Integrative Analyses of Circulating Proteins and Metabolites Reveal Sex Differences in the Associations with Cardiac Function among DCM Patients.

Dilated cardiomyopathy (DCM) is characterized by reduced left ventricular ejection fraction (LVEF) and left or biventricular dilatation. We evaluated sex-specific associations of circulating proteins and metabolites with structural and functional heart parameters in DCM. Plasma samples (297 men, 71 women) were analyzed for proteins using Olink assays (targeted analysis) or LC-MS/MS (untargeted analysis), and for metabolites using LC MS/MS (Biocrates AbsoluteIDQ p180 Kit). Associations of proteins (n = 571) or metabolites (n = 163) with LVEF, measured left ventricular end diastolic diameter (LVEDDmeasured), and the dilation percentage of LVEDD from the norm (LVEDDacc. to HENRY) were examined in combined and sex-specific regression models. To disclose protein-metabolite relations, correlation analyses were performed. Associations between proteins, metabolites and LVEF were restricted to men, while associations with LVEDD were absent in both sexes. Significant metabolites were validated in a second independent DCM cohort (93 men). Integrative analyses demonstrated close relations between altered proteins and metabolites involved in lipid metabolism, inflammation, and endothelial dysfunction with declining LVEF, with kynurenine as the most prominent finding. In DCM, the loss of cardiac function was reflected by circulating proteins and metabolites with sex-specific differences. Our integrative approach demonstrated that concurrently assessing specific proteins and metabolites might help us to gain insights into the alterations associated with DCM.

Serum microRNA-125b-5p expression in patients with dilated cardiomyopathy combined with heart failure and its effect on myocardial fibrosis.

OBJECTIVE: This paper was performed to decipher the serum microRNA (miR)-125b-5p expression in patients with dilated cardiomyopathy (DCM) combined with heart failure (HF) and its effect on myocardial fibrosis. METHODS: Serum miR-125b-5p expression, LVEDD, LVESD, LVEF, LVFS, and NT-proBNP levels were evaluated in clinical samples. A rat DCM model was established by continuous intraperitoneal injection of adriamycin and treated with miR-125b-5p agomir and its negative control. Cardiac function, serum TNF-α, hs-CRP, and NT-proBNP levels, pathological changes in myocardial tissues, cardiomyocyte apoptosis, and the expression levels of miR-125b-5p and fibrosis-related factors were detected in rats. RESULTS: In comparison to the control group, the case group had higher levels of LVEDD, LVESD, and NT-pro-BNP, and lower levels of LVEF, LVFS, and miR-125b-5p expression levels. Overexpression of miR-125b-5p effectively led to the improvement of cardiomyocyte hypertrophy and collagen arrangement disorder in DCM rats, the reduction of blue-stained collagen fibers in the interstitial myocardium, the reduction of the levels of TNF-α, hs-CRP, and NT-proBNP and the expression levels of TGF-1ß, Collagen I, and α-SMA, and the reduction of the number of apoptosis in cardiomyocytes. CONCLUSION: Overexpression of miR-125b-5p is effective in ameliorating myocardial fibrosis.

Metabolomic insights in advanced cardiomyopathy of chronic chagasic and idiopathic patients that underwent heart transplant.

Heart failure (HF) studies typically focus on ischemic and idiopathic heart diseases. Chronic chagasic cardiomyopathy (CCC) is a progressive degenerative inflammatory condition highly prevalent in Latin America that leads to a disturbance of cardiac conduction system. Despite its clinical and epidemiological importance, CCC molecular pathogenesis is poorly understood. Here we characterize and discriminate the plasma metabolomic profile of 15 patients with advanced HF referred for heart transplantation - 8 patients with CCC and 7 with idiopathic dilated cardiomyopathy (IDC) - using gas chromatography/quadrupole time-of-flight mass spectrometry. Compared to the 12 heart donor individuals, also included to represent the control (CTRL) scenario, patients with advanced HF exhibited a metabolic imbalance with 21 discriminating metabolites, mostly indicative of accumulation of fatty acids, amino acids and important components of the tricarboxylic acid (TCA) cycle. CCC vs. IDC analyses revealed a metabolic disparity between conditions, with 12 CCC distinctive metabolites vs. 11 IDC representative metabolites. Disturbances were mainly related to amino acid metabolism profile. Although mitochondrial dysfunction and loss of metabolic flexibility may be a central mechanistic event in advanced HF, metabolic imbalance differs between CCC and IDC populations, possibly explaining the dissimilar clinical course of Chagas' patients.

Prognosis value of galectin-3 in patients with dilated cardiomyopathy: a meta-analysis.

Background: Accurate prediction and assessment of myocardial fibrosis (MF) and adverse cardiovascular events (MACEs) are crucial in patients with dilated cardiomyopathy (DCM). Several studies indicate that galectin-3 (gal-3) as a promising prognostic predictor in patients with DCM. Methods: A comprehensive search was conducted in PubMed, EMBASE, the Cochrane Library, and Web of Science for relevant studies up to August 2023. The hazard ratios (HRs) of gal-3 for MACEs in DCM patients, and for MACEs in LGE(+) versus LGE(-) groups, were evaluated. Statistical analysis was performed using STATA SE 14.0 software. Results: Seven studies, encompassing 945 patients, met the eligibility criteria. In DCM patients, abnormally elevated gal-3 levels were indicative of an increased MACEs risk (HR = 1.10, 95% CI [1.00-1.21], I2 = 65.7%, p = 0.008). Compared with the LGE(-) group, the level of gal-3 in LGE(+) group was higher (HR = 1.12, 95% CI [1.05-1.19], I2 = 31.4%, p = 0.233), and the combination of gal-3 and LGE significantly improved the prediction of MACEs. Sensitivity analysis confirmed the robustness of all results. Conclusions: This study's findings suggest that elevated gal-3 levels significantly correlate with increased MACE risk in DCM, highlighting its potential as a biomarker. However, significant heterogeneity among studies necessitates further research to ascertain gal-3's predictive and diagnostic value in DCM prognosis, particularly in conjunction with LGE. PROSPERO ID: CRD42023471199.

Prevalencia de serología positiva para Trypanosoma cruzi en pacientes con diagnóstico clínico de miocardiopatía dilatada en el Estado de Campeche, México / Prevalence of positive serology to Trypanosoma cruzi in patients with clinical diagnosis of dilated myocardiopathy in the state of Campeche

Se desconoce la prevalencia de cardiopatía chagásica crónica como causa de miocardiopatía dilatada en el estado de Campeche, por lo que se decidió estudiar la prevalencia de serología positiva para Trypanosoma cruzi en pacientes con diagnóstico clínico de miocardiopatía dilatada. De un total de 127 enfermos diagnosticados con miocardiopatía dilatada, se estudiaron 91 con dos pruebas serológicas positivas para Trypanosoma cruzi. Se identificaron 14 casos positivos para una prevalencia de cardiopatía chagásica crónica de 15%. Esta prevalencia es similar a la informada para el resto de la península de Yucatán.

The prevalence of chronic Chagas' heart disease as a cause of dilated cardiomyopathy is unknown in the State of Campeche, Mexico. A study was conducted to determine the prevalence of positive serology for Trypanosoma cruzi in patients with clinical diagnosis of dilated cardiomyopathy. Of a total of 127 patients diagnosed with dilated cardiomyopathy, we studied 91 with two positive serological tests for T. cruzi. We identified 14 positive cases for a prevalence of 15 % of chronic Chagas' heart disease. This prevalence is similar to that reported for the rest of the Yucatan Peninsula.

Desempenho hemodinâmico e resposta inflamatória durante o uso do DAV-InCor como ponte para o transplante / Hemodynamic performance and inflammatory response during the use of VAD-InCor as a bridge to transplant

FUNDAMENTO: O transplante cardíaco enfrenta o grave problema da escassez de doadores. Estima-se que entre 20 por cento e 40 por cento dos pacientes falecem na fila de espera. Para esses pacientes, a utilização de dispositivos de assistência circulatória é, muitas vezes, a única possibilidade de sobrevivência durante a espera do doador. No Brasil, não existe nenhum programa regular de utilização desses dispositivos como ponte para transplante. OBJETIVO: Avaliar o desempenho hemodinâmico e a resposta inflamatória durante a utilização do DAV-InCor como ponte para transplante. MÉTODOS: Entre outubro de 2003 e abril de 2006, 11 pacientes, indicados em caráter de prioridade para o transplante cardíaco, evoluíram em choque cardiogênico refratário. O implante do DAV-InCor foi realizado em sete pacientes. O diagnóstico etiológico foi cardiopatia chagásica em cinco pacientes e cardiomiopatia dilatada idiopática em dois. RESULTADOS: A assistência mecânica ao ventrículo esquerdo foi mantida nos sete pacientes por períodos entre 14 e 42 dias (média 26,2). O desempenho hemodinâmico foi adequado, com a normalização do índice cardíaco, dos níveis de saturação venosa de O2 e do lactato. O transplante foi realizado em dois pacientes, os outros cinco faleceram por infecção sistêmica ou falência de múltiplos órgãos. CONCLUSÃO: O desempenho do DAV-Incor, no comportamento hemodinâmico dos pacientes estudados, foi adequado para a manutenção de uma condição circulatória satisfatória durante o período estudado. Houve melhora dos parâmetros de perfusão tecidual e manutenção de sinais de resposta inflamatória sistêmica. Houve alta incidência de complicações; contudo, não foram demonstradas complicações relacionadas ao dispositivo que comprometam a segurança da utilização do mesmo.

BACKGROUND: Cardiac transplantation faces the serious problem of lack of donors and it is estimated that 20 to 40 percent of the patients die while waiting for heart transplantation. For these patients, the use of mechanical circulatory assist devices is the only choice of survival while waiting for a donor. In Brazil, the experience with mechanical circulatory support is limited and there is no regular program regarding the use of these devices as a bridge to heart transplantation. OBJECTIVE: To evaluate the hemodynamic performance and the systemic inflammatory response during the clinical use of the InCor-type ventricular assist device (VAD-InCor) as a bridge to heart transplantation. METHODS: Between October 2003 and April 2006, 11 patients in the waiting list for heart transplantation presented hemodynamic deterioration due to refractory cardiogenic shock. Seven of these patients were submitted to VAD-InCor implantation for left ventricular assistance. The etiologic diagnosis was Chagas' disease in 5 patients and idiopathic dilated cardiomyopathy in 2. RESULTS: The duration of left ventricular assistance ranged from 14 to 42 days (mean 26.2 days). During this period, the hemodynamic performance of the DAV-InCor was adequate to support a normal hemodynamic state. There was normalization of central venous oxygen saturation and serum lactate. Two patients were submitted to heart transplantation, while the other 5 patients died under assistance due to infection and multiple organ failure. CONCLUSION: The performance of the VAD-InCor, in the hemodynamic behavior of the studied patients, was adequate for the maintenance of a satisfactory circulatory state during the studied period. There was improvement in the tissue perfusion parameters and maintenance of systemic inflammatory response signs. There was a high incidence of complications; however, complications related to the device, which could compromise the safety of its use, were not demonstrated.

Anticuerpos contra Trypanosoma cruzi en pacientes con miocardiopatía dilatada en Tuxtla Gutiérrez, Chiapas / Antibodies against Trypanosoma cruzi in patients with dilated cardiomyopathy in Tuxtla Gutierrez, Chiapas

La enfermedad de Chagas es causada por el protozoario flagelado Trypanosoma cruzi. Encuestas seroepidemiológicas realizadas en Chiapas informan individuos seropositivos en comunidades rurales, y cabe la posibilidad de que la forma crónica de la enfermedad ocurra en el estado. La expresión clínica dominante en la enfermedad de Chagas crónica es cardíaca. Material y métodos: Con el objeto de conocer la frecuencia de cardiopatía chagásica crónica (CCC) se hizo una encuesta serológica a pacientes con miocardiopatía dilatada (MD) internados entre octubre de 2002 a octubre de 2003, en el Servicio de Cardiología del Hospital General Regional "Dr. Rafael Pascacio Gamboa" de Tuxtla Gutiérrez, Chiapas. El diagnóstico fue establecido en forma independiente y el estudio seroinmunológico fue ciego. Resultados: Quince (54%) de 28 sujetos con MD tenían anticuerpos a T. cruzi. Todos provenían de medio rural pobre, su cuadro clínico incluyó insuficiencia cardíaca y/o trastornos del ritmo o conducción. Conclusiones: Esta evidencia sugiere que en Chiapas, una zona endémica de enfermedad de Chagas, hay CCC. Dentro del estudio de la MD, la etiología chagásica, debe ser considerada, ya que las condiciones socioeconómicas, culturales y regionales favorecen su presencia.

Chagas disease is caused by the flagellate protozoan T. cruzi. Seroepidemiological surveys in Chiapas, Mexico have shown seropositive individuals, therefore, we searched for people affected by the chronic form of Chagas disease which involves the heart, causing a chronic, progressive and fatal disease called Chronic Chagasic Cardiopathy (CCC). Material and methods: To establish the frequency of CCC we studied 28 patients seen at the Hospital General Regional "Dr. Rafael Pascacio Gamboa" during October 2002 through October 2003 in Tuxtla Gutierrez, Chiapas, the State capital city, with diagnosis of dilated cardiomyopathy (DC), a serological survey for antibodies against T. cruzi was done. This hospital cares for people from all parts of Chiapas, Mexico. Clinical diagnosis of DC was established there and blind serological studies were performed in Mexico City. Results: Fifteen out of 28 DC patients (54%) had anti T. cruzi antibodies. All of them came from poor rural villages and they had heart failure and/or arrhythmia or heart blockade on EKG. Conclusions: This observation suggest that in Chiapas were Chagas disease is endemic, there are CCC patients. Any case with a clinical diagnosis of DC should be tested for antibodies against T. cruzi. The low socioeconomic status, culture and environment in this Mexican State favour the presence and transmission of this parasitic disease.

The Origin of Proinflammatory Cytokines in Patients with Idiopathic Dilated Cardiomyopathy

Proinflammatory cytokines and their receptors are increased in the peripheral blood of patients with heart failure. We measured cytokines and their receptors in systemic artery (SA), coronary sinus (CS) and infra-renal inferior vena cava (IVC), in order to investigate their origin and influential factors. Thirty patients with idiopathic dilated cardiomyopathy were performed echocardiography at admission, and right heart catheterization after stabilization. Blood was drawn from 3 sites for measurement of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and soluble tumor necrosis factor- receptor (sTNFR) I, II. TNF-alpha at CS (3.25+/-0.34 pg/mL) was higher than those of SA (1.81+/-0.39 pg/mL) and IVC (1.88+/-0.38 pg/mL, p<0.05). IL-6 at CS (18.3+/-3.8 pg/mL) was higher than that of SA (5.8+/-1.2 pg/mL, p<0.01). The levels of sTNFR I, II showed increasing tendency in sequence of SA, IVC and CS. TNF-alpha and sTNFR I, II from all sites were proportional to worsening of functional classes at admission (p<0.05). E/Ea by Doppler study at admission, which reflects left ventricular end-diastolic pressure (LVEDP) was positively correlated with TNF-alpha from SA (R=0.71, p<0.01), CS (R=0.52, p<0.05) and IVC (R=0.46, p<0.05). Thus, elevated LVEDP during decompensation might cause cytokine release from myocardium in patients with idiopathic dilated cardiomyopathy.

A Case of Polymyositis with Dilated Cardiomyopathy Associated with Interferon alpha Treatment for Hepatitis B

Polymyositis is a rare complication of interferon alpha treatment as a result of immunemodulating role of the drug itself. In this case, interferon alpha induced polymyositis and cardiomyopathy is diagnosed in a 33-yr-old male patient with history of chronic hepatitis B. To treat hepatitis B, interferon alpha was administered until the proximal muscle weakness developed. Thereafter, sixteen cycles of immunoglobulin treatment (400 mg/kg) along with corticosteroids were instituted and led to an improvement in subjective symptoms with decreases in level of CPK and LDH. However, dilated cardiomyopathy has not improved in spite of the cessation of interferon treatment. Unlike the persistently elevated serum HBV DNA level, the serum ALT and AST levels have gradually decreased. Our case shows that clinical symptoms of polymyositis improved with steroid and immunoglobulin treatment without deterioration of the hepatitis B. To our knowledge, this is the first case of polymyositis associated with dilated cardiomyopathy after the administration of interferon in a patient with hepatitis B.

Utilidad de la determinación de mioglobina,isoenzima MB de creatinina fosfocinasa, deshidrogenasa lactica y aspartato amino transferasa, en el diagnostico de infarto agudo del miocardio / Biomarkers in the diagnosis of acute myocardial infarction

El diagnóstico de infarto agudo del miocardio mediante biomarcadores incluye ahora la cuantificación de proteínas estructurales del miocardio como la mioglobina (MG), y de enzimas, algunas de ellas selectivas, creatina fosfocinasa en su isoenzima MB (CKMB) y otras no selectivas, como la deshidrogenasa láctica (DHL) y la aspartato aminotransferasa (AST). Se encontró que las dos primeras tienen sensibilidad (71 por ciento-50 por ciento), especifidad 886 por ciento-100 por ciento respectivamente) y valores predictivos de utilidad clínica, en tanto que DHL y AST son inútiles en el concepto actual de diagnóstico temprano