Atrioventricular Nodal Function Research Articles

Model-based estimation of AV-nodal refractory period and conduction delay trends from ECG.

Introduction: Atrial fibrillation (AF) is the most common arrhythmia, associated with significant burdens to patients and the healthcare system. The atrioventricular (AV) node plays a vital role in regulating heart rate during AF by filtering electrical impulses from the atria. However, it is often insufficient in regards to maintaining a healthy heart rate, thus the AV node properties are modified using rate-control drugs. Moreover, treatment selection during permanent AF is currently done empirically. Quantifying individual differences in diurnal and short-term variability of AV-nodal function could aid in personalized treatment selection. Methods: This study presents a novel methodology for estimating the refractory period (RP) and conduction delay (CD) trends, and their uncertainty in the two pathways of the AV node during 24 h using non-invasive data. This was achieved by utilizing a network model together with a problem-specific genetic algorithm and an approximate Bayesian computation algorithm. Diurnal variability in the estimated RP and CD was quantified by the difference between the daytime and nighttime estimates, and short-term variability was quantified by the Kolmogorov-Smirnov distance between adjacent 10-min segments in the 24-h trends. Additionally, the predictive value of the derived parameter trends regarding drug outcome was investigated using several machine learning tools. Results: Holter electrocardiograms from 51 patients with permanent AF during baseline were analyzed, and the predictive power of variations in RP and CD on the resulting heart rate reduction after treatment with four rate control drugs was investigated. Diurnal variability yielded no correlation to treatment outcome, and no prediction of drug outcome was possible using the machine learning tools. However, a correlation between the short-term variability for the RP and CD in the fast pathway and resulting heart rate reduction during treatment with metoprolol (ρ = 0.48, p < 0.005 in RP, ρ = 0.35, p < 0.05 in CD) were found. Discussion: The proposed methodology enables non-invasive estimation of the AV node properties during 24 h, which-indicated by the correlation between the short-term variability and heart rate reduction-may have the potential to assist in treatment selection.

Pacing in Pediatric Patients with Postoperative Atrioventricular Block.

Surgery for congenital heart disease may compromise atrioventricular (AV) nodal conduction, potentially resulting in postoperative AV block. In the majority of cases, AV nodal function recovers during the early postoperative period and may only require short-term pacing support, typically provided via temporary epicardial wires. Permanent pacing is indicated when the postoperative AV block persists for more than 7 to 10days due to the risk of mortality if a pacemaker is not implanted. Although there is a subset of patients who may have late recovery of AV nodal function, those with continued postoperative AV block will need lifelong pacing therapy.

Head up tilt test response patterns in patients undergoing cardioneuroablation

Abstract Funding Acknowledgements Type of funding sources: None. Background Vasovagal syncope (VVS) is the most common cause of transient loss of consciousness. It severely affects quality of life and can often lead to severe trauma and fatal accidents. Effective treatment of some of these patients can be obtained with cardioneuroablation (CNA). Head-up tilt test (HUT) plays a major role during the evaluation of syncope patients and helps to differentiate syncope subtypes. Data on the HUT response patterns and its usefulness for the recommendation of CNA and the evaluation of the results is lacking. Purpose To assess HUT response patterns before and after CNA. Methods We included patients with repetitive episodes or considered clinically relevant episodes of vasovagal syncope in the previous 6 months and symptomatic patients with documentation of functional sinus bradycardia or functional AV node block. Before performing CNA, all patients underwent a comprehensive baseline evaluation to analyze sinus node and AV node function. CNA was considered in those patients in whom intrinsic sinus node or AV node disease has been excluded in the electrophysiological study (response to atropine was also assessed), had a VASIS type 2A, 2B or type 1 (mixed) response to the HUT and provided signed informed consent. CNA was performed under general anesthesia and ablation strategy was based on presumed anatomical localization of GP. Follow-up of these patients was performed in the outpatient clinic with scheduled visits at 1, 6 and 12 months including 24-hour Holter monitoring. A control HUT was performed at 3 months. Results We included 36 patients. 22 males (61.1%), mean age 51 (18-82 years). The average number of syncope events per year per patient prior to the procedure was 5 ±3. The mean HR on Holter Pre CNA was 65 ± 12 and 72 ± 9 post CNA. Of the HUT, 9 (25%) had mixed type response; 9 (25%) cardioinhibitory type 2A and 18 (50%) cardioinhibitory type 2B. The response in type 2B was sinus arrest in 12 (33.3%), AV block in 5 (13.9%) and both in 1 (2.8%) patient. During a mean of 9 ±4 months follow-up, only 3 patients had a syncope recurrence. At the three-month HUT we observed complete elimination of the cardioinhibitory component present prior to CNA in 34 (94.4%) patients. During the HUT, 18 (50%) had no syncope whereas the remaining 17 had HUT-induced syncope. In 16 (44.4%) of them due to vasodepressor mechanism and only 1 due to cardioinhibitory type 2A response (Figure 1). This patient also had a syncopal recurrence in the follow up. We did not perform the control HUT in 1 patient because of an early recurrence and the patient decided to undergo a pacemaker implantation. We had another recurrence at 11 months post CNA in a patient in whom the control tilt test was negative. The syncope-free survival curve can be seen in Figure 2. Conclusions CNA changes the response pattern of the HUT by eliminating the cardioinhibitory component and can be useful in the evaluation of the long-term CNA outcomes.

Ganglionated plexi ablation in the right atrium for the treatment of cardioinhibitory syncope.

Neurocardiogenic syncope, also called vasovagal syncope, represents one of the clinical manifestations of neurally mediated syncopal syndrome. Generally, the prognosis of the cardioinhibitory form of neurocardiogenic syncope is good, but quality of life is seriously compromised in patients who experience severe forms. Drug therapy has not achieved good clinical results and very heterogeneous data come from studies regarding permanent cardiac pacing. In this scenario, the ganglionated plexi ablation has been proposed as an effective and safe method in patients with cardioinhibitory neurocardiogenic syncope, especially in young patients in order to avoid or prolong, as much as possible, the timing of definitive cardiac pacing. Certainly, making this procedure less extensive and limiting the ablation in the right atrium (avoiding the potential complications of a left atrial approach) and at level of anatomical regions of the most important ganglionated plexy, considered 'gateway' of the sino-atrial and atrio-ventricular node function (through the recognition of specific endocardial potentials), could be very advantageous in this clinical scenario. Finally, randomized, multicentre, clinical trials on a large population are needed to better understand which is the best ablation treatment (right-only or bi-atrial) and provide evidence for syncope guidelines.

Medetomidine/midazolam/fentanyl narcosis alters cardiac autonomic tone leading to conduction disorders and arrhythmias in mice

Arrhythmias are critical contributors to cardiovascular morbidity and mortality. Therapies are mainly symptomatic and often insufficient, emphasizing the need for basic research to unveil the mechanisms underlying arrhythmias and to enable better and ideally causal therapies. In translational approaches, mice are commonly used to study arrhythmia mechanisms in vivo. Experimental electrophysiology studies in mice are performed under anesthesia with medetomidine/midazolam/fentanyl (MMF) and isoflurane/fentanyl (IF) as commonly used regimens. Despite evidence of adverse effects of individual components on cardiac function, few data are available regarding the specific effects of these regimens on cardiac electrophysiology in mice. Here we present a study investigating the effects of MMF and IF narcosis on cardiac electrophysiology in vivo in C57BL/6N wild-type mice. Telemetry transmitters were implanted in a group of mice, which served as controls for baseline parameters without narcosis. In two other groups of mice, electrocardiogram and invasive electrophysiology studies were performed under narcosis (with either MMF or IF). Basic electrocardiogram parameters, heart rate variability parameters, sinus node and atrioventricular node function, and susceptibility to arrhythmias were assessed. Experimental data suggest a remarkable influence of MMF on cardiac electrophysiology compared with IF and awake animals. While IF only moderately reduced heart rate, MMF led to significant bradycardia, spontaneous arrhythmias, heart rate variability alterations as well as sinus and AV node dysfunction, and increased inducibility of ventricular arrhythmias. On the basis of these observed effects, we suggest avoiding MMF in mice, specifically when studying cardiac electrophysiology, but also whenever a regular heartbeat is required for reliable results, such as in heart failure or imaging research.

Tolerability and Safety of Lacosamide in Neonatal Population.

Lacosamide is a newer antiepileptic medication used in refractory neonatal seizures with limited safety and efficacy data. This case series spans 4 years and includes 38 neonates cared for in the neonatal, pediatric, and cardiovascular intensive care units, who received lacosamide for refractory seizures. Because lacosamide affects atrioventricular node function in adults, among other metrics, electrocardiogram (ECG) changes were monitored closely in these neonates. Within this cohort, 2 neonates were found to have atrial bigeminy on ECG and telemetry. Otherwise, lacosamide was generally well tolerated with sleepiness being the most common symptom noted. This case series reports data on the tolerability of lacosamide and emphasizes the importance of monitoring key cardiac intervals with ECG before and after the use of lacosamide in this population.

Overlapping and Distinct Features of Cardiac Pathology in Inherited Human and Murine Ether Lipid Deficiency.

Inherited deficiency in ether lipids, a subgroup of glycerophospholipids with unique biochemical and biophysical properties, evokes severe symptoms in humans resulting in a multi-organ syndrome. Mouse models with defects in ether lipid biosynthesis have widely been used to understand the pathophysiology of human disease and to study the roles of ether lipids in various cell types and tissues. However, little is known about the function of these lipids in cardiac tissue. Previous studies included case reports of cardiac defects in ether-lipid-deficient patients, but a systematic analysis of the impact of ether lipid deficiency on the mammalian heart is still missing. Here, we utilize a mouse model of complete ether lipid deficiency (Gnpat KO) to accomplish this task. Similar to a subgroup of human patients with rhizomelic chondrodysplasia punctata (RCDP), a fraction of Gnpat KO fetuses present with defects in ventricular septation, presumably evoked by a developmental delay. We did not detect any signs of cardiomyopathy but identified increased left ventricular end-systolic and end-diastolic pressure in middle-aged ether-lipid-deficient mice. By comprehensive electrocardiographic characterization, we consistently found reduced ventricular conduction velocity, as indicated by a prolonged QRS complex, as well as increased QRS and QT dispersion in the Gnpat KO group. Furthermore, a shift of the Wenckebach point to longer cycle lengths indicated depressed atrioventricular nodal function. To complement our findings in mice, we analyzed medical records and performed electrocardiography in ether-lipid-deficient human patients, which, in contrast to the murine phenotype, indicated a trend towards shortened QT intervals. Taken together, our findings demonstrate that the cardiac phenotype upon ether lipid deficiency is highly heterogeneous, and although the manifestations in the mouse model only partially match the abnormalities in human patients, the results add to our understanding of the physiological role of ether lipids and emphasize their importance for proper cardiac development and function.

An atrioventricular node model incorporating autonomic tone.

The response to atrial fibrillation (AF) treatment is differing widely among patients, and a better understanding of the factors that contribute to these differences is needed. One important factor may be differences in the autonomic nervous system (ANS) activity. The atrioventricular (AV) node plays an important role during AF in modulating heart rate. To study the effect of the ANS-induced activity on the AV nodal function in AF, mathematical modelling is a valuable tool. In this study, we present an extended AV node model that incorporates changes in autonomic tone. The extension was guided by a distribution-based sensitivity analysis and incorporates the ANS-induced changes in the refractoriness and conduction delay. Simulated RR series from the extended model driven by atrial impulse series obtained from clinical tilt test data were qualitatively evaluated against clinical RR series in terms of heart rate, RR series variability and RR series irregularity. The changes to the RR series characteristics during head-down tilt were replicated by a 10% decrease in conduction delay, while the changes during head-up tilt were replicated by a 5% decrease in the refractory period and a 10% decrease in the conduction delay. We demonstrate that the model extension is needed to replicate ANS-induced changes during tilt, indicating that the changes in RR series characteristics could not be explained by changes in atrial activity alone.

Incidence and recovery of post-surgical heart block in children following cardiac surgery.

A subset of patients who develop post-surgical heart block have recovery of atrioventricular node function. Factors predicting recovery are not understood. We investigated our centre's incidence of post-surgical heart block and examine factors associated with recovery of atrioventricular node function. We conducted a single-centre retrospective study of patients 0 - 21 years who underwent cardiac surgery between January 2010 and December 2019 and experienced post-operative heart block. Data including patient and clinical characteristics and operative variables were collected and analysed. Of 6333 surgical hospitalisations, 128 (2%) patients developed post-operative heart block. Of the 128 patients, 90 (70%) had return of atrioventricular node function, and 38 (30%) had pacemaker placement. Of the 38 patients who underwent pacemaker placement, 6 (15.8%) had recovery of atrioventricular node function noted on long-term follow-up. Median time from onset of heart block to late atrioventricular node recovery was 13 days (Interquartile range: 5 - 117). Patients with single-ventricle physiology (p = 0.04), greater weight (p = 0.03), and shorter cardiopulmonary bypass time (p = 0.015) were more likely to have recovery. The use of post-operative steroids was similar between all groups (p = 0.445). Infectious or wound complications were similar between pacemaker groups (p = 1). Two per cent of patients who underwent congenital cardiac surgery developed post-operative heart block, and 0.6% underwent pacemaker placement. Early recovery of atrioventricular node was associated with greater weight at the time of surgery, single-ventricle physiology, and shorter cardiopulmonary bypass time. Late recovery of atrioventricular node conduction following pacemaker placement occurred in 15.8% of patients.

Effect on sinus cycle length and atrioventricular node function after high-power short-duration versus conventional radiofrequency catheter ablation in paroxysmal atrial fibrillation

BackgroundThe efficacy and safety of high-power, short-duration (HPSD) radiofrequency catheter ablation for atrial fibrillation (AF) have been demonstrated in several studies. We aimed to evaluate and compare the effects of the conventional method and the HPSD method for AF ablation on the sinus and AV node function in patients with paroxysmal AF.MethodsThe medical records of patients with paroxysmal AF who underwent pulmonary vein isolation (PVI) were retrieved from a prospectively collected AF ablation registry at a large-sized tertiary center. The HPSD group (n = 41) was distinguished from the conventional ablation group (n = 198) in terms of the power (50 W vs. 20–40 W) and duration (6–10 s vs. 20–30 s) of radiofrequency energy delivery during PVI. Peri-procedural changes in cardiac autonomy were assessed in terms of the changes in sinus cycle length (SCL), block cycle length (BCL), and effective refractory period (ERP) of the atrioventricular node (AVN).ResultsThe SCL, BCL, and ERP of the AVN at baseline and post-ablation were not significantly different between the conventional ablation group and the HPSD group. Shortening of the SCL, BCL, and ERP of the AVN was observed immediately after AF ablation in both groups. One-year recurrence of AF/atrial flutter (35.1% vs. 20.3%; P = 0.011) and atrial flutter (13.8% vs. 4.7%; P = 0.015) were higher in the HPSD group than in the conventional ablation group.ConclusionBoth the HPSD and the conventional ablation method resulted in post-ablation vagal modification as evidenced by the shortening of SCL, BCL, and ERP of the AVN. One-year recurrence of atrial flutter and AF/atrial flutter was higher in patients who underwent the HPSD method.

PO-630-08 INFLUENCE OF TWO NARCOSIS REGIMENS ON CARDIAC ELECTROPHYSIOLOGY IN MICE

Mouse models are commonly used to study arrhythmia mechanisms in vivo. Different narcosis regimens have proven feasibility in rodents with medetomidine (0.5 mg/kg), midazolam (5 mg/kg) and fentanyl (0.005 mg/kg) (MMF) and isoflurane (1-3 %)/fentanyl (0.05 mg/kg) (IF) among the most commonly used regimens, but little data is available regarding their effects on cardiac electrophysiology. To investigate the effects of MMF and IF narcosis in C57BL/6 wildtype mice on cardiac electrophysiology in vivo. Telemetry transmitters were implanted in 4 C57/BL6 mice which served as controls for ECG analysis without narcosis. In 22 mice ECG and invasive electrophysiology studies were performed under narcosis (n=10 MMF, n=12 IF). We assessed ECG, heart rate variability (HRV), sinus node recovery time (SNRT), atrial, atrioventricular and ventricular refractory periods (AERP, AVERP and VERP), Wenckebach point, VA conduction and arrhythmia inducibility by burst stimulation. MMF causes significant bradycardia (452 bpm baseline vs. 271 bpm MMF, ****p < 0.0001), affects HRV indicated by increased pRR50 (1.6 % baseline vs. 67.4 % MMF, ****p < 0.0001), reduced LF/HF ratio (0.62 baseline vs. 0.16 MMF, *p = 0.019) and both increased SD1 (15 ms baseline vs. 94 ms MMF, ****p < 0.0001) and SD2 (19.6 ms baseline vs. 48.5 ms MMF *p =0.017), and prolongs QRS duration (8.1 ms baseline vs. 11.6 ms MMF, *p = 0.015) and QT interval (50 ms baseline vs. 68 ms MMF, ****p < 0.0001). MMF prolongs SNRT (at 120 ms basic cycle length 234 ms MMF vs. 145 ms IF, ***p < 0.001), antegrade (69 ms MMF vs. 56 ms IF, ****p < 0.0001), and retrograde conduction in the AV node (118 ms MMF vs. 89 ms IF, ***p < 0.001), AVERP (67 ms MMF vs. 50 ms IF, **p < 0.01) and ultimately leads to increased susceptibility for ventricular arrhythmias (1.3 % MMF vs. 0 % IF, **p < 0.01) compared to IF. Our results highlight a significant impact of MMF narcosis on cardiac electrophysiology in mice. While IF only moderately reduces heart rate, MMF leads to significant bradycardia, QRS/QT prolongation and HRV alterations as well as impaired sinus node and AV node function, ultimately resulting in an increased inducibility of ventricular arrhythmias. Based on these effects we suggest using IF narcosis to study cardiac electrophysiology in mice.

Electrocardiographic characteristics of trained and untrained standardbred racehorses.

BackgroundLong‐term exercise induces cardiac remodeling that potentially influences the electrical properties of the heart.Hypothesis/objectivesWe assessed whether training alters cardiac conduction in Standardbred racehorses.AnimalsTwo hundred one trained and 52 untrained Standardbred horses.MethodsCross‐sectional study. Resting ECG recordings were analyzed to assess heart rate (HR) along with standard ECG parameters and for identification of atrial and ventricular arrhythmias. An electrophysiological study was performed in 13 horses assessing the effect of training on sinoatrial (SA) and atrioventricular (AV) nodal function by sinus node recovery time (SNRT) and His signal recordings. Age and sex adjustments were implemented in multiple and logistic regression models for comparison.ResultsResting HR in beats per minute (bpm) was lower in trained vs untrained horses (mean, 30.8 ± 2.6 bpm vs 32.9 ± 4.2 bpm; P = .001). Trained horses more often displayed second‐degree atrioventricular block (2AVB; odds ratio, 2.59; P = .04). No difference in SNRT was found between groups (n = 13). Mean P‐A, A‐H, and H‐V intervals were 71 ± 20, 209 ± 41, and 134 ± 41 ms, respectively (n = 7). We did not detect a training effect on AV‐nodal conduction intervals. His signals were present in 1 horse during 2AVB with varying H‐V interval preceding a blocked beat.Conclusions and Clinical ImportanceWe identified decreased HR and increased frequency of 2AVB in trained horses. In 5 of 7 horses, His signal recordings had variable H‐V intervals within each individual horse, providing novel insight into AV conduction in horses.

Early Versus Delayed Pacemaker for Heart Block After Valve Surgery: A Cost-Effectiveness Analysis

BackgroundA significant percentage of patients who acutely develop high-grade atrioventricular block after valve surgery will ultimately recover, yet the ability to predict recovery is limited. The purpose of this analysis was to evaluate the cost-effectiveness of two different management strategies for the timing of permanent pacemaker implantation for new heart block after valve surgery. MethodsA cost-effectiveness model was developed using costs and probabilities of short- and long-term complications of pacemaker placement, short-term atrioventricular node recovery, intensive care unit stays, and long-term follow-up. We aggregated the total expected cost and utility of each option over a 20-y period. Quality-adjusted survival with a pacemaker was estimated from the literature and institutional patient-reported outcomes. Primary decision analysis was based on an expected recovery rate of 36.7% at 12 d with timing of pacemaker implantation: early placement (5 d) versus watchful waiting for 12 d. ResultsA strategy of watchful waiting was more costly ($171,798 ± $45,695 versus $165,436 ± $52,923; P < 0.0001) but had a higher utility (9.05 ± 1.36 versus 8.55 ± 1.33 quality-adjusted life years; P < 0.0001) than an early pacemaker implantation strategy. The incremental cost-effectiveness ratio of watchful waiting was $12,724 per quality-adjusted life year. The results are sensitive to differences in quality-adjusted survival and rates of recovery of atrioventricular node function. ConclusionsWatchful waiting for pacemaker insertion is a cost-effective management strategy compared with early placement for acute atrioventricular block after valve surgery. Although this is cost-effective from a population perspective, clinical risk scores predicting recovery will aid in personalized decision-making.

Sodium-Calcium Exchanger (NCX1) is Essential for Atrioventricular Node Automaticity and Conduction, as Revealed through Atrial-Specific Knockout of NCX1

The atrioventricular node (AVN), unlike the sinoatrial node (SAN), can act as an oscillator and conductor of the proximal cardiac conduction system. Using a sarcolipin cre-induced atrial-specific sodium-calcium exchanger 1 (NCX1) KO mouse, we previously demonstrated that NCX1 (and the calcium clock) is an essential component of SAN automaticity (Groenke et al., 2013; Torrente et al., 2015). Here, we used the same mouse to test the hypothesis that NCX1 and the calcium clock are necessary components of AVN automaticity and conduction. qPCR analysis confirmed a 79% reduction of NCX mRNA in AVN tissue, and ECGs demonstrated a slow junctional escape rhythm driving the heart rate. Voltage mapping and confocal imaging of isolated NCX1 KO AVN tissue showed slowed or absent AVN automaticity compared to WT, as action potential and calcium transient rates decreased by 94% (p <0.05) and 78% (p <0.01), respectively. To characterize the conduction properties of the AVN in NCX1 KO mice, we used in vivo catheter pacing of the atrium and simultaneous recording of surface ECG. Resting heart rates in control mice were 542 +/- 16.65 BPM (cycle length of 111 +/- 3.32 ms) and could be paced up to 954 +/- 18.86 BPM (63 +/- 1.23 ms) before developing atrioventricular block (43% increase). In line with their slow junctional rhythm at rest, NCX KO mice had a reduced resting heart rate of 356.8 +/- 12.24 BPM (169 +/- 5.83 ms) and could only tolerate a 17% increase in pacing rate (436 +/-27.48 BPM or 140 +/- 10.44 ms) before exhibiting AV Block. Thus, lack of NCX1 in atrial tissue results in abnormal AVN automaticity and conduction. These data indicate an essential role for NCX1 in AVN function.

Initial experience with ablation of the innervation surrounding sinus and atrioventricular nodes to treat paroxysmal bradyarrhythmia.

BackgroundThe symptomatic bradyarrhythmia is Class I indication for pacing therapy which is not a radical cure. The present study aimed to assess the feasibility and to present the initial results of the restricted ablation of the parasympathetic innervation surrounding sinus and atrioventricular (AV) nodes for treating patients with bradyarrhythmia.MethodsA total of 13 patients with cardiogenic syncope were included from May 2008 to June 2015. Under the guidance of fluoroscopy and /or three-dimensional geometry by 64-slice spiral computed tomography, atrial activation sequence in sinus rhythm was mapped. Chamber geometry was reconstructed manually or automatically using the Niobe II magnetic navigation system integrated with the CARTO-remote magnetic technology (RMT) system. Cardioneuroablation was targeted at the high-amplitude fractionated electrograms surrounding the regions of His bundle and the site with the earliest activation in sinus rhythm. Areas surrounding the sinus node, AV node, and the phrenic nerve were avoided.ResultsThirteen patients completed the studies. Ablation was successfully performed in 12 patients and failed in one. The high-frequency potential was recorded in atrial electrograms surrounding the sinus or AV nodes in all the patients and disappeared in 15 s after radiofrequency applications. The vagal reaction was observed before the improvement of the sinus and AV node function. No complications occurred during the procedures. Patients were followed up for a mean of 13.0 ± 5.9 months. During the follow up ten patients remained free of symptoms, and two patients had a permanent cardiac pacemaker implanted due to spontaneous recurrence of syncope. The heart rate of post-ablation was higher than pre-ablation (69.0 ± 11.0 vs. 49.0 ± 10.0 beats/min, t = 4.56, P = 0.008). The sinus node recovery time, Wenckebach block point, and atrium-His bundle interval were significantly shorter after ablation (1386.0 ± 165.0 vs. 921.0 ± 64.0 ms, t = 7.45, P = 0.002; 590.0 ± 96.0 vs. 464.0 ± 39.0 ms, t = 2.38, P = 0.023; 106.0 ± 5.0 vs. 90.0 ± 12.0 ms, t = 9.80, P = 0.013 before and after ablation procedure, respectively).ConclusionsAblation of sinoatrial and AV nodal peripheral fibrillar myocardium electrical activity might provide a new treatment to ameliorate paroxysmal sinus node dysfunction, high degree AV block, and vagal-mediated syncope.

Differential effects of sevoflurane and propofol on swine cardiac conduction system

ObjectiveTo compare the effects of sevoflurane and propofol on the porcine cardiac conduction system. Study designA prospective, comparative study of electrophysiological properties of anaesthetics agents in an experimental porcine model. AnimalsA total of 36 hybrid Landrace-Large White pigs. MethodsAfter premedication with 20 mg kg−1 of intramuscular ketamine, anaesthesia was induced with 4.5 mg kg−1propofol intravenously. In 18 consecutive animals, anaesthesia was maintained with propofol (13 mg kg−1 hour−1) and in the remaining 18 animals with 2.66% sevoflurane. The femoral artery and vein were canalized for invasive monitoring, analytical blood gas sampling and intracardiac catheter insertion. Following instrumentation and after a period of stabilization, a customary electrophysiological evaluation was performed. We compared the electrophysiology of the sinus and atrioventricular node (AV) node under sevoflurane or propofol anaesthesia, and the effects of both anaesthetics on atrial and ventricular refractoriness. ResultsThere was a significant difference in sinus node recovery time between sevoflurane and propofol (907 ± 231 versus 753 ± 146 ms, p = 0.02). Sevoflurane in comparison with propofol significantly prolonged specialized AV conduction times, represented by an increased Wenckebach cycle length (272 ± 54 versus 235 ± 40 ms, p = 0.03) and AV nodal refractoriness (327 ± 34 versus 287 ± 30 ms, p = 0.002). In addition, sevoflurane prolonged ventricular refractoriness (298 ± 27 versus 255 ± 38 ms, p = 0.007) and the QT corrected interval (0.50 ± 0.05 versus 0.46 ± 0.09 ms, p = 0.005). Conclusions and clinical relevanceSevoflurane in comparison with propofol, depresses several parameters of sinus and AV nodal function and prolongs the ventricular refractoriness of the porcine cardiac conduction system. These findings should be taken into consideration for the choice of anaesthetic agents in clinical and experimental settings.

Electrophysiological properties of the South Asian heart

ObjectiveThe South Asian population has a lower burden of arrhythmia compared with Caucasians despite a higher prevalence of traditional cardiovascular risk factors. We aimed to determine whether this was due...

Temporary Pacemakers - Step by Step

Symptomatic bradycardia is usually caused by abnormalities of atrioventricular conduction or sinus node dysfunction. Reversible and irreversible causes must be considered.Temporary pacemakers are used in the emergency treatment in case of severe bradyarrhythmia.They help to bridge the acute phase until spontaneous restoration of atrioventricular or sinus node function or -if spontaneous restoration fails- until a permanent pacemaker system was implanted.In the following article we discuss the commonly used temporary pacemaker systems. We demonstrate their use and correct programming by an illustrated step by step explanation. For troubleshooting a flow chart was added.

Increased sodium/calcium exchanger activity enhances beta-adrenergic–mediated increase in heart rate: Whole-heart study in a homozygous sodium/calcium exchanger overexpressor mouse model

The cardiac sodium/calcium (Na+/Ca2+) exchanger (NCX) contributes to diastolic depolarization in cardiac pacemaker cells. Increased NCX activity has been found in heart failure and atrial fibrillation. The influence of increased NCX activity on resting heart rate, beta-adrenergic-mediated increase in heart rate, and cardiac conduction properties is unknown. The purpose of this study was to investigate the influence of NCX overexpression in a homozygous transgenic whole-heart mouse model (NCX-OE) on sinus and AV nodal function. Langendorff-perfused, beating whole hearts of NCX-OE and the corresponding wild-type (WT) were studied ± isoproterenol (ISO; 0.2 μM). Epicardial ECG, AV nodal Wenckebach cycle length (AVN-WCL), and retrograde AVN-WCL were obtained. At baseline, basal heart rate was unaltered between NCX-OE and WT (WT: cycle length [CL] 177.6 ± 40.0 ms, no. of hearts [n] = 20; NCX-OE: CL 185.9 ± 30.5 ms, n = 18; P = .21). In the presence of ISO, NCX-OE exhibited a significantly higher heart rate compared to WT (WT: CL 133.4 ± 13.4 ms, n = 20; NCX-OE: CL 117.7 ± 14.2 ms, n = 18; P <.001). ISO led to a significant shortening of the anterograde and retrograde AVN-WCL without differences between NCX-OE and WT. This study is the first to demonstrate that increased NCX activity enhances beta-adrenergic increase of heart rate. Mechanistically, increased NCX inward mode activity may promote acceleration of diastolic depolarization in sinus nodal pacemaker cells, thus enhancing chronotropy in NCX-OE. These findings suggest a novel potential therapeutic target for heart rate control in the presence of increased NCX activity, such as heart failure.

Adrenomedullin Stimulates Porcine Sinus Node Automaticity

Adrenomedullin (AM) is a vasodilatory and chronotropic peptide that has cardioprotective properties in settings of ischemia-reperfusion. Specifically, the 52-amino acid peptide hormone has been shown to reduce infarct size and potentially be protective against malignant arrhythmias. AM reduces L-type calcium currents in rabbit ventricular myocytes, and can possibly be utilized as an antiarrhythmic drug. However, at present it is unclear whether AM has cardiac electrophysiological effects in vivo. In the present study, we investigated whether AM affects sinus and atrioventricular nodal functions, cardiac pacing thresholds, refractory properties and intracardiac conduction intervals in an intact porcine model (Norwegian landrace and Yorkshire hybrids; n=12). Hemodynamic and electrophysiological parameters were recorded at baseline and following 60 min of AM-infusion (100 ng/kg/min). The hemodynamic effects of AM were characterized by a reduced mean arterial pressure (76 ± 9 vs. 57 ± 6; p<0.05; mmHg), tachycardia (91 ± 13 vs. 112 ± 15; p<0.05; beats/min) and an augmented cardiac index (131 ± 20 vs. 176 ± 28; p<0.05; ml/min/kg). The sinus cycle length was reduced (674 ± 89 vs. 546 ± 73; p<0.05; ms), sinoatrial conduction time was unaltered (79 ± 24 vs. 72 ± 19; ns; ms), and the sinus node recovery time (SNRT) was reduced at paced cycle lengths of 425 ms, 375 ms and 325 ms (average SNRT 1034 ± 449 vs.704 ± 141; p<0.05; ms). Diastolic pacing thresholds, effective refractory periods, Wenckebach cycle length and intracardiac conduction intervals were unaffected by AM. In conclusion, AM stimulates sinus node function with a reduced sinus cycle length and increased automaticity but has no further detectable intracardiac electrophysiological effects. Whether the increased automaticity is a direct effect on the sinus node or an indirect effect mediated through the autonomic nervous system remains to be determined.