Atrioventricular Node Dysfunction Research Articles

Atrioventricular and sinus node dysfunction in mild acute COVID-19 disease: a case series

Atrioventricular and sinus node dysfunction in mild acute COVID-19 disease: a case series

POPDC1 Variants Cause Atrioventricular Node Dysfunction and Arrhythmogenic Changes in Cardiac Electrophysiology and Intracellular Calcium Handling in Zebrafish.

Popeye domain-containing (POPDC) proteins selectively bind cAMP and mediate cellular responses to sympathetic nervous system (SNS) stimulation. The first discovered human genetic variant (POPDC1S201F) is associated with atrioventricular (AV) block, which is exacerbated by increased SNS activity. Zebrafish carrying the homologous mutation (popdc1S191F) display a similar phenotype to humans. To investigate the impact of POPDC1 dysfunction on cardiac electrophysiology and intracellular calcium handling, homozygous popdc1S191F and popdc1 knock-out (popdc1KO) zebrafish larvae and adult isolated popdc1S191F hearts were studied by functional fluorescent analysis. It was found that in popdc1S191F and popdc1KO larvae, heart rate (HR), AV delay, action potential (AP) and calcium transient (CaT) upstroke speed, and AP duration were less than in wild-type larvae, whereas CaT duration was greater. SNS stress by β-adrenergic receptor stimulation with isoproterenol increased HR, lengthened AV delay, slowed AP and CaT upstroke speed, and shortened AP and CaT duration, yet did not result in arrhythmias. In adult popdc1S191F zebrafish hearts, there was a higher incidence of AV block, slower AP upstroke speed, and longer AP duration compared to wild-type hearts, with no differences in CaT. SNS stress increased AV delay and led to further AV block in popdc1S191F hearts while decreasing AP and CaT duration. Overall, we have revealed that arrhythmogenic effects of POPDC1 dysfunction on cardiac electrophysiology and intracellular calcium handling in zebrafish are varied, but already present in early development, and that AV node dysfunction may underlie SNS-induced arrhythmogenesis associated with popdc1 mutation in adults.

Concomitant ablation of atrial fibrillation: New pacemakers and early rhythm recovery

ObjectiveNew permanent pacemaker (PPM) implantation after concomitant atrial fibrillation (AF) ablation has been associated with surgical ablation (SA). We sought to determine factors for PPM use as well as early rhythm recovery. MethodsFrom 2004 through 2019, 6135 patients underwent valve surgery and were grouped: No AF (n = 4584), AF no SA (n = 346), and AF with SA (n = 1205) to evaluate predischarge PPM and 3-month rhythm recovery (intrinsic heart rate >40 beats per minute). ResultsOverall, 282 (4.6%) patients required a predischarge PPM: atrioventricular node dysfunction in 75.3%, sick sinus syndrome in 19.1%, both (5%), and indeterminate (0.7%). Patients with AF had more PPMs: AF with SA (7.9%) versus AF no SA (6.9%) versus No AF (3.6%) (P < .001). For patients with AF, PPM rates were not significantly higher for ablation patients (7.6% SA vs 6.9% AF no SA; P = .56). There were differences in PPM by SA lesion set (biatrial 12.8%; left atrial only 6.1%; pulmonary vein isolation 3.0%; P < .001). Among patients with AF treated with 3-month PPM follow-up, rhythm recovery was common (35 out of 62 [56.5%]) and did not differ by lesion set. Rhythm recovery was seen in 63 out of 141 (44.7%) in the atrioventricular node dysfunction group versus 24 out of 35 (68.6%) in the sick sinus syndrome group (P = .011). In propensity score-matched groups, late survival was similar (P = .63) for new PPM patients. ConclusionsAvoiding conduction system trauma and delaying implantation reduces the need for postoperative PPM. Rhythm recovery within 3 months is frequent, especially for patients with sick sinus syndrome. A conservative approach to the implantation of a new PPMs is warranted.

Atrioventricular node dysfunction in pressure overload-induced heart failure-Involvement of the immune system and transcriptomic remodelling.

Heart failure is associated with atrioventricular (AV) node dysfunction, and AV node dysfunction in the setting of heart failure is associated with an increased risk of mortality and heart failure hospitalisation. This study aims to understand the causes of AV node dysfunction in heart failure by studying changes in the whole nodal transcriptome. The mouse transverse aortic constriction model of pressure overload-induced heart failure was studied; functional changes were assessed using electrocardiography and echocardiography and the transcriptome of the AV node was quantified using RNAseq. Heart failure was associated with a significant increase in the PR interval, indicating a slowing of AV node conduction and AV node dysfunction, and significant changes in 3,077 transcripts (5.6% of the transcriptome). Many systems were affected: transcripts supporting AV node conduction were downregulated and there were changes in transcripts identified by GWAS as determinants of the PR interval. In addition, there was evidence of remodelling of the sarcomere, a shift from fatty acid to glucose metabolism, remodelling of the extracellular matrix, and remodelling of the transcription and translation machinery. There was evidence of the causes of this widespread remodelling of the AV node: evidence of dysregulation of multiple intracellular signalling pathways, dysregulation of 109 protein kinases and 148 transcription factors, and an immune response with a proliferation of neutrophils, monocytes, macrophages and B lymphocytes and a dysregulation of 40 cytokines. In conclusion, inflammation and a widespread transcriptional remodelling of the AV node underlies AV node dysfunction in heart failure.

Pathophysiology of Cav1.3 L-type calcium channels in the heart.

Ca2+ plays a crucial role in excitation-contraction coupling in cardiac myocytes. Dysfunctional Ca2+ regulation alters the force of contraction and causes cardiac arrhythmias. Ca2+ entry into cardiomyocytes is mediated mainly through L-type Ca2+ channels, leading to the subsequent Ca2+ release from the sarcoplasmic reticulum. L-type Ca2+ channels are composed of the conventional Cav1.2, ubiquitously expressed in all heart chambers, and the developmentally regulated Cav1.3, exclusively expressed in the atria, sinoatrial node, and atrioventricular node in the adult heart. As such, Cav1.3 is implicated in the pathogenesis of sinoatrial and atrioventricular node dysfunction as well as atrial fibrillation. More recently, Cav1.3 de novo expression was suggested in heart failure. Here, we review the functional role, expression levels, and regulation of Cav1.3 in the heart, including in the context of cardiac diseases. We believe that the elucidation of the functional and molecular pathways regulating Cav1.3 in the heart will assist in developing novel targeted therapeutic interventions for the aforementioned arrhythmias.

Mitochondrial Dysfunction in Cardiac Arrhythmias.

Electrophysiological and structural disruptions in cardiac arrhythmias are closely related to mitochondrial dysfunction. Mitochondria are an organelle generating ATP, thereby satisfying the energy demand of the incessant electrical activity in the heart. In arrhythmias, the homeostatic supply-demand relationship is impaired, which is often accompanied by progressive mitochondrial dysfunction leading to reduced ATP production and elevated reactive oxidative species generation. Furthermore, ion homeostasis, membrane excitability, and cardiac structure can be disrupted through pathological changes in gap junctions and inflammatory signaling, which results in impaired cardiac electrical homeostasis. Herein, we review the electrical and molecular mechanisms of cardiac arrhythmias, with a particular focus on mitochondrial dysfunction in ionic regulation and gap junction action. We provide an update on inherited and acquired mitochondrial dysfunction to explore the pathophysiology of different types of arrhythmias. In addition, we highlight the role of mitochondria in bradyarrhythmia, including sinus node dysfunction and atrioventricular node dysfunction. Finally, we discuss how confounding factors, such as aging, gut microbiome, cardiac reperfusion injury, and electrical stimulation, modulate mitochondrial function and cause tachyarrhythmia.

Respiratory disturbance index as a predictor of atrial fibrillation

Abstract Background Obstructive sleep apnea (OSA) is a risk factor for development of atrial fibrillation (AF). Recent pacemakers have specific algorithms for detecting of OSA based on impedance measurement. Purpose The aim was to determine the burden of AF in patients with high respiratory disturbance index (RDI). It was also intended to determine if the onset of continuous positive airway pressure (CPAP) reduced the AF burden. Methods Retrospective observational study carried out through the analysis of the patient records. It included patients with pacemakers evaluated in an outpatient clinic during the first 8 months of 2018. All had the RDI algorithm. AF burden was assessed according to automatic mode switch (AMS) duration. The percentage of nights with an RDI&amp;gt;20/h was analysed to assess the risk of OSA. Results 108 patients were included (mean age=70.3±9.0 years; 56.5% men). The most prevalent indication for cardiac pacing was atrioventricular node dysfunction (59.3%). The average percentage of nights with an RDI&amp;gt;20/h was 44.2%. The average follow-up (FU) period was 4.1 years. Of all cardiovascular risk factors, diabetes mellitus was the only one associated with a higher incidence of AF at FU (p=0.044). Considering just the patients with an RDI &amp;gt;20/h in more than 20% of nights (RDI20%), male gender was associated with higher rate of major adverse cardiovascular events [(acute myocardial infarction, stroke, acute heart failure and death) (p=0.019)]. Considering patients with AF prior to pacemaker implantation (n=34), 76% of patients had an RDI &amp;gt;20/h in more than 20% of nights (mean of 58.1%). 23 of these patients had long standing persistent AF at the end of FU (vs 17 at the beginnig of FU). Considering patients who developed AF after pacemaker implantation (n=24), 58% of patients had an RDI&amp;gt;20/h in more than 20% of nights (mean of 45.3%). Most patients had paroxismal AF (83%). Patients with prior paroxysmal AF or those who developed AF during FU (n=37) had a higher burden of AF at the end of FU when they had RDI &amp;gt;20/h in more than 50% of nights (mean burden of 24.66% vs 14.69%, p=0.005). There was no statistically significant correlation between the percentage of nights with RDI &amp;gt;20/h and the Apnea Hypopnea Index (AHI) value. Patients who underwent polysomnography (n=30) had a mean AHI of 16/h (which corresponds to moderately severe OSA). 63% of patients who were referred from the pacemaker consultation to pneumology and performed polysomnography started CPAP. CPAP use was not associated with a statistically significant reduction in any endpoints or AF burden. Conclusion A high RDI was associated with onset of de novo AF and higher AF burden in patients with paroxysmal AF. Thus, there is a rationale for early diagnosis and treatment of OSAS to prevent and reduce AF progression. In this study, CPAP was not shown to significantly reduce this endpoint, probably due to reduced polysomnography and CPAP treatment. Funding Acknowledgement Type of funding sources: None.

Dynamic changes of atrioventricular conduction during Covid-19 infection: Does inflammation matter?

BackgroundThe primary manifestation of COVID-19 infection was pulmonary involvement. However, it can also manifest as a cardiovascular problem.MethodsWe report a case of 82-year-old male COVID-19 patient who experienced atrioventricular (AV) conduction disturbance.ResultsThe rhythm was degenerated from sinus rhythm to complete AV block. We observe dynamic AV node dysfunction associated with inflammatory response. His bundle pacing successfully captured distal His region.ConclusionThe severe inflammatory response during COVID-19 infection might permanently damage cardiac conduction system resulted in a complete AV node block.

Understanding Pacing-Induced Cardiomyopathy: a mini review

Patients with total atrioventricular block or sinus node dysfunction will need pacemaker implantation to improve the physiologic function of the heart. It is known that chronic pacing such as right ventricular pacing could deteriorate the cardiac function (decreased left ventricular ejection fraction) due to dyssynchrony. This condition is knows as pacing-induced cardiomyopathy (PICM). The incidence of PICM could reach 19.5% during 3 years follow-up. The right ventricle is one of the locations for implantation. Chronic right ventricular pacing may cause interventricular dyssynchrony and disrupt the contraction mechanism in the heart. These will lead to cardiac remodeling and eventually impair the left ventricular function. Therapy is needed in patients with PICM to improve the symptoms and maintain the cardiac function. This article will further highlight the definition, mechanism, risk factor, treatment and preventive strategy for patients with PICM.

Atrioventricular Conduction in Mesial Temporal Lobe Seizures.

Purpose: Asymmetric cerebral representation of autonomic function could help to stratify cardiac complications in people with epilepsy, as some seizures are associated with potentially deleterious arrhythmias including bradycardia and atrioventricular (AV) conduction block. We investigated seizure-related changes in AV conduction and ascertained whether these alterations depend on the hemisphere in mesial temporal lobe epilepsy (mTLE).Methods: EEG and ECG data of people with pharmacoresistant mTLE undergoing pre-surgical video-EEG telemetry with seizures independently arising from both hippocampi, as determined by intracranial depths electrodes were reviewed. RR and PR intervals were measured using one-lead ECG. Statistics were done with paired student's t-tests and linear regression analysis. Data are given as mean ± SD.Results: Fifty-six seizures of 14 patients (5 men, age 34.7 ± 9.8 years) were included (2 seizures per hemisphere and patient). There were no differences of absolute PR intervals and HR before and during unilateral ictal activity between left- and right-sided hippocampal seizures. Peri-ictal modulation of AV conduction, however, appeared greater with left-sided seizures, as the slope of the PR/HR correlations was significantly steeper with seizures originating in the left hippocampus. PR lengthening >200 ms or full block did not occur in any seizure.Conclusions: Our data show that on average, PR intervals shortens with mesial temporal lobe seizures with more prominent effects in seizures with left-sided onset, supporting the notion of lateralized cerebral control of cardiac function. The clinical relevance of this subtle finding is unclear but may indicate a lateralized susceptibility to seizure-related AV node dysfunction in mTLE.

Heart rate distribution in paced and non-paced patients with severe recurrent reflex syncope and tilt-induced asystole: Findings from the BIOSync CLS study

BackgroundUndiagnosed sinus or atrioventricular node dysfunction may bias estimation of the real efficacy of cardiac pacing in preventing vasovagal reflex syncope. We assessed this hypothesis in the BIOSync CLS trial which showed that dual-chamber pacing with closed loop stimulation (CLS) remarkably reduced recurrences of syncope. Methods and resultsIn the study patients aged 40 years or older with ≥2 episodes of loss of consciousness in the last year and an asystolic response to Tilt-Table test were randomized to pacing ON (DDD-CLS mode) or pacing OFF (ODO mode). We utilized the available pacemaker diagnostic data in a total of 103 patients (52 pacing ON, 51 pacing OFF) to generate cumulative distribution charts for heart rate (HR) and percentage of pacing. At 12 months, we did not find evidence of suspected sinus or atrioventricular node dysfunction. Beats were similarly distributed between groups (p = 0.96), with an average HR of 76 ± 8 bpm (pacing ON) versus 77 ± 7 bpm (pacing OFF). In the active group, the median percentage of atrial and ventricular pacing was 47% and 0%, respectively. Intolerance to high pacing rates was reported in only one patient (1.6%) and was easily resolved by reprogramming the maximum CLS pacing rate. ConclusionsWe did not find evidence of suspected sinus or atrioventricular node dysfunction in the BIOSync CLS patients. The benefit of pacing should be ascribed to pacing prevention of pure vasovagal episodes. CLS algorithm modulated pacing rates over a wide frequency range, consistently competing with sinus node.

Intrinsic Electrical Remodeling Underlies Atrioventricular Block in Athletes.

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Sick sinus syndrome and hyperthyroidism: A rare phenomenon

Cardiovascular complications play a very crucial part in hyperthyroidism and increased mortality and morbidity risk. Besides tachyarrhythmia, impaired systolic ventricular dysfunction and diastolic dysfunction may cause thyrotoxic cardiomyopathy in a small percentage of the patients, as another high mortality complication. Bradycardia in hyperthyroidism is a rare phenomenon which is associated with the sinus node dysfunction, atrioventricular node dysfunction, and conduction disturbance, or due to the effect of the drugs, i.e. beta-blockers. A 70-year-old female patient was brought to the emergency department with the history of feeling dizziness, lightheadedness, and bradycardia. While waiting in emergency, she had an episode of syncope, followed by regain of consciousness after 20 min. The patient was shifted for pacemaker insertion. Furthermore, hyperthyroidism and sick sinus syndrome are rare phenomena; it is highlighted mainly among patients with Graves' disease.

Procedural Logistics of Physiological (His-bundle or Left Septal) Pacing

Physiological pacing for atrioventricular node dysfunction with His-bundle or left septal pacing produces narrow paced QRS complexes and results in better left ventricular ejection fraction compared to right ventricular pacing. However, longer procedural and fluoroscopy times have been reported. We sought to examine the procedural logistics of physiological pacing, as a single centre experience.

Mobitz Type II Second-Degree Atrioventricular Block in a Pilot : To Pace or Not to Pace?

Background: Atrioventricular (AV) block is a threatening condition that caused sudden loss of consciousness and death, notably if happened to aircraft pilot will compromise the reliability of flight operations and safety. Cardiac arrhythmia is well known as one of the main disqualifier for loss of flying license, and discriminating between benign and potentially significant rhythm abnormalities remains a challenge. The present case describes the electrophysiological feature of a high-grade AV block in an aircraft pilot.&#x0D; Case illustration: A 60-year-old male worked as commercial aircraft pilot presented with asymptomatic high-grade AV block during inflight Holter monitoring. He had never experienced any remarkable symptoms nor history of near syncope, but had a history of percutaneous coronary intervention (PCI) with one stent at left circumflex (LCx) coronary artery. Electrophysiology (EP) study revealed AH interval of 105 ms, HV interval of 50 ms, AV node effective refractory period of 280 ms and Weckenbach point of 330 ms, suggesting a normal EP study. Stimulation with atrial pacing and ATP showed prolongation of AH interval without changes in HV interval, showing the presence of a supra-Hisian AV node dysfunction. The highly demanding physiological environment in aircraft elucidate the likelihood of vagotonic cause of his condition and pacemaker implantation was not warranted.&#x0D; Conclusion: Atrioventricular (AV) block is an AV conduction disorder that can manifests in various symptoms and severity. Electrophysiology study is considered as a modality to locate the site of block that allows the avoidance of unnecessary permanent pacing and the appropriate prophylactic pacing.

High-grade Atrioventricular Block in Pilot

Background: Atrioventricular (AV) block is a threatening condition that caused sudden loss of consciousness and death, notably if happened to aircraft pilot will compromise the reliability of flight operations and safety. Cardiac arrhythmia is well known as one of the main disqualifier for loss of flying license, and discriminating between benign and potentially significant rhythm abnormalities remains a challenge. The present case describes the electrophysiological feature of a high-grade AV block in an aircraft pilot.&#x0D; Case illustration: A 60-year-old male worked as commercial aircraft pilot presented with asymptomatic high-grade AV block during inflight Holter monitoring. He had never experienced any remarkable symptoms nor history of near syncope, but had a history of percutaneous coronary intervention (PCI) with one stent at left circumflex (LCx) coronary artery. Electrophysiology (EP) study revealed AH interval of 105 ms, HV interval of 50 ms, AV node effective refractory period of 280 ms and Weckenbach point of 330 ms, suggesting a normal EP study. Stimulation with atrial pacing and ATP showed prolongation of AH interval without changes in HV interval, showing the presence of a supra-Hisian AV node dysfunction. The highly demanding physiological environment in aircraft elucidate the likelihood of vagotonic cause of his condition and pacemaker implantation was not warranted.&#x0D; Conclusion: Atrioventricular (AV) block is an AV conduction disorder that can manifests in various symptoms and severity. Electrophysiology study is considered as a modality to locate the site of block that allows the avoidance of unnecessary permanent pacing and the appropriate prophylactic pacing.

Mechanisms of atrial fibrillation in aged rats with heart failure with preserved ejection fraction

Although ∼20% of the elderly population develops atrial fibrillation (AF), little is known about the mechanisms. Heart failure with preserved ejection fraction (HFpEF), which is associated with AF, is more common in aged women than in men. The purpose of this study was to identify potential mechanisms of AF in an age-related HFpEF model. In aged female Fischer F344 rats (21- to 24-month-old), which are prone to HFpEF, we induced AF by atrial pacing. Young Fischer F344 female rats (3- to 4-month-old) and age-matched Sprague Dawley female rats (27-month-old) served as controls. Phenotyping included echocardiography to assess left ventricular structure/function; invivo electrophysiology and exvivo high-resolution optical mapping to assess AF vulnerability; systemic and atrial inflammatory profiling; atrial histology; and expression of inflammasome signaling proteins. Aged rats developed left ventricular hypertrophy, left atrial enlargement, diastolic dysfunction, and pulmonary congestion, without ejection fraction impairment, thus meeting the criteria for HFpEF. Increased serum inflammatory markers, hypertension, and obesity further characterize aged females. Sinoatrial and atrioventricular node dysfunction was associated with the high inducibility of AF in aged rats. Exvivo electrical activation mapping revealed abnormal β-adrenergic responsiveness and slowed conduction velocity. Atrial inflammasome signaling was enhanced in aged rats, which may contribute to fibrotic remodeling and high AF susceptibility. Together, our data demonstrate that aging-related atrial remodeling and HFpEF are associated with atrial enlargement, fibrosis, conduction abnormalities, and nodal dysfunction, favoring a substrate conducive to AF.

Batter Up.

Batter Up.

ELectrophysiological mechanisms underlying the Inhibitory CArdiac syncope without asystolic significant pause: Therapeutic and prognostic implications. The ELICA randomized trial.

Background:The aim of this study was to investigate syncope recurrence in patients with a 2A cardioinhibitory response to the head up tilt testing (HUT).Methods:In this study, we enrolled 72 consecutive patients affected by syncope with cardioinhibitory response without asystolic significant pause to HUT (2A type). In these patients, we randomly performed electrophysiological study (ES). In case of sino-atrial node, atrio-ventricular node dysfunction, and sustained arrhythmias induction, the ES resulted positive. ES was positive in 9 patients (group A), then treated by catheter ablation, and/or by devices implants. Otherwise, ES resulted negative (group B), and these patients did not receive an interventional treatment. However, after ES, we evaluated syncope recurrence during 360 days follow-up.Results:There was a lower statistical significant syncope recurrence at follow-up, comparing group A to group B of patients [n of events 9 (40.9%) vs 8 (57.1%), P < .05]. At multivariate analysis, ES result was the only factor predicting syncope recurrence at follow-up (hazard ratio = 27.63, 95% confidence interval = 1.02–54.24, P < .005).Conclusion:The positivity to ES study, and successful interventional therapies may reduce the burden of syncope recurrence at 360 days follow-up in 2A HUT subjects.Clinical trial number: NCT02861274.

Structural and functional remodeling of the atrioventricular node with aging in rats: The role of hyperpolarization-activated cyclic nucleotide–gated and ryanodine 2 channels

BackgroundAging is associated with an increased incidence of atrioventricular nodal (AVN) dysfunction.ObjectiveThe aim of this study was to investigate the structural and functional remodeling in the atrioventricular junction (AVJ) with aging.MethodsElectrophysiology, histology, and immunohistochemistry experiments on male Wistar Hannover rats aged 3 months (n = 24) and 2 years (n = 15) were performed. Atrio-His (AH) interval, Wenkebach cycle length (WBCL), and AVN effective refractory period (AVNERP) were measured. Cesium (2 mM) was used to block hyperpolarization-activated cyclic nucleotide–gated (HCN) channels, while ryanodine (2 μM) was used to block ryanodine 2 (RyR2) channels. Protein expression from different regions of the AVJ was studied using immunofluorescence. The expression of connexins (connexin 43 and connexin 40), ion channels (Hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), voltage sensitive sodium channel (Nav1.5), and L-Type calcium channel (Cav1.3)), and calcium handling proteins (RyR2 and sarco/endoplasmic reticulum calcium ATPaset type 2a (SERCA2a)) were measured. Morphological characteristics were studied with histology.ResultsWithout drugs to block HCN and RyR2 channels, there was prolongation of the AH interval, WBCL, and AVNERP (P < .05) with aging. In young rats only, cesium prolonged the AH interval, WBCL, and AVNERP (P < .01). Ryanodine prolonged the AH interval and WBCL (P < .01) in both young and old rats. Immunofluorescence revealed that with aging, connexin 43, HCN4, Nav1.5, and RyR2 downregulate in the regions of the AVJ and connexin 40, SERCA2a, and Cav1.3 upregulate (P < .05). Aging results in cellular hypertrophy, loosely packed cells, a decrease in the number of nuclei, and an increase in collagen content.ConclusionHeterogeneous ion channel expression changes were observed in the AVJ with aging. For the first time, we have shown that HCN and RyR2 play an important role in AVN dysfunction with aging.