Leadless Pacing with Mechanical Atrial Sensing and Variable AV ConductionJason Cook, MDTravis D. Richardson, MDFrom Vanderbilt University Medical Center. Nashville, TennesseeCorresponding author:Travis D. Richardson, MDAssistant Professor Cardiac ElectrophysiologyVanderbilt Heart and Vascular Institute1215 21st Ave S. Nashville, TNMedical Center East, South Tower, Suite 5209ph (615) 936-7537fax (615) firstname.lastname@example.orgWord Count:1331Disclosures: The authors report no relevant financial disclosures.Funding: NoneThe MicraTM leadless transcatheter pacing system (Medtronic Inc., Mounds View, MN) has been shown to be an effective alternative to transvenous pacing with excellent implantation success rates and durable long-term performance.1–3 The first generation device provided single chamber right ventricular pacing with rate responsiveness enabled by a 3-axis accelerometer.Recently, the MARVEL 2 study (Micra Atrial tRacking using a Ventricular accELerometer 2) reported the ability of software enhancements to allow a leadless pacemaker to deliver single chamber atrioventricular (AV) synchronized pacing.4 In contrast to dual-chamber transvenous pacemakers which sense atrial electrograms, the MARVEL 2 algorithm adjudicates atrial events using mechanically sensed atrial activity from the 3-axis accelerometer. During initial programming, the relative timing of mechanical events to the ventricular electrogram allows for identification of A3 (passive ventricular filling) and A4 (atrial contraction). Atrial-sensed events are then defined by the A4 signal, and tracking may occur. MARVEL 2 reported VDD pacing was achieved at rest in an impressive 89.2% of patients.The Micra AVTM system’s unique programming includes three basic pacing modes: VDD, VVI and VDIR (Figure 1). Additionally, two mode switch algorithms are available and by default programmed on: the AV conduction mode switch and the activity mode switch. Unlike mode switch algorithms in dual chamber pacing systems, which are intended to avoid inappropriate tracking of atrial arrhythmias, these algorithms are intended to 1) minimize ventricular pacing, and 2) to improve rate support during patient activity respectively.When the AV conduction mode switch algorithm is enabled, the device periodically switches from VDD to VVI at 40 bpm to allow for intrinsic AV conduction. If ventricular sensing occurs above a rate of 40 bpm, in order to reduce right ventricular pacing, VVI 40 programming will continue regardless of the programmed lower rate limit. However, if two of any window of four beats are paced at VVI 40, the device reverts to VDD. Thereafter, reassessments of AV conduction are performed at increasing intervals starting at 2 minutes until either AV conduction is detected or 8 hours is reached at which point subsequent testing occurs at regular 8 hour intervals.The activity mode switch algorithm utilizes the sensor indicated rate in an attempt to ensure adequate ventricular rate support during patient activity regardless of AV conduction. The sensor in the MicraTM is always running. If at any time 1) the sensor indicated rate is above the device programmed ADL rate, and 2) the current ventricular rate is >20 BPM below the sensor rate, the activity mode switch will change the device to VDIR mode with heart rates determined by the sensor. This switch may occur from either the VDD mode or VVI in the setting of AV conduction. The device will revert to VDD mode when the sensor rate drops below the ADL rate.With the added functionality of atrial sensing and the incorporation of the MARVEL 2 algorithms described above, in this issue of the Journal of Cardiovascular Electrophysiology, Garweg et al. examined the pacing behavior of the Micra AVTM in the presence of variable AV conduction, atrial arrhythmias, sinus bradycardia (< 40 bpm), sinus arrhythmia, and periods of atrial and ventricular ectopy (Reference). During the data collection period in MARVEL 2, ECG, electrogram, accelerometer waveforms, and device marker data were obtained; this was collected either after initial implant and follow-up or, for patients with previously placed devices, during a single encounter. The average monitoring period was 153 minutes. The study included 73 patients with normal sinus node function and varying degrees of AV block.While the number of patients with variable AV conduction was small (5), the investigators found that the rhythm checks allowed for appropriate mode adjustments during the study period. During periods of AV block, as expected, 99.9% ventricular pacing was observed while during 1:1 AV conduction only 0.2% pacing was observed. Ventricular pacing was monitored in patients with 1:1 AV conduction using conventional VVI pacing and MARVEL 2 programming. MARVEL 2 programming using the AV conduction mode switch algorithm resulted in a reduction in ventricular pacing from 22.8% to 0.2% (n=18). Reducing the burden of ventricular pacing is an important enhancement to the system with the potential to minimize pacing-induced cardiomyopathy.5One potential pitfall of atrial sensing addressed by this study is tracking of atrial arrhythmias. While the sample size was small (n=7), tracking of atrial fibrillation resulting in pacing at the upper tracking rate was not observed in any of the patients. In one patient with atrial flutter, intermittent atrial tracking did occur but did not result in tachycardia. In contrast to atrial rate based mode switching used in conventional dual-chamber pacemakers, the behavior of the MARVEL 2 algorithm during atrial fibrillation is dictated by the sensed ventricular rate. With the AV conduction mode switch enabled, if the ventricular rate is above 40 bpm, the pacing mode will be VVI at 40 bpm. If rates are less than 40 bpm, the pacing mode will be VDD. In the context of atrial fibrillation, reduced atrial contractility results in lack of mechanical sensing, and pacing at the lower rate is observed. In this small sample size, atrial arrhythmias did not result in device tracking resulting in tachycardia. Further investigation in a larger number of patients is warranted to better characterize these findings and to assess pacing behavior during more organized atrial arrhythmias which could result in mechanical sensing (atrial tachycardia and atrial flutter, for example).While the MARVEL 2 programming seems to perform well in the setting of atrial fibrillation or intermittent complete AV block, there are some potential pitfalls. AV conduction mode switch behavior is based on sensed ventricular rates with a threshold of 40 bpm; this cutoff is not currently programmable. Any ventricular sensed rhythm with a rate greater than 40 bpm will result in the device continuing at VVI 40. For example, in a patient with sinus rhythm at 90 bpm and 2:1 AV conduction, the device would not track the atrium and pace at 90 bpm, but rather remain VVI 40 because the ventricular sensed rate is above 40 bpm. The same would be observed in patients with junctional or ventricular escape rhythms >40 bpm. In this sense, pacing could be inappropriately inhibited during a potentially hemodynamically significant rhythm. For this reason, in our opinion, the AV conduction mode switch algorithm should be disabled in the majority of patients with AV block as this physiology is dynamic and sudden loss of rate support can have deleterious consequences. While the activity mode switch algorithm may address some of these concerns real world data are needed for validation.There is no question that the functionality and indications for leadless pacemakers will continue to expand. In current guidelines, which predate the development of the Micra AVTM, single chamber ventricular pacing is only recommended in patients with AV block and permanent atrial fibrillation, a low burden of anticipated pacing, or substantial comorbidities.6 Given the potential for lower complication rates compared with transvenous systems, Micra AV may be a superior option in some patients with complete heart block and preserved ventricular function. However, with the advent of conduction system pacing, the decreased risks of a leadless system have to be balanced with the relative risk of long term right ventricular pacing. Although the results will need to be validated with larger, longer-term studies, which are underway (Clinical trials.gov NCT04245345), these data indicate that Micra AVTM is likely to perform well in the setting of atrial arrhythmias. In patients with variable AV conduction, there are certainly pitfalls to the AV conduction mode switch algorithm, many of which could be avoided by the ability to program the mode switch VVI rate. While leadless pacing is often considered in patients with multiple comorbidities at high risk of complications from a transvenous system, we may be on the cusp of a dramatic paradigm shift. The technological developments and success of leadless pacing to date prompt the question of when, and not if, leadless dual chamber pacing and potentially even cardiac resynchronization will be available.References:1. Reynolds D, Duray GZ, Omar R, et al. A Leadless Intracardiac Transcatheter Pacing System. https://doi.org/10.1056/NEJMoa1511643. doi:10.1056/NEJMoa15116432. El-Chami MF, Al-Samadi F, Clementy N, et al. Updated performance of the Micra transcatheter pacemaker in the real-world setting: A comparison to the investigational study and a transvenous historical control. Heart Rhythm . 2018;15(12):1800-1807. doi:10.1016/j.hrthm.2018.08.0053. Duray GZ, Ritter P, El-Chami M, et al. Long-term performance of a transcatheter pacing system: 12-Month results from the Micra Transcatheter Pacing Study. Heart Rhythm . 2017;14(5):702-709. doi:10.1016/j.hrthm.2017.01.0354. Steinwender C, Khelae SK, Garweg C, et al. Atrioventricular Synchronous Pacing Using a Leadless Ventricular Pacemaker: Results From the MARVEL 2 Study. JACC Clin Electrophysiol . 2020;6(1):94-106. doi:10.1016/j.jacep.2019.10.0175. Merchant FM, Mittal S. Pacing induced cardiomyopathy. J Cardiovasc Electrophysiol . 2020;31(1):286-292. doi:10.1111/jce.142776. Kusumoto Fred M., Schoenfeld Mark H., Barrett Coletta, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation . 2019;140(8):e382-e482. doi:10.1161/CIR.0000000000000628
Background: Left pulmonary vein (PV) obstruction can occur due to compression between the left atrium (LA) and the descending aorta (DA). One of the effective solutions for this problem is posterior aortopexy. In this study, we have reported five cases of posterior aortopexy to relieve left PV obstruction between the LA and the DA. Methods: Since August 2012, five patients have undergone posterior aortopexy for compression of the left PV between the LA and the DA. The median age and weight of the patients at the time of operation were 5.5 months (range, 1-131 months) and 5.2 kg (range, 4.2-29.5 kg), respectively. The left PV obstruction was initially diagnosed on echocardiography in four patients and computed tomography angiography in one patient. The median peak pressure gradient across the obstructed left PV was 7.3 mmHg (range, 4-20 mmHg). Concomitant procedures were ventricular septal defect closure in one patient and patent ductus arteriosus ligation in one patient. Results: There was no PV obstruction on echocardiography in any of the patients after the operation except in the case of one patient who had diffuse pulmonary vein stenosis. The median follow-up duration was 34 months (range, 14-89 months), and during follow-up no incidence of the left PV obstruction was observed in any of the surviving patients. Conclusions: The posterior aortopexy technique could be a good surgical option for the left PV obstruction caused by compression between the LA and the anteriorly positioned DA.
Reply to “Additional Data Protection of the Esophagus During Catheter Ablation of Atrial Fibrillation”Mahmoud Houmsse, MD, and Emile G. Daoud, MDDepartment of Medicine, Division of Cardiology, Richard M. Ross Heart HospitalThe Ohio State University Medical Center, Columbus, OHRunning Title: Protection of EsophagusAddress for correspondence: Emile Daoud, MDDHLRI 473 W. 12th Avenue, Suite 200 Columbus, OH 43210-1252 Telephone: 877-478-2478 FAX : 614-293-5614E-Mail: email@example.comFunding: NoneDisclosure: Emile Daoud and The Ohio State University have equity ownership and serve as consultants to S4 Medical Corp, which is manufacturing the Esoultion esophageal retractor.Disclosure: Mahmoud Houmsse has no conflict of interestWe Thank Dr.Clark and Dr. Kulstad for their interest in our recent review manuscript “protection of the esophagus during catheter ablation of atrial fibrillation”We agree with Dr. Clark and Dr. Kulstad that utilization of luminal esophageal temperature (LET) monitoring during atrial fibrillation ablation is inadequate method to avoid esophageal injury. These have been reported in multiple studies that were referenced in our manuscript. The newer published studies regrading monitoring LET during atrial fibrillation ablation, which were reported by Dr. Clark and Dr. Kulstad, have been published during our manuscript publication process. Nevertheless, these studies that reported by Dr. Clark and Dr. Kulstad showed same conclusion of inadequate LET monitoring in preventing esophageal injury 1-3.Regarding active cooling, Dr. Clark and Dr. Kulstad reported recent published studies. First study small pilot study that showed active cooling is much more protective than manual liquid instillation4. The second pilot RCT that compared LET and active cooling showed same outcome like the IMPACT study that we reported in our manuscript 5,6.We agree with Dr. Clark and Kulstad, growing interest in the area of esophageal protection during atrial fibrillation ablation.We do believe, as we stated in the conclusion of our manuscript, that “a reliable method to protect the esophagus is of clinical value, but the ancillary value of reducing physician concern during AF ablation, reducing interruption to ablation work flow, perhaps enhancing AF ablation results and simplifying post procedure management of patient symptoms are also of high importance. Considering the ease of use, minimal side effects, and low costs associated with esophageal protection devices, these features offer compelling evidence for use of esophageal protection as routine care for AF ablation”.
Anaemia in pregnancy remains a global health problem In this issue of BJOG Hull et al …… et al report on an important study from South Africa regarding anaemia in pregnancy and the response to iron therapy. They report that in HIV-positive women the response was slower than in HIV-negative women. The underlying causes of anaemia varied and included iron deficiency (as assessed by ferritin levels) as well as concurrent infections (urinary tract infections and tuberculosis)Anaemia in pregnancy (blood haemoglobin Hb<11.0g/dl) occurs in > 40% of women living in low- and middle-income countries (LMIC) and in some settings in Asia prevalence is >60%. (McCauley et al, BMJ Global Health, 2018; 3(3):e000625) The latest WHO recommendations on antenatal care consider anaemia as the world’s second leading cause of disability and one of the most serious global public health problems (WHO Geneva 2016 ) .Although globally the focus has largely been on anaemia in pregnancy resulting from either iron deficiency or malaria, this is an incomplete approach at best. Iron deficiency is hard to measure and confirm as; i) this requires a functioning laboratory to be in place, ii) indicators for iron deficiency are influenced by the presence of concurrent infection, or, iii) repeated measures of Hb are needed to check whether the anaemia is responsive to treatment with iron. By contrast, malaria is relatively easy to diagnose via rapid diagnostic tests or microscopic examination of a stained blood smear slide. The handful of studies which have comprehensively assessed aetiology of anaemia in pregnant women demonstrate that anaemia is most commonly the result of complex multiple underlying factors including nutritional deficiencies as well as infectious diseases. Both nutritional deficiency and other infections (malaria, tuberculosis) are more likely with HIV-infection which itself can lead to anaemia probably through direct suppression of erythropoiesis.Hull et al show what was possible in a real-life clinical practice setting. This example of integration of research into clinical practice is laudable and is illustrative of how such integration could result in better services being made available for women in LMIC where burden of disease is high, but diagnostic tests are largely unavailable. It is sobering to realise that the majority of women world-wide will still only be screened for anaemia during pregnancy using ‘conjunctival inspection’ which is highly inaccurate. (van den Broek et al. Bull WHO 1999; 77(1):15-21) Rapid diagnostic tests are available for Hb, malaria, syphilis, HIV and, more recently, for tuberculosis. We are doing women a dis-service if we cannot offer at least these basic diagnostic tests as part of antenatal care.To prevent anaemia during pregnancy, the ‘fall-back’ position is to offer all women daily iron prophylaxis (30-60mg elemental iron) - with luck tablets are available that include folic acid (0.4mg) - along with presumptive treatment of malaria (various regimes) in endemic areas. Multi-micronutrients (including the required amount of iron and folic acid) might actually be better but cannot be recommended because of lack of evidence and they are still three times as expensive as iron and folic acid supplementation alone (3$ vs 1$ approximately).WHO recently recommended a better understanding of the aetiology of anaemia. A search on PubMed shows a clear lack of papers on the topic and more good research is needed. Investment in the antenatal care package offered to women is also much needed if we are aiming for a global ‘Health for All’.
The outcome of coronary artery bypass surgery depends on complete revascularization. In our paper, we attempt to demonstrate that Off-pump coronary artery bypass (OPCAB) is applicable to coronary heart disease patients with low LVEF. Low LVEF does not affect cardiac revascularization. Low LVEF is an independent risk factor for the outcome of CABG patients, but it does not mean that the OPCAB procedure leads to poor outcomes. In our hospital, we used on-pump CABG or conventional bypass surgery for coronary heart disease patients with low LVEF before 2010.With the accumulation of cases, OPCAB is now used in more than 95% of coronary artery bypass grafts in our center. Our data suggest that OPCAB is safe and reliable for patients with low LVEF.
Despite being first described over 30 years ago, focal radiofrequency (RF) continues to be the most widely used energy modality for catheter ablation. The fact that it has managed to hold its own against stiff competition from alternative energy sources used for pulmonary vein isolation (PVI) is down to continuous evolution based on enhancements in our understanding of its biophysical principles. In particular, the advent of contact-force (CF) based integrated indices such as Ablation Index have improved both efficacy and safety. However, a significant limitation of this approach is the absence of tissue feedback during lesion creation, which results in a blunt ‘one-size-fits-all’ approach. This limitation has been further brought into focus by the recent appreciation of the much greater importance of circuit impedance rather than delivered power as a fundamental determinant of RF lesion size.
We have read with great interest the article “Efficacy of Catheter Ablation for Premature Ventricular Contractions (PVC) in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)” by Assis F.R. et. al. PVC ablation in ARVC was previously studied by Aras D. et al and they presented successful results.In this study, we believe that the study should not be considered as unsuccessful since 2 patients showed a decrease in PVC burden by more than 80% and in the other three patients between 45-70%. The demonstration of a decrease in PVC burden with catheter ablation in ARVD patients indicates that a second ablation may increase the success rate and decrease symptoms. The fact that ARVC has a complex substrate and the disease can progress is undoubtedly the most important factor in achieving the desired success with PVC ablation. Epicardial ablation with endocardial ablation has increased the chance of success in this patient group. In addition, given that BCSD ablation and basal heart rate are guaranteed by ICD implantation, we think that administration of the maximum dose of antiarrhythmic medication may create a significant improvement in these patients. And another factor, contact force sensing plays an important role in evaluating the effectiveness of the process. We suggest that with the current treatment modalities, a pharmacoablative combination therapy and re-ablation when necessary would be appropriate for such a complicated disease.
The enormous complexity of the eukaryotic ribosome has been a real challenge in unlocking the mechanistic aspects of its amazing molecular function during mRNA translation and many non-canonical activities of ribosomal proteins in eukaryotic cells. While exploring the uncanny nature of ribosomal P proteins in malaria parasites Plasmodium falciparum, the 60S stalk ribosomal P2 protein has been shown to get exported to the infected erythrocyte (IE) surface as an SDS resistant oligomer during the early to mid trophozoite stage. Inhibiting IE surface P2 either by monoclonal antibody or through genetic knockdown resulted in nuclear division arrest of the parasite. This very strange and serendipitous finding has led us to explore more about un-canonical cell biology and structural involvement of P2 protein in Plasmodium in the search for a novel biochemical role during parasite propagation in the human host.
A fundamental aspect of evolutionary biology is natural selection on trait variation. Classically, selection has been estimated primarily on external morphological traits such as beak size and coloration, or on easily-assayable physiological traits such as heat-tolerance. As technologies and methods improved, evolutionary biologists began examining selection on molecular traits such as protein sequences and cellular processes. In a From the Cover manuscript in this issue of Molecular Ecology, Ahmad et al. (2021) continue this trend by estimating parasite driven selection on the molecular trait of transcript abundance in a wild population of brown trout (Salmo trutta) by uniquely combining a mark-recapture experimental design with non-invasive RNA sampling. Using transcript abundance to estimate selection allows for many different traits (each unique gene’s transcript counts) to be tested in a single experiment, providing the opportunity to examine trends in selection. Ahmad et al.(2021) find directional selection strength on transcript counts is generally low and normally distributed. Surprisingly, transcripts under non-linear selection showed a disruptive selection bias contradicting previous comparative studies and theoretical work. This highlights the importance of within-generation selection studies, where mechanisms may differ from longer time frames. Their manuscript also highlights the benefits of an improved 3’ RNA sequencing technique to measure gene expression.
1. Restoration ecology has historically focused on reconstructing communities of highly visible taxa whilst less visible taxa, such as invertebrates and microbes, are ignored. This is problematic as invertebrates and microbes make up the vast bulk of biodiversity and drive many key ecosystem processes, yet they are rarely actively reintroduced following restoration, potentially limiting ecosystem function and biodiversity in these areas. 2. In this review, we discuss the current (limited) incorporation of invertebrates and microbes in restoration and rewilding projects. We argue that these groups should be actively rewilded during restoration to improve biodiversity and ecosystem function outcomes and highlight how they can be used to greater effect in the future. For example, invertebrates and microbes are easily manipulated, meaning whole communities can potentially be rewilded through habitat transplants in a practice that we refer to as “whole-of-community” rewilding. 3. We provide a framework for whole-of-community rewilding and describe empirical case studies as practical applications of this under-researched restoration tool that land managers can use to improve restoration outcomes. 4. We hope this new perspective on whole-of-community restoration will promote applied research into restoration that incorporates all biota, irrespective of size, whilst also enabling a better understanding of fundamental ecological theory, such as colonisation- competition trade-offs. This may be a necessary consideration as invertebrates that are important in providing ecosystem services are declining globally; targeting invertebrate communities during restoration may be crucial in stemming this decline.
Letter to the Editor, BJOG Title:Deceleration Area and Deceleration Capacity: Promising predictors of fetal acidaemia in human labour? Visual versus computerised cardiotocographyRe: Georgieva A, Lear CA, Westgate JA, Kasai M, Miyagi E, Ikeda T, Gunn AJ, Bennet L. Deceleration area and capacity during labour-like umbilical cord occlusions identify evolving hypotension: a controlled study in fetal sheep. BJOG 2021; https://doi.org/10.1111/1471-0528.16638.Author: Mr. Shashikant L SHOLAPURKARMD, DNB, MRCOGDept of Obstetrics & Gynaecology,Royal United Hospital, Bath, BA1 3NG, UKEmail:firstname.lastname@example.org; email@example.com; Tel: 07906620662Short Running Title: Deceleration area and capacity in labourWord count: 500Corresponding Author: Mr. Shashikant L SHOLAPURKARMD, DNB, MRCOGDept of Obstetrics & Gynaecology,Royal United Hospital, Bath, BA1 3NG, UKStatement of interest: The author has no conflict of interest or funding to declare.
This paper begs an ontological question about the nature of health and challenges some underpinning assumptions in western healthcare. In its analysis, the structure of health, in its various statuses, is framed as a complex adaptive system made up of dynamically interacting subsystems that include the physiological, psychological, spiritual, social, cultural, and more, realms. Furthermore, openness in complex systems such as health, is necessary for the exchange of energy, information, and resources. Yet, within healthcare much effort is invested in constraining systems’ behaviours, whether they be systems of knowledge, states of health, models of care, and more. This paper draws on the complexity sciences and Levinasian philosophy to explicate the essential role of system openness in individual and population health, and the viability of healthcare systems. It highlights holism to be ‘not whole-ism’, and system openness to be, not just a reality, but a critical feature of viability. Hence requisite openness is advocated as essential to efficacious and ethical healthcare practice and strategy, and vital for good quality health.