RESUMEN
Although the benefits of carvedilol in patients with heart failure and depressed ejection fraction (EF) have been elucidated, those in patients with preserved EF are not understood. We enrolled 40 patients with mild or moderate heart failure and EF >/=45%. They were randomly assigned to carvedilol (n = 19) or conventional therapy (n = 21). After 12 months of treatment, carvedilol significantly improved all end points (plasma concentration of B-type natriuretic peptide [BNP] from 175 (35 to 209) to 106 (52 to 160) pg/ml, mean (95% confidence interval) p <0.01; New York Heart Association functional class from 2.37 (2.13 to 2.61) to 1.56 (1.21 to 1.91), p <0.01; exercise capacity estimated with the Specific Activity Scale from 4.75 (4.50 to 5.00) to 5.68 (5.22 to 6.14) METs, p <0.02), whereas conventional therapy did not (plasma BNP concentration from 150 (114 to 186) to 174 (100 to 248) pg/ml; New York Heart Association functional class from 2.29 (2.08 to 2.50) to 2.11 (1.73 to 2.49); exercise capacity from 4.57 (4.34 to 4.80) to 4.72 (4.41 to 5.03) METs). Univariate regression analyses showed that only the use of carvedilol was correlated with the decrease in plasma BNP concentration (p <0.03). Multivariate analyses demonstrated that an ischemic cause of heart failure (p <0.02), high plasma concentration of BNP (p <0.02), left ventricular dilation (p <0.03), and use of carvedilol (p <0.04) at baseline were predictive of a decrease in plasma concentration of BNP. In conclusion, carvedilol potentially decreased neurohumoral activation, decreased symptoms, and increased exercise capacity in patients with heart failure and preserved EF.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Carbazoles/uso terapéutico , Gasto Cardíaco Bajo/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Péptido Natriurético Encefálico/sangre , Propanolaminas/uso terapéutico , Actividades Cotidianas/clasificación , Antagonistas Adrenérgicos beta/efectos adversos , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Carbazoles/efectos adversos , Gasto Cardíaco Bajo/sangre , Carvedilol , Glicósidos Digitálicos/efectos adversos , Glicósidos Digitálicos/uso terapéutico , Diuréticos/efectos adversos , Diuréticos/uso terapéutico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Prueba de Esfuerzo/efectos de los fármacos , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/clasificación , Insuficiencia Cardíaca/etiología , Humanos , Masculino , Propanolaminas/efectos adversos , Volumen Sistólico/efectos de los fármacos , Resultado del TratamientoRESUMEN
AIMS: To elucidate the cellular mechanisms of cardioprotection of beta-blockers in patients with heart failure, we investigated the effects of beta-blockers on collagen synthesis in patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: We examined the gene expression before and 4 months after the administration of a beta-blocker in 17 DCM patients. The messenger ribonucleic acid expression of collagen Types I and III (Col I and III) and transforming growth factor-beta(1) (TGF-beta(1)) of right ventricular tissues obtained by the endomyocardial biopsy were assessed by quantitative reverse transcriptase-polymerase chain reaction. Cardiac sympathetic nerve activity was assessed by the washout rate (WR) of (123)I-metaiodobenzylguanidine from the heart. Left ventricular ejection fraction (21 +/- 7 vs. 35 +/- 9%) and WR (53+/-14 vs. 42 +/- 13%) improved significantly. Before the beta-blocker treatment, the expressions of both Col I (r = 0.560, P = 0.041) and Col III (r = 0.630, P = 0.008) genes were correlated with WR. The expression levels of both Col I (1.08 +/- 0.72 vs. 0.65 +/- 0.26, P = 0.024) and Col III (2.06 +/- 1.81 vs. 1.05 +/- 0.74, P = 0.018) were reduced by a beta-blocker. Changes in TGF-beta(1) correlated with those in WR (r = 0.606, P = 0.002). CONCLUSION: beta-Blockers are considered to inhibit the expression of collagen-related genes in DCM, which seems to be mediated by TGF-beta(1).