Impact of atrial rhythm on pulmonary vein signals in cryoballoon ablation - Sinus rhythm predicts real-time observation of pulmonary vein isolation.

PURPOSE: Real-time observation of pulmonary vein (PV) potentials with a spiral mapping catheter has emerged as a key electrogram-based procedural parameter to estimate lesion quality and titrate cryoenergy application during PV isolation (PVI) with the cryoballoon. Whether correct PV electrogram interpretation and thus PVI real-time observation rate depends on atrial rhythm during cryoballoon PVI is unknown. We compared observation rates of time-to PV isolation (TTI) during sinus rhythm (SR group) and during atrial fibrillation (AFib group) in cryoballoon PVI. METHODS: We prospectively included 157 consecutive patients undergoing cryoballoon PVI and compared the incidence of PVI real-time recording of each pulmonary vein during SR and in AFib. RESULTS: Overall PVI real-time observation rate was 82.1% (491/598 PV) with significantly higher TTI observation rate in the SR group (315/365 PV, 86.3%) compared to the AFib group (176/233 PV, 75.5%; p < 0.001). Per vein analysis demonstrated that only TTI observation rate in the left superior pulmonary vein (LSPV) was significantly higher during SR (85/92, 92.4%) compared to AFib (37/54, 68.5%; p < 0.001). Regression analysis revealed that atrial rhythm is a strong and independent predictor of PVI real-time observation in the LSPV with an odds ratio of 4.98 (95%-CI: 1.86-13.34, p = 0.001) to detect TTI during SR. CONCLUSIONS: Our results demonstrate that correct interpretation of PV electrograms and thus PVI real-time observation is more likely in SR than in AFib. Hence, cardioversion of patients in AFib at the beginning of the procedure should be considered to yield higher PVI real-time observation rates facilitating TTI guided cryoenergy titration.

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.

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.

Telmisartan inhibits CD4-positive lymphocyte migration independent of the angiotensin type 1 receptor via peroxisome proliferator-activated receptor-gamma.

Migration of CD4-positive lymphocytes into the vessel wall represents an important step in early atherogenesis. Telmisartan is an angiotensin type 1 receptor (AT1R) blocker with peroxisome proliferator-activated receptor (PPAR)-gamma-activating properties. The present study examined the effect of telmisartan on CD4-positive cell migration and the role of PPARgamma in this context. CD4-positive lymphocytes express both the AT1R and PPARgamma. Stimulation of CD4-positive lymphocytes with stromal cell-derived factor (SDF)-1 leads to a 4.1+/-3.1-fold increase in cell migration. Pretreatment of cells with telmisartan reduces this effect in a concentration-dependent manner to a maximal 1.6+/-0.7-fold induction at 10 mumol/L of telmisartan (P<0.01 compared with SDF-1-treated cells; n=22). Three different PPARgamma activators, rosiglitazone, pioglitazone, and GW1929, had similar effects, whereas eprosartan, a non-PPARgamma-activating AT1R blocker, did not affect chemokine-induced lymphocyte migration. Telmisartan's effect on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced phosphatidylinositol 3-kinase activity. Downstream, telmisartan inhibited F-actin formation, as well as intercellular adhesion molecule-3 translocation. Transfection of CD4-positive lymphocytes with PPARgamma small interfering RNA abolished telmisartan's effect on migration, whereas blockade of the AT1R had no such effect. Telmisartan inhibits chemokine-induced CD4-positive cell migration independent of the AT1R via PPARgamma. These data provide a novel mechanism to explain how telmisartan modulates lymphocyte activation by its PPARgamma-activating properties.