Atrioventricular Nodal Conduction Research Articles

ECG-based estimation of respiration-induced autonomic modulation of AV nodal conduction during atrial fibrillation

Introduction: Information about autonomic nervous system (ANS) activity may offer insights about atrial fibrillation (AF) progression and support personalized AF treatment but is not easily accessible from the ECG. In this study, we propose a new approach for ECG-based assessment of respiratory modulation in atrioventricular (AV) nodal refractory period and conduction delay.Methods: A 1-dimensional convolutional neural network (1D-CNN) was trained to estimate respiratory modulation of AV nodal conduction properties from 1-minute segments of RR series, respiration signals, and atrial fibrillatory rates (AFR) using synthetic data that replicates clinical ECG-derived data. The synthetic data were generated using a network model of the AV node and 4 million unique model parameter sets. The 1D-CNN was then used to analyze respiratory modulation in clinical deep breathing test data of 28 patients in AF, where an ECG-derived respiration signal was extracted using a novel approach based on periodic component analysis.Results: We demonstrated using synthetic data that the 1D-CNN can estimate the respiratory modulation from RR series alone with a Pearson sample correlation of r = 0.805 and that the addition of either respiration signal (r = 0.830), AFR (r = 0.837), or both (r = 0.855) improves the estimation.Discussion: Initial results from analysis of ECG data suggest that our proposed estimate of respiration-induced autonomic modulation, aresp, is reproducible and sufficiently sensitive to monitor changes and detect individual differences. However, further studies are needed to verify the reproducibility, sensitivity, and clinical significance of aresp.

HE EFFECT OF PROBENECID ON α-1-ADRENOCEPTOR STIMULATION INDUCED PROARRHYTHMIC CONDUCTION IN THE ATRIOVENTRICULAR NODE OF RAT HEART

Cardiac tissue contains adrenergic receptors (AR) not only of the beta type, but also of the alpha type (α-AR). Both types of ARs play signifi cant role in regulation of cardiomyocytes electrophysiology in diff erent parts of the heart, including the atrioventricular node (AVN). An augmentation of α1-AR mediated component of adrenergic signaling results in impaired conduction of excitation in the heart and onset of various rhythm disturbances including AVNassociated arrhythmias. The activation of α1-AR facilitates anionic transmembrane transport causing electrophysiological changes in myocytes. Current study is aimed to the investigation of the eff ects of anion/chloride blockade on α1-AR-mediated proarrhythmic alteration of AVN functioning. Functional characteristics of AVN including AVN conduction time, AVN refractoriness and the AVN conduction alterations were examined via recording of surface electrograms in Langendorff -perfused isolated rat heart (Wistar, 250 ± 30 g). Phenylephrine was used as α1-AR agonist. Probenecid demonstrating anion/chloride transmembrane conductance blocking activity was used to modify Phe-induced α1-AR-mediated eff ects in AVN. The activation of α1-AR by Phe results in a signifi cant increase in the duration of AV intervals (N = 10, p < 0.001) and eff ective refractory period (ERP) in the AVN (by 9.8% ± 1.2%, n = 10, p < 0.001). Also, Phe induces AV-blocks of conduction and oscillations in atrioventricular delay (N = 10) at the stimulation rates close to ERP. Probenecid signifi cantly reduces the magnitude of AVD oscillations during non-stationary conduction in the AV node. In addition, probenecid attenuates ERP prolongation caused by Phe (107 ± 4 ms, N = 6) and 114.2 ± 5.35 ms (N = 10) in presence of only Phe and Phe with probenecid, respectively, returning its values toward typical for normal conditions. In conclusion, probenecid maintains physiological mode of AVN conduction when α1-AR are stimulated. This also suggests that chloride ion channels and anion carriers may contribute to the α1-AR-mediated AVN arrhythmias.

Pharmacokinetics and Pharmacodynamics of Etripamil, an Intranasally Administered, Fast-Acting, Nondihydropyridine Calcium Channel Blocker.

Etripamil, a fast-acting nondihydropyridine L-type calcium channel blocker, is under investigation for potential self-administration for the acute treatment of supraventricular tachyarrhythmias in a medically unsupervised setting. We report detailed pharmacokinetics and pharmacodynamics of intranasally administered etripamil in healthy adults from 2 Phase 1, randomized, double-blind studies: Study MSP-2017-1096 (sequential dose-escalation, crossover study design, n = 64) and NODE-102 (single dose, 4-way crossover study, n = 24). Validated bioanalytical assays determined plasma concentrations of etripamil and its inactive metabolite. Noncompartmental pharmacokinetic parameters were calculated. Pharmacodynamic parameters were determined for PR interval, blood pressure, and heart rate. Etripamil was rapidly absorbed intranasally, with time to maximal plasma concentration of 5-8.5 minutes, corresponding to a rapid greater than 10% increase in mean maximum PR interval from baseline within 4-7 minutes of doses of 60mg or greater. Following peak plasma concentrations, systemic etripamil levels declined rapidly within the first 15 minutes following dosing and decreased more gradually thereafter. PR interval prolongation greater than 10% from baseline was generally sustained for about 45 minutes at doses of 60mg or greater. The mean terminal half-life ranged from about 1.5 hours with 60mg to about 2.5-3 hours for the 70- and 105-mg doses. Etripamil was generally well tolerated without symptomatic hypotension. Adverse events were primarily mild to moderate and related to the administration site; no serious adverse events or episodes of atrioventricular block occurred. Intranasal etripamil administration, at doses of 60mg or greater, produced rapidly occurring slowing of atrioventricular nodal conduction with a limited duration of effect without hemodynamic or electrocardiographic safety signals in healthy volunteers.

An Overview Of The Level Of Occupational Stress Of Anesthesiologists In The Surgical Room Of The Hospital In The Banyumas District Area

Exercise can indeed improve the quality of health if it is done in accordance with the rules or program. However, excessive exercise without considering the capacity of the organs, especially the heart, can result in disease, one of which is heart disease, namely heart rhythm disturbances. The death rate for athletes in 2022 will still be at 29% during competition. In this case, it proves that Holter monitoring (ambulatory ECG monitoring) is better in assessing heart rhythm in athletes. Arrhythmias in athletes are caused by inadequate cardiac remodeling, causing ion channels in the atrioventricular node to undergo immunohistochemical labeling, where L-type calcium (Ca2+) channels that carry inward current are known to play a major role in the diastolic depolarization of the atrioventricular node, and regulate the excitability and increase in axis potentiation. . In the important Ca2+ channels in the heart, a slowing process occurs which results in a barrier to atrioventricular node conduction. A decrease in the axis action potential phase process where calcium cannot replace potassium in cells results in electrical impulse disturbances.

Atypical Wenckebach without grouped beating due to dual AV nodal conduction

A 31-year-old woman reported dizziness in the early postpartum period after receiving dexmedetomidine. The ECG was misinterpreted as complete heart block; however, more careful analysis revealed an atypical Wenckebach pattern with dual AV nodal conduction and termination of nonconducted P waves with junctional escape beats. The patient's rhythm returned to sinus after stopping dexmedetomidine.Atypical Wenckebach patterns account for greater than 50% of patients with Mobitz Type I AV block and can be misinterpreted as high-grade AV block. This case highlights the causes of atypical Wenckebach patterns and how careful analysis of intervals can help clinicians avoid misdiagnosis.

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.

Abstract 18348: Causes and Predictors of 30-Day Readmissions Following Permanent Pacemaker Implantation in Patients With Cardiac Amyloidosis: From National Readmission Database (2016-2020)

Introduction: Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy where local deposition of amyloid fibrils causes heart failure, arrhythmias, and conduction system abnormalities. Involvement of the AV nodal and infra-hisian conduction system increases the need for a permanent pacemaker (PPM). Studies have noted worse outcomes in patients with implantable-cardioverter defibrillator placement in amyloidosis, but a comparison with PPM is lacking. We sought to analyze readmissions in CA patients following PPM placement utilizing National Readmission Database (NRD). Methods: NRD (2016 to 2020) was queried to identify adults with a diagnosis of CA who underwent PPM implantation using ICD-10 CM and PCS codes. The primary outcome was a 30-day readmission rate. Secondary outcomes were in-hospital mortality, length of stay (LOS), total hospital charge (THC), and predictors of readmission. Multivariate/univariate logistic and linear regression analyses were used to analyze the outcomes and adjust for possible confounders. Results: A total of 1,027 encounters of CA who underwent PPM were identified, of which 975 were discharged alive. Within 30 days from discharge, 141 (14.5%) were readmitted. Those readmitted had a longer LOS and higher burden of comorbidities while were similar in age, sex, hospital characteristics, and household income status. Readmissions lead to an additional mean THC of $55,079 and a mean LOS of 6.3 days. The top five causes of readmissions were heart failure (23%), sepsis (6.6%), hypertensive heart disease (4%), bradycardia (3.5%), and acute kidney injury (3.2%). Figure-1 shows the forest plot of a multivariate analysis of independent factors associated with readmissions. Conclusions: Our findings show that up to 15% of patients with CA who undergo PPM implantation get readmitted with heart failure being the most common etiology. Optimizing comorbidities with PPM implantation in CA may provide better outcomes and reduce admissions.

Novel method to avoid serious injurious effects on the atrioventricular nodal (AVN) conduction during catheter ablation of the AVN slow pathway utilizing cryofreezing energy

BackgroundSlow pathway elimination of the atrioventricular node (AVN) is essential to treat AVN reentrant tachycardia (AVNRT). However, injury to the AVN conduction (IAVN) is one of the serious complications. Cryofreezing energy is expected to reduce the incidence of IAVN. This study aimed to investigate the usefulness of a novel method to avoid IAVN during cryoablation of AVNRT. MethodsA total of 157 patients (average age, 65.8 years; male, 71) suffering from AVNRT were included. Once the AVNRT terminated during cryo-ablation, then rapid atrial constant pacing (RACP) was performed during freezing at a rate lower 10 bpm than that inducing Wenchebach AV block in 74 (47.1 %) patients (Group A). The RACP rate was decreasingly reduced by 10 bpm in case of the occurrence of IAVN. When the RACP reached 100 bpm, the cryoablation was prematurely terminated. Group B patients (83 = 52.9 %) underwent cryoablation during sinus rhythm. All patients were allocated in a randomized fashion. We compared the severity of the IAVN between Groups A and B. ResultsThere were no significant differences at 12 months regarding the freedom from the AVNRT between Groups A and B. However, the duration of the IAVN was significantly longer in Group B than A (p = 0.02). There were no significant differences regarding the distance between the His recording sites and successful ablation sites between Groups A and B. No permanent IAVN requiring pacemaker implantation was provoked in either group. ConclusionRACP was useful to avoid sustained and serious IAVN during cryoablation of AVNRT.

Atrioventricular Conduction: Physiology and Autonomic Influences.

Atrioventricular (AV) nodal conduction is decremental and very prone to alterations in autonomic tone. Conduction through the His-Purkinje system (HPS) is via fast channel tissue and typically not that dependent on autonomic perturbations. Applying these principles, when the sinus rate is stable and then heart block suddenly occurs preceded by even a subtle slowing of heart rate, it typically is caused by increased vagal tone, and block occurs in the AV node. Heart block with activity strongly suggests block in the HPS. Enhanced sympathetic tone and reduced vagal tone can facilitate induction of both AV and atrioventricular node reentry.

The Case Files

The Case Files

Incidence and outcome of arrhythmias and electrical disease in patients with Trisomy 18.

Patients with Trisomy 18 have a high incidence of cardiac anomalies and are associated with early death. Because of early mortality, electrical system disease and arrhythmia has been difficult to delineate and the incidence remain unknown. We sought to describe the association and clinical outcomes of electrical system disease and cardiac tachy-arrhythmias in patients with Trisomy 18. This was a retrospective, single institutional study. All patients with Trisomy 18 were included in the study. Patient characteristics, congenital heart disease (CHD), conduction system and clinical tachy-arrhythmia data were collected on all patients. Outcomes including cardiac surgical interventions, electrical system interventions and death were collected until the time of study. Patients with tachy-arrhythmias/electrical system involvement were compared to those without to identify potential associated variables. A total of 54 patients with Trisomy 18 were included in analysis. The majority of patients was female and had associated CHD. AV nodal conduction system abnormalities with either first or second degree AV block were common (15%) as was QTc prolongation (37%). Tachy-arrhythmias were common with 22% of patients having at least one form of tachy-arrhythmia and associated with concomitant conduction system disease (p = 0.002). Tachy-arrhythmias were typically treatable with monitoring or medication with eventual resolution without need for procedural intervention. Although early death was common, there were no causes of death associated with tachy-arrhythmia or conduction system disease. In conclusion, patients with Trisomy 18 have a high incidence of conduction system abnormalities and burden of clinical tachy-arrhythmias. Although frequent, electrical system disease did not affect patient outcome or difficultly of care delivery.

FDG-PET/CT and rest myocardial perfusion imaging to predict high-degree atrioventricular block recovery in cardiac sarcoidosis.

High-degree atrioventricular block (AVB) recovery in CS has been shown to be highly variable despite immunosuppressive treatment, with no reliable tool available to predict odds of reversibility. This study sought to evaluate the potential of combined fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and resting myocardial perfusion imaging (rMPI) to predict reversibility of newly diagnosed high-grade AVB in cardiac sarcoidosis (CS). We performed a single-center, retrospective analysis of patients with CS presenting with high-grade AVB who underwent combined FDG-PET/CT and rMPI. The 2016 JCS and the 2014 HRS diagnostic criteria were used for the diagnosis of CS. Patients with a history of coronary artery disease or prior immunosuppressive treatment were excluded. Patients were divided into AVB recovery and non-recovery subgroups. CS disease staging was based on FDG-PET and rMPI findings: (Stage 0) normal FDG-PET and rMPI (Stage 1) positive FDG-PET and normal rMPI (Stage 2) positive FDG-PET with perfusion deficits on rMPI (Stage 3) normal FDG-PET with perfusion deficits on rMPI. Twenty-seven patients, including 13 demonstrating AVB recovery, were identified. Eleven out of fourteen (78.6%) patients presenting with stage 1 CS demonstrated AVB recovery. Stage 1 CS was significantly more present in the recovery group compared to the non-recovery group (84.6% vs 21.4%, P = .002). Eleven presented with stage 2 CS, with only 2 (18.2%) recovering AV nodal conduction. Stage 2 CS presented more frequently in the non-recovery group (64.3% vs 15.4%, P = .020). Combined FDG-PET and rMPI employed to stage CS disease presenting with high-degree AVB appears to have good performance for predicting likelihood of recovery.

Mid-term follow-up of atrioventricular node ablation and conduction system pacing without a ventricular backup lead in atrial fibrillation-induced tachycardiomyopathy - a single-center experience

Abstract Funding Acknowledgements Type of funding sources: None. In the permanent form of atrial fibrillation (AF), ablation is not recommended or has failed and the only option is rate control. The most effective rate control strategy is atrioventricular node (AVN) ablation, but this renders the patient pacing-dependent. Several observational studies have shown that both His bundle pacing (HBP) and left bundle branch area pacing (LBBAP), provide a narrower QRS complex and a more synchronous ventricular activation compared to right ventricular pacing. Current guidelines recommend placing a ventricular backup lead as a safety measure. We present our mid-term follow-up data on the feasibility of AVN ablation and physiological pacing without a ventricular backup lead in patients with tachycardiomyopathy due to rapidly conducted permanent AF. MATERIAL AND METHODS A total of 25 patients with permanent AF and HF and rate control failure with AVN-blocking drugs, that underwent physiological pacing and AVN ablation at our institution, were included in this retrospective review. During the procedure, HBP was the first option, followed by LBBAP if the His bundle was not captured at a threshold below 2.5V at 1 ms. The lead was connected to a single chamber pacemaker, without a backup pacing lead. In the same setting, using a femoral vein approach, a 4-mm tip ablation catheter was used to perform AVN ablation. Patient and procedural characteristics were recorded as well as the electrical parameters and complications at the follow-up visits. Results The mean age of the patients was 69 ± 12.4 years and 64% were males. The heart rate was 133±20.43 bpm and the ejection fraction was 28.84±9.02 %. 17 patients had normal QRS complex, 3 had right bundle branch block and 5 had left bundle branch block patterns. HBP was successful in 9 patients (36%) and LBBAP in 16 patients (64%). In patients with a baseline-wide QRS, physiological pacing significantly reduced the QRS duration (135.25±17.58 vs. 159±32.38 ms, p=0.04). The paced QRS complex was significantly narrower in HBP than LBBAP (95.67±14.37 vs. 129.88±17.46 ms, p<0.001). There was a significantly lower pacing threshold for LBBAP (0.77±0.3 V at 1 ms vs. 0.87±0.72 V at 0.4 ms, p<0.05) and better sensitivity for LBBAP (6.23±4.56 mV vs. 10.2±5.19 mV, p=0.66). The fluoroscopy time was non-statistically different between HBP and LBBAP (13.21±15.47 min vs. 18.72±12.95 min, p=0.35). AV node ablation was successful in all patients. The mean follow-up period was 524±110.2 days. 11 patients became pacemaker-dependent. There was no significant difference in pacing thresholds for both LBBAP (0.67±0.27 V at 0.4 ms, p=0.24) and HBP (0.87±0.56 V at 1 ms, p=0.485) patients and there was no recurrence in AV node conduction. No lead dislodgements were recorded. Conclusions AVN ablation and physiological pacing is feasible and safe without the need for a backup ventricular pacing lead, thus minimizing the risks and costs associated with a higher lead burden.

Prediction of ablation success of idiopathic premature ventricular contractions with an inferior axis using the twelve-lead electrocardiogram

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Catheter ablation is the first line treatment for idiopathic premature ventricular contractions (PVCs) from the right ventricular outflow tract (RVOT) but not left ventricular outflow tract (LVOT). However, differentiating the two using the twelve-lead electrocardiogram (ECG) is challenging. As an alternative strategy to guide clinical decision-making, we sought to find ECG criteria that predict outcome of catheter ablation directly rather than focus only. Methods This observational single center study included patients undergoing an ablation procedure for idiopathic PVCs with an inferior axis (positive QRS in leads II, III and aVF) at Hannover Heart Rhythm Center between 2012 and 2020. Patients were excluded if no activation mapping was performed because of low PVC activity. A complete suppression of the index PVC at the end of the ablation procedure was considered as ablation success. PVC axis was estimated with the help of the hexaxial reference system, and as an objective control was also calculated measuring QRS voltages and using three formulas: Arctan (aVF/I), Arctan ((2*II-I)/(Sqr(3)*I)) and +/-Arctan ((2*aVF)/(Sqr(3)*I)). Results The analysis included 108 patients (53% male, age 53 ± 17 years) with a PVC count of 22063 ± 14426 /24h. The dominant PVC had Left Bundle Branch Block (LBBB) like morphology in 80%, a mean transition (TZ)-score of 2.3 ± 1.2 and a mean axis of 87 ± 15°, estimated with the help of the hexaxial system. There was no significant difference between axis as estimated with the help of the hexaxial system compared to calculation via any of the formulas (87 ± 14, 87 ± 12 and 86 ± 16°, respectively). Overall ablation success was 82%. Considering ablation outcome according to the identified PVC localization, 46 of 47 cases (97.9%) of RVOT focus and 38 of 39 cases (97.4%) of LVOT focus were successful. On the other hand, all 8 cases with a parahisian focus were not successful and only 4 of 14 cases (28.6%) with a CS/LV summit focus were successful. Two ECG criteria were found to predict ablation failure: a more leftward PVC axis (p=0.015), which was associated with a parahisian focus (p<0.001), and an early precordial transition compared to the QRS complex during AV-nodal conduction (p=0.016), which was associated with a CS/LV summit focus (p<0.001). Using ROC statistics, a cutoff value of 75° for PVC axis and of 2.75 for TZ-Score index predicted ablation success with a positive predictive value of 93% if neither parameter applied (prediction of ablation failure, if either applied, 53 %). Conclusion Two ECG criteria – a more leftward PVC axis and an early precordial transition compared to sinus rhythm – predicted ablation failure and a parahisian or CS/LV summit focus. These parameters should be considered when evaluating a patient for catheter ablation of PVCs with an inferior axis.

His bundle pacing and AV nodal ablation for non-controlled atrial arrhythmia: a technical challenge with major clinical benefits

Abstract Funding Acknowledgements Type of funding sources: None. Background His bundle pacing (HBP) is an appealing alternative to right ventricular pacing in patients referred for permanent ventricular pacing and AV nodal ablation (AVNA) as it preserves physiological ventricular activation. Only limited amount of data is available in the literature regarding HBP combined with AVNA. Purpose To provide further evidence on the feasibility and efficacy of this therapeutic approach in patients with uncontrolled atrial arrhythmia. Methods We prospectively included all patients who underwent AVNA after HBP in three different hospitals between 2017 and 2022. Results AVNA following HBP lead implantation was performed in 75 patients. A complete AV block was obtained in 58 patients (77%) whereas significant modulation of the AV node conduction (heart rate < 60bpm) was obtained in 12 (16%). AVNA failure was observed in 5 (7%). The recording of an atrial signal by the HBP lead was more frequently observed in patients with AVNA modulation/failure compared to patients with complete AV block (11/17 vs 5/58; p < 0.001). There was no lead dislodgment during the AVNA procedures. Acute HB capture threshold increase > 1V occurred in 11 patients (15%) with return to baseline value at day one in 9. NYHA class and LVEF significantly improved from baseline to last follow-up (3.0 ± 0.7 vs 1.6 ± 0.5, p < 0.001; 47 ± 14% vs 60 ± 9%; p < 0.0001, respectively), Conclusion AVNA combined with HBP for non-controlled atrial arrhythmia was feasible and clinically efficient. Implanting the HB lead on the ventricular aspect of the tricuspid annulus avoiding atrial signal recording can facilitate AVNA.

PO-01-067 ATRIO-VENTRICULAR DELAY AFTER DELIVERY OF PULSED FIELD ABLATION OF THE PULMONARY VEINS

Pulsed field ablation (PFA) has been introduced as a new ablation modality for PV isolation. While PFA appears to have increased safety through a lack of thermal injury leading to lower risks of collateral damage to bystander anatomical structures, PFA is known to cause sinus bradycardia, hypotension, and atrial fibrillation, probably mediated by high electrical field induced autonomic stimulation. However, the effect on atrioventricular (AV) nodal conduction is unknown. To measure AV delay immediately after PFA. 412 PFA deliveries recorded in 12 patients were analyzed using a novel electrophysiology recording system (ECGenius System, CathVison, Denmark). Each pulmonary vein was treated with a minimum of eight pulses of energy with a 20 electrodes pentaspline catheter. Energy was delivered in two anatomical positions with the catheter able to achieve two delivery shapes. Ten seconds of electrogram information was recoded pre and post every delivery and the PR interval was manually measured, with prolongations of 10 ms or more post ablation considered significant (Figure 1). Recovery of AV conduction was measured from the end of the energy delivery pulse to the first beat conducted with a delay of less than 10 ms from the measured pre-delivery baseline. The study enrolled 12 patients (4 female) with a mean age of 63.3 years (SD = 13.2). In total, 412 lesions were delivered. Two patients presented and were treated in an atrial arrhythmia and three patients had no measurable change in AV conduction. However, seven patients had 49 measurable delays in AV conduction after PFA energy delivery ranging from 10 ms to 214 ms with a mean delay of 36.2 ms (SD = 34.4 ms). Eight measured intervals exceeded 200 ms post delivery. Recovery from AV delay took an average of 5.17 sec (SD = 4.2 sec) with the longest recovery time being 25 sec. Table 1. shows delay and recovery by vein. This report details the observation of the occurrence of AV-delay after the delivery of PFA. The incidence of this phenomenon was 58.3% of patients in the study. Pulsed field ablation appears to have a transient effect on the intrinsic cardiac autonomic nervous system manifested in changes to atrioventricular node response.

PO-05-018 GIANT INTRASEPTAL HEMATOMA COMPLICATING LEFT BUNDLE BRANCH PACING: AN UNUSUAL CLINICAL CHALLENGE

Left bundle branch pacing (LBBP) is an excellent alternative to His bundle pacing (HBP). Due to its non-traditional intraseptal lead placement, rare but unusual complications have been described. We present the case of a unique complication of a very large septal hematoma following LBBP. n/a An 88-year-old female with Coronary disease, renal insufficiency, and uncontrolled atrial fibrillation was referred for AV node ablation and conduction system pacing. Due to high HBP thresholds, a LBBP lead was implanted in proximal location (Stim-V6 peak=70ms, QRSd=135ms) with a backup second LBBP lead at a slightly distal location (Stim-V6 peak=61ms, QRSd=121ms) with low capture thresholds. She was discharged home the same day. She was readmitted a-day later with nausea, weakness, and significant dyspnea. Echocardiogram revealed a very large septal hematoma (61mm x 40mm) with complete obliteration of right ventricle cavity and no pericardial effusion (Figure 1A). IV fluid bolus was given, and Apixaban/Clopidogrel/ASA were held. Angiography and possible embolization of bleeding septal perforator was considered but not performed due to her CKD and hemodynamic stability. Serial echo revealed improved RV filling, stable hematoma and absent effusion. She was discharged on day 7 in stable condition. Anticoagulation was resumed after 2 weeks. Repeat echo at 6 weeks showed complete resolution of interventricular septal hematoma and lead parameters were stable (Figure 1B). This is a unique and rare case of a giant interventricular septal hematoma post LBBP, successfully managed with conservative management. Given rarity of complication, maintaining a broad differential for early recognition and treatment remains paramount. Avoiding a very proximal and anterior left bundle area, if possible, can be considered to avoid a major septal perforator. Repeat imaging and close hemodynamic monitoring is recommended in such patients. Angiography to localize the bleeding septal perforator and possible embolization may be considered for hemodynamic instability. This was deferred in our patient due to severe renal insufficiency, as well as lack of pericardial effusion and improving hemodynamics not requiring inotropic support. However, we recommend a multidisciplinary heart team and critical care approach, as was used in this case, to help personalize management.

PO-04-078 WHEN THE Q RUNS AWAY FROM P: A CASE OF EXTREME MOBITZ TYPE I

Advanced infranodal conduction disease usually presents with Mobitz 2 pattern and normal or mildly prolonged conducted PR intervals, whereas advanced AV node disease presents with Mobitz 1 pattern and more pronounced PR prolongation of conducted beats. AV node conduction properties can vary, with some patients demonstrating markedly prolonged PR intervals. We present a case of extreme PR prolongation and highly unusual Mobitz 1 patterns. To emphasize the variable presentation of AV node disease. N/A A 60 year old man with a history of Tetralogy of Fallot had serial repair surgeries over the years, including a Blalock Tausig shunt, Tetralogy of Fallot repair with pulmonary valve replacement, tricuspid valvuloplasty with chordal re-attachment, and closure of a cleft in the septal tricuspid valve leaflet. He had a dual chamber pacemaker for second degree AV block and RBBB. Due to recurrent tricuspid valve dysfunction, his pacemaker and leads were explanted at the time of repeat tricuspid valve surgery. Post-operatively, the surgical temporary epicardial pacing wires were not initially used, and various forms of asymptomatic Mobitz type 1 AV block were seen on serial ECGs. Careful scrutiny of the ECGs showed that the PR interval ranged from 640 ms to over 1300 ms. The markedly prolonged PR intervals led to highly unusual AV relationships, including overlapping PR intervals, as well as 1:1 and 2:1 AV conduction patterns that could only be properly deciphered in the context of other ECGs. When 2:1 AV conduction was seen, temporary pacing was implemented. He subsequently underwent bi-v pacemaker implantation to achieve proper AV and VV synchrony, in the context of concurrent LV dysfunction. AV conduction patterns can become complex in the setting of AV node disease, and more dramatically so in the context of congenital heart disease and valve surgery. Associations between specific P waves and QRS complexes should be ascertained to properly appreciate AV node disease severity. In the presented case, cursory ECG assessment led the ICU clinical team to conclude that AV conduction in the post-op setting followed a simple Mobitz 1 pattern with typical PR intervals. Therefore surgical temporary pacing wires were not utilized until the patient developed 2:1 AV conduction with more marked bradycardia. With careful ECG analysis, the severity of AV node dysfunction could be properly assessed and managed.

Effectiveness of the repurposed drug isotretinoin in an experimental murine model of Chagas disease

Benznidazole and nifurtimox are the drugs currently used for the treatment of Chagas disease, however its side effects may affect patient adherence. In the search for new alternative therapies, we previously identified isotretinoin (ISO), an FDA-approved drug widely used for the treatment of severe acne through a drug repurposing strategy. ISO shows a strong activity against Trypanosoma cruzi parasites in the nanomolar range, and its mechanism of action is through the inhibition of T. cruzi polyamine and amino acid transporters from the Amino Acid/Auxin Permeases (AAAP) family. In this work, a murine model of chronic Chagas disease (C57BL/6 J mice), intraperitoneally infected with T. cruzi Nicaragua isolate (DTU TcI), were treated with different oral administrations of ISO: daily doses of 5 mg/kg/day for 30 days and weekly doses of 10 mg/kg during 13 weeks. The efficacy of the treatments was evaluated by monitoring blood parasitemia by qPCR, anti-T. cruzi antibodies by ELISA, and cardiac abnormalities by electrocardiography. No parasites were detected in blood after any of the ISO treatments. The electrocardiographic study of the untreated chronic mice showed a significant decrease in heart rate, while in the treated mice this negative chronotropic effect was not observed. Atrioventricular nodal conduction time in untreated mice was significantly longer than in treated animals. Mice treated even with ISO 10 mg/kg dose every 7 days, showed a significant reduction in anti-T. cruzi IgG levels. In conclusion, the intermittent administration of ISO 10 mg/kg would improve myocardial compromise during the chronic stage.

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.