Coronary Atherosclerotic Precursors of Acute Coronary Syndromes

Chang, Hyuk-Jae,Lin, Fay Y.,Lee, Sang-Eun,Andreini, Daniele,Bax, Jeroen,Cademartiri, Filippo,Chinnaiyan, Kavitha,Chow, Benjamin J.W.,Conte, Edoardo,Cury, Ricardo C.,Feuchtner, Gudrun,Hadamitzky, Marti Elsevier 2018 JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY - Vol.71 No.22

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>The association of atherosclerotic features with first acute coronary syndromes (ACS) has not accounted for plaque burden.</P> <P><B>Objectives</B></P> <P>The purpose of this study was to identify atherosclerotic features associated with precursors of ACS.</P> <P><B>Methods</B></P> <P>We performed a nested case-control study within a cohort of 25,251 patients undergoing coronary computed tomographic angiography (CTA) with follow-up over 3.4 ± 2.1 years. Patients with ACS and nonevent patients with no prior coronary artery disease (CAD) were propensity matched 1:1 for risk factors and coronary CTA–evaluated obstructive (≥50%) CAD. Separate core laboratories performed blinded adjudication of ACS and culprit lesions and quantification of baseline coronary CTA for percent diameter stenosis (%DS), percent cross-sectional plaque burden (PB), plaque volumes (PVs) by composition (calcified, fibrous, fibrofatty, and necrotic core), and presence of high-risk plaques (HRPs).</P> <P><B>Results</B></P> <P>We identified 234 ACS and control pairs (age 62 years, 63% male). More than 65% of patients with ACS had nonobstructive CAD at baseline, and 52% had HRP. The %DS, cross-sectional PB, fibrofatty and necrotic core volume, and HRP increased the adjusted hazard ratio (HR) of ACS (1.010 per %DS, 95% confidence interval [CI]: 1.005 to 1.015; 1.008 per percent cross-sectional PB, 95% CI: 1.003 to 1.013; 1.002 per mm<SUP>3</SUP> fibrofatty plaque, 95% CI: 1.000 to 1.003; 1.593 per mm<SUP>3</SUP> necrotic core, 95% CI: 1.219 to 2.082; all p < 0.05). Of the 129 culprit lesion precursors identified by coronary CTA, three-fourths exhibited <50% stenosis and 31.0% exhibited HRP.</P> <P><B>Conclusions</B></P> <P>Although ACS increases with %DS, most precursors of ACS cases and culprit lesions are nonobstructive. Plaque evaluation, including HRP, PB, and plaque composition, identifies high-risk patients above and beyond stenosis severity and aggregate plaque burden.</P> <P><B>Central Illustration</B></P> <P>[DISPLAY OMISSION]</P>

Impact of Non-obstructive left main disease on the progression of coronary artery disease: A PARADIGM substudy

Weir-McCall, Jonathan R.,Blanke, Philipp,Sellers, Stephanie L.,Ahmadi, Amir A.,Andreini, Daniele,Budoff, Matthew J.,Cademartiri, Filippo,Chinnaiyan, Kavitha,Choi, Jung Hyun,Chun, Eun Ju,Conte, Edoardo Elsevier 2018 Journal of cardiovascular computed tomography Vol.12 No.3

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>The aim of the study is examine the impact of non-obstructive (<50%stenosis) left main (LM) disease on the natural history of coronary artery disease using serial coronary computed tomography angiography (CTA).</P> <P><B>Methods</B></P> <P>CTAs from the PARADIGM (Progression of atherosclerotic plaque determined by computed tomographic angiography imaging) study, a prospective multinational registry of patients who underwent serial CTA at a ≥2 year interval were analyzed. Those without evidence of CAD on their baseline scan were excluded, as were those with obstructive left main disease. Coronary artery vessels and their branches underwent quantification of: plaque volume and composition; diameter stenosis; presence of high-risk plaque.</P> <P><B>Results</B></P> <P>Of 944 (62 ± 9 years, 60% male) who had evidence of CAD at baseline, 444 (47%) had LM disease. Those with LM disease had a higher baseline plaque volume (194.8 ± 221mm3 versus 72.9 ± 84.3mm3, p < 0.001) and a higher prevalence of high-risk plaque (17.5% versus 13%, p < 0.001) than those without LM disease. On multivariable general linear model, patients with LM disease had greater annual rates of progression of total (26.5 ± 31.4mm3/yr versus 14.9 ± 20.1mm3/yr, p < 0.001) and calcified plaque volume (17 ± 24mm3/yr versus 7 ± 11mm3/yr, p < 0.001), with no difference in fibrous, fibrofatty or necrotic core plaque components.</P> <P><B>Conclusion</B></P> <P>The presence of non-obstructive LM disease is associated with greater rates of plaque progression and a higher prevalence of high-risk plaque throughout the entire coronary artery tree compared to CAD without LM involvement. Our data suggests that non-obstructive LM disease may be a marker for an aggressive phenotype of CAD that may benefit from more intensive treatment strategies.</P>

Prognostic implications of coronary artery calcium in the absence of coronary artery luminal narrowing

Cho, Iksung,ó,Hartaigh, Brí,ain,Gransar, Heidi,Valenti, Valentina,Lin, Fay Y.,Achenbach, Stephan,Berman, Daniel S.,Budoff, Matthew J.,Callister, Tracy Q.,Al-Mallah, Mouaz H.,Cademartiri, F Elsevier 2017 Atherosclerosis Vol.262 No.-

<P><B>Abstract</B></P> <P><B>Background and aims</B></P> <P>Coronary artery calcium (CAC) scoring is a predictor of future adverse clinical events, and a surrogate measure of overall coronary artery plaque burden. Coronary computed tomographic angiography (CCTA) is a contrast-enhanced method that allows for visualization of plaque as well as whether that plaque causes luminal narrowing. To date, the prognosis of individuals with CAC but without stenosis has not been reported. We explored the prevalence of CAC>0 and its prognostic utility for future mortality for patients without luminal narrowing by CCTA.</P> <P><B>Methods</B></P> <P>From 17 sites in 9 countries, we identified patients without known coronary artery disease, who underwent CAC scoring and CCTA, and were followed for >3 years. CCTA was graded for % stenosis according to a modified American Heart Association 16-segment model. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) for incident mortality and compared risk of death for patients as a function of presence or absence of CAC and presence or absence of luminal narrowing by CCTA.</P> <P><B>Results</B></P> <P>Among 6656 patients who underwent CCTA and CAC scoring, 399 patients (6.0%) had no coronary luminal narrowing but CAC>0. During a median follow-up of 5.1 years (IQR: 3.9–5.9 years), 456 deaths occurred. Compared to individuals without luminal narrowing or CAC, individuals without luminal narrowing but CAC>0 were older, more likely to be male and had higher rates of diabetes, hypertension, and dyslipidemia. Individuals without luminal narrowing but CAC experienced a 2-fold increased risk of mortality, with increasing risk of mortality with higher CAC score. Following adjustment, incident death persisted (HR, 1.8; 95% CI, 1.1–2.9, <I>p</I> = 0.02) among patients without luminal narrowing but with CAC>0 compared with patients whose CACS = 0. Individuals without luminal narrowing but CAC ≥100 had mortality risks similar to individuals with non-obstructive CAD (0 < stenosis<50%) by CCTA [HR 2.5 (95% CI 1.3–4.9) and 2.2 (95% CI 1.6–3.0), respectively].</P> <P><B>Conclusions</B></P> <P>Patients without luminal narrowing but with CAC experience greater risk of 5-year mortality. Patients with CAC score ≥100 and no coronary luminal narrowing experience death rates similar to those with non-obstructive CAD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The prevalence of individuals without coronary stenosis but with evident coronary calcium was identified in this large international coronary CT angiography registry. </LI> <LI> Coronary plaques with positive remodeling reflect a potential mechanism for the presence of coronary calcium without luminal narrowing. </LI> <LI> The current study observed a worsened prognosis among those without luminal narrowing but with coronary artery calcium. </LI> </UL> </P>

Prognostic value of chronic total occlusions detected on coronary computed tomographic angiography

Opolski, Maksymilian P,Gransar, Heidi,Lu, Yao,Achenbach, Stephan,Al-Mallah, Mouaz H,Andreini, Daniele,Bax, Jeroen J,Berman, Daniel S,Budoff, Matthew J,Cademartiri, Filippo,Callister, Tracy Q,Chang, Hy BMJ Group 2019 Heart Vol.105 No.3

<P><B>Objective</B></P><P>Data describing clinical relevance of chronic total occlusion (CTO) identified by coronary CT angiography (CCTA) have not been reported to date. We investigated the prognosis of CTO on CCTA.</P><P><B>Methods</B></P><P>We identified 22 828 patients without prior known coronary artery disease (CAD), who were followed for a median of 26 months. Based on CCTA, coronary lesions were graded as normal (no atherosclerosis), non-obstructive (1%–49%), moderate-to-severe (50%–99%) or totally occluded (100%). All-cause mortality, and major adverse cardiac events defined as mortality, non-fatal myocardial infarction and late coronary revascularisation (≥90 days after CCTA) were assessed.</P><P><B>Results</B></P><P>The distribution of patients with normal coronaries, non-obstructive CAD, moderate-to-severe CAD and CTO was 10 034 (44%), 7965 (34.9%), 4598 (20.1%) and 231 (1%), respectively. The mortality rate per 1000 person-years of CTO patients was non-significantly different from patients with moderate-to-severe CAD (22.95; 95% CI 12.71 to 41.45 vs 14.46; 95% CI 12.34 to 16.94; p=0.163), and significantly higher than of those with normal coronaries and non-obstructive CAD (p<0.001 for both). Among 14 382 individuals with follow-up for the composite end point, patients with CTO had a higher rate of events than those with moderate-to-severe CAD (106.56; 95% CI 76.51 to 148.42 vs 65.45; 95% CI 58.01 to 73.84, p=0.009). This difference was primarily driven by an increase in late revascularisations in CTO patients (27 of 35 events). After multivariable adjustment, compared with individuals with normal coronaries, the presence of CTO conferred the highest risk for adverse cardiac events (14.54; 95% CI 9.11 to 23.20, p<0.001).</P><P><B>Conclusions</B></P><P>The detection of CTO on non-invasive CCTA is associated with increased rate of late revascularisation but similar 2-year mortality as compared with moderate-to-severe CAD.</P><P><B>Trial registration number</B></P><P> NCT01443637.</P>

Prognostic value of age adjusted segment involvement score as measured by coronary computed tomography: a potential marker of vascular age

Ayoub, Chadi,Kritharides, Leonard,Yam, Yeung,Chen, Li,Hossain, Alomgir,Achenbach, Stephan,Al-Mallah, Mouaz H.,Andreini, Daniele,Berman, Daniel S.,Budoff, Matthew J.,Cademartiri, Filippo,Callister, Tra Springer-Verlag 2018 Heart and vessels Vol.33 No.11

Improved 5-year prediction of all-cause mortality by coronary CT angiography applying the CONFIRM score

Deseive, Simon,Shaw, Leslee J.,Min, James K.,Achenbach, Stephan,Andreini, Daniele,Al-Mallah, Mouaz H.,Berman, Daniel S.,Budoff, Matthew J.,Callister, Tracy Q.,Cademartiri, Filippo,Chang, Hyuk-Jae,Chin Oxford University Press 2017 European heart journal cardiovascular Imaging Vol.18 No.3

Rationale and design of the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry: A comprehensive exploration of plaque progression and its impact on clinical outcomes from a multicenter serial

Lee, S.E.,Chang, H.J.,Rizvi, A.,Hadamitzky, M.,Kim, Y.J.,Conte, E.,Andreini, D.,Pontone, G.,Volpato, V.,Budoff, M.J.,Gottlieb, I.,Lee, B.K.,Chun, E.J.,Cademartiri, F.,Maffei, E.,Marques, H.,Leipsic, J C. V. Mosby Co 2016 American Heart Journal Vol.182 No.-

<P>Background The natural history of coronary artery disease (CAD) in patients with low-to-intermediate risk is not well characterized. Although earlier invasive serial studies have documented the progression of atherosclerotic burden, most were focused on high-risk patients only. The PARADIGM registry is a large, prospective, multinational dynamic observational registry of patients undergoing serial coronary computed tomographic angiography (CCTA). The primary aim of PARADIGM is to characterize the natural history of CAD in relation to clinical and laboratory data. Design The PARADIGM registry (ClinicalTrials. gov NCT02803411) comprises >= 2,000 consecutive patients across 9 cluster sites in 7 countries. PARADIGM sites were chosen on the basis of adequate CCTA volume, site CCTA proficiency, local demographic characteristics, and medical facilities to ensure a broad-based sample of patients. Patients referred for clinically indicated CCTA will be followed up and enrolled if they had a second CCTA scan. Patients will also be followed up beyond serial CCTA performance to identify adverse CAD events that include cardiac and noncardiac death, myocardial infarction, unstable angina, target vessel revascularization, and CAD-related hospitalization. Summary The results derived from the PARADIGM registry are anticipated to add incremental insight into the changes in CCTA findings in accordance with the progression or regression of CAD that confer prognostic value beyond demographic and clinical characteristics.</P>