Su Wilber, Coulombe Nicolas, Kirchhof Nicole, Grassl Erin, Wittenberger Dan
Banner University Medical Center- Phoenix and University of Arizona, 755 E. McDowell Rd, 4th Floor, Phoenix, AZ, 85006, USA.
Medtronic CryoCath, Pointe-Claire, Canada.
J Interv Card Electrophysiol. 2018 Dec;53(3):293-300. doi: 10.1007/s10840-018-0346-y. Epub 2018 Apr 14.
Rigid time-based dosing protocol(s) currently used in the clinic for cryoballoon ablation of atrial fibrillation may be inadequate to guide the circumferential and transmural cryothermal energy transfer across the pulmonary vein (PV) and may result in injury to collateral tissues or electrical gaps between the PV and left atrium (LA).
A physiologic endpoint (e.g., acute time-to-PV isolation a.k.a. time-to-effect; TTE) may be effective in the determination of a transmural lesion formation and may allow for individualized ablation dosing across each PV.
Thirty PVs from 15 dogs were randomized into five dosing protocols, including (1) TTE + 60 s, (2) TTE + 90 s, (3) TTE + 120 s, (4) TTE + 150 s, and (5) 2 × 180 s. Ablations were conducted with a 23-mm second-generation cryoballoon, and TTE was assessed during a freeze by pacing from an inner balloon-lumen circular diagnostic catheter to a quadripolar diagnostic catheter in the coronary sinus. After ablation, animals were survived for 30 to 34 days, and repeat electrophysiology assessment of PV isolation was conducted after which animals were euthanized for gross anatomy and histological examination.
At study termination, efficacy endpoint evaluations were based on maintenance of PV electrical isolation, gross anatomy assessment of PV lesions, and histological examination of PVs. Five efficacy endpoint failures were noted, including the following: 1 PV in the TTE + 90 sec group; 2 PVs in the TTE + 120 sec group; 1 PV in the TTE + 150 s group; and 1 PV in the 2 × 180 s group. Regarding safety, one phrenic nerve injury was observed in the 2 × 180 s cohort. No other complications were observed.
In a canine model, effective PV isolation could be found even in the shortest duration dosing cohort (TTE + 60 s). One complication (phrenic nerve injury) was observed in the longest duration dosing group (2 × 180 s). Further studies will be required to correlate these results to a 28-mm cryoballoon (more commonly used in the cryoablation of a human LA); however, to date, this is the first reporting of a successful cryoablation using TTE + 60 s dosing (approximately 90 s total duration of freezing).
目前临床上用于房颤冷冻球囊消融的基于时间的刚性给药方案可能不足以指导跨肺静脉（PV）的圆周和透壁冷冻热能传递，可能会导致侧支组织损伤或肺静脉与左心房（LA）之间的电间隙。
生理终点（例如，急性肺静脉隔离时间，即起效时间；TTE）可能有助于确定透壁病变的形成，并可能允许对每个肺静脉进行个体化消融给药。
将15只犬的30个肺静脉随机分为五种给药方案，包括（1）TTE + 60秒，（2）TTE + 90秒，（3）TTE + 120秒，（4）TTE + 150秒，和（5）2×180秒。使用23毫米第二代冷冻球囊进行消融，并在冷冻过程中通过从球囊内腔圆形诊断导管向冠状窦中的四极诊断导管起搏来评估TTE。消融后，动物存活30至34天，然后进行重复电生理评估肺静脉隔离，之后对动物实施安乐死以进行大体解剖和组织学检查。
在研究结束时，疗效终点评估基于肺静脉电隔离的维持、肺静脉病变的大体解剖评估以及肺静脉的组织学检查。记录到5个疗效终点失败案例，包括：TTE + 90秒组中的1个肺静脉；TTE + 120秒组中的2个肺静脉；TTE + 150秒组中的1个肺静脉；以及2×180秒组中的1个肺静脉。关于安全性，在2×180秒队列中观察到1例膈神经损伤。未观察到其他并发症。
在犬模型中，即使在最短给药时间队列（TTE + 60秒）中也能实现有效的肺静脉隔离。在最长给药时间组（2×180秒）中观察到1例并发症（膈神经损伤）。需要进一步研究将这些结果与28毫米冷冻球囊（更常用于人类左心房冷冻消融）相关联；然而，迄今为止，这是首次报告使用TTE + 60秒给药（冷冻总时长约90秒）成功进行冷冻消融。
