Prognostic value of metabolic dysfunction-associated steatotic liver disease over coronary computed tomography angiography findings: comparison with no-alcoholic fatty liver disease.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the proposed name change for non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the association of cardiovascular disease risk with MASLD and NAFLD in patients who underwent clinically indicated coronary computed tomography angiography (CCTA). METHODS: This retrospective study included 2289 patients (60% men; mean age: 68 years) with no history of coronary artery disease who underwent CCTA. The steatotic liver was defined as a hepatic-to-spleen attenuation ratio of < 1.0 on CT just before CCTA. MASLD is defined as the presence of hepatic steatosis along with at least one of the five cardiometabolic risk factors. Adverse CCTA findings were defined as obstructive and/or high-risk plaques. Major adverse cardiac events (MACE) encompassed composite coronary events, including cardiovascular death, acute coronary syndrome, and late coronary revascularization. RESULTS: MASLD and NAFLD were identified in 415 (18%) and 368 (16%) patients, respectively. Adverse CCTA findings were observed in 40% and 38% of the patients with MASLD and with NAFLD, respectively. Adverse CCTA findings were significantly associated with MASLD (p = 0.007) but not NAFLD (p = 0.253). During a median follow-up of 4.4 years, 102 (4.4%) MACE were observed. MASLD was significantly associated with MACE (hazard ratio 1.82, 95% CI 1.18-2.83, p = 0.007), while its association with NAFLD was not significant (p = 0.070). By incorporating MASLD into a prediction model of MACE, including the risk score and adverse CCTA findings, global chi-squared values significantly increased from 87.0 to 94.1 (p = 0.008). CONCLUSIONS: Patients with MASLD are likely to have a higher risk of cardiovascular disease than those with NAFLD. Concurrent assessment of MASLD during CCTA improves the identification of patients at a higher risk of cardiovascular disease among those with clinically indicated CCTA.

Computed Tomography Angiography Characteristics of Thin-Cap Fibroatheroma in Patients With Diabetes.

BACKGROUND: It was recently reported that thin-cap fibroatheroma (TCFA) detected by optical coherence tomography was an independent predictor of future cardiac events in patients with diabetes. However, the clinical usefulness of this finding is limited by the invasive nature of optical coherence tomography. Computed tomography angiography (CTA) characteristics of TCFA have not been systematically studied. The aim of this study was to investigate CTA characteristics of TCFA in patients with diabetes. METHODS AND RESULTS: Patients with diabetes who underwent preintervention CTA and optical coherence tomography were included. Qualitative and quantitative analyses were performed for plaques on CTA. TCFA was assessed by optical coherence tomography. Among 366 plaques in 145 patients with diabetes, 111 plaques had TCFA. The prevalence of positive remodeling (74.8% versus 50.6%, P<0.001), low attenuation plaque (63.1% versus 33.7%, P<0.001), napkin-ring sign (32.4% versus 11.0%, P<0.001), and spotty calcification (55.0% versus 34.9%, P<0.001) was significantly higher in TCFA than in non-TCFA. Low-density noncalcified plaque volume (25.4 versus 15.7 mm3, P<0.001) and remodeling index (1.30 versus 1.20, P=0.002) were higher in TCFA than in non-TCFA. The presence of napkin-ring sign, spotty calcification, high low-density noncalcified plaque volume, and high remodeling index were independent predictors of TCFA. When all 4 predictors were present, the probability of TCFA increased to 82.4%. CONCLUSIONS: The combined qualitative and quantitative plaque analysis of CTA may be helpful in identifying TCFA in patients with diabetes. REGISTRATION INFORMATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194.

High-risk coronary plaque of sudden cardiac death victims: postmortem CT angiographic features and histopathologic findings.

High-risk coronary plaques (HRP) are characterized in clinical radiological imaging by the presence of low plaque attenuation, a napkin-ring sign (NRS), spotty calcifications (SC) and a positive remodeling index (RI). To evaluate if these signs are detectable in postmortem imaging by a multi-phase postmortem CT angiography (MPMCTA), a retrospective study of a series of autopsy well-documented coronary plaques related to sudden cardiac death (SCD) was performed. Then correlations between histological and radiological findings were described. Fourty SCD cases due to acute coronary syndrome based on clinical history and confirmed at autopsy were selected (28 men and 12 women, age 53.3 ± 10.9). The culprit lesion was mainly situated in the proximal segments of coronary arteries, in the right coronary artery in 23 cases (57.5%), the left anterior descending artery in 13 cases (32.5%), the circumflex artery in 3 cases (7.5%) and in one case in the left main stem. MPMCTA showed a positive RI (≥ 1.1) in 75% of cases with a mean RI 1.39 ± 0.71. RI values were lower in cases with fibrotic plaques. NRS was observed in 40% of cases, low attenuation plaque in 46.3%, and SC in 48.7% of cases. There were significant correlations of the radiological presence of NRS for fibrolipid composition of the plaque (p-value 0.007), severe intraplaque inflammation (p-value 0.017), severe adventitial inflammation (p-value 0.021) and an increased vasa vasorum (p-value 0.012). A significant correlation (p-value 0.002) was observed between the presence of SC at radiological examination and the presence of punctuate/fragmented calcification at histology. In addition, in 58.3% of cases, plaque enhancement was observed, which correlated with plaque inflammation and the fibrolipid composition of the plaque. The coronary artery calcium score was 314 (± 455). There was a poor agreement between stenosis of the lumen at histology versus radiology. Our study shows that the various radiological signs of HRP can be detected in all plaques by MPMCTA, but individually only to a variable extent; plaque enhancement appeared as a new sign of vulnerability. In the postmortem approach, these radiological markers of HRP, should always be applied in combination, which can be useful for developing a predictive model for diagnosing coronary SCD.

A Combined Measure of the Triglyceride Glucose Index and Trimethylamine N-Oxide in Risk Stratification of ST-Segment Elevation Myocardial Infarction Patients with High-Risk Plaque Features Defined by Optical Coherence Tomography: A Substudy of the OCTAMI Registry Study.

Background and Aim: An elevated triglyceride-glucose (TyG) level is associated with increased risk of mortality in patients with CAD. Trimethylamine N-oxide (TMAO) has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is correlated with adverse outcomes. However, the incremental prognostic value of TMAO and TyG in the cohort of optical coherence tomography (OCT)-defined high-risk ST-segment elevation myocardial infarction (STEMI) patients is unknown. Methods: We studied 274 consecutive aged ≥18 years patients with evidence of STEMI and detected on pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019. Outcomes: There were 22 (22.68%), 27 (27.84%), 26 (26.80%), and 22 (22.68%) patients in groups A-D, respectively. The baseline characteristics according to the level of TMAO and TyG showed that patients with higher level in both indicators were more likely to have higher triglycerides (p < 0.001), fasting glucose (p < 0.001) and higher incidence of diabetes (p = 0.008). The group with TMAO > median and TyG ≤ median was associated with higher rates of MACEs significantly (p = 0.009) in fully adjusted analyses. During a median follow-up of 2.027 years, 20 (20.6%) patients experienced MACEs. To evaluate the diagnostic value of the TyG index combined with TMAO, the area under the receiver operating characteristic curve for predicting MACEs after full adjustment was 0.815 (95% confidence interval, 0.723-0.887; sensitivity, 85.00%; specificity, 72.73%; cut-off level, 0.577). Among the group of patients with TMAO > median and TyG ≤ median, there was a significantly higher incidence of MACEs (p=0.033). A similar tendency was found in the cohort with hyperlipidemia (p=0.016) and diabetes mellitus (p=0.036). Conclusion: This study demonstrated the usefulness of combined measures of the TyG index and TMAO in enhancing risk stratification in STEMI patients with OCT-defined high-risk plaque characteristics. Trial Registration: This study was registered at ClinicalTrials.gov as NCT03593928.

Role of 18F-sodium fluoride positron emission tomography in imaging atherosclerosis.

Atherosclerosis involving vascular beds across the human body remains the leading cause of death worldwide. Coronary and peripheral artery disease, which are almost universally a result of atherosclerotic plaque, can manifest clinically as myocardial infarctions, ischemic stroke, or acute lower-limb ischemia. Beyond imaging myocardial perfusion and blood-flow, nuclear imaging has the potential to depict the activity of the processes that are directly implicated in the atherosclerotic plaque progression and rupture. Out of several tested tracers to date, the literature is most advanced for 18F-sodium fluoride positron emission tomography. In this review, we present the latest data in the field of atherosclerotic 18F-sodium fluoride positron emission tomography imaging, discuss the advantages and limitation of the techniques, and highlight the aspects that require further research in the future.

Prognostic implications of pre-transcatheter aortic valve replacement computed tomography-derived coronary plaque characteristics and stenosis severity.

OBJECTIVES: The study aimed to investigate the prognostic value of pre-transcatheter aortic valve replacement (TAVR) computed tomography angiography (CTA) in assessing physiological stenosis severity (CTA-derived fractional flow reserve (CT-FFR)) and high-risk plaque characteristics (HRPC). MATERIALS AND METHODS: Among TAVR patients who underwent pre-procedure CTA, the presence and number of HRPCs (minimum lumen area of < 4 mm2, plaque burden ≥ 70%, low-attenuating plaques, positive remodeling, napkin-ring sign, or spotty calcification) as well as CT-FFR were assessed. The risk of vessel-oriented composite outcome (VOCO, a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death) was compared according to the number of HRPC and CT-FFR categories. RESULTS: Four hundred and twenty-seven patients (68.4% were male) with 1072 vessels were included. Their mean age was 70.6 ± 10.6 years. Vessels with low CT-FFR (≤ 0.80) (41.7% vs. 15.8%, adjusted hazard ratio (HRadj) 1.96; 95% confidence interval (CI): 1.28-2.96; p = 0.001) or lesions with ≥ 3 HRPC (38.7% vs. 16.0%, HRadj 1.81; 95%CI 1.20-2.71; p = 0.005) demonstrated higher VOCO risk. In the CT-FFR (> 0.80) group, lesions with ≥ 3 HRPC showed a significantly higher risk of VOCO than those with < 3 HRPC (34.7% vs. 13.0%; HRadj 2.04; 95%CI 1.18-3.52; p = 0.011). However, this relative increase in risk was not observed in vessels with positive CT-FFR (≤ 0.80). CONCLUSIONS: In TAVR candidates, both CT-FFR and the presence of ≥ 3 HRPC were associated with an increased risk of adverse clinical events. However, the value of HRPC differed with the CT-FFR category, with more incremental predictability among vessels with negative CT-FFR but not among vessels with positive CT-FFR. CLINICAL RELEVANCE STATEMENT: In transcatheter aortic valve replacement (TAVR) candidates, pre-TAVR CTA provided the opportunity to assess coronary physiological stenosis severity and high-risk plaque characteristics, both of which are associated with worse clinical outcomes. KEY POINTS: • The current study investigated the prognostic value of coronary physiology significance and plaque characteristics in transcatheter aortic valve replacement patients. • The combination of coronary plaque vulnerability and physiological significance showed improved accuracy in predicting clinical outcomes in transcatheter aortic valve replacement patients. • Pre-transcatheter aortic valve replacement CT can be a one-stop-shop tool for coronary assessments in clinical practice.

Proteomics associated with coronary high-risk plaques by optical coherence tomography.

Biomarkers are widely used for the diagnosis and monitoring of cardiovascular disease. However, markers for coronary high-risk plaques have not been identified. The aim of this study was to identify proteins specific to coronary high-risk plaques. Fifty-one patients (71.2 ± 11.1 years, male: 66.7%) who underwent intracoronary optical coherence tomography imaging and provided blood specimens for proteomic analysis were prospectively enrolled. A total of 1470 plasma proteins were analyzed per patient using the Olink® Explore 1536 Reagent Kit. In patients with thin-cap fibroatheroma, the protein expression of Calretinin (CALB2), Corticoliberin (CRH) and Alkaline phosphatase, placental type (ALPP) were significantly increased, while the expression of Neuroplastin (NPTN), Folate receptor gamma (FOLR3) and Serpin A12 (SERPINA12) were significantly decreased. In patients with macrophage infiltration, the protein expressions of Fatty acid-binding protein, intestinal (FABP2), and Fibroblast growth factor 21 (FGF21) were significantly decreased. In patients with lipid-rich plaques, the protein expression of Interleukin-17 C (IL17C) was significantly increased, while the expression of Fc receptor-like protein 3 (FCRL3) was significantly decreased. These proteins might be useful markers in identifying patients with coronary high-risk plaques. Clinical Trial Registration: https://www.umin.ac.jp/ctr/ , UMIN000041692.

Protruding Aortic Plaque and Coronary Plaque Vulnerability.

BACKGROUND: Protruding aortic plaque is known to be associated with an increased risk for future cardiac and cerebrovascular events. However, the relationship between protruding aortic plaque and coronary plaque characteristics has not been systematically investigated. METHODS AND RESULTS: A total of 615 patients who underwent computed tomography angiography, and preintervention optical coherence tomography imaging were included. Coronary plaque characteristics were compared to evaluate coronary plaque vulnerability in patients with protruding aortic plaque on computed tomography angiography. 615 patients, the 186 (30.2%) patients with protruding aortic plaque were older and had more comorbidities such as hypertension, chronic kidney disease, and a prior myocardial infarction than those without. They also had a higher prevalence of coronary plaques with vulnerable features such as thin-cap fibroatheroma (85 [45.7%] versus 120 [28.0%], P<0.001), lipid-rich plaque (165 [88.7%] versus 346 [80.7%], P=0.014), macrophages (147 [79.0%] versus 294 [68.5%], P=0.008), layered plaque (117 [62.9%] versus 213 [49.7%], P=0.002), and plaque rupture (96 [51.6%] versus 111 [25.9%], P<0.001). Patients with protruding aortic plaque experienced more major adverse cardiac and cerebrovascular events, including all-cause mortality, nonfatal acute coronary syndromes, and stroke (27 [14.7%] versus 21 [4.9%], P<0.001; 8 [4.3%] versus 1 [0.2%], P<0.001; 5 [2.7%] versus 3 [0.7%], P=0.030; and 5 [2.7%] versus 2 [0.5%], P=0.013, respectively). CONCLUSIONS: The current study demonstrates that patients with protruding aortic plaque have more features of coronary plaque vulnerability and are at increased risk of future adverse events.

Phenotyping coronary plaque by computed tomography in premature coronary artery disease.

AIMS: Premature coronary artery disease (CAD) is an aggressive disease with multiple recurrences mostly related to new coronary lesions. This study aimed to compare coronary plaque characteristics of individuals with premature CAD with those of incidental plaques found in matched individuals free of overt cardiovascular disease, using coronary computed tomography angiography (CCTA). METHODS AND RESULTS: Of 1552 consecutive individuals who underwent CCTA, 106 individuals with history of acute or stable obstructive CAD ≤45 years were matched by age, sex, smoking status, cardiovascular heredity, and dyslipidaemia with 106 controls. CCTA were analysed for Coronary Artery Disease Reporting and Data System score, plaque composition, and high-risk plaque (HRP) features, including spotty calcification, positive remodelling, low attenuation, and napkin-ring sign. The characteristics of 348 premature CAD plaques were compared with those of 167 incidental coronary plaques of matched controls. The prevalence of non-calcified plaques was higher among individuals with premature CAD (65.1 vs. 30.2%, P < 0.001), as well as spotty calcification (42.5 vs. 17.9%, P < 0.001), positive remodelling (41.5 vs. 9.4%, P < 0.001), low attenuation (24.5 vs. 3.8%, P < 0.001), and napkin-ring sign (1.9 vs. 0.0%). They exhibited an average of 2.2 (2.7) HRP, while the control group displayed 0.4 (0.8) HRP (P < 0.001). Within a median follow-up of 24 (16, 34) months, individuals with premature CAD and ischaemic recurrence (n = 24) had more HRP [4.3 (3.9)] than those without ischaemic recurrence [1.5 (1.9)], mostly non-calcified with low attenuation and positive remodelling. CONCLUSION: Coronary atherosclerosis in individuals with premature CAD is characterized by a high and predominant burden of non-calcified plaque and unusual high prevalence of HRP, contributing to disease progression with multiple recurrences. A comprehensive qualitative CCTA assessment of plaque characteristics may further risk stratify our patients, beyond cardiovascular risk factors.

High-Risk Plaques on Coronary Computed Tomography Angiography: Correlation With Optical Coherence Tomography.

BACKGROUND: Although patients with high-risk plaque (HRP) on coronary computed tomography angiography (CTA) are reportedly at increased risk for future cardiovascular events, individual HRP features have not been systematically validated against high-resolution intravascular imaging. OBJECTIVES: The aim of this study was to correlate HRP features on CTA with plaque characteristics on optical coherence tomography (OCT). METHODS: Patients who underwent both CTA and OCT before coronary intervention were enrolled. Plaques in culprit vessels identified by CTA were evaluated with the use of OCT at the corresponding sites. HRP was defined as a plaque with at least 2 of the following 4 features: positive remodeling (PR), low-attenuation plaque (LAP), napkin-ring sign (NRS), and spotty calcification (SC). Patients were followed for up to 3 years. RESULTS: The study included 448 patients, with a median age of 67 years and of whom 357 (79.7%) were male, and 203 (45.3%) presented with acute coronary syndromes. A total of 1,075 lesions were analyzed. All 4 HRP features were associated with thin-cap fibroatheroma. PR was associated with all OCT features of plaque vulnerability, LAP was associated with lipid-rich plaque, macrophage, and cholesterol crystals, NRS was associated with cholesterol crystals, and SC was associated with microvessels. The cumulative incidence of the composite endpoint (target vessel nontarget lesion revascularization and cardiac death) was significantly higher in patients with HRP than in those without HRP (4.7% vs 0.5%; P = 0.010). CONCLUSIONS: All 4 HRP features on CTA were associated with features of vulnerability on OCT. (Massachusetts General Hospital and Tsuchiura Kyodo General Hospital Coronary Imaging Collaboration; NCT04523194).

Preventative Imaging with Coronary Computed Tomography Angiography.

PURPOSE OF REVIEW: Coronary computed tomography angiography (CCTA) is the diagnostic modality of choice for patients with stable chest pain. In this review, we scrutinize the evidence on the use of CCTA for the screening of asymptomatic patients. RECENT FINDINGS: Clinical evidence suggests that CCTA imaging enhances cardiovascular risk stratification and prompts the timely initiation of preventive treatment leading to reduced risk of major adverse coronary events. Visualization of coronary plaques by CCTA also helps patients to comply with preventive medications. The presence of non-obstructive plaques and total plaque burden are prognostic for cardiovascular events. High-risk plaque features and pericoronary fat attenuation index, enrich the prognostic output of CCTA on top of anatomical information by capturing information on plaque vulnerability and coronary inflammatory burden. Timely detection of atherosclerotic disease or coronary inflammation by CCTA can assist in the deployment of targeted preventive strategies and novel therapeutics to prevent cardiovascular disease.

Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events in Atherosclerotic Patients and Lesions: A Systematic Review and Meta-Analysis.

BACKGROUND: The clinical value of high-risk coronary plaque characteristics (CPCs) to inform intensified medical therapy or revascularization of non-flow-limiting lesions remains uncertain. OBJECTIVES: The authors performed a systematic review and meta-analysis to study the prognostic impact of CPCs on patient-level and lesion-level major cardiovascular adverse events (MACE). METHODS: Thirty studies (21 retrospective, 9 prospective) with 30,369 patients evaluating the association of CPCs with MACE were included. CPCs included high plaque burden, low minimal lumen area, thin cap fibroatheroma, high lipid core burden index, low-attenuation plaque, spotty calcification, napkin ring sign, and positive remodeling. RESULTS: CPCs were evaluated with the use of intracoronary modalities in 9 studies (optical coherence tomography in 4 studies, intravascular ultrasound imaging in 3 studies, and near-infrared spectroscopy intravascular ultrasound imaging in 2 studies) and by means of coronary computed tomographic angiography in 21 studies. CPCs significantly predicted patient-level and lesion-level MACE in both unadjusted and adjusted analyses. For most CPCs, accuracy for MACE was modest to good at the patient level and moderate to good at the lesion level. Plaques with more than 1 CPC had the highest accuracy for lesion-level MACE (AUC: 0.87). Because the prevalence of CPCs among plaques was low, estimated positive predictive values for lesion-level MACE were modest. Results were mostly consistent across imaging modalities and clinical presentations, and in studies with prevailing hard outcomes. CONCLUSIONS: Characterization of CPCs identifies high-risk atherosclerotic plaques that place lesions and patients at risk for future MACE, albeit with modest sensitivity and positive predictive value (Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events Among Atherosclerotic Patients and Lesions; CRD42021251810).

Cardiometabolic predictors of high-risk CCTA phenotype in a diverse patient population.

Introduction: Low-attenuation non-calcified plaque (LAP) burden and vascular inflammation by pericoronary adipose tissue (PCAT) measured from coronary CT angiography (CCTA) have shown to be predictors of cardiovascular outcomes. We aimed to investigate the relationships of cardiometabolic risk factors including lipoprotein(a) and epicardial adipose tissue (EAT) with CCTA high-risk imaging biomarkers, LAP and vascular inflammation. Methods: The patient population consisted of consecutive patients who underwent CCTA for stable chest pain and had a complete cardiometabolic panel including lipoprotein(a). Plaque, PCAT and EAT were measured from CT using semiautomated software. Elevated LAP burden and PCAT attenuation were defined as ≥4% and ≥70.5 HU, respectively. The primary clinical end-point was a composite of myocardial infarction, revascularization or cardiovascular death. Results: A total of 364 consecutive patients were included (median age 56 years, 64% female); the majority of patients were of Hispanic (60%), and the rest were of non-Hispanic Black (21%), non-Hispanic White (6%) and non-Hispanic Asian (4%) race/ethnicity. The prevalence of elevated LAP burden and PCAT attenuation was 31 and 18%, respectively, while only 8% had obstructive stenosis. There were significant differences in plaque characteristics among different racial/ethnic groups (p<0.001). Lipoprotein(a) correlated with LAP burden in Hispanic patients. Patients with elevated LAP were older, more likely to be have diabetes, hypertension, hyperlipidemia and smoke with higher CAC and EAT volume (all P<0.05). Patients with elevated LAP were more likely to develop the primary clinical outcome (p<0.001) but those with elevated PCAT were not (p=0.797). Conclusion: The prevalence of LAP and PCAT attenuation were 31 and 18%, respectively. Lipoprotein(a) levels correlated with LAP burden in Hispanic patients. Age, male sex, hypertension and hyperlipidemia increased the odds of elevated LAP, which showed prognostic significance.

Glagov revisited: coronary artery disease phenotype on non-invasive imaging provides rationale for implementing preventive pharmacotherapy-a case report.

Background: Glagov et al. showed that no reduction in vessel lumen occurred until the atherosclerotic plaque burden exceeded 40% of the vessel area. Most major adverse cardiac events occurring in the first 4 years after a myocardial infarction arise from untreated angiographically mild, non-flow-limiting lesions at the time of the index event. We report how computed tomography (CT) coronary angiography (CCTA) can be used to non-invasively risk stratify a patient with non-obstructive coronary artery disease (CAD) and guide further management. Case summary: A 69-year-old non-smoking female with hypertension, dyslipidaemia, and hypothyroidism presented with atypical chest pain. Electrocardiogram and left ventricular ejection fraction were normal. Her lipidic profile was normal. CCTA showed a lipid-rich plaque with very low attenuation (<30 HU) in the left main stem (LMS) extending into the proximal left anterior descending (LAD) and in the mid LAD artery. The maximum plaque burden in the LMS was 67% with a remodelling index of 1.375, and an area stenosis of 22%. Tissue characterization showed a lipid-rich plaque with a thin fibrous cap. The perivascular fat attenuation index (FAI) in the proximal LAD was suggestive of (-69 HU) inflamed perivascular fat. Shear stress analysis of the LMS plaque showed normal wall shear stress (WSS); however, the axial plaque stress was high. Her medications were intensified to rosuvastatin 20 mg once daily (OD) and ezetimibe 10 mg OD. The patient remained asymptomatic at 6 months follow-up. Discussion: Our case exemplifies the value of CCTA as a diagnostic 'one-stop shop' (CCTA, finite element analysis, computed tomographic density [CTD], tissue characterization analysis, FAI analysis, WSS and wall strain, and etc.) when stratifying a patient with non-obstructive CAD. With further development of novel potent anti-lipidaemic and anti-inflammatory drugs, non-obstructive lesions with adverse plaque and haemodynamic parameters will have the opportunity to be treated with additional preventive pharmacological therapy.

Non-Contrast and Contrast-Enhanced Cardiac Computed Tomography Imaging in the Diagnostic and Prognostic Evaluation of Coronary Artery Disease.

In recent decades, cardiac computed tomography (CT) has emerged as a powerful non-invasive tool for risk stratification, as well as the detection and characterization of coronary artery disease (CAD), which remains the main cause of morbidity and mortality in the world. Advances in technology have favored the increasing use of cardiac CT by allowing better performance with lower radiation doses. Coronary artery calcium, as assessed by non-contrast CT, is considered to be the best marker of subclinical atherosclerosis, and its use is recommended for the refinement of risk assessment in low-to-intermediate risk individuals. In addition, coronary CT angiography (CCTA) has become a gate-keeper to invasive coronary angiography (ICA) and revascularization in patients with acute chest pain by allowing the assessment not only of the extent of lumen stenosis, but also of its hemodynamic significance if combined with the measurement of fractional flow reserve or perfusion imaging. Moreover, CCTA provides a unique incremental value over functional testing and ICA by imaging the vessel wall, thus allowing the assessment of plaque burden, composition, and instability features, in addition to perivascular adipose tissue attenuation, which is a marker of vascular inflammation. There exists the potential to identify the non-obstructive lesions at high risk of progression to plaque rupture by combining all of these measures.

Impact of statins based on high-risk plaque features on coronary plaque progression in mild stenosis lesions: results from the PARADIGM study.

AIMS: To investigate the impact of statins on plaque progression according to high-risk coronary atherosclerotic plaque (HRP) features and to identify predictive factors for rapid plaque progression in mild coronary artery disease (CAD) using serial coronary computed tomography angiography (CCTA). METHODS AND RESULTS: We analyzed mild stenosis (25-49%) CAD, totaling 1432 lesions from 613 patients (mean age, 62.2 years, 63.9% male) and who underwent serial CCTA at a ≥2 year inter-scan interval using the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (NCT02803411) registry. The median inter-scan period was 3.5 ± 1.4 years; plaques were quantitatively assessed for annualized percent atheroma volume (PAV) and compositional plaque volume changes according to HRP features, and the rapid plaque progression was defined by the ≥90th percentile annual PAV. In mild stenotic lesions with ≥2 HRPs, statin therapy showed a 37% reduction in annual PAV (0.97 ± 2.02 vs. 1.55 ± 2.22, P = 0.038) with decreased necrotic core volume and increased dense calcium volume compared to non-statin recipient mild lesions. The key factors for rapid plaque progression were ≥2 HRPs [hazard ratio (HR), 1.89; 95% confidence interval (CI), 1.02-3.49; P = 0.042], current smoking (HR, 1.69; 95% CI 1.09-2.57; P = 0.017), and diabetes (HR, 1.55; 95% CI, 1.07-2.22; P = 0.020). CONCLUSION: In mild CAD, statin treatment reduced plaque progression, particularly in lesions with a higher number of HRP features, which was also a strong predictor of rapid plaque progression. Therefore, aggressive statin therapy might be needed even in mild CAD with higher HRPs. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02803411.

CT-derived fractional flow reserve for prediction of major adverse cardiovascular events in diabetic patients.

OBJECTIVES: To investigate the prognostic value of computed tomography fractional flow reserve (CT-FFR) in patients with diabetes and to establish a risk stratification model for major adverse cardiac event (MACE). METHODS: Diabetic patients with intermediate pre-test probability of coronary artery disease were prospectively enrolled. All patients were referred for coronary computed tomography angiography and followed up for at least 2 years. In the training cohort comprising of 957 patients, two models were developed: model1 with the inclusion of clinical and conventional imaging parameters, model2 incorporating the above parameters + CT-FFR. An internal validation cohort comprising 411 patients and an independent external test cohort of 429 patients were used to validate the proposed models. RESULTS: 1797 patients (mean age: 61.0 ± 7.0 years, 1031 males) were finally included in the present study. MACE occurred in 7.18% (129/1797) of the current cohort during follow- up. Multivariate Cox regression analysis revealed that CT-FFR ≤ 0.80 (hazard ratio [HR] = 4.534, p < 0.001), HbA1c (HR = 1.142, p = 0.015) and low attenuation plaque (LAP) (HR = 3.973, p = 0.041) were the independent predictors for MACE. In the training cohort, the Log-likelihood test showed statistical significance between model1 and model2 (p < 0.001). The C-index of model2 was significantly larger than that of model1 (C-index = 0.82 [0.77-0.87] vs. 0.80 [0.75-0.85], p = 0.021). Similar findings were found in internal validation and external test cohorts. CONCLUSION: CT-FFR was a strong independent predictor for MACE in diabetic cohort. The model incorporating CT-FFR, LAP and HbA1c yielded excellent performance in predicting MACE.

Assessment of myocardial bridging and the pericoronary fat attenuation index on coronary computed tomography angiography: predicting coronary artery disease risk.

BACKGROUND: The fat attenuation index (FAI) is a radiological parameter that represents pericoronary adipose tissue (PCAT) inflammation, along with myocardial bridging (MB), which leads to pathological shear stress in the coronary vessels; both are associated with coronary atherosclerosis. In the present study, we assessed the predictive value of FAI values and MB parameters through coronary computed tomography angiography (CCTA) for predicting the risk of coronary atherosclerosis and vulnerable plaque in patients with MB. METHODS: We included 428 patients who underwent CCTA and were diagnosed with MB. FAI values, MB parameters, and high-risk coronary plaque (HRP) characteristics were recorded. The subjects were classified into two groups (A and B) according to the absence or presence of coronary plaque in the segment proximal to the MB. Group B was further divided into Groups B1 (HRP-positive) and B2 (HRP-negative) according to the HRP characteristic classification method. The differences among the groups were analysed. Multiple logistic regression analysis was performed to determine the independent correlation between FAI values and MB parameters and coronary atherosclerosis and vulnerable plaque risk. RESULTS: Compared to the subjects in Group A, those in Group B presented greater MB lengths, MB depths and muscle index values, more severe MB systolic stenosis and higher FAIlesion values (all P < 0.05). In multivariate logistic analysis, age (OR 1.076, P < 0.001), MB systolic stenosis (OR 1.102, P < 0.001) and FAIlesion values (OR 1.502, P < 0.001) were independent risk factors for the occurrence of coronary atherosclerosis. Compared to subjects in Group B2, those in Group B1 presented greater MB lengths and higher FAI values (both P < 0.05). However, only the FAIlesion value was an independent factor for predicting HRP (OR 1.641, P < 0.001). CONCLUSION: In patients with MB, MB systolic stenosis was associated with coronary plaque occurrence in the segment proximal to the MB. The FAI value was not only closely related to coronary atherosclerosis occurrence but also associated with plaque vulnerability. FAI values may provide more significant value in the prediction of coronary atherosclerosis than MB parameters in CCTA.