Long-term all-cause death prediction by coronary, aortic, and valvular calcification in patients with acute ST-segment elevation myocardial infarction.

BACKGROUND: To determine the prognostic value of cumulative calcification score of coronary artery calcification (CAC), thoracic aortic calcification (TAC) and aortic valve calcification (AVC) in acute ST segment elevation myocardial infarction (STEMI) patients. METHODS: This was a retrospective, single-center cohort study. A total of 332 STEMI patients who received primary percutaneous coronary intervention (PPCI) were enrolled in this study between January 2010 to October 2018. We assessed the calcification in the left anterior descending branch (LAD), left circumflex branch (LCX), right coronary artery (RCA), thoracic aorta, and aortic valve. Calcification of each part was counted as 1 point, and the cumulative calcification score was calculated as the sum of all points. The primary endpoint was all-cause mortality. Multivariate Cox proportional hazards models were used to determine association of cumulative calcification score with end points. The performance of the score was evaluated by receiver operating characteristic (ROC) curve analysis and absolute net reclassification improvement (NRI), compared with the Global Registry of Acute Coronary Events (GRACE) risk score. RESULTS: The overall population's calcification score was 2.0 ± 1.6. During a mean follow-up time of 69.8 ± 29.3 months, the all-cause mortality rate was 12.1%. Kaplan-Meier curve showed that the score was significantly associated with mortality (log-rank p < 0.001). The multivariable Cox proportional hazard analyses showed that a calcification score of 4-5 was independently associated with all-cause death in STEMI patients [hazard ratio (HR) = 2.32, 95% confidence interval (CI): 1.01-5.31, p = 0.046]. The area under the ROC curve (AUC) of the calcification score was 0.67 (95% CI: 0.61-0.72), and the AUC of the GRACE score was 0.80 (95% CI: 0.75-0.84). There was no statistical difference in the predictive value between both scores for 3-year mortality in STEMI patients after PPCI (p = 0.06). Based on the NRI analysis, the calcification score showed better risk classification compared with the GRACE score (absolute NRI = 6.63%, P = 0.027). CONCLUSION: The cumulative calcification score is independently associated with the long-term prognosis of STEMI patients after PPCI.

Cardiovascular events in patients with coronary artery disease with and without myocardial ischemia: Long-term follow-up.

BACKGROUND: After the results of the ISCHEMIA Trial, the role of myocardial ischemia in the prognosis of coronary artery disease (CAD) was under debate. We sought to comparatively evaluate the long-term prognosis of patients with multivessel CAD with or without documented myocardial ischemia. METHODS: This is a single-center, retrospective, observational cohort study that included patients with CAD obtained from the research protocols database of "The Medicine, Angioplasty or Surgery Study," the MASS Study Group. Patients were stratified according to the presence or absence of myocardial ischemia. Cardiovascular events (overall mortality and myocardial infarction) were tracked from the registry entry up to a median follow-up of 8.7 years. Myocardial ischemia was assessed at baseline by a functional test with or without imaging. RESULTS: From 1995 to 2018, 2015 patients with multivessel CAD were included. Of these, 1001 presented with conclusive tests at registry entry, 790 (79%) presenting with ischemia and 211 (21%) without ischemia. The median follow-up was 8.7 years (IQR 4.04 to 10.07). The primary outcome occurred in 228 (28.9%) patients with ischemia and in 64 (30.3%) patients without ischemia (plog-rank=0.60). No significant interaction was observed with the presence of myocardial ischemia and treatment strategies in the occurrence of the combined primary outcome (pinteration=0.14). CONCLUSIONS: In this sample, myocardial ischemia was not associated with a worse prognosis compared with no ischemia in patients with multivessel CAD. These results refer to debates about the role of myocardial ischemia in the occurrence of cardiovascular events.

High-Sensitivity Troponin I and Cardiovascular Events in Stable Coronary Artery Disease: Insights from a Longitudinal Outpatient Study.

Numerous studies have been published suggesting that troponin levels are related to adverse outcomes in chronic cardiac and non-cardiac conditions. Our study investigated whether troponin levels gathered from unselected blood samples taken during outpatient care are associated with adverse outcomes in a population with stable coronary artery disease. In a cohort of 949 patients with stable coronary artery disease, an average age of 67.5 ± 9.5 years, 69.5% male, 52.1% diabetics, 51.6% with previous myocardial infarction, and 57.9% with triple-vessel disease, 21.7% of patients encountered new events during an average period of monitoring of 2.07 ± 0.81 years. Troponin I/99th percentile categorized into tertiles emerged as an independent predictor of death and combined events risk (hazard ratio: 2.02 (1.13-3.60), p = 0.017; 2.30 (1.37-3.88, p = 0.002, respectively). A troponin ratio > 0.24 was able to identify 53.3% of patients at risk of death and heart failure hospitalization. In patients with stable coronary artery disease who are adherent to treatment, troponin levels are independently associated with death and heart failure hospitalization in a medium-term follow-up.

Long-term outcomes of patients with stable coronary disease and chronic kidney dysfunction: 10-year follow-up of the Medicine, Angioplasty, or Surgery Study II Trial.

BACKGROUND: Chronic kidney disease (CKD) is associated with a worse prognosis in patients with stable coronary artery disease (CAD); however, there is limited randomized data on long-term outcomes of CAD therapies in these patients. We evaluated long-term outcomes of CKD patients with CAD who underwent randomized therapy with medical treatment (MT) alone, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). METHODS: Baseline estimated glomerular filtration rate (eGFR) was obtained in 611 patients randomized to one of three therapeutic strategies in the Medicine, Angioplasty, or Surgery Study II trial. Patients were categorized in preserved renal function and mild or moderate CKD groups depending on their eGFR (≥90, 89-60 and 59-30 mL/min/1.73 m2, respectively). The primary clinical endpoint, a composite of overall death and myocardial infarction, and its individual components were analyzed using proportional hazards regression (Clinical Trial registration information: http://www.controlled-trials.com. Registration number: ISRCTN66068876). RESULTS: Of 611 patients, 112 (18%) had preserved eGFR, 349 (57%) mild dysfunction and 150 (25%) moderate dysfunction. The primary endpoint occurred in 29.5, 32.4 and 44.7% (P = 0.02) for preserved eGFR, mild CKD and moderate CKD, respectively. Overall mortality incidence was 18.7, 23.8 and 39.3% for preserved eGFR, mild CKD and moderate CKD, respectively (P = 0.001). For preserved eGFR, there was no significant difference in outcomes between therapies. For mild CKD, the primary event rate was 29.4% for PCI, 29.1% for CABG and 41.1% for MT (P = 0.006) [adjusted hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.07-0.88; P = 0.03 for PCI versus MT; and adjusted HR = 0.48; 95% CI 0.31-0.76; P = 0.002 for CABG versus MT]. We also observed higher mortality rates in the MT group (28.6%) compared with PCI (24.1%) and CABG (19.0%) groups (P = 0.015) among mild CKD subjects (adjusted HR = 0.44, 95% CI 0.25-0.76; P = 0.003 for CABG versus MT; adjusted HR = 0.56, 95% CI 0.07-4.28; P = 0.58 for PCI versus MT). Results were similar with moderate CKD group but did not achieve significance. CONCLUSIONS: Coronary interventional therapy, both PCI and CABG, is associated with lower rates of events compared with MT in mild CKD patients >10 years of follow-up. More study is needed to confirm these benefits in moderate CKD.

Comparative cost-effectiveness of surgery, angioplasty, or medical therapy in patients with multivessel coronary artery disease: MASS II trial.

BACKGROUND: The costs for treating coronary artery disease (CAD) are high worldwide. We performed a prespecified analyses of cost-effectiveness of three therapeutic strategies for multivessel CAD. METHODS: From May 1995 to May 2000, a total of 611 patients were randomly assigned to coronary artery bypass graft (CABG), n = 203; percutaneous coronary intervention (PCI), n = 205; or medical treatment (MT), n = 203. This cost analysis study was based on the perspective of the Public Health Care System. Initial procedural and follow-up costs for medications, cardiology examinations, and hospitalizations for complications were calculated after randomization. Life-years and quality-adjusted life years (QALYs) were used as effectiveness measures. Incremental cost-effectiveness ratios (ICER) were obtained by using nonparametric bootstrapping methods with 5000 resamples. RESULTS: Initial procedural costs were lower for MT. However, the subsequent 5-year cumulative costs were lower for CABG. Compared with baseline, the three treatment options produced significant improvements in QALYs. After 5 years, PCI and CABG had better QALYs results compared with MT. The ICER results favored CABG and PCI, and favored PCI over CABG in 61% of the drawings. On the other hand, sensitivity analysis showed MT as the preferred therapy compared with CABG and PCI, in the analysis considering higher costs. CONCLUSIONS: At 5-year follow-up, the three treatment options yielded improvements in quality of life, with comparable and acceptable costs. However, despite higher initial costs, the comparison of cost-effectiveness after 5 years of follow-up among the three treatments showed both interventions (CABG and PCI) to be cost-effective strategies compared with MT.Trial registration ISRCTN, ISRCTN66068876, Registered 06/10/1994, http://www.controlled-trials.com/ISRCTN66068876.

Biomarker release after percutaneous coronary intervention in patients without established myocardial infarction as assessed by cardiac magnetic resonance with late gadolinium enhancement.

OBJECTIVES: This study aimed to evaluate the amount and pattern of cardiac biomarker release after elective percutaneous coronary intervention (PCI) in patients without evidence of a new myocardial infarction (MI) after the procedure as assessed by cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE). BACKGROUND: The release of myocardial necrosis biomarkers after PCI frequently occurs. However, the correlation between biomarker release and the diagnosis of procedure-related MI type 4a has been controversial. METHODS: Patients with normal baseline cardiac biomarkers who were referred for elective PCI were prospectively included. CMR with LGE was performed in all of the patients before and after the intervention. Measurements of troponin I (TnI) and creatine kinase MB fraction (CK-MB) were systematically performed before and after the procedure. Patients with a new LGE on the post-procedure CMR were excluded. RESULTS: Of the 56 patients with no evidence of a procedure-related MI as assessed by CMR after the PCI, 48 (85.1%) exhibited an elevation of TnI above the 99th percentile. In 32 patients (57.1%), the peak was greater than five times this limit. Additionally, 17 patients (30.4%) had a CK-MB peak above the 99th percentile limit, but this peak was greater than five times the 99th percentile in only two patients (3.6%). The median peak release of TnI was 0.290 (0.061-1.09) ng/mL, which was 7.25-fold higher than the 99th percentile. CONCLUSIONS: In contrast to CK-MB, an abnormal release of TnI often occurs after an elective PCI procedure, despite the absence of a new LGE on CMR.

Type 2 diabetes mellitus and myocardial ischemic preconditioning in symptomatic coronary artery disease patients.

BACKGROUND: 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.

Troponin in diabetic patients with and without chronic coronary artery disease.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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: http://www.controlled-trials.com REGISTRATION NUMBER: ISRCTN26970041.

Long-term analysis of left ventricular ejection fraction in patients with stable multivessel coronary disease undergoing medicine, angioplasty or surgery: 10-year follow-up of the MASS II trial.

BACKGROUND: Assuming that coronary interventions, both coronary bypass surgery (CABG) and percutaneous coronary intervention (PCI), are directed to preserve left ventricular function, it is not known whether medical therapy alone (MT) can achieve this protection. Thus, we evaluated the evolution of LV ejection fraction (LVEF) in patients with stable coronary artery disease (CAD) treated by CABG, PCI, or MT as a post hoc analysis of a randomized controlled trial with a follow-up of 10 years. METHODS: Left ventricle ejection fraction was assessed with transthoracic echocardiography in patients with multivessel CAD, participants of the MASS II trial before randomization to CABG, PCI, or MT, and re-evaluated after 10 years of follow-up. RESULTS: Of the 611 patients, 422 were alive after 10.32 ± 1.43 years. Three hundred and fifty had LVEF reassessed: 108 patients from MT, 111 from CABG, and 131 from PCI. There was no difference in LVEF at the beginning (0.61 ± 0.07, 0.61 ± 0.08, 0.61 ± 0.09, respectively, for PCI, CABG, and MT, P = 0.675) or at the end of follow-up (0.56 ± 0.11, 0.55 ± 0.11, 0.55 ± 0.12, P = 0.675), or in the decline of LVEF (reduction delta of -7.2 ± 17.13, -9.08 ± 18.77, and -7.54 ± 22.74). Acute myocardial infarction (AMI) during the follow-up was associated with greater reduction in LVEF. The presence of previous AMI (OR: 2.50, 95% CI: 1.40-4.45; P = 0.0007) and during the follow-up (OR: 2.73, 95% CI: 1.25-5.92; P = 0.005) was associated with development of LVEF <45%. CONCLUSION: Regardless of the therapeutic option applied, LVEF remains preserved in the absence of a major adverse cardiac event after 10 years of follow-up. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Registration number ISRCTN66068876.

The unexpected silent manifestation of myocardial infarctions in ischemic heart failure patients: Insights from a case-control study.

BACKGROUND: Recent studies show Silent Myocardial Infarction (SMI) as a quite frequent event. However, regarding severe tertiary care patients that frequently present consequences of Coronary Artery Disease (CAD) and Left Ventricular Dysfunction (LVD), the occurrence of this manifestation is unexpected and its associated factors aren't clear in the literature. AIM: To compare clinical, laboratorial, ventricular and angiographic factors between silent and classical presentation of MI in patients with CAD and LVD. METHODS: Patients with multivessel CAD with over 70 % obstructive lesions and LVD with EF less than 35 % were evaluated for MASS VI trial and later included in the present study. The ventricular function and coronary assessment were measured by echocardiography and SYNTAX score, respectively. The population was stratified in a SMI group and Clinically Manifested Myocardial Infarction (CMMI) group based on MI presentation for a comparison of medical parameters. RESULTS: From 132 patients, 47 (35.6 %) were classified as SMI and 85 (64.4 %) as CMMI. No differences were observed between groups regarding age, sex, diabetes mellitus, SYNTAX score, or collateral circulation. Higher proportion of NYHA II classification, inferior wall MI and lower creatinine clearance were found in SMI group. After multivariate analysis, peripheral diabetic neuropathy (OR = 4.6 [1.1‒12.7] p = 0.032) and inferior wall MI (OR = 4.1 [1.5‒11.4] p = 0.007) were significantly associated with SMI. CONCLUSION: Peripheral diabetic neuropathy and inferior wall MI were associated with SMI presentation. Overall, associated factors tend to be similar comparing SMI and CMMI, but in the specific population of diabetic patients with chronic neuropathy a special care should be taken.

Unveiling myocardial microstructure shifts: exploring the impact of diabetes in stable CAD patients through CMR T1 mapping.

BACKGROUND: This study investigates myocardial structural changes in stable coronary artery disease (CAD) patients with type 2 diabetes (T2D) using cardiac magnetic resonance (CMR) strain and T1 mapping. METHODS: A total of 155 stable CAD patients underwent CMR examination, including left ventricular (LV) morphology and function assessment, late gadolinium enhancement (LGE), and feature tracking (CMR-FT) for LV global longitudinal, circumferential, and radial strain. T1 mapping with extracellular volume (ECV) evaluation was also performed. RESULTS: Among the enrolled patients, 67 had T2D. Diabetic patients exhibited impaired LV strain and higher ECV compared to non-diabetics. Multivariate analysis identified T2D as an independent predictor of increased ECV and decreased strain. CONCLUSIONS: CMR-based strain and T1 mapping highlighted impaired myocardial contractility, elevated ECV, and potential interstitial fibrosis in diabetic patients with stable CAD. This suggests a significant impact of diabetes on myocardial health beyond CAD, emphasizing the importance of a comprehensive assessment in these individuals. TRIAL REGISTRATION: http://www.controlled-trials.com/ISRCTN09454308.

Cost-effectiveness analysis for surgical, angioplasty, or medical therapeutics for coronary artery disease: 5-year follow-up of medicine, angioplasty, or surgery study (MASS) II trial.

BACKGROUND: The Second Medicine, Angioplasty, or Surgery Study (MASS II) included patients with multivessel coronary artery disease and normal systolic ventricular function. Patients underwent coronary artery bypass graft surgery (CABG, n=203), percutaneous coronary intervention (PCI, n=205), or medical treatment alone (MT, n=203). This investigation compares the economic outcome at 5-year follow-up of the 3 therapeutic strategies. METHODS AND RESULTS: We analyzed cumulative costs during a 5-year follow-up period. To analyze the cost-effectiveness, adjustment was made on the cumulative costs for average event-free time and angina-free proportion. Respectively, for event-free survival and event plus angina-free survival, MT presented 3.79 quality-adjusted life-years and 2.07 quality-adjusted life-years; PCI presented 3.59 and 2.77 quality-adjusted life-years; and CABG demonstrated 4.4 and 2.81 quality-adjusted life-years. The event-free costs were $9071.00 for MT; $19,967.00 for PCI; and $18,263.00 for CABG. The paired comparison of the event-free costs showed that there was a significant difference favoring MT versus PCI (P<0.01) and versus CABG (P<0.01) and CABG versus PCI (P=0.01). The event-free plus angina-free costs were $16,553.00, $25,831.00, and $24,614.00, respectively. The paired comparison of the event-free plus angina-free costs showed that there was a significant difference favoring MT versus PCI (P=0.04), and versus CABG (P<0.001); there was no difference between CABG and PCI (P>0.05). CONCLUSIONS: In the long-term economic analysis, for the prevention of a composite primary end point, MT was more cost effective than CABG, and CABG was more cost-effective than PCI. CLINICAL TRIAL REGISTRATION INFORMATION: www.controlled-trials.com. REGISTRATION NUMBER: ISRCTN66068876.

Effect of complete revascularization on 10-year survival of patients with stable multivessel coronary artery disease: MASS II trial.

BACKGROUND: The importance of complete revascularization remains unclear and contradictory. This current investigation compares the effect of complete revascularization on 10-year survival of patients with stable multivessel coronary artery disease (CAD) who were randomly assigned to percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). METHODS AND RESULTS: This is a post hoc analysis of the Second Medicine, Angioplasty, or Surgery Study (MASS II), which is a randomized trial comparing treatments in patients with stable multivessel CAD, and preserved systolic ventricular function. We analyzed patients who underwent surgery (CABG) or stent angioplasty (PCI). The survival free of overall mortality of patients who underwent complete (CR) or incomplete revascularization (IR) was compared. Of the 408 patients randomly assigned to mechanical revascularization, 390 patients (95.6%) underwent the assigned treatment; complete revascularization was achieved in 224 patients (57.4%), 63.8% of those in the CABG group and 36.2% in the PCI group (P=0.001). The IR group had more prior myocardial infarction than the CR group (56.2% × 39.2%, P=0.01). During a 10-year follow-up, the survival free of cardiovascular mortality was significantly different among patients in the 2 groups (CR, 90.6% versus IR, 84.4%; P=0.04). This was mainly driven by an increased cardiovascular specific mortality in individuals with incomplete revascularization submitted to PCI (P=0.05). CONCLUSIONS: Our study suggests that in 10-year follow-up, CR compared with IR was associated with reduced cardiovascular mortality, especially due to a higher increase in cardiovascular-specific mortality in individuals submitted to PCI. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.controlled-trials.com. REGISTRATION NUMBER: ISRCTN66068876.

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.

INTRODUCTION: 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 non-diabetic 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.

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.

Myocardial tissue microstructure with and without stress-induced ischemia assessed by T1 mapping in patients with stable coronary artery disease.

BACKGROUND: Stress-induced myocardial ischemia seems not to be associated with cardiovascular events. However, its effects on myocardial tissue characteristics remain under debate. Thus, we sought to assess whether documented stress-induced ischemia is associated with changes in myocardial microstructure evaluated by magnetic resonance native T1 map and extracellular volume fraction (ECV). METHODS: This is a single-center, analysis of the previously published MASS V Trial. Multivessel patients with a formal indication for myocardial revascularization and with documented stress-induced ischemia were included in this study. Native T1 and ECV values evaluated by cardiac magnetic resonance imaging of ischemic and nonischemic myocardial segments at rest and after stress were compared. Myocardial ischemia was detected by either nuclear scintigraphy or stress magnetic cardiac resonance protocol. RESULTS: Between May 2012 and March 2014, 326 prospective patients were eligible for isolated CABG or PCI and 219 were included in the MASS V trial. All patients underwent resting cardiac magnetic resonance imaging. Of a total of 840 myocardial segments, 654 were nonischemic segments and 186 were ischemic segments. Native T1 and ECV values of ischemic segments were not significantly different from nonischemic segments, both at rest and after stress induction. In addition, native T1 and ECV values of myocardial segments supplied by vessels with obstructive lesions were similar to those supplied by nonobstructive ones. CONCLUSION AND RELEVANCE: In this study, cardiac magnetic resonance identified similar T1 mapping values between ischemic and nonischemic myocardial segments. This finding suggests integrity and stability of myocardial tissue in the presence of stress-induced ischemia.

Myocardial microstructure assessed by T1 mapping after on-pump and off-pump coronary artery bypass grafting.

Background: The correlation between the release of cardiac biomarkers after revascularization, in the absence of late gadolinium enhancement (LGE) or myocardial edema, and the development of myocardial tissue damage remains unclear. This study sought to identify whether the release of biomarkers is associated with cardiac damage by assessing myocardial microstructure on T1 mapping after on-pump (ONCAB) and off-pump coronary artery bypass grafting (OPCAB). Methods: Seventy-six patients with stable multivessel coronary artery disease (CAD) and preserved systolic ventricular function were included. T1 mapping, high-sensitive cardiac troponin I (cTnI), creatine kinase myocardial band (CK-MB) mass, and ventricular dimensions and function were measured before and after procedures. Results: Of the 76 patients, 44 underwent OPCAB, and 32 ONCAB; 52 were men (68.4%), and the mean age was 63±8.5 years. In both OPCAB and ONCAB the native T1 values were similar before and after surgeries. An increase in extracellular volume (ECV) values after the procedures was observed, due to the decrease in hematocrit levels during the second cardiac resonance. However, the lambda partition coefficient showed no significant difference after the surgeries. The median peak release of cTnI and CK-MB were higher after ONCAB than after OPCAB [3.55 (2.12-4.9) vs. 2.19 (0.69-3.4) ng/mL, P=0.009 and 28.7 (18.2-55.4) vs. 14.3 (9.3-29.2) ng/mL, P=0.009, respectively]. Left ventricular ejection fraction (LVEF) was similar in both groups before and after surgery. Conclusions: In the absence of documented myocardial infarction, T1 mapping did not identify structural tissue damage after surgical revascularization with or without cardiopulmonary bypass (CPB), despite the excessive release of cardiac biomarkers.

Chronic troponin elevation assessed by myocardial T1 mapping in patients with stable coronary artery disease.

BACKGROUND: Cardiac troponin detected with sensitive assays can be chronically elevated, in the absence of unstable coronary syndromes. In patients with chronic coronary artery disease, clinically silent ischemic episodes may cause chronic troponin release. T1 mapping is a cardiovascular magnetic resonance technique useful in quantitative cardiac tissue characterization. We selected patients with anatomically and functionally normal hearts to investigate associations between chronic troponin release and myocardial tissue characteristics assessed by T1 mapping. METHODS: We investigated the relationship between cardiac troponin I concentrations and cardiovascular magnetic resonance T1 mapping parameters in patients with stable coronary artery disease enrolled in MASS V study before elective revascularization. Participants had no previous myocardial infarction, negative late gadolinium enhancement, normal left ventricular function, chamber dimensions and wall thickness. RESULTS: A total of 56 patients were analyzed in troponin tertiles: nativeT1 and extracellular volume (ECV) values (expressed as means ±â€…standard deviations) increased across tertiles: nativeT1 (1006 ±â€…27 ms vs 1016 ±â€…27 ms vs 1034 ±â€…37 ms, ptrend = 0.006) and ECV (22 ±â€…3% vs 23 ±â€…1.9% vs 25 ±â€…3%, ptrend = 0.007). Cardiac troponin I concentrations correlated with native T1(R = 0.33, P = .012) and ECV (R = 0.3, P = .025), and were independently associated with nativeT1 (P = .049) and ventricular mass index (P = .041) in multivariable analysis. CONCLUSION: In patients with chronic coronary artery disease and structurally normal hearts, troponin I concentrations correlated with T1 mapping parameters, suggesting that diffuse edema or fibrosis scattered in normal myocardium might be associated with chronic troponin release.

Abnormal release of cardiac biomarkers in the presence of myocardial oedema evaluated by cardiac magnetic resonance after uncomplicated revascularization procedures.

AIMS: To analyse the association of myocardial oedema (ME), observed as high T2 signal intensity (HT2) in cardiac magnetic resonance imaging, with the release of cardiac biomarkers, ventricular ejection, and clinical outcomes after revascularization. METHODS AND RESULTS: Patients with stable coronary artery disease with the indication for revascularization were included. Biomarker levels [troponin I (cTnI) and creatine kinase MB (CK-MB)] and T2-weighted and late gadolinium enhancement (LGE) images were obtained before and after the percutaneous or surgical revascularization procedures. The association of HT2 with the levels of biomarkers, with and without LGE, evolution of left ventricular ejection fraction (LVEF), and 5-year clinical outcomes were assessed. A total of 196 patients were divided into 2 groups: Group 1 (HT2, 40) and Group 2 (no HT2, 156). Both peak cTnI (8.9 and 1.6 ng/mL) and peak CK-MB values (44.7 and 12.1 ng/mL) were significantly higher in Group 1. Based on the presence of new LGE, patients were stratified into Groups A (no HT2/LGE, 149), B (HT2, 9), C (LGE, 7), and D (both HT2/LGE, 31). The peak cTnI and CK-MB values were 1.5 and 12.0, 5.4 and 44.7, 5.0 and 18.3, and 9.8 and 42.8 ng/mL in Groups A, B, C, and D, respectively, and were significantly different. The average LVEF decreased by 4.4% in Group 1 and increased by 2.2% in Group 2 (P = 0.057). CONCLUSION: ME after revascularization procedures was associated with increased release of cardiac necrosis biomarkers, and a trend towards a difference in LVEF, indicating a role of ME in cardiac injury after interventions.

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.