Idiopathic ventricular arrhythmias (VA) is defined as premature ventricular complexes (PVCs) or ventricular tachycardias (VT) that occur in the absence of structural heart disease. Endocardial radiofrequency (RF) ablation is often curative for idiopathic VA. The success of the procedure depends on the ability to localize the abnormal foci accurately. These arrhythmias typical originate from the right ventricular outflow tract (RVOT), specifically from the superior septal aspect, but can also originate from the left ventricular outflow tract (LVOT) and the coronary cusps.1 The QRS electrocardiogram (ECG) characteristics have been helpful in patients with VAs, patient with accessory pathways and patients who have pacemakers.2 VAs originating from the RVOT have typical ECG findings with a left bundle branch block (LBBB) morphology and an inferior axis.3In the current issue of the Journal of Cardiovascular Electrophysiology, Hisazaki et al. describe five patients with idiopathic VA suggestive of RVOT origin and who required ablation in the left-sided outflow tract (OT) in addition to the initial ablation in the RVOT for cure to be achieved. Patients exhibited monomorphic, LBBB QRS pattern with an inferior axis on ECG, consistent with the morphology of VAs originating from the RVOT. Interestingly, all patients had a common distinct ECG pattern: qs or rs (r ≤ 5 mm) pattern in lead I, Q wave ratio[aVL/aVR]>1, and dominant S-waves in leads V1 and V2. Mapping of the right ventricle demonstrated early local activation time during the VA in the posterior portion of the RVOT, matching the QRS morphology obtained during pacemapping. Despite RF energy delivery to the RV, the VAs recurred shortly after ablation in four patients and had no effect at all in one patient. A change in the QRS morphology was noted on the ECG that had never been observed before the procedure. The new patterns were suggestive of left-sided OT origin: the second VAs exhibited an increase in the Q wave ratio [aVL/aVR] and R wave amplitude in lead V1, decrease in the S wave amplitude in lead V1, and a counterclockwise rotation of the precordial R-wave transition. Early activation of the second VA could not be found in the RVOT, and the earliest activation time after mapping the LV was found to be relatively late. Real-time intracardiac echocardiography and 3D mapping systems were used to determine the location immediately contralateral to the initial ablation site in the RVOT. Energy was then delivered to that site which successfully eliminated the second VA. The authors postulated that the second VAs shared the same origins as the first VAs, and the change in QRS morphology is likely attributed to a change in the exit point or in the pathway from the origin to the exit point. The authors further explained that the VAs originated from an intramural area of the superior basal LV surrounded by the RVOT, LVOT and the transitional zone from the great cardiac vein to the anterior interventricular vein (GCV-AIV).A limitation of this study is that GCV-AIV ablation was not attempted; however, the authors’ approach is safer and was successful in eliminating VA. Another limitation is that left-sided OT mapping was not initially performed. Nevertheless, given the ECG characteristics, local activation time, and mapping, it was appropriate to attempt a RVOT site ablation.Overall, the authors should be commended for their effort to describe in detail patients with idiopathic VAs that required ablation in the left-sided OT following ablation in the RVOT. Although change in QRS morphology after ablation has been previously described, the authors were the first to describe the ECG patterns of these patients.4–7 The results of this study have important clinical implications. First, the authors have demonstrated the importance of anatomical approach from the left-sided OT for cure to be achieved. Second, insight into the location of the origin of the VA may be helpful to physicians managing patients with VAs from the RVOT. Finally, continuous monitoring of the ECG during ablation for a change in QRS morphology should be considered to identify patients who will require further ablation. We have summarized in Table 1 important ECG characteristics indicative VA of specific origins, based on the findings of this study and previous studies in the literature.3,8–15
A Cardiac Sodium Channel Mutation Associated with Epinephrine-Induced Marked QT-ProlongationMohamad N. El Moheb MD1, Marwan M. Refaat MD21Division of Trauma Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Boston, Massachusetts - USA2Division of Cardiology, Department of Internal Medicine, American University of Beirut Medical Center Beirut, LebanonRunning Title: SCN5A mutation associated with epinephrine-induced LQTSWords (excluding references): 746Disclosures: NoneFunding: NoneKeywords: Long QT Syndrome, Genetics, Variants, Cardiac Arrhythmias, Cardiovascular DiseasesCorrespondence:Marwan M. Refaat, MD, FACC, FAHA, FHRS, FASE, FESC, FACP, FRCPAssociate Professor of MedicineDirector, Cardiovascular Fellowship ProgramDepartment of Internal Medicine, Cardiovascular Medicine/Cardiac ElectrophysiologyDepartment of Biochemistry and Molecular GeneticsAmerican University of Beirut Faculty of Medicine and Medical CenterPO Box 11-0236, Riad El-Solh 1107 2020- Beirut, LebanonFax: +961-1-370814Clinic: +961-1-350000/+961-1-374374 Extension 5800Office: +961-1-350000/+961-1-374374 Extension 5353 or Extension 5366 (Direct)Email: firstname.lastname@example.orgThe hereditary long QT syndrome (LQTS) is an important cause of polymorphous ventricular tachycardia (torsades de pointes) and sudden cardiac death in otherwise young and healthy individuals. Clinically, this condition is caused by delayed ventricular repolarization and manifests as an abnormally prolonged QT interval on the electrocardiogram (ECG). The most common subtypes of LQTS are LQT1, LQT2, and LQT3 (1-10). The life-threatening arrhythmias occur most frequently during exercise in LQT1, upon auditory stimulation or emotional stress in LQT2, and at rest or during sleep in LQT3 (11). Patients with LQT1 have a mutation in the KCNQ1 gene which codes for the subunit of the slow outward potassium current channel (IKs) while patients with LQT3 have a mutation in the SCN5A gene, which codes for the cardiac voltage-dependent sodium channel (INa) (12). LQT1-affected individuals are more vulnerable to β-adrenergic modulation than LQT3-affected individuals. Exercise and epinephrine-infusion ECG tests are therefore useful in differentiating between the LQTS subtypes and optimizing therapeutic strategies in order to prevent sudden cardiac death. While beta-blockers have been established as the standard of care for the treatment of the LQT1 and LQT2 subtypes, their use in LQT3 remains controversial (13, 14). A new missense mutation has been recently identified in the SCN5A-encoding INA channels and was found to be associated with sinus node dysfunction and epinephrine-induced QT prolongation (1). This atypical phenotype of LQT3 has so far been observed in only one patient. Whether other mutations exist that can cause a similar manifestation has yet to determined.In the current issue of the Journal of Cardiovascular Electrophysiology, Nakajima et al. describe a family with LQT3 that exhibited epinephrine-induced marked QT prolongation. The SCN5A V1667I mutation was found to be responsible for this atypical phenotype which resulted in prolongation of the QT interval in the proband as well as in family members carrying the mutation. The SCN5A V1667I mutation is a gain of function mutation located in domain IV-segment 5 (DIV-S5) of the sodium channel encoding SCN5A gene. To elucidate the pathophysiology of the disease, the authors transfected a human kidney cell line (tsA-201) to induce expression of wild-type and mutated sodium channels and measured the membrane sodium currents (INA). They showed that SCN5A V1667I mutation was associated with larger INA peak density, depolarizing shift in steady-state inactivation (SSI) leading to increased window current, and accelerated recovery from depolarization. Additionally, an increased hump in the INA of V1667I mutant cells (V1667I-INA) was observed during a ramp pulse protocol consistent with increased window current. There was no difference in fast inactivation rate and steady-state activation between the V1667I-INA and wild-type INA(WT-INA). The authors further examined the effects of protein kinase A (PKA) activation on V1667I-INA to mimic the effect of epinephrine. PKA activation resulted in a less significant hyperpolarizing shift in SSI in V1667I-INA compared to WT-INA leading to increased window current. Additionally, V1667I mutation was found to be associated with accelerated recovery from depolarization, and increased hump during ramp pulse protocol in the setting of PKA activation. Chen et al. have also reported the case of an individual with a mutation in SCN5A who exhibited marked QT-prolongation after epinephrine infusion (1). However, contrary to the SCN5A V1667I mutation described by Nakajima et al, the SCN5A V2016M defect was a loss of function mutation causing a decrease in INA peak density. The clinical manifestations of the SCN5A mutations described by Chen et al. and Nakajima et al. are more comparable to individuals with the LQT1 subtype than those with the LQT3 subtype. Therefore, it should be considered whether certain patients with SCN5A would benefit from beta-blocker therapy.Overall, the authors should be commended on their efforts to describe for the first time a family with the SCN5A V1667I mutation and show that this mutation is associated with epinephrine-induced marked QT prolongation. The authors have also provided important insight into the electrophysiological properties of the mutant channels and the structure-function relationship of SCN5A. Further studies are needed to elucidate the precise molecular mechanisms of PKA activation on WT-INa and V1667I-INa. The results of this study have important clinical implications. The efficacy of beta-blockers for the treatment of LQTS has so far only been proven for the LQT1 and LQT2 subtypes, with conflicting results for the LQT3 subtype (13, 14). Given the marked QT prolongation in response to epinephrine infusion in carriers of the SCN5A V1667I mutation, certain LQT3 patients may benefit from beta-blocker therapy. Future studies should clarify whether beta-blockers are effective in these patients.
Catheter ablation is the current standard of care for the management of symptomatic atrial fibrillation (AFib) refractory to pharmacological therapy. One of the complications of this procedure is thermal injury to the esophagus due to its anatomical proximity to the posterior wall of the left atrium (1). Rarely (<1%), an atrioesophageal fistula can form connecting the lumen of damaged esophagus to the atrial chamber (2). This complication is almost always fatal and can result in exsanguination, air embolism, and sepsis (3, 4). With a growing number of catheter ablations being performed each year, the rate of atrioesophageal fistulas is only expected to rise (5). Other more frequent complications include esophageal wall erosions and ulcers (47%), and thermal injury to the vagus nerve plexus leading to esophageal dysmotility and gastroparesis (17%) (6, 7). Therefore, protecting the esophagus from thermal injuries is paramount in ablative procedures and several strategies have been devised to help mitigate this risk. Many physicians monitor the luminal esophageal temperature (LET) [ as a surrogate for intramural esophageal tissue temperature] with a single sensor or multisensor temperature probe and interrupt energy delivery when LET reaches 38°C or 39°C during radiofrequency ablation. However, this technique significantly impacts the procedural workflow due to the waiting periods for LET to return to baseline. Alternative strategies involve cooling of the esophagus with ice water or reducing the ablation lesion power, contact force and/or duration but this strategy may increase the chances for pulmonary vein reconnection (8). To that end, there has been a growing interest in mechanical devices capable of deflecting the esophagus away from the atrium protecting it from thermal injury.In the current issue of the Journal of Cardiovascular Electrophysiology, Houmsse et al. introduce a novel device capable of mobilizing the esophagus laterally to protect it from injury when performing catheter ablation for AFib. Although other devices have been developed and/or used for this purpose (such as the transesophageal echocardiography probe, endotracheal stylet, Esosure stylet and DV8 shaped balloon retractor), this is the only one to operate using vacuum suction allowing it to latch onto the esophageal wall. The device consists of four main components: outer extrusion, inner stacking plates, deflecting arm and control handle. The outer extrusion is inserted via a trochanter or a bougie into the esophagus and is the only portion of the retractor that comes in contact with the surrounding tissues. Small perforations at the distal end allow for vacuum suction to adhere to the esophagus and for a radiocontrast agent to be delivered to delineate the esophageal contour. The inner stacking plates are then introduced through the outer extrusion and are designed to allow movement of the deflecting arm in the medio-lateral plane only. The deflecting arm is connected to the distal end of the stacking plates through a pivot point and can be steered using the control handle. The authors have evaluated the effectiveness and safety of the device on canine and swine animal models by measuring the distance and direction of displacement of the esophagus, examining the cellular architecture after prolonged suction, measuring the LET, and assessing compatibility of device with electroanatomical mapping systems. A total of 68 deviations were performed on four canine models. The average rightward deflection was equal to 26.6 ± 2.5mm compared to 18.7 ± 2.3mm for the direct leftward deflection (p<0.001), and 96% of deviations did not have an esophageal trailing edge. With the exception of one study, the average distance displaced using the suction retractor was superior to other devices (9-13). The substantial distance of deflection and the minimal esophageal trailing edge significantly decreased the rise in LET from baseline (mean increase of 0.2°C vs 2.5°C without deflection). Examination of the esophageal tissue integrity following one hour of continuous suctioning revealed no change in the esophageal cellular architecture, and only minimal circular areas of hyperemia in mucosa due to the suction ports without injury to the muscularis layer. Finally, the retractor did not interfere with the electroanatomical mapping systems used (CARTO and EnSite).Despite its interesting findings, this study has several limitations that should be acknowledged. First, the study was performed on swine and canine animal models, which are known to have an anatomy close to humans; however, the safety profile of the device and its effectiveness in displacing the esophagus may not translate in humans. Second, subjects may exhibit symptoms secondary to extreme deviation of the esophagus in the absence of distortion of the cellular architecture. Clinical studies are needed to assess the safety profile and side effects of this esophageal retractor. Third, it is unclear whether these results would be reproducible under monitored anesthesia care. Finally, the fluoroscopic equipment tools lacked electronic caliper capabilities, and the measurements were performed using radiopaque rulers.Overall, the authors should be commended on their efforts to introduce and evaluate an inexpensive and innovative tool for esophageal protection during AFib ablation. This retractor addresses the limitations of other products that serve a similar purpose. In fact, the suctioning power of the product minimizes the trailing edge of the esophagus that could not be managed with other devices which left esophageal tissue in the ablation field (10, 13). In addition, the control handle offers significant flexibility in device manipulation allowing physicians to choose the site of angulation and the angle of deflection depending on the patient’s anatomy. Future studies should focus on evaluating the safety and effectiveness of this device in humans. Given the growing number of esophageal retracting devices, studies should also aim to determine the device that produces the best esophageal protection and most desirable outcomes of ablation.REFERENCES1. Chung MK, Refaat M, Shen WK, Kutyifa V, Cha YM, Di Biase L, Baranchuk A, Lampert R, Natale A, Fisher J, Lakkireddy DR. Atrial Fibrillation: JACC Council Perspectives. J Am Coll Cardiol. Apr 2020; 75 (14): 1689-1713.2. D’Avila A, Ptaszek LM, Yu PB, Walker JD, Wright C, Noseworthy PA, Myers A, Refaat M, Ruskin JN. Left Atrial-Esophageal Fistula After Pulmonary Vein Isolation. Circulation May 2007; 115(17): e432-3.3. Aryana A, Arthur A, O’ Neill PG, D’Avila A. Catastrophic manifestations of air embolism in a patient with atrioesophageal fistula following minimally invasive surgical ablation of atrial fibrillation. Journal of cardiovascular electrophysiology. 2013;24(8):933-4.4. Stöckigt F, Schrickel JW, Andrié R, Lickfett L. Atrioesophageal fistula after cryoballoon pulmonary vein isolation. Journal of cardiovascular electrophysiology. 2012;23(11):1254-7.5. Oral H, Siontis KC. Prevention of Atrioesophageal Fistula After Catheter Ablation: If the Esophagus Cannot Stand the Heat (Cold), Can It Be Moved to the Sidelines? : JACC: Clinical Electrophysiology; 2017.6. Shah D, Dumonceau J-M, Burri H, Sunthorn H, Schroft A, Gentil-Baron P, et al. Acute pyloric spasm and gastric hypomotility: an extracardiac adverse effect of percutaneous radiofrequency ablation for atrial fibrillation. Journal of the American College of Cardiology. 2005;46(2):327-30.7. Schmidt M, Nölker G, Marschang H, Gutleben K-J, Schibgilla V, Rittger H, et al. Incidence of oesophageal wall injury post-pulmonary vein antrum isolation for treatment of patients with atrial fibrillation. Europace. 2008;10(2):205-9.8. Tran VN, Kusa S, Smietana J, Tsai W-C, Bhasin K, Teh A, et al. The relationship between oesophageal heating during left atrial posterior wall ablation and the durability of pulmonary vein isolation. Ep Europace. 2017;19(10):1664-9.9. Mateos JCP, Mateos EIP, Peña TGS, Lobo TJ, Mateos JCP, Vargas RNA, et al. Simplified method for esophagus protection during radiofrequency catheter ablation of atrial fibrillation-prospective study of 704 cases. Brazilian Journal of Cardiovascular Surgery. 2015;30(2):139-47.10. Bhardwaj R, Naniwadekar A, Whang W, Mittnacht AJ, Palaniswamy C, Koruth JS, et al. Esophageal Deviation During Atrial Fibrillation Ablation: Clinical Experience With a Dedicated Esophageal Balloon Retractor. JACC Clin Electrophysiol. 2018;4(8):1020-30.11. Herweg B, Johnson N, Postler G, Curtis AB, Barold SS, Ilercil A. Mechanical esophageal deflection during ablation of atrial fibrillation. Pacing and clinical electrophysiology. 2006;29(9):957-61.12. Palaniswamy C, Koruth JS, Mittnacht AJ, Miller MA, Choudry S, Bhardwaj R, et al. The extent of mechanical esophageal deviation to avoid esophageal heating during catheter ablation of atrial fibrillation. JACC: Clinical Electrophysiology. 2017;3(10):1146-54.13. Parikh V, Swarup V, Hantla J, Vuddanda V, Dar T, Yarlagadda B, et al. Feasibility, safety, and efficacy of a novel preshaped nitinol esophageal deviator to successfully deflect the esophagus and ablate left atrium without esophageal temperature rise during atrial fibrillation ablation: The DEFLECT GUT study. Heart Rhythm. 2018;15(9):1321-7.