Loss of pace capture after radiofrequency application predicts the formation of uniform transmural lesions

Abstract

Aims

Lesion transmurality is critical to procedural success in radiofrequency catheter ablation. We sought to determine whether loss of pace capture (PC) with high-output unipolar and/or bipolar pacing predicts the formation of uniform transmural lesions.

Methods and results

Ten juvenile swine were anaesthetized and prepped under sterile conditions. Seventy-seven isolated radiofrequency applications (RFAs) using a 3.5 mm tip-irrigated catheter were available for analysis. Pace capture was assessed before and after RFA at 10 mA/2 ms and catheter stability verified with a three-dimensional mapping system. Pace capture was defined as 1 : 1 or intermittent local capture per paced beat. Myocardial contact and catheter orientation were assessed using intracardiac echo. Endocardial and epicardial lesion areas were measured after sacrifice using 2,3,5-triphenyltetrazolium chloride staining. A uniform transmural lesion was defined as an epicardial-to-endocardial surface ratio (epi/endo) ≥ 76%. Seventy-four per cent of lesions were transmural and 55.8% of lesions had an epi/endo ratio ≥ 76%. In all, 79.2% of lesions associated with loss of bipolar PC were uniform whereas 20.8% of lesions with loss of bipolar PC were non-uniform (P = 0.006). Loss of bipolar PC was associated with higher mean epicardial/endocardial ratio compared with lesions with persistent PC (P = 0.019). Echocardiographic evidence of optimal catheter contact during RFA improved the predictive accuracy of uniform lesion formation when loss of bipolar PC was noted after RFA.

Conclusion

Loss of bipolar PC after RFA is associated with the formation of uniform lesions in atrial tissue. Optimal catheter contact further improves the predictive accuracy associated with loss of PC.

Introduction

Catheter ablation procedures are an established treatment for supraventricular and ventricular arrhythmias.¹ It has recently become apparent that linear lesions are often required for supraventricular arrhythmias such as atrial fibrillation and macro-reentrant atrial flutter.^2–4 Permanent conduction block across linear lesions requires transmural necrosis.⁵ It is widely recognized that the main culprit for the re-emergence of pulmonary vein (PV) conduction is discontinuity in lines of ablation.^6–8 Lesion homogeneity on the endocardial and epicardial surfaces may be an important determinant of ablation efficacy, since in theory, even large endocardial lesions may penetrate a very small epicardial surface area and leave significant epicardial bridges of conduction.

Indirect approaches to assessing effective tissue heating and durable lesion formation have been investigated, including electrogram amplitude change, bipolar and unipolar electrogram wave front direction, and contact pressure sensing as a guide for the duration of radiofrequency application (RFA) and power titration.^3,9–11 We and others have recently shown that loss of pace capture (PC) on the circumferential ablation line correlates with entrance block in the PV consistent with the creation of deep intramural lesions^12,13 and when used as an additional endpoint in PV isolation (PVI) procedures, lowers the risk of recurrent atrial arrhythmias. Based on these observations, we sought to determine whether there is a direct relationship between the formation of a uniform transmural lesion and loss of PC.

Methods

Animal preparation

The experimental protocol was approved by the Institutional Ethical Committee for animal research at the Brigham and Women's Hospital and complies with the Declaration of Helsinki. Ten juvenile female swine between 30 and 35 kg were fasted for 8–12 h prior to the induction of anaesthesia. On the day of the procedure, anaesthesia was induced via a subcutaneous injection with a butterfly needle into the cervical area containing Telazol at 4.4 mg/kg combined with atropine at 0.02–0.04 mg/kg. Subsequently, the swine were placed recumbent and general anaesthesia was induced with inhaled Isoflurane between 1 and 4% combined with between 1 and 3 L/min of oxygen via an anaesthesia mask placed over the snout until intubation was possible, while being continuously monitored with a pulse oximeter and a capnograph. Following oral intubation, vital signs and depth of anaesthesia were continuously maintained and monitored with a combination of a pulse oximeter, end tidal CO₂ monitor, respiration volume/rate, pulse rate, electrocardiogram, rectal temperature probe, and tactile manipulation. The femoral and internal jugular veins were exposed and intravascular sheaths were inserted using a percutaneous cutdown approach. Transeptal puncture was performed by means of intracardiac echocardiography and fluoroscopic guidance.

Catheter ablation

Using electroanatomical mapping (NaVX Ensite, SJM), three-dimensional maps of the atria were created. Radiofrequency catheter ablation was performed during sinus rhythm using a 3.5 mm tip-irrigated unidirectional catheter with a 2-5-2 mm interelectrode distance (Thermocool, Biosense Webster) under single plane fluoroscopy, intracardiac echocardiography (Acuson, VividI, GE) and continuous electroanatomical mapping. The inferior and superior right atrium (RA) posterior to the crista terminalis, interatrial septum from the left or right atrium, the roof of the left atrium (LA), the right and left PV regions, the mitral annulus, and the coronary sinus (CS) were targeted. Lesions placed inadvertently in trabeculated myocardium were excluded from the analysis. Catheter orientation was noted with intracardiac echocardiography to be either parallel or perpendicular relative to the endocardial surface. Catheter contact was also noted with intracardiac echocardiography and was labelled as optimal (catheter moving with the endocardium) or non-optimal (all other catheter contact).

Radiofrequency energy (500 KHz) was delivered in power control mode at 30 W for 30 s. All lesions were recorded using the electroanatomical mapping system and were correlated with the electrophysiological and histological data of the ablation sites. For each ablation site, PC before and immediately after ablation was documented using unipolar and bipolar pacing at 600 ms at a fixed pacing output of 10 mA at 2 ms strength duration. Pace capture was defined as present (1 : 1 or intermittent capture) or absent. Bipolar and unipolar PC were confirmed to be present prior to RF application for all sites tested. Other electrophysiological parameters documented for each ablation lesion were minimum and maximum temperature, impedance before and at the end of RFA and total voltage amplitude change before and after ablation. Catheter tip location was monitored using echocardiography and electroanatomical mapping. At the procedure's end, the swine was injected with 50 cc of 2,3,5-triphenyltetrazolium chloride (TTC), euthanized, and the heart was excised. The heart was soaked for 2h in TTC stain and each lesion was identified macroscopically and correlated with electroanatomical, electrophysiological, and echocardiographic data. The ablation lesion was identified as a zone of necrosis that did not stain with TTC. Border zones of haemorrhage were excluded from measurement.¹⁴ The endocardial and epicardial surface of each lesion was carefully measured and the largest endocardial and epicardial lesion diameter was documented (Figure 1).

Statistical analysis

All continuous variables are expressed as mean ± SE. Binary variables are presented as number or percentage. The Yates 2 × 2 χ² test or Fisher's exact test were used for categorical variables. Two-tailed Wilcoxon t-test was used to compare paired variables. P < 0.05 was considered statistically significant.

Results

Lesion localization and catheter orientation and contact

Point-by-point ablation was performed at a total of 122 sites of which 77 sites (40 LA and RA, 24 antral PV, 6 CS, and 7 mitral and tricuspid annulus) were adequate for analysis. Parallel (43 lesions, 55.8%) and perpendicular (31 lesions, 40.3%) catheter tip orientation relative to the endocardial surface was noted; catheter tip orientation was not noted in three lesions because the catheter was not consistently visible in the echocardiographic field. Catheter contact identified by intracardiac echocardiography demonstrated optimal catheter contact with the ablation catheter in 37 (48.1%) of lesions. For 23 lesions, the ablation catheter was sliding on the endocardium (29.9%) and for 11 lesions the catheter was bouncing off the endocardium (14.3%). For the remaining six lesions (7.8%) catheter contact was not adequately assessed due to intermittent visibility in the field or variation in contact.

Characteristics of transmural lesions

Of the 77 analysed lesions, 57 were transmural (74%) and 20 were non-transmural (26%). Forty-nine lesions (63.6%) were discrete and smooth and 28 (36.4%) were associated with either crater formation and/or intramural haemorrhage. Twenty-four lesions (31.2%) demonstrated lack of unipolar and bipolar capture after RFA whereas 53 lesions (68.8%) demonstrated either unipolar or bipolar PC after RFA. Intermittent unipolar or bipolar PC after RFA was noted in 13 (16.9%) and 8 (10.4%) lesions, respectively, and was considered part of the PC group for data analysis. Bipolar non-capture after RFA did not independently predict whether a lesion was transmural (P = 0.130).

Characteristics of uniform lesions

Endocardial and epicardial lesion diameter and length were measured macroscopically and the ratio of the epicardial/endocardial surface area was calculated for each lesion (Figure 1). Lesions were distributed in quartiles based on the epicardial/endocalrdial surface area ratio. A uniform lesion was defined as an epicardial/endocardial (epi/en) lesion surface ratio ≥ 76%. Lesion characteristics based on lesion uniformity are described in Table 1. Of the 77 lesions, 43 (55.8%) were uniform and 34 (44.2%) were non-uniform and/or non-transmural. Uniform lesion formation was equally observed in the PV antra (58.3%), posterior wall of the LA (57.5%), valve annulus (42.9%), and CS (50%) (P = 0.881), and 60.5% of the uniform lesions were smooth and discrete whereas 39.5% were hemorrhagic or cratered (P = 0.515).

Loss of post-radiofrequency application pace capture predicts lesion uniformity

Electrophysiological, anatomical, and morphological characteristics of uniform and non uniform lesions are noted in Table 1. Loss of bipolar PC post-RFA was associated with higher mean epicardial/endocardial ratio compared with lesions with either persistent or intermittent bipolar PC post-RFA (P = 0.019) (Figure 2A) and was independently predictive of uniform lesion formation (P = 0.004) (Figure 2B). Lesions with intermittent bipolar PC exhibited significantly lower mean epicardial/endocardial ratios compared with lesions with loss of bipolar capture post-RFA, implying that intermittent capture may develop due to catheter instability and is more akin to 1 : 1 PC (Figure 2). Lesions with loss of both unipolar and bipolar PC post-RFA had a significantly higher mean epicardial/endocardial surface area compared to lesions with bipolar or unipolar PC after RFA (135.86 ± 27.95 vs 72.99 ± 11.06, P = 0.014). Loss of bipolar PC was always associated with loss of unipolar PC, but not vice versa. Loss of bipolar PC was associated with the creation of a uniform lesion in 79.2% of lesions, whereas 20.8% were non-uniform (P = 0.006). Loss of unipolar capture exclusively was not independently predictive of uniform lesion formation (P = 0.508). The mean epicardial/endocardial ratio was not significantly higher in lesions with lack of unipolar capture after RFA (P = 0.369). The positive predictive value of loss of bipolar capture was 85% with a specificity and sensitivity of 78 and 65% in predicting lesion uniformity, respectively.

Voltage, impedance, and temperature changes do not predict lesion uniformity

Mean voltage, impedance, and temperature change during RFA did not vary significantly between uniform and non-uniform lesions (Table 1).

Optimal catheter contact improves the diagnostic accuracy of loss of pace capture in predicting lesion uniformity

We sought to determine whether combining loss of bipolar PC with other study variables would improve its ability to predict uniform lesion formation. In lesions with loss of bipolar PC, neither impedance change by 5% (P = 0.660), voltage change >50% (P = 0.143), nor temperature change >10% (P = 0.186) improved diagnostic accuracy. In contrast, optimal catheter contact significantly improved the predictive accuracy of loss of bipolar PC. Loss of bipolar PC after RFA was associated with lesion uniformity in 100% of lesions with optimal catheter contact and in 50% of lesions with suboptimal catheter contact (P = 0.003) (Figure 3).

Discussion

This study correlates histological features of radiofrequency ablation lesions with loss of PC in swine atria. We demonstrated that loss of bipolar but not unipolar PC after RFA predicts the formation of a uniform lesion. Further, when loss of bipolar PC is observed in lesion sites with optimal catheter tip contact relative to the endocardium, the formation of a uniform transmural lesion can be accurately predicted.

Prior studies

Unipolar and bipolar pacing is utilized to provide guidance in scar-related ventricular tachycardia ablation before and after ablation.^15,16 Loss of PC in that setting is used to determine whether additional RFA are necessary in a myocardial region of interest. Recent clinical studies have demonstrated that pacing along an ablation line in the atrium is a valuable technique in assessing conduction block and finding gaps.^12,13 Our group has shown that more ablation is required to achieve loss of PC post-RF application than to achieve entrance blocks in the PVs and the endpoint of an unexciteable line in patients undergoing PVI may lower the risk of recurrent atrial arrhythmas, indicating that this pacing technique may result in more uniform and effective lesions.¹² In the current study, we expanded on this clinical observation and demonstrated that loss of bipolar PC post-RF application is associated with a transmural lesion expanding uniformly from the endocardial to the epicardial surface.

Uniform transmural lesions

With healing of tissue injury, there is a significant decrease in the final effective lesion diameter, primarily on the epicardial surface, allowing for recovery of conduction.¹⁷ We present the concept of a uniform lesion, indicating similar epicardial : endocardial surface areas as defined by a epicardial:endocardial surface area ratio ≥ 76% ratio. We hypothesized that inhomogeneous lesions would leave potential epicardial conduction gaps.

Loss of bipolar pace capture

We showed that loss of both bipolar and unipolar PC indicates the presence of a uniform lesion but unipolar pacing did not independently have the same predictive value. This finding indicates that the smaller ‘antenna span’ of unipolar pacing is not as predictive of lesion quality. The larger surface area of bipolar pacing indicates more extensive tissue damage, extending beyond the ring electrode. This theory is corroborated by the observation that loss of unipolar pacing is always observed prior to loss of bipolar capture. This discrepancy between unipolar and bipolar PC results has important clinical reverberations, since clinical studies to date have been performed with unipolar pacing only. We further noted that lack of bipolar PC is not 100% predictive of uniform lesion formation except when lack of bipolar capture is noted with concurrent optimal catheter contact. This may be related to factors such as catheter tip orientation or lesion geometry. Furthermore, the area of bipolar capture may be larger than the lesion diameter, particularly in a catheter tip orientation where the ring electrode is in contact with the myocardium.

Predictive ability of other commonly observed eletrophysiological parameters

Several parameters have been clinically tested to address whether adequate energy has been delivered to tissue to allow for deep effective lesion formation. Novel parameters estimating contact force sensing have been correlated with lesion transmurality¹⁸ but are not easily applicable in daily clinical practice. Change in impedance has been correlated with lesion volume during irrigated ablation; however, tissue characteristic were not addressed.¹⁹ Further, Ozaydin et al.²⁰ demonstrated a significant correlation between voltage amplitude reduction >50% and cavotricuspid isthmus block but this was a clinical study with no tissue visualization. Gepstein et al.²¹ showed that transmural lesions are formed with non-irrigated RFA when the unipolar amplitude is decreased by >80%. Lastly, in agreement with our findings, Yokoyama et al.⁹ showed that when an irrigated tip catheter is utilized, the catheter tip temperature does not predict myocardial tissue heating and lesion transmurality.

Catheter contact assessed by intracardiac echocardiography

Catheter contact has been associated with larger lesion formation for any given power setting during RFA.²² In keeping with these data, we observed a significant incremental predictive value of optimal catheter contact assessed in predicting uniform lesion formation. Different levels of contact pressure may explain the lack of consistent uniform lesion formation with optimal contact as supported a study by Holmes et al.¹⁸ providing evidence of a direct correlation between contact pressure and lesion depth.

Study limitations

In the present study, we did not utilize microscopic examination of lesions. Further, the lesion number was limited in order to allow accurate analysis of single lesions without overlap. Lesions were limited primarily to smooth atrial wall and as such these results may not apply to ventricular myocardium or trabeculated tissue. We tested a fixed, high pacing output with a 3.5 mm catheter tip and electrode spacing of 2-5-2 mm. The results may not apply to different-sized catheter tips with different spacing of electrodes. We did not test different pacing outputs to determine if there was a threshold that proved to have better discrimination of lesion quality. We also did not test lines of ablation so as to analyse lesion variables independently.

Conclusion

Loss of bipolar PC after single RFA has a significant predictive value for the formation of uniform transmural lesions. Optimal catheter contact further improves the diagnostic accuracy of loss of PC post-RFA. This methodology may apply to clinical practice to allow for an assessment of ablation efficacy and requirement for additional RFA in the atrium.

Conflict of interest: G.F.M. has received honoraria from Medtronic, Boston Scientific, and Biosense-Webster. All other authors declare no conflict of interest.

References

Author notes