Anson M. Lee

Vagal Denervation and Reinnervation after Ablation of Ganglionated Plexi

OBJECTIVE Surgical ablation of ganglionated plexi has been proposed to increase efficacy of surgery for atrial fibrillation. This experimental canine study examined electrophysiologic attenuation and recovery of atrial vagal effects after ganglionated plexi ablation alone or with standard surgical lesion sets for atrial fibrillation. METHODS Dogs were divided into 3 groups: group 1 (n = 6) had focal ablation of the 4 major epicardial ganglionated plexi fat pads, group 2 (n = 6) had pulmonary vein isolation with ablation, and group 3 (n = 6) had posterior left atrial isolation with ablation. All fat pads were ablated. Sinus and atrioventricular interval changes during bilateral vagosympathetic trunk stimulation were examined before and both immediately and 4 weeks after ablation. Vagally induced effective refractory period changes and mean QRST area changes (index of local innervation) were examined in 5 atrial regions. RESULTS Sinus and atrioventricular interval changes and heart rate variability decreased immediately after ablation, but only sinus interval changes were restored significantly after 4 weeks in all groups. Ablation-modified vagal effects on effective refractory period or QRST area changed heterogeneously in groups 1 and 2. In group 3, regional vagal effects were attenuated extensively postablation in both atria. Posterior left atrial isolation with ablation incrementally denervated the atria. In the long term, vagal stimulation increased QRST area changes relative to control values in all groups. Heart rate variability was also assessed. CONCLUSIONS Ganglionated plexi ablation significantly reduced atrial vagal innervation. Restoration of vagal effects at 4 weeks suggests early atrial reinnervation.

Atrial fibrillation propagates through gaps in ablation lines: Implications for ablative treatment of atrial fibrillation

BACKGROUND It has been hypothesized that atrial lesions must be transmural to successfully cure atrial fibrillation (AF). However, ablation lines often do not extend completely across the atrial wall. OBJECTIVE The purpose of this study was to determine the effect of residual gaps on conduction properties of atrial tissue. METHODS Canine right atria (n = 13) were isolated, perfused, and mounted on a 250-lead electrode plaque. The atria were divided with a bipolar radiofrequency ablation clamp, leaving a gap that was progressively narrowed. Conduction velocities at varying pacing rates and AF frequencies were measured before and after ablations. AF was induced with an extra stimulus and acetylcholine. RESULTS Gap widths from 11.2 to 1.1 mm were examined. Conduction velocities through gaps were dependent cycle length (P = .002) and gap size (P <.001). Overall, 253 (97%) of a total of 260 gaps allowed paced propagation; 51 (91%) of 56 gaps 1-3 mm in width permitted paced propagation, as did 202 (99%) of 204 gaps >or=3.0 mm. Similarly, 253 (97%) of a total of 260 gaps allowed propagation of AF. For AF, 51 (93%) of 55 gaps 1-3 mm allowed AF to pass through, as did 202 (99%) of 205 gaps >or=3.0 mm. Gaps as small as 1.1 mm conducted paced and AF impulses. CONCLUSIONS Conduction velocities were slowed through residual gaps. However, propagation of wave fronts during pacing and AF occurred through the majority of residual gaps, down to sizes as small as 1.1 mm. Leaving viable tissue in ablation lines for the treatment of AF could account for failures.

Animal studies of epicardial atrial ablation

The Cox maze procedure is an effective treatment of atrial fibrillation, with a long-term freedom from recurrence greater than 90%. The original procedure was highly invasive and required cardiopulmonary bypass. Modifications of the procedure that eliminate the need for cardiopulmonary bypass have been proposed, including use of alternative energy sources to replace cut-and-sew lesions with lines of ablation made from the epicardium on the beating heart. This has been challenging because atrial wall muscle thickness is extremely variable, and the muscle can be covered with an epicardial layer of fat. Moreover, the circulating intracavitary blood acts as a potential heat sink, making transmural lesions difficult to obtain. In this report, we summarize the use of nine different unidirectional devices (four radiofrequency, two microwave, two lasers, one cryothermic) for creating continuous transmural lines of ablation from the atrial epicardium in a porcine model. We define a unidirectional device as one in which all the energy is applied by a single transducer on a single heart surface. The maximum penetration of any device was 8.3 mm. All devices except one, the AtriCure Isolator pen, failed to penetrate 2 mm in some nontransmural sections. Future development of unidirectional energy sources should be directed at increasing the maximum depth and the consistency of penetration.

The Surgical Treatment of Atrial Fibrillation

Atrial fibrillation is a complex disease affecting a significant portion of the general population. Although medical therapy is the mainstay of treatment, intervention plays an important role in selected patients. The Cox-Maze procedure is the gold standard for the surgical treatment of atrial fibrillation and has more than 90% success in eliminating atrial fibrillation. Ablation technologies have played a key role in simplifying this technically demanding procedure and making it available to more patients. A myriad of new lesion sets and approaches were introduced over the last decade which has made the operative treatment of atrial fibrillation less invasive and more confusing.

Importance of atrial surface area and refractory period in sustaining atrial fibrillation: Testing the critical mass hypothesis

OBJECTIVE The critical mass hypothesis for atrial fibrillation (AF) was proposed in 1914; however, there have been few studies defining the relationship between atrial surface area and AF. This study evaluated the effect of tissue area and effective refractory period (ERP) on the probability of sustaining AF in an in vivo model. METHODS Domestic pigs (n = 9) underwent median sternotomy. Epicardial activation maps were constructed from bipolar electrograms recorded from form-fitting electrode templates placed on the atria. Baseline ERPs were determined. ERP was lowered with a continuous infusion of acetylcholine (0.005-0.04 mg/Kg/min) until AF could be sustained after burst pacing. The atria were sequentially partitioned using bipolar radiofrequency ablation. ERPs were lowered using acetylcholine until AF could be sustained in each subdivision of atrial tissue. Each subdivision was further divided until AF was no longer inducible. At study completion, the heart was excised and the surface area of each section was measured. RESULTS Over a range of ERPs from 75 to 250 ms, the probability of AF was correlated with increasing tissue area (range, 19.5-105 cm(2)) and decreasing ERP. Logistic regression analysis identified shorter ERP (P < .001) and larger area (P = .006) as factors predictive of an increased probability of sustained AF (area under the curve of the receiver-operator characteristic = 0.878). CONCLUSIONS The probability of sustained AF was significantly associated with increasing tissue area and decreasing ERP. These data may lead to a greater understanding of the mechanism of AF and help to design better interventional procedures.

Differential calcium handling in two canine models of right ventricular pressure overload

BACKGROUND The purpose of this investigation was to characterize differential right atrial (RA) and ventricular (RV) molecular changes in Ca(2+)-handling proteins consequent to RV pressure overload and hypertrophy in two common, yet distinct models of pulmonary hypertension: dehydromonocrotaline (DMCT) toxicity and pulmonary artery (PA) banding. METHODS A total of 18 dogs underwent sternotomy in four groups: (1) DMCT toxicity (n = 5), (2) mild PA banding over 10 wk to match the RV pressure rise with DMCT (n = 5); (3) progressive PA banding to generate severe RV overload (n = 4); and (4) sternotomy only (n = 4). RESULTS In the right ventricle, with DMCT, there was no change in sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) or phospholamban (PLB), but we saw a trend toward down-regulation of phosphorylated PLB at serine-16 (p[Ser-16]PLB) (P = 0.07). Similarly, with mild PA banding, there was no change in SERCA or PLB, but p(Ser-16)PLB was down-regulated by 74% (P < 0.001). With severe PA banding, there was no change in PLB, but SERCA fell by 57% and p(Ser-16)PLB fell by 67% (P < 0.001). In the right atrium, with DMCT, there were no significant changes. With both mild and severe PA banding, p(Ser-16)PLB fell (P < 0.001), but SERCA and PLB did not change. CONCLUSIONS Perturbations in Ca(2+)-handling proteins depend on the degree of RV pressure overload and the model used to mimic the RV effects of pulmonary hypertension. They are similar, but blunted, in the atrium compared with the ventricle.

Chronic performance of a novel radiofrequency ablation device on the beating heart: Limitations of conduction delay to assess transmurality

OBJECTIVE The creation of consistently transmural lesions with epicardial ablation on the beating heart has represented a significant challenge for current technology. This study examined the chronic performance of the AtriCure Coolrail device (AtriCure Inc, West Chester, Ohio), an internally cooled, bipolar radiofrequency ablation device designed for off-pump epicardial ablation. The study also examined the reliability of using acute intraoperative conduction delay to evaluate lesion integrity. METHODS Seven swine underwent median sternotomy. The right atrial appendage and inferior vena cava were isolated with a bipolar radiofrequency clamp. Linear ablation lines were created between these structures with the AtriCure Coolrail. Paced activation maps were recorded with epicardial patch electrodes acutely before and after ablation and after keeping the animals alive for 4 weeks. The conduction time across the linear ablation was calculated from these maps. The lesions were histologically evaluated with trichrome staining. RESULTS Only 76% of cross-sections of Coolrail lesions were transmural, and only 1 of 12 ablation lines was transmural in every cross-section examined. Mapping data were available in 5 of the animals. Significant conduction delay was present after the creation of each line of ablation acutely; however, after 4 weeks, conduction time returned to preablation values, demonstrating lack of transmurality. CONCLUSIONS The AtriCure Coolrail failed to reliably create transmural lesions. Although the Coolrail was able to create acute conduction delay, its failure to transmurally ablate the atrial myocardium left gaps along the length of the lesion, which resulted in neither chronic conduction block nor delay across any line of ablation.

Quantification of the functional consequences of atrial fibrillation and surgical ablation on the left atrium using cardiac magnetic resonance imaging.

OBJECTIVES The effect of atrial fibrillation (AF) on left atrial (LA) function has not been well defined and has been largely based on limited echocardiographic evaluation. This study examined the effect of AF and a subsequent Cox-Maze IV (CMIV) procedure on atrial function. METHODS Cardiac magnetic resonance imaging (cMRI) was performed in 20 healthy volunteers, 8 patients with paroxysmal atrial fibrillation (PAF) and 7 patients with persistent or long-standing persistent atrial fibrillation (LSP AF). Six of the PAF patients underwent surgical ablation with the CMIV procedure and 5 underwent both pre- and postoperative cMRIs. The persistent or LSP AF patients underwent only postoperative cMRIs because all scans were performed with patients in normal sinus rhythm. Volume-time curves throughout the cardiac cycle and regional wall shortening were evaluated using the cine images and compared across groups. RESULTS Compared with normal volunteers, patients with PAF had significantly decreased reservoir contribution to left ventricular (LV) filling (P = 0.0010), an increased conduit function contribution (P = 0.04) and preserved booster pump function (P = 0.14). Following the CMIV procedure, significant reductions were noted with respect to reservoir and booster pump function, with corresponding increases in conduit function. These differences were more drastic in patients with persistent/LSP AF. Regional wall motion was significantly reduced by PAF in all wall segments (P < 0.05), but was not further reduced by the CMIV. Despite changes in LA function, LV function was preserved following surgery. CONCLUSIONS PAF significantly altered LA function and has a detrimental effect on regional wall motion. Surgical intervention further altered LA function, but the reasons for this are likely multifactorial and not entirely related to the lesion set itself.

Evaluation of a novel cryoablation system: in vivo testing in a chronic porcine model.

ObjectiveCryoablation is commonly used at present in the surgical treatment of atrial fibrillation (AF). However, there have been few studies examining the efficacy of the commonly used ablation devices. This report compares the efficacy of two cryoprobes in creating transmural endocardial lesions on the beating heart in a porcine model for chronic AF. MethodsIn six Hanford miniature swine, the right atrial appendage and the inferior vena cava were isolated using a bipolar radiofrequency clamp to create areas of known conduction block. A connecting ablation line was performed endocardially via a purse string with the novel malleable 10-cm Cryo1 probe for 2 minutes at −40°C. Additional ablation lines were created with the Cryo1 and the 3.5-cm 3011 Maze Linear probe on the right and the left atrial wall. Epicardial activation mapping was performed before and immediately after ablation as well as 14 days postoperatively. Histologic examination was performed 14 days postoperatively. ResultsTransmural lesions were confirmed in 83/84 cross-sections (99%) for the Cryo1 probe and in 40/41 cross-sections (98%) for the 3011 Maze Linear probe. There was no difference between the devices in lesion width (mean ± SD, Cryo1, 10.7 ± 3.5 mm; 3011, 10.0 ± 3.9 mm; P = 0.31), lesion depth (Cryo1, 4.5 ± 1.7 mm; 3011, 4.6 ± 1.5 mm; P = 0.74), or atrial wall thickness (Cryo1, 4.5 ± 1.8 mm; 3011, 4.7 ± 1.7 mm; P = 0.74). There was a conduction delay across the right atrial ablation line (20 ± 2 milliseconds vs 51 ± 8 milliseconds, P < 0.001) that remained unchanged at 14 days (51 ± 8 milliseconds vs 52 ± 10 milliseconds, P = 0.88). ConclusionsThe Cryo1 probe created transmural lesions on the beating heart, resulting in sustained conduction delay. Both probes had a similar performance in lesion geometry in this chronic animal model.

Dose Response Curves for Microwave Ablation in the Cardioplegia-Arrested Porcine Heart

INTRODUCTION Microwave ablation has been used clinically for the surgical treatment of atrial fibrillation, particularly during valve procedures. However, dose- response curves have not been established for this surgical environment. The purpose of this study was to examine dosimetry curves for the Flex 4 and Flex 10 microwave devices in an acute cardioplegia-arrested porcine model. METHODS Twelve domestic pigs (40-45 kg) were acutely subjected to Flex 4 (n = 6) and Flex 10 (n = 6) ablations. On a cardioplegically arrested heart maintained at 10-15(o)C, six endocardial atrial and seven epicardial ventricular lesions were created in each animal. Ablations were performed for 15 s, 30 s, 45 s, 60 s, 90 s, 120 s, and 150 s (65 W, 2.45 GHz). The tissue was stained with 2,3,5-triphenyl-tetrazolium chloride and lesions were sectioned at 5 mm intervals. Lesion depth and width were determined from digital photomicrographs of each lesion (resolution +/- .03 mm). RESULTS Average atrial thickness was 2.88 +/- .4 mm (range 1.0 to 8.0 mm). 94% of ablated atrial sections created by the FLEX 4 (n = 16) and the FLEX 10 (n = 16) were transmural at 45 seconds. 100% of atrial sections were transmural at 90 seconds with the FLEX 10 (n = 14) and at 60 seconds with the Flex 4 device (n = 15). Lesion width and depth increased with duration of application. CONCLUSION Both devices were capable of producing transmural lesions on the cardioplegically arrested heart at 65 W. These curves will allow surgeons to ensure transmural ablation by tailoring energy delivery to the specific atrial geometry.