Initiating Home Parenteral Nutrition Therapy in a Patient at High Risk of Refeeding Syndrome After COVID-19 Infection

Background: An emerging finding about COVID-19 is its effect on nutrition and weight loss. The COVID-19 symptoms of fatigue, altered taste or smell, and lack of appetite are well known. But COVID-19 may have a more profound effect on clinical nutrition status. Two recent studies have identified that approximately one-third of ambulatory COVID-19 patients are at risk of experiencing weight loss >= 5% (Anker, et al;di Filippo, et al). The case study presented here discusses home start total parenteral nutrition (TPN) in a patient recently diagnosed with COVID-19 at high risk for refeeding syndrome. Method(s): N/A Results: Case Study: A 92-year-old patient was diagnosed with COVID-19 on June 8, 2022. Over the next week, she was hospitalized twice to manage symptoms of acute mental status changes, lethargy, aphasia, hypotension, and loss of appetite. The patient received nirmatrelvir/ritonavir, remdesivir, and bebtelovimab to treat COVID-19 at different times between June 9, 2022, and June 18, 2022. She remained COVID positive and continued to deteriorate clinically. On June 20, 2022, the patient began receiving 24/7 homecare, including intravenous (IV) fluids of dextrose 5% in normal saline (D5NS) 1000 mL daily for three days. She continued to experience loss of appetite and had no bowel movement for 3 days. On June 23, 2022, she was referred to this specialty infusion provider to initiate TPN therapy in the home setting. The patient's BMI was 18.2 kg/m2. Lab results revealed potassium 3.0 mmol/L, phosphate 1.6 mg/dL, and magnesium 1.6 mg/dL. High risk of refeeding syndrome was identified by the level of hypophosphatemia and hypokalemia. The specialty infusion provider's registered dietitian recommended to discontinue D5NS and begin NS with added potassium, phosphate, and magnesium. Thiamine 200mg daily was added to prevent Wernicke's encephalopathy. The patient's clinical status and lab values were monitored closely each day until her electrolyte levels stabilized (Table 1). Home TPN therapy was initiated on June 28, 2022, with <10% dextrose and 50% calorie requirement with 85% protein and 1.0 g/kg lipids. Three-day calorie count and nutrition education were performed four days post TPN initiation. Oral intake met only 25% of estimated needs. Over several days, theTPN formula was gradually increased to goal calories and the infusion cycle was slowly decreased. The following week, the patient's oral intake improved to 60%-75% of estimated needs. Her constipation resolved, and she showed improvement in functional status and mobility. Her appetite drastically improved when the TPN was cycled. Another three-day calorie count was performed when TPN calories reached goals. Oral intake demonstrated 100% estimated calorie and protein needs. TPN therapy was ultimately discontinued on July 14, 2022. As of September 30, 2022, the patient has stabilized at her pre-COVID weight of 45 kg with full recovery of appetite, function, and cognition. Discussion(s): The ASPEN Consensus Recommendations for Refeeding Syndrome (da Silva, et al) describe the repletion of electrolyte levels before introducing calories to prevent end-organ damage associated with refeeding syndrome (respiratory muscle dysfunction, decreased cardiac contractility, cardiac arrhythmias, and encephalopathy). Conclusion(s): This case study highlights the successful initiation of home TPN therapy in a patient at high risk of refeeding syndrome post COVID-19 infection. Although home start TPN and the risk of refeeding syndrome are not new concepts, they must be considered in the setting of COVID-19. Given the effects COVID-19 has on taste, smell, and appetite and the recent finding that one-third of patients with COVID infection may experience weight loss of >= 5%, nutrition support and patient education are vital components of overall patient care. (Figure Presented).

The Effect Of Rhabdomyomas On Underlying Cardiomyopathy: A Case Report

Case Presentation: Term male infant born to SARS-CoV-2 positive mother with infant testing negative. ECG for perinatal bradycardia revealed ventricular pre-excitation. Echocardiogram showed asymmetric LV hypertrophy with prominent trabeculations, subaortic narrowing with no pressure gradient, and normal biventricular systolic function. Rapid increase in RV pressure estimates and NT-proBNP in first week if life concerning for diastolic dysfunction. Anti-arrhythmic therapy initiated for SVT with subsequent resolution. Later, developed progressive LV dilation and systolic dysfunction. Myocardium showed regions resembling non-compaction and others concerning for infiltrative process. Cardiac MRI showed no obvious tumors, but rhabdomyomas could not be ruled out given similar appearance to myocardium. Due to worsening heart failure, everolimus therapy initiated to target potential rhabdomyomas while awaiting genetic testing for tuberous sclerosis. Subaortic narrowing and LV hypertrophy improved within days, and LV appearance became more consistent with non-compaction. Genetic testing revealed a TSC2 gene variant consistent with tuberous sclerosis. Systolic function improved, and patient discharged on afterload reduction. Echocardiogram 6 months post-discharge shows continued LV dilation and mild systolic dysfunction. Discussion(s): Although outflow obstruction and arrhythmias are common with cardiac rhabdomyomas and can cause dysfunction, our patient developed progressive dysfunction in the absence of outflow tract gradient or prolonged arrhythmia. As rhabdomyomas subsided, it became clearer that he had an underlying cardiomyopathy. We suspect that rhabdomyomas in the setting of abnormal myocardium led to abnormalities in myocardial contractility and compliance causing combined systolic and diastolic dysfunction. After complete resolution of rhabdomyomas, cardiac function has improved. However, he continues to have ventricular dilation and mild dysfunction attributable to cardiomyopathy. It is unlikely that mother's SARS-CoV-2 infection played a role as infant tested negative and clinical picture was not consistent with myocarditis.

Dynamics of global and segmental strain as a marker of right ventricular contractility recovery in patients after COVID-19 pneumonia.

Aim. To study the changes of morphological and functional right ventricular (RV) parameters depending on the severity of coronavirus infection 2019 (COVID-19) pneumonia over long-term follow-up. Material and methods. A total of 200 patients (men, 51,5%, mean age, 51,4+/-10,9 years) were examined at 2 control visits (3, 12 months after receiving two negative polymerase chain reaction tests). Patients were divided into following groups: group I (n=94) - lung tissue involvement >=50% according to inhospital chest computed tomography (chest CT), group II (n=106) - lung tissue involvement <50% according to chest CT. Results. The groups were comparable in key clinical and functional parameters 3 months after COVID-19 pneumonia. Speckle tracking echocardiography (STE) revealed a significant increase in following global longitudinal strain (LS) parameters: RV free wall endocardial LS (-22,7+/-3,2% and-24,3+/-3,8% in group I, p<0,001;-23,2+/-3,5% and-24,5+/-3,4% in group II, p<0,001), and RV endocardial LS (-21,0+/-3,1% and-22,5+/-3,7% in group I, p<0,001,-21,5+/-3,2% and-22,6+/-3,3% in group II, p=0,001). Significant increase of segmental endocardial LS was revealed in group I in the basal segments of RV free wall (-26,2+/-5,1% and-28,1+/-5,1%, p=0,004) and interventricular septum (IVS) (-16,2 [13,9;19,5]% and-17,5 [14,6;21,4]%, p=0,024), IVS middle segment (-20,3+/-4,1% and-21,5+/-4,8%, p=0,030), as well as in group II in the apical segments of RV free wall (-21,9+/-6,7% and-24,4+/-5,2%, p=0,001) and IVS (-23,7+/-4,7% and-24,9+/-4,8%, p=0,014). Conclusion. Recovery of RV function during a 12-month follow-up period in patients with both severe and moderate/mild lung involvement in COVID-19 was detected using the STE method.Copyright © 2023, Silicea-Poligraf. All rights reserved.

Dynamics of global and segmental strain as a marker of right ventricular contractility recovery in patients after COVID-19 pneumonia.

Aim. To study the changes of morphological and functional right ventricular (RV) parameters depending on the severity of coronavirus infection 2019 (COVID-19) pneumonia over long-term follow-up. Material and methods. A total of 200 patients (men, 51,5%, mean age, 51,4+/-10,9 years) were examined at 2 control visits (3, 12 months after receiving two negative polymerase chain reaction tests). Patients were divided into following groups: group I (n=94) - lung tissue involvement >=50% according to inhospital chest computed tomography (chest CT), group II (n=106) - lung tissue involvement <50% according to chest CT. Results. The groups were comparable in key clinical and functional parameters 3 months after COVID-19 pneumonia. Speckle tracking echocardiography (STE) revealed a significant increase in following global longitudinal strain (LS) parameters: RV free wall endocardial LS (-22,7+/-3,2% and-24,3+/-3,8% in group I, p<0,001;-23,2+/-3,5% and-24,5+/-3,4% in group II, p<0,001), and RV endocardial LS (-21,0+/-3,1% and-22,5+/-3,7% in group I, p<0,001,-21,5+/-3,2% and-22,6+/-3,3% in group II, p=0,001). Significant increase of segmental endocardial LS was revealed in group I in the basal segments of RV free wall (-26,2+/-5,1% and-28,1+/-5,1%, p=0,004) and interventricular septum (IVS) (-16,2 [13,9;19,5]% and-17,5 [14,6;21,4]%, p=0,024), IVS middle segment (-20,3+/-4,1% and-21,5+/-4,8%, p=0,030), as well as in group II in the apical segments of RV free wall (-21,9+/-6,7% and-24,4+/-5,2%, p=0,001) and IVS (-23,7+/-4,7% and-24,9+/-4,8%, p=0,014). Conclusion. Recovery of RV function during a 12-month follow-up period in patients with both severe and moderate/mild lung involvement in COVID-19 was detected using the STE method.Copyright © 2023, Silicea-Poligraf. All rights reserved.

Dynamics of global and segmental strain as a marker of right ventricular contractility recovery in patients after COVID-19 pneumonia.

Aim. To study the changes of morphological and functional right ventricular (RV) parameters depending on the severity of coronavirus infection 2019 (COVID-19) pneumonia over long-term follow-up. Material and methods. A total of 200 patients (men, 51,5%, mean age, 51,4+/-10,9 years) were examined at 2 control visits (3, 12 months after receiving two negative polymerase chain reaction tests). Patients were divided into following groups: group I (n=94) - lung tissue involvement >=50% according to inhospital chest computed tomography (chest CT), group II (n=106) - lung tissue involvement <50% according to chest CT. Results. The groups were comparable in key clinical and functional parameters 3 months after COVID-19 pneumonia. Speckle tracking echocardiography (STE) revealed a significant increase in following global longitudinal strain (LS) parameters: RV free wall endocardial LS (-22,7+/-3,2% and-24,3+/-3,8% in group I, p<0,001;-23,2+/-3,5% and-24,5+/-3,4% in group II, p<0,001), and RV endocardial LS (-21,0+/-3,1% and-22,5+/-3,7% in group I, p<0,001,-21,5+/-3,2% and-22,6+/-3,3% in group II, p=0,001). Significant increase of segmental endocardial LS was revealed in group I in the basal segments of RV free wall (-26,2+/-5,1% and-28,1+/-5,1%, p=0,004) and interventricular septum (IVS) (-16,2 [13,9;19,5]% and-17,5 [14,6;21,4]%, p=0,024), IVS middle segment (-20,3+/-4,1% and-21,5+/-4,8%, p=0,030), as well as in group II in the apical segments of RV free wall (-21,9+/-6,7% and-24,4+/-5,2%, p=0,001) and IVS (-23,7+/-4,7% and-24,9+/-4,8%, p=0,014). Conclusion. Recovery of RV function during a 12-month follow-up period in patients with both severe and moderate/mild lung involvement in COVID-19 was detected using the STE method.Copyright © 2023, Silicea-Poligraf. All rights reserved.

Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study.

Background: COVID-19 is associated with subclinical myocardial injury. Exogenous ketone esters acutely improve left myocardial function in healthy participants and patients with heart failure, but the effects have not been investigated in participants previously hospitalized for COVID-19. Methods: This is a randomized placebo-controlled double-blind crossover study comparing a single oral ketone ester dose of 395 mg/kg with placebo. Fasting participants were randomized to either placebo in the morning and oral ketone ester in the afternoon or vice versa. Echocardiography was performed immediately after intake of the corresponding treatment. Primary outcome was left ventricular ejection fraction (LVEF). Secondary outcomes were absolute global longitudinal strain (GLS), cardiac output and blood oxygen saturation. Linear mixed effects models were used to assess differences. Results: We included 12 participants previously hospitalized for COVID-19 with a mean (±SD) age of 60 ± 10 years. The mean time from hospitalization was 18 ± 5 months. Oral ketone esters did not increase LVEF between placebo and oral ketone ester [mean difference: -0.7% (95% CI -4.0 to 2.6%), p = 0.66], but increased GLS [1.9% (95% CI: 0.1 to 3.6%), p = 0.04] and cardiac output [1.2 L/min (95% CI: -0.1 to 2.4 L/min), p = 0.07], although non-significant. The differences in GLS remained significant after adjustment for change in heart rate (p = 0.01). There was no difference in blood oxygen saturation. Oral ketone esters increased blood ketones over time (peak level 3.1 ± 4.9 mmol/L, p < 0.01). Ketone esters increased blood insulin, c-peptide, and creatinine, and decreased glucose and FFA (all p ≤ 0.01) but did not affect glucagon, pro-BNP, or troponin I levels (all p > 0.05). Conclusion: In patients previously hospitalized with COVID-19, a single oral dose of ketone ester had no effect on LVEF, cardiac output or blood oxygen saturation, but increased GLS acutely. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT04377035.

Pathophysiological Mechanisms of Cardiac Dysfunction in Transgenic Mice with Viral Myocarditis.

Viral myocarditis is pathologically associated with RNA viruses such as coxsackievirus B3 (CVB3), or more recently, with SARS-CoV-2, but despite intensive research, clinically proven treatment is limited. Here, by use of a transgenic mouse strain (TG) containing a CVB3ΔVP0 genome we unravel virus-mediated cardiac pathophysiological processes in vivo and in vitro. Cardiac function, pathologic ECG alterations, calcium homeostasis, intracellular organization and gene expression were significantly altered in transgenic mice. A marked alteration of mitochondrial structure and gene expression indicates mitochondrial impairment potentially contributing to cardiac contractile dysfunction. An extended picture on viral myocarditis emerges that may help to develop new treatment strategies and to counter cardiac failure.

SARS-CoV-2 infection causes cardiomyocyte swelling, cardiac pericyte loss, increased permeability, and diastolic dysfunction in a hamster model

Background/Introduction: Recovered COVID-19 patients often display cardiac dysfunction, even after a relatively mild infection. Purpose: We present an in-depth physiological and histological timeline of the cardiac consequences of SARS-CoV-2 infection using a hamster model. Methods: We used several methods, including transthoracic echocardiography, RNA sequencing on in vitro cultures, and in-situ hybridization techniques, complemented with histological analysis. Results: We analysed cardiac function by echocardiography over a period of 35 dpi. Already by 14 dpi and continuing at 35 dpi, infected hamsters presented with an increased E/E', decreased MV deceleration time, and an increased isovolumetric contraction time as compared to control, indicating the presence of diastolic dysfunction. Histologically, cardiomyocytes were enlarged already by 4 dpi and remained enlarged over 5 weeks. We observed the presence of fibrin-rich microthrombi at 4 dpi, which were resolved by 14 dpi. SARS-CoV-2 RNA was present in cardiac pericytes, accompanied by reduced pericyte coverage of capillaries at 4 dpi and 14 dpi, which mostly recovered by 35 dpi. At 14 dpi, the reduced pericyte coverage coincided with increased vascular permeability, suggesting that SARS-CoV-2 infection of pericytes affects microvascular integrity. SARS-CoV-2 infection of pericytes in vitro induced the expression of genes involved in viral defence, and affected genes involved in pericyte contractility and extracellular matrix proteins. Loss of cardiac pericytes was observed in cardiac biopsies from patients recovered from SARSCoV- 2 infection. Conclusion(s): Overall, our results demonstrate that SARS-CoV-2 infection causes a phenotype similar to ischemia-reperfusion, without overt ischemia. We propose that partial occlusion by microthrombi and microvascular dilation caused by pericyte loss induces regional variations in blood flow, and results in a stiffer ;swollen' heart that shows diastolic dysfunction.

Life-threatening rhythm and conduction disorders by a child with MIS-C

Background and Aim: Cardiac involvement is seen in the majority of cases with multisystem inflammatory syndrome in children (MIS-C). Various rhythm and conduction disturbances, as well as repolarization abnormalities, have been described by more than 50% of the patients, while there are few cases with complete heart block or with asystole. Method(s): Case report Results: 8-year old girl presented with a 5-day history of fever, cough, headache, and abdominal pain. Because of the critical con-dition, with respiratory insufficiency and heart failure symptoms, the child was intubated and started on inotropic support. ECG showed complete AV-block with a ventricular rate of 75/min and with ST-T changes;echocardiography revealed dilated left ventricle with reduced contractility, CT-scan of the lungs showed bilateral pneumonia, the inflammatory markers were elevated, in combination with high troponin levels, and positive SARS-CoV2-IgG antibodies. The diagnosis MIS-C was made and treatment with immunoglobulins, antibiotics, corticosteroids, and anticoagulants was initiated. During the next 2 days, the cardiac function deteriorated further, and while still on mechanical ventilation and inotropic support, extreme bradycardia with a ventricular rate of 35/min was regis-tered, and the patient was indicated for temporary emergency pac-ing. Upon induction of anesthesia, the child became asystolic, requiring extensive resuscitation. After circulation recovery, the ECG showed nodal tachycardia with a heart rate of 140-170/min. A temporary transvenous pacemaker (PM) was inserted, and the patient was started on intravenous amiodarone which resulted in a slower ventricular rate of 70/min. 3 days later sinus rhythm was restored, with first-degree AV-block, which allowed removal of the PM 5 days after its insertion. Left ventricular dimensions were normalized and contractility remained low-normal (EF 56%). During the 6-month follow-up, the ECG and the Holter-monitoring showed sinus rhythm with first-degree AV-block. Magnetic resonance imaging (MRI) on day 15 of the hospital stay demonstrated scattered areas of myocarditis and ischemia predominantly in the left ventricle, as well as thickening of the basal septum. Six months later the MRI changes were reduced but still persistent. Conclusion(s): MIS-C can present with serious and life-threatening rhythm and conduction disturbances in children;this is why extensive cardiac monitoring is obligatory by all patients.

IDIOPATHIC TROPONEMIA AFTER TRANSCAROTID ARTERY REVASCULARIZATION

SESSION TITLE: Etiologies of Cardiovascular Disease Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Troponin level (Tnl) is usually used as confirmation of acute myocardial infarction (AMI) and is a sensitive marker. It is usually increased within 2-3 hours after AMI. In most cases, increased in Tnl is associated with symptomatic chest pain, cardiac ischemia, chronic coronary syndromes, etc. It can also be elevated in other conditions without cardiac injuries, like critical illness: COVID infection, septic shock, acute stroke and burns. CASE PRESENTATION: A 72 y/o man with history of b/l internal carotid artery (ICA) stenosis (70% in R-ICA and 80-90% in L-ICA) underwent elective left trans-carotid artery revascularization (TCAR). He was transferred to ICU after an uneventful procedure, for monitoring. His history was significant for HTN, HLD, Meniere's disease, gout, prior CVA of L-frontal lacunar and R-PICA (posterior inferior cerebellar artery). Postop vitals: BP 114/60 mmHg, HR 65, RR 16, O2 sat 98%. Tnl increased to 1.95 and then declined (normal 0 - 0.4 ng/ml). He was AAOx4, and asymptomatic. Post-op serial EKGs: normal sinus rhythm with no ST/T wave changes. Echo: EF 60%, normal biventricular size and function. LDL <70, A1C 5.9, normal TSH, no CPK elevation. Other labs: normal, No new neurological deficits. He was continued on ASA, clopidogrel, metoprolol, amlodipine and lisinopril. His hospital stay was uneventful, and he was discharged on post-op day 3. DISCUSSION: Cardiac troponin complex has its distinct subunits according to their functions: highly conserved Ca2+ binding subunit (cTnC);actomyosin ATPase inhibitory subunit and tropomyosin binding subunit. They play the pivotal role in regulating myocardial muscle contraction and relaxation and demonstrate as sensitive biomarkers for the myocardial injuries. Interestingly, there are many other causes that lead to increased cardiac troponin level without remarkable myocardial injuries or ischemia. Elevated Tnl after TCAR procedure can also be due to its surgical complication of a chance of hypoperfusion during the procedure. Our patient's surgery was uneventful. In one randomized controlled trial, it is stated that the risk of having CVA and AMI is higher in carotid endarterectomy compared to revascularization in patients with carotid artery stenosis. Our patient did not have any post-op complication, and only had an idiopathic elevation of troponin. CONCLUSIONS: The role of Tnl plays an important role in confirmation of myocardial infarction or ischemia but it can be idiopathic. Unpublished data from our institution revealed no increase in troponin s/p TCAR after uneventful procedures. This is the first reported case presenting with elevated troponin level without any pertinent positive findings (EKG changes/symptoms). Maybe in uneventful TCAR procedure troponin should not be ordered? Reference #1: Defilippi, C.R., Tocchi, M., Parmar, R.J., Rosanio, S., Abreo, G., Potter, M.A., Runge, M.S., & Uretsky, B.F. (2000). Cardiac troponin T in chest pain unit patients without ischemic electrocardiographic changes: angiographic correlates and long-term clinical outcomes. Journal of the American College of Cardiology, 35 7, 1827-34. Reference #2: Gordon AM, Homsher E, Regnier M. Regulation of contraction in striated muscle. Physiol Rev. 2000 Apr;80(2):853-924. doi: 10.1152/physrev.2000.80.2.853. PMID: 10747208. Reference #3: Brott, T.G., Hobson, R.W., Howard, G., Roubin, G.S., Clark, W.M., Brooks, W., Mackey, A., Hill, M.D., Leimgruber, P.P., Sheffet, A.J., Howard, V.J., Moore, W.S., Voeks, J., Hopkins, L.N., Cutlip, D.E., Cohen, D.J., Popma, J.J., Ferguson, R.D., Cohen, S.N., Blackshear, J.L., Silver, F.L., Mohr, J.P., Lal, B.K., & Meschia, J.F. (2010). Stenting versus endarterectomy for treatment of carotid-artery stenosis. The New England journal of medicine, 363 1, 11-23. DISCLOSURES: No relevant relationships by Moses Bachan No relevant relationships by Zin Min Htet No relevant relationships by Z nobia Khan No relevant relationships by Zin Oo

Unexplained hypoxia requiring prone ventilation in a patient with acute disseminated encephalomyelitis

Introduction: Acute Disseminated Encephalomyelitis (ADEM) is a rare, immune-mediated, demyelinating disorder of the central nervous system characterized by acute encephalopathy with neurologic deficits and MRI findings consistent with multifocal demyelination requiring immunosuppression for therapy.1,2 Patients seldom develop hypoxia during the course of the illness, requiring prone ventilation to improve oxygenation which is the first line of therapy and a proven standard of care in patients with ARDS.3,4We would like to present a case of ADEM where a patient developed unexplained hypoxia requiring prone ventilation. Case description: A 35-year-old male with no significant past medical history presented to our neuro-specialist centre with one day history of severe lower back pain associated with lower limb weakness and numbness. His symptoms, which commenced 10 days post his Covid vaccination, rapidly progressed over 2 days of hospital admission to involve right upper limb & facial weakness. MRI scan of brain and spine showed features of ADEM and pulse Methylprednisolone was initiated. CT thorax and abdomen on admission was unremarkable. He was transferred to the critical care unit in view of progressive ascending paralysis and was intubated on his 5th inpatient day due to involvement of respiratory muscles. Following 4 cycles of plasma exchange with albumin (day 6,7,9 and 10 of hospital admission), he developed unexplained hypoxic episodes which eventually resulted in sustained hypoxia, requiring 100% oxygen. Airway pressures and lung compliance were within normal range. Bedside ultrasound demonstrated good lung sliding in all lung fields and good left ventricular contractility with no evidence of right ventricular dilatation. There was no evidence of pericardial/pleural effusion. CT thorax repeated on day 9 showed no features of acute thromboembolic disease and there were no signs of lung parenchymal involvement. Formal echocardiography with bubble test showed normal heart with no evidence of patent foramen ovale. Multi-disciplinary discussions involving cardiology, respiratory, neurology teams and regional ECMO centre could not explain the enigma of impaired oxygenation. The patient responded well to 16 hours of prone ventilation on day 10 with decreasing oxygen requirements. In the subsequent 3 months of his inpatient stay, he was weaned off oxygen and was tracheostomised in view of his neurological illness. He continues to receive physiotherapy and neuro rehabilitation which had led to clinical improvement. Conclusion: The possible reason for hypoxia could be impaired tissue oxygenation post plasma exchange. However, it could be a coincidental finding and there is not much literature to explain this phenomenon and warrants further research.5.

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.

Eosinophilic Granulomatosis with Polyangiitis in a Twelve-Year-Old BoyReceiving Montelukast: A Case Report

Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystem disorder characterized by asthma, prominent peripheral blood eosinophilia, and small-vessel vasculitis. We report a case of EGPA in an adolescent with uncontrolled asthma who was receiving montelukast. Case: A 12-year-old boy who is known to have asthma and allergic rhinitis which were previously controlled on ICS, intranasal steroids, and prolonged use of montelukast for 4 years. He presented with cough and nasal blockage for 2 months. He also reported an increase in the frequency of asthma attacks and received multiple courses of systemic steroids. Subsequently, his asthma controller medications were upgraded to ICS/LABA few weeks prior to admission. His symptoms were also associated with weight loss, diarrhoea and haematochezia. He was vitally stable and maintained oxygen saturation on room air. Physical examination revealed nasal polyps, purple skin flat lesions on palms and feet (Figure1), and bilateral crackles on chest auscultation. His blood investigations were significant for leukocytosis with marked eosinophilia (11x103/uL, (51%)), high inflammatory markers and total-IgE (1975 kU/L). Initial chest XR showed bilateral interstitial thickening and small pleural effusions (Figure2). Chest CT showed centrilobular nodules and peripheral ground-glass opacities, tree-in-bud appearance with no peripheral sparing in addition to moderate pericardial effusion and bilateral mild pleural effusion (Figure3). Sinus CT showed extensive sino-nasal polyposis with pansinusitis (Figure4). Initial echocardiography showed moderate pericardial effusion with normal biventricular function. Patient was started on IV furosemide. During his hospitalization, patient developed chest pain. His serial troponin was rising and LV contractility was depressed. ECG showed ST-segment depression. Therefore, EGPA with cardiac involvement was suspected. Cardiac MR showed features of a peri-myocarditis. IVIG was commenced for suspicion of coronary artery involvement, which was later disputed by cardiac cath. He was also started on IV pulse steroids at a dose of 30 mg/kg for 3 days which resulted in dramatic decrease in troponin level, eosinophil count and CRP. Skin biopsy, which was later performed after administration of steroids, showed perivascular non-necrotizing granulomas. His ANA, ANCA and COVID-19 PCR came negative. Serum chemistries and urine microscopy were unremarkable. Patient was later started on Rituximab with significant clinical, serological and radiological (Figure5,6) improvement after 10-months of follow-up. Discussion: EGPA is rare but should be considered in children with uncontrolled asthma, eosinophilia and rhino-sinusitis. This case shows the importance of being aware that montelukast could cause EGPA, in spite of the uncertainty about its mechanism. (Figure Presented).

Two Neonates With Cyanotic Heart Disease and COVID-19

We herein describe 2 neonates with cyanotic-type congenital heart disease and COVID-19. The first case was a boy at 37 weeks of gestational age (GA) who had cyanosis (SpO2 <90%) on the second day of the birth. He was transferred to the neonatal intensive care unit (NICU) for COVID-19 patients for infection treatment following a positive COVID-19 PCR test. Finally, he had a cardiopulmonary arrest, and cardiopulmonary resuscitation failed. The second case was a boy at 38 weeks of GA. His fetal echocardiography showed a hypoplastic right ventricle with decreased contractility, an atretic tricuspid valve, a hypoplastic pulmonary valve, and a small echogenic focus in the left ventricle. He was then diagnosed with COVID-19 and treated with Kaletra. Follow-up echocardiography showed a functioning shunt, a relieved pericardial effusion, and a normal ejection fraction. He was discharged a week later in good general condition.

DON'T BLAME THE VACCINE

Background: The mRNA COVID vaccine is a rare cause of myocarditis in young patients. We describe a case of cardiogenic shock with extensive workup ruling out COVID vaccine induced myocarditis. Case: 42-year-old female who drinks 5 Monster energy drinks and 3-4 cups of coffee daily presented to the hospital with palpitations two weeks following her mRNA COVID vaccine. EKG showed atrial tachycardia with heart rates of 160 beats per minute. Adenosine and Lopressor were administered resulting in hemodynamic instability requiring norepinephrine. An echocardiogram showed dilated cardiomyopathy with ejection fraction of 15%. Right heart catheterization was performed, and the cardiac index was 1.22 L/min/m², systemic vascular resistance was 1918 dynes*sec*cm-5 and wedge pressure was 31 mm Hg. The patient was started on nitroprusside, furosemide, and milrinone drips and she began to improve. The patient was adamant the vaccine is what triggered her heart failure and extensive testing was performed to rule out COVID vaccine induced myocarditis. Workup showed normal coronary arteries and no evidence of infiltrative disease or myocarditis on cardiac MRI. The etiology was from tachycardia induced cardiomyopathy triggered by excessive stimulants and the patient had successful atrial tachycardia ablation of the right superior pulmonary vein. She was discharged on medical therapy for heart failure and advised to stop drinking energy drinks. Decision-making: Once the patient did not respond to the rate controlling agents an echocardiogram showed reduced ejection fraction. Right heart catheterization confirmed cardiogenic shock and nitroprusside and milrinone were started to help reduce afterload and improve contractility. Workup to exclude COVID induced myocarditis lead to the diagnosis of tachycardia induced cardiomyopathy and atrial tachycardia ablation was performed. Conclusion: We report a case of cardiogenic shock with workup diagnosing tachycardia induced cardiomyopathy induced from a combination of excessive monster energy drinks and coffee. She was treated successfully with afterload reduction, inotrope support, and atrial tachycardia ablation.

Preintubation echocardiographic assessment using subcostal-only view (easy) exam: A case series

INTRODUCTION/HYPOTHESIS: Induction and intubation can cause cardiovascular instability, hypoxemia, and cardiac arrest. The EASy exam is a subcostal four-chamber view (SC4C), followed by inferior vena cava (IVC) and upper lung field views performed in quick succession. The goal of this study was to evaluate the impact of single-day EASy training on management prior to induction and intubation. METHODS: EASy training consists of a combination of a web-based curriculum, live lecture, and 10 exams performed under direct supervision. The EASy protocol was performed before emergency intubation on five critically ill patients. In this case series, we describe findings and management based on the EASy phenotypes (pattern recognition). RESULTS: Five resident-obtained EASy studies were performed in the ICU for emergency intubation. Two patients had COVID-19. Three had hyperdynamic ventricles with a small left ventricular (LV) cavity size with a < 1.5cm fully collapsible IVC consistent with hypovolemia (two of which had thickened LV walls indicating likely diastolic dysfunction). These three patients received a 10 mL/kg IV fluid bolus to counteract vasodilation and decreased venous return, and were started on phenylephrine. The fourth had normal contractility and diastolic cavity size with a normal-sized collapsible IVC. The fifth patient had biventricular dilation with reduced systolic function and a plethoric IVC. For this patient, no fluid bolus was given, and a vasopressor with inotropic properties (norepinephrine) was started. Etomidate was used for induction and intubation. The mean time for completion was 3 minutes (range 2 to 4 minutes). Three studies were deemed “good” quality and two were deemed “adequate” by an attending physician proficient in critical care ultrasound. Vitals were monitored for 15 minutes post-intubation, and all patients maintained hemodynamic stability with MAP ≥ 65 mmHg. CONCLUSIONS: EASy exam aids clinical decision-making in the pre-induction and intubation period, where interventions can have deleterious and even fatal consequences.

ECHOCARDIOGRAPHIC FINDINGS IN PATIENTS UNDER MECHANICAL VENTILATION WITH COVID-19 ACUTE RESPIRATORY DISTRESS SYNDROME

Coronavirus disease 2019 (COVID-19) produces a significant burden to severely ill patients affected by acute respiratory failure. The aim of this study was to describe echocardiographic findings in a series of mechanically ventilated patients with moderate and severe acute respiratory distress syndrome (ARDS) due to COVID-19. This was a single center, descriptive and cross-sectional study of prospectively collected data. Patients had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate or severe ARDS. Initial echocardiogram was performed within 7 days of intensive care unit admission and every 15 days until mechanical ventilation ended, 28 days or death. Time spent by the physician for each study was measured. Multiple echographic measurements were acquired;33 patients were analyzed. Total number of echocardiograms performed was 76. The median imaging time required to complete a standard study was 13 [10-15] minutes. Chronic structural abnormalities were present in 16 patients (48%), being LV hypertrophy the main finding in 11 patients (33%). The most frequent acute or dynamic finding was RV enlargement (43%) when considering all echocardiograms performed from admission to day 28 of follow-up. Other findings were: pulmonary hypertension (15%), new or dynamic left ventricle (LV) regional wall motion abnormalities (15%), new or dynamic LV global contractility deterioration (6%) and hypercontractility (12%).

Longitudinal myocardial mechanics in covid19 survivors with normal left ventricular ejection fraction, a single center study

Introduction: Subclinical cardiovascular involvement in COVID-19 patients has not been well described. 2D-Speckle Tracking Echocardiography derived global longitudinal strain (GLS) and systolic and early diastolic strain rate (SRs, SRe) measurements are more sensitive than standard echocardiographic parameters to diagnose subclinical mechanical dysfunction in patients with normal Left Ventricle Ejection Fraction (LVEF). Hypothesis: Evaluate subclinical myocardial mechanical function and reserve in active COVID-19 systemic disease patients with normal LVEF vs controls and between survivors and non survivors of COVID-19 in the longitudinal domain of contractility. Methods &Results: 166 adult patients with active COVID 19 having normal LVEF were included and compared to 89 healthy volunteers. Baseline parameters were recorded. Peak GLS, SRs and SRe, were measured offline. Mean age was 62.53 ± 18.96 years and 87 (52%) were males and Mean LVEF was 62±5%. COVID-19 patients had higher GLS compared to controls (-20.93%±0.30 vs. -18.48%±0.40;p value <0.0001), SRs was similar (-0.97 s-1±0.10 vs. -0.98 s-1±0.02, p value 0.2528) and SRe was lower (0.85 s-1±0.0 vs. 1.05 s-1±0.02;p value <0.0001) respectively. After adjusting for age and sex, GLS, SRs and SRe was significant (p<0.001). GLS, SRs and SRe were similar in survivors vs. non survivors (p NS), both groups had elevated biomarkers (cardiac troponin, NT-pro BNP, CRP), but non survivors had higher levels (3.22±0.18 vs 3.62±0.28, p = 0.2371, 5.86±0.19 vs 7.15±0.27, p = 0.0004, 3.75±0.14 vs 4.31±0.21, p = 0.0422, 7.64±0.17 vs 8.26±0.25, p=0.0487 respectively) (Table 1). Conclusions: In our cohort, COVID-19 patients had better systolic reserve and abnormal relaxation compared to controls. There was no significant difference in strain (GLS) and strain rate (SRs &SRe) amongst survivors and non survivors in the longitudinal domain of contractility despite of higher inflammatory biomarkers in non-survivors.

Outcomes of IV Methylprednisolone monotherapy in MIS-C: is IVIG always necessary

Introduction: Multisystem inflammatory syndrome in children (MISC), or paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), is a newly described pediatric syndrome, partially overlapping with Kawasaki Disease (KD) and Macrophage Activation Syndrome. According to the literature, MIS-C requires ICU admission in 73,3% of cases, with 1.9% overall mortality. Patients may develop coronary artery anomalies (CAA), either dilatations (11,6%) or aneurysms (10,3%). Most physicians have been treating MIS-C like KD, so far. Conversely, based on our experience, since April 2020 we have been treating MIS-C patients with IV methylprednisolone (MP) as a first-tier monotherapy: herein, we present the outcome of the first 23 consecutive patients treated according to our treatment protocol. Objectives: To evaluate the outcome (ICU admission, inotropic support, coronary abnormalities) of a cohort of consecutive MIS-C patients treated with MP as first-line monotherapy. Methods: Patients satisfying the WHO preliminary case definition of MIS-C, with no need of inotropic support at admission, have been treated with fluid restriction and MP monotherapy, the dose depending on the presence/absence of myocardial involvement: if hypotension according to age, gender, and height adjusted chart, or Ejection Fraction (EF) <50%, or NT-proBNP ≥1500 pg/ml are present, the patient receives high-dose pulse IV MP 10 mg/ Kg/day for 3-5 days, otherwise low dose IV MP 2 mg/Kg/day is administered. After 48 hours, if CRP increases and/or fever persists, the treatment is intensified either with a MP dose increase or with subcutaneous Anakinra 5 mg/ Kg/day. IVIG is reserved for patients with suspected CAA at any ultrasound evaluation (defined according to American Heart Association 2017 Guidelines for KD), or presenting persistent symptoms despite defervescence and CRP reduction. We retrospectively collected and analyzed clinical data of a cohort of consecutive MIS-C patients treated with MP mono-therapy between the 1st of April and the 31st of January 2021, at Regina Margherita Children Hospital (Turin, Italy). Clinical data were retrospectively collected;as primary outcomes we considered: rate of ICU admission, rate of inotropic support need, and incidence of CAA. As secondary outcomes we evaluated: CRP halving time, MP and NT-proBNP halving time, and days between first pathological echocardiogram and EF normalization. Results: Twenty-three MIS-C patients were included. 18 patients (78,3%) showed myocardial involvement and were treated with highdose pulse MP (Group A), 4 needed anakinra due to persistent fever. 5 patients with no cardiac damage (21,7%) were treated with low dose MP (Group B), in 2 of these (40,0%) MP dose was intensified due to persistent fever. All of the patients recovered;1 (4.3%) needed ICU admission with inotropic support, 1 developed a CAA six days after MP start. Median CRP halving time was 2 days (2 days in Group A and 5 days in Group B), NT-pro-BNP halved in 3 days in Group A, while EF normalized in 4.5 days. One patient needed ICU admission and inotropic support (4.3%), 1 patient of group A developed a small coronary aneurysm (5 mm, z score 4). Conclusion: Despite some limitations, including the sample size and the absence of a control group treated with IVIG, our data suggest that early administration of MP together with fluid restriction can rapidly decrease the inflammation and restore myocardial contractility in MIS-C, considerably reducing the need of ICU admission and/or inotropic support. Encouragingly enough, the incidence of CAA in our cohort is low compared to published cohorts (4.3% vs 20%). Further studies in bigger cohorts are needed to confirm our findings.

Comprehensive Cardiotoxicity Assessment of COVID-19 Treatments Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Coronavirus disease 2019 (COVID-19) continues to spread across the globe, with numerous clinical trials underway seeking to develop and test effective COVID-19 therapies, including remdesivir. Several ongoing studies have reported hydroxychloroquine-induced cardiotoxicity, including development of torsade de pointes (TdP). Meanwhile, human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are expected to serve as a tool for assessing drug-induced cardiotoxicity, such as TdP and contraction impairment. However, the cardiotoxicity of COVID-19 treatments has not been fully assessed using hiPSC-CMs. In this study, we focused on drug repurposing with various modes of actions and examined the TdP risk associated with COVID-19 treatments using field potential using multi-electrode array system and motion analysis with hiPSC-CMs. Hydroxychloroquine induced early after depolarization, while remdesivir, favipiravir, camostat, and ivermectin had little effect on field potentials. We then analyzed electromechanical window, which is defined as the difference between field potential and contraction-relaxation durations. Hydroxychloroquine decreased electromechanical window of hiPSC-CMs in a concentration-dependent manner. In contrast, other drugs had little effect. Our data suggest that hydroxychloroquine has proarrhythmic risk and other drugs have low proarrhythmic risk. Thus, hiPSC-CMs represent a useful tool for assessing the comprehensive cardiotoxicity caused by COVID-19 treatments in nonclinical settings.