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huasha qi

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Camellia drupifera is a main tea-oil Camellia species, and understanding its genetic variation, origin and evolution will facilitate protection and utilization of its genetic resources. However, the differentiation, genetic variation, origin and evolution of C. drupifera remains unknown. Here, SRAP markers and chloroplast sequences of 32 C. drupifera populations were used to determine genetic variation and differentiation and infer the origin and evolutionary history of the species. Genetic diversity is low (H=0.200, Hd=0.861, Pi=0.00238), with obvious pedigree geographical structure among populations (Nst=0.612, Gst=0.117). Genetic differentiation is high (Gst=0.400, SRAP; Fst=0.68080, cpDNA), but gene exchange is low (Nm = 0.749 for nrDNA, Nm = 0.358 for cpDNA). The phylogenetic tree and PCA showed that this differentiation is mainly due to separation of the Hainan Island and mainland populations. Geographical isolation and island effects caused the pedigree structure, with large genetic differentiation, and reduced genetic diversity. STRUCTURE analysis revealed that compared with the Hainan Island population, the mainland population has a single genetic background. The TCS network showed that H17 was the original haplotype on Hainan Island; the H41 haplotype was important in the expansion of C. drupifera from Hainan Island to mainland China. Haplotype historical dynamics revealed expansion of the Hainan Island populations (Tajima’s D=-2.31467**, Fu’s Fs=-2.45270*). Comprehensive analysis suggests that C. drupifera originated on Hainan Island and expanded its range to mainland China. These results provide a scientific basis for the protection, development and utilization of C. drupifera resources and a good example of how geographic isolation and island effects can drive plant lineage differentiation.

Ilya Sukhanov

and 3 more

Background and Purpose: Phosphodiesterases (PDEs) are a family of enzymes, which hydrolyze cAMP and cGMP. PDE10A is expressed mainly in the medium spiny neurons of the striatum that provides an opportunity to modulate the movement control pathways of the basal ganglia: “direct” (D1 receptor-dependent) and “indirect” (D2 receptor-dependent). Thus, inhibition of PDE10A can functionally mimic the action of both D1 receptor agonists and D2 receptor antagonists, although much less attention has been paid to the assessment of D1 receptor agonist-like effects. The purpose of the present study was (1) to confirm the motor stimulatory effects of PDE10A inhibitors and (2) to test whether these effects are subject to the development of tolerance. Experimental Approach: The ability of single or repeated (5 or 10 days) administration of selective PDE10A inhibitors, MP-10 (0,3-5 mg/kg) and RO5545965 (0.1-0.9 mg/kg), to stimulate locomotor activity was assessed in rats after single tetrabenazine challenge (3 mg/kg). The study was pre-registered on Key Results: PDE-10A inhibition exerted paradoxical motor stimulatory properties in a dose-dependent manner. However, repeated administration of PDE10A inhibitors led to a reduction of their effects. Conclusion and Implications: PDE-10A inhibition produces a paradoxical increase in motor activity in animals with low dopamine tone. After repeated administration of PDE-10A inhibitors, these effects disappeared. The development of tolerance similar to that previously observed for D1-receptor agonists may limit the potential clinical use of the stimulatory effects of PDE10A inhibitors. Further studies aimed at analyzing the molecular mechanisms of this tolerance are warrant

Neda Davaryari

and 5 more

Objective: the exact link between COVID-19 pandemic and different adverse outcomes of pregnancy remains unclear. Plus, large-scale research is lacking. In the present study, we aimed to compare the maternal and fetal health outcomes during the COVID-19 pandemic with the same last year duration in Iran. Design: Two retrospective cohorts (pre-COVID-19 and during COVID-19) were studied. The pre-COVID-19 cohort include pregnant women who had given birth between 1 January 2019 and 31 December 2019. The COVID-19 cohort, who had given birth between 1 January 2020 and 31 December 2020. The characteristics of pregnant women before COVID-19 and during COVID-19 pandemic were compared with Fisher’s exact test. Uni-variate and multivariate log-binomial regression models were used to determine the risk ratios of the impacts of the COVID-19 pandemic on adverse pregnancy outcomes. Results: among 128968 women showed that women who had given birth during the pandemic were more likely to be of young age, lower rates of alcohol consumption and smoking, lower weight gain, and higher rates of using synthetic milk for feeding neonates (P<0.05). Also, the risks of preterm labor were high (cOR 95% CI, 1.13 to 1.31; p<0.01) and the risk of caesarian were low (cOR 95% CI, 0.95 0.92 to 0.98; p<0.01) among pregnant women who gave birth during the COVID-19 pandemic compared with those who gave birth before the pandemic. Conclusions: In summary, we found that during the COVID-19 pandemic there were the higher risks of preterm labor and lower risk of caesarean among pregnant women.

Alexander Dickie

and 10 more

Objectives: Nasopharyngeal (NP) depth prediction is clinically relevant in performing medical procedures, and enhancing technique precision and safety for patients. Nonetheless, clinical predictive variables and normative data in adults remain limited. This study aimed to determine normative data on NP depth and its correlation to external facial measurements. Methods: A multicenter cross-sectional study obtained data from adults presenting to otolaryngology clinics at five sites in Canada, Italy, and Spain. Investigators compared the endoscopically measured depth from sill to nasopharynx along the nasal floor to the facial measurements “curved distance from the alar-facial groove along the face to the tragus” and “distance from the tragus to a plane perpendicular to the philtrum.” When sinus CT images were available, the distance from the nasopharynx to nasal sill was also collected. Results: 371 patients participated in the study (41% women; 51 years old, SD 18). The average endoscopic depth was 9.4 cm (SD 0.86) and 10.1 cm (SD 0.9) for women and men, respectively (p<0.001; 95% CI 0.46 to 0.86). Perpendicular distance was strongly correlated to NP depth (r=0.775; p<0.001), with an average underestimation of 0.1 cm (SD 0.65; 95% CI 0.06 to 0.2). The equation: ND(cm) = perpendicular distance*0.773 + 2.344, generated from 271 randomly selected participants, and validated on 100 participants, resulted in a 0.03 cm prediction error (SD 0.61; 95% CI -0.08 to 0.16). Conclusions: Nasopharyngeal depth can be accurately approximated by the distance from the tragus to a plane perpendicular to philtrum. The generated predictive equation was most accurate but not likely clinically relevant.

Akanksha Varanasi

and 1 more

In the early 2010s, scientists realized that CRISPR/Cas9, a bacterial immune defense system against viruses that involves the CRISPR-associated protein #9 (Cas9) endonuclease enzyme, single-guide RNAs (sgRNAs), and PAM recognition, could be used to intentionally manipulate genes, essentially changing gene expression and regulation in such a way that would allow for a customized genome. Since then, CRISPR technology has revolutionized medical research and the biotechnology industry, and its newfound capabilities have scientists asking if CRISPR can be used to modify genes in such a way that would cure or treat certain harmful or life-threatening diseases. There have been CRISPR-based clinical studies done to treat β-thalassemia (TDT), sickle-cell disease (SCD), the human immunodeficiency virus (HIV), and several other genetic and non-hereditary diseases, but there is still a long way to go before CRISPR can become a widespread treatment for many more such diseases (Ebina et al., 2013; Esrick et al., 2021; Frangoul et al., 2021). Currently, researchers are looking to see if CRISPR is an accurate, specific, non-harmful, and effective treatment for these diseases, which means addressing and eliminating potential concerns about its safety and efficacy through extensive pre-clinical and clinical research, as well as overcoming moral and social obstacles. In this review, I will look at how the CRISPR/Cas9 gene-editing system can be applied in humans to prevent, cure, or treat these diseases, as well as what needs to be done before the CRISPR/Cas9 system can be made publicly available as a medical treatment for diseases.

Christopher Andrews

and 2 more

The Ponto-Caspian Bloody-red mysid shrimp (Hemimysis anomala) was discovered in a large freshwater reservoir in the south-east of England in 2020 (Abberton reservoir, Essex, UK). The shrimp was discovered while carrying out aquatic invertebrate surveys across a range of permanent, semi-permanent and seasonal habitats between October and December 2020. The shrimp were found in semi-permanent lagoons adjacent to and connected to the main reservoir and in shallow water bays in the main reservoir. Surveys conducted in January 2021 along a reservoir wall also found the shrimp but no accurate abundance estimates were made. Surveys conducted across the same sites with increased effort in July 2021 did not find any individuals in lagoons, bays or off the reservoir wall in either shallow or deep shelves. The identity of the species was confirmed with high magnification inverted light microscopy due to the shape and setae distribution of the antennal scale and telson in addition to the characteristic bloody red colour of the shrimp pre-preservation. Previous introductions of this species to the UK have been identified before, but whether these propagules arrived from natural or anthropogenic introductions was not clear. Abberton reservoir has no public access for boating or recreational activities other than a small, restricted local angling group but is an internationally important site for migratory and overwintering waterfowl and waders. The migration routes of several waterfowl species for which Abberton is noted would mean that this new shrimp species is likely to have been introduced from either its native range or from its expanded non-native range in the UK or Netherlands by birds. It is not yet confirmed that this discovery represents a successful invasion of this species at Abberton and if it is, when it arrived or what effects it may be having on the food web of this site.

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Omar Sharaf

and 4 more

Background: Dysphagia following cardiac surgery is common and associated with adverse outcomes. Among patients receiving left ventricular assist device (LVAD), we evaluated the impact of fiberoptic endoscopic evaluation of swallowing (FEES) on outcomes. Methods: A single-center pilot study was conducted in adults (≥18 years of age) undergoing durable LVAD (February 2019-January 2020). Six patients were prospectively enrolled, evaluated, and underwent FEES within 72 hours of extubation—they were compared to 12 control patients. Demographic, surgical, and postoperative outcomes were collected. Unpaired two-sided t-tests and Fisher’s Exact tests were performed. Results: Baseline characteristics were similar between groups. Intraoperative criteria including duration of transesophageal echo (314 ± 86 min) and surgery (301 ± 74 min) did not differ. Mean time of intubation was comparable (57.3 vs. 68.7 hours, p=0.77). In the entire cohort, 30-day, 1-year, 2-year, and 3-year mortality were 0%, 5.6%, 5.6%, and 16.7%, respectively. Sixty-seven percent of the patients that underwent FEES had inefficient swallowing function. The FEES group trended to a shorter hospital length of stay (LOS) (29.1 vs. 46.6 days, p=0.098), post-implantation LOS (25.3 vs 30.7 days, p=0.46), and lower incidence of postoperative pneumonia (16.7% vs. 50%, p=0.32) and sepsis (0% vs. 33.3%, p=0.25). Conclusions: FEES did not impact 30-day, 1-year, 2-year, or 3-year mortality. Patients who underwent FEES trended toward shorter LOS, and lower postoperative pneumonia and sepsis rates, though not statistically significant. A higher incidence of dysphagia among patients undergoing FEES despite comparable baseline risk factors with controls suggests FEES may detect subclinical dysphagia.

Joshua Sink

and 1 more

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
Title: Percutaneous Lead Extraction in Patients with Large Vegetations: Limiting our Aspirations.Robert D. Schaller, DO11The Section of Cardiac Electrophysiology, Cardiovascular Division, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PennsylvaniaFunding: This work was supported in part by the Mark Marchlinski EP Research & Education FundKey words: Lead extraction, vegetation, pulmonary embolism, thrombus, aspirationDisclosures: NoneWord count: 1547Transvenous lead extraction (TLE) in the 1960’s involved orthopedic-style pulley systems that joined the exposed portion of the lead to progressively heavier weights hanging from the bed. Sustained tension on the lead was maintained until the patient experienced discomfort, ventricular arrhythmias, or noticeable resistance developed, and was maintained for minutes to days. The location of the lead within the chest was monitored with daily chest radiographs and the ensuingbang of the weight hitting the floor of the intensive care unit signified case conclusion; at which point the patient was assessed. Complications were erratic and included lead laceration and possible migration, injury to the tricuspid valve (TV), myocardial avulsion, tamponade, and death.1 Due to the immature nature of the procedure at that time, it was relegated to infectious indications including lead-related endocarditis, at that time referred to as “catheter fever”.Contemporary TLE has evolved into a highly refined practice with a multitude of tools and predictable results, and procedural indications that now span infection, venous occlusion, management of redundant leads, and access to magnetic resonance imaging.2Procedural imaging with computed tomography (CT) and real-time ultrasound-based tools have similarly changed the TLE experience with identification of adhesions, thrombi, vegetations, and complications.3 Large lead-related masses have historically caused angst due to the possibility of being sheared off by the extraction sheath and embolizing to the lung, and still represent a relative contraindication to percutaneous TLE.2In this issue of the Journal of Cardiovascular Electrophysiology , Giacopelli, et al.4 present the outcomes of 25 consecutive patients (mean age 64 years, 68% male) including 5 with pacemakers, 10 with implantable cardioverter-defibrillators, and 10 with cardiac resynchronization therapy devices, who underwent TLE with vegetations ≥10 mm on transesophageal echocardiography (TEE). Contrast-enhanced CT was performed before and after TLE with 18 (72%) patients showing subclinical pulmonary embolism (PE). Vegetation size (median of 17.5 mm and maximum of 30 mm) did not differ in those with and without PE (20.0 mm vs. 14.0 mm, p=0.116). Complete TLE success was achieved in all patients with 76% requiring advanced tools and 2 needing femoral snaring, and there were no significant procedural complications. In the group with pre-TLE PE, a post-TLE scan confirmed the presence of PE in only 14/18 (78%) and there were no patients with new PE formation. During a median follow-up period of 19.4 months, no re-infection of the new implanted systems was reported and there were 5 deaths (20%); with no differences between the groups. The authors concluded that subclinical PE was common in this clinical scenario but did not influence the complexity or safety of the procedure.Several aspects of this paper warrant comment. No data are reported on the size or location of the PEs nor the time between the first and second CT. It is possible that small PEs would not be identified on subsequent studies days after antibiotics had already been started. Patients also received acute and chronic anticoagulation if PE was identified, which in the setting of vegetations, is generally not indicated and could potentially lead to bleeding. The authors did not provide information regarding infectious pathogens or the timing of culture clearance, which could influence treatment. Additionally, it is unclear which patients received new CIED systems including the type and timing of reimplantation, which might influence subsequent infectious risk. A vascular occlusion balloon was not used in any patients in this report. While this tool is associated with a reduced risk of death in the setting of a superior vena cava laceration when used properly, it has also been shown to be thrombogenic during long dwell times,5 and use could impact post-operative CTs in future studies. Despite utilizing transthoracic echocardiography during TLE, neither TEE nor intracardiac echocardiography were used intraoperatively and thus no information regarding the precise location of the vegetations within the heart is known. Importantly, no information regarding the characteristics of the vegetations other than size was reported.Not all lead-related masses are created equal with two distinct sub-types previously described.6 The first is composed of thickened endocardium and fibrous tissue covering the leads and ultimately forming into connective tissue. These masses, commonly found on leads behind the TV, are caused by a vortical flow pattern leading to low shear stress on the lead surface and provoking neointimal hyperplasia,7 and range from small fibrous strands to large, smooth organized thrombus (Figure, left column). Despite their sterile nature, TLE in the setting of a large, mature thrombus could result in embolization and obstruction of the pulmonary artery resulting in symptomatic PE. The second type, frequently seen in the setting of infective endocarditis, is composed of inflammatory cells, platelets, adhesion molecules, fresh fibrin, and bacteria binding to coagulum and forming vegetations. They are typically longer, more likely to be multi-lobular, and commonly span several chambers of the heart (Figure, right column). These vegetations that are typically acute, with friable finger-like projections, characteristically break apart upon being sheared off during TLE, with reports showing low risk of symptomatic PE.8 Vegetations that are lobular, however, have been associated with worse outcomes.9Despite acute procedural success in the setting of lead-related vegetations, mortality rates at 1 year approach 25%.10 Indeed, despite successful TLE in this report, 20% of patients were dead at 1.5 years. Although complete understanding of the mechanism of these poor outcomes remains unknown, septic emboli, lung abscesses, and infected lead “ghosts” have been implicated.11 Vegetation removal prior to TLE has thus represented an appealing therapeutic option with reports of successful percutaneous aspiration prior to TLE showing promising results, albeit with unknown long-term benefit.12,13 Although the lack of new PEs after TLE in this report does not directly support the effort, cost, and added risk of such a strategy, “debulking” of infectious burden remains a tempting complementary treatment. Importantly, the acute safety of TLE with large vegetations in this study should not be extrapolated to chronic, large lead-related masses, which are more like to cause acute PE if embolized. While aspiration of these sterile masses prior to TLE is appealing from a procedural outcome perspective, their morphologic characteristics, and the imperfect, but evolving, aspiration sheaths currently available are limiting, and requires consideration of surgical extraction. Further advancements in aspiration catheter technology and the development of right ventricular outflow track filters might influence future management.TLE continues to represent the gold standard for the management of lead-related infection.2 Due to the extensive work of the pathfinders in the vanguard of procedural development, the sound of crashing weights has been supplanted by those that power advancing sheaths. Yet despite the safe and predictable nature of modern-day TLE, the sobering long-term mortality of patients with infectious indications remains out of proportion to acute procedural success. While infectious “debulking” continues to represent the most attractive and practical complementary option to address this incongruity, future studies should concentrate both on identification of mass characteristics that suggest success, as well as determining if long-term benefits exist above and beyond lead removal. However, if improvement in clinical outcomes that warrant this added cost and effort are not identified, we should likely limit our aspirations.

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