Elevated levels of circulating DNA and chromatin are independently associated with severe coronary atherosclerosis and a prothrombotic state.

OBJECTIVE: Aberrant neutrophil activation occurs during the advanced stages of atherosclerosis. Once primed, neutrophils can undergo apoptosis or release neutrophil extracellular traps. This extracellular DNA exerts potent proinflammatory, prothrombotic, and cytotoxic properties. The goal of this study was to examine the relationships among extracellular DNA formation, coronary atherosclerosis, and the presence of a prothrombotic state. APPROACH AND RESULTS: In a prospective, observational, cross-sectional cohort of 282 individuals with suspected coronary artery disease, we examined the severity, extent, and phenotype of coronary atherosclerosis using coronary computed tomographic angiography. Double-stranded DNA, nucleosomes, citrullinated histone H4, and myeloperoxidase-DNA complexes, considered in vivo markers of cell death and NETosis, respectively, were established. We further measured various plasma markers of coagulation activation and inflammation. Plasma double-stranded DNA, nucleosomes, and myeloperoxidase-DNA complexes were positively associated with thrombin generation and significantly elevated in patients with severe coronary atherosclerosis or extremely calcified coronary arteries. Multinomial regression analysis, adjusted for confounding factors, identified high plasma nucleosome levels as an independent risk factor of severe coronary stenosis (odds ratio, 2.14; 95% confidence interval, 1.26-3.63; P=0.005). Markers of neutrophil extracellular traps, such as myeloperoxidase-DNA complexes, predicted the number of atherosclerotic coronary vessels and the occurrence of major adverse cardiac events. CONCLUSIONS: Our report provides evidence demonstrating that markers of cell death and neutrophil extracellular trap formation are independently associated with coronary artery disease, prothrombotic state, and occurrence of adverse cardiac events. These biomarkers could potentially aid in the prediction of cardiovascular risk in patients with chest discomfort.

BMI is not independently associated with coronary artery calcification in a large single-center CT cohort.

Objective: Obesity is associated with cardiovascular disease (CVD) and CVD mortality. However, previous reports showed a paradoxical protective effect in patients with known CVD referred as "obesity paradox". Therefore, the aim of the present study was to investigate the association of body mass index (BMI) with coronary artery calcification (CAC) in a large outpatient cardiac CT cohort. Methods: 4.079 patients who underwent cardiac CT between December 2007-May 2014 were analyzed. BMI and clinical risk factors (current smoking, diabetes mellitus type 2, family history, systolic blood pressure, lipid spectrum) were assessed. Missing values were imputed using multiple imputation. CAC extent was categorized as absent (0), mild (>0-100), moderate (>100-400) and severe (>400). Results: Multivariable multinomial logistic regression analysis, including all risk factors as independent variables, showed no association between BMI and CAC. Using absence of calcification as reference category, the odds ratios per unit increase in BMI were 1.01 for mild; 1.02 for moderate; and 1.00 for severe CAC (p-values ≥0.103). Conclusions: No statistically significant association was observed between BMI and CAC after adjustment for other risk factors.

Restrictive Atrial Dysfunction in Cardiac Amyloidosis: Differences between Immunoglobulin Light Chain and Transthyretin Cardiac Amyloidosis Patients.

Background: In cardiac amyloidosis, the prevalence of thromboembolic events and atrial fibrillation is higher in transthyretin amyloidosis compared to immunoglobulin light chain amyloidosis. Therefore, we hypothesize that transthyretin cardiac amyloidosis patients have worse atrial function. Purpose: To explore the left atrial function by conventional ultrasound and strain analysis in immunoglobulin light chain- and transthyretin cardiac amyloidosis patients. Methods: In cardiac amyloidosis patients in our Amyloidosis Expert Center, echocardiographic strain analysis was performed using speckle tracking. Results: The data of 53 cardiac amyloidosis patients (83% male, mean age 70 years) were analyzed. Transthyretin cardiac amyloidosis patients (n = 24, 45%) were older (75 ± 5.6 vs. 65 ± 7.2 years, p < 0.001) and had more left ventricular (LV) hypertrophy than immunoglobulin light chain cardiac amyloidosis patients (n = 29, 55%). However, LV systolic and diastolic function did not differ, nor did left atrial dimensions (LAVI 56(24) vs. 50(31) mL/m2). Left atrial reservoir strain was markedly lower in transthyretin cardiac amyloidosis (7.4(6.2) vs. 13.6(14.7), p = 0.017). This association was independent of other measurements of the left atrial and ventricular function. Conclusions: Transthyretin cardiac amyloidosis patients had lower left atrial reservoir function compared to immunoglobulin light chain cardiac amyloidosis patients although the left atrial geometry was similar. Interestingly, this association was independent of left atrial- and LV ejection fraction and global longitudinal strain. Further research is warranted to assess the impact of impaired left atrial dysfunction in transthyretin cardiac amyloidosis on atrial fibrillation burden and prognosis.

Comparison of Framingham, PROCAM, SCORE, and Diamond Forrester to predict coronary atherosclerosis and cardiovascular events.

BACKGROUND: Cardiologists are often confronted with patients presenting with chest pain, in whom clinical risk profiling is required. We studied four frequently used risk scores in their ability to predict for coronary artery disease (CAD) and major adverse cardiovascular events in patients presenting with stable chest pain at the cardiology outpatient clinic. METHODS AND RESULTS: We enrolled 1,296 stable chest pain patients, who underwent cardiac computed tomographic angiography (CCTA) to assess CAD (any, significant: stenosis ≥50%). Framingham (FRS), PROCAM, SCORE risk score, and Diamond Forrester pre-test probability were calculated. All patients were followed up for a mean 19 ± 9 months for all cardiovascular events (mortality, acute coronary syndrome, revascularization >90 days after CCTA). In ROC-analysis for prediction of significant CAD, the areas under the curve for FRS; 0.68 (95% confidence interval: 0.64-0.72) and for SCORE; 0.69 (95% confidence interval: 0.65-0.72) were significantly higher than for PROCAM; 0.64 (95% confidence interval: 0.61-0.68; P ≤ .001), as well as marginally higher than for Diamond Forrester; 0.65 (95% confidence interval: 0.61-0.68; P ≤ .05). Low FRS category showed the lowest number of patients with significant CAD, compared to patients with low risk using PROCAM, SCORE or Diamond Forrester (P < .001). Also, low FRS category showed less events (compared to PROCAM and SCORE; P < .001, for Diamond Forrester; P = .14). CONCLUSION: Our data show that in a stable chest pain population, the ability of FRS and SCORE to predict for CAD was similar and better compared to PROCAM and Diamond Forrester. The number of low risk patients showing significant CAD or events was lower using FRS. Consequently, risk categorization using FRS seems to be safest to stratify stable chest pain patients prior to CCTA.

Unstable coronary plaque characteristics are associated with high-sensitivity cardiac troponin T and N-terminal Pro-Brain Natriuretic Peptide.

BACKGROUND: Unstable plaque characteristics on coronary CT angiography (CTA), serum high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) concentrations are associated with cardiovascular events. OBJECTIVE: To investigate the association between coronary CTA defined quantifiable plaque characteristics, hs-cTnT and NT-proBNP. METHODS: 81 consecutive stable chest pain patients with an intermediate-to-high risk were analyzed. Coronary CTA was performed using a 64-slice multidetector-row CT-scanner. Total coronary plaque volume, calcified volume, non-calcified volume, plaque burden, remodeling index (RI) and number of plaques were measured using dedicated software. A total plaque score ("Sum plaque score") incorporating total plaque volume, RI, plaque burden and number of plaques was defined. Hs-cTnT and NT-proBNP concentrations were measured in serum samples before coronary CTA. RESULTS: Univariate regression analysis demonstrated significant associations of hs-cTnT and NT-proBNP with total plaque volume (r hs-cTnT = .256; r NT-proBNP = .270), calcified volume (r hs-cTnT = .344; r NT-proBNP = .344), RI (r hs-cTnT = .335; r NT-proBNP = .342) and number of plaques (r hs-cTnT = .355; r NT-proBNP = .301) (all P values ≤ .021). Non-calcified plaque volume showed no association with hs-cTnT and NT-proBNP (r hs-cTnT = .050; r NT-proBNP = .087; P value = .660 and P value = .442). The "Sum plaque score" showed the highest correlation compared to other plaque parameters (r hs-cTnT = .362; r NT-proBNP = .409; P value = .001 and P value ≤ .001). CONCLUSION: Our data suggest that coronary plaque morphology parameters, derived by dedicated software, are associated with serum hs-cTnT and NT-proBNP concentrations.

High-Sensitivity Cardiac Troponin Concentrations in Patients with Chest Discomfort: Is It the Heart or the Kidneys As Well?

BACKGROUND: High-sensitivity cardiac troponins (hs-cTn) are the preferred biomarkers to detect myocardial injury, making them promising risk-stratifying tools for patients with symptoms of chest pain. However, circulating hs-cTn are also elevated in other conditions like renal dysfunction, complicating appropriate interpretation of low-level hs-cTn concentrations. METHODS: A cross-sectional analysis was performed in 1864 patients with symptoms of chest discomfort from the cardiology outpatient department who underwent cardiac computed tomographic angiography (CCTA). Serum samples were analyzed using hs-cTnT and hs-cTnI assays. Renal function was measured by the estimated glomerular filtration rate (eGFR), established from serum creatinine and cystatin C. On follow-up, the incidence of adverse events was assessed. RESULTS: Median hs-cTnT and hs-cTnI concentrations were 7.2(5.8-9.2) ng/L and 2.6(1.8-4.1) ng/L, respectively. Multivariable regression analysis revealed that both assay results were more strongly associated with eGFR (hs-cTnT:stß:-0.290;hs-cTnI:stß:-0.222) than with cardiac imaging parameters, such as coronary calcium score, CCTA plaque severity score and left ventricular mass (all p<0.01). Furthermore, survival analysis indicated lower relative risks in patients with normal compared to reduced renal function for hs-cTnT [HR(95%CI), 1.02(1.00-1.03) compared to 1.07(1.05-1.09)] and hs-cTnI [1.01(1.00-1.01) compared to 1.02(1.01-1.02)] (all p<0.001). CONCLUSION: In patients with chest discomfort, we identified an independent influence of renal function on hs-cTn concentrations besides CAD, that affected the association of hs-cTn concentrations with adverse events. Estimating renal function is therefore warranted when interpreting baseline hs-cTn concentrations.

Automated quantification of epicardial adipose tissue (EAT) in coronary CT angiography; comparison with manual assessment and correlation with coronary artery disease.

BACKGROUND: Epicardial adipose tissue (EAT) is emerging as a risk factor for coronary artery disease (CAD). OBJECTIVE: The aim of this study was to determine the applicability and efficiency of automated EAT quantification. METHODS: EAT volume was assessed both manually and automatically in 157 patients undergoing coronary CT angiography. Manual assessment consisted of a short-axis-based manual measurement, whereas automated assessment on both contrast and non-contrast-enhanced data sets was achieved through novel prototype software. Duration of both quantification methods was recorded, and EAT volumes were compared with paired samples t test. Correlation of volumes was determined with intraclass correlation coefficient; agreement was tested with Bland-Altman analysis. The association between EAT and CAD was estimated with logistic regression. RESULTS: Automated quantification was significantly less time consuming than automated quantification (17 ± 2 seconds vs 280 ± 78 seconds; P < .0001). Although manual EAT volume differed significantly from automated EAT volume (75 ± 33 cm(³) vs 95 ± 45 cm(³); P < .001), a good correlation between both assessments was found (r = 0.76; P < .001). For all methods, EAT volume was positively associated with the presence of CAD. Stronger predictive value for the severity of CAD was achieved through automated quantification on both contrast-enhanced and non-contrast-enhanced data sets. CONCLUSION: Automated EAT quantification is a quick method to estimate EAT and may serve as a predictor for CAD presence and severity.

Combined use of exercise electrocardiography, coronary calcium score and cardiac CT angiography for the prediction of major cardiovascular events in patients presenting with stable chest pain.

BACKGROUND: The usual diagnostic work-up of chest pain patients includes clinical risk profiling and exercise-ECG, possibly followed by additional tests. Recently cardiac computed tomographic angiography (CCTA) has been employed. We evaluated the prognostic value of the combined use of exercise-ECG and CCTA for the development of cardiovascular endpoints. METHODS: In 283 patients (143 male, mean age 54 ± 10 years) with intermediate pre-test probability for coronary artery disease presenting with stable chest pain, exercise-ECG, CCTA and calcium score were performed. Patients were followed-up for combined endpoint of acute coronary syndrome (ACS) and revascularization. RESULTS: After a median follow-up of 769 days (interquartile range 644-1007), 6 ACS and 9 revascularizations were recorded. A positive exercise-ECG predicted for the combined endpoint, [hazard ratio (HR) 5.14 (95% confidence interval (CI) 1.64-16.13), p=0.005], as well as a positive calcium score [HR 4.59 (95% CI 1.30-16.28), p=0.02] and a ≥ 50% stenosis on CCTA [HR 45.82 (95% CI 6.02-348.54), p<0.001]. ROC-analysis showed an area under the curve (AUC) of 0.79 (95% CI 0.67-0.90) for exercise-ECG, which increased significantly when CCTA was added: 0.91 (95% CI; 0.86-0.97; p=0.006). Multivariable Cox regression showed exercise-ECG predicted independently [HR 3.6, (95% CI 1.1-11.2), p=0.03], as well as CCTA [HR 31.4 (95% CI 4.0-246.6), p=0.001], but not calcium score [HR 0.6 (95% CI 0.2-2.3), p=0.5]. CONCLUSIONS: The combined subsequent use of exercise-ECG for functional information and CCTA for anatomical information provides a high diagnostic yield in stable chest pain patients with an intermediate pre-test probability for coronary artery disease.

Additive value of semiautomated quantification of coronary artery disease using cardiac computed tomographic angiography to predict future acute coronary syndrome.

OBJECTIVES: The purpose of this study was to investigate whether the use of a semiautomated plaque quantification algorithm (reporting volumetric and geometric plaque properties) provides additional prognostic value for the development of acute coronary syndromes (ACS) as compared with conventional reading from cardiac computed tomography angiography (CCTA). BACKGROUND: CCTA enables the visualization of coronary plaque characteristics, of which some have been shown to predict ACS. METHODS: A total of 1,650 patients underwent 64-slice CCTA and were followed up for ACS for a mean 26 ± 10 months. In 25 patients who had ACS and 101 random controls (selected from 993 patients with coronary artery disease but without coronary event), coronary artery disease was evaluated using conventional reading (calcium score, luminal stenosis, morphology), and then independently quantified using semiautomated software (plaque volume, burden area [plaque area divided by vessel area times 100%], noncalcified percentage, attenuation, remodeling). Clinical risk profile was calculated with Framingham risk score (FRS). RESULTS: There were no significant differences in conventional reading parameters between controls and patients who had ACS. Semiautomated plaque quantification showed that compared to controls, ACS patients had higher total plaque volume (median: 94 mm(3) vs. 29 mm(3)) and total noncalcified volume (28 mm(3) vs. 4 mm(3), p ≤ 0.001 for both). In addition, per-plaque maximal volume (median: 56 mm(3) vs. 24 mm(3)), noncalcified percentage (62% vs. 26%), and plaque burden (57% vs. 36%) in ACS patients were significantly higher (p < 0.01 for all). A receiver-operating characteristic model predicting for ACS incorporating FRS and conventional CCTA reading had an area under the curve of 0.64; a second model also incorporating semiautomated plaque quantification had an area under the curve of 0.79 (p < 0.05). CONCLUSIONS: The semiautomated plaque quantification algorithm identified several parameters predictive for ACS and provided incremental prognostic value over clinical risk profile and conventional CT reading. The application of this tool may improve risk stratification in patients undergoing CCTA.

Accelerated in vivo thrombin formation independently predicts the presence and severity of CT angiographic coronary atherosclerosis.

OBJECTIVES: This study sought to investigate the association between thrombin generation in plasma and the presence and severity of computed tomography angiographically defined coronary atherosclerosis in patients with suspected coronary artery disease (CAD). BACKGROUND: Besides its pivotal role in thrombus formation, experimental data indicate that thrombin can induce an array of pro-atherogenic and plaque-destabilizing effects. Although thrombin plays a role in the pathophysiology of atherosclerosis progression and vascular calcification, the clinical evidence remains limited. METHODS: Using 64-slice coronary computed tomographic angiography, we assessed the presence and characteristics of CAD in patients (n = 295; median age 58 years) with stable chest pain. Coronary artery calcification was graded as absent (Agatston score 0), mild (Agatston score 1 to 100), moderate (Agatston score 101 to 400), and severe (Agatston score >400). Calibrated automated thrombography was used to assess endogenous thrombin potential in plasma in vitro. Thrombin-antithrombin complex (TATc) levels were measured as a marker for thrombin formation in vivo. RESULTS: TATc plasma levels were substantially higher in patients with CAD versus patients without CAD (p = 0.004). Significant positive correlations were observed between steadily increasing TATc levels and the severity of CAD (r = 0.225, p < 0.001). In multinomial logistic regression models, after adjusting for established risk factors, TATc levels predicted the degree of coronary artery calcification: mild (odds ratio: 1.56, p = 0.006), moderate (odds ratio: 1.56, p = 0.007), and severe (odds ratio: 1.67, p = 0.002). Trends were comparable between the groups when stratified according to the degree of coronary luminal stenosis. CONCLUSIONS: This study provides novel clinical evidence indicating a positive independent association between enhanced in vivo thrombin generation and the presence and severity of coronary atherosclerosis, which may suggest that thrombin plays a role in the pathophysiology of vascular calcification and atherosclerosis progression.

Relation between mild to moderate chronic kidney disease and coronary artery disease determined with coronary CT angiography.

BACKGROUND: Both end-stage and milder stages of chronic kidney disease (CKD) are associated with an increased risk of adverse cardiovascular events. Several studies found an association between decreasing renal function and increasing coronary artery calcification, but it remains unclear if this association is independent from traditional cardiovascular risk factors. Therefore, the aim of this study was to investigate whether mild to moderate CKD is independently associated with coronary plaque burden beyond traditional cardiovascular risk factors. METHODS: A total of 2,038 patients with symptoms of chest discomfort suspected for coronary artery disease underwent coronary CT-angiography. We assessed traditional risk factors, coronary calcium score and coronary plaque characteristics (morphology and degree of luminal stenosis). Patients were subdivided in three groups, based on their estimated glomerular filtration rate (eGFR) Normal renal function (eGFR ≥90 mL/min/1.73 m(2)); mild CKD (eGFR 60-89 mL/min/1.73 m(2)); and moderate CKD (eGFR 30-59 mL/min/1.73 m(2)). RESULTS: Coronary calcium score increased significantly with decreasing renal function (P<0.001). Coronary plaque prevalence was higher in patients with mild CKD (OR 1.83, 95%CI 1.52-2.21) and moderate CKD (OR 2.46, 95%CI 1.69-3.59), compared to patients with normal renal function (both P<0.001). Coronary plaques with >70% luminal stenosis were found significantly more often in patients with mild CKD (OR 1.67 (95%CI 1.16-2.40) and moderate CKD (OR2.36, 95%CI 1.35-4.13), compared to patients with normal renal function (both P<0.01). After adjustment for traditional cardiovascular risk factors, the association between renal function and the presence of any coronary plaque as well as the association between renal function and the presence of coronary plaques with >70% luminal stenosis becomes weaker and were no longer statistically significant. CONCLUSION: Although decreasing renal function is associated with increasing extent and severity of coronary artery disease, mild to moderately CKD is not independently associated with coronary plaque burden after adjustment for traditional cardiovascular risk factors.

Epicardial adipose tissue volume as a predictor for coronary artery disease in diabetic, impaired fasting glucose, and non-diabetic patients presenting with chest pain.

AIMS: Epicardial adipose tissue (EAT) volume has been associated with coronary artery disease (CAD). As diabetes mellitus type 2 (DM2) patients have higher EAT volumes, it has been suggested that EAT may play a role in promoting CAD in these patients. The aim of this study was to examine the association between EAT and CAD in DM2, impaired fasting glucose (IFG) and control patients presenting with stable chest pain. METHODS AND RESULTS: A total of 410 stable chest pain patients underwent multidetector cardiac computed tomography angiography (CCTA) to assess the presence of CAD. The extent of CAD was expressed as the number of affected segments. The EAT volume was measured using three-dimensional volumetric quantification. The EAT was compared using ANOVA, logistic and linear regression models were used to assess its predictive value. Multivariable regression analysis corrected for traditional risk factors was performed. Eighty-three patients had DM2, 118 IFG and there were 209 controls. DM2 as well as IFG patients had higher EAT volumes compared with controls (98 ± 41, 92 ± 39, and 75 ± 34 cm(3), respectively; P < 0.001). EAT predicted the presence (OR: 1.01; P < 0.001) and the extent of CAD (B: 0.01; P < 0.001). The associations were equal in all subgroups. However, in a multivariable regression model corrected for traditional cardiovascular risk factors, EAT was not an independent predictor for the presence or extent of CAD (OR: 1.00; P = 0.88 and B: -0.11; P = 0.68, respectively). CONCLUSION: The EAT volume is associated with CAD in DM2, IFG, and control patients. However, EAT is not an independent predictor for CAD in patients presenting with stable chest pain.

High-sensitivity cardiac troponin T: risk stratification tool in patients with symptoms of chest discomfort.

BACKGROUND: Recent studies have demonstrated the association between increased concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and the incidence of myocardial infarction, heart failure, and mortality. However, most prognostic studies to date focus on the value of hs-cTnT in the elderly or general population. The value of hs-cTnT in symptomatic patients visiting the outpatient department remains unclear. The aim of this study was to investigate the prognostic value of hs-cTnT as a biomarker in patients with symptoms of chest discomfort suspected for coronary artery disease and to assess its additional value in combination with other risk stratification tools in predicting cardiac events. METHODS: We studied 1,088 patients (follow-up 2.2 ± 0.8 years) with chest discomfort who underwent coronary calcium scoring and coronary CT-angiography. Traditional cardiovascular risk factors and concentrations of hs-cTnT, N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP) were assessed. Study endpoint was the occurrence of late coronary revascularization (>90 days), acute coronary syndrome, and cardiac mortality. RESULTS: Hs-cTnT was a significant predictor for the composite endpoint (highest quartile [Q4]>6.7 ng/L, HR 3.55; 95%CI 1.88-6.70; P<0.001). Survival analysis showed that hs-cTnT had significant predictive value on top of current risk stratification tools (Chi-square change P<0.01). In patients with hs-cTnT in Q4 versus

Performance of angiographic, electrocardiographic and MRI methods to assess the area at risk in acute myocardial infarction.

Objective Validation of methods to assess the area at risk (AAR) in patients with ST elevation myocardial infarction is limited. A study was undertaken to test different AAR methods using established physiological concepts to provide a reference standard. Main outcome measured In 78 reperfused patients with first ST elevation myocardial infarction, AAR was measured by electrocardiographic (Aldrich), angiographic (Bypass Angioplasty Revascularization Investigation (BARI), APPROACH) and cardiovascular magnetic resonance methods (T2-weighted hyperintensity and delayed enhanced endocardial surface area (ESA)). The following established physiological concepts were used to evaluate the AAR METHODS: (1) AAR size is always ≥ infarct size (IS); (2) in transmural infarcts AAR size=IS; (3) correlation between AAR size and IS increases as infarct transmurality increases; and (4) myocardial salvage ((AAR-IS)/AAR×100) is inversely related to infarct transmurality. Results Overall, 65%, 87%, 76%, 87% and 97% of patients using the Aldrich, BARI, APPROACH, T2-weighted hyperintensity and ESA methods obeyed the concept that AAR size is ≥IS. In patients with transmural infarcts (n=22), Bland-Altman analysis showed poor agreement (wide 95% limits of agreement) between AAR size and IS for the BARI, Aldrich and APPROACH methods (95% CI -22.9 to 29.6, 95% CI -28.3 to 21.3 and 95% CI -16.9 to 20.0, respectively) and better agreement for T2-weighted hyperintensity and ESA (95% CI -6.9 to 16.6 and 95% CI -4.3 to 18.0, respectively). Increasing correlation between AAR size and IS with increasing infarct transmurality was observed for the APPROACH, T2-weighted hyperintensity and ESA methods, with ESA having the highest correlation (r=0.93, p<0.001). The percentage of patients within a narrow margin (±30%) of the inverse line of identity between salvage extent and infarct transmurality was 56%, 76%, 65%, 77% and 92% for the Aldrich, BARI, APPROACH, T2-weighted hyperintensity and ESA methods, respectively, where higher percentages represent better concordance with the concept that the extent of salvage should be inversely related to infarct transmurality. Conclusions For measuring AAR, cardiovascular magnetic resonance methods are better than angiographic methods, which are better than electrocardiographic methods. Overall, ESA performed best for measuring AAR in vivo.