Electrogram characteristics at successful cryoablation sites in slow-fast atrioventricular nodal reentrant tachycardia.

PURPOSE: Cryoablation is a safe alternative to radiofrequency (RF) ablation for slow-fast atrioventricular reentrant tachycardia (AVNRT); however, optimal electrogram parameters for site selection remain unknown. We retrospectively investigated local electrograms for slow pathway (SP) modification in cryoablation. METHODS: Forty-five consecutive patients with slow-fast AVNRT who underwent cryoablation using a 6-mm-tip catheter were enrolled. Electrogram parameters for sites of successful SP modification (success-sites) were investigated; these included the interval between atrial activation at His and the last deflection of SP potential, defined as the His(A)-SPP interval. In 8 patients, 3-dimensional mapping by multi-electrode catheter was performed pre-ablation for more detailed SP assessment. RESULTS: Twenty-seven of 45 patients had successful SP modification by 1 cycle of freeze-thaw-freeze cryoablation at a single site with a low amplitude and fragmented SP potential. Among a total of 76 cryoablation sites in all patients, the His(A)-SPP interval at success-sites (45 sites) was significantly longer than that at unsuccess-sites (31 sites) (86 ± 9 vs.78 ± 10 msec, p < 0.0001). The AV amplitude ratio was not significantly different between success-and unsuccess-sites (0.21 ± 0.22 vs.0.25 ± 0.23, p = 0.429). The cutoff value of the His(A)-SPP interval for successful cryoablation was 82 msec with a sensitivity of 0.67 and specificity of 0.71 (AUC: 0.739; 95%CI: 0.626-0.852; p < 0.0001). Three-dimensional mapping in all 8 patients showed that sites with the most delayed atrial activation and the last deflection of the fragmented SP potential within the Koch's triangle coincided with success-sites. CONCLUSION: A longer His(A)-SPP interval and fractionated SP potential were characteristics of successful cryoablation for SP modification in slow-fast AVNRT.

Long-term outcomes after second-generation cryoballoon ablation of paroxysmal atrial fibrillation - Feasibility of a single short freeze strategy without bonus applications.

BACKGROUND: A paucity of data exists about long-term outcomes after second-generation cryoballoon ablation (2nd-CBA), and the feasibility of short freeze strategies remains under debate. We assessed the long-term follow-up outcomes. METHODS: This study included 186 paroxysmal atrial fibrillation (PAF) patients (62 ± 11 years, 136 men) who underwent 2nd-CBAs with a 28-mm balloon and single 3-min freeze strategy without bonus applications. Fourteen-day consecutive monitoring was performed to detect early AF recurrences (ERAFs). RESULTS: Overall, 713/736(96.9%) PVs were isolated with CBs. The total number of applications/patient was 5.3 ± 1.5. The total procedure and fluoroscopic times were 79.9 ± 28.1 and 24.4 ± 14.2 min. Asymptomatic right phrenic nerve injury occurred in 11 patients, however, all recovered during the follow-up. A total of 76(41.7%) patients experienced ERAFs. During a median 45.0 [30.0-51.0] month follow-up, the single procedure AF freedom was 76.1, 73.5, 70.5, and 63.7% at 1, 2, 3, and 4 years, respectively. At a median of 7.0 [4.0-12.0] months after the initial procedure, 35 (18.8%) patients underwent second procedures, and 106/137 (77.4%) PVs were still isolated. The multiple procedure AF freedom was 91.7, 89.3, 86.8, and 81.3% at 1, 2, 3, and 4 years, respectively. A Cox's proportional hazards model determined that the presence of ERAF was associated with a greater risk of recurrence after the last procedure (Hazard ratio = 2.830; 95% confidence interval = 1.173-6.833; p = 0.021). The percentage of continuation of anticoagulation therapy after the initial procedure was 33.1, 23.5, 21.7, and 21.7% at 1, 2, 3, and 4 years, respectively. CONCLUSIONS: Our long-term follow-up data demonstrated the feasibility of a single short freeze strategy in PAF patients.

The mechanisms of recurrent atrial arrhythmias after second-generation cryoballoon ablation.

BACKGROUND: In patients with paroxysmal atrial fibrillation (PAF), 10%-15% of patients require repeat procedures after second-generation cryoballoon pulmonary vein isolation (CB-PVI). We sought to explore the mechanisms of recurrences after cryoballoon ablation. METHODS: The data of 122 PAF patients who underwent second procedures for recurrent arrhythmias 7.0 (4.0-12.0) months after the CB-PVI were analyzed. During second procedures, non-PV AF foci were explored with isoproterenol, adenosine, and repetitive cardioversions. RESULTS: In total, 378/487 (77.6%) PVs remained isolated, and reconnections were not observed in any PVs in 59 (48.4%) patients. PV reconnections were associated with recurrences in 38 (31.1%) patients, of whom 33 (86.8%) had reconnections of at least 1 upper PV. In 6 (4.9%) patients, non-PV AF foci were identified in the upper PV antra where cryoballoons cannot isolate but within the circumferential radiofrequency PVI line. Non-PV AF foci were identified in the superior vena cava, right atrial body, left atrial body, and atrial septum in 28 (23.0%), 18 (14.7%), 4 (3.3%), and 5 (4.1%) patients, respectively. Twelve (9.8%) patients had multiple non-PV AF foci. Four (3.3%), 3 (2.4%), and 8 (6.5%) patients underwent second procedures for atrioventricular nodal reentrant tachycardia, atrial flutter, and atrial tachycardias. During 16.0 (8.0-24.0) months of follow-up, freedom from any atrial arrhythmia at 1 year and 2 years after the second procedure was 79.2% and 60.6%. Nineteen (15.5%) patients had antiarrhythmic drug therapy at the last follow-up. CONCLUSIONS: Our study suggested that improvement in the upper PV PVI durability, eliminating arrhythmogenic superior vena cavae and coexisting atrial arrhythmias, and bonus cryoballoon applications at PV antra might improve the single procedure outcome in cryoballoon ablation.

Predictors of durable pulmonary vein isolation after second-generation cryoballoon ablation with a single short freeze strategy - Different criteria for the best freeze of the 4 individual PVs.

BACKGROUND: Parameters predicting the second-generation cryoballoon pulmonary vein isolation (CB-PVI) durability of each individual PV have not been investigated. OBJECTIVE: We explored the PVI durability predictors after left superior (LS), left inferior (LI), right superior (RS), and right inferior (RI) PV CB-PVI. METHODS: Data from 101 consecutive patients who underwent repeat procedures 7.0 [4.5-10.0] months after index cryoballoon procedures with single short freeze strategies were analyzed. RESULTS: Among 369 PVs successfully isolated by cryoballoons with mean freezing times of 207 s, 82/94 (87.2%) LSPVs, 78/93 (83.9%) LIPVs, 80/98 (81.6%) RSPVs, and 63/84 (75.0%) RIPVs were durable. In the remaining 25 PVs requiring touch-up ablation, 20 (83.3%) PVs had reconnections. In analyzing all PVs together, lower nadir balloon temperature, faster freezing speed (FS), slower thawing speed (TS), and shorter time-to-isolation were significantly associated with higher PVI durability, however, all parameters significantly differed among the 4 individual PVs (p < 0.0001). In individual analyses, for the LSPV, faster FS to -40 °C predicted higher PVI durability, but younger patients more likely had reconnections. For the LIPV, faster FS to -30 °C predicted higher PVI durability. For the RSPV, a lower nadir temperature, faster FS (to -30 and -40 °C), slower TS (to 0 and 15 °C), shorter time-to-isolation, and smaller PV diameter predicted higher PVI durability. For the RIPV, a slower TS (to 0 and 15 °C) predicted higher PVI durability. CONCLUSIONS: The durability of the CB-PVI was high even with a single short freeze strategy. The parameters predicting the PVI durability differed among the 4 PVs, suggesting that best freeze criterion should be considered separately for each of the 4 PVs.

Circulatory dynamics changes are an additional predictor of successful pulmonary vein isolation during cryoballoon ablation.

The association between circulatory dynamics changes during cryoballoon applications and a successful pulmonary vein isolation (PVI) is unknown. Seventy atrial fibrillation patients who underwent PVI with 28-mm second-generation cryoballoons and single 3-min freezes were included. Intra-procedural parameters including circulatory dynamics changes during cryoapplications, were compared between 113 successful applications (30 left superior PVs[LSPVs], 30 left inferior PVs[LIPVs], 25 right superior PVs[RSPVs], and 28 right inferior PVs[RIPVs]) and 47 failed applications (10 LSPVs, 9 LIPVs, 8 RSPVs, and 20 RIPVs). In all individual PVs, lower nadir balloon temperatures (MinTemps) and longer thawing times (ThawTimes) significantly predicted a successful PVI. In addition, greater systolic blood pressure drops following releasing the PV occlusion (SBP-drops) significantly predicted a successful right PV PVI, and longer elapse times during SBP-drops significantly predicted a successful RIPV PVI. Composite parameters incorporating MinTemps and ThawTimes, SBP-drops, and ThawTimes showed the highest area under the curve to predict a successful left PV (0.876 for LSPVs, 0.851 for LIPVs) and right PV (0.927 for RSPVs, 0.980 for RIPVs) PVI, respectively. If the ThawTime (≥ 30 s) and SBP-drop (≤ - 21 mmHg) cutoff values were achieved for the RIPVs, the positive predictive value was 100%. In contrast, if both criteria were not achieved for the RIPVs, the negative predictive value was 100%. In the second-generation cryoballoon PVI, the MinTemp and ThawTime were significantly associated with acute success for all four PVs. In addition, SBP-drops further improved the accuracy of predicting a successful right PV PVI, especially of the RIPV.

A case of bidirectional conduction block within the superior vena cava induced by cryoballoon pulmonary vein isolation.

A 53-year-old male underwent a pulmonary vein isolation (PVI) of atrial fibrillation (AF) with a second-generation cryoballoon (CB). Although the patient maintained sinus rhythm after the PVI, a superior vena cava (SVC) fibrillation was recorded by a circular-multipolar-electrode catheter positioned inside the SVC that suggested conduction block between the right atrium (RA)-SVC connection. An adenosine triphosphate intravenous injection induced a dormant reconnection of the SVC myocardial sleeve and converted sinus rhythm to an AF rhythm. This case demonstrated that a CB application for the isolation of a right superior pulmonary vein could induce an electrical conduction block between the RA-SVC connection.

Impact of electrical connections between ipsilateral pulmonary veins on the second-generation cryoballoon ablation procedure.

BACKGROUND: Electrical connections between ipsilateral pulmonary veins (PVs) have been reported histologically and electrophysiologically. This study investigated the impact of electrical connections between ipsilateral PVs on PV isolation using second-generation cryoballoons (CB2-PVI). METHODS: Five hundred eleven atrial fibrillation patients, without any PV anomalies, underwent CB2-PVI using one 28-mm balloon and a single 3-minute freeze strategy without any bonus applications. RESULTS: Overall, 1966 of 2044 (96.2%) PVs were isolated exclusively by using 28-mm cryoballoons. Among them, 13 left superior PV (LSPVs) and two right superior PV were not persistently isolated by the first application despite a complete vein occlusion, but were isolated by subsequent applications targeting other ipsilateral PVs. Among the 13 LSPVs, six were transiently isolated by 87 (62-146) second time-to-isolation LSPV applications, but were immediately reconnected after the application. The nadir balloon temperature during the LSPV application was similar between the 13 LSPVs not isolated by the LSPV application but were not so by subsequent left inferior PV (LIPV) applications and the 488 LSPVs persistently isolated by LSPV applications (-49.4℃ ± 4.3℃ vs -50.8℃ ± 5.1℃; P = 0.328). In 59 patients in whom the initial LSPV application failed despite a complete occlusion, LIPVs were targeted for the second applications in 31 patients, and both the LSPV and LIPV were simultaneously isolated in 13 of 31 (41.9%). CONCLUSIONS: Electrical connections between ipsilateral PVs could have an impact on the CB2-PVI procedure. When the vein isolation failed despite a complete occlusion, especially for left ipsilateral PVs, it was reasonable to target the other ipsilateral PV instead of repeatedly targeting the same vein.

Utility of low-dose adenosine triphosphate sensitivity in slow-fast atrioventricular nodal reentrant tachycardia.

PURPOSE: Low-dose adenosine triphosphate (LD-ATP) is useful for diagnosing ATP-sensitive atrial tachycardia. However, the clinical implications of the sensitivity of LD-ATP in atrioventricular nodal reentrant tachycardia (AVNRT) still remain unknown. This study aimed to evaluate the mechanism of LD-ATP sensitivity in slow-fast AVNRT. METHODS: We estimated the sensitivity of LD-ATP in slow-fast AVNRT by a 2-4-mg ATP intravenous injection during the tachycardia. We evaluated the atrial-His (A-H) interval, tachycardia termination mode, prevalence of a lower common pathway (LCP), and successful ablation site in slow-fast AVNRT with LD-ATP sensitivity. LCPs were defined as His-atrial interval differences of at least 5 ms between that during ventricular pacing at the tachycardia cycle length and that during the tachycardia. RESULTS: Twenty-eight patients (mean age = 58 ± 11 years old, 18 females) with slow-fast AVNRT, who underwent catheter ablation of the antegrade slow pathway, were enrolled. Seventeen of 28 (61%) patients had LD-ATP sensitivity defined as termination of the tachycardia and/or a prolongation of the A-H interval of over 30 ms after an LD-ATP injection. The patients with LD-ATP sensitivity had a significantly higher prevalence of an LCP than those without (15/17 vs0/11, P < 0.0001). The successful ablation site in the LD-ATP sensitive group was significantly closer to the His bundle area than that in the LD-ATP nonsensitive group (13.3 ± 3.8 vs 20.5 ± 5.4 mm; distance to His bundle area in the left anterior oblique fluoroscopic view, P < 0.0001). CONCLUSIONS: LD-ATP sensitivity in slow-fast AVNRT may suggest the existence of an LCP. The successful ablation site in patients with LD-ATP sensitivity could be closer to the His bundle region.

Atrioventricular conduction disturbance during pulmonary vein isolation using the second-generation cryoballoon - Vagal impact of cryoballoon ablation.

BACKGROUND: Vagal reactions of the sinus node during pulmonary vein isolation (PVI) have been reported, however, data on intra-procedural atrioventricular conduction disturbances have been sparse. The present study aimed to investigate the clinical characteristics of atrioventricular conduction block (AVB) during PVI using second-generation cryoballoons. METHODS: A total of 2252 PVs among 568 consecutive atrial fibrillation patients undergoing PVI with 28-mm cryoballoons were analyzed. In 44 patients, left superior PVs (LSPVs) were initially targeted (initial-LSPV-group). In the remaining 524 patients, LSPVs were targeted following right superior PVs (RSPVs) (initial-RSPV-group). RESULTS: Marked sinus arrests/bradycardia occurred in 14 patients only in the initial-LSPV-group, and the incidence was significantly higher in the initial-LSPV than initial-RSPV-group (14/44 vs. 0/524, p < 0.001). Intra-procedural AVB with 3.6 [1.9-8.2] second maximal RR intervals appeared in 12 patients during freezing (n = 1) or after balloon deflation following freezing (n = 11). The targeted PVs were the LSPV, left common PV, right inferior PV, and RSPV in 8, 1, 2, and 1 patients, respectively. The incidence was similar between the initial-LSPV and initial-RSPV-groups (1/44 vs. 11/524, p = 0.938). Four patients exhibited complete AVB with more than a 6 s maximal RR interval. Three patients experienced AVB during atrial fibrillation. AVB was observed a median of 23.0 [15.0-70.0] seconds after balloon deflation and 76.0 [60.0-125.0] seconds after freezing termination. AVB persisted for 56.0 [36.0-110.0] seconds, and all recovered spontaneously with or without requiring back-up pacing. CONCLUSIONS: A marked transient AV conduction disturbance could occur after balloon deflation, especially during LSPV ablation, regardless of the order of targeted PVs.

Persistence of an iatrogenic atrial septal defect after a second-generation cryoballoon ablation of atrial fibrillation.

Persistent iatrogenic atrial septal defects (iASDs) can be observed after intervention requiring a left atria (LA) access, including pulmonary vein isolation (PVI) of atrial fibrillation (AF). We investigated the incidence of iASDs post-second-generation cryoballoon ablation and the pre-procedural predictors. Eighty-three paroxysmal AF patients underwent PVI using second-generation cryoballoons. The LA was accessed with single 15-Fr steerable sheaths following a radiofrequency transseptal puncture, and the iASD was evaluated with transthoracic echocardiography (TTE), a median of 9.3 (7.1-13.3) months post-procedure. All patients underwent pre-procedural contrast-enhanced multi-detector computed tomography (CT) to evaluate the LA and PV anatomy. iASDs were detected by TTE in 7 (8.4%) patients, a median of 15.5 (6.8-17.3) months post-procedure. Patients with iASDs had significantly larger LA volumes and smaller atrial septal angles, defined as the angle between the atrial septum and sagittal line on the horizontal section at the height of the fossa ovalis, which could be the transseptal puncture site measured on CT, and more likely hypertension than those without. Multivariate analyses revealed that the atrial septal angle was the sole predictor of iASDs [odds ratio 0.764, 95% confidence interval (CI) 0.624-0.935, p = 0.009], and the optimal cut-off value was 57.5° (sensitivity 85.7%, specificity 88.2%, 95% CI 0.873-0.995, p < 0.0001). Patients with iASDs were asymptomatic and had no adverse clinical events during a 17.7 (14.4-25.8) month median follow-up. iASDs were still detectable in 8.4% of patients a median of 15.5 months after the second-generation CB ablation, and the atrial septal angle might aid in predicting persistent iASDs.

Characteristics of Phrenic Nerve Injury During Pulmonary Vein Isolation Using a 28-mm Second-Generation Cryoballoon and Short Freeze Strategy.

BACKGROUND: The reported incidence of phrenic nerve injury (PNI) varies owing to different definitions, balloon generations, balloon size, freezing regimen, and protective maneuvers. We evaluated the incidence, predictors, and outcome of PNI during cryoballoon pulmonary vein isolation in a large population. METHODS AND RESULTS: Five hundred fifty atrial fibrillation patients underwent pulmonary vein isolation using one 28-mm second-generation cryoballoon and single 3-minute freeze strategy under diaphragmatic compound motor action potential (CMAP) monitoring. A total of 34 (6.2%) patients experienced PNI during the right superior and inferior pulmonary vein ablation in 30 and 4 patients, respectively. Applications were interrupted using double-stop techniques after 136 [104-158] second applications, and a pulmonary vein isolation was already achieved in all but one case. The baseline CMAP amplitude and timing of deflation (CMAPdef) were 0.75±0.30 and 0.17±0.17 mV, respectively. Persistent atrial fibrillation, larger right superior pulmonary vein ostia, and deeper balloon positions were associated with higher incidences of PNI. The CMAPdef predicted a PNI recovery delay, and the best cutoff value for predicting PNI recovery by the next day was 0.20 mV (sensitivity 57.1%, specificity 100%). Among 6 patients undergoing second procedures 8.5 (6.7-15.0) months later, the right superior pulmonary vein was durable in 3 with >120 second applications. Despite active balloon deflation, no significant pulmonary vein stenosis was observed in 15 right superior pulmonary veins evaluated 6 (5-9) months later. No patients had symptoms, and the PNI recovered 1 day and 1 month postprocedure in 21 and 4 patients, respectively. CONCLUSIONS: PNI resulting from cryoballoon ablation was reversible. The double-stop technique is safe, and immediate active deflation following a CMAP decrease appears to be essential for faster PNI recovery.

Additional cryoapplications at the pulmonary vein antrum using a 28-mm second-generation cryoballoon: a pilot study of extra-pulmonary vein ablation.

Isolation areas post-28-mm cryoballoon pulmonary vein isolation (CB-PVI) are smaller than post-radiofrequency PV antrum isolation at the left superior PV (LSPV) antrum and recurrent atrial fibrillation (AF) can originate from this area. This pilot study evaluated the impact of additional extra-PV CB applications at the LSPV antrum following conventional CB-PVI. Eighteen paroxysmal AF patients underwent CB-PVI with single 3-min freeze techniques. Following the CB-PVI, 2-min CB applications were added once or twice at the LSPV antrum. Before and after extra-PV ablation, left atrial (LA) 3-D electroanatomical maps were created. Seventy-two total PVs were successfully isolated with 4.2 ± 0.4 applications/patient with 28-mm CBs. The mean LA posterior wall (LAPW) and non-isolated LAPW areas were 14.9 ± 3.6 and 6.9 ± 2.8 cm2, respectively. After 1.6 ± 0.5 mean extra-PV applications, the upper non-isolated LAPW area significantly decreased from 3.3 ± 1.8 to 2.5 ± 1.8 cm2 (p < 0.001). The lowest esophageal temperatures during the extra-PV ablation were 27 °C. The total procedure and fluoroscopic times were 72.8 ± 13.1 and 15.2 ± 5.9 min, respectively. Silent gastric hypomotility was detected in 2/9 patients 1 day later, and mild PV stenosis was observed in 4/72 PVs 3 months later, but did not progress. At 12-month after single procedures, 16 (88.9%) patients were free from recurrent AF off antiarrhythmic drugs. A median of 8.0 [6.0-10.0] months later, PV reconnections were detected in 3/12 (25.0%) PVs. The non-isolated LAPW area was significantly larger in the chronic than acute phase (14.3 ± 5.2 cm2, p = 0.016). This pilot study suggested the potential feasibility of additional LSPV antral cryoapplications following a conventional CB-PVI. The strategy warrants further study in more patients.

Thromboembolic Risks of the Procedural Process in Second-Generation Cryoballoon Ablation Procedures: Analysis From Real-Time Transcranial Doppler Monitoring.

BACKGROUND: Atrial fibrillation ablation is associated with substantial risks of silent cerebral events (SCEs) or silent cerebral lesions. We investigated which procedural processes during cryoballoon procedures carried a risk. METHODS AND RESULTS: Forty paroxysmal atrial fibrillation patients underwent pulmonary vein isolation using second-generation cryoballoons with single 28-mm balloon 3-minute freeze techniques. Microembolic signals (MESs) were monitored by transcranial Doppler throughout all procedures. Brain magnetic resonance imaging was obtained pre- and post-procedure in 34 patients (85.0%). Of 158 pulmonary veins, 152 (96.2%) were isolated using cryoablation, and 6 required touch-up radiofrequency ablation. A mean of 5.0±1.2 cryoballoon applications was applied, and the left atrial dwell time was 76.7±22.4 minutes. The total MES counts/procedures were 522 (426-626). Left atrial access and Flexcath sheath insertion generated 25 (11-44) and 34 (24-53) MESs. Using radiofrequency ablation for transseptal access increased the MES count during transseptal punctures. During cryoapplications, MES counts were greatest during first applications (117 [81-157]), especially after balloon stretch/deflations (43 [21-81]). Pre- and post-pulmonary vein potential mapping with Lasso catheters generated 57 (21-88) and 61 (36-88) MESs. Reinsertion of once withdrawn cryoballoons and subsequent applications produced 205 (156-310) MESs. Touch-up ablation generated 32 (19-62) MESs, whereas electric cardioversion generated no MESs. SCEs and silent cerebral lesions were detected in 11 (32.3%) and 4 (11.7%) patients, respectively. The patients with SCEs were older than those without; however, there were no significant factors associated with SCEs. CONCLUSIONS: A significant number of MESs and SCE/silent cerebral lesion occurrences were observed during second-generation cryoballoon ablation procedures. MESs were recorded during a variety of steps throughout the procedure; however, the majority occurred during phases with a high probability of gaseous emboli.

Circulatory Dynamics During Pulmonary Vein Isolation Using the Second-Generation Cryoballoon.

BACKGROUND: Circulatory dynamics change during pulmonary vein (PV) isolation using cryoballoons. This study sought to investigate the circulatory dynamics during cryoballoon-based PV isolation procedures and the contributing factors. METHODS AND RESULTS: This study retrospectively included 35 atrial fibrillation patients who underwent PV isolation with 28-mm second-generation cryoballoons and single 3-minute freeze techniques. Blood pressures were continuously monitored via arterial lines. The left ventricular function was evaluated with intracardiac echocardiography throughout the procedure in 5 additional patients. Overall, 126 cryoapplications without interrupting freezing were analyzed. Systolic blood pressure (SBP) significantly increased during freezing (138.7±28.0 to 148.0±27.2 mm Hg, P<0.001) and sharply dropped (136.3±26.0 to 95.0±17.9 mm Hg, P<0.001) during a mean of 21.0±8.0 seconds after releasing the occlusion during thawing. In the multivariate analyses, the left PVs (P=0.008) and lower baseline SBP (P<0.001) correlated with a larger SBP rise, whereas a higher baseline SBP (P<0.001), left PVs (P=0.017), lower balloon nadir temperature (P=0.027), and female sex (P=0.045) correlated with larger SBP drops. These changes were similarly observed regardless of preprocedural atropine administration and the target PV order. PV occlusions without freezing exhibited no SBP change. PV antrum freezing without occlusions similarly increased the SBP, but the SBP drop was significantly smaller than that with occlusions (P<0.001). The SBP drop time-course paralleled the left ventricular ejection fraction increase (66.8±8.1% to 79.3±6.7%, P<0.001) and systemic vascular resistance index decrease (2667±1024 to 1937±513 dynes-sec/cm2 per m2, P=0.002). CONCLUSIONS: With second-generation cryoballoon-based PV isolation, SBP significantly increased during freezing owing to atrial tissue freezing and dropped sharply after releasing the occlusion, presumably because of the peripheral vascular resistance decrease mainly by circulating chilled blood.

Chromosome 4q25 variants and recurrence after second-generation cryoballoon ablation in patients with paroxysmal atrial fibrillation.

BACKGROUND: Chromosome 4q25 single-nucleotide polymorphisms (SNPs) are associated with atrial fibrillation (AF) recurrence after radiofrequency catheter ablation, however the underlying mechanism is unknown. Pulmonary vein (PV) reconnections are common post-radiofrequency ablation. We explored the pre-procedural parameters, including AF susceptibility SNPs, predicting the response to PV isolation (PVI) using second-generation cryoballoons. METHODS: One hundred fifty-seven paroxysmal AF patients undergoing PVI using second-generation cryoballoons and genetic testing were enrolled. The top 6 AF-associated Japanese ancestry SNPs were evaluated. Fourteen-day consecutive monitoring was performed to detect AF recurrences. RESULTS: Early recurrence of AF (ERAF) was detected in 74(47.1%) patients, and the AF-free survival at 12-months after single procedures was 72.1%. Cox's proportional models determined that higher pro-BNP values (hazard ratio [HR]=1.001; 95% confidence interval [CI]=1.000-1.001; p=0.003) and the rs1906617 risk allele (HR=2.440; 95% CI=1.062-5.605; p=0.035) were independently associated with ERAFs, and the rs1906617 risk allele (HR=4.339; 95% CI=1.044-18.028; p=0.043) was the sole factor significantly associated with AF recurrence. Second procedures were performed in 41 patients a median of 6.0[5.0-9.5] months later, and 42/162(25.9%) PVs were reconnected. Reconnections were similarly observed in rs1906617 risk allele carriers and wild-type patients. Risk allele carriers at rs1906617 were more likely to have non-PV foci, but did not reach statistical significance (10/35 vs. 0/6, p=0.132). CONCLUSIONS: AF risk alleles on chromosome 4q25 modulated the risk of AF recurrence after PVI using second-generation cryoballoons in patients with paroxysmal AF. Our study results suggested that non-PV foci might be the more likely mechanism of a high AF recurrence in chromosome 4q25 variant carriers.

Autonomic nervous system modulation and clinical outcome after pulmonary vein isolation using the second-generation cryoballoon.

BACKGROUND: The intrinsic cardiac autonomic nervous system (ANS) plays a significant role in atrial fibrillation (AF) mechanisms. This study evaluated the incidence and impact of intraprocedural vagal reactions and ANS modulation by pulmonary vein isolation (PVI) using second-generation cryoballoons on outcomes. METHODS: One hundred three paroxysmal AF patients underwent PVI with one 28-mm second-generation balloon. The median follow-up was 15.0 (12.0-18.0) months. ANS modulation was defined as a >20% cycle length decrease on 3-minute resting electrocardiograms at 1, 3, 6, and 12 months postindex procedure relative to baseline if sinus rhythm was maintained. RESULTS: Marked sinus arrests/bradycardia and atrioventricular block (intraprocedural vagal reaction) occurred in 14 and 2 patients, and all sinus arrest/bradycardia occurred in 44 patients with left superior pulmonary veins (PVs) targeted before right PVs. ANS modulation was identified in 66 of 95 (69.5%) patients, and it persisted 12-month postprocedure in 36 (37.9%) patients. Additional ß-blocker administration was required in 9 patients for sinus tachycardia. ANS modulation was similarly observed in patients with and without intraprocedural vagal reactions (P = 0.443). Forty-eight (46.6%) patients experienced early recurrences, and the single procedure success at 12 months was 72.7%. Neither intraprocedural vagal reactions nor ANS modulation predicted AF freedom within or after the blanking period. Thirty-three patients underwent second procedures, and reconnections were detected in 39 of 130 (30.0%) PVs among 23 (69.7%) patients. The incidence of reconnections was similar in patients with and without ANS modulation. CONCLUSIONS: Increased heart rate persisted in 37.9% of patients even at 12-month post-second-generation cryoballoon PVI. Neither intraprocedural vagal reactions nor increased heart rate predicted a single procedure clinical outcome.

Validation of electrical ostial pulmonary vein isolation verified with a spiral inner lumen mapping catheter during second-generation cryoballoon ablation.

BACKGROUND: Achieve catheters are cryoballoon guidewires that enable pulmonary vein (PV) potential mapping. The single catheter approach in conjunction with the Achieve catheter is currently standard practice in second-generation cryoballoon ablation, yet circumferential mapping catheters are the gold standard for evaluating PV isolation (PVI). The study sought to validate the ostial PVI verified by an Achieve catheter alone. METHODS: One hundred fifty-one paroxysmal atrial fibrillation patients undergoing PVI using exclusively 28-mm second-generation cryoballoons were enrolled. PV recordings were analyzed during (real-time recordings) and after cryoballoon applications with 20-mm Achieve mapping catheters, and subsequently validated by 20-mm conventional circumferential mapping catheters. RESULTS: Out of 596 PVs, 576 (96.6%) were isolated using cryoballoons, and 20 required touch-up ablation. PVI was verified during cryoballoon applications with real-time monitoring in 299, and after applications in 280 PVs by Achieve catheters alone. The time-to-isolation was 27.2 ± 22.0 seconds. Validation with standard circumferential mapping catheters confirmed ostial PVIs in 296 of 299 (99.0%) PVs that real-time PVI was obtained during applications, and in 242 of 280 (86.5%) PVs that PV activities were not visible during applications and PVI was verified after the applications. The accuracy of ostial PVIs with Achieve catheters in PVs without obtaining real-time PV recordings was 40/47 (85.1%), 58/65 (89.2%), 77/79 (97.5%), 61/81 (75.3%), and 6/8 (75.0%) in left superior, left inferior, right superior, right inferior, and left common PVs, respectively. CONCLUSIONS: In second-generation 28-mm cryoballoon ablation, verification of ostial PVIs using Achieve mapping catheters alone might not be sufficient to accurately confirm an ostial PVI when real-time PVI was not obtained.

Gastric hypomotility after second-generation cryoballoon ablation-Unrecognized silent nerve injury after cryoballoon ablation.

BACKGROUND: Few data are available on gastric hypomotility (GH) after cryoballoon pulmonary vein isolation. Also, the use of esophageal temperature monitoring for the prevention of endoscopically detected esophageal lesions (EDELs) is not well established. OBJECTIVE: The purpose of this study was to investigate GH and the impact of an esophageal probe on EDELs during second-generation cryoballoon ablation. METHODS: One hundred four patients with paroxysmal atrial fibrillation undergoing second-generation cryoballoon ablation under conscious sedation followed by esophagogastroscopy were prospectively included. Temperature probes were used in the first 40 (38.5%) patients, but not in the latter 64 (61.5%). Pulmonary vein isolation was performed with one 28-mm balloon using single 3-minute freeze techniques. RESULTS: Clinical and procedural characteristics were similar between the groups. Esophagogastroscopy 1.4 ± 0.5 days postablation demonstrated GH and EDELs in 18 (17.3%) and 9 (8.7%) patients. The incidence of GH was similar (7 of 40 vs 11 of 64; P = .967) between the groups, while that of EDELs was significantly higher in the former than in the latter group (8 of 40 vs 1 of 64; P < .0001). In multivariate analyses, the esophagus-right inferior pulmonary vein ostium distance (hazard ratio 0.870; 95% confidence interval 0.798-0.948; P = .002) was the sole predictor of GH, and the optimal cutoff for the prediction was 18.2 mm (sensitivity 88.1%; specificity 77.8%). The use of esophageal probes was the sole predictor of EDELs (hazard ratio 15.750; 95% confidence interval 1.887-131.471; P = .011). All collateral damage was asymptomatic and healed on repeat esophagogastroscopy at a mean of 2 ± 1 months postprocedure. CONCLUSION: Second-generation cryoballoon ablation is associated with an increased incidence of silent periesophageal nerve injury even using short freeze times, and anatomical information aids identifying high-risk populations. The use of esophageal probes increases the risk of EDELs.