RESUMO
Heart failure (HF) is characterized by a progressive decline in cardiac function and represents one of the largest health burdens worldwide. Clinically, 2 major types of HF are distinguished based on the left ventricular ejection fraction (EF): HF with reduced EF and HF with preserved EF. While both types share several risk factors and features of adverse cardiac remodeling, unique hallmarks beyond ejection fraction that distinguish these etiologies also exist. These differences may explain the fact that approved therapies for HF with reduced EF are largely ineffective in patients suffering from HF with preserved EF. Improving our understanding of the distinct cellular and molecular mechanisms is crucial for the development of better treatment strategies. This article reviews the knowledge of the immunologic mechanisms underlying HF with reduced and preserved EF and discusses how the different immune profiles elicited may identify attractive therapeutic targets for these conditions. We review the literature on the reported mechanisms of adverse cardiac remodeling in HF with reduced and preserved EF, as well as the immune mechanisms involved. We discuss how the knowledge gained from preclinical models of the complex syndrome of HF as well as from clinical data obtained from patients may translate to a better understanding of HF and result in specific treatments for these conditions in humans.
Assuntos
Insuficiência Cardíaca , Volume Sistólico , Remodelação Ventricular , Humanos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/imunologia , Animais , Miocardite/fisiopatologia , Miocardite/imunologia , Função Ventricular Esquerda , Miocárdio/patologia , Miocárdio/metabolismo , Miocárdio/imunologiaRESUMO
Advances in the etiological classification of myocarditis and inflammatory cardiomyopathy (ICM) have reached a consensus. However, the mechanism of myocarditis/ICM remains unclear, which affects the development of treatment and the improvement of outcome. Cellular transcription and metabolic reprogramming, and the interactions between cardiomyocytes and non-cardiomyocytes, such as the immune cells, contribute to the process of myocarditis/ICM. Recent efforts have been made by multi-omics techniques, particularly in single-cell RNA sequencing, to gain a better understanding of the cellular landscape alteration occurring in disease during the progression. This article aims to provide a comprehensive overview of the latest studies in myocarditis/ICM, particularly as revealed by single-cell sequencing.
Assuntos
Cardiomiopatias , Miocardite , Humanos , Miocardite/fisiopatologia , Miocardite/metabolismo , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Miocárdio/patologia , Miocárdio/metabolismo , Análise de Célula Única/métodosRESUMO
BACKGROUND: Myocarditis substantially increases the risk of ventricular arrhythmia. Approximately 30% of all ventricular arrhythmia cases in patients with myocarditis originate from the right ventricular outflow tract (RVOT). However, the role of NLRP3 signaling in RVOT arrhythmogenesis remains unclear. METHODS: Rats with myosin peptide-induced myocarditis (experimental group) were treated with an NLRP3 inhibitor (MCC950; 10 mg/kg, daily for 14 days) or left untreated. Then, they were subjected to electrocardiography and echocardiography. Ventricular tissue samples were collected from each rat's RVOT, right ventricular apex (RVA), and left ventricle (LV) and examined through conventional microelectrode and histopathologic analyses. In addition, whole-cell patch-clamp recording, confocal fluorescence microscopy, and Western blotting were performed to evaluate ionic currents, intracellular Ca2+ transients, and Ca2+-modulated protein expression in individual myocytes isolated from the RVOTs. RESULTS: The LV ejection fraction was lower and premature ventricular contraction frequency was higher in the experimental group than in the control group (rats not exposed to myosin peptide). Myocarditis increased the infiltration of inflammatory cells into cardiac tissue and upregulated the expression of NLRP3; these observations were more prominent in the RVOT and RVA than in the LV. Furthermore, experimental rats treated with MCC950 (treatment group) improved their LV ejection fraction and reduced the frequency of premature ventricular contraction. Histopathological analysis revealed higher incidence of abnormal automaticity and pacing-induced ventricular tachycardia in the RVOTs of the experimental group than in those of the control and treatment groups. However, the incidences of these conditions in the RVA and LV were similar across the groups. The RVOT myocytes of the experimental group exhibited lower Ca2+ levels in the sarcoplasmic reticulum, smaller intracellular Ca2+ transients, lower L-type Ca2+ currents, larger late Na+ currents, larger Na+-Ca2+ exchanger currents, higher reactive oxygen species levels, and higher Ca2+/calmodulin-dependent protein kinase II levels than did those of the control and treatment groups. CONCLUSION: Myocarditis may increase the rate of RVOT arrhythmogenesis, possibly through electrical and structural remodeling. These changes may be mitigated by inhibiting NLRP3 signaling.
Assuntos
Arritmias Cardíacas , Miocardite , Proteína 3 que Contém Domínio de Pirina da Família NLR , Transdução de Sinais , Animais , Ratos , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/metabolismo , Furanos/farmacologia , Indenos , Miocardite/metabolismo , Miocardite/fisiopatologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos Sprague-Dawley , Sulfonamidas/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/fisiologiaRESUMO
This article describes the case of a 40-year-old individual who presented with fulminant myocarditis. Initial ECG displayed sinus tachycardia with a heart rate of 117 bpm, QS complexes in leads V1-V3, ST-segment depression in leads II, III, aVF, V5-V6, and ST-segment elevation >0.2 mV in leads V1 through V3. The initial clinical assessment suggested an acute anteroseptal myocardial infarction. However, subsequent diagnostic evaluation through coronary angiography disclosed that the coronary arteries were normal. Therefore, clinicians should carefully consider the differential diagnosis between these conditions, as their management strategies differ markedly. Two hours after admission, the patient unexpectedly developed syncope. The ECG findings were consistent with the typical characteristics of bidirectional ventricular tachycardia. Our report described the appearance and morphology as well as mechanism of bidirectional ventricular tachycardia in detail. Additionally, we delineate differential diagnoses for disease that can cause bidirectional ventricular tachycardia, such as aconite poisoning, digoxin overdose, immune checkpoint inhibitor (ICI), myocardial ischemia, and hereditary channelopathies, such as catecholaminergic polymorphic ventricular tachycardia (CPVT) and Andersen-Tawil syndrome. Therefore, clinicians should recognize this ECG finding immediately and initiate appropriate treatment promptly as these measures may be vital in saving the patient's life.
Assuntos
Eletrocardiografia , Humanos , Eletrocardiografia/métodos , Adulto , Diagnóstico Diferencial , Masculino , Taquicardia/diagnóstico , Taquicardia/fisiopatologia , Miocardite/diagnóstico , Miocardite/fisiopatologia , Miocardite/complicações , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologiaRESUMO
BACKGROUND: Transthoracic echocardiography (TTE) plays a key role in the initial work-up of myocarditis where the identification of pathologic structural and functional changes may assist in its diagnosis and management. The aim of this systematic review was to appraise the evidence for the utility of echocardiographic parameters of cardiac structure and function in the diagnosis of myocarditis in adult populations. METHODS: A systematic literature search of medical databases was performed using PRISMA principles to identify all relevant studies assessing TTE parameters in adult patients with myocarditis (1995-2020; English only; PROSPERO registration CRD42021243598). Data for a range of structural and functional TTE parameters were individually extracted and those with low heterogeneity were then meta-analyzed using a random-effects model for effect size, and assessed through standardized mean difference (SMD). RESULTS: Available data from six studies (with a pooled total of 269 myocarditis patients and 240 controls) revealed that myocarditis can be reliably differentiated from healthy controls using echocardiographic measures of left ventricular (LV) size and systolic function, in particular LV end-diastolic diameter, LV ejection fraction (LVEF) and LV global longitudinal strain (LV-GLS) (p ≤ .01 for all). LV-GLS demonstrated the highest overall effect size, followed by LVEF and LVEDD (SMD: |0.46-1.98|). Two studies also demonstrated that impairment in LV-GLS was associated with adverse cardiovascular outcomes in this population, irrespective of LVEF. CONCLUSIONS: LV-GLS demonstrated the greatest overall effect size and therefore ability to differentiate myocarditis populations from healthy controls. GLS was also shown to be a predictor of adverse cardiovascular outcomes, in this population. HIGHTLIGHTS: What is already known on this subject? Myocarditis is a disease process that is often a diagnosis of exclusion, as it frequently mimics other acute cardiac pathologies. Transthoracic echocardiography is traditionally the initial imaging modality used for noninvasive structural assessment in populations with myocarditis. What might this study add? This study demonstrates that left ventricular (LV) global longitudinal strain, LV ejection fraction and LV end-diastolic diameter can differentiate between myocarditis patients and healthy controls. LV-GLS demonstrated the greatest overall effect size when comparing these two populations, in comparison to the other measures. How might this impact on clinical practice? This study demonstrates that assessment of myocardial deformation indices allows for sensitive discrimination between myocarditis patients from healthy controls. Routine assessment of LV-GLS may serve as an important diagnostic tool in the acute care setting.
Assuntos
Ecocardiografia , Miocardite , Humanos , Miocardite/fisiopatologia , Miocardite/diagnóstico por imagem , Miocardite/complicações , Ecocardiografia/métodos , Doença Aguda , Adulto , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Função Ventricular Esquerda/fisiologiaRESUMO
PURPOSE OF THE REVIEW: Cardiac involvement in systemic sarcoidosis or isolated cardiac sarcoidosis plays a pivotal role in the clinical manifestation and prognostication. Active-inflammatory cardiac sarcoidosis is associated with a regional impairment of coronary microvascular function that may confer further detrimental effects on myocardial function needing further characterization. RECENT FINDINGS: Clinical investigations with cardiac positron emission tomography/computed tomography in conjunction with 18F-fluorodeoxyglucose to determine myocardial inflammation and 13N-ammonia to quantify myocardial blood flow (MBF) in patients with known or suspected cardiac sarcoidosis outlined that sarcoidosis-induced myocardial inflammation was associated with adverse effects on corresponding regional coronary microvascular function. Notably, immune-suppressive treatment caused reductions in myocardial inflammation were paralleled by improvements of coronary microvascular dysfunction outlining direct adverse effect of inflammation on coronary arteriolar function. This review summarizes contributions of cardiac PET imaging in the identification and characterization of active-inflammatory cardiac sarcoidosis, its effect on coronary microvascular function, treatment responses, and prognostic implications.
Assuntos
Cardiomiopatias , Circulação Coronária , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Sarcoidose , Humanos , Sarcoidose/fisiopatologia , Sarcoidose/diagnóstico por imagem , Cardiomiopatias/fisiopatologia , Cardiomiopatias/diagnóstico por imagem , Fluordesoxiglucose F18 , Prognóstico , Inflamação/fisiopatologia , Miocárdio/patologia , Compostos Radiofarmacêuticos , Tomografia por Emissão de Pósitrons , Microcirculação , Miocardite/fisiopatologia , Miocardite/diagnóstico por imagemRESUMO
Objective: To investugate the unique electrocardiogram (ECG) characteristics of fulminant myocarditis (FM) patients and provide important clues for the diagnosis of FM. Methods: This was a retrospective study. Patients diagnosed with acute myocarditis at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from February 2017 to April 2022 were enrolled and divided into fulminant myocarditis group (FM) and non-fulminant myocarditis group (NFM) according to clinical diagnosis. A total of 246 healthy people who underwent physical examination in the Health examination Center of Tongji Hospital at the same period were selected as the control group. The clinical data and ECG characteristics of the above 3 groups were analyzed and compared. Logistic regression model was used to analyze the influence of ECG parameters on left ventricular ejection fraction in FM patients. Receiver operating curves were constructed to evaluate the predictive value of different ECG parameters for FM. Results: A total of 180 patients were included in this study (FM group: n=123; NFM group: n=57), with an age of (35.0±16.2) years and 106 males (58.89%). Compared with NFM group, ECG was significantly abnormal in FM group, with a higher incidence of sinus tachycardia, ventricular tachycardia or ventricular fibrillation, escape rhythm, right bundle branch block, third degree atrioventricular block, ST-segment elevation, low voltage, prolonged QTc interval, and widened QRS wave in the FM group (all P<0.05). The ECG parameters showed that the amplitude of the full lead QRS wave in FM group was lower than that in NFM group (P<0.01). The average heart rate and QTc interval of FM group were significantly higher than those of NFM and control groups (all P<0.05). Although ST-segment elevation had a higher incidence in the FM group, ECG parameters showed that except for leads â ¢ and aVF, the ST segment levels in all leads in the FM group were lower than those in the control group (all P<0.05). There was a statistically significant difference in some ST segment changes between FM and NFM groups, while there was no statistical difference between the NFM and control groups. Multivariate regression analysis showed that widened QRS wave and increased heart rate were the influencing factors for left ventricular systolic dysfunction in FM patients (OR=16.914, 95%CI: 1.367-209.224, P=0.028; OR=1.026, 95%CI: 1.010-1.042, P=0.001). Receiver operating curve analysis showed that heart rate>86.90 beat/min, QTc>431.50 ms, and RV5+SV1<1.72 mV had certain predictive value for FM diagnosis. Conclusions: FM patients displayed marked and severe ECG abnormalities, and characteristic changes in ECG can provide important first clues for the diagnosis of FM.
Assuntos
Eletrocardiografia , Miocardite , Humanos , Miocardite/fisiopatologia , Miocardite/diagnóstico , Masculino , Eletrocardiografia/métodos , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Doença Aguda , Fibrilação Ventricular/fisiopatologia , Fibrilação Ventricular/diagnósticoRESUMO
BACKGROUND: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth. METHODS: We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings. Myocarditis cases were classified as confirmed or probable on the basis of the Centers for Disease Control and Prevention definitions. RESULTS: We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1-20.3; interquartile range [IQR], 14.5-17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0-22; IQR, 1-3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0-10; IQR, 2-3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50-15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25-1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction <55% on echocardiogram. Of 97 patients who underwent cardiac MRI at a median 5 days (range, 0-88; IQR, 3-17) from symptom onset, 75 (77.3%) had abnormal findings: 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria. Among 26 patients with left ventricular ejection fraction <55% on echocardiogram, all with follow-up had normalized function (n=25). CONCLUSIONS: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons <21 years have a mild clinical course with rapid resolution of symptoms. Abnormal findings on cardiac MRI were frequent. Future studies should evaluate risk factors, mechanisms, and long-term outcomes.
Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Miocardite/diagnóstico por imagem , Miocardite/fisiopatologia , Adolescente , Criança , Eletrocardiografia/métodos , Feminino , Humanos , Imagem Cinética por Ressonância Magnética/métodos , Masculino , Miocardite/sangue , Miocardite/etiologia , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: The association between COVID-19 infection and the development of autoimmune diseases is currently unknown, but there are already reports presenting induction of different autoantibodies by SARS-CoV-2 infection. Kikuchi-Fuimoto disease (KFD) as a form of histiocytic necrotizing lymphadenitis of unknown origin. OBJECTIVE: Here we present a rare case of KFD with heart involvement after COVID-19 infection. To our best knowledge only a few cases of COVID-19-associated KFD were published so far. Based on presented case, we summarize the clinical course of KFD and its association with autoimmune diseases, as well we discuss the potential causes of perimyocarditis in this case. METHODS: We reviewed the literature regarding cases of "Kikuchi-Fujimoto disease (KFD)" and "COVID-19" and then "KFD" and "heart" or "myocarditis" by searching medical journal databases written in English in PubMed and Google Scholar. RESULTS: Only two cases of KFD after COVID infection have been described so far. CONCLUSION: SARS-CoV-2 infection can also be a new, potential causative agent of developing KFD.
Assuntos
COVID-19/fisiopatologia , Hepatomegalia/fisiopatologia , Linfadenite Histiocítica Necrosante/fisiopatologia , Miocardite/fisiopatologia , Esplenomegalia/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , COVID-19/complicações , Teste de Ácido Nucleico para COVID-19 , Teste Sorológico para COVID-19 , Ecocardiografia , Hepatomegalia/diagnóstico por imagem , Hepatomegalia/etiologia , Linfadenite Histiocítica Necrosante/etiologia , Linfadenite Histiocítica Necrosante/patologia , Humanos , Masculino , Miocardite/diagnóstico por imagem , Miocardite/etiologia , SARS-CoV-2 , Esplenomegalia/diagnóstico por imagem , Esplenomegalia/etiologia , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologiaRESUMO
Coronavirus disease 2019 (COVID-19) is a rapidly expanding global pandemic caused by severe acute respiratory syndrome coronavirus 2, resulting in significant morbidity and mortality. A substantial minority of patients hospitalized develop an acute COVID-19 cardiovascular syndrome, which can manifest with a variety of clinical presentations but often presents as an acute cardiac injury with cardiomyopathy, ventricular arrhythmias, and hemodynamic instability in the absence of obstructive coronary artery disease. The cause of this injury is uncertain but is suspected to be related to myocarditis, microvascular injury, systemic cytokine-mediated injury, or stress-related cardiomyopathy. Although histologically unproven, severe acute respiratory syndrome coronavirus 2 has the potential to directly replicate within cardiomyocytes and pericytes, leading to viral myocarditis. Systemically elevated cytokines are also known to be cardiotoxic and have the potential to result in profound myocardial injury. Prior experience with severe acute respiratory syndrome coronavirus 1 has helped expedite the evaluation of several promising therapies, including antiviral agents, interleukin-6 inhibitors, and convalescent serum. Management of acute COVID-19 cardiovascular syndrome should involve a multidisciplinary team including intensive care specialists, infectious disease specialists, and cardiologists. Priorities for managing acute COVID-19 cardiovascular syndrome include balancing the goals of minimizing healthcare staff exposure for testing that will not change clinical management with early recognition of the syndrome at a time point at which intervention may be most effective. This article aims to review the best available data on acute COVID-19 cardiovascular syndrome epidemiology, pathogenesis, diagnosis, and treatment. From these data, we propose a surveillance, diagnostic, and management strategy that balances potential patient risks and healthcare staff exposure with improvement in meaningful clinical outcomes.
Assuntos
Doenças Cardiovasculares/etiologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Enzima de Conversão de Angiotensina 2 , Antivirais/uso terapêutico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/terapia , Biomarcadores , COVID-19 , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/terapia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/fisiopatologia , Síndrome da Liberação de Citocina/terapia , Citocinas/metabolismo , Gerenciamento Clínico , Hemodinâmica , Humanos , Imunização Passiva , Imunoglobulinas Intravenosas/uso terapêutico , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Interleucina-6/antagonistas & inibidores , Terapia de Alvo Molecular , Miocardite/diagnóstico , Miocardite/etiologia , Miocardite/fisiopatologia , Miocardite/terapia , Especificidade de Órgãos , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/tratamento farmacológico , Receptores Virais/fisiologia , Fatores de Risco , Serina Endopeptidases/fisiologia , Síndrome Respiratória Aguda Grave/terapia , Glicoproteína da Espícula de Coronavírus/fisiologia , Tropismo Viral , Soroterapia para COVID-19RESUMO
Background Myocardial injury and inflammation at cardiac MRI in patients with COVID-19 have been described in recent publications. Concurrently, a chronic COVID-19 syndrome (CCS) after SARS-CoV-2 infection has been observed and manifests with symptoms such as fatigue and exertional dyspnea. Purpose To explore the relationship between CCS and myocardial injury and inflammation as an underlying cause of the persistent complaints in previously healthy individuals. Materials and Methods In this prospective study from January 2021 to April 2021, study participants without known cardiac or pulmonary diseases prior to SARS-CoV-2 infection who had persistent CCS symptoms such as fatigue or exertional dyspnea after convalescence and healthy control participants underwent cardiac MRI. The cardiac MRI protocol included evaluating the T1 and T2 relaxation times, extracellular volume, T2 signal intensity ratio, and late gadolinium enhancement (LGE). Student t tests, Mann-Whitney U tests, and χ2 tests were used for statistical analysis. Results Forty-one participants with CCS (mean age, 39 years ± 13 [standard deviation]; 18 men) and 42 control participants (mean age, 39 years ± 16; 26 men) were evaluated. The median time between the initial incidence of mild to moderate COVID-19 not requiring hospitalization and undergoing cardiac MRI was 103 days (interquartile range, 88-158 days). Troponin T levels were normal. Parameters indicating myocardial inflammation and edema were comparable between participants with CCS and control participants (T1 relaxation times: 978 msec ± 23 vs 971 msec ± 25 [P = .17]; T2 relaxation times: 53 msec ± 2 vs 52 msec ± 2 [P = .47]; T2 signal intensity ratios: 1.6 ± 0.2 vs 1.6 ± 0.3 [P = .10]). Visible myocardial edema was present in none of the participants. Three of 41 (7%) participants with CCS demonstrated nonischemic LGE, whereas no participants in the control group demonstrated nonischemic LGE (0 of 42 [0%]; P = .07). None of the participants fulfilled the 2018 Lake Louise criteria for the diagnosis of myocarditis. Conclusion Individuals with chronic COVID-19 syndrome who did not undergo hospitalization for COVID-19 did not demonstrate signs of active myocardial injury or inflammation at cardiac MRI. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lima and Bluemke in this issue.
Assuntos
COVID-19/diagnóstico , COVID-19/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Miocardite/diagnóstico por imagem , Miocardite/fisiopatologia , Adulto , COVID-19/complicações , Doença Crônica , Feminino , Coração/diagnóstico por imagem , Coração/fisiopatologia , Humanos , Masculino , Miocardite/etiologia , Gravidade do Paciente , Estudos Prospectivos , SARS-CoV-2 , Fatores de TempoRESUMO
The monocyte ß2-integrin Mac-1 is crucial for leukocyte-endothelium interaction, rendering it an attractive therapeutic target for acute and chronic inflammation. Using phage display, a Designed-Ankyrin-Repeat-Protein (DARPin) was selected as a novel binding protein targeting and blocking the αM I-domain, an activation-specific epitope of Mac-1. This DARPin, named F7, specifically binds to activated Mac-1 on mouse and human monocytes as determined by flow cytometry. Homology modelling and docking studies defined distinct interaction sites which were verified by mutagenesis. Intravital microscopy showed reduced leukocyte-endothelium adhesion in mice treated with this DARPin. Using mouse models of sepsis, myocarditis and ischaemia/reperfusion injury, we demonstrate therapeutic anti-inflammatory effects. Finally, the activated Mac-1-specific DARPin is established as a tool to detect monocyte activation in patients receiving extra-corporeal membrane oxygenation, as well as suffering from sepsis and ST-elevation myocardial infarction. The activated Mac-1-specific DARPin F7 binds preferentially to activated monocytes, detects inflammation in critically ill patients, and inhibits monocyte and neutrophil function as an efficient new anti-inflammatory agent.
Assuntos
Anti-Inflamatórios/farmacologia , Proteínas de Repetição de Anquirina Projetadas/farmacologia , Antígeno de Macrófago 1/metabolismo , Monócitos/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Miocardite/tratamento farmacológico , Miocárdio/metabolismo , Sepse/tratamento farmacológico , Animais , Técnicas de Visualização da Superfície Celular , Células Cultivadas , Proteínas de Repetição de Anquirina Projetadas/genética , Modelos Animais de Doenças , Epitopos , Oxigenação por Membrana Extracorpórea , Humanos , Antígeno de Macrófago 1/genética , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Simulação de Acoplamento Molecular , Monócitos/imunologia , Monócitos/metabolismo , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Miocardite/imunologia , Miocardite/metabolismo , Miocardite/fisiopatologia , Miocárdio/imunologia , Miocárdio/patologia , Estudo de Prova de Conceito , Ligação Proteica , Infarto do Miocárdio com Supradesnível do Segmento ST/imunologia , Infarto do Miocárdio com Supradesnível do Segmento ST/metabolismo , Sepse/imunologia , Sepse/metabolismo , Sepse/fisiopatologia , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
Clinical heterogeneity, unpredictable course and flares are characteristics of systemic lupus erythematosus (SLE). Although SLE is-by and large-a systemic disease, occasionally it can be organ-dominant, posing diagnostic challenges. To date, diagnosis of SLE remains clinical with a few cases being negative for serologic tests. Diagnostic criteria are not available and classification criteria are often used for diagnosis, yet with significant caveats. Newer sets of criteria (European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019) enable earlier and more accurate classification of SLE. Several disease endotypes have been recognised over the years. There is increased recognition of milder cases at presentation, but almost half of them progress overtime to more severe disease. Approximately 70% of patients follow a relapsing-remitting course, the remaining divided equally between a prolonged remission and a persistently active disease. Treatment goals include long-term patient survival, prevention of flares and organ damage, and optimisation of health-related quality of life. For organ-threatening or life-threatening SLE, treatment usually includes an initial period of high-intensity immunosuppressive therapy to control disease activity, followed by a longer period of less intensive therapy to consolidate response and prevent relapses. Management of disease-related and treatment-related comorbidities, especially infections and atherosclerosis, is of paramount importance. New disease-modifying conventional and biologic agents-used alone, in combination or sequentially-have improved rates of achieving both short-term and long-term treatment goals, including minimisation of glucocorticoid use.
Assuntos
Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/terapia , Anemia Hemolítica Autoimune/fisiopatologia , Anemia Hemolítica Autoimune/terapia , Anticorpos Monoclonais Humanizados/uso terapêutico , Autoanticorpos/imunologia , Azatioprina/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Ciclofosfamida/uso terapêutico , Gerenciamento Clínico , Feminino , Glucocorticoides/uso terapêutico , Doenças das Valvas Cardíacas/fisiopatologia , Doenças das Valvas Cardíacas/terapia , Humanos , Hidroxicloroquina/uso terapêutico , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/terapia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Nefrite Lúpica/fisiopatologia , Nefrite Lúpica/terapia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/terapia , Síndrome de Ativação Macrofágica/fisiopatologia , Síndrome de Ativação Macrofágica/terapia , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Miocardite/fisiopatologia , Miocardite/terapia , Avaliação de Resultados em Cuidados de Saúde , Pericardite/fisiopatologia , Pericardite/terapia , Fenótipo , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/fisiopatologia , Complicações na Gravidez/terapia , Prognóstico , Púrpura Trombocitopênica Idiopática/fisiopatologia , Púrpura Trombocitopênica Idiopática/terapia , Qualidade de Vida , Recidiva , Rituximab/uso terapêutico , Índice de Gravidade de Doença , Taxa de Sobrevida , Neoplasias do Colo do Útero/epidemiologiaRESUMO
OBJECTIVE: To better define the clinical distinctions between the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related paediatric inflammatory multisystem syndrome (PIMS) and Kawasaki disease (KD). METHODS: We compared three groups of patients: group 1, cases from our national historic KD database (KD-HIS), before the SARS-CoV-2 pandemic; group 2, patients with KD admitted to an intensive care unit (KD-ICU) from both our original cohort and the literature, before the SARS-CoV-2 pandemic; and group 3, patients with PIMS from the literature. RESULTS: KD-HIS included 425 patients [male:female ratio 1.3, mean age 2.8 years (s.d. 2.4)], KD-ICU 176 patients [male:female ratio 1.3, mean age 3.5 years (s.d. 3.1)] and PIMS 404 patients [male:female ratio 1.4, mean age 8.8 years (s.d. 3.7)]. As compared with KD-HIS patients, KD-ICU and PIMS patients had a higher proportion of cardiac failure, digestive and neurological signs. KD-ICU and PIMS patients also had a lower frequency of typical KD-mucocutaneous signs, lower platelet count, higher CRP and lower sodium level. As compared with KD-HIS and KD-ICU patients, PIMS patients were older and more frequently had myocarditis; they also had fewer coronary abnormalities and lower sodium levels. Unresponsiveness to IVIG was more frequent in KD-ICU than KD-HIS and PIMS patients. CONCLUSION: On clinical grounds, KD-HIS, KD-ICU and PIMS might belong to a common spectrum of non-specific pathogen-triggered hyperinflammatory states. The causes of increasing inflammation severity within the three entities and the different effects on the heart remain to be determined.
Assuntos
COVID-19/fisiopatologia , Doença das Coronárias/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Miocardite/fisiopatologia , Derrame Pericárdico/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Direita/fisiopatologia , Adolescente , Aspirina/uso terapêutico , Proteína C-Reativa/metabolismo , COVID-19/sangue , COVID-19/terapia , Estudos de Casos e Controles , Criança , Pré-Escolar , Doenças do Sistema Digestório/fisiopatologia , Feminino , França , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Pediátrica , Masculino , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/terapia , Miocardite/sangue , Doenças do Sistema Nervoso/fisiopatologia , Fenótipo , Inibidores da Agregação Plaquetária/uso terapêutico , Contagem de Plaquetas , Sódio/sangue , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/terapiaRESUMO
Myocarditis is an inflammatory condition of the myocardium and is usually categorised as acute nonfulminant and acute fulminant myocarditis. Myocardial injury can result via viral infections, direct injury or immune responses. Fulminant myocarditis can be characterised by severe and sudden cardiac inflammation that may result from cardiogenic shock, ventricular arrhythmias or multi-organ system failure. Extracorporeal membrane oxygenation (ECMO), also known as extracorporeal life support, is an effective technique for patients with fulminant myocarditis, providing heart and lung support and adequate gas exchange or perfusion to sustain life. Essentially, ECMO pumps blood out of the body to an oxygenator that acts as an artificial lung, which adds oxygen to the blood and removes carbon dioxide. This report aims to review recent advances in ECMO and relate case studies of fulminant myocarditis patients. The types of ECMO, predictive factors for success, clinical studies and recent technological advances in the field will be discussed.
Assuntos
Sistema Cardiovascular/fisiopatologia , Oxigenação por Membrana Extracorpórea , Miocardite/terapia , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/mortalidade , Humanos , Miocardite/diagnóstico , Miocardite/mortalidade , Miocardite/fisiopatologia , Resultado do TratamentoRESUMO
Myocarditis is generally a mild and self-limited consequence of systemic infection of cardiotropic viruses. However, patients can develop a temporary or permanent impairment of cardiac function including acute cardiomyopathy with hemodynamic compromise or severe arrhythmias. In this setting, specific causes of inflammation are associated with variable risks of death and transplantation. Recent translational studies suggest that treatments tailored to specific causes of myocarditis may impact clinical outcomes when added to guideline-directed medical care. This review summarizes recent advances in translational research that influence the utility of endomyocardial biopsy for the management of inflammatory cardiomyopathies. Emerging therapies for myocarditis based on these mechanistic hypotheses are entering clinical trials and may add to the benefits of established heart failure treatment.
Assuntos
Cardiomiopatias/terapia , Insuficiência Cardíaca/terapia , Miocardite/terapia , Animais , Cardiomiopatias/diagnóstico , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Progressão da Doença , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Miocardite/diagnóstico , Miocardite/etiologia , Miocardite/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Messenger RNA (mRNA) coronavirus disease of 2019 (COVID-19) vaccine are known to cause minor side effects at the injection site and mild global systemic symptoms in first 24-48 h. Recently published case series have reported a possible association between acute myocarditis and COVID-19 vaccination, predominantly in young males. METHODS: We report a case series of 5 young male patients with cardiovascular magnetic resonance (CMR)-confirmed acute myocarditis within 72 h after receiving a dose of an mRNA-based COVID-19 vaccine. RESULTS: Our case series suggests that myocarditis in this setting is characterized by myocardial edema and late gadolinium enhancement in the lateral wall of the left ventricular (LV) myocardium, reduced global LV longitudinal strain, and preserved LV ejection fraction. All patients in our series remained clinically stable during a relatively short inpatient hospital stay. CONCLUSIONS: In conjunction with other recently published case series and national vaccine safety surveillance data, this case series suggests a possible association between acute myocarditis and COVID-19 vaccination in young males and highlights a potential pattern in accompanying CMR abnormalities.
Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Imagem Cinética por Ressonância Magnética/métodos , Miocardite/diagnóstico por imagem , Doença Aguda , Adulto , Coração/diagnóstico por imagem , Coração/fisiopatologia , Humanos , Masculino , Miocardite/fisiopatologia , Valor Preditivo dos Testes , SARS-CoV-2 , Adulto JovemRESUMO
BACKGROUND: Half of U.S. adults have received at least one dose of the COVID-19 vaccines produced by either Pfizer, Moderna, or Johnson and Johnson, which represents a major milestone in the ongoing pandemic. Given the emergency use authorizations for these vaccines, their side effects and safety were assessed over a compressed time period. Hence, ongoing monitoring for vaccine-related adverse events is imperative for a full understanding and delineation of their safety profile. CASE PRESENTATION: An 22-year-old Caucasian male presented to our hospital center complaining of pleuritic chest pain. Six months prior he had a mild case of COVID-19, but was otherwise healthy. He had received his first dose of the Moderna vaccine three days prior to developing symptoms. Laboratory analysis revealed a markedly elevated troponin and multiple imaging modalities during his hospitalization found evidence of wall motion abnormalities consistent with a diagnosis of perimyocarditis. He was started on aspirin and colchicine with marked improvement of his symptoms prior to discharge. CONCLUSIONS: We present a case of perimyocarditis that was temporally related to COVID-19 mRNA vaccination in an young male with prior COVID-19 infection but otherwise healthy. Our case report highlights an albeit rare but important adverse event for clinicians to be aware of. It also suggests a possible mechanism for the development of myocardial injury in our patient.
Assuntos
Vacinas contra COVID-19/efeitos adversos , Miocardite/induzido quimicamente , Vacina de mRNA-1273 contra 2019-nCoV , Anti-Inflamatórios/uso terapêutico , Aspirina/uso terapêutico , Vacinas contra COVID-19/administração & dosagem , Colchicina/uso terapêutico , Humanos , Esquemas de Imunização , Masculino , Miocardite/diagnóstico por imagem , Miocardite/tratamento farmacológico , Miocardite/fisiopatologia , Recuperação de Função Fisiológica , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Under physiological conditions, the myocardial extracellular matrix (ECM) is maintained by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). However, changes in the balance between MMPs and TIMPs can lead to pathological remodeling of the ECM, which contributes to cardiovascular and kidney diseases. The aim of our study was to assess levels of MMPs and TIMP-2 in patients with myocarditis and their relationship to renal function. MATERIALS AND METHODS: Forty five patients with myocarditis who underwent CMR were included, comprising 11 with concurrent chronic kidney disease (CKD). Blood samples were obtained to assess serum levels of MMP-2, MMP-3, MMP-9, and TIMP-2. RESULTS: Serum MMP-2, MMP-3, and TIMP-2 levels negatively correlated with the ejection fraction in patients with myocarditis, while MMP-3 levels correlated with longitudinal deformation (p < 0.05). Serum MMP-2, MMP-3, and TIMP-2 levels also negatively correlated with renal function, as assessed by the estimated glomerular filtration rate (eGFR) (p < 0.05). Patients with myocarditis and concurrent CKD had higher levels of MMP-2 and TIMP-2 than those without kidney damage. CONCLUSIONS: (1) We demonstrated that MMP-2, MMP-3, and TIMP-2 concentrations were related to left-ventricular ejection fraction, and MMP-3 levels correlated with longitudinal deformation, indicating MMPs play an important role in the post-inflammatory remodeling of the myocardium. (2) A negative correlation between the eGFR and MMP-2, MMP-3, and TIMP-2 and a positive correlation between creatinine and MMP-3 levels indicate the role of MMPs and TIMP-2 in renal dysfunction.
Assuntos
Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 3 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Miocardite/sangue , Insuficiência Renal Crônica/sangue , Inibidor Tecidual de Metaloproteinase-2/sangue , Adulto , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Masculino , Miocardite/complicações , Miocardite/fisiopatologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologiaRESUMO
We report an effective therapeutic approach of mechanical circulatory support for a patient with cardiogenic shock and respiratory insufficiency due to fulminant myocarditis. An Impella® 5.0 was utilized as a left ventricular assist device (VAD) and percutaneous veno-pulmonary extracorporeal membrane oxygenation (ECMO) as a right VAD. These devices were implanted without sternotomy or thoracotomy. Although a combination of Impella and veno-arterial ECMO has been reported as percutaneous biventricular support, there are concerns that this combination is not beneficial for myocardial recovery in patients with respiratory insufficiency, because Impella expels insufficiently oxygenated blood from the left ventricle to the coronary arteries. Our approach took advantage of percutaneous implantation of ECMO and temporary VAD, eliminating the drawbacks of both devices, thus providing a more effective and less invasive form of temporary biventricular support.