Lessons from individualized cryoballoon sizing. Is there a role for the small balloon?

BACKGROUND: Cryoablation for paroxysmal atrial fibrillation (PAF) is well established. The single-big-balloon strategy has been preferred for pulmonary vein isolation (PVI) using the second generation cryoballoon (CBG2). Individual PV-morphologies raise the question if an individualized anatomic approach using the 23-mm or 28-mm CB is reasonable. METHODS: Consecutive patients were prospectively enrolled in the non-randomized single-center study. Patients were treated with the 28-mm CB, if any PV was >21mm, the 23-mm CB, if all PV were ≤21mm, or both sizes, if PVI was difficult. The primary endpoint was arrhythmia-free survival. The secondary endpoint considered procedural results and complications. RESULTS: Overall, 197 patients with symptomatic PAF (64±11 years, 36% female) were included. Acute PVI was achieved in 99.9% of PV. Based on preprocedural imaging, the 28-mm CB was applied as the primary catheter in 47% (92/197 patients), the 23-mm CB in 53% (105/197, p=0.23). The 23-mm CB group included more females, patients with short left atrial (LA)-diameters (each p<0.01), and smaller patients (p=0.04). Both CB-sizes were used in 24% (47/197). Additional 23-mm CB usage was necessary in 23% (21/92) of patients, mainly because of insufficient PV-occlusion with the 28-mm CB. Additional 28-mm CB usage was necessary in 25% (26/105, p=0.82), mainly because PV diameters were larger than initially measured. Both CB-sizes were equally safe and effective with a low complication rate and an overall success rate of 86% at 12 and 71% at 18 months (6% on antiarrhythmic drugs). No predictors for AF-recurrence were identified. CONCLUSION: CB ablation can sometimes be challenging. The 28-mm CB is the preferred catheter in all patients. If balloon positioning is difficult, the 23-mm CB is an option to achieve PVI in small veins. Further studies need to investigate if the 23-mm CB could be beneficial as the primary CB in females with small body height and short LA diameter.

Cryoballoon ablation for persistent atrial fibrillation - Large single-center experience.

BACKGROUND: Different catheter ablation (CA) strategies have been established in the treatment of persistent atrial fibrillation (persAF). Pulmonary vein isolation (PVI) only might be an option for the initial ablation procedure. There is a paucity of outcome data on second-generation cryoballoon (CBG2) PVI in persAF. METHODS: Patients with symptomatic drug-refractory persAF who underwent initial CA of AF were prospectively enrolled and PVI was performed with CBG2. The primary composite endpoint was freedom from AF, atrial tachycardia, or related symptoms after a 3-month blanking period. The secondary endpoint referred to periprocedural complications. RESULTS: One hundred seventy-three consecutive patients (64±10 years, 29% female) with symptomatic drug-refractory persAF were identified. Acute PVI was achieved in 100% of pulmonary veins with the CB technique. The left atrial procedure time was 112±30min. Major complications occurred in 1.7% (3 of 173 patients) including two phrenic nerve palsies (1%), which resolved until discharge, and one pericardial effusion (0.6%). Follow-up ≥12 months was completed for 157 of 173 patients (91%). Median follow-up was 14 months. At 12 months, the primary composite endpoint was achieved in 129 of 157 patients (82%). However, 22 of 129 patients at risk (17%) were still on antiarrhythmic drugs. A relapse during the blanking period was identified as the only independent predictor for AF recurrence. CONCLUSION: PVI using the second-generation cryoballoon is a reasonable treatment option for patients with symptomatic drug-refractory persAF with a favorable rate of freedom from AF and a low complication rate.

Outcome of paroxysmal atrial fibrillation ablation with the cryoballoon using two different application times: the 4- versus 3-min protocol.

PURPOSE: The second-generation cryoballoon (CBG2) is highly effective for pulmonary vein isolation (PVI) in paroxysmal atrial fibrillation (PAF). One-year outcome data are consistent among different research groups. First results suggest that a shortened application time might be equally effective. The objective of the study was to compare procedural and outcome data for a 240 and 180-s protocol. METHODS: Prospectively, consecutive patients with symptomatic PAF underwent initial PVI with CBG2. In succession, two groups were created: the application time was 240 s in group 1 and 180 s in group 2. In both groups, a bonus application was applied. Periprocedural data, complications, and freedom from atrial fibrillation (AF)/AT/symptoms were compared between the groups. RESULTS: From May 2012 to June 2013, 114 patients (57 per group, 38% female) were included. The mean left atrial dwelling time decreased by 19 min (-16%) in group 2 compared to group 1 (p = 0.005). Intraprocedural pulmonary vein (PV) reconduction occurred infrequently (0.4% in both groups, p = 1.0). One persistent PNP occurred and resolved during the follow-up. Complications were without significant differences. One patient was lost to follow-up. The cumulative rates of freedom from recurrence at 12 months are 76.8% in group 1 and 83.6% in group 2. After a mean follow-up of 491 ± 208 days, the rates of freedom from AF/AT/symptoms at last visit were 38/57 (67%) and 44/56 (78.6%) in groups 1 and 2 (p = 0.14), respectively. Female sex was identified as a predictor for recurrence. CONCLUSIONS: Compared to a protocol with cryoballoon applications of 240 s, a shortened application time to 180 s results in a faster procedure with comparable high rates of freedom from AF at 16 months. Female sex seems to be predictive for recurrences; this finding has to be reconfirmed in a larger population.

Expression Profile of Sonic Hedgehog Pathway Members in the Developing Human Fetal Brain.

The Sonic Hedgehog (SHH) pathway plays a central role in the developing mammalian CNS. In our study, we aimed to investigate the spatiotemporal SHH pathway expression pattern in human fetal brains. We analyzed 22 normal fetal brains for Shh, Patched, Smoothened, and Gli1-3 expression by immunohistochemistry. In the telencephalon, strongest expression of Shh, Smoothened, and Gli2 was found in the cortical plate (CP) and ventricular zone. Patched was strongly upregulated in the ventricular zone and Gli1 in the CP. In the cerebellum, SHH pathway members were strongly expressed in the external granular layer (EGL). SHH pathway members significantly decreased over time in the ventricular and subventricular zone and in the cerebellar EGL, while increasing levels were found in more superficial telencephalic layers. Our findings show that SHH pathway members are strongly expressed in areas important for proliferation and differentiation and indicate a temporal expression gradient in telencephalic and cerebellar layers probably due to decreased proliferation of progenitor cells and increased differentiation. Our data about the spatiotemporal expression of SHH pathway members in the developing human brain serves as a base for the understanding of both normal and pathological CNS development.

Elevated HLA-E levels in human glioblastomas but not in grade I to III astrocytomas correlate with infiltrating CD8+ cells.

HLA-E is a ligand for the immune-inhibitory NKG2A receptor expressed on NK and T cells. To investigate HLA-E expression and immune cell infiltration in human astrocytic tumors in vivo, we analyzed normal CNS controls and astrocytomas of all WHO grades by immunohistochemistry. Both, CD8(+) immune cell infiltration and HLA-E expression were significantly higher in astrocytic tumors than in normal brain. Further, HLA-E expression levels and immune cell infiltration were significantly correlated in WHO grade IV glioblastomas. Thus, HLA-E overexpression in glioblastomas may be triggered by T and NK cell infiltration.