Yeonyee E. Yoon

Noninvasive Diagnosis of Ischemia-Causing Coronary Stenosis Using CT Angiography : Diagnostic Value of Transluminal Attenuation Gradient and Fractional Flow Reserve Computed From Coronary CT Angiography Compared to Invasively Measured Fractional Flow Reserve

OBJECTIVES The aim of this study was to compare the diagnostic performance of coronary computed tomography angiography (CCTA)-derived computed fractional flow reserve (FFR(CT)) and transluminal attenuation gradient (TAG) for the diagnosis of lesion-specific ischemia. BACKGROUND Although CCTA is commonly used to detect coronary artery disease (CAD), it cannot reliably assess the functional significance of CAD. Novel technologies based on CCTA were developed to integrate anatomical and functional assessment of CAD; however, the diagnostic performance of these methods has never been compared. METHODS Fifty-three consecutive patients who underwent CCTA and coronary angiography with FFR measurement were included. Independent core laboratories determined CAD severity by CCTA, TAG, and FFR(CT). The TAG was defined as the linear regression coefficient between intraluminal radiological attenuation and length from the ostium; FFR(CT) was computed from CCTA data using computational fluid dynamics technology. RESULTS Among 82 vessels, 32 lesions (39%) had ischemia by invasive FFR (FFR ≤0.80). Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratio of TAG (≤ -0.654 HU/mm) for detection of ischemia were 38%, 88%, 67%, 69%, 3.13, and 0.71, respectively; and those of FFR(CT) were 81%, 94%, 90%, 89%, 13.54, and 0.20, respectively. Receiver-operating characteristic curve analysis showed a significantly larger area under the curve (AUC) for FFR(CT) (0.94) compared to that for TAG (0.63, p < 0.001) and CCTA stenosis (0.73, p < 0.001). In vessels with noncalcified plaque or partially calcified plaque, FFR(CT) showed a larger AUC (0.94) compared to that of TAG (0.63, p < 0.001) or CCTA stenosis (0.70, p < 0.001). In vessels with calcified plaque, AUC of FFR(CT) (0.92) was not statistically larger than that of TAG (0.75, p = 0.168) or CCTA stenosis (0.80, p = 0.195). CONCLUSIONS Noninvasive FFR computed from CCTA provides better diagnostic performance for the diagnosis of lesion-specific ischemia compared to CCTA stenosis and TAG.

Diagnostic performance of intracoronary gradient-based methods by coronary computed tomography angiography for the evaluation of physiologically significant coronary artery stenoses: a validation study with fractional flow reserve

AIMS We validated and compared transluminal attenuation gradient (TAG) and corrected coronary opacification (CCO) of coronary computed tomography angiography (CCTA) with invasively measured fractional flow reserve (FFR). BACKGROUND One of the major limitations of CCTA is the discrepancy between angiographical stenosis and ischaemia-causing stenosis. Recently two new CCTA analysis methods, TAG and CCO, have been attempted to overcome this limitation but without physiological validation. METHODS AND RESULTS We measured TAG and CCO of 97 major epicardial coronary arteries from 63 patients who underwent CCTA and followed by invasive coronary angiography and FFR. Diagnostic performance of TAG and CCO was assessed using FFR <0.80 as the reference standard. The overall diagnostic performance of TAG and CCO on a per-vessel basis was moderate and similar (c-statistic = 0.696 vs. 0.637, P = 0.29). The sensitivity, specificity, positive, and negative predictive values of TAG cut-off ≤-0.654 for FFR <0.80 were 47.5, 91.2, 79.2, and 71.2%, and those of CCO cut-off >0.063 were 65.0, 61.4, 54.2, and 71.4%. TAG showed an incremental value to the diagnostic performance of CCTA but CCO did not (c-statistic =0.726 vs. 0.809, P = 0.025; c-statistic =0.726 vs. 0.784, P = 0.09). In net reclassification improvement (NRI) analysis, addition of TAG to CCTA did not result in significant reclassification (NRI = 1.0%, P = 0.41) and addition of CCO to CCTA resulted in negative reclassification (NRI = -9.3%, P = 0.036). CONCLUSION Intracoronary attenuation-based CCTA analyses, TAG and CCO, showed moderate correlation with physiological coronary artery stenosis. The incremental value of TAG or CCO to the evaluation of haemodynamically stenosis by CCTA seemed to be limited.

Detection of occult coronary artery disease in asymptomatic individuals with diabetes mellitus using non-invasive cardiac angiography

INTRODUCTION/OBJECTIVES Cardiovascular disease is the leading cause of death for individuals with diabetes mellitus. Controversy exists regarding the screening of asymptomatic diabetics for occult coronary artery disease (CAD). The purpose of this study is to describe the prevalence of occult CAD in a group of asymptomatic subjects with diabetes using non-invasive coronary angiography, as well as to investigate the predictive accuracy of current guidelines with regards to their recommended criteria for further cardiac diagnostic testing in this patient population. METHODS We prospectively enrolled 217 asymptomatic Korean outpatients with type 2 diabetes who had no prior history of CAD. All underwent non-invasive coronary angiography using a 64-slice multi-detector computed tomography scanner. RESULTS The mean age of the study participants was 59+/-8 years; 66% were men. Diabetes duration was 7+/-7 years, mean Framingham risk score was 13%, and mean hemoglobin A1C level was 7%. Of the 217 outpatients, 138 (64%) had occult CAD based on cardiac computed tomography angiography (CCTA) findings. Thirty-six (36/138; 26%) had a significant stenosis on CCTA. Nearly half of the individuals (62/138; 45%) had a combination of non-calcified and calcified plaques. Only 5 out of 217 (2%) individuals with significant stenosis would have been missed using the American Diabetes Association (ADA) criteria for further cardiac testing. CONCLUSION Almost two thirds of asymptomatic diabetics have occult CAD, including obstructive disease. Based on CCTA findings, the ADA criteria for further cardiac diagnostic testing would identify most individuals who have a significant coronary stenosis.

Association of traditional cardiovascular risk factors with coronary plaque sub-types assessed by 64-slice computed tomography angiography in a large cohort of asymptomatic subjects.

OBJECTIVE Although prior studies have shown that traditional cardiovascular (CV) risk factors are associated with the burden of coronary atherosclerosis, less is known about the relationship of risk factors with coronary plaque sub-types. Coronary computed tomography angiography (CCTA) allows an assessment of both, total disease burden and plaque characteristics. In this study, we investigate the relationship between traditional CV risk factors and the presence and extent of coronary plaque sub-types in a large group of asymptomatic individuals. METHODS The study population consisted of 1015 asymptomatic Korean subjects (53+/-10 years; 64% were males) free of known CV disease who underwent 64-slice CCTA as part of a health screening evaluation. We analyzed plaque characteristics on a per-segment basis according to the modified American Heart Association classification. Plaques in which calcified tissue occupied more than 50% of the plaque area were classified as calcified (CAP), <50% calcified area as mixed (MCAP), and plaques without any calcium as non-calcified (NCAP). RESULTS A total of 215 (21%) subjects had coronary plaque while 800 (79%) had no identifiable disease. Multivariate regression analysis demonstrated that increased age (per decade) and gender are the strongest predictors for the presence of any coronary plaque or the presence of at least one segment of CAP and MCAP (any plaque-age: OR 2.89; 95% CI 2.34, 3.56; male gender: OR 5.21; 95% CI 3.20, 8.49; CAP-age: OR 2.75; 95% CI 2.12, 3.58; male gender: 4.78; 95% CI 2.48, 9.23; MCAP-age: OR 2.62; 95% CI 2.02, 3.39; male gender: OR 4.15; 95% CI 2.17, 7.94). The strongest predictors for the presence of any NCAP were gender (OR 3.56; 95% CI 1.96-6.55) and diabetes mellitus (OR 2.87; 95% CI 1.63-5.08). When looking at the multivariate association between the presence of >/=2 coronary segments with a plaque sub-type and CV risk factors, male gender was the strongest predictor for CAP (OR 7.31; 95% CI 2.12, 25.20) and MCAP (OR 5.54; 95% CI 1.84, 16.68). Alternatively, smoking was the strongest predictor for the presence of >/=2 coronary segments with NCAP (OR 4.86; 95% CI 1.68, 14.07). Low-density lipoprotein cholesterol (LDL-C) was only a predictor for the presence and extent of mixed coronary plaque. CONCLUSION Age and gender are overall the strongest predictors of atherosclerosis as assessed by CCTA in this large asymptomatic Korean population and these two risk factors are not particularly associated with a specific coronary plaque sub-type. Smoking is a strong predictor of NCAP, which has been suggested by previous reports as a more vulnerable lesion. Whether a specific plaque sub-type is associated with a worse prognosis is yet to be determined by future prospective studies.

Impact of Coronary Computed Tomographic Angiography Results on Patient and Physician Behavior in a Low-Risk Population

BACKGROUND The impact of screening coronary computed tomographic angiography (CCTA) on physician and patient behavior is unclear. METHODS We studied asymptomatic patients from a health-screening program. Our study population comprised 1000 patients who underwent CCTA as part of a prior study and a matched control group of 1000 patients who did not. We assessed medication use, secondary test referrals, revascularizations, and cardiovascular events at 90 days and 18 months. RESULTS A total of 215 patients in the CCTA group had coronary atherosclerosis (CCTA positive). Medication use was increased in the CCTA-positive group compared with both the CCTA-negative (no atherosclerosis) and control groups at 90 days (statin use, 34% vs 5% vs 8%, respectively; aspirin use, 40% vs 5% vs 8%, respectively), and 18 months (statin use, 20% vs 3% vs 6%, respectively; aspirin use, 26% vs 3% vs 6%, respectively). After multivariable risk adjustment, the odds ratios for statin and aspirin use in the CCTA-positive group at 18 months were 3.3 (95% confidence interval [CI], 1.3-8.3) and 4.2 (95% CI, 1.8-9.6), respectively. At 90 days, in the total CCTA group vs controls, there were more secondary tests (55 [5%] vs 22 [2%]; P < .001) and revascularizations (13 [1%] vs 1 [0.1%]; P < .001). One cardiovascular event occurred in each group over 18 months. CONCLUSIONS An abnormal screening CCTA result was predictive of increased aspirin and statin use at 90 days and 18 months, although medication use lessened over time. Screening CCTA was associated with increased invasive testing, without any difference in events at 18 months. Screening CCTA should not be considered a justifiable test at this time.

Prognostic value of coronary magnetic resonance angiography for prediction of cardiac events in patients with suspected coronary artery disease.

OBJECTIVES This study sought to determine whether whole-heart coronary magnetic resonance angiography (CMRA) can predict cardiac events in patients with suspected coronary artery disease. BACKGROUND Recent studies demonstrated that the presence of stenosis on coronary computed tomography angiography has a significant prognostic impact on the prediction of cardiac events. However, the prognostic value of whole-heart CMRA is unknown. METHODS We studied 207 patients with suspected coronary artery disease who underwent non-contrast-enhanced free-breathing whole-heart CMRA acquired with a 1.5-T MR system and 32-channel cardiac coils. The presence of significant coronary stenosis (≥50% diameter reduction) was visually determined on sliding thin- maximum intensity projection images. Follow-up information was obtained for occurrence of severe cardiac events (cardiac death, myocardial infarction, and unstable angina) and all cardiac events (additionally including revascularization>90 days after CMRA). RESULTS During a median follow-up of 25 months, 10 cardiac events, of which 5 were severe, were observed in 84 patients with significant stenosis. Whereas, in 123 patients without significant stenosis, only 1 cardiac event with no severe event was observed. Kaplan-Meier curves demonstrated a significant difference in event-free survival between the 2 groups for severe events (annual event rate, 3.9% and 0%, respectively; log-rank test, p = 0.003), as well as for all cardiac events (6.3% and 0.3%; p < 0.001). Cox regression analysis showed that presence of significant stenosis on CMRA was associated with a >20-fold hazard increase for all cardiac events (hazard ratio: 20.78; 95% confidence interval: 2.65 to 162.70; p = 0.001). CONCLUSIONS Whole-heart CMRA is useful for predicting the future risk for cardiac events in patients with suspected coronary artery disease.

Association between high-sensitivity C-reactive protein and coronary plaque subtypes assessed by 64-slice coronary computed tomography angiography in an asymptomatic population

Background— Elevated levels of C-reactive protein (CRP) are associated with poor cardiovascular outcomes, even after accounting for traditional cardiovascular risk factors. We sought to analyze the relationship between levels of CRP and coronary plaque subtypes as assessed by coronary computed tomography angiography. Methods and Results— We evaluated 1004 asymptomatic South Korean subjects (mean age, 49±9.3 years) who underwent coronary computed tomography angiography as part of a health screening evaluation. We examined the association between increasing CRP levels and plaque subtypes using multivariable linear and logistic regression analysis. Coronary plaque was observed in 211 of 1004 individuals (21%). Subjects with high CRP (≥2 mg/L) had an increased prevalence of any plaque type (30.7% versus 16.7% P<0.001) and mixed calcified arterial plaque (MCAP) (19.3% versus 6.3% P<0.001) as compared with subjects with low-normal CRP. Multivariable logistic regression analysis demonstrated that elevated CRP predicted the presence of any MCAP (high versus low-normal CRP group; odds ratio, 2.81; 95% confidence interval, 1.62 to 4.89). When examining the multivariable logistic regression analysis between the presence of ≥2 plaques and CRP, subjects with high CRP were more likely to have MCAP than those with low-normal CRP levels (odds ratio, 3.78; 95% confidence interval, 1.49 to 9.55). Conclusions Elevated levels of CRP are associated with an increased prevalence of MCAP as assessed by coronary computed tomography angiography. Longitudinal studies will determine if the excess risk observed in persons with elevated CRP may be mediated, at least in part, by an increased burden of MCAP.

Association between increasing levels of hemoglobin A1c and coronary atherosclerosis in asymptomatic individuals without diabetes mellitus.

BackgroundEarlier studies have shown an association between high-normal glucose and increasing glycosylated hemoglobin (HbA1c) levels and cardiovascular events. The objective of this investigation was to study the association between increasing levels of HbA1c in asymptomatic individuals without diabetes mellitus (DM) and coronary plaque characteristics. MethodsThe study population consisted of 1043 asymptomatic Korean individuals without DM who underwent 64-slice cardiac computed tomography angiography as part of a health screening evaluation. We excluded 147 individuals with known history of DM and/or fasting glucose of at least 126 mg/dl, no HbA1c data, or missing risk factor information. The associations between coronary atherosclerosis and plaque subtype burden with increasing HbA1c levels were assessed using multivariable regression analyses. ResultsThe final study population consisted of 906 individuals without DM (mean age: 49±9 years, 62% males); 19 and 9% of the population had any and two or more segments with coronary plaque, respectively. Unadjusted analysis showed a positive association between increasing levels of HbA1c and the number of coronary segments with any (P<0.001) and with mixed coronary plaques (P<0.0001). The association persisted even when traditional risk factors were taken into account. No significant relationship was found between increasing HbA1c levels and the burden of noncalcified or calcified plaque. ConclusionIncreasing levels of HbA1c in asymptomatic individuals without DM are associated with the presence of coronary atherosclerosis, but more specifically with the presence and burden of mixed coronary plaques. Elements of plaque instability have been associated with mixed coronary plaques.

Prognostic Significance of Unrecognized Myocardial Infarction Detected with MR Imaging in Patients with Impaired Fasting Glucose Compared with Those with Diabetes

PURPOSE To investigate whether the presence of myocardial infarction (MI) detected with late gadolinium-enhanced magnetic resonance (MR) imaging is an independent predictor of major adverse cardiac events (MACEs) in patients with impaired fasting glucose (IFG) and those with overt diabetes mellitus (DM). MATERIALS AND METHODS Institutional review board approval was obtained for this study, and all subjects provided written informed consent. Late gadolinium-enhanced and cine MR imaging were performed in 190 patients with IFG and 160 patients with DM without known previous MI to evaluate the presence and extent of late gadolinium enhancement as well as global and regional left ventricular function. MACEs were defined as cardiac death, MI, unstable angina, heart failure, and ventricular arrhythmia. The Cox proportional hazards model was used to investigate the relationship between clinical and MR imaging variables and MACEs. RESULTS Follow-up information was obtained in 181 of the 190 patients with IFG (95%) and 151 of the 160 patients with DM (94%). MACEs were observed in 15 of the 181 patients with IFG (8.3%) and 24 of the 151 with DM (15.9%). Late gadolinium enhancement was an independent predictor for MACE in both the IFG group (adjusted hazard ratio, 5.186; P = .003) and DM group (adjusted hazard ratio, 3.229; P = .015). MACE-free survival was significantly higher in patients with IFG than in those with DM (P = .019, log-rank test). However, the MACE-free survival curve for patients with IFG and late gadolinium enhancement was similar to that for patients with DM and late gadolinium enhancement (P = .735). CONCLUSION The presence of MI detected with late gadolinium-enhanced MR imaging is the strongest multivariable predictor of adverse cardiac events in patients with IFG. Late gadolinium-enhanced MR imaging may help identify a subpopulation of subjects in the prediabetic stage who may benefit from more intensive treatments.

The value of brachial-ankle pulse wave velocity as a predictor of coronary artery disease in high-risk patients.

Background and Objectives Arterial stiffness has been known as an independent contributory factor for coronary artery disease (CAD). Brachial-ankle pulse wave velocity (baPWV) is widely used as a simple noninvasive measure of arterial stiffness. The aim of our study was to test whether baPWV had predictive value for CAD in the subset of patients with high pretest probability. Subjects and Methods We enrolled 174 consecutive patients who were referred for evaluation of suspected CAD, and who underwent both baPWV measurement and computed tomography (CT) for coronary artery calcium scoring (CACS) as part of a diagnostic work-up. Subsequently, 160 of those patients underwent invasive coronary angiography. The CAD indices consisted of 1) CACS, 2) modified Gensini scoring system, and 3) presence of obstructive CAD and 4) multi-vessel obstructive CAD. Results baPWV correlated with CACS (r=0.25, p=0.001), but not with modified Gensini scoring (r=0.10, p=0.19). However, after adjustment for factors influencing PWV, baPWV no longer correlated with CACS (r=0.14, p=0.14). By receiver operating characteristic (ROC) curve analysis, baPWV was neither a sensitive nor specific index for predicting the presence of obstructive CAD or multi-vessel obstructive CAD (sensitivity: 53% and 59%; specificity: 50% and 55%, respectively). Conclusion Our findings demonstrated that baPWV is associated with CACS, however, this may be primarily attributed to common risk factors, such as age. Furthermore, baPWV may be of limited value in identifying patients at risk for CAD.