Victor Sarli Issa

I Latin American Guidelines for the assessment and management of decompensated heart failure

Edimar Alcides Bocchi, Fabio Vilas-Boas, Sergio Perrone, Angel G Caamano, Nadine Clausell, Maria da Consolacao VMoreira, Jorge Thierer, Hugo Omar Grancelli, Carlos Vicente Serrano Junior, Denilson Albuquerque, Dirceu Almeida,Fernando Bacal, Luis Felipe Moreira, Adonay Mendonza, Antonio Magana, Arturo Tejeda, Daniel Chafes, Efraim Gomez,Erick Bogantes, Estela Azeka, Evandro Tinoco Mesquita, Francisco Jose Farias B Reis, Hector Mora, Humberto Vilacorta,Jesus Sanches, Joao David de Souza Neto, Jose Luis Vuksovic, Juan Paes Moreno, Julio Aspe y Rosas, Lidia ZytynskiMoura, Luis Antonio de Almeida Campos, Luis Eduardo Rohde, Marcos Parioma Javier, Martin Garrido Garduno, MucioTavares, Pablo Castro Galvez, Raul Spinoza, Reynaldo Castro de Miranda, Ricardo Mourilhe Rocha, Roberto Paganini,Rodolfo Castano Guerra, Salvador Rassi, Sofia Lagudis, Solange Bordignon, Solon Navarette, Waldo Fernandes, AntonioCarlos Pereira Barretto, Victor Issa, Jorge Ilha Guimaraes.

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.

Mychophenolate Mofetil Increased Chagas Disease Reactivation in Heart Transplanted Patients: Comparison Between Two Different Protocols

Heart transplantation (HT) remains the treatment of choice for advanced chagasic cardiomyopathy. New immunosuppression protocols have provided better control of rejection (RJ) and cardiac allograft vasculopathy. However, their influence on infection and Chagas disease reactivation (CDR) is not well established. The aim of this study was to compare the CDR rate in patients under two different immunosuppression protocols. We studied 39 chagasic patients who had undergone orthotopic HT between April, 1987 and June, 2004. They were divided into two groups, one taking azathioprine (group 1 = 24 patients) and the other taking mycophenolate mofetil (group 2 = 15 patients), in the standard doses (2 mg/kg/day and 2 g/day, respectively), beside prednisone and cyclosporine, in equivalent doses. The number of CDR and RJ episodes were analyzed in the first and second years after HT. CDR rates were 8%± 5% at 1 year and 12%± 6% at 2 years of follow‐up in group 1. Otherwise, patients in group 2 presented CDR rates of 75%± 10% and 81%± 9% at the same periods, respectively (p < 0.0001, hazard ratio = 6.06). When comparing RJ rates in the first year after HT, both groups had similar behavior under both immunosuppression protocols (p = 0.88). These data show that current prescribed doses of mycophenolate mofetil increase the early risk of CDR without changing RJ incidence in this period.

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.

Exhaled Acetone as a New Biomarker of Heart Failure Severity

BACKGROUND Heart failure (HF) is associated with poor prognosis, and the identification of biomarkers of its severity could help in its treatment. In a pilot study, we observed high levels of acetone in the exhaled breath of patients with HF. The present study was designed to evaluate exhaled acetone as a biomarker of HF diagnosis and HF severity. METHODS Of 235 patients with systolic dysfunction evaluated between May 2009 and September 2010, 89 patients (HF group) fulfilled inclusion criteria and were compared with sex- and age-matched healthy subjects (control group, n = 20). Patients with HF were grouped according to clinical stability (acute decompensated HF [ADHF], n = 59; chronic HF, n = 30) and submitted to exhaled breath collection. Identification of chemical species was done by gas chromatography-mass spectrometry and quantification by spectrophotometry. Patients with diabetes were excluded. RESULTS The concentration of exhaled breath acetone (EBA) was higher in the HF group (median, 3.7 μg/L; interquartile range [IQR], 1.69-10.45 μg/L) than in the control group (median, 0.39 μg/L; IQR, 0.30-0.79 μg/L; P < .001) and higher in the ADHF group (median, 7.8 μg/L; IQR, 3.6-15.2 μg/L) than in the chronic HF group (median, 1.22 μg/L; IQR, 0.68-2.19 μg/L; P < .001). The accuracy and sensitivity of this method in the diagnosis of HF and ADHF were about 85%, a value similar to that obtained with B-type natriuretic peptide (BNP). EBA levels differed significantly as a function of severity of HF (New York Heart Association classification, P < .001). There was a positive correlation between EBA and BNP (r = 0.772, P < .001). CONCLUSIONS EBA not only is a promising noninvasive diagnostic method of HF with an accuracy equivalent to BNP but also a new biomarker of HF severity.

Mode of Death on Chagas Heart Disease: Comparison with Other Etiologies. A Subanalysis of the REMADHE Prospective Trial

Background Sudden death has been considered the main cause of death in patients with Chagas heart disease. Nevertheless, this information comes from a period before the introduction of drugs that changed the natural history of heart failure. We sought to study the mode of death of patients with heart failure caused by Chagas heart disease, comparing with non-Chagas cardiomyopathy. Methods and results We examined the REMADHE trial and grouped patients according to etiology (Chagas vs non-Chagas) and mode of death. The primary end-point was all-cause, heart failure and sudden death mortality; 342 patients were analyzed and 185 (54.1%) died. Death occurred in 56.4% Chagas patients and 53.7% non-Chagas patients. The cumulative incidence of all-cause mortality and heart failure mortality was significantly higher in Chagas patients compared to non-Chagas. There was no difference in the cumulative incidence of sudden death mortality between the two groups. In the Cox regression model, Chagas etiology (HR 2.76; CI 1.34–5.69; p = 0.006), LVEDD (left ventricular end diastolic diameter) (HR 1.07; CI 1.04–1.10; p<0.001), creatinine clearance (HR 0.98; CI 0.97–0.99; p = 0.006) and use of amiodarone (HR 3.05; CI 1.47–6.34; p = 0.003) were independently associated with heart failure mortality. LVEDD (HR 1.04; CI 1.01–1.07; p = 0.005) and use of beta-blocker (HR 0.52; CI 0.34–0.94; p = 0.014) were independently associated with sudden death mortality. Conclusions In severe Chagas heart disease, progressive heart failure is the most important mode of death. These data challenge the current understanding of Chagas heart disease and may have implications in the selection of treatment choices, considering the mode of death. Trial Registration ClinicalTrails.gov NCT00505050 (REMADHE)

Antitrypanosomal agents: treatment or threat?

768 www.thelancet.com Vol 376 September 4, 2010 Authors’ reply Allergic dermatitis, the most common adverse eff ect of benznidazole, is selflimiting, usually of mild-to-moderate intensity, easily manageable with corticosteroids, and in most patients does not require interruption of therapy. Polyneuropathy (5–10% of patients) occurs late in the treatment course, is dose-dependent, can be avoided by decreasing the cumulative or daily dose of benznidazole (≤300 mg/day), and is always reversible. Serious side-eff ects, such as bone-marrow depression, are extremely rare (<0·1–0·5%). The possible mutagenic eff ects of benznidazole and nifurtimox have been described only in animals. Of thousands of patients treated in several countries for many decades, this eff ect has never been directly linked to either nifurtimox or benznidazole. Regarding post-chemotherapy assess ment at a later stage of chronic infection, seroconversion might not be the most appropriate criterion for monitoring drug effi cacy. Not only can it take decades for serological test results to convert from positive to negative potentially negative consequences for many patients.

Hypertonic saline solution for prevention of renal dysfunction in patients with decompensated heart failure

BACKGROUND Renal dysfunction is associated with increased mortality in patients with decompensated heart failure. However, interventions targeted to prevention in this setting have been disappointing. We investigated the effects of hypertonic saline solution (HSS) for prevention of renal dysfunction in decompensated heart failure. METHODS In a double-blind randomized trial, patients with decompensated heart failure were assigned to receive three-day course of 100mL HSS (NaCl 7.5%) twice daily or placebo. Primary end point was an increase in serum creatinine of 0.3mg/dL or more. Main secondary end point was change in biomarkers of renal function, including serum levels of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin-NGAL and the urinary excretion of aquaporin 2 (AQP2), urea transporter (UT-A1), and sodium/hydrogen exchanger 3 (NHE3). RESULTS Twenty-two patients were assigned to HSS and 12 to placebo. Primary end point occurred in two (10%) patients in HSS group and six (50%) in placebo group (relative risk 0.3; 95% CI 0.09-0.98; P=0.01). Relative to baseline, serum creatinine and cystatin C levels were lower in HSS as compared to placebo (P=0.004 and 0.03, respectively). NGAL level was not statistically different between groups, however the urinary expression of AQP2, UT-A1 and NHE3 was significantly higher in HSS than in placebo. CONCLUSIONS HSS administration attenuated heart failure-induced kidney dysfunction as indicated by improvement in both glomerular and tubular defects, a finding with important clinical implications. HSS modulated the expression of tubular proteins involved in regulation of water and electrolyte homeostasis.

Solução salina hipertônica para prevenção de insuficiência renal em pacientes com insuficiência cardíaca descompensada e hiponatremia

BACKGROUND: Hyponatremia and congestive phenomena indicate a bad prognosis in decompensated heart failure. The occurrence of renal failure is associated to an increased death risk. OBJECTIVE: To evaluate the safety and efficacy of the hypertonic saline solution in patients with decompensated heart failure for renal failure prevention. METHODS: Patients with decompensated heart failure, congestion and hyponatremia participated in the study. In addition to the standard treatment, the patients received hypertonic saline solution and were submitted to clinical as well as laboratory assessment. RESULTS: Nine patients were enrolled in the study. Mean age was 55 + 14.2 years, being 5 male (55.5%) and 4 (44.5%) female patients. All of them presented functional class III-IV of the New York Heart Association (NYHA), and 5 (55.5%) received dobutamine. All of them presented initial creatinine > 1.4 mg/dl. The mean tonicity of the solution was 4.39% + 0.018% (2.5% to 7.5%) and the duration of treatment was 4.9 days + 4.1 days (1-15 days). There were no severe adverse effects; none of the patients presented clinical worsening or neurologic disorders; hypokalemia occurred in 4 cases (44.5%). The comparison of the variables before and after treatment showed a decrease in urea (105 mg/dl + 74.8 mg/dl vs. 88 mg/dl + 79.4 mg/dl; p = 0.03) and increase in the urinary volume (1,183 ml/day vs. 1,778 ml/day; p = 0.03); there was no tendency to creatinine decrease (2.0 mg/dl + 0.8 mg/dl vs. 1.7 mg/dl + 1.0 mg/dl; p = 0.08). Despite the elevation in sodium levels (131 mEq/l + 2.8 mEq/l vs. 134 mEq/l + 4.9 mEq/l) and weight decrease (69.5 kg + 18.6 kg vs. 68.2 kg + 17.1 kg), there was no statistically significant difference. CONCLUSION: The use of hypertonic saline solution in patients with decompensated heart failure can be a safe therapeutic method and potentially related to clinical improvement and renal failure prevention.

Duration of symptoms in patients with infective endocarditis

Despite progress in the management of infective endocarditis, delays in diagnosis or prior antimicrobial treatment may adversely influence the symptom duration and outcome. The duration of symptoms in patients with infective endocarditis was studied in 683 cases among 653 patients with 703 episodes of the disease; patients were hospitalized within 10 days of symptom onset in 169 (24.7%) cases. Antimicrobial therapy before hospital admission was administered to 257 (36.5%) patients. Overall mortality was 25.6%. Symptom duration was longer when antimicrobials were administered before diagnosis (58.8+/-78.1 vs. 44.8+/-54.9 days), when vegetations were detected on echocardiogram (53.5+/-68.2 vs. 38.8+/-47.3) and among patients admitted before 1990 (42.3+/-67.1 vs. 54.2+/-62.4 days). Symptom duration was shorter in patients with prosthetic valve endocarditis (26.8+/-34.2 vs. 59.3+/-71.6 days). In 54 (26.5%) episodes of prosthetic valve endocarditis, patients had symptoms for more than 30 days. Staphylococcus aureus was the most frequent agent among patients with symptoms up to 10 days (41.2%) and Streptococcus among those with symptoms over 20 days (53.9%). Symptom duration did not significantly differ in regard to medical (51.3+/-69.2 days) or surgical (46.7+/-55.7 days) treatment. Mortality increased as symptom duration decreased and was highest for patients who experienced symptoms for less than 10 days (36.1%). In some patients medical care may be delivered relatively late in the course of infective endocarditis. Administration of antibiotics previous to hospital admission increased duration of symptoms, and cardiac valve prosthesis, staphylococcal infection and death were associated with more acute disease.