Anti-N-Methyl-D-Aspartate Receptor Encephalitis and Life-Threatening Sinus Node Dysfunction: A Case Report, Literature Review, and Analysis of 23 Cases.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common form of autoimmune encephalitis, presenting with various psychiatric manifestations, including behavioral and cognitive impairments, movement disorders, decreased consciousness, dysphasia, seizures, and autonomic dysfunction. Autonomic dysfunction may involve hyperthermia, apnea, hypotension, tachycardia, and life-threatening manifestations of sinus node dysfunction (SND), such as bradycardia, sinus pause or arrest, and asystole. The severity and significance of SND are critical, as it is not uncommon for these patients to progress into asystolic cardiac arrest, potentially contributing to morbidity and mortality. Accordingly, we present the case of an 18-year-old female with anti-NMDAR encephalitis who experienced multiple episodes of sinus pause/arrest and asystolic cardiac arrest, achieving a return of spontaneous circulation after successful CPR in all instances, ultimately requiring permanent pacemaker implantation. Additionally, we performed a literature review and analyzed 23 similar anti-NMDAR encephalitis cases with SND manifestations, including sinus pause/arrest or asystolic cardiac arrest, to identify common risk factors and describe management strategies and outcomes. Moreover, we investigated the potential association between teratoma and permanent pacemaker use in SND.

Repeated Syncope Following COVID-19 Infection.

A 74-year-old woman presented to our hospital with syncope after a coronavirus disease 2019 (COVID-19) infection. Upon admission, she passed out, and an 8 second sinus arrest was detected during telemetry monitoring. During the next syncope episode, telemetry monitoring showed that her heart rate decreased from 80 to 36 bpm, accompanied by a 2.4 second pause. A permanent pacemaker was implanted; however, the patient still experienced syncope. The head-up tilt test revealed a vasodepressor reflex syncope. The need for permanent pacemakers in patients with syncope following COVID-19 therefore remains controversial.

Hypothyroidism and sinus dysfunction associated with lithium-paliperidone combination therapy for bipolar disorder with psychotic symptoms: a case report.

Background and aim: Lithium is considered to be the first-line treatment for bipolar disorder, and paliperidone was approved for the treatment of schizophrenia and acute bipolar manic/mixed episodes. However, both agents have been associated with thyroid dysfunction and cardiovascular adverse effects like subclinical hypothyroidism, bradycardia, and sinus arrest, even at therapeutic doses. Case presentation: Here, we reported a case of a 17-year-old Han Chinese female who developed symptomatic hypothyroidism, sinus bradycardia, and sinus arrest while being treated with lithium and paliperidone for bipolar disorder with psychotic features including auditory hallucinations. Her workup suggested that these adverse effects might be related to the combined lithium and paliperidone treatment, although other causes could not be ruled out. After discontinuing both medications, her thyroid function and heart rhythm normalized over 20 days. Conclusion: To our knowledge, hypothyroidism, sinus bradycardia, and sinus arrest associated with the combined use of lithium and paliperidone had not been reported previously. Further research is warranted to elucidate the potential risks and benefits of this combination therapy for bipolar disorder with psychotic symptoms.

Transient Sinus Node Dysfunction Associated with Herpes Simplex Encephalitis.

Sinus arrest and inappropriate sinus bradycardia are sinus node dysfunction (SND), which cause loss of consciousness. Cardiac pacing is recommended in patients with symptoms, such as syncope or dizziness. Several conditions can induce these arrhythmias; however, whether or not intracranial infectious diseases, such as herpes simplex encephalitis (HSE), can cause secondary SND is unclear. We encountered a patient with sinus arrest and transient sinus bradycardia associated with HSE. Since cardiac pause was never monitored and the bradycardia improved after HSE treatment, HSE was suspected to be the cause of SND. Although the underlying mechanisms have not yet been completely elucidated, HSE may cause secondary SND.

The Rate of Asystolic Reflex Syncope Is Not Influenced by Age.

BACKGROUND: The head-up tilt test (HUT) and other evidence suggest that the vagal effect on the heart decreases with age. OBJECTIVES: The main aim of the study was to assess whether this age effect also affects the rate of asystole in spontaneous reflex syncope (RS). METHOD: We performed an analysis of pooled individual data from 4 studies that recruited patients ≥40 years of age affected by certain or suspected RS who received an implantable loop recorder (ILR) and reported follow-up data on syncope recurrence. We assessed the presence of asystolic syncope of >3 seconds or nonsyncopal asystole of >6 seconds recorded by ILR and compared the findings to tilt test results on the same patients. RESULTS: A total of 1,046 patients received ILR because of unexplained syncope. Of these, 201 (19.2%) had a documentation of an asystolic event of 10-second (Q1-Q3: 6- to 15-second) duration. They were subdivided in 3 age tertiles: ≤60 years (n = 64), 61 to 72 years (n = 72), and ≥73 years (n = 65). The rate of asystolic events was similar in the 3 subgroups (50.1%, 50.1%, and 49.2%, respectively; P = 0.99). Conversely, the rate of asystolic syncope induced during HUT (performed in 169 of 201) was greatly age dependent (31.0%, 12.1%, and 11.1% in increasing age tertiles, respectively; P = 0.009). CONCLUSIONS: The rate of the spontaneous asystolic form of RS documented by ILR is constant at any age >40 years. Conversely, the rate of asystolic syncope induced by HUT is higher in younger patients and decreases with age. The contrasting results between spontaneous and tilt-induced events cast doubt on the concept that asystole in RS is less common in older patients.

Cardioneuroablation for successful treatment of symptomatic bradycardia in a 12-year-old child after a 6-month follow-up.

Background: Cardioneuroablation (CNA) is recognized as a promising therapeutic option for adults with severe symptomatic bradycardia caused by excessive vagal tone. However, no pediatric cases have been reported to date. Therefore, the aim of this study is to evaluate the feasibility and efficacy of CNA in children. Methods: A 12-year-old male patient was hospitalized with symptoms of fatigue, palpitations, and syncope for more than 2 months, and was definitively diagnosed with functional sinoatrial node dysfunction by using a 12-lead electrocardiogram, 24-h Holter monitoring, loading dose of atropine test (0.04 mg/kg), and treadmill exercise test. Simultaneously, whole-exome sequencing was performed on the child and his core family members. After completing the preoperative examination and signing the informed consent form, the child underwent CNA therapy. Results: First, the electroanatomic structures of both atria were mapped out by using the Carto 3 system, according to the protocol of purely anatomy-guided and local fractionated intracardiac electrogram-guided CNA methods. Then, the local fractionated intracardiac electrograms of each cardiac ganglionated plexus (GP), including the GP between the aortic root and the medial wall of the superior vena cava, the GP between the posterior wall of the coronary sinus ostium and the left atrium, the GP between the anterior antrum of the right superior pulmonary vein and the superior vena cava, the GP in the superolateral area around the root of the left superior pulmonary vein, the GP around the root of the right inferior pulmonary vein, and the GP around the root of the left inferior pulmonary vein, were used as targets for ablation at a power of 30 W with an ablation index of 350-400. At a 6-month follow-up, the child's heart rhythm saw a complete restoration to sinus rhythm and clinical symptoms disappeared. Conclusion: The first application of CNA in a child with symptomatic sinus bradycardia was achieved with better clinical outcomes. CNA can be carried out cautiously in children under suitable indications.

An incidentally discovered paraganglioma that caused sinus arrest after resection.

Paragangliomas are neural-crest-derived nonepithelial neuroendocrine tumors distributed along the parasympathetic and sympathetic nerves. To our knowledge, no studies were reported regarding sinus arrest on day 4 after paraganglioma resection. A 66-year-old female patient with a history of pulmonary vein isolation visited our department for sigmoid colon cancer treatment. Enhanced computed tomography revealed an enhanced small nodule-like lymph node near the root of the inferior mesenteric artery. The patient underwent laparoscopic colectomy with regional lymph node dissection. Postoperatively, paroxysmal atrial fibrillation attacks developed, and the patient resumed oral medication. Additionally, sinus arrest after tachycardia developed. Changing the oral medication could maintain her circulatory dynamics. Pathological examination revealed that differentiated tubular adenocarcinoma infiltrated the submucosa. Immunohistochemically, the excised nodule as a lymph node was considered a functional paraganglioma. Our case indicates that paraganglioma resection and oral medication resumption may contribute to sinus arrest. When arrhythmias affecting the circulation occur perioperatively, the presence of a catecholamine-producing tumor should be considered in addition to cardiac disease. J. Med. Invest. 70 : 503-507, August, 2023.

Sick sinus syndrome diagnosed after a sinus arrest during treatment for zygomatic fracture: a case report.

BACKGROUND: Intraoperative sinus arrest is rarely seen during zygomatic fracture treatment. The patient was diagnosed with sick sinus syndrome based on repeated postoperative sinus arrest, which could have resulted in death if diagnosed late, making this case very significant to report. CASE PRESENTATION: Sick sinus syndrome is an arrhythmia associated with reduced automaticity of the sinoatrial node or impaired sinoatrial node conduction. We report the case of a 67-year-old man diagnosed with the syndrome after a sinus arrest that occurred during a zygomatic fracture treatment. The patient had cheek pain and mouth opening disorder, dizziness after fainting and sustaining a facial injury. Preoperative examination determined that the syncope was due to drug-induced arrhythmia, and surgery was authorized after drug withdrawal. During the operation, sinus arrest was observed due to trigeminal vagal reflex, and heart rate was restarted by stopping the operation and chest compressions. After the surgery, the patient showed symptoms of dizziness and palpitations, and sinus arrest following atrial fibrillation and supraventricular tachycardia, which was diagnosed as sick sinus syndrome, and a pacemaker was implanted. Currently, 8 years have passed since the surgery, and there are no symptoms of mouth opening disorder, dizziness, or palpitations. CONCLUSIONS: In the case of maxillofacial injuries due to syncope, cardiogenic syncope is a possibility, and repeated syncope is a risk for death due to delayed diagnosis. There are no reports of maxillofacial trauma leading to a diagnosis of sick sinus syndrome. The purpose of this case report is to disseminate the importance of diagnosing the cause of syncope as well as injury treatment.

Sinus Arrest Related to Dexmedetomidine Infusion in an Infant; a Case Report and Review of Current Literature.

Background: Dexmedetomidine, an alpha 2 agonist, has emerged as a desirable sedative agent in the pediatric intensive care unit due to its minimal effect on respiratory status and reduction in delirium. Bradycardia and hypotension are common side effects, however there are emerging reports of more serious cardiovascular events, including sinus arrest and asystole. These case reports have been attributed to high vagal tone or underlying cardiac conduction dysfunction. Objectives: To describe the development of sinus arrest during sedation with dexmedetomidine in a patient without clinical features of high vagal tone, underlying cardiac conduction dysfunction, or intervening episodes of bradycardia. Case Presentation: An 11 month-old patient requiring sedation during mechanical ventilation for acute respiratory failure secondary to Adenovirus. To facilitate sedation, a dexmedetomidine infusion was initiated at .5 mcg/kg/hr and increased to maximum 1 mcg/kg/hr. Within 8 hours of initiating therapy, the patient had three episodes of sinus arrest. There was no intervening bradycardia between episodes and no further episodes occurred following discontinuation of dexmedetomidine. The patient did not have any clinical features associated with high vagal tone or underlying cardiac conduction dysfunction. Conclusions: As result of these findings, understanding risk factors for bradycardia, or more serious hemodynamic instability with dexmedetomidine infusions, is important to help identify high risk patients and weigh the associated risks and benefits of its administration.

Syncope With Sinus Arrest Following a Single Dose of a COVID-19 Vaccine.

Vaccines against the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) are of paramount importance in combating the current coronavirus disease 2019 (COVID-19) pandemic. Syncopal episodes following routine vaccinations are well-reported; however, only a few cases of syncope following SARS-CoV-2 vaccines exist in the literature. This is a case report of a 21-year-old female patient who developed recurrent syncopal attacks over three months that started one day after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine (Pfizer, New York City; BioNTech, Mainz, Germany). Holter monitoring during successive episodes showed progressive bradycardia followed by a prolonged sinus arrest. The patient eventually required pacemaker placement that resulted in the total resolution of her symptoms. Further studies are required to investigate a possible correlation and the mechanisms involved.

Lidocaine Tape Application for 3 Hours Prevents Vasovagal Syncope During Venipuncture: A Case Series.

Vasovagal syncope (VVS) or reflex is usually caused by physical and mental stress-related factors, like pain, anxiety, and fear, and it is one of the most frequent complications during dental treatment. Two patients, both with histories of dental phobia and of VVS during vaccination, venipuncture, and dental treatment with local anesthetics, were scheduled for dental treatment under intravenous (IV) sedation. However, both experienced episodes of VVS that occurred during venipuncture using a 24-gauge indwelling needle. We determined that pain was the main trigger of VVS for these patients and attempted to reduce venipuncture-associated pain using 60% lidocaine tape applied 3 hours before venipuncture at their next dental visits, respectively. Use of the lidocaine tape was successful and permitted comfortable placement of the IV catheter without any onset of VVS.

Translational implications of bradyarrhythmia in hibernating brown bears.

The brown bear Ursus arctos undergoes exceptional physiological adaptions during annual hibernation that minimize energy consumption, including profound decrease in heart rate, cardiac output, and respiratory rate. These changes are completely reversible after the bears reenter into the active state in spring. In this case report, we show episodes of sinus arrest in a hibernating Scandinavian brown bear and in humans, recorded by implantable loop recorders and discuss the possible underlying mechanisms. Lessons learned from cardiac adaptations in hibernating bears might prove useful in the treatment of patients with sinus node dysfunction.

Sinus arrest in a p.Arg160X-DSP-positive patient without evidence of desmoplakin-mediated cardiomyopathy: a case report.

Background: Pathogenic/Likely pathogenic variants in DSP-encoded desmoplakin are strongly associated with arrhythmogenic cardiomyopathy (ACM). However, their contribution towards sinus node dysfunction has not been well-delineated. Case summary: A 74-year-old man with a pathogenic variant of DSP-encoded desmoplakin (c.478C >T; p.Arg160X) but no evidence of ACM presented with one episode of syncope in the setting of a gastrointestinal illness. Workup including echocardiography, cardiac magnetic resonance imaging, and Holter monitor did not show evidence of ACM or significant arrhythmias. One month later, he experienced several closely-spaced episodes of syncope associated with long sinus pauses and sinus arrest documented on telemetry. He underwent urgent dual chamber pacemaker implantation, during which a ventricular programmed stimulation study was performed and was negative for sustained ventricular arrhythmias. His syncopal episodes resolved and he had no recurrent events on three-month follow-up. Discussion: As highlighted here, DSP-encoded desmoplakin pathogenic/Likely pathogenic variants may contribute to isolated sinus node dysfunction. This clinical link should be further explored in larger studies involving patients with DSP variants.

A dog presenting with syncope due to two different etiologies.

Objective: The treatment of syncope depends largely on its possible etiology. Therefore, identifying the cause of syncope is very important in treatment planning. Herein, we report an etiology of syncope caused by pulmonary hypertension (PH) associated with canine filariasis, followed by syncope due to bradyarrhythmia 1 year later. Materials and Methods: An 8-year-old male English Cocker Spaniel was referred to our hospital for a second opinion regarding syncope that the dog had started experiencing approximately 2 months prior. Based on the examination findings, we diagnosed that the fainting was due to heartworm disease and associated PH. After increasing the dose of pimobendan (0.50 mg/kg, q12h), the syncope subsided. However, syncope recurred on the 215th day of the first episode. Results: The findings that differed from those during the initial examination were that cardiac arrest was observed for approximately 5 sec during auscultation, along with sinus arrest. Therefore, to further investigate for syncope, a Holter electrocardiograph was obtained for 3 days. Consequently, sinus arrest was identified as the etiology of the recurrent syncope, and the patient was diagnosed with sick sinus syndrome, Rubenstein classification type II. Following cilostazol (10 mg/kg, q12h) administration, the syncope subsided. Conclusion: This case reports syncope in a dog, which typically occurs due to different etiologies. When a dog has PH, it may be important to think about the possibility of arrhythmias caused by a bigger right heart.

A phenotype-based forward genetic screen identifies Dnajb6 as a sick sinus syndrome gene.

Previously we showed the generation of a protein trap library made with the gene-break transposon (GBT) in zebrafish (Danio rerio) that could be used to facilitate novel functional genome annotation towards understanding molecular underpinnings of human diseases (Ichino et al, 2020). Here, we report a significant application of this library for discovering essential genes for heart rhythm disorders such as sick sinus syndrome (SSS). SSS is a group of heart rhythm disorders caused by malfunction of the sinus node, the heart's primary pacemaker. Partially owing to its aging-associated phenotypic manifestation and low expressivity, molecular mechanisms of SSS remain difficult to decipher. From 609 GBT lines screened, we generated a collection of 35 zebrafish insertional cardiac (ZIC) mutants in which each mutant traps a gene with cardiac expression. We further employed electrocardiographic measurements to screen these 35 ZIC lines and identified three GBT mutants with SSS-like phenotypes. More detailed functional studies on one of the arrhythmogenic mutants, GBT411, in both zebrafish and mouse models unveiled Dnajb6 as a novel SSS causative gene with a unique expression pattern within the subpopulation of sinus node pacemaker cells that partially overlaps with the expression of hyperpolarization activated cyclic nucleotide gated channel 4 (HCN4), supporting heterogeneity of the cardiac pacemaker cells.

Cardiogenic cerebral embolism due to sinus arrest associated with coronary intervention for the right coronary artery: A case report.

Percutaneous coronary artery intervention (PCI) carries the risk of occlusion of the sinus node branch (SNB) which can lead to sinus arrest (SA). Generally, PCI-related SA recovers spontaneously, with a favorable clinical course. Herein, we describe a case of SNB occlusion after PCI for the right coronary artery which resulted in SA, subsequent left atrial appendage thrombus, and cardiogenic cerebral embolism (CE). Ultimately, the patient died due to cardiogenic CE. We report on the mechanism of intracardiac thrombus formation and discuss CE prevention strategies after PCI. Based on our experience, the possibility of adverse events due to PCI-induced SA must be considered, although PCI-induced SA is generally expected to resolve. .

Successful cerebral intravascular thrombectomy stops the heart stopping.

A 65-year-old man presented with an acute ischaemic stroke due to right posterior cerebral artery occlusion, complicated by episodes of sinus arrest in the absence of intrinsic cardiac disease. His neurological deficits and sinus node dysfunction resolved following mechanical thrombectomy. We believe this to be a novel case where thrombectomy resulted in successful treatment of cerebral ischaemia mediated cardiac autonomic dysfunction.

Sinus Arrest in Asymptomatic COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) is a viral respiratory tract syndrome capable of affecting a multitude of major organs in the human body. It is a known cause of severe vascular compromise, myocardial ischemia, myocarditis, and various cardiac dysrhythmias. Dysfunction of the sinoatrial (SA) node, the primary pacemaker of the heart, can arise from structural heart disease, medications, electrolyte abnormalities, and hypothyroidism. We report and discuss a case of a 50-year-old female with no significant past medical history (PMH) and no SA dysfunction risk factors, who experienced multiple syncopal events and an episode of sinus arrest characterized by transient asystole captured with telemetry monitoring. The patient was incidentally found to be COVID-19 positive and displayed no signs or symptoms concerning the viral illness. Despite our patient's lack of respiratory issues or other symptomatology, a significant and potentially fatal relationship exists between her viral infection and cardiac sequelae.