The value of the accessory pathway potential in ablation within coronary sinus

Background In accessory pathway-related supraventricular tachycardia ablation, coronary sinus (CS) ablation has received more and more attention, but there are no accurate criteria for catheter selection. Objectives We intended to develop a new method for the reasonable selection of electrode for coronary sinus ablation via assessing the relationship between the accessory pathway (AP) potential and time of successful ablation. Methods the detected the and


Introduction
Radiofrequency catheter ablation (RFCA) is currently considered the preferred treatment for patients with accessory pathway-related supraventricular tachycardia (AP-SVT). Previous studies have shown that the success rate for catheter ablation is greater than 95% [1][2][3], and can be even higher when the AP is located in the posterior mitral valve [4]. However, some bypass tracts are near the epicardium of the valve, which is not easy to be ablated within the endocardium pathway. In such situations, ablation within the coronary sinus (CS) can signi cantly improve ablation success rates. However, procedure-related complications such as coronary vessel injury and CS thrombosis can be more serious [5,6].
Temperature control catheter (TCC) and irrigated-tip catheter (ITC) are two common options in AP-SVT radiofrequency ablation therapy. Compared with TCC, ITC perfused with cold saline can maintain a lower temperature at the electrode-tissue interface, increase thermal osmosis, and the transmission energy of ablation, thus generate a deeper and larger injury [7,8]. TCC with 4-mm tips have been adequate to ablate APs located near the endocardium. However, these catheters are insu cient enough for the ablation of APs located near the epicardium. Given that ITC is more expensive and traumatic, the conventional process is the rst choice TCC, if it fails, then choose ITC. However, using ITC directly can cause unnecessary myocardial damage and is more costly than using TCC. Using ITC after TCC failure can cause prolonged surgical time and additional myocardial damage. Thus, it is of great signi cance to nd a suitable indicator that can guide catheter selection. AP potential, generated by atrioventricular bypass conduction, located after A wave and before delta wave, is deemed to have the potential to guide catheter ablation. Generally, the farther away from the bypass, the smaller the AP potential. The AP potential can be recorded in 89% of patients with AP by ventricular or atrial pacing from the side producing the longer local VA or local AV interval, respectively [9].
In this study, we recorded AP potential by temperature-controlled catheter and analyzed the correlation between AP potential and the time of successful ablation to explore its guiding signi cance in the electrode selection in CS ablation.

Study population
This study retrospectively reviewed the records of 360 patients with AP-SVT who had detectable AP potentials in 1545 patients undergoing catheter ablation from 1/1/2015 to 12/31/2019. Essential information included patient characteristics, ECG and electrophysiological ndings were collected. Those with structural heart disease were excluded based on echocardiography, cardiac magnetic resonance imaging, or coronary angiography ndings. The work was conducted in accordance with the latest declaration of Helsinki (2013) and the International Conference on Harmoni-zation Good Clinical Practice Guidelines (ICHGCP). The ethical review board of Hospital approved the study protocol (approval no.201901287). All patients were given written in-formed consent.

Electrophysiological study
All procedures were performed under local anesthesia. Two quadripolar catheters were then placed into each patient: one in the right atrium and another in the right ventri-cle. In addition, one decapolar catheter was positioned in the CS through a femoral ap-proach. An electrode in the inferior vena cava (25cm from the tip of a right atrial catheter) was used as the reference electrode for unipolar recordings (Ablation electrode is the posi-tive pole; inferior vena cava electrode is the negative pole; and lter settings of 1 to 500 Hz reduce baseline drift during respiration), and recorded with a digital electrophysiological register system (EP-Work Mate / Work Mate Claris, St.Jude Medical, St.Paul, MN, USA). Programmed electrical stimulation was used to evaluate the atrium, ventricle, AV node, and AP conduction, and induce tachycardia. Tachycardia can also be induced by intra-venous isoproterenol (1-4 mg/min), if needed.
Mapping and recording of accessory pathway potential Endocardial and CS mapping were performed to identify optimal target sites for ab-lation. A 7F quadripolar temperature-controlled catheter with a 4-mm tip(Cordis Webster Inc., Baldwin Park, CA, USA)was inserted through the right femoral vein and positioned in the tricuspid annulus, or in the mitral annulus via trans-septal puncture, or in CS to map and record AP. The tricuspid/mitral annulus was mapped via the right femoral vein during tachycardia, as well as xed ventricular pacing. Ideal ablation targets were those with AP potential or the earliest excited V wave or reverse A wave. If there were no ideal targets after endocardium mapping, or always a distance between A-V/V-A, or the bypass cannot be blocked by ablating at the earliest excited point of V-wave or A-wave. Then the ablation catheter was inserted into the CS or its branch for further mapping. If an ideal target can be found in CS, try to ablate by TCC for 10 seconds, and ITC is performed when the TCC ablation fails.
Electrophysiological register system recorded a sharp potential between A wave and P wave. When pacing the atria with a xed-frequency (S1S1), and then stimulating the right ventricle (S1S2) in advance, as S2 gradually advanced, a sharp potential has nothing to do with A wave, V wave, which is termed as This AP potential.

Endocardial and CS Ablation
Ablation was performed with 4-mm temperature controlled catheter (Cordis Webster Inc., Baldwin Park, CA, USA) or irrigated 4-mm catheter (Thermocool SF, Biosense Web-ster, Diamond Bar, CA, USA). During endocardium ablation, we used temperature con-trolled ablation catheters (40-50℃, 30-40 W). In CS ablation, a radiofrequency application was set with target temperatures of 40-50℃ and maximum power outputs of 20-30 W for the non-irrigated catheter and (43℃, 15-25 W) for the irrigated catheter, respectively. Prior to ablation, a weight-adjusted bolus of unfractioned heparin was administered intravenously. And meanwhile, coronary angiography was performed to prevent injury to the coronary artery. Effective ablation will be achieved with a consolidation discharge lasting 60-90 seconds. Ablation success criteria were the disappearance of the delta wave on the surface ECG and elimination of antegrade and retrograde conduction over the AP in the postablation electrophysiological study with an isoproterenol infusion. If the antegrade and retrograde blocks were achieved, wait 30 minutes to evaluate whether the operation wasssss successful.
Blood sample collection and cTnI assay Cardiac troponin I (cTnI) levels were measured in all patients 24 hours before and 6 hours after ablation.
Plasma was collected after centrifugation, stored at − 80°C. The am-plitudes of the AP potentials were measured using the digital electrophysiological register system. Following surgery, all patients underwent ECG monitoring for at least 24 hours.

Patient follow-up
After surgery, patients received antithrombotic therapy with aspirin for 1 month. Af-ter discharge from the hospital, patients were examined at our arrhythmia clinic or by their referring cardiologists every 3 to 6 months for the rst year and annually thereafter.

Statistics
Continuous variables are presented as the median with the interquartile range. Con-tinuous variables of independent groups were compared using the Mann-Whitney U test, and comparisons of paired groups were analyzed using the Wilcoxon Signed-Rank test. To assess the predictive performance of the AP potential with respect to catheter selection, a receiver operating characteristics (ROC) curve was plotted.
Subsequently, cut-off values of the AP potential were determined based on the Youden index from the ROC curve. A P value less than 0.05 was considered statistically signi cant. All statistical analyses were performed using SPSS22 (SPSS Inc., Chicago, IL, USA).

Results
In the 360 patients, ablation within the endocardium was applied in CS ablation in 30 patients. In CS, 15 cases were ablated via TCC successfully, and 15 cases were performed with ITC after TCC ablation failure (Fig. 1). The baseline characteristics of 30 patients undergoing CS ablation are shown in Fig. 2 and Table 1. The median age was 41 years in the TCC (IQR 34-36 years; one male patient) and 43 years (IQR 33-37 years; three male patients; p = 0.884) in the ITC + TCC groups. The left ventricular ejection fraction was 55% (IQR 54-56%) and 56% (IQR 54-58%; p = 0.365), and cTnI levels were 0.21 ng/mL (IQR 0.16-0.28 ng/mL) and 0.22 ng/mL (IQR 0.15-0.36 ng/mL; p = 0.204) in the TCC and ITC + TCC groups, respectively. After patients undergoing CS ablation by ITC + TCC, three patients had st-segment elevation and two patients had chest pain, while the other patients had no underlying cardiomyopathy.  (Table 3). Data are presented as median (interquartile range). RF = radiofrequency; AP = accessory pathway; Table 3 Changes in cTnI levels (ng/mL) before and after ablation using different catheters in CS  Table 2). In CS ablation,the optimal cut-off amplitude of AP potentials to predict whether TCC ablation has been successful was determined by ROC analyses. The mean AUC value of the amplitudes of the AP potentials was 0.870 (95% CI 0.657-1.0)(p = 0.023). The optimal cut-off amplitude to maximize the sum of the sensitivity and speci city for overall survival was 1.07 mV (Fig. 3).

Discussion
In bypass-induced tachycardia, ablation near the endocardium tends to have a higher success rate. However, the extension of the CS myocardial coat through the posterior cor-onary vein, middle cardiac vein, or diverticulum neck, and its connection to the left ven-tricular epicardium, can form an epicardial posteroseptal AP, which is not easy to be blocked via an endocardial approach. Therefore, CS ablation has become a common ap-proach choice for bypass ablation. Injuries to the coronary vein is the most intractable complications of CS ablation. In addition, manipulations in the CS may also cause a CS thrombosis [4]. The relationship between the CS and coronary arteries should be evaluated prior to performing CS ablation to avoid unnecessary damage [10]. Our study demonstrates that cTnI levels are increased in patients after RFCA, consistent with results of previous studies [11][12][13].
Conventional RF catheters have modest e cacy in ablating substrates located deep within the myocardium. An irrigated RF catheter with a high RF power can be used without increasing the impedance, creating a greater RF lesion volume [14,15]. Further re-search found that in animal experiments, compared with TCC, ITC increased tissue damage by 30-50% [14]. The damaged tissue can approach 1 cm deep and 14 mm in di-ameter [16]. In addition, tissue damage caused by 25W irrigated catheter ablation was similar to that caused by 50w conventional catheter ablation [17]. Therefore, using non-irrigated catheters as well as cryoablation, was proved to be comparably effective in CS [18]. In this study, patients in whom TCCs were used had lower serum cTnI levels after ablation than in patients in whom TCCs + ITCs were used. It is may be that ITC causes more harm to patients, and patients who fail TCC have underwent more the number of RF applications and duration of RFCA procedure, which make patients undergoing TCC + ITC experience more lesions and larger cumulative lesion area.
APs have been thought to course perpendicular to the AV groove. However, most APs have an oblique course [19]. If we placed a multipolar electrode between the atrium and the ventricle. The electrode spacing is relatively small, and a local potential can be rec-orded. This potential exists independently of A wave and V wave, which is termed as AP potential. A retrograde AP potential is differentiated from the local atrial and ventricular potentials by use of atrial extrastimuli. A late atrial extrastimulus advances the local atrial potential without advancing the AP potential, differentiating the AP potential from local atrial activation. An earlier atrial extrastimulus advances the AP potential without ad-vancing the local ventricular potential, differentiating the AP potential from local ventric-ular activation [20]. After bypass blockade, the potential disappears without affecting the ventricular or atrial waveform. We found a signi cant correlation between the AP poten-tial and the time of successful ablation in endocardium. Meanwhile, we compared data from patients who had undergone successful ablation using TCC with those who had unsuccessful ablation using TCC. The amplitudes of the AP potentials in the successful group were signi cantly higher than those in the unsuccessful group, which indicates that the AP potential may be related to the ablation time. In CS, the higher amplitudes of AP potentials was, the higher the success rate of TCC ablation was. This may be related to the distance between the bypass and the electrode.
In conclusion, we con rmed that the higher amplitude of the AP potential, the higher the ablation success rate by TCC in CS ablation. Such a rational selection of ablation catheters (TCC/ITC) by the amplitude of AP can reduce myocardial damage, surgical time, and costs for patients. However, a large sample size, multicenter prospec-tive study is needed for further support of these ndings. Flow-chart of selecting the study population. Coronary sinus venography shows a diverticulum with a narrow neck (red round dots) near the ostium. c) The white spots are the locations where 30 cases of ablation in coronary sinus .