FERNANDO BACAL
Projetos de Pesquisa
Unidades Organizacionais
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
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
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- Heart Failure – Pathophysiology and Current Therapeutic Implications(2020) BELLO, Mariana Vieira de Oliveira; BACAL, Fernando
article BRAZILIAN DIRECTOR OF CARDIO-ONCOLOGY OF THE BRAZILIAN CARDIOLOGY SOCIETY ACHIEVEMENT(2011) KALIL FILHO, Roberto; HAJJAR, Ludhmila Abrahao; BACAL, Fernando; HOFF, Paulo Marcelo Gehm; DIZ, Maria Del Pilar Estevez; GALAS, Filomena Regina Barbosa Gomes; FUKUSHIMA, Julia Tizue; ALMEIDA, Juliano Pinheiro de; NAKAMURA, Rosana Ely; TRIELLI, Thalia Rodrigues; BITTAR, Cristina Salvadori; SANTOS, Marilia Harumi dos; GALDEANO, Flavia Gomes; AULER JUNIOR, Jose Otavio da Costa; SILVESTRINI, Anderson Arantes; ALENCAR, Aristoteles; MOTA, Augusto Cesar de Andrade; GUSMAO, Cid Abreu Buarque de; ALMEIDA, Dirceu Rodrigues; SIMOES, Claudia Marques; BOCCHI, Edimar Alcides; LIMA, Enaldo Melo de; FERNANDES, Fabio; SILVEIRA, Fabio Serra; VILAS-BOAS, Fabio; SILVA NETO, Luis Beck da; ROHDE, Luis Eduardo Paim; MONTERA, Marcelo Westerlund; BARBOSA, Marcia; MANO, Max Senna; RIECHELMANN, Rachel Simoes; ARAI, Roberto Jun; MARTINS, Silvia M.; FERREIRA, Silvia Moreira Ayub; SANTOS, Veronica- 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.
- Prescribing and Regulating Exercise with RPE after Heart Transplant: A Pilot Study(2015) CIOLAC, Emmanuel Gomes; CASTRO, Rafael Ertner; GREVE, Julia Maria D'Andrea; BACAL, Fernando; BOCCHI, Edimar Alcides; GUIMARAES, Guilherme VeigaPurpose The objective of this study is to analyze the use of the 6-20 RPE scale for prescribing and self-regulating heated water-based exercise (HEx) and land-based exercise (LEx) in heart transplant recipients. Methods Fifteen (five females) clinically stable heart transplant recipients (time since surgery = 4.0 2.5 yr) age 46.7 11.8 yr underwent a symptom-limited maximal graded exercise test on a treadmill to determine their HR at anaerobic threshold (HRAT), respiratory compensation point (HRRCP), and maximal effort (HRmax). After a week, patients were randomized to perform 30 min of both HEx (walking inside the pool) and LEx (treadmill walking) sessions at a pace between 11 and 13 on the 6-20 RPE scale and had their HR measured every 4 min. The interval between sessions was 48-72 h. Results No significant differences between sessions were found in the average HR during HEx and LEx. Patients showed a delay in HR increase during both interventions, with the stabilization beginning after 8 min of exercise. Exercise HR was maintained between the HRAT and HRRCP (in the aerobic exercise training zone) for the most part of both HEx (72% of HR measurements) and LEx (66% of HR measurements). Only a few HR measurements stayed below HRAT (HEx = 9%, LEx = 13%) or above HRRCP (HEx = 19%, LEx = 21%) during both exercise sessions. Conclusion Exercise HR was maintained in the aerobic exercise training zone (between HRAT and HRRCP) for the most part of both sessions, suggesting that the 6-20 RPE scale may be an efficient tool for prescribing and self-regulating HEx and LEx in heart transplant recipients.
- Impact of Exhaled Breath Acetone in the Prognosis of Patients with Heart Failure with Reduced Ejection Fraction (HFrEF). One Year of Clinical Follow-up(2016) MARCONDES-BRAGA, Fabiana G.; BATISTA, Guilherme L.; GUTZ, Ivano G. R.; SALDIVA, Paulo H. N.; MANGINI, Sandrigo; ISSA, Victor S.; AYUB-FERREIRA, Silvia M.; BOCCHI, Edimar A.; PEREIRA, Alexandre Costa; BACAL, FernandoBackground The identification of new biomarkers of heart failure (HF) could help in its treatment. Previously, our group studied 89 patients with HF and showed that exhaled breath acetone (EBA) is a new noninvasive biomarker of HF diagnosis. However, there is no data about the relevance of EBA as a biomarker of prognosis. Objectives To evaluate whether EBA could give prognostic information in patients with heart failure with reduced ejection fraction (HFrEF). Methods After breath collection and analysis by gas chromatography-mass spectrometry and by spectrophotometry, the 89 patients referred before were followed by one year. Study physicians, blind to the results of cardiac biomarker testing, ascertained vital status of each study participant at 12 months. Results The composite endpoint death and heart transplantation (HT) were observed in 35 patients (39.3%): 29 patients (32.6%) died and 6 (6.7%) were submitted to HT within 12 months after study enrollment. High levels of EBA (>= 3.7 mu g/L, 50th percentile) were associated with a progressively worse prognosis in 12-month follow-up (log-rank = 11.06, p = 0.001). Concentrations of EBA above 3.7 mu g/L increased the risk of death or HT in 3.26 times (HR = 3.26, 95% CI = 1.56-6.80, p = 0.002) within 12 months. In a multivariable cox regression model, the independent predictors of all-cause mortality were systolic blood pressure, respiratory rate and EBA levels. Conclusions High EBA levels could be associated to poor prognosis in HFrEF patients.
- Physical Exercise and MicroRNAs: New Frontiers in Heart Failure(2012) FERNANDES-SILVA, Miguel Morita; CARVALHO, Vagner Oliveira; GUIMARAES, Guilherme Veiga; BACAL, Fernando; BOCCHI, Edimar AlcidesAlthough the impact of exercise on survival of patients with heart failure has been recently questioned, exercise training improves quality of life, functional capacity, inflammation, endothelial and autonomic function. In recent years, interest has increased regarding a group of small non-protein coding RNAs called microRNAs. Studies have shown that the expression of these molecules changes in several pathological conditions, such as myocardial infarction, myocardial ischemia and heart failure, and when clinical improvement occurs, they seem to normalize. With the potential for practical applicability, markers that may be useful in diagnostic and prognostic assessment of heart failure have been identified, such as miR-423-5p. In addition, results of experimental studies have indicated that there are potential therapeutic effects of microRNAs. MicroRNAs are involved in the regulation of gene expression during fetal development and in adult individuals, increasing or decreasing in the heart in response to physiological stress, injury or hemodynamic overload. Thus, the study of the behavior of these molecules in physical exercise has brought important information about the effects of this therapeutic modality and represents a new era in the understanding of heart failure. This review aims to integrate the evidence on microRNAs in heart failure with greater relevance in the study of physical exercise.
- Hypertonic saline solution for prevention of renal dysfunction in patients with decompensated heart failure(2013) ISSA, Victor S.; ANDRADE, Lucia; AYUB-FERREIRA, Silvia M.; BACAL, Fernando; BRAGANCA, Ana C. de; GUIMARAES, Guilherme V.; MARCONDES-BRAGA, Fabiana G.; CRUZ, Fatima D.; CHIZZOLA, Paulo R.; CONCEICAO-SOUZA, Germano E.; VELASCO, Irineu T.; BOCCHI, Edimar A.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 100 mL HSS (NaCl 7.5%) twice daily or placebo. Primary end point was an increase in serumcreatinine of 0.3 mg/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 (AQP(2)), urea transporter (UT-A(1)), 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.
- Value-based health care in heart failure: Quality of life and cost analysis(2023) GHISLENI, Eduarda Chiesa; ASTOLFI, Vit oria Rech; ZIMMERMANN, Larissa; LIRA, Camila Nogueira Leandro; NASCIMENTO, Eduarda Faria do; ETGES, Ana Paula Beck da Silva; MARCONDES-BRAGA, Fabiana G.; BACAL, Fernando; DANZMANN, Luiz Claudio; POLANCZYK, Carisi Anne; BIOLO, AndreiaObjectives: To measure Quality of Life (QoL) and costs of Heart Failure (HF) outpatients in Brazil as an introduction to the Value-Based Health Care (VBHC) concept.Materials and methods: Cross-sectional study, patients with HF, with ejection fraction <50%, were recruited from three hospitals in Brazil. Two QoL (36-Item Short Form Survey [SF-36] and Minnesota Living with Heart Failure Questionnaire [MLHFQ]) and two anxiety/depression questionnaires were applied. SF-36 scores were stratified by domains. Treatment costs were calculated using the Time-Driven Activity-Based Costing (TDABC) method. Results were stratified by NYHA functional class and sex.Results: From October 2018 to January 2021, 198 patients were recruited, and the median MLHFQ (49.5 [IQR 21.0, 69.0]) and SF-36 scores demonstrated poor QoL, worse at higher NYHA classes. A third of patients had moderate/severe depression and anxiety symptoms, and women had higher anxiety scores. Mean costs of outpatient follow-up were US$ 215 +/- 238 for NYHA I patients, US$ 296 +/- 399 for NYHA II and US$ 667 +/- 1012 for NYHA III/IV. Lab/exam costs represented 30% of the costs in NYHA I, and 74% in NYHA III/IV (US $ 63.26 vs. US$ 491.05).Conclusion: Patients with HF in Brazil have poor QoL and high treatment costs; both worsen as the NYHA classifi-cation increases. It seems that HF has a greater impact on the mental health of women. Costs increase mostly related to lab/exams. Accurate and crossed information about QoL and costs is essential to drive care and reim-bursement strategies based on value.
- Survival of Heart Transplant Patients with Chagas' Disease Under Different Antiproliferative Immunosuppressive Regimens(2023) FURQUIM, Silas Ramos; GALBIATI, Luana Campoli; AVILA, Monica S.; MARCONDES-BRAGA, Fabiana G.; FUKUSHIMA, Julia; MANGINI, Sandrigo; SEGURO, Luis Fernando Bernal da Costa; CAMPOS, Iascara Wozniak de; STRABELLI, Tania Mara Varejao; BARONE, Fernanda; PAULO, Audrey Rose da Silveira Amancio de; OHE, Luciana Akutsu; GALANTE, Mariana Cappelletti; GAIOTTO, Fabio Antonio; BACAL, FernandoBackground: Chagas' disease (CD) is an important cause of heart transplantation (HT). The main obstacle is Chagas' disease reactivation (CDR), usually associated to high doses of immunosuppressants. Previous studies have suggested an association of mycophenolate mofetil with increased CDR. However, mortality predictors are unknown.Objectives: To identify mortality risk factors in heart transplant patients with CD and the impact of antiproliferative regimen on survival.Methods: Retrospective study with CD patients who underwent HT between January 2004 and September 2020, under immunosuppression protocol that prioritized azathioprine and change to mycophenolate mofetil in case of rejection. We performed univariate regression to identify mortality predictors; and compared survival, rejection and evidence of CDR between who received azathioprine, mycophenolate mofetil and those who changed from azathioprine to mycophenolate mofetil after discharge (""Change"" group). A p-value < 0.05 was considered statistically significant. Results: Eighty-five patients were included, 54.1% men, median age 49 (39-57) years, and 91.8% were given priority in waiting list. Nineteen (22.4%) used azathioprine, 37 (43.5%) mycophenolate mofetil and 29 (34.1%) switched therapy; survival was not different between groups, 2.9 (1.6-5.0) x 2.9 (1.8-4.8) x 4.2 (2.0-5.0) years, respectively; p=0.4. There was no difference in rejection (42%, 73% and 59% respectively; p=0.08) or in CDR (T. cruzi positive by endomyocardial biopsy 5% x 11% x 7%; p=0.7; benznidazole use 58% x 65% x 69%; p=0.8; positive PCR for T. cruzi 20% x 68% x 42% respectively; p=0.1) rates.Conclusions: This retrospective study did not show difference in survival in heart transplant patients with CD receiving different antiproliferative regimens. Mycophenolate mofetil was not associated with statistically higher rates of CDR or graft rejection in this cohort. New randomized clinical trials are necessary to address this issue.
- Exercise training improves ambulatory blood pressure but not arterial stiffness in heart transplant recipients(2015) PASCOALINO, Lucas Nobilo; CIOLAC, Emmanuel Gomes; TAVARES, Aline Cristina; CASTRO, Rafael Ertner; AYUB-FERREIRA, Silvia Moreira; BACAL, Fernando; ISSA, Victor Sarli; BOCCHI, Edimar Alcides; GUIMARAES, Guilherme VeigaBACKGROUND: Hypertension is the most prevalent comorbidity after heart transplantation (HT). Exercise training (ET) is widely recommended as a key non-pharmacologic intervention for the prevention and management of hypertension, but its effects on ambulatory blood pressure (ABP) and some mechanisms involved in the pathophysiology of hypertension have not been studied in this population. The primary purpose of this study was to investigate the effects of ET on ABP and arterial stiffness of HT recipients. METHODS: 40 HT patients, randomized to ET (n = 31) or a control group (n = 9) underwent a maximal graded exercise test, 24-hour ABP monitoring, and carotid-femoral pulse wave velocity (PWV) assessment before the intervention and at a 12-week follow-up assessment. The ET program was performed thrice-weekly and consisted primarily of endurance exercise (40 minutes) at similar to 70% of maximum oxygen uptake (Vo(2MAX)) RESULTS: The ET group had reduced 24-hour (4.0 +/- 1.4 mm Hg, p < 0.01) and daytime (4.8 +/- 1.6 mm Hg, p < 0.01) systolic ABP, and 24-hour (7.0 +/- 1.4 mm Hg, p < 0.001) daytime (7.5 +/- 1.6 mm Hg, p < 0.001) and nighttime (5.9 +/- 1.5 mm Hg, p < 0.001) diastolic ABP after the intervention. The ET group also had improved Vo(2MAX) (9.7% +/- 2.6%, p < 0.001) after the intervention. However, PWV did not change after ET. No variable was changed in the control group after the intervention. CONCLUSIONS: The 12-week ET program was effective for reducing ABP but not PWV in heart transplant recipients. This result suggesfs that endurance ET may be a tool to counteract hypertension in this high-risk population.