ROSA MARIA RAHMI GARCIA
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- Myocardial injury in diabetic patients with multivessel coronary artery disease after revascularization interventions(2017) REZENDE, Paulo Cury; HUEB, Whady; RAHMI, Rosa Maria; SCUDELER, Thiago Luis; AZEVEDO, Diogo Freitas Cardoso de; GARZILLO, Cibele Larrosa; SEGRE, Carlos Alexandre Wainrober; RAMIRES, Jose Antonio Franchini; KALIL FILHO, RobertoBackground: Diabetic patients may be more susceptible to myocardial injury after coronary interventions. Thus, the aim of this study was to assess the release of cardiac biomarkers, CK-MB and troponin, and the findings of new late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) in patients with type 2 diabetes mellitus after elective revascularization procedures for multivessel coronary artery disease (CAD). Methods: Patients with multivessel CAD and preserved systolic ventricular function underwent either elective percutaneous coronary intervention (PCI), off-pump or on-pump bypass surgery (CABG). Troponin and CK-MB were systematically collected at baseline, 6, 12, 24, 36, 48 and 72 h after the procedures. CMR with LGE was performed before and after the interventions. Patients were stratified according to diabetes status at study entry. Biomarkers and CMR results were compared between diabetic and nondiabetics patients. Analyses of correlation were also performed among glycemic and glycated hemoglobin (A1c) levels and troponin and CK-MB peak levels. Patients were also stratified into tertiles of fasting glycemia and A1c levels and were compared in terms of periprocedural myocardial infarction (PMI) on CMR. Results: Ninety (44.5%) of the 202 patients had diabetes mellitus at study entry. After interventions, median peak troponin was 2.18 (0.47, 5.14) and 2.24 (0.69, 5.42) ng/mL (P = 0.81), and median peak CK-MB was 14.1 (6.8, 31.7) and 14.0 (4.2, 29.8) ng/mL (P = 0.43), in diabetic and nondiabetic patients, respectively. The release of troponin and CK-MB over time was statistically similar in both groups and in the three treatments, besides PCI. New LGE on CMR indicated that new myocardial fibrosis was present in 18.9 and 17.3% (P = 0.91), and myocardial edema in 15.5 and 22.9% (P = 0.39) in diabetic and nondiabetic patients, respectively. The incidence of PMI in the glycemia tertiles was 17.9% versus 19.3% versus 18.7% (P = 0.98), and in the A1c tertiles was 19.1% versus 13.3% versus 22.2% (P = 0.88). Conclusions: In this study, diabetes mellitus did not add risk of myocardial injury after revascularization interventions in patients with multivessel coronary artery disease.
- Type 2 diabetes mellitus and myocardial ischemic preconditioning in symptomatic coronary artery disease patients(2015) REZENDE, Paulo Cury; RAHMI, Rosa Maria; UCHIDA, Augusto Hiroshi; COSTA, Leandro Menezes Alves da; SCUDELER, Thiago Luis; GARZILLO, Cibele Larrosa; LIMA, Eduardo Gomes; SEGRE, Carlos Alexandre Wainrober; GIRARDI, Priscyla; TAKIUTI, Myrthes; SILVA, Marcela Francisca; HUEB, Whady; RAMIRES, Jose Antonio Franchini; FILHO, Roberto KalilBackground: The influence of diabetes mellitus on myocardial ischemic preconditioning is not clearly defined. Experimental studies are conflicting and human studies are scarce and inconclusive. Objectives: Identify whether diabetes mellitus intervenes on ischemic preconditioning in symptomatic coronary artery disease patients. Methods: Symptomatic multivessel coronary artery disease patients with preserved systolic ventricular function and a positive exercise test underwent two sequential exercise tests to demonstrate ischemic preconditioning. Ischemic parameters were compared among patients with and without type 2 diabetes mellitus. Ischemic preconditioning was considered present when the time to 1.0 mm ST deviation and rate pressure-product were greater in the second of 2 exercise tests. Sequential exercise tests were analyzed by 2 independent cardiologists. Results: Of the 2,140 consecutive coronary artery disease patients screened, 361 met inclusion criteria, and 174 patients (64.2 +/- 7.6 years) completed the study protocol. Of these, 86 had the diagnosis of type 2 diabetes. Among diabetic patients, 62 (72%) manifested an improvement in ischemic parameters consistent with ischemic preconditioning, whereas among nondiabetic patients, 60 (68%) manifested ischemic preconditioning (p = 0.62). The analysis of patients who demonstrated ischemic preconditioning showed similar improvement in the time to 1.0 mm ST deviation between diabetic and nondiabetic groups (79.4 +/- 47.6 vs 65.5 +/- 36.4 s, respectively, p = 0.12). Regarding rate pressure-product, the improvement was greater in diabetic compared to nondiabetic patients (3011 +/- 2430 vs 2081 +/- 2139 bpm x mmHg, respectively, p = 0.01). Conclusions: In this study, diabetes mellitus was not associated with impairment in ischemic preconditioning in symptomatic coronary artery disease patients. Furthermore, diabetic patients experienced an improvement in this significant mechanism of myocardial protection.
- The Influence of Diabetes Mellitus in Myocardial Ischemic Preconditioning(2016) REZENDE, Paulo Cury; RAHMI, Rosa Maria; HUEB, WhadyIschemic preconditioning (IP) is a powerful mechanism of protection discovered in the heart in which ischemia paradoxically protects the myocardium against other ischemic insults. Many factors such as diseases and medications may influence IP expression. Although diabetes poses higher cardiovascular risk, the physiopathology underlying this condition is uncertain. Moreover, although diabetes is believed to alter intracellular pathways related to myocardial protective mechanisms, it is still controversial whether diabetes may interfere with ischemic preconditioning and whether this might influence clinical outcomes. This review article looks at published reports with animal models and humans that tried to evaluate the possible influence of diabetes in myocardial ischemic preconditioning.
- Impact of diabetes mellitus on ischemic cardiomyopathy. Five-year follow-up. REVISION-DM trial(2018) HUEB, Thiago; ROCHA, Mauricio S.; SIQUEIRA, Sergio F.; NISHIOKA, Silvana Angelina D'Orio; PEIXOTO, Giselle L.; SACCAB, Marcos M.; LIMA, Eduardo Gomes; GARCIA, Rosa Maria Rahmi; RAMIRES, Jos Antonio F.; KALIL FILHO, Roberto; MARTINELLI FILHO, MartinoBackground: Patients with ischemic cardiomyopathy and severe left ventricular dysfunction have a worse survival prognosis than patients with preserved ventricular function. The role of diabetes in the long-term prognosis of this patient group is unknown. This study investigated whether the presence of diabetes has a long-term impact on left ventricular function. Methods: Patients with coronary artery disease who underwent coronary artery bypass graft surgery, percutaneous coronary intervention, or medical therapy alone were included. All patients had multivessel disease and left ventricular ejection fraction measurements. Overall mortality, nonfatal myocardial infarction, stroke, and additional interventions were investigated. Results: From January 2009 to January 2010, 918 consecutive patients were selected and followed until May 2015. They were separated into 4 groups: G1, 266 patients with diabetes and ventricular dysfunction; G2, 213 patients with diabetes without ventricular dysfunction; G3, 213 patients without diabetes and ventricular dysfunction; and G4, 226 patients without diabetes but with ventricular dysfunction. Groups 1, 2, 3, and 4, respectively, had a mortality rate of 21.6, 6.1, 4.2, and 10.6% (P < .001); nonfatal myocardial infarction of 5.3, .5, 7.0, and 2.6% (P < .001); stroke of .40, .45, .90, and .90% (P = NS); and additional intervention of 3.8, 11.7, 10.3, and 2.6% (P < .001). Conclusion: In this sample, regardless of the treatment previously received patients with or without diabetes and preserved ventricular function experienced similar outcomes. However, patients with ventricular dysfunction had a worse prognosis compared with those with normal ventricular function; patients with diabetes had greater mortality than patients without diabetes.
- Association of Longitudinal Values of Glycated Hemoglobin With Cardiovascular Events in Patients With Type 2 Diabetes and Multivessel Coronary Artery Disease(2020) REZENDE, Paulo Cury; HLATKY, Mark Andrew; HUEB, Whady; GARCIA, Rosa Maria Rahmi; SELISTRE, Luciano da Silva; LIMA, Eduardo Gomes; GARZILLO, Cibele Larrosa; SCUDELER, Thiago Luis; BOROS, Gustavo Andre Boeing; RIBAS, Fernando Faglioni; SERRANO, Carlos Vicente; RAMIRES, Jose Antonio Franchini; KALIL FILHO, RobertoQuestion Are longitudinal glycated hemoglobin values associated with cardiovascular events in patients with type 2 diabetes and stable multivessel coronary artery disease? Findings In this cohort study of 725 patients with type 2 diabetes and multivessel coronary artery disease, a 1-point increase in glycated hemoglobin values during follow-up was independently associated with higher risk of the combined outcome of death, myocardial infarction, or ischemic stroke, after adjustment for baseline clinical factors. Meaning Longitudinal increase of glycated hemoglobin was associated with higher rates of cardiovascular events in patients with type 2 diabetes and multivessel coronary artery disease, and the mechanisms underlying this association require further investigation. This cohort study examines whether longitudinal variation of glycated hemoglobin (HbA(1c)) is associated with cardiovascular events in patients with diabetes and multivessel coronary artery disease (CAD). Importance Glycated hemoglobin (HbA(1c)) values are used to guide glycemic control, but in patients with type 2 diabetes and multivessel coronary artery disease (CAD), the association of the longitudinal values of HbA(1c) with cardiovascular outcomes is unclear. Objective To assess whether longitudinal variation of HbA(1c) is associated with cardiovascular events in long-term follow-up among patients with diabetes and multivessel CAD. Design, Setting, and Participants This cohort study included 888 patients with type 2 diabetes and multivessel CAD in the Medicine, Angioplasty, or Surgery Study (MASS) Registry of the Heart Institute of the University of Sao Paulo from January 2003 to December 2007. Data were analyzed from January 15, 2018, to October 15, 2019. Exposure Longitudinal HbA(1c) values. Main Outcomes and Measures The combined outcome of all-cause mortality, myocardial infarction, and ischemic stroke. Results Of 888 patients with type 2 diabetes and multivessel CAD, 725 (81.6%; median [range] age, 62.4 [55.7-68.0] years; 467 [64.4%] men) had complete clinical and HbA(1c) information during a median (interquartile range) follow-up period of 10.0 (8.0-12.3) years, with a mean (SD) of 9.5 (3.8) HbA(1c) values for each patient. The composite end point of death, myocardial infarction, or ischemic stroke occurred in 262 patients (36.1%). A 1-point increase in the longitudinal value of HbA(1c) was significantly associated with a 14% higher risk of the combined end point of all-cause mortality, myocardial infarction, and ischemic stroke (hazard ratio, 1.14; 95% CI, 1.04-1.24; P = .002) in the unadjusted analysis. After adjusting for baseline factors (ie, age, sex, 2-vessel or 3-vessel CAD, initial CAD treatments, ejection fraction, and creatinine and low-density lipoprotein cholesterol levels), a 1-point increase in the longitudinal value of HbA(1c) was associated with a 22% higher risk of the combined end point (hazard ratio, 1.22; 95% CI, 1.12-1.35; P < .001). Conclusions and Relevance Longitudinal increase of HbA(1c) was independently associated with higher rates of cardiovascular events in patients with type 2 diabetes and multivessel CAD.
- Hypotheses, rationale, design, and methods for evaluation of ischemic preconditioning assessed by sequential exercise tests in diabetic and non-diabetic patients with stable coronary artery disease - a prospective study(2013) REZENDE, Paulo Cury; GARCIA, Rosa Maria Rahmi; UCHIDA, Augusto Hiroshi; COSTA, Leandro Menezes Alves; SCUDELER, Thiago Luis; MELO, Rodrigo Morel Vieira; OIKAWA, Fernando Teiichi Costa; GARZILLO, Cibele Larrosa; LIMA, Eduardo Gomes; SEGRE, Carlos Alexandre Wainrober; FAVARATO, Desiderio; GIRARDI, Priscyla; TAKIUTI, Myrthes; STRUNZ, Celia Cassaro; HUEB, Whady; RAMIRES, Jose Antonio Franchini; KALIL FILHO, RobertoBackground: Ischemic preconditioning is a powerful mechanism of myocardial protection and in humans it can be evaluated by sequential exercise tests. Coronary Artery Disease in the presence of diabetes mellitus may be associated with worse outcomes. In addition, some studies have shown that diabetes interferes negatively with the development of ischemic preconditioning. However, it is still unknown whether diabetes may influence the expression of ischemic preconditioning in patients with stable multivessel coronary artery disease. Methods/Design: This study will include 140 diabetic and non-diabetic patients with chronic, stable coronary artery disease and preserved left ventricular systolic function. The patients will be submitted to two sequential exercise tests with 30-minutes interval between them. Ischemic parameters will be compared between diabetic and non-diabetic patients. Ischemic preconditioning will be considered present when time to 1.0 mm ST-segment deviation is greater in the second of two sequential exercise tests. Exercise tests will be analyzed by two independent cardiologists. Discussion: Ischemic preconditioning was first demonstrated by Murry et al. in dog's hearts. Its work was reproduced by other authors, clearly demonstrating that brief periods of myocardial ischemia followed by reperfusion triggers cardioprotective mechanisms against subsequent and severe ischemia. On the other hand, the demonstration of ischemic preconditioning in humans requires the presence of clinical symptoms or physiological changes difficult to be measured. One methodology largely accepted are the sequential exercise tests, in which, the improvement in the time to 1.0 mm ST depression in the second of two sequential tests is considered manifestation of ischemic preconditioning. Diabetes is an important and independent determinant of clinical prognosis. It's a major risk factor for coronary artery disease. Furthermore, the association of diabetes with stable coronary artery disease imposes worse prognosis, irrespective of treatment strategy. It's still not clearly known the mechanisms responsible by these worse outcomes. Impairment in the mechanisms of ischemic preconditioning may be one major cause of this worse prognosis, but, in the clinical setting, this is not known. The present study aims to evaluate how diabetes mellitus interferes with ischemic preconditioning in patients with stable, multivessel coronary artery disease and preserved systolic ventricular function.
- Effect of chronic kidney disease in ischemic cardiomyopathy Long-term follow-up-REVISION-DM2 trial(2019) HUEB, Thiago Ovanessian; LIMA, Eduardo Gomes; ROCHA, Mauricio S.; SIQUEIRA, Sergio F.; NISHIOKA, Silvana Angelina Dorio; PEIXOTO, Giselle L.; SACCAB, Marcos M.; GARCIA, Rosa Maria Rahmi; RAMIRES, Jose Antonio F.; KALIL FILHO, Roberto; MARTINELLI FILHO, MartinoA strong association exists between chronic kidney disease (CKD) and coronary artery disease (CAD). The role of CKD in the long-term prognosis of CAD patients with versus those without CKD is unknown. This study investigated whether CKD affects ventricular function. From January 2009 to January 2010, 918 consecutive patients were selected from an outpatient database. Patients had undergone percutaneous, surgical, or clinical treatment and were followed until May 2015. In patients with preserved renal function (n = 405), 73 events (18%) occurred, but 108 events (21.1%) occurred among those with CKD (n = 513) (P < .001). Regarding left ventricular ejection fraction (LVEF) <50%, we found 84 events (21.5%) in CKD patients and 12 (11.8%) in those with preserved renal function (P < .001). The presence of LVEF <50% brought about a modification effect. Death occurred in 22 (5.4%) patients with preserved renal function and in 73 (14.2%) with CKD (P < .001). In subjects with LVEF <50%, 66 deaths (16.9%) occurred in CKD patients and 7 (6.9%) in those with preserved renal function (P = .001). No differences were found in CKD strata regarding events or overall death among those with preserved LVEF. In a multivariate model, creatinine clearance remained an independent predictor of death (P < .001). We found no deleterious effects of CKD in patients with CAD when ventricular function was preserved. However, there was a worse prognosis in patients with CKD and ventricular dysfunction. Resgistry number is ISRCTN17786790 at .
- Troponin in diabetic patients with and without chronic coronary artery disease(2015) SEGRE, Carlos Alexandre Wainrober; HUEB, Whady; GARCIA, Rosa Maria Rahmi; REZENDE, Paulo Cury; FAVARATO, Desiderio; STRUNZ, Celia Maria Cassaro; SPRANDEL, Marilia da Costa Oliveira; ROGGERIO, Alessandra; CARVALHO, Ana Luiza de Oliveira; MARANHAO, Raul Cavalcante; RAMIRES, Jose Antonio Franchini; KALIL FILHO, RobertoBackground: Cardiac-specific troponin detected with the new high-sensitivity assays can be chronically elevated in response to cardiovascular comorbidities and confer important prognostic information, in the absence of unstable coronary syndromes. Both diabetes mellitus and coronary artery disease are known predictors of troponin elevation. It is not known whether diabetic patients with coronary artery disease have different levels of troponin compared with diabetic patients with normal coronary arteries. To investigate this question, we determined the concentrations of a level 1 troponin assay in two groups of diabetic patients: those with multivessel coronary artery disease and those with angiographically normal coronary arteries. Methods: We studied 95 diabetic patients and compared troponin in serum samples from 50 patients with coronary artery disease (mean age = 63.7, 58 % male) with 45 controls with angiographically normal coronary arteries. Brain natriuretic peptide and the oxidative stress biomarkers myeloperoxidase, nitrotyrosine and oxidized LDL were also determined. Results: Diabetic patients with coronary artery disease had higher levels of troponin than did controls (median values, 12.0 pg/mL (95 % CI:10-16) vs 7.0 pg/mL (95 % CI: 5.9-8.5), respectively; p = 0.0001). The area under the ROC curve for the diagnosis of CAD was 0.712 with a sensitivity of 70 % and a specificity of 66 %. Plasma BNP levels and oxidative stress variables (myeloperoxidase, nitrotyrosine, and oxidized LDL) were not different between the two groups. In a multivariate analysis, gender (p = 0.04), serum glucose (0.03) and Troponin I (p = 0.01) had independent statistical significance. Conclusion: Troponin elevation is related to the presence of chronic coronary artery disease in diabetic patients with multiple associated cardiovascular risk factors. Troponin may serve as a biomarker in this high-risk population.
- Utility and quality-adjusted life-years in coronary artery disease Five-year follow-up of the MASS II trial(2017) BRANDAO, Sara Michelly Goncalves; HUEB, Whady; JU, Yang Ting; LIMA, Antonio Carlos Pedroso de; POLANCZYK, Carisi Anne; CRUZ, Luciane Nascimento; GARCIA, Rosa Maria Rahmi; TAKIUTI, Myrthes Emy; BOCCHI, Edimar AlcidesObjectives: This study evaluated the utility and quality-of-life year measurements for patients with coronary artery disease who underwent any of 3 therapeutic strategies with a 5-year follow-up. Methods: Quality-of-life data were obtained from the Medicine, Angioplasty, or Surgery Study II trial. To obtain utilities, the 36-Item Short-Form questionnaire was converted to a 6-Dimensional Health State Classification System. Results: Of the 611 initial patients, 579 completed the questionnaire. In all, 188 patients received the surgical treatment-194 the percutaneous, and the remaining 197 the medical. The median utility scores for the 5 years analyzed were 0.809 (95% confidence interval [CI] 0.794-0.842) for patients assigned to percutaneous coronary intervention, 0.755 (95% CI 0.723-0.774) for medical treatment, and 0.780 (95% CI 0.761-0.809) for coronary artery bypass graft surgery. The difference between percutaneous coronary intervention and medical treatment was statistically significant (P<.05, Dunn test). The median cumulative quality-of-life years across the 5 years were 3.802 (95% CI 3.668-3.936) for percutaneous, 3.540 (95% CI 3.399-3.681) for medical, and 3.764 (95% CI 3.638-3.890) for surgery. Additionally, the median quality-of-life years between percutaneous and medical treatment was 0.262 (95% CI 0.068-0.456), between surgery and medical treatment it was 0.224 (95% CI 0.036-0.413), and between surgery and percutaneous coronary intervention it was -0.038 (95% CI -0.221 to -0.146). Conclusion: Coronary artery bypass surgery and percutaneous coronary intervention were similar regarding cumulative quality-of-life years; however, they were both superior to that of medical treatment. The results presented are valuable data for further cost-utility studies.
- Hypotheses, rationale, design, and methods for prognostic evaluation of cardiac biomarker elevation after percutaneous and surgical revascularization in the absence of manifest myocardial infarction. A comparative analysis of biomarkers and cardiac magnetic resonance. The MASS-V Trial(2012) HUEB, Whady; GERSH, Bernard J.; REZENDE, Paulo Cury; GARZILLO, Cibele Larrosa; LIMA, Eduardo Gomes; VIEIRA, Ricardo D'Oliveira; GARCIA, Rosa Maria Rahmi; FAVARATO, Desiderio; SEGRE, Carlos Alexandre W.; PEREIRA, Alexandre Costa; SOARES, Paulo Rogerio; RIBEIRO, Expedito; LEMOS, Pedro; PERIN, Marco A.; STRUNZ, Celia Cassaro; DALLAN, Luis A. O.; JATENE, Fabio B.; STOLF, Noedir A. G.; HUEB, Alexandre Ciappina; DIAS, Ricardo; GAIOTTO, Fabio A.; COSTA, Leandro Menezes Alves da; OIKAWA, Fernando Teiichi Costa; MELO, Rodrigo Morel Vieira de; SERRANO JUNIOR, Carlos Vicente; AVILA, Luiz Francisco Rodrigues de; VILLA, Alexandre Volney; PARGA FILHO, Jose Rodrigues; NOMURA, Cesar; RAMIRES, Jose A. F.; KALIL FILHO, RobertoBackground: Although the release of cardiac biomarkers after percutaneous (PCI) or surgical revascularization (CABG) is common, its prognostic significance is not known. Questions remain about the mechanisms and degree of correlation between the release, the volume of myocardial tissue loss, and the long-term significance. Delayed-enhancement of cardiac magnetic resonance (CMR) consistently quantifies areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac biomarkers, we will evaluate the extent of irreversible injury in patients undergoing PCI and CABG and relate it to postprocedural modifications in cardiac biomarkers and long-term prognosis. Methods/Design: The study will include 150 patients with multivessel coronary artery disease (CAD) with left ventricle ejection fraction (LVEF) and a formal indication for CABG; 50 patients will undergo CABG with cardiopulmonary bypass (CPB); 50 patients with the same arterial and ventricular condition indicated for myocardial revascularization will undergo CABG without CPB; and another 50 patients with CAD and preserved ventricular function will undergo PCI using stents. All patients will undergo CMR before and after surgery or PCI. We will also evaluate the release of cardiac markers of necrosis immediately before and after each procedure. Primary outcome considered is overall death in a 5-year follow-up. Secondary outcomes are levels of CK-MB isoenzyme and I-Troponin in association with presence of myocardial fibrosis and systolic left ventricle dysfunction assessed by CMR. Discussion: The MASS-V Trial aims to establish reliable values for parameters of enzyme markers of myocardial necrosis in the absence of manifest myocardial infarction after mechanical interventions. The establishments of these indices have diagnostic value and clinical prognosis and therefore require relevant and different therapeutic measures. In daily practice, the inappropriate use of these necrosis markers has led to misdiagnosis and therefore wrong treatment. The appearance of a more sensitive tool such as CMR provides an unprecedented diagnostic accuracy of myocardial damage when correlated with necrosis enzyme markers. We aim to correlate laboratory data with imaging, thereby establishing more refined data on the presence or absence of irreversible myocardial injury after the procedure, either percutaneous or surgical, and this, with or without the use of cardiopulmonary bypass.