Pembrolizumab-induced myocarditis with complete atrioventricular block and concomitant myositis in a metastatic bladder cancer patient: a case report and review of the literature.

BACKGROUND: The cardiovascular system is among the least systems affected by immune-related adverse events. We report a rare life-threatening case of pembrolizumab-induced myocarditis with complete atrioventricular block and concomitant myositis in a metastatic bladder cancer patient. CASE PRESENTATION: An 82-year-old Caucasian female with invasive urothelial carcinoma, started on first-line pembrolizumab, was admitted four days after receiving her second dose for severe asthenia, diffuse muscle aches, neck pain, and lethargy. In the emergency department, she had several episodes of bradycardia reaching 40 beats per minute associated with general discomfort and fatigue. Electrocardiography showed a third-degree atrioventricular heart block, while the patient remained normotensive. Cardiac damage parameters were altered with elevated levels of creatine phosphokinase of 8930 U/L, suggestive of immune checkpoint inhibitor-induced myositis, and troponin T of 1.060 ng/mL. Transthoracic echocardiography showed a preserved ejection fraction. Pembrolizumab-induced myocarditis was suspected. Therefore, treatment was initiated with high-dose glucocorticoids for 5 days, followed by a long oral steroid taper. A pacemaker was also implanted. Treatment resulted in the resolution of heart block and a decrease in creatine phosphokinase to the normal range. CONCLUSION: Life-threatening cardiac adverse events in the form of myocarditis may occur with pembrolizumab use, warranting vigilant cardiac monitoring. Troponin monitoring in high-risk patients, along with baseline echocardiography may help identify this complication promptly to prevent life-threatening consequences.

The Antiarrhythmic Action of the Na+/Ca2+ Exchanger Inhibitor SEA0400 on Drug-Induced Long QT Syndrome Depends on the Severity of Proarrhythmic Conditions in Anesthetized Atrioventricular Block Rabbits.

To clarify the pharmacological properties of the Na+/Ca2+ exchanger (NCX) inhibitor SEA0400 as an antiarrhythmic agent, we assessed its effects on rapid component of delayed rectifier K+ current (IKr) blocker-induced torsade de pointes (TdP) in isoflurane-anesthetized rabbits. Atrioventricular block was induced in rabbits using a catheter ablation technique, and the monophasic action potential (MAP) of the right ventricle was measured under electrical pacing at 60 beats/min. In non-treated control animals, intravenous administration of low-dose (0.3 mg/kg) or high-dose nifekalant (3 mg/kg) prolonged the MAP duration (MAP90) by 113 ± 11 ms (n = 5) and 237 ± 39 ms (n = 5), respectively, where TdP was induced in 1/5 animals treated with a low dose and in 3/5 animals treated with a high dose of nifekalant. In SEA0400-treated animals, low- and high-dose nifekalant prolonged the MAP90 by 65 ± 13 ms (n = 5) and 230 ± 20 ms (n = 5), respectively. No TdP was induced by the low dose but 1/5 animals treated with a high dose of nifekalant developed TdP. In verapamil-treated animals, low-dose and high-dose nifekalant prolonged MAP90 by 50 ± 12 ms (n = 5) and 147 ± 30 ms (n = 5), respectively, without inducing TdP. These results suggest that SEA0400 has the potential to inhibit low-dose nifekalant-induced TdP by suppressing the MAP-prolonging action of nifekalant, whereas the drug inhibited high-dose nifekalant-induced TdP without affecting the MAP-prolonging action of nifekalant. This may reveal that, in contrast to verapamil, the antiarrhythmic effects of SEA0400 on IKr blocker-induced TdP may be multifaceted, depending on the severity of the proarrhythmogenic conditions present.

Failure of diltiazem to prevent 1:1 conduction of atrial flutter: a case report.

BACKGROUND: Atrial flutter with 1:1 conduction to the ventricles is a dangerous cardiac arrhythmia. Contemporary guidelines recommend atrioventricular nodal blocking agents should be co-administered with class 1C anti-arrhythmics, as prophylaxis against 1:1 flutter. No guidance is provided on the type or strength of atrioventricular nodal blockade required, and in practice, these agents are frequently prescribed at low dose, or even omitted, due to their side effect profile. CASE PRESENTATION: A 62 year old Caucasian man with a history of paroxysmal atrial fibrillation treated with flecainide, presented with atrial flutter with 1:1 conduction to the ventricles and was cardioverted. Diltiazem was added to prevent this complication and he again presented with atrial flutter with 1:1 conduction to the ventricles, despite prophylaxis with coadministration of diltiazem. CONCLUSIONS: This case report demonstrates failure of diltiazem to prevent 1:1 flutter in a patient chronically treated with flecainide for paroxysmal atrial fibrillation.

Cardiac and renal AL amyloidosis controlled by autologous stem cell transplantation for 17 years accompanying late onset atrial fibrillation and complete atrioventricular block.

Amyloid light chain (AL) amyloidosis is a rare hematologic disease that may involve multiple organs. Amongst the organs, cardiac involvement causes the greatest concern as its treatment is challenging. Diastolic dysfunction rapidly progresses to decompensated heart failure, pulseless electrical activity, and atrial standstill due to electro-mechanical dissociation resulting in death. High-dose melphalan plus autologous stem cell transplantation (HDM-ASCT) is the most radical treatment but its risk is very high and thus only less than 20% of patients can receive this therapy under criteria that can suppress treatment-related mortality. In substantial proportion of patients, levels of M protein remain elevated, and organ response cannot be achieved. Moreover, relapse may occur, making prediction of treatment response and judgement of disease eradication very difficult. Herein we report a case of AL amyloidosis who was treated with HDM-ASCT, resulting in preserved cardiac function and resolution of proteinuria for more than 17 years after HDM-ASCT ensuing atrial fibrillation and complete atrioventricular block required management by catheter ablation and pacemaker implantation 10 years and 12 years after transplantation, respectively.

Adenosine as adjunctive therapy in acute coronary syndrome: a meta-analysis of randomized controlled trials.

AIMS: Adenosine has been tested in several randomized controlled trials (RCTs) to minimize the incidence of coronary microvascular obstruction (CMVO). The aim of this study was to pool all the RCTs comparing intracoronary or intravenous adenosine versus placebo in patients with acute coronary syndrome (ACS) undergoing myocardial revascularization. METHODS AND RESULTS: PubMed and Scopus electronic databases were scanned for eligible studies up to 5th June 2022. A total of 26 RCTs with 5843 patients were included. Efficacy endpoints were major adverse cardiac events (MACE), all-cause death, non-fatal myocardial infarction, and heart failure. Atrioventricular blocks and ventricular fibrillation/sustained ventricular tachycardia (VF/SVT) were the safety endpoints. Myocardial blush grade, thrombolysis in myocardial infarction (TIMI) flow grade, left ventricular ejection fraction (LVEF), infarct size, and ST-segment resolution were also assessed. Adenosine administration was not associated with any clinical benefit in terms of MACE, all-cause death, non-fatal myocardial infarction, and heart failure. However, adenosine was associated with an increased rate of advanced atrioventricular blocks and of VF/SVT in studies with total mean ischaemic time >3 h, compared to placebo. Remarkably, among patients undergoing percutaneous coronary intervention, adenosine was associated with reduced myocardial blush grade 0-1 and TIMI flow grade 0-2, compared to placebo. Furthermore, adenosine did not show favourable effects on LVEF and infarct size. CONCLUSION: Adenosine infusion, as adjunctive therapy in ACS, was associated with an increased risk of advanced atrioventricular blocks and increased rates of adenosine-triggered ventricular arrhythmias in patients with long ischaemic time, without providing any clinical benefit compared to placebo.

Adalimumab for the treatment of cardiac sarcoidosis with multiple arrhythmias.

A 45-year-old male with cardiac sarcoidosis verified by cardiac biopsy presented with multiple coexisting arrhythmias, including ventricular tachycardia of more than 1000 episodes per 24 h, paroxysmal atrial fibrillation, and third-degree atrioventricular block. He did not respond to corticosteroids dose of 20-60 mg once daily and mycophenolate mofetil dose of 1 g twice daily for 6 months. Cardiac magnetic resonance (CMR) demonstrated inflammation and late gadolinium enhancement on right ventricular wall and interventricular septum. Positron emission tomography-computed tomography (PET-CT) showed multifocal 18 F-fluorodeoxyglucose uptake in the heart. We replaced mycophenolate mofetil with adalimumab, a tumour necrosis factor-α inhibitor. After 3 months, his arrhythmias improved significantly, manifesting as premature ventricular contractions of only 500 beats per 24 h and first-degree atrioventricular block. CMR showed a significant reduction in inflammation and late gadolinium enhancement, and PET-CT showed a complete resolution of fluorodeoxyglucose uptake.

A critical review of ozanimod for the treatment of adults with moderately to severely active ulcerative colitis.

INTRODUCTION: Ozanimod is a sphingosine-1-phosphate (S1P) modulator that inhibits lymphocyte trafficking from lymph nodes to the circulation. It is approved by the US Food and Drug Administration (FDA) for the treatment of relapsing multiple sclerosis and most recently for the management of moderate-severe ulcerative colitis (UC). AREAS COVERED: Here we review the status of drugs approved for moderate-severe UC, the unmet needs in the management of UC, proposed mechanisms of action of S1P modulators, clinical data regarding ozanimod in UC, and emerging S1P modulators being evaluated in inflammatory bowel disease. EXPERT OPINION: Ozanimod is superior to placebo in inducing and maintaining clinical and endoscopic remission in UC. Adverse events include transient asymptomatic bradycardia, first-degree atrioventricular blocks, transient asymptomatic hepatotoxicity, macular edema in patients with preexisting risk factors, and increased risk of nasopharyngitis. Ozanimod is contraindicated in patients with clinically significant cardiovascular diseases, type II second-, or third-degree atrioventricular blocks, and females of childbearing age who do not use contraception. Ozanimod is the first S1P modulator to be approved for UC, offering a new therapeutic class option for patients. It has the advantages of being convenient with a once-daily oral administration, non-immunogenic, and overall safe when used in patients without contraindications.

NAFTNet retrospective report on the treatment of anti-Ro/SSA mediated fetal heart block with dexamethasone.

BACKGROUND: Complete atrioventricular block (CAVB) is a complication of maternal antibody positivity and treatment of fetal disease is controversial in terms of efficacy and safety. We hypothesized that dexamethasone treatment for fetal anti-Ro/SSA antibody-mediated cardiac disease leads to better pregnancy outcomes than expectant management. METHODS: A retrospective multi-center cohort study of anti-Ro/SSA antibody positive pregnancies with fetal conduction disease reported by participating North American Fetal Therapy Network (NAFTNet) centers between January 2010 and December 2018. The primary outcomes included: fetal death, oligohydramnios, growth restriction, preterm delivery, and new maternal comorbidities. Secondary outcomes included: pacemaker prior to 28 days, transplantation, and neonatal death in maternal/fetal dyads treated with dexamethasone versus not. RESULTS: In 127 anti-Ro/SSA positive pregnancies, 98 were treated with dexamethasone and 29 were not. Of those treated, 61/96 (63.5%) met the primary outcome including 45/91 (49.4%) premature deliveries; 20 mothers developed comorbidities during treatment (fetal death 5, 10 growth restriction, 14 oligohydramnios, two new/worsening gestational diabetes). In the untreated group, 15/25 (60%) met the primary outcome including 11/22 (50%) premature deliveries and four mothers developing comorbidities during their pregnancy (fetal death 3, one growth restriction, one new onset maternal hypertension). Regarding secondary outcomes, 37/96 (43%) treated fetuses required a pacemaker or died by 28 days, while untreated 13/25 (52%) required pacemaker placement, died prior to 28 days or required listing for transplantation. Excluding terminations, survival without transplant was 17 (68%) in untreated and 85 (89%) in treated patients (p<.01). CONCLUSIONS: While the use of dexamethasone in anti-Ro/SSA positive pregnancies is associated with a high rate of poor pregnancy outcomes, there was an unexpected similarly high rate in untreated positive pregnancies. This suggests that the maternal disease itself is influencing pregnancy complications independent of dexamethasone. Our data, which show that treatment decreases neonatal morbidity and overall mortality without increasing overall pregnancy complications, warrant further study.

Rotors anchored by refractory islands drive torsades de pointes in an experimental model of electrical storm.

BACKGROUND: Electrical storm (ES) is a life-threatening emergency in patients at high risk of ventricular tachycardia/ventricular fibrillation (VF), but the pathophysiology and molecular basis are poorly understood. OBJECTIVE: The purpose of this study was to explore the electrophysiological substrate for experimental ES. METHODS: A model was created by inducing chronic complete atrioventricular block in defibrillator-implanted rabbits, which recapitulates QT prolongation, torsades des pointes (TdP), and VF episodes. RESULTS: Optical mapping revealed island-like regions with action potential duration (APD) prolongation in the left ventricle, leading to increased spatial APD dispersion, in rabbits with ES (defined as ≥3 VF episodes/24 h). The maximum APD and its dispersion correlated with the total number of VF episodes in vivo. TdP was initiated by an ectopic beat that failed to enter the island and formed a reentrant wave and perpetuated by rotors whose centers swirled in the periphery of the island. Epinephrine exacerbated the island by prolonging APD and enhancing APD dispersion, which was less evident after late Na+ current blockade with 10 µM ranolazine. Nonsustained ventricular tachycardia in a non-ES rabbit heart with homogeneous APD prolongation resulted from multiple foci with an electrocardiographic morphology different from TdP driven by drifting rotors in ES rabbit hearts. The neuronal Na+-channel subunit NaV1.8 was upregulated in ES rabbit left ventricular tissues and expressed within the myocardium corresponding to the island location in optically mapped ES rabbit hearts. The NaV1.8 blocker A-803467 (10 mg/kg, intravenously) attenuated QT prolongation and suppressed epinephrine-evoked TdP. CONCLUSION: A tissue island with enhanced refractoriness contributes to the generation of drifting rotors that underlies ES in this model. NaV1.8-mediated late Na+ current merits further investigation as a contributor to the substrate for ES.

The canine chronic atrioventricular block model in cardiovascular preclinical drug research.

Ventricular cardiac arrhythmia is a life threating condition arising from abnormal functioning of many factors in concert. Animal models mirroring human electrophysiology are essential to predict and understand the rare pro- and anti-arrhythmic effects of drugs. This is very well accomplished by the canine chronic atrioventricular block (CAVB) model. Here we summarize canine models for cardiovascular research, and describe the development of the CAVB model from its beginning. Understanding of the structural, contractile and electrical remodelling processes following atrioventricular (AV) block provides insight in the many factors contributing to drug-induced arrhythmia. We also review all safety pharmacology studies, efficacy and mechanistic studies on anti-arrhythmic drugs in CAVB dogs. Finally, we compare pros and cons with other in vivo preclinical animal models. In view of the tremendous amount of data obtained over the last 100 years from the CAVB dog model, it can be considered as man's best friend in preclinical drug research. LINKED ARTICLES: This article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc.

Torsadogenic Potential of HCN Channel Blocker Ivabradine Assessed in the Rabbit Proarrhythmia Model.

Torsadogenic effects of ivabradine, an inhibitor of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, were assessed in an in vivo proarrhythmia model of acute atrioventricular block rabbit. Ivabradine at 0.01, 0.1, and 1 mg/kg was intravenously administered to isoflurane-anesthetized rabbits (n = 5) in the stable idioventricular rhythm. Ivabradine at 0.01 and 0.1 mg/kg hardly affected the atrial and ventricular automaticity, QT interval, or the monophasic action potential duration of the ventricle. Additionally administred ivabradine at 1 mg/kg decreased the atrial and ventricular rate significantly but increased the QT interval and duration of the monophasic action potential. Meanwhile, torsade de pointes arrhythmias were detected in 1 out of 5 animals and in 2 out of 5 animals after the administration of 0.1 and 1 mg/kg, respectively. Importantly, torsade de pointes arrhythmias could be observed only in 2 rabbits showing more potent suppressive effects on ventricular automaticity. These results suggest that the torsadogenic potential of ivabradine may become evident when its expected bradycardic action appears more excessively.

Complete heart block in cardiac sarcoidosis reversed by corticosteroid therapy: time course of resolution.

A 53-year-old man was admitted for recurrent syncope and found to have complete heart block (CHB). Cardiac magnetic resonance imaging MRI) showed extensive patchy late gadolinium enhancement in the apical and lateral walls, consistent with cardiac sarcoidosis (CS) but no scar in the septum. A fluorodeoxyglucose (FDG)-positron emission tomography showed FDG uptake in the septum and basal lateral walls. Imaging suggested active inflammation in the septum affecting atrioventricular (AV) conduction but no irreversible fibrosis. Diagnosis of isolated CS requires a high level of suspicion and multidisciplinary teamwork involving heart failure specialists, electrophysiologists and rheumatologists. After specialist and patient discussion, treatment of the disease was initiated with prednisone 40 mg daily, 11 months after presenting with CHB. Three weeks later, ECG with pacing inhibited showed second-degree AV block Mobitz type II and 4 weeks later, AV conduction recovery. This highlights the importance of immediate therapy in reversing AV conduction abnormalities in CS.

Effects of Transplacental Dexamethasone Therapy on Fetal Immune-Mediated Complete Heart Block.

INTRODUCTION: Antibody-mediated complete atrioventricular block (CAVB) is considered irreversible. We sought to examine the effects of transplacental steroids on fetal AV conduction. METHODS: Fifty-nine fetuses diagnosed with CAVB at our center from 1996 to 2018 were reviewed. Routine dexamethasone administration to birth was used to limit cardiac inflammatory damage. Restoration of fetal AV conduction was classified as "unexpected" treatment response. RESULTS: CAVB resolved in 5/29 (17%) fetuses first treated ≤24-week gestation with 8 mg/day of dexamethasone, when compared with 0/30 (0%) when treatment was initiated later and/or at a starting dose of 4 mg/day (odds ratio 13.69; 95% confidence interval 0.72-260.13; p = 0.024). Treatment response was also associated with a faster ventricular rate at diagnosis (median [range]: 80 [60-97] beats per minute [bpm] vs. 58 [38-92] bpm; p = 0.0036). CAVB reappeared in all 5 responders either prenatally (n = 1) or postnatally before (n = 3) or after (n = 1) the first year of life. When compared with infants with treatment-resistant CAVB (median follow-up 10.3 years), responders (median follow-up 12.3 years) required postnatal pacing less frequent (2/5 [40%] vs. 45/49 [92%]; p = 0.013). CONCLUSIONS: In a subgroup of CAVB fetuses, dexamethasone transiently restored AV conduction. This was associated with a lower rate of postnatal pacing when compared with nonresponders.

Immune-Mediated Fetal Complete Atrioventricular Block: Can Dexamethasone Therapy Revert the Process?

BACKGROUND: Fetal complete atrioventricular block (CAVB) is usually autoimmune mediated. The risk of developing CAVB is 2% to 3% in anti-Ro/SS-A seropositive pregnancies and it increases 10 times after previous CAVB in siblings. Despite being a rare complication, CAVB carries a 20% mortality rate and substantial morbidity, as about 65% of newborns will eventually need life-long pacing. Once found, fetal CAVB is almost always irreversible, despite aggressive immunotherapy. This poor outcome prompted some research groups to address this situation. All groups followed anti-Ro/SS-A seropositive pregnancies on a weekly basis during the second trimester of pregnancy and tried to detect first degree atrioventricular block (AVB) using accurate echocardiographic tools, assuming they may characterize the initiation of the immune damage to the A-V conduction system, at which point the process might still be reversible. Some of the groups treated fetuses with first degree AVB with maternal oral fluorinated steroids. We summarized the results of all groups, including our group. We describe a case of a fetus that developed CAVB 6 days after normal sinus rhythm (NSR), who under aggressive dexamethasone therapy gradually reverted to NSR. This fetus had a previous sibling with CAVB. We assumed the immune damage to the conduction system in this small group of fetuses with a previous CAVB sibling may have occurred more quickly than usual. We therefore recommend a twice-weekly follow-up with these fetuses.

Risperidone alone did not induce torsade de pointes: Experimental evidence from the chronic atrioventricular block model dogs.

We assessed torsadogenic action of risperidone, which can potently inhibit IKr as well as α1-adrenoceptor. A toxic dose of 3 mg/kg of risperidone was intravenously administered over 10 min to chronic atrioventricular block dogs without anesthesia with monitoring Holter electrocardiogram (n = 4). Risperidone increased atrial/ventricular rate for 1-12 h/1-6 h and prolonged QTcF at 6 h after its administration, whereas it did not increase short-term variability of repolarization or induced torsade de pointes. These results suggest that α1-adrenoceptor blockade-dependent, hypotension-induced, reflex-mediated increase of sympathetic tone by risperidone might play a role in protecting the heart from IKr inhibition-associated torsade de pointes.

In vivo analysis of the effects of intravenously as well as orally administered moxifloxacin on the pharmacokinetic and electrocardiographic variables along with its torsadogenic action in the chronic atrioventricular block cynomolgus monkeys.

We analyzed the effects of intravenously as well as orally administered moxifloxacin on the pharmacokinetic and electrocardiographic variables along with its torsadogenic action using the chronic atrioventricular block cynomolgus monkeys with a cross-over design. Initially, moxifloxacin was intravenously administered in doses of 60 mg/kg/2 h, 60 mg/kg/1 h and 105 mg/kg/1.75 h with an interval of >1 week (n = 3), which provided Cmax of 19.7, 25.4 and 37.8 µg/mL, and induced torsade de pointes in 1, 0 and 3 out of 3 animals, respectively. Next, moxifloxacin was orally administered in doses of 10, 30 and 100 mg/kg with an interval of >1 week (n = 6), which provided Cmax of 1.8, 4.2 and 8.9 µg/mL, and induced torsade de pointes in 0, 0 and 2 out of 6 animals, respectively. A close analysis of pharmacokinetic and electrocardiographic variables indicates that torsade de pointes was induced in animals that had experienced larger systemic exposure of moxifloxacin and/or greater peak QTcF, although Cmax by itself did not necessarily reflect the incidence of torsade de pointes when its administration route was different. These findings may provide a basic guide how to use moxifloxacin in safe for patients with labile repolarization process.

Analysis of electropharmacological effects of AVE0118 on the atria of chronic atrioventricular block dogs: characterization of anti-atrial fibrillatory action by atrial repolarization-delaying agent.

AVE0118, an inhibitor of IKur, Ito and IK,ACh, was in the drug pipeline for atrial fibrillation. To investigate the limitation of AVE0118 as an anti-atrial fibrillatory drug, we studied its electropharmacological effects particularly focusing on the anti-atrial fibrillatory action as reverse translational research. We adopted the chronic atrioventricular block beagle dogs (n = 4), having a pathophysiology of bradycardia-associated, volume overload-induced chronic heart failure, in which the atrial fibrillation was induced by 10 s of burst pacing on atrial septum. AVE0118 in doses of 0.24 and 1.2 mg/kg, i.v. over 10 min hardly altered electrophysiological variables. Meanwhile, AVE0118 in a dose of 6 mg/kg, i.v. over 10 min delayed the inter-atrial conduction in a frequency-dependent manner and prolonged the atrial effective refractory period in a reverse frequency-dependent manner, whereas it did not significantly alter the duration of atrial fibrillation or its cycle length. The increment of atrial effective refractory period was 3.3 times greater compared with that of ventricular one at a basic cycle length of 400 ms. Torsade de pointes was not induced during the experimental period. Thus, AVE0118 may possess a favorable cardiac safety pharmacological profile, but its weak anti-atrial fibrillatory effect would indicate the limitation of atrial repolarization-delaying agents for suppressing atrial fibrillation.

Myocarditis with Advanced Atrioventricular Block after Allogeneic Stem Cell Transplantation: A Case Report and Literature Review.

A 51-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia underwent a second cord blood transplantation followed by maintenance therapy with interferon-α. After 33 months, she developed cardiogenic shock caused by advanced atrioventricular block. Laboratory tests revealed increased myocardium enzymes, and ultrasonic cardiography demonstrated mild thickening of the left ventricular wall. She was diagnosed with myocarditis and successfully treated using prednisolone. Myocarditis after allogeneic stem cell transplantation is a rare but potentially fatal complication. However, it is important for physicians to be aware of this complication because all of the symptoms may be reversed with immunosuppressive treatment.

Spontaneous brain arteriovenous malformation rupture with atrioventricular block in a pediatric patient.

This case reports 9 year-old-female with atrioventricular block and seizure. Careful evaluation, including electrocardiogram (ECG) and computerized tomography (CT) revealed a high-grade atrioventricular block and spontaneous brain arteriovenous malformation (AVM) rupture. The patient had complete resolution of her bradycardia and AV block following atropine. This case is to our knowledge the first description of a pediatric spontaneous brain AVM rupture presenting with high degree AV block responsive to intravenous atropine.