Percutaneous atrial septal defect (ASD) closure is the mainstay treatment for ostium secundum ASD and patent foramen ovale1. Patients with ASD may develop atrial fibrillation (AF), mostly due to structural atrial remodeling creating the substrate for macroreentry2,3. Timing of ASD closure is crucial to prevent further development of electrophysiological heterogeneity, thereby reducing morbidity associated with AF, even though patients with ASD closure devices remain at high risk of developing AF4.The rising number of patients undergoing percutaneous ASD closure poses a new challenge in the treatment of coexistent AF. Furthermore, the reduction of surgical ASD treatment with concurrent cryo- or radiofrequency ablation (modified Maze procedure) is contributing to increase the number of patients who would benefit from catheter ablation after transcatheter ASD closure. Although some studies have shown a high acute success rate of catheter ablation in this population5, this treatment is often denied due the higher perceived risk of performing the transseptal puncture (TSP) after percutaneous repair of the defect.Given the lack of definitive data on this topic, in this issue of the Journal, Garg et al. performed the first meta-analysis evaluating the safety and the efficacy of catheter ablation for AF in this subset of high-risk patients with ASD closure devices.

Aims: A prolonged PR interval may adversely affect ventricular filling and therefore cardiac function. AV delay can be corrected using right-ventricular-pacing (RVP) but this induces ventricular dyssynchrony, itself harmful. Therefore, in intermittent heart-block, pacing-avoidance algorithms are often implemented. We tested His-bundle pacing (HBP) as an alternative. Methods: Out-patients with a long PR interval(>200ms) and intermittent need for ventricular pacing were recruited. We measured within patient differences in high-precision haemodynamics between AV-optimized RVP, and HBP, as well as a pacing-avoidance algorithm [Managed Ventricular Pacing (MVP)]. Results We recruited 18 patients. Mean left ventricular ejection fraction was 44.3±9%. Mean intrinsic PR interval was 266±42ms and QRS duration was 123±29ms. RVP lengthened QRS duration(+54 ms, 95%CI 42 to 67ms, p<0.0001) whilst HBP delivered a shorter QRS duration than RVP(-56 ms, 95%CI -67 to -46ms, p<0.0001). HBP did not increase QRS duration(-2ms 95%CI -8 to 13ms, p=0.6). HBP improved acute systolic blood pressure by mean of 5.0 mmHg(95%CI 2.8 to 7.1mmHg, p<0.0001) compared to RVP and by 3.5 mmHg(95%CI 1.9 to 5.0mmHg, p=0.0002) compared to the pacing avoidance algorithm. There was no significant difference in haemodynamics between RVP and ventricular pacing avoidance (p=0.055). Conclusions HBP provides better acute cardiac function than pacing avoidance algorithms and RVP, in patients with prolonged PR intervals. HBP allows normalisation of prolonged AV delays (unlike pacing avoidance) and does not cause ventricular dyssynchrony (unlike RVP). Clinical trials may be justified to assess whether these acute improvements translate into longer term clinical benefits in patients with bradycardia indications for pacing.

A document by Leonell Freytes. Click on the document to view its contents.

Incisional atrial tachycardia (AT) with multiple penetrating points on one surgical incision has not been reported. We present a case of incisional AT following mitral annuloplasty with a superior transseptal approach, in which two reconduction sites were part of the reentrant circuit. Radiofrequency ablation at the reconduction site successfully terminated the tachycardia. A total of four penetrating points were found on the incision line, and radiofrequency ablation at these sites was completed. Detailed mapping with consideration of possible reconduction sites along the incision line should be performed to avoid further instances of AT following open heart surgery.

Combined use of hydroxychloroquine and azithromycin was globally adopted, in part due to paucity and high cost of alternative therapies. However the utility of these medications has been questioned; and thus safety becomes a major concern given clinical equipoise regarding efficacy. Both hydroxychloroquine and azithromycin continue to be administered in US clinical trials examining their potential role in prevention of infection, treatment of mild infection in ambulatory patients, and in combination with other medical regimens in treatment of patients with severe disease. These drugs also continue to be clinically utilized in hospitalized patients around the globe, often without continuous telemetry due to lack of resources. Concern regarding use of hydroxychloroquine without adequate rhythm monitoring in clinical trials has been recently expressed.1 A review of clinicaltrials.gov at the time of submission of this correspondence reveals actively recruiting trials of combined hydroxychloroquine/azithromycin with or without additional COVID-19 therapies, for both ambulatory and hospitalized patients within and outside the US. The potential for hydroxychloroquine and azithromycin to cause QT prolongation is counterbalanced by very low risk of pro-arrhythmia in the general population, and emerging evidence of relatively low risk of Torsades de Pointes (TdP) in COVID-19 patients.2,3,4,5 Thus delineation of the determinants of significant QTc prolongation and pro-arrhythmic risk for hydroxychloroquine/azithromycin is very important, especially given mounting evidence of inefficacy in COVID-19 treatment.

A document by Shailee Shah. Click on the document to view its contents.

Introduction: A novel ablation catheter that can measure local impedance (LI) was recently launched. We aimed to explore target LI measurements at each radiofrequency application (RFA) for creating sufficient ablation lesions during pulmonary vein (PV) isolation. Methods: This prospective study included 15 consecutive patients scheduled to undergo an initial ablation of paroxysmal atrial fibrillation (AF). Circumferential ablation around both ipsilateral PVs was performed using a 4-mm irrigated ablation catheter with an LI sensor. Point-by-point ablation was used with a 4-mm inter-ablation-point distance. Operators were blinded to LI measurements during the procedure. Creation of sufficient ablation lesions was assessed by the absence of a conduction gap. Results: After first-pass encircling PV antrum ablation, left atrium to PV conduction remained in 12 of 30 (40%) ipsilateral PVs. Mapping using the mini-basket catheter identified 48 ablation points through which the propagation wave entered the PV. At ablation points with a gap, the LI drop during RFA was half that at points without a gap (12 ± 7 vs. 23 ± 12 ohm, p<0.001). The GI drop did not differ between ablation points with and without a gap (12 ± 7 vs. 14 ± 10 ohm, p=0.10). An LI drop of 15 ohm predicted sufficient lesion formation without a gap with a sensitivity of 0.71, specificity of 0.81, and predictive accuracy of 0.75. Conclusion: A target LI drop of 15 ohm at each RFA with a 4-mm distance between adjacent ablation points may facilitate creation of sufficient ablation lesions during PV isolation

Are all Non-sustained Ventricular Tachycardia the Same in Hypertrophic Cardiomyopathy Risk Stratification for Sudden Cardiac Death?Mohamad Khaled Sabeh MD1, Marwan M. Refaat MD21Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, Massachusetts - USA2Division of Cardiology, Department of Internal Medicine, American University of Beirut Medical Center Beirut, LebanonRunning Title: NSVT in HCM SCD Risk StratificationWords (excluding references): 664Disclosures: NoneFunding: NoneKeywords: Hypertrophic Cardiomyopathy, Non-sustained Ventricular Tachycardia, 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: [email protected] with reduced systolic function predispose to sudden cardiac death (SCD) and many studies helped in decreasing that risk by Implantable Cardioverter Defibrillator (ICD) implantation and pharmacologic management (1-4). Many types of cardiomyopathies with preserved systolic function, including hypertrophic cardiomyopathy (HCM), can predispose to malignant ventricular arrhythmias and SCD. HCM is the most common inherited cardiac disease that affects 1 in 200 live births (5,6). SCD remains one of the main causes of death in HCM and the SCD rate peaks in early adulthood (7-14). Data from ICDs suggest that SCD in HCM is most commonly caused by ventricular fibrillation (VF) (15). One major clinical challenge is identifying patients at risk for SCD. Multiple studies showed that non-sustained ventricular tachycardia (NSVT) is a risk actor for SCD (16,17). However the strength of the data was variable across these studies due to difference in populations and the low sensitivity of Holter ECG. Moreover, other studies looked at the rate and duration of the ventricular arrhythmias and their relationship to SCD in HCM (17-19) yet the effect of the morphology of NSVT on SCD has not been well investigated.In this single center study Adduci et al . explore the prognostic impact of different NSVT morphologies in a cohort of 109 consecutive HCM patients. The study included patients who had an ICD implanted in the authors’ institution from January 2001 to December 2018. The ICDs were mostly implanted for primary prevention in HCM patient with 1) one or more risk factor including maximal LV thickness ≥30 mm, family history of SD in at least 1 first-degree relative <50 years of age, non-sustained ventricular tachycardia (NSVT), recent (≤ 6 months) unexplained syncope, 2) hypotensive blood pressure during exercise with at least one additional major risk factor for SD 3) end-stage HCM regardless of other established risk markers of SCD. Devices were interrogated on evaluation every 3 to 6 months and the data was assessed for appropriate or inappropriate ICD therapies. Two independent electrophysiologists analyzed the ICD near field and far field EGMs from the ventricular tachycardia runs. They classified the VTs as either monomorphic (MMVT) or polymorphic (PMVT).During a mean follow up of 71+/- 48 months, 377 NSVT episodes of NSVT were retrieved from ICD memory in 46 patients; of these episodes, 7(2%) were polymorphic and 370 (98%) were monomorphic (MM). The mean HR of The MM NSVT had an average HR of 171+/- 32 BPM and lasted for 17 +/- 12 beats while the PMVT were faster at 241BPM +/- and longer at 28+/- 16 beats. The appropriate intervention rate was 5.1% per year and interestingly NSVT did not predict the occurrence of ICD therapy. However patients with polymorphic NSVT had a statistically higher risk for ICD intervention as compared to monomorphic NSVT. Further analysis noted a trend for increased risk of ICD therapy with patients with >1 NSVT morphology. Moreover 75% of the treated VTs had been previously observed as NSVT.Risk stratification is very important in this young patient population; decreasing the risk threshold for ICD implants leads to missed arrhythmias and bad outcomes while increasing it increases the risk for complications from unnecessarily implanted devices. There are several types of ICDs: Transvenous ICD, Subcutaneous ICD and Extravascular ICD. The results of this study suggest that the risk of SCD in patients with PMVT and/or NSVT with multiple morphologies is different from that of patients with a MMVT, and that the presence of short MMVT doe not predict the future ICD therapies. As such, one may consider a conservative approach in low-risk patients with short bursts of slow MM NSVT, and a more aggressive approach in patients with frequent, rapid rate burst of PMVT. Although this study suggests that different NSVT morphologies affect the prognosis in HCM patients, the low number of events lacked the statistical power to redefine ICD candidacy. Larger multicenter studies are needed to confirm these findings and to help delineate the “at risk patients” who would truly benefit from ICDs.

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: [email protected] 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.

Introduction: Patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) require chronic anticoagulation due to a high thromboembolic risk. Evidence supporting use of non-vitamin K oral anticoagulants (NOACs) in patients with HCM remains sparse, and there are no data regarding the use of NOACs in HCM patients undergoing catheter ablation of AF. Methods: Observational non-randomised study in 4 European Centres. We aimed to investigate the safety and efficacy of NOACs compared with vitamin-K antagonists (VKAs) in patients with HCM undergoing catheter ablation for AF. Results: One hundred thirty-seven HCM patients (mean age 55.0±13.4, 29.1% female) underwent 230 catheter ablations for AF (1.7±1.0 per patient). A total of 55 patients (39.4%) underwent 70 procedures (30.4%) on NOAC, while the remaining were on VKA. Warfarin (97.6%) and rivaroxaban (56.4%) were the most frequently used agents in the respective groups. No procedure-related deaths were reported. We observed no significant difference in the rate of thromboembolism (VKA 0.6%; NOAC 0%; p=1.0) or minor bleeding (VKA 0.6%; NOAC 1.4%; p=0.54). There was a non-significant trend towards a lower incidence of major bleeding (VKA 6.8%; NOAC 1.4%; p=0.09). Conclusion: These preliminary data suggest that NOACs are at least as safe and effective as VKAs in patients with HCM undergoing catheter ablation for AF.

A document by Francesco Zanon. Click on the document to view its contents.

Cardiac pacing is the only effective therapy for patients with symptomatic brady-arrhythmia. Traditional right ventricular apical pacing causes electrical and mechanical dyssynchrony resulting in left ventricular dysfunction, recurrent heart failure and atrial arrhythmias. Physiological pacing activates the normal cardiac conduction thereby providing synchronized contraction of ventricles. Though His bundle pacing (HBP) acts as an ideal physiological pacing modality, it is technically challenging and associated with troubleshooting issues during follow up. Left bundle branch pacing (LBBP) has been suggested as an effective alternative to overcome the limitations of HBP as it provides low and stable pacing threshold, lead stability and correction of distal conduction system disease. This paper will focus on the implantation technique, troubleshooting, clinical implications and a review of published literature of LBBP

“Atrial Fibrillation and Premature Ventricular Complexes” – is there a unifying diagnosis?

Irregular narrow QRS complex tachycardia with intermittent atrioventricular dissociation: What is the mechanism?Atsushi Doi, MD, PhD; Naoko Miyazaki, MD; Tomohiko Goda, MD; Haruya Yamane, MD; Kei Tanaka, MD; Ryo Araki, MD,PhD; Fumi Sato, MD, PhD; Takayuki Yamada, MD.Department of Cardiovascular Medicine, Otemae Hospital, 1-5-34 Otemae, Chuo-ku, Osaka, 540-0008, Japan.Correspondence to Atsushi Doi, MD, PhD. Department of Cardiovascular Medicine, Otemae Hospital, 1-5-34 Otemae, Chuo-ku, Osaka, 540-0008, Japan.Tel: 81-6-6941-0484, Fax: 81-6-6942-2848E-mail; [email protected]

Letter to the Editor

Background Data on the optimal location of the ECG leads for the diagnosis of drug-induced long QT syndrome (diLQTS) with Torsades de Pointes (TdP) are lacking. Methods We systematically reviewed the literature for ECGs of patients with diLQTS and subsequent TdP. We assessed T-wave morphology in each lead and measured the longest QT interval in the limb and chest leads in a standardized fashion. Results Of 84 patients, 61.9% were female and mean age was 58.8 years. QTc was significantly longer in chest versus limb leads (mean (standard deviation) 671 (102) vs 655 (97) ms, p=0.02). Using only limb leads for QT interpretation, 18 (21.4%) ECGs were non-interpretable: 10 (11.9%) due to too flat T-waves, 7 (8.3%) due to frequent, early PVCs and 1 (1.2%) due to too low ECG recording quality. In the chest leads, ECGs were non-interpretable in 9 (10.7%) patients: 6 (7.1%) due to frequent, early PVCs, 1 (1.2%) due to insufficient ECG quality, 2 (2.4%) due to missing chest leads but none due to too flat T-waves. The most common T-wave morphologies in the limb leads were flat (51.0%), broad (14.3%) and late peaking (12.6%) T-waves. Corresponding chest lead morphologies were inverted (35.5%), flat (19.6%) and biphasic (15.2%) T-waves. Conclusions Our results indicate that QT evaluation by limb leads only underestimates the incidence of diLQTS experiencing TdP and favors the screening using both limb and chest lead ECG.

Background Atrial tachyarrhythmias (ATAs) are common within the three-month blanking period following catheter ablation of atrial fibrillation (AF). However, little evidence is available regarding the current guidelines on the blanking period after surgical AF ablation. We investigate the incidence and significance of early recurrence of atrial tachyarrhythmia (ERAT) and evaluate the optimal blanking period after surgical AF ablation. Methods Data from 259 patients who underwent surgical AF ablation from 2009 to 2016 were collected. ERAT was defined as documented ATA episodes lasting for 30 seconds. A multivariate Cox proportional hazard model was constructed to evaluate the role of ERAT as a predictor of late recurrences (LR) for AF. Results In total, 127 patients (49.0%) experienced their last episodes of ERAT during the first (n=65), second (n=14), or third (n=48) month of the three-month blanking period (p<0.001). One-year freedom from ATAs was 97.8% in patients without ERAT compared with 95.4%, 64.3%, and 8.3% in patients with ERAT in the first, second, and third month after the index procedure, respectively (p<0.001). Hazard ratios of LR according to the timing of the last episode of ERAT first, second, and third month after the procedure were 2.84, 16.70, and 119.75, respectively. Conclusions The ERAT occurred in 49.0% of patients within the first three months after surgical ablation. The occurrence of ERAT within three months after surgical AF ablation was a significant independent predictor of LR. Hence, the currently accepted three-month blanking period needs to be redefined in patients with AF surgical ablation.

To the Editor,We have read with great interest the article entitled ‘Management of Patients with Interrupted Inferior Vena Cava Requiring Electrophysiology Procedures’ by Hanley et al1 in the latest issue of the journal. We would like to thank the authors for their difficult case series with interrupted vena cava inferior and for successfully performed electrophysiologic studies. Electrophysiologic procedures including mapping and percutaneous catheter ablation of left-sided accessory pathways via the retrograde transaortic approach have been successfully applied techniques in patients with supraventricular tachycardia with and without Wolff-Parkinson-White electrocardiographic pattern for a long time.2 If no anatomic obstacles are found, a deflectable mapping catheter can easily be advanced from the femoral artery and positioned in the mitral annulus to localize the accessory pathway, even in patients with congenital anomalies.3 One should keep in mind that the retrograde transaortic approach has the potential adverse events related to percutaneous arterial access and tight contact with valvular leaflets although it seems as a simpler and less time consuming approach requiring less specialized equipment compared to the transseptal way.Mapping and percutaneous catheter ablation of the atrioventricular node or the His bundle can also be performed from the left side via the retrograde transaortic approach. Some electrophysiologists prefer the retrograde transaortic route as a first-line approach although most operators perform catheter ablation from the venous side.The electrophysiologists’ preferences are generally based on experience, familiarity with the equipment and the procedure, and personal thoughts about the patient.Keywords: ablation; left-sided; retrograde transaortic approach