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1.
Dis Markers ; 2019: 6487152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31320942

RESUMO

The aim of this study was to compare NT-proBNP using the absolute values and NT-proBNP/ULN values that were standardized by age and gender between three subgroups: those without ischemia (negative hs-troponin I and no anginal pain (hsTnI-/AP-)), those with painless ischemia (hsTnI+/AP-), and those with painful ischemia (hsTnI+/AP+). Additionally, echocardiographic parameters were compared in these three subgroups. The absolute value of NT-proBNP was significantly higher in the painful ischemia subgroup (hsTnI-/AP- vs. hsTnI+/AP- vs. hsTnI+/AP+: 502 (174-833) vs. 969 (363-1346) vs. 2053 (323-3283) pg/ml; p = 0.018 for the whole-model analysis). The standardized value of NT-proBNP/ULN was gradually increased (hsTnI-/AP- vs. hsTnI+/AP- vs. hsTnI+/AP+: 3.61 + 0.63 vs. 6.90 + 1.31 vs. 9.35 + 1.87; p = 0.001 for the whole-model analysis). In the comparison between subgroups (hsTnI-/AP- vs. hsTnI+/AP- vs. hsTnI+/AP+), two echocardiographic parameters increased significantly. The left ventricular maximum wall thickness (LVMWT) at diastole was 1.99 ± 0.08 cm vs. 2.28 ± 0.13 cm vs. 2.49 ± 0.15 cm (p = 0.004 for the whole-model analysis). The maximal gradient of the provoked left ventricular outflow tract (LVOT) gradient increased significantly in only the painful-ischemia subgroup (11 (7-30) mmHg vs. 12 (9.35-31.5) mmHg vs. 100 (43-120) mmHg). In conclusion, both painless ischemia and painful ischemia are associated with a gradual, significant increase in NT-proBNP/ULN in comparison to the double-negative hsTnI/AP subgroup. In contrast, NT-proBNP is significantly higher in only the subgroup with painful ischemia.


Assuntos
Cardiomiopatia Hipertrófica/sangue , Isquemia Miocárdica/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Troponina I/sangue , Disfunção Ventricular/sangue , Adulto , Biomarcadores/sangue , Cardiomiopatia Hipertrófica/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Sensibilidade e Especificidade , Disfunção Ventricular/diagnóstico
2.
Pediatr Cardiol ; 40(6): 1165-1170, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31175403

RESUMO

The objective is to examine the correlation between plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and tissue Doppler imaging (TDI) echocardiographic parameters in the first 28 days of life in very-low-birth-weight infants (VLBWI). VLBWI admitted to the Neonatal Intensive Care Unit (NICU) at Hospital Puerta del Mar, Spain, from January 2015 to January 2017 were prospectively enrolled. Weekly determination of plasma NT-proBNP (pg/mL), and echocardiograms were done during the first 28 days of life. 101 preterm infants with a mean GA of 28.85 weeks (± 1.85 SD) and mean birth weight of 1152 g (± 247.4 SD) were included. A total of 483 echocardiograms and 139 NT-proBNP determinations were performed. We found a negative correlation between plasma NT-proBNP levels and diastolic velocities: mitral A' (ρ = - 0.15, p = 0.04), mitral E' (ρ = - 0.17, p = 0.02), tricuspid A' (ρ = - 0.20, p = 0.006), tricuspid E' (ρ = - 0.24, p = 0.0009). In the first 24 h of life, NT-proBNP levels were strongly correlated with mitral A' and E' velocities in patients with no patent ductus arteriosus (PDA) (ρ = - 0.75, p = 0.04). In preterm patients, elevated NT-proBNP levels are related to worse diastolic myocardial function. In the first 24 h, this correlation is much stronger in the absence of PDA.


Assuntos
Doenças do Prematuro/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Disfunção Ventricular/diagnóstico , Biomarcadores/sangue , Ecocardiografia Doppler , Feminino , Humanos , Lactente , Recém-Nascido Prematuro , Doenças do Prematuro/sangue , Doenças do Prematuro/genética , Recém-Nascido de muito Baixo Peso , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha , Disfunção Ventricular/sangue
3.
Circ J ; 82(8): 2049-2054, 2018 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-29794411

RESUMO

BACKGROUND: N-Terminal pro B-type natriuretic peptide (NT-proBNP) is widely used as a marker of ventricular dysfunction. However, data regarding the association of NT-proBNP with blood pressure (BP) and pulse pressure (PP) in the elderly population are limited.Methods and Results:The present cross-sectional study involved 6,529 participants, aged ≥70 years, without cardiovascular disease (CVD), who underwent general health examinations. Serum NT-proBNP concentrations were determined, with high NT-proBNP concentrations defined as those ≥125 pg/mL. Subjects were divided into five groups based on PP (<50, ≥50 to <60, ≥60 to <70, ≥70 to <80, and ≥80 mmHg). NT-proBNP was positively associated with systolic BP, whereas a U-shaped association was found between diastolic BP and NT-proBNP. The odds ratios for high NT-proBNP concentrations in the PP ≥80 and ≥70 to <80 mmHg groups (OR 1.83 [P<0.001] and 1.40 [P<0.005], respectively) were significantly higher than in the PP <50 mmHg group. All data were adjusted for age, sex, body mass index, hemoglobin concentration, serum creatinine, pulse rate, smoking, alcohol intake, and antihypertensive medication intake, and the presence of diabetes and dyslipidemia. CONCLUSIONS: The results suggest that NT-proBNP concentrations may be a marker of not only ventricular dysfunction, but also arterial stiffness in the elderly population without CVD.


Assuntos
Pressão Sanguínea , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Idoso , Biomarcadores/sangue , Estudos Transversais , Diástole , Feminino , Humanos , Masculino , Razão de Chances , Sístole , Rigidez Vascular , Disfunção Ventricular/sangue , Disfunção Ventricular/diagnóstico
4.
J Crit Care ; 44: 383-387, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29304488

RESUMO

PURPOSE: We aimed to investigate the factors that are associated with increased cardiac troponin I (cTnI) leakage in the acute pulmonary embolism (PTE) setting and their alignment with patient outcome. METHODS: Adult patients with a diagnosis of PTE were enrolled in this prospective cohort study. The primary endpoint of interest was major adverse cardio-pulmonary events (MACPE), defined as the composite of in-hospital all-cause mortality, need for thrombolysis and mechanical ventilation and surgical embolectomy during index hospitalization. Multivariable regression analysis is used to assess factors associated with MACPE. RESULTS: 16.6% of 627 patients with acute PTE, had elevated serum cTnI. MACPE occurred in 56.7% of patients with positive cTnI and in 28.8% of patients with negative cTnI (p<0.001). Blood urea nitrogen (BUN) (OR 1.048; 1.001-1.096), alanine transaminase (ALT) (OR 1.007; 1.001-1.014), and neutrophil-lymphocyte ratio (NLR) (OR 0.829; 0.698-0.984) were independent predictors of elevated cTnI. Elevated cTnI increased the risk of MACPE 2.72 times (p<0.001). CONCLUSION: cTnI was an independent predictor of short-term outcome following an episode of PTE. BUN and ALT were directly and NLR was inversely associated with the leakage of cTnI and therefore, they could potentially serve as useful markers of risk assessment after PTE.


Assuntos
Embolia Pulmonar/sangue , Troponina I/sangue , Disfunção Ventricular/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Embolia Pulmonar/complicações , Embolia Pulmonar/fisiopatologia , Fatores de Risco , Disfunção Ventricular/etiologia , Disfunção Ventricular/fisiopatologia , Adulto Jovem
5.
PLoS One ; 12(11): e0188597, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29161313

RESUMO

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson's correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-ß and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-ß1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis.


Assuntos
Biomarcadores/sangue , Síndrome Cardiorrenal/fisiopatologia , Hidronefrose/cirurgia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Idoso , Biomarcadores/urina , Síndrome Cardiorrenal/sangue , Síndrome Cardiorrenal/complicações , Síndrome Cardiorrenal/cirurgia , Diástole/fisiologia , Ecocardiografia , Feminino , Humanos , Hidronefrose/sangue , Hidronefrose/complicações , Hidronefrose/fisiopatologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Stents , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/urina , Disfunção Ventricular/sangue , Disfunção Ventricular/complicações , Disfunção Ventricular/fisiopatologia , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/cirurgia
6.
Dis Markers ; 2017: 2714095, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28566800

RESUMO

BACKGROUND: Echocardiographic evaluation of left ventricular (LV) structural and functional alterations in hypertension has some limitations, potentially overcome by using biomarkers. ST2, a prognostic biomarker for heart failure and myocardial infarction patients, was less studied in hypertension. AIM: To analyze the relationship between serum ST2 levels and diastolic dysfunction (DD) in hypertension. METHOD: We enrolled 88 hypertensive outpatients (average age 65 years, 69.3% females) in a prospective study, stratified for presence of LV hypertrophy (LVH). For each patient clinical examination, lab workup (routine and serum ST2 levels) and echocardiography were performed. RESULTS: Hypertensive patients with LVH had higher age, pulse pressure, mean arterial pressure, and serum ST2, while having lower serum albumin than those without LVH. Serum ST2 levels correlate with parameters of LV remodeling and DD. We found that 5.3% of ST2 level variability was caused by a 1-unit variation of cardiovascular risk. We identified cut-off values for discriminating hypertension with LVH versus that without LVH and grade 2 DD versus normal diastolic performance. CONCLUSION: ST2 could be used as diagnostic biomarker for cardiac remodeling and altered diastolic performance in hypertension, providing additional data to echocardiography. It could represent a milestone in early detection of cardiac performance alteration.


Assuntos
Hipertensão/sangue , Hipertrofia Ventricular Esquerda/sangue , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Disfunção Ventricular/sangue , Idoso , Biomarcadores/sangue , Diástole , Ecocardiografia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Disfunção Ventricular/complicações , Disfunção Ventricular/diagnóstico por imagem
7.
Am J Pathol ; 187(4): 700-712, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28183533

RESUMO

Our understanding of the pathophysiological basis of chronic thromboembolic pulmonary hypertension (CTEPH) will be accelerated by an animal model that replicates the phenotype of human CTEPH. Sprague-Dawley rats were administered a combination of a single dose each of plastic microspheres and vascular endothelial growth factor receptor antagonist in polystyrene microspheres (PE) + tyrosine kinase inhibitor SU5416 (SU) group. Shams received volume-matched saline; PE and SU groups received only microspheres or SU5416, respectively. PE + SU rats exhibited sustained pulmonary hypertension (62 ± 13 and 53 ± 14 mmHg at 3 and 6 weeks, respectively) with reduction of the ventriculoarterial coupling in vivo coincident with a large decrement in peak rate of oxygen consumption during aerobic exercise, respectively. PE + SU produced right ventricular hypokinesis, dilation, and hypertrophy observed on echocardiography, and 40% reduction in right ventricular contractile function in isolated perfused hearts. High-resolution computed tomographic pulmonary angiography and Ki-67 immunohistochemistry revealed abundant lung neovascularization and cellular proliferation in PE that was distinctly absent in the PE + SU group. We present a novel rodent model to reproduce much of the known phenotype of CTEPH, including the pivotal pathophysiological role of impaired vascular endothelial growth factor-dependent vascular remodeling. This model may reveal a better pathophysiological understanding of how PE transitions to CTEPH in human treatments.


Assuntos
Hipertensão Pulmonar/etiologia , Embolia Pulmonar/complicações , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Cardiomegalia/sangue , Cardiomegalia/complicações , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Doença Crônica , Testes de Função Cardíaca , Hemodinâmica/efeitos dos fármacos , Hiperplasia , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/fisiopatologia , Hipóxia/complicações , Hipóxia/patologia , Hipóxia/fisiopatologia , Indóis/farmacologia , Antígeno Ki-67/metabolismo , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Microesferas , Consumo de Oxigênio/efeitos dos fármacos , Selectina-P/sangue , Pressão Parcial , Condicionamento Físico Animal , Inibidor 1 de Ativador de Plasminogênio/sangue , Poliestirenos , Embolia Pulmonar/sangue , Embolia Pulmonar/fisiopatologia , Pirróis/farmacologia , Ratos Sprague-Dawley , Inibidor Tecidual de Metaloproteinase-1/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismo , Disfunção Ventricular/sangue , Disfunção Ventricular/complicações , Disfunção Ventricular/fisiopatologia
8.
J Infect Dis ; 215(3): 387-395, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28003350

RESUMO

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects 7 million people in Latin American areas of endemicity. About 30% of infected patients will develop chronic Chagas cardiomyopathy (CCC), an inflammatory cardiomyopathy characterized by hypertrophy, fibrosis, and myocarditis. Further studies are necessary to understand the molecular mechanisms of disease progression. Transcriptome analysis has been increasingly used to identify molecular changes associated with disease outcomes. We thus assessed the whole-blood transcriptome of patients with Chagas disease. Microarray analysis was performed on blood samples from 150 subjects, of whom 30 were uninfected control patients and 120 had Chagas disease (1 group had asymptomatic disease, and 2 groups had CCC with either a preserved or reduced left ventricular ejection fraction [LVEF]). Each Chagas disease group displayed distinct gene expression and functional pathway profiles. The most different expression patterns were between CCC groups with a preserved or reduced LVEF. A more stringent analysis indicated that 27 differentially expressed genes, particularly those related to natural killer (NK)/CD8+ T-cell cytotoxicity, separated the 2 groups. NK/CD8+ T-cell cytotoxicity could play a role in determining Chagas disease progression. Understanding genes associated with disease may lead to improved insight into CCC pathogenesis and the identification of prognostic factors for CCC progression.


Assuntos
Cardiomiopatia Chagásica/genética , Disfunção Ventricular/genética , Linfócitos T CD8-Positivos/imunologia , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/fisiopatologia , Citotoxicidade Imunológica/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Células Matadoras Naturais/imunologia , Análise em Microsséries , Pessoa de Meia-Idade , Miocárdio/patologia , Reação em Cadeia da Polimerase em Tempo Real , Disfunção Ventricular/sangue , Disfunção Ventricular/parasitologia
9.
J Interv Card Electrophysiol ; 48(1): 81-88, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27815796

RESUMO

PURPOSE: The purpose of this study was to investigate the relationship between the accessory pathway location and brain natriuretic peptide (BNP) level in patients with Wolff-Parkinson-White (WPW) syndrome. METHODS: We divided 102 WPW syndrome patients with normal left ventricular systolic function into four groups: those with manifest right (MR, n = 14), manifest septal (MS, n = 11), manifest left (ML, n = 30), and concealed (C, n = 47) accessory pathways. BNP level and electrophysiological properties, including difference in timing of the ventricular electrogram between the His bundle area and the distal coronary sinus area (His-CS delay), which indicate intraventricular dyssynchrony, were compared. RESULTS: BNP levels (pg/dl) were higher in the MR and MS groups than in the ML and C groups (MR, 64 ± 58; MS, 55 ± 45; ML, 17 ± 15; C, 25 ± 21; P < 0.001). AV intervals (ms) were shorter in the MR and MS groups than in the ML and C groups (MR, 76 ± 16; MS, 83 ± 6; ML, 101 ± 19; C, 136 ± 20; P < 0.001). His-CS delay (ms) was longer in the MR group than in the other groups (MR, 50 ± 15; MS, 21 ± 7; ML, 23 ± 10; C, 19 ± 8; P < 0.001). The AV interval (P < 0.01) and the His-CS delay (P < 0.001) were negatively and positively correlated, respectively, with the BNP level. CONCLUSION: Anterograde conduction with a right or septal accessory pathway increased the BNP level in WPW syndrome patients with normal cardiac function.


Assuntos
Feixe Acessório Atrioventricular/sangue , Feixe Acessório Atrioventricular/patologia , Peptídeo Natriurético Encefálico/sangue , Disfunção Ventricular/sangue , Síndrome de Wolff-Parkinson-White/sangue , Feixe Acessório Atrioventricular/diagnóstico , Biomarcadores/sangue , Eletrocardiografia , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Disfunção Ventricular/diagnóstico , Síndrome de Wolff-Parkinson-White/diagnóstico
10.
J Thorac Cardiovasc Surg ; 151(6): 1518-26, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26926385

RESUMO

OBJECTIVE: We tested the hypotheses that volume overload and cyanosis observed in the pre-Fontan single ventricular circulation are associated with increased ventricular fibrogenesis, that the Fontan procedure helps to reduce fibrogenesis, and that persistently increased fibrogenesis in the Fontan ventricle is associated with ventricular diastolic dysfunction. METHODS: Levels of serum amino-terminal procollagen type III, a marker of tissue fibrogenesis, were measured in 172 patients with single ventricle circulation and 149 controls. Patients were divided into 3 groups according to surgical stage: 59 patients after Blalock-Taussig shunt or pulmonary banding, 60 patients after Glenn surgery (Glenn group), and 53 patients after Fontan surgery (Fontan group). RESULTS: Serum amino-terminal procollagen type III levels were significantly higher among the 3 single ventricle groups than among control patients, but decreased with each surgical stage (0.604, 0.176, 0.143, and 0.073 U/mL, for Blalock-Taussig shunt or pulmonary banding, Glenn, Fontan, and controls, respectively). Severity of volume load and cyanosis were independent determinants of increased amino-terminal procollagen type III levels in patients before Fontan surgery, and persistently increased amino-terminal procollagen type III after Fontan surgery was associated with ventricular diastolic stiffening (r = 0.494, P = .009). Data also indicated close associations between amino-terminal procollagen type III levels and activation of the renin-angiotensin-aldosterone system, suggesting potential involvement of this hormonal system in the increased fibrogenesis after Fontan surgery. CONCLUSIONS: These results suggest that serum amino-terminal procollagen type III may provide important diagnostic information on myocardial fibrosis in patients with single ventricle circulation and raise the possibility that ventricular fibrogenesis may be a potential therapeutic target in this population.


Assuntos
Técnica de Fontan/métodos , Ventrículos do Coração/patologia , Miocárdio/patologia , Fragmentos de Peptídeos/sangue , Complicações Pós-Operatórias/etiologia , Pró-Colágeno/sangue , Disfunção Ventricular/etiologia , Biomarcadores/sangue , Procedimento de Blalock-Taussig , Estudos de Casos e Controles , Criança , Pré-Escolar , Colágeno Tipo III/metabolismo , Feminino , Fibrose , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/fisiopatologia , Humanos , Síndrome do Coração Esquerdo Hipoplásico/sangue , Síndrome do Coração Esquerdo Hipoplásico/patologia , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Lactente , Modelos Lineares , Masculino , Miocárdio/metabolismo , Complicações Pós-Operatórias/sangue , Atresia Pulmonar/sangue , Atresia Pulmonar/patologia , Atresia Pulmonar/cirurgia , Resultado do Tratamento , Atresia Tricúspide/sangue , Atresia Tricúspide/patologia , Atresia Tricúspide/cirurgia , Disfunção Ventricular/sangue
11.
PLoS One ; 11(3): e0150745, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26959365

RESUMO

OBJECTIVE: Although dipeptidyl peptidase-4 (DPP-4) inhibitors have been suggested to have a non-glucoregulatory protective effect in various tissues, the effects of long-term inhibition of DPP-4 on the micro- and macro-vascular complications of type 2 diabetes remain uncertain. The aim of the present study was to investigate the organ-specific protective effects of DPP-4 inhibitor in rodent model of type 2 diabetes. METHODS: Eight-week-old diabetic and obese db/db mice and controls (db/m mice) received vehicle or one of two doses of gemigliptin (0.04 and 0.4%) daily for 12 weeks. Urine albumin excretion and echocardiography measured at 20 weeks of age. Heart and kidney tissue were subjected to molecular analysis and immunohistochemical evaluation. RESULTS: Gemigliptin effectively suppressed plasma DPP-4 activation in db/db mice in a dose-dependent manner. The HbA1c level was normalized in the 0.4% gemigliptin, but not in the 0.04% gemigliptin group. Gemigliptin showed a dose-dependent protective effect on podocytes, anti-apoptotic and anti-oxidant effects in the diabetic kidney. However, the dose-dependent effect of gemigliptin on diabetic cardiomyopathy was ambivalent. The lower dose significantly attenuated left ventricular (LV) dysfunction, apoptosis, and cardiac fibrosis, but the higher dose could not protect the LV dysfunction and cardiac fibrosis. CONCLUSION: Gemigliptin exerted non-glucoregulatory protective effects on both diabetic nephropathy and cardiomyopathy. However, high-level inhibition of DPP-4 was associated with an organ-specific effect on cardiovascular complications in type 2 diabetes.


Assuntos
Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Albuminúria/sangue , Albuminúria/complicações , Animais , Apoptose/efeitos dos fármacos , Cardiomegalia/sangue , Cardiomegalia/complicações , Cardiomegalia/fisiopatologia , Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Dipeptidil Peptidase 4/sangue , Inibidores da Dipeptidil Peptidase IV/farmacologia , Modelos Animais de Doenças , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/metabolismo , Peptídeo 1 Semelhante ao Glucagon/sangue , Hemoglobina A Glicada/metabolismo , Imuno-Histoquímica , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Camundongos , NADPH Oxidases/metabolismo , Piperidonas/farmacologia , Piperidonas/uso terapêutico , Podócitos/efeitos dos fármacos , Podócitos/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Disfunção Ventricular/sangue , Disfunção Ventricular/complicações , Disfunção Ventricular/fisiopatologia
12.
Neuromuscul Disord ; 26(2): 165-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26707596

RESUMO

Left ventricular hypertrabeculation/noncompaction (LVHT/LVNC), characterized by prominent trabeculations and intertrabecular recesses within the left ventricle, is a cardiac abnormality of unclear etiology. Although the left ventricle is the most commonly affected site, a few cases of biventricular involvement have also been reported. We report a 31-year-old woman who presented with mild cardiac symptoms and progressive bilateral limb muscle weakness following exercise which she had also been experiencing for about 5 years. Abnormal serum levels of creatine kinase, lactic acid and pyruvic acid, combined with the results of modified lactate stress test, needle EMG and muscle biopsy indicated that she had mitochondrial myopathy. The transthoracic echocardiography, together with magnetic resonance imaging (MRI), revealed biventricular hypertrabeculation.


Assuntos
Miopatias Mitocondriais/diagnóstico , Disfunção Ventricular/diagnóstico , Adulto , Ecocardiografia , Feminino , Humanos , Imagem por Ressonância Magnética , Miopatias Mitocondriais/sangue , Miopatias Mitocondriais/diagnóstico por imagem , Disfunção Ventricular/sangue , Disfunção Ventricular/diagnóstico por imagem
13.
Interact Cardiovasc Thorac Surg ; 21(5): 598-603, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26265068

RESUMO

OBJECTIVES: Oxidative stress following ischaemia and reperfusion, as well as inflammation, are thought to be important for the development of cardiac dysfunction after cardiac surgery. Our main objective was to investigate whether the inflammatory biomarkers C-reactive protein (CRP), lactoferrin, neopterin and the terminal complement complex (TCC) were associated with cardiac dysfunction after cardiac surgery. Another objective was to assess whether the biomarkers could improve prediction of postoperative cardiac dysfunction compared with clinical variables only. METHODS: Blood samples and clinical data from 1018 consecutive patients undergoing cardiac surgery from 1 April 2008 to 19 April 2010 at St. Olavs University Hospital, Trondheim, Norway, were collected prospectively. The end-point was postoperative cardiac dysfunction, defined as the need for more than one inotropic agent or an intra-aortic balloon pump occurring after the operation and until the patient was discharged from the department. CRP, lactoferrin, neopterin and TCC were analysed in plasma, and we used logistic regression to evaluate the association of the biomarkers with postoperative cardiac dysfunction. We adjusted for the following clinical variables previously associated with postoperative cardiac dysfunction: urgent operation, operation type, previous cardiac surgery, chronic heart failure, pulmonary hypertension, previous myocardial infarction and haemoglobin. The likelihood ratio test, the integrated discrimination improvement and receiver operating characteristic (ROC) curves were used to assess whether the biomarkers could improve prediction of postoperative cardiac dysfunction compared with clinical variables alone. RESULTS: Neopterin was the only biomarker significantly associated with postoperative cardiac dysfunction (odds ratio 2.73, 95% confidence interval 1.65-4.51) after adjustment for clinical variables. Neopterin improved risk prediction of cardiac dysfunction following heart surgery compared with clinical variables alone according to the likelihood ratio test (P < 0.0001) and the integrated discrimination improvement (P = 0.02), particularly for patients with intermediate risks. CONCLUSIONS: Neopterin was associated with cardiac dysfunction following cardiac surgery, and improved the accuracy of risk prediction of postoperative cardiac dysfunction. At present, we do not suggest that neopterin should be measured routinely before heart surgery, but our findings support the hypothesis of the role of oxidative stress and inflammation in development of cardiac dysfunction following heart surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Neopterina/sangue , Complicações Pós-Operatórias/sangue , Disfunção Ventricular/sangue , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Feminino , Seguimentos , Humanos , Incidência , Masculino , Noruega/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Tempo , Disfunção Ventricular/epidemiologia
14.
Eur J Clin Invest ; 45(8): 842-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26077878

RESUMO

BACKGROUND: Prognosis of heart failure patients has been defined in hospital-based or retrospective studies. This study aimed to characterize prognosis of outpatients with new-onset preserved or reduced ejection fraction heart failure; to explore the role of collagen turnover biomarkers (MMP2, MMP9, TIMP1) in predicting prognosis; and to analyse their relationship with echocardiographic parameters and final diagnosis. METHODS: This is an observational, prospective, longitudinal study. Outpatients with new-onset heart failure symptoms referred to a one-stop clinic were included. Echocardiography and biomarkers plasma levels determination were performed at the inclusion. A prospective follow-up was conducted to report cardiovascular events. The discriminant analysis was applied to identify the parameters related to cardiovascular outcomes. RESULTS: A total of 172 patients (75 ± 9 years) were included, 67% with heart failure (64% preserved and 36% with reduced ejection fraction). During follow-up (median 34.5 months), 32.6% had at least one cardiovascular event and 9.9% died. Heart failure groups showed no differences in cardiovascular outcomes with a higher rate of events than nonheart failure patients. MMP2 and TIMP1 were correlated with diastolic dysfunction (Rho 0.349 and 0.294, P < 0.001). In the discriminant analysis, the combination of biomarkers with clinical, biochemical and echocardiographic parameters was useful to predict cardiovascular outcomes (AUC ROC 0.806, Wilks lambda 0.7688, P < 0.001). CONCLUSIONS: Prognosis of outpatients with new-onset heart failure symptoms is comparable between heart failure with preserved or reduced subgroups. The addition of biomarkers specially MMP2 and high sensitive troponin I to other clinical, biochemical and echocardiographic variables can predict cardiovascular prognosis at the time of diagnosis.


Assuntos
Colágeno/metabolismo , Insuficiência Cardíaca/sangue , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Inibidor Tecidual de Metaloproteinase-1/sangue , Disfunção Ventricular/sangue , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial , Biomarcadores/sangue , Análise Discriminante , Ecocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/mortalidade , Humanos , Estudos Longitudinais , Masculino , Peptídeo Natriurético Encefálico/sangue , Prognóstico , Estudos Prospectivos , Volume Sistólico , Troponina I/sangue , Disfunção Ventricular/diagnóstico por imagem
15.
Adv Clin Chem ; 69: 139-59, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25934361

RESUMO

Heart failure is a commonly encountered condition associated with increased morbidity, mortality, and healthcare cost. For years, its management has been strongly influenced by the use of B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide biomarkers. In some cases, this approach does not always identify patients with heart failure accurately and may not provide the best prognostic assessment, particularly in the presence of comorbidities. Biomarkers that help refine diagnosis and risk stratification are needed. Soluble ST2, a peptide belonging to the interleukin-1 receptor family, is secreted when cardiomyocytes and cardiac fibroblasts are subjected to mechanical strain. Although preliminary results on this novel biomarker are encouraging, additional and more comprehensive studies are clearly needed to establish its role in the management of patients with heart failure. The purpose of this chapter is to provide an overview of data currently available.


Assuntos
Biomarcadores/sangue , Insuficiência Cardíaca/diagnóstico , Receptores de Superfície Celular/sangue , Disfunção Ventricular/sangue , Animais , Doenças Cardiovasculares/sangue , Dispneia/sangue , Feminino , Insuficiência Cardíaca/sangue , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1 , Masculino , Valor Preditivo dos Testes , Prognóstico , Receptores de Interleucina/sangue , Valores de Referência
16.
Int J Cardiol ; 195: 7-14, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26011405

RESUMO

BACKGROUND: High sensitivity troponin T (hsTnT) assays enable us to detect chronic heart failure (CHF). Adult congenital heart disease (ACHD) patients are classified as being in at least stage B of CHF. The purpose of the study was to assess hsTnT levels in ACHD patients and determine its clinical significance. METHODS: This is a prospective cross-sectional study. We assessed hsTnT in 131 ACHD patients and in 30 healthy controls. All ACHD patients underwent routine clinical and echocardiographic evaluation and had hsTnT and N-terminal brain natriuretic peptide (NT-pro-BNP) level measurements. RESULTS: The cut-off value defining an abnormal hsTnT level was established as >0.005 ng/mL. 35.1% (n=46) of ACHD patients had abnormal hsTnT compared to 6.7% (n=2) of healthy controls (p=0.002). The prevalence of elevated hsTnT did not differ between simple and complex and between non-cyanotic and cyanotic congenital heart disease (CHD). The sensitivity and specificity of hsTnT for the detection of moderate or severe (significant) systemic ventricular dysfunction was 78.6% and 69.8%, respectively (OR 8.49; CI 95% 2.23-32.30; p<0,0001) whereas for significant pulmonary ventricular dysfunction it was 66.7% and 68.2%, respectively (OR 4.29; CI 95% 1.56-11.79; p=0.003). In multivariate logistic regression models elevated hsTnT, but not NT-pro-BNP, was independently associated with both significant systemic ventricular dysfunction (p=0.004) and significant pulmonary ventricular dysfunction (p=0.011). CONCLUSIONS: A troponin leak is observed in a substantial number of ACHD patients and is associated with significant systemic and pulmonary ventricular impairment. Compared to NT-pro-BNP, hsTnT is a more specific independent predictor of ventricular dysfunction in ACHD.


Assuntos
Cardiopatias Congênitas/sangue , Troponina T/sangue , Adulto , Biomarcadores/sangue , Estudos Transversais , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Sensibilidade e Especificidade , Ultrassonografia , Disfunção Ventricular/sangue , Adulto Jovem
17.
Pediatr Crit Care Med ; 16(6): 529-34, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25856472

RESUMO

OBJECTIVES: In children, elevated amino-terminal pro-B-type natriuretic peptide levels are associated with impaired heart function. The predictive value of serial monitoring of amino-terminal pro-B-type natriuretic peptide levels in acute decompensated heart failure is unclear. DESIGN: Prospective observational study. SETTING: Single, tertiary referral pediatric critical care unit. PATIENTS: Patients aged 0-21 years with primary myocardial dysfunction and acute decompensated heart failure. INTERVENTIONS: Amino-terminal pro-B-type natriuretic peptide levels were obtained on enrollment, day 2, and day 7. Clinical, laboratory, and imaging data were collected on enrollment. Adverse cardiovascular outcome was defined as heart transplant, ventricular assist device placement, extracorporeal membrane oxygenation, or death at 1 year after admission. Aminoterminal pro-B-type natriuretic peptide levels and the percent change from day 0 to day 2 and day 0 to day 7 were calculated and compared between those with and without adverse cardiovascular outcome. MEASUREMENTS AND MAIN RESULTS: Sixteen consecutive patients were enrolled. Adverse cardiovascular outcome occurred in six patients (37.5%, four heart transplant and two ventricular assist device). In patients with an adverse cardiovascular outcome, median amino-terminal pro-B-type natriuretic peptide levels at day 7 were significantly higher (7,365 vs 1,196 pg/mL; p = 0.02) and the percent decline in amino-terminal pro-B-type natriuretic peptide was significantly smaller (28% vs 73%; p = 0.02) compared with those without an adverse cardiovascular outcome. Receiver operating curve analysis revealed that a less than 55% decline in amino-terminal pro-B-type natriuretic peptide levels at day 7 had a sensitivity and specificity of 83% and 90%, respectively, in predicting an adverse cardiovascular (area under the curve, 0.86; 95% CI, 0.68-1.0; p = 0.02). CONCLUSIONS: In conclusion, children with primary myocardial dysfunction and acute decompensated heart failure, a persistently elevated amino-terminal pro-B-type natriuretic peptide, and/or a lesser degree of decline in amino-terminal pro-B-type natriuretic peptide during the first week of presentation were strongly associated with adverse cardiovascular outcome. Serial amino-terminal pro-B-type natriuretic peptide monitoring may allow the early identification of children at risk for worse outcome.


Assuntos
Insuficiência Cardíaca/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Disfunção Ventricular/sangue , Doença Aguda , Adolescente , Criança , Pré-Escolar , Oxigenação por Membrana Extracorpórea , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Transplante de Coração , Coração Auxiliar , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC
18.
Clin Chem Lab Med ; 53(8): 1291-6, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25781544

RESUMO

BACKGROUND: The aim of the study was to investigate serum NT-proBNP levels in adult patients with transposition of the great arteries (d-TGA) corrected by atrial switch procedures (Mustard or Senning) operation and to assess the relationship with ventricular impairment and NYHA class. METHODS: Serum NT-proBNP levels were measured in a group of 81 consecutive adult patients (59 males, mean age 27 years and 22 females, mean age 28 years) with transposition of the great arteries (TGA) after surgical correction in childhood, and in a control group of 25 healthy individuals (16 males, mean age 32 years, and 9 females, mean age 29 years). Age-matched correlation of NT-proBNP concentrations in TGA patients after Mustard or Senning correction was performed, but this correlation was considered not significant (p=0.08). RESULTS: Concentrations of NT-proBNP in patients with TGA were significantly elevated compared to the control group of healthy individuals (203 ng/L vs. 41 ng/L, p<0.0001). Patients after the Mustard repair had significantly higher NT-proBNP values than patients after the Senning operation (234 ng/L vs. 148 ng/L, p=0.0023). NT-proBNP correlated negatively with the systemic right ventricular ejection fraction with the greatest significance in patients after Mustard correction (r=-0.32, p<0.0001). The concentration of NT-proBNP was also associated with NYHA functional class (p=0.0035) with the greatest significance in patients with Mustard correction (p=0.028). CONCLUSIONS: Elevated levels of NT-proBNP appear to be a useful tool in assessing heart failure in patients with transposition of the great arteries after atrial switch correction.


Assuntos
Transposição das Grandes Artérias/efeitos adversos , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Transposição dos Grandes Vasos/sangue , Disfunção Ventricular/sangue , Adulto , Feminino , Humanos , Masculino , Transposição dos Grandes Vasos/cirurgia , Disfunção Ventricular/cirurgia
19.
Cardiovasc Diabetol ; 13: 125, 2014 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-25142437

RESUMO

BACKGROUND: Abnormal ventricular repolarization is a predictor of cardiovascular mortality. In this study, we tested the hypothesis that glycemic control reverses abnormal ventricular repolarization in patients with type 2 diabetes. METHODS: We analyzed longitudinal changes in repolarization indices of electrocardiograms in retrospectively enrolled 44 patients with type 2 diabetes and 44 age-matched healthy subjects. RESULTS: In the diabetic group, BMI was greater, levels of HbA1c (10.0 ± 1.6 vs. 5.6 ± 0.3%) and triglyceride were higher and level of HDL cholesterol was lower than those in the control group. Although mean QTc intervals were similar (413.6 ± 18.5 vs. 408.3 ± 22.7 ms), QT dispersion (41.8 ± 15.4 vs. 28.7 ± 7.7 ms) and Tpeak-Tend in lead V5 (83.6 ± 13.6 vs. 71.3 ± 10.3 ms) were significantly longer in the diabetic group than in the control group, indicating increased heterogeneity of ventricular repolarization in type 2 diabetes. During follow-up of 36 patients in the diabetic group for 787 ± 301 days, HbA1c level decreased to 7.3 ± 1.6%, while BMI did not significantly change. In contrast to HbA1c, QT dispersion (45.8 ± 15.0 ms) and Tpeak-Tend in lead V5 (83.6 ± 10.6 ms) were not significantly reduced during the follow-up period. There was no correlation between the change in HbA1c and the change in QT dispersion or Tpeak-Tend. CONCLUSIONS: Increased heterogeneity of ventricular repolarization in type 2 diabetic patients was not reduced during the relatively short follow-up period despite significantly improved glycemic control.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Índice Glicêmico/fisiologia , Disfunção Ventricular/sangue , Disfunção Ventricular/fisiopatologia , Idoso , Eletrocardiografia/métodos , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Heart Fail Clin ; 10(1): 43-56, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24275294

RESUMO

Most adults with congenital heart disease show high levels of natriuretic peptide (NP) when compared with normal controls. Levels of norepinephrine and NP were strongly related to outcome in studies that included many symptomatic patients, especially those with unrepaired congenital heart disease, Eisenmenger syndrome, and pulmonary hypertension. Limited data are available regarding serial assessment of biomarkers; such information could provide additional important information to help identify patients at risk, as demonstrated during patient follow-up and pregnancy.


Assuntos
Cardiopatias Congênitas , Insuficiência Cardíaca , Peptídeos Natriuréticos/sangue , Norepinefrina/sangue , Adulto , Biomarcadores/sangue , Feminino , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/fisiopatologia , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Gravidez , Prognóstico , Estatística como Assunto , Disfunção Ventricular/sangue
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