AUGUSTO HIROSHI UCHIDA
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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.
- 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.
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- 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.
conferenceObject 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: 1202-228conferenceObject Role of Hypoglycemic Agents on Ischemic Preconditioning in Diabetic Patients with Stable Multivessel Coronary Artery Disease(2012) GARCIA, Rosa M.; HUEB, Whady; UCHIDA, Augusto H.; REZENDE, Paulo C.; LIMA, Eduardo G.; GARZILLO, Cibele L.; SEGRE, Carlos A.; FAVARATO, Desiderio; RAMIRES, Jose A.; KALIL FILHO, Roberto- Effect of Hypoglycemic Agents on Ischemic Preconditioning in Patients With Type 2 Diabetes and Symptomatic Coronary Artery Disease(2013) RAHMI, Rosa Maria; UCHIDA, Augusto Hiroshi; REZENDE, Paulo Cury; LIMA, Eduardo Gomes; GARZILLO, Cibele Larrosa; FAVARATO, Desiderio; STRUNZ, Celia M. C.; TAKIUTI, Myrthes; GIRARDI, Priscyla; HUEB, Whady; KALIL FILHO, Roberto; RAMIRES, Jose A. F.OBJECTIVE-To assess the effect of two hypoglycemic drugs on ischemic preconditioning (IPC) patients with type 2 diabetes and coronary artery disease (CAD). RESEARCH DESIGN AND METHODS-We performed a prospective study of 96 consecutive patients allocated into two groups: 42 to group repaglinide (R) and 54 to group vildagliptin (V). All patients underwent two consecutive exercise tests (ET1 and ET2) in phase 1 without drugs. In phase 2, 1 day after ET1 and -2, 2 mg repaglinide three times daily or 50 mg vildagliptin twice daily was given orally to patients in the respective group for 6 days. On the seventh day, 60 min after 6 mg repaglinide or 100 mg vildagliptin, all patients underwent two consecutive exercise tests (ET3 and ET4). RESULTS-In phase 1, IPC was demonstrated by improvement in the time to 1.0 mm ST-segment depression and rate pressure product (RPP). All patients developed ischemia in ET3; however, 83.3% of patients in group R experienced ischemia earlier in ET4, without significant improvement in RPP, indicating the cessation of IPC (P < 0.0001). In group V. only 28% of patients demonstrated IPC cessation, with 72% still having the protective effect (P < 0.0069). CONCLUSIONS-Repaglinide eliminated myocardial IPC, probably by its effect on the K-ATP channel. Vildagliptin did not damage this protective mechanism in a relevant way in patients with type 2 diabetes and CAD, suggesting a good alternative treatment in this population.
conferenceObject Prognostic Value of Exercise Stress Testing in Patients With Multivessel Coronary Disease Undergoing Medicine, Angioplasty or Surgery: 10-year Follow-Up of the Mass II Trial(2013) GARZILLO, Cibele L.; REZENDE, Paulo C.; LIMA, Eduardo G.; UCHIDA, Augusto H.; SANTOS, Cibelle D.; CESAR, Luiz A.; COSTA, Leandro M.; HUEB, Whady; RAMIRES, Jose A.; KALIL FILHO, Roberto- Effect of ischemic preconditioning on cardiovascular outcomes in patients with symptomatic coronary artery disease: a cohort study(2019) RAHMI, Rosa M.; HUEB, Whady; REZENDE, Paulo C.; GARZILLO, Cibele L.; UCHIDA, Augusto H.; SCUDELER, Thiago L.; RAMIRES, Jose A. F.; FILHO, Roberto K.Background Despite the powerful myocardial protection of ischemic preconditioning (IP) observed in experimental studies, it remains a challenge to observe such protection in humans. Thus, the aim of this study was to evaluate the possible effects of IP on clinical outcomes in patients with coronary artery disease (CAD). Patients and methods In this cohort study, patients with multivessel CAD, preserved systolic ventricular function, and stable angina were prospectively selected. They underwent two sequential exercise stress tests (EST) to evaluate IP presence. IP was considered present if patients had an improvement in the time to the onset of 1.0-mm STsegment deviation in the second EST. The primary end point was the composite rate of cardiac death, nonfatal myocardial infarction, or revascularization during 1-year follow-up. Patients with (IP+) and without (IP-) the cardioprotective mechanism were compared regarding clinical end points. Results A total of 229 patients completed EST and had IP evaluated: 165 (72%) were IP+ and 64 (28%) were IP - patients. Of these, 218 patients had complete follow-up. At 1-year, event-free survival regarding the primary end point was 95.5 versus 83.6% (P = 0.0024) and event-free survival regarding cardiac death or myocardial infarction was 99.4 versus 91.7% (P=0.0020), respectively, in IP + and IP - groups. The unadjusted hazard ratio (IP + /IP-) for the primary end point was 4.63 (1.52-14.08). After multivariate analysis, IP was still significantly associated with better clinical outcomes (P = 0.0025). Conclusion This data suggest that IP may contribute to better clinical outcomes in patients with ischemic heart disease.