Cardiovascular Safety of Hydroxychloroquine-Azithromycin in 424 COVID-19 Patients.

Background and Objectives: Hydroxychloroquine (HCQ) combined with azithromycin (AZM) has been widely administered to patients with COVID-19 despite scientific controversies. In particular, the potential of prolong cardiac repolarization when using this combination has been discussed. Materials and Methods: We report a pragmatic and simple safety approach which we implemented among the first patients treated for COVID-19 in our center in early 2020. Treatment contraindications were the presence of severe structural or electrical heart disease, baseline corrected QT interval (QTc) > 500 ms, hypokalemia, or other drugs prolonging QTc that could not be interrupted. Electrocardiogram and QTc was evaluated at admission and re-evaluated after 48 h of the initial prescription. Results: Among the 424 consecutive adult patients (mean age 46.3 ± 16.1 years; 216 women), 21.5% patients were followed in conventional wards and 78.5% in a day-care unit. A total of 11 patients (2.6%) had contraindications to the HCQ-AZ combination. In the remaining 413 treated patients, there were no arrhythmic events in any patient during the 10-day treatment regimen. QTc was slightly but statistically significantly prolonged by 3.75 ± 25.4 ms after 2 days of treatment (p = 0.003). QTc prolongation was particularly observed in female outpatients <65 years old without cardiovascular disease. Ten patients (2.4%) developed QTc prolongation > 60 ms, and none had QTc > 500 ms. Conclusions: This report does not aim to contribute to knowledge of the efficacy of treating COVID-19 with HCQ-AZ. However, it shows that a simple initial assessment of patient medical history, electrocardiogram (ECG), and kalemia identifies contraindicated patients and enables the safe treatment of COVID-19 patients with HCQ-AZ. QT-prolonging anti-infective drugs can be used safely in acute life-threatening infections, provided that a strict protocol and close collaboration between infectious disease specialists and rhythmologists are applied.

Atrio-Ventricular Conduction Abnormalities in Multisystem Inflammatory Syndrome in Children

Purpose of study Since mid-April 2020 in Europe and North America, clusters of pediatric cases with a newly described severe systemic inflammatory response with shock have appeared. Patients had persistent fevers >38.5 C, hypotension, features of myocardial dysfunction, coagulopathy, gastrointestinal symptoms, rash, and elevated inflammatory markers without other causes of infection. The World Health Organization, Centers for Disease Control, and Royal College of Paediatrics associated these symptoms with SARS-CoV-2 as multisystem inflammatory syndrome in children (MIS-C). Cardiac manifestations include coronary artery aneurysms, left ventricular systolic dysfunction evidenced by elevation of troponin-T (TnT) and pro-B-type naturietic peptide (proBNP), and electrocardiogram (ECG) abnormalities. We report the clinical course of three children with MIS-C while focusing on the unique atrioventricular (AV) conduction abnormalities. Case #1:19-year-old previously healthy Hispanic male presented with abdominal pain, fever, and non-bloody diarrhea for three days. He was febrile and hypotensive (80/47 mmHg) requiring fluid resuscitation. Symptoms, lab findings, and a positive COVID-19 antibody test were consistent with MIS-C. Methylprednisolone, intravenous immunoglobulin (IVIG), and enoxaparin were started. He required epinephrine for shock and high flow nasal cannula for respiratory distress. Initial echocardiogram demonstrated a left ventricular ejection fraction (LVEF) of 40% with normal appearing coronaries. Troponin and proBNP were 0.41 ng/mL and proBNP 15,301 pg/mL respectively. ECG showed an incomplete right bundle branch block. He eventually became bradycardic to the 30s-50s and cardiac tracing revealed a complete AV block (figure 1a). Isoproterenol, a B1 receptor agonist, supported the severe bradycardia until the patient progressed to a type 2 second degree AV block (figure 1b). A second dose of IVIG was administered improving the rhythm to a type 1 second degree AV block. An IL-6 inhibitor, tocilizumab was given as the rhythm would not improve, and the patient soon converted to a first-degree AV block. Cardiac magnetic resonance imaging showed septal predominant left ventricular hypertrophy and subepicardial enhancement along the basal inferior/anteroseptal walls typical for myocarditis. Case #2: 9-year-old previously healthy Hispanic male presented after three days of daily fevers, headaches, myalgias, diffuse abdominal pain, and ageusia. He was febrile, tachycardic, and hypotensive (68/39 mmHg). Hypotension of 50s/20s mmHg required 3 normal saline boluses of 20 ml/kg and initiation of an epinephrine drip. Severe hypoxia required endotracheal intubation. After the MIS-C diagnosis was made, he was treated with IVIG, mehtylprednisolone, enoxaparin, aspirin, and ceftriaxone. Due to elevated inflammatory markers by day 4 and patient's illness severity, a 7-day course of anakinra was initiated. Initial echocardiogram showed mild tricuspid and mitral regurgitation with a LVEF of 35-40%. Despite anti-inflammatory therapy, troponin and proBNP were 0.33 ng/mL and BNP of 25,335 pg/mL. A second echocardiogram confirmed poor function so milrinone was started. Only, after two doses of anakinra, LVEF soon normalized. Despite that, he progressively became bradycardic to the 50's. QTc was prolonged to 545 ms and worsened to a max of 592 ms. The aforementioned therapies were continued, and the bradycardia and QTc improved to 405 ms. Patient #3: 9-year-old African American male presented with four days of right sided abdominal pain, constipation, and non-bilious non-bloody emesis. He had a negative COVID test and unremarkable ultrasound of the appendix days prior. His history, elevated inflammatory markers, and positive COVID- 19 antibody were indicative of MIS-C. He was started on the appropriate medication regimen. Initial ECG showed sinus rhythm with normal intervals and echocardiogram was unremarkable. Repeat imaging by day three showed a decreased LVEF of 50%. ECG had since changed to a right bundle branch block. Anakinra as started and steroid dosing was increased. By day 5, he became bradycardic to the 50s and progressed to a junctional cardiac rhythm. Cardiac function normalized by day 7, and anakinra was subsequently stopped. Thereafter, heart rates ranged from 38-48 bpm requiring transfer to the pediatric cardiac intensive care unit for better monitoring and potential isoproterenol infusion. He remained well perfused, with continued medical management, heart rates improved. Methods used Retrospective Chart Review. Summary of results Non-specific T-wave, ST segment changes, and premature atrial or ventricular beats are the most often noted ECG anomalies. All patients initially had normal ECGs but developed bradycardia followed by either PR prolongation or QTc elongation. Two had mild LVEF dysfunction prior to developing third degree heart block and/or a junctional escape rhythm;one had moderate LVEF dysfunction that normalized before developing a prolonged QTc. Inflammatory and cardiac markers along with coagulation factors were the highest early in disease course, peak BNP occurred at approximately hospital day 3-4, and patient's typically had their lowest LVEF at day 5-6. Initial ECGs were benign with PR intervals below 200 milliseconds (ms). Collectively the length of time from initial symptom presentation till when ECG abnormalities began tended to be at day 8-9. Patients similarly developed increased QTc intervals later in the hospitalization. When comparing with the CRP and BNP trends, it appeared that the ECG changes (including PR and QTc elongation) occurred after the initial hyperinflammatory response. Conclusions Although the mechanism for COVID-19 induced heart block continues to be studied, it is suspected to be secondary to inflammation and edema of the conduction tissue. Insufficiency of the coronary arterial supply to the AV node and rest of the conduction system also seems to play a role. Although our patients had normal ECG findings, two developed bundle branch blocks prior to more complex rhythms near the peak of inflammatory marker values. Based on the premise that MIS-C is a hyperinflammatory response likely affecting conduction tissue, our group was treated with different regimens of IVIG, steroids, anakinra, and/or tocilizumab. Anakinra, being an IL-1 inhibitor, has been reported to dampen inflammation in viral myocarditis and tocilizumab has improved LVEF in rheumatoid arthritis patients. Based on our small case series, patient's with MISC can have AV nodal conduction abnormalities. The usual cocktail of IVIG and steroids helps;however, when there are more serious cases of cardiac inflammation, adjuvant immunosuppresants like anakinra and toculizumab can be beneficial. (Figure Presented).

Using Objective Electrocardiographic Data To Better Predict Mortality In Patients Hospitalized With COVID-19

Background: The impact of SARS-CoV-2 infection on intrinsic myocardial conduction continues to be an area of focus amongst the medical community. Our objective was to investigate if specific myocardial conduction abnormalities were independently associated with mortality in patients hospitalized with COVID 19. Method(s): Under IRB exemption, the electronic medical records of COVID-19 patients (N=3840) undergoing index hospitalization were reviewed to extract presentation ECG conduction data, demographics, and laboratory results (within 8h). This patient cohort was then separated into two groups based on mortality vs. no mortality (N=520). Logistical regression was used to test association of ECG conduction intervals with mortality. A subgroup analysis of 651 patients who underwent at least 1 ECG in the 12 months prior to their COVID hospitalization were analyzed to detect statistically significant differences in conduction intervals pre and post SARS-CoV-2 infection. Result(s): According to our nominal logistic fit for hospital mortality, Heart Rate (HR) >100 (p=0.0007;LW 4.14), QRS duration > 120 ms (p=0.0053;LW 2.27), and QTc prolongation (defined as QTc > 450ms in males;QTc > 460ms in females) (p=0.0089;LW 2.04) were independently associated with higher risk of mortality. LogWorth (LW) calculations were included in an effort to estimate the proportional effect each variable has on overall mortality. LW > 2 were shown to be statistically significant with p< 0.05 with HR > 100 (LW 4.14) having the highest proportional effect on mortality followed by QRSd (LW 2.27) then QTc prolongation (LW 2.04). PR interval> 200ms (p=0.30) and QRS axis (p=0.15) were not associated with higher risk of mortality. Our subgroup analysis of the 651 patients mentioned above yielded no statistically significant differences in conduction intervals pre & post SARS-CoV-2 infection. Conclusion(s): : Amongst our patient cohort, HR > 100, QRSd > 120ms, and QTc prolongation (QTc > 450 in males;QTc > 460 in females) were each independently associated with higher risk of mortality in patients hospitalized with COVID 19. Subgroup analysis of 651 patients showed no statistically significant differences in conduction intervals pre and post SARS-CoV-2 infection. These findings support the use of objective ECG data in risk stratifying patients hospitalized with COVID 19.Copyright © 2022

The natural history of QTc interval and its clinical impact in coronavirus disease 2019 survivors after 1 year.

Background and objective: Prolonged QTc interval on admission and a higher risk of death in SARS-CoV-2 patients have been reported. The long-term clinical impact of prolonged QTc interval is unknown. This study examined the relationship in COVID-19 survivors of a prolonged QTc on admission with long-term adverse events, changes in QTc duration and its impact on 1-year prognosis, and factors associated with a prolonged QTc at follow-up. Methods: We conducted a single-center prospective cohort study of 523 SARS-CoV-2-positive patients who were alive on discharge. An electrocardiogram was taken on these patients within the first 48 h after diagnosis and before the administration of any medication with a known effect on QT interval and repeated in 421 patients 7 months after discharge. Mortality, hospital readmission, and new arrhythmia rates 1 year after discharge were reviewed. Results: Thirty-one (6.3%) survivors had a baseline prolonged QTc. They were older, had more cardiovascular risk factors, cardiac disease, and comorbidities, and higher levels of terminal pro-brain natriuretic peptide. There was no relationship between prolonged QTc on admission and the 1-year endpoint (9.8% vs. 5.5%, p = 0.212). In 84% of survivors with prolonged baseline QTc, it normalized at 7.9 ± 2.2 months. Of the survivors, 2.4% had prolonged QTc at follow-up, and this was independently associated with obesity, ischemic cardiomyopathy, chronic obstructive pulmonary disease, and cancer. Prolonged baseline QTc was not independently associated with the composite adverse event at 1 year. Conclusions: Prolonged QTc in the acute phase normalized in most COVID-19 survivors and had no clinical long-term impact. Prolonged QTc at follow-up was related to the presence of obesity and previously acquired chronic diseases and was not related to 1-year prognosis.

Tocilizumab- a Treatment Option for Torsades De Pointes in Covid-19 Patients

Background The incidence of ventricular arrhythmias (VA) in Coronavirus disease 2019 (COVID-19) patients ranges from 1.6 to 5.9%. COVID-19 can trigger a systemic inflammatory response, which may unmask arrhythmias. Here we discuss a challenging case of COVID-19 that manifested as recurrent Torsades de Pointes (TdP). Case A 39-year-old female with no known past medical history presented with a complaint of multiple syncopal episodes in the last two days. Initial electrocardiograms (EKG) showed a heart rate of 62 with frequent premature ventricular contractions (PVCs) and a prolonged corrected QT(QTc) interval of 520ms. Frequent PVCs soon converted to TdP with loss of consciousness which was managed with successful direct current cardioversion (DCCV). However, the patient relapsed into TdP, warranting another successful DCCV. COVID-19 workup came back positive. Electrolytes were within normal limits;however, C-reactive protein (CRP) and troponin T levels were elevated. Decision-making The patient was started on intravenous (IV) magnesium for 24 hours. Following another episode of self-limiting TdP, IV isoproterenol was started, and tocilizumab was given. An echocardiogram showed no evidence of structural heart disease. During the hospital course, telemetry showed PVCs that decreased in frequency paralleled with a decrease in CRP and troponins. Repeat EKGs showed normalization of QTc interval. The patient declined implantable device placement or procedures and was eventually discharged with a heart monitor and a beta blocker. On follow-up, the patient denied any symptoms since the discharge, QTc remained normal, and the heart monitor did not show any VA. Conclusion Management of TdP generally involves magnesium, IV isoproterenol, and transvenous pacing. However, as described in this case, tocilizumab can cause QT interval shortening and a reduction in CRP and cytokine levels and may be beneficial for use in COVID-19 patients with QT prolongation and VA, including TdP. There are no strict guidelines for arrhythmias in COVID-19 patients. Accordingly, more studies need to be done to follow this patient population managed with tocilizumab for their eventual outcomes.Copyright © 2023 American College of Cardiology Foundation

Electrocardiographic predictors of disease severity, mortality, and advanced ventilatory support among hospitalized covid-19 patients: a two year single center retrospective, cohort study

Introduction: For detecting myocardial injury in severe and critical COVID-19, the electrocardiogram (ECG) is neither sensitive nor specific;but in a resource-poor environment, it remains relevant. Changes in the ECG can be a potential marker of severe and critical COVID-19 to be used for predicting not only disease severity but also the prognosis for recovery. Method(s): The admitting and interval ECGs of 1,333 COVID-19 patients were reviewed in a two-year, single-center, retrospective cohort study. Each was evaluated for 29 pre-defined ECG patterns under the categories of rhythm, rate, McGinn-White and RV overload patterns, axis and QRS abnormalities, ischemia/infarct patterns, and AV blocks before univariate and multivariate regression analyses for correlation with disease severity;need for advanced ventilatory support;and in-hospital mortality. Result(s): Of the 29 ECG patterns, 18 showed a significant association with the dependent variables on univariate analysis. Multivariate analysis revealed that atrial fibrillation, HR >100 bpm, low QRS voltage, QTc >500msec, diffuse nonspecific T-wave changes, and 'any AMI' ECG patterns correlate with disease severity;need for advanced ventilatory support and in-hospital mortality. S1Q3 and S1Q3T3 increased the odds of critical disease and need for high oxygen requirement by 2.5-3 fold. Fractionated QRS increased odds of advanced ventilatory support. Conclusion(s): The ECG can be useful for predicting the severity and outcome of more than moderate COVID-19. Their use can facilitate rapid triage, predict disease trajectory, and prompt a decision to intensify therapy early in the disease to make a positive impact on clinical outcomes.

Cardiovascular Profile of patients with COVID-19 infection admitted at a tertiary hospital

Introduction: In December 2019, a novel Coronavirus disease 2019 (COVID-19) was discovered and spread rapidly worldwide. The virus spared no country in its contagiousness. The most common clinical manifestations are respiratory symptoms;but COVID-19 may induce arrhythmias, myocardial infarction, heart failure, and other cardiovascular diseases due to the systemic inflammatory response coupled with localized vascular inflammation. The study aims to provide knowledge about the clinical profile, cardiovascular complications, and clinical outcomes among adult COVID-19 patients admitted to a tertiary hospital. Method(s): This study is a single-centered cross-sectional retrospective study of hospitalized adult COVID-19 patients between March 2020 to May 2022. COVID-19 confirmed patients who met the inclusion criteria with clinical data upon hospitalization are followed up for occurrence of critical illness. The study's primary outcome is determining the demographic profile and clinical course of COVID-19 infection regarding cardiovascular signs and symptoms. Data were retrieved from electronic health records. All outcomes were obtained with standardized data collection forms, and clinical severity was defined based on the National Institute of Health guidelines. Result(s): A total of 1341 hospitalized adult COVID-19 patients were admitted with a mean age of 50.41+/-15.92 years. More males than females account for 60.2% of the total number of patients. Hypertension is the most common comorbidity among COVID-19 patients, comprising 44% of cases, followed by diabetes at 31.9% and dyslipidemia at 11.4%. About 5.4% had coronary artery disease, followed by heart disease 6 (3.6%) and arrhythmia (0.6%). Most COVID-19 patients were smokers 12% and alcoholic beverage drinkers (11.4%). A univariate analysis associated with mortality showed diabetes mellitus (odds ratio 2.7, p = 0.029) and hypertension (odds ratio 3.4, p = 0.11). In the multiple logistic regression analysis, factors' age (OR 1.095, estimate coefficient 0.091, standard error 0.028, p-value <0.05) and admission duration (OR 0.906, estimate coefficient -0.099, standard error 0.028, p-value <0.05) were significantly associated with mortality. Based on the fitted model, older people are more likely to be deceased than younger people. The log odds for mortality increase by 0.091 units for each year. During hospital admission, 24.43% of patients developed acute COVID-19 infection, with an in-hospital casefatality rate of 13.89%. During hospital stay, COVID-19 patients had a significant QTc (.43 +/- 0.04, p'0.001). Patients admitted to Non-ICU had lower QTc (.44 +/- 0.045) compared to ICU patients (.45 +/- .05). Conclusion(s): Myocardial injury and significant cardiovascular risk factors increased mortality among critically-ill COVID-19 patients. Hence, aside from risk factor modification, emphasis on cardiovascular protection should also be considered during treatment for COVID-19.

Risk factors for heart failure in patients with COVID-19.

Aim. To establish risk factors for heart failure (HF) in patients with coronavirus disease 2019 (COVID-19). Material and methods. Medical records of 151 patients treated in an infectious disease hospital from November 3, 2020 to February 2, 2021 with a confirmed diagnosis of COVID-19 were retrospectively selected. The collection of clinical, history and laboratory data were carried out by analyzing electronic medical records. We analyzed information on age, sex, body mass index, smoking, and comorbidities. Following laboratory studies were analyzed: complete blood count, biochemical blood tests, coagulation profile, acute phase proteins (C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH)), procalcitonin. The diagnosis of HF was confirmed by clinical performance, echocardiography, and elevated levels of the N-terminal pro-brain natriuretic peptide (NT-proBNP). The risk of HF was taken as the endpoint of the study. Results. The studied sample of patients was divided into two groups depending on HF: the 1st group included 46 patients with HF, the 2nd group - 105 patients without HF. The median age was 66,2 (50-92) years (women, 91 (60,3%)). Laboratory indicators, such as the levels of CRP, LDH, procalcitonin, creatinine, bilirubin, differed significantly from each other, and the median values were higher in patients with HF. The neutrophil-to-lymphocyte ratio (NLR) showed significant intergroup differences: in the group of patients with HF, the median was 4,97% vs 3,62% (p=0,011) in the group of patients without HF. There were following most significant predictors increasing the HF risk: age >=66 years (odds ratio, 8,038, p<0,001), procalcitonin level, which increases the HF risk in patients by 3,8 times (p<0,001), NLR >=4,11% (p=0,010), thrombocytopenia <=220x109/l (p=0,010), history of chronic kidney disease (CKD) (p=0,018). Conclusion. The following predictors of HF were established: age >=66 years, procalcitonin >=0,09 ng/ml, NLR >=4,11%, thrombocytopenia <=220x109/l, history of CKD, LDH >=685 U/l and creatinine >=102 micromol/l, international normalized ratio >=1,19, QTc interval >=407,5 ms, bilirubin <=10,7 micromol/l. It is worth noting that the best accuracy values are demonstrated by the Random Forest algorithm (88,5% on the validation set), but the mathematical model of the neural network turned out to be the most sensitive (90,0% on the validation set).Copyright © 2023, Silicea-Poligraf. All rights reserved.

Risk factors for heart failure in patients with COVID-19.

Aim. To establish risk factors for heart failure (HF) in patients with coronavirus disease 2019 (COVID-19). Material and methods. Medical records of 151 patients treated in an infectious disease hospital from November 3, 2020 to February 2, 2021 with a confirmed diagnosis of COVID-19 were retrospectively selected. The collection of clinical, history and laboratory data were carried out by analyzing electronic medical records. We analyzed information on age, sex, body mass index, smoking, and comorbidities. Following laboratory studies were analyzed: complete blood count, biochemical blood tests, coagulation profile, acute phase proteins (C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH)), procalcitonin. The diagnosis of HF was confirmed by clinical performance, echocardiography, and elevated levels of the N-terminal pro-brain natriuretic peptide (NT-proBNP). The risk of HF was taken as the endpoint of the study. Results. The studied sample of patients was divided into two groups depending on HF: the 1st group included 46 patients with HF, the 2nd group - 105 patients without HF. The median age was 66,2 (50-92) years (women, 91 (60,3%)). Laboratory indicators, such as the levels of CRP, LDH, procalcitonin, creatinine, bilirubin, differed significantly from each other, and the median values were higher in patients with HF. The neutrophil-to-lymphocyte ratio (NLR) showed significant intergroup differences: in the group of patients with HF, the median was 4,97% vs 3,62% (p=0,011) in the group of patients without HF. There were following most significant predictors increasing the HF risk: age >=66 years (odds ratio, 8,038, p<0,001), procalcitonin level, which increases the HF risk in patients by 3,8 times (p<0,001), NLR >=4,11% (p=0,010), thrombocytopenia <=220x109/l (p=0,010), history of chronic kidney disease (CKD) (p=0,018). Conclusion. The following predictors of HF were established: age >=66 years, procalcitonin >=0,09 ng/ml, NLR >=4,11%, thrombocytopenia <=220x109/l, history of CKD, LDH >=685 U/l and creatinine >=102 micromol/l, international normalized ratio >=1,19, QTc interval >=407,5 ms, bilirubin <=10,7 micromol/l. It is worth noting that the best accuracy values are demonstrated by the Random Forest algorithm (88,5% on the validation set), but the mathematical model of the neural network turned out to be the most sensitive (90,0% on the validation set).Copyright © 2023, Silicea-Poligraf. All rights reserved.

Whole blood drug levels do not correlate with QTc intervals in hydroxychloroquine treated systemic lupus erythematosus patients.

OBJECTIVES: Hydroxychloroquine is recommended for all patients with systemic lupus erythematous, but reports of cardiac toxicity in SARS CoV-2 patients raised concerns. We aimed to study the relationship between hydroxychloroquine blood levels and QTc intervals. METHODS: Cohort 1 is a retrospective review of 90 SLE patients with data collected regarding demographics, QTc interval and chronic kidney disease (CKD). Cohort 2 is a prospective study of 84 SLE patients with data collected regarding demographics, dose of HCQ, duration of HCQ treatment, presence of echocardiographic abnormalities, and CKD simultaneous with whole blood HCQ levels measured by high performance liquid chromatography. Statistical analysis utilized one way ANOVA, Pearson's correlation coefficient and t test. RESULTS: In the retrospective cohort there was no significant difference in mean QTc based on 75 HCQ-treated (437.91 +/- 20.02) as compared with 15 untreated (434.6 +/- 27.49) patients. In patients with CKD mean QTc in HCQ users (448 +/- 23.37) as compared with non-users (444.5 +/- 24.61) was also with no significant difference. In the prospective cohort HCQ levels did not correlate with QTc interval (r = 0.017) and this applied regardless of dose prescribed (r = 0.113 for 400 mg and r = 0.06 for 200 mg), duration of exposure (p= 0.36 for 0-5, 5-10, or > 10 years), CKD (r = 0.482) or underlying cardiac abnormalities (r = 0.430). CONCLUSION: This is the first study relying on measured blood levels demonstrating the absence of clinically consequential increase in QTc levels in HCQ treated SLE patients.

Effect Of Covid-19 Infection On Qtc Prolongation

Background Objective: What is the association between COVID-19 infection and QTc changes? Coronavirus SARS-COV2 uses angiotensin-converting enzyme receptors 2 (ACE2) on host cells to enter into human cells. These receptors are expressed on the heart cells among other major cells. This is one of the most accepted theories for direct cardiac cell injury of COVID-19disease and associated cardiorespiratory manifestations. COVID-19 infection leads to unstable myocardial cell membranes, by causing hypoxia, myocarditis, myocardial ischemia, and abnormal host immune response. This is the main reason behind Arrhythmia and EKG changes during COVID19 infection. But the specific effect on QTc has not been studied well so far, so our research try to study this connection. Method(s): This is an observational retrospective hospital chart review involving 320 adult participants diagnosed with COVID-19 infection at our facility. After applying the exclusion criteria, 130 participants remained, who were distributed into two groups. One group with long QTc and one group with normal QTc. Data was collected and demographics were recorded using Excel and SPSS, then compared using a student's t-test for independent groups. The quantitative data are summarized by the mean and standard deviation (SD). Statistical significance was taken as P <0.05. Result(s): A total of 63 participants (48.4% of total 130 participants) met the criteria for long QTc, and a total of 67 participants(51.5%) had normal QTc (P < 0.001). There was no statistically significant mortality outcome (0.8% vs. 3.8%, P = 0.21). Conclusion(s): Our study showed 48.4% participants having an increase in QTc during COVID-19 infection, (20% of 320 total admissions). This observation is very important to help healthcare providers to gaina better understanding of this disease.

Cardiac findings and short-term outcomes of multisystem inflammatory syndrome associated with COVID-19 single center experiences from turkiye

Background and Aim: Multi-system inflammatory syndrome in chil-dren (MISC) associated with COVID-19 has been described as a potentially life-threatening disease. In this study, we aimed to evaluate cardiovascular findings in children diagnosed with MISC at initial presentation and follow up. Method(s): Between November 2020 and November 2021, 35 children diagnosed with MISC based on WHO criteria were evaluated in this retrospective study.Cardiac markers, electrocardi-ography and echocardiography were performed in all cases at pre-sentation. Cardiac evaluation were repeated at the mean of 10th week after discharge(range:5 to 33weeks). Result(s): At this period, 633 children had positive PCR test of Covid-19. The freguency of MISC was 5.5% in our cohort. The median age was 9 years at diagnosis. Comorbid diseases were found in 20% cases, but none had preexisting heart disease. All patients had high grade fever and laboratory evidence of hyperin-flammation. Most cases had mild form disease, however 12 patients had been hospitalized in ICU median 6 day. 27 cases (77%) had cardiovascular involvement.Kawasaki-like findings were found in 10 patients and 5 cases were presented with shock(Figure-1) Echocardiography;Left ventricular (LV)systolic dysfunction (EFlt;57%) was detected in 11 cases (31.4%) and coronary artery (CA) dilatation(z scoregt;2)was found in five(14.2%) cases. Pericardial effusion was seen in 12 cases. Electrocardiography: Sinus tachycardia was the most common finding. 2 cases had pro-longed QTc interval and four cases had T wave alterations. Four cases had experienced complex ventricular arrhythmia. Cardiac markers:24 cases had high Pro-BNP level. 18 cases also had high Troponin T levels. Pro-BNP and Troponin T levels were not found to be correlated with LVEF. Only one adolescent boy who had severe cardiac dysfunction died during the acute period. Followup:There were two cases with persistent cardiac symptom, but no case had LV systolic dysfunction. The mean PR intervale was significantly lower than initial measurements. The mean of QT and QTc at follow up were not different from basal measurements.The mean LVEF was significantly higher than the initial levels. The basal CA z scores normalized at followup. Conclusion(s): MISC is characterized predominantly by cardio-vascular system involvement, but the children with MISC have good cardiac outcomes at short term follow up.

Cardiovascular manifestations in multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19

Background and Aim: Cardiac involvement in multisystem inflam-matory syndrome in children (MIS-C) associated with Coronavirus 2019 disease (COVID-19) is often observed with high risk of hearth failure. Early diagnosis and treatment are man-datory for a good outcome. The aim is to describe cardiovascular involvement, management and early outcome for patients with MIS-C and to analyze the differences in cardiovascular manifesta-tions between two groups: younger and older than 6 years old. Method(s): This retrospective observational study describes cardio-vascular clinical manifestations, laboratory findings, cardiac imag-ing, according to different age groups, and treatment in patients with diagnosis of MIS-C admitted to the Pediatric Istitute Giannina Gaslini between March 2020 and September 2021. Result(s): We collected 25 patients. Median age at onset of symptoms was 5 years old (interquartile range IQR, 3-12 y), 12 boys (56%). Immunoglobulin G antibodies were positive in 70% cases, Polymerase chain reaction (PCR) nasal/throat swab test for COVID-19 was positive in 15% cases, at the admission. The remaining cases had close contacts of COVID-19 positive cases. Predominant coronary artery abnormalities were observed in age group up to 6 years old (n.13) with development of small and medium aneurysms in half of cases and low rate of mild ventricular dysfunction. While children between 7-18 years of age present myopericardial involvement with ventricular dysfunction in 67% cases, from mild to moderate. Only two cases of transient coronary dilatation. Frequent electrocardiogram abnormalities: ventricular repolarization anomalies and reversibile QTc prolon-gation interval. Laboratory findings showed rised inflammatory markers and only mild elevation of cardiac enzymes compared to an early and significant NT-pro-BNP increase. All patients were treated with intravenous immunoglobulin and corticosteroids. Some cases needed anakinra. Aspirin and heparin was adminis-trated. No inotropes requied but only cardioprotective therapy. No need of Intensive Care Unit. Conclusion(s): This case-series shows the frequent cardiovascular involvement in MIS-C with a peculiar distribution, according to differents age's group: coronary artery anomalies in young ones, myopericardial disease in old ones. Prompt multi target anti-inflammatory therapy could have an effect to favorable outcome.

TIME TO SLOW DOWN: A DEEPER LOOK INTO REMDESIVIR-ASSOCIATED BRADYCARDIA

SESSION TITLE: Drug-Induced and Associated Critical Care Cases Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: The use of remdesivir in critical care setting has been utilized treatment of covid, but not without risk. Many cases have reported severe cardiac effects with bradycardia being the most common. CASE PRESENTATION: The patient was a 15-year-old female with a history of asthma, hyperinsulinemia who required hospitalization for acute hypoxic respiratory failure secondary to COVID-19 pneumonia. She received ceftriaxone, azithromycin, and a 10-day course of remdesivir (RDV). On her third day of admission, the patient developed significant sinus bradycardic with heart rate nadir of 30-40 bpm but denied any symptoms. She completed her remdesivir course on day five of hospitalization and was discharged on day nine with a heart rate of 47 bpm. She later presented to ED the night of discharge following acute onset of lightheadedness and blurry vision at home secondary to orthostatic hypotension and bradycardia. Her pulse was 48 bpm, temperature 36.1 C, respirations 24/min, blood pressure 119/50 mmHg and SpO2 99% on room air. Her physical exam was unremarkable. EKG showed sinus bradycardia with a PR interval of 124 ms and QTc of 406 ms. Echocardiogram showed normal cardiac anatomy and function. Patient was diagnosed with persistent RDV-associated bradycardia and discharged home with a Holter monitor and cardiology follow-up. Bradycardia resolved by her follow-up visit two weeks later. DISCUSSION: According to the WHO pharmacovigilance database, bradycardia is a relatively new adverse effect and 3.6% of the 2,603 adverse effects reported since the onset of the pandemic, with 2 million RDV doses administered during this time [1]. The mechanism of RDV-associated bradycardia is proposed to be an effect of adenosine triphosphate, an active metabolite, which reduces SA node automaticity via stimulation of vagal nerve, as well as RDV cross-reactivity with mRNA polymerase, leading to cardiotoxicity that usually resolves within 24 hours of medication discontinuation. In our patient's case bradycardia did not resolve until eight days after discontinuation of medication [2]. Review of previously case reports does not identify any association with patient age but could be related to timing of when medication reaches therapeutic window, as many patients had onset of bradycardia on day 3 of treatment [3]. We report a pediatric case of severe acute COVID-19 who developed sinus bradycardia on day 3 of RDV treatment as previously described, but the bradycardia persisted long after the discontinuation of RDV. CONCLUSIONS: With over 50 thousand pediatric COVID-19 hospitalizations to date, this case serves as a timely reminder that medication side effects should be monitored closely, and that more research needs to be done into the effects of RDV on cardiac function in pediatric patients. Reference #1: Jung SY, Kim MS, Li H, Lee KH, Koyanagi A, Solmi M, Kronbichler A, Dragioti E, Tizaoui K, Cargnin S, Terrazzino S, Hong SH, Abou Ghayda R, Kim NK, Chung SK, Jacob L, Salem JE, Yon DK, Lee SW, Kostev K, Kim AY, Jung JW, Choi JY, Shin JS, Park SJ, Choi SW, Ban K, Moon SH, Go YY, Shin JI, Smith L. Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database. Clin Transl Sci. 2022 Feb;15(2):501-513. doi: 10.1111/cts.13168. Epub 2021 Oct 31. PMID: 34719115;PMCID: PMC8841455. Reference #2: Touafchia A, Bagheri H, Carrié D, Durrieu G, Sommet A, Chouchana L, Montastruc F. Serious bradycardia and remdesivir for coronavirus 2019 (COVID-19): a new safety concerns. Clin Microbiol Infect. 2021 Feb 27;27(5):791.e5–8. doi: 10.1016/j.cmi.2021.02.013. Epub ahead of print. PMID: 33647441;PMCID: PMC7910147. Reference #3: Rau, Cornelius MPhil;Apostolidou, Sofia MD;Singer, Dominique MD, PhD;Avataneo, Valeria PhD;Kobbe, Robin MD Remdesivir, Sinus Bradycardia and Therapeutic Drug Monitoring in Children With Severe CO

BOOZE, BETAS, AND A FATTY SOLUTION TO SPARE PANDEMIC WOES

SESSION TITLE: Cases of Overdose, OTC, and Illegal Drug Critical Cases Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: The COVID-19 pandemic raised economic strife, social isolation, fear from contagion, and anxiety to a level where 45% of surveyed U.S. adults report a detriment to their mental health. With U.S. suicide rates up from 10 to 14 cases per 100,000 over the past 20 years, the health and safety of a vulnerable mental health population becomes more of a concern. We report a case of an individual with depression who was resuscitated after severe toxicity from alcohol and beta-blocker ingestions. CASE PRESENTATION: A 58-year-old woman with prior suicide attempts was found in an obtunded state after finishing a 20-pack of beer and swallowing a propranolol 20 mg pill bottle. On admission, she presented with bradycardia, hypotension, and alteration to a Glasgow Coma Scale of 9 with emesis residue on her face. Her blood gas revealed an anion-gap metabolic acidosis with a pH of 7.26, lactate of 2.53, normal potassium and calcium, and glucose of 134 mg/dL. Toxicity labs were notable for an alcohol of 199 mg/dL. Her EKG demonstrated a junctional bradycardia with a p-wave complex after the QRS consistent with retrograde depolarization of the atrium (Image 1). She was intubated to protect her airway. She subsequently developed cardiac arrest secondary to pulseless electrical activity. She underwent CPR for 33 minutes with boluses of intravenous epinephrine, glucagon, insulin, calcium gluconate, and sodium bicarbonate prior to return of spontaneous circulation. Due to failure of transcutaneous pacing, a transvenous pacer was placed. In concert with Poison Control, she was started on an a euglycemic insulin drip and an intralipid infusion. Her hemodynamics improved, and she was weaned off pacing and ICU interventions within 24 hours. She was discharged a week after admission with no residual morbidities. DISCUSSION: Overdose from nonselective beta-blockers can result in bradycardia, hypotension, seizures, QRS widening, QTc prolongation with ventricular tachy-arrhythmias, hyperkalemia, and hypoglycemia. Understanding the pharmacodynamics of beta-blocker toxicity enables targeted interventions to improve: chronotropy with epinephrine, glucagon, and pacing;inotropy with insulin, calcium, glucagon, and phosphodiesterase inhibitors;QRS widening with sodium bicarbonate;and QTc prolongation with magnesium or lidocaine. The high lipid solubility of propanol allows for intravenous lipid infusions to aid in drug elimination for patients in refractory cardiogenic shock. CONCLUSIONS: Despite a lack of labs for monitoring beta blocker toxicity, our case demonstrates successful resuscitation in a severe overdose. Perhaps an absence of hyperkalemia, hypoglycemia, QRS and QTc changes, and tachy-arrhythmias in this incident portended to a decreased morbidity and mortality. Ultimately, we reaffirmed the role of intralipid infusions as a critical treatment adjunct for recovery from cardiogenic shock secondary to beta blockade. Reference #1: Sher L. The impact of the COVID-19 pandemic on suicide rates. QJM. 2020;113(10):707-712. Reference #2: Kerns W 2nd. Management of beta-adrenergic blocker and calcium channel antagonist toxicity. Emerg Med Clin North Am. 2007;25(2):309-viii. Reference #3: Anderson AC. Management of beta-adrenergic blocker poisoning. Clin Pediatr Emerg Med. 2008;9(1):4–16. DISCLOSURES: No relevant relationships by Jackie Hayes No relevant relationships by Andrew Salomon

QT Interval Prolongation Is a Novel Predictor of 1-Year Mortality in Patients With COVID-19 Infection.

Background: QT interval prolongation is common in critically ill patients and is associated with increased mortality. However, the predictive value of a prolonged corrected QT interval (QTc) for myocardial injury and long-term mortality among patients hospitalized with COVID-19 infection is not well known. Purpose: To evaluate the association of prolonged QTc with myocardial injury and with 1-year mortality among patients hospitalized with COVID-19 infection. Materials and Methods: A total of 335 consecutive patients hospitalized with COVID-19 infection were prospectively studied. All patients underwent a comprehensive echocardiographic evaluation within 48 h from admission. Using the Bazett formula, the QTc interval was calculated from the first ECG tracing recorded at the ER. QTc ≥ 440 ms in males and ≥450 ms in females was considered prolonged. Patients with elevated cardiac biomarkers and/or echocardiographic signs of myocardial dysfunction were considered to have myocardial injury. The predictive value of QTc prolongation for myocardial injury was calculated using a multivariate binary regression model. One-year mortality rate of patients with and without QTc prolongation was compared using the log-rank test, and a multivariate Cox regression model adjusting for multiple covariates was performed to evaluate the 1-year mortality risk. Results: One-hundred and nine (32.5%) patients had a prolonged QTc. Compared to patients without QTc prolongation, patients with prolonged QTc were older (70 ± 14.4 vs. 62.7 ± 16.6, p < 0.001), had more comorbidities, and presented with a more severe disease. Prolonged QTc was an independent predictor for severe or critical disease (adjusted HR 2.14, 95% CI 1.3-3.5; p = 0.002) and myocardial injury (adjusted HR 2.07, 95% CI 1.22-3.5; p = 0.007). One-year mortality of patients with prolonged QTc was higher than those with no QTc prolongation (40.4% vs. 15.5; p < 0.001). Following adjustment to multiple covariates including myocardial injury and disease severity, QTc prolongation was found to be associated with increased 1-year mortality risk (HR 1.69, 95% CI 1.06-2.68, p = 0.027). Conclusion: Prolonged QTc is associated with disease severity, myocardial injury and 1-year mortality among patients hospitalized with COVID-19 infection.

A PHASE 1 STUDY EVALUATING SAFETY AND EFFICACY OF PARSACLISIB IN COMBINATION WITH BENDAMUSTINE + OBINUTUZUMAB IN PATIENTS WITH RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA (CITADEL-102)

Background: Patients (pts) with follicular lymphoma (FL) generally respond well to first-line CD20-targeted therapies, such as obinutuzumab or rituximab-based regimens. However, many pts relapse and studies suggest that each subsequent relapse is associated with shorter durations of response to the next treatment. Parsaclisib is a potent and highly selective next generation PI3Kδ inhibitor. The combination of bendamustine + obinutuzumab is approved for pts with relapsed/refractory (R/R) FL. We hypothesized that adding parsaclisib may improve clinical benefit with a manageable safety profile in this pt population. Aims: CITADEL-102 (NCT03039114) is an open-label, phase 1, dose-finding study that investigated safety and efficacy of parsaclisib in combination with bendamustine + obinutuzumab in pts with R/R FL following rituximabcontaining regimens. Methods: Pts enrolled were ≥18 years with histologically confirmed CD20-positive FL, R/R to any prior rituximabcontaining regimen, ECOG PS 0-2, ≥1 measurable lesion, and ≤4 prior therapies. Pts received parsaclisib 20 mg orally once daily (QD) for 8 weeks then 20 mg once weekly (QW);bendamustine 90 mg/m2 infusion on days 1 and 2 of cycles 1-6;and obinutuzumab 1000 mg infusion on days 1, 8, and 15 of cycle 1, and day 1 of cycles 2-6, and on every second cycle of cycles 8-30 in pts having complete response/complete metabolic response (CR/CMR), partial response/partial metabolic response (PR/PMR), or stable disease/no metabolic response. Part 1 (safety run-in) used a 3+3 design with dose de-escalation to identify the maximum tolerated dose (MTD) of parsaclisib in combination with bendamustine + obinutuzumab. In Part 2 (dose expansion), the safety and efficacy of this combination were further evaluated. The primary study endpoint was safety and tolerability;secondary endpoints included efficacy outcomes (ORR, DOR, PFS, and OS). Results: A total of 26 pts were enrolled and treated;median (range) age was 65.0 (44-80) years, 25 (96.2%) had ECOG PS ≤1, 11 (42.3%) had ≥2 prior systemic therapies, and 6 (23.1%) had received prior bendamustine. Median (range) parsaclisib exposure was 10.6 (0.4-32.8) months. Main reasons for treatment discontinuation included adverse events (AEs) (8 pts, 30.8%) and progressive disease (6 pts, 23.1%). All pts experienced treatment-emergent AEs (TEAEs);most common any-grade TEAEs (≥10 pts) were pyrexia (53.8%), neutropenia (50%), diarrhea (46.2%), thrombocytopenia, and nausea (each 38.5%). Grade ≥3 TEAEs were experienced by 88.5% of pts;most common grade ≥3 TEAEs (≥2 pts) were neutropenia (34.6%), febrile neutropenia (23.1%), thrombocytopenia (19.2%), ALT and AST increase (each 11.5%), and diarrhea, neutrophil count decreased, and rash maculopapular (each 7.7%). One of 6 evaluable pts in Part 1 had a DLT of grade 4 QTc elongation. The MTD was not reached, and parsaclisib 20 mg QD for 8 weeks then 20 mg QW was the selected dosage for dose expansion in Part 2. Treatment discontinuation due to TEAEs was 30.8%, 7.7%, and 15.4% for parsaclisib, bendamustine, and obinutuzumab, respectively. One fatal TEAE (COVID-19 pneumonia) occurred. ORR (95% CI) as reported by the investigator was 76.9% (56.4-91.0), with 17 pts (65.4%) achieving CR/CMR and 3 pts (11.5%) achieving PR/PMR as the best overall response. Median DOR, PFS, and OS were not reached. Summary/Conclusion: Parsaclisib in combination with bendamustine + obinutuzumab appears to have a manageable safety profile and demonstrated promising efficacy in pts with R/R FL.

ANTIMALARIAL DRUGS and ELECTROCARDIOGRAPHIC ALTERATIONS in PATIENTS with SYSTEMIC LUPUS ERYTHEMATOSUS

Background: During the frst months of the Sars-CoV-2 pandemic, antimalarial drugs were the central axis of the treatment of patients with acute respiratory infection. After that, several studies reported a risk of prolongation of corrected QT interval (QTc) at the electrocardiogram (ECG). Historically, these drugs, have been the common denominator in the treatment of patients with Systemic Lupus Erythematosus (SLE). Objectives: To analyze the possible relationship between the use of antima-larial drugs ant the electrocardiographic alterations in patients diagnosed with SLE. Methods: Cross-sectional study in patients diagnosed with SLE (SLICC 2012). In all of them, we performed a 12-lead ECG at rest. We measured the QT interval: manually and automatically, ant its correction was made according to the Hodge formule (QTc). Results: 91 patients diagnosed with SLE were included in the study. Of the total of patients included in the study, 64 were in current treatment with an antimalar-ial drug, with a mean of 9.09 (5.73) years of treatment, and a mean cumulative dosage of 813.16 (436.12) gr. Of the patients on current treatment with antimalarial drugs, 4.69% had a prolonged QTc, compared to 3.7% of the patients without current treatment with these drugs. We analyzed the possible relationship between the QTc interval, the current treatment with antimalarial drugs, and the cumulated dosage of this medication. We corrected the lineal regression models by the years of disease evolution, the presence or absence of known heart disease, the women gender, and other treatments such as antiarrhythmics or beta-blockers. We found a statistically signifcant association between taking antimalarial drugs and the elongated QTc interval (p= 0,001). Nevertheless, in the multivariate analysis, we did not found a signifcant relationship between the ECG alterations and the treatment with antimalarial drugs. Conclusion: In our study, we did not observe a direct relationship between the intake of antimalarial drugs and the alteration of the corrected QT interval.

USING OBJECTIVE ELECTROCARDIOGRAPHIC DATA TO BETTER PREDICT MORTALITY IN PATIENTS HOSPITALIZED WITH COVID 19

BACKGROUND: The impact of SARS-CoV-2 infection on intrinsic myocardial conduction continues to be an area of focus amongst the medical community. Our objective was to investigate if specific myocardial conduction abnormalities were independently associated with mortality in patients hospitalized with COVID 19. METHODS: Under IRB exemption, the electronic medical records of COVID-19 patients (N=3840) undergoing index hospitalization were reviewed to extract presentation ECG conduction data, demographics, and laboratory results (within 8h). This patient cohort was then separated into two groups based on mortality vs. not (N=520). Logistical regression was used to test association of ECG conduction intervals with mortality. RESULTS: According to our nominal logistic fit for hospital mortality, Heart Rate (HR) >100 (p=0.0007;LW 4.14), QRS duration > 120 ms (p=0.0053;LW 2.27), and QTc prolongation (defined as QTc > 450ms in males;QTc > 460ms in females) (p=0.0089;LW 2.04) were independently associated with higher risk of mortality. LogWorth (LW) calculations were included in an effort to estimate the proportional effect each variable has on overall mortality. LW > 2 were shown to be statistically significant with p< 0.05 with HR > 100 (LW 4.14) having the highest proportional effect on mortality followed by QRSd (LW 2.27) then QTc prolongation (LW 2.04). PR interval> 200ms (p=0.30) and QRS axis (p=0.15) were not associated with higher risk of mortality. CONCLUSIONS: Amongst our patient cohort, HR > 100, QRSd > 120ms, and QTc prolongation (QTc > 450 in males;QTc > 460 in females) were each independently associated with higher risk of mortality in patients hospitalized with COVID 19. These findings support the use of objective ECG data in risk stratifying patients hospitalized with COVID 19.

The effect of coronavirus infection on QT and QTc intervals of hospitalized patients in Qazvin, Iran

Electrocardiographic (ECG) changes have been investigated in the condition of coronavirus disease (COVID-19) indicating that COVID-19 infection exacerbates arrhythmias and triggers conduction abnormalities. However, the specific type of ECG abnormalities in COVID-19 and their impact on mortality fail to have been fully elucidated. The present retrospective, tertiary care hospital-based cross-sectional study was conducted by reviewing the medical records of all patients diagnosed with COVID-19 infection who were admitted to Booali Sina Hospital in Qazvin, Iran from March to July 2020. Demographic information, length of hospital stay, treatment outcome, and electrocardiographic information (heart rate, QTc interval, arrhythmias, and blocks) were extracted from the medical records of the patients. Finally, a total of 231 patients were enrolled in the study. Atrial fibrillation was a common arrhythmia, and the left anterior fascicular block was a common cardiac conduction defect other than sinus arrhythmia. The deceased patients were significantly older than the recovered ones (71 ± 14 vs. 57 ± 16 years, p < 0.001). Longer hospital stay (p = 0.036), non-sinus rhythm (p < 0.001), bundle and node blocks (p = 0.002), ST-T waves changes (p = 0.003), and Tachycardia (p = 0.024) were significantly prevalent in the deceased group. In baseline ECGs, no significant difference was observed in terms of the absolute size of QT;however, a prolonged QTc in the deceased was about twice of the recovered patients (using Bazett, Sagie, and Fridericia’s formula). Serial ECGs are recommended to be taken from all hospitalized patients with COVID-19 due to increased in-hospital mortality in patients with prolonged QTc interval, non-sinus rhythms, ST-T changes, tachycardia, and bundle, and node blocks. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.