Phospholamban Mutation Leading to Recurrent Short-Coupled Polymorphic Ventricular Tachycardia and Fibrillation in Patient without Apparent Structural Heart Disease

Background Phospholamban (PLN), an inhibitor of sarcoplasmic reticulum (SR) Ca2+-ATPase, is a regulator of Ca2+ release during excitation-contraction coupling. We present a case of recurrent polymorphic ventricular tachycardia (PMVT)/ventricular fibrillation (VF) due to a PLN mutation. Case 38 year-old male presents after resuscitation following VF arrest. An ICD was implanted. Seven years later, he presented with VF storm requiring ventricular assist device support and he underwent catheter ablation of PVC triggers of VF arising from the moderator band. Because he had an ECG that was concerning for early repolarization syndrome, he was placed on quinidine and metoprolol. After an episode of VT in 2020 in the setting of COVID infection, whole genome sequencing was obtained and identified a pathogenic PLN mutation. PLN L39Ter has been associated with dilated and hypertrophic cardiomyopathy as well as sudden death. The patient has a history of normal left ventricular function and wall thickness by echocardiography. Decision-making Given the involvement of PLN on SR handling of Ca2+, flecainide may be a more effective therapy for the treatment of PMVT/VF in this patient. Conclusion PLN mutations have been associated with cardiomyopathies. This case illustrates a patient with the pathogenic PLN L39X variant with short-coupled PMVT with no imaging evidence of structural heart disease. Whether a more targeted therapy such as flecainide may be more effective in this patient remains to be determined. [Formula presented]Copyright © 2023 American College of Cardiology Foundation

BABESIA MICROTI INFECTION WITH LOW-GRADE PARASITEMIA CAUSING ARDS IN AN IMMUNOCOMPETENT PATIENT

SESSION TITLE: Unusual Critical Care SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Babesiosis can have a clinical spectrum ranging from mild illness in most cases to more severe manifestations in immunosuppressed individuals or in those with high-grade parasitemia. This patient had severe babesiosis resulting in ARDS and shock in spite of being immunocompetent and having low-grade parasitemia, making it a rare presentation. CASE PRESENTATION: A 49-year-old, previously healthy woman, was admitted with high-grade fevers. Physical exam findings were normal, except for fever (103 F). Initial lab results were significant for hemolytic anemia and thrombocytopenia. Chest radiography was normal. Other microbiology studies, including COVID-19, were negative. Empiric antibiotic therapy with piperacillin-tazobactam and doxycycline was started. Peripheral smear identified rare, minute intracellular ring forms, suspicious for babesia. IV azithromycin and oral atovaquone were started. PCR was done to confirm the diagnosis and Babesia microti DNA was detected. As peripheral smear showed parasitemia of only 1% (percentage of red blood cells infected), exchange transfusion was not considered as a treatment option. Two days after admission, worsening hemodynamic and respiratory status was noted with increasing oxygen requirements. CT chest now revealed diffuse interstitial infiltrates. ARDS ensued and the patient was intubated and started on mechanical ventilation with vasopressor support. Immunodeficiency workup was normal. In view of clinical deterioration, the antimicrobials were switched from atovaquone and azithromycin to IV clindamycin and quinidine for 14 days. After a protracted ICU stay, the patient showed gradual clinical improvement, parasitemia resolved, and she was eventually discharged to a rehabilitation facility. DISCUSSION: Babesiosis is a tick-borne infectious disease endemic to the North-East and Midwest United States. Majority of the infections are self-limited. However, in immunocompromised individuals and in those with high-grade parasitemia (>10%), it manifests as a severe illness with ARDS, severe hemolysis, or shock. Diagnosis is made by identifying parasites on thin peripheral blood smears with Giemsa/Wright stains. PCR can be used for species identification and for confirming the diagnosis in cases with low-grade parasitemia (<4%). IV azithromycin plus oral atovaquone is the preferred initial regimen and IV clindamycin plus quinidine is an alternative combination that can be used in severe infection. Red blood cell exchange transfusion can be considered in patients with high-grade parasitemia or organ failure. CONCLUSIONS: Babesiosis can very rarely cause ARDS and shock in immunocompetent patients with low-grade parasitemia. Prompt diagnosis and escalation of antimicrobial regimens to clindamycin and quinidine in such cases can lead to improved clinical outcomes. Exchange transfusion can serve as a treatment option in patients with high-grade parasitemia. Reference #1: Ord RL, Lobo CA. Human babesiosis: Pathogens, prevalence, diagnosis, and treatment. Current clinical microbiology reports. 2015 Dec;2(4):173-81. Reference #2: Ripoll JG, Rizvi MS, King RL, Daniels CE. Severe Babesia microti infection presenting as multiorgan failure in an immunocompetent host. Case Reports. 2018 May 30;2018:bcr-2018. Reference #3: Sanchez E, Vannier E, Wormser GP, Hu LT. Diagnosis, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: a review. Jama. 2016 Apr 26;315(16):1767-77. DISCLOSURES: No relevant relationships by Shankar Chhetri No relevant relationships by Vasudev Malik Daliparty No relevant relationships by Preethi Dendi No relevant relationships by samer talib

THE BIG IMPACT OF SMALL CHANGES IN NARROW THERAPEUTIC INDEX DRUGS

CASE: An 84-year-old woman with atrial fibrillation on Digoxin presented with acute onset of confusion associated with a week history of abdominal pain, vomiting, and poor fluid intake. A few days prior, Amiodarone was added to her drug regimen which included Lasix. Additionally, she received the COVID-19 booster vaccine which led to a viral-like syndrome resulting in dehydration. The patient was afebrile, normotensive, but bradycardic. EKG showed a prolonged PR interval and scooped ST segments. Labs showed hyperkalemia, pre-renal acute kidney injury (AKI), and a Digoxin level of 4.3 ng/mL (therapeutic range: 0.8-2.0 ng/mL). Digoxin and Lasix were held and Digoxin antidote, Digibind, was administered with normalizing heart rate, potassium, and clinical improvement. IMPACT/DISCUSSION: Digoxin is used to slow conduction in atrial fibrillation and increase cardiac contractility in heart failure. It inhibits the membrane sodium-potassium-adenosine triphosphatase pump (Na/K ATPase), resulting in increased cytosolic calcium and subsequent cardiac contractility and automaticity. In turn, this can also cause premature ventricular contractions and tachycardia. In the carotid sinus, increased baroreceptor firing and subsequent increased vagal tone occurs which can cause bradycardia, atrioventricular blocks, hypotension, and GI symptoms. In skeletal muscle, hyperkalemia can result due to the abundance of Na/K ATPase pumps. Digoxin has a narrow therapeutic index with serum levels easily affected by many commonly prescribed drugs by way of decreasing renal clearance, inhibiting P-glycoprotein, and inducing secondary electrolyte disturbances. That said, drug dosing should be individualized with close monitoring to avoid potentially life-threatening effects that may result with even mildly increased digoxin levels. Acute toxicity manifests as non-specific GI, and neurologic symptoms (confusion, lethargy, visual changes), hyperkalemia, and brady or tachy-arrhythmias. Treatment is with digoxin specific fragment antigen binding (Fab) antibody, Digibind, which binds digoxin, inactivating it within 6-8 hours. Postadministration, digoxin serum testing cannot distinguish free verse bound drug;therefore, drug levels remain elevated for days to weeks until the FabDigoxin complex is excreted. In the case above, the viral-like-syndrome after the booster vaccine with subsequent AKI secondary to dehydration likely precipitated Digoxin toxicity. Accompanying drug interactions of diuretics causing dehydration and hypokalemia, P-glycoprotein inhibitors (Amiodarone, Verapamil, Diltiazem, Quinidine), and ACE inhibitors can further worsen renal clearance and culminate in Digoxin toxicity. CONCLUSION: Given Digoxin's narrow therapeutic index, small clinical changes such as post COVID-19 vaccine flu-like symptoms, dehydration, and medication changes can manifest drug toxicity. Therefore, attentive monitoring of accompanying comorbidities and drug interactions is imperative at preventing catastrophic toxic effects.

COVID-19 Amyotrophic Lateral Sclerosis(ALS) Registry NCT04559009

Objective: To capture the impact of COVID-19 on ALS by creating a patient-facing observational registry. Background: This observational registry is aimed to assess the impact of COVID-19 on ALS disease trajectory to help guide future directions of care, especially the role of COVID-19 on respiratory compromise and corroborate other demographic features. Design/Methods: ALS patients, and/or caregivers invited to report demographics, COVID-19 diagnosis and treatment details via a secure registry questionnaire through a REDCap Database. Patients are recruited by open announcement/email invitations via Center for Disease Control (CDC), National ALS Registry, ALS Association (national), ALS patient support organizations, Letter to MDA, ALSA and Northeast ALS Consortium Centers as well as ClinicalTrials.gov. Results: Registered ALS patients with documented COVID-19 infection [14] completed the survey to date: 9 - males;5- females. All participants were Caucasian. Mean BMI was 26.31. 62.5% had no history of tobacco use. Concomitant ALS medications included: riluzole - 60%, edaravone -13.3%, dextromethorphan/quinidine -13.3%, no medications - 33.3 %. COVID-19 infection interrupted clinical trial participation - 20.0%. COVID-19 infection was treated at home in 73.3% while 26.7% were hospitalized. 13.3% were on NIV while 86.7% were not. Concomitant COVID-19 medications included Remdesivir - 14.3%, Azithromycin - 21.4%, Corticosteroids 28.6%, no COVID-19 directed therapies - 57.1%. All of the 26.7 % hospitalized patients were discharged home. Pre COVID-19 total ALSFRS R scores (28 to 47) changed minimally during COVID-19 (27 to 47). Conclusions: In this COVID 19 ALS Registry participants to date, there were no COVID-19 related deaths in all Caucasian, predominately riluzole treated cohort and all have returned to home care with no significant change in ALSFRS R Scores post COVID. Further recruitment is ongoing to enrich COVID-19 infected ALS patients on wider range of ALS modifying therapies and expanding spectrum of COVID-19 modifying therapies from different periods of this ongoing pandemic to define in more detail their experience.