Management of cardiovascular complications of BTKis: Are we complying with the good practice guidelines?

Bruton tyrosine kinase inhibitors (BTKis) were approved for use at the end of 2013 and have since been used for indications including chronic lymphocytic leukaemia (CLL), Waldenstrom's macroglobulinaemia and mantle cell lymphoma. The use of BTKis has increased significantly in the UK since they achieved NICE (National Institute for Health and Care Excellence) approval for frontline treatment of CLL in 2021. However, they are associated with significant adverse cardiovascular events. In September 2021 the British Journal of Haematology published good practice guidelines for the management of cardiovascular complications of BTKis. Our aim was to see whether these guidelines had been adhered to for patients taking BTKis. Method(s): Data was collected for all patients being prescribed BTKis (ibrutinib and acalabrutinib) in the South Tees NHS Trust in July 2022. Patients' medical records were used to assess whether their management adhered to the good practice guidelines. Data was collated for 67 patients in total. Result(s): The data showed that although all patients were consented for the risk of atrial fibrillation only 6% were consented for hypertension and only 1.5% for ventricular arrhythmias and sudden cardiac death. The guidelines recommend a baseline ECG (electrocardiogram) on commencement of treatment;however, only 7% had this completed and 0% had the minimum monitoring recommendation of 6-monthly ECGs. Thirty patients (45%) had an indication for a baseline echocardiogram;however, only one had this completed. For patients reporting symptoms of syncope, dizziness or palpitations only 50% had an ECG completed. Three patients developed worsening heart failure. The recommendations suggest referral to a cardio-oncologist;however, due to lack of availability of this service the referrals were instead made to the usual cardiologist. Conclusion(s): Although there was a lack of compliance with guideline recommendations, it should be considered that most usual checks were affected by COVID-19 outbreaks and a drop in face-to- face clinics, which were replaced by phone clinics and home delivery of medications. However, the premade consent forms for BTKis need to be updated to include consent for ventricular arrhythmias and sudden cardiac death. There also needs to be routine procedures in place to ensure that regular blood pressure testing and ECG monitoring occurs and that there is prompt recognition of cardiovascular complications. Action and implementation: To ensure improved compliance with these guidelines we plan to update our consent forms and create a proforma for clinic use to ensure that clinicians are aware of the various monitoring criteria required.

PPP1R13L-Related Cardiomyopathy Stability Following IL1 Inhibition

Introduction: Variants in PPP1R13L are associated with severe childhood-onset cardiomyopathy resulting in rapid progression to death or cardiac transplantation. PPP1R13L is proposed to encode a protein that limits the transcriptional activity of the NFkappaB pathway leading to elevated IL-1, IL-6, and TNF-alpha production in murine models. Optimal medical management for PPP1R13L-related cardiomyopathy is unknown. Here we report usage of a targeted anti-IL-1 immuno-modulatory therapy resulting in cardiac stabilization in a pediatric patient with congenital cardiomyopathy secondary to PPP1R13L variants. Case Report: A 4-year-old boy presented acutely with fever in the setting of persistent abdominal pain, vomiting, fatigue, and decreased appetite for two months following a mild COVID-19 related illness. Echocardiogram revealed severely depressed biventricular systolic function with an ejection fraction of 30%. Due to acute decompensated heart failure symptoms with hemodynamic instability, he was intubated and placed on continuous inotropic infusions with aggressive diuresis. Cardiac MRI demonstrated extensive subepicardial to near transmural fibrosis by late gadolinium enhancement in right and left ventricles. An implantable cardioverter-defibrillator (ICD) was placed due to frequent runs of polymorphic non-sustained ventricular tachycardia. Testing for viral pathogens was positive for rhino/enterovirus. Initial genetic testing was non-diagnostic (82-gene cardiomyopathy panel) but given the patient's significant presentation whole genome sequencing was pursued that showed two separate PPP1R13L variants in trans (c.2167A>C,p.T723P and c.2179_2183del,p. G727Hfs*25, NM_006663.4). Patient serum cytokine testing revealed elevations in IL-10 (4.7 pg/mL) and IL-1beta (20.9 pg/mL). Given the patient's tenuous circumstances and concern for continued progression of his cardiac disease, a trial of IL-1 inhibition via anakinra dosed at 3 mg/kg or 45 mg daily was initiated following hospital discharge. With approximately 6 months of therapy, the patient's cardiac function is stable with normalization of IL-10 and IL-1beta serum levels. Notably, the ventricular arrhythmia decreased after initiation of anakinra with no ICD shocks given. Therapy overall has been well tolerated without infectious concerns. Conclusion(s): In patients with PPP1R13L-related cardiomyopathy, immuno-modulatory therapies should be considered in an attempt to slow cardiac disease progression.Copyright © 2023 Elsevier Inc.

A Potential Therapeutic Target Underling Binge Alcohol-Triggered Spontaneous Arrhythmia Onset in the Aged Heart

Background: Aging and binge alcohol abuse are both known as independent risk factors for both atrial and ventricular arrhythmias. With the COVID-19 pandemic, increased social isolation has significantly increased alcohol consumption worldwide. Older adults are a high-risk drinking group and alcohol significantly enhances the risk of arrhythmia onset. Yet, how alcohol (a secondary stressor) drives spontaneous atrial and ventricular arrhythmia onset in the aged heart (a primary stressor) remains unclear. Objective(s): We recently reported the stress-response kinase c-jun N-terminal kinase 2 (JNK2) underlies alcohol-enhanced atrial arrhythmia vulnerability (pacing-induced) in healthy young hearts. Here, we reveal a critical role of JNK2 in alcohol-driven arrhythmia onset in the aged heart in vivo. Method(s): Ambulatory ECGs were recorded using wireless telemeters in binge alcohol-exposed aged (24 months) and young mice (2 months). Spontaneous premature atrial and ventricular contractions (PACs, PVCs), atrial and ventricular tachycardia (AT, VT) were quantified as previously described. The role of JNK2 in triggered arrhythmic activities was assessed using a well-evaluated JNK2-specific inhibitor and our unique cardiac-specific MKK7D and MKK7D-JNK2dn mouse models with tamoxifen inducible overexpression of constitutively active MKK7 (a JNK upstream activator) or co-expression of MKK7D and inactive dominant negative JNK2 (JNK2dn). Result(s): We found that binge alcohol exposure in aged mice (n=14) led to spontaneous PACs/PVCs (75% of the mice), and AT/VT episodes (50%) along with a 21% mortality rate. However, alcohol-exposed young (n=5) and non-alcohol-exposed aged mice (n=11) were absent of any spontaneous arrhythmic activities or premature death. Intriguingly, JNK2-specific inhibition in vivo abolished those alcohol-associated triggered activities and mortality in aged mice. The causative role of JNK2 in triggered arrhythmias and premature death was further supported by the high frequency of spontaneous PACs/PVCs and nonsustained AT/VT episodes along with a 50% mortality rate in MKK7D mice (n=10), which was strikingly alleviated in MKK7D-JNK2dn mice (n=5) with cardiac-specific JNK2 competitive inhibition. Conclusion(s): Our findings are the first to reveal that stress kinase JNK2 underlies binge alcohol-evoked atrial and ventricular arrhythmia initiation in aged mice. Modulating JNK2 could be a novel therapeutic strategy to treat and/or prevent binge drinking-evoked cardiac arrhythmias.Copyright © 2023

Effects of COVID-19 infection on ECG parameters in outpatients

Objective: Covid-19 infection has been declared as a pandemic disease by the World Health Organization (WHO) and has been associated with increased morbidity and mortality. More than 400 million people diagnosed with the disease has been reported until February 2022 [1]. Covid-19 infection mostly progresses with lung involvement and pneumonia, however, its effects on the cardiovascular system are also well-known. Studies have reported that Covid 19 infection can trigger cardiac events such as acute myocardial damage, acute myocarditis, acute coronary syndrome (ACS), ventricular arrhythmias, cardiogenic shock, and cardiac arrest [2]. Electrocardiogram (ECG) is an important tool to diagnose cardiac involvement. QTc interval, QT dispersion, Tp-e interval, Tp-e/QTc ratio are defined as ventricular repolarization parameters and these parameters are associated with increased risk of ventricular arrhythmia [3,4]. In our study, we aimed to evaluate to predict ventricular arrhythmia by ECG in Covid-19 patients. Method(s): Our study is a single-center, cross-sectional study. Patients diagnosed with Covid-19 in our center between July and October 2020 were included. 408 patients with positive SARS-CoV2 PCR test were detected and the ECGs of the patients were recorded at admission and 15 days after symptomatic recovery. After the exclusion criteria, remained 91 patients were analyzed. Conduction parameters (PR and QRS durations) and repolarization parameters (QTc interval, QT dispersion, Tp-e interval and Tp-e/QTc ratio) were evaluated in 12-lead ECG recordings. Result(s): Ninety-one patients with Covid-19 infection were included. The group were consisted of 47 male (52%) and 44 female (48%). The mean age was 50.4 years. As a result of the statistical analysis, no significant difference was observed between the groups in terms of PR interval (142.2+/-21.4 ms vs. 140.1+/-19.0 ms;p=0.312). QRS duration was found significantly higher during active infection (91.4+/-12.2 ms vs. 88.8+/-10.9 ms;p=0.022). The mean QTc duration was detected longer in the first ECG, but no statistically significant difference was observed between the two groups (426.1+/-23.6 ms vs. 422.5+/-26.2 ms;p=0.237). QT dispersion (35.2+/-7.3 ms vs. 27.7+/-7.8 ms;p<0.001), Tp-e interval (86.7+/-10.1 ms vs. 76.1+/-9.9 ms;p<0.001) and Tp-e/QTc ratio (0.204+/-0.026 vs 0.180+/-0.025;p<0.001) were found significantly higher during active infection Conclusion(s): In our study, QRS complex, QT dispersion, Tp-e interval, Tpe/ QTc ratio were significantly higher during active infection. We considered these parameters as a contributor of the increased mortality by inducing ventricular arrhythmia and sudden death in Covid-19 patients during active infection.

COVID-19 Vaccines: Fabrication Techniques and Current Status

The year 2020 was the most challenging period due to the havoc caused by the outbreak of novel coronavirus SARS-CoV-2. Scientists and researchers all around the world have endeav-ored every possible approach to find solutions in context to therapeutics and vaccines to control the spread of this life-threatening virus. The acceleration instigated by the outbreak of SARS-CoV-2 and its mutated strains has leveraged the use of numerous platform technologies for the development of vaccines against this unfathomable disease. Vaccines could play an important role in miti-gating the effects of COVID-19 and reducing the ongoing health crisis. Various innovative plat-forms like proteins, nucleic acids, viruses, and viral vectors have been exploited to fabricate vaccines depicting almost 90% of efficacy like BNT162b2, AZD1222, Ad5-nCoV, etc. Some of these vaccines are multipotent and have shown potent activity against newly emerged malicious strains of SARS-CoV-2 like B.1.351 and B.1.1.7. In this review article, we have gathered key findings from various sources of recently popularized vaccine candidates, which will provide an overview of potential vaccine candidates against this virus and will help the researchers to investi-gate possible ways to annihilate this menace and design new moieties.Copyright © 2022 Bentham Science Publishers.

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

The arrhythmic events and short-term cardiovascular outcomes in patients hospitalized with COVID-19 infection in Taiwan

Objective: The aim of this study is to investigate the arrhythmic events and short-term cardiovascular (CV) outcomes in patients hospitalized with COVID-19 infection in a single Taiwan tertiary center. Method(s): A retrospective study was carried out on 186 confirmed COVID-19 infection patients admitted to our hospital between May, 2021 and September, 2021. We investigate their CV symptoms, vital signs, laboratory examinations, arrhythmic events, and major adverse cardiovascular events (MACE), including ischemic stroke or systemic embolism, myocardial infarction, CV death, and heart failure (HF) during hospitalization. Result(s): During the hospitalization, 29.6% of patients had an elevation of cardiac enzymes, 67.2% had an elevation of d-dimer level, and 7.5% had abnormal NT-pro BNP level. The most common recorded arrhythmia is sinus tachycardia (22%), followed by atrial arrhythmia (12.4%, including atrial fibrillation 7.0%), sinus bradycardia (3.2%), ventricular arrhythmia (1.6%), and paroxysmal supraventricular tachycardia (1.1%). A total of 68 patients (36.6%) had arrhythmic events during hospitalization. During the mean follow-up of 2.8 months, 17 patients (9.1%) developed MACE, including 6 ischemic strokes, one pulmonary embolism, one peripheral artery occlusive disease, 3 HF, and 7 CV death. The total mortality rate is 19.9%. The hospitalized patients with arrhythmic events were associated with a higher incidence of intubation (32% vs 15%, p = 0.0062), MACE (22% vs 2%, p < 0.001), and mortality (37% vs 10%, p < 0.001) than those without arrhythmic events. Conclusion(s): The patients hospitalized with COVID-19 infection were associated with higher CV manifestations and arrhythmic events in Taiwan. Those patients with arrhythmic events were associated with higher morbidity and mortality.

Evaluation of ventricular electrophysiological balance index in COVID-19 patients with SIRS

Background and Aim: Malignant ventricular arrhythmia is an important cause of mortality in COVID-19 patients (1-3). In our study, we aimed to investigate the cardiac electrophysiological balance index (ICEB), which predicts the risk of malignant ventricular arrhythmia in patients with COVID-19 who developed SIRS (systemic inflammatory response syndrome). Method(s): After exclusion criteria (atrial fibrillation, left bundle branch block, pre-excitation), a total of 533 COVID-19 patients, of whom 197 (37%) were SIRS, were included in the study. Result(s): The average age in the study population was 62 (49-72), and the gender distribution was 49% (261) female, 51% (272) male. The patients were divided into two groups as the control group with SIRS and the control group without SIRS. The clinical, laboratory and demographic characteristics of the patients were compared in Table 1. The QTc/QRS ratio (ICEBc) in the SIRS group was 5.1 (4.64-5.1) and was significantly higher than 4.98 (4.5-5.45) in the control group (p=0.004). The QTc interval was 450 (422-474) and 427 (407-447) significantly longer in the SIRS group than the control group (p=0.001). As a result of multivariable linear regression analysis, a significant correlation was found between ICEBc and SIRS, age, gender and CRP. Conclusion(s): Malign ventricular arrhythmias developing in COVID-19 patients are an important cause of mortality. ICEBc and QTc were significantly higher in the SIRS group than in the control group. It was thought that ICEBc could be used to predict malignant ventricular arrhythmias in the patient group developing SIRS.

Therapeutic Plasma Exchange to Alleviate Ventricular Tachycardia after Diphenhydramine Ingestion

INTRODUCTION: The Covid-19 pandemic has adversely affected the mental health of children causing an increased incidence of suicide attempts. Diphenhydramine is a common household medication and is frequently ingested by children. Toxic doses of diphenhydramine can affect the cardiovascular and central nervous system. In the heart, diphenhydramine blocks fast sodium channels and potassium channels which can result in conduction abnormalities including sinus tachycardia, widening of QRS duration, ventricular tachycardia and torsades de pointes. Massive ingestion can cause severe cardiovascular collapse which may require ECMO support. We describe the case of a patient with diphenhydramine ingestion and refractory ventricular arrhythmias that was successfully treated with therapeutic plasma exchange (TPE). DESCRIPTION: A 13-year-old female with history of depression presented with confusion following an intentional ingestion of 1500 mg of diphenhydramine. On admission, she had frequent PVC's, bigeminy, ventricular couplets and a run of non-sustained polymorphic ventricular tachycardia with pulse despite magnesium and sodium bicarbonate. She converted to normal sinus rhythm spontaneously but continued to have frequent PVC's and prolonged QTc. Shortly thereafter, her rhythm deteriorated to non-sustained monomorphic ventricular tachycardia with a pulse which was treated with calcium gluconate, sodium bicarbonate and intralipid infusion. Due to refractory hypotension and refractory arrhythmia, we offered TPE to remove plasma protein bound drug molecules from circulation. We performed a 1.7 plasma volume TPE using 5% albumin as a replacement fluid. The serum level of diphenhydramine decreased from 1300 ng/ml to 770 ng/ml. The patient's hemodynamics improved, and she did not have any further arrhythmias. DISCUSSION: Diphenhydramine toxidrome is usually managed with medical therapy and ECMO if needed for hemodynamic support. TPE is traditionally not performed in this clinical setting as the data regarding its utility is limited. The decrease in drug levels before and after TPE treatment was associated with improvement in the patient's hemodynamics and rhythm. This case report is unique because, to the best of our knowledge, the use of TPE in diphenhydramine toxicity has not been reported in medical literature.

Relationship between index of cardio-electrophysiological balance and hydroxychloroquine in patients with COVID-19

Hydroxychloroquine (HCQ) treatment is frequently prescribed for coronavirus disease 2019 (COVID-19). Electrocardiographic (ECG) monitorization is recommended because HCQ causes QT interval prolongation. The index of cardioelectrophysiological balance (iCEB), calculated as the ratio of QT interval / QRS duration. In recent years, iCEB has been described as an important marker for dysrhthmias. Decreased or increased iCEB is related with lethal ventricular arrhythmias. In our research, we purposed to investigate the relationship between iCEB and HCQ in patients with COVID-19. 200 patients (males, 84;females, 116;60.4 +/- 13.8 years) with PCR positive and chest tomography findings compatible with COVID-19 pneumonia were registered in the research. Demographic, clinical, and laboratory data for all patients were collected. ECG was recorded from all patients on admission to COVID-19 clinic, in oral treatment with HCQ (200 mg, twice daily) for at least 5 days. iCEB (QT/QRS) was calculated from the 12-lead electrocardiogram.The mean age of the patients was 60.4 +/- 13.8 years. Compared to admission ECG, ECG on day 5 showed significant increases in heart rate, QT interval, corrected QT (QTc) interval, and iCEB. Our results suggested that iCEB is related with HCQ treatment in patients with COVID-19. Previous studies stated that high iCEB is related with torsade de Pointes (TdP), ventricular tachycardia. Copyright © 2022 Ondokuz Mayis Universitesi. All rights reserved.

Acute STEMI During the COVID-19 Pandemic at a Regional Hospital: Incidence, Clinical Characteristics, and Outcomes

Objectives: The aim of this study was to describe the characteristics and in-hospital outcomes of patients with acute ST-segment elevation myocardial infarction (STEMI) during the early COVID-19 pandemic at Piedmont Athens Regional (PAR), a 330-bed tertiary referral center in Northeast Georgia. Method(s): A retrospective study was conducted at PAR to evaluate patients with acute STEMI admitted over an 8-week period during the initial COVID-19 outbreak. This study group was compared to patients admitted during the corresponding period in 2019. The primary endpoint of this study was defined as a composite of sustained ventricular arrhythmia, congestive heart failure (CHF) with pulmonary congestion, and/or in-hospital mortality. Result(s): This study cohort was composed of 64 patients with acute STEMI;30 patients (46.9%) were hospitalized during the COVID-19 pandemic. Patients with STEMI in both the COVID-19 and control groups had similar comorbidities, Killip classification score, and clinical presentations. The median (interquartile range) time from symptom onset to reperfusion (total ischemic time) increased from 99.5 minutes (84.8-132) in 2019 to 149 minutes (96.3-231.8;P= .032) in 2020. Hospitalization during the COVID-19 period was associated with an increased risk for combined in-hospital outcome (odds ratio, 3.96;P= .046). Conclusion(s): Patients with STEMI admitted during the first wave of the COVID-19 outbreak experienced longer total ischemic time and increased risk for combined in-hospital outcomes compared to patients admitted during the corresponding period in 2019. Copyright © 2022 Turner White Communications Inc.. All rights reserved.

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.

PFIZER COVID-19 VACCINE CAUSES SHORTNESS OF BREATH IN A 24-YEAR-OLD PATIENT: A CASE REPORT

SESSION TITLE: Variety in Risk Factors and Treatment of VTE SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: The year of 2020 will be a year never forgotten when the COVID-19 pandemic began. The healthcare system is going into a crisis facing a disease that is unknown and overwhelming. Companies were frantic to find a solution to help prevent so many unnecessary deaths. Pfizer mRNA COVID-19 vaccine was granted emergency use by the FDA after proving efficacy in early trials. Many side effects were unknown and discovered as time went on. Unprovoked isolated pulmonary embolisms are rare. CASE PRESENTATION: A 24 year old male with no significant past medical history presented to the emergency department due to shortness of breath, hemoptysis and chest pain. He denied any family history or personal history of clotting disorders. He received the mRNA COVID-19 Pfizer vaccine 5 days prior to symptom onset. He describes it as constant sharp pain with varying intensity that he rates a 6/10 and can reach a 10/10 pain exacerbated with lying flat and deep breathing. He also states he has been coughing up a teaspoon amount of blood with this chest pain. Physical examination revealed reduced breath sounds in the left lower lobe. Patient was hemodynamically stable. Labs were stable and hemoglobin was stable throughout the hospital course. Fibrinogen was elevated and hypercoagulable work-up was negative. CTA of chest was performed and revealed left-sided pulmonary emboli involving the left lower lobe with pulmonary infarction. Therefore, he was managed by Eliquis. DISCUSSION: Pfizer released a safety and efficacy report of the BNT162b2 mRNA Covid-19 Vaccine. Many of the common side effects reported were pain at the injection site, fatigue, headache, and fever [1]. Adverse events that were reported were shoulder injury, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia [1]. Isolated PE in a young healthy patient was never reported as an adverse event from the Pfizer safety and efficacy report. Severe acute respiratory syndrome-coronavirus-2 has been proven to increase the risk of venous thromboembolism because it is a prothrombotic virus [2]. Vaccination reports of pulmonary embolism are increasing, however, isolated PE without a DVT is still very underreported and rare. The literature states that a lot of patients that are having PE after mRNA vaccine also have associated thrombocytopenia, however, this is not what this patient demonstrates [3]. A total of 43, 548 participants were observed for the safety and efficacy report of the Pfizer COVID-19 report and not a single patient demonstrated an isolated pulmonary embolism event [1]. CONCLUSIONS: This case is a demonstration of a rare occurrence of isolated PE with no evidence of DVT in such close proximity to receiving the mRNA COVID-19 Pfizer vaccination.There are few reports of pulmonary embolism in healthy patients with no history of clotting disorders and further data are needed to support this association. Reference #1: Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577 Reference #2: Hesam-Shariati S, Fatehi P, Abouzaripour M, Fathi F, Hesam-Shariati N, Hesam Shariati MB. Increased pulmonary embolism in patients with COVID-19: a case series and literature review. Trop Dis Travel Med Vaccines. 2021;7(1):16. Published 2021 Jun 12. doi:10.1186/s40794-021-00145-3 Reference #3: Muster V, Gary T, Raggam RB, Wölfler A, Brodmann M. Pulmonary embolism and thrombocytopenia following ChAdOx1 vaccination. Lancet. 2021;397(10287):1842. doi:10.1016/S0140-6736(21)00871-0 DISCLOSURES: No relevant relationships by Muhammad Azaz Cheema No relevant relationships by Morcos Fahmy No relevant relationships by Christina Gearges No relevant relationships by Asma Iftikhar

Cardiovascular screening in olympic athletes before and after SARS-CoV-2 infection

Background: Conflicting results on the cardiovascular involvement after SARS-CoV-2 infection generated concerns on the safety of return-to-play (RTP) in the athletic population. However, these data are mainly based on Troponin and imaging findings. Purpose: Aim of the study was to evaluate the prevalence of cardiac involvement after COVID-19 in Olympic athletes, who had previously been screened in our pre-participation program. Methods: Since November 2020, all consecutive Olympic athletes presented to our Institute after COVID-19 prior RTP were enrolled. The protocol was dictated by the Italian governing bodies and comprised: 12-lead ECG, blood test, cardiopulmonary exercise test (CPET), 24-hours ECG monitoring, spirometry. Cardiovascular Magnetic Resonance (CMR) was also performed. All Athletes were previously screened in our Institute as part of their periodical pre-participation evaluation. Results: Forty-seven Italian Olympic athletes were enrolled: 83% asymptomatic, 13% mildly asymptomatic, 4% had pneumonia. The evaluation was performed after a median of 9 days from negative SARS-CoV-2 swab. Uncommon premature ventricular contractions (PVCs) were found in 13% athletes, however, only 6% (n=3) were newly detected. All newly diagnosed uncommon PVCs were detected by CPET. One of these three athletes had evidence for acute myocarditis by CMR, along with Troponin raise;another had mild pericardial effusion. No one of the remaining athletes had abnormalities detected by CMR (Figure). Conclusions: Cardiac abnormalities in Olympic athletes screened after COVID-19 resolution were detected in a minority and were associated with new ventricular arrhythmias. Only one had evidence for acute myocarditis (in presence of symptoms and elevated biomarkers). No one of the remaining athletes had abnormalities by imaging or laboratory test. Our data support the efficacy of the clinical assessment including exercise-ECG to raise suspicion for cardiovascular abnormalities after COVID-19. Instead, the routine use of CMR as a screening tool appears not justified. (Figure Presented).

COVID MYOCARDITIS, A POST-COVID SYNDROME

Case Report Learning Objective Recognizing Covid Myocarditis in Post covid syndrome Case Presentation A 56-year-old female with a medical history of hypertension and unvaccinated to COVID presented with sudden onset of chest pain radiating to the arm, 7/10 intensity aggravated with excretion, associated with palpitation and worsening bilateral leg swelling for last two weeks. She was recently tested positive for COVID infection four weeks ago. However, she did not seek medical treatment as she was asymptomatic at the time of infection. In the ER, she was diagnosed with A.Fib with RVR in hypotension needing two liters of oxygen and volume overload state with mildly elevated Troponin and EKG showing LBBB, grossly elevated BNP, all her inflammatory markers, and white cell counts within the reference range. She was admitted to ICU with cardiogenic shock needing two pressors and IV amiodarone. Urgent LHC was performed, showing normal coronary arteries with severely reduced EF of less than 20% with global hypokinesia on LV gram. Impella device was placed, and gradual diuresis with pressor support was administered. Overall hemodynamics improved, and pressors were weaned with continued aggressive diuresis. She improved well and was discharged with lifevest and an outpatient cardiology follow-up plan. Discussion The clinical features of myocarditis are usually non-specific, such as myalgias with a history of recent upper respiratory infection and typical age at onset varying between 20 to 50 years. New-onset HF over two weeks to three months with classical symptoms and non-specific changes EKG showing bundle branch block, atrioventricular (AV) block, or ventricular arrhythmias. Myocarditis should be suspected with or without cardiac signs and symptoms with elevated cardiac biomarkers, ECG changes suggestive of acute myocardial injury, arrhythmia, or global or regional abnormalities of LV systolic function, mainly if the clinical findings are new and unexplained. The clinical presentation of myocarditis is highly variable and can mimic other noninflammatory cardiac disorders;a high level of clinical suspicion is required. Conclusion We conclude that this new-onset HF with no evidence of acute coronary disease or any cardiac and familial risk factors with recent COVID infection makes us think that viral myocarditis is a possible cause of this acute presentation. Cardiovascular magnetic resonance (CMR) imaging is indicated in patients with suspected myocarditis if T2-based and T1- based imaging meet Lake Louise Criteria. Viral myocarditis should be an important consideration in patients with Covid- 19 and those who have recovered from even minor infections.

Gentle Giant: An Unusual Cause of Heart Block

Introduction: Inflammatory cardiomyopathies can be a diagnostic dilemma. Early management can lead to reduced morbidity and mortality for patients. We describe a rare presentation of an unusual cardiomyopathy. Case Report: A 58-year-old female presented with a 10-day prodrome of cough, NYHA class III dyspnea, and fatigue with minimal symptoms of orthopnea, paroxysmal nocturnal dyspnea or peripheral edema. She was previously healthy with no cardiac medications. Family history was significant for granulomatosis with polyangiitis. COVID-19 swab was negative. She was symptomatic with transient complete heart block and junctional escape of 20bpm. A temporary transvenous pacemaker was placed. Echocardiogram showed biventricular dysfunction with left ventricular ejection fraction < 30%. Troponin and brain-natriuretic peptide were elevated. Coronary angiogram showed no significant occlusions. CT excluded pulmonary embolism, pneumonia, or adenopathy. She was initiated on heart failure medications but beta blocker was not started given heart block. Six days into admission, her heart failure improved but she developed transient complete heart block without junctional escape. There was no ventricular ectopy. Evaluation for rheumatologic, infectious, and inflammatory causes showed elevated C-reactive protein and antineutrophil cytoplasmic antibodies. The remainder of the workup was negative. Leading diagnoses were idiopathic giant cell myocarditis or cardiac sarcoidosis. An endomyocardial biopsy revealed multinucleated giant cells and myocyte necrosis. She was diagnosed with giant cell myocarditis. Prior to discharge, she had defibrillator insertion and was initiated on prednisone and tacrolimus. Shortly after this time, she returned with critical cardiogenic shock despite intensification of immunosuppressive therapies and was listed for cardiac transplant. Giant cell myocarditis (GCM) is a rare and often fatal autoimmune cause of heart failure. Patients frequently present with congestive heart failure, ventricular arrhythmia and a rapid progression of symptoms. In GCM, it is rare to present with atrioventricular conduction delays. Given the crossover in symptoms with sarcoidosis and GCM, diagnosis may be challenging. In this case of an acute presentation of heart failure and complete heart block, endomyocardial biopsy was central to the diagnosis and management of GCM.

Index of cardiac electrophysiological balance (iCEB) in patients with COVID-19

Aims: We aimed to examine whether there is abnormal value of index of cardiac electrophysiological balance (iCEB=QT/QRS) in patients with confirmed coronavirus disease 2019 (COVID-19), which can predict ventricular arrhythmias (VAs), including non-Torsades de Pointes-like ventricular tachycardia/ventricular fibrillation (non- TdPs-like VT/VF) in low iCEB and Torsades de Pointes (TdPs) in high iCEB. We also investigated low voltage ECG among COVID-19 group. Methods and Results: This is a cross-sectional, single center study with a total of 53 newly diagnosed COVID-19 patients (confirmed with polymerase chain reaction (PCR) test) and 63 age and sex-matched control subjects were included in the study. Electrocardiographic marker of iCEB were calculated manually from 12-lead ECG. Low voltage ECG defined as peak-to-peak QRS voltage less than 5mm in all limb leads and less than 10mm in all precordial leads. Patients with COVID-19 more often had low iCEB, defined as iCEB below 3.24 compared to control group (56.6% vs 11.1%), (OR=10.435;95%CI 4.015 - 27.123;p=0.000). There were no significant association between COVID-19 and high iCEB, defined as iCEB above 5.24 (OR=1.041;95%CI 0.485 - 2.235;p=0.917). There were no significant difference of the number of low voltage ECG between COVID-19 and control groups (15.1% vs 6.3%), (OR=2.622;95%CI 0.743 - 9.257, p=0.123). Conclusion: In this study showed that patients with COVID-19 are more likely to have low iCEB, suggesting that patients with COVID-19 may be proarrhytmic (towards non- TdPs-like VT/VF event), due to the alleged myocardial involvement in SARS-CoV-2 infection.

CARBOPLATIN-PACLITAXEL INDUCED ACUTE MULTI-VESSEL CORONARY THROMBOSIS

Background: Delayed cancer screenings during COVID-19 pandemic are expected to increase use of chemotherapy agents like paclitaxel. Paclitaxel has been implicated in rare cases of acute myocardial infarction from chemotoxicity. We present a rare case and literature review of Paclitaxel-induced acute multiple vessel coronary thrombosis in absence of native coronary artery atherosclerosis. Case: A 68-year-old man with a history of metastatic stage IV non-small cell lung cancer, hypertension, hyperlipidemia, normal baseline left ventricular systolic function and without coronary disease on recent heart catheterization, was found unresponsive with telemetry showing monomorphic ventricular tachycardia six hours post Carboplatin-Paclitaxel infusion. Decision-making: The patient was emergently cardioverted at bedside, intubated, and started on amiodarone, lidocaine, and norepinephrine infusions. The patient was thrombocytopenic at 61K, leukopenic at 1.2K, and anemic at 7.1 with INR of 1.8. ECG showed new ST-elevation in inferior leads. Bedside echocardiogram revealed global hypokinesis with apical akinesis and a newly reduced LVEF 25%. Troponin measured 0.5 ng/mL (normal <0.04 ng/mL), creatinine 1.4, K+ 3.4, and Mg2+ 1.8. After cardio-oncology led multidisciplinary discussion, a decision was made to pursue invasive angiogram. Found to have de novo triple-vessel coronary thrombosis in mid-LAD, proximal OM1 and mid RCA (Figure 2), percutaneous intervention was performed with drug-eluting stents placed in mid-LAD and mid-RCA, with staged PCI planned on proximal OM1 if needed. Patient responded well to the intervention and was extubated the same day. Patient remained medically stable at 3-month follow-up despite continued chemotherapy. Staged PCI to OM1 was not needed. Conclusion: Paclitaxel based therapy can cause ventricular arrhythmias and sudden cardiac death secondary to acute multi-vessel coronary thrombosis in patients without underlying coronary artery disease in the setting of pronounced thrombocytopenia. Prompt recognition of this severe adverse effect and timely utilization of multidisciplinary care models led by a cardio-oncologist achieves optimal outcomes.

Nonsustained ventricular tachycardia in adolescents after mRNA-SARS-CoV-2 vaccine: Report of two cases

Background: In young adults and adolescent males, myocarditis has been described as a rare complication of SARS-CoV-2 mRNA-vaccination. Reported findings include chest pain, elevated troponin levels, and cardiac MRI abnormalities. ECG abnormalities include ST-elevation but to our knowledge, ventricular arrhythmia has not been yet described. In the vast majority of reported cases, symptoms were relatively mild and patients recovered fully. Method: Here, we report two male adolescents (15 resp. 13 years old) admitted to our hospital with nonsustained (ns) VT and chest pain (patient no. 1) and near syncope (patient no. 2) after receiving an mRNA-SARS-CoV-2 vaccine (patient no. 1: 4 days after the second dose and patient no. 2: 15 days after days after the first dose). Further workup included family history, standard 12 lead ECG, the Holter monitoring, heart catheterization, myocardial biopsy, invasive programmed RV stimulation, and cardiac MRI. Results: Both patients did not have elevated troponin levels nor specific ECG findings. Family history was free for cardiac diseases, sudden cardiac death, or syncopal episodes. The Holter monitoring showed recurrent ns VT in one patient. Cardiac MRI and myocardial biopsy in both patients did not show evidence of myocarditis, but both patients showed severe thickening of the arterioles in myocardial biopsy. Invasive RV-stimulation did not trigger VT. Ultimately, both patients did not meet diagnostic criteria for myocarditis and β-blockers were started for ns VT. As of today, four more patients in age group 12 to 17 years were diagnosed with vaccine-associated myocarditis in our institution and one male with COVID-19 associated myocarditis. Notably, none of these patients had ventricular tachycardia or other cardiac arrhythmia. Conclusion: We observed ventricular tachycardia after SARS-CoV-2-mRNA vaccination in two adolescent males. This manifestation seems to be distinct from the well-described vaccine-associated myocarditis. Interestingly in both patients, perivascular thickening of arterioles was noted in biopsy. The mechanism and causality of ventricular arrhythmia in association with SARS-CoV-2 mRNA vaccines remain unclear and requires further observation.

Vasopressor use and 60-day outcomes among covid-19 patients in the intensive care unit

Introduction: Vasopressor use has been associated with higher mortality rates in patients with COVID-19, the association between the maximum number of concurrent vasopressors with mortality has not yet been studied. Methods: A retrospective cohort study was conducted on patients admitted with COVID-19 to the intensive care unit (ICU) at Rush University System for Health in Illinois between March and October 2020. Multivariable logistic regression, adjusted for age, BMI, history of CAD and diabetes, was used to determine if an increasing number of vasopressors is associated with higher 60-day mortality. Results: A total of 637 patients met the inclusion criteria. Composite 60-day mortality was 28.6%. Of the 637 patients who met inclusion criteria, 338 (53.1%) required the support of at least one vasopressor. When compared to patients with no vasopressor requirement, those who required 1 (adjusted OR [aOR] 3.27, p<0.01), 2 (aOR 4.71, p<0.01), 3 (aOR 26.2, p<0.01), and 4 or 5 (aOR 106.38, p<0.01) vasopressor(s) were at increased risk of 60-day mortality (Figure 1). Additionally, the incidence of mechanical ventilation, venous thromboembolism, ventricular arrhythmia, and new renal replacement therapy increased with additional vasopressor requirement (p < 0.001 for each outcome;Table 1). There was no statistical difference in the incidence of MACE between the groups (p = 0.139). Conclusion: In this cohort, each additional vasopressor added was associated with escalating 60-day mortality. Identifying these high-risk patients can help determine prognostic outcomes and guide decision-making.