Alexandre F. Amaral

Beta-Blocker Therapy and Mortality of Patients with Chagas' Cardiomyopathy—a subanalysis of the REMADHE prospective trial.

Background— Peculiar aspects of Chagas cardiomyopathy raise concerns about efficacy and safety of sympathetic blockade. We studied the influence of β-blockers in patients with Chagas cardiomyopathy. Methods and Results— We examined REMADHE trial and grouped patients according to etiology (Chagas versus non-Chagas) and β-blocker therapy. Primary end point was all-cause mortality or heart transplantation. Altogether 456 patients were studied; 27 (5.9%) were submitted to heart transplantation and 202 (44.3%) died. Chagas etiology was present in 68 (14.9%) patients; they had lower body mass index (24.1±4.1 versus 26.3±5.1, P =0.001), smaller end-diastolic left ventricle diameter (6.7±1.0 mm versus 7.0±0.9 mm, P =0.001), smaller proportion of β-blocker therapy (35.8% versus 68%, P <0.001), and higher proportion of spironolactone therapy (74.6% versus 57.8%, P =0.003). Twenty-four (35.8%) patients with Chagas disease were under β-blocker therapy and had lower serum sodium (136.6±3.1 versus 138.4±3.1 mEqs, P =0.05) and lower body mass index (22.5±3.3 versus 24.9±4.3, P =0.03) compared with those who received β-blockers. Survival was lower in patients with Chagas heart disease as compared with other etiologies. When only patients under β-blockers were considered, the survival of patients with Chagas disease was similar to that of other etiologies. The survival of patients with β-blockers was higher than that of patients without β-blockers. In Cox regression model, left ventricle end-diastolic diameter (hazard ratio, 1.78; CI, 1.15 to 2.76; P =0.009) and β-blockers (hazard ratio, 0.37; CI, 0.14 to 0.97; P =0.044) were associated with better survival. Conclusions— Our study suggests that β-blockers may have beneficial effects on survival of patients with heart failure and Chagas heart disease and warrants further investigation in a prospective, randomized trial. Clinical Trial Registration— clinicaltrials.gov. Identifier: [NCT00505050][1]. Received June 1, 2009; accepted November 11, 2009. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00505050&atom=%2Fcirchf%2F3%2F1%2F82.atomBackground—Peculiar aspects of Chagas cardiomyopathy raise concerns about efficacy and safety of sympathetic blockade. We studied the influence of &bgr;-blockers in patients with Chagas cardiomyopathy. Methods and Results—We examined REMADHE trial and grouped patients according to etiology (Chagas versus non-Chagas) and &bgr;-blocker therapy. Primary end point was all-cause mortality or heart transplantation. Altogether 456 patients were studied; 27 (5.9%) were submitted to heart transplantation and 202 (44.3%) died. Chagas etiology was present in 68 (14.9%) patients; they had lower body mass index (24.1±4.1 versus 26.3±5.1, P=0.001), smaller end-diastolic left ventricle diameter (6.7±1.0 mm versus 7.0±0.9 mm, P=0.001), smaller proportion of &bgr;-blocker therapy (35.8% versus 68%, P<0.001), and higher proportion of spironolactone therapy (74.6% versus 57.8%, P=0.003). Twenty-four (35.8%) patients with Chagas disease were under &bgr;-blocker therapy and had lower serum sodium (136.6±3.1 versus 138.4±3.1 mEqs, P=0.05) and lower body mass index (22.5±3.3 versus 24.9±4.3, P=0.03) compared with those who received &bgr;-blockers. Survival was lower in patients with Chagas heart disease as compared with other etiologies. When only patients under &bgr;-blockers were considered, the survival of patients with Chagas disease was similar to that of other etiologies. The survival of patients with &bgr;-blockers was higher than that of patients without &bgr;-blockers. In Cox regression model, left ventricle end-diastolic diameter (hazard ratio, 1.78; CI, 1.15 to 2.76; P=0.009) and &bgr;-blockers (hazard ratio, 0.37; CI, 0.14 to 0.97; P=0.044) were associated with better survival. Conclusions—Our study suggests that &bgr;-blockers may have beneficial effects on survival of patients with heart failure and Chagas heart disease and warrants further investigation in a prospective, randomized trial. Clinical Trial Registration—clinicaltrials.gov. Identifier: NCT00505050.

β-Blocker Therapy and Mortality of Patients With Chagas CardiomyopathyCLINICAL PERSPECTIVE

Background— Peculiar aspects of Chagas cardiomyopathy raise concerns about efficacy and safety of sympathetic blockade. We studied the influence of β-blockers in patients with Chagas cardiomyopathy. Methods and Results— We examined REMADHE trial and grouped patients according to etiology (Chagas versus non-Chagas) and β-blocker therapy. Primary end point was all-cause mortality or heart transplantation. Altogether 456 patients were studied; 27 (5.9%) were submitted to heart transplantation and 202 (44.3%) died. Chagas etiology was present in 68 (14.9%) patients; they had lower body mass index (24.1±4.1 versus 26.3±5.1, P =0.001), smaller end-diastolic left ventricle diameter (6.7±1.0 mm versus 7.0±0.9 mm, P =0.001), smaller proportion of β-blocker therapy (35.8% versus 68%, P <0.001), and higher proportion of spironolactone therapy (74.6% versus 57.8%, P =0.003). Twenty-four (35.8%) patients with Chagas disease were under β-blocker therapy and had lower serum sodium (136.6±3.1 versus 138.4±3.1 mEqs, P =0.05) and lower body mass index (22.5±3.3 versus 24.9±4.3, P =0.03) compared with those who received β-blockers. Survival was lower in patients with Chagas heart disease as compared with other etiologies. When only patients under β-blockers were considered, the survival of patients with Chagas disease was similar to that of other etiologies. The survival of patients with β-blockers was higher than that of patients without β-blockers. In Cox regression model, left ventricle end-diastolic diameter (hazard ratio, 1.78; CI, 1.15 to 2.76; P =0.009) and β-blockers (hazard ratio, 0.37; CI, 0.14 to 0.97; P =0.044) were associated with better survival. Conclusions— Our study suggests that β-blockers may have beneficial effects on survival of patients with heart failure and Chagas heart disease and warrants further investigation in a prospective, randomized trial. Clinical Trial Registration— clinicaltrials.gov. Identifier: [NCT00505050][1]. Received June 1, 2009; accepted November 11, 2009. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00505050&atom=%2Fcirchf%2F3%2F1%2F82.atomBackground—Peculiar aspects of Chagas cardiomyopathy raise concerns about efficacy and safety of sympathetic blockade. We studied the influence of &bgr;-blockers in patients with Chagas cardiomyopathy. Methods and Results—We examined REMADHE trial and grouped patients according to etiology (Chagas versus non-Chagas) and &bgr;-blocker therapy. Primary end point was all-cause mortality or heart transplantation. Altogether 456 patients were studied; 27 (5.9%) were submitted to heart transplantation and 202 (44.3%) died. Chagas etiology was present in 68 (14.9%) patients; they had lower body mass index (24.1±4.1 versus 26.3±5.1, P=0.001), smaller end-diastolic left ventricle diameter (6.7±1.0 mm versus 7.0±0.9 mm, P=0.001), smaller proportion of &bgr;-blocker therapy (35.8% versus 68%, P<0.001), and higher proportion of spironolactone therapy (74.6% versus 57.8%, P=0.003). Twenty-four (35.8%) patients with Chagas disease were under &bgr;-blocker therapy and had lower serum sodium (136.6±3.1 versus 138.4±3.1 mEqs, P=0.05) and lower body mass index (22.5±3.3 versus 24.9±4.3, P=0.03) compared with those who received &bgr;-blockers. Survival was lower in patients with Chagas heart disease as compared with other etiologies. When only patients under &bgr;-blockers were considered, the survival of patients with Chagas disease was similar to that of other etiologies. The survival of patients with &bgr;-blockers was higher than that of patients without &bgr;-blockers. In Cox regression model, left ventricle end-diastolic diameter (hazard ratio, 1.78; CI, 1.15 to 2.76; P=0.009) and &bgr;-blockers (hazard ratio, 0.37; CI, 0.14 to 0.97; P=0.044) were associated with better survival. Conclusions—Our study suggests that &bgr;-blockers may have beneficial effects on survival of patients with heart failure and Chagas heart disease and warrants further investigation in a prospective, randomized trial. Clinical Trial Registration—clinicaltrials.gov. Identifier: NCT00505050.

Glycemia and prognosis of patients with chronic heart failure--subanalysis of the Long-term Prospective Randomized Controlled Study Using Repetitive Education at Six-Month Intervals and Monitoring for Adherence in Heart Failure Outpatients (REMADHE) trial.

BACKGROUND Heart failure and diabetes often occur simultaneously in patients, but the prognostic value of glycemia in chronic heart failure is debatable. We evaluated the role of glycemia on prognosis of heart failure. METHODS Outpatients with chronic heart failure from the Long-term Prospective Randomized Controlled Study Using Repetitive Education at Six-Month Intervals and Monitoring for Adherence in Heart Failure Outpatients (REMADHE) trial were grouped according to the presence of diabetes and level of glycemia. All-cause mortality/heart transplantation and unplanned hospital admission were evaluated. RESULTS Four hundred fifty-six patients were included (135 [29.5%] female, 124 [27.2%] with diabetes mellitus, age of 50.2 +/- 11.4 years, and left-ventricle ejection fraction of 34.7% +/- 10.5%). During follow-up (3.6 +/- 2.2 years), 27 (5.9%) patients were submitted to heart transplantation and 202 (44.2%) died; survival was similar in patients with and without diabetes mellitus. When patients with and without diabetes were categorized according to glucose range (glycemia < or = 100 mg/dL [5.5 mmol/L]), as well as when distributed in quintiles of glucose, the survival was significantly worse among patients with lower levels of glycemia. This finding persisted in Cox proportional hazards regression model that included gender, etiology, left ventricle ejection fraction, left ventricle diastolic diameter, creatinine level and beta-blocker therapy, and functional status (hazard ratio 1.45, 95% CI 1.09-1.69, P = .039). No difference regarding unplanned hospital admission was found. CONCLUSION We report on an inverse association between glycemia and mortality in outpatients with chronic heart failure. These results point to a new pathophysiologic understanding of the interactions between diabetes mellitus, hyperglycemia, and heart disease.

β-Blocker Therapy and Mortality of Patients With Chagas Cardiomyopathy A Subanalysis of the REMADHE Prospective Trial

Background— Peculiar aspects of Chagas cardiomyopathy raise concerns about efficacy and safety of sympathetic blockade. We studied the influence of β-blockers in patients with Chagas cardiomyopathy. Methods and Results— We examined REMADHE trial and grouped patients according to etiology (Chagas versus non-Chagas) and β-blocker therapy. Primary end point was all-cause mortality or heart transplantation. Altogether 456 patients were studied; 27 (5.9%) were submitted to heart transplantation and 202 (44.3%) died. Chagas etiology was present in 68 (14.9%) patients; they had lower body mass index (24.1±4.1 versus 26.3±5.1, P =0.001), smaller end-diastolic left ventricle diameter (6.7±1.0 mm versus 7.0±0.9 mm, P =0.001), smaller proportion of β-blocker therapy (35.8% versus 68%, P <0.001), and higher proportion of spironolactone therapy (74.6% versus 57.8%, P =0.003). Twenty-four (35.8%) patients with Chagas disease were under β-blocker therapy and had lower serum sodium (136.6±3.1 versus 138.4±3.1 mEqs, P =0.05) and lower body mass index (22.5±3.3 versus 24.9±4.3, P =0.03) compared with those who received β-blockers. Survival was lower in patients with Chagas heart disease as compared with other etiologies. When only patients under β-blockers were considered, the survival of patients with Chagas disease was similar to that of other etiologies. The survival of patients with β-blockers was higher than that of patients without β-blockers. In Cox regression model, left ventricle end-diastolic diameter (hazard ratio, 1.78; CI, 1.15 to 2.76; P =0.009) and β-blockers (hazard ratio, 0.37; CI, 0.14 to 0.97; P =0.044) were associated with better survival. Conclusions— Our study suggests that β-blockers may have beneficial effects on survival of patients with heart failure and Chagas heart disease and warrants further investigation in a prospective, randomized trial. Clinical Trial Registration— clinicaltrials.gov. Identifier: [NCT00505050][1]. Received June 1, 2009; accepted November 11, 2009. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00505050&atom=%2Fcirchf%2F3%2F1%2F82.atomBackground—Peculiar aspects of Chagas cardiomyopathy raise concerns about efficacy and safety of sympathetic blockade. We studied the influence of &bgr;-blockers in patients with Chagas cardiomyopathy. Methods and Results—We examined REMADHE trial and grouped patients according to etiology (Chagas versus non-Chagas) and &bgr;-blocker therapy. Primary end point was all-cause mortality or heart transplantation. Altogether 456 patients were studied; 27 (5.9%) were submitted to heart transplantation and 202 (44.3%) died. Chagas etiology was present in 68 (14.9%) patients; they had lower body mass index (24.1±4.1 versus 26.3±5.1, P=0.001), smaller end-diastolic left ventricle diameter (6.7±1.0 mm versus 7.0±0.9 mm, P=0.001), smaller proportion of &bgr;-blocker therapy (35.8% versus 68%, P<0.001), and higher proportion of spironolactone therapy (74.6% versus 57.8%, P=0.003). Twenty-four (35.8%) patients with Chagas disease were under &bgr;-blocker therapy and had lower serum sodium (136.6±3.1 versus 138.4±3.1 mEqs, P=0.05) and lower body mass index (22.5±3.3 versus 24.9±4.3, P=0.03) compared with those who received &bgr;-blockers. Survival was lower in patients with Chagas heart disease as compared with other etiologies. When only patients under &bgr;-blockers were considered, the survival of patients with Chagas disease was similar to that of other etiologies. The survival of patients with &bgr;-blockers was higher than that of patients without &bgr;-blockers. In Cox regression model, left ventricle end-diastolic diameter (hazard ratio, 1.78; CI, 1.15 to 2.76; P=0.009) and &bgr;-blockers (hazard ratio, 0.37; CI, 0.14 to 0.97; P=0.044) were associated with better survival. Conclusions—Our study suggests that &bgr;-blockers may have beneficial effects on survival of patients with heart failure and Chagas heart disease and warrants further investigation in a prospective, randomized trial. Clinical Trial Registration—clinicaltrials.gov. Identifier: NCT00505050.

-Blocker Therapy and Mortality of Patients With Chagas Cardiomyopathy: A Subanalysis of the REMADHE Prospective Trial

Background— Peculiar aspects of Chagas cardiomyopathy raise concerns about efficacy and safety of sympathetic blockade. We studied the influence of β-blockers in patients with Chagas cardiomyopathy. Methods and Results— We examined REMADHE trial and grouped patients according to etiology (Chagas versus non-Chagas) and β-blocker therapy. Primary end point was all-cause mortality or heart transplantation. Altogether 456 patients were studied; 27 (5.9%) were submitted to heart transplantation and 202 (44.3%) died. Chagas etiology was present in 68 (14.9%) patients; they had lower body mass index (24.1±4.1 versus 26.3±5.1, P =0.001), smaller end-diastolic left ventricle diameter (6.7±1.0 mm versus 7.0±0.9 mm, P =0.001), smaller proportion of β-blocker therapy (35.8% versus 68%, P <0.001), and higher proportion of spironolactone therapy (74.6% versus 57.8%, P =0.003). Twenty-four (35.8%) patients with Chagas disease were under β-blocker therapy and had lower serum sodium (136.6±3.1 versus 138.4±3.1 mEqs, P =0.05) and lower body mass index (22.5±3.3 versus 24.9±4.3, P =0.03) compared with those who received β-blockers. Survival was lower in patients with Chagas heart disease as compared with other etiologies. When only patients under β-blockers were considered, the survival of patients with Chagas disease was similar to that of other etiologies. The survival of patients with β-blockers was higher than that of patients without β-blockers. In Cox regression model, left ventricle end-diastolic diameter (hazard ratio, 1.78; CI, 1.15 to 2.76; P =0.009) and β-blockers (hazard ratio, 0.37; CI, 0.14 to 0.97; P =0.044) were associated with better survival. Conclusions— Our study suggests that β-blockers may have beneficial effects on survival of patients with heart failure and Chagas heart disease and warrants further investigation in a prospective, randomized trial. Clinical Trial Registration— clinicaltrials.gov. Identifier: [NCT00505050][1]. Received June 1, 2009; accepted November 11, 2009. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00505050&atom=%2Fcirchf%2F3%2F1%2F82.atomBackground—Peculiar aspects of Chagas cardiomyopathy raise concerns about efficacy and safety of sympathetic blockade. We studied the influence of &bgr;-blockers in patients with Chagas cardiomyopathy. Methods and Results—We examined REMADHE trial and grouped patients according to etiology (Chagas versus non-Chagas) and &bgr;-blocker therapy. Primary end point was all-cause mortality or heart transplantation. Altogether 456 patients were studied; 27 (5.9%) were submitted to heart transplantation and 202 (44.3%) died. Chagas etiology was present in 68 (14.9%) patients; they had lower body mass index (24.1±4.1 versus 26.3±5.1, P=0.001), smaller end-diastolic left ventricle diameter (6.7±1.0 mm versus 7.0±0.9 mm, P=0.001), smaller proportion of &bgr;-blocker therapy (35.8% versus 68%, P<0.001), and higher proportion of spironolactone therapy (74.6% versus 57.8%, P=0.003). Twenty-four (35.8%) patients with Chagas disease were under &bgr;-blocker therapy and had lower serum sodium (136.6±3.1 versus 138.4±3.1 mEqs, P=0.05) and lower body mass index (22.5±3.3 versus 24.9±4.3, P=0.03) compared with those who received &bgr;-blockers. Survival was lower in patients with Chagas heart disease as compared with other etiologies. When only patients under &bgr;-blockers were considered, the survival of patients with Chagas disease was similar to that of other etiologies. The survival of patients with &bgr;-blockers was higher than that of patients without &bgr;-blockers. In Cox regression model, left ventricle end-diastolic diameter (hazard ratio, 1.78; CI, 1.15 to 2.76; P=0.009) and &bgr;-blockers (hazard ratio, 0.37; CI, 0.14 to 0.97; P=0.044) were associated with better survival. Conclusions—Our study suggests that &bgr;-blockers may have beneficial effects on survival of patients with heart failure and Chagas heart disease and warrants further investigation in a prospective, randomized trial. Clinical Trial Registration—clinicaltrials.gov. Identifier: NCT00505050.

β-Blocker Therapy and Mortality of Patients With Chagas CardiomyopathyCLINICAL PERSPECTIVE: A Subanalysis of the REMADHE Prospective Trial

Background— Peculiar aspects of Chagas cardiomyopathy raise concerns about efficacy and safety of sympathetic blockade. We studied the influence of β-blockers in patients with Chagas cardiomyopathy. Methods and Results— We examined REMADHE trial and grouped patients according to etiology (Chagas versus non-Chagas) and β-blocker therapy. Primary end point was all-cause mortality or heart transplantation. Altogether 456 patients were studied; 27 (5.9%) were submitted to heart transplantation and 202 (44.3%) died. Chagas etiology was present in 68 (14.9%) patients; they had lower body mass index (24.1±4.1 versus 26.3±5.1, P =0.001), smaller end-diastolic left ventricle diameter (6.7±1.0 mm versus 7.0±0.9 mm, P =0.001), smaller proportion of β-blocker therapy (35.8% versus 68%, P <0.001), and higher proportion of spironolactone therapy (74.6% versus 57.8%, P =0.003). Twenty-four (35.8%) patients with Chagas disease were under β-blocker therapy and had lower serum sodium (136.6±3.1 versus 138.4±3.1 mEqs, P =0.05) and lower body mass index (22.5±3.3 versus 24.9±4.3, P =0.03) compared with those who received β-blockers. Survival was lower in patients with Chagas heart disease as compared with other etiologies. When only patients under β-blockers were considered, the survival of patients with Chagas disease was similar to that of other etiologies. The survival of patients with β-blockers was higher than that of patients without β-blockers. In Cox regression model, left ventricle end-diastolic diameter (hazard ratio, 1.78; CI, 1.15 to 2.76; P =0.009) and β-blockers (hazard ratio, 0.37; CI, 0.14 to 0.97; P =0.044) were associated with better survival. Conclusions— Our study suggests that β-blockers may have beneficial effects on survival of patients with heart failure and Chagas heart disease and warrants further investigation in a prospective, randomized trial. Clinical Trial Registration— clinicaltrials.gov. Identifier: [NCT00505050][1]. Received June 1, 2009; accepted November 11, 2009. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00505050&atom=%2Fcirchf%2F3%2F1%2F82.atomBackground—Peculiar aspects of Chagas cardiomyopathy raise concerns about efficacy and safety of sympathetic blockade. We studied the influence of &bgr;-blockers in patients with Chagas cardiomyopathy. Methods and Results—We examined REMADHE trial and grouped patients according to etiology (Chagas versus non-Chagas) and &bgr;-blocker therapy. Primary end point was all-cause mortality or heart transplantation. Altogether 456 patients were studied; 27 (5.9%) were submitted to heart transplantation and 202 (44.3%) died. Chagas etiology was present in 68 (14.9%) patients; they had lower body mass index (24.1±4.1 versus 26.3±5.1, P=0.001), smaller end-diastolic left ventricle diameter (6.7±1.0 mm versus 7.0±0.9 mm, P=0.001), smaller proportion of &bgr;-blocker therapy (35.8% versus 68%, P<0.001), and higher proportion of spironolactone therapy (74.6% versus 57.8%, P=0.003). Twenty-four (35.8%) patients with Chagas disease were under &bgr;-blocker therapy and had lower serum sodium (136.6±3.1 versus 138.4±3.1 mEqs, P=0.05) and lower body mass index (22.5±3.3 versus 24.9±4.3, P=0.03) compared with those who received &bgr;-blockers. Survival was lower in patients with Chagas heart disease as compared with other etiologies. When only patients under &bgr;-blockers were considered, the survival of patients with Chagas disease was similar to that of other etiologies. The survival of patients with &bgr;-blockers was higher than that of patients without &bgr;-blockers. In Cox regression model, left ventricle end-diastolic diameter (hazard ratio, 1.78; CI, 1.15 to 2.76; P=0.009) and &bgr;-blockers (hazard ratio, 0.37; CI, 0.14 to 0.97; P=0.044) were associated with better survival. Conclusions—Our study suggests that &bgr;-blockers may have beneficial effects on survival of patients with heart failure and Chagas heart disease and warrants further investigation in a prospective, randomized trial. Clinical Trial Registration—clinicaltrials.gov. Identifier: NCT00505050.