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Radiology Sep 2023Background Patients who developed myocarditis following SARS-CoV-2 vaccination show abnormalities on cardiac MRI. However, whether myocardial changes occur in...
Background Patients who developed myocarditis following SARS-CoV-2 vaccination show abnormalities on cardiac MRI. However, whether myocardial changes occur in asymptomatic individuals following vaccination is not well established. Purpose To assess myocardial Fluorine-fluorodeoxyglucose (F-FDG) uptake on PET/CT in asymptomatic SARS-CoV-2 vaccinated patients compared to nonvaccinated patients. Materials and Methods This retrospective study included patients who underwent F-FDG PET/CT for indications unrelated to myocarditis during the period before (11/1/2020 - 2/16/2021) and after (2/17/20121 - 3/31/2022) SARS-CoV-2 vaccines were available. Myocardial and axillary FDG uptake were quantitatively assessed using maximum standardized uptake value (SUVmax). SUVmax values in all patients and in patients stratified by sex (male/female), age (<40, 41-60, >60 years), and time interval between vaccination and PET/CT were compared using Mann-Whitney U test or Kruskal-Wallis test with post ad -hoc Dwass, Steel, Critchlow-Fligner multiple comparison analysis. Results The study included 303 nonvaccinated patients (mean age, 52.9 years ± 14.9 [SD]; 157 females) and 700 vaccinated patients (mean age, 56.8 years ± 13.7 [SD]; 344 females). Vaccinated patients had overall higher myocardial FDG uptake compared to nonvaccinated patients (median SUVmax, 4.8 [IQR: 3.0-8.5] vs median SUVmax, 3.3 [IQR: 2.5-6.2]; < .0001). Myocardial SUVmax was higher in vaccinated patients regardless of sex (median range, 4.7-4.9 [IQR: 2.9-8.6]) or patient age (median range, 4.7-5.6 [IQR: 2.9-8.6]) compared to corresponding nonvaccinated groups (sex median range, 3.2-3.9 [IQR: 2.4-7.2]; age median range, 3.3-3.3 [IQR: 2.3-6.1]; range, <.001-.015). Furthermore, increased myocardial FDG uptake was observed in patients imaged 1-30, 31-60, 61-120, and 121-180 days after their second vaccination (median SUVmax range, 4.6-5.1 [IQR: 2.9-8.6]) and increased ipsilateral axillary uptake was observed in patients imaged 1-30, 31-60, 61-120 days after their 2nd vaccination (median SUVmax range, 1.5-2.0 [IQR: 1.2-3.4]) compared to the nonvaccinated patients ( range, <.001-<.001). Conclusion Compared to nonvaccinated patients, asymptomatic patients who received their 2nd vaccination 1-180 days prior to imaging showed increased myocardial FDG uptake on PET/CT. See also the editorial by Bluemke in this issue.
Topics: Humans; Female; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Myocarditis; COVID-19 Vaccines; SARS-CoV-2; Retrospective Studies; COVID-19
PubMed: 37724969
DOI: 10.1148/radiol.230743 -
Primary Care Mar 2024Pericarditis typically presents with classic symptoms of acute sharp, retrosternal, and pleuritic chest pain. It can have several different underlying causes including... (Review)
Review
Pericarditis typically presents with classic symptoms of acute sharp, retrosternal, and pleuritic chest pain. It can have several different underlying causes including viral, bacterial, and autoimmune etiologies. The mainstays of pericarditis treatment are nonsteroidal anti-inflammatory drugs and colchicine with glucocorticoids or other immunosuppressive drugs used for refractory cases and relapse. Myocarditis is an inflammatory disease of the cardiac muscle that is caused by a variety of infectious and noninfectious conditions. It mainly affects young adults (median age 30-45 years), and men more than women. The clinical manifestations of myocarditis are highly variable, so a high level of suspicion in the early stage of disease is important to facilitate diagnosis. The treatment of myocarditis includes nonspecific treatment aimed at complications such as heart failure and arrhythmia, as well as specific treatment aimed at underlying causes. Pericarditis and myocarditis associated with vaccine have been extremely rare before coronavirus disease 2019 (COVID-19). There is a small increase of incidence after COVID-19 messenger ribonucleic acid vaccine, but the relative risk for pericarditis and myocarditis due to severe acute respiratory syndrome coronavirus 2 infection is much higher. Therefore, vaccination against COVID-19 is currently recommended for everyone aged 6 years and older.
Topics: Male; Young Adult; Humans; Female; Adult; Middle Aged; Myocarditis; Affect; COVID-19; COVID-19 Vaccines; Pericarditis; Vaccination
PubMed: 38278565
DOI: 10.1016/j.pop.2023.07.006 -
Circulation Jan 2024Immune checkpoint inhibitors (ICIs), antibodies targeting PD-1 (programmed cell death protein 1)/PD-L1 (programmed death-ligand 1) or CTLA4 (cytotoxic...
BACKGROUND
Immune checkpoint inhibitors (ICIs), antibodies targeting PD-1 (programmed cell death protein 1)/PD-L1 (programmed death-ligand 1) or CTLA4 (cytotoxic T-lymphocyte-associated protein 4), have revolutionized cancer management but are associated with devastating immune-related adverse events including myocarditis. The main risk factor for ICI myocarditis is the use of combination PD-1 and CTLA4 inhibition. ICI myocarditis is often fulminant and is pathologically characterized by myocardial infiltration of T lymphocytes and macrophages. Although much has been learned about the role of T-cells in ICI myocarditis, little is understood about the identity, transcriptional diversity, and functions of infiltrating macrophages.
METHODS
We used an established murine ICI myocarditis model ( mice) to explore the cardiac immune landscape using single-cell RNA-sequencing, immunostaining, flow cytometry, in situ RNA hybridization, molecular imaging, and antibody neutralization studies.
RESULTS
We observed marked increases in CCR2 (C-C chemokine receptor type 2) monocyte-derived macrophages and CD8 T-cells in this model. The macrophage compartment was heterogeneous and displayed marked enrichment in an inflammatory CCR2 subpopulation highly expressing (chemokine [C-X-C motif] ligand 9), (chemokine [C-X-C motif] ligand 10), (interferon-induced guanylate-binding protein 2b), and (Fc receptor, IgG, low affinity IV) that originated from CCR2 monocytes. It is important that a similar macrophage population expressing , , and CD16α (human homologue of mouse FcgR4) was expanded in patients with ICI myocarditis. In silico prediction of cell-cell communication suggested interactions between T-cells and macrophages via IFN-γ (interferon gamma) and CXCR3 (CXC chemokine receptor 3) signaling pathways. Depleting CD8 T-cells or macrophages and blockade of IFN-γ signaling blunted the expansion of macrophages in the heart and attenuated myocarditis, suggesting that this interaction was necessary for disease pathogenesis.
CONCLUSIONS
These data demonstrate that ICI myocarditis is associated with the expansion of a specific population of IFN-γ-induced inflammatory macrophages and suggest the possibility that IFN-γ blockade may be considered as a treatment option for this devastating condition.
Topics: Humans; Mice; Animals; Immune Checkpoint Inhibitors; CD8-Positive T-Lymphocytes; Myocarditis; Programmed Cell Death 1 Receptor; CTLA-4 Antigen; Ligands; Chemokines; Macrophages; RNA
PubMed: 37746718
DOI: 10.1161/CIRCULATIONAHA.122.062551 -
Global Heart 2023Dengue is a viral disease transmitted by the bite of a female arthropod, prevalent primarily in tropical and subtropical regions. Its manifestations include asymptomatic... (Review)
Review
Dengue is a viral disease transmitted by the bite of a female arthropod, prevalent primarily in tropical and subtropical regions. Its manifestations include asymptomatic infections, dengue fever, and a severe form called or . Atypical manifestations can also occur, called . We describe the case of a 43-year-old man with an unusual presentation of dengue, demonstrating a workup suggestive of myocardial and pericardial damage. Symptoms and markers indicative of cardiac compromise improved after five days on anti-inflammatory treatment. Dengue myocarditis is considered an uncommon complication of dengue, although its reported incidence is likely an underestimation. In general, most cases of dengue myocarditis are self-limited, with only a minority at risk of progressing to heart failure. In order to improve recognition and prevent progression, healthcare providers should maintain a high degree of suspicion regarding potential cardiac complications in patients with dengue.
Topics: Male; Humans; Female; Adult; Myocarditis; Dengue; Severe Dengue; Heart Diseases; Heart Failure
PubMed: 37547170
DOI: 10.5334/gh.1254 -
Clinical Medicine (London, England) Sep 2023The development of safe and effective vaccines against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was a major turning point in the fight against the... (Review)
Review
The development of safe and effective vaccines against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was a major turning point in the fight against the Coronavirus 2019 (COVID-19) pandemic. However, pharmacovigilance has revealed a small but significant incidence of cardiac inflammation manifesting clinically as myocarditis or pericarditis, particularly in younger vaccine recipients. The incidence is the highest among men under age 40 within a week of receiving the second dose of the mRNA vaccine. In this review, we summarise the evidence for, and guidelines in relation to, SARS-CoV2 vaccine-related myocarditis.
Topics: Male; Humans; Adult; COVID-19 Vaccines; Myocarditis; RNA, Viral; COVID-19; SARS-CoV-2; Pericarditis; Vaccination
PubMed: 37775180
DOI: 10.7861/clinmed.2023-0049 -
Circulation Aug 2023
Topics: Humans; COVID-19; COVID-19 Vaccines; Myocarditis
PubMed: 37523760
DOI: 10.1161/CIRCULATIONAHA.123.064772 -
Circulation Aug 2023Immune checkpoint inhibitors (ICIs) are approved for multiple cancers but can result in ICI-associated myocarditis, an infrequent but life-threatening condition....
BACKGROUND
Immune checkpoint inhibitors (ICIs) are approved for multiple cancers but can result in ICI-associated myocarditis, an infrequent but life-threatening condition. Elevations in cardiac biomarkers, specifically troponin-I (cTnI), troponin-T (cTnT), and creatine kinase (CK), are used for diagnosis. However, the association between temporal elevations of these biomarkers with disease trajectory and outcomes has not been established.
METHODS
We analyzed the diagnostic accuracy and prognostic performances of cTnI, cTnT, and CK in patients with ICI myocarditis (n=60) through 1-year follow-up in 2 cardio-oncology units (APHP Sorbonne, Paris, France and Heidelberg, Germany). A total of 1751 (1 cTnT assay type), 920 (4 cTnI assay types), and 1191 CK sampling time points were available. Major adverse cardiomyotoxic events (MACE) were defined as heart failure, ventricular arrhythmia, atrioventricular or sinus block requiring pacemaker, respiratory muscle failure requiring mechanical ventilation, and sudden cardiac death. Diagnostic performance of cTnI and cTnT was also assessed in an international ICI myocarditis registry.
RESULTS
Within 72 hours of admission, cTnT, cTnI, and CK were increased compared with upper reference limits (URLs) in 56 of 57 (98%), 37 of 42 ([88%] =0.03 versus cTnT), and 43 of 57 ([75%] <0.001 versus cTnT), respectively. This increased rate of positivity for cTnT (93%) versus cTnI ([64%] <0.001) on admission was confirmed in 87 independent cases from an international registry. In the Franco-German cohort, 24 of 60 (40%) patients developed ≥1 MACE (total, 52; median time to first MACE, 5 [interquartile range, 2-16] days). The highest value of cTnT:URL within the first 72 hours of admission performed best in terms of association with MACE within 90 days (area under the curve, 0.84) than CK:URL (area under the curve, 0.70). A cTnT:URL ≥32 within 72 hours of admission was the best cut-off associated with MACE within 90 days (hazard ratio, 11.1 [95% CI, 3.2-38.0]; <0.001), after adjustment for age and sex. cTnT was increased in all patients within 72 hours of the first MACE (23 of 23 [100%]), whereas cTnI and CK values were less than the URL in 2 of 19 (11%) and 6 of 22 (27%) of patients (<0.001), respectively.
CONCLUSIONS
cTnT is associated with MACE and is sensitive for diagnosis and surveillance in patients with ICI myocarditis. A cTnT:URL ratio <32 within 72 hours of diagnosis is associated with a subgroup at low risk for MACE. Potential differences in diagnostic and prognostic performances between cTnT and cTnI as a function of the assays used deserve further evaluation in ICI myocarditis.
Topics: Humans; Myocarditis; Immune Checkpoint Inhibitors; Biomarkers; Creatine Kinase; Prognosis; Troponin T
PubMed: 37317858
DOI: 10.1161/CIRCULATIONAHA.123.062405 -
The Lancet. Neurology Dec 2023Neurological immune-related adverse events associated with immune checkpoint inhibitors can have several clinical manifestations, but the syndromes and prognostic... (Review)
Review
BACKGROUND
Neurological immune-related adverse events associated with immune checkpoint inhibitors can have several clinical manifestations, but the syndromes and prognostic factors are still not well known. We aimed to characterise and group the clinical features, with a special focus in patients presenting with encephalopathy, and to identify predictors of response to therapy and survival.
METHODS
This retrospective observational study included patients with neurological immune-related adverse events from 20 hospitals in Spain whose clinical information, serum samples, and CSF samples were studied at Hospital Clinic de Barcelona, Barcelona, Spain. Patients with pre-existing paraneoplastic syndromes or evidence of alternative causes for their neurological symptoms were excluded. We reviewed the clinical information, classified their clinical features, and determined the presence of neural antibodies. Neurological status was assessed by the treating physician one month after adverse event onset (as improvement vs no improvement) and at the last evaluation (complete recovery or modified Rankin Scale score decrease of at least 2 points, indicating good outcome, vs all other modified Rankin Scale scores, indicating poor outcome); if the participant had died, the date and cause of death were recorded. We used Fisher's exact tests and Mann-Whitney U tests to analyse clinical features, and multivariable logistic regression to analyse prognostic factors.
FINDINGS
From Jan 1, 2018, until Feb 1, 2023, 83 patients with suspected neurological immune-related adverse events after use of immune checkpoint inhibitors were identified, of whom 64 patients were included. These patients had a median age of 67 years (IQR 59-74); 42 (66%) were male and 22 (34%) were female. The predominant tumours were lung cancer (30 [47%] patients), melanoma (13 [21%] patients), and renal cell carcinoma (seven [11%] patients). Neural antibodies were detected in 14 (22%) patients; 52 (81%) patients had CNS involvement and 12 (19%) had peripheral nervous system involvement. Encephalopathy occurred in 45 (70%) patients, 12 (27%) of whom had antibodies or well defined syndromes consistent with definite paraneoplastic or autoimmune encephalitis, 24 (53%) of whom had encephalitis without antibodies or clinical features characteristic of a defined syndrome, and nine (20%) of whom had encephalopathy without antibodies or inflammatory changes in CSF or brain MRI. Nine (14%) of 64 patients had combined myasthenia and myositis, five of them with myocarditis. Even though 58 (91%) of 64 patients received steroids and 31 (48%) of 64 received additional therapies, 18 (28%) did not improve during the first month after adverse event onset, and 11 of these 18 people died. At the last follow-up for the 53 remaining patients (median 6 months, IQR 3-13), 20 (38%) had a poor outcome (16 deaths, one related to a neurological immune-related adverse event). Mortality risk was increased in patients with lung cancer (vs those with other cancers: HR 2·5, 95% CI 1·1-6·0) and in patients with encephalopathy without evidence of CNS inflammation or combined myocarditis, myasthenia, and myositis (vs those with the remaining syndromes: HR 5·0, 1·4-17·8 and HR 6·6, 1·4-31·0, respectively).
INTERPRETATION
Most neurological immune-related adverse events involved the CNS and were antibody negative. The presence of myocarditis, myasthenia, and myositis, of encephalopathy without inflammatory changes, or of lung cancer were independent predictors of death. Most deaths occurred during the first month of symptom onset. If our findings are replicated in additional cohorts, they could confirm that these patients need early and intensive treatment.
FUNDING
The Instituto de Salud Carlos III and the European Union.
Topics: Humans; Male; Female; Middle Aged; Aged; Immune Checkpoint Inhibitors; Retrospective Studies; Spain; Myocarditis; Lung Neoplasms; Syndrome; Brain Diseases; Myositis; Observational Studies as Topic
PubMed: 37977714
DOI: 10.1016/S1474-4422(23)00335-6 -
Postgraduate Medical Journal Sep 2023There has been much interest in the possible adverse events associated with available anti-coronavirus disease of 2019 (COVID-19) vaccines, given the rapid pace at which...
There has been much interest in the possible adverse events associated with available anti-coronavirus disease of 2019 (COVID-19) vaccines, given the rapid pace at which they had to be developed during the pandemic. One such adverse event is myocarditis post-COVID-19 vaccination. Several pathophysiological mechanisms have been proposed that might help us understand the relationship between the messenger ribonucleic acid (mRNA) vaccine and the occurrence of myocarditis, though we are yet to ascertain the causal link between them. Although the actual absolute incidence of myocarditis post-COVID-19 vaccination remains low among the large, general population that has been vaccinated, there has been a high relative incidence of this adverse event. We aim to review the existing literature and bring to light what we have so far understood with respect to the association between COVID-19 vaccination and myocarditis. This will help in better understanding the burden of the pathology along with alleviating apprehensions associated with it.
Topics: Humans; COVID-19; COVID-19 Vaccines; Myocarditis; Pandemics; Vaccination
PubMed: 37334983
DOI: 10.1093/postmj/qgad030 -
Science China. Life Sciences Sep 2023Myocarditis is an inflammatory cardiac disease characterized by the destruction of myocardial cells, infiltration of interstitial inflammatory cells, and fibrosis, and... (Review)
Review
Myocarditis is an inflammatory cardiac disease characterized by the destruction of myocardial cells, infiltration of interstitial inflammatory cells, and fibrosis, and is becoming a major public health concern. The aetiology of myocarditis continues to broaden as new pathogens and drugs emerge. The relationship between immune checkpoint inhibitors, severe acute respiratory syndrome coronavirus 2, vaccines against coronavirus disease-2019, and myocarditis has attracted increased attention. Immunopathological processes play an important role in the different phases of myocarditis, affecting disease occurrence, development, and prognosis. Excessive immune activation can induce severe myocardial injury and lead to fulminant myocarditis, whereas chronic inflammation can lead to cardiac remodelling and inflammatory dilated cardiomyopathy. The use of immunosuppressive treatments, particularly cytotoxic agents, for myocarditis, remains controversial. While reasonable and effective immunomodulatory therapy is the general trend. This review focuses on the current understanding of the aetiology and immunopathogenesis of myocarditis and offers new perspectives on immunomodulatory therapies.
Topics: Humans; Myocarditis; COVID-19; Inflammation; Myocytes, Cardiac; Immunomodulation
PubMed: 37002488
DOI: 10.1007/s11427-022-2273-3