Intracardiac Pacing Research Articles

Eight year Follow-Up Data on a Leadless Pacing System Real life experience in comparison to data of the prospective trial

Abstract Introduction The Micra leadless intracardiac pacing system has been introduced and implemented into clinical routine in 2015, with its next generation MICRA AV in 2020. Feasibility, implantation safety, and acute success have been proven in the setting of controlled studies. Even apart from controlled studies, this new technology was beneficial for the individual patient. We aimed to report our single center follow-up (FU) data with a follow-up of up to six years. Methods In 292 patients (146 men; age: 81±5,7 y), Micra implantation was performed. Pacemaker interrogation was performed one to seven days after implantation and during FU (1; 3; 6, then every 6 month) up to 84 months. Data were assessed in a real-life setting and compared with existing data of a controlled prospective trial. Results The implantation was successful in all 292 attempts with only one pericardial effusion as major complication. During follow up there were two patients developing severe heart failure symptoms resulting in an implantation of a CRT-device and switching of the leadless pacemaker system. The average acute thresholds, sensing and impedance after system release were: 0.57±0.34V@0.24ms; 10,02±3,96mV and 752±1201Ohm. During follow up of up to 8 years neither, pacemaker failure, nor infections were reported. Measurements were reevaluated for long-term thresholds, sensing and impedance: 0.75 ± 0.38V @ 0.24 ms; 18,38 ±2,75 mV and 525 ± 102 Ohm. During eight years, no significant changes from acute to long-term measurements were detectable. In comparison to the controlled trial, our measurements of this real-life cohort were very similar. Conclusion In a real-life setting, the implantation of the leadless Micra system demonstrates a high rate of implantation success without major complications. We were also able to show stable long-term system parameters in the clinical setting of up to seven years of follow up with a very good battery longevity of about 12,3 years.

Abstract Or102: Macrophage-Mediated Interleukin-6 Signaling Drives Ryanodine Receptor-2 Calcium Leak in Postoperative Atrial Fibrillation

Postoperative atrial fibrillation (poAF) is self-limited AF that occurs days after cardiac surgery in one-third of patients. The degree of perioperative increase in systemic inflammation, particularly involving interleukin (IL)-6, correlates with poAF risk. However, no studies to-date have identified the cell types involved nor mechanistically linked IL-6 signaling to fundamental arrhythmia mechanisms. To study poAF, we developed a mouse model consisting of atrial pericardiectomy and transient aortic cross-clamping followed by intracardiac burst pacing on postoperative day three to assess poAF inducibility. Single-cell RNA sequencing of atrial non-myocytes revealed macrophages to be the most prominently altered atrial cell type – increased 2.4-fold ( P <0.001) in mice with versus without poAF. Pseudotime trajectory analyses revealed IL-6 to be the top cytokine altered in macrophages, which we confirmed by western blot demonstrating a 1.7-fold ( P =0.012) increase in atrial IL-6 protein in mice with versus without poAF. Indeed, both macrophage depletion and conditional knockout of IL-6Ra in macrophages decreased poAF inducibility by 5.2-fold ( P =0.048) and 5.5-fold ( P =0.027), respectively. Downstream inhibition using an FDA-approved STAT3 inhibitor also rescued poAF (6.0-fold decrease, P =0.022). At the single atrial cardiomyocyte (ACM) level, IL-6 challenge led to a 6.3-fold ( P <0.001) increase in calcium (Ca 2+ ) spark frequency after normalization to sarcoplasmic reticulum Ca 2+ load, indicative of ryanodine receptor-2 (RyR2) dysfunction. Indeed, RyR2 phosphorylation at Ser2814, the target of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII), was increased in the atria of mice with poAF, and CaMKII inhibition was sufficient to rescue arrhythmogenic Ca 2+ sparks in ACMs from mice with poAF. We corroborated our findings in human ACMs and atrial tissue to demonstrate translational relevance. Taken together, we use an integrated approach incorporating mouse and human biochemical, functional, and single-cell sequencing data to demonstrate that infiltrating atrial macrophages, specifically IL-6Ra from macrophages, are fundamentally required for poAF development ( Fig. 1 ). Molecularly, enhanced atrial IL-6 signaling led to arrhythmogenic RyR2 dysfunction through CaMKII. Our findings portend therapeutic utility by providing mechanistic evidence that targeting the IL-6 axis may be used for poAF prevention and treatment in a clinically amenable timeframe.

Study of the cardiac sodium channel in a mouse model of Scn5a haploinsufficiency towards a novel approach of therapy

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Sorbonne Université doctoral scolarship INSERM Introduction Brugada syndrome (BrS) is an inherited cardiac arrhythmia that greatly increases the risk of sudden death as a result of ventricular fibrillation. Approximately 20% of BrS cases can be attributed to a mutation in SCN5A, the gene encoding the alpha-subunit Nav1.5 of the cardiac sodium-channel, which carries the sodium current INa. These mutations typically lead to loss-of-function of Nav1.5, resulting in a decrease in INa and most of them (»70 %) are responsible for haploinsufficiency. In the Scn5a+/- mouse model, a sodium-channel dysfunction phenotype is observed, characterized by conduction abnormalities (PR and QRS interval prolongation), a 50% reduction in INa, and an increased susceptibility to arrhythmias. Aim The aim of this study was to assess the impact of the overexpression of a Nav1.5-peptide, which has been found to enhance INa, in Scn5a+/- mice, as a novel approach of therapy. Methods We used AAV9-systemic injection to overexpress the Nav1.5-peptide into the heart of Scn5a+/- mice to gauge their susceptibility to arrhythmias induced by intracardiac pacing. We also examined the Nav1.5-peptide effects on endogenous Nav1.5 expression through molecular biology and biochemistry analyses. Results The duration of PR and QRS intervals in the hearts of Scn5a+/- mice was restored to normal by overexpression of the Nav1.5-peptide (PR interval = 46.3 ± 0.9 ms, n=22 in Scn5a+/- mice vs 40.4 ± 0.8 ms, n= 23 in WT mice, P<0.0001 and 42.6 ± 0.9 ms, n=11 in Scn5a+/- +Nav1.5-peptide, P<0.05; QRS interval = 15.2 ± 0.4, n=22 ms in Scn5a+/- mice vs 13.2 ± 0.4 ms, n=23 in WT mice, P<0.01 and 13.6 ± 0.4 ms, n=14 in Scn5a+/- +Nav1.5-peptide, P<0.05). Additionally, overexpression of the Nav1.5-peptide seemed to protect Scn5a+/- mice from induced arrhythmic events caused by programmed-ventricular stimulation (total premature beats = 1.3 ± 0.4 in Scn5a+/- mice, n = 13 vs 0.2 ± 0.2, n = 6 in injected Scn5a+/- mice, NS and 0.2 ± 0.2, n = 12 in WT mice, P< 0.05). There were no significant differences in total Nav1.5 expression between injected and non-injected mice as shown by RT-qPCR and Western-blots, but the expression of Nav1.5 at the plasma membrane appeared to be restored by overexpression of the Nav1.5-peptide (Nav1.5/N-cadherin ratio = 0.50 ± 0.08, n = 11 in Scn5a+/- mice vs 1 ± 0.15, n= 11 in WT mice, P< 0.05 and 0.94 ± 0.13, n = 11 in injected Scn5a+/- mice, P< 0.05). Conclusion Gene therapy with Nav1.5-peptide can attenuate both conduction defects and increased arrhythmia inducibility observed in Scn5a+/- mice. Although additional studies will be needed to confirm and explore further our results, this could be promising to treat patients with « sodium-channel dysfunction » such as BrS.

The association between GJB2 gene (producing Cx26 protein) and the ventricular storm: A case report.

A structural heart disease or functional electrical abnormalities can cause an electrical storm. We present a young boy with an electrical storm who had no cardiac risk factors and a positive family history of sudden cardiac death. The stepwise diagnostic approach was ineffective in determining previously known causes as the origin of the electrical storm. However, whole-exome sequencing (with Next Generation Illumina Sequencing) revealed a mutation in the GJB2 (NM_004004:exon2:c.G71A:p.W24X) gene. A mutation in the GJB2 gene, which forms the connexin 26 protein, a crucial component of the myocytes' intercalated disc of gap junction complex between the myocytes, results in an abnormal electrical cell-by-cell conductance, and, eventually, ventricular storm. General anesthesia was used to control the storm, and intracardiac pacing was fruitful in ceasing the subsequent VT storms.

Muscarinic acetylcholine receptors M2 are upregulated in the atrioventricular nodal tract in horses with a high burden of second-degree atrioventricular block.

Second-degree atrioventricular (AV) block at rest is very common in horses. The underlying molecular mechanisms are unexplored, but commonly attributed to high vagal tone. To assess whether AV block in horses is due to altered expression of the effectors of vagal signalling in the AV node, with specific emphasis on the muscarinic acetylcholine receptor (M2) and the G protein-gated inwardly rectifying K+ (GIRK4) channel that mediates the cardiac IK,ACh current. Eighteen horses with a low burden of second-degree AV block (median 8 block per 20 h, IQR: 32 per 20 h) were assigned to the control group, while 17 horses with a high burden of second-degree AV block (median: 408 block per 20 h, IQR: 1,436 per 20 h) were assigned to the AV block group. Radiotelemetry ECG recordings were performed to assess PR interval and incidence of second-degree AV block episodes at baseline and on pharmacological blockade of the autonomic nervous system (ANS). Wenckebach cycle length was measured by intracardiac pacing (n = 16). Furthermore, the expression levels of the M2 receptor and the GIRK4 subunit of the IKACh channel were quantified in biopsies from the right atrium, the AV node and right ventricle using immunohistochemistry and machine learning-based automated segmentation analysis (n = 9 + 9). The AV block group had a significantly longer PR interval (mean ± SD, 0.40 ± 0.05 s; p < 0.001) and a longer Wenckebach cycle length (mean ± SD, 995 ± 86 ms; p = 0.007) at baseline. After blocking the ANS, all second-degree AV block episodes were abolished, and the difference in PR interval disappered (p = 0.80). The AV block group had significantly higher expression of the M2 receptor (p = 0.02), but not the GIRK4 (p = 0.25) in the AV node compared to the control group. Both M2 and GIRK4 were highly expressed in the AV node and less expressed in the atria and the ventricles. Here, we demonstrate the involvement of the m2R-IK,ACh pathway in underlying second-degree AV block in horses. The high expression level of the M2 receptor may be responsible for the high burden of second-degree AV blocks seen in some horses.

Eight year follow-up data on a leadless pacing system real life experience in comparison to data of the prospective trial

Abstract Introduction The Micra™ leadless intracardiac pacing system has been introduced and implemented into clinical routine in 2015, with its next generation MICRA AV ™ in 2020. Feasibility, implantation safety, and acute success have been proven in the setting of controlled studies. Even apart from controlled studies, this new technology was beneficial for the individual patient. We aimed to report our single center follow-up (FU) data with a follow-up of up to six years. Methods In 272 patients (136 men; age: 81±5,7 y), Micra™ implantation was performed. Pacemaker interrogation was performed one to seven days after implantation and during FU (1; 3; 6, then every 6 month) up to 84 months. Data were assessed in a real-life setting and compared with existing data of a controlled prospective trial. Results The implantation was successful in all 272 attempts with only one pericardial effusion as major complication. During follow up there were two patients developing severe heart failure symptoms resulting in an implantation of a CRT-device and switching of the leadless pacemaker system. The average acute thresholds, sensing and impedance after system release were: 0.57±0.34V@0.24ms; 10,02±3,96mV and 752±1201Ohm. During follow up of up to 7 years neither, pacemaker failure, nor infections were reported. Measurements were reevaluated for long-term thresholds, sensing and impedance: 0.75 ± 0.38V @ 0.24 ms; 18,38 ±2,75 mV and 525 ± 102 Ohm. During seven years, no significant changes from acute to long-term measurements were detectable. In comparison to the controlled trial, our measurements of this real-life cohort were very similar. Conclusion In a real-life setting, the implantation of the leadless Micra™ system demonstrates a high rate of implantation success without major complications. We were also able to show stable long-term system parameters in the clinical setting of up to seven years of follow up with a very good battery longevity of about 12,3 years.

Continuous monitoring with implantable loop recorder detects arrhythmic risk in adults with systemic right ventricle following atrial switch

Abstract Background Patients with a systemic right ventricular circulation following atrial switch are at high risk of sudden death despite current monitoring strategies and advances in heart failure management. Arrhythmia represents a significant risk factor and early detection and intervention is of great value. The current surveillance approach with intermittent ambulatory monitoring is limited and cumbersome. Purpose We hypothesise that continuous rhythm monitoring with an implantable loop recorder (ILR) in the systemic right ventricle population will allow early detection of clinically significant arrhythmias. Methods Patients under follow up with a systemic right ventricular circulation following atrial switch were offered ILR implantation as an alternative to the standard of care (ambulatory 24-hour ECG). Patients with pre-existing intra-cardiac pacing devices or palliative were excluded. Following implantation, recordings made with symptoms or automatically following detection of significant arrhythmias. This included pauses over 3 seconds, atrioventricular block or supraventricular tachycardia. Transmission were reviewed daily and significant findings discussed in an adult congenital heart disease and electrophysiology MDT. Patients otherwise had routine clinical care. Results 24 patients had implantation of a loop recorder (67% of eligible cohort). They were aged 29-49 years (median 35 years) and 50% had additional lesions. Right ventricular function was normal in 42% and 29% had moderate or severe tricuspid regurgitation. 75% of the cohort were NYHA classification I. All but one patient were in sinus rhythm and 8 (33%) had previous intra-atrial re-entry tachycardia (IART). No patient had previously documented significant conduction disease. Implants were undertaken over 6 years without complications. 18 patients (75%) had automated or symptom activated recordings (52% automated) with a median of 2.8 recordings per patient (range 0 – 8 per patient) over 39.5 months (1.6 – 72.5 months). The recordings were clinically significant in 64% of the cohort (Table). This included 2 (9% of entire cohort) patients with atrioventricular block only, 11 patients (46%) with IART only and 4 patients (17%) with both IART and conduction disease (1 with atrioventricular block). These recordings resulted in 5 pacemaker implants (3 for atrioventricular block) and 2 further patients declined a device (1 subsequent death). 4 patients underwent, or are awaiting, ablation for IART. Risk scoring for sudden death did not predict arrhythmia events or atrioventricular block (1) (Figure). Conclusions Empirical ILR implantation in this low-risk systemic right ventricle cohort was well tolerated and detected a high burden of significant arrhythmias requiring intervention. Arrythmias were not predicted by risk scoring. This monitoring approach is an effective alternative to intermittent ambulatory surveillance however the impact on sudden death is unclear.

CD44 regulates Epac1-mediated β-adrenergic-receptor-induced Ca2+-handling abnormalities: implication in cardiac arrhythmias

BackgroundSustained, chronic activation of β-adrenergic receptor (β-AR) signaling leads to cardiac arrhythmias, with exchange proteins directly activated by cAMP (Epac1 and Epac2) as key mediators. This study aimed to evaluate whether CD44, a transmembrane receptor mediating various cellular responses, participates in Epac-dependent arrhythmias.MethodsThe heart tissue from CD44 knockout (CD44−/−) mice, cultured HL-1 myocytes and the tissue of human ventricle were used for western blot, co-immunoprecipitaiton and confocal studies. Line-scanning confocal imaging was used for the study of cellular Ca2+ sparks on myocytes. Optical mapping and intra-cardiac pacing were applied for arrhythmia studies on mice’s hearts.ResultsIn mice, isoproterenol, a β-AR agonist, upregulated CD44 and Epac1 and increased the association between CD44 and Epac1. Isoproterenol upregulated the expression of phospho-CaMKII (p-CaMKII), phospho-ryanodine receptor (p-RyR), and phospho-phospholamban (p-PLN) in mice and cultured myocytes; these effects were attenuated in CD44−/− mice compared with wild-type controls. In vitro, isoproterenol, 8-CPT-cAMP (an Epac agonist), and osteopontin (a ligand of CD44) significantly upregulated the expression of p-CaMKII, p-RyR, and p-PLN; this effect was attenuated by CD44 small interfering RNA (siRNA). In myocytes, resting Ca2+ sparks were induced by isoproterenol and overexpressed CD44, which were prevented by inhibiting CD44. Ex vivo optical mapping and in vivo intra-cardiac pacing studies showed isoproterenol-induced triggered events and arrhythmias in ventricles were prevented in CD44−/− mice. The inducibility of ventricular arrhythmias (VAs) was attenuated in CD44−/− HF mice compared with wild-type HF controls. In patients, CD44 were upregulated, and the association between CD44 and Epac1 were increased in ventricles with reduced contractility.ConclusionCD44 regulates β-AR- and Epac1-mediated Ca2+-handling abnormalities and VAs. Inhibition of CD44 is effective in reducing VAs in HF, which is potentially a novel therapeutic target for preventing the arrhythmias and sudden cardiac death in patients with diseased hearts.

Overview of programmed electrical stimulation to assess atrial fibrillation susceptibility in mice.

Atrial fibrillation (AF) is the most common human arrhythmia and is associated with increased risk of stroke, dementia, heart failure, and death. Among several animal models that have been used to investigate the molecular determinants of AF, mouse models have become the most prevalent due to low cost, ease of genetic manipulation, and similarity to human disease. Programmed electrical stimulation (PES) using intracardiac or transesophageal atrial pacing is used to induce AF as most mouse models do not develop spontaneous AF. However, there is a lack of standardized methodology resulting in numerous PES protocols in the literature that differ with respect to multiple parameters, including pacing protocol and duration, stimulus amplitude, pulse width, and even the definition of AF. Given this complexity, the selection of the appropriate atrial pacing protocol for a specific model has been arbitrary. Herein we review the development of intracardiac and transesophageal PES, including commonly used protocols, selected experimental models, and advantages and disadvantages of both techniques. We also emphasize detection of artifactual AF induction due to unintended parasympathetic stimulation, which should be excluded from results. We recommend that the optimal pacing protocol to elicit an AF phenotype should be individualized to the specific model of genetic or acquired risk factors, with an analysis using several definitions of AF as an endpoint.

Six year follow-up data on a leadless pacing system real life experience in comparison to data of the prospective trial

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The Micra™ leadless intracardiac pacing system has been introduced and implemented into clinical routine in 2015, with its next generation MICRA AV ™ in 2020. Feasibility, implantation safety, and acute success have been proven in the setting of controlled studies. Even apart from controlled studies, this new technology was beneficial for the individual patient. We aimed to report our single center follow-up (FU) data with a follow-up of up to six years. Methods In 246 patients (134 men; age: 79±8 y), Micra™ implantation was performed. Pacemaker interrogation was performed one to seven days after implantation and during FU (1; 3; 6, then every 6 month) up to 72 months. Data were assessed in a real-life setting and compared with existing data of a controlled prospective trial. Results The implantation was successful in all 246 attempts with only one pericardial effusion as major complication. During follow up there were two patients developing severe heart failure symptoms resulting in an implantation of a CRT-device and switching of the leadless pacemaker system. The average acute thresholds, sensing and impedance after system release were: 0.62±0.45V@0.24ms; 10,55±3,61mV and 697±178Ohm. During follow up of up to 5 years neither, pacemaker failure, nor infections were reported. Measurements were reevaluated for long-term thresholds, sensing and impedance: 0.44 ± 0.07V @ 0.24 ms; 17,25 ±4,65 mV and 572 ± 80 Ohm. During five years, no significant changes from acute to long-term measurements were detectable. In comparison to the controlled trial, our measurements of this real-life cohort were very similar. Conclusion In a real-life setting, the implantation of the leadless Micra™ system demonstrates a high rate of implantation success without major complications. We were also able to show stable long-term system parameters in the clinical setting of up to six years of follow up with a very good battery longevity of about 12 years.

Partial and complete loss of myosin binding protein H-like cause cardiac conduction defects

A premature truncation of MYBPHL in humans and a loss of Mybphl in mice is associated with dilated cardiomyopathy, atrial and ventricular arrhythmias, and atrial enlargement. MYBPHL encodes myosin binding protein H-like (MyBP-HL). Prior work in mice indirectly identified Mybphl expression in the atria and in small puncta throughout the ventricle. Because of its genetic association with human and mouse cardiac conduction system disease, we evaluated the anatomical localization of MyBP-HL and the consequences of loss of MyBP-HL on conduction system function. Immunofluorescence microscopy of normal adult mouse ventricles identified MyBP-HL-positive ventricular cardiomyocytes that co-localized with the ventricular conduction system marker contactin-2 near the atrioventricular node and in a subset of Purkinje fibers. Mybphl heterozygous ventricles had a marked reduction of MyBP-HL-positive cells compared to controls. Lightsheet microscopy of normal perinatal day 5 mouse hearts showed enrichment of MyBP-HL-positive cells within and immediately adjacent to the contactin-2-positive ventricular conduction system, but this association was not apparent in Mybphl heterozygous hearts. Surface telemetry of Mybphl-null mice revealed atrioventricular block and atrial bigeminy, while intracardiac pacing revealed a shorter atrial relative refractory period and atrial tachycardia. Calcium transient analysis of isolated Mybphl-null atrial cardiomyocytes demonstrated an increased heterogeneity of calcium release and faster rates of calcium release compared to wild type controls. Super-resolution microscopy of Mybphl heterozygous and homozygous null atrial cardiomyocytes showed ryanodine receptor disorganization compared to wild type controls. Abnormal calcium release, shorter atrial refractory period, and atrial dilation seen in Mybphl null, but not wild type control hearts, agree with the observed atrial arrhythmias, bigeminy, and atrial tachycardia, whereas the proximity of MyBP-HL-positive cells with the ventricular conduction system provides insight into how a predominantly atrial expressed gene contributes to ventricular arrhythmias and ventricular dysfunction.

Electrical activity in exercise trained infarcted rat hearts

Myocardial infarction (MI) is a major cause of cardiac arrhythmias. The aim of the study was to determine if exercise training changes the electrical conduction into, within and emerging from an infarcted area of a rat heart. Rats were divided into three groups: sedentary sham, sedentary MI, and exercise training MI. The impact of MI and exercise training on susceptibility to ventricular tachycardias (VTs) was evaluated by in vivo intra-cardiac pacing. Rats with sustained VTs were converted before sacrifice and electrophysiological experiments and optical imaging with voltage-sensitive dye were performed on perfused hearts.

In-depth characterization of a mouse model of postoperative atrial fibrillation.

Postoperative atrial fibrillation (POAF), characterized as AF that arises 1-3 days after surgery, occurs after 30%-40% of cardiac and 10%-20% of non-cardiac surgeries, and is thought to arise due to transient surgery-induced triggers acting on a preexisting vulnerable atrial substrate often associated with inflammation and autonomic nervous system dysfunction. Current experimental studies often rely on human atrial tissue samples, collected during surgery prior to arrhythmia development, or animal models such as sterile pericarditis and atriotomy, which have not been robustly characterized. To characterize the demographic, electrophysiologic, and inflammatory properties of a POAF mouse model. A total of 131 wild-type C57BL/6J mice were included in this study. A total of 86 (65.6%) mice underwent cardiothoracic surgery (THOR), which consisted of bi-atrial pericardiectomy with 20 s of aortic cross-clamping; 45 (34.3%) mice underwent a sham procedure consisting of dissection down to but not into the thoracic cavity. Intracardiac pacing, performed 72 h after surgery, was used to assess AF inducibility. THOR mice showed greater AF inducibility (38.4%) compared to Sham mice (17.8%, P = 0.027). Stratifying the cohort by tertiles of age showed that the greatest risk of POAF after THOR compared to Sham occurred in the 12-19-week age group. Stratifying by sex showed that cardiothoracic (CT) surgery increased POAF risk in females but had no significant effect in males. Quantitative polymerase chain reaction of atrial samples revealed upregulation of transforming growth factor beta 1 (TGF-β1) and interleukin 6 (IL6) and 18 (IL18) expression in THOR compared to Sham mice. Here, we demonstrate that the increased POAF risk associated with CT surgery is most pronounced in female and 12-19-week-old mice, and that the expression of inflammatory cytokines is upregulated in the atria of THOR mice prone to inducible AF.

Leadless intracardiac transcatheter pacing system: 20 months follow up in adult Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is an X-linked muscular dystrophy in relation with dystrophin deficient. Heart and respiratory function are classically involved and affect long-term prognosis. Significant atrio-ventricular block may occur in some patients. Implantation of traditional pacemaker may be challenging in patients with tracheotomy and on permanent home mechanical ventilation. We report the first case of a successful leadless intra-cardiac trans-catheter pacing system implantation in an adult DMD on wheelchair and on permanent home mechanical ventilation.

The deleterious effect of intracardiac pacing leads on right ventricular function.

Aim: The aim of this study was to evaluate the progression of tricuspid regurgitation (TR) in patients with pacemaker leads across the tricuspid valve and assess the clinical effect on right ventricular (RV) function.Methods: Patients who had undergone permanent pacemaker implantation at our institution over an 8-year period were identified. Those who had an echo (for any indication) pre- and postdevice implantation were included in this study, and their data assessed. Clinical information was obtained from their medical records. A total of 65 patients (mean age 70 ± 13 years, 31 (48%) males, and 34 (52%) females) were enrolled in the study.Results: The median interval of echo after implantation was 12 (12 to 24) months. Before implantation, 29 patients had TR, which increased to 51 (78%) during follow up, indicating that 22 patients developed new TR. Of those with preexisting TR, the grade of TR had worsened by at least one grade in 17 patients. RV function as measured by tricuspid annular plane systolic excursion (TAPSE) had decreased from 1.87 ± 0.44 to 1.68 ± 0.42 (p = 0.002). Eighteen patients had developed signs of right heart failure (either breathlessness with raised jugular venous pressure or pedal edema or both), of which 13 had only new pedal edema.Conclusion: There is a definite progression of TR in patients with a pacing lead across the tricuspid valve (TV) associated with an increase in the incidence of right heart failure. Patients with a pacing lead across the TV should be followed closely for signs of right heart failure.

Kv1.1 potassium channel subunit deficiency alters ventricular arrhythmia susceptibility, contractility, and repolarization.

Epilepsy‐associated Kv1.1 voltage‐gated potassium channel subunits encoded by the Kcna1 gene have traditionally been considered absent in heart, but recent studies reveal they are expressed in cardiomyocytes where they could regulate intrinsic cardiac electrophysiology. Although Kv1.1 now has a demonstrated functional role in atria, its role in the ventricles has never been investigated. In this work, electrophysiological, histological, and gene expression approaches were used to explore the consequences of Kv1.1 deficiency in the ventricles of Kcna1 knockout (KO) mice at the organ, cellular, and molecular levels to determine whether the absence of Kv1.1 leads to ventricular dysfunction that increases the risk of premature or sudden death. When subjected to intracardiac pacing, KO mice showed normal baseline susceptibility to inducible ventricular arrhythmias (VA) but resistance to VA under conditions of sympathetic challenge with isoproterenol. Echocardiography revealed cardiac contractile dysfunction manifesting as decreased ejection fraction and fractional shortening. In whole‐cell patch‐clamp recordings, KO ventricular cardiomyocytes exhibited action potential prolongation indicative of impaired repolarization. Imaging, histological, and transcript analyses showed no evidence of structural or channel gene expression remodeling, suggesting that the observed deficits are likely electrogenic due to Kv1.1 deficiency. Immunoblots of patient heart samples detected the presence of Kv1.1 at relatively high levels, implying that Kv1.1 contributes to human cardiac electrophysiology. Taken together, this work describes an important functional role for Kv1.1 in ventricles where its absence causes repolarization and contractility deficits but reduced susceptibility to arrhythmia under conditions of sympathetic drive.

Abstract 13184: A New Intraprocedural Automated System for Localizing Idiopathic Ventricular Arrhythmia Origin Sites

Introduction: Few intraprocedural localization systems have been developed to predict idiopathic ventricular arrhythmia (IVA) source sites. However, an accurate and bi-ventricular patient-specific automated site of origin localization system remains elusive. To address this issue, we have developed a new automatic arrhythmia origin localization (AAOL) system that determines the sites of earliest activation in both ventricles and provides superior accuracy. Hypothesis: We hypothesized that the AAOL system can use electroanatomic mapping (EAM) geometry and accurately localize IVA source sites on patient-specific geometry of LV, RV and neighboring vessels using 3-lead ECGs. Methods: Twenty patients undergoing IVA catheter ablation had a 12-lead ECG recorded during clinical arrhythmia and during pacing at various locations identified on EAM geometries. The AAOL system combined 3-lead (III, V2, V6) 120-ms QRS integrals and patient-specific EAM geometry with intracardiac pacing to predict the site of earliest ventricular activation. The predicted site was projected onto the EAM geometry using the EAM triangular-mesh site nearest to the tip of the predicted site. Results: Twenty-three IVA source sites were clinically identified by activation mapping and/or pace mapping (8 RV, 15 LV, including 8 from the posteromedial papillary muscle; 2 from the aortic root; and 1 from the distal coronary sinus). The new system achieved a mean localization accuracy of 3.6 mm for the 23 mapped IVAs (Figure 1D), better than that achieved by previous systems. Conclusions: The new AAOL system offers highly accurate localization of IVA source sites in both ventricles and neighboring vessels, which could facilitate ablation procedures for patients with IVAs.

The leadless pacemaker and cardiac nursing care

A leadless intracardiac transcatheter pacing system has been designed to overcome the need for a pacemaker pocket and transvenous lead. Currently, the leadless pacemaker only offers VVI/R pacing and cannot provide atrial pacing. Additional clinical data are required to enable comparison with transvenous devices. In order to prepare a patient for the procedure, nurses need to understand the rationale and treatment options, including risk factors to ensure that patient safety remains central to all care. This article reviews leadless pacemakers as a treatment option, explores the key aspects of nursing care and analyses the complications of these pacemakers.

Initial implantation experience and short-term follow-up results of implanting leadless intracardiac transcatheter pacing system

Objective: To explore the utility and safety of leadless intracardiac transcatheter pacing system. Methods: The study was a prospective observational study. Patients underwent Micra transcatheter pacing system in Beijing Anzhen hospital from December 2019 to January 2020 were enrolled. The baseline characteristics, platelet count, hemoglobin, anticoagulation and/or antiplatelet therapy, mean procedural time, average fluoroscopy time, number of deployment and electrical parameters (threshold, R-wave amplitude, impedance) were recorded. Ultrasonography of bilateral femoral and iliac veins was performed in all patients. Patients were followed including access site complication, adverse event and device evaluation at implant, hospital discharge, 1 and 3 months post-implant. R-wave≥5 mV, impedance between 400 and 1 500 Ω and threshold increase≤1.5 V than implant is considered a stable parameter. Femoral access site complications included hematoma, hemorrhage, pseudoaneurysm, and arteriovenous fistula. Adverse events included dislodgement, cardiac effusion/perforation and infection. Left ventricular end diastolic diameter and ejection fraction before and at 1 month after implant were reported. Results: Five patients were enrolled and pacemaker implantation was successful in all 5 patients. Patients were all males and the average age was (78.4±8.4) years. 2 patients received aspirin and clopidogrel therapy, 1 patient suffered from anemia and thrombocytopenia occurred in 1 patient. No stenosis, occlusion and vascular malformation of bilateral femoral and iliac veins was observed. The mean implant time was (39.6±1.7) minutes. The average fluoroscopy time was (9.2±1.3) minutes and the number of deployment was (1.40±0.55). Electrical parameters(threshold, R-Wave amplitude and impedance) were as follows: (0.40±0.10) V/0.24 ms, (10.80±3.72) mV and (822.00±162.23) Ω at implant; (0.45±0.07) V/0.24 ms, (13.04±2.41) mV, and (748.0±91.5) Ω at discharge, (0.40±0.06) V/0.24 ms, (14.26±4.11) mV, and (700.0±91.7) Ω at 1 month post-implant and (0.39±0.05) V/0.24 ms, 14.40±3.97 mV, and (682.0±96.0) Ω at 3 months post-implant, respectively. Threshold increase was ≤1.5 V compared to that during implantation, electrical parameters were acceptable and stable. There was no difference in LVEDD [(44.00±5.24) mm vs. (44.00±5.34) mm,P=1.000] and EF [(62.00±3.39)% vs. (62.20±3.56)%, P=0.861] before and 1 month post-implant. No incidence of access site complications, cardiac effusion/perforation, dislodgment or infections occurred during the 3 months. Conclusions: The leadless transcatheter pacemaker implantation performed in our study archived a high implant success rate and favorable safety profile as well as associated with low and stable pacing thresholds. The long-term safety and benefit of leadless pacemaker need to be evaluated in future clinical studies.

Abstract MP111: Loss of Myosin Binding Protein H-like Causes Cardiacconduction Abnormalities

A premature truncation variant in MYBPHL in humans and a loss of Mybphl in mice associates with dilated cardiomyopathy (DCM), atrial and ventricular arrhythmias, and atrial enlargement. MYBPHL encodes myosin binding protein H-like (MyBP-HL) and is expressed highly in the atria and in foci throughout the ventricle. We hypothesize that MyBP-HL is required for proper formation and function of the conduction system. Surface telemetry found atrioventricular block and atrial bigeminy, while intracardiac pacing revealed a faster atrial relative refractory period and atrial tachycardia in Mybphl -null mice. Ca 2+ transient analysis revealed that isolated Mybphl -null atrial cardiomyocytes had an increased occurrence of triggered Ca 2+ waves and more heterogenous Ca 2+ release than wild-type (WT) controls. Super-resolution microscopy revealed ryanodine receptor disorganization in Mybphl het and null atrial cardiomyocytes compared to WT controls. Immunofluorescence microscopy in WT adult mouse ventricles identified MyBP-HL-positive ventricular cardiomyocytes that co-localized with the ventricular conduction system marker contactin-2 near the atrioventricular node and in a subset of Purkinje fibers. Mybphl heterozygous ventricles showed 10% as many MyBP-HL-positive cells compared to WT. Lightsheet microscopy of perinatal day 5 hearts showed enrichment of MyBP-HL-positive cells within and immediately adjacent to the Cntn2-positive ventricular conduction system in WT hearts, but this association was not apparent in Mybphl heterozygous null hearts. These data, abnormal Ca 2+ release, shorter atrial refractory period, and atrial dilation could account for the observed atrial arrhythmias, bigeminy, and atrial tachycardia, whereas the proximity of MyBP-HL-positive cells with the ventricular conduction system provides insight into how a predominantly atrial expressed gene could cause ventricular arrhythmias.