Acute Shrinkage of the Pulmonary Vein Ensuing From Radiofrequency and Cryoablations1

Over 5 × 106 Americans are currently affected by atrial fibrillation (AF), and as the population continues to age the incidence is expected to rise 2.5 fold by 2050 [1]. Radiofrequency (RF) and cryoablation are routinely used to treat AF to hopefully be a curative treatment. Yet, development of pulmonary vein (PV) stenosis is facilitated following cardiac ablation procedures. Although it is frequently asymptomatic, it may become a potentially life threatening condition: as the degree of stenosis escalates typically the severities of symptoms increase as well.Noteworthy in one study, 15.6% (3.4% severe, 4.4% moderate, and 7.7% mild PV stenosis) of patients were reported to develop PV narrowing 3.5 months after RF ablation procedures; it was considered that PV stenosis progression subsides 3 months following ablation procedures [2]. However, it has also been reported that 2 yr following RF ablation, up to 28% of patients are affected by PV stenosis and/or occlusion. Furthermore, it is important to acknowledge that distal ablations inside the PVs compared to ostial ones were associated with over a fivefold increase in the development of stenosis [3]. In cryoablation procedures, PV stenosis incidence rates were 3.1%, and it has been suggested that cryoablation is less likely to elicit stenosis compared to RF ablation [4]. Clearly, a concerning portion of AF treated patients develops PV stenoses. There have been several chronic studies examining this phenomenon. However, this study aims to investigate the development of stenosis in the distal and ostial PVs on an acute time scale using translational approaches to understand and reduce its occurrence.Fresh PV samples from Yorkshire Cross swine (n = 25) were carefully dissected into 1 cm2 squares and the orientation relative to the PV anatomy was noted. Human tissue (n = 3) acquired from nonviable organ transplant donors through our local organ procurement organization LifeSource (St. Paul, MN) was also used. PV specimens were sorted into ostia and 1 cm distal to the ostia groups.Four sutures were attached to each side of the PV samples, and they were subsequently mounted in a biaxial testing machine (Fig. 1). Each specimen was used as its own control in this experimental paradigm. Samples were subjected to five preconditioning cycles of 10% strain initially, stretched to 20% strain, thus mimicking changes associated with normal physiological function, and then a randomized ablation modality of RF or cryoablation was applied tangentially (Fig. 2). RF ablation was applied employing a 7 Fr Marinr® catheter (Medtronic, Minneapolis, MN) using 25 W with a 65 °C temperature limit for 1 min. Cryoablation was applied with a Freezer Max catheter (Medtronic, Minneapolis, MN) for 2 min. The resulting stresses in the axial and circumferential directions were measured for 6 and 3 min following the ablation.Normalized resultant circumferential stresses following the ablations were significantly different in the distal RF ablation group compared to the nontreatment controls for the porcine PV tissues as shown in Fig. 3 (p < 0.05). Cryoablation was significantly different immediately following the ablation, but this effect subsided following ice thaw. Of note, there was a trend in reduced circumferential stresses between the human RF ostia and swine RF ostia groups following ablation as shown in Fig. 4 (p = 0.07). However, significance was not achieved likely due to the limited available human samples utilized in this study. Importantly, this trend was not observed with the swine tissue. There were no noteworthy findings in the axial domain. Interestingly, a number of the results discussed herein support clinical observations and fall in agreement with similar in vitro investigations.In the circumferential direction, cryo energies initially significantly increased the stresses associated with the presence of ice, but following thaw the stresses remained only somewhat elevated. It is considered that cryoablation causes the realignment of fibers, dehydration of tissues, yet leaves the extracellular matrix intact. Also, it shifts the stress–strain relationship resulting in higher stresses in physiological ranges [5]. Our study used a strain of 20% and then we observed similar stress behaviors following cryoablation. In contrast, RF ablations induced significant increase in stresses that were sustained. RF ablation therapy is considered to: (1) denature structural proteins, (2) cause a loss of compliance, and (3) induce shifts of stress strain curve [6]. These described phenomena with RF ablation were observed in our studies for both the porcine and human tissue samples investigated.It is suggested that such increases in induced tissue stresses and loss of PV compliances, which occurs following ablations, likely initiates the development of PV stenosis in patients. Importantly, cryoablation is less likely to facilitate the development of stenoses compared to RF ablation [2,4]. We observed here, that although both ablation modalities increased circumferential stresses following treatment, only RF was significantly different compared to the nontreatment controls. These data may support the supposition that following an ablation procedure the increased stress state leads to a greater likelihood of PV stenosis development.Here, we also noted that the ostia and more distal ablations of the PV also provoked interesting insights. Minimal circumferential stress changes were induced for the swine ostia versus more distal PV tissue, however, there were differences for the human tissue. In the swine model, there is a distinct transition from muscular atrial to PV tissue, whereas in the human anatomy this transition lacks a clear demarcation and muscular tissue typically extended partially into the PV. In this experimental paradigm, swine tissue appeared uniform in both location groups while human tissue was not. Further studies are needed to investigate the discrepancy of the swine model as it relates to the human patient populations of interest: a translational approach is essential for investigations of underlying mechanisms. This data are particularly novel since it addresses anatomical differences between species and circumferential stress changes as it relates to clinical ablation complications. RF and cryoablations cause an increase in circumferential stresses that may potentially spark the developments of PV stenoses.