RESUMO
Troponin elevation correlates with an increased short and long-term mortality in patients with acute decompensated heart failure (AHF). However, it has not been included in the development of multiple validated predictive models of mortality. We aim to determine whether the addition of high-sensitivity troponin T (hs-TnT) to clinical risk scores improves the prediction of in-hospital mortality in patients with AHF. A retrospective analysis of a prospective and consecutive cohort was performed. Adult patients hospitalized between 2015 and 2019 with a primary diagnosis of AHF were included. Hs-TnT was measured on admission. OPTIMIZE-HF, GWTG-HF, and ADHERE risks score were calculated for each patient. The primary endpoint was all-cause in-hospital mortality. Discrimination of isolated hs-TnT and the risk scores with and without the addition of hs-TnT were evaluated using the area under the ROC curve (AUC-ROC). A subanalysis was performed according to left ventricular ejection fraction (LVEF). Of 712 patients, 562 (79%) had hs-TnT measurement upon admission, and was elevated in 91%. In-hospital mortality was 8.7% (n = 49). The AUC-ROC was 0.70 (95% CI 0.63-0.77) for isolated hs-TnT, and 0.80 (0.74-0.87), 0.79 (0.72 -0.86) and 0.79 (0.71-0.86) for the OPTIMIZE-HF, GWTG-HF and ADHERE scores, respectively. The addition of hs-TnT to the models did not increase the AUC: 0.72 (0.66-0.79) for the OPTIMIZE-HF + hs-TnT score (difference between AUC - 0.08 p = 0.04), 0.74 (0.68-0.80) for GWTG-HF (difference between AUC-0.04, p = 0.2) and 0.7 (0.63-0.77) for ADHERE (difference between AUC - 0.085 p = 0.07). The models presented good calibration (p > 0.05). In the sub-analysis, no differences were found between risk scores with the addition of hs-TnT in the population with LVEF < 40% and ≥ 40%. Elevated hs-TnT on admission was frequent and its incorporation into the validated risk scores did not prove an incremental prognostic benefit in patients hospitalized for AHF, regardless of LVEF. Isolated hs-TnT had a modest ability to predict hospital mortality. Additional prospective studies are needed to validate these findings.
Assuntos
Insuficiência Cardíaca , Troponina T/química , Troponina/química , Adulto , Insuficiência Cardíaca/diagnóstico , Mortalidade Hospitalar , Humanos , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Volume Sistólico , Troponina/metabolismo , Troponina T/metabolismo , Função Ventricular EsquerdaRESUMO
BACKGROUND: Hypertrophic cardiomyopathy (HC) is the most prevalent genetic cardiac disease caused by a mutation in sarcomeres, Z-disks, or calcium-handling genes and is characterized by unexplained left ventricular hypertrophy. The aim of this study was to determine the genetic profile of Brazilian patients with HC and correlate the genotype with the phenotype. METHODS: We included 268 index patients from São Paulo city and 3 other cities in Brazil and extracted their DNA from whole blood. We amplified the coding sequencing of MYH7, MYBPC3, and TNNT2 genes and sequenced them with an automatic sequencer. RESULTS: We identified causal mutations in 131 patients (48.8%). Seventy-eight (59.5%) were in the MYH7 gene, 50 (38.2%) in the MYBPC3 gene, and 3 (2.3%) in the TNNT2 gene. We identified 69 mutations, 24 not previously described. Patients with an identified mutation were younger at diagnosis and at current age, had a higher mean heart rate and higher nonsustained ventricular tachycardia frequency compared with those without a mutation. Patients with MYH7 gene mutations had a larger left atrium and higher frequency of atrial fibrillation than did patients with MYBPC3 gene mutations. CONCLUSION: The presence of a mutation in one of the genes suggests a worse prognosis. Mutations in the MYH7 gene, rather than in the MYBPC3 gene, were also related to a worse prognosis. This is the first work characterizing HC molecular epidemiology in the Brazilian population for the 3 most important genes.
Assuntos
Miosinas Cardíacas/genética , Cardiomiopatia Hipertrófica/genética , Proteínas de Transporte/genética , DNA/genética , Testes Genéticos/métodos , Mutação , Cadeias Pesadas de Miosina/genética , Troponina T/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Miosinas Cardíacas/metabolismo , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/epidemiologia , Cardiomiopatia Hipertrófica/metabolismo , Proteínas de Transporte/metabolismo , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Cadeias Pesadas de Miosina/metabolismo , Miosinas , Fenótipo , Reação em Cadeia da Polimerase , Prevalência , Troponina T/metabolismo , Adulto JovemRESUMO
BACKGROUND: Half of patients with acute heart failure syndromes (AHFS) have preserved left ventricular ejection fraction (PLVEF). In this setting, the role of minor myocardial damage (MMD), as identified by cardiac troponin T (cTnT), remains to be established. AIM: To evaluate the prevalence and long-term prognostic significance of cTnT elevations in patients with AHFS and PLVEF. PATIENTS AND METHODS: This retrospective, multicenter, collaborative study included 500 patients hospitalized for AHFS with PLVEF (ejection fraction ≥40%) between October 2000 and December 2006. Blood samples were collected within 12 hours after admission and were assayed for cTnT. MMD was defined as a cTnT value of ≥0.020 ng/mL. RESULTS: Mean age was 73 ± 12 years, 47% were female, 38% had an ischemic etiology, and New York Heart Association (NYHA) class was 2.2 ± 0.7. Mean cTnT value was 0.149 ± 0.484 ng/mL, and cTnT was directly correlated with serum creatinine (Spearman's Rho = 0.35, P < .001) and NYHA class (0.25, P < .001). MMD was diagnosed in 220 patients (44%). Patients with MMD showed lower left ventricular ejection fraction (P < .05), higher serum creatinine (P < .001), higher prevalence of ischemic etiology and diabetes mellitus, a worse NYHA class (P < .001), and higher natriuretic peptide levels (P < .001) as compared with patients without MMD. At 6-month follow-up, overall event-free survival was 55% and 75% in patients with and without MMD (P < .001), respectively. On multivariate Cox regression analysis, only NYHA class (HR = 1.50; P = .002) and MMD (HR = 1.81; P = .001) were identified as predictors of events. CONCLUSIONS: Increased cTnT levels were detected in approximately 50% of patients with AHFS with preserved systolic function, and were found to correlate with clinical measures of disease severity. The presence of MMD was associated with a worse long-term outcome, lending support to cTnT-based risk stratification in the setting of AHFS.
Assuntos
Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Sístole/fisiologia , Troponina T/metabolismo , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/metabolismo , Síndrome Coronariana Aguda/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , Comportamento Cooperativo , Feminino , Seguimentos , Insuficiência Cardíaca/metabolismo , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Retrospectivos , Síndrome , Tempo , Troponina T/biossíntese , Adulto JovemRESUMO
The mechanisms of exercise-induced fatigue have not been investigated using proteomic techniques, an approach that could improve our understanding and generate novel information regarding the effects of exercise. In this study, the proteom alterations of rat skeletal muscle were investigated during exercise-induced fatigue. The proteins were extracted from the skeletal muscle of SD rat thigh, and then analyzed by two-dimensional electrophoresis and PDQuest software. Compared to control samples, 10 significantly altered proteins were found in exercise samples, two of them were upregulated and eight of them were downregulated. These proteins were identified by MALDI TOF-MS. The two upregulated proteins were identified as MLC1 and myosin L2 (DTNB) regulatory light-chain precursors. The eight decreased proteins are Glyceraldehyde-3-phosphate Dehydrogenas (GAPDH); Beta enolase; Creatine kinase M chain (M-CK); ATP-AMP Transphosphorylase (AK1); myosin heavy chain (MHC); actin; Troponin I, fast-skeletal muscle (Troponin I fast-twitch isoform), fsTnI; Troponin T, fast-skeletal muscle isoforms (TnTF). In these proteins, four of the eight decreased proteins are related directly or indirectly to exercise induced fatigue. The other proteins represent diverse sets of proteins including enzymyes related to energy metabolism, skeletal muscle fabric protein and protein with unknown functions. They did not exhibit evident relationship with exercise-induced fatigue. Whereas the two identified increased proteins exhibit evident relationship with fatigue. These findings will help in understanding the mechanisms involved in exercise-induced fatigue.
Assuntos
Fadiga Muscular/fisiologia , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Esforço Físico/fisiologia , Animais , Peso Corporal/fisiologia , Eletroforese em Gel Bidimensional , Metabolismo Energético/fisiologia , Masculino , Espectrometria de Massas , Modelos Animais , Proteínas Musculares/química , Proteômica , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Natação/fisiologia , Troponina I/química , Troponina I/metabolismo , Troponina T/química , Troponina T/metabolismoRESUMO
The mechanisms of exercise-induced fatigue have not been investigated using proteomic techniques, an approach that could improve our understanding and generate novel information regarding the effects of exercise. In this study, the proteom alterations of rat skeletal muscle were investigated during exercise-induced fatigue. The proteins were extracted from the skeletal muscle of SD rat thigh, and then analyzed by two-dimensional electrophoresis and PDQuest software. Compared to control samples, 10 significantly altered proteins were found in exercise samples, two of them were upregulated and eight of them were downregulated. These proteins were identified by MALDI TOF-MS. The two upregulated proteins were identified as MLC1 and myosin L2 (DTNB) regulatory light-chain precursors. The eight decreased proteins are Glyceraldehyde-3-phosphate Dehydrogenas (GAPDH); Beta enolase; Creatine kinase M chain (M-CK); ATP-AMP Transphosphorylase (AK1); myosin heavy chain (MHC); actin; Troponin I, fast-skeletal muscle (Troponin I fast-twitch isoform), fsTnI; Troponin T, fast-skeletal muscle isoforms (TnTF). In these proteins, four of the eight decreased proteins are related directly or indirectly to exercise induced fatigue. The other proteins represent diverse sets of proteins including enzymyes related to energy metabolism, skeletal muscle fabric protein and protein with unknown functions. They did not exhibit evident relationship with exercise-induced fatigue. Whereas the two identified increased proteins exhibit evident relationship with fatigue. These findings will help in understanding the mechanisms involved in exercise-induced fatigue.
Assuntos
Animais , Masculino , Ratos , Fadiga Muscular/fisiologia , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Esforço Físico/fisiologia , Peso Corporal/fisiologia , Eletroforese em Gel Bidimensional , Metabolismo Energético/fisiologia , Espectrometria de Massas , Modelos Animais , Proteínas Musculares/química , Proteômica , Distribuição Aleatória , Ratos Sprague-Dawley , Natação/fisiologia , Troponina I/química , Troponina I/metabolismo , Troponina T/química , Troponina T/metabolismoRESUMO
BACKGROUND: Despite a broad spectrum of structural studies, it is not yet clear whether the D/E helix of troponin C (TnC) contributes to the interaction of TnC with troponin I (TnI). Redox modifications at Cys 98 in the D/E helix were explored for clues to TnC binding to the thin filament off-state, using recombinant wild-type TnC and an engineered mutant without Cys (Cys98Leu). METHODS: Recombinant proteins and rabbit psoas skinned fibres were reduced with dithiothreitol (DTT) and variously recombined. Changes in affinity of reduced or oxidised TnC for the thin filament were evaluated via TnC binding and dissociation, using a standardized test for maximal force as an index of fibre TnC content. RESULTS: All oxidation and reduction effects observed were reversible and led to changes in TnC content. Oxidation (H(2)O(2)) reduced TnC affinity for the filament; reduction (DTT) increased it. Reducing other fibre proteins had no effect. Binding of the Cys-less TnC mutant was not altered by DTT, nor was dissociation of wild-type TnC from reconstituted hybrids (skeletal TnC in cardiac trabeculae). Thus when Cys 98 in the D/E helix of TnC is fully reduced, its binding affinity for the thin filament of skeletal muscle is enhanced and helps to anchor it to the filament. GENERAL SIGNIFICANCE: Signal transmission between TnC and the other proteins of the regulatory complex is sensitive to the redox state of Cys 98.
Assuntos
Cisteína/metabolismo , Músculo Estriado/metabolismo , Troponina C/metabolismo , Vertebrados/metabolismo , Animais , Galinhas , Cisteína/química , Ditiotreitol/metabolismo , Oxirredução , Ligação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Coelhos , Ratos , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Troponina C/química , Troponina I/metabolismo , Troponina T/metabolismoRESUMO
The Mexican axolotl, Ambystoma mexicanum, has been a useful animal model to study heart development and cardiac myofibrillogenesis. A naturally-occurring recessive mutant, gene "c", for cardiac non-function in the Mexican axolotl causes a failure of myofibrillogenesis due to a lack of tropomyosin expression in homozygous mutant (c/c) embryonic hearts. Myofibril-inducing RNA (MIR) rescues mutant hearts in vitro by promoting tropomyosin expression and myofibril formation thereafter. We have studied the effect of MIR on the expression of various isoforms of cardiac troponin T (cTnT), a component of the thin filament that binds with tropomyosin. Four alternatively spliced cTnT isoforms have been characterized from developing axolotl heart. The expression of various cTnT isoforms in normal, mutant, and mutant hearts corrected with MIR, is evaluated by real-time RT-PCR using isoform specific primer pairs; MIR affects the total transcription as well as the splicing of the cTnT in axolotl heart.
Assuntos
Ambystoma mexicanum/embriologia , Coração/embriologia , Miocárdio/metabolismo , Miofibrilas/fisiologia , RNA/metabolismo , Troponina T/genética , Troponina T/metabolismo , Ambystoma mexicanum/genética , Animais , Animais Geneticamente Modificados , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Coração/fisiologia , RNA/genética , Relação Estrutura-AtividadeRESUMO
The Mexican axolotl, Ambystoma mexicanum, is an excellent animal model for studying heart development because it carries a naturally occurring recessive genetic mutation, designated gene c, for cardiac nonfunction. The double recessive mutants (c/c) fail to form organized myofibrils in the cardiac myoblasts resulting in hearts that fail to beat. Tropomyosin expression patterns have been studied in detail and show dramatically decreased expression in the hearts of homozygous mutant embryos. Because of the direct interaction between tropomyosin and troponin T (TnT), and the crucial functions of TnT in the regulation of striated muscle contraction, we have expanded our studies on this animal model to characterize the expression of the TnT gene in cardiac muscle throughout normal axolotl development as well as in mutant axolotls. In addition, we have succeeded in cloning the full-length cardiac troponin T (cTnT) cDNA from axolotl hearts. Confocal microscopy has shown a substantial, but reduced, expression of TnT protein in the mutant hearts when compared to normal during embryonic development.
Assuntos
Ambystoma mexicanum/metabolismo , Miocárdio/metabolismo , Troponina T/metabolismo , Ambystoma mexicanum/embriologia , Ambystoma mexicanum/fisiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Embrião não Mamífero/metabolismo , Imunoquímica , Dados de Sequência Molecular , Contração Muscular , Mutação , Miocárdio/citologia , Ligação Proteica , Homologia de Sequência de Aminoácidos , Tropomiosina/metabolismo , Troponina T/genéticaRESUMO
BACKGROUND: Markers of myocardial necrosis and natriuretic peptides are risk predictors in decompensated heart failure (DHF). We prospectively studied the optimal timing of combined cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements for long-term risk stratification. METHODS: cTnT and NT-proBNP were measured upon admission, and before discharge in 76 patients hospitalized for DHF (mean age 62.3 +/- 15 years; 71% men). RESULTS: During a mean follow-up of 252 +/- 120 days, 39.5% of patients died or were re-hospitalized for DHF. From receiver-operator-characteristic (ROC) curves, the selected cut-off values for cTnT and NT-proBNP were 0.026 ng/ml and 3,700 pg/ml on admission, and 0.030 ng/ml and 3,200 pg/ml, respectively, at discharge. Depending upon measurements above vs below cut-off, the population was distributed on admission and before discharge for three groups: both negative (24% and 30% of patients); one positive (43% and 42%); and both positive (33% and 28%). For the admission groups, the 1-year DHF-free re-hospitalization survival rates were 85%, 60% and 34%, respectively (p = 0.0047). One-year survival rates for DHF-free re-hospitalization were 63%, 71% and 26% (p = 0.0029), respectively, for the discharge groups. In the Cox proportional hazards model, systolic blood pressure (hazard ratio [HR]: 0.98; 95% confidence interval [CI]: 0.96 to 0.99), heart rate (HR: 0.97; 95% CI: 0.94 to 0.98), one positive biomarker on admission (HR: 10.5; 95% CI: 1.3 to 83.7) and two positive biomarkers on admission (HR: 13.9; 95% CI: 1.8 to 98.5) were independent predictors of long-term outcomes. However, NT-proBNP on admission was the most important predictor of long-term prognosis (HR: 5.1; 95% CI: 2.3 to 12.2). CONCLUSIONS: The combined measurements of cTnT and NT-proBNP on hospital admission were more reliable than their measurements before discharge in the long-term risk stratification of DHF. A single positive measurement on admission predicted a poor long-term outcome.
Assuntos
Insuficiência Cardíaca/fisiopatologia , Miocárdio/metabolismo , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Troponina T/sangue , Idoso , Biomarcadores/sangue , Feminino , Insuficiência Cardíaca/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Admissão do Paciente , Prognóstico , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Tempo , Troponina T/metabolismoRESUMO
INTRODUCTION: Autonomic disturbances in tetanus are traditionally associated with adrenergic variations and/or cardiac dysfunction, based on case report data. The objective of this study was to measure catecholamines, (TNF)-alpha and troponin T relative to and left ventricular ejection fraction (LVEF) in patients with severe tetanus. METHODS: This prospective study was carried out at two general Intensive Care Units and included 21 patients consecutively admitted with severe tetanus. Catecholamines (dopamine, norepinephrine, epinephrine and total catecholamines), tumor necrosis factor (TNF)-alpha and LVEF were assessed during the first week of autonomic instability and following tetanus recovery. Troponin T was measured during autonomic instability only. RESULTS: Mean age of patients was 46 +/- 17 years, median Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 8 (range 1-23). All patients had both blood pressure and heart rate instability. Two patients were recuperated from cardiac arrest. Intensive Care Unit mortality was 14% (3 cases). No increase in total catecholamines or in TNF-alpha levels was observed during autonomic instability or in the recovery period. Six patients had troponin T > 0.01 ng/ml and six had > 0.1 ng/ml. Mean LVEF was similar during autonomic instability and after tetanus recovery, 67 +/- 7% and 65 +/- 7%, respectively. Troponin T levels correlated with pressoric instability during autonomic instability. CONCLUSION: Our study demonstrated that in patients with severe tetanus no significant increased levels of catecholamines or TNF-alpha or evidence of cardiac systolic dysfunction was observed either during autonomic instability or in the recovery period. Elevated values of troponin T detected during autonomic instability were not associated with left ventricular dysfunction. Our data do not support the hypothesis that autonomic disturbances in tetanus are associated with adrenergic variations or cardiac dysfunction.