65 years were invited to participate. After digital consent, participants were given access to a smartphone application for 14 days of self-screening (two recordings per day recommended). Screen-positive participants without known AF were invited to present to a cardiologist for AF confirmation with a 14-day ECG event recorder. PPG recordings were first analyzed by algorithm using a combination of linear and non-linear methods. The quality of pathological (classified by algorithm) PPG and all ECG recordings were checked by a telecare service. Primary outcomes included adherence to the screening protocol defined as the proportion of participants performing at least 14 PPG recordings (or until documentation of absolute arrhythmia) and the proportion of pathological PPG and all ECG recordings rejected by the telecare center. RESULTS: A total of 215 participants registered. Of these, 204 (95%) performed at least one recording and 169 (79%) reached the performance target of two sufficient measurements per day; 75 PPG recordings were automatically classified as pathological by algorithm; 14 (19%) were rejected by the telecare service due to poor quality. Of the 12 participants with a suspected first diagnosis of AF, five visited a cardiologist as part of the study. Of 1090 ECG recordings obtained, 390 (36%) were qualified as non-diagnostic. AF was confirmed in three cases. CONCLUSIONS: A digital AF screening program with initial self-screening and referral of screen-positive cases to a cardiologist-attended ECG-confirmation service is feasible with meaningful results in an elderly risk population. However, the availability of the target population of persons > 65 years of age for such a digital screening program appears to be limited despite extensive public relations activities.

Cryo-balloon catheter localization in X-Ray fluoroscopy using U-net.

PURPOSE: Automatic identification of interventional devices in X-ray (XR) fluoroscopy offers the potential of improved navigation during transcatheter endovascular procedures. This paper presents a prototype implementation of fully automatic 3D reconstruction of a cryo-balloon catheter during pulmonary vein isolation (PVI) procedures by deep learning approaches. METHODS: We employ convolutional neural networks (CNN) to automatically identify the cryo-balloon XR marker and catheter shaft in 2D fluoroscopy during PVI. Training data are generated exploiting established semiautomatic techniques, including template-matching and analytical graph building. A first network of U-net architecture uses a single grayscale XR image as input and yields the mask of the XR marker. A second network of the similar architecture is trained using the mask of the XR marker as additional input to the grayscale XR image for the segmentation of the cryo-balloon catheter shaft mask. The structures automatically identified in two 2D images with different angulations are then used to reconstruct the cryo-balloon in 3D. RESULTS: Automatic identification of the XR marker was successful in 78% of test cases and in 100% for the catheter shaft. Training of the model for prediction of the XR marker mask was successful with 3426 training samples. Incorporation of the XR marker mask as additional input for the model predicting the catheter shaft allowed to achieve good training result with only 805 training samples. The average prediction time per frame was 14.47 ms for the XR marker and 78.22 ms for the catheter shaft. Localization accuracy for the XR marker yielded on average 1.52 pixels or 0.56 mm. CONCLUSIONS: In this paper, we report a novel method for automatic detection and 3D reconstruction of the cryo-balloon catheter shaft and marker from 2D fluoroscopic images. Initial evaluation yields promising results thus indicating the high potential of CNNs as alternatives to the current state-of-the-art solutions.

Safety of conscious sedation in electroanatomical mapping procedures and cryoballoon pulmonary vein isolation.

Immobilization of patients during electrophysiological procedures, to avoid complications by patients' unexpected bodily motion, is achieved by moderate to deep conscious sedation using benzodiazepines and propofol for sedation and opioids for analgesia. Our aim was to compare respiratory and hemodynamic safety endpoints of cryoballoon pulmonary vein isolation (PVI) and electroanatomical mapping (EAM) procedures. Included patients underwent either cryoballoon PVI or EAM procedures. Sedation monitoring included non-invasive blood pressure measurements, transcutaneous oxygen saturation (tSpO2) and transcutaneous carbon-dioxide (tpCO2) measurements. We enrolled 125 consecutive patients, 67 patients underwent cryoballoon atrial fibrillation ablation and 58 patients had an EAM and radiofrequency ablation procedure. Mean procedure duration of EAM procedures was significantly longer (p < 0.001) and propofol doses as well as morphine equivalent doses of administered opioids were significantly higher in EAM patients compared to cryoballoon patients (p < 0.001). Cryoballoon patients display higher tpCO2 levels compared to EAM patients at 30 min (cryoballoon: 51.1 ± 7.0 mmHg vs. EAM: 48.6 ± 6.2 mmHg, p = 0.009) and at 60 min (cryoballoon: 51.4 ± 7.3 mmHg vs. EAM: 48.9 ± 6.6 mmHg, p = 0.07) procedure duration. Mean arterial pressure was significantly higher after 60 min (cryoballoon: 84.7 ± 16.7 mmHg vs. EAM: 76.7 ± 13.3 mmHg, p = 0.017) in cryoballoon PVI compared to EAM procedures. Regarding respiratory and hemodynamic safety endpoints, no significant difference was detected regarding hypercapnia, hypoxia and episodes of hypotension. Despite longer procedure duration and deeper sedation requirement, conscious sedation in EAM procedures appears to be as safe as conscious sedation in cryoballoon ablation procedures regarding hemodynamic and respiratory safety endpoints.

Acute Hemoptysis Following Cryoballoon Pulmonary Vein Isolation: A Multicenter Study.

OBJECTIVES: This study sought to assess the incidence, procedural characteristics, contributing factors, and clinical outcome of cryoballoon-based pulmonary vein isolation (CB-PVI)-related hemoptysis in a multicenter study. BACKGROUND: Hemoptysis has been described as a rare complication of CB-PVI. However, the precise mechanism and the etiology of this complication are poorly characterized. METHODS: Consecutive patients undergoing CB-PVI for paroxysmal or persistent atrial fibrillation at 4 German hospitals were included in this observational analysis. RESULTS: A total of 4,331 CB-PVI procedures were performed between 2006 and 2019. Fifteen patients (9 men, mean age 68.1 ± 9.8 years) developed acute hemoptysis during or within 24 h after CB-PVI, resulting in a hemoptysis frequency of 0.35%. Hemoptysis occurred in 6 of 720 procedures using the first-generation CB (0.83%) and in 9 of 3,611 procedures using the second-, third-, or fourth-generation CB (0.25%) (p = 0.015). Bronchoscopy was performed in 8 patients and showed bleeding exclusively due to mucosal injury or due to a coagulum at a bronchus adjacent to the ablation site. Hemoptysis resolved spontaneously without any long-term sequelae in all patients, except for a 92-year-old patient who died 13 days after CB-PVI due to pneumonia. No specific endobronchial treatment was necessary. CONCLUSIONS: Acute hemoptysis after CB-PVI is a rare but potentially life-threatening complication that is usually self-limiting. Direct thermal injury of bronchi adjacent to a pulmonary vein seems to be the most likely mechanism.

Atrial fibrillation ablation in heart failure patients: improved systolic function after cryoballoon pulmonary vein isolation.

AIMS: Atrial fibrillation (AF) and heart failure (HF) are the most common cardiac diseases and often coexist leading to increased mortality and morbidity compared with AF patients without HF. As shown previously, AF ablation using radio frequency (RF) in HF patients leads to a reduction of AF burden, an increase of left ventricular ejection fraction (LVEF) and consequently to reduced hospitalization and mortality. Previous AF ablation studies on HF patients have been liberal about additional targets beyond pulmonary vein isolation (PVI). Thus, the aim of this study was to assess systematically the impact of a straightforward PVI-only strategy on LVEF, NYHA functional class, and cardiovascular hospitalization rate in HF patients. METHODS AND RESULTS: Out of 414 consecutive patients undergoing PVI, only with the cryoballoon 113 patients with reduced LVEF [mean: 38.4 ± 10.8%, reduced ejection fraction (rEF) group] and 301 patients with normal LVEF (>55%) at baseline were identified [normal ejection fraction (nEF) group]. Remarkably, even though freedom from arrhythmia recurrence after 1 year was significantly lower in the rEF group (64.9%) compared with the nEF group (71.2%, P = 0.036), mean LVEF improved from 38.4 ± 10.8% to 52.5 ± 17.2% (P < 0.001) after cryoballoon ablation in the rEF group. Accordingly, HF-related symptoms as well as hospitalization rate declined significantly in the rEF group during follow-up compared with baseline. CONCLUSIONS: The results of the present study suggest that catheter ablation restricted to a straightforward PVI-only strategy using the cryoballoon leads to improved left ventricular ejection fraction as well as improvement of NYHA functional class and increased freedom from cardiovascular rehospitalization.

Pulmonary vein isolation with the cryoballoon in obese atrial fibrillation patients - Does weight have an impact on procedural parameters and clinical outcome?

INTRODUCTION: Obesity is a known risk factor for the incidence and prevalence of atrial fibrillation (AF). Pulmonary vein isolation (PVI) is an established therapeutic option for AF patients, however clinical benefit of AF ablation remains controversial in overweight and obese patients. We investigated the impact of overweight and obesity in AF patients undergoing cryoballoon PVI on procedural characteristics and clinical outcome. METHODS: We included consecutive patients undergoing cryoballoon PVI at Ulm University Medical center. Normal weight was defined as a body mass index (BMI) of 18.5-24.9 kg/m2, overweight as a BMI of 25.0-29.9 kg/m2 and obesity as a BMI of ≥30.0 kg/m2. RESULTS: Evaluating 600 patients, mean age was 66.3±10.8 years and 43% patients were female. 41% of the patients were classified as overweight and 34% as obese. Regarding procedural characteristics, overweight and obese patients had longer fluoroscopy area dose product (p<0.001) and obese patients a higher fluoroscopy time (p<0.05). Analyses of ablation related procedural characteristics revealed no relevant differences regarding number and duration of ablation, time to isolation and nadir temperature. Importantly, recurrence of atrial arrhythmia was statistically not different comparing normal weight, overweight and obese patients. CONCLUSION: Besides higher radiation exposure, cryoballoon PVI in overweight and obese patients is as safe and efficient as in normal weight patients. It is reasonable to proceed with cryoballoon PVI on overweight and obese patients as would be done in normal weight patients, since this might encourage overweight and obese patients to exercise.

Second-Generation Cryoballoon Atrial Fibrillation Ablation in Patients With Persistent Left Superior Caval Vein.

OBJECTIVES: This study sought to assess the acute success rate, periprocedural complications, and long-term outcomes in patients with atrial fibrillation (AF) and persistent left superior vena cava (PLSVC) treated with second-generation 28-mm cryoballoon (CB2). BACKGROUND: PLSVC is a cardiac anomaly associated with AF. METHODS: Between July 2012 and October 2018, 8 patients from 4 German high-volume centers referred for pulmonary vein isolation (PVI) demonstrated a PLSVC. PVI and ablation within the PLSVC was performed using the CB2. RESULTS: A total of 2,876 patients were treated with CB2-based PVI. Eight patients (0.28%; mean 65 ± 7 years of age, 2 paroxysmal, 6 with persistent AF, mean left atrial size of 44 ± 4 mm) presenting with PLSVC were evaluated. All patients underwent PVI, and 3 of 8 patients with documented triggered activity from PLSVC underwent PLSVC ablation with CB2. Electrical isolation of PLSVC was achieved in 2 of 3 patients. Mean procedure and fluoroscopy times were 120 ± 22 min and 32 ± 18 min, respectively. In 2 of 8 patients, major complications (right phrenic nerve palsy) occurred during right PV ablation. After 3 months, 1 of 2 patients recovered from right phrenic nerve palsy. Two patients underwent a redo procedure after AF recurrence, demonstrating PV reconnection but no triggers from PLSVC. Freedom from AF after 332 days of follow-up was 63%. CONCLUSIONS: CB2 ablation for AF in patients with PLSVC is feasible, with an increased risk for right phrenic nerve palsy. Electrical isolation of PLSVC can be achieved with the CB2 in most patients.

Novel spiral mapping catheter facilitates observation of the time-to-pulmonary vein isolation during cryoballoon ablation.

Observation of the time-to-pulmonary vein isolation (TTI) by a spiral mapping catheter has emerged as a valuable procedural parameter in cryoballoon pulmonary vein isolation (PVI). The 1st generation spiral mapping catheter (Achieve, SMC1) has been available as an 8-polar catheter with a distal loop diameter of 15 or 20 mm. The novel spiral mapping catheter (Achieve Advance, SMC2) was designed as a true guidewire and is available, in addition to the sizes of the SMC1, as a 10-polar mapping catheter with a distal loop diameter of 25 mm. Whether these novel features of SMC2 influence procedural characteristics of Cryo-PVI in comparison to SMC1 has not been reported. In this prospective cohort study 158 patients (age 65.1 ± 12.4 years, female 39%, paroxysmal AF 60%) undergoing PVI with the 2nd generation cryoballoon were included. SMC1 was used in 57 patients (36%), whereas 101 patients (64%) underwent Cryo-PVI with the SMC2. All PVs (623/623, 100%) were isolated successfully. Mean procedure duration was 72.0 ± 18.9 min in the SMC1 group and 74.4 ± 19.1 min in the SMC2 group (p = 0.432). Mean fluoroscopy time was also not different between both study groups (SMC1 15.7 ± 6.6 min, SMC2 15.7 ± 7.3 min, p = 0.593). TTI was observed in 68.6% of pulmonary veins in the SMC1 group, whereas TTI observation rate was 82.6% in the SMC2 group (p < 0.001). Number of freezes (5.5 ± 1.5 vs. 6.5 ± 1.9; p = 0.001) and total freeze duration (14.1 ± 4.5 vs. 17.6 ± 5.6; p < 0.001) were increased in the SMC2 group. SMC2 significantly increases TTI observation rate during Cryo-PVI. Procedure duration and fluoroscopy time are similar and number of freezes and total freeze duration are increased compared to PVI with SMC1 due to decreased stability and maneuverability of SMC2.

Single-Procedure Outcomes and Quality-of-Life Improvement 12 Months Post-Cryoballoon Ablation in Persistent Atrial Fibrillation: Results From the Multicenter CRYO4PERSISTENT AF Trial.

OBJECTIVES: The CRYO4PERSISTENT AF (Cryoballoon Ablation for Early Persistent Atrial Fibrillation) trial aims to report long-term outcomes after a single pulmonary vein isolation (PVI)-only ablation procedure using the second-generation cryoballoon in persistent atrial fibrillation (PerAF) patients. BACKGROUND: Pulmonary vein isolation is recognized as the cornerstone of atrial fibrillation (AF) ablation, including ablation of PerAF. METHODS: The CRYO4PERSISTENT AF trial (NCT02213731) is a prospective, multicenter, single-arm trial designed to assess single-procedure outcomes of PVI using the cryoballoon. The primary endpoint was freedom from AF, atrial flutter, or atrial tachycardia ≥30 s after a 90-day blanking period. After enrollment, but before ablation, patients without 100% AF burden (18-h Holter monitoring or 3 consecutive electrocardiograms in a time frame ≥14 days) were excluded. Patients were followed at 3, 6, and 12 months, with 48-h Holter monitoring at 6 and 12 months. Quality of life and symptoms were evaluated at baseline and 12 months. Arrhythmia recurrence and adverse events were adjudicated by an independent committee. RESULTS: A total of 101 patients (62 ± 11 years of age, 74% men, left ventricular ejection fraction 56 ± 8%, left atrial diameter 43 ± 5 mm) meeting criteria, undergoing cryoballoon-based PVI, with follow-up data, were included. Kaplan-Meier estimate of freedom from AF, atrial flutter, or atrial tachycardia recurrence was 60.7% at 12 months. Compared with baseline, there were significantly fewer patients with arrhythmia-related symptoms at 12 months (16% vs. 92%; p < 0.0001). The symptom reduction was supported by significant improvement in 36-Item Short Form Health Survey composite scores and European Heart Rhythm Association score at 12 months. The only device related event was transient phrenic nerve injury in 2 (2%) patients, with resolution pre-discharge. CONCLUSIONS: Cryoballoon ablation for treatment of PerAF demonstrated 61% single-procedure success at 12 months post-ablation in addition to significant reduction in arrhythmia-related symptoms and improved quality of life. (Cryoballoon Ablation for Early Persistent Atrial Fibrillation [Cryo4 Persistent AF]; NCT02213731).

Mutation of the Na+/K+-ATPase Atp1a1a.1 causes QT interval prolongation and bradycardia in zebrafish.

The genetic underpinnings that orchestrate the vertebrate heart rate are not fully understood yet, but of high clinical importance, since diseases of cardiac impulse formation and propagation are common and severe human arrhythmias. To identify novel regulators of the vertebrate heart rate, we deciphered the pathogenesis of the bradycardia in the homozygous zebrafish mutant hiphop (hip) and identified a missense-mutation (N851K) in Na+/K+-ATPase α1-subunit (atp1a1a.1). N851K affects zebrafish Na+/K+-ATPase ion transport capacity, as revealed by in vitro pump current measurements. Inhibition of the Na+/K+-ATPase in vivo indicates that hip rather acts as a hypomorph than being a null allele. Consequently, reduced Na+/K+-ATPase function leads to prolonged QT interval and refractoriness in the hip mutant heart, as shown by electrocardiogram and in vivo electrical stimulation experiments. We here demonstrate for the first time that Na+/K+-ATPase plays an essential role in heart rate regulation by prolonging myocardial repolarization.

Time-to-isolation guided titration of freeze duration in 3rd generation short-tip cryoballoon pulmonary vein isolation - Comparable clinical outcome and shorter procedure duration.

BACKGROUND: The optimal freeze duration in cryoballoon pulmonary vein isolation (PVI) is unknown. The 3rd generation cryoballoon facilitates observation of the time-to-isolation (TTI) and thereby enables individualized cryoenergy titration. To evaluate the efficacy of an individualized freeze duration we compared the clinical outcome of patients treated with a TTI-guided ablation protocol to the outcome of patients treated with a fixed ablation protocol. METHODS: We compared 100 patients treated with the 3rd generation cryoballoon applying a TTI-based protocol (TTI group) to 100 patients treated by a fixed freeze protocol (fixed group). In the fixed group a 240s freeze cycle was followed by a 240s bonus freeze after acute PV isolation. In the TTI group freeze duration was 180s if TTI was ≥30s and reduced to only 120s, if TTI was <30s. In case of a TTI >60s a 180s bonus freeze was applied. RESULTS: Freedom from atrial arrhythmia recurrence off class I/III antiarrhythmic drugs after one year was not different between the TTI group (73.6%) and the fixed group (75.7%; p=0.75). Mean procedure duration was 85.8±27.3min in the TTI group compared to 115.7±27.1min in the fixed group (p<0.001). Mean fluoroscopy time was 17.5±6.6min in the TTI group and 22.5±9.8min in the fixed group (p<0.001). CONCLUSIONS: TTI-guided cryoenergy titration leads to reduced procedure duration and fluoroscopy time and appears to be as effective as a fixed ablation strategy. A single 2-minute freeze seems to be sufficient in case of short TTI.

Clinical outcome of 2nd generation cryoballoon pulmonary vein isolation in patients over 75 years of age.

BACKGROUND: Pulmonary vein isolation is an established therapy for symptomatic atrial fibrillation. Despite the fact that incidence and prevalence of atrial fibrillation increases with age, patients over 75 years of age have been excluded in all major atrial fibrillation ablation trials. Pulmonary vein isolation with the cryoballoon has been shown to be equally effective compared to irrigated radiofrequency catheter ablation, but patients over 75 years have also been excluded. The 2nd generation cryoballoon has shown superior efficacy compared to the 1st generation cryoballoon. The aim of the study was to assess the efficacy of pulmonary vein isolation with the 2nd generation cryoballoon for symptomatic atrial fibrillation in elderly patients over 75 years. METHODS: Patients over 75 years of age presenting with symptomatic paroxysmal or persistent atrial fibrillation refractory or intolerant to at least one class I or class III antiarrhythmic drug who underwent pulmonary vein isolation with the 2nd generation cryoballoon were included in this single-center observational study. RESULTS: A total of 40 patients with a mean age of 78.3±2.7 years with paroxysmal (n=31; 77.5%) or persistent (n=9; 22.5%) atrial fibrillation were identified. All patients had a successful pulmonary vein isolation procedure with 100% of veins isolated. After a 3-month blanking period during a mean follow-up of 15.1±8.2 months there were 9 (22.5%) arrhythmia recurrences, while 31 patients (77.5%) maintained stable sinus rhythm. Freedom from arrhythmia recurrence was 86.4% at 12 months and 80.2% at 24 months. CONCLUSIONS: Pulmonary vein isolation with the 2nd generation cryoballoon appears to be an effective treatment for symptomatic atrial fibrillation also in patients over 75 years of age.

Increased rate of observed real-time pulmonary vein isolation with third-generation short-tip cryoballoon.

PURPOSE: Pulmonary vein isolation (PVI) with the cryoballoon is an established treatment for symptomatic atrial fibrillation. The second-generation cryoballoon increased efficacy in comparison to the first-generation cryoballoon. The third-generation cryoballoon was designed with a shorter distal tip to facilitate real-time recording of pulmonary vein (PV) isolation. Here, we compared the rate of real-time recordings of PVI of the second- and third-generation cryoballoon. METHODS: The incidence of real-time recording of PV isolation and time to PV isolation of the first 37 patients treated with the new third-generation cryoballoon at our center were compared to the last 37 patients treated with the second-generation cryoballoon. RESULTS: One hundred forty-nine pulmonary veins (PVs) were identified in each group. All PVs were isolated successfully with the second- or third-generation cryoballoon. Real-time registration of PVI occurred in 83 PVs (55.7 %) with the second-generation cryoballoon and in 124 PVs (83.2 %) with the third-generation cryoballoon (p < 0.001). The rate of observed real-time PVI was significantly higher with the third-generation cryoballoon for each individual PV. The time-to-isolation was 44 ± 25 s with the second-generation cryoballoon vs. 42 ± 22 s with the third-generation cryoballoon (p = 0.25). In a short-term clinical follow-up, there was no significant difference in atrial arrhythmia recurrence rates between both groups. CONCLUSIONS: The third-generation cryoballoon facilitates real-time recording of PV isolation with significantly higher rates of observed time-to-isolation. The time to PV isolation is not different between second- and third-generation cryoballoon.