Atrioventricular Node Research Articles

Temporal trends of catheter ablation procedures in patients with atrial fibrillation and atrial flutter: A nationwide cohort study

BackgroundCatheter ablation is a well-established treatment to prevent atrial fibrillation (AF) and atrial flutter (AFL) recurrences and to relieve symptoms, whereas pacemaker implantation and atrioventricular node (AVN) ablation is used for rate control when medical therapy fails. AimsWe investigated temporal trends and patient characteristics in catheter ablation procedures for AF, AFL and AVN in Finland between 2012–2018. MethodsFinnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a registry-based study including all patients with AF or AFL in Finland between 2012–2018. ResultsThe number of patients with AF or AFL diagnosis in Finland increased from 185057 to 243802 between 2012–2018 and a total of 8954 first-time catheter ablation procedures were performed. Of them, 4909 (54.8 %) were AF ablations, 2731 (30.5 %) AFL ablations and 1314 (14.7 %) AVN ablations. The procedural numbers increased from 457/year to 934/year for AF, from 223/year to 553/year for AFL and from 114/year to 238/year for AVN. Altogether, 0.65% of all patients with diagnosed AF or AFL underwent AF, AFL or AVN ablation in 2018. The mean age of the patients increased in all ablation groups. Patients undergoing AF and AFL ablations were predominantly men (69.7 % and 74.6 % respectively) whereas patients undergoing AVN ablation were more often women (56.9%). ConclusionsThe use of catheter ablation more than doubled during 2012–2018 and the increase was particularly seen in the elderly patients. Nevertheless, only a minority of AF and AFL patients were treated with catheter ablations.

Comparing Low-to-Zero Fluoroscopic Navigation Systems for AVNRT Catheter Ablation: A Network Meta-Analysis.

Low-to-zero fluoroscopic navigation systems lower radiation exposure which improves health outcomes. Conventional x-ray fluoroscopy (CF) has long been the standard to guide to catheter location for cardiac ablation. With advancements in technology, alternative safety navigation systems have been developed. Three primary modalities commonly utilized are three-dimensional electroanatomic mapping (3D-EAM), magnetic navigation system (MNS), and intracardiac echocardiography (ICE), all of which can reduce radiation exposure during the procedure. We aim to compare the efficacy and safety among ICE, EAM, MNS, and CF in ablation of atrioventricular nodal reentrant tachycardia (AVNRT). This is a meta-analysis consisting of observational studies and randomized controlled trials, which evaluated the performance of navigation systems of catheter ablation in AVNRT patients. Primary endpoint was to access the AVNRT recurrence after the procedure during follow-up periods. Secondary endpoints were technical success, fluoroscopic time, fluoroscopic dose area product, radiofrequency ablation time, and adverse events. Random-effect model was applied for pooled estimated effects of included studies. A total of 21 studies (21 CF, 2 ICE, 9 EAM, 11 MNS) including 1716 patients who underwent catheter ablation for AVNRT treatment were analyzed. Of these, 16 were observational studies and 5 were randomized controlled trials. Point estimation of AVNRT recurrence showed ICE exhibited a pooled odds ratio (ORs) of 1.06 (95% confidence interval [CI]: 0.064-17.322), MNS with ORs of 0.51 (95% CI: 0.214-1.219], and EAM with ORs of 0.394 (95% CI: 0.119-1.305) when compared to CF. EAM had significant higher technical success with ORs of 2.781 (95% CI: 1.317-5.872) when compared to CF. Regarding fluoroscopy time, EAM showed the lowest time with mean differences (MD) of -10.348 min (95% CI: -13.385 to -7.3101) and P-score of 0.998. It was followed by MNS with MD of -3.712 min (95% CI: -7.128 to -0.295) and P-score of 0.586, ICE with MD of -1.150 min (95% CI: -6.963 to 4.662) with a P-score of 0.294 compared to CF, which has a P-score of 0.122. There were insignificant adverse events across the procedures. AVNRT ablation navigated by low-to-zero fluoroscopic navigation systems achieves higher efficacy and comparable safety to conventional fluoroscopywhile also reducing risk of radiation exposure time.

His bundle pacing is continually relevant for patients with atrial fibrillation and bradycardia without prior atrioventricular nodal ablation, data from mid-term follow-up.

In patients with atrial fibrillation (AF) and symptomatic bradycardia, His Bundle pacing (HBP) is used to achieve an appropriate heart rate and physiological depolarization of the left ventricle (LV). We aimed to evaluate the impact of HBP on LV function in two different populations: normal LV ejection fraction (LVEF) and low LVEF (<50%). Patients who received HBP as de novo therapy or as an upgrade were divided into two groups based on initial LVEF, followed by echocardiographic and device monitoring. One hundred and twenty three patients (aged 76.0 [69.2-79.8] years, 74.0% men) with AF and bradycardia received HBP and completed follow-up with a median of 6.2 months (6.0-8.0). LV function remained unchanged in initially normal LV function patients (65 participants, LVEF 59.0% [55.0 - 62.0] vs. 58.0% [55.0-63.0]). In patients with low LVEF (58 participants), there was an increase in LVEF (37.5% [30.0-43.0] vs. 44.0% [35.0-50.0]; p < 0.0001), reduction of indexed LV end-systolic volume (62.4 [20.7] ml vs. 51.5 [21.5] ml; p = 0.001) and indexed LV end-diastolic volume (97.5 [26.2] ml vs. 88.1 [25.1] ml; p = 0.009), and improvement in the New York Heart Association class (2.3 [0.71] to 1.6 [0.9]; p < 0.0001). With permanent HBP, patients with AF and bradycardia and without prior atrioventricular nodal ablation did not experience LV systolic function deterioration. Those with reduced baseline LVEF experienced improvements in LV function and its reverse remodeling at the mid-term follow-up.

Clinical features of suspected and unsuspected fatal pulmonary emboli in hospitalized patients.

Pulmonary embolism (PE) is often unsuspected by treating clinicians. Since the adoption of clinical prediction scores for PE and the widespread availability of computed tomography (CT)-pulmonary angiogram, there are few reports of clinical presentations of hospitalized patients who died of PE. To compare the clinical signs, symptoms, and comorbidities of hospitalized patients who died of PE for whom PE was suspected versus not suspected antemortem. Case-control study from January 1999 to December 2018 in one Veterans Affairs (VA) hospital. We compared groups to examine differences in clinical presentations of fatal PE over the two decades. Among 1345 autopsies performed during the study period, 52 patients (4%) with fatal PE were included in the final analyses. PE was unsuspected before death in 29/52 patients (56%). Comparing groups, there were significant differences for: dyspnea (suspected 91%; unsuspected: 59%, p = 0.01); active malignancy (suspected 74%; unsuspected: 28%, p = 0.002); and atrioventricular (AV) nodal blocking treatment (suspected: 62%; unsuspected 30%,p= 0.03). A greater proportion of patients with unsuspected PE lacked symptoms of PE (suspected 0%; unsuspected: 31%, p = 0.003). Fatal PE remains a common, unsuspected cause of inpatient death in the modern era. Symptoms of PE, active malignancy, and potentially confounding AV nodal blocking treatment were less frequent in patients with unsuspected PE. These data highlight the variation in presentation and the challenge of making the diagnosis in many hospitalized patients, particularly those without typical symptoms.

Rationale and Design of OPT-RATE AF: A Randomized Clinical Trial of Increased Physiologic Pacing Rates in Heart Failure With Preserved Ejection Fraction

Cardiac physiologic pacing (CPP) after atrioventricular node (AVN) ablation for persistent atrial fibrillation (AF) has improved outcomes in patients with heart failure with reduced and preserved ejection fraction (HFpEF). Emerging evidence suggests patients with HFpEF benefit from higher heart rates, yet the optimal pacing rate after AVN ablation remains unknown. OPT-RATE AF is a prospective, randomized crossover study of patients with HFpEF following AVN ablation for persistent AF (NCT06445439). Approximately 60 patients with AF and AVN ablation, CPP, and HF with left ventricular ejection fraction ≥50% will be enrolled. Participants will be randomly assigned 1:1 to a pacing lower rate limit of 60 beats-per-minute (bpm) for 3 months and then switched to a rate of 80 bpm for 3 months, and vice versa. The primary endpoint is change in exercise capacity assessed by the 6-minute walk test. Notable secondary outcomes will include change in Kansas City Quality of Life Questionnaire (KCCQ-12), creatinine and natriuretic peptide, and clinical events. Patient mortality and HF hospitalizations will be recorded at each phase. EKG, echocardiogram, pacemaker interrogation, and primary and secondary outcomes will be recorded at baseline, 3 months, and 6 months. Study enrollment is ongoing and estimated to be completed by 2026. OPT-RATE AF is a randomized clinical trial that will determine the effect of a higher pacing rate in patients with persistent AF and HFpEF following AVN ablation and/or CPP. Study findings will provide insight on the role of chronotropy in improving QoL and other important cardiovascular outcomes.

Relevance of Anatomical Significance of AV Nodal Structures within Koch's Triangle and Pyramid.

The exploration of the cardiac conduction system evolved over a century, marked by groundbreaking discoveries in atrioventricular (AV) nodal physiology. Atrioventricular nodal re-entrant tachycardia (AVNRT), the most prevalent regular tachycardia in humans, remains enigmatic despite extensive research. Detailed examinations of AV nodal anatomy and histology reveal variations in location and shape, influencing electrophysiological properties. Variability in AV nodal extensions and their embryological origins contribute to the complexity of the conduction system. Physiologically, the AV node plays a crucial role in modulating AV conduction, introducing delays for ventricular filling and filtering atrial impulses. Dual-pathway physiology involving fast and slow pathways further complicates AVNRT circuitry. Integrated approaches combining pre-procedural imaging with electroanatomical mapping enhance our understanding of AV nodal structures and high-definition mapping improves precision in identifying ablation targets. Electrophysiological-anatomical correlations may unveil the specific roles of conduction axis components, aiding in the optimization of ablation strategies. This review traces the historical journey from Tawara's pioneering work to recent integrated approaches aimed at unraveling the intricacies of AV nodal structures while emphasizing the importance of a multidimensional approach, incorporating technological advancements, anatomical understanding, and clinical validation in human mapping studies.

Formulation, Optimization, and Evaluation of Solid-lipid Formulation for Bioavailability Enhancement Utilizing Diltiazem Hydrochloride

Background: Cardiac arrhythmia is a health concern, requiring effective medication for proper treatment. Diltiazem hydrochloride (DTZ.HCL), a class IV anti-arrhythmic calcium channel blocker, was used as a model drug due to its ability to block Ca++ channels in the SA and AV nodes, reducing calcium entry into cardiac cells and subsequently decreasing the force of contraction and oxygen consumption by the heart. Despite its good oral absorption, DTZ.HCL bioavailability is reduced to approximately 40% due to extensive first-pass metabolism. A nano-enabled drug delivery system has the advantage of incorporating both lipophilic and hydrophilic drugs with improved physical stability and enhanced bioavailability. Objective: The objective of this study was to develop a solid-lipid formulation utilizing diltiazem hydrochloride and evaluate it for its bioavailability enhancement. Method: In the experimental study, SLNs were prepared using the microemulsion technique. A blend ratio (1:1) of lipid (stearic acid: compritol 888 ATO), span 80, PEG 200, and water was selected based on the microemulsion region obtained from the Triplot (4.1) ternary phase diagram. The hydrophilic drug diltiazem hydrochloride was incorporated into the lipid blend, and a preheated Smix was maintained at 80°C to obtain a transparent microemulsion, which then crystallized to form SLNs upon subsequent dispersion in cold water (1:25). Critical process parameters, including magnetic stirring speed, homogenizer speed, and probe sonication cycle, were optimized using Design Expert 10 software to achieve the desired particle size diameter, PDI, and entrapment efficiency. Results: The results revealed that the particle size and PDI were significantly influenced by the span 80 and PEG 200. An increase in the concentration of the lipid blend resulted in large particle sizes. The optimized formulation showed a particle size of 415.4±0.2 nm, PDI of 0.184±0.01, and zeta potential of -24.19±0.12 mV. These results were corroborated by DSC thermograms, which indicated reduced enthalpy associated with the reduced particle size of SLNs. Given that diltiazem hydrochloride is a hydrophilic drug with high water solubility, the entrapment efficiency was relatively 30.6% ±0.45. In vitro release studies demonstrated an initial burst release, followed by a sustained release of 85% over 24 hours. The optimized SLNs followed the Higuchi matrix model, with a coefficient of correlation (R²) value of 0.9369. Conclusion: Results concluded successful development of SLNs with improved bioavailability when compared by way of in-vitro method with marketed preparations.

Electrocardiographic Clues for Early Diagnosis of Ventricular Pre-Excitation and Non-Invasive Risk Stratification in Athletes: A Practical Guide for Sports Cardiologists.

Ventricular pre-excitation (VP) is a cardiac disorder characterized by the presence of an accessory pathway (AP) that bypasses the atrioventricular node (AVN), which, although often asymptomatic, exposes individuals to an increased risk of re-entrant supraventricular tachycardias and sudden cardiac death (SCD) due to rapid atrial fibrillation (AF) conduction. This condition is particularly significant in sports cardiology, where preparticipation ECG screening is routinely performed on athletes. Professional athletes, given their elevated risk of developing malignant arrhythmias, require careful assessment. Early identification of VP and proper risk stratification are crucial for determining the most appropriate management strategy and ensuring the safety of these individuals during competitive sports. Non-invasive tools, such as resting electrocardiograms (ECGs), ambulatory ECG monitoring, and exercise stress tests, are commonly employed, although their interpretation can sometimes be challenging. This review aims to provide practical tips and electrocardiographic clues for detecting VP beyond the classical triad (short PR interval, delta wave, and prolonged QRS interval) and offers guidance on non-invasive risk stratification. Although the diagnostic gold standard remains invasive electrophysiological study, appropriate interpretation of the ECG can help limit unnecessary referrals for young, often asymptomatic, athletes.

Atrioventricular node ablation for atrial fibrillation in the era of conduction system pacing.

Despite key advances in catheter-based treatments, the management of persistent atrial fibrillation (AF) remains a therapeutic challenge in a significant subset of patients. While success rates have improved with repeat AF ablation procedures and the concurrent use of antiarrhythmic drugs, the likelihood of maintaining sinus rhythm during long-term follow-up is still limited. Atrioventricular node ablation (AVNA) has returned as a valuable treatment option given the recent developments in cardiac pacing. With the advent of conduction system pacing, AVNA has seen a revival where pacing-induced cardiomyopathy after AVNA is felt to be overcome. This review will discuss the role of permanent pacemaker implantation and AVNA for AF management in this new era of conduction system pacing. Specifically, this review will discuss the haemodynamic consequences of AF and the mechanisms through which 'pace-and-ablate therapy' enhances outcomes, analyse historical and more recent literature across various pacing methods, and work to identify patient groups that may benefit from earlier implementation of this approach.

Sinusoidal Atrial Fibrillation (Yasser’s Fibrillation) and Partial SAN Function in COVID-19 Pneumonia; a New Cardiovascular Discovery Change in Atrial Fibrillation Directory

Introduction: Atrial fibrillation (AF) is one of the most common and probable serious arrhythmias and a hallmark of an increasing risk of pathological thrombus formation. Interestingly, normal sinus rhythm (NSR) is the standard rhythm in a normal person. The sino-atrial node (SAN) is the heart's pacemaker and generator of the normal electrical conduction system of the heart which allows for the generating of electrical impulses. In AF, the normal regular electrical impulses generated by the sinoatrial node are overwhelmed by disorganized electrical waves, usually originating from the roots of the pulmonary veins. These disorganized waves conduct intermittently through the atrioventricular node (AVN) leading to irregular activation of the ventricles that generate the heartbeat. Cases presentation: Four different cases were described. 1. An elderly female patient presented to the ICU with metastatic complicated Mantle cell lymphoma, COVID-19 pneumonia, and irregular heart rate. 2. A senile male patient presented to the intensive care unit (ICU) with an aortic aneurysm, COVID-19 pneumonia, consumptive thrombocytopenia, lung fibrosis, and irregular heart rate. 3. A middle-aged female presented to the ICU with chronic renal failure (CRF) on regular hemodialysis, liver cell failure (LCF), pseudo-orange abdominal cellulitis, valvular heart replacement, and irregular heart rate. 4. An elderly female patient presented with cardiomyopathy, global cardiomegaly, irregular heart rate, diabetes, pseudo-orange abdominal cellulitis, liver cirrhosis, and COVID-19 pneumonia. Method of study and patients: Retrospective-Observational four case report series study was conducted in Kafr El-Bateekh Central Hospital staring from January 21, 2023 and ending on June 24, 2024 on COVID-19 pneumonia and atrial fibrillations. Conclusion: Sinusoidal atrial fibrillations (Yasser’s fibrillation) or mixed AF are a new cardiovascular discovery. The partial sino-atrial nodal function has essential role in the presence of Sinusoidal atrial fibrillations (Yasser’s fibrillation) or mixed AF and its interpretation. Sinusoidal atrial fibrillations (Yasser’s fibrillation) or mixed AF may be balanced between AF and normal sinus rhythm. The percentages of normal sinus beats to AF beats in the cases of Sinusoidal atrial fibrillations (Yasser’s fibrillation) may be a guide for approximate healthy or sick part of the sinoatrial node. Widening the research for the Sinusoidal atrial fibrillations (Yasser’s fibrillation) or mixed AF will be recommended.

Beta-adrenergic reactivity of erythrocyte membranes in adolescents with supraventricular and ventricular arrhythmias before and after radiofrequency ablation

Aim. To evaluate β-adrenergic reactivity of erythrocyte membranes (β-ARM) in adolescents with ventricular and supraventricular arrhythmias before and after radiofrequency ablation (RFA) of heart rhythm disturbances.Materials and methods. The study included 49 adolescents aged 11–17 years, of which 15 had Wolff – Parkinson – White pattern (WPW), 13 – WPW syndrome, 10 – atrioventricular nodal reentry tachycardia (AVNRT), and 11 – ventricular arrhythmia (VA). The control group consisted of 11 adolescents without cardiovascular pathology. All patients received surgical treatment for heart rhythm disturbances (HRD) using RFA. In patients with HRD, β-ARM was determined by a set of reagents BETA-ARM AGAT (AGAT LLC, Russia) before RFA and 3 days after it. In the control group, the parameter was determined at the stage of inclusion in the study.Results. In adolescents with supraventricular arrhythmias, median values of β-ARM did not differ significantly from the control group. RFA in adolescents in these groups did not affect the value of β-ARM on day 3 after the surgery. In adolescents with VA, the median value of β-ARM was initially higher than in the control group (p = 0.026). On day 3 after RFA, an increase in β-ARM was noted in this group (p = 0.028) compared to baseline values.Conclusion. Activation of the sympathetic nervous system plays a significant role in the pathogenesis of VA in adolescence. The study showed the possibility of using β-ARM to assess the state of the sympathetic nervous system in patients with methodological limitations in analyzing heart rate variability.

Rhythm and rate control strategies in patients with long-standing persistent atrial fibrillation treated with cardiac resynchronization: the results of the randomized Pilot-CRAfT study.

Atrial fibrillation (AF) is common in cardiac resynchronization therapy (CRT) recipients. It is a marker of impaired CRT response mainly mediated by the reduction of effectively captured biventricular paced beats (BiVp). There are no randomized trials comparing strategies to maintain high BiVp percentage. To compare the efficacy of rhythm vs rate control strategies in CRT recipients with long-standing persistent AF. We performed a randomized trial including CRT recipients with persistent AF resulting in low BiVp%. All patients received amiodarone, the rhythm control group received external electrical cardioversion (EC), and the rate control group received atrioventricular node ablation, if needed. The primary end-point was 12-month BiVp% (NCT). 43 patients were included in the analysis. The mean age was 68.4 (SD: ± 8.3) years and the mean BiVp% 82.4% ± 9.7%. AF lasted 25 ± 19 months. The mean baseline left ventricular ejection fraction (LVEF), left atrium area, and the maximal oxygen uptake (VO2max) were: 30 ± 8%, 33 ± 7 cm2, and 14 ± 5 mL/(kg*min), respectively. The EC success rate was 58%. 38% patients remained in sinus rhythm (SR) after 12 months. BiVp% increased similarly in both arms reaching 99% [95% CI 97.3-99.8] and 98% [94.0-99.0], P = 0.14 in rhythm and rate control groups, respectively. LVEF raised significantly only in the rhythm control group (ΔLVEF 4.1 (± 7.3), P = 0,018) which was driven by the patients who maintained SR. No differences in VO2max, QoL, clinical and safety end-points were observed. Despite comparable BiVp% in both groups, only restoration of SR led to improved left ventricular ejection fraction in CRT patients with long-standing AF. NCT01850277 registered on 22/04/2013.

Macrophages enhance sodium channel expression in cardiomyocytes.

Cardiac macrophages facilitate electrical conduction through the atrioventricular-node (AV) in mice. A possible role for cardiomyocyte-macrophage coupling on the effect of antiarrhythmic therapy has not been investigated yet. Holter monitoring was conducted in LysMCrexCsf1rLsL-DTR mice (MMDTR) under baseline conditions and after an elctrophysiological stress test by flecainide. In vivo effects were recapitulated in vitro by patch-clamp experiments. The underlying mechanism was characterized by expression and localization analysis of connexin43 (Cx43) and voltage-gated-sodium-channel-5 (Nav1.5). ECG monitoring in MMDTR mice did not show any significant conduction abnormalities but a significantly attenuated flecainide-induced extension of RR- and PP-intervals. Patch-clamp analysis revealed that the application of flecainide to neonatal rat ventricular cardiomyocytes (CMs) changed their resting-membrane-potential (RMP) to more negative potentials and decreased action-potential-duration (APD50). Coupling of macrophages to CMs significantly enhances the effects of flecainide, with a further reduction of the RMP and APD50, mediated by an upregulation of Cx43 and Nav1.5 surface expression. Macrophage depletion in mice does not correlate with cardiac electric conduction delay. Cardiac macrophages amplify the effects of flecainide on electrophysiological properties of cardiomyocytes in vivo and in vitro. Mechanistically, formation of macrophage-cardiomyocyte cell-cell-contacts via Cx43 facilitates the recruitment of Nav1.5 to the cell membrane increasing flecainide effects.

Recurrence rate and predictors in non-ischemic reversible bradyarrhythmias.

Non-ischemic symptomatic reversible bradyarrhythmia is a poorly characterized yet common clinical challenge. This study aimed to assess the incidence and predictors of recurrence and the need for permanent cardiac pacing in patients with non-ischemic symptomatic reversible bradyarrhythmia. This prospective single-center study enrolled 124 consecutive adult patients with non-ischemic symptomatic reversible bradyarrhythmia who were followed up for up to 24 months after conservative management during index hospitalization. The primary endpoint was a recurrence of bradyarrhythmia requiring permanent cardiac pacing. The secondary endpoint was a composite of recurrence requiring permanent pacing, readmission, or death. Univariate and multivariate analyses were conducted to determine the predictors of the endpoints. Sinus node and atrioventricular node diseases were seen in 66.1% and 33.9% of patients, respectively. The most common causes of bradyarrhythmia were negative chronotropic drugs (58.1%) and hyperkalemia (55.6%). Permanent pacing was required in 21.8% of patients after a recurrence. Advanced atrioventricular block at presentation (HR: 6.10, 95% CI: 2.45-15.20, p < 0.001) and bifascicular block at discharge (HR: 3.63, 95% CI: 1.58-8.33, p = 0.002) during index hospitalization were significant independent predictors of recurrence requiring cardiac pacing. Non-ischemic symptomatic reversible bradyarrhythmia is associated with a high risk of recurrence. Permanent cardiac pacing should be considered during index hospitalization in patients with advanced atrioventricular block and/or bifascicular block.

Adaptive control of cardiac rhythms

Cardiac rhythms are related to heart electrical activity, being the essential aspect of the cardiovascular physiology. Usually, these rhythms are represented by electrocardiograms (ECGs) that are useful to detect cardiac pathologies. Essentially, the heart activity starts in the sinoatrial node (SA) node, the natural pacemaker, propagating to the atrioventricular node (AV), and finally reaching the His-Purkinje complex (HP). This paper investigates the control of cardiac rhythms in order to induce normal rhythms from pathological responses. A mathematical model that presents close agreement with experimental measurements is employed to represent the heart functioning. The adopted model comprises a network of three nonlinear oscillators that represent each one of the cardiac nodes, connected by delayed couplings. The pathological behavior is induced by an external stimulus in the SA node. An adaptive controller is proposed acting in the SA node considering an strategy based on the signal obtained by the natural pacemaker and its regularization. The incorporation of adaptive compensation in a Lyapunov-based control scheme allows the compensation for the unknown dynamics. The controller ability to deal with interpatient variability is evaluated by assuming that the heart model is not available to the controller design, being used only in the simulator to assess the control performance. Results show that the adaptive term can reduce the control effort by around 3% while reducing the tracking error by 20%, when compared to the conventional feedback approach. Additionally, the controller can avoid abnormal rhythms, turning the ECG closer to the expected normal behavior and preventing critical cardiac responses. Therefore, this work demonstrates that an adaptive controller can be used to regulate the ECG signal without prior information about the system and disregarding inter- and intrapatient variability.

Assessing post-TAVR cardiac conduction abnormalities risk using an electromechanically coupled beating heart.

Transcatheter aortic valve replacement (TAVR) has rapidly displaced surgical aortic valve replacement (SAVR). However, certain post-TAVR complications persist, with cardiac conduction abnormalities (CCA) being one of the major ones. The elevated pressure exerted by the TAVR stent onto the conduction fibers situated between the aortic annulus and the His bundle, in proximity to the atrioventricular (AV) node, may disrupt the cardiac conduction leading to the emergence of CCA. In this study, an in silico framework was developed to assess the CCA risk, incorporating the effect of a dynamic beating heart and preprocedural parameters such as implantation depth and preexisting cardiac asynchrony in the new onset of post-TAVR CCA. A self-expandable TAVR device deployment was simulated inside an electromechanically coupled beating heart model in five patient scenarios, including three implantation depths and two preexisting cardiac asynchronies: (i) a right bundle branch block (RBBB) and (ii) a left bundle branch block (LBBB). Subsequently, several biomechanical parameters were analyzed to assess the post-TAVR CCA risk. The results manifested a lower cumulative contact pressure on the conduction fibers following TAVR for aortic deployment (0.018MPa) compared to nominal condition (0.29MPa) and ventricular deployment (0.52MPa). Notably, the preexisting RBBB demonstrated a higher cumulative contact pressure (0.34MPa) compared to the nominal condition and preexisting LBBB (0.25MPa). Deeper implantation and preexisting RBBB cause higher stresses and contact pressure on the conduction fibers leading to an increased risk of post-TAVR CCA. Conversely, implantation above the MS landmark and preexisting LBBB reduces the risk.

Calmodulin kinase II inhibition suppresses atrioventricular conduction by regulating intracellular Ca2+ homeostasis

BackgroundCa2+/calmodulin-dependent protein kinase II (CaMKII) inhibition decelerates atrioventricular node (AVN) conduction, providing a potential treatment of tachycardia. However, the effectiveness of CaMKII inhibition on tachycardia and its underlying mechanism remains unclear. ObjectiveWe aimed to assess the effectiveness of CaMKII inhibition in reducing ventricular rates during atrial fibrillation and to elucidate the underlying mechanism in affecting AVN electrophysiology. MethodsCardiac CaMKII inhibition (AC3-I) mice were used. Transesophageal atrial pacing was performed to evaluate AVN conduction function and to induce atrial fibrillation. Patch-clamp techniques were employed to record action potentials and ionic currents in AVN cells. Intracellular Ca2+ transients and sarcomere length measurements were obtained with the IonOptix system. Masson trichrome stain was used to evaluate fibrosis in the AVN region. Western blotting and immunofluorescence techniques were employed to detect connexin expression and localization. ResultsCaMKII inhibition decreased the ventricular rate during atrial fibrillation and isoproterenol-induced tachycardia. Esophageal electrocardiogram results from AC3-I mice showed longer AVN conduction than in wild-type mice. AN- and N-type AVN cells from AC3-I mice exhibited slower action potential frequencies and diastolic depolarization rates than those of wild-type mice. The study revealed that CaMKII inhibition reduced AVN cell sarcoplasmic reticulum (SR) Ca2+ content, Ca2+ release rate from the SR during diastole, Ca2+ transient amplitude, and SR Ca2+ uptake rate. In addition, CaMKII inhibition prolonged the sarcomere diastole duration and enhanced the sensitivity of sarcomeres to Ca2+. ConclusionCaMKII inhibition effectively decreases the ventricular rate during atrial fibrillation and tachycardia by slowing down AVN conduction through suppressing Ca2+ overload in AVN cells.

Analysis of junctional beats during slow pathway ablation: illuminating the mechanism of typical and atypical AV nodal re-entrant tachycardia

Analysis of junctional beats during slow pathway ablation: illuminating the mechanism of typical and atypical AV nodal re-entrant tachycardia

Cardiac Conduction System as an OAR in Radiation Therapy: Doses to SA/AV Nodes and Their Reduction

PurposeDespite advancements in radiation techniques, concerns persist regarding the adverse effects of radiation therapy, particularly cardiotoxicity or radiation-induced heart disease. Recently, arrhythmogenic toxicity has come to the forefront—the impact of radiation therapy on the cardiac conduction system. Our objective was to conduct a dosimetric study and subsequently investigate the feasibility of optimizing the sinoatrial (SA) and atrioventricular (AV) nodes as organs at risk (OARs) in proton radiation therapy for non–small cell lung cancer with N3 disease. Patients and MethodsThirty-two non–small cell lung cancer patients with N3 disease undergoing proton radiation therapy were included. Sinoatrial and AV nodes, along with standard OARs, were delineated. Dosimetric analysis and optimization were performed using intensity-modulated proton therapy. ResultsPatients surpassing a predefined SA node dose threshold underwent dose optimization. Proton radiation therapy with pencil beam scanning demonstrated a significant reduction in SA and AV node doses without compromising target volume coverage or significant shift in the dose to other monitored OARs. ConclusionDose reduction to the SA and AV nodes for pencil beam scanning is a relatively simple task, and the reduction can be very substantial. Larger cohort studies and diverse radiotherapeutic modalities are needed for further validation and refinement of dose constraints.

BRAНH syndrome: clinical case

The article describes a clinical case of BRAHH syndrome in a patient with arterial hypertension and permanent atrial fibrillation (AF). The patient took perindopril 10 mg, indapamide 2.5 mg, amlodipine 10 mg, bisoprolol 2.5-5 mg daily. She was admitted to a hospital complaining of severe weakness, a heart rate decreases to 38 beats per minute against the background of high blood pressure. During the examination, she was diagnosed with complete atrioventricular block against the background of AF, stage 4 chronic kidney disease and severe hyperkalemia (potassium 8.7 mmol/l). The patient was prescribed treatment aimed at eliminating hyperkalemia, and temporary pacing was established. Against this background, her condition improved, and the complete atrioventricular blockade was resolved. This clinical example meets the criteria of BRAHH syndrome, since against the background of taking an atrioventricular node blocker in a small dose, a patient with chronic kidney disease and severe hyperkalemia developed complete atrioventricular block against the background of AF, accompanied by high blood pressure.