ROSA MARIA RAHMI GARCIA
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- Role of Trimetazidine in Ischemic Preconditioning in Patients With Symptomatic Coronary Artery Disease(2015) COSTA, Leandro M. A.; REZENDE, Paulo C.; GARCIA, Rosa M. R.; UCHIDA, Augusto H.; SEGURO, Luis Fernando B. C.; SCUDELER, Thiago L.; BOCCHI, Edimar A.; KRIEGER, Jose E.; HUEB, Whady; RAMIRES, Jose Antonio F.; KALIL FILHO, RobertoIschemic preconditioning (IP) is a powerful cardioprotective cellular mechanism that has been related to the warm-up phenomenon or walk-through angina, and has been documented through the use of sequential exercise tests (ETs). It is known that several drugs, for example, cromokalim, pinacidil, adenosine, and nicorandil, can interfere with the cellular pathways of IP. The purpose of this article is to report the effect of the anti-ischemic agent trimetazidine (TMZ) on IP in symptomatic coronary artery disease (CAD) patients.We conducted a prospective study evaluating IP by the analysis of ischemic parameters in 2 sequential ETs. In phase I, without TMZ, patients underwent ET1 and ET2 with a 30-minute interval between them. In phase II, after 1 week of TMZ 35mg twice daily, all patients underwent 2 consecutive ETs (ET3 and ET4). IP was considered present when the time to 1.0-mm segment ST on electrocardiogram deviation (T-1.0mm) and rate pressure product (RPP) were greater in the second of 2 tests. The improvement in T-1.0mm and RPP were compared in the 2 phases: without TMZ and after 1-week TMZ to assess the action of such drug in myocardial protective mechanisms. ETs were analyzed by 2 independent cardiologists.From 135 CAD patients screened, 96 met inclusion criteria and 62 completed the study protocol. Forty patients manifested IP by demonstrating an improvement in T-1.0mm in ET2 compared with ET1, without the use of any drugs (phase I). In phase II, after 1-week TMZ, 26 patients (65%) did not show any incremental result in ischemic parameters in ET4 compared with ET3. Furthermore, of these patients, 8 (20%) had IP blockage.In this study, TMZ did not add any benefit to IP in patients with stable symptomatic CAD.
- 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.
conferenceObject Expression of Ischemic Preconditioning in Patients With Stable Multivessel Coronary Artery Disease With and Without Diabetes Mellitus(2013) REZENDE, Paulo C.; GARCIA, Rosa M.; UCHIDA, Augusto H.; LIMA, Eduardo G.; GARZILLO, Cibele L.; SEGRE, Carlos A.; CESAR, Luiz A.; HUEB, Whady; RAMIRES, Jose A.; KALIL FILHO, Roberto- 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.
conferenceObject Impact of Chronic Kidney Dysfunction Among Patients With Stable Coronary Artery Disease: Ten-Year Follow-Up of Mass II Trial(2016) LIMA, Eduardo G.; HUEB, Whady; GARZILLO, Cibele L.; FAVARATO, Desiderio; HUEB, Alexandre C.; REZENDE, Paulo C.; SILVA, Expedito E.; GARCIA, Rosa M.; SCUDELER, Thiago L.; RAMIRES, Jose A.; KALIL FILHO, Roberto- 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.