Left atrial posterior wall isolation in conjunction with pulmonary vein isolation using cryoballoon for treatment of persistent atrial fibrillation (PIVoTAL): study rationale and design

Abstract

Background: There is growing evidence in support of pulmonary vein isolation (PVI) with concomitant posterior wall isolation (PWI) for the treatment of patients with symptomatic persistent atrial fibrillation (persAF). However, there is limited data on the safety and efficacy of this approach using the cryoballoon.

Objective: The aim of this multicenter, investigational device exemption trial (G190171) is to prospectively evaluate the acute and long-term outcomes of PVI versus PVI+PWI using the cryoballoon in patients with symptomatic persAF.

Methods: The PIVoTAL is a prospective, randomized controlled study ( ClinicalTrials.gov : NCT04505163) in which patients with symptomatic persAF refractory/intolerant to ≥ 1 class I-IV antiarrhythmic drug, undergoing first-time catheter ablation, will be randomized to PVI (n = 183) versus PVI+PWI (n = 183) using the cryoballoon in a 1:1 fashion. The design will be double-blind until randomization immediately after PVI, beyond which the design will transform into a single-blind. PVI using cryoballoon will be standardized using a pre-specified dosing algorithm. Other empiric ablations aside from documented arrhythmias/arrhythmias spontaneously induced during the procedure will not be permitted. The primary efficacy endpoint is defined as AF recurrence at 12 months, after a single procedure and a 90-day blanking period. Arrhythmia outcomes will be assessed by routine electrocardiograms and 7-14 day ambulatory electrocardiographic monitoring at 3, 6, and 12 months post-ablation.

Conclusion: The PIVoTAL is a prospective, randomized controlled trial designed to evaluate the outcomes of PVI alone versus PVI+PWI using the cryoballoon, in patients with symptomatic persAF. We hypothesize that PVI+PWI will prove to be superior to PVI alone for prevention of AF recurrence.

Keywords: Catheter ablation; Cryoablation; Cryoballoon; Persistent atrial fibrillation; Posterior wall isolation.

© 2020. Springer Science+Business Media, LLC, part of Springer Nature.

Figures

Fig. 1

The PV component. A A cardiac computed tomography scan image showing a posterior projection of the LA PW including the PVs and the tissue that lies between them, the so-called PV component (shaded area). B On the other hand, the “true” LA PW spans from the inferior border of the inferior PVs to the superior margin of the vestibule which represents the region surrounding the mitral valve orifice. Thus, in essence, the PV component (shaded area) represents the dome of the LA. LAA = LA appendage; LIPV = left inferior PV; LSPV = left superior PV; MV = mitral valve; RIPV = right inferior PV; RSPV = right superior PV

Fig. 2

Anatomic examinations of the LA PW and the PVs. A An artist’s rendition illustrating the orientation of the myofibrils of the LA PW and the PVs created based on histopathological examinations. As shown, circular muscular fibers arising from the main LA wall fibers (arrow) wrap around the PV ostia forming sphincter-like structures, whereas other fibers extend over the PVs as myocardial sleeves. Yet, no definite anatomic boundaries can be identified to clearly demarcate the PV ostia or antra from the remaining LA PW (Adopted from: Nathan H, et al. Circulation 1966;34:412–22). B A gross anatomic examination of the myofibrils that cover the LA PW and the PVs in the human, highlighting the same observations (Courtesy of: Becker AE). C–F Several cardiac computed tomographic scan images obtained in patients with AF, illustrating variations in LA/PV anatomy. Arguably, in most of these cases, the precise boundaries between the LA PW and the PVs remain rather obscure. LIPV = left inferior PV; LSPV = left superior PV; RIPV = right inferior PV; RSPV = right superior PV

Fig. 3

Techniques for ablation of the LA PW. A One technique involves a surgical approach using endoscopically delivered epicardial lesions. The catheter-based strategies include the “box” lesion (B) or direct LA PW ablation/“debulking” using point-by-point radiofrequency (C) or the cryoballoon (D). LAA = LA appendage; LIPV = left inferior PV; LSPV = left superior PV; MV = mitral valve; RFA, radiofrequency ablation; RIPV = right inferior PV; RSPV = right superior PV

Fig. 4

The limitation of the “box” lesion approach: 3-D electroanatomic maps demonstrating incomplete PWI. A When performing radiofrequency PWI using the “box” lesion approach, in many cases despite seemingly perfect/continuous lesion sets, pacing maneuvers from inside the “box” can result both in pace-capture inside the “box” region and 1:1 conduction to the LA (inset). Therefore, ablation within the “box” itself, within the mid-PW (B), is commonly required to achieve complete isolation of the “box” region (C). This has been attributed to the presence of epicardial connections on the PW. ESO = anatomical location of the esophagus; LIPV = left inferior PV; LSPV = left superior PV; RIPV = right inferior PV; RSPV = right superior PV

Fig. 5

A flowchart illustrating the study protocol in a step-by-step manner. Step1: At baseline, a cardioversion will be performed. Step 2: A pre-ablation 3-D voltage map will be created using a high-density mapping catheter, in sinus rhythm. Step 3: PVI using the cryoballoon will be performed guided by a pre-specified dosing algorithm. PVI will always be performed prior to PW ablation. Step 4: Randomization will be performed. If the subject is randomized to PVI + PWI, then PWI will be performed within the PV component using the cryoballoon in the described manner. Step 5: Following completion of PVI or PVI+PWI (as applicable), a repeat post-ablation 3-D voltage map will be created using the high-density mapping catheter once again in sinus rhythm. Cardioversion will be performed prior to mapping if AF were to recur. Step 6: Lastly, presence of PVI or PVI + PWI will be confirmed in sinus rhythm by way of 3-D mapping and high-output pacing maneuvers

Fig. 6

The pre-specified cryoballoon ablation dosing algorithm to guide PVI. Between 1 and 2 effective cryoapplications will be delivered to each PV, to achieve PVI. As illustrated, a single cryoapplication will be delivered to a PV if time-to-PVI (TT-PVI) measures ≤ 60 s (Route 1). The duration of the application will consist of TT-PVI + 2 min. If TT-PVI > 60 s but ≤ 90 s, an additional (second) application will be delivered to the same PV (Route 2). If TT-PVI cannot be achieved within 90 s, the cryoapplication will be terminated and the cryoballoon repositioned to achieve a suitable TT-PVI (Route 1 or 2). Lastly, if despite all efforts, TT-PVI can simply not be measured, an empiric 3-min followed by a 2-min cryoapplication will be delivered to the PV (Route 3)

Fig. 7

Cryoballoon ablation approaches to PVI versus PVI+PWI. 3-D electroanatomic voltage maps (CARTO, posterior projection) demonstrating post-cryoballoon PVI (A) and PVI+PWI (B) in patients with persAF. The maps confirm successful ablation of all 4 PVs (A) versus the 4 PVs and the LA PW in the region of the PV component (B). Areas shown in red correspond to a voltage < 0.1 mV and those in pink correspond to regions bearing normal voltage. LIPV = left inferior PV; LSPV = left superior PV; PVc = PV component; RIPV = right inferior PV; RSPV = right superior PV

Fig. 8

High-output pacing to evaluate PVI or PVI+PWI. A post-cryoballoon ablation 3-D electroanatomic voltage map (CARTO, posterior projection) illustrating 8 pre-specified PV/LA segments (1–8). In patients randomized to PVI alone, high-output pacing (> 10 mA) will be performed from segments 1 to 4. In those randomized to PVI+PWI, high-output pacing will be performed from segments 1 to 8. These LA segments include the following: 1 = left superior PV, 2 = left inferior PV, 3 = right superior PV, 4 = right inferior PV, 5 = left superior PV component, 6 = left inferior PV component, 7 = right superior PV component and 8 = right inferior PV component. LIPV = left inferior PV; LSPV = left superior PV; PVc = PV component; RIPV = right inferior PV; RSPV = right superior PV