Peri-coronary inflammation is associated with findings on coronary computed tomography angiography and fractional flow reserve.
Peri-coronary adipose tissue attenuation expressed by fat attenuation index (FAI) on coronary CT angiography (CCTA) reflects peri-coronary inflammation and is associated with cardiac mortality. We aimed to investigate the association between FAI and whole vessel and lesion plaque quantification on CCTA in stable patients with intermediate epicardial stenosis evaluated by fractional flow reserve (FFR).
A total of 187 left anterior descending arteries (LAD) with intermediate stenosis who underwent FFR measurement and CCTA were studied. FAI was assessed by the crude analysis of the mean CT attenuation value of LAD on CCTA. Determinants of FAI and FFR were explored. Furthermore, the impact of combined baseline data, CCTA-derived lesion plaque assessment, whole vessel quantification, cardiac mass and FAI on discrimination efficacy for ischemia was evaluated as FFR used for a reference standard.
The mean FAI and the median FFR values were -73.0 and 0.77, respectively. Multivariate analysis revealed that male, CCTA-derived positive remodeling, lower minimum lumen area, higher target vessel total cardiac mass, and lower FFR were independent predictors of FAI. CCTA-derived two-dimensional and three-dimensional analysis and FAI were independently and significantly associated with FFR values. Net reclassification index and integrated discrimination improvement index were both significantly improved when FAI was added to the baseline model for lesions with FFR <0.75, but not for FFR≤0.80.
FAI was associated with FFR, CCTA-derived two-dimensional and three-dimensional lumen and plaque quantification and cardiac mass in patients with intermediate lesions in LAD, indicating that comprehensive CTA assessment may provide risk-stratification.
Hoshino M
，Yang S
，Sugiyama T
，Zhang J
，Kanaji Y
，Yamaguchi M
，Hada M
，Sumino Y
，Horie T
，Nogami K
，Ueno H
，Misawa T
，Usui E
，Murai T
，Lee T
，Yonetsu T
，Kakuta T
... -
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Standardized measurement of coronary inflammation using cardiovascular computed tomography: integration in clinical care as a prognostic medical device.
Coronary computed tomography angiography (CCTA) is a first-line modality in the investigation of suspected coronary artery disease (CAD). Mapping of perivascular fat attenuation index (FAI) on routine CCTA enables the non-invasive detection of coronary artery inflammation by quantifying spatial changes in perivascular fat composition. We now report the performance of a new medical device, CaRi-Heart®, which integrates standardized FAI mapping together with clinical risk factors and plaque metrics to provide individualized cardiovascular risk prediction.
The study included 3912 consecutive patients undergoing CCTA as part of clinical care in the USA (n = 2040) and Europe (n = 1872). These cohorts were used to generate age-specific nomograms and percentile curves as reference maps for the standardized interpretation of FAI. The first output of CaRi-Heart® is the FAI-Score of each coronary artery, which provides a measure of coronary inflammation adjusted for technical, biological, and anatomical characteristics. FAI-Score is then incorporated into a risk prediction algorithm together with clinical risk factors and CCTA-derived coronary plaque metrics to generate the CaRi-Heart® Risk that predicts the likelihood of a fatal cardiac event at 8 years. CaRi-Heart® Risk was trained in the US population and its performance was validated externally in the European population. It improved risk discrimination over a clinical risk factor-based model [Δ(C-statistic) of 0.085, P = 0.01 in the US Cohort and 0.149, P < 0.001 in the European cohort] and had a consistent net clinical benefit on decision curve analysis above a baseline traditional risk factor-based model across the spectrum of cardiac risk.
Mapping of perivascular FAI on CCTA enables the non-invasive detection of coronary artery inflammation by quantifying spatial changes in perivascular fat composition. We now report the performance of a new medical device, CaRi-Heart®, which allows standardized measurement of coronary inflammation by calculating the FAI-Score of each coronary artery. The CaRi-Heart® device provides a reliable prediction of the patient's absolute risk for a fatal cardiac event by incorporating traditional cardiovascular risk factors along with comprehensive CCTA coronary plaque and perivascular adipose tissue phenotyping. This integration advances the prognostic utility of CCTA for individual patients and paves the way for its use as a dual diagnostic and prognostic tool among patients referred for CCTA.
Oikonomou EK
，Antonopoulos AS
，Schottlander D
，Marwan M
，Mathers C
，Tomlins P
，Siddique M
，Klüner LV
，Shirodaria C
，Mavrogiannis MC
，Thomas S
，Fava A
，Deanfield J
，Channon KM
，Neubauer S
，Desai MY
，Achenbach S
，Antoniades C
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Non-invasive detection of coronary inflammation using computed tomography and prediction of residual cardiovascular risk (the CRISP CT study): a post-hoc analysis of prospective outcome data.
Coronary artery inflammation inhibits adipogenesis in adjacent perivascular fat. A novel imaging biomarker-the perivascular fat attenuation index (FAI)-captures coronary inflammation by mapping spatial changes of perivascular fat attenuation on coronary computed tomography angiography (CTA). However, the ability of the perivascular FAI to predict clinical outcomes is unknown.
In the Cardiovascular RISk Prediction using Computed Tomography (CRISP-CT) study, we did a post-hoc analysis of outcome data gathered prospectively from two independent cohorts of consecutive patients undergoing coronary CTA in Erlangen, Germany (derivation cohort) and Cleveland, OH, USA (validation cohort). Perivascular fat attenuation mapping was done around the three major coronary arteries-the proximal right coronary artery, the left anterior descending artery, and the left circumflex artery. We assessed the prognostic value of perivascular fat attenuation mapping for all-cause and cardiac mortality in Cox regression models, adjusted for age, sex, cardiovascular risk factors, tube voltage, modified Duke coronary artery disease index, and number of coronary CTA-derived high-risk plaque features.
Between 2005 and 2009, 1872 participants in the derivation cohort underwent coronary CTA (median age 62 years [range 17-89]). Between 2008 and 2016, 2040 patients in the validation cohort had coronary CTA (median age 53 years [range 19-87]). Median follow-up was 72 months (range 51-109) in the derivation cohort and 54 months (range 4-105) in the validation cohort. In both cohorts, high perivascular FAI values around the proximal right coronary artery and left anterior descending artery (but not around the left circumflex artery) were predictive of all-cause and cardiac mortality and correlated strongly with each other. Therefore, the perivascular FAI measured around the right coronary artery was used as a representative biomarker of global coronary inflammation (for prediction of cardiac mortality, hazard ratio [HR] 2·15, 95% CI 1·33-3·48; p=0·0017 in the derivation cohort, and 2·06, 1·50-2·83; p<0·0001 in the validation cohort). The optimum cutoff for the perivascular FAI, above which there is a steep increase in cardiac mortality, was ascertained as -70·1 Hounsfield units (HU) or higher in the derivation cohort (HR 9·04, 95% CI 3·35-24·40; p<0·0001 for cardiac mortality; 2·55, 1·65-3·92; p<0·0001 for all-cause mortality). This cutoff was confirmed in the validation cohort (HR 5·62, 95% CI 2·90-10·88; p<0·0001 for cardiac mortality; 3·69, 2·26-6·02; p<0·0001 for all-cause mortality). Perivascular FAI improved risk discrimination in both cohorts, leading to significant reclassification for all-cause and cardiac mortality.
The perivascular FAI enhances cardiac risk prediction and restratification over and above current state-of-the-art assessment in coronary CTA by providing a quantitative measure of coronary inflammation. High perivascular FAI values (cutoff ≥-70·1 HU) are an indicator of increased cardiac mortality and, therefore, could guide early targeted primary prevention and intensive secondary prevention in patients.
British Heart Foundation, and the National Institute of Health Research Oxford Biomedical Research Centre.
Oikonomou EK
，Marwan M
，Desai MY
，Mancio J
，Alashi A
，Hutt Centeno E
，Thomas S
，Herdman L
，Kotanidis CP
，Thomas KE
，Griffin BP
，Flamm SD
，Antonopoulos AS
，Shirodaria C
，Sabharwal N
，Deanfield J
，Neubauer S
，Hopewell JC
，Channon KM
，Achenbach S
，Antoniades C
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