RESPONSE FOR THE LETTER TO THE EDITORDon’t miss a chance taking the best shot!!Kunihiko KiuchiDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineAddress for correspondence:Kunihiko Kiuchi, MD, FHRSSection of Arrhythmia, Division of Cardiovascular Medicine,Department of Internal Medicine, Kobe University Graduate School of Medicine7-5-2 Kusunoki-chou chuou-ku, Kobe, Hyogo, JapanTelephone: (81)-78-382-5846Fax: (81)-78-382-5859E-mail: firstname.lastname@example.orgDisclosures:The Section of Arrhythmia was supported by an endowment from Medtronic JAPAN and Abbott JAPAN. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.Funding: NoneTo the Editor,We thank Dr. Althoff and Mont for their interest, comments, and suggestions related to our paper.1 In our study, as they suggested, LGE-MRI was acquired 1-3 months after the ablation. An animal study reported that ablation lesions are fully formed by 3 weeks and are dense with collagen and fat deposition by 6 weeks.2 In our pilot study, the ablation lesion area dramatically diminished from 1 week to 6 weeks after the procedure in most of the patients. Furthermore, the ablation lesion area was comparable between 6 weeks and just 3 months after the ablation. Of interest, the ablation lesion disappeared after 5-6 months following the procedure in some patients without AF recurrence. We speculated that the shrinkage of the ablation lesion might have occurred during the pathophysiological healing process and reverse remodeling of the left atrium. Therefore, we considered that the time point of taking the “best shot” might have been earlier than we expected. Furthermore, the dose of the contrast agent was important for determining the time point. Our dose of the contrast agent was 0.1mmol/kg, which was relatively lower than that of the other groups. To address this issue, further study will be needed.As for an internal reference for normalization, the threshold of the signal intensity was initially determined according to the signal intensity histogram on the “whole LA wall” in our previous studies.3,4 However, as the authors suggested, neither the ablation lesion nor atrial fibrosis could be accurately visualized in some patients with advanced atrial remodeling. Therefore, the internal reference was changed from the “whole LA wall” to the “healthy LA wall” in our recent studies.1,5 We believed that this simple but important tip might make it possible to sensitively identify pre-existing atrial fibrosis, particularly interstitial fibrosis. The signal intensity of ablation lesion was significantly higher than that of the pre-existing atrial fibrosis. Our question is whether the ablation lesion characteristics dramatically differed between the different references in patients without atrial remodeling. Although we re-analyzed the LGE-MRI with two different references (“whole LA wall” and “healthy LA wall”), no significant difference in the lesion characteristics could be found. Cryoballoon ablation and RF ablation with contact-force sensing catheter induced intensive inflammation which followed by the artificial fibrosis.6 In this study, we focused on the visualization of the ablation lesion not the pre-existing atrial fibrosis, and patients without atrial remodeling were enrolled. We considered that the impact of the difference in the reference could be less than we expected, when we focused on the ablation lesions in patients without atrial remodeling.To visualize the atrial fibrosis and the ablation lesion, different visualization methods were developed. However, very few histological validations could be found. Furthermore, the dose of the contrast agents, MRI system, and visualization software completely differed due to the regulations in each institution. Therefore, it is not surprising that the image differed between each visualization technique. It is important to note the reproducibility of the visualization method and clinical implication of the best shot. The authors had already reported the reproducibility of their method.7 However, this issue is still in debate.8 We would like to challenge to improve the quality of our “best shot” and strengthen both reproducibility and clinical implication in a further study.References1. Kurose J, Kiuchi K, Fukuzawa K, et al. Lesion characteristics between cryoballoon ablation and radiofrequency ablation with a contact-force sensing catheter: late-gadolinium enhancement magnetic resonance imaging assessment. J Cardiovasc Electrophysiol. 2020.2. Avitall B, Kalinski A. Cryotherapy of cardiac arrhythmia: From basic science to the bedside. Heart Rhythm. 2015;12(10):2195-2203.3. Shigenaga Y, Kiuchi K, Ikeuchi K, et al. Fusion of Delayed-enhancement MR Imaging and Contrast-enhanced MR Angiography to Visualize Radiofrequency Ablation Scar on the Pulmonary Vein. Magn Reson Med Sci. 2015;14(4):367-372.4. Kiuchi K, Okajima K, Shimane A, et al. Visualization of the radiofrequency lesion after pulmonary vein isolation using delayed enhancement magnetic resonance imaging fused with magnetic resonance angiography. J Arrhythm. 2015;31(3):152-158.5. Akita T, Kiuchi K, Fukuzawa K, et al. Lesion distribution after cryoballoon ablation and hotballoon ablation: Late-gadolinium enhancement magnetic resonance imaging analysis. J Cardiovasc Electrophysiol. 2019.6. Kiuchi K, Fukuzawa K, Mori S, Watanabe Y, Hirata KI. Feasibility of Imaging Inflammation in the Left Atrium Post AF Ablation Using PET Technology. JACC Clin Electrophysiol. 2017;3(12):1466-1467.7. Benito EM, Carlosena-Remirez A, Guasch E, et al. Left atrial fibrosis quantification by late gadolinium-enhanced magnetic resonance: a new method to standardize the thresholds for reproducibility.Europace. 2017;19(8):1272-1279.8. Kamali R, Schroeder J, DiBella E, et al. Reproducibility of Clinical Late Gadolinium Enhancement Magnetic Resonance Imaging in Detecting Left Atrial Scar after Atrial Fibrillation Ablation. J Cardiovasc Electrophysiol. 2020 in press.
Is Otsu Thresholding the Answer to Reproducible Quantification of Left Atrial Scar from Late Gadolinium-Enhancement MRI?Suvai Gunasekaran, PhDa, Daniel Kim, PhDa,ba Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, United Statesb Department of Biomedical Engineering, Northwestern University, Evanston, IL, United StatesPlease send correspondence to:Daniel Kim, PhDDepartment of RadiologyNorthwestern University737 N. Michigan Avenue Suite 1600Chicago, IL 60611 email@example.com O:312.926.1733 F:312.926.5991
Kurose et al. report on a lower number of gaps in RF-lesions compared to Cryo-lesions as determined by late gadolinium enhancement MRI (LGE-MRI). However, unlike claimed by the authors, there is ample evidence based on LGE-MRI in this context. Most importantly we have specifically compared RF and Cryo lesions in a recent case control study on AF Ablation. In contrast to the results of Kurose et al., our study, despite larger sample size, did not detect a difference in the number of gaps between the two energy sources. While numerous factors may account for the conflicting results, two points should be considered in particular. 1. The time point of LGE-MRI at a mean of 55 days post ablation has never been validated for chronic lesion formation, and is considerably earlier than the validated and well-established 3-months timepoint chosen by most groups. In fact, according to previous reports, gadolinium enhancement at earlier time points may, at least in part, reflect a transient inflammatory response rather than chronic scar formation. 2. The method of Kurose et al. is based on the definition of an area of healthy atrial tissue in each patient as an internal reference. However, it appears almost impossible to define a truly healthy area in the atrium of patients with atrial fibrillation. Thus the method is likely to underestimate ablation-induced fibrosis in patients with advanced disease and/or underlying pathologies and to overestimate it in younger, rather healthy patients.
We thank Medina et al. for their interest in our recent work on QTc prolongation associated with treatment of COVID-19 patients with hydroxychloroquine and azithromycin. As they appropriately point out in their letter, genetic variation is likely a significant determinant of QT prolongation in the population at large and in COVID-19 patients specifically. While drugs causing acquired long QT syndrome and torsades de pointes are generally blockers of IKr, repolarization results from the aggregate of multiple inward and outward currents. Patients with sub-clinical defects in any of these ion channels can have normal or only slightly prolonged baseline QT intervals, but may possess decreased repolarization reserve leading to an exaggerated response to IKr blockade (1). In our study, a baseline QTc of > 460 ms was associated with excessive QTc prolongation, and this likely represents a group of patients with sub-clinical cardiac ion channel mutations (so called “first hit”) (2). We also agree that many patients with latent mutations demonstrate a normal baseline QT, which gets prolonged with the addition of a drug or a change in the clinical condition “second hit” (3). The patients in our study who exhibited QTc prolongation were generally acutely ill, and displayed “multiple hits” that led to QTc prolongation and it is certainly plausible that many may have had sub-clinical cardiac ion mutations. We therefore wholeheartedly agree that pharmacogenetics should be considered in studies of drug-induced QT prolongation, however this information is rarely available to include for acutely ill patients. And while it makes sense to obtain genetic profiles prior to administration of QT-prolonging medications, that can only be performed in the elective outpatient setting, while taking into consideration medical, ethical and social issues related to asymptomatic genetic screening (e.g. cost, reimbursement, informed consent, etc…). There is significant interest in building genomic databases, and when this becomes a reality for the population at large we believe that genetic information should certainly be included in studies of QT prolongation.Roden DM Long QT syndrome: reduced repolarization reserve and the genetic link. J Intern Med. 2006 Jan; 259(1):59-69.Napolitano C, Schwartz PJ, Brown AM, et al. Evidence for a cardiac ion channel mutation underlying drug-induced QT prolongation and life-threatening arrhythmias. J Cardiovasc Electrophysiol. 2000;11:691–6Sauer AJ and Newton-Cheh C. Clinical and genetic determinants of torsade de pointes risk. Circulation. 2012;125:1684-94.
Background: The abnormal conduction zone (ACZ) in the left atrium (LA) has attracted attention as an arrhythmia source in atrial fibrillation (AF). We investigated the hypothesis that the ACZ is related to the low voltage area (LVA) or the LA anatomical contact areas (CoAs) with other organs. Methods and Results: We studied 100 patients (49 non-paroxysmal AF, 66 males, 67.9±9.9 years) who received catheter ablation for AF. High-density LA mapping during high right atrial pacing was constructed. Isochronal activation maps were created at 5-ms interval setting, and the ACZ was identified on the activation map by locating a site with isochronal crowding of ≥3 isochrones, which are calculated as ≤27 cm/s. The LVA was defined as the following; mild (<1.3 mV), moderate (<1.0 mV), and severe LVA (<0.5 mV). The CoAs (ascending aorta-anterior LA, descending aorta-posterior LA, and vertebrae-posterior LA) were assessed using computed tomography. The ACZ was linearly distributed, and observed in 95 patients (95%). The ACZ was most frequently observed in the anterior wall region (77%). A longer ACZ was significantly associated with a larger LA size and a prevalence of non-PAF. The 51.2±36.2% of ACZ overlapped with mild LVA, 32.9±32.8% of ACZ with moderate LVA, and 14.6±22.0% of ACZ with severe LVA. In contrast, only 25.6±28.0 % of ACZ matched with the CoAs. Conclusion: The abnormal conduction zone reflects LA electrical remodeling and may be a precursor finding of the low voltage zone and not the LA contact areas in patients with atrial fibrillation.
Our article reported risk factors for ICD lead failure at our medical center, and we found an elevated risk of ICD lead failure in multiple lead ICD systems implanted via cephalic venous access.(1) Our analysis was prompted by recent literature related to durability of the Linox ICD lead (Biotronik, Inc., Berlin, Germany), and we found similar, elevated risk of ICD lead failure implanted in multiple lead systems via cephalic access in Linox and non-Linox ICD leads. Given the small number of total lead failures in the overall cohort (6 of 660), and the retrospective, single-center nature of our analysis, we reviewed prior Linox ICD lead durability manuscripts for evidence of increased risk of failure in multiple lead ICD systems implanted via cephalic venous access. While no prior manuscript evaluated this specific risk, we did find a trend towards increased risk of lead failure in cohorts with greater proportions of multiple lead systems, and greater proportions of systems implanted via cephalic access, however these variables were included in the analysis in a minority of prior studies.Dr. Maas and colleagues express surprise at the high failure rate when implanting multiple leads in our cohort. We would clarify that we reported ICD lead failure in 4 of the 304 patients in our cohort with multiple ICD leads, and that the frequency of lead failure in multiple lead ICD systems was not statistically significantly different compared to that of single lead ICD systems. In contrast, and surprisingly to us, 3 of 30 patients with multiple lead ICD systems implanted via cephalic access experienced ICD lead failure, and the frequency of ICD lead failure was significantly greater in this group compared to the remaining cohort in Kaplan-Meier survival analyses.Maas and colleagues question the reason for utilization of cephalic access in 18% of patients, hypothesize that suboptimal implantation technique may be responsible for the elevated lead failure rate, and request clarification of lead failure mechanism. We did not systematically collect rationale for venous access technique, and venous access techniques was at the discretion of the implanting physician. Of the 6 lead failures, 3 were related to lead noise, and 3 were related to rising pacing thresholds. Of the three lead failures amongst patients with multiple lead systems implanted via cephalic venous access, 2 were related to lead noise, and 1 was related to a rising pacing threshold. We believe that the lead noise may be related to insulation breach that may be predisposed by lead-lead interactions in the region of the cephalic vein. ICD leads were returned to the manufacturer on an ad hoc basis, and no specific feedback was received from manufacturers related to leads included in our analysis. All implanting physicians were experienced operators, and there were no significant differences in frequency of ICD lead failure by operator. We agree that implantation technique may play an important role in lead failure risk, and our analysis should prompt extra caution when implanting multiple leads via cephalic venous access.Citing the above limitations of our analysis, Dr Maas and colleagues state that it is “too early to abandon cephalic vein access, even for multiple lead systems.” They also review recent literature reporting favorable acute outcomes of ultrasound guided axillary venous access. We agree that our analysis paired with our literature review is best considered hypothesis generating, and we hope that our analysis encourages future studies to consider our findings when selecting variables of interest in ICD lead durability studies. We share Dr. Maas and colleagues’ favorable view of data supporting axillary venous access, particularly in combination with ultrasound guidance. As a result, given the available evidence of acceptable alternative techniques, our practice is to favor axillary venous access during implantation of multiple lead ICD systems, but we would not hesitate to implant via cephalic venous access in the appropriate clinical scenario.References1. Barbhaiya CR, Niazi O, Bostrom J et al. Early ICD lead failure in defibrillator systems with multiple leads via cephalic access. Journal of cardiovascular electrophysiology 2020;31:1462-1469.
Sudden Cardiac Death (SCD) remains a global threat.1The most common causes of SCD are ischemic heart diseases and structural cardiomyopathies in the elderly. Additional causes can be arrhythmogenic, respiratory, metabolic, or even toxigenic.2,3,4 Despite the novel diagnostic tools and our deeper understanding of pathologies and genetic associations, there remains a subset of patients for whom a trigger is not identifiable. When associated with a pattern of Ventricular Fibrillation, the diagnosis of exclusion is deemed Idiopathic Ventricular Fibrillation (IVF).2,5 IVF accounts for 5% of all SCDs6 – and up to 23% in the young male subgroup5 – and has a high range of recurrence rates (11-45%).7,8,9 There are still knowledge gaps in the initial assessment, follow-up approach, risk stratification and subsequent management for IVF.1,10,11 While subsets of IVF presentations have been better characterized into channelopathies, such as Brugada’s syndrome (BrS), Long QT Syndrome (LQTS), Early Repolarization Syndrome (ERS), Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), much remains to be discovered.12,13 Implantable Cardioverter Device (ICD) placement as secondary prevention for IVF is the standard of care. This is warranted in the setting of high recurrence rates of arrhythmias (11-43%). Multiple studies have shown potential complications from ICDs and a significant number of cases experiencing inappropriate shock after ICD placement.14In their article, Stampe et al. aim to further understand clinical presentation and assessment, and risk factors for recurrent ventricular arrhythmias in IVF patients. Using a single-centered retrospective study, they followed a total of 84 Danish patients who were initially diagnosed with IVF and received a secondary ICD placement between December 2007 and June 2019. Median follow-up time was 5.2 years (ICR=2-7.6). To ensure detection of many possible underlying etiologies ranging from structural, ischemic, arrhythmogenic, metabolic, or toxicologic, the researchers found that a wide array of diagnostic tools were necessary: standard electrocardiograms (ECGs), high-precordial leads ECGs, standing ECGs, Holter monitoring, sodium-channel blocker provocation tests, exercise stress tests, echocardiograms, cardiac magnetic resonance imaging, coronary angiograms, cardiac computed tomography, electrophysiological studies, histological assessment, blood tests, toxicology screens, and genetic analysis.The study by Stampe et al. highlights the importance of thorough and continuous follow-up with rigorous evaluation: Three (3.6%) patients initially diagnosed with IVF were later found to have underlying cardiac abnormalities (LQTS and Dilated Cardiomyopathy) that explained their SCA. Like other studies, the burden of arrhythmia was found to be high, but unlike reported data, the overall prognosis of IVF was good. Despite the initial pattern of ventricular fibrillation in those who experienced appropriate ICD placement (29.6%), ventricular tachycardia and ventricular fibrillation had a comparable predominance. As for patients with inappropriate ICD placements, atrial fibrillation was a commonly identified pathological rhythm (16.7%). Recurrent cardiac arrest at presentation (19.8%) was a risk factor for appropriate ICD therapy (HR=2.63, CI=1.08-6.40, p=0.033). However, in contrast to previous studies, early repolarization detected on baseline ECG (12.5%), was not found to be a risk factor (p=0.842).The study by Stampe et al. has few limitations. First, the study design, a retrospective cohort, precluded standardized follow-up frequencies and diagnostic testing. Second, while the study was included many of the cofounders tested in previous studies (baseline characteristics, baseline ECG patterns, comorbidities), medication use was not included. Third, the follow-up period may have been insufficient to detect effect from some of the confounding factors. Finally, the sample size was small and it was from a single center.There are several strengths of the Stampe et al. study. Firstly, the wide range of diagnostic tests used at index presentation and during the follow-up period ensured meticulous detection of most underlying etiologies. Secondly, appropriate and well-defined inclusion and exclusion criteria were used. Thirdly, funding by independent parties ensured no influence on study design, result evaluation, and interpretation. Finally, the study has succeeded in improving our understanding of IVF. Future studies should include though a larger population size and a more diverse population.References:1.AlJaroudi WA, Refaat MM, Habib RH, Al-Shaar L, Singh M, et al. Effect of Angiotensin Converting Enzyme Inhibitors and Receptor Blockers on Appropriate Implantable Cardiac Defibrillator Shock: Insights from the GRADE Multicenter Registry. Am J Cardiol Apr 2015; 115 (7): 115(7):924-31.2. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: executive summary. J Am Coll Cardiol 2018;72:e91–e220.3. Refaat MM, Hotait M, London B: Genetics of Sudden Cardiac Death. Curr Cardiol Rep Jul 2015; 17(7): 6064. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013;10:1932–1963.5. Priori SG, Blomström-Lundqvist C, Mazzanti A, et al. ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J 2015;36(41):2793-2867.6. Zipes DP, Wellens HJ. Sudden cardiac death. Circulation. 1998;98:2334–2351.7. Ozaydin M, Moazzami K, Kalantarian S, Lee H, Mansour M, Ruskin JN. Long-term outcome of patients with idiopathic ventricular fibrillation: a meta-analysis. J Cardiovasc Electrophysiol 2015;26:1095–1104.8. Herman AR, Cheung C, Gerull B, Simpson CS, Birnie DH, Klein GJ, et al. Outcome of apparently unexplained cardiac arrest: results from investigation and follow-up of the prospective cardiac arrest survivors with preserved ejection fraction registry. Circ Arrhythm Electrophysiol 2016;9:e003619.9. Siebermair J, Sinner MF, Beckmann BM, Laubender RP, Martens E, Sattler S, et al.Early repolarization pattern is the strongest predictor of arrhythmia recurrence in patients with idiopathic ventricular fibrillation: results from a single centre long-term follow-up over 20 years. Europace 2016;18:718-25.10. Refaat MM, Hotait M, Tseng ZH: Utility of the Exercise Electrocardiogram Testing in Sudden Cardiac Death Risk Stratification. Ann Noninvasive Electrocardiol 2014; 19(4): 311-318.11. Gray B, Ackerman MJ, Semsarian C, Behr ER. Evaluation after sudden death in the young: a global approach. Circ Arrhythm Electrophysiol 2019;12: e007453.12. Herman AR, Cheung C, Gerull B, Simpson CS, Birnie DH, Klein GJ, et al. Response to Letter Regarding Article, Outcome of apparently unexplained cardiac arrest: results from investigation and follow-up of the prospective cardiac arrest survivors with preserved ejection fraction registry”. Circ Arrhythm Electrophysiol 2016;9:e004012.13. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, Potenza D, et al. Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature 1998;392:293–296.14. Baranchuk A, Refaat M, Patton KK, Chung M, Krishnan K, et al. What Should You Know About Cybersecurity For Cardiac Implantable Electronic Devices? ACC EP Council Perspective. J Am Coll Cardiol Mar 2018; 71(11):1284-1288.
Case report A 74-year-old man presented with frequent palpitations, described as “the heart beating on the neck.” He also had a history of two syncope episodes; the most recent was more than six months before his admission. By careful history taking, we found that the syncope episodes did not seem to occur as a result of vasovagal reflex. The patient’s resting electrocardiogram (ECG) showed a right bundle branch block (RBBB) pattern (Figure 1 ). Holter monitoring and exercise tests revealed a bundle branch block alternating between the right and left bundles. His echocardiogram was normal with preserved ejection fraction (EF) (66%).After this initial evaluation, he was subjected to an electrophysiological study (EPS) and the basic intervals measured were as follows: PR, 186 ms; QRS, 153 ms (RBBB); AH, 86 ms (basal); and HV, 60 ms. Atrial electrical stimulation (AES) induced a wide QRS complex tachycardia (Figure 2A ), with predominantly RBBB morphology, some of the QRS having a left bundle branch block (LBBB) pattern, and some atrial beats being blocked to the ventricles below the bundle of His (Figure 2B ).
The field of electrophysiology continues to move further towards low fluoroscopy procedures. The deleterious effects of radiation exposure and of the radiation protection clothing themselves are the primary drivers of this approach. Radiation exposure is known to increase the risk of cancer and cataracts for all operators, and namely those who are subjected to accumulating doses of radiation over time. (1). Proper radiation protective clothing can significantly decrease these risks however this strategy has serious weaknesses. For instance, the protective clothing does not cover the whole body, leaving the face and the skull exposed. Roguin et al (2) showed that the risk of radiation exposure to the unprotected areas of the body is real and has serious consequences. In a cohort of 31 interventional cardiologists who developed brain cancer, the investigators showed that 22 (85%) of them had left sided tumors, and 17 (55%) of them had glioblastoma multiforme. This remarkable finding suggests that the dose left side of the brain, the side that gets more radiation exposure, is much more likely to develop a cancer that carries a poor prognosis and a median expected survival of 12 months. Furthermore, the radiation protective clothing itself can cause orthopedics injuries common among interventional cardiologists such those of the spine and the knees. Given the deleterious effects of radiation, low fluoroscopy approaches are welcomed by the electrophysiology community if they can show a safety profile similar to that with the use of fluoroscopy.The transseptal puncture (TSP) is arguably the most critical step during which fluoroscopy is used. In this study Singh et al describe an approach for TSP under electoanatomic guidance. The authors then retrospectively compare the total procedure duration, fluoroscopy time, radiation exposures, and complications related to the TSP using this method with those of conventional fluoroscopy. This was a single center study that included 145 consecutive patients, with no previous history of cardiac surgery, who underwent de novo and redo AF ablations between June 2018 and April 2019. These patients were then compared to cases performed by the same operators before June 2018. The procedure was done under conscious sedation. A dense electroanatomic map of the right atrium was acquired using CARTO 3 Fast Anatomical Mapping and Confidence Software, with emphasis on the atrial septum, His Bundle, coronary sinus ostium, and superior vena cava. The authors observed that the fossa ovalis was an area of low voltage potential (0.37±0.19 mV vs 1.73±0.74 mV) and low impedance (125±11 Ω vs 138±15 Ω), and electrically distinct from the rest of the atrial septum. The authors were able to localize the fossa ovalis using a combination of anatomical landmarks and the use of a voltage threshold of 0.75mV. The transseptal needle was then advanced through this desired location. The authors reported no significant complications related to the TSP.The authors argue that the safety profile is like the TSP under fluoroscopy, however this is a single center study. In fact the most senior operator performed three- quarters of all the procedures. Given the high risk of such an approach, the main question for the wide adoption of such a technique will again be safety in the hands of less experienced operators. A major factor that can increase the safety profile as well as the preciseness of the TSP is the routine use of ICE. ICE can confirm the precise positioning of the needle even in cases with unusual atrial septal anatomies (floppy, bulging, hypertrophic septum or in the presence of devices such as CardioSEAL or other atrial septal defect occlusion devices). Furthermore, ICE can confirm the location of the needle in the LA with microbubble injections after the TSP; it can confirm the location of the wire thus making it safer to advance the sheath knowing that it will not end up in the LAA or causing a perforation. As such ICE is arguably more important in the low fluoroscopy approach than in a one with fluoroscopy.Low fluoroscopy approach to TSP is a welcomed change in the field of electrophysiology given the significant adverse outcomes of radiation and radiation protective clothing to providers. The main concern in such a change is the safety and precise localization of the TSP. New technologies are allowing the development of new approaches such as the one described by Troisi et al to achieve the goal of safe low fluoroscopy procedures.References:Klein LW, Miller DL, Balter S, et al. Occupational health hazards in the interventional laboratory: time for a safer environment. Radiology 2009; 250:538-544.Roguin A, Goldstein J, Bar O, Goldstein JA. Brain and neck tumors among physicians performing interventional procedures. Am J Cardiol 2013;111(9):1368-72.
Objective: To compare multiple-procedure catheter ablation outcomes of a stepwise approach versus left atrial posterior wall isolation (LA PWI) in patients undergoing non-paroxysmal atrial fibrillation (NPAF) ablation. Background: Unfavorable outcomes for stepwise ablation of NPAF in large clinical trials may be attributable to pro-arrhythmic effects of incomplete ablation lines. It is unknown if a more extensive initial ablation strategy results in improved outcomes following multiple ablation procedures. Methods: 222 consecutive patients with NPAF underwent first-time ablation using a contact-force sensing ablation catheter utilizing either a stepwise (Group 1, n=111) or LA PWI (Group 2, n=111) approach. The duration of follow-up was 36 months. The primary endpoint was freedom from atrial arrhythmia >30s. Secondary endpoints were freedom from persistent arrhythmia, repeat ablation, and recurrent arrhythmia after repeat ablation. Results: There was similar freedom from atrial arrhythmias after index ablation for both stepwise and LA PWI groups at 36 months (60% vs. 69%, p=0.1). The stepwise group was more likely to present with persistent recurrent arrhythmia (29% vs 14%, p=0.005) and more likely to undergo second catheter ablation (32% vs. 12%, p<0.001) compared to LA PWI patients. Recurrent arrhythmia after repeat ablation was more likely in the stepwise group compared to the LA PWI group (15% vs 4%, p=0.003). Conclusions: Compared to a stepwise approach, LA PWI for patients with NPAF resulted in a similar incidence of any atrial arrhythmia, lower incidence of persistent arrhythmia, and fewer repeat ablations. Results for repeat ablation were not improved with a more extensive initial approach.
Long QT syndrome (LQTS) is characterized by prolongation of the QT interval on the electrocardiogram (ECG). Clinically, LQTS is associated with the development of Torsades de Pointes (TdP), a well-defined polymorphic ventricular tachycardia and the development of sudden cardiac death (1). The most common type is the acquired form caused mainly by drugs, it is also known as the drug induced LQTS (diLQTS) (2-5). The diLQTS is caused by certain families of drugs which can markedly prolong the QT interval on the ECG most notably antiarrhythmic drugs (class IA, class III), anti-histamines, antipsychotics, antidepressants, antibiotics, antimalarial, and antifungals (2-5). Some of these agents including the antimalarial drug hydroxycholoquine and the antibiotic azithromycin which are being used in some countries as therapies for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(6,7). However, these drugs have been implicated in causing prolongation of the QT interval on the ECG (2-5).There is a solution for monitoring this large number of patients which consists of using mobile ECG devices instead of using the standard 12-lead ECG owing to the difficulty of using the 12-lead ECG due to its medical cost and increased risk of transmitting infection. These mobile ECG devices have been shown to be effective in interpreting the QT interval in patients who are using QT interval prolonging drugs (8, 9). However, the ECG mobile devices have been associated with decreased accuracy to interpret the QT interval at high heart rates (9). On the other hand, some of them have been linked with no accuracy to interpret the QT interval (10). This can put some patients at risk of TdP and sudden cardiac death.In this current issue of the Journal of Cardiovascular electrophysiology, Krisai P et al. reported that the limb leads underestimated the occurrence of diLQTS and subsequent TdP compared to the chest leads in the ECG device, this occurred in particular with the usage of mobile standard ECG devices which use limb leads only. To illuminate these findings, the authors have studied the ECGs of 84 patients who have met the requirements for this study, which are diLQTS and subsequent TdP. Furthermore, the patients in this study were also taking a QT interval prolonging drug. Krisai P et al. additionally reported the morphology of the T-wave in every ECG and classified them into flat, broad, notched, late peaked, biphasic and inverted. The authors showed that in 11.9% of these patients the ECG was non reliable in diagnosing diLQTS and subsequent Tdp using only limb leads due to T-wave flattening in these leads, in contrast to chest leads where the non- interpretability of the QT interval was never attributable to the T-wave morphology but to other causes. The authors further examined the QT interval duration in limb leads and chest leads and found that the QT interval in limb leads was shorter compared to that of the chest leads, but reported a high variability in these differences. Therefore, it should be taken into account when screening patients with diLQTS using only mobile ECG devices and these patients should be screened using both limb leads and chest leads. Moreover, the authors have highlighted the limitations of using ECG mobile devices as limb leads to interpret the QT interval especially in high heart rates (when Bazett’s equation overcorrects the QTc and overestimates the prevalence of the QT interval) and have advocated the usage of ECG mobile devices as chest leads instead of limb leads due to their superior ability to interpret the QT interval.The authors should be praised for their efforts in illustrating the difference in the QT interval interpretability between the chest leads and the limb leads in patients with diLQTS. The authors also pointed out the limitation of using mobile ECG devices as limb leads for the diagnosis of diLQTS and recommended their usage as chest leads by applying their leads onto the chest due to their better diagnostic accuracy for detecting the diLQTS. The study results are very relevant, it further expanded the contemporary knowledge about the limitation of the QT interval interpretability using ECG mobile device only (11). Future investigation is needed to elucidate the difference in chest and limb leads interpretability of the QT interval and to assess the ability of the mobile ECG devices to interpret the QT interval.ReferencesRefaat MM, Hotait M, Tseng ZH: Utility of the Exercise Electrocardiogram Testing in Sudden Cardiac Death Risk Stratification. Ann Noninvasive Electrocardiol 2014; 19(4): 311-318.Kannankeril P, Roden D, Darbar D. Drug-Induced Long QT Syndrome. Pharmacological Reviews. 2010;62(4):760-781.Nachimuthu S, Assar M, Schussler J. Drug-induced QT interval prolongation: mechanisms and clinical management. Therapeutic Advances in Drug Safety. 2012;3(5):241-253.Jankelson L, Karam G, Becker M, Chinitz L, Tsai M. QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review. Heart Rhythm. 2020 ; S1547-5271(20)30431-8.Li M, Ramos LG. Drug-Induced QT Prolongation And Torsades de Pointes. P T . 2017;42(7):473-477.Singh A, Singh A, Shaikh A, Singh R, Misra A. Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2020;14(3):241-246.Hashem A, Alghamdi B, Algaissi A, Alshehri F, Bukhari A, Alfaleh M et al. Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: A narrative review. Travel Medicine and Infectious Disease. 2020; 35:101735.Chung E, Guise K. QTC intervals can be assessed with the AliveCor heart monitor in patients on dofetilide for atrial fibrillation. J Electrocardiol. 2015;48(1):8-9.Garabelli P, Stavrakis S, Albert M et al. Comparison of QT Interval Readings in Normal Sinus Rhythm Between a Smartphone Heart Monitor and a 12-Lead ECG for Healthy Volunteers and Inpatients Receiving Sotalol or Dofetilide. Journal Cardiovasc Electrophysiol. 2016;27(7):827-832.Bekker C, Noordergraaf F, Teerenstra S, Pop G, Bemt B. Diagnostic accuracy of a single‐lead portable ECG device for measuring QTc prolongation. Annals Noninvasive Electrocardiol. 2019;25(1): e12683.Malone D, Gallo T, Beck J, Clark D. Feasibility of measuring QT intervals with a portable device. American Journal of Health-System Pharmacy. 2017;74(22):1850-1851.
Introduction: Although the presence of left atrial low-voltage areas (LVAs) is strongly associated with the recurrence of atrial fibrillation (AF) after ablation, few methods are available to classify the prevalence of LVAs. The purpose of this study was to establish a risk score for predicting the prevalence of LVAs in patients undergoing ablation for AF. Methods: We enrolled 1004 consecutive patients who underwent initial ablation for AF (age, 68 ± 10 years old; female, 346 (34%); persistent atrial fibrillation, 513 (51%)). LVAs were deemed present when the voltage map after pulmonary vein isolation demonstrated low-voltage areas with a peak-to-peak bipolar voltage of <0.5 mV covering ≥5 cm2 of the left atrium. Results: LVAs were present in 206 (21%) patients. The SPEED score was obtained as the total number of independent predictors as identified on multivariate analysis, namely female sex (odds ratio (OR) 3.4 [95% confidence interval (CI) 2.2-5.2], p <0.01), persistent AF (OR 1.8 [95% CI 1.1-3.0], p=0.02), age ≥70 years (OR 2.3 [95% CI 1.5-3.4], p <0.01), elevated brain natriuretic peptide ≥100 pg/ml or N-terminal pro-brain natriuretic peptide ≥400 pg/ml (OR 1.7 [95% CI 1.02-2.8], p=0.04), and diabetes mellitus (OR 1.8 [95% CI 1.1-2.8], p=0.02). LVAs were more frequent in patients with a higher SPEED score, and prevalence increased with each additional SPEED score point (OR 2.4 [95% CI 2.0-2.8], p <0.01). Conclusion: The SPEED score accurately predicts the prevalence of LVAs in patients undergoing ablation for AF.
Atrial fibrillation (AF) is the most common cardiac arrhythmia and often occurs with heart failure (HF) . AF prevalence increases with increasing severity of HF: for instance its prevalence ranges from 5 percent in patients with New York Heart Association (NYHA) functional class I HF to 40 percent in patients with NYHA class IV HF . Its presence with HF plays a significant prognostic role and increases morbidity and mortality. Heart Failure with reduced ejection fraction (HFrEF) is associated with cardiac arrhythmias . HFrEF is also one of the indications for Cardiac resynchronization therapy (CRT) placement . Therefore, many patients undergoing CRT implantation will concomitantly have HF and AF. As the benefit from CRT in HF patients has been established, the data on patients with both HF and AF is limited, because patients with atrial arrhythmias were excluded from most of the major CRT trials, such as CARE-HF and COMPANION . However, a number of observational studies and small randomized clinical trials suggest a benefit from CRT in AF and HF patients such as a CRT-mediated ejection fraction (EF) increase [6, 7]. Other studies showed a high non-response rate in patients with AF as compared to those in sinus rhythm (SR) . Thus, it is important to determine whether CRT has a beneficial role in these patients to decide on adding an atrial lead at the time of CRT implantation especially in patients with longstanding-persistent AF.In their published study, Ziegelhoeffer et al. investigated the outcomes of CRT placement with an atrial lead in patients with HF and AF. This was done by conducting a retrospective analysis of all patients with AF who received CRT for HF at the Kerckhoff Heart Center since June 2004 and were observed until July 2018- completing a 5-year follow-up. The authors identified 328 patients and divided them into 3 subgroups: paroxysmal (px) AF, persistent (ps) AF, and longstanding-persistent (lp) AF, with all patients receiving the same standard operative management. During the observation period, the authors analyzed the rhythm course of the patients, cardiac parameters (NYHA class, MR, LVEF, left atrial diameter) and performed a subgroup analysis for patients who received an atrial lead. The study showed that all groups had a high rate of sinus rate (SR) conversion and rhythm maintenance at 1 and 5 years. Specifically, the patients who received an atrial lead among the lp AF group were shown to have a stable EF, less pronounced left ventricular end-systolic diameter (LVESD) and left ventricular end diastolic diameter (LVEDD) and lower mitral regurgitation (MR) rates at one year follow-up as compared to the group without atrial lead placement. Moreover, the results of the lp group were similar to the ps-AF group, although the latter had a lower number of participants (n=4) without initial implantation of the atrial lead. The authors attributed the improvement in cardiac function and SR conversion to CRT and the implantation of an additional atrial lead.Although some studies showed that CRT therapy reduced secondary MR in HF [9, 10], this study additionally suggests that CRT with an atrial lead was associated with improved myocardial function and improvement of interventricular conduction delay triggering cardiac remodeling in patients with HF and AF. Although the results showed better cardiac function in the subgroup analysis of the patients with an additional atrial lead, these results were reported as percentages with no level of significance specified, hence statistical significance of the difference in the described parameters (such as LVESD, LVEDD) could not be determined. Further investigation via prospective studies is needed with larger sample size in the future to further support the results of the study especially that it was done in a single center and had a relatively small sample size.References:1. Chung MK, Refaat M, Shen WK, et al. Atrial Fibrillation: JACC Council Perspectives. J Am Coll Cardiol. Apr 2020; 75 (14): 1689-1713.2. Maisel, W.H. and L.W. Stevenson, Atrial fibrillation in heart failure: epidemiology, pathophysiology, and rationale for therapy. Am J Cardiol, 2003. 91 (6a): p. 2d-8d.3. AlJaroudi WA, Refaat MM, Habib RH, et al. Effect of Angiotensin Converting Enzyme Inhibitors and Receptor Blockers on Appropriate Implantable Cardiac Defibrillator Shock: Insights from the GRADE Multicenter Registry. Am J Cardiol Apr 2015; 115 (7): 115(7):924-31.4. Yancy, C.W., et al., 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol, 2013. 62 (16): p. e147-239.5. Cleland, J.G., et al., The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med, 2005.352 (15): p. 1539-49.6. Leclercq, C., et al., Comparative effects of permanent biventricular and right-univentricular pacing in heart failure patients with chronic atrial fibrillation. Eur Heart J, 2002. 23 (22): p. 1780-7.7. Upadhyay, G.A., et al., Cardiac resynchronization in patients with atrial fibrillation: a meta-analysis of prospective cohort studies. J Am Coll Cardiol, 2008. 52 (15): p. 1239-46.8. Wilton, S.B., et al., Outcomes of cardiac resynchronization therapy in patients with versus those without atrial fibrillation: a systematic review and meta-analysis. Heart Rhythm, 2011. 8 (7): p. 1088-94.9. van Bommel, R.J., et al., Cardiac resynchronization therapy as a therapeutic option in patients with moderate-severe functional mitral regurgitation and high operative risk. Circulation, 2011.124 (8): p. 912-9.10. Breithardt, O.A., et al., Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure. J Am Coll Cardiol, 2003. 41 (5): p. 765-70.
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
Pulmonary Vein Isolation (PVI) remains the cornerstone for catheter ablation for atrial fibrillation (AF). Achieving durable PVI safely with Radiofrequency Catheter Ablation (RFCA) has proven challenging until recently, even with the use of Contact Force (CF) sensing catheters and electroanatomical mapping1. Ablation success rates improve markedly, including in persistent AF, when permanent PVI can be achieved1,2, which only underscores the critical role of the Pulmonary Veins (PV) in AF arrhythmogenesis.Historically, the only way to assess PVI durability has been through invasive electrophysiology study, with all its associated risk, inconvenience, and costs. This price appears particularly galling to pay if the PVs are found to be isolated at repeat study, as is now becoming increasingly common3. Multiple randomised studies have failed to show additional benefit from ablating extra-PV structures4,5, and the best outcomes following repeat AF ablation procedures are restricted to those where PV reconnection is identified and treated6. As such, there remains a pressing need for a non-invasive tool that can accurately assess PVI durability, and ideally, the size and location of residual gaps. As Magnetic Resonance Imaging (MRI) has increasingly been shown capable of delineating atrial scar, there is much anticipation that it may serve this important purpose7.RFCA and Cryoballoon ablation (CBA) are by far the most common modalities used for PVI, and there is remarkable equivalence in their clinical results8. However, the handling of the two technologies in the catheter laboratory is very different, and ultrahigh density mapping has shown important differences in the number and location of chronic gaps between the two9. The use of MRI in characterizing these differences has not been well described so far.In this issue of the journal, Kurose and colleagues present a small but elegant study10, in which 30 consecutive patients who underwent PVI (18 with CBA, 12 with RFCA) were assessed by LGE-MRI two months later, where lesion width and visual gap(s) around each vein were assessed. The RF applications were delivered using a CF sensing catheter, with a target lesion size index (LSI) of 5, and an inter-lesion distance of <6mm. They found that the mean lesion width on MRI was significantly wider in the CBA group (8.1±2.2 mm) as compared to the RFCA group (6.3±2.2 mm), p=0.032. However, there were more visual gaps seen in the CBA group, especially in the bottom segments of the two inferior veins. In the RFCA group, gaps were seen most often seen in the left posterior segments where the target LSI value could not be achieved because of esopheageal temperature rise. Furthermore, the number of gaps visualised on MRI was linked to freedom from AF at 12 months; receiver operating characteristic curve analysis suggested a cut off value of less than 5 visual gaps per patient as being predictive of a good outcome.The authors deserve to be congratulated for their study, which builds on their previous work where LGE-MRI was used to compare chronic lesions between CBA and RFCA with non-CF sensing catheters11. It is notable that whilst the lesion width in their previous study was also significantly greater in the CBA group than the RFCA group, the mean number of gaps in the RFCA group was higher. This suggests that the modern technique of delivering LSI-guided contiguous RFCA lesions has resulted in a material improvement in PVI durability, something that is borne out in clinical studies too3.Some limitations of the work should be mentioned. Patients were not randomised to RFCA or CBA; rather, patients undergoing CBA were pre-selected with those with left common PV or large PVs excluded. The ablation technique used for CBA was unusual in that the use of RFCA was allowed if PVI could not be achieved after a single 3-minute freeze. This low bar for defining CBA failure led to as many as 3 patients out of 25 being excluded from the study. Many readers will feel that the mean procedural times of 129 minutes and fluoroscopy times of 39 minutes for CBA are much longer than what is the norm today. They may also find the RF powers used in this study unusual; only 30W was used on the anterior wall, and 20-25W on the posterior wall, which was reduced even further if esophageal temperature rise was observed. The field is moving towards using higher power short duration (HPSD) RF applications, and as HPSD lesions have been shown to be wider12, it is possible that the gaps on the posterior wall identified in this study may not have been present had HPSD applications been used. Finally, the definition of visual gap on MRI used in this study, a non-LGE site larger than 4 mm, almost certainly overestimated the number of true gaps. For instance, the authors observed at least one visual gap in each of the 16 segments around the PVs in more than 10% CB patients; this is at odds with data obtained with ultrahigh density mapping9, and also with the good clinical outcomes reported here. Future research should look at correlating these MRI-visualised gaps with actual gaps seen on repeat electrophysiological study, so that the clinical significance of these can be better defined.What can we take away from this study? Firstly, the use of MRI to assess post-ablation scar is now a reality in many labs, allowing assessment of PVI durability to help decide whether or not to offer a repeat procedure to a patient with AF recurrence. Secondly, the evolution of the RFCA technique to include target lesion indices and inter-lesion distance has made RFCA at least as effective as CBA in achieving durable PVI. Finally, this is an area ripe for further research, and we look forward to similarly valuable contributions from Kurose and colleagues in the future.