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.

Reversible Second-Degree Heart Block Attributed to Ondansetron: A Rare Side Effect.

A primigravida at 36 weeks with gestational diabetes mellitus and hypothyroidism and no prior chronic medical illness was admitted for safe confinement. A cesarean section was required to deliver the baby with breech presentation complicated by a slow progression of labor. Asymptomatic sinus bradycardia with a heart rate of 40 per minute was observed during the induction of anesthesia. Before bupivacaine administration for spinal anesthesia, she was administered pantoprazole 40 mg and ondansetron 4 mg intravenously. ECG recording showed a type 1 Mobitz second-degree heart block. Follow-up ECG showed progression of heart block to type 2 Mobitz second-degree heart block. The second-degree heart block persisted for 16 hours, during which the patient was asymptomatic, and the ventricular rate was maintained at a range of 60-80 per minute. After normalization of rhythm, the patient was observed in the ICU. She received another dose of ondansetron 4 mg intravenously for vomiting, and the heart block recurred. The rhythm disturbance was attributed to ondansetron. Her rhythm normalized after 36 hours, and she was subsequently discharged home three days later.

Fetal bradycardia and acidosis during maternal parenteral iron: Case reports and literature review.

Iron deficiency anemia is an important problem among pregnant women, and intravenous (IV) iron infusions have been increasingly used. Whether fetal monitoring is required during infusion has been debated, with a recent guideline by Hematologists recommending against such. We report two cases of fetal bradycardia after iron isomaltoside (IIM), in women with otherwise good maternal and fetal health. Both developed dyspnea with desaturation minutes from infusion, followed by persistent fetal bradycardia. Both underwent category 1 CS, with cord arterial pH of 7.08 and 6.94 respectively. Upon literature review, only three case reports on fetal bradycardia in IV iron were identified. For older IV iron formulations, a case was reported after IV dextran test dose, while two cases after ferric gluconate were reported. For the new formulation IIM, only one case was reported so far, but in a woman with Crohn's disease and intrauterine growth restriction. IV iron in pregnancy carries risk of anaphylactic or hypersensitivity reactions, even with the newest formulations and in women with good maternal and fetal health. While rarely reported so far, fetal bradycardia is a possible consequence, commonly preceded by respiratory symptoms. Fetal monitoring should therefore be considered during infusion.

A case report of fludarabine associated ectopic atrial bradycardia and literature review of fludarabine induced bradycardia.

BACKGROUND: Fludarabine is a chemotherapeutic agent with lymphodepleting effects that is increasingly used as part of a conditioning regimen prior to allogeneic stem cell transplantation. Fludarabine is generally considered a relatively safe medication with only rare cases of cardiotoxic side effects. CASE PRESENTATION: Here, we present a case of a 30-year-old woman who was undergoing conditioning for a haploidentical cell transplantation for treatment of Fanconi anemia with a 5-day course of daily fludarabine infusion. After her second fludarabine infusion, she was noted to have ectopic atrial bradycardia that resolved with supportive therapy and completion of fludarabine infusion. CONCLUSION: We report the first case of ectopic atrial bradycardia associated with fludarabine. Although rare and transient, clinicians should recognize this rare cardiotoxic side effect of fludarabine.

Effect of Bedside Ultrasound-Guided Versus Fluoroscopy-Guided Transvenous Cardiac Temporary Pacing in Children with Bradyarrhythmia.

To compare the efficacy and safety of bedside ultrasound-guided and fluoroscopy-guided transvenous cardiac temporary pacing in the treatment of bradyarrhythmia in children. Children treated by temporary intravenous cardiac pacing from January 2016 to June 2023 in Hunan Provincial Children's Hospital were enrolled, and the characteristics and data of the cases were summarized. Patients were divided into bedside ultrasound-guided group (ultrasound group) and fluoroscopy-guided group (fluoroscopy group) according to the implantation guidance methods. The efficacy, safety, and incidence of complications in children were compared, and follow-up analysis was carried out. A total of 30 children were enrolled, including 18 males and 12 females, with a median age of 5.5 (2.9, 10.0) years and a median weight of 18.7 (12.7, 32.7) kg. The most common primary diseases were fulminant myocarditis (13/30 cases) and congenital high-grade AVB (10/30 cases). Among them, the proportion of congenital high AVB in the fluoroscopy group was significantly higher than that in the ultrasound group, and the difference was statistically significant (p = 0.007). The implantation process was successful in all 30 children. From the time of pacing decision to implantation, the median time of ultrasound group was 56 (30, 60) min and that of fluoroscopy group was 154 (78,180) min, with a statistically significant difference (P < 0.001). A total of 5 cases developed complications. There was no statistically significant difference between the two groups (P > 0.05). Compared with traditional fluoroscopic temporary pacing, bedside ultrasound-guided temporary pacing technology can effectively shorten the operation time and reduce the occurrence of complications and has become a better choice for children's emergency and critical care treatment. The right internal jugular vein is preferred for intravenous implantation.

Long-Term Incidence of Bradycardia and Pacemaker Implantations Among Cross-Country Skiers: A Cohort Study.

BACKGROUND: Bradycardia is more common among well-trained athletes than in the general population, but the association with pacemaker implantations is less known. We investigated associations of endurance training with incidence of bradycardia and pacemaker implantations, including sex differences and long-term outcome, in a cohort of endurance trained individuals. METHODS: All Swedish skiers who completed >1 race in the cross-country skiing event Vasaloppet between 1989 and 2011 (n=209 108) and a sample of 532 290 nonskiers were followed until first event of bradycardia, pacemaker implantation, or death, depending on end point. The Swedish National Patient Register was used to obtain diagnoses. Cox regression was used to investigate associations of number of completed races and finishing time in Vasaloppet with incidence of bradycardia and pacemaker implantations. In addition, Cox regression was used to investigate associations of pacemaker implantations with death in skiers and nonskiers. RESULTS: Male skiers had a higher incidence of bradycardia (adjusted hazard ratio [aHR], 1.19 [95% CI, 1.05-1.34]) and pacemaker implantations (aHR, 1.17 [95% CI, 1.04-1.31]) compared with male nonskiers. Those who completed the most races and had the best performances exhibited the highest incidence. For female skiers in Vasaloppet, the incidence of bradycardia (aHR, 0.98 [95% CI, 0.75-1.30]) and pacemaker implantations (aHR, 0.98 [95% CI, 0.75-1.29]) was not different from that of female nonskiers. The indication for pacemaker differed between skiers and nonskiers, with sick sinus syndrome more common in the former and third-degree atrioventricular block in the latter. Skiers had lower overall mortality rates than nonskiers (aHR, 0.16 [95% CI, 0.15-0.17]). There were no differences in mortality rates by pacemaker status among skiers. CONCLUSIONS: In this study, male endurance skiers had a higher incidence of bradycardia and pacemaker implantations compared with nonskiers, a pattern not seen in women. Among male skiers, those who completed the most races and had the fastest finishing times had the highest incidence of bradycardia and pacemaker implantations. Within each group, mortality rates did not differ in relation to pacemaker status. These findings suggest that bradycardia associated with training leads to a higher risk for pacemaker implantation without a detrimental effect on mortality risk.

Newborn heart rate monitoring methods at birth and clinical outcomes: A systematic review.

Aim: Compare heart rate assessment methods in the delivery room on newborn clinical outcomes. Methods: A search of Medline, SCOPUS, CINAHL and Cochrane was conducted between January 1, 1946, to until August 16, 2023. (CRD 42021283438) Study Selection was based on predetermined criteria. Reviewers independently extracted data, appraised risk of bias and assessed certainty of evidence. Results: Two randomized controlled trials involving 91 newborns and 1 nonrandomized study involving 632 newborns comparing electrocardiogram (ECG) to auscultation plus pulse oximetry were included. No studies were found that compared any other heart rate measurement methods and reported clinical outcomes. There was no difference between the ECG and control group for duration of positive pressure ventilation, time to heart rate ≥ 100 beats per minute, epinephrine use or death before discharge. In the randomized studies, there was no difference in rate of tracheal intubation [RR 1.34, 95% CI (0.69-2.59)]. No participants received chest compressions. In the nonrandomized study, fewer infants were intubated in the ECG group [RR 0.75, 95% CI (0.62-0.90)]; however, for chest compressions, benefit or harm could not be excluded. [RR 2.14, 95% (CI 0.98-4.70)]. Conclusion: There is insufficient evidence to ascertain clinical benefits or harms associated with the use of ECG versus pulse oximetry plus auscultation for heart rate assessment in newborns in the delivery room.

Early bolus epinephrine administration during pediatric cardiopulmonary resuscitation for bradycardia with poor perfusion: an ICU-resuscitation study.

BACKGROUND: Half of pediatric in-hospital cardiopulmonary resuscitation (CPR) events have an initial rhythm of non-pulseless bradycardia with poor perfusion. Our study objectives were to leverage granular data from the ICU-RESUScitation (ICU-RESUS) trial to: (1) determine the association of early epinephrine administration with survival outcomes in children receiving CPR for bradycardia with poor perfusion; and (2) describe the incidence and time course of the development of pulselessness. METHODS: Prespecified secondary analysis of ICU-RESUS, a multicenter cluster randomized trial of children (< 19 years) receiving CPR in 18 intensive care units in the United States. Index events (October 2016-March 2021) lasting ≥ 2 min with a documented initial rhythm of bradycardia with poor perfusion were included. Associations between early epinephrine (first 2 min of CPR) and outcomes were evaluated with Poisson multivariable regression controlling for a priori pre-arrest characteristics. Among patients with arterial lines, intra-arrest blood pressure waveforms were reviewed to determine presence of a pulse during CPR interruptions. The temporal nature of progression to pulselessness was described and outcomes were compared between patients according to subsequent pulselessness status. RESULTS: Of 452 eligible subjects, 322 (71%) received early epinephrine. The early epinephrine group had higher pre-arrest severity of illness and vasoactive-inotrope scores. Early epinephrine was not associated with survival to discharge (aRR 0.97, 95%CI 0.82, 1.14) or survival with favorable neurologic outcome (aRR 0.99, 95%CI 0.82, 1.18). Among 186 patients with invasive blood pressure waveforms, 118 (63%) had at least 1 period of pulselessness during the first 10 min of CPR; 86 (46%) by 2 min and 100 (54%) by 3 min. Sustained return of spontaneous circulation was highest after bradycardia with poor perfusion (84%) compared to bradycardia with poor perfusion progressing to pulselessness (43%) and bradycardia with poor perfusion progressing to pulselessness followed by return to bradycardia with poor perfusion (62%) (p < 0.001). CONCLUSIONS: In this cohort of pediatric CPR events with an initial rhythm of bradycardia with poor perfusion, we failed to identify an association between early bolus epinephrine and outcomes when controlling for illness severity. Most children receiving CPR for bradycardia with poor perfusion developed subsequent pulselessness, 46% within 2 min of CPR onset.

Severe Bradycardia Associated with the Use of Terlipressin: A Case Report.

Introduction: Although terlipressin is known to cause bradycardia, this adverse effect is usually described in association with hypertension and is considered a benign compensatory response mediated by arterial baroreceptors. Cardiac monitoring for patients receiving terlipressin is not routinely recommended. Case Presentation: A 77-year-old female patient with no history of coronary artery disease and no other coexisting risk factors for cardiac arrhythmias or conduction disturbances was admitted to intensive care unit with severe cholangitis, complicated by variceal bleeding. She developed severe sinus bradycardia following the use of terlipressin, which was associated with significant hypotension that required the infusion of norepinephrine. The bradycardia occurred again when terlipressin therapy was reattempted. Conclusion: Vasopressin is known to sensitize baroreceptor reflexes by a central mechanism though its actions on V1a receptors in the area postrema, and we speculate that vasopressin analogues such as terlipressin may act in the same manner. That this effect is not widely described in terlipressin safety literature may be due to the overall younger age range of the trial population. This raises the possibility that cardiac monitoring may be warranted for elderly patients receiving terlipressin.

Non-Surgical Bleeding and Transurethral Resection of the Prostate (TURP) Syndrome after TURP Surgery: A Case Report and Literature Review.

Patients undergoing transurethral resection of the prostate (TURP) surgery can develop TURP syndrome and post-TURP bleeding. Post-TURP bleeding can be surgical, from arteries or venous sinuses, or non-surgical, due to coagulopathy preventing clot formation. Non-surgical post-TURP bleeding may be due to high concentrations of urokinase and tissue plasminogen activator (tPA) in the urine that cause fibrinolytic changes and increase bleeding risk. Urine urokinase and tPA may have both local and systemic fibrinolytic effects that may prevent blood clot formation locally at the site of surgery, and cause fibrinolytic changes systemically through leaking into the blood stream. Another post-TURP complication that may happen is TURP syndrome, due to absorption of hypotonic glycine fluid through the prostatic venous plexus. TURP syndrome may present with hyponatremia, bradycardia, and hypotension, which may be preceded by hypertension. In this case report, we had a patient with benign prostatic hyperplasia (BPH) who developed both TURP syndrome and non-surgical post-TURP bleeding. These complications were transient for one day after surgery. The local effect of urine urokinase and tPA explains the non-surgical bleeding after TURP by preventing clot formation and inducing bleeding. Coagulation studies showed fibrinolytic changes that may be explained by urokinase and tPA leakage into the blood stream. In conclusion, non-surgical bleeding after TURP can be explained by the presence of fibrinolytic agents in the urine, including urokinase and tPA. There is a deficiency in existing studies explaining the pathophysiology of the fibrinolytic changes and risk of bleeding after TURP. Herein, we discuss the possible pathophysiology of developing fibrinolytic changes after TURP. More research effort should be directed to explore this area to investigate the appropriate medications to treat and prevent post-TURP bleeding. We suggest monitoring patients' coagulation profiles and electrolytes after TURP because of the risk of developing severe acute hyponatremia, TURP syndrome, fibrinolytic changes, and non-surgical bleeding. In our review of the literature, we discuss current clinical trials testing the use of an antifibrinolytic agent, Tranexamic acid, locally in the irrigation fluid or systemically to prevent post-TURP bleeding by antagonizing the fibrinolytic activity of urine urokinase and tPA.

Uterine sacrifice in obstetric emergencies case series: Complex cases of fetal distress, labor challenges, and life-saving interventions.

This study highlights the complexities and challenges in managing obstetric emergencies, detailing critical interventions and outcomes in various high-risk cases. A retrospective analysis was conducted on four high-risk obstetric cases, each characterized by distinct complications necessitating immediate medical interventions. The study specifically examined cases involving: Fetal Distress cases where fetal health was compromised, necessitating interventions such as emergency cesarean sections. Complex Labor Dynamics detailed examinations of labor complications such as obstructed labor, precipitate labor, or labor complicated by malpresentation. Early pregnancy complications analysis focused on emergencies arising in the first trimester or early second trimester, including ectopic pregnancies and complications in pregnancies with a history of multiple cesarean sections. Severe postpartum hemorrhage investigations into cases of significant blood loss post-delivery, which required interventions ranging from pharmacological management to surgical procedures like hysterectomy. The first case concerned a 28-year-old primigravida with fetal bradycardia and thick meconium, requiring an emergency cesarean section. Postoperative complications included gestational thrombocytopenia and anemia, necessitating a total abdominal hysterectomy for severe sepsis. The newborn showed good recovery, indicated by Apgar scores. In Case 2, the need for a hysterectomy following complications during the third stage of labor was likely due to the presence of Placenta Accreta Spectrum, specifically placenta accreta or increta. While a retained placenta typically can be managed with less invasive methods, the situation escalates when the placenta is abnormally adherent to, or deeply invasive into, the uterine muscle. This can lead to uncontrollable bleeding, making a hysterectomy necessary and justified as a life-saving measure to control the severe hemorrhage while the histology confirms the diagnosis for the placenta accreta. In the third case, the decision to perform a dilation and curettage over manual vacuum aspiration was influenced by several factors. Given the severity of the patient's hemorrhage and the presence of a suspicious echogenic structure, a dilation and curettage provided a more controlled environment for thorough evacuation and immediate bleeding control. This approach was also supported by the combination technique using both Karman aspiration and a curette, allowing for effective management of complicated cases, particularly in patients with a history of multiple cesareans and potential scar tissue. The fourth case involved a 37-year-old multipara with severe postpartum hemorrhage from uterine atony, treated with surgery and managed for diabetic ketoacidosis, leading to discharge on the fourth day. This underscores the urgency and complexity of managing obstetric emergencies effectively.

Favipiravir-induced bradycardia: A case report.

Key Clinical Message: The purpose of this case report is to reveal one of the cardiovascular side effects of favipiravir, sinus bradycardia. Abstract: Favipiravir has emerged as a potential treatment for COVID-19, with its antiviral properties showing promise in inhibiting viral replication. However, concerns regarding its safety profile, particularly its cardiac adverse effects, remain a subject of debate. We present the case of a 58-year-old man with a history of diabetes mellitus and chronic obstructive pulmonary disease who developed bradycardia following treatment with favipiravir for COVID-19 pneumonia. Despite being asymptomatic, the patient exhibited sinus bradycardia, which resolved upon discontinuation of favipiravir. Favipiravir has been associated with QT prolongation and sinus bradycardia, though the exact mechanisms remain unclear. Our case adds to the growing body of evidence highlighting the potential cardiac complications of favipiravir therapy in COVID-19 patients. Further research is warranted to clarify the underlying mechanisms and optimize patient management strategies. Clinicians should be cautious for cardiac adverse events when prescribing favipiravir for COVID-19 treatment, especially in patients with preexisting cardiac conditions. Continued research is essential to ensure the safe and effective use of favipiravir in the management of COVID-19.

Chronic clinical performance of a novel subxiphoidal pacemaker system: Early feasibility study design.

BACKGROUND: Extravascular and leadless pacemakers are a new class of cardiac devices that may reduce the rate of complications common to traditional cardiac pacemakers with intracardiac leads. These devices also have the potential of expanding access to cardiac pacing therapy by simplifying the complexity and cost of implantation. The objective of this study is to evaluate the implantation, chronic safety, and performance of a novel subxiphoidal pacemaker. METHODS: This study is an open-label, non-randomized, early feasibility study. Ten patients indicated for implantation of a single-chamber ventricular pacemaker will be enrolled and implanted with the investigational device. The pacemaker will be inserted underneath the ribcage and clipped to the xiphoid process, with stimulation electrodes positioned on the cardiac pericardium. Patients will be programmed to chronic pacing; pacing capture threshold, sensing amplitude, and lead impedance will be measured at implant and regularly scheduled follow-up visits. 24-h Holter ECG and cardiac troponin will also be periodically measured. Adverse events will be recorded throughout the study period. CONCLUSION: This study is designed to assess the feasibility, safety, and chronic performance of a novel extravascular pacemaker, and will provide valuable data on whether this device has the potential to be a viable alternative to conventional pacemakers.

Neuronavigation assisted percutaneous balloon compression of the gasserian ganglion for trigeminal neuralgia. How I do it.

BACKGROUND: Surgical treatment for trigeminal neuralgia includes percutaneous techniques, including balloon compression, first described in 1983 by Mullan and Lichtor (J Neurosurg 59(6):1007-1012, 6). METHOD: Here we present a safe and simple navigation-assisted percutaneous technique for balloon compression, which can also be used for glycerol injection. CONCLUSION: The navigation-assisted percutaneous technique for balloon compression for trigeminal neuralgia is a quick and safe treatment for patients not candidates for microvascular decompression.

Procedural and Intermediate-term Results of the Electroanatomical-guided Cardioneuroablation for the Treatment of Supra-Hisian Second- or Advanced-degree Atrioventricular Block: the PIRECNA multicentre registry.

AIMS: Prior case series showed promising results for cardioneuroablation in patients with vagally induced atrioventricular blocks (VAVBs). We aimed to examine the acute procedural characteristics and intermediate-term outcomes of electroanatomical-guided cardioneuroablation (EACNA) in patients with VAVB. METHODS AND RESULTS: This international multicentre retrospective registry included data collected from 20 centres. Patients presenting with symptomatic paroxysmal or persistent VAVB were included in the study. All patients underwent EACNA. Procedural success was defined by the acute reversal of atrioventricular blocks (AVBs) and complete abolition of atropine response. The primary outcome was occurrence of syncope and daytime second- or advanced-degree AVB on serial prolonged electrocardiogram monitoring during follow-up. A total of 130 patients underwent EACNA. Acute procedural success was achieved in 96.2% of the cases. During a median follow-up of 300 days (150, 496), the primary outcome occurred in 17/125 (14%) cases with acute procedural success (recurrence of AVB in 9 and new syncope in 8 cases). Operator experience and use of extracardiac vagal stimulation were similar for patients with and without primary outcomes. A history of atrial fibrillation, hypertension, and coronary artery disease was associated with a higher primary outcome occurrence. Only four patients with primary outcome required pacemaker placement during follow-up. CONCLUSION: This is the largest multicentre study demonstrating the feasibility of EACNA with encouraging intermediate-term outcomes in selected patients with VAVB. Studies investigating the effect on burden of daytime symptoms caused by the AVB are required to confirm these findings.

A Case of BRASH (Bradycardia, Renal Dysfunction, Atrioventricular Node Blockade, Shock, and Hyperkalemia) Syndrome Following Initiation of a Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitor and a Loop Diuretic.

BRASH (bradycardia, renal dysfunction, atrioventricular node blockade, shock, and hyperkalemia) syndrome is a recently recognized clinical process that can be fatal if not adequately and promptly treated. As such, it is important for clinicians to recognize the syndrome. This case demonstrates an example of BRASH syndrome in a 73-year-old patient with heart failure occurring after initiation of dapagliflozin, a drug not previously associated with this phenomenon in the literature. Given the increasingly appreciated clinical utility of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, prescribers must respect their potential side effects in patients with underlying comorbidities and remember the importance of re-evaluating renal function after initiation of these medications. Here, we review the pathophysiology of BRASH, the renal effects of SGLT-2 inhibitors, and the importance of educating patients on volume management and diuretic dose titration at home.

Isolated Cardiac Sarcoidosis Presenting as High-Degree Atrioventricular Block.

Isolated cardiac sarcoidosis is a rare phenomenon of systemic sarcoidosis, with presentation ranging from asymptomatic to sudden cardiac death. Controversy exists on diagnostic and therapeutic options, creating an ongoing challenge for clinicians in providing patient care. A 79-year-old male presented status post looposcopy and interval ureteral stent replacement with sinus bradycardia and high-degree atrioventricular block. A comprehensive examination was performed that conclusively ruled out common etiologies of atrioventricular block, including coronary artery disease, electrolyte abnormalities, and medications. This prompted an investigation using advanced cardiac imaging modalities that demonstrated cardiac sarcoidosis. Computed tomography of the chest was negative for lymphadenopathy or infiltrates indicative of pulmonary involvement. The lack of extracardiac manifestations, in combination with imaging findings, led to a probable diagnosis of isolated cardiac sarcoidosis. The patient underwent biventricular implantable cardioverter defibrillator placement and was started on oral corticosteroids.

Symptomatic bradycardia associated with topical brimonidine gel (Mirvaso) administration: a case report.

Background: Bradycardia can have a number of different aetiologies, including as a side effect of medications. Brimonidine is a rare, but recognized, cause of bradycardia. Brimonidine is indicated in the treatment of facial erythema in rosacea when given as topical brimonidine gel (Mirvaso). It may also be administered as eye drops for raised intraocular pressure in open-angle glaucoma and ocular hypertension. Brimonidine is an alpha-2 agonist, which if systemically absorbed can present with bradycardia, hypotension, and dizziness. The authors are unaware of any other case reports regarding topical administration of Mirvaso in an adult and symptomatic bradycardia. Case summary: We present the case of a 78-year-old man with a background of rosacea, benign prostatic hyperplasia, and hypertension who had two separate admissions with symptomatic bradycardia. Electrocardiograms showed sinus bradycardia with AV block first degree, with rate recorded as low as 31 b.p.m. during a syncopal episode. These episodes of symptomatic bradycardia were intermittent and had a temporal association with topical administration of Mirvaso. He had no further episodes of bradycardia on discontinuation of Mirvaso and has remained symptom free for over 6 months. Discussion: The topical administration of Mirvaso should be avoided to broken or inflamed skin. This is owing to the increased risk of systemic absorption, which as in this case report, may present with bradycardia. This case reiterates the importance of completing a full medication history including all topical and parenteral medications in patients with arrhythmia.

Embryonic Exposure to Organophosphate Flame Retardants (OPFRs) Differentially Induces Cardiotoxicity in Rare Minnow (Gobiocypris rarus).

Organophosphorus flame retardants (OPFRs) such as triphenyl phosphate (TPHP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) were reported to impair cardiac function in fish. However, limited information is available regarding their cardiotoxic mechanisms. Using rare minnow (Gobiocypris rarus) as a model, we found that both TPHP and TDCIPP exposures decreased heart rate at 96 h postfertilization (hpf) in embryos. Atropine (an mAChR antagonist) can significantly attenuate the bradycardia caused by TPHP, but only marginally attenuated in TDCIPP treatment, suggesting that TDCIPP-induced bradycardia is independent of mAChR. Unlike TDCIPP, although TPHP-induced bradycardia could be reversed by transferring larvae to a clean medium, the inhibitory effect of AChE activity persisted compared to 96 hpf, indicating the existence of other bradycardia regulatory mechanisms. Transcriptome profiling revealed cardiotoxicity-related pathways in treatments at 24 and 72 hpf in embryos/larvae. Similar transcriptional alterations were also confirmed in the hearts of adult fish. Further studies verified that TPHP and TDCIPP can interfere with Na+/Ca2+ transport and lead to disorders of cardiac excitation-contraction coupling in larvae. Our findings provide useful clues for unveiling the differential cardiotoxic mechanisms of OPFRs and identifying abnormal Na+/Ca2+ transport as one of a select few known factors sufficient to impair fish cardiac function.