RESUMO
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
P19 cells, a pluripotent cell line derived from a teratocarcinoma induced in C3H/HeHa mice, have been widely used as a model system to study cardiac differentiation. We have used these cells to evaluate the extent to which exposure to DMSO and/or cardiogenol C for 4 days in suspension culture enhanced their differentiation into cardiomyocytes. Cardiac differentiation was assessed by observing beating clusters and further confirmed using immunocytochemical, biochemical, and pharmacological approaches. The presence of functional gap junctions in differentiated P19 cells was identified through calcium wave analyses. Proliferation rate and cell death were analyzed by BrdU incorporation and activated caspase-3 immunodetection, respectively. Beating clusters of differentiated P19 cells were only found in cultures treated with DMSO. In addition, groups treated with DMSO up-regulated cardiac troponin-T expression. However, when DMSO was used together with cardiogenol C the up-regulation was less than that with DMSO alone, approximately 1.5 times. Moreover, P19 cells cultured in DMSO or DMSO plus 0.25 microM cardiogenol C had lower proliferation rates and higher numbers of activated caspase-3-positive cells. In summary, using several methodological approaches we have demonstrated that DMSO can induce cardiac differentiation of P19 cells but that cardiogenol C does not.
Assuntos
Compostos de Anilina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Dimetil Sulfóxido/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Pirimidinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Sinalização do Cálcio/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Células-Tronco de Carcinoma Embrionário/metabolismo , Células-Tronco de Carcinoma Embrionário/patologia , Ativação Enzimática/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C3H , Microscopia Confocal , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Fator 3 de Transcrição de Octâmero/biossíntese , Troponina T/biossíntese , Regulação para Cima/efeitos dos fármacosRESUMO
BACKGROUND: Heart failure progression is associated with ventricular remodeling and ongoing myofibrillar degradation. We hypothesized that myocardial damage, detected by high levels of troponin T, would correlate with echocardiographic measurements of left ventricular remodeling and worse in-hospital course in decompensated heart failure. MATERIAL/METHODS: 159 patients with decompensated heart failure without acute coronary event were included. A troponin T value >0.2 ng/ml in samples taken 6, 12 or 24 hours after admission was considered abnormal. RESULTS: High troponin T levels were identified in 24 patients (15%) (Group 1). Mean age for group 1 was 65.9 vs. 63.7 years in patients with troponin T<0.2 (Group 2) (p=ns). Ischemic etiology in groups 1 and 2 was found in 58.3 and 38.5% (p=0.07). Two-dimensional echocardiograms in groups 1 and 2 revealed higher left ventricular diameters, diastolic (61.7+/-10 vs. 56.9+/-10.3 mm, p=0.041) as well as systolic (49.4+/-13.5 vs. 42.0+/-12.0 mm, p=0.012), and lower ejection fraction (30.1+/-14 vs. 39.0+/-17.7%, p=0.03). Incidence of combined end point of death or refractory heart failure was 20.8 and 3.7% in groups 1 and 2 (p=0.007; OR=6.8; CI95%=1.5-31.2). In a multiple regression model, a history of infarction and chronic obstructive pulmonary disease, tissue hypoperfusion, radiographic pulmonary edema, and high troponin T levels emerged as the independent predictors. CONCLUSIONS: High troponin T levels were found in 15% of patients with acute exacerbation of heart failure; this finding was independently associated with worse prognosis. Echocardiograms suggested that more severe ventricular remodeling is one subjacent mechanism related with biochemically detected myocardial injury in this setting.