Single-Chamber Leadless Cardiac Pacemaker in Patients Without Atrial Fibrillation: Findings From Campania Leadless Registry

Introduction:Little is known about the clinical performance of single-chamber leadless pacemaker (LLPM) in patients without atrial fibrillation (AF) as pacing indication. The aim of this study was to describe the clinical characteristics of patients who underwent single chamber LLPM implantation at three tertiary referral centers and to compare the safety and effectiveness of the single-chamber LLPM among patients with or without AF.Materials and Methods:All the consecutive patients who underwent LLPM implantation at three referral centers were analyzed. The indications to LLPM in a real-world setting were described. The study population was divided into two groups according to AF as pacing indication. We assessed the procedure-related complications; moreover, we compared syncope, cardiac hospitalization, pacemaker syndrome, and all-cause death recurrence during the follow-up between patients with and without AF as pacing indication.Results:A total of 140 consecutive patients (mean age, 76.7 ± 11.24 years, men 64.3%) were included in the study. The indication to implantation of LLPM was permanent AF with slow ventricular response (n: 67; 47.8%), sinus node dysfunction (n: 25; 17.8%), third atrioventricular block (AVB) (n: 20; 14.2%), second-degree AVB (n: 18; 12.8%), and first degree AVB (n: 10; 7.1%). A total of 7 patients (5%) experienced perioperative complications with no differences between the AF vs. non-AF groups. During a mean follow-up of 606.5 ± 265.9 days, 10 patients (7.7%) died and 7 patients (5.4%) were reported for cardiac hospitalization; 5 patients (3.8%) experienced syncope; no patients showed pacemaker syndrome. No significant differences in the clinical events between the groups were shown. The Kaplan–Meier analysis for the combined endpoints did not show significant differences between the AF and non-AF groups [hazard ratio (HR): 0.94, 95% CI: 0.41–2.16; p = 0.88].Conclusion:Our real-world data suggest that LLPM may be considered a safe and reasonable treatment in patients without AF in need of pacing. Further studies are needed to confirm these preliminary results.

Late-Onset Ictal Asystole and Falls Related to Severe Coronary Artery Stenosis: A Case Report

Introduction: Ictal asystole (IA) is a rare, underestimated, and life-threatening cause of transient loss of consciousness and fall. Current treatment options for seizures associated with IA usually include cardiac pacemaker implantation. We report, for the first time, a case of IA that is related to coronary stenosis, which was resolved after coronary angioplasty.Case Presentation: A 73-year-old man had a 2-year history of focal seizures with impaired awareness. Three months before our observation, he started to have sudden falls resulting in injury on several occasions. General and neurological examinations, as well as brain MRI, were unremarkable. Interictal electroencephalography (EEG) showed bitemporal spiking. Ictal video-polygraphy revealed a diffuse electrodecrement, followed by a buildup of rhythmic 4–6 Hz sharp activity, which was more evident in the left temporal region. After the seizure onset, the ECG showed sinus bradycardia, followed by sinus arrest that was associated with the patient's fall from the standing position. Afterwards, sinus rhythm returned spontaneously. A diagnosis of IA was made. A comprehensive cardiologic evaluation revealed a sub-occlusive stenosis of the left anterior descending artery. Successful coronary angioplasty resolved IA, levetiracetam was added, and no seizure or fall has occurred in the following 20 months. Moreover, he underwent a 7-day Holter ECG monitoring, and no asystole was depicted.Conclusion: The present case was unique as it shows the potential association between IA and coronary stenosis, also suggesting a possible therapeutic role for coronary angioplasty. It also highlights the importance of carefully investigating epilepsy patients with falls, especially in the elderly, since IA-related falls can be easily misdiagnosed in older age. Thus, if IA is identified, a deeper cardiac evaluation should be considered. As seen in our patient, non-invasive diagnostic examination including routine, prolonged, and exercise ECG, as well as echocardiogram, were readily available and were informative in diagnosing cardiac abnormalities that are amenable to specific treatment.

A compact and miniaturized implantable antenna for ISM band in wireless cardiac pacemaker system

A tiny and compact implantable antenna for wireless cardiac pacemaker systems is designed. The antenna works in the Industrial Scientific Medical (ISM) frequency band (2.4–2.48 GHz). The size of the antenna is greatly reduced with the adoption of a high dielectric constant medium and a folded meander structure. The volume of the antenna is 4.5 mm3, and the size is only 3 mm × 3 mm × 0.5 mm. Based on the literature research, it was found that the design was the smallest among the same type of implanted antenna. The antenna is optimized and loaded with a defective slotted structure, which improves the efficiency of the overall performance of the antenna and thus the gain thereof. The antenna maintains good impedance matching in the ISM frequency band, covering the entire ISM frequency band. The actual bandwidth of the antenna is 22%, with the peak gain of − 24.9 dBi. The antenna is processed and manufactured in such a manner that the simulation keeps consistent with the actual measurement. In addition, the specific absorption rate of the antenna is also evaluated and analyzed. The result shows that this kind of antenna is the best choice to realize the wireless biological telemetry communication in the extremely compact space of the wireless cardiac pacemaker system.

Cross-talk between cAMP and Ca2+ signalling in cardiac pacemaker cells involves IP3-evoked Ca2+ release and stimulation of adenylyl cyclase 1

Atrial arrhythmias, such as atrial fibrillation (AF), are a major mortality risk and a leading cause of stroke. The IP3 signalling pathway has been proposed as an atrial specific target for AF therapy, and atrial IP3 signalling has been linked to the activation of calcium sensitive adenylyl cyclases AC1 and AC8. Here we investigated the involvement of AC1 in the response of intact mouse atrial tissue and isolated guinea pig atrial and sinoatrial node (SAN) cells to the α-adrenoceptor agonist phenylephrine (PE) using the selective AC1 inhibitor ST034307. The maximum rate change of spontaneously beating mouse right atrial tissue exposed to PE was reduced from 14.46 % to 8.17% (P = 0.005) in the presence of 1 μM ST034307, whereas the increase in tension generated in paced left atrial tissue in the presence of PE was not inhibited by ST034307 (Control = 14.20 %, ST034307 = 16.32 %; P > 0.05). Experiments were performed using isolated guinea pig atrial and SAN cells loaded with Fluo-5F-AM to record changes in calcium transient amplitude (CaT) generated by 10μM PE in the presence and absence of 1μM ST034307. ST034307 significantly reduced the beating rate of SAN cells (0.34-fold decrease; P = 0.004), but did not result in an inhibition of CaT amplitude increase in response to PE in atrial cells. The results presented here demonstrate the involvement of AC1 in the downstream response of atrial pacemaker activity to α-adrenoreceptor stimulation and IP3R calcium release.

CLINICAL PROFILES OF PATIENTS UNDERGOING PACEMAKER IMPLANTATION

Background and Objective: The implantation of a permanent cardiac pacemaker for the treatment of bradyarrhythmia is one of the most popular cardiac interventions. The goal of this study is to look at the clinical profiles of individuals who have permanent pacemakers implanted Material and Methods: The study was conducted using observational methods. The study included patients who received a permanent pacemaker for bradyarrhythmias between November 2019 and November 2021. A thorough review of the demographic profile and indications was performed. Results: The vast majority of the 312 patients were older, with the majority being between the ages of 56 and 88 years old (75 % ). Pacemakers were implanted in more men than in women. Complete heart block was the most common ECG finding and the most common presenting symptom was syncope. The most prevalent sign of pacing was acquired A-V block, and the most common pacemaker mode was single chamber (VVI/VVIR). Conclusion: Acquired A-V block and SSS were found to be the most common reasons for pacemaker implantation in our study. Higher implantation rates were linked to advanced age and male gender.

Functional heterogeneity of cell populations increases robustness of pacemaker function in a numerical model of the sinoatrial node tissue

Each heartbeat is initiated by specialized pacemaker cells operating within the sinoatrial node (SAN). While individual cells within SAN tissue exhibit substantial heterogeneity of their electrophysiological parameters and Ca cycling, the role of this heterogeneity for cardiac pacemaker function remains mainly unknown. Here we investigated the problem numerically in a 25x25 square grid of coupled-clock Maltsev-Lakatta cell models and tested the hypothesis that functional heterogeneity of cell populations increases robustness of SAN function. The tissue models were populated by cells with different degree of heterogeneity of the two key model parameters of the coupled-clock system, maximum L-type Ca current conductance (gCaL) and sarcoplasmic reticulum Ca pumping rate (Pup). Our simulations showed that in the areas of Pup-gCaL parametric space at the edge of the system stability where action potential (AP) firing was absent or dysrhythmic in tissues populated by identical cells, rhythmic AP generation was rescued in tissues populated by cells with uniformly random distributions of gCaL or Pup (but keeping the same average values). This effect to increase robust AP generation was synergistic with respect to heterogeneity in both gCaL and Pup and was further strengthened by clustering of cells with higher gCaL or Pup. The effect of functional heterogeneity was not due to a simple summation of activity of intrinsically firing cells naturally present in SAN; rather AP firing cells locally and critically interacted with non-firing/dormant cells. When firing cells prevailed, they recruited many dormant cells to fire, strongly enhancing overall SAN function. And vice versa, prevailing dormant cells suppressed AP firing in cells with intrinsic automaticity and halted SAN automaticity.

Phosphoprotein Phosphatase 1 but Not 2A Activity Modulates Coupled-Clock Mechanisms to Impact on Intrinsic Automaticity of Sinoatrial Nodal Pacemaker Cells

Spontaneous AP (action potential) firing of sinoatrial nodal cells (SANC) is critically dependent on protein kinase A (PKA) and Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent protein phosphorylation, which are required for the generation of spontaneous, diastolic local Ca2+ releases (LCRs). Although phosphoprotein phosphatases (PP) regulate protein phosphorylation, the expression level of PPs and phosphatase inhibitors in SANC and the impact of phosphatase inhibition on the spontaneous LCRs and other players of the oscillatory coupled-clock system is unknown. Here, we show that rabbit SANC express both PP1, PP2A, and endogenous PP inhibitors I-1 (PPI-1), dopamine and cyclic adenosine 3′,5′-monophosphate (cAMP)-regulated phosphoprotein (DARPP-32), kinase C-enhanced PP1 inhibitor (KEPI). Application of Calyculin A, (CyA), a PPs inhibitor, to intact, freshly isolated single SANC: (1) significantly increased phospholamban (PLB) phosphorylation (by 2–3-fold) at both CaMKII-dependent Thr17 and PKA-dependent Ser16 sites, in a time and concentration dependent manner; (2) increased ryanodine receptor (RyR) phosphorylation at the Ser2809 site; (3) substantially increased sarcoplasmic reticulum (SR) Ca2+ load; (4) augmented L-type Ca2+ current amplitude; (5) augmented LCR’s characteristics and decreased LCR period in intact and permeabilized SANC, and (6) increased the spontaneous basal AP firing rate. In contrast, the selective PP2A inhibitor okadaic acid (100 nmol/L) had no significant effect on spontaneous AP firing, LCR parameters, or PLB phosphorylation. Application of purified PP1 to permeabilized SANC suppressed LCR, whereas purified PP2A had no effect on LCR characteristics. Our numerical model simulations demonstrated that PP inhibition increases AP firing rate via a coupled-clock mechanism, including respective increases in the SR Ca2+ pumping rate, L-type Ca2+ current, and Na+/Ca2+-exchanger current. Thus, PP1 and its endogenous inhibitors modulate the basal spontaneous firing rate of cardiac pacemaker cells by suppressing SR Ca2+ cycling protein phosphorylation, the SR Ca2+ load and LCRs, and L-type Ca2+ current.

Сardiorenal Syndrome in Patients on Renal Replacement Therapy

In this chapter authors discusses cardiorenal relationships in patients with renal replacement therapy (RRT) which are considered as a separate type of cardiorenal syndrome (CRS). Frequency and severity of CRS in patients on dialysis are correlated with quantity of years of the dialysis treatment; depend on quality of dialysis regimen and level of residual renal function. RRT-associated cardiac pathology are including left ventricular hypertrophy, ischemic cardiomyopathy, congestive heart failure, coronary atherosclerosis and calcinosis, severe arrhythmias. The article analyzes role of malnutrition and dialysis-induced cachexia, bio-incompatibility of dialysis membranes, oxidative stress and inflammation, arterio-venous fistula, decrease of residual renal function in the development of dialysis-induced CRS. The review examines the mechanisms of progressive myocardial ischemia induced by dialysis: myocardial stunning, hemodialysis-induced hypotension, uremic small vessel disease. Prevention of dialysis-induced CRS includes a choice of the optimal RRT method (peritoneal dialysis or hemodialysis), соntrol of dialysis regimen, residual renal function, biocompatibility of membrane, inflammatory markers, body mass index, serum level albumin, phosphate, calcium, parathyroid hormone, fibroblast growth factor-23. Electrocardiogram, ultrasonic monitoring and coronarography reveals indications for соnservative cardioprotective therapy and angioplasty interventions, including coronary artery bypass surgery and cardiac pacemaker implantation, in patients with dialysis-induced CRS.

810. Cardiac Pacemaker Implantation Surgery: Automated Prediction of Surgical Site Infection

Background A research focused on surgical site infection (SSI) was performed in patients undergoing cardiac pacemaker implantation surgery. The main objective is to statistically evaluate such incidences and enable a study of the prediction power of SSI through pattern recognition algorithms, in this case the Multilayer Perceptron (MLP). Methods Data were collected from five hospitals in the city of Belo Horizonte (more than 3,000,000 inhabitants), between July 2016 and June 2018, on SSI by the Hospital Infection Control Committees (CCIH) of the hospitals involved in the search. All data used in the analysis during their routine SSI surveillance procedures were collected. So, three procedures were performed: a treatment of the collected database for use of intact samples; a statistical analysis on the profile of the hospitals collected and; an assessment of the predictive power of five types of MLP (Backpropagation Standard, Momentum, Resilient Propagation, Weight Decay, and Quick Propagation) for SSI prediction. MLPs were tested with 3, 5, 7, and 10 hidden layer neurons and a database split for the resampling process (65% and 75% for testing, 35% and 25% for validation). They were compared by measuring AUC (Area Under the Curve - from 0 to 1) presented for each of the configurations. Results From 1394, 572 records were: 21% of deaths and 2.4% patients had SSI; from the confirmed SSI cases, approximately 64.3% had sites classified as “clean”; length of hospital stay ranged from 0 to 175 days (from 1 to 70 days); the average age is 67 years. The prediction power of SSI, the experiments achieved from 0.409 to 0.722. Conclusion Despite the considerable loss rate of more than 65% of the database samples due to the presence of noise, it was possible to have a relevant sampling for the profile evaluation of Belo Horizonte hospitals. Moreover, for the predictive process, although some configurations reached 0.722. To optimize data collection and enable other hospitals to use the SSI prediction tool (available in www.nois.org.br ), two mobile application were developed: one for monitoring the patient in the hospital and the other for monitoring after hospital discharge. Disclosures All Authors: No reported disclosures