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 on 10-year outcomes of patients with multivessel coronary artery disease in the Medicine, Angioplasty, or Surgery Study II (MASS II) trial(2013) LIMA, Eduardo Gomes; HUEB, Whady; GARCIA, Rosa Maria Rahmi; PEREIRA, Alexandre Costa; SOARES, Paulo Rogerio; FAVARATO, Desiderio; GARZILLO, Cibele Larrosa; VIEIRA, Ricardo D'Oliveira; REZENDE, Paulo Cury; TAKIUTI, Myrthes; GIRARDI, Priscyla; HUEB, Alexandre Ciappina; RAMIRES, Jose A. F.; KALIL FILHO, RobertoIntroduction Diabetes mellitus is a major cause of coronary artery disease (CAD). Despite improvement in the management of patients with stable CAD, diabetes remains a major cause of increased morbidity and mortality. There is no conclusive evidence that either modality is better than medical therapy alone for the treatment of stable multivessel CAD in patients with diabetes in a very long-term follow-up. Our aim was to compare 3 therapeutic strategies for stable multivessel CAD in a diabetic population and non-diabetic population. Methods It was compared medical therapy (MT), percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) in 232 diabetic patients and 379 nondiabetic patients with multivessel CAD. Endpoints evaluated were overall and cardiac mortality. Results Patients (n = 611) were randomized to CABG (n = 203), PCI (n = 205), or MT (n = 203). In a 10-year follow-up, more deaths occurred among patients with diabetes than among patients without diabetes (P = .001) for overall mortality. In this follow-up, 10-year mortality rates were 32.3% and 23.2% for diabetics and non-diabetics respectively (P = .024). Regarding cardiac mortality, 10-year cardiac mortality rates were 19.4% and 12.7% respectively (P = .031). Considering only diabetic patients and stratifying this population by treatment option, we found mortality rates of 31.3% for PCI, 27.5% for CABG and 37.5% for MT (P = .015 for CABG vs MT) and cardiac mortality rates of 18.8%, 12.5% and 26.1% respectively (P = .005 for CABG vs MT). Conclusions/interpretation Among patients with stable multivessel CAD and preserved left ventricular ejection fraction, the 3 therapeutic regimens had high rates of overall and cardiac-related deaths among diabetic compared with nondiabetic patients. Moreover, better outcomes were observed in diabetic patients undergoing CABG compared to MT in relation to overall and cardiac mortality in a 10-year follow-up.
- Effect of diabetic kidney disease on therapeutic strategies for coronary artery disease: ten year follow-up(2021) BATISTA, Daniel Valente; HUEB, Whady; LIMA, Eduardo Gomes; REZENDE, Paulo Cury; GARZILLO, Cibele Larrosa; GARCIA, Rosa Maria Rahmi; LINHARES FILHO, Jaime Paula Pessoa; MARTINS, Eduardo Bello; SERRANO JUNIOR, Carlos Vicente; RAMIRES, Jose Antonio Franchini; KALIL FILHO, RobertoBackground: The best treatment for coronary artery disease (CAD) in patients with type 2 diabetes (DM2) and chronic kidney disease is unknown. Methods: This retrospective study included MASS registry patients with DM2 and multivessel CAD, stratified by kidney function. Primary endpoint was combined of mortality, myocardial infarction, or additional revascularization. Results: Median follow-up was 9.5 years. Primary endpoint occurrences among strata 1 and 2 were 53.4% and 40.7%, respectively (P=.020). Mortality rates were 37.4% and 24.6% in strata 1 and 2, respectively (P<.001). We observed a lower rate of major adverse cardiovascular events (MACE) (P=.027 for stratum 1 and P<.001 for stratum 2) and additional revascularization (P=.001 for stratum 1 and P<.001 for stratum 2) for those in the surgical group. In a multivariate analysis, eGFR was an independent predictor of MACE (P=.034) and mortality (P=.020). Conclusions: Among subjects with DM2 and CAD the presence of lower eGFR rate was associated with higher rates of MACE and mortality, irrespective of treatment choice. CABG was associated with lower rates of MACE in both renal function strata. eGFR was an independent predictor of MACE and mortality in a 10-year follow-up.
- 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.
- Impact of Chronic Kidney Disease on Long-Term Outcomes in Type 2 Diabetic Patients With Coronary Artery Disease on Surgical, Angioplasty, or Medical Treatment(2016) LIMA, Eduardo Gomes; HUEB, Whady; GERSH, Bernard J.; REZENDE, Paulo Cury; GARZILLO, Cibele Larrosa; FAVARATO, Desiderio; HUEB, Alexandre Ciappina; GARCIA, Rosa Maria Rahmi; RAMIRES, Jose Antonio Franchini; KALIL FILHO, RobertoBackground. Coronary artery disease (CAD) among patients with diabetes and chronic kidney disease (CKD) is not well studied, and the best treatment for this condition is not established. Our aim was to compare three therapeutic strategies for CAD in diabetic patients stratified by renal function. Methods. Patients with multivessel CAD that underwent coronary artery bypass graft (CABG), angioplasty (percutaneous coronary intervention [PCI]), or medical therapy alone (MT) were included. Data were analyzed according to glomerular filtration rate in three strata: normal (>90 mL/min), mild CKD (60 to 89 mL/min), and moderate CKD (30 to 59 mL/min). End points comprised overall rate of mortality, acute myocardial infarction, and need for additional revascularization. Results. Among patients with normal renal function (n = 270), 122 underwent CABG, 72 PCI, and 76 MT; among patients with mild CKD (n = 367), 167 underwent CABG, 92 PCI, and 108 MT; and among patients with moderate CKD (n = 126), 46 underwent CABG, 40 PCI, and 40 MT. Event-free survival was 80.4%, 75.7%, 67.5% for strata 1, 2, and 3, respectively (p = 0.037). Survival rates among patients with no, mild, and moderate CKD are 91.1%, 89.6%, and 76.2%, respectively (p = 0.001) (hazard ratio 0.69; 95% confidence interval 0.51 to 0.95; p = 0.024 for stratum 1 versus 3). We found no differences for overall number of deaths or acute myocardial infarctions irrespective of strata. The need of new revascularization was different in all strata, favoring CABG (p < 0.001, p < 0.001, and p = 0.029 for no, mild, and moderate CKD, respectively). Conclusions. Mortality rates were higher in patients with mild and moderate CKD. Higher event-free survival was observed in the CABG group among patients with no and mild CKD. Besides, CABG was associated with less need for new revascularization compared with PCI and MT in all renal function strata. This trial was registered at http://www.controlled-trials.com as ISRCTN66068876. (C) 2016 by The Society of Thoracic Surgeons
conferenceObject EVOLUTION OF VENTRICULAR FUNCTION IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE SUBMITTED TO ON-PUMP OR OFF-PUMP CORONARY ARTERY BYPASS GRAFT IN MASS III TRIAL(2012) STASZKO, Kamila F.; HUEB, Whady; LIMA, Eduardo; BISELLI, Bruno; GARCIA, Rosa Maria Rahmi; VIEIRA, Ricardo D. O.; GARZILLO, Cibele Larrosa; PEREIRA, Alexandre Costa; HUEB, Alexandre Ciappina; REZENDE, Paulo Cury; CASELLA-FILHO, Antonio; RAMIRES, Jose; KALIL-FILHO, RobertoBackground Ventricular function is a major determinant of prognosis in patients with coronary artery disease (CAD). Few data are available to assess the evolution of ventricular function among patients submitted to off-pump coronary artery bypass graft surgery (OPCAB). Purpose To compare the evolution of ventricular function in a long-term follow-up among patients with stable CAD submitted to OPCAB or On-Pump coronary artery bypass graft (ONCAB) Methods Patients with stable CAD and preserved systolic left ventricular function were randomized to OPCAB or ONCAB and followed for 5 years. Patients who undergone a new evaluation of ventricular function in this follow-up were studied. Left ventricular ejection fraction (LVEF) was assessed by echocardiogram. Results Of 308 patients randomized to OPCAB (n=155) or ONCAB (n=153), 91 had a new assessment of ventricular function by echocardiogram in a 5-year follow-up: 49 in ONCAB group and 42 in OPCAB group. In ONCAB group the initial and final mean of LVEF was respectively 59.85% and 56.16% (p=0.10). In OPCAB group the initial and final mean of LVEF was respectively 59.18 % and 56.07 (p=0.17). Conclusion There was no difference in the evolution of LVEF among patients with stable CAD randomized to ONCAB or OPCAB in a 5-year follow-up. ACC Moderated Poster Contributions McCormick Place South, Hall A Monday, March 26, 2012, 9:30 a.m.-10:30 a.m. Session Title: Fresh CABG: Good for SIHD? Abstract Category: 3. Chronic CAD/Stable Ischemic Heart Disease: Therapy Presentation Number: 1208-409conferenceObject DIRECT COMPARISON BETWEEN TWO HYPOGLYCEMIC AGENTS: EFFECTS ON MYOCARDIAL ISCHEMIC PRECONDITIONING IN DIABETIC PATIENTS WITH SYMPTOMATIC CORONARY DISEASE(2012) GARCIA, Rosa Maria Rahmi; HUEB, Whady; UCHIDA, Augusto; REZENDE, Paulo Cury; MOFFA, Paulo Jorge; GARZILLO, Cibele Larrosa; LIMA, Eduardo; SOARES, Paulo; RAMIRES, Jose; KALIL-FILHO, RobertoIntroduction It is well known that hypoglycemic agents (sulfonylureas and Glinides) can have direct effects on ischemic preconditioning (IPC) because of the effect on the extrapancreatic ATP-dependent K+ channels. Some hypoglycemic drugs can abolish the IPC, affecting the infarct size and contractile function contributing to a worse prognosis. The Vildagliptin's mode of action is distinct from established antidiabetic medications. This study was performed to compare the effects of 2 hypoglycemic agents on myocardial IPC in patients with type 2 diabetes and multivessel coronary disease. Methods We evaluated 81 patients with type 2 diabetes, a positive exercise test and double and triple-vessel coronary disease confirmed by coronary angiography. Forty-two of these patients received repaglinide 2 mg, and 38 patients received Vildagliptin 100 mg (groups A and B, respectively). In phase I, all patients underwent 2 consecutive treadmill exercise tests (T1 and T2). The patients received hypoglycemic drugs for one week and underwent 2 more sequential tests (T3 and T4) during phase 2. The time interval between the exercise tests was 30 minutes. Results In phase 1, IPC was demonstrated by improvement in the time to 1 mm of ST segment depression (T-1.0mm). All patients developed myocardial ischemia in T3; however, 83.3% of patients in group A experienced myocardial ischemia earlier in T4, indicating the cessation of IPC (p<0.0001). In group B, only 28% of patients demonstrated IPC atenuation, with 72% still preserving the protective effect (p<0.0069). Conclusions These results show that Vildagliptin maintains myocardial IPC, while Repaglinide might be able to prevent it. This is of particular interest because we could demonstrate the safety of this new class of oral antidiabetic agents known as dipeptidyl peptidase IV inhibitors with respect to cardiovascular side effects ACC Moderated Poster Contributions McCormick Place South, Hall A Monday, March 26, 2012, 11:00 a.m.-Noon Session Title: Lipids, Hypertension, Hyperglycemia: New Tricks for Old Targets Abstract Category: 2. Chronic CAD/Stable Ischemic Heart Disease: Clinical Presentation Number: 1202-228