718 Cardiac injury following immunization with mRNA SARS-CoV-2 vaccines

Aims Cardiac involvement as myocarditis and/or pericarditis is now recognized as a rare but possible adverse event following SARS-CoV-2 mRNA vaccines. In this brief report we describe a series of four subjects: three of them with myocarditis and one with pericarditis probably due to hypersensitivity and developed in temporal association with COVID-19 mRNA vaccination. Methods and results During last summer, we observed a series of four young Caucasian male [median (range) age, 25 (18–32) years] presenting to the Emergency Department with severe acute chest pain within few days after second dose COVID-19 mRNA vaccine administration [median (range), 3 (2–5) days]. All of these were previously healthy and fitness males. All patients had abnormal electrocardiogram (EKG) and three of them had elevated high sensitive cardiac I troponin (hs-cTnI) levels. These latter three were diagnosed as having myocarditis and undergone cardiac magnetic resonance imaging (CMR). None had acute or prior COVID-19 or pulmonary disease on chest X-ray. Moreover, ischaemic injury, other infections, adverse drug reactions or any autoimmune diseases were excluded by appropriate tests. All patients underwent ecocardiography which showed preserved ejection fraction and no wall motion abnormalities and it excluded coronary origin abnormalities in each patient. The hospital course was uneventful for all four patients and they were discharged within few days of hospitalization [median (range), 6 (3–8) days] after a conservative treatment. The four patients met CDC criteria for probable myocarditis and pericarditis. To date, it is recognized a possible clinical correlation between cardiac injury and SARS-CoV-2 mRNA vaccination. The following elements support this hypothesis: (i) short time lapse between vaccine administration and symptoms onset; (ii) onset after the second dose suggesting an immune-mediated pathogenesis needing a previous sensibilization; (iii) exclusion of other possible damage causes (ischaemia, infections, other immune-mediated diseases, toxicity). In particular, we did not perform coronary angiography given the low pre-test probability of coronary heart disease. Although compending a small sample, our report includes a patient series with clinical features similar to those frequently encountered into other papers: i.e. a prevalence in young males without risk factors; symptoms onset within few days second dose administration; an eventful clinical course. This benign course, seen in the majority of cases in literature, raises the question of the need for specific therapy or an empirical one for symptoms control only. Our report suggest that possible cardiac involvement can range from isolated pericarditis to myocarditis with significant hs-cTnI raise and signs of acute inflammation at CMR or even a myocardial injury with a mild hs-cTnI raise in absence of pathological signs at CMR. This latter case suggests also a possible cardiac injury with subclinical course. Conclusions To date, we are observing a temporal association linking mRNA SARS-CoV-2 vaccines administration and cardiac involvement. According to the majority of papers, our experience suggests an acute benign course of such cardiac involvement; a longer follow-up will also reveal a long-term benign course or conversely the presence of any sequelae. Clinicians should adequately inform patients when receiving vaccine to ensure prompt symptoms recognition and consequently put in place the best management of myocarditis/pericarditis. Finally, it is important to keep in mind that the benefits of vaccines far outweigh the risks.

Review of Mechanisms, Pharmacological Management, Psychosocial Implications, and Holistic Treatment of Pain in Fabry Disease

Fabry disease is a progressive X-linked lysosomal storage disease caused by a mutation in the GLA gene, encoding the lysosomal hydrolase α-galactosidase A. The consequent reduced enzyme activity results in the toxic accumulation of glycosphingolipids, particularly globortriaosylceramide (Gb3 or GL3), in blood vessels, renal epithelia, myocardium, peripheral nervous system, cornea and skin. Neuropathic pain is the most common manifestation of Fabry disease and can be extremely debilitating. This often develops during childhood and presents with episodes of burning and sharp pain in the hands and feet, especially during exercise and it is worse with increased heat or fever. It is thought to be due to ischaemic injury and metabolic failure, leading to the disruption of neuronal membranes and small fibre neuropathy, caused by a reduced density of myelinated Aδ and unmyelinated C-fibres and alterations in the function of ion channels, mediated by Gb3 and lyso Gb3. It is important to confirm small fibre neuropathy before any Fabry disease treatment modality is considered. There is a clinical need for novel techniques for assessing small fibre function to improve detection of small fibre neuropathy and expand the role of available therapies. The current Fabry disease guidelines are in favour of pharmacological management as the first-line treatment for pain associated with Fabry disease. Refractory cases would benefit from a rehabilitation approach with interdisciplinary input, including medical, physiotherapy and psychological disciplines and including a Pain Management Programme.

Delirium and neuropsychological outcomes in critically Ill patients with COVID-19: a cohort study

ObjectiveTo characterise the clinical course of delirium for patients with COVID-19 in the intensive care unit, including postdischarge neuropsychological outcomes.DesignRetrospective chart review and prospective survey study.SettingIntensive care units, large academic tertiary-care centre (USA).ParticipantsPatients (n=148) with COVID-19 admitted to an intensive care unit at Michigan Medicine between 1 March 2020 and 31 May 2020 were eligible for inclusion.Primary and secondary outcome measuresDelirium was the primary outcome, assessed via validated chart review method. Secondary outcomes included measures related to delirium, such as delirium duration, antipsychotic use, length of hospital and intensive care unit stay, inflammatory markers and final disposition. Neuroimaging data were also collected. Finally, a telephone survey was conducted between 1 and 2 months after discharge to determine neuropsychological function via the following tests: Family Confusion Assessment Method, Short Blessed Test, Patient-Reported Outcomes Measurement Information System Cognitive Abilities 4a and Patient-Health Questionnaire-9.ResultsDelirium was identified in 108/148 (73%) patients, with median (IQR) duration lasting 10 (4–17) days. In the delirium cohort, 50% (54/108) of patients were African American and delirious patients were more likely to be female (76/108, 70%) (absolute standardised differences >0.30). Sedation regimens, inflammation, delirium prevention protocol deviations and hypoxic-ischaemic injury were likely contributing factors, and the most common disposition for delirious patients was a skilled care facility (41/108, 38%). Among patients who were delirious during hospitalisation, 4/17 (24%) later screened positive for delirium at home based on caretaker assessment, 5/22 (23%) demonstrated signs of questionable cognitive impairment or cognitive impairment consistent with dementia and 3/25 (12%) screened positive for depression within 2 months after discharge.ConclusionPatients with COVID-19 commonly experience a prolonged course of delirium in the intensive care unit, likely with multiple contributing factors. Furthermore, neuropsychological impairment may persist after discharge.

MiR-126-3p Is Dynamically Regulated in Endothelial-to-Mesenchymal Transition during Fibrosis

In fibrotic diseases, myofibroblasts derive from a range of cell types including endothelial-to-mesenchymal transition (EndMT). Increasing evidence suggests that miRNAs are key regulators in biological processes but their profile is relatively understudied in EndMT. In human umbilical vein endothelial cells (HUVEC), EndMT was induced by treatment with TGFβ2 and IL1β. A significant decrease in endothelial markers such as VE-cadherin, CD31 and an increase in mesenchymal markers such as fibronectin were observed. In parallel, miRNA profiling showed that miR-126-3p was down-regulated in HUVECs undergoing EndMT and over-expression of miR-126-3p prevented EndMT, maintaining CD31 and repressing fibronectin expression. EndMT was investigated using lineage tracing with transgenic Cdh5-Cre-ERT2; Rosa26R-stop-YFP mice in two established models of fibrosis: cardiac ischaemic injury and kidney ureteric occlusion. In both cardiac and kidney fibrosis, lineage tracing showed a significant subpopulation of endothelial-derived cells expressed mesenchymal markers, indicating they had undergone EndMT. In addition, miR-126-3p was restricted to endothelial cells and down-regulated in murine fibrotic kidney and heart tissue. These findings were confirmed in patient kidney biopsies. MiR-126-3p expression is restricted to endothelial cells and is down-regulated during EndMT. Over-expression of miR-126-3p reduces EndMT, therefore, it could be considered for miRNA-based therapeutics in fibrotic organs.

MINOCA-induced apical ballooning case report: a diagnostic conundrum

Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a recently described phenomenon where no flow-limiting lesions are noted on coronary angiography in a patient with electrocardiogram changes, elevated cardiac biomarkers, and symptoms suggesting acute myocardial infarction. Patients with MINOCA can also potentially develop structural cardiac defects through ischaemic injury. Therefore, the absence of a flow-limiting lesion on angiography coupled with structural defects (e.g. apical ballooning) can very easily result in a diagnosis of Takotsubo cardiomyopathy (TTC). This can lead to potentially serious consequences since treatment options between TTC and MINOCA are different. Case summary We report a case of a patient presenting with features suggestive of TTC but where the final diagnosis was of a MINOCA that induced an apical ventricular septal defect (VSD). Reaching the correct diagnosis proved challenging given that there is no gold standard diagnostic modality for diagnosing MINOCA. Conclusion Imaging adjuncts played a vital role in both diagnosing the underlying MINOCA as well as revealing and planning closure of the resultant VSD. Cardiovascular magnetic resonance imaging played an instrumental role in establishing the patient’s primary pathology and in planning a remediation of the structural defect. Structural myocardial defects in a patient with a diagnosis of TTC should prompt clinicians to further investigate whether there is an underlying infarct aetiology (MINOCA).