Relationships between plasma cytokine balance and cardiac magnetic resonance imaging in long-term post-COVID follow-up: A cross-sectional preliminary study

Background: COVID-19 infection can lead to a constellation of longlasting post-infectious sequelae, including myocardial dysfunction, whose outcome is strongly affected by a fine-tuned balance between pro-and anti-inflammatory systemic immune responses. Plasma cytokines are key mediators of this immunological balance. In this preliminary study we evaluated the cross-sectional association between the circulating levels of the main pro-and anti-inflammatory cytokines and cardiac magnetic resonance (CMR) abnormalities. Method(s): 71 subjects (59% female, mean age 52+/-14) with previous diagnosis of COVID-19 infection were enrolled at our institution for MULTICOVID protocol, comprehensive of CMR and biomarkers assessment performed >3 months and <1 year following the first negative swab test. CMR protocols consisted of conventional sequences (cine, T2-weighted imaging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume [ECV] mapping). Plasma levels of cytokines TNF-alpha, IL-1beta, IL-1alpha, IFN-alpha2, IL-6, IL-8, IL-13, IL-10, IL-17A, IL-18, IP-10, MIG and MCP-1 were quantified by Multiplex Immunoassays on the Luminex technology platform. Soluble cardiologic and biochemical biomarkers were measured by routine laboratory analysis. Result(s): After a median of 9 (IQR 6-11) months following negative swab, CMR was normal in 48 subjects, while in 23 (32%) it revealed tissue characterization abnormalities (myocardial late enhancement and/or edema). By multivariate regression analysis (adjusted for age, sex, vaccination, severity degrees of the initial COVID disease, presence of comorbidities, smoke, time interval between COVID diagnosis and CMR assessment) the cytokine ratio TNF-alpha/(IL-10+IL-13) was independently associated (OR=2.89, 95% CI 1.19-7.04, p=0.02) with CMR abnormalities. Interestingly, the cumulative pro-/anti-inflammatory cytokine ratio (IL-1beta+TNF-alpha+IFN-alpha2+IL-6+IL-17A+IL-8)/(IL-10+IL-13) showed a positive (OR=1.70, 95% CI: 1.04-2.75) and significant (p=0.03) association with CMR imaging aspects. Also, the ratio IFN-alpha2/(IL-10+IL-13), although without achieving a complete statistical significance (p=0.09), was associated positively with CMR findings. Conclusion(s): The preliminary results of this cross-sectional study suggest that the systemic inflammatory environment, long-lasting unbalanced towards a prevalent cytokine-driven pro-inflammatory condition following COVID infection, could affect the development of CMR-detectable myocardial edema and fibrosis in long-term post-COVID subjects.

Evaluation of cardiac involvement in patients with clinical post-COVID-19 syndrome

Introduction: The underlying pathophysiology of Post-COVID-19 syndrome remains unknown, but increased cardiometabolic demand and state of mitochondrial dysfunction have emerged as candidate mechanisms. Cardiovascular magnetic resonance (CMR) provides insight into pathophysiological mechanisms underlying cardiovascular disease and 31-phosphorus magnetic resonance spectroscopy (31P-MRS) allows noninvasive assessment of the myocardial energetic state. Purpose(s): We sought to assess whether Post-COVID-19 syndrome is associated with abnormalities of myocardial structure, function, perfusion and tissue characteristics or energetic derangement. Method(s): Prospective case-control study. A total of 20 patients with a clinical diagnosis of Post-COVID-19 syndrome (seropositive) and no prior underlying cardiovascular disease (CVD) and ten matching controls underwent 31P-MRS and CMR at 3T at a single time point. (Figure 1) All patients had been symptomatic with acute COVID-19, but none required hospital admission. Result(s): Between the Post-COVID-19 syndrome patients and matched contemporary controls there were no differences in myocardial energetics (phosphocreatine to ATP ratio), in cardiac structure (biventricular volumes, left ventricular mass), function (biventricular ejection fractions, global longitudinal strain), tissue characterization (T1 and extracellular volume [ECV] fraction mapping, late gadolinium enhancement) or perfusion (myocardial rest and stress blood flow, myocardial perfusion reserve). One patient with Post-COVID-19 syndrome showed subepicardial hyperenhancement on the late gadolinium enhancement imaging compatible with prior myocarditis, but no accompanying abnormality in cardiac size, function, perfusion, ECV, T1, T2 mapping or energetics. This patient was excluded from statistical analyses. (Table 1) Conclusion(s): In this study, the overwhelming majority of patients with a clinical Post-COVID-19 syndrome with no prior CVD did not exhibit any abnormalities in myocardial energetics, structure, function, blood flow or tissue characteristics.

A case of mRNA COVID-19 vaccine-associated myocarditis in a child

Background and Aim: Accumulation of cases is needed to determine whether vaccines should be recommended for children because of their potential to cause myocarditis in healthy children. Method(s): We report a case in which changes in laboratory data, electrocardiogram (ECG), and magnetic resonance imaging (MRI) were tracked at our hospital. Result(s): A 12-year-old girl developed fever a day after receiving the second dose of the COVID-19 vaccine. Three days after vaccina-tion, she also developed chest pain and went to a hospital. ECG showed ST-T segment elevation. However, the symptoms were mild, and she was treated with antipyretics and analgesics. The next day, she visited the hospital again because she had mild chest pain. ECG showed a negative T-wave, and she was referred to our hos-pital. Her real-time reverse-transcription polymerase chain reac-tion tests for COVID-19 yielded negative results. Computed tomography revealed no anatomical abnormalities of the coronary arteries. The serum concentration of troponin T was elevated by 131 ng/L. Echocardiography showed the left ventricular ejection fraction to be 64%. MRI showed a normal T2 value on T2-weighted imaging;however, extracellular volume increased by 33%. Although the Lake Louise criteria was not met, we diagnosed the condition as myocarditis. She was hospitalized for 2 days and discharged without the need for steroids or gamma globulin treat-ment to relieve her symptoms. Although these findings improved 17 days after vaccination, late gadolinium enhancement was noticed on MRI. Conclusion(s): The COVID-19 vaccine-related myocarditis (C-VAM) in this case was mild and like as cases in Europe and the United States. The risk of COVID-19 associated myocarditis is more than three times the risk of C-VAM. In addition, the mor-tality rate for COVID-19 associated myocarditis is higher than that for C-VAM. The need for a vaccine to protect populations from COVID-19 should be properly recognized. However, because the symptoms of C-VAM are mild, there may be many potential patients with C-VAM. Therefore, it may be advisable to avoid strenuous exercise for approximately 1 week after vaccination. Further research is needed to determine the long-term outcomes of C-VAM because of the late enhancement identified on MRI.

Dynamic change of an electrocardiogram in myocarditis following mRNA COVID-19 vaccination

Background and Aim: Coronavirus disease (COVID-19) is a pandemic infectious disease caused by the SARS-CoV-2 virus. At the begin-ning of 2021, the Food and Drug Administration (FDA) of the United States issued an emergency use authorization (EUA) for the Pfizer-BioNTech COVID-19 vaccine to prevent COVID-19 infection. Cases of myocarditis and pericarditis after the vaccination in adolescents and young adults have been reported, especially more often after the second dose. There are very few case reports in Asia. We aim to present a case of confirmed myocarditis after the Pfizer-BioNTech COVID-19 vaccine in Thailand and the remarkable dynamic change in an electrocardiogram (ECG). Method(s): Case report. We reported the case and reviewed serial electrocardiogram and echocardiographic findings, including car-diac magnetic resonance imaging (MRI) in a case of confirmed myocarditis after the Pfizer-BioNTech COVID-19 vaccine. Result(s): A previously healthy 13-year-old boy presented with chest pain and shortness of breath within 20 hours following the second dose of the Pfizer-BioNTech COVID-19 vaccine. Electrocardiogram (ECG) revealed diffuse ST-segment elevation with significant improvement within 3 hours. The peak level of high sensitivity cardiac troponin T was 1,546 ng/L. No alternative etiology of myocarditis was identified. Echocardiogram revealed mildly depressed left ventricular septal wall motion. Cardiac MRI showed abnormal native T1, T2 mapping, and extracellular volume (ECV) that were compatible with myocarditis. His symp-toms were relieved with ibuprofen. He was discharged on the fifth day of admission. In a 1-week follow-up, the ECG showed an incomplete right bundle branch block. Conclusion(s): This case illustrates the potential of myocarditis follow-ing mRNA COVID-19 vaccination with striking dynamic change and transition of the ECG. The possible mechanism for myocar-ditis after vaccination is molecular mimicry between viral spike protein and cardiac protein. More data and long-term follow-up are needed to understand the association between the COVID-19 vaccine and myopericarditis.

A CASE OF TRACHEOBRONCHIAL AMYLOIDOSIS PRESENTING AS SYNCOPE

SESSION TITLE: Systemic Diseases with Deceptive Pulmonary Manifestations SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Amyloidosis of the respiratory tract is rare. We present a case of tracheobronchial amyloid presenting as multifactorial cough with syncope. CASE PRESENTATION: The patient is a 65-year-old man with history of hypertension, hyperlipidemia, and allergic rhinitis who presented to the ED after a syncopal event. Two weeks prior, he had a new-onset myalgias and severe persistent cough, not resolving with over-the-counter medications. During a coughing paroxysm, he experienced a brief loss of consciousness. On arrival, his vital signs and physical exam were within normal limits except for Mallampati II, BM of 38.8 kg/m2. Basic laboratory testing was also unremarkable except for troponin T of 251 nl/dL and NT-ProBNP of 1181 pg/mL. NP swab for Sars-CoV-19 (PCR), Influenza A and B were not detected. CT of the chest revealed an area of circumferential mural soft tissue thickening in the left lower lobe bronchi. Cardiac MRI showed an area of subepicardial delayed enhancement, suggestive of myocardial inflammation or edema. Flexible bronchoscopy confirmed that the left lower lobe bronchus and proximal subsegmental bronchi had an infiltrative process with a friable, erythematous irregular mucosal surface. Forceps biopsy sampling and staining with Congo red, sulfate Alcian blue and Trichome stain were positive for amyloid deposits. Immunostain revealed predominantly CD3 positive T-Cells. Mass spectometry showed AL (lamda)-type amyloid deposition. GMS and AFB stains were negative. Telemetry showed 2-3 second pauses, correlated with episodes of cough. DISCUSSION: Amyloidosis is a disorder caused by misfolding of proteins and fibril accumulation in the extracellular space. It can present as a diffuse or localized process to one organ system. Several patterns of lung involvement have been described: nodular pulmonary, diffuse alveolar-septal, cystic, pleural, and tracheobronchial amyloidosis. Tracheobronchial amyloidosis is usually limited and not associated with systemic disease or hematologic malignancy. It can be asymptomatic, or can present with cough, dyspnea or signs of obstruction, including postobstructive pneumonia. Congo Red stained samples reveal green birefringence under polarized light microscopy. Further analysis of proteins usually reveals localized immunoglobulin light chains (AL). Cough syncope is due to increased intrathoracic pressure, decreased venous return and cardiac output, stimulation of baroreceptors, decreased chronotropic response, arterial hypotension and decreased cerebral perfusion. Our patient presented with multifactorial cough (possible viral infection, upper airway cough syndrome, amyloidosis) causing sinus pauses and syncope, on underlying myocarditis. CONCLUSIONS: Amyloid infiltration of the respiratory system is rare, but it should be considered in the differential diagnosis of airway disorders, nodular or cystic lung diseases, and pleural processes. Reference #1: Milani P, Basset M, Russo F, et al. The lung in amyloidosis. Eur Respir Rev 2017;26: 170046 [https://doi.org/10.1183/16000617.0046-2017]. Reference #2: Utz JP, Swensen SJ, Gertz MA. Pulmonary amyloidosis. The Mayo Clinic experience from 1980 to 1993. Ann Intern Med. 1996 Feb 15;124(4):407-13. doi: 10.7326/0003-4819-124-4-199602150-00004 Reference #3: Dicpinigaitis PV, Lim L, Farmakidis C. Cough syncope. Respir Med. 2014 Feb;108(2):244-51. doi: 10.1016/j.rmed.2013.10.020. Epub 2013 Nov 5. PMID: 24238768. DISCLOSURES: No relevant relationships by Amarilys Alarcon-Calderon No relevant relationships by Ashokakumar Patel

A case of severe rhabdomyolysis and acute myocarditis in an adolescent female

INTRODUCTION: Rhabdomyolysis describes a condition where muscle tissue destruction occurs. Mortality and morbidity can be significant especially when multi-organ injury ensues. In very few instances, myocarditis has been described in association with this condition. DESCRIPTION: An 11-year-old previously healthy female presents with vomiting, diarrhea, tactile fever, worsening severe bilateral leg pain and gross hematuria for four days. At the Emergency Department, her ECG showed ST depression in lateral leads and abnormal Q waves. Laboratory studies were notable for significantly elevated CK >330,000 U/L. Elevated Troponin T and Troponin I at 3.60 ng/ml and 0.54 ng/mL, respectively. Elevation of CRP 23.5 mg/dl, ALT 1,966 U/L, AST 5,956 U/L, and Ferritin 712.1 ng/ml. Patient had dark brown urine, which was positive for blood, and urine myoglobin peaked at 2690 ng/mL. Her renal function was normal with blood urea nitrogen 8 mg/dl and creatinine 0.4 mg/dl. C3 and C4 levels were decreased, 45 mg/dl and 5 mg/dl, respectively. Anti-dsDNA negative, ANCA negative, and ANA negative. Nasopharyngeal PCR was negative for Mycoplasma pneumoniae, influenza A and B. Blood enterovirus PCR negative. COVID PCR and antibodies negative. Neuromuscular genetic testing was non-diagnostic. Her echocardiography showed thin rim of pericardial effusion and normal ejection fraction. Cardiac MRI demonstrated myocardial edema and regional sub-epicardial delayed enhancement consistent with acute myocarditis. Patient was started on hyperhydration therapy, Solumedrol and intravenous immunoglobulin. The rhabdomyolysis resulted in severe extremity weakness requiring prolonged rehabilitation. Her condition and biomarkers normalized and was subsequently discharged home. Follow up cardiac MRI 6 months later showed increased extracellular volume (ECV) of 38% suggestive of focal and diffuse areas of fibrosis. Patient remains under physical activity restrictions and is being followed by cardiology service. DISCUSSION: Our case highlights severe rhabdomyolysis in association with acute myocarditis and subsequent cardiac structural abnormalities. Although it remains unclear whether myocarditis evolved as a complication of rhabdomyolysis or was triggered by same inciting agent, an infectious etiology overall remains the most likely culprit.

Longitudinal trajectory of cardiac magnetic resonance and cardiopulmonary exercise testing findings in moderate to severe COVID-19 and association with symptoms

Background: Cardiac magnetic resonance (CMR) and cardiopulmonary exercise testing (CPET) have provided important insights into the prevalence of early cardiopulmonary abnormalities in COVID-19 patients. It is currently unknown whether such abnormalities persist over time and relate to ongoing symptoms. Purpose: To describe the longitudinal trajectory of cardiopulmonary abnormalities on CMR and CPET in moderate to severe COVID-19 patients and assess their relationship with ongoing symptoms. Methods: Fifty-eight previously hospitalised COVID-19 patients and 30 age, sex, body mass index, comorbidity-matched controls underwent CMR, CPET and a symptom-based questionnaire at 2-3 months (2-3m). Repeat assessments (including gas transfer) were performed in 46 patients at 6 months (6m). Results: During admission, 1/3rd of patients needed ventilation or intensive care (Table 1) and three (5%) had a raised troponin. On CMR, patients had preserved left (LV) and right ventricular (RV) volumes and function at 2-3m from infection. By 6m, LV function did not change but RV end diastolic volume decreased (mean difference -4.3 mls/m2, p=0.005) and RV function increased (mean difference +3.2%, p<0.001, Fig. 1A). Patients had higher native T1 (a marker of fibroinflammation) at 2-3m compared to controls (Table 1, Fig. 1B), which normalised by 6m. Extracellular volume was normal and improved by 6m. Native T2, a marker of myocardial oedema, did not differ between patients and controls on serial CMR. At 2- 3m, late gadolinium enhancement (LGE) was higher in patients (p=0.023) but became comparable to controls by 6m (p=0.62). Six (12%) patients had LGE in a myocarditis pattern and one (2%) had myocardial infarction. None had active myocarditis using the Modified Lake Louise Criteria. Lung imaging (T2-weighted) revealed parenchymal abnormalities in 2/3rds of patients at 2-3 and 6 months. The extent of abnormalities improved on serial imaging (Table 1). Gas transfer (DLco) was worse in those with lung abnormalities (77% vs 91% of predicted, p=0.009). CPET revealed reduced peak oxygen consumption (pVO2) in patients at 2-3m, which normalised by 6m (80.5% to 93.3% of predicted, p=0.001) (Table 1, Fig. 1C). At 2-3m, 49% of patients had submaximal tests (respiratory exchange ratio <1.1), reducing to 25% by 6m (p=0.057). VE/VCO2 slope, a marker of lung efficiency, was abnormal in patients but improved on serial CPET (Table 1, Fig. 1D). Cardiac symptoms (chest pain, dyspnoea, palpitations, dizziness or syncope) were present in 83% of patients at 2-3m, reducing to 52% by 6m (p<0.001). There was no significant association between CMR or CPET parameters and persistent cardiac symptoms at 6m (Fig. 1E). Conclusions: Cardiopulmonary parameters (on CMR and CPET) improved in moderate-severe COVID-19 patients from 2-3 to 6 months post infection. Despite this, patients continued to experience cardiac symptoms which had no relationship with measured parameters. (Figure Presented).