RESUMEN
BACKGROUND: Previous studies have shown disappointing results for immunosuppressive treatment in patients with dilated cardiomyopathy. Therefore, we studied the effectiveness of such therapy in patients with HLA upregulation on biopsy. METHODS AND RESULTS: Of 202 patients with dilated cardiomyopathy, 84 patients with increased HLA expression were randomized to receive either immunosuppression or placebo for 3 months; they were then followed for 2 years. After 2 years, there were no significant differences in the primary end point (a composite of death, heart transplantation, and hospital readmission) between the 2 study groups (22.8% for the immunosuppression group and 20.5% for the placebo). The secondary efficacy end point included changes in ejection fraction, end-diastolic diameter, end-diastolic volume, end-systolic volume and NYHA class; left ventricular ejection fraction increased significantly in the immunosuppression group compared with the placebo group (95% CI, 4.20 to 13.12; P<0.001) after 3 months of follow-up. The early favorable effects of immunosuppressive therapy on left ventricular volume, left ventricular diastolic dimension, and New York Heart Association class were also present. This improvement was maintained in the immunosuppression group at 2 years (ejection fraction: 95% CI, 6.94 to 19.04; P<0.001). In addition, on the basis of the protocol-specified definition of improvement, 71.8% patients in the immunosuppression group versus 20.9% patients in the placebo group met the criteria of improvement after 3 months (P<0.001). At the end of the follow-up period, 71.4% patients from the immunosuppression group versus 30.8% patients from the placebo group were improved (P=0.001). CONCLUSIONS: These data demonstrate a long-term benefit of immunosuppressive therapy in patients with dilated cardiomyopathy and HLA upregulation on biopsy specimens. Thus, restoration of immunosuppressive therapy for such patients should be considered.
Asunto(s)
Cardiomiopatía Dilatada/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Miocarditis/tratamiento farmacológico , Adulto , Azatioprina/efectos adversos , Azatioprina/uso terapéutico , Biopsia , Cardiomiopatía Dilatada/complicaciones , Cardiomiopatía Dilatada/inmunología , Cardiomiopatía Dilatada/patología , Enfermedad Crónica , Quimioterapia Combinada , Determinación de Punto Final , Femenino , Estudios de Seguimiento , Antígenos HLA/biosíntesis , Humanos , Hipertensión/inducido químicamente , Inmunosupresores/efectos adversos , Masculino , Miocarditis/complicaciones , Miocarditis/inmunología , Miocarditis/patología , Miocardio/inmunología , Miocardio/metabolismo , Miocardio/patología , Prednisona/efectos adversos , Prednisona/uso terapéutico , Estudios Prospectivos , Volumen Sistólico/efectos de los fármacos , Resultado del Tratamiento , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
Hypertrophic cardiomyopathy (HCM) is phenotypically and genotypically heterogeneous disease of heart. Nine chromosomal loci responsible for this condition have been identified: beta-myosin heavy chain, essential and regulatory myosin light chains, troponin T and I subunits, alpha-tropomosin, cardiac myosin binding protein C, cardiac actin and titin. These genes code for proteins involved in the contraction mechanism or in the control of contraction, therefore HCM has been classified as a disease of cardiac sarcomere. Over 107 mutations have been identified. More then half of them have been detected in the beta-myosin heavy chain gene (beta-MHC). Some mutations in beta-MHC gene are associated with a benign prognosis, other are associated with high incidence of sudden cardiac death (SCD) and severe hypertrophy. Mutations in myosin binding protein C are associated with mild, delayed expression of cardiac hypertrophy and benign prognosis. Mutations in cardiac troponinT are associated with a mild degree of hypertrophy but a high incidence of SCD. Study of genes responsible for HCM will assume role in the context of clinical management of HCM, in particular regarding diagnosis and prognosis patients and families with HCM.
Asunto(s)
Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/genética , Expresión Génica/genética , Humanos , Proteínas de Microfilamentos/genética , Cadenas Pesadas de Miosina/genética , Mutación Puntual/genética , Pronóstico , Troponina I/genética , Troponina T/genéticaRESUMEN
The objective of this paper was to analyze the choice of treatment in two-vessel coronary artery disease and to evaluate the effectiveness of the chosen treatment. The data of sixty-five patients with two-vessel coronary artery disease was analyzed. Two-vessel coronary artery disease was recognized when critical stenoses were present in two arteries with a diameter no less than 2 mm across. Patients who had a CABG were excluded. Patients were divided into three groups according to their treatment: those treated with CABG (29 patients), those treated with coronary angioplasty (20 patients), and those treated conservatively (16 patients). The mean follow-up was 29.3 months (12-48 mo). There were two groups of data collected. The first group consisted of data which might have influenced the decision-making and state of the patients after they had been introduced to the selected treatment. The second group consisted of data necessary to evaluate the state of the patients during the follow-up period. The statistical analysis was divided into three stages. In the first stage, clinical data connected to the selected treatments was studied. In the second, the effects of the chosen treatment were examined. During the third stage of analysis, variables which influenced the effectiveness of the specific treatment were evaluated. Decision-making in patients with two-vessel coronary artery disease depended on the co-existence of hypertension, diabetes, lower-limb ischemia and earlier-performed coronary angioplasty. The only statistically important angiographic feature was the condition of the proximal LAD. Objective improvements in the states of patients (evaluated by exercise tests) were frequently connected to CABG treatment. Subjective improvements in the states of patients were more often connected to conservative treatment. Elevated cholesterol levels were connected to the progression of the disease both in those treated conservatively and interventionally.