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2.
Life Sci ; 259: 118199, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32781064

RESUMO

Cellular senescence, a process whereby cells enter a state of permanent growth arrest, appears to regulate cardiac pathological remodeling and dysfunction in response to various stresses including myocardial infarction (MI). However, the precise role as well as the underlying regulatory mechanism of cardiac cellular senescence in the ischemic heart disease remain to be further determined. Herein we report an inhibitory role of Nrf2, a key transcription factor of cellular defense, in regulating cardiac senescence in infarcted hearts as well as a therapeutic potential of targeting Nrf2-mediated suppression of cardiac senescence in the treatment of MI-induced cardiac dysfunction. MI was induced by left coronary artery ligation for 28 days in mice. Heart tissues from the infarct border zone were used for the analyses. The MI-induced cardiac dysfunction was associated with increased myocardial cell senescence, oxidative stress and apoptosis in adult wild type (WT) mice. In addition, a downregulated Nrf2 activity was associated with upregulated Keap1 levels and increased phosphorylation of JAK and FYN in the infarcted border zone heart tissues. Nrf2 Knockout (Nrf2-/-) enhanced the MI-induced myocardial, cardiac dysfunction and senescence. Qiliqiangxin (QLQX), a herbal medicine which could reverse the MI-induced suppression of Nrf2 activity, significantly inhibited the MI-induced cardiac senescence, apoptosis, and cardiac dysfunction in WT mice but not in Nrf2-/- mice. These results indicate that MI downregulates Nrf2 activity thus promoting oxidative stress to accelerate cellular senescence in the infarcted heart towards cardiac dysfunction and Nrf2 may be a drug target for suppressing the cellular senescence-associated pathologies in infarcted hearts.


Assuntos
Cardiomiopatias/genética , Cardiomiopatias/patologia , Senescência Celular/genética , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miocárdio/patologia , Fator 2 Relacionado a NF-E2/genética , Animais , Cardiomiopatias/diagnóstico por imagem , Ecocardiografia , Inativação Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/diagnóstico por imagem , Miócitos Cardíacos/metabolismo , RNA Interferente Pequeno/farmacologia , Remodelação Ventricular/fisiologia
3.
J Cardiovasc Magn Reson ; 22(1): 60, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32814579

RESUMO

BACKGROUND: Tissue characterisation with cardiovascular magnetic resonance (CMR) parametric mapping has the potential to detect and quantify both focal and diffuse alterations in myocardial structure not assessable by late gadolinium enhancement. Native T1 mapping in particular has shown promise as a useful biomarker to support diagnostic, therapeutic and prognostic decision-making in ischaemic and non-ischaemic cardiomyopathies. METHODS: Convolutional neural networks (CNNs) with Bayesian inference are a category of artificial neural networks which model the uncertainty of the network output. This study presents an automated framework for tissue characterisation from native shortened modified Look-Locker inversion recovery ShMOLLI T1 mapping at 1.5 T using a Probabilistic Hierarchical Segmentation (PHiSeg) network (PHCUMIS 119-127, 2019). In addition, we use the uncertainty information provided by the PHiSeg network in a novel automated quality control (QC) step to identify uncertain T1 values. The PHiSeg network and QC were validated against manual analysis on a cohort of the UK Biobank containing healthy subjects and chronic cardiomyopathy patients (N=100 for the PHiSeg network and N=700 for the QC). We used the proposed method to obtain reference T1 ranges for the left ventricular (LV) myocardium in healthy subjects as well as common clinical cardiac conditions. RESULTS: T1 values computed from automatic and manual segmentations were highly correlated (r=0.97). Bland-Altman analysis showed good agreement between the automated and manual measurements. The average Dice metric was 0.84 for the LV myocardium. The sensitivity of detection of erroneous outputs was 91%. Finally, T1 values were automatically derived from 11,882 CMR exams from the UK Biobank. For the healthy cohort, the mean (SD) corrected T1 values were 926.61 (45.26), 934.39 (43.25) and 927.56 (50.36) for global, interventricular septum and free-wall respectively. CONCLUSIONS: The proposed pipeline allows for automatic analysis of myocardial native T1 mapping and includes a QC process to detect potentially erroneous results. T1 reference values were presented for healthy subjects and common clinical cardiac conditions from the largest cohort to date using T1-mapping images.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Miocárdio/patologia , Redes Neurais de Computação , Automação , Teorema de Bayes , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Estudos de Casos e Controles , Humanos , Valor Preditivo dos Testes , Controle de Qualidade , Reprodutibilidade dos Testes , Volume Sistólico , Incerteza , Função Ventricular Esquerda
4.
PLoS One ; 15(8): e0236814, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756572

RESUMO

BACKGROUND: The present study aims to explore the setting of consultation and communication between physicians and patients affected by genetic cardiomyopathies, investigating how the two parts of the therapeutic relationship participate and share information. METHODS AND RESULTS: 45 adult patients affected by various cardiomyopathies took part in a prospective case study while attending consultations at a cardiologic outpatient clinic constituting an Italian referral centre for cardiomyopathies. A researcher observed the consultations, which were audio-recorded and transcribed. Transcripts were coded and an analysis of setting, type of communication implemented and participation of doctors and patients in terms of word-count and type of questions/answers was carried out. Overall word-count was significantly higher for physicians than for patients (t(44) = 9,506; p<0.001). Doctors were prone to ask closed questions (t(44) = -11,90; p<0.001) while patients preferred open answers (t(44) = 5.58; p<0.001), enriched with subjective issues related to their illness experience. Partial correlation highlights a significant positive relation between doctors' closed question and patients' open answers (r = .838; p<0.001). CONCLUSIONS: Findings emphasize patients' need for adequate time and space to share their subjective illness experience with the physician, within an approach informed by the insights and recommendations of Narrative Medicine. These findings are instrumental to improving the specific clinical setting for individuals with genetic cardiomyopathies.


Assuntos
Cardiomiopatias/diagnóstico , Encaminhamento e Consulta , Adulto , Idoso , Cardiomiopatias/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Assistência ao Paciente , Pacientes/psicologia , Relações Médico-Paciente , Médicos/psicologia , Estudos Prospectivos
5.
Am J Physiol Heart Circ Physiol ; 319(2): H443-H455, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32618511

RESUMO

Neuregulin-1 (NRG1) is a paracrine growth factor, secreted by cardiac endothelial cells (ECs) in conditions of cardiac overload/injury. The current concept is that the cardiac effects of NRG1 are mediated by activation of erythroblastic leukemia viral oncogene homolog (ERBB)4/ERBB2 receptors on cardiomyocytes. However, recent studies have shown that paracrine effects of NRG1 on fibroblasts and macrophages are equally important. Here, we hypothesize that NRG1 autocrine signaling plays a role in cardiac remodeling. We generated EC-specific Erbb4 knockout mice to eliminate endothelial autocrine ERBB4 signaling without affecting paracrine NRG1/ERBB4 signaling in the heart. We first observed no basal cardiac phenotype in these mice up to 32 wk. We next studied these mice following transverse aortic constriction (TAC), exposure to angiotensin II (ANG II), or myocardial infarction in terms of cardiac performance, myocardial hypertrophy, myocardial fibrosis, and capillary density. In general, no major differences between EC-specific Erbb4 knockout mice and control littermates were observed. However, 8 wk following TAC both myocardial hypertrophy and fibrosis were attenuated by EC-specific Erbb4 deletion, albeit these responses were normalized after 20 wk. Similarly, 4 wk after ANG II treatment, myocardial fibrosis was less pronounced compared with control littermates. These observations were supported by RNA-sequencing experiments on cultured endothelial cells showing that NRG1 controls the expression of various hypertrophic and fibrotic pathways. Overall, this study shows a role of endothelial autocrine NRG1/ERBB4 signaling in the modulation of hypertrophic and fibrotic responses during early cardiac remodeling. This study contributes to understanding the spatiotemporal heterogeneity of myocardial autocrine and paracrine responses following cardiac injury.NEW & NOTEWORTHY The role of NRG1/ERBB signaling in endothelial cells is not completely understood. Our study contributes to the understanding of spatiotemporal heterogeneity of myocardial autocrine and paracrine responses following cardiac injury and shows a role of endothelial autocrine NRG1/ERBB4 signaling in the modulation of hypertrophic and fibrotic responses during early cardiac remodeling.


Assuntos
Comunicação Autócrina , Cardiomiopatias/metabolismo , Células Endoteliais/metabolismo , Hipertrofia Ventricular Esquerda/metabolismo , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Neuregulina-1/metabolismo , Receptor ErbB-4/metabolismo , Função Ventricular Esquerda , Remodelação Ventricular , Animais , Cardiomiopatias/genética , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Células Cultivadas , Modelos Animais de Doenças , Fibrose , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Hipertrofia Ventricular Esquerda/genética , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miócitos Cardíacos/patologia , Neovascularização Fisiológica , Comunicação Parácrina , Receptor ErbB-4/deficiência , Receptor ErbB-4/genética , Transdução de Sinais
7.
Cardiovasc Pathol ; 49: 107256, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32721819

RESUMO

BACKGROUND: Heart failure is a frequently occurring complication in patients on maintenance hemodialysis (HD). However, the histological features of right ventricular endomyocardial biopsy (RVEMB) samples remain unclear. METHODS: The clinical characteristics and histological findings of consecutive patients undergoing HD with available RVEMB samples (HD group; n=28) were retrospectively compared with those of patients with dilated cardiomyopathy (n=56) and hypertensive heart disease (n=15). RESULTS: The mean myocyte diameter was significantly larger in the HD group than in the other groups (P<.001), whereas the mean percent area of fibrosis did not differ among the three groups. Immunohistochemical analysis revealed that the capillary density was significantly lower in the HD group compared with the other groups (P<.001), and it was positively associated with left ventricular ejection fraction (P=.014). The number of CD68-positive macrophages, which was significantly higher in the HD group compared with the other two groups (P<.001), was associated with cardiovascular mortality (P=.020; log-rank test). CONCLUSIONS: Myocyte hypertrophy, macrophage infiltration, and reduced capillary density were characteristic histological features of the RVEMB samples in patients undergoing HD, which may be related to the pathogenesis of cardiac dysfunction.


Assuntos
Cardiomiopatias/patologia , Cardiomiopatia Dilatada/patologia , Miocárdio/patologia , Diálise Renal , Insuficiência Renal Crônica/terapia , Adulto , Idoso , Biópsia , Capilares/patologia , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Cardiomiopatia Dilatada/fisiopatologia , Tamanho Celular , Feminino , Fibrose , Humanos , Hipertensão/complicações , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/patologia , Valor Preditivo dos Testes , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Estudos Retrospectivos , Fatores de Risco
8.
Methodist Debakey Cardiovasc J ; 16(2): 122-129, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670472

RESUMO

With its high temporal and spatial resolution and relatively low radiation exposure, positron emission tomography (PET) is increasingly being used in the management of cardiac patients, particularly those with inflammatory cardiomyopathies such as sarcoidosis. This review discusses the role of PET imaging in assessing myocardial viability, inflammatory cardiomyopathies, and endocarditis; describes the different protocols needed to acquire images for specific imaging tests; and examines imaging interpretation for each image dataset-including identification of the mismatch defect in viability imaging, which is associated with significant improvement in LV function after revascularization. We also review the role of fluorodeoxyglucose PET in cardiac sarcoidosis diagnosis, the complementary role of magnetic resonance imaging in inflammatory cardiomyopathy, and the emerging use of cardiac PET in prosthetic valve endocarditis.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Endocardite/diagnóstico por imagem , Miocárdio/patologia , Tomografia por Emissão de Pósitrons , Infecções Relacionadas à Prótese/diagnóstico por imagem , Sarcoidose/diagnóstico por imagem , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Endocardite/patologia , Endocardite/fisiopatologia , Próteses Valvulares Cardíacas/efeitos adversos , Humanos , Imagem por Ressonância Magnética , Valor Preditivo dos Testes , Infecções Relacionadas à Prótese/patologia , Infecções Relacionadas à Prótese/fisiopatologia , Sarcoidose/patologia , Sarcoidose/fisiopatologia , Sobrevivência de Tecidos , Função Ventricular Esquerda
9.
Dtsch Med Wochenschr ; 145(11): 755-760, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: covidwho-545794

RESUMO

Current pandemic caused by SARS-CoV-2 inducing viral COVID-19 pneumonia, is categorized in 3 stages. Some biomarkers could be assigned to one of these stages, showing a correlation to mortality in COVID-19 patients. Laboratory findings in COVID-19, especially when serially evaluated, may represent individual disease severity and prognosis. These may help planning and controlling therapeutic interventions. Biomarkers for myocardial injury (high sensitive cardiac troponin, hsTn) or hemodynamic stress (NTproBNP) may occur in COVID-19 pneumonia such as in other pneumonias, correlating with severity and prognosis of the underlying disease. In hospitalized COVID-19 patients' mild increases of hsTn or NTproBNP may be explained by cardiovascular comorbidities and direct or indirect cardiac damage or stress caused by or during COVID-19 pneumonia. In case of suspected NSTE-ACS and COVID-19, indications for echocardiography or reperfusion strategy should be carefully considered against the risk of contamination.


Assuntos
Cardiomiopatias/virologia , Infecções por Coronavirus/complicações , Pandemias/classificação , Pneumonia Viral/classificação , Adulto , Biomarcadores , Cardiomiopatias/epidemiologia , Cardiomiopatias/patologia , Comorbidade , Infecções por Coronavirus/classificação , Infecções por Coronavirus/genética , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Humanos , Masculino , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Fenótipo , Pneumonia Viral/genética , Risco , Troponina C/metabolismo
10.
Dtsch Med Wochenschr ; 145(11): 755-760, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-32492745

RESUMO

Current pandemic caused by SARS-CoV-2 inducing viral COVID-19 pneumonia, is categorized in 3 stages. Some biomarkers could be assigned to one of these stages, showing a correlation to mortality in COVID-19 patients. Laboratory findings in COVID-19, especially when serially evaluated, may represent individual disease severity and prognosis. These may help planning and controlling therapeutic interventions. Biomarkers for myocardial injury (high sensitive cardiac troponin, hsTn) or hemodynamic stress (NTproBNP) may occur in COVID-19 pneumonia such as in other pneumonias, correlating with severity and prognosis of the underlying disease. In hospitalized COVID-19 patients' mild increases of hsTn or NTproBNP may be explained by cardiovascular comorbidities and direct or indirect cardiac damage or stress caused by or during COVID-19 pneumonia. In case of suspected NSTE-ACS and COVID-19, indications for echocardiography or reperfusion strategy should be carefully considered against the risk of contamination.


Assuntos
Cardiomiopatias/virologia , Infecções por Coronavirus/complicações , Pandemias/classificação , Pneumonia Viral/classificação , Adulto , Biomarcadores , Cardiomiopatias/epidemiologia , Cardiomiopatias/patologia , Comorbidade , Infecções por Coronavirus/classificação , Infecções por Coronavirus/genética , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Humanos , Masculino , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Fenótipo , Pneumonia Viral/genética , Risco , Troponina C/metabolismo
12.
Curr Opin Organ Transplant ; 25(3): 218-230, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32374574

RESUMO

PURPOSE OF REVIEW: Cardiomyopathies are rare in the pediatric population, but significantly impact on morbidity and mortality. The present review aims to provide an overview of cardiomyopathies in children and some practical guidelines for their prognostic stratification and management. RECENT FINDINGS: Pediatric cardiomyopathies may present as isolated cardiac muscle disease or in the context of complex clinical syndromes. The etiologic characterization represents an important step in the diagnosis and treatment of cardiomyopathies because of its impact on prognosis and on therapeutic measures. Indeed, replacement therapy is nowadays widely available and changes the natural history of the disease. More complex is the management of isolated cardiomyopathies, which lack specific therapies, mainly aimed at symptomatic relief. In this context, heart transplantation shows excellent outcomes in children, but wait-list mortality is still very high. Device therapy for sudden cardiac death prevention and the use of mechanical assist devices are becoming more common in the clinical practice and may help to reduce mortality. SUMMARY: Providing insight into pediatric cardiomyopathies classification helps in the prognostication and management of such diseases. Recent years witnessed a significant improvement in mortality, but future research is still needed to improve quality of life and life expectations in the pediatric population.


Assuntos
Cardiomiopatias , Qualidade de Vida/psicologia , Cardiomiopatias/classificação , Cardiomiopatias/diagnóstico , Cardiomiopatias/patologia , Cardiomiopatias/terapia , Criança , Humanos
13.
Prog Cardiovasc Dis ; 63(3): 271-307, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32330463

RESUMO

Sarcoidosis is a relatively rare inflammatory condition which potentially carries high morbidity and substantial mortality. Due to the fact that it does not subject patients to ionizing radiation, has high temporal, spatial and contrast resolutions, cardiovascular magnetic resonance imaging (CMR) has become an important diagnostic and prognostic modality in the evaluation for cardiac involvement in this condition. This review provides relevant clinical and pathophysiological background on cardiac sarcoidosis, whilst detailing the role of CMR imaging in the diagnosis, and management of this condition.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Imagem por Ressonância Magnética , Miocárdio/patologia , Sarcoidose/diagnóstico por imagem , Cardiomiopatias/patologia , Cardiomiopatias/terapia , Diagnóstico Diferencial , Fibrose , Humanos , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Sarcoidose/patologia , Sarcoidose/terapia
14.
Ecotoxicol Environ Saf ; 197: 110605, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32311614

RESUMO

Fluorosis is a worldwide public health problem, and its adverse effects on the heart have been confirmed by many studies. Abnormal myocardial contractions are often associated with impairment of cardiac function as a cause or consequence. We designed two-part experiments to search for biomarkers and clarify the underlying molecular mechanism of fluoride on myocardial contraction. First, we used Pressure-volume Loop analysis to evaluate changes in myocardial function indexes with multiple fluoride exposure levels in mice (0, 30, 70, and 150 mg/L) exposed for 4 weeks. The results showed that fluoride exposure affects the heart pump function and reduces cardiac contractility. Then, we established a rat model of fluoride exposure (0, 30, 60, and 90 mg/L) for 6 months to carry out proteomic analysis of fluoride-induced myocardial contractile injury. Hematoxylin-eosin (H&E) staining was used to determine the severity of myocardial injury, and myocardial tissue samples were submitted for isobaric tags for relative and absolute quantitation (ITRAQ) analysis. A total of 1607 proteins were successfully identified with 294 differentially expressed proteins (DEPs) in fluoride treated groups. According to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, 12 DEPs were confirmed to be involved in pathways related to myocardial contraction. Furthermore, we constructed a protein-protein interaction (PPI) network for these 12 core DEPs to illustrate the role and location of each DEP in the myocardial contraction pathway. The results of this study are helpful for identify a potential mechanism and biomarkers of fluoride-induced myocardial contraction function damage, moreover, which can provide a new insight into the heart toxicity of fluoride in animals at the proteomics level.


Assuntos
Cardiomiopatias/induzido quimicamente , Fluoretos/toxicidade , Contração Miocárdica/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Ontologia Genética , Masculino , Camundongos , Mapeamento de Interação de Proteínas , Proteínas/metabolismo , Proteômica/métodos , Ratos
15.
Am J Cardiol ; 125(11): 1745-1748, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32284175

RESUMO

Advanced interatrial block (A-IAB) has been associated to atrial fibrillation (AF) and ischemic stroke, raising the question as to whether such patients, even when still in sinus rhythm without documented AF, could benefit from oral anticoagulation. AF and A-IAB are both markers of stroke. The anatomical substrate in both is fibrotic atrial cardiomyopathy, resulting in atrial electromechanical dyssynchrony, dysfunction, and left atrial remodelling, that favour blood stasis and hypercoagulation. Under these conditions thrombogenic cascade may be triggered, resulting in systemic embolization. Before proposing oral anticoagulation in the management of selected patients with A-IAB, as is currently recommended in patients with AF and high CHA2DS2-Vasc score, a randomized clinical trial will have to demonstrate efficacy and safety of anticoagulation in this setting. In the meantime, an individualized approach may be considered based on the recognition of those patients at a higher risk of stroke. These may be elderly patients with A-IAB and several risk factors and, thus, with a high CHA2DS2-Vasc score and the presence of environmental arrhythmias.


Assuntos
Fibrilação Atrial/epidemiologia , Bloqueio Interatrial/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/fisiopatologia , Remodelamento Atrial/fisiologia , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Fibrose , Átrios do Coração/patologia , Humanos , Bloqueio Interatrial/complicações , Bloqueio Interatrial/fisiopatologia , Índice de Gravidade de Doença , Acidente Vascular Cerebral/prevenção & controle , Trombofilia/fisiopatologia
16.
J Cardiovasc Magn Reson ; 22(1): 22, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32272936

RESUMO

BACKGROUND: Idiopathic inflammatory myopathy (IIM) manifest as systematic muscle involvement. Multiparametric cardiovascular magnetic resonance (CMR) could be a useful technique to detect systemic involvement and disease progression in IIM patients. This study aimed to describe the tissue characteristics and dynamic changes in myocardial and skeletal muscles after treatment in IIM patients. METHODS: Forty-four consecutively recruited IIM patients (49.0 ± 12.0 years; 22 males) underwent 3 T CMR at first diagnosis, and 28 patients underwent follow-up scan after receiving standard treatment for more than 1 year. Thirty age- and sex-matched healthy subjects served as controls. The CMR protocol included: cines, T2-weighted (T2w), late gadolinium enhancement (LGE), T1 and T2 mapping, and extracellular volume (ECV) evaluated for the myocardium, and T1 and T2 mapping and ECV evaluated for skeletal muscles. Correlations between laboratory biomarkers and myocardial and skeletal tissue characteristics were analyzed. Comparisons between baseline and follow-up scans were performed using paired t-tests. RESULTS: At baseline, IIM patients showed significantly decreased hematocrit, higher left ventricular (LV) mass index, right ventricular (RV) volume index, myocardial and skeletal native T1, T2 mapping, and ECV than healthy controls. Significant correlations were found among myocardial native T1, T2 mapping, and ECV values and N-terminal pro b-type natriuretic peptide (NT-proBNP) levels, and significant correlations between skeletal T2 mapping and inflammatory biomarkers in IIM patients. During the follow-up, 28 patients underwent repeated CMR scan (median interval, 14.5 months, interquartile range: 13.2-15.5 months). Significant relief from clinical symptoms and decreased inflammatory biomarkers levels were observed. Significant reduction in myocardial native T1, T2, ECV, and skeletal native T1, T2, and ECV were observed during the follow-up assessment. CONCLUSIONS: Both myocardial and skeletal muscles in newly diagnosed IIM patients show distinct characteristics on multiparametric CMR. In addition, significant changes were observed in patients showing clinical remission after effective treatment, which suggests that quantitative T1, T2, and ECV techniques may have potential clinical value in IIM patients.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Músculo Esquelético/diagnóstico por imagem , Miocárdio/patologia , Miosite/diagnóstico por imagem , Adulto , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Cardiomiopatias/terapia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Miosite/patologia , Miosite/fisiopatologia , Miosite/terapia , Valor Preditivo dos Testes , Estudos Prospectivos , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento , Remodelação Ventricular
17.
Lab Med ; 51(2): 143-150, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32155272

RESUMO

BACKGROUND: Cardiomyopathic manifestations induced by continuous blood transfusion are the leading cause of death among patients with thalassemia major (TM). Despite introduction of chelation therapy, heart failure after cardiomyopathic manifestations is still a major threat to patients. METHODS: We performed a search of relevant English-language literature, retrieving publications from the PubMed database and the Google Scholar search engine (2005-2018). We used "thalassemia major", "cardiomyopathy", "iron overload", "cardiac magnetic resonance T2" "chelation therapy", and "iron burden" as keywords. RESULTS: The results of the studies we found suggest that cardiac hepcidin is a major regulator of iron homeostasis in cardiac tissue. Unlike previous assumptions, the heart appears to have a limited regeneration capability, originating from a small population of hypoxic cardiomyocytes. CONCLUSIONS: Oxygen levels determine cardiomyocyte gene-expression patterns. Upregulation of cardiac hepcidin in hypoxia preserves cardiomyocytes from forming out of reactive oxygen species catalyzed by free cellular iron in cardiomyocytes. Using the limited regeneration capacity of cardiac cells and gaining further understanding of the cellular aspects of cardiomyopathic manifestations may help health care professionals to develop new therapeutic strategies.


Assuntos
Cardiomiopatias/diagnóstico , Cardiomiopatias/terapia , Terapia por Quelação/métodos , Testes Diagnósticos de Rotina/métodos , Gerenciamento Clínico , Sobrecarga de Ferro/complicações , Talassemia/complicações , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Humanos , Talassemia/terapia
18.
PLoS One ; 15(3): e0230386, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32218573

RESUMO

Probenecid has been used for decades in the treatment of gout but recently has also been found to improve outcomes in patients with heart failure via stimulation of the transient receptor potential vanilloid 2 (TRPV2) channel in cardiomyocytes. This study tested the use of probenecid on a novel mouse model of peripartum cardiomyopathy (PPCM) as a potential treatment option. A human mutation of the human heat shock protein 20 (Hsp20-S10F) in mice has been recently shown to result in cardiomyopathy, when exposed to pregnancies. Treatment with either probenecid or control sucrose water was initiated after the first pregnancy in both wild type and Hsp20-S10F mice. Serial echocardiography was performed during subsequent pregnancies and hearts were collected after the third pregnancies for staining and molecular analysis. Hsp20-S10F mice treated with probenecid had decreased mortality, hypertrophy, TRPV2 expression and molecular parameters of heart failure. Probenecid treatment also decreased apoptosis as evidenced by an increase in the level of Bcl-2/Bax. Probenecid improved survival in a novel mouse model of PPCM and may be an appropriate therapy for humans with PPCM as it has a proven safety and tolerability in patients with heart failure.


Assuntos
Canais de Cálcio/genética , Cardiomiopatias/tratamento farmacológico , Proteínas de Choque Térmico HSP20/genética , Insuficiência Cardíaca/tratamento farmacológico , Probenecid/farmacologia , Canais de Cátion TRPV/genética , Animais , Apoptose/efeitos dos fármacos , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/genética , Cardiomiopatias/patologia , Modelos Animais de Doenças , Ecocardiografia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologia , Humanos , Camundongos , Mutação/genética , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Período Periparto/efeitos dos fármacos , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Complicações Cardiovasculares na Gravidez/genética
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