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1.  Alterations in lipid transfers to HDL associated with the presence of coronary artery disease in patients with type 2 diabetes mellitus 
We previously showed that unesterified-cholesterol transfer to high-density lipoprotein (HDL), a crucial step in cholesterol esterification and role in reverse cholesterol transport, was diminished in non-diabetic patients with coronary artery disease (CAD). The aim was to investigate whether, in patients with type 2 diabetes mellitus (T2DM), the occurrence of CAD was also associated with alterations in lipid transfers and other parameters of plasma lipid metabolism.
Seventy-nine T2DM with CAD and 76 T2DM without CAD, confirmed by cineangiography, paired for sex, age (40–80 years), BMI and without statin use, were studied. In vitro transfer of four lipids to HDL was performed by incubating plasma of each patient with a donor emulsion containing radioactive lipids during 1 h at 37 °C. Lipids transferred to HDL were measured after chemical precipitation of non-HDL fractions and the emulsion. Results are expressed as % of total radioactivity of each lipid in HDL.
In T2DM + CAD, LDL-cholesterol and apo B were higher than in T2DM. T2DM + CAD also showed diminished transfer to HDL of unesterified cholesterol (T2DM + CAD = 7.6 ± 1.2; T2DM = 8.2 ± 1.5 %, p < 0.01) and of cholesteryl-esters (4.0 ± 0.6 vs 4.3 ± 0.7, p < 0.01). Unesterified cholesterol in the non-HDL serum fraction was higher in T2DM + CAD (0.93 ± 0.20 vs 0.85 ± 0.15, p = 0.02) and CETP concentration was diminished (2.1 ± 1.0 vs 2.5 ± 1.1, p = 0.02). Lecithin-cholesterol acyltransferase activity, HDL size and lipid composition were equal.
Reduction in T2DM + CAD of cholesterol transfer to HDL may impair cholesterol esterification and reverse cholesterol transport and altogether with simultaneous increased plasma unesterified cholesterol may facilitate CAD development in T2DM.
PMCID: PMC4535391  PMID: 26268997
Coronary artery disease; Type 2 diabetes; Lipid transfers; High-density lipoprotein; HDL; Nanoparticles; Cholesterol
2.  Troponin in diabetic patients with and without chronic coronary artery disease 
Cardiac-specific troponin detected with the new high-sensitivity assays can be chronically elevated in response to cardiovascular comorbidities and confer important prognostic information, in the absence of unstable coronary syndromes. Both diabetes mellitus and coronary artery disease are known predictors of troponin elevation. It is not known whether diabetic patients with coronary artery disease have different levels of troponin compared with diabetic patients with normal coronary arteries. To investigate this question, we determined the concentrations of a level 1 troponin assay in two groups of diabetic patients: those with multivessel coronary artery disease and those with angiographically normal coronary arteries.
We studied 95 diabetic patients and compared troponin in serum samples from 50 patients with coronary artery disease (mean age = 63.7, 58 % male) with 45 controls with angiographically normal coronary arteries. Brain natriuretic peptide and the oxidative stress biomarkers myeloperoxidase, nitrotyrosine and oxidized LDL were also determined.
Diabetic patients with coronary artery disease had higher levels of troponin than did controls (median values, 12.0 pg/mL (95 % CI:10–16) vs 7.0 pg/mL (95 % CI: 5.9-8.5), respectively; p = 0.0001). The area under the ROC curve for the diagnosis of CAD was 0.712 with a sensitivity of 70 % and a specificity of 66 %. Plasma BNP levels and oxidative stress variables (myeloperoxidase, nitrotyrosine, and oxidized LDL) were not different between the two groups. In a multivariate analysis, gender (p = 0.04), serum glucose (0.03) and Troponin I (p = 0.01) had independent statistical significance.
Troponin elevation is related to the presence of chronic coronary artery disease in diabetic patients with multiple associated cardiovascular risk factors. Troponin may serve as a biomarker in this high-risk population.
Trial registration Registration number:ISRCTN26970041
PMCID: PMC4508806  PMID: 26195004
Biological markers; Troponin; Diabetes mellitus; Coronary artery disease
3.  Type 2 diabetes mellitus and myocardial ischemic preconditioning in symptomatic coronary artery disease patients 
The influence of diabetes mellitus on myocardial ischemic preconditioning is not clearly defined. Experimental studies are conflicting and human studies are scarce and inconclusive.
Identify whether diabetes mellitus intervenes on ischemic preconditioning in symptomatic coronary artery disease patients.
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.
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).
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.
PMCID: PMC4451743  PMID: 26025451
Ischemic preconditioning; Myocardial ischemia; Coronary artery disease; Diabetes mellitus
4.  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.
PMCID: PMC4317610  PMID: 25685763
Coronary artery disease; Angina pectoris; Myocardial revascularization; Coronary angioplasty; Myocardial infarction; Prognosis; Disease-free survival
5.  A case of mid-apical obstructive hypertrophic cardiomyopathy treated with a transapical myectomy approach: a case report 
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.
A transapical myectomy should be taken into consideration for patients with mid-apical obstructive hypertrophic cardiomyopathy that is refractory to medical treatment.
PMCID: PMC4232228  PMID: 25384531
Hypertrophic cardiomyopathy; Surgery; Transapical myectomy
6.  On-pump versus off-pump coronary artery bypass surgery in patients older than 60 years: five-year follow-up of MASS III trial 
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.
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.
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.
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: Registration number: ISRCTN59539154.
PMCID: PMC4304776  PMID: 25096030
Coronary artery disease; Coronary artery bypass grafts; CABG; Cardiopulmonary bypass; CPB
7.  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.
PMCID: PMC4058730  PMID: 24936247
Ischemic preconditioning; Myocardial ischemia; Coronary artery disease; Hypoglycemic agents; Diabetes mellitus
8.  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.
To assess the effect of two hypoglycemic drugs on ischemic preconditioning (IPC) patients with type 2 diabetes and coronary artery disease (CAD).
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).
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).
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.
PMCID: PMC3661846  PMID: 23250803
9.  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 
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.
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.
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.
PMCID: PMC4029531  PMID: 24330253
Ischemic preconditioning; Exercise test; Coronary heart disease; Angina; Myocardial ischemia
10.  Factors Related to the Selection of Surgical versus Percutaneous Revascularization in Diabetic Patients with Multivessel Coronary Artery Disease in the BARI 2D Trial 
We evaluated demographic, clinical and angiographic factors influencing the selection of coronary artery bypass graft (CABG) surgery versus percutaneous coronary intervention (PCI) in diabetic patients with multivessel coronary artery disease (CAD) in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.
Factors guiding selection of mode of revascularization for patients with DM and multivessel CAD are not clearly defined.
In BARI 2D, the selected revascularization strategy, CABG or PCI, was based on physician discretion, declared independent of randomization to either immediate or deferred revascularization if clinically warranted. We analyzed factors favoring selection of CABG versus PCI in 1593 diabetic patients with multivessel CAD enrolled between 2001 and 2005.
Selection of CABG over PCI was declared in 44% of patients and was driven by angiographic factors including: triple vessel disease (OR=4.43), left anterior descending (LAD) stenosis ≥70% (OR=2.86), proximal LAD stenosis ≥50% (OR=1.78), total occlusion (OR=2.35), and multiple class C lesions (OR=2.06), (all p< 0.005). Non-angiographic predictors of CABG included: age ≥ 65 years (OR=1.43, p=0.011), and non-US region (OR=2.89, p=0.017). Absence of prior PCI (OR=0.45, p<0.001), and the availability of drug-eluting stents (DES) conferred a lower probability of choosing CABG (OR=0.60, p=0.003).
The majority of diabetic patients with multivessel disease were selected for PCI rather than CABG. Preference for CABG over PCI was largely based on angiographic features related to the extent, location, and nature of CAD, as well as geographic, demographic and clinical factors.
PMCID: PMC3625397  PMID: 19463459
Revascularization selection; Diabetes; Percutaneous Coronary Intervention; Coronary Artery Bypass Graft
11.  Association between UCP2 A55V polymorphism and risk of cardiovascular events in patients with multi-vessel coronary arterial disease 
BMC Medical Genetics  2013;14:40.
UCP2 (uncoupling protein 2) plays an important role in cardiovascular diseases and recent studies have suggested that the A55V polymorphism can cause UCP2 dysfunction. The main aim was to investigate the association of A55V polymorphism with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease and preserved left ventricular function.
The participants of the MASS II were genotyped for the A55V polymorphism using allele-specific PCR assay. Survival curves were calculated with the Kaplan–Meier method and evaluated with the log-rank statistic. The relationship between baseline variables and the composite end-point of cardiac death, acute myocardial infarction (AMI), refractory angina requiring revascularization and cerebrovascular accident were assessed using a Cox proportional hazards survival model.
There were no significant differences for baseline variables according genotypes. After 2 years of follow-up, dysglycemic patients harboring the VV genotype had higher occurrence of AMI (p=0.026), Death+AMI (p=0.033), new revascularization intervention (p=0.009) and combined events (p=0.037) as compared with patients carrying other genotypes. This association was not evident in normoglycemic patients.
These findings support the hypothesis that A55V polymorphism is associated with UCP2 functional alterations that increase the risk of cardiovascular events in patients with previous coronary artery disease and dysglycemia.
PMCID: PMC3621277  PMID: 23537071
UCP2; A55V polymorphism; Coronary artery disease; Diabetes
12.  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 
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.
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.
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.
PMCID: PMC3468382  PMID: 22898311
Cardiopulmonary bypass; Necrosis markers; Myocardial infarction; PCI; CABG
13.  Higher incidence of death in multi-vessel coronary artery disease patients associated with polymorphisms in chromosome 9p21 
We investigated whether 9p21 polymorphisms are associated with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function.
The participants of the MASS II were genotyped for 9p21 polymorphisms (rs10757274, rs2383206, rs10757278 and rs1333049). Survival curves were calculated with the Kaplan–Meier method and compared with the log-rank statistic. We assessed the relationship between baseline variables and the composite end-point of death, death from cardiac causes and myocardial infarction using a Cox proportional hazards survival model.
We observed significant differences between patients within each polymorphism genotype group for baseline characteristics. The frequency of diabetes was lower in patients carrying GG genotype for rs10757274, rs2383206 and rs10757278 (29.4%, 32.8%, 32.0%) compared to patients carrying AA or AG genotypes (49.1% and 39.2%, p = 0.01; 52.4% and 40.1%, p = 0.01; 47.8% and 37.9%, p = 0.04; respectively).
Significant differences in genotype frequencies between double and triple vessel disease patients were observed for the rs10757274, rs10757278 and rs1333049. Finally, there was a higher incidence of overall mortality in patients with the GG genotype for rs2383206 compared to patients with AA and AG genotypes (19.5%, 11.9%, 11.0%, respectively; p = 0.04). Moreover, the rs2383206 was still significantly associated with a 1.75-fold increased risk of overall mortality (p = 0.02) even after adjustment of a Cox multivariate model for age, previous myocardial infarction, diabetes, smoking and type of coronary anatomy.
Our data are in accordance to previous evidence that chromosome 9p21 genetic variation may constitute a genetic modulator in the cardiovascular system in different scenarios. In patients with established CAD, we observed an association between the rs2383206 and higher incidence of overall mortality and death from cardiac causes in patients with multi-vessel CAD.
PMCID: PMC3469382  PMID: 22856518
Coronary artery disease; Polymorphism; Genetics; Chromosome 9p21
14.  Teratoma of the mediastinum: a case report 
This case report illustrates a rare case of teratoma of the mediastinum which was continuous to the pericardium and caused extrinsic compression to the right atrium.
Case presentation
A 22-year-old Caucasian man with no complaints or comorbid conditions presented to our hospital with obliteration of the right cardiophrenic sinus by a mass. A non-invasive investigation demonstrated a tumoral mass which was continuous to the pericardium and caused extrinsic compression to the right atrium. The clinical suspicion was a pericardial or bronchogenic cyst. Surgical and anatomopathologic findings led to the diagnosis of a mature cystic teratoma with atrophic thymic tissue at the external teratoma surface.
We present an original report of a mature teratoma causing obliteration of the right cardiophrenic sinus with extrinsic heart compression. The diagnosis of this tumor is very difficult through non-invasive investigation.
PMCID: PMC3118208  PMID: 21599893
15.  Genetic Variants of Diabetes Risk and Incident Cardiovascular Events in Chronic Coronary Artery Disease 
PLoS ONE  2011;6(1):e16341.
To determine whether information from genetic risk variants for diabetes is associated with cardiovascular events incidence.
From the about 30 known genes associated with diabetes, we genotyped single-nucleotide polymorphisms at the 10 loci most associated with type-2 diabetes in 425 subjects from the MASS-II Study, a randomized study in patients with multi-vessel coronary artery disease. The combined genetic information was evaluated by number of risk alleles for diabetes. Performance of genetic models relative to major cardiovascular events incidence was analyzed through Kaplan-Meier curve comparison and Cox Hazard Models and the discriminatory ability of models was assessed for cardiovascular events by calculating the area under the ROC curve.
Genetic information was able to predict 5-year incidence of major cardiovascular events and overall-mortality in non-diabetic individuals, even after adjustment for potential confounders including fasting glycemia. Non-diabetic individuals with high genetic risk had a similar incidence of events then diabetic individuals (cumulative hazard of 33.0 versus 35.1% of diabetic subjects). The addition of combined genetic information to clinical predictors significantly improved the AUC for cardiovascular events incidence (AUC = 0.641 versus 0.610).
Combined information of genetic variants for diabetes risk is associated to major cardiovascular events incidence, including overall mortality, in non-diabetic individuals with coronary artery disease.
Clinical Trial Registration Information
Medicine, Angioplasty, or Surgery Study (MASS II). Unique identifier: ISRCTN66068876 URL.
PMCID: PMC3024434  PMID: 21283728
16.  Five-year follow-up of angiographic disease progression after medicine, angioplasty, or surgery 
Progression of atherosclerosis in coronary artery disease is observed through consecutive angiograms. Prognosis of this progression in patients randomized to different treatments has not been established. This study compared progression of coronary artery disease in native coronary arteries in patients undergoing surgery, angioplasty, or medical treatment.
Patients (611) with stable multivessel coronary artery disease and preserved ventricular function were randomly assigned to CABG, PCI, or medical treatment alone (MT). After 5-year follow-up, 392 patients (64%) underwent new angiography. Progression was considered a new stenosis of ≥ 50% in an arterial segment previously considered normal or an increased grade of previous stenosis > 20% in nontreated vessels.
Of the 392 patients, 136 underwent CABG, 146 PCI, and 110 MT. Baseline characteristics were similar among treatment groups, except for more smokers and statin users in the MT group, more hypertensives and lower LDL-cholesterol levels in the CABG group, and more angina in the PCI group at study entry. Analysis showed greater progression in at least one native vessel in PCI patients (84%) compared with CABG (57%) and MT (74%) patients (p < 0.001). LAD coronary territory had higher progression compared with LCX and RCA (P < 0.001). PCI treatment, hypertension, male sex, and previous MI were independent risk factors for progression. No statistical difference existed between coronary events and the development of progression.
The angioplasty treatment conferred greater progression in native coronary arteries, especially in the left anterior descending territories and treated vessels. The progression was independently associated with hypertension, male sex, and previous myocardial infarction.
PMCID: PMC2987924  PMID: 20977758
17.  Efficacy of aneurysmectomy in patients with severe left ventricular dysfunction: favorable short‐ and long‐term results in ischemic cardiomyopathy 
Clinics  2010;65(10):947-952.
The purpose of this study was to (1) identify the functional results after aneurysm surgery in patients with ischemic cardiomyopathy and (2) identify predictors of favorable outcomes.
Patients (n = 169) with angiographic left ventricular ejection fraction of 22±5% underwent aneurysm surgery and were prospectively followed for three years. Prior to surgery, 40% and 60% of the patients were in congestive heart failure NYHA class I/II and III/IV, respectively. Concomitant revascularization was performed on 95% of the patients.
Cumulative in‐hospital and 36‐month mortalities were 7% and 15%, respectively. These respective rates varied according to preoperative parameters: CHF class I‐II, 4% and 13%; CHF class III‐IV, 8% and 16%; LVEF<20%, 12% and 26%; LVEF 21‐30%, 2% and 6%; gated LVEF exercise/rest >5%, <1% and 4%; and gated LVEF exercise/rest ≤5%, 17% and 38%. Higher LVEF ex/rest ratio (p = 0.01), male sex (p = 0.05), and a higher number of grafts (p = 0.01) were predictive of improvement in CHF class at follow‐up based on the results of a multivariate analysis. After three years of follow‐up, 84% of the patients were in class I/II, LVEF was 45±7%, and gated LVEF ex/rest ratio was 13% higher (p<0.01) compared to the beginning of the study.
These data suggest that aneurysmectomy among patients with severe LV dysfunction result in short‐ and long‐term favorable functional outcome and survival. Selection of appropriate surgical candidates may substantially improve survival rates among these patients.
PMCID: PMC2972609  PMID: 21120292
Myocardial revascularization; Ventricular dysfunction; Ischemic cardiomyopathy; Cardiac surgery; Aneurysmectomy
18.  Hypotheses, rationale, design, and methods for prognostic evaluation in type 2 diabetic patients with angiographically normal coronary arteries. The MASS IV-DM Trial 
The MASS IV-DM Trial is a large project from a single institution, the Heart Institute (InCor), University of São Paulo Medical School, Brazil to study ventricular function and coronary arteries in patients with type 2 diabetes mellitus.
The study will enroll 600 patients with type 2 diabetes who have angiographically normal ventricular function and coronary arteries. The goal of the MASS IV-DM Trial is to achieve a long-term evaluation of the development of coronary atherosclerosis by using angiograms and coronary-artery calcium scan by electron-beam computed tomography at baseline and after 5 years of follow-up. In addition, the incidence of major cardiovascular events, the dysfunction of various organs involved in this disease, particularly microalbuminuria and renal function, will be analyzed through clinical evaluation. In addition, an effort will be made to investigate in depth the presence of major cardiovascular risk factors, especially the biochemical profile, metabolic syndrome inflammatory activity, oxidative stress, endothelial function, prothrombotic factors, and profibrinolytic and platelet activity. An evaluation will be made of the polymorphism as a determinant of disease and its possible role in the genesis of micro- and macrovascular damage.
The MASS IV-DM trial is designed to include diabetic patients with clinically suspected myocardial ischemia in whom conventional angiography shows angiographically normal coronary arteries. The result of extensive investigation including angiographic follow-up by several methods, vascular reactivity, pro-thrombotic mechanisms, genetic and biochemical studies may facilitate the understanding of so-called micro- and macrovascular disease of DM.
PMCID: PMC2956708  PMID: 20920271
19.  TCF7L2 Polymorphism rs7903146 Is Associated with Coronary Artery Disease Severity and Mortality 
PLoS ONE  2009;4(11):e7697.
TCF7L2 polymorphisms have been consistently associated with type 2 diabetes mellitus in different populations and type 2 diabetes mellitus is a major risk factor for cardiovascular disease, especially coronary artery disease. This study aimed to evaluate the association between TCF7L2 polymorphism rs7903146 and coronary artery disease in diabetic and non-diabetic subjects.
Methods and Results
two populations were studied in order to assess severity of coronary artery disease and cardiovascular events incidence. Eight-hundred and eighty nine subjects who were referred for cardiac catheterization for coronary artery disease diagnosis were cross-sectionally evaluated for coronary lesions (atherosclerotic burden) and 559 subjects from the MASS-II Trial were prospectively followed-up for 5 years and assessed for major cardiovascular events incidence. As expected, rs7903146 T allele was associated with diabetes. Although diabetic patients had a higher prevalence of coronary lesions, no association between TCF7L2 genotype and coronary lesions was found in this subgroup. However, non-diabetic individuals carrying the T allele were associated with a significantly higher frequency of coronary lesions than non-diabetic non-carriers of the risk allele (adjusted OR  = 2.32 95%CI 1.27–4.24, p = 0.006). Moreover, presence of multi-vessel coronary artery disease was also associated with the CT or TT genotypes in non-diabetics. Similarly, from the prospective sample analysis, non-diabetics carrying the CT/TT genotypes had significantly more composite cardiovascular end-points events than CC carriers (p = 0.049), mainly due to an increased incidence of death (p = 0.004).
rs7903146 T allele is associated with diabetes and, in non-diabetic individuals, with a higher prevalence and severity of coronary artery disease and cardiovascular events. name of registry site (see list below), registration number, trial registration URL in brackets.
Clinical Trial Registration Information
Medicine, Angioplasty, or Surgery Study (MASS II): Unique identifier: ISRCTN66068876.
PMCID: PMC2773425  PMID: 19924244
20.  A randomized comparative study of patients undergoing myocardial revascularization with or without cardiopulmonary bypass surgery: The MASS III Trial 
Trials  2008;9:52.
The MASS III Trial is a large project from a single institution, The Heart Institute of the University of Sao Paulo, Brazil (InCor), enrolling patients with coronary artery disease and preserved ventricular function. The aim of the MASS III Trial is to compare medical effectiveness, cerebral injury, quality of life, and the cost-effectiveness of coronary surgery with and without of cardiopulmonary bypass in patients with multivessel coronary disease referred for both strategies. The primary endpoint should be a composite of cardiovascular mortality, cerebrovascular accident, nonfatal myocardial infarction, and refractory angina requiring revascularization. The secondary end points in this trial include noncardiac mortality, presence and severity of angina, quality of life based on the SF-36 Questionnaire, and cost-effectiveness at discharge and at 5-year follow-up. In this scenario, we will analyze the cost of the initial procedure, hospital length of stay, resource utilization, repeat hospitalization, and repeat revascularization events during the follow-up. Exercise capacity will be assessed at 6-months, 12-months, and the end of follow-up. A neurocognitive evaluation will be assessed in a subset of subjects using the Brain Resource Center computerized neurocognitive battery. Furthermore, magnetic resonance imaging will be made to detect any cerebral injury before and after procedures in patients who undergo coronary artery surgery with and without cardiopulmonary bypass.
Clinical Trial registration information
ISRCTN59539154 Off-pump vs. on-pump surgery in patients with Stable CAD MASS III
PMCID: PMC2553048  PMID: 18755039

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