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.

Stand-alone Focal Impulse and Rotor Modulation (FIRM) ablation versus second-generation cryoballoon pulmonary vein isolation for paroxysmal atrial fibrillation.

INTRODUCTION: Focal Impulse and Rotor Modulation (FIRM) guided catheter ablation aiming at stable rotors has been investigated as a treatment option in patients with atrial fibrillation (AF). The objective of this study was to compare the safety and efficacy of FIRM-guided ablation with second-generation cryoballoon pulmonary vein isolation (CB2-PVI) in paroxysmal AF. METHODS: Consecutive patients (n = 22, mean age 60 ± 11 years, 59.1% of males) who were treated with a stand-alone FIRM-guided ablation were included in this retrospective single-center study. Procedural data and arrhythmia-free survival at 12 months were compared with n = 86 consecutive patients (mean age 62 ± 13 years, 62.4% of males) who received de-novo CB2-PVI. RESULTS: Median procedure duration was significantly longer in the FIRM group than in the CB2-PVI group (152 [IQR 120-176] minutes vs. 122 [110-145] minutes; p = .031). One patient (1.2%) in the CB2-PVI group and five patients (22.7%) in the FIRM group had vascular access complications. Atrial tachyarrhythmias recurred in 15 patients in the FIRM group and 11 in the CB2-PVI group. Kaplan-Meier estimation of single-procedure arrhythmia-free survival at 12 months was 25% (95% confidence interval [CI] 6%-44%) in the FIRM group and 87% (95% CI 78%-96%) in the CB2-PVI group (p < .001). Repeat ablations were performed in 14/20 (70.0%) patients in the FIRM group and in 12/85 (14.1%) in the CB2-PVI group (p < .001). CONCLUSION: De novo ablation of AF using FIRM-guided AF ablation results in shorter arrhythmia-free survival after 12 months compared to CB2-PVI and a need for repeat ablation in the majority of patients to achieve stable sinus rhythm.

Decreasing time between first diagnosis of paroxysmal atrial fibrillation and cryoballoon ablation positively affects long-term consequences.

BACKGROUND: Patients with atrial fibrillation (AF) usually experience a worsening of their AF burden over time. We aimed to investigate timing of pulmonary vein isolation (PVI) by cryoballoon (CB-2) after the first clinical diagnosis of AF on ablation-related outcomes. METHODS: A total of 132 consecutive patients with paroxysmal AF undergoing PVI by CB-2 were included in the study. The patients were retrospectively sorted into two groups to evaluate differences in AF recurrence risk associated with early ablation (n = 89), defined as within 365 days of first AF diagnosis, and late ablation (n = 365), defined as > 365 days after first AF diagnosis. AF-free survival during follow-up was compared between groups. RESULTS: Although mean procedure times were comparable between groups, mean fluoroscopy times were lower in the early ablation group. For the whole study group, median (interquartile range) time from AF diagnosis to first ablation was 4.0 (2.0-11.3) months [3.0 (1.0-4.0) vs 14.0 (12.0-22.5) months in the early and late ablation groups, respectively]. Median follow-up for the whole population was 12.0 (12.0-18.0) months, and after the blanking period, 14 (10.6%) patients had arrhythmia recurrence (2 in the early and 12 in the late ablation groups). In the univariable Cox regression analysis and propensity score adjusted penalized Cox regression analysis, there was a significant association between delay in ablation time and AF recurrence (unadjusted hazard ratio = 7.74, 95% CI 2.26-40.1, p < 0.001, adjusted hazard ratio = 7.50, 95% CI 2.23-38.6, p < 0.001). CONCLUSION: Delays in treatment with CB-2 ablation may negatively affect AF-free survival rates among patients with paroxysmal AF.

Catheter Ablation for Atrial Fibrillation in Patients ≤30 Years of Age.

Pulmonary vein (PV) automaticity is an established trigger for paroxysmal atrial fibrillation (PAF), making PV isolation (PVI) the cornerstone of catheter ablation. However, data on triggers for atrial fibrillation (AF) and catheter ablation strategy in very young patients aged <30 years are sparse. A total of 51 young patients (mean age 24.0 ± 4.2 years, 78.4% men) with drug-refractory PAF underwent electrophysiology (EP) study and ablation at 5 EP centers. None of the patients had structural heart disease or family history of AF. EP study induced supraventricular tachycardia (SVT) in 12 patients (n = 12, 23.5%): concealed accessory pathway mediated orthodromic atrioventricular reentrant tachycardia in 3 patients, typical atrioventricular nodal reentrant tachycardia in 6 patients, left superior PV tachycardia in 1 patient, left atrial appendage tachycardia in 1 patient, and typical atrial flutter in 1 patient. In patients with induced SVTs, SVT ablation without PVI was performed as an index procedure, except for the patient with atrial flutter who received cavotricuspid isthmus ablation in addition to PVI. Remaining patients underwent radiofrequency (n = 15, 29.4%) or second-generation cryoballoon-based PVI (n = 24, 47%). There were no major complications related to ablation procedures. Follow-up was based on outpatient visits including 24-hour Holter-electrocardiogram at 3, 6, and 12 months after ablation, or additional Holter-electrocardiogram was ordered in case of symptoms suggesting recurrence. Recurrence was defined as any atrial tachyarrhythmia (ATA) episode >30 seconds after a 3-month blanking period. A total of 2 patients with atrioventricular nodal reentrant tachycardia, 1 with left atrial appendage tachycardia, experienced AF recurrence within the first 3 months and received PVI. After the 3-month blanking period, during a median follow-up of 17.0 ± 10.1 months, 44 of 51 patients (86.2%) were free of ATA recurrence. In the PVI group, 33 of 39 patients (84.6%) experienced no ATA recurrence. In conclusion, SVT substrate is identified in around a quarter of young adult patients with history of AF, and targeted ablation without PVI may be sufficient in the majority of these patients. PVI is needed in the majority and is safe and effective in this population.

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.

The benefit of cardioneuroablation to reduce syncope recurrence in vasovagal syncope patients: a case-control study.

BACKGROUND: Adequate and effective therapy for resistant vasovagal syncope patients is lacking and the benefit of cardioneuroablation (CNA) in this cohort is still debated. The aim of this study is to assess the long-term effect of CNA versus conservative therapy (CT) in a retrospectively followed cohort. METHODS: A total of 2874 patients underwent head-up tilt test (HUT) and 554 (19.2 %) were reported as positive, with VASIS type 2B response or > 3 s asystole in 130 patients. After exclusion of 29 patients under 18 years and over 65 years of age, 101 patients were included final analysis. Fifty-one patients (50.4%) underwent CNA and 50 (49.6%) patients received CT. After propensity score matching, 19 pairs of patients were successfully matched. The recurrence rate of syncope was compared between groups. RESULTS: During a median follow-up of 22 months (IQR, 13-35), syncope was seen in 12 (11.8%) cases. In the 19 propensity-matched patients, recurrent syncope was observed in 8 patients in the CT group and in 2 patients in the CNA group, respectively. In mixed effect Cox regression analysis, CNA was associated with less syncope recurrence risk at follow-up (HR 0.23, 95% CI 0.03-0.99, p = 0.049). The 4-year Kaplan-Meier syncope free rate was 0.86 (95% CI, 0.63-1.00) for CNA group and 0.50 (95% CI, 0.30-0.82) for CT group in the matched cohort. CONCLUSIONS: In highly selected patients with HUT-induced cardioinhibitory response, CNA is associated with a significant reduction in syncope recurrence during follow-up when compared to CT.

Filtering electrocardiogram: Music, math, and ST-elevation myocardial infarction.

Clinicians should have a basic understanding of the working principle of the instruments they use to avoid potential pitfalls caused by post-processing of the acquired biological signals. An electrocardiogram (ECG) is no exception; many different errors can arise during the acquisition or the processing of the ECG data, which may result in dangerous misdiagnoses. We present a case where the use of an inappropriate high-pass filter led to a false diagnosis of ST-elevation myocardial infarction. In addition, this report discusses the basic mechanisms of this frequently overlooked phenomenon and methods to avoid it.

Effect of conscious sedation and deep sedation on the vagal response characteristics during ganglionated plexus ablation.

INTRODUCTION: We aimed to determine the effects of conscious and deep sedation on vagal response (VR) characteristics during ganglionated plexus (GP) ablation. METHODS: Forty consecutive patients undergoing GP ablation for vasovagal syncope were divided to receive conscious sedation with midazolam (Group 1, n = 29) or deep sedation with the midazolam-propofol combination (Group 2, n = 11). VR was defined on three levels. R-R interval increase of >50% (Level 1); R-R interval increase of 20%-50% (Level 2); and R-R interval increase of <20% (Level 3). RESULTS: The ratio of Level 1 VR during ablation on left superior and inferior GPs was significantly lower in Group 2 (p < .0001 and p = .034, respectively). Once the cut-off for VR was decreased to Level 2, the ratio of (+) VR was similar between groups during ablation of left-sided GPs. Positive VR in any level was lower than 20% during ablation of right-sided GPs. CONCLUSIONS: The autonomic tone might be affected in different ways by the level or type of intravenous sedation. Awareness of anesthesia-related differences may be important if GP ablation will be performed by using VR characteristics during ablation.

Effects of permanent cardiac pacing on ventricular repolarization when compared to cardioneuroablation.

INTRODUCTION: The impact of cardioneuroablation (CNA) on ventricular repolarization by using corrected QT interval (QTc) measurements has been recently demonstrated. The effects of cardiac pacing (CP) on ventricular repolarization have not been studied in patients with vasovagal syncope (VVS). We sought to compare ventricular repolarization effects of CNA (group 1) with CP (group 2) in patients with VVS. METHODS: We enrolled 69 patients with age 38 ± 13 years (53.6% male), n = 47 in group 1 and n = 22 in group 2. Clinical diagnosis of cardioinhibitory type was supported by cardiac monitoring or tilt testing. QTc was calculated at baseline (time-1), at 24 h after ablation (time-2), and at 9-12 months (time-3) in the follow-up. RESULTS: In the group 1, from time-1 to time-2, a significant shortening in QTcFredericia (from 403 ± 27 to 382 ± 27 ms, p < 0.0001), QTcFramingham (from 402 ± 27 to 384 ± 27 ms, p < 0.0001), and QTcHodges (from 405 ± 26 to 388 ± 24 ms, p < 0.0001) was observed which remained lower than baseline in time-3 (373 ± 29, 376 ± 27, and 378 ± 27 ms, respectively). Although the difference between measurements in time-1 and time-2 was not statistically significant for QTcBazett, a significant shortening was detected between time-1 and time-3 (from 408 ± 30 to 394 ± 33, p = 0.005). In the group 2, there was no time-based changes on QTc measurements. In the linear mixed model analysis, the longitudinal reduction tendency in the QTcFredericia and QTcFramingham was more pronounced in group 1. CONCLUSIONS: Our results demonstrate that CNA reduces QTc levels through neuromodulation effect whereas CP has no effect on ventricular repolarization in patients with VVS.

Macroscopic T-wave alternans in a patient presenting with hepatic encephalopathy.

Macroscopic T-wave alternans (TWA) is the beat-to-beat variation in the amplitude or shape of the T wave on a surface electrocardiogram (ECG) and known to be a harbinger of impending malignant ventricular arrhythmias such as polymorphic ventricular tachycardia. We herein report a case with hepatic encephalopathy, who developed TWA, followed by polymorphic ventricular tachycardia.

Medium-term results of cardioneuroablation for clinical bradyarrhythmias and vasovagal syncope: effects on QT interval and heart rate.

PURPOSE: Although parasympathetic effects of cardioneuroablation (CNA) in vagally mediated bradyarrhythmias (VMB) were studied, sympathetic effects have not been elucidated, yet. We aimed to investigate the acute and medium-term outcomes of CNA as well as the impact of CNA on ventricular repolarization by using corrected QT interval (QTc) measurements. METHODS: Sixty-five patients (58.5% men; age 39.4 ± 14 years) undergoing CNA were included in the study. Patients who underwent CNA due to VMB were divided into two groups: (1) bi-atrial CNA and (2) right-sided CNA. QTc was calculated at 3 time points: before the procedure (time point 1); 24 h post-ablation (time point 2); and at the last follow-up visit (time point 3). RESULTS: The mean follow-up time was 20.0 ± 20 months. Acute success was achieved in 64 (98.4%) of cases. In the whole cohort, from time point 1 to 2, a significant shortening in QTcFredericia, QTcFramingham, and QTcHodges was observed which remained lower than baseline in time point 3. Although the difference between measurements in time point 1 and 2 was not statistically significant for QTcBazett, a significant shortening was detected between time point 1 and 3. There was significant difference between groups for shortening in QTcFredericia and QTcFramingham (p = 0.01). Event-free survival was detected in 90.7% (59/65) of cases. CONCLUSIONS: Our results demonstrate a significant shortening of QTc in addition to high acute and medium-term success rates after CNA. The most likely mechanism is the effect of CNA on the sympathetic system as well as on the parasympathetic system. Bi-atrial ablation was found related to higher QTc shortening effect.

Selective vagal innervation principles of ganglionated plexi: step-by-step cardioneuroablation in a patient with vasovagal syncope.

Cardioneuroablation (CNA) is an endocardial ablation technique aiming to prevent the autonomic imbalance occurring in vasovagal syncope (VVS). A 46-year-old female was referred to our center for pacemaker implantation due to recurrent syncopal episodes despite conventional treatments. A 22-s asystole was detected on head-up tilt testing. After a discussion with the patient and her family, we decided to perform CNA. Positive response was confirmed, and procedural endpoints were defined using pre-procedural atropine response test. Ganglionated plexus (GP) sites were detected and ablated by using fractionated electrogram (FE)-based strategy. During baseline electrophysiological study, AA and PR intervals were calculated as 810 ms and 164 ms, respectively. Based on our ablation order, radiofrequency ablation (RFA) was started from the left inferior and left superior GPs, respectively. A significant vagal response with sinus pauses and atrioventricular (AV) block was detected during RFA. Ablation of the right superior GP caused a significant increase of sinus rate with continuing AV block. After completion of ablation on the right superior and inferior GPs, PR interval was still 164 ms although AA interval decreased to 640 ms. After RFA on the posteromedial left GP which provides mainly vagal innervation of AV node, PR interval and cycle length of sinus node were detected as 134 ms and 540 ms, respectively. Selective parasympathetic innervation principles of the sinus node and AV node were previously demonstrated. We described a case of successful parasympathetic denervation of the sinus node and AV nodes using CNA.

Usefulness of post-procedural heart rate response to predict syncope recurrence or positive head up tilt table testing after cardioneuroablation.

AIMS: Previous reports have suggested that cardioneuroablation (CNA) can be effective in reducing syncopal recurrences in patients with vasovagal syncope (VVS). This study assessed the efficacy of CNA in preventing a positive response to head-up tilt testing (HUT). METHODS AND RESULTS: This is a single-centre retrospective study reviewing prospectively collected data. Fifty-one consecutive patients with VVS were included in the study. After confirmation of >3 s asystole on HUT, all patients underwent CNA. Head-up tilt testing was repeated 1 month after CNA. The main outcome measures were recurrence of syncope episode and positive response on HUT. During a median follow-up period of 11 months (interquartile range 3-27 months), all but 3 (5.8%) of 51 patients were free of syncope. Repeated HUTs were negative in 44 (86.2%) patients. When patients with recurrent syncope were excluded, vasodepressor response was seen in three cases and cardioinhibitory response in one case, respectively. Cardioneuroablation caused significant and durable shortening of RR interval in all cases. This effect was significantly higher in patients without positive HUT responses. CONCLUSION: This pilot study shows that CNA can effectively prevent recurrent syncopal episodes in patients with refractory VVS. Head-up tilt testing seems as a valuable diagnostic tool not only to select suitable candidates and but also to evaluate success of CNA.

Fractionation mapping software to map ganglionated plexus sites during sinus rhythm.

Ablation of ganglionated plexuses (GPs) is a relatively new technique in patients with vasovagal syncope. Due to individual variation of GP settlement, reproducible GP detection methods are needed to during electrophysiologic study. In the present case, fractionation mapping software of Ensite system was tested to detect localization of GPs and first compared with previously validated fractionated electrograms based strategy.

Efficacy and Safety of Cryoballoon Ablation in Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction　- A Multicenter Study.

BACKGROUND: Second-generation cryoballoon (CB2)-based pulmonary vein isolation (PVI) has demonstrated encouraging results in the treatment of atrial fibrillation (AF). This study sought to assess data on the safety, efficacy and clinical success of CB2-based PVI in patients with heart failure (HF) and reduced ejection fraction (HFrEF).Methods and Results:CB2-based PVI was performed in 551 consecutive patients in 3 highly experienced EP centers. Patients with HF and LVEF ≤40% were included (HFrEF group, n=50/551, 9.1%). Data were compared with propensity score-matched patients without HF and preserved left ventricular EF (LVEF) (n=50, control group). The median LVEF was HFrEF: 37% (35, 40) and control: 55% (55, 55), P<0.0001. Major periprocedural complications were registered in 4/50 (8%, HFrEF group) and 3/50 (6%, control group), P=0.695. The 12-month freedom from AF recurrence was 73.1% (95% confidence interval (CI): 61-88, HFrEF group) and 72.6% (95% CI: 61-87, control group), P=0.25. NYHA class decreased from 2.4±0.8 (baseline) to 1.7±0.8 at 12-month follow-up (P<0.0001). LVEF improved from a median of 37% (35, 40) prior to ablation to a median of 55% (40, 55), P<0.0001. CONCLUSIONS: CB2-based PVI in patients with HFrEF appeared to be safe, was associated with comparable periprocedural complications and showed promising clinical success rates equal to those for patients with preserved LVEF. NYHA class and LVEF significantly improved at 12-month follow-up.

Mechanism, underlying substrate and predictors of atrial tachycardia following atrial fibrillation ablation using the second-generation cryoballoon.

BACKGROUND: Data regarding atrial tachycardia (AT) following second-generation cryoballoon ablation (CBA) of atrial fibrillation (AF) are limited. AIM: To describe the incidence, mechanisms, and clinical predictors of ATs following CBA. METHODS AND RESULTS: In this retrospective single-center study 238 patients undergoing CBA for treatment of paroxysmal (91/238; 38.2%) or persistent AF were analyzed. During a mean follow-up of 11.9 ± 5.5 months recurrence of AF occurred in 49/238 patients (20.6%) and AT in 27/238 (11.3%). Twenty-six patients with AT and 14 with AF only underwent a redo ablation. The prevailing mechanism of AT was macroreentry [typical atrial flutter (AFL) (n = 10), left atrial macroreentry (n = 14), focal left-AT (n = 2)]. Non-cavotricuspid-isthmus-dependent macroreentry right-AT was mapped and ablated in 3 patients after initial AFL ablation. In a multivariate regression model, persistent type of AF (HR = 3.3; CI = 1.2-9.4), cardiomyopathy (HR = 3.5; CI = 1.5-8.4), treatment with beta-blockers (HR = 0.3; CI = 0.1-0.6), and pulmonary vein-abnormality (HR = 4.6; CI = 2.1-10.4) were independent predictors of AT. Substrate analysis revealed a significantly higher number of low voltage areas in the left atrium in patients with left-AT in comparison to patients with AF recurrence only (2.0; IQR=2.0-4.0 vs. 0.5; IQR = 0.0-2.25; p = 0.005). CONCLUSION: In this study, AT after CBA occurred in 11.3% of patients with macroreentry being the prevalent mechanism. All patients with left-AT presented with low voltage areas in the left atrium, suggesting a more progressive underlying fibrotic disease in these patients.

What role might cardioneuroablation strategy have in syncope guidelines?

Vasovagal syncope (VVS) is the most common type of syncope. Although it is not related to an increase in mortality, recurrent syncope episodes may be disabling and reduce the quality of life. There are no optimal treatment strategies currently available, especially for the cardioinhibitory type of VVS. Cardioneuroablation (CNA) is a relatively novel technique that aims to eliminate vagal efferent output during VVS. The objective of this review was to explore the potential role of CNA strategy in syncope guidelines.