Evidence Of Myocarditis Research Articles

P39 Primary antiphospholipid syndrome before development of severe systemic lupus erythematosus – a case report

Abstract Introduction Antiphospholipid syndrome (APS) has long been associated with systemic lupus erythematosus (SLE). Graham Hughes first reported APS in 1983 in cohorts of SLE patients with recurrent thrombosis. We present a case of a young man who developed severe manifestations of SLE 7 years after the diagnosis of primary APS and we look at the literature for predictors in primary APS to develop into SLE. Case description A 28 year old Caucasian male with Turkish ancestry was diagnosed with triple positive primary APS at the age of 21 when he presented with bilateral pulmonary embolisms. He was stable on warfarin with target INR between 3-4. He had been having occasional mouth ulcers, lethargy, mild paraesthesia of his feet and headaches for 2 months. He then presented in February 2024 with short history of pleuritic chest pain and marked breathlessness. Initial cross sectioning imaging did not reveal pulmonary embolism. A week later, echocardiogram demonstrated large global pericardial effusion and small pleural effusions. Ejection fraction was preserved. Interval MRI scan showed pericarditis without evidence of myocarditis. Almost 600 mls of heavily blood stained pericardial fluid was drained. Analysis of the pericardial fluid showed inflammatory processes with macrophages, neutrophil and lymphocytes. Culture was negative including for tuberculosis and cytology negative for malignancy. Immunology revealed ANA 1:160, ENA normal, dsDNA was initially negative but upon interval testing was high at 27.5 IU/mL, IgG 13.1 g/L, C3 1.2 g/L, C4 <0.1 g/L, CRP 143, ESR 30. He had anaemia, lymphopenia and positive direct antiglobulin test. ANCA and rheumatoid factor were unremarkable. Renal and joints were unaffected. Due to his Turkish ancestry, he was extensively investigated for the possibility of Behcet’s with normal femoral vein ultrasound and negative HLA-B51 genotype. His manifestations fulfilled the SLICC criteria to be diagnosed with SLE. His response to intravenous methylprednisolone infusions and subsequent oral steroid was marked. He was initiated on dual treatment of hydroxychloroquine and mycophenolate mofetil and is currently recovering. Discussion We relooked at this immunology when he was first diagnosed with primary APS in 2017. He was strongly positive for ANA at titre of 1:640 but did not have manifestations of SLE then. We researched literature on the predictors for primary APS to develop into SLE. Both disease spectrums have several overlapping manifestations including haemolytic anaemia, thrombocytopenia, lymphopenia, neurological symptoms, renal manifestations and livedo reticularis. Freire et al (1) retrospectively analysed 80 patients with primary APS and found 14 (17.5%) progressed to develop APS-SLE in 5.2 +/- 4 years. ANA positivity was found in 100% those who eventually developed APS-SLE. Other specific autoantibodies including anti-dsDNA, anti-ribosomal P, anti-Ro, anti-La and anti-U1RNP are found more commonly in the cohort too. In their APS-SLE cohort, they also found a correlation with younger age at the time of diagnosis of APS and the duration of the disease. Andreoli L et al (2) demonstrated anti-nucleosome antibody (anti-NCS) was frequently found in their cohort of APS-SLE patients but no relationship between clinical-serological was found, except for a weak correlation between anti-dsDNA antibodies. 2 of their primary APS who developed severe SLE had displayed high titres of anti-NCS years before. Tarr T et al (3) found 4 of their primary APS who developed SLE all presented with cerebrovascular events as the thrombotic manifestation. Key learning points • Primary APS has been associated with the development of SLE • Certain antibody profile such as ANA, anti-nucleosome antibody may predict the development of SLE in primary APS patients • Younger age, cerebrovascular events as thrombotic manifestation at diagnosis of primary APS and the length of duration of primary APS may be associated with the development of SLE at a later stage

Cardiovascular risks of PD1 inhibitor therapy in cancer: impact of prior ischemic events on heart failure - a retrospective cohort study

Abstract Introduction Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, but concerns remain about their cardiac risks. Limited recent basic evidence suggests a possible link between ICIs that target PD1 and adverse cardiac events such as heart failure. Purpose This study explores the connection between PD1 inhibitor therapy and incident heart failure in cancer patients. Methods In our retrospective study at a tertiary medical center, 1,671 cancer patients receiving PD1 inhibitors were analyzed. Individuals with a history of heart failure, who developed myocarditis on PD-1, or had missing data were excluded. Data from pharmacy records and the Research Patient Data Registry provided clinical and ICI-related details. Cases were defined as patients who developed incident heart failure after ICI started. Controls were patients who did not develop incident heart failure after ICI start. Sensitivity analyses, including propensity score matching and comparison with non-ICI-treated cancer patients, ensured result robustness. Multivariate logistic regressions were performed. Results Among 1,671 ICI treated patients, 109 (6.5%) developed heart failure without evidence of myocarditis over a median follow-up of 332.0 days. In both the full cohort and the 3:1 matched cohort (n=380), multivariate logistic regression showed increased odds of incident heart failure in patients with prior ischemic cardiac events: 2.34 (95%CI 1.26-4.16, p=0.005) and 2.11 (95%CI 1.05-4.2, p=0.033) respectively. Among the non-ICI treated cancer patients, multivariate logistic regression found no association between prior ischemic events and incident heart failure (1.23, 95%CI 0.53-2.63, p=0.6), but hypertension showed an association (1.74, 95%CI 1.07-2.87, p=0.027). Conclusion This study emphasizes vigilance for cardiovascular complications in PD1 inhibitor-treated cancer patients. The incidence of heart failure was 6.5% over a follow-up period of less than 1 year. Prior ischemic events correlate with increased heart failure risk, suggesting a need for nuanced patient management. Understanding ICIs' cardiovascular safety is crucial for risk assessment, treatment optimization, and patient well-being.

Atrial Arrhythmia and Bradycardia as a Presentation of Congenital Long QT Syndrome.

We present a term newborn with atrial arrhythmia on the first day of life (DOL). An echocardiogram showed normal structure and normal function; laboratory testing showed normal electrolytes and thyroid function. After initiation of flecainide, the EKG on DOL 2 showed significant and increasing bradycardia with atrial arrhythmia and extremely prolonged QTc interval. Flecainide was stopped and esmolol started. After 6h of treatment, atrial tachycardia was suppressed, and the rhythm converted to sinus. Genetic testing found variants of unknown significance in the ALPK3 gene and KCNQ1 gene, which has been associated with long QT syndrome (LQTs). LQTs in infants can present as bradycardia, 2:1 AV block, or torsades de pointes. Our review of the literature found only one other case report of atrial arrhythmia in a newborn with congenital LQTs.Diagnosis of LQTs via EKG alone is difficult in neonates since the ST segment and T wave on the first DOL are usually flattened, making correct measurement of the QTc interval difficult. β-blockers, the first line of treatment for LQTs, are known to shorten QTc intervals and prevent arrhythmia events. As in our patient, β-blockers may be helpful for atrial arrhythmia prevention in patients with adrenergically mediated atrial tachycardia.In conclusion, atrial arrhythmia with bradycardia can be a presentation of congenital LQTs and be difficult to recognize. For neonates with this presentation with no evidence of myocarditis, congenital heart disease, or significant respiratory illness, genetic congenital LQTs should be highly suspected, especially when associated with low resting heart rates.

A Phase 2 Study of Nivolumab for Relapsed/Refractory Multiple Myeloma or Non-Hodgkin Lymphoma Following CAR-T Therapy

Background: Treatment options are limited for patients with relapsed multiple myeloma (MM) or non-Hodgkin lymphoma (NHL) after CAR-T failure. While checkpoint inhibition may theoretically improve T-cell effector activity following CAR-T, a prospective trial of pembrolizumab (a monoclonal antibody targeting PD-1 on T-cells) following CD19 CAR-T in NHL showed an ORR of only 25% (Chong Blood 2022). In a recent multicenter NHL cohort (Major Blood Advances 2023), responses were similarly low with both pembrolizumab and nivolumab (nivo). However, nivo has not been studied prospectively in this setting, and the efficacy of checkpoint inhibition after CAR-T failure in MM has not been characterized. Methods: We conducted a single-center phase 2 trial (NCT04205409) of nivo for MM or NHL pts with relapse following any CAR-T product (including investigational products) as their last line of therapy. Nivo monotherapy was dosed 480mg IV every 4 weeks until PD or toxicity. The primary endpoint was overall response rate (ORR) by IMWG or Lugano criteria. Secondary endpoints included safety data for AEs and immune-related AEs (irAEs) using CTCAE v5.0 as well as post-nivo CRS/ICANS using ASTCT criteria. Other endpoints included duration of response (DoR), PFS, CAR-T expansion following first nivo dose, and PD-L1/PD-1 IHC expression on tumor biopsies. Results: We enrolled 20 pts (11 MM, 9 NHL) as detailed in Table 1. Prior to nivo, the best response to CAR-T had been CR in 64% of MM pts and 44% of NHL pts, while 1 MM pt and 1 NHL pt had experienced PD as best response. Median time between CAR-T infusion & C1D1 nivo was 624 days (range 59-1211) in MM and 149 days (range 34-506) in NHL. The ORR was 15% overall: 18% (2/11) for MM and 11% (1/9) for NHL. Characteristics of the 3 responders are detailed in Table 2. Both responders with MM had previously received fully human CAR-T therapies; in NHL, the sole response was in a patient who had received commercial axi-cel. In all 3 cases, clinical benefit was evident following a single nivo dose. Both MM patients achieved a VGPR by light chains (>95% reduction) within 4 weeks; in one patient, PET-CT showed complete resolution of a plasmacytoma that had measured 8.6cm one week before C1D1 nivo. DoR was 687 days for this patient and ≥198 days (ongoing) in the other responder with MM. In NHL, the responding patient - who had had a DS4 response at Day +30 then a DS5 response at Day +60 following axi-cel before starting nivo one month later - achieved a complete response (DS3) including resolution of hepatic and splenic lymphomatous lesions. Conversely, in all non-responders, PD was uniformly evident within a month of nivo as well. The most common Grade 3+ AEs were neutropenia (25%), anemia (15%), and sepsis (15%). One MM patient developed secondary MDS. Two irAEs (one Gr2 pneumonitis, one Gr2 rash) occurred, both in non-responders, and both resolved with brief courses of prednisone. CRS or ICANS did not occur following nivo in any pt. There were 3 deaths within 100 days of nivo initiation, all unrelated to treatment and, all in non-responders: two clearly due to PD and one due to hypotensive cardiac arrest (no evidence of myocarditis). The results of ongoing correlative analyses will be presented at the meeting, including post-nivo CAR T-cell expansion data, nivolumab binding assays on T-cells, and PD-L1 tissue expression on tumor biopsies. Conclusions: We found that responses to PD-1 blockade following CAR-T failure are uncommon, confirming prior studies in NHL which demonstrate poor activity in this setting. Our 18% ORR with post-CAR-T nivo in R/R MM (2/11 pts) is notably higher than the 4% ORR (1/27 pts) reported with nivo monotherapy in R/R MM (Lesokhin JCO 2016), although conclusions are difficult to draw with small n. Day +28 responses following a single dose of nivo 480mg were uniformly predictive of long-term efficacy. irAEs were relatively uncommon and manageable with steroids, while CRS and ICANS did not occur. To our knowledge, this is the first prospective evaluation of nivo following CAR-T failure. Given the non-curative nature of BCMA CAR-T, there may be certain pts with MM for whom checkpoint inhibition leads to a meaningful clinical benefit without unacceptable risks. Better tools to identify such patients are needed, and novel correlative data to help identify pre-nivolumab features of responders - particularly in MM - will be presented at the meeting.

Atrial and ventricular arrhythmias with immune checkpoint inhibitor therapy in patients without evidence of myocarditis

Abstract Background Immune checkpoint inhibitor (ICI) therapy has improved the prognosis of many cancer types. Immune-related adverse events (irAEs) are common and recent studies suggest ICI therapy may be associated with an increased risk of arrhythmias. However, data on arrhythmias after ICI therapy has been limited by small sample sizes, the inclusion of patients with ICI myocarditis, or an incomplete characterization of the factors that drive arrhythmias with an ICI. Purpose This study aimed to characterize the association between ICIs and arrhythmias in patients without evidence of myocarditis. Methods We conducted a hospital network-wide retrospective cohort study on all patients treated with ICI who were free from arrhythmias at the start of ICI therapy, and had no evidence of immune-related myocarditis. We used a historical pre-ICI therapy era cohort of cancer patients of similar age and tumor types, diagnosed between 2008-2012. The main study outcome was the incidence of atrial fibrillation, atrial flutter, supraventricular tachycardia, and ventricular tachycardia after ICI therapy. International Classification of Diseases 9th and 10th edition codes were used to ascertain baseline characteristics and to detect the study outcomes. Myocarditis cases were identified through the application of natural language processing techniques to electronic health records. Patients on ICI therapy and controls were followed from the start of ICI therapy, and from the first visit after 2008, respectively, up to three years after the index date. Results The study population consisted of 7441 patients on ICI therapy and 2311 controls. Patients on ICI therapy were older (65±13 vs. 63±13 years, p<0.001) and more frequently had arterial hypertension (52% vs. 47%, p<0.001), but had lower rates of prior congestive heart failure (6% vs. 11%, p<0.001). Over a median follow-up period of 36 months, 9.8% on ICI therapy were diagnosed with any incident atrial or ventricular arrhythmia, compared to 7.1% in the control group (p<0.001) with corresponding incidence rates of 4.4 and 2.3 cases per 100 person-years, respectively (Fig. 1). When correcting for age, sex, cancer type, prior congestive heart failure, and cardiovascular risk factors, patients on ICI therapy had a higher risk of a composite outcome of any arrhythmia (hazard ratio [HR] 1.68, 95% confidence interval [CI]: 1.39-2.04, p<0.001), atrial fibrillation (HR 1.29, 95%CI: 1.02-1.63, p=0.034) and ventricular tachycardia (HR 2.01, 95%CI: 1.34-3.04, p<0.001). In a multivariable logistic regression model, the occurrence of a non-cardiovascular irAE was a predictor of an incident arrhythmia (odds ratio 1.81, 95%CI: 1.56-2.23, p<0.001). Conclusion This study, to the best of our knowledge, is the largest to report on ICI therapy-related arrhythmias and the first to show the occurrence of non-cardiovascular irAEs as a predictor of arrhythmia risk in patients on ICI therapy without evidence of myocarditis.Fig. 1

No Evidence for Myocarditis or Other Organ Affection by Induction of an Immune Response against Critical SARS-CoV-2 Protein Epitopes in a Mouse Model Susceptible for Autoimmunity.

After Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) developed into a global pandemic, not only the infection itself but also several immune-mediated side effects led to additional consequences. Immune reactions such as epitope spreading and cross-reactivity may also play a role in the development of long-COVID, although the exact pathomechanisms have not yet been elucidated. Infection with SARS-CoV-2 can not only cause direct damage to the lungs but can also lead to secondary indirect organ damage (e.g., myocardial involvement), which is often associated with high mortality. To investigate whether an immune reaction against the viral peptides can lead to organ affection, a mouse strain known to be susceptible to the development of autoimmune diseases, such as experimental autoimmune myocarditis (EAM), was used. First, the mice were immunized with single or pooled peptide sequences of the virus's spike (SP), membrane (MP), nucleocapsid (NP), and envelope protein (EP), then the heart and other organs such as the liver, kidney, lung, intestine, and muscle were examined for signs of inflammation or other damage. Our results showed no significant inflammation or signs of pathology in any of these organs as a result of the immunization with these different viral protein sequences. In summary, immunization with different SARS-CoV-2 spike-, membrane-, nucleocapsid-, and envelope-protein peptides does not significantly affect the heart or other organ systems adversely, even when using a highly susceptible mouse strain for experimental autoimmune diseases. This suggests that inducing an immune reaction against these peptides of the SARS-CoV-2 virus alone is not sufficient to cause inflammation and/or dysfunction of the myocardium or other studied organs.

A STUDY OF CARDIAC COMPLICATIONS BASED ON ECG CHANGES IN COVID 19 POSITIVE PATIENTS

Aims & Objectives Ÿ To study the cardiac complications based on ECG changes in COVID 19 positive patients. Materials And Methods Ÿ It is a Prospective case study with sample size of 500 done in East point Medical College and Research hospital, Bangalore. Results: 300 patients had normal sinus rhythm.130 patients had tachycardia, 70 patients had bradycardia. 30 patients had arrhythmia, 27 patients had evidence of cardiac injury.154 patients had evidence of myocarditis. 40 patients had evidence of heart failure and 15 patients had cardiomyopathy. 50 patients had an evidence of venous thromboembolic events. Cardiac invol Conclusion: vement is very common in SARS –Cov-2 infection. Myocarditis is more common, though it may not be fatal in most cases, it can be problematic in case of associated co-morbid conditions

ECG CHANGES IN DENGUE FEVER

Background: Dengue is one of the most important viral diseases globally and a majority of symptomatic infections result in a benign course. However, a small number of patients develop severe manifestations, including myocardial impairment, arrhythmias, and fulminant myocarditis. Dengue is known to affect various systems. The cardiovascular system is one of them. This study was conducted to observe the presence of electrocardiographic (ECG) changes in patients presenting with dengue fever. Material and method: This was a cross sectional analytical study conducted at Jhalawar medical college and hospital, Jhalawar, Rajasthan. 146 cases were selected after taking into account the inclusion and exclusion criteria from serologically confirmed dengue cases. The details of the patient's clinical presentation and examination was noted.ECG was carried out to all patients. Results: Out of 146 patients,58 patients had normal ECG. Abnormal ECG findings like sinus bradycardia ,tachycardia ,ST-T changes,bundle branch block were noted among 88 patients. Conclusion: ECG changes can occur in dengue infection, most common finding were sinus bradycardia. ECG abnormalities were common but all the ECG changes were reversible. There was no evidence of myocarditis in any of the patients

Abstract 14421: Avoid Pericardiectomy in Transient Constrictive Pericarditis

Case Presentation: A male in his 40s presented for chest pain, dyspnea and bilateral leg edema. He has a history of hypertrophic cardiomyopathy treated with septal myectomy complicated by constrictive pericarditis (CP) that was treated with right-sided pericardiectomy, NSAIDs, colchicine, and steroids. Echo showed LVEF of 55% with thickening of the pericardium, abnormal septal bounce, tethering of the right atrium, respiratory variation in flow across the mitral and tricuspid valves and IVC plethora. Cardiac MRI showed diffuse mild thickening of residual left-sided pericardium, mild diffuse circumferential pericardial enhancement, mild diastolic septal bounce, diastolic restraint, exaggerated inspiratory flattening and conical deformity of the ventricles without evidence of myocardial inflammation or scarring. Right heart catheterization showed near equalization of RV and LV pressures, RV and LV respiratory concordance, aortic pulsus paradoxus with an inspiratory decrease of 15 mmHg, and Kussmaul’s sign with an inspiratory increase in RA pressure of 68 mmHg. Left heart catheterization showed normal coronaries. The patient was diagnosed with CP and underwent repeat pericardiectomy and was treated with NSAIDs and diuretics. On follow-up, patient had symptomatic improvement but still had evidence of residual constriction on echocardiogram. Discussion: Pericardiectomy is the definitive treatment for CP, however it carries high morbidity and mortality rates. Recurrence of constrictive pericarditis requiring repeat pericardiectomy is very rare and risk factors for recurrence are not well-defined. His initial pericardiectomy was complicated with evidence of active visceral epicarditis with epicardial constriction. This case suggests that active inflammation at the time of pericardiectomy is a potential risk factor for recurrent CP requiring repeat pericardiectomy, and surgery should be deferred until the active inflammation has subsided.

Abstract 11186: Clinical Presentation and Outcome of Myocarditis After Covid-19 Vaccination Among Adolescents: A Systematic Review and Meta-Analysis

Introduction: The association of the COVID-19 vaccination with myocarditis has been reported in adolescents. However, evidence of myocarditis after COVID-19 vaccination among adolescents is scarce compared to adults. We aimed to investigate the clinical features and outcomes of COVID-19 mRNA vaccination-related myocarditis in adolescents. Methods: PubMed and EMBASE were searched through April 2022 to investigate the characteristics of vaccine-associated myocarditis in adolescent patients (aged 12-20 years) through observational studies, case series, and correspondence according to PRISMA guidelines. Data regarding patient characteristics, the type, and dose of the vaccine, laboratory data, imaging studies, mortality, and treatments were extracted from each article. One-group meta-analysis in a random-effects model was performed. Results: 22 observational studies were identified, including 861 cases of vaccine-associated myocarditis. The mean age was 16.0 (95%CI, 15.5-16.5), and the male was predominant at 90.8%. Three-quarters of myocarditis occurred after the second dose (78.2%, 95% CI, 62.4- 94.0). The incident rate was higher after the second dose (12.7 -118.7 per million persons) than the first dose (0.6-10.0 per million persons). Chest pain (85.2%) was the common presenting symptom. Although 16.0% of patients (51/302) had left ventricular (LV) systolic dysfunction (LV ejection fraction [EF] < 55%), most of the cases (40/289) were mildly reduced LVEF as 45-54% (12.0% of total patients). Interestingly, cardiac magnetic resonance imaging revealed late gadolinium enhancement in 80.5% (95% CI, 65.7-95.2) of the cases. Overall, 92.8% of patients required hospitalization, and 14.7% required intensive care unit admission. However, no in-hospital mortality was observed (0/230), and the length of stay at the hospital was less than 5 days. Conclusions: This systematic review and meta-analysis demonstrate a low incident rate and largely favorable outcomes of COVID-19 vaccine-associated myocarditis in adolescents. Our findings would help better understand myocarditis following COVID-19 mRNA vaccination among adolescents and decision-making for parents with vaccine hesitancy.

Acute Q Fever with Atrioventricular Block, Israel.

Cardiac involvement in acute Q fever is rare. We report 2 cases of an advanced atrioventricular block in young adult patients in Israel who sought care for acute Q fever without evidence of myocarditis. Q fever should be suspected in unexplained conduction abnormalities, especially in febrile young patients residing in disease-endemic areas.

Effect of Immunosuppressive Therapy and Biopsy Status in Monitoring Therapy Response in Suspected Cardiac Sarcoidosis

BackgroundPatients with suspected cardiac sarcoidosis frequently undergo fluorodeoxyglucose (FDG)–positron emission tomography (PET)/computed tomography (CT) imaging to assess disease activity at baseline and after treatment initiation. ObjectivesThis study investigated the effect of immunosuppressive therapy and biopsy status to achieve complete treatment response (CTR), partial treatment response (PTR), or no response (NR) on myocardial FDG-PET/CT. MethodsThis study analyzed 83 patients with suspected cardiac sarcoidosis (aged 53 ± 1.8 years, 71% were male, 69% were White, 61% had a history of biopsy-confirmed sarcoidosis) who were treatment naive, had evidence of myocardial FDG at baseline, and underwent repeat PET imaging after treatment initiation. CTR was graded visually, and PTR/NR were measured both visually and quantitatively using the total glycolytic activity. Patients were also evaluated for the occurrence of death, sustained ventricular arrhythmias, and heart failure admissions. ResultsOverall, 59 patients (71%) achieved CTR/PTR (30%/41%) at follow-up scan (P = 0.04). Total glycolytic activity and visual estimate of PTR/NR had excellent agreement (κ = 0.86 [95% CI: 0.72-0.99]; P < 0.0001). In patients receiving prednisone only, the highest rates of CTR/PTR were observed in patients initiated on moderate or high dose (P < 0.01). In a regression model, moderate prednisone start dose (P = 0.03) was more strongly associated with achieving CTR/PTR than was high prednisone start dose. However, the latter patients were tapered faster between start dose and follow-up scan (P < 0.01). After a median follow-up of 4.7 (IQR: 3.1-7.8) years, patients who were biopsy-proven (vs non-biopsy-proven; P = 0.029) and with preserved left ventricular function (P = 002) were less likely to experience major adverse cardiac events. Outcomes based on treatment response status (CTR vs PTR vs NR; P = 0.23) were not significantly different. ConclusionsAmong patients with suspected sarcoidosis and evidence of myocardial inflammation, treatment response by serial FDG-PET was variable, but a favorable response was more common when using moderate-to-high intensity prednisone dose. Biopsy-proven individuals and those with preserved systolic function were less likely to experience adverse outcomes during follow-up.

DILATED CARDIOMYOPATHY ASSOCIATED WITH IMMUNE CHECKPOINT INHIBITOR, NIVOLUMAB

TYPE: Case Report TOPIC: Pharmacotherapeutics INTRODUCTION: Cardiomyopathy related to immune checkpoint inhibitor (ICI) is an infrequent adverse event, and the mechanism is still unclear. The most plausible mechanism is via hyper-infiltration of T- cells that damage the myocardial tissue. CASE PRESENTATION: An 88-year-old female with metastatic melanoma receiving treatment with Nivolumab and Talimogene laherparevec (intralesional), presented with of progressive dyspnea for five days. The patient was diagnosed with acute hypoxic respiratory failure secondary to acute heart failure. Initial laboratory values included brain natriuretic peptide (BNP) level of 530 pg/ml, and high sensitivity troponin level of 130 ng/L. Electrocardiogram showed normal sinus rhythm without evidence of acute ST-changes. Computed tomography angiogram of the chest confirmed evidence of bilateral pleural effusions without evidence of pulmonary embolism (Figure 1). Patient underwent left thoracocentesis performed by interventional radiology. Echocardiogram showed LVEF of 20-25% with severe global hypokinesis. Pleural fluid analysis was consistent with transudate. There was no evidence of malignancy on cytology or infection on gram stain. Cardiac magnetic resonance imaging was performed indicating LVEF of 23%, but no evidence of myocarditis or any infiltrative process. Left heart catherization showed no evidence of coronary artery disease. The medical recommendation was to discontinue Nivolumab therapy. DISCUSSION: Our clinical case highlights the importance of long-term follow-up of cancer patients consuming ICI since there are rare cardiac adverse events that presents after several months. Unfortunately, our patient died within 30 days of discharge. CONCLUSIONS: Cardiomyopathy is a rare, but potentially life-threatening complication of ICI therapy and should be considered when discussing treatment modalities with patients, especially the elderly. DISCLOSURE: Nothing to declare. KEYWORD: nivolumab

Low Risk of Cardiac Complications in Collegiate Athletes After Asymptomatic or Mild COVID-19 Infection.

The objective of this study was to determine the utility of "standard" cardiac screening with EKG, echocardiography, and serum troponin T (hs-Tn T) testing after COVID infection in competitive college athletes. Prospective cohort study. Tertiary cardiology clinic, university training room. Sixty-five Division 1 athletes recovered from COVID-19 and 465 controls. All COVID-recovered athletes underwent cardiac screening on return to campus in fall 2020. Controls were screened if indicated by preparticipation examination. Students cleared for sports participation were followed for the development of cardiac complications. Incidence of cardiac complications after COVID infection. Infected athletes experienced mild (26/65), moderate (8/65), or no (31/65) COVID symptoms. No athletes had severe symptoms. Men were more likely to have been asymptomatic (20/31), and women were more likely to have had moderate (7/8) symptoms (P = 0.015). All athletes, except 2 with anosmia, were asymptomatic at the time of cardiac testing. One athlete had persistently elevated hs-Tn T but no evidence of myocarditis on cardiac MRI. All other cardiac testing was negative. No athletes were diagnosed with myocarditis (95% CI: 0%-5.5%). All athletes were cleared for athletic participation. None suffered complications over the next 9 months. After COVID-19 infection, no college athletes with mild, moderate, or no symptoms had signs of myocarditis, and all returned to play without cardiac complication. These findings support consensus opinion recommendations that college-age athletes who recovered from COVID-19 and who experienced mild or no symptoms may return to play without cardiac testing.

Concomitant myocarditis and painless thyroiditis after AstraZeneca coronavirus disease 2019 vaccination: a case report

BackgroundIncidence of myocarditis following messenger RNA coronavirus disease 2019 vaccination has been widely described, but this clinical scenario after adenoviral vector coronavirus disease 2019 vaccination has only been rarely reported. In addition, a few case reports of thyroiditis after adenoviral vector coronavirus disease 2019 vaccination have been published.Case presentationA 55-year-old Thai woman presented with palpitation without neck pain 14 days after receiving AstraZeneca coronavirus disease 2019 vaccination. Electrocardiography revealed sinus tachycardia. Her blood tests showed elevation of cardiac troponin and free triiodothyronine with suppressed serum thyroid stimulating hormone, reflecting a hyperthyroid status. Evidence of myocardial inflammation and necrosis from cardiac magnetic resonance imaging supported the diagnosis of recent myocarditis. Laboratory results and imaging findings were consistent with thyroiditis. After 3 weeks of symptomatic treatment, her symptom and blood tests had returned to normal.ConclusionsThis case demonstrates that the adenoviral vector coronavirus disease 2019 vaccine could possibly cause myocarditis and painless thyroiditis. Clinicians should have a high index of suspicion and promptly evaluate these conditions, despite minimal symptoms.

CORRELATION OF CARDIAC MANIFESTATIONS IN DENGUE

Objectives: This study was done to study the prevalence of cardiac manifestations of dengue fever in patients presenting to our hospital and to find out the correlation of cardiac manifestations with the warning signs of dengue infection The study was conducted at Government Villupuram Medical College and Hospital,a tertiary careMethods: hospital in the month of July to December 2021. One hundred consecutive patients aged 15 years or more with positive dengue serology were interviewed and examined. ECG was done for all patients and selected patients underwent echo evaluation and troponin testing. The data was analyzed using statistical significance tests Thirty-three patientsResults: had no warning signs, 59 patients had one warning sign or the other. Eight patients had severe dengue. The minimum pulse rate was 32/ minute. The most common cardiac abnormalities noted were rhythm abnormalities of which the commonest was sinus bradycardia, found in 34 percent. There was statistically significant correlation between cardiac manifestations and all the warning signs except persistent vomiting. Among severe dengue, fluid accumulation causing respiratory distress was found to have a significant correlation with the cardiac manifestations The mostConclusions: common cardiac manifestations noted were transient rhythm abnormalities, of which sinus bradycardia was the commonest. There was no evidence of Myocarditis in any of the patients .There was statistically significant correlation between cardiac manifestations and all the warning signs except persistent vomiting. Among severe dengue, fluid accumulation causing respiratory distress was found to have a significant correlation with the cardiac manifestations.

PO-684-06 ARRHYTHMIC MITRAL VALVE PROLAPSE WITH ONLY MILD OR MODERATE MITRAL REGURGITATION: CHARACTERIZATION BY PET/MRI

Mitral valve prolapse (MVP) has been associated with ventricular arrhythmias and sudden cardiac death (SCD). A majority of MVP-related SCD occurs in patients with only mild or moderate MR. Replacement fibrosis, which is known to occur in the absence of severe MR, may be preceded and accompanied by an inflammatory response. We previously reported on a series of patients with severe MR planned for elective mitral valve surgery who underwent Hybrid PET-MRI imaging, and demonstrated that >90% of those patients with complex ventricular ectopy had evidence of FDG uptake, suggestive of ongoing subclinical inflammation. To evaluate the presence of myocardial inflammation/fibrosis and VA burden in a cohort of patients with MVP (Barlow’s) and less than severe MR. 10 patients with degenerative MVP and mild or moderate MR by transthoracic echocardiography underwent 18F-FDG PET/MRI (“Hybrid” PET/MRI). Focal 18F-FDG uptake was evaluated as a surrogate of inflammation, and LGE imaging was evaluated for myocardial fibrosis. Ambulatory extended ECG monitoring was performed to assess VA burden and severity. Mean age was 56.3 ±11.4 years, and 70% were female. Mean LVEF and LV end-diastolic diameter were 61.8 ±5.6% and 48.3±6.2 mm. Focal 18F-FDG uptake and LGE (PET+/MRI+) were present in 70% (n=7) of patients (Figure); 1 patient had focal 18F-FDG uptake and LGE was not performed. Only 2 patients had neither inflammation or fibrosis (PET-/MRI-). Complex ventricular ectopy was detected in 80% (n=8). In a cohort of patients with only mild or moderate MR, of which a majority had complex ventricular ectopy, 70% had evidence of myocardial inflammation and fibrosis. These findings may provide insight into the observation that a majority of sudden deaths in patients with MVP occur in patients with less than severe MR, as inflammation and fibrosis are both known to be pro-arrhythmic. Future studies are needed to determine whether the presence of myocardial inflammation impacts the natural history of degenerative MVP.

Morphologically, immunohistochemically and PCR proven lymphocytic viral peri-, endo-, myocarditis in patients with fatal COVID-19

BackgroundDespite a reported cardiac injury in patients with new coronavirus infection, the possibility and specifics of genuine viral myocarditis in COVID-19 remains not fully clear.PurposeTo study the presence of SARS-CoV-2 in the myocardium and the morphological properties of myocarditis in patients with severe coronavirus infection (COVID-19).MethodsAutopsy data of eight elderly patients (75.6 ± 7.4 years), four male and four female, with severe new coronavirus infection were studied. The lifetime diagnosis of COVID-19 is based on a positive result of the PCR study. The inclusion criterion was the presence of morphological signs of myocarditis according to the Dallas criteria. A standard histological examination included staining by hematoxylin and eosin, toluidin blue and Van Gieson. An immunohistochemical study was performed using antibodies to CD3, CD 68, CD20, perforin, toll-like receptor (TLR) types 4 and 9. PCR in real-time was performed to determine the viral RNA in the myocardium.ResultsAll patients had severe bilateral viral pneumonia. In all cases, myocarditis was not clinically diagnosed. Morphological examination of the heart found signs of active lymphocytic myocarditis. PCR identified the SARS-Cov2 RNA in all cases. There were also signs of destructive coronaritis in all cases, thrombovasculitis, lymphocytic pericarditis (in 3 cases) and endocarditis (in 2 cases). The absence of neutrophils confirms the aseptic nature of inflammation. An immunohistochemical study showed the CD3-positive T lymphocytes in the infiltrates. Increased expression of TLR type 4 and less 9 was also detected.ConclusionMorphological and immunohistochemical evidence of myocarditis in COVID-19 was presented. Lymphocytic infiltrations and positive PCR confirm the viral nature of inflammation. Myocarditis in COVID-19 is also characterized by coronaritis with microvascular thrombosis and associated with lymphocytic endo- and pericarditis.

Clinical and histopathological features of immune checkpoint inhibitor-related myositis in patients with advanced non-small cell lung cancer

Objective: To investigate the clinicopathologic features and outcome of myositis in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors. Methods: The patients diagnosed with immune checkpoint inhibitor-related (ICI) myositis in the database of Respiratory Pathology Center of The First Affiliated Hospital, Guangzhou Medical University from June 2019 to December 2020 were retrospectively analyzed. We reported the muscle histology and main clinical manifestations of the patients in this study. Seven patients with advanced non-small cell lung cancer and ICI related myositis were examined; all of the patients were male, with a median age of 64 (range 42-79) years. Results: All seven patients developed myositis under therapy (three for pembrolizumab, three for sintilimab, and one for camrelizumab). Median delay between ICI initiation and myositis onset was 45 (range 15-176) days. Clinical manifestations were dominated by acute or subacute myalgia and limb weakness. Four patients had evidence of myocarditis. In all of the 7 patients, creatine kinase levels were elevated (median 2 354.4, range 468.6-19 709.2 U/L), while myositis-associated antibodies Ro-52 were positive in four patients. Muscle biopsy showed evident multifocal necrotic myofibers and infiltration of inflammation in two patients. Other patients only showed non-specific endomysial inflammation. Infiltration of inflammation mainly consisted of CD8+ T cells and CD68+ histocytes. After the identification of ICI related myositis, ICI treatment was withdrawn in all patients; 6 patients received corticosteroids therapy. All patients had shown marked clinical improvement. Conclusions: ICI myositis presents with remarkably homogeneous and unique clinicopathologic features, and half of the patients exhibit heightened risk for adverse cardiovascular events, which can be life-threatening if not treated in time. Timely identification of these patients, ICI withdrawal and rapid initiation of corticosteroids therapy can significantly improve patient outcome and/or save patients' lives.

A Rare Case of Mesalazine-Induced Acute Myocarditis in a 19-Year-Old Female With Ulcerative Colitis

Mesalazine is a commonly used first-line therapy to treat acute mild to moderate ulcerative colitis (UC). Myocarditis is a rare complication of inflammatory bowel disease. This is a case report of a 19-year-old female with myocarditis induced after commencing mesalazine for UC. She was admitted with pleuritic-type chest pain associated with severe dyspnoea and was hemodynamically unstable during admission. She had elevated troponin and N-terminal pro-B-type natriuretic peptide. Transthoracic echocardiogram (TTE) results suggested there was evidence of myocarditis with reduced ejection fraction, which was later confirmed by cardiac magnetic resonance imaging. There was a rapid improvement of cardiac status after stopping mesalazine within two weeks.