EDIMAR ALCIDES BOCCHI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cardio-Pneumologia, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Mode of Death on Chagas Heart Disease: Comparison with Other Etiologies. A Subanalysis of the REMADHE Prospective Trial(2013) AYUB-FERREIRA, Silvia M.; MANGINI, Sandrigo; ISSA, Victor S.; CRUZ, Fatima D.; BACAL, Fernando; GUIMARAES, Guilherme V.; CHIZZOLA, Paulo R.; CONCEICAO-SOUZA, Germano E.; MARCONDES-BRAGA, Fabiana G.; BOCCHI, Edimar A.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.
- Diagnostic discrepancies in clinical practice An autopsy study in patients with heart failure(2017) ISSA, Victor Sarli; DINARDI, Layara Fernanda Lipari; PEREIRA, Thiago Vicente; ALMEIDA, Lyna Kyria Rodrigues de; BARBOSA, Thaisa Silveira; BENVENUTTI, Luiz Alberto; AYUB-FERREIRA, Silvia Moreira; BOCCHI, Edimar AlcidesAutopsies are the gold standard for diagnostic accuracy; however, no recent study has analyzed autopsies in heart failure (HF). We reviewed 1241 autopsies (January 2000-May 2005) and selected 232 patients with HF. Clinical and autopsy diagnoses were analyzed and discrepancies categorized according to their importance regarding therapy and prognosis. Mean age was 63.3 +/- 15.9 years; 154 (66.4%) patients were male. The causes of death at autopsy were end-stage HF (40.9%), acute myocardial infarction (17.2%), infection (15.9), and pulmonary embolism 36 (15.5). Diagnostic discrepancies occurred in 191 (82.3%) cases; in 56 (24.1%), discrepancies were related to major diagnoses with potential influence on survival or treatment; pulmonary embolism was the cause of death for 24 (42.9%) of these patients. In 35 (15.1%), discrepancies were related to a major diagnosis with equivocal influence on survival or treatment; in 100 (43.1%), discrepancies did not influence survival or treatment. In multivariate analysis, age (OR: 1.03, 95% CI: 1.008-1.052, P=0.007) and presence of diabetes mellitus (OR: 0.359, 95% CI: 0.168-0.767, P=0.008) influenced the occurrence discrepancies. Diagnostic discrepancies with a potential impact on prognosis are frequent in HF. These findings warrant reconsideration in diagnostic and therapeutic practices with HF patients.
- Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial(2018) BOCCHI, Edimar Alcides; RASSI, Salvador; GUIMARAES, Guilherme VeigaAimsThe SHIFT trial showed that ivabradine reduced heart rate (HR) and the risk of cardiovascular outcomes. Concerns remain over the efficacy and safety of ivabradine on heart failure (HF) due to Chagas disease (ChD). We therefore conducted a post hoc analysis of the SHIFT trial to investigate the effect of ivabradine in these patients. Methods and resultsSHIFT was a randomized, double-blind, placebo-controlled trial in symptomatic systolic stable HF, HR70b.p.m., and in sinus rhythm. The ChD HF subgroup included 38 patients, 20 on ivabradine, and 18 on placebo. The ChD HF subgroup showed high prevalence of bundle branch right block and, compared with the overall SHIFT population, lower systolic blood pressure; higher use of diuretics, cardiac glycosides, and antialdosterone agents; and lower use of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker or target daily dose of beta-blocker. ChD HF presented a poor prognosis (all-cause mortality at 2years was similar to 60%). The mean twice-daily dose of ivabradine was 6.261.15mg and placebo 6.43 +/- 1.55mg. Ivabradine reduced HR from 77.9 +/- 3.8 to 62.3 +/- 10.1b.p.m. (P=0.005) and improved functional class (P=0.02). A trend towards reduction in all-cause death was observed in ivabradine arm vs. placebo (P=0.07). Ivabradine was not associated with serious bradycardia, atrioventricular block, hypotension, or syncope. ConclusionsChD HF is an advanced form of HF with poor prognosis. Ivabradine was effective in reducing HR in these patients and improving functional class. Although our results are based on a very limited sample and should be interpreted with caution, they suggest that ivabradine may have a favourable benefit-risk profile in ChD HF patients.
- Renal denervation in patients with heart failure secondary to Chagas' disease: A pilot randomized controlled trial(2019) SPADARO, Andre G.; BOCCHI, Edimar A.; SOUZA, Germano E.; FILHO, Antonio E.; MARIANI JR., Jose; CAMPOS, Carlos M.; LEMOS, Pedro A.Introduction Chagas disease is one of the most relevant endemic parasitic diseases in Latin America, affecting approximately 6 million people. Overt Chagas heart disease is an ominous condition, occurring in 20-30% of infected individuals, which has besides the persistent myocarditis a peculiar intracardiac ganglionic neuronal depletion and dysautonomy. This study aims to evaluate the safety and feasibility of renal denervation for patients with advanced symptomatic Chagas cardiomyopathy. Methods Open-label prospective pilot study that randomized patients with Chagas heart disease to either renal denervation or conservative treatment (2:1 ratio). The primary endpoint was the incidence of major adverse events at 9 months, defined as a composite of all-cause death, myocardial infarction, stroke, need for renal artery invasive treatment, or worsening renal function. Results A total of 17 patients were allocated for renal denervation (n = 11) or conservative treatment (n = 6). Included patients had severe symptomatic heart disease, with markedly depressed left ventricular function (average ejection fraction 26.7 +/- 4.9%). For patients randomized to renal denervation, the procedure was performed successfully and uneventfully. After 9 months, the primary endpoint occurred in 36.4% of patients in the renal denervation group and 50.0% in the control arm (p = .6). After 9 months, clinical, laboratory, functional, echocardiographic, and quality of life parameters were similar between groups. Conclusions This pilot study suggests that renal denervation is safe and feasible in patients with Chagas cardiomyopathy, warranting future studies to better evaluate the clinical efficacy of the interventional strategy in improving the prognosis of this high-risk population.
- Clinical findings and prognosis of patients hospitalized for acute decompensated heart failure: Analysis of the influence of Chagas etiology and ventricular function(2018) TERHOCH, Caique Bueno; MOREIRA, Henry Fukuda; AYUB-FERREIRA, Silvia Moreira; CONCEICAO-SOUZA, Germano Emilio; SALEMI, Vera Maria Cury; CHIZZOLA, Paulo Roberto; OLIVEIRA JR., Mucio Tavares; LAGE, Silvia Helena Gelas; BOCCHI, Edimar Alcides; ISSA, Victor SarliAims Explore the association between clinical findings and prognosis in patients with acute decompensated heart failure (ADHF) and analyze the influence of etiology on clinical presentation and prognosis. Methods and results Prospective cohort of 500 patients admitted with ADHF from Aug/2013-Feb/2016; patients were predominantly male (61.8%), median age was 58 (IQ(25-75%) 47-66 years); etiology was dilated cardiomyopathy in 141 (28.2%), ischemic heart disease in 137 (27.4%), and Chagas heart disease in 113 (22.6%). Patients who died (154 [30.8%]) or underwent heart transplantation (53[10.6%]) were younger (56 years [IQ(25-75%) 45-64 vs 60 years, IQ(25-75%) 4967], P=0.032), more frequently admitted for cardiogenic shock (20.3% vs 6.8%, P<0.001), had longer duration of symptoms (14 days [IQ(25-75%) 4-32.8 vs 7.5 days, IQ(25-75%) 2-31], P=0.004), had signs of congestion (90.8% vs 76.5%, P<0.001) and inadequate perfusion more frequently (45.9% vs 28%, P<0.001), and had lower blood pressure (90 [IQ(25-75%) 80-100 vs 100, IQ(25-75%) 90-120], P<0.001). In a logistic regression model analysis, systolic blood pressure (P<0.001, OR 0.97 [95% CI 10.96-0.98] per mmHg) and jugular distention (P=0.004, OR 1.923 [95% CI 1.232-3.001]) were significant. Chagas patients were more frequently admitted for cardiogenic shock (15%) and syncope/arrhythmia (20.4%). Pulmonary congestion was rare among Chagas patients and blood pressure was lower. The rate of in hospital death or heart transplant was higher among patients with Chagas (50.5%). Conclusions A physical exam may identify patients at higher risk in a contemporaneous population. Our findings support specific therapies targeted at Chagas patients in the setting of ADHF.
- Reply: Sacubitril/valsartan for Chagas' heart disease heart failure?(2018) BOCCHI, Edimar Alcides; RASSI, Salvador; GUIMARAES, Guilherme Veiga
- Sex Differences in Heart Failure Mortality with Preserved, Mildly Reduced and Reduced Ejection Fraction: A Retrospective, Single-Center, Large-Cohort Study(2022) MANSUR, Antonio de Padua; CARLO, Carlo Henrique Del; GONCALINHO, Gustavo Henrique Ferreira; AVAKIAN, Solange Desiree; RIBEIRO, Lucas Carrara; IANNI, Barbara Maria; FERNANDES, Fabio; CESAR, Luiz Antonio Machado; BOCCHI, Edimar Alcides; PEREIRA-BARRETTO, Antonio CarlosBackground: Heart failure (HF) is one of the leading causes of death worldwide. Studies show that women have better survival rates than men despite higher hospitalizations. However, little is known about differences in mortality and predictors of death in women and men with HF with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF). Methods: From February 2017 to September 2020, mortality and predictors of death were analyzed in women and men with HF. Baseline data included clinical characteristics and echocardiographic findings. Results: A total of 11,282 patients, 63.9 +/- 14.4 years, including 6256 (55.4%) males, were studied. Females were older, had a higher baseline mean left ventricular ejection fraction (LVEF) and lower left ventricular diastolic diameter. During follow-ups, 1375 (22%) men and 925 (18.4%) women died. Cumulative incidence of death was higher in men with HFrEF but similar for HFmrEF and HFpEF. Cox regression for death showed renal dysfunction, stroke, diabetes, atrial fibrillation, age, LVEF, valve disease, MI, and hypertensive CMP as independent death predictors for all HF patients. Conclusions: Women had a better prognosis than men in HFrEF and similar mortality for HFmrEF and HFpEF, but sex was not an independent predictor of death for all HF subtypes.
- Management of Cardiovascular Disease in Patients With COVID-19 and Chronic Chagas Disease: Implications to Prevent a Scourge Still Larger(2022) BESTETTI, Reinaldo Bulgarelli; BOCCHI, Edimar Alcides; BESTETTI, Renato; ISSA, Victor Sarli; FURLAN-DANIEL, Rosemary Aparecida; NAKAZONE, Marcelo ArrudaCardiovascular diseases (CVD) are the most important cause of morbidity and mortality in the general population. Because the high prevalence of COVID-19 and chronic Chagas disease (CCD) where the latter is endemic, all such diseases will likely be observed in the same patient. While COVID-19 can provoke generalized endotheliitis, which can lead to a cytokine storm and a hyper-coagulable state culminating into in-site and at a distance thrombosis. Therefore, small-vessel coronary artery disease (CAD), cerebrovascular disease, thromboembolism, and arrhythmias are prominent findings in COVID-19. In CCD, small-vessel CAD, cardioembolic stroke, pulmonary embolism, heart failure and arrhythmias are frequently observed as a result of a similar but less intense mechanism. Consequently, the association of CCD and COVID-19 will likely increase the incidence of CVD. Thus, doctors on the frontline should be on the alert for this diagnostic possibility so that the proper treatment can be given without any delay.
- Archaea Symbiont of T. cruzi Infection May Explain Heart Failure in Chagas Disease(2018) HIGUCHI, Maria de Lourdes; KAWAKAMI, Joyce T.; IKEGAMI, Renata N.; REIS, Marcia M.; PEREIRA, Jaqueline de Jesus; IANNI, Barbara M.; BUCK, Paula; OLIVEIRA, Luanda Mara da Silva; SANTOS, Marilia H. H.; HAJJAR, Ludhmila A.; BOCCHI, Edimar A.Background: Archaeal genes present in Trypanosoma cruzi may represent symbionts that would explain development of heart failure in 30% of Chagas disease patients. Extracellular vesicles in peripheral blood, called exosomes (<0.1 mu m) or microvesicles (>0.1 mu m), present in larger numbers in heart failure, were analyzed to determine whether they are derived from archaea in heart failure Chagas disease. Methods: Exosomes and microvesicles in serum supernatant from 3 groups were analyzed: heart failure Chagas disease (N = 26), asymptomatic indeterminate form (N = 21) and healthy non-chagasic control (N = 16). Samples were quantified with transmission electron microscopy, flow cytometer immunolabeled with anti-archaemetzincin-1 antibody (AMZ 1, archaea collagenase) and probe anti-archaeal DNA and zymography to determine AMZ1 (Archaeal metalloproteinase) activity. Results: Indeterminate form patients had higher median numbers of exosomes/case vs. heart failure patients (58.5 vs. 25.5, P < 0.001), higher exosome content of AMZ1 antigens (2.0 vs. 0.0; P < 0.001), and lower archaeal DNA content (0.2 vs. 1.5, P = 0.02). A positive correlation between exosomes and AMZ1 content was seen in indeterminate form (r = 0.5, P < 0.001), but not in heart failure patients (r = 0.002, P = 0.98). Higher free archaeal DNA (63.0 vs. 11.1, P < 0.001) in correlation with exosome numbers (r = 0.66, P = 0.01) was seen in heart failure but not in indeterminate form (r = 0.29, P = 0.10). Flow cytometer showed higher numbers of AMZ1 microvesicles in indeterminate form (64 vs. 36, P = 0.02) and higher archaeal DNA microvesicles in heart failure (8.1 vs. 0.9, P < 0.001). Zymography showed strong% collagenase activity in HF group, mild activity in IF compared to non-chagasic healthy group (121 +/- 14, 106 +/- 13 and 100; P < 0.001). Conclusions: Numerous exosomes, possibly removing and degrading abnormal AMZ1 collagenase, are associated with indeterminate form. Archaeal microvesicles and their exosomes, possibly associated with release of archaeal AMZ1 in heart failure, are future candidates of heart failure biomarkers if confirmed in larger series, and the therapeutic focus in the treatment of Chagas disease.
- Cost-Effectiveness Benefits of a Disease Management Program: The REMADHE Trial Results(2018) BOCCHI, Edimar Alcides; CRUZ, Fatima das Dores da; BRANDAO, Sara Michelly; ISSA, Victor; AYUB-FERREIRA, Silvia Moreira; ROCCA, Hans-Peter Brunner la; WIJK, Sandra Sanders vanBackground: Published studies have generated mixed, controversial results regarding the Cost-effectiveness of heart failure disease management programs (HF-DMPs). This study assessed the cost-effectiveness of an HF-DMP in ambulatory patients compared with usual care (UC). Methods: In the prospective randomized REMADHE trial, we evaluated incremental costs per quality adjusted life-year (QALY) and life-year (LY) gained as effectiveness ratios (ICERs) over a study period of 2.47 +/- 1.75 years. Results: The REMADHE HF-DMP was more effective and less costly than UC in terms of both QALYs and LYs (95% and 55% chance of dominance, respectively). Average saving was US$7345 (2.5%-97.5% bootstrapped confidence interval similar to 16,573 to +921). The chance of DMP being cost-effective at a willingness to pay US$10,000 per QALY or LY was 99% and 96%, respectively. Cost-effectiveness of HF-DMP was highest in subgroups with left ventricular ejection fraction <35%, age >50 years, male sex, New York Heart Association (NYHA) functional class >= III, and ischemic etiology. The chance of DMP being cost-effective at a willingness to pay US$10,000 per QALY was >= 90% in all subgroups apart from NYHA functional class I-II, where it was 70%. Even when the intervention costs increased by 500% or when excluding outliers in costs, DMP had a high chance of being cost-effective (87%-99%). Conclusions: The HF-DMP of the REMADHE trial, which encompasses long-term repeated education alongside telephone monitoring, has a high probability of being cost-effective in ambulatory patients with HF.