Germano Emilio Conceição Souza

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.

Effect of a sequential education and monitoring programme on quality-of-life components in heart failure

Trials of disease management programmes (DMP) in heart failure (HF) have shown controversial results regarding quality of life. We hypothesized that a DMP applied over the long‐term could produce different effects on each of the quality‐of‐life components.

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.

Bloqueio simpático esquerdo por videotoracoscopia no tratamento da cardiomiopatia dilatada

BACKGROUND The level of sympathetic nervous activity is a major determinant of prognosis in patients with heart failure. OBJECTIVE The purpose of this investigation was to perform a proof-of-principle trial of therapeutic endoscopic left thoracic sympathetic blockade in heart failure patients to assess safety and immediate effects. METHODS Fifteen patients with dilated cardiomyopathy and left ventricular ejection fraction (LVEF) < 40%, New York Heart Association functional class II or III, and heart rate > 65 bpm, despite either adequate betablocker use or intolerant to it, were enrolled. Ten patients underwent left infra-stellate ganglion plus T3-T4 interspinal space clipping through videothoracoscopy, while the other five patients were randomized to a control group. RESULTS None of the treated patients had any procedure-related adverse cardiovascular events at the perioperative period. Two patients from the surgical group died due to pulmonary thromboembolism or myocardial infarction within 6 months of the initial follow-up, while three patients from the control group had heart failure progression and died or developed cardiogenic shock during the same period. Treated patients presented improvement in quality of life, level of physical activity and LVEF (from 25 ± 9% to 32 ± 8%, p=0.024) at 6 months of follow-up, whereas these parameters did not change in control patients. CONCLUSION Endoscopic left thoracic sympathetic blockade is feasible and appears to be safe in severe heart failure patients. This initial study suggests that this procedure might be an effective alternative approach to sympathetic blockade in the treatment of dilated cardiomyopathies.

Anemia and renal failure as predictors of risk in a mainly non-ischemic heart failure population

Anemia and renal failure (RF) are related to poor prognosis in chronic heart failure (HF). Anemia appear early in the course of RF and its value as predictor of risk in HF may be overlap by the value of RF. We aimed to establish the prognostic value of anemia and RF in a Brazilian HF population.

Endoscopic left sympathetic blockade in the treatment for dilated cardiomyopathy

BACKGROUND The level of sympathetic nervous activity is a major determinant of prognosis in patients with heart failure. OBJECTIVE The purpose of this investigation was to perform a proof-of-principle trial of therapeutic endoscopic left thoracic sympathetic blockade in heart failure patients to assess safety and immediate effects. METHODS Fifteen patients with dilated cardiomyopathy and left ventricular ejection fraction (LVEF) < 40%, New York Heart Association functional class II or III, and heart rate > 65 bpm, despite either adequate betablocker use or intolerant to it, were enrolled. Ten patients underwent left infra-stellate ganglion plus T3-T4 interspinal space clipping through videothoracoscopy, while the other five patients were randomized to a control group. RESULTS None of the treated patients had any procedure-related adverse cardiovascular events at the perioperative period. Two patients from the surgical group died due to pulmonary thromboembolism or myocardial infarction within 6 months of the initial follow-up, while three patients from the control group had heart failure progression and died or developed cardiogenic shock during the same period. Treated patients presented improvement in quality of life, level of physical activity and LVEF (from 25 ± 9% to 32 ± 8%, p=0.024) at 6 months of follow-up, whereas these parameters did not change in control patients. CONCLUSION Endoscopic left thoracic sympathetic blockade is feasible and appears to be safe in severe heart failure patients. This initial study suggests that this procedure might be an effective alternative approach to sympathetic blockade in the treatment of dilated cardiomyopathies.

Recovery of Renal Function in Heart Transplantation Patients After Conversion From a Calcineurin Inhibitor-Based Therapy to Sirolimus

BACKGROUND Renal failure is the most important comorbidity in patients with heart transplantation, it is associated with increased mortality. The major cause of renal dysfunction is the toxic effects of calcineurin inhibitors (CNI). Sirolimus, a proliferation signal inhibitor, is an imunossupressant recently introduced in cardiac transplantation. Its nonnephrotoxic properties make it an attractive immunosuppressive agent for patients with renal dysfunction. In this study, we evaluated the improvement in renal function after switching the CNI to sirolimus among patients with new-onset kidney dysfunction after heart transplantation. METHODS The study included orthotopic cardiac transplant (OHT) patients who required discontinuation of CNI due to worsening renal function (creatinine clearance < 50 mL/min). We excluded subjects who had another indication for initiation of sirolimus, that is, rejection, malignancy, or allograft vasculopathy. The patients were followed for 6 months. The creatinine clearance (CrCl) was estimated according to the Cockcroft-Gault equation using the baseline weight and the serum creatinine at the time of introduction of sirolimus and 6 months there after. Nine patients were included, 7 (78%) were males and the overall mean age was 60.1 +/- 12.3 years and time since transplantation 8.7 +/- 6.1 years. The allograft was beyond 1 year in all patients. There was a significant improvement in the serum creatinine (2.98 +/- 0.9 to 1.69 +/- 0.5 mg/dL, P = .01) and CrCl (24.9 +/- 6.5 to 45.7 +/- 17.2 mL/min, P = .005) at 6 months follow-up. CONCLUSION The replacement of CNI by sirolimus for imunosuppressive therapy for patients with renal failure after OHT was associated with a significant improvement in renal function after 6 months.

Perfil do tratamento da insuficiência cardíaca na era dos betabloqueadores

OBJECTIVES The inhibition of the rennin-angiotensin-aldosterone system (RAAS) and sympathetic autonomous nervous system has increased the perspective of survival in these patients, as well as allowing the improvement of the quality of life. The aim of this study was to evaluate the reality of the treatment employed and its impact on the disease in patients followed at a specialized heart failure (HF) outpatient clinic. METHODS A sample of 96 patients followed at the HF and Transplant Outpatient Clinic of Heart Institute of the University of São Paulo School of Medicine (InCor -HCFMUSP) were evaluated. The data were collected during the ambulatory consultation from the medical files and through physical examination. Patients were randomly selected for the study. RESULTS Most of the patients were Functional Class II (42.3%) and evolution stage C (94.9%). The medical prescription given to the patients was quite similar to the one recommended by the directives. Approximately 95% of them received RAAS inhibitors (ACE inhibitor--enalapril and captopril--or angiotensin receptor antagonist--losartan), whereas 85% of the patients additionally received beta blockers (carvedilol). The mean dose prescribed was also similar to the one used in large studies and reached more than 60% of the maximum dose for each medication. The hemodynamic data show that patients were stable, despite the intensity of the dysfunction and ventricular remodeling observed in these patients. CONCLUSION Patients with HF followed by a specialized medical team receive a medical prescription that is closer to the recommended one. These patients, despite the marked characteristics of disease severity, achieve hemodynamic and clinical stability with an adequate therapeutic optimization.

Immunohistochemical Quantification of Inflammatory Cells in Endomyocardial Biopsy Fragments After Heart Transplantation: A New Potential Method to Improve the Diagnosis of Rejection After Heart Transplantation

Inconsistencies in cardiac rejection grading systems corroborate the concept that the evaluation of inflammatory intensity and myocyte damage seems to be subjective. We studied in 36 patients the potential role of the immunohistochemical (IHC) counting of inflammatory cells in endomyocardial biopsy (EMB) as an objective tool, testing the hypothesis of correlation between the International Society for Heart and Lung Transplantation 2004 rejection and IHC counting of inflammatory cells. We observed a progressive increment in CD68+ cells/mm(2) (P = .000) and CD3+ cells/mm(2) (P = .000) with higher rejection grade. A strong correlation between the grade of cellular rejection and both CD68+ cells/mm(2) and CD3+ cells/mm(2) was obtained (P = .000). One patient with CD3+ and CD68+ cells/mm(2) above the upper limit of the 95% confidence interval for cells/mm(2) found in rejection grade 1R evolved to rejection grade 2R without treatment. In patients with 2R that did not respond to treatment the values of CD68+ or CD3+ cells were higher than the overall median values for rejection grade 2R. For diagnosis of rejection needing treatment, the CD68+ and CD3+ cells/mm(2) areas under the receiver operating characteristic curves were 0.956 and 0.934, respectively. IHC counting of mononuclear inflammatory infiltrate in EMB seems to have additive potential role in evaluation of EMB for the diagnosis and prognosis of rejection episodes.