Employing New Criteria for Confirmation of Conduction Pacing – Achieving True Left Bundle Branch Pacing May Be Harder Than Meets the EyeJoshua Sink, MD1, Nishant Verma, MD, MPH2Northwestern University, Feinberg School of Medicine, Department of Internal MedicineNorthwestern University, Feinberg School of Medicine, Division of CardiologyCorresponding Author:Nishant Verma, MD, MPH251 East Huron Street, Feinberg 8-503Chicago, IL 60611312-926-2148Nishant.Verma@nm.orgFunding: NoneDisclosures: Dr. Sink has nothing to disclose. Dr. Verma receives speaker honoraria from Medtronic, Biotronik and Baylis Medical and consulting fees from Boston Scientific, Biosense Webster, AltaThera Pharmaceuticals and Knowledge 2 Practice.Word Count: 1200In recent years, conduction system pacing (CSP) has garnered significant attention from the electrophysiology (EP) community. This movement has been driven by the hypothesis that using the natural conduction system activation is desirable and clinically beneficial in patients with advanced conduction disease and ventricular desynchrony. Permanent His-bundle pacing (PHBP) is generally seen as the purest form of conduction system activation. (Figure 1) PHBP was first described over 20 years ago but the idea has attracted substantial investigative effort in recent years. When successfully achieved, His bundle pacing has been associated with reduction in mortality, reduction in heart failure (HF) admissions, and improvement in left ventricular (LV) function compared to right ventricular (RV) pacing.1 Despite this, consistent achievability in real-world practice remains limited due to a variety of factors including narrow anatomic targetability, lead stability, high pacing thresholds, low ventricular sensing, and inability to correct the QRS in bundle branch block.2Thus, while waiting for the next iteration of improved delivery techniques, pacing leads and programming algorithms,, alternative methods of conductive system pacing have emerged, with the potential to surmount the challenges described.Left bundle branch pacing (LBBP) has recently emerged as an alternative method of CSP. The technique was first described by Huang et al. in 2017 and has seen a momentous rise in interest since.3 In 2019, Huang et al. produced a user manual for a successful LBBP procedure, and in it they attempted to develop the first iteration of criteria for the confirmation of LBBP.4 Utilizing these criteria, or close variations of them, a number of studies were published afterwards that demonstrated preliminary safety, feasibility, and efficacy of LBBP.5,6,7 LBBP became an attractive alternative to His bundle pacing because of the lower thresholds, improved lead stability, and higher procedural success rates. When compared against RV pacing in patients requiring a high burden of pacing, LBBP has demonstrated reduced mortality, HF admissions, and need for upgrade to a BiV device.8 In a small, non-randomized patient sample, LBBP showed greater improvement in LV ejection fraction (EF) compared to BiV pacing.9 Most notably, perhaps, is the astonishing rate of lead placement success, with achievement rates reported as high as 98% in sizable studies.6Differences between the two forms of CSP were apparent from the beginning, including in the appropriate QRS morphology after a successful case. Unlike PHBP, LBBP did not reproduce the native QRS and the QRS duration was often greater than at baseline (Figure 2). The arena of LBBP underwent a notable shift in the Fall of 2021 when Wu et al. proposed new criteria to prove LBBP.10 In this study, they presented an exquisite display of fundamental electrophysiologic principles by using mapping catheters positioned on the His and LV septum during LBB lead placement. Through this painstaking work, they clarified the difference between true LBBP and left bundle branch area pacing (LBBAP), which can incorporate both LBBP and left ventricular septal pacing (LVSP). In their proposed framework, without the presence of a His or LV septum mapping catheter, output dependent QRS transition from non-selective (NS-LBBP) to selective-LBBP (S-LBBP) or LVSP is necessary to prove LBBP and had a sensitivity and specificity of 100%.The present study by Shimeno et al, published in the current issue of the Journal of Cardiovascular Electrophysiology , is the first known effort to document achievement rates of LBBP by utilizing the modified criteria proposed by Wu et al.11 The primary finding of the study is that achieving true LBBP with an acceptable pacing threshold is likely harder than previously realized. As expected, there was improvement after a learning curve, but even in the last third of patients enrolled, the achievement rate of LBBP was only 50%. This is dramatically lower than previously reported achievement rates using the original Huang et al. criteria, and it suggests that not all patients in the previously described studies were actually achieving true LBBP. An unknown subset of patients in these studies was likely only achieving LVSP. This is probably due to a prior reliance on indicators such as a paced right bundle branch block (RBBB) pattern, identification of an intrinsic LBB potential, and/or use of V6 R-wave peak time cutoffs (RWPT) without clear output-dependent QRS transition. It is also worth noting that a variety of RWPT cutoffs have been used seemingly arbitrarily as ‘evidence of LBBP’. This presents a major dilemma and highlights the need for a clear set of LBBP criteria to be defined by the collective EP community. Despite these caveats, many of these previous studies did not fully confirm LBBP in their patients, yet the outcomes from these studies were still clinically promising. This raises the obvious question, does obtaining true LBBP matter? Future studies will need to explore the differences in clinical outcomes between true LBBP and LVSP.Secondarily, Shimeno et al. have provided a useful tool in identifying that LBB potential to QRS-onset ≥ 22ms had a specificity of 98% in predicting LBBP.11 This target measure can help future operators ensure proximal enough engagement of the LBB conduction system. Additionally, the group took a close look at validating a RWPT cutoff time for the prediction of LBBP. Unfortunately, a RWPT cutoff of 68 ms (in non-LBBB patients), determined by the ROC curve, was not highly predictive. This runs contrary to previous reports by Wu et al. and Jastrzebski et al., which reported higher predictive value of RWPT cutoffs10,12 Looking at the data surrounding RWPT cutoffs as a collective, it likely should not be used as a primary metric for confirming LBBP due to imperfect sensitivity and specificity, but it may be an alternative if output dependent QRS transition or change in RWPT of ≥10 ms is not observed. Additionally, in the event that capture thresholds are similar between the LBB and the adjacent myocardium, programmed stimulation is an option to try to reveal a QRS transition by exploiting differences in refractory periods.This study also highlighted one of the unique complications of LBBP by demonstrating a high rate of septal perforation. Paradoxically, more perforations were seen with increased experience, likely highlighting that deeper penetration into the septum is often sought as operators become more familiar with the procedure. The long-term clinical implications of this complication are, thus far, unknown.Looking forward, clear guidelines for confirmation of LBBP need to be defined. This is necessary to ensure quality before undertaking multi-center randomized controlled trials to assess LBBP in comparison to current pacing methods. To date, Wu et al. seem to have provided the best framework to achieve this.10 That said, there are concerns given that this has only been validated in 30 patients (and only 9 with LBBB). In an ideal world, these criteria would be validated in a larger population, though the work to accomplish this would be meticulous given the current gold standard of using an LV septal mapping catheter to prove conduction system capture. Shimeno et al. should be congratulated for their effort in putting this framework to practice. In their work, they have demonstrated that achieving true LBBP as defined by Wu et al. may be harder than meets the eye, and this is very important in assessing the practicality of using LBBP as a widespread alternative to other pacing methods.References:Abdelrahman M, Subzposh FA, Beer D, et al. Clinical Outcomes of His Bundle Pacing Compared to Right Ventricular Pacing. J Am Coll Cardiol . 2018;71(20):2319-2330. doi:10.1016/j.jacc.2018.02.048Zanon F, Abdelrahman M, Marcantoni L, et al. Long term performance and safety of His bundle pacing: A multicenter experience. J Cardiovasc Electrophysiol . 2019;30(9):1594-1601. doi:10.1111/jce.14063Huang W, Su L, Wu S, et al. A Novel Pacing Strategy With Low and Stable Output: Pacing the Left Bundle Branch Immediately Beyond the Conduction Block. Can J Cardiol . 2017;33(12):1736.e1-1736.e3. doi:10.1016/j.cjca.2017.09.013Huang W, Chen X, Su L, Wu S, Xia X, Vijayaraman P. A beginner’s guide to permanent left bundle branch pacing. Heart Rhythm . 2019;16(12):1791-1796. doi:10.1016/j.hrthm.2019.06.016Padala SK, Master VM, Terricabras M, et al. Initial Experience, Safety, and Feasibility of Left Bundle Branch Area Pacing: A Multicenter Prospective Study. JACC Clin Electrophysiol . 2020;6(14):1773-1782. doi:10.1016/j.jacep.2020.07.004Su L, Wang S, Wu S, et al. Long-Term Safety and Feasibility of Left Bundle Branch Pacing in a Large Single-Center Study. Circ Arrhythm Electrophysiol . 2021;14(2):e009261. doi:10.1161/CIRCEP.120.009261Huang W, Wu S, Vijayaraman P, et al. Cardiac Resynchronization Therapy in Patients With Nonischemic Cardiomyopathy Using Left Bundle Branch Pacing. JACC Clin Electrophysiol . 2020;6(7):849-858. doi:10.1016/j.jacep.2020.04.011Sharma PS, Patel NR, Ravi V, et al. Clinical outcomes of left bundle branch area pacing compared to right ventricular pacing: Results from the Geisinger-Rush Conduction System Pacing Registry. Heart Rhythm . 2022;19(1):3-11. doi:10.1016/j.hrthm.2021.08.033Wu S, Su L, Vijayaraman P, et al. Left Bundle Branch Pacing for Cardiac Resynchronization Therapy: Nonrandomized On-Treatment Comparison With His Bundle Pacing and Biventricular Pacing. Can J Cardiol . 2021;37(2):319-328. doi:10.1016/j.cjca.2020.04.037Wu S, Chen X, Wang S, et al. Evaluation of the Criteria to Distinguish Left Bundle Branch Pacing From Left Ventricular Septal Pacing. JACC Clin Electrophysiol . 2021;7(9):1166-1177. doi:10.1016/j.jacep.2021.02.018Shimeno K, Tamura S, Hayashi Y, et al. Achievement Rate and Learning Curve of Left Bundle Branch Capture in Left Bundle Branch Area Pacing Procedure Performed to Demonstrate Output-Dependent QRS Transition.J Cardiovasc Electrophysiol . 2022Jastrzębski M, Kiełbasa G, Curila K, et al. Physiology-based electrocardiographic criteria for left bundle branch capture. Heart Rhythm . 2021;18(6):935-943. doi:10.1016/j.hrthm.2021.02.021Figure LegendsFigure 1: Permanent His Bundle PacingPanel A: A 12-lead electrocardiogram (EKG) shows baseline conduction in a patient with exertional intolerance. The PR interval is markedly prolonged and, with exercise, this patient developed AV block. A permanent His-bundle pacemaker was implantedPanel B: An EKG demonstrating permanent His-bundle pacing in the same patient as panel A. Selective His-bundle capture results in reproduction of the intrinsic QRS complex.Figure 2: Non-Selective Left Bundle Branch PacingA 12-Lead electrocardiogram showing non-selective left bundle branch pacing. The paced QRS morphology is not a direct match for native conduction and the QRS duration is longer than at baseline. However, conduction system capture was confirmed with an output dependent QRS morphology change.FiguresFigure 1: Permanent His-Bundle Pacing
On Time Surgery Start: Is Standardization The Answer?Olufunke Folasade Dada MD, Tanaya Sparkle M.B.B.S.University of Toledo Medical Center, Anesthesiology Department,3000 Arlington Avenue, Toledo, Ohio, USACorresponding Author: Dr. Tanaya Sparkle, M.B.B.S.Address for correspondence:University of Toledo Medical Center, Anesthesiology Department,3000 Arlington Avenue, Toledo, Ohio - 43614E-mail: firstname.lastname@example.orgPhone: 419-383-3531
Background: Hemostatic disturbances with coronavirus disease 2019 (COVID-19) can predispose to tricuspid and right heart thrombi in very rare instances. Aim: We describe a 29-year-old female patient without previous cause of thrombosis who developed large tricuspid valve thrombus (TVT) and moderate-to-severe tricuspid regurgitation (TR) during the course of COVID-19 infection. Materials and methods: Persistant fever and tachycardia with thrombocytopenia and high D-dimer increased the index of suspicion. The diagnosis was made by bedside transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR). Surgery was performed for thrombectomy and tricuspid valve replacement with a tissue valve. Discussion and conclusion: Detection of TVT in COVID-19 patients on the basis of high index of suspicion, bedside TTE and non-invasive CMR helps early surgical treatment and subsequent reduction of mortality and hospital stay.
The MitraClip technique has been increasingly used for correction of mitral valve regurgitation in patients in whom surgical mitral repair is considered contraindicated or very risky, but off label use occurs often. Failure of the procedure, translated into moderate to severe rates of residual or recurrent mitral regurgitation, is observed in up to one-third of the patients, and surgery has been used to correct it in a number of cases, in what can be called an “operation for the inoperable”. That is precisely the subtitle of a paper published in this issue of the JOCS by Gerfen and colleagues, who analyse their institutional experience with a series of 17 patients. In this Editorial, I comment on this series and the possible reasons for failure of the MitraClip, and on the indications for reintervention and its constraints, which I hope can contribute to the discussion about “further exploration and refinement of patient selection criteria and identify predictors for MitraClip failure”, as the authors suggest.
Flooding is a frequent disaster that has a wide-spread footprint globally with significant financial and societal impacts. With availability of Earth observation data from private and public entities at varying spatial, temporal, and spectral resolution as well as data from crowdsourcing, there is no shortage of models. In fact, models and algorithms are abundant and proliferating. However, the question remains where is a global flood model when we need one? Just because models are available does not mean they are usable or accessible and adequate for emergency managers, first responders and other stakeholders who use the model outputs for preparedness, response and resource planning. Often the issue of usability stems from the fact that the models are not always reproducible or replicable. The accuracy and uncertainty associated with the models and how they change based on the scale of analysis and the resolution of input and output datasets are often not communicated properly to stakeholders so they can be part of their decision-making process. The proliferation of machine learning and data driven models that rely on historical data also adds to this problem. This paper discusses several important issues associated with global flood models and provides recommendations that could be used to increase the usability of these models.
This case illustrates another promising example of the recent advances within pediatric interventional bronchoscopy. As innovative medical therapies continue to make their way into the pediatric realm (e.g. a 1.1-mm flexible cryoprobe has been recently developed by Erbe), opportunities for novel approaches and techniques will continue to present themselves.
Title: Letter to the Editor: Management of aortic arch hypoplasia in neonates and infantsArticle type : Letter to the Editor.Correspondence: 1. Maida QaziContact: 03332132159 Email: email@example.comInstitution: DOW University Of Health SciencesAddress: Bihar Colony, Al-Falah Road, Karachi.Co-authors : 2. Satesh KumarContact: +923325252902 Email: firstname.lastname@example.orgInstitute: Shaheed Mohtarma Benazir Bhutto Medical College Liyari, KarachiAddress: Parsa citi, Garden East, Karachi
Title pageTitle: Reply to Jasinski M et al.: ´Indeed, there is still room for improvement in long‐term durability of BAV repair´Authors: Tomas Holubec, MD, PhD, Mojyan Safari, MD, Arnaud Van Linden, MD, Anton Moritz, MDInstitutions and Affiliations: Department of Cardiovascular Surgery, University Hospital Frankfurt and Goethe University Frankfurt, Frankfurt, GermanyCorresponding author: Assoc. Prof. Tomas Holubec, MD, PhD, Theodor-Stern-Kai 7, 60596 Frankfurt/Main, Germany, Tel.: +49 69 6301 80094, Email: email@example.com
- The Gerbode type of ventricular septal defect is rare and can be congenital or acquired. - The defect can be closed retrograde or through the transvenous approach. - Short term follow-up suggests that transcatheter closure of the Gerbode type defect is feasible, safe, and effective and should be considered an alternative to surgical repair
Significant dilemma exists regarding management of the aortic root pathology in acute aortic dissections. Several strategies for both repair and replacement exist and there is a lack of clarity on the superiority of one over the other. Important factors that influence management strategies include involvement of the sinuses, competence of the aortic valve, presence of Marfan's syndrome and connective tissue disorders, as well as availability of surgical expertise. The wide variability in these factors makes it unlikely for any one technique to be suitable for management of all aortic roots and the root pathology has to be tailored to an individual patient.
Editorial to the special issue “Environmental influences on childhood asthma”Back in 1892, Sir William Osler gave an accurate description of asthma as a disease that is associated with “spasm of the bronchial muscles, inflammation of the smaller bronchioles, bizarre and extraordinary variety of circumstances and cold infections, often running in families (1,2). This is basically a true reflection of our modern understanding of asthma which states that asthma is a complex genetic disorder that involves interactions between genetic and environmental factors.Since the human genetic makeup has not changed significantly in the last couple of decades, there is reason to believe that the overall increase in asthma prevalence (3) can be attributed to the changing environmental conditions of modern life. The role of environment in asthma is not limited to its role in the pathogenesis of the disease. Since it is currently not possible to change the genetic make-up of an individual underlying a complex genetic disorder such as asthma, modification of environmental conditions emerges as a significant tool for its treatment. Therefore, understanding the environmental factors that play an important role in asthma is crucial in understanding the disease pathogenesis as well as modification of factors that modulate the inception and progress of the disease as well as its treatment.Various studies published in the last years in the journal and included in this virtual issue have addressed these questions. Garcia-Serna et al. have found out that gestational exposure to traffic-related air pollutants (TRAP) may increase the pro-inflammatory and Th2-related cytokines in newborns which might influence immune system responses later in life (4). Similarly, Pesce et al. (5) have investigated the association between prenatal exposures to heavy metals and atopic diseases. The serum concentrations of lead, cadmium and manganese were assessed in maternal blood samples collected during pregnancy and in cord blood of 651 mother-children pairs. The authors have concluded that the levels of cadmium in cord blood were associated with greater risk of asthma at the age of 8. Baek et al. have documented that exposure to phthalates are associated with airway dysfunction in childhood and this effect was partially attributable to increased serum periostin levels (6). Regarding the association between the genes and environment, Theodorou et al. (7) have investigated the role of mitogen-activated protein kinase (MAPK) pathway in 232 children who were selected from two cross-sectional cohorts and one birth cohort study. They have isolated peripheral blood mononuclear cells (PBMC) from children with asthma along with healthy controls and stimulated them with farm-dust extracts or lipopolysaccharide. The results have shown that the children with asthma have expressed significantly less dual-specificity phosphatase-1 (DUSP1) which is the negative regulator of MAPK pathway. They have conclusively indicated the possible role of DUSP1 for future therapeutical interventions regarding the anti-inflammatory features of farming environments.In an effort to further elucidate the environmental factors that are central to our understanding of asthma, the journal has started a review series to provide a comprehensive picture on the role of environment on various aspect of asthma. Major subheadings includedBiodiversityUrban exposuresGene-environment interactionsFarm effectAir pollutionClimate changeAllergensDiet microbiome and obesityIn the virtual issue of the journal Tari Haahtela (8) has focused on the effect of biodiversity. Evidence supports that the immunomodulating roles of different micro-organisms may be protective for asthma and allergic diseases. The studies from the neighboring Finnish and Russian Karelia regions, which the author named as “the living laboratory”, have shown strong evidence for the central role of environment and lifestyle which modify the human microbiome, immune balance, and thus allergy and asthma risk. Diversity of the human microbiome as well as the diversity of the natural environment that we live in and more contact with the nature are important determinants of physical health.Grant et al. (9) have focused on the influence of urban exposures on childhood asthma. The authors have meticulously summarized and analyzed the results of previous studies which aimed to investigate the interaction between indoor allergens, microbes, indoor and outdoor pollutants, social determinants and childhood asthma along with the opportunities for intervention. Multiple environmental exposures and influences contribute to the increased incidence of asthma and excess asthma morbidity among children with asthma living in urban communities. Indoor pest allergen and mold exposures have been repeatedly linked to increased asthma diagnosis, symptoms, and exacerbations in urban children. However, studies in high-risk urban populations also found that early life pest allergen exposure, along with microbial and endotoxin exposure may be associated with a decreased risk of wheezing and asthma suggesting that the association is more complex than previously thought.Since asthma prevalence varies widely depending on the socio-economical level, changes to help reduce inequities and inequalities in social determinants of health such as poverty, housing disrepair, higher rates of obesity, and chronic stress may produce positive effects at the population-level.Hernandez-Pacheco et al (10) have reviewed the latest gene-environment interaction (GxE) studies in childhood asthma. They have summarized the role of various environmental exposures and the current state of knowledge on asthma genetics. The field of GxE in asthma has drastically evolved together with technological advances over the last years. However, despite reports on the effect of numerous environmental factors on childhood asthma, the availability of detailed and diverse exposure data is limited. Tobacco smoke remains to be the most accessible and extensively explored factor followed by traffic-related air pollution in GxE studies.Airway epithelium seems to be central in gene-environment interactions. The effect of the exposure to certain environmental factors early in life on the modification of the risk and severity of asthma later in childhood is partially dependent on the functionality and integrity of the airway epithelium. It is known that the environmental exposures can trigger an inflammatory response and the disruption of the barrier and mucociliary function.Although there are several methodological and conceptual challenges with GxE interaction studies, recent data have led to new insights into childhood asthma pathophysiology which is best exemplified by the 17q12-21 asthma locus. Some of the SNPs at this locus seem to be associated with the onset of childhood asthma, thereby highlighting the importance of age related factors in gene environment interactions.The need for longitudinal and functional studies which provide insights into the biological mechanisms underlying the observed associations between environmental exposures and epigenetic changes that modify the asthma risk is highlighted.Another extensively studied environmental factor that is associated with childhood as is the so called “farm effect”. Frei et al. (11) have summarized the current knowledge on how “farm effect” influences the immune homeostasis during the intrauterine period and in childhood with a focus on immune mechanisms induced by environmental microbial diversity and microbial components. Farming lifestyle factors including nutrition influence the immune homeostasis either by regulating the innate immune system or by induction of regulatory T cells or TH1. We see diversity as a significant factor also in the farm effect. Diversity of environmental microbes, the diversity of the gut microbiome, or the diversity of the nutrition emerge as significant factors.Paciencia et al. (12) investigated the association and mechanisms between air pollution and asthma in children along with the precautions that should be taken to reduce the burden of air pollution on asthma. Environmental conditions are not shared equally across the populations, regions, and settings where people live, work, and spend their time. Urban conditions and air quality are not only important features for national and local authorities to shape healthy cities and protect their citizens from environmental and health risks, but they also provide opportunities to mitigate inequalities in the most deprived areas where the environmental burden is highest. Actions to avoid exposure to indoor and outdoor air pollutants should be complementary at different levels –individual, local, and national levels – to take strong measures to protect children.Taken together, these reviews provide a very comprehensive coverage on the role of environmental factors on childhood asthma and suggest that efforts to modify these factors may have beneficial effects not only on the individual level but also at the population level.S. Tolga Yavuz1Ömer Kalayci2Philippe A. Eigenmann3
Title Page:Title: Letter To The Editor: Long-Term Renal Function After Venoarterial Extracorporeal Membrane Oxygenation.Article Type: Letter To The EditorCorrespondence: 1. Rohit KumarContact No: +923332669103 Email: firstname.lastname@example.orgInstitute: Dow Medical CollegeAddress: Baba-e-urdu road, KarachiCo-Authors: 2. Sunil KumarContact No: +923008088669. Email: email@example.comInstitute: Liaquat University of Medical and Health Sciences.Word Count: 476Conflict of interest : NoneAcknowledgment : NoneDeclaration: NoneDisclosure : NoneFunding : None
H Syndrome is a rare genodermatosis. It may include facial involvement such as : facial telangiectasia, both hypo- and hyperpigmented lesions, hirsutism, swollen cheeks due to subcutaneous infiltration and eczematous lesions. We describe a new facial phenotype with dermoscopic and histological features in the spectrum of non-Langerhans cell histiocytosis.
The thinning of the skin over the pocket is an occasional phenomenon in patients with cardiac implantable electronic devices (CIEDs) most often associated with the technique of implantation of the device. It is likely that the thinning of the skin over the generator is a risk factor for the development of infectious complications in patients with CIED. Analysis of large database of 3706 patients undergoing transvenous lead extraction (TLE) showed higher number of points of PADIT score and more often previous pocket plastic surgery in patients with too shallow pocket. Most likely, diagnosing only a too shallow CIED pocket is often an early symptom of infection.