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.

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.

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.

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.

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.

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.

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.

Long-term analysis of ventricular function in patients with symptomatic coronary disease who underwent on-pump or off-pump coronary artery bypass grafting.

BACKGROUND: Systemic deleterious effects of cardiopulmonary bypass have been observed in the postprocedural period. Long-term assessment, including ventricular function (VF), is unclear. The objective of this study was to compare the change of left ventricular ejection fractions (LVEFs) during a long-term follow-up of coronary artery disease (CAD) patients who underwent off-pump (OPCAB) or on-pump coronary artery bypass grafting (ONCAB). METHODS: This study is a prespecified analysis of the MASS III trial, which was a single-center and prospective study that enrolled stable CAD patients with preserved VF. The CAD patients in our study were randomized to OPCAB or ONCAB. A transthoracic echocardiogram was performed during follow-up and a LVEF value was obtained. The primary endpoint was the difference between the final LVEF and the baseline LVEF. RESULTS: Of the 308 randomized patients, ventricular function were observed in 225 over a mean of 5.9 years of follow-up: 113 in the ONCAB group and 112 in the OPCAB group. Baseline characteristics were similar between the two groups, but there was a larger proportion of subjects with 3-vessel disease in the ONCAB group. There was no difference in the LVEF at the beginning (P = 0.08), but there was a slight decrease in the LVEF in the ONCAB and OPCAB groups (P < 0.001 in both groups) at 5.9 years. The decline was not significantly different between the two groups (delta of -6% for ONCAB and -5% for OPCAB; P = 0.78). In a multivariate analysis, myocardial infarction in the follow-up was a predictor of an LVEF < 40%. CONCLUSIONS: There was no difference in the long-term development of ventricular function between the surgical techniques, despite a decline in the LVEF in both groups. Trial registration Clinical Trial Registration Information-URL: http://www.controlled-trials.com . REGISTRATION NUMBER: ISRCTN59539154. Date of first registration: 10/03/2008.

Protective or Inhibitory Effect of Pharmacological Therapy on Cardiac Ischemic Preconditioning: A Literature Review.

Ischemic preconditioning (IP) is an innate phenomenon, triggered by brief, non-lethal cycles of ischemia/reperfusion applied to a tissue or organ that confers tolerance to a subsequent more prolonged ischemic event. Once started, it can reduce the severity of myocardial ischemia associated with some clinical situations, such as percutaneous coronary intervention (PCI) and intermittent aortic clamping during coronary artery bypass graft surgery (CABG). Although the mechanisms underlying IP have not been completely elucidated, several studies have shown that this phenomenon involves the participation of cell triggers, intracellular signaling pathways, and end-effectors. Understanding this mechanism enables the development of preconditioning mimetic agents. It is known that a range of medications that activate the signaling cascades at different cellular levels can interfere with both the stimulation and the blockade of IP. Investigations of signaling pathways underlying ischemic conditioning have identified a number of therapeutic targets for pharmacological manipulation. This review aims to present and discuss the effects of several medications on myocardial IP.

Diagnostic Management and Surgical Treatment of Isolated Tricuspid Regurgitation.

Severe tricuspid regurgitation is especially caused by pulmonary hypertension. Primary tricuspid regurgitation in the absence of pulmonary hypertension and of unknown etiology is a very rare condition with scarce data about its diagnosis, treatment, and follow-up. The particularities of surgery indication and outcomes are still not clearly known. A 72-year-old woman with a medical history of coronary artery bypass grafting three years ago presented with shortness of breath and low limb edema. Physical examination revealed a prominent bilateral jugular turgescence, hepatomegaly, peripheral edema, and a left midsternal border holosystolic murmur, suggestive of tricuspid regurgitation. The echocardiogram confirmed the diagnosis and showed preserved right and left ventricular dimensions and function. Coronary angiography showed no new obstructive lesions and patent surgical grafts. Right cardiac catheterization revealed mild pulmonary hypertension and increased right atrium pressure. Cardiac magnetic resonance showed mild right ventricular dilation with normal systolic function and normal left chambers. No late gadolinium enhancement was detected. Because of persistent symptoms, even after optimization of medical therapy, the patient was submitted to tricuspid valve replacement surgery. Immediately after the surgery, the patient developed significant right ventricular dysfunction, with the need of continuous hemodynamic support. She had progressive clinical recovery that was confirmed by serial echocardiograms that showed improvement in right ventricular volume and function. The patient was discharged with no signs or symptoms of right heart failure. The histopathological examination showed significant and diffuse myxomatous degeneration of the leaflets. No signs of infection or vegetation nor disruption of strands were observed. This report illustrates a very rare case of symptomatic primary isolated severe tricuspid regurgitation caused by myxomatous degeneration of the leaflets. The thoroughly diagnostic workup is presented, and only the histopathological analysis of the leaflets revealed the etiologic process. Surgical treatment indicated before the onset of right ventricular failure was essential to patient's full recovery.

Surgical and percutaneous revascularization outcomes based on SYNTAX I, II, and residual scores: a long-term follow-up study.

BACKGROUND: The objective of this study was to evaluate the association of SYNTAX scores I, II, and residual with cardiovascular outcomes of patients undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) and compare both procedures in a long-term follow-up. METHODS: This is a retrospective single-center study from the MASS registry at the Heart Institute of the University of São Paulo, Brazil in which 969 patients with stable coronary artery disease undergoing CABG (559) or PCI (410) were included. We assessed the SYNTAX scores I, II and residual in both interventions. Clinical endpoints were the first occurrence of a composite of overall death, myocardial infarction, stroke, or repeat revascularization (MACCE) and the total occurrence of each component of MACCE. RESULTS: In the CABG sample, SSI had a median of 23 (IQR 17-29.5), median SSII of 25.4 (IQR 19.2-32.8), and median rSS of 2 (IQR 0-6.5); in PCI SSI had a median of 14 (IQR 10-19.1), median SSII of 28.7 (IQR 23-34.2), and median rSS of 4.7 (IQR 0-9). Total of 174 events were documented and CABG patients had a lower rate of MACCE (15.6% vs. 21.2%; adjusted HR 1.98; 95% CI 1.13-3.47; P = 0.016) and repeat revascularization (3.8% vs. 11.5%; adjusted HR 4.35; CI 95% 1.74-10.85; P = 0.002) compared with PCI. No SYNTAX score tertile found a difference in death rate between procedures. In a multivariate analysis, the rSS was an independent predictor for MACCE (HR 1.04; 95% CI 1.01-1.06; P = 0.001). Regarding death, the only independent predictors were ejection fraction and renal function. CONCLUSION: Surgical revascularization resulted in a more complete revascularization and lower rates of major cardiac or cerebrovascular events in a long-term follow-up. Also, grading the incompleteness of revascularization through the residual SYNTAX score identified a higher event rate, suggesting that complete revascularization is associated with a better prognosis.

Effect of diabetic kidney disease on therapeutic strategies for coronary artery disease: ten year follow-up.

BACKGROUND: The best treatment for coronary artery disease (CAD) in patients with type 2 diabetes (DM2) and chronic kidney disease is unknown. METHODS: This retrospective study included MASS registry patients with DM2 and multivessel CAD, stratified by kidney function. Primary endpoint was combined of mortality, myocardial infarction, or additional revascularization. RESULTS: Median follow-up was 9.5 years. Primary endpoint occurrences among strata 1 and 2 were 53.4% and 40.7%, respectively (P=.020). Mortality rates were 37.4% and 24.6% in strata 1 and 2, respectively (P<.001). We observed a lower rate of major adverse cardiovascular events (MACE) (P=.027 for stratum 1 and P<.001 for stratum 2) and additional revascularization (P=.001 for stratum 1 and P<.001 for stratum 2) for those in the surgical group. In a multivariate analysis, eGFR was an independent predictor of MACE (P=.034) and mortality (P=.020). CONCLUSIONS: Among subjects with DM2 and CAD the presence of lower eGFR rate was associated with higher rates of MACE and mortality, irrespective of treatment choice. CABG was associated with lower rates of MACE in both renal function strata. eGFR was an independent predictor of MACE and mortality in a 10-year follow-up.

Continuous glucose monitoring in obese pregnant women with no hyperglycemia on glucose tolerance test.

OBJECTIVE: The objective of the present study was to compare 24-hour glycemic levels between obese pregnant women with normal glucose tolerance and non-obese pregnant women. METHODS: In the present observational, longitudinal study, continuous glucose monitoring was performed in obese pregnant women with normal oral glucose tolerance test with 75 g of glucose between the 24th and the 28th gestational weeks. The control group (CG) consisted of pregnant women with normal weight who were selected by matching the maternal age and parity with the same characteristics of the obese group (OG). Glucose measurements were obtained during 72 hours. RESULTS: Both the groups were balanced in terms of baseline characteristics (age: 33.5 [28.7-36.0] vs. 32.0 [26.0-34.5] years, p = 0.5 and length of pregnancy: 25.0 [24.0-25.0] vs. 25.5 [24.0-28.0] weeks, p = 0.6 in the CG and in the OG, respectively). Pre-breakfast glycemic levels were 77.77 ± 10.55 mg/dL in the CG and 82.02 ± 11.06 mg/dL in the OG (p<0.01). Glycemic levels at 2 hours after breakfast were 87.31 ± 13.10 mg/dL in the CG and 93.48 ± 18.74 mg/dL in the OG (p<0.001). Daytime blood glucose levels were 87.6 ± 15.4 vs. 93.1 ± 18.3 mg/dL (p<0.001) and nighttime blood glucose levels were 79.3 ± 15.8 vs. 84.7 ± 16.3 mg/dL (p<0.001) in the CG and in the OG, respectively. The 24-hour, daytime, and nighttime values of the area under the curve were higher in the OG when compared with the CG (85.1 ± 0.16 vs. 87.9 ± 0.12, 65.6 ± 0.14 vs. 67.5 ± 0.10, 19.5 ± 0.07 vs. 20.4 ± 0.05, respectively; p<0.001). CONCLUSION: The results of the present study showed that obesity in pregnancy was associated with higher glycemic levels even in the presence of normal findings on glucose tolerance test.

Hypotheses, rationale, design, and methods for prognostic evaluation of a randomized comparison between patients with coronary artery disease associated with ischemic cardiomyopathy who undergo medical or surgical treatment: MASS-VI (HF).

BACKGROUND: Ischemic cardiomyopathy and severe left ventricular dysfunction are well established to represent the main determinants of poor survival and premature death compared with preserved ventricular function. However, the role of myocardial revascularization as a therapeutic alternative is not known to improve the long-term prognosis in this group of patients. This study will investigate whether myocardial revascularization contributes to a better prognosis for patients compared with those treated with drugs alone and followed over the long term. METHODS: The study will include 600 patients with coronary artery disease associated with ischemic cardiomyopathy. The surgical or drug therapy option will be randomized, and the events considered for analysis will be all-cause mortality, nonfatal infarction, unstable angina requiring additional revascularization, and stroke. The events will be analyzed according to the intent-to-treat principle. Patients with multivessel coronary disease and left ventricular ejection fraction measurements of less than 35% will be included. In addition, myocardial ischemia will be documented by myocardial scintigraphy. Markers of myocardial necrosis will be checked at admission and after the procedure. DISCUSSION: The role of myocardial revascularization (CABG) in the treatment of patients with coronary artery disease and heart failure is not clearly established. The surgical option of revascularizing the myocardium is a procedure designed to reduce the load of myocardial hibernation in patients with heart failure caused by coronary artery disease. On the other hand, the assessment of myocardial viability is frequently used to identify patients with left ventricular ischemic dysfunction in which CABG may add survival benefit. However, the effectiveness of this option is uncertain. The great difficulty in establishing the efficacy of surgical intervention is based on the understanding of viability without ischemia. Thus, this study will include only patients with viable and truly ischemic myocardium to correct this anomaly. TRIAL REGISTRATION: Evaluation of a randomized comparison between patients with coronary artery disease associated with ischemic cardiomyopathy submitted to medical or surgical treatment: MASS-VI (HF), ISRCTN77449548, Oct 10th, 2019 (retrospectively registered).

Significant association of SYNTAX score on release of cardiac biomarkers in uncomplicated post-revascularization procedures among patients with stable multivessel disease: MASS-V Study group.

This study investigated the relationship between angiographic complexities of coronary artery disease (CAD) assessed by SYNTAX Score synergy between percutaneous coronary intervention with taxus and cardiac surgery score (SYNTAX Score) and cardiac biomarker elevation after revascularization procedures.This is a post-hoc analysis of the medicine, angioplasty or surgery study V study of patients with stable CAD. High-sensitivity troponin 1 (hs-TnI) and creatinine kinase-muscle/brain (CK-MB) were assessed before and after cardiovascular procedures. Baselines SYNTAX Scores (SXScores) were calculated by blinded investigators to patient characteristics.Of the 202 patients studied, the mean SXScore was 21.25 ±â€Š9.24; 40.10 ±â€Š7.09 in the high SXScore group and 19.06 ±â€Š6.61 in low/mid SXscore group (P < .0001). Positive correlations existed between SXScore and median peaks after procedural hs-TnI (r = 0.18, P = .009) and CK-MB (r = 0.24, P = .001) levels. In patients with high SXScores (≥33), the median peaks of post-procedural hs-TnI (P = .034)and CK-MB (P = .004) levels were higher than in low/mid SXScore group (<33).The release of hs-TnI at 6 (P = .002), 12 (P = .008), and 24 hours (P = .039) was higher in high SXScore group than in low/mid SXscore group (<33) as was the release of CK-MB at 6 (P < .0001), 12 (P < .0001), 24 (P = .001), 36 (P = .007), 48 (P = .008), and 72 hours (P = .023). After multivariable analysis, high SXScore was a significant independent predictor of release of CK-MB and hs-TnI peaks higher than the median.The increase in release of cardiac biomarkers was significantly associated with the extent of atherosclerosis identified by the SYNTAX Score.

Association of Longitudinal Values of Glycated Hemoglobin With Cardiovascular Events in Patients With Type 2 Diabetes and Multivessel Coronary Artery Disease.

Importance: Glycated hemoglobin (HbA1c) values are used to guide glycemic control, but in patients with type 2 diabetes and multivessel coronary artery disease (CAD), the association of the longitudinal values of HbA1c with cardiovascular outcomes is unclear. Objective: To assess whether longitudinal variation of HbA1c is associated with cardiovascular events in long-term follow-up among patients with diabetes and multivessel CAD. Design, Setting, and Participants: This cohort study included 888 patients with type 2 diabetes and multivessel CAD in the Medicine, Angioplasty, or Surgery Study (MASS) Registry of the Heart Institute of the University of São Paulo from January 2003 to December 2007. Data were analyzed from January 15, 2018, to October 15, 2019. Exposure: Longitudinal HbA1c values. Main Outcomes and Measures: The combined outcome of all-cause mortality, myocardial infarction, and ischemic stroke. Results: Of 888 patients with type 2 diabetes and multivessel CAD, 725 (81.6%; median [range] age, 62.4 [55.7-68.0] years; 467 [64.4%] men) had complete clinical and HbA1c information during a median (interquartile range) follow-up period of 10.0 (8.0-12.3) years, with a mean (SD) of 9.5 (3.8) HbA1c values for each patient. The composite end point of death, myocardial infarction, or ischemic stroke occurred in 262 patients (36.1%). A 1-point increase in the longitudinal value of HbA1c was significantly associated with a 14% higher risk of the combined end point of all-cause mortality, myocardial infarction, and ischemic stroke (hazard ratio, 1.14; 95% CI, 1.04-1.24; P = .002) in the unadjusted analysis. After adjusting for baseline factors (ie, age, sex, 2-vessel or 3-vessel CAD, initial CAD treatments, ejection fraction, and creatinine and low-density lipoprotein cholesterol levels), a 1-point increase in the longitudinal value of HbA1c was associated with a 22% higher risk of the combined end point (hazard ratio, 1.22; 95% CI, 1.12-1.35; P < .001). Conclusions and Relevance: Longitudinal increase of HbA1c was independently associated with higher rates of cardiovascular events in patients with type 2 diabetes and multivessel CAD.

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.

Association Between Stress Testing-Induced Myocardial Ischemia and Clinical Events in Patients With Multivessel Coronary Artery Disease.

IMPORTANCE: The long-term prognostic implications of myocardial ischemia documented during stress testing in patients with multivessel coronary artery disease (CAD) are unclear. OBJECTIVE: To assess whether documented stress testing-induced myocardial ischemia is associated with major adverse cardiovascular events or ventricular function changes in patients with stable multivessel CAD. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study was conducted using data from a single-center randomized clinical trial (Medicine, Angioplasty, or Surgery Study [MASS] II) to examine the association of myocardial ischemia documented during stress testing at baseline with cardiovascular events and ventricular function changes during follow-up. Participants were previously randomized (May 1, 1995, to May 31, 2000) to medical therapy, percutaneous coronary intervention with bare metal stents, or coronary artery bypass grafting. Event-free survival was estimated by the Kaplan-Meier method, and multivariable Cox regression models were calculated to assess the association between ischemia and the primary composite end point. The vital status was determined on February 28, 2011. Data were analyzed from February 1, 2016, to April 1, 2017. MAIN OUTCOMES AND MEASURES: Cardiovascular events (overall mortality, myocardial infarction, and revascularization for refractory angina) were tracked from the time of randomization to the end of the 10-year follow-up (mean [SD] duration, 11.4 [4.3] years). Myocardial ischemia was assessed at baseline and at 1-year intervals by exercise stress testing, and ventricular function (left ventricular ejection fraction) was assessed by echocardiography at baseline and after 10 years. Patients with documented ischemia were compared with those without ischemia regarding the outcomes and changes in ventricular function. RESULTS: Of 611 participants, 535 underwent exercise stress testing at baseline: 270 with documented ischemia and 265 without. Of these 535 patients, 373 (69.7%) were men, and the mean (SD) age for the entire cohort was 59.7 (9.2) years. No association was found between the presence of ischemia at baseline and survival free of combined cardiovascular events (hazard ratio, 1.00; 95% CI, 0.80-1.27; P = .95) after multivariable adjustment that included CAD initial randomized treatments. In addition, among 320 patients who underwent echocardiographic evaluation, the slight decline in left ventricular ejection fraction after 10 years was similar in both groups (median [SD] difference, -4.9% [18.7%] vs -6.6% [20.0%], respectively, for groups with and without ischemia; P = .97). CONCLUSIONS AND RELEVANCE: In this study, regardless of the therapeutic strategy applied, the presence of documented myocardial ischemia did not appear to be associated with an increased occurrence of major adverse cardiovascular events or changes in ventricular function in patients with multivessel CAD during a long-term follow-up.

Clinical significance of chronic myocardial ischemia in coronary artery disease patients.

Myocardial ischemia is considered the cornerstone of the treatment of patients with coronary artery disease (CAD). Although the deleterious effects of myocardial infarction, the maximum expression of ischemia, have been extensively studied and described, the clinical effects of chronic, documented myocardial ischemia are not completely clarified. The first studies that compared therapies for coronary disease focused on the presence of anatomical features and assessed ischemia based on the interpretation of the findings of obstructive atherosclerotic lesions. They suggested that revascularization interventions did not confer any clinical advantage over medical therapy (MT), in terms of cardiac or overall death. Other retrospective studies that were dedicated to assessing the impact of documented stress-induced ischemia on cardiovascular outcomes have suggested a prognostic impact of chronic ischemia. However, this has been questioned in recent studies. Moreover, the previous understanding that chronic ischemia could lead to worsening of ventricular function was not confirmed in a recent study. Thus, the prognostic significance of stress-induced ischemia has been questioned. Regarding treatment options, although some previous analyses have suggested that interventional therapies would reduce cardiovascular events in CAD patients with documented ischemia, recent post-hoc studies and metanalysis have shown distinct results. In this review article, the authors discuss myocardial ischemia, the different responses of the myocardium to ischemic insults, ischemic preconditioning, and the main findings of recent studies about the clinical aspects and treatment of patients with chronic, documented myocardial ischemia.