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1.  Conservative strategy for treatment of stable coronary artery disease 
Patients with coronary artery disease vary widely in terms of prognosis, which is mainly dependent on ventricular function. In relation to the major outcomes of death and myocardial infarction, it is not clear in the literature if an invasive strategy of myocardial revascularization is superior to a conservative strategy of optimized medical therapy. Moreover, with the exception of patients with left main coronary disease, this similarity in prognosis also occurs in different subgroups of patients.
doi:10.12998/wjcc.v3.i2.163
PMCID: PMC4317610
Coronary artery disease; Angina pectoris; Myocardial revascularization; Coronary angioplasty; Myocardial infarction; Prognosis; Disease-free survival
2.  Impact of hypoglycemic agents on myocardial ischemic preconditioning 
World Journal of Diabetes  2014;5(3):258-266.
Murry et al in 1986 discovered the intrinsic mechanism of profound protection called ischemic preconditioning. The complex cellular signaling cascades underlying this phenomenon remain controversial and are only partially understood. However, evidence suggests that adenosine, released during the initial ischemic insult, activates a variety of G protein-coupled agonists, such as opioids, bradykinin, and catecholamines, resulting in the activation of protein kinases, especially protein kinase C (PKC). This leads to the translocation of PKC from the cytoplasm to the sarcolemma, where it stimulates the opening of the ATP-sensitive K+ channel, which confers resistance to ischemia. It is known that a range of different hypoglycemic agents that activate the same signaling cascades at various cellular levels can interfere with protection from ischemic preconditioning. This review examines the effects of several hypoglycemic agents on myocardial ischemic preconditioning in animal studies and clinical trials.
doi:10.4239/wjd.v5.i3.258
PMCID: PMC4058730  PMID: 24936247
Ischemic preconditioning; Myocardial ischemia; Coronary artery disease; Hypoglycemic agents; Diabetes mellitus
3.  A case of mid-apical obstructive hypertrophic cardiomyopathy treated with a transapical myectomy approach: a case report 
Introduction
Hypertrophic cardiomyopathy is a genetic cardiac disease characterized by marked variability in morphological expression and natural history. The hypertrophic myocardium is often confined to the septum or lateral wall of the left ventricle, but it can also be encountered in the middle or apical segments of the myocardium. Treatment is based on medical therapy. Others therapies, such as embolization of the septal artery or ventriculomyectomy, are indicated in special situations. Surgery is the standard treatment, and it is classically done via a transaortic approach; however, in cases in which the hypertrophic myocardium is confined to mid-apical segments, a transapical approach is an option. Only a few cases of mid-apical obstructive hypertrophic cardiomyopathy treated with a myectomy using a transapical approach have been reported in the English-language literature. In this report, we present a case of a patient with mid-apical obstructive hypertrophic cardiomyopathy treated using this new approach.
Case presentation
A 63-year-old Caucasian woman presented with a history of chest pain and shortness of breath causing significant limitations on her daily life activities. She had a history of coronary artery disease. Her physical examination was unremarkable. Transthoracic echocardiography revealed normal systolic function and significant concentric left ventricular hypertrophy that was greater in the mid-apical region. Nuclear magnetic resonance imaging confirmed significant hypertrophy of the median segments of the left ventricle. The patient had persistent symptoms despite receiving optimized medical treatment, and a surgical approach was indicated. As a myectomy using transaortic technique was thought to be difficult to perform in her case, a transapical approach was used. No complications occurred, and her symptoms resolved.
Conclusion
A transapical myectomy should be taken into consideration for patients with mid-apical obstructive hypertrophic cardiomyopathy that is refractory to medical treatment.
doi:10.1186/1752-1947-8-364
PMCID: PMC4232228  PMID: 25384531
Hypertrophic cardiomyopathy; Surgery; Transapical myectomy
4.  On-pump versus off-pump coronary artery bypass surgery in patients older than 60 years: five-year follow-up of MASS III trial 
Background
We aim to evaluate in-hospital events and long-term clinical outcomes in patients over 60 years of age with stable coronary artery disease and preserved left ventricular ejection fraction undergoing off-pump or on-pump coronary artery bypass grafting.
Methods
The MASS III was a single-center randomized trial that evaluate 308 patients with stable coronary artery disease and preserved ventricular function assigned for: 155 to off-pump and 153 to on-pump CABG. Of this, 176 (58.3%) patients were 60 years or older at the time of randomization (90 of-pump and 86 on-pump). The primary short-term end point was a composite of myocardial infarction, stroke, and overall mortality occurring within 30 days after surgery or before discharge, whichever was later. The primary long-term end point was death from any cause within 5 years, non-fatal myocardial infarction between 30 days and 5 years, or additional revascularization between 30 days and 5 years.
Results
On-pump CABG had a higher incidence of 30-day composite outcome than off-pump CABG (15,1% and 5.6%, respectively; P = 0.036). However, after the multivariate analysis, this association lost statistical significance, P = 0.05. After 5-year follow-up, there were no significant differences between both strategies of CABG in the composite end points 16.7% and 15.1%; Hazard Ratio 1.07; CI 0.41 – 1.82; P = 0.71, for off-pump and on-pump CABG respectively.
Conclusions
On-pump and off-pump CABG achieved similar results of combined events at short-term and 5-year follow-up.
Trial registration
Clinical Trial Registration Information—URL: http://www.controlled-trials.com. Registration number: ISRCTN59539154.
doi:10.1186/1749-8090-9-136
PMCID: PMC4304776  PMID: 25096030
Coronary artery disease; Coronary artery bypass grafts; CABG; Cardiopulmonary bypass; CPB
5.  Effect of Hypoglycemic Agents on Ischemic Preconditioning in Patients With Type 2 Diabetes and Symptomatic Coronary Artery Disease 
Diabetes Care  2013;36(6):1654-1659.
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.
doi:10.2337/dc12-1495
PMCID: PMC3661846  PMID: 23250803
6.  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 
Background
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.
doi:10.1186/1471-2261-13-117
PMCID: PMC4029531  PMID: 24330253
Ischemic preconditioning; Exercise test; Coronary heart disease; Angina; Myocardial ischemia
7.  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 
Background
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.
doi:10.1186/1471-2261-12-65
PMCID: PMC3468382  PMID: 22898311
Cardiopulmonary bypass; Necrosis markers; Myocardial infarction; PCI; CABG

Results 1-7 (7)