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1.
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
2.
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
3.
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
4.
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
6.
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
7.
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
8.
Medicine (Baltimore) ; 98(44): e17710, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689804

RESUMO

Tropomyosin 1 (TPM1) is a protein that constitutes the sarcomere filaments and is encoded by the TPM1 gene. The aim of the present study is to investigate the correlation between the 3' untranslated region (3'UTR) single nucleotide polymorphisms (SNPs) of the TPM1 gene and dilated cardiomyopathy (DCM).A total of 245 patients with DCM and 245 healthy controls were recruited with 5 ml of venous blood. Genomic DNA was extracted to analyze the TPM1 gene rs12148828, rs11558748, rs707602, rs6738, rs7178040 loci genotypes, and the plasma miR-21 level was analyzed by reverse transcription-PCR (RT-PCR).The risk of DCM development in the rs6738 locus G allele carriers were 1.69 times more than A allele carriers (95% CI: 1.22-2.33, P = .001). Age and gender had no effect on the association of TPM1 gene SNPs with DCM risk (P > .05). The plasma miR-21 level of TPM1 gene rs6738 locus AA carriers was significantly higher than that of the AG and GG genotypes (P < .001).The SNPs of TPM1 gene rs6738 locus is associated with the risk of DCM, which may be related to the abnormal increase of miR-21 level in DCM patients, but further research is needed to prove the causal relationship between miR-21 level and DCM risk.


Assuntos
Regiões 3' não Traduzidas/genética , Cardiomiopatia Dilatada/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Tropomiosina/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Cardiomiopatia Dilatada/sangue , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Fatores de Risco
9.
Int J Mol Sci ; 20(16)2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31404946

RESUMO

Heart failure (HF) patients frequently have elevated plasma renin activity. We examined the significance of elevated plasma renin activity in a translationally-relevant model of dilated cardiomyopathy (DCM), which replicates the progressive stages (A-D) of human HF. Female mice with DCM and elevated plasma renin activity concentrations were treated with a direct renin inhibitor (aliskiren) in a randomized, blinded fashion beginning at Stage B HF. By comparison to controls, aliskiren treatment normalized pathologically elevated plasma renin activity (p < 0.001) and neprilysin levels (p < 0.001), but did not significantly alter pathological changes in plasma aldosterone, angiotensin II, atrial natriuretic peptide, or corin levels. Aliskiren improved cardiac systolic function (ejection fraction, p < 0.05; cardiac output, p < 0.01) and significantly reduced the longitudinal development of edema (extracellular water, p < 0.0001), retarding the transition from Stage B to Stage C HF. The normalization of elevated plasma renin activity reduced the loss of body fat and lean mass (cachexia/sarcopenia), p < 0.001) and prolonged survival (p < 0.05). In summary, the normalization of plasma renin activity retards the progression of experimental HF by improving cardiac systolic function, reducing the development of systemic edema, cachexia/sarcopenia, and mortality. These data suggest that targeting pathologically elevated plasma renin activity may be beneficial in appropriately selected HF patients.


Assuntos
Amidas/uso terapêutico , Cardiomiopatia Dilatada/tratamento farmacológico , Fumaratos/uso terapêutico , Renina/antagonistas & inibidores , Renina/sangue , Animais , Caquexia/sangue , Caquexia/complicações , Caquexia/tratamento farmacológico , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/complicações , Modelos Animais de Doenças , Edema/sangue , Edema/complicações , Edema/tratamento farmacológico , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Camundongos , Camundongos Endogâmicos C57BL
10.
Biomarkers ; 24(7): 652-658, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31305163

RESUMO

Background: The course of newly diagnosed dilated cardiomyopathy (DCM) varies from persistent reduction of left ventricular ejection fraction (LVEF) to recovery or even worsening. The aim of the present study was to examine the prognostic value of selected biomarkers with regard to changes in LVEF. Methods: Main inclusion criterion was LVEF ≤45% with exclusion of coronary artery or valvular heart disease. The primary endpoint was LVEF ≤35% in the follow-up echocardiogram. Galectin-3, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) were related to the endpoint. Results: Data from 80 DCM patients (55 male, mean age 53 years) were analyzed. Median LVEF was 25% (IQR 25-30). The endpoint was met for 24 patients (30%). These had higher baseline levels of galectin-3 (median 20.3 ng/mL [IQR 14.3-26.9] vs. 14.7 ng/mL [IQR 10.9-17.7], p = 0.007) and NT-proBNP (3089 pg/mL [IQR 1731-6694] vs. 1498 pg/mL [IQR 775-3890]; p = 0.004) in univariate Cox regression analysis. ROC analysis revealed that CRP (median 0.4 mg/dL [IQR 0.2-1.2]) was also related to the endpoint (p = 0.043). Conclusion: Higher levels of galectin-3, NT-proBNP, and CRP were associated with LVEF ≤35% in our cohort. An approach utilizing a combination of biomarkers for patient management should be assessed in further studies.


Assuntos
Cardiomiopatia Dilatada/sangue , Galectina 3/sangue , Função Ventricular Esquerda/fisiologia , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Prognóstico
11.
Cardiology ; 142(3): 167-174, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31189164

RESUMO

PURPOSE: The aim of this study was to quantify the value of various clinical, laboratory, and instrumental signs in the diagnosis of myocarditis in comparison with morphological studies of the myocardium. METHODS: In 100 patients (65 men, 44.7 ± 12.5 years old) with "idiopathic" arrhythmias (n = 20) and dilated cardiomyopathy (DCM; n = 80), we performed the following: 71 endomyocardial biopsies (EMB), 13 intraoperative biopsies, 5 studies of explanted hearts, and 11 autopsies with virus investigation (real-time PCR) of the blood and myocardium. Antiheart antibodies (AHA) were also measured as well as cardiac CT (n = 45), MRI (n = 25), and coronary angiography (n = 47). The comparison group included 50 patients (25 men, 53.7 ± 11.7 years old) with noninflammatory heart diseases who underwent open heart surgery. RESULTS: Active/borderline myocarditis was diagnosed in 76.0% of the study group and in 21.6% of patients in the comparison group (p < 0.001). The myocardial viral genome was observed more frequently in patients in the comparison group than in the study group (65.0 and 40.2%; p < 0.01). We evaluated the diagnostic value of noninvasive markers of myocarditis. The panel of AHA had the greatest importance in the identification of myocarditis: sensitivity was 81.5%, and the positive and negative predictive values were 75.0 and 60.5%. This defined the diagnostic value of noninvasive markers of myocarditis and established a diagnostic algorithm providing an individual assessment of the likelihood of myocarditis development. CONCLUSION: AHA have the greatest significance in the diagnosis of latent myocarditis in patients with "idiopathic" arrhythmias and DCM. The use of a complex of noninvasive criteria allows the probability of myocarditis to be estimated and the indications for EMB to be determined.


Assuntos
Anticorpos/análise , Arritmias Cardíacas/diagnóstico , Cardiomiopatia Dilatada/diagnóstico , Miocardite/diagnóstico , Miocárdio/patologia , Adulto , Antiestreptolisina/sangue , Arritmias Cardíacas/sangue , Biópsia , Técnicas de Imagem Cardíaca , Cardiomiopatia Dilatada/sangue , Diagnóstico Diferencial , Feminino , Genoma Viral , Humanos , Infecções/imunologia , Masculino , Pessoa de Meia-Idade , Miocardite/sangue , Miocárdio/imunologia , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Federação Russa
12.
Can J Cardiol ; 35(6): 727-735, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31151708

RESUMO

BACKGROUND: Prognosis in patients with pediatric dilated cardiomyopathy (PDCM) is urgently required to identify high-risk patients. Elevated soluble ST2 (sST2) is associated with prognosis in adult patients with heart failure. This study aimed to assess the prognostic value of sST2 in PDCM. METHODS: Ninety-four patients with PDCM were enrolled after admission from 2 centres in China and followed up for adverse events (death, cardiac transplantation, and heart-failure-related rehospitalization). B-type natriuretic peptide (BNP) and sST2 levels were measured. RESULTS: Over a median of 678 (interquartile range [IQR]: 533-785) days, 28 (29.8%) adverse events occurred. Patients in the highest tertile of sST2 levels had increased risk of short-term (< 6 months) (adjusted hazard ratio [HR]: 8.36, 95% confidence interval [CI], 1.02-73.52; P < 0.05) and long-term adverse events (2 years) (adjusted HR: 4.23; 95% CI, 1.32-13.60; P < 0.01) than those in lower tertiles. The C-statistic was increased with addition of sST2 to BNP from 0.697 (95% CI, 0.541-0.852) to 0.812 (95% CI, 0.697-0.939) for short-term and from 0.712 (95% CI, 0.604-0.819) to 0.798 (95% CI, 0.697-0.899) for prediction of long-term adverse events. An intermediate-risk subgroup was identified, and 24% had adverse events. When serial measurements were taken in a nested case-control subgroup, sST2 levels were constantly high in patients with late adverse events (> 6 months) but gradually decreased in nonadverse-event controls compared with 3-month and 6-month baseline levels. CONCLUSIONS: In patients with PDCM, serum sST2 levels are associated with adverse events and have robust prognostic value. Serial measurements of sST2 could help in managing patients for monitoring outcomes of treatment.


Assuntos
Cardiomiopatia Dilatada/sangue , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Medição de Risco/métodos , Biomarcadores/sangue , Cardiomiopatia Dilatada/epidemiologia , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Pré-Escolar , China , Feminino , Seguimentos , Humanos , Imunoensaio , Incidência , Masculino , Peptídeo Natriurético Encefálico/sangue , Prognóstico , Estudos Prospectivos , Receptores de Interleucina-1 , Taxa de Sobrevida/tendências , Função Ventricular Esquerda/fisiologia
13.
Biochim Biophys Acta Mol Basis Dis ; 1865(7): 1845-1852, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31109452

RESUMO

Establishing molecular and cellular indicators that reflect the extent of dilation of the left ventricle (LV) after myocardial infarction (MI) may improve diagnostic and prognostic capabilities. We queried the Mouse Heart Attack Research Tool (mHART) 1.0 for day 7 post-MI mice (age 3-9 months, untreated males and females) with serial echocardiographic data at days 0, 1, and 7 (n = 51). Mice were classified into two subgroups determined by a median fold change of 1.6 in end-diastolic dimensions (EDD) normalized to pre-MI values; n = 26 fell below (moderate; mean of 1.42 ±â€¯0.01) and n = 25 fell above this cut-off (extreme; mean of 1.79 ±â€¯0.01; p < 0.001 vs. moderate). Plasma proteomic profiling of 34 analytes measured at day 7 post-MI from male mice (n = 12 moderate and 12 extreme) were evaluated as the test dataset, and receiver operating curve (ROC) analysis was used to assess strength of biomarkers. Females (n = 6 moderate and 9 extreme) were used as the validation dataset. Both by t-test and characteristic (ROC) curve analysis, lower macrophage inflammatory protein-1 gamma (MIP-1γ), lymphotactin, and granulocyte chemotactic protein-2 (GCP-2) were identified as plasma indicators for dilation status (p < 0.05 for all). Macrophage numbers were decreased and complement C5, laminin 1, and Ccr8 gene levels were significantly higher in the LV infarcts of the extreme dilation group (p < 0.05 for all). A composite panel including plasma MIP-1γ, lymphotactin, and GCP-2, and LV infarct Ccr8 and macrophage numbers strongly mirrored LV dilation status (AUC = 0.92; p < 0.0001). Using the mHART 1.0 database, we determined that a failure to mount sufficient macrophage-mediated inflammation was indicative of exacerbated LV dilation.


Assuntos
Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/patologia , Ventrículos do Coração/patologia , Infarto do Miocárdio/complicações , Animais , Cardiomiopatia Dilatada/sangue , Quimiocina CXCL6/sangue , Quimiocinas CC/sangue , Bases de Dados Factuais , Feminino , Linfocinas/sangue , Proteínas Inflamatórias de Macrófagos/sangue , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteômica , Sialoglicoproteínas/sangue
14.
Hum Immunol ; 80(7): 517-522, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30853363

RESUMO

INTRODUCTION: Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), is the fourth most important tropical disease, which affects approximately 7 million people worldwide. The mechanisms involved in the development of this disease are not completely well understood. An important protective role of regulatory T cells (Treg) in Chagas disease has been observed; however, the specific mechanisms remain unclear. We evaluated apoptosis as a possible mechanism mediated by Treg cells (CD4+CD25HighFOXP3+) to orchestrate the immune response in chronic Chagas disease. METHODS AND RESULTS: Patients with Chagas disease were grouped as the indeterminate (IND; asymptomatic patients with Chagas disease; n = 10) and dilated cardiomyopathy (CARD; n = 10). Healthy T. cruzi-negative individuals (NI; n = 10) were included as a control group. In order to evaluate the apoptotic cell profile, the expression of PD1, PD1L, CD39, CD95, CD95L molecules were investigated. We also evaluated the proportion of CD14+ cells expressing caspase 3. The IND group presented a substantially higher expression of CD39 by Treg cells as compared to the CARD group. On the other hand, the CARD group showed higher expression of PD-1 by Treg cells than both NI and IND groups. Significant positive correlations were observed between Treg CD95L+ cells and CD14 cells expressing caspase 3 as well as between Treg CD39 cells and CD14+ Caspase3+ cells in the IND group. CONCLUSION: Our data indicate that the expressions of different molecules that induce apoptosis are associated with suppressive mechanisms mediated by Treg cells and suggest a possible role for PD1 and PDL1 molecules in the morbidity of chronic Chagas disease.


Assuntos
Antígeno B7-H1/metabolismo , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Chagásica/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T Reguladores/imunologia , Trypanosoma cruzi/imunologia , Adulto , Idoso , Antígenos de Protozoários/imunologia , Apoptose/imunologia , Apirase/metabolismo , Antígenos CD4/metabolismo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Masculino , Pessoa de Meia-Idade , Testes Sorológicos
15.
Vet J ; 244: 16-22, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30825889

RESUMO

The study objective was to investigate heart-fatty acid binding protein (HFABP) concentrations in dogs with degenerative valvular disease (MVD) and dilated cardiomyopathy (DCM), and its potential as a prognostic factor. Plasma HFABP, N-terminal pro brain natriuretic peptide (NTproBNP) and serum cardiac troponin I (cTnI) levels were measured in 21 control dogs, 23 dogs with MVD and 13 dogs with DCM, with repeated sampling at 1 and 3 months after initial presentation. All dogs were followed up after 6 and 12 months to verify survival. Heart-fatty acid binding protein concentrations were significantly higher in dogs with MVD and DCM than controls at initial presentation, and after 1 month in dogs with MVD. For dogs with DCM, a significant reduction in HFABP levels over time was observed. Comparing ACVIM stages, highest HFABP concentrations were detected in ACVIM stage C dogs compared to stage B, with the lowest levels seen in controls, and a reduction over time in stage C dogs was present. Similarly, cTnI concentrations were higher in DCM and stage C in comparison to control dogs and reduced over time, while NTproBNP concentrations were only higher in diseased dogs at 1 month. Heart-fatty acid binding protein and cTnI levels at initial presentation and ACVIM disease stage were independent predictors of survival in a univariate analysis. The elevation of HFABP in dogs with MVD and DCM in comparison to controls, its association with disease severity, and its potential in predicting reduced survival, suggest that HFABP might be useful as marker for canine MVD and DCM.


Assuntos
Biomarcadores/metabolismo , Cardiomiopatia Dilatada/veterinária , Doenças do Cão/metabolismo , Proteína 3 Ligante de Ácido Graxo/metabolismo , Doenças das Valvas Cardíacas/veterinária , Animais , Biomarcadores/sangue , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/metabolismo , Estudos de Casos e Controles , Doenças do Cão/sangue , Cães , Proteína 3 Ligante de Ácido Graxo/sangue , Feminino , Doenças das Valvas Cardíacas/sangue , Doenças das Valvas Cardíacas/metabolismo , Masculino , Peptídeo Natriurético Encefálico/sangue , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/metabolismo , Valor Preditivo dos Testes , Troponina I/sangue , Troponina I/metabolismo
16.
J Pineal Res ; 66(4): e12564, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30715754

RESUMO

BACKGROUND: Melatonin is a multifunctional indolamine and has a cardioprotective role in a variety of cardiovascular processes via antioxidant, anti-inflammatory, antihypertensive, antithrombotic, and antilipemic effects. It has been reported that lower levels of circulating melatonin are significantly associated with a higher risk of acute myocardial infarction (AMI) and later cardiac remodeling. However, levels of melatonin in patients with dilated cardiomyopathy (DCM) and associations between melatonin levels and cardiac function remain unclear. METHODS AND RESULTS: We measured and compared plasma levels of melatonin in 61 control subjects, 81 AMI patients, and 77 DCM patients. Plasma levels of melatonin were progressively decreased from 71.9 pg/mL in the control group to 52.6 pg/mL in the DCM group and 21.9 pg/mL in the AMI group. Next, we examined associations of melatonin levels with parameters of laboratory data, echocardiography, and right-heart catheterization. In the DCM patients, circulating melatonin showed significant correlations with both high-sensitivity troponin T (R = -0.422, P < 0.001) and cardiac output (R = 0.431, P = 0.003), but not with B-type natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), pulmonary artery wedge pressure, or pulmonary artery pressure. CONCLUSION: Patients with not only AMI but also DCM had lower circulating melatonin levels. Circulating melatonin levels appear to correlate with myocardial injury and cardiac output in DCM patients.


Assuntos
Cardiomiopatia Dilatada/sangue , Melatonina/sangue , Doença Aguda , Idoso , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Peptídeo Natriurético Encefálico/sangue , Troponina/sangue
17.
PLoS One ; 14(1): e0210971, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30673749

RESUMO

Galectin-3 is a ß-galactoside-binding lectin which is important in cell proliferation and apoptotic regulation. Recently, serum galectin-3 has been shown to have prognostic value as a biomarker in heart failure. Encephalomyocarditis virus (EMCV) can cause severe myocarditis, congestive heart failure and dilated cardiomyopathy as well as encephalitis in various animals including mice. The pathophysiological role of galectin-3 in acute myocarditis following viral infection is not fully understood. The goal of this study is to determine the cardiac localization and the time-course of galectin-3 expression in heart failure after viral inoculation with EMCV. At 12, 24, 48, 96 hours, 7 and 10 days after intraperitoneal EMCV inoculation, animals were examined histologically and analyzed for the expression of galectin-3 and Iba1. Galectin-3 was up-regulated in degenerated fibrotic lesions of cardiac tissues 96 hours after viral inoculation and were followed by myocardial fibrosis. At the same time, Iba1 positive macrophages were observed within the inflammatory sites. A time-course correlation between the number of galectin-3 positive cells and the cardiac area of degenerated fibrotic lesions was detected-serum galectin-3 increased at 96 hours and correlated well with the number of cardiac galectin-3 positive cells. Our results indicate that galectin-3 expression may be a useful biomarker of cardiac fibrotic degeneration in acute myocarditis following viral infection. In addition, measuring serum galectin-3 levels might be an early diagnostic method for detecting cardiac degeneration in acute myocarditis.


Assuntos
Infecções por Cardiovirus/sangue , Infecções por Cardiovirus/metabolismo , Vírus da Encefalomiocardite , Galectina 3/sangue , Galectina 3/metabolismo , Miocardite/sangue , Miocardite/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/metabolismo , Infecções por Cardiovirus/patologia , Modelos Animais de Doenças , Vírus da Encefalomiocardite/patogenicidade , Fibrose , Imuno-Histoquímica , Cinética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas dos Microfilamentos/metabolismo , Miocardite/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Prognóstico , Sarcoglicanas/deficiência , Sarcoglicanas/genética
18.
Clin Cardiol ; 42(1): 120-128, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30447088

RESUMO

BACKGROUND: The association between thyroid-stimulating-hormone (TSH) and prognosis of nonischemic dilated cardiomyopathy (NIDCM) in patients with normal thyroid function remains unclear. HYPOTHESIS: Our aim was to investigate the association between TSH and major adverse cardiovascular events in euthyroid NIDCM patients. METHODS: The original cohort consisted of 216 consecutive euthyroid NIDCM patients, with left ventricular ejection fraction (LVEF) ≤35%, who were observed from 2010 to 2013. Patients with persistent ventricular arrhythmia (VA) histories, amiodarone taken for VA prevention, or on heart transplant list within 1 year were excluded. A follow-up evaluation was performed, and VA events, heart failure (HF) exacerbation/heart transplant, cardiac death, or death from any cause were separately evaluated. RESULTS: A total of 184 patients were enrolled, and 97.8% (180/184) ultimately received follow-up evaluations. During the median 4.6-year follow-up, 24 VA events, 28 cardiac deaths, 30 all-cause deaths, 40 HF exacerbations, and 11 heart transplant events occurred. Serum TSH levels showed good predictive efficacies for VA events (area under the curve [AUC] = 0.702, 95% confidence interval [CI]: 0.629-0.767), and the risk of VA events increased, according to serum TSH quarters, as determined by Kaplan-Meier analysis (2.2% vs 13.4% vs 21.0% vs 30.0%, Q1-Q4, P = 0.011). Multivariable Cox analysis showed that patients at the Q4 level of serum TSH (>2.67 mIU/L) suffered an increased risk of VA events, compared with those at the Q1 level of TSH (hazard ratio [HR] = 15.88, 95% CI: 2.01-65.15) or those at the other three quarters (HR = 3.17, 95% CI: 1.38-7.26). However, the Q4 TSH level was not associated with other adverse cardiac events. CONCLUSION: An association between TSH levels and the risk of VA events may exist in euthyroid NIDCM patients.


Assuntos
Cardiomiopatia Dilatada/sangue , Morte Súbita Cardíaca/epidemiologia , Tireotropina/sangue , Disfunção Ventricular Esquerda/sangue , Função Ventricular Esquerda/fisiologia , Adulto , Biomarcadores/sangue , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/fisiopatologia , China/epidemiologia , Ecocardiografia , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Incidência , Masculino , Estudos Prospectivos , Valores de Referência , Volume Sistólico/fisiologia , Taxa de Sobrevida/tendências , Fatores de Tempo , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/fisiopatologia
19.
Can J Physiol Pharmacol ; 97(2): 140-145, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30557036

RESUMO

Metabolic, inflammatory, and autonomic nervous system (ANS) dysfunction are present in patients with heart failure. However, whether these changes are due to left ventricular dysfunction or heart failure etiology is unknown. We evaluated metabolism and inflammatory activity in patients with idiopathic dilated cardiomyopathy (IDC) and Chagas cardiomyopathy (CHG) and their correlation with the ANS. Forty-six patients were divided into 3 groups: IDC, CHG, and control. We evaluated adiponectin, leptin, insulin, interleukin-6, and tumor necrosis factor-alpha. ANS were analyzed by heart rate variability in time and frequency domains on a 24-hour Holter monitor. Levels of glucose, cholesterol, leptin, and adiponectin did not show differences between groups. Insulin levels were lower in CHG group (5.4 ± 3.3 µU/mL) when compared with control (8.0 ± 4.9 µU/mL) and IDC (9.9 ± 5.0 µU/mL) groups (p = 0.007). Insulin was positively associated with LFr/HFr ratio (r = 0.562; p = 0.029) and with the LFr component (r = 0.562; p = 0.029) and negatively associated with adiponectin (r = -0.603; p = 0.017) in CHG group. The addition of an adiponectin unit reduced average insulin by 0.332 µg/mL. Insulin levels were decreased in the CHG group when compared with the IDC group and were associated with ANS indexes and adiponectin levels.


Assuntos
Adipocinas/sangue , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Chagásica/metabolismo , Insulina/sangue , Adipocinas/metabolismo , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/fisiopatologia , Ecocardiografia Doppler , Eletrocardiografia , Feminino , Coração , Frequência Cardíaca/fisiologia , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade
20.
J Vet Intern Med ; 33(1): 54-63, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30536428

RESUMO

BACKGROUND: Echocardiography and 24-hour ECG are the gold standard tests to diagnose dilated cardiomyopathy (DCM) in Doberman Pinschers (DP), but myocardial damage might be detected earlier using a high-sensitivity cardiac troponin I (hs-cTnI) assay. OBJECTIVE: To evaluate and compare an hs-cTnI assay (Advia Centaur TnI-Ultra assay) with a conventional cTnI assay in DP with different stages of DCM and in healthy DP. ANIMALS: Three hundred forty-five examinations from 162 DP with and 179 DP without DCM. METHODS: Prospective longitudinal study. Dogs were allocated into 6 groups based on echocardiographic and 24-hour ECG criteria: (1) healthy group (179 dogs), (2) last-normal group (29 dogs), which included dogs that were considered to be healthy at the time of their examination but were assigned to the last-normal group retrospectively when DCM was diagnosed at their next examination within 1.5 years, (3) only arrhythmias (45 dogs, 119 examinations), (4) only echocardiographic changes (24 dogs, 61 examinations), (5) echocardiographic changes with ventricular premature complexes (41 dogs, 100 examinations), and (6) decompensated (23 dogs, 36 examinations). Hs-cTnI and conventional cTnI concentration measurements were performed and compared. RESULTS: A cutoff value of hs-cTnI concentration >0.113 ng/mL had a sensitivity of 81.2% and a specificity of 73.2% to identify the presence of DCM. The conventional cTnI assay showed a similar test performance, but the hs-cTnI assay identified more dogs (21/29 dogs, 72%) in the last-normal group compared to the conventional cTnI test (18/29 dogs, 62%). CONCLUSIONS AND CLINICAL IMPORTANCE: The hs-cTnI is an additional test with good potential to identify early DCM.


Assuntos
Cardiomiopatia Dilatada/veterinária , Doenças do Cão/sangue , Animais , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico , Estudos de Casos e Controles , Doenças do Cão/diagnóstico , Cães/sangue , Ecocardiografia/veterinária , Eletrocardiografia/veterinária , Feminino , Estudos Longitudinais , Masculino , Estudos Prospectivos , Troponina I
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