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1.
Genes (Basel) ; 12(7)2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34356086

RESUMO

Emery-Dreifuss muscular dystrophy (EDMD) is a rare genetic disease that affects the musculoskeletal system, including the heart, causing rhythm disorders and cardiomyopathy, sometimes requiring an implantable cardioverter-defibrillator (ICD) or heart transplantation due to severe heart damage. The case described herein concerns a 16-year-old girl, with grade II obesity, without other known pathological antecedents or cardiac pathology diagnosis given an annual history of cardiological investigations. She was admitted to the Infectious Diseases Department with SARS-CoV-2 virus infection. The anamnesis showed that the cardiological investigations performed in the past were completed due to the medical history antecedents of her sister, who had been diagnosed with dilated cardiomyopathy, having undergone the placement of an ICD and a heart transplant. Numerous investigations were performed during hospitalization, which revealed high levels of high-sensitive cardiac troponin I (hs-cTnI), creatine kinase (CK) and N-terminal pro b-type natriuretic peptide (NT-proBNP). Dynamic electrocardiographic evaluations showed ventricular extrasystoles, without clinical manifestations. The patient presented stage 2 arterial hypertension (AHT) during hospitalization. A cardiac ultrasound was also performed, which revealed suspected mild subacute viral myocarditis with cardiomyopathy, and antihypertensive medication was initiated. A heart MRI was performed, and the patient was diagnosed with dilated cardiomyopathy, refuting the suspicion of viral subacute myocarditis. After discharge, as the patient developed gait disorders with an impossible heel strike upon walking and limitation of the extension of the arms and ankles, was hospitalized in the Neurology Department. Electrocardiograms (ECGs) were dynamically performed, and because the rhythm disorders persisted, the patient was transferred to the Cardiology Department. On Holter monitoring, non-sustained ventricular tachycardia (NSVT) was detected, so antiarrhythmic treatment was initiated, and placement of an ICD was subsequently decided and was diagnosed with EDMD. Genetic tests were also performed, and a mutation of the lamin A/C gene was detected (LMNA gene exon 2, variant c448A > C (p.Thr150pro), heterozygous form, AD).


Assuntos
COVID-19 , Cardiomiopatia Dilatada , Distrofia Muscular de Emery-Dreifuss , SARS-CoV-2/metabolismo , Adolescente , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/fisiopatologia , COVID-19/terapia , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/terapia , Feminino , Humanos , Distrofia Muscular de Emery-Dreifuss/sangue , Distrofia Muscular de Emery-Dreifuss/diagnóstico por imagem , Distrofia Muscular de Emery-Dreifuss/fisiopatologia , Distrofia Muscular de Emery-Dreifuss/terapia
2.
Int J Mol Sci ; 22(11)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073616

RESUMO

Non-ischemic dilated cardiomyopathy encompasses a wide spectrum of myocardial disorders, characterized by left ventricular dilatation with systolic impairment and increased risk of sudden cardiac death. In spite of all the therapeutic progress that has been made in recent years, dilated cardiomyopathy continues to be an important cause of cardiac transplant, being associated with an enormous cost burden for health care systems worldwide. Predicting the prognosis of patients with dilated cardiomyopathy is essential to individualize treatment. Late gadolinium enhancement-cardiac magnetic resonance imaging, microvolt T-wave alternans, and genetic testing have emerged as powerful tools in predicting sudden cardiac death occurrence and maximizing patient's selection. Despite all these new diagnostic modalities, additional tests to complement or replace current tools are required for better risk stratification. Therefore, biomarkers are an easy and important tool that can help to detect patients at risk of adverse cardiovascular events. Additionally, identifying potential biomarkers involved in dilated cardiomyopathy can provide us important information regarding the diagnostic, prognostic, risk stratification, and response to treatment for these patients. Many potential biomarkers have been studied in patients with dilated cardiomyopathy, but only a few have been adopted in current practice. Therefore, the aim of our review is to provide the clinicians with an update on the well-known and novel biomarkers that can be useful for risk stratification of patients with non-ischemic dilated cardiomyopathy.


Assuntos
Cardiomiopatia Dilatada , Meios de Contraste/uso terapêutico , Gadolínio/uso terapêutico , Imageamento por Ressonância Magnética , Biomarcadores/sangue , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico por imagem , Humanos , Medição de Risco
3.
BMC Vet Res ; 17(1): 176, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902566

RESUMO

BACKGROUND: Inflammation and oxidative stress can contribute to the development and progression of heart failure. This study aimed to investigate the association between inflammatory and oxidative stress markers in dogs with congestive heart failure (CHF). Associations between the disease severity marker N-terminal pro-B-type natriuretic peptide (NT-proBNP) and markers of inflammation and oxidative stress were also determined. RESULTS: Thirty-seven dogs with cardiovascular diseases (dilated cardiomyopathy, DCM (16 dogs), myxomatous mitral valve disease, MMVD (21 dogs)) and ten healthy dogs were included in this prospective study. The patients were further divided into groups with (26) and without CHF (11). We found a significantly higher serum concentration of C-reactive protein (P = 0.012), white blood cell (P = 0.001), neutrophil (P = 0.001) and monocyte counts (P = 0.001) in patients with CHF compared to control dogs. The concentration of tumor necrosis factor-alpha (TNF-α) was significantly higher in patients with CHF compared to patients without CHF (P = 0.030). No significant difference was found in most of the measured parameters between MMVD and DCM patients, except for glutathione peroxidase (GPX) and NT-proBNP. In patients with CHF, TNF-α correlated positively with malondialdehyde (P = 0.014, r = 0.474) and negatively with GPX (P = 0.026, r = - 0.453), and interleukin-6 correlated negatively with GPX (P = 0.046, r = - 0.412). NT-proBNP correlated positively with malondialdehyde (P = 0.011, r = 0.493). In patients without CHF none of the inflammatory and oxidative stress markers correlated significantly. Furthermore, in the group of all cardiac patients, GPX activity significantly negatively correlated with NT-proBNP (P = 0.050, r = - 0.339) and several markers of inflammation, including TNF-α (P = 0.010, r = - 0.436), interleukin-6 (P = 0.026, r = - 0.382), white blood cell (P = 0.032, r = - 0.369), neutrophil (P = 0.027, r = - 0.379) and monocyte counts (P = 0.024, r = - 0.386). CONCLUSION: Inflammatory and oxidative stress markers are linked in canine CHF patients, but not in patients without CHF. These results suggest complex cross communication between the two biological pathways in advanced stages of CHF.


Assuntos
Doenças do Cão/sangue , Insuficiência Cardíaca/veterinária , Inflamação/veterinária , Estresse Oxidativo , Animais , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/veterinária , Cães , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/metabolismo , Doenças das Valvas Cardíacas/sangue , Doenças das Valvas Cardíacas/veterinária , Contagem de Leucócitos/veterinária , Masculino , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Fator de Necrose Tumoral alfa/sangue
4.
Biomed Res Int ; 2021: 6653802, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33860048

RESUMO

Objective: Multiple genes have been identified to cause dilated cardiomyopathy (DCM). Nevertheless, there is still a lack of comprehensive elucidation of the molecular characteristics for DCM. Herein, we aimed to uncover putative molecular features for DCM by multiomics analysis. Methods: Differentially expressed genes (DEGs) were obtained from different RNA sequencing (RNA-seq) datasets of left ventricle samples from healthy donors and DCM patients. Furthermore, protein-protein interaction (PPI) analysis was then presented. Differentially methylated genes (DMGs) were identified between DCM and control samples. Following integration of DEGs and DMGs, differentially expressed and methylated genes were acquired and their biological functions were analyzed by the clusterProfiler package. Whole exome sequencing of blood samples from 69 DCM patients was constructed in our cohort, which was analyzed the maftools package. The expression of key mutated genes was verified by three independent datasets. Results: 1407 common DEGs were identified for DCM after integration of the two RNA-seq datasets. A PPI network was constructed, composed of 171 up- and 136 downregulated genes. Four hub genes were identified for DCM, including C3 (degree = 24), GNB3 (degree = 23), QSOX1 (degree = 21), and APOB (degree = 17). Moreover, 285 hyper- and 321 hypomethylated genes were screened for DCM. After integration, 20 differentially expressed and methylated genes were identified, which were associated with cell differentiation and protein digestion and absorption. Among single-nucleotide variant (SNV), C>T was the most frequent mutation classification for DCM. MUC4 was the most frequent mutation gene which occupied 71% across 69 samples, followed by PHLDA1, AHNAK2, and MAML3. These mutated genes were confirmed to be differentially expressed between DCM and control samples. Conclusion: Our findings comprehensively analyzed molecular characteristics from the transcriptome, epigenome, and genome perspectives for DCM, which could provide practical implications for DCM.


Assuntos
Cardiomiopatia Dilatada/genética , Epigenoma , Genoma Humano , Genômica , Transcriptoma/genética , Cardiomiopatia Dilatada/sangue , Metilação de DNA/genética , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Mapas de Interação de Proteínas/genética , Reprodutibilidade dos Testes , Sequenciamento Completo do Exoma
5.
PLoS Negl Trop Dis ; 15(3): e0008906, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33755669

RESUMO

Chagas' disease (CD), caused by the hemoflagellate protozoan, Trypanosoma cruzi, is endemic in most countries of Latin America. Heart failure (HF) is often a late manifestation of chronic CD, and is associated with high morbidity and mortality. Inflammatory processes mediated by cytokines play a key role in the pathogenesis and progression of CD. Keeping in view the inflammatory nature of CD, this study investigated the possible role of 21 different inflammatory cytokines as biomarkers for prediction and prognosis of CD. The plasma concentration of these cytokines was measured in a group of patients with CD (n = 94), and then compared with those measured in patients with dilated cardiomyopathy (DCM) from idiopathic causes (n = 48), and with control subjects (n = 25). Monovariately, plasma levels of cytokines such as stem cell growth factor beta (SCGF beta), hepatocyte growth factor (HGF), monokine induced by interferon gamma (CXCL9), and macrophage inhibitory factor (MIF) were significantly increased in CD patients with advanced HF compared to control group. None of the cytokines could demonstrate any prognostic potency in CD patients, and only MIF and stromal derived factor-1 alpha (CXCL12) showed significance in predicting mortality and necessity for heart transplant in DCM patients. However, multivariate analysis prognosticated a large proportion of CD and DCM patients. In CD patients, HGF and Interleukin-12p40 (IL-12p40) together separated 81.9% of 3-year survivors from the deceased, while in DCM patients, CXCL12, stem cell factor (SCF), and CXCL9 together discriminated 77.1% of survivors from the deceased. The significant increase in plasma concentrations of cytokines such as HGF and CXCL9 in CD patients, and the ability of these cytokines to prognosticate a large proportion of CD and DCM patients multivariately, encourages further studies to clarify the diagnostic and prognostic potential of cytokines in such patients.


Assuntos
Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/mortalidade , Doença de Chagas/diagnóstico , Doença de Chagas/mortalidade , Citocinas/sangue , Biomarcadores/sangue , Doença de Chagas/sangue , Doença de Chagas/patologia , Quimiocina CXCL9/sangue , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/parasitologia , Fatores de Crescimento de Células Hematopoéticas/sangue , Fator de Crescimento de Hepatócito/sangue , Humanos , Oxirredutases Intramoleculares/sangue , Lectinas Tipo C/sangue , Fatores Inibidores da Migração de Macrófagos/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Trypanosoma cruzi/fisiologia
6.
BMC Cardiovasc Disord ; 21(1): 88, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579193

RESUMO

BACKGROUND: Necrotizing autoimmune myopathy (NAM) is pathologically characterized by myofiber necrosis and regeneration with paucity or absence of inflammatory cells in muscle biopsy. Two autoantibodies, namely anti-signal recognition particle (SRP)-antibodies and anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)-antibodies, are typically specific with NAM. Anti-SRP-positive NAM can be associated with cardiomyopathy which responds well to immunotherapy. Here we reported an anti-SRP-antibody and anti-MDA5-antibody NAM patient who developed severe cardiomyopathy after gaining significant improvement of myopathy and subsequently accepted heart transplantation. CASE PRESENTATION: A NAM case with both positive anti-SRP and MDA-5 antibodies who gained significant improvement of the skeletal muscle weakness with immunotherapy, but 3 years later he developed severe dilated cardiomyopathy and at last received heart transplantation. Myocardial biopsy showed disarranged and atrophic myofibers, remarkable interstitial fibrosis without inflammatory infiltrates. Immunohistochemistry analysis revealed increased polyubiquitin-binding protein p62/SQSTM1 protein expression and the positive staining of cleaved-caspase 3 in a few cardiomyocytes. After the transplantation, the patient was symptom-free on oral prednisone (10 mg/day) and tacrolimus (2 mg/day). CONCLUSIONS: We described the first case of anti-SRP and anti-MAD5 positive NAM who had received heart transplantation because of cardiopathy. Though the myopathy had been clinically improved after immunotherapy, the cardiomyopathy remained progressive and lethal. The processes of dysfunctional autophagy and augmented apoptosis were putatively pathophysiological mechanisms underlying cardiac damage in anti-SRP and anti-MAD5 positive NAM.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/tratamento farmacológico , Cardiomiopatia Dilatada/terapia , Imunossupressores/uso terapêutico , Helicase IFIH1 Induzida por Interferon/imunologia , Músculo Esquelético/efeitos dos fármacos , Doenças Musculares/tratamento farmacológico , Partícula de Reconhecimento de Sinal/imunologia , Adulto , Doenças Autoimunes/sangue , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Biomarcadores/sangue , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/imunologia , Feminino , Transplante de Coração , Humanos , Músculo Esquelético/imunologia , Músculo Esquelético/patologia , Doenças Musculares/sangue , Doenças Musculares/diagnóstico , Doenças Musculares/imunologia , Necrose , Fatores de Tempo , Resultado do Tratamento
7.
BMC Nephrol ; 21(1): 544, 2020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-33349246

RESUMO

BACKGROUND: An arteriovenous fistula (AVF) is the first choice when considering access for haemodialysis (HD). When a forearm AVF fails an upper arm AVF is a frequent subsequent dialysis access option. The latter may cause cardiac strain. NT-pro-B-type natriuretic peptide (NT-NT-proBNP) is a marker used to estimate volume overload and cardiac strain. This case report shows the benefit of using longitudinal individual follow-up of pre-dialysis NT-proBNP in clinical practice to detect changes in cardiac condition that may be due to high-output AVF. CASE PRESENTATION: An 18 years old patient performed HD via an upper arm AVF before he was admitted to our unit. NT-proBNP was above the upper detection level of 70,000 ng/L. Echocardiography revealed a left-ventricular cardiac insufficiency. Interdialytic weight gain (IDWG) was above 5%. He was instructed to lower fluid intake and IDWG towards 2%. Four months later NT-proBNP surpassed 70,000 ng/L again. Flow in the brachial artery was at 3034 ml/min. Reconstructive surgery of the AVF did not reduce flow and NT-proBNP in the long run. Clinically, he worsened to NYHA class III-IV. It was decided to close the upper arm AVF and to replace it with a lower arm AVF leading to a reduced artery flow of 1344 mL/min. The clinical condition successively recovered and NT-proBNP decreased to 7000 ng/L. CONCLUSIONS: Pre-dialysis NT-proBNP should be considered as a suitable routine marker for cardiac strain such as caused by high-output AVF besides variables such as IDWG. Brachial artery flow besides AVF flow measurement is helpful.


Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Cardiomiopatia Dilatada/sangue , Falência Renal Crônica/terapia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Complicações Pós-Operatórias/sangue , Diálise Renal , Disfunção Ventricular Esquerda/sangue , Adolescente , Artéria Braquial , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/fisiopatologia , Ecocardiografia , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Reoperação , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia
8.
BMC Cardiovasc Disord ; 20(1): 402, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894050

RESUMO

BACKGROUND: Asprosin is a novel fasting glucogenic adipokine discovered in 2016. Asprosin induces rapid glucose releases from the liver. However, its molecular mechanisms and function are still unclear. Adaptation of energy substrates from fatty acid to glucose is recently considered a novel therapeutic target in heart failure treatment. We hypothesized that the asprosin is able to modulate cardiac mitochondrial functions and has important prognostic implications in dilated cardiomyopathy (DCM) patients. METHODS: We prospectively enrolled 50 patients (86% male, mean age 55 ± 13 years) with DCM and followed their 5-year major adverse cardiovascular events from 2012 to 2017. Comparing with healthy individuals, DCM patients had higher asprosin levels (191.2 versus 79.7 ng/mL, P < 0.01). RESULTS: During the 5-year follow-up in the study cohort, 16 (32.0%) patients experienced adverse cardiovascular events. Patients with lower asprosin levels (< 210 ng/mL) were associated with increased risks of adverse clinical outcomes with a hazard ratio of 7.94 (95% CI 1.88-33.50, P = 0.005) when compared patients with higher asprosin levels (≥ 210 ng/mL). Using cardiomyoblasts as a cellular model, we showed that asprosin prevented hypoxia-induced cell death and enhanced mitochondrial respiration and proton leak under hypoxia. CONCLUSIONS: In patients with DCM, elevated plasma asprosin levels are associated with less adverse cardiovascular events in five years. The underlying protective mechanisms of asprosin may be linked to its functions relating to enhanced mitochondrial respiration under hypoxia.


Assuntos
Cardiomiopatia Dilatada/sangue , Fibrilina-1/sangue , Adulto , Idoso , Animais , Biomarcadores/sangue , Cardiomiopatia Dilatada/diagnóstico , Estudos de Casos e Controles , Hipóxia Celular , Linhagem Celular , Metabolismo Energético , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias Cardíacas/metabolismo , Miócitos Cardíacos/metabolismo , Prognóstico , Estudos Prospectivos , Ratos , Fatores de Tempo , Regulação para Cima
9.
Dis Markers ; 2020: 9356738, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774516

RESUMO

Background: Pediatric patients show an impressive capacity of cardiac regeneration. In contrast, severely deteriorated adult hearts do usually not recover. Since cardiac remodeling-involving the expression of fetal genes-is regarded as an adaptation to stress, we compared hearts of adult patients suffering from dilated cardiomyopathy (DCM) with remodeling of cultured neonatal (NRC) as well as adult (ARC) rat cardiomyocytes and the developing postnatal myocardium. Methods: NRC and ARC were stimulated with serum and cardiac morphogens derived from DCM hearts. Protein synthesis (PS) as well as protein accumulation (PA) was measured, and cell survival was determined under ischemic conditions. Fetal markers were investigated by Western blot. Biomarkers of remodeling were analyzed in controls, DCM, and 2- to 6-month-old children with tetralogy of Fallot as well as in neonatal and adult rats by immunofluorescence. Results: In NRC, serum and morphogens strongly stimulated PS and PA and the reestablishment of cell-cell contacts (CCC). In ARC, both stimulants increased PS and CCC, but PA was only elevated after serum stimulation. In contrast to serum, morphogen treatment resulted in the expression of fetal genes in ARC as determined by nonmuscle α-actinin-1 and α-actinin-4 expression (NM-actinins) and was associated with increased survival under ischemia. NM-actinins were present in cardiomyocytes of DCM in a cross-striated pattern reminiscent of sarcomeres as well as in extensions of the area of the intercalated disc (ID). NM-actinins are expressed in NRC and in the developing heart. Radixin staining revealed remodeling of the area of the ID in DCM almost identical to stimulated cultured ARC. Conclusions: Remodeling was similar in ARC and in cardiomyocytes of DCM suggesting evolutionary conserved mechanisms of regeneration. Despite activation of fetal genes, the atrophy of ARC indicates differences in their regenerative capacity from NRC. Cardiac-derived factors induced NM-actinin expression and increased survival of ischemic ARC while circulating molecules were less effective. Identification of these cardiac-derived factors and determination of their individual capacity to heal or damage are of particular importance for a biomarker-guided therapy in adult patients.


Assuntos
Actinina/metabolismo , Cardiomiopatia Dilatada/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas de Membrana/metabolismo , Miócitos Cardíacos/citologia , Tetralogia de Fallot/metabolismo , Idoso , Animais , Animais Recém-Nascidos , Cardiomiopatia Dilatada/sangue , Sobrevivência Celular , Células Cultivadas , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos , Tetralogia de Fallot/sangue
10.
Int Heart J ; 61(4): 739-747, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32684600

RESUMO

The metabolism of branched-chain amino acids (BCAAs) is reported to change in heart failure (HF) and correlate with cardiac function. However, the effect of BCAAs on HF remains controversial. We investigate the prognostic value of the plasma BCAA level in nonischemic dilated cardiomyopathy (NIDCM).This study enrolled 39 NIDCM patients, who underwent plasma amino acid (AA) analysis. The ratio of BCAAs to total AAs was calculated. All patients were divided into two groups at the median of BCAA/total AA ratio; high BCAA/total AA group (≥ 0.15, n = 20) and low BCAA/total AA group (< 0.15, n = 19). A cardiac event was defined as a composite of cardiac death, hospitalization for worsening HF, and lethal arrhythmia.The mean age was 51.1 ± 12.3 years and left ventricular ejection fraction (LVEF) was 32.7 ± 10.1%. In the low BCAA/total AA group, the body mass index and the total cholesterol level were lower than in the high BCAA/total AA group. The BCAA/total AA ratio was positively correlated with LVEF (r = 0.35, P = 0.031) and negatively correlated with brain natriuretic peptide (r = -0.37, P = 0.020). The low BCAA/total AA group had a lower cardiac event-free rate (5-year: 100% versus 73%; P = 0.019). In univariate analysis, angiotensin converting enzyme inhibitor or angiotensin II receptor blocker (hazard ratio: 0.045, P = 0.0014), hemoglobin (hazard ratio: 0.49 per 1 g/dL, P = 0.0022), and BCAA/total AA ratio < 0.15 (hazard ratio: not available, P = 0.0066) were major predictors for cardiac events.The BCAA/total AA ratio might be a useful predictor for future cardiac events in patients with NIDCM.


Assuntos
Aminoácidos/sangue , Cardiomiopatia Dilatada/sangue , Adulto , Idoso , Cardiomiopatia Dilatada/diagnóstico por imagem , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Clin Biochem ; 83: 37-42, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32504703

RESUMO

INTRODUCTION: Elevated plasma levels of asymmetric dimethylarginine (ADMA), an inhibitor of NO synthase, are associated with adverse outcome. There is no data available, whether ADMA levels are associated with arrhythmic death (AD) in patients with ischemic cardiomyopathy (ICM) or non-ischemic, dilated cardiomyopathy (DCM). METHODS AND RESULTS: A total of 110 ICM, 52 DCM and 30 control patients were included. Primary outcome parameter of this prospective study was arrhythmic death (AD) or resuscitated cardiac arrest (RCA). Plasma levels of ADMA were significantly higher in ICM (p < 0.001) and in DCM (p < 0.001) patients compared to controls. During a median follow-up of 7.0 years, 62 (32.3%) patients died. AD occurred in 26 patients and RCA was observed in 22 patients. Plasma levels of ADMA were not associated with a significantly increased risk of AD or RCA in ICM (hazard ratio (HR) = 1.37, p = 0.109) or in DCM (HR = 1.06, p = 0.848) patients. No significant association was found with overall mortality in ICM (HR = 1.39, p = 0.079) or DCM (HR = 1.10, p = 0.666) patients. Stratified Kaplan-Meier curves for ADMA levels in the upper tertile (>0.715 µmol/l) or the two lower tertiles (≤0.715 µmol/l) did not show a higher risk for AD or RCA (p = 0.221) or overall mortality (p = 0.548). In patients with left ventricular ejection fraction ≤ 35%, ADMA was not associated with AD or RCA (HR = 1.35, p = 0.084) or with overall mortality (HR = 1.24, p = 0.162). CONCLUSIONS: Plasma levels of ADMA were elevated in patients with ICM or DCM as compared to controls, but were not significantly predictive for overall mortality or the risk for arrhythmic death.


Assuntos
Arginina/análogos & derivados , Arritmias Cardíacas/sangue , Arritmias Cardíacas/mortalidade , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/mortalidade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/mortalidade , Idoso , Arginina/sangue , Arritmias Cardíacas/etiologia , Cardiomiopatia Dilatada/complicações , Estudos de Casos e Controles , Feminino , Parada Cardíaca/sangue , Parada Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Estudos Prospectivos , Fatores de Risco , Disfunção Ventricular Esquerda/sangue
12.
Heart Surg Forum ; 23(3): E276-E280, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32524978

RESUMO

BACKGROUND: Chemerin is a newly discovered adipokine, which has been reported to be associated with the presence of dilated cardiomyopathy (DCM). The present study aims to evaluate the prognostic value of serum chemerin in patients with DCM. METHODS: A total of 214 patients with DCM was recruited and divided into 4 groups, according to quartiles of chemerin levels. Kaplan-Meier analysis was conducted to compare the survival rates among patients with different levels of chemerin, using the log-rank test. Multivariate Cox regression analysis was performed to assess the association of serum chemerin levels and occurrence of major adverse cardiac events (MACEs), including cardiac mortality, stroke and myocardial infarction. RESULTS: The Kaplan-Meier survival analysis indicated that patients with higher concentration of chemerin had shorter event-free survivals for MACEs (P < .01). Cox regression analysis showed that chemerin was a significant predictor of MACEs (Quartile 3 versus Quartile 1: HR=1.79, 95% CI: 1.31-2.79; Quartile 4 versus Quartile 1: HR=2.87, 95% CI: 1.79-4.25) and all-cause death (Quartile 3 versus Quartile 1: HR=1.56, 95% CI: 1.20-2.42; Quartile 4 versus Quartile 1: HR=2.28, 95% CI: 1.52-3.96) after adjusting for potential risk factors. CONCLUSION: Serum chemerin should be a potential prognostic indicator in patients with DCM.


Assuntos
Cardiomiopatia Dilatada/sangue , Quimiocinas/sangue , Função Ventricular Esquerda/fisiologia , Adulto , Biomarcadores/sangue , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/fisiopatologia , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências
13.
PLoS One ; 15(5): e0233206, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32413894

RESUMO

INTRODUCTION: A surge in Food and Drug Administration (FDA) consumer complaints identified concerns that legume-rich, grain-free diets were associated with nutritionally-mediated dilated cardiomyopathy (DCM). Golden retrievers represent the most reported breed affected by this condition and previous studies documented the disease is responsive to dietary change and taurine supplementation. Although dietary findings across cases are compelling, prospective studies with control groups are lacking. The role of diet in developing taurine deficiency and echocardiographic changes consistent with DCM in healthy dogs is unknown. OBJECTIVES: We hypothesized that golden retrievers eating non-traditional diets are at a higher risk of having taurine deficiency and nutritionally-mediated DCM compared with those eating traditional commercial diets. We aimed to compare taurine concentrations and echocardiographic indices of systolic function between golden retrievers in each diet group and elucidate associations between diet and these variables. Additionally, we aimed to generate breed-specific reference intervals for whole blood and plasma taurine concentrations. ANIMALS: 86 golden retrievers. METHODS: Golden retrievers eating traditional or non-traditional diets were evaluated and diet history, taurine concentrations and echocardiographic data were collected. Dietary features, taurine concentrations and echocardiographic findings were compared between diet groups. Relative risks were calculated for the likelihood of echocardiographic abnormalities and taurine deficiency in each diet group. Breed-specific reference intervals were constructed for taurine concentrations in dogs from the traditional diet group. RESULTS: Golden retrievers eating non-traditional diets had significantly lower taurine concentrations and more frequent systolic dysfunction. Breed specific reference intervals are higher than previously reported across breeds. CONCLUSIONS: Non-traditional diets, which were typically grain-free and contained legumes in this study, were significantly associated with and have increased relative risk for the identification of taurine deficiency and echocardiographic abnormalities consistent with nutritionally-mediated DCM. These findings were identifiable in the absence of clinical signs and support the findings of multiple previous studies and the ongoing FDA investigation.


Assuntos
Ração Animal/análise , Cardiomiopatia Dilatada/veterinária , Dieta/veterinária , Doenças do Cão/epidemiologia , Taurina/sangue , Taurina/deficiência , Ração Animal/efeitos adversos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/epidemiologia , Dieta/efeitos adversos , Doenças do Cão/sangue , Doenças do Cão/diagnóstico por imagem , Cães , Ecocardiografia , Grão Comestível , Fabaceae/efeitos adversos , Feminino , Masculino , Estudos Prospectivos , Valores de Referência , Fatores de Risco
14.
Cell Mol Biol (Noisy-le-grand) ; 66(2): 198-203, 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32415948

RESUMO

This experiment aimed to study the effect of trimetazidine combined with perindopril on NT-proBNP levels in rats with dilated cardiomyopathy (DCM). 40 SD rats were selected and 10 rats were randomly selected to continue to be fed as the blank group. The other 30 rats were injected with adriamycin to establish the DCM rat model. Then they were divided into 3 groups, namely control group (without any drug intervention), trimetazidine group (with trimetazidine single-agent intervention) and combination drug group (with trimetazidine combined with perindopril intervention), with 10 DCM rats in each group. After 4 weeks of intervention, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic diameter (LVESD) of rats were measured by echocardiography. The changes of plasma brain natriuretic peptide (BNP) level and n-terminal pro-brain natriuretic peptide (NT-proBNP) were detected by ELISA. RT-PCR was used to detect the regulation of angiotensin II type 1 receptor (AT1Rs) and lamin A mRNA expression in rat myocardium. After the intervention, the LVEF%, LVEDD and LVESD measured values of the rats in the combination drug group were significantly better than those in the trimetazidine group and the control group (P< 0.05). The BNP, NT-proBNP and AT1Rs levels of the rats in the combination drug group were significantly lower than those in the trimetazidine group and the control group. The difference was statistically significant (p< 0.05). The lamin A expression of the rats in the combination drug group was significantly higher than that in the trimetazidine group and the control group. The difference was statistically significant (P< 0.05). Compared with trimetazidine single-agent, trimetazidine combined with perindopril can significantly improve the cardiac function of rats with dilated cardiomyopathy, reduce the serum NT-proBNP level and improve the expression of AT1Rs and lamin A in rats.


Assuntos
Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/tratamento farmacológico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Perindopril/uso terapêutico , Trimetazidina/uso terapêutico , Animais , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/fisiopatologia , Diástole/efeitos dos fármacos , Lamina Tipo A/metabolismo , Masculino , Perindopril/farmacologia , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/metabolismo , Volume Sistólico/efeitos dos fármacos , Análise de Sobrevida , Sístole/efeitos dos fármacos , Trimetazidina/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos
15.
Adv Clin Exp Med ; 29(3): 285-293, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32207584

RESUMO

BACKGROUND: Left ventricular reverse remodeling (LVRR) determines clinical status and outcomes in dilated cardiomyopathy (DCM). The extent of myocardial fibrosis is connected to the systolic function of the heart. The recent discovery of the contribution of microRNAs (miRs) to the regulation of cardiac remodeling, LVRR and fibrosis warrants exploration. OBJECTIVES: The aim of the study was to examine the predictive value of circulating and myocardial miR expression for LVRR in DCM. MATERIAL AND METHODS: Seventy consecutive DCM patients (age 48 ±12.1 years, 90% male, ejection fraction (EF) 24.4% ±7.4%) were included in the study. At baseline, all patients underwent clinical assessment, echocardiography, venous blood sampling, and right ventricular endomyocardial biopsy. Circulating and myocardial miRs (miR-21, -26, -29, -30, -133a, and -423) were measured with quantitative real-time polymerase chain reaction (qRT-PCR). LVRR was defined as an increase in EF ≥ 10%, accompanied by a decrease in left ventricle end-diastolic diameter (LVEDd) ≥10% or LVEDd ≤ 33 mm/m2 between baseline and 3-month follow-up. RESULTS: At the 3-month follow-up, 4 patients had died and 3 patients had incomplete data. The remaining patients were divided according to the presence of LVRR into LVRR-present (n = 32, 51%) and LVRR-absent (n = 31, 49%) groups. Out of all the circulating and tissue miRs under study, only myocardial expression of miR-133a significantly differed between the LVRR-present and LVRR-absent group (1.22 (0.47-1.90) vs 0.61 (0.25-0.99) ΔCq, respectively, p < 0.01). miR-133a was found to be a significant LVRR predictor in unadjusted (odds ratio (OR) = 2.81 (1.23-6.40), p < 0.05) and adjusted for duration of disease, left ventricle end-diastolic (LVED) volume (LVEDvol), hs-troponin-T, and NT-proBNP (OR = 5.20 (1.13-24.050, p < 0.05) models. CONCLUSIONS: From all of the circulating and tissue miRs, only myocardial miR-133a showed increased expression in LVRR-present patients and was found an independent LVRR predictor. This indicates a link between miR-133 and cardiac remodeling in DCM.


Assuntos
Cardiomiopatia Dilatada/sangue , MicroRNAs/sangue , Miocárdio/patologia , Remodelação Ventricular , Adulto , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Função Ventricular Esquerda
17.
Can J Cardiol ; 36(4): 554-563, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32046906

RESUMO

BACKGROUND: Dilated cardiomyopathy with ataxia syndrome (DCMA) is an understudied autosomal recessive disease caused by loss-of-function mutations in the poorly characterized gene DNAJC19. Clinically, DCMA is commonly associated with heart failure and early death in affected children through an unknown mechanism. DCMA has been linked to Barth syndrome, a rare but well-studied disorder caused by deficient maturation of cardiolipin (CL), a key mitochondrial membrane phospholipid. METHODS: Peripheral blood mononuclear cells from 2 children with DCMA and severe cardiac dysfunction were reprogrammed into induced pluripotent stem cells (iPSCs). Patient and control iPSCs were differentiated into beating cardiomyocytes (iPSC-CMs) using a metabolic selection strategy. Mitochondrial structure and CL content before and after incubation with the mitochondrially targeted peptide SS-31 were quantified. RESULTS: Patient iPSCs carry the causative DNAJC19 mutation (rs137854888) found in the Hutterite population, and the iPSC-CMs demonstrated highly fragmented and abnormally shaped mitochondria associated with an imbalanced isoform ratio of the mitochondrial protein OPA1, an important regulator of mitochondrial fusion. These abnormalities were reversible by incubation with SS-31 for 24 hours. Differentiation of iPSCs into iPSC-CMs increased the number of CL species observed, but consistent, significant differences in CL content were not seen between patients and control. CONCLUSIONS: We describe a unique and novel cellular model that provides insight into the mitochondrial abnormalities present in DCMA and identifies SS-31 as a potential therapeutic for this devastating disease.


Assuntos
Cardiomiopatia Dilatada/sangue , Ataxia Cerebelar/sangue , Células-Tronco Pluripotentes Induzidas , Leucócitos Mononucleares/citologia , Erros Inatos do Metabolismo/sangue , Mitocôndrias Cardíacas/fisiologia , Miopatias Mitocondriais/sangue , Miócitos Cardíacos , Diferenciação Celular , Células Cultivadas , Humanos
18.
Cardiovasc Res ; 116(13): 2131-2141, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32053144

RESUMO

AIMS: Sex differences impact the occurrence, presentation, prognosis, and response to therapy in heart disease. Particularly, the phenotypic presentation of patients with non-ischaemic dilated cardiomyopathy (NIDCM) differs between men and women. However, whether the response to mesenchymal stem cell (MSC) therapy is influenced by sex remains unknown. We hypothesize that males and females with NIDCM respond similarly to MSC therapy. METHODS AND RESULTS: Male (n = 24) and female (n = 10) patients from the POSEIDON-DCM trial who received MSCs via transendocardial injections were evaluated over 12 months. Endothelial function was measured at baseline and 3 months post-transendocardial stem cell injection (TESI). At baseline, ejection fraction (EF) was lower (P = 0.004) and end-diastolic volume (EDV; P = 0.0002) and end-systolic volume (ESV; P = 0.0002) were higher in males vs. females. In contrast, baseline demographic characteristics, Minnesota Living with Heart Failure Questionnaire (MLHFQ), and 6-min walk test (6MWT) were similar between groups. EF improved in males by 6.2 units (P = 0.04) and in females by 8.6 units (P = 0.04; males vs. females, P = 0.57). EDV and ESV were unchanged over time. The MLHFQ score, New York Heart Association (NYHA) class, endothelial progenitor cell-colony forming units, and serum tumour necrosis factor alpha improved similarly in both groups. CONCLUSION: Despite major differences in phenotypic presentation of NIDCM in males and females, this study is the first of its kind to demonstrate that MSC therapy improves a variety of parameters in NIDCM irrespective of patient sex. These findings have important clinical and pathophysiologic implications regarding the impact of sex on responses to cell-based therapy for NIDCM.


Assuntos
Cardiomiopatia Dilatada/cirurgia , Transplante de Células-Tronco Mesenquimais , Adulto , Idoso , Biomarcadores/sangue , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/fisiopatologia , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Tolerância ao Exercício , Feminino , Florida , Estado Funcional , Disparidades nos Níveis de Saúde , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Pessoa de Meia-Idade , Qualidade de Vida , Recuperação de Função Fisiológica , Fatores Sexuais , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue , Função Ventricular Esquerda , Remodelação Ventricular
19.
Medicina (Kaunas) ; 56(1)2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31936691

RESUMO

Background and objectives: T-cadherin (T-cad) is one of the adiponectin receptors abundantly expressed in the heart and blood vessels. Experimental studies show that T-cad sequesters adiponectin in cardiovascular tissues and is critical for adiponectin-mediated cardio-protection. However, there are no data connecting cardiac T-cad levels with human chronic heart failure (HF). The aim of this study was to assess whether myocardial T-cad concentration is associated with chronic HF severity and whether the T-cad levels in human heart tissue might predict outcomes in patients with non-ischemic dilated cardiomyopathy (NI-DCM). Materials and Methods: 29 patients with chronic NI-DCM and advanced HF were enrolled. Patients underwent regular laboratory investigations, echocardiography, coronary angiography, and right heart catheterization. TNF-α and IL6 in serum were detected by enzyme-linked immunosorbent assay (ELISA). Additionally, endomyocardial biopsies were obtained, and the levels of T-cad were assessed by ELISA and CD3, CD45Ro, CD68, and CD4- immunohistochemically. Mean pulmonary capillary wedge pressure (PCWP) was used as a marker of HF severity, subdividing patients into two groups: mean PCWP > 19 mmHg vs. mean PCWP < 19 mmHg. Patients were followed-up for 5 years. The study outcome was composite: left ventricular assist device implantation, heart transplantation, or death from cardiovascular causes. Results: T-cad shows an inverse correlation with the mean PCWP (rho = -0.397, p = 0.037). There is a tendency towards a lower T-cad concentration in patients with more severe HF, as indicated by the mean PCWP > 19 mmHg compared to those with mean PCWP ≤ 19 mmHg (p = 0.058). Cardiac T-cad levels correlate negatively with myocardial CD3 cell count (rho = -0.423, p = 0.028). Conclusions: Univariate Cox regression analysis did not prove T-cad to be an outcome predictor (HR = 1, p = 0.349). However, decreased T-cad levels in human myocardium can be an additional indicator of HF severity. T-cad in human myocardium has an anti-inflammatory role. More studies are needed to extend the role of T-cad in the outcome prediction of patients with NI-DCM.


Assuntos
Caderinas/análise , Insuficiência Cardíaca/sangue , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Caderinas/sangue , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/fisiopatologia , Angiografia Coronária/métodos , Ecocardiografia/métodos , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Lituânia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangue
20.
Dis Markers ; 2020: 9385472, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998421

RESUMO

Objective: To investigate plasma cytokines (interferon gamma, interleukin-4, and interleukin-17) in patients with viral myocarditis (VMC) and evaluate their predictive value in the progression from VMC to dilated cardiomyopathy (DCM). Methods: A prospective, multicenter, observational study included 536 patients with newly diagnosed VMC admitted in cardiology departments of 24 tertiary super specialised university-affiliated hospitals in the China registry from January 2012 to June 2016. Demographics and clinical characteristics at baseline and after three months were collected, including laboratory blood tests, ECG, echocardiography, and drug treatment in each participating site. The plasma anti-viral antibodies (Abs), anti-heart autoimmune Abs, and cytokines were detected by ELISA. Results: Of the 536 patients, 534 were included for analysis after two patients died in less than a month. The plasma levels of IFN-γ, IL-4, and IL-17 were continually higher in patients with incident DCM than in those without incident DCM at baseline, from the 1st month and the 3rd month; all had a P value of <0.0001. There was a positive correlation between IL-4 and LVEDd (r = 0.30, P < 0.0001) and between IL-17 and LVEDd (r = 0.11, P = 0.02). When all these covariates have entered the model simultaneously, elevated IL-4 and IL-17 were still significantly associated with DCM incidence. The RR (95% CI) of DCM incidence were 1.04 (1.02-1.06) for IL-4 and 5.24 (2.81-9.79) for IL-17. Conclusion: The continued elevation of plasma IL-4 and IL-17 in VMC patients were associated with a high incidence of DCM at three months, and these two cytokines were independent predictors for the progression from VMC to DCM.


Assuntos
Cardiomiopatia Dilatada/sangue , Interleucina-17/sangue , Interleucina-4/sangue , Miocardite/sangue , Viroses/sangue , Adulto , Biomarcadores/sangue , Cardiomiopatia Dilatada/patologia , Feminino , Humanos , Interferon gama/sangue , Masculino , Pessoa de Meia-Idade , Miocardite/patologia , Miocardite/virologia , Viroses/patologia
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