Augusto Hiroshi Uchida

The Effects of Glibenclamide, a KATP Channel Blocker, on the Warm-Up Phenomenon

Background: The warm‐up phenomenon observed after the second of two sequential exercise tests is characterized by an increased time to ischemia and ischemic threshold, and the latter is related to ischemic preconditioning. Previous studies have demonstrated that a single dose of glibenclamide, a cardiac ATP‐sensitive K (KATP) channel blocker, prevents ischemic preconditioning. This study aimed to investigate the effects of chronic treatment with glibenclamide during two sequential exercise tests.

Effect of Hypoglycemic Agents on Ischemic Preconditioning in Patients With Type 2 Diabetes and Symptomatic Coronary Artery Disease

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 KATP 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.

Electrovectorcardiographic Diagnosis of Left Septal Fascicular Block: Anatomic and Clinical Considerations

Several publications considering anatomical, histological, pathological, electrocardiographic, vectorcardiographic, and electrophysiologic studies have shown that the left bundle branch splits into three fascicles or in a “fan‐like interconnected network” in the vast majority of human hearts. The left His system is trifascicular with a left anterior, a left posterior, and a left septal fascicle (LSF). Consequently, the classic term “hemiblock,” to describe the block of one of the fascicles, established several decades ago by the Rosembaums school, should be updated.

Wellens syndrome associated with prominent anterior QRS forces: an expression of left septal fascicular block?

Wellens syndrome is a clinical-electrocardiographic entity also referred to as left anterior descending (LAD) coronary T-wave syndrome or acute coronary T-wave syndrome. It is a complex of symptoms and signals indicating the existence of an undesirable condition secondary to critical high-grade proximal stenosis of the LAD coronary artery characterized by the association of prior history of acute coronary syndrome with little or no elevation of markers of myocardial damage (unstable angina) and characteristic electrocardiographic changes consistent with subepicardial anterior ischemic pattern (persistently symmetrical, deep negative and broad-based T waves) or plus-minus T waves with inversion of the terminal portion in the LAD coronary artery territory (V1 through V5 or V6). We present a case of a variant of Wellens syndrome that reveals association and, transitorily, the criteria described in literature for left septal fascicular block.

Electrocardiographic score: application in exercise test for the assessment of ischemic preconditioning

FUNDAMENTO: O tempo para 1,0 mm de depressao do segmento ST (T-1,0 mm), adotado para caracterizar o precondicionamento isquemico (PCI) em testes ergometricos sequenciais, e consistente e reprodutivel, porem, possui varias limitacoes. OBJETIVO: Aplicar um escore eletrocardiografico de isquemia miocardica em testes ergometricos sequenciais, comparando-o com o classico indice T-1,0 mm. METODOS: Avaliamos 61 pacientes, com idade media de 62,2 ± 7,5 anos, sendo 86,9% homens. Foram analisados 151 exames, sendo 116 de pacientes que completaram duas fases de avaliacao. A primeira fase compreendia dois testes ergometricos sequenciais para documentacao do PCI e a segunda fase, apos uma semana, mais dois testes sob efeito de repaglinida. Dois observadores aplicaram o escore de forma cega. RESULTADOS: Observou-se concordância perfeita inter e intraobservador (Kendall Tau-b = 0,96, p < 0,0001, Kendall Tau-b = 0,98,p < 0,0001, respectivamente). Os valores de sensibilidade, especificidade, valor preditivo negativo, valor preditivo positivo e acuracia foram de 72,41%, 89,29%, 75,8%, 87,5% e 81,0%, respectivamente. CONCLUSAO: O escore de isquemia e um metodo consistente e reprodutivel para documentacao do PCI, representando uma alternativa factivel ao indice T-1,0 mm.BACKGROUND the time for 1.0 mm ST-segment depression (T-1.0mm) adopted to characterize ischemic preconditioning (IPC) in sequential exercise tests is consistent and reproducible; however, it has several limitations. OBJECTIVE to apply an electrocardiographic score of myocardial ischemia in sequential exercise tests, comparing it to the conventional T-1.0 mm index. METHODS sixty one patients with mean age of 62.2 ± 7.5 years were evaluated; 86.9% were males. A total of 151 tests were analyzed, 116 of which were from patients who completed two assessment phases. The first phase comprised two sequential exercise tests for the documentation of IPC; the second phase, initiated one week later, comprised two more tests carried out under the effect of repaglinide. Two observers who were blind to the tests applied the score. RESULTS Perfect inter and intraobserver agreement was found (Kendall tau-b = 0.96, p < 0.0001, and Kendall tau-b = 0.98, p < 0.0001, respectively). Values of sensitivity and specificity, negative predictive value, positive predictive value and accuracy were 72.41%, 89.29%, 75.8%, 87.5% and 81.0%, respectively. CONCLUSION the ischemic score is a consistent and reproducible method for the documentation of IPC, and is a feasible alternative to T-1.0 mm.

O eletrocardiograma de alta resolução da ativação atrial em pacientes com ou sem fibrilação atrial paroxística

OBJECTIVE: To analyze the parameters of the time domain P-wave signal-averaged electrocardiogram (P-SAECG) and compare them with the P-wave duration on the conventional electrocardiogram (P on ECG) as well as the left atrium diameter (LAD) and left ventricular ejection fraction (EF) obtained on the echocardiogram in order to evaluate patients with paroxysmal atrial fibrillation (PAF). METHODS: One hundred and eighty-one patients were included in the study: 117 with confirmed PAF and 64 without PAF. The P-SAECG parameters used were: the filtered P-wave duration (FPD), the root mean square (RMS) voltages in the last 40, 30 and 20 ms of the filtered P-wave (RMS 40, RMS 30 and RMS 20), the root mean square voltage of the filtered P-wave potentials (RMS P), the integral of the potentials during the filtered P-wave (Integral P) and the filtered P-wave late potential durations below 3 µV (PL<3). RESULTS: The parameters that presented significant statistical differences between the groups were: FPD, RMS 40, 30 and 20, PL<3, P on ECG and LAD. The ROC curve calculations demonstrated the best cut-off points and performance estimates for each parameter: sensitivity, specificity, area under the curve and p-value (p). CONCLUSION: The time domain P-SAECG proved to be a superior method to identify patients with paroxysmal atrial fibrillation than the conventional electrocardiogram and echocardiogram.

Escore eletrocardiográfico: aplicação em ergometria para avaliação do precondicionamento isquêmico

FUNDAMENTO: O tempo para 1,0 mm de depressao do segmento ST (T-1,0 mm), adotado para caracterizar o precondicionamento isquemico (PCI) em testes ergometricos sequenciais, e consistente e reprodutivel, porem, possui varias limitacoes. OBJETIVO: Aplicar um escore eletrocardiografico de isquemia miocardica em testes ergometricos sequenciais, comparando-o com o classico indice T-1,0 mm. METODOS: Avaliamos 61 pacientes, com idade media de 62,2 ± 7,5 anos, sendo 86,9% homens. Foram analisados 151 exames, sendo 116 de pacientes que completaram duas fases de avaliacao. A primeira fase compreendia dois testes ergometricos sequenciais para documentacao do PCI e a segunda fase, apos uma semana, mais dois testes sob efeito de repaglinida. Dois observadores aplicaram o escore de forma cega. RESULTADOS: Observou-se concordância perfeita inter e intraobservador (Kendall Tau-b = 0,96, p < 0,0001, Kendall Tau-b = 0,98,p < 0,0001, respectivamente). Os valores de sensibilidade, especificidade, valor preditivo negativo, valor preditivo positivo e acuracia foram de 72,41%, 89,29%, 75,8%, 87,5% e 81,0%, respectivamente. CONCLUSAO: O escore de isquemia e um metodo consistente e reprodutivel para documentacao do PCI, representando uma alternativa factivel ao indice T-1,0 mm.BACKGROUND the time for 1.0 mm ST-segment depression (T-1.0mm) adopted to characterize ischemic preconditioning (IPC) in sequential exercise tests is consistent and reproducible; however, it has several limitations. OBJECTIVE to apply an electrocardiographic score of myocardial ischemia in sequential exercise tests, comparing it to the conventional T-1.0 mm index. METHODS sixty one patients with mean age of 62.2 ± 7.5 years were evaluated; 86.9% were males. A total of 151 tests were analyzed, 116 of which were from patients who completed two assessment phases. The first phase comprised two sequential exercise tests for the documentation of IPC; the second phase, initiated one week later, comprised two more tests carried out under the effect of repaglinide. Two observers who were blind to the tests applied the score. RESULTS Perfect inter and intraobserver agreement was found (Kendall tau-b = 0.96, p < 0.0001, and Kendall tau-b = 0.98, p < 0.0001, respectively). Values of sensitivity and specificity, negative predictive value, positive predictive value and accuracy were 72.41%, 89.29%, 75.8%, 87.5% and 81.0%, respectively. CONCLUSION the ischemic score is a consistent and reproducible method for the documentation of IPC, and is a feasible alternative to T-1.0 mm.

Role of Trimetazidine in Ischemic Preconditioning in Patients With Symptomatic Coronary Artery Disease.

AbstractIschemic 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 35 mg 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-1.0 mm) and rate pressure product (RPP) were greater in the second of 2 tests. The improvement in T-1.0 mm 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-1.0 mm 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.

Avaliação prognóstica da doença coronária estável através de um novo escore

FUNDAMENTO: A necessidade de melhorar a acuracia do teste de esforco, determinou o desenvolvimento de escores, cuja aplicabilidade ja foi amplamente reconhecida. OBJETIVO: Avaliacao prognostica do coronariopata estavel atraves de um novo escore simplificado. METODOS: Um novo escore foi aplicado em 372 coronariopatas multiarteriais e funcao ventricular preservada, 71,8% homens, idade media 59,5 (± 9,07) anos, randomizados para angioplastia, revascularizacao cirurgica e tratamento clinico, acompanhados por 5 anos. Obito cardiovascular foi o desfecho primario. Infarto do miocardio nao-fatal, obito e re-intervencao formaram o desfecho combinado secundario. O escore baseou-se numa equacao previamente validada resultante da soma de 1 ponto para: sexo masculino, historia de infarto, angina, diabete, uso de insulina e ainda 1 ponto para cada decada de vida a partir dos 40 anos. Teste positivo adicionou 1 ponto. RESULTADOS: Ocorreram 36 obitos (10 no grupo angioplastia, 15 no grupo revascularizacao e 11 no grupo clinico), p = 0,61. Observou-se 93 eventos combinados: 37 no grupo angioplastia, 23 no grupo revascularizacao e 33 no grupo clinico (p = 0,058). 247 pacientes apresentaram escore clinico > 5 pontos e 216 > 6 pontos. O valor de corte > 5 ou > 6 pontos identificou maior risco, com p = 0,015 e p = 0,012, respectivamente. A curva de sobrevida mostrou uma incidencia de obito apos a randomizacao diferente naqueles com escore > 6 pontos (p = 0,07), e uma incidencia de eventos combinados diferente entre pacientes com escore 6 pontos (p = 0,02). CONCLUSAO: O novo escore demonstrou consistencia na avaliacao prognostica do coronariopata estavel multiarterial.BACKGROUND The need to improve the exercise testing accuracy, pushed the development of scores, whose applicability was already broadly recognized. OBJECTIVE Prognostic evaluation of stable coronary disease through a new simplified score. METHODS A new score was applied in 372 multivessel coronary patients with preserved ventricular function, 71.8% male, age: 59.5 (± 9.07) years old, randomized to medical treatment, surgery (CABG) or angioplasty (PTCA), with 5 years of follow-up. Cardiovascular death was considered the primary endpoint. Non-fatal myocardial infarction, death and re-intervention were considered for a combined secondary endpoint. The score was based on an equation previously validated, resulting from a sum of one point for: male gender, infarction history, angina, diabetes, insulin use and one point for each decade of life after 40 years old. Positive exercise testing summed one additional point. RESULTS Thirty six deaths was observed (10 in group PTCA, 15 in CABG and 11 in the clinical group), p = 0.61. We observed 93 combined events: 37 in PTCA group, 23 in CABG and 33 in the clinical group (p = 0.058). 247 patients presented clinical score ≥ 5 points and 216 ≥ 6 points. The cutoff point ≥ 5 or ≥ 6 points identified higher risk, p = 0.015 and p = 0.012, respectively. The survival curve showed a different death incidence after the randomization when score reached 06 points or more (p = 0.07), and a distinct incidence of combined events between the patients with score < 6 and ≥ 6 points (p = 0.02). CONCLUSION The new score was consistent for multiarterial stable coronary disease risk stratification.

New prognostic score for stable coronary disease evaluation

FUNDAMENTO: A necessidade de melhorar a acuracia do teste de esforco, determinou o desenvolvimento de escores, cuja aplicabilidade ja foi amplamente reconhecida. OBJETIVO: Avaliacao prognostica do coronariopata estavel atraves de um novo escore simplificado. METODOS: Um novo escore foi aplicado em 372 coronariopatas multiarteriais e funcao ventricular preservada, 71,8% homens, idade media 59,5 (± 9,07) anos, randomizados para angioplastia, revascularizacao cirurgica e tratamento clinico, acompanhados por 5 anos. Obito cardiovascular foi o desfecho primario. Infarto do miocardio nao-fatal, obito e re-intervencao formaram o desfecho combinado secundario. O escore baseou-se numa equacao previamente validada resultante da soma de 1 ponto para: sexo masculino, historia de infarto, angina, diabete, uso de insulina e ainda 1 ponto para cada decada de vida a partir dos 40 anos. Teste positivo adicionou 1 ponto. RESULTADOS: Ocorreram 36 obitos (10 no grupo angioplastia, 15 no grupo revascularizacao e 11 no grupo clinico), p = 0,61. Observou-se 93 eventos combinados: 37 no grupo angioplastia, 23 no grupo revascularizacao e 33 no grupo clinico (p = 0,058). 247 pacientes apresentaram escore clinico > 5 pontos e 216 > 6 pontos. O valor de corte > 5 ou > 6 pontos identificou maior risco, com p = 0,015 e p = 0,012, respectivamente. A curva de sobrevida mostrou uma incidencia de obito apos a randomizacao diferente naqueles com escore > 6 pontos (p = 0,07), e uma incidencia de eventos combinados diferente entre pacientes com escore 6 pontos (p = 0,02). CONCLUSAO: O novo escore demonstrou consistencia na avaliacao prognostica do coronariopata estavel multiarterial.BACKGROUND The need to improve the exercise testing accuracy, pushed the development of scores, whose applicability was already broadly recognized. OBJECTIVE Prognostic evaluation of stable coronary disease through a new simplified score. METHODS A new score was applied in 372 multivessel coronary patients with preserved ventricular function, 71.8% male, age: 59.5 (± 9.07) years old, randomized to medical treatment, surgery (CABG) or angioplasty (PTCA), with 5 years of follow-up. Cardiovascular death was considered the primary endpoint. Non-fatal myocardial infarction, death and re-intervention were considered for a combined secondary endpoint. The score was based on an equation previously validated, resulting from a sum of one point for: male gender, infarction history, angina, diabetes, insulin use and one point for each decade of life after 40 years old. Positive exercise testing summed one additional point. RESULTS Thirty six deaths was observed (10 in group PTCA, 15 in CABG and 11 in the clinical group), p = 0.61. We observed 93 combined events: 37 in PTCA group, 23 in CABG and 33 in the clinical group (p = 0.058). 247 patients presented clinical score ≥ 5 points and 216 ≥ 6 points. The cutoff point ≥ 5 or ≥ 6 points identified higher risk, p = 0.015 and p = 0.012, respectively. The survival curve showed a different death incidence after the randomization when score reached 06 points or more (p = 0.07), and a distinct incidence of combined events between the patients with score < 6 and ≥ 6 points (p = 0.02). CONCLUSION The new score was consistent for multiarterial stable coronary disease risk stratification.