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>

Development and Validation of a Simple-to-Use Nomogram for Predicting 5-, 10-, and 15-Year Survival in Asymptomatic Adults Undergoing Coronary Artery Calcium Scoring

Ó,Hartaigh, Brí,ain,Gransar, Heidi,Callister, Tracy,Shaw, Leslee J.,Schulman-Marcus, Joshua,Stuijfzand, Wijnand J.,Valenti, Valentina,Cho, Iksung,Szymonifka, Jackie,Lin, Fay Y.,Berman, Dan Elsevier 2018 JACC CARDIOVASCULAR IMAGING Vol.11 No.3

<P><B>Abstract</B></P> <P><B>Objectives</B></P> <P>The purpose of this study was to develop and validate a simple-to-use nomogram for prediction of 5-, 10-, and 15-year survival among asymptomatic adults.</P> <P><B>Background</B></P> <P>Simple-to-use prognostication tools that incorporate robust methods such as coronary artery calcium scoring (CACS) for predicting near-, intermediate- and long-term mortality are warranted.</P> <P><B>Methods</B></P> <P>In a consecutive series of 9,715 persons (mean age: 53.4 ± 10.5 years; 59.3% male) undergoing CACS, we developed a nomogram using Cox proportional hazards regression modeling that included: age, sex, smoking, hypertension, dyslipidemia, diabetes, family history of coronary artery disease, and CACS. We developed a prognostic index (PI) summing the number of risk points corresponding to weighted covariates, which was used to configure the nomogram. Validation of the nomogram was assessed by discrimination and calibration applied to a separate cohort of 7,824 adults who also underwent CACS.</P> <P><B>Results</B></P> <P>A total of 936 and 294 deaths occurred in the derivation and validation sets at a median follow-up of 14.6 years (interquartile range: 13.7 to 15.5 years) and 9.4 years (interquartile range: 6.8 to 11.5 years), respectively. The developed model effectively predicted 5-, 10-, and 15-year probability of survival. The PI displayed high discrimination in the derivation and validation sets (C-index 0.74 and 0.76, respectively), indicating suitable external performance of our nomogram model. The predicted and actual estimates of survival in each dataset according to PI quartiles were similar (though not identical), demonstrating improved model calibration.</P> <P><B>Conclusions</B></P> <P>A simple-to-use nomogram effectively predicts 5-, 10- and 15-year survival for asymptomatic adults undergoing screening for cardiac risk factors. This nomogram may be considered for use in clinical care.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Incremental prognostic value of coronary computed tomography angiography over coronary calcium scoring for major adverse cardiac events in elderly asymptomatic individuals

Han, Donghee,Hartaigh, Brí,ain Ó,Gransar, Heidi,Lee, Ji Hyun,Rizvi, Asim,Baskaran, Lohendran,Schulman-Marcus, Joshua,Dunning, Allison,Achenbach, Stephan,Al-Mallah, Mouaz H,Berman, Daniel S Oxford University Press 2018 European heart journal cardiovascular Imaging Vol.19 No.6

<P><B>Abstract</B></P><P><B>Aims</B></P><P>Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults.</P><P><B>Methods and results</B></P><P>Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1–49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18–41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, <I>P</I>-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; <I>P</I>-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles.</P><P><B>Conclusion</B></P><P>CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults.</P>

Prevalence and Distribution of Coronary Artery Calcification in Asymptomatic United States and Korean Adults — Cross-Sectional Propensity-Matched Analysis —

Han, Donghee,Hartaigh, Brí,ain ó,Gransar, Heidi,Lee, Ji Hyun,Choi, Su-Yeon,Chun, Eun Ju,Sung, Jidong,Han, Hae-Won,Park, Sung Hak,Callister, Tracy UNKNOWN 2016 CIRCULATION JOURNAL Vol.80 No.11

<P>Background: The incidence of coronary artery disease (CAD) varies depending on ethnicity, but the precise differences remain to be firmly established. This study therefore evaluated the disparity in coronary artery calcification (CAC), as a marker of CAD, in asymptomatic US and Korean adults. Methods and Results: CAC score was compared between asymptomatic Korean (n=15,128) and US (n=7,533) adults. Propensity score matching was performed according to age, gender, hypertension, diabetes, dyslipidemia, and current smoking, which generated 2 cohorts of 5,427 matched pairs. Both cohorts were categorized according to age group: 45-54, 55-64, and 65-74 years. Overall, the prevalence of CAC score >0, >100, and >400 in Korean adults was lower than in US adults (P<0.001, all). According to increasing age groups, the likelihood of CAC was most often lower in Korean adults, especially in Korean women. The odds of having CAC >400 in Korean adults aged 65-74 years was 0.66 (95% CI: 0.48-0.91) overall, 0.78 (95% CI: 0.52-1.19) in men, and 0.50 (95% CI: 0.29-0.86) in women, compared with US counterparts. Conclusions: Korean adults have a lower prevalence and severity of atherosclerotic burden as assessed on CAC, compared with US adults, but the disparity in CAC according to ethnicity may decline with older age.</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>

Coronary revascularization vs. medical therapy following coronary-computed tomographic angiography in patients with low-, intermediate- and high-risk coronary artery disease: results from the CONFIRM long-term registry

Schulman-Marcus, Joshua,Lin, Fay Y.,Gransar, Heidi,Berman, Daniel,Callister, Tracy,DeLago, Augustin,Hadamitzky, Martin,Hausleiter, Joerg,Al-Mallah, Mouaz,Budoff, Matthew,Kaufmann, Philipp,Achenbach, S Oxford University Press 2017 European heart journal cardiovascular Imaging Vol.18 No.8

<P><B>Abstract</B></P><P><B>Aims</B></P><P>To identify the effect of early revascularization on 5-year survival in patients with CAD diagnosed by coronary-computed tomographic angiography (CCTA).</P><P><B>Methods and results</B></P><P>We examined 5544 stable patients with suspected CAD undergoing CCTA who were followed a median of 5.5 years in a large international registry. Patients were categorized as having low-, intermediate-, or high-risk CAD based on CCTA findings. Two treatment groups were defined: early revascularization within 90 days of CCTA (<I>n</I> = 1171) and medical therapy (<I>n</I> = 4373). To account for the non-randomized referral to revascularization, we developed a propensity score by logistic regression. This score was incorporated into Cox proportional hazard models to calculate the effect of revascularization on all-cause mortality. Death occurred in 363 (6.6%) patients and was more frequent in medical therapy. In multivariable models, when compared with medical therapy, the mortality benefit of revascularization varied significantly over time and by CAD risk (<I>P</I> for interaction 0.04). In high-risk CAD, revascularization was significantly associated with lower mortality at 1 year (hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.11–0.47) and 5 years (HR 0.31, 95% CI 0.18–0.54). For intermediate-risk CAD, revascularization was associated with reduced mortality at 1 year (HR 0.45, 95% CI 0.22–0.93) but not 5 years (HR 0.63, 95% CI 0.33–1.20). For low-risk CAD, there was no survival benefit at either time point.</P><P><B>Conclusions</B></P><P>Early revascularization was associated with reduced 1-year mortality in intermediate- and high-risk CAD detected by CCTA, but this association only persisted for 5-year mortality in high-risk CAD.</P>

Warranty Period of Zero Coronary Artery Calcium Score for Predicting All-Cause Mortality According to Cardiac Risk Burden in Asymptomatic Korean Adults

Lee, Ji Hyun,Han, Donghee,Hartaigh, Brí,ain ó,Rizvi, Asim,Gransar, Heidi,Park, Hyung-Bok,Park, Hyo Eun,Choi, Su-Yeon,Chun, Eun Ju,Sung, Jidong UNKNOWN 2016 CIRCULATION JOURNAL Vol.80 No.11

<P>Background: The aim of this study was to examine whether zero coronary artery calcium (CAC) score is associated with favorable prognosis of all-cause mortality (ACM) according to a panel of conventional risk factors (RF) in asymptomatic Korean adults. Methods and Results: A total of 48,215 individuals were stratified according to presence/absence of CAC, and the following RF were examined: hypertension, diabetes, current smoking, high low-density lipoprotein cholesterol, and low high-density lipoprotein cholesterol. The RF were summed on composite score as 0, 1-2, or >= 3 RF present. The warranty period was defined as the time to cumulative mortality rate >1%. Across a median follow-up of 4.4 years (IQR, 2.7-6.6), 415 (0.9%) deaths occurred. Incidence per 1,000 person-years for ACM was consistently higher in subjects with any CAC, irrespective of number of RF. The warranty period was substantially longer (eg, 9 vs. 5 years) for CAC=0 compared with CAC >0. The latter observation did not change materially according to pre-specified RF, but difference in warranty period according to presence/absence of CAC reduced somewhat when RF burden increased. Conclusions: In asymptomatic Korean adults, the absence of CAC evoked a strong protective effect against ACM as reflected by longer warranty period, when no other RF were present. The usefulness of zero CAC score and its warranty period requires further validation in the presence of multiple RF.</P>

Influence of symptom typicality for predicting MACE in patients without obstructive coronary artery disease: From the CONFIRM Registry (Coronary Computed Tomography Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry)

Lee, Ji Hyun,Han, Donghee,Hartaigh, Brí,ain ó,Gransar, Heidi,Lu, Yao,Rizvi, Asim,Park, Mahn Won,Roudsari, Hadi Mirhedayati,Stuijfzand, Wijnand J.,Berman, Daniel S.,Callister, Tracy Q.,DeLa Wiley (John WileySons) 2018 Clinical cardiology Vol.41 No.5

<P>Our objective was to assess the prognostic value of symptom typicality in patients without obstructive coronary artery disease (CAD), determined by coronary computed tomographic angiography (CCTA). We identified 4215 patients without prior history of CAD and without obstructive CAD (<50% CCTA stenosis). CAD severity was categorized as nonobstructive (1%-49%) and none (0%). Based upon the Diamond-Forrester criteria for angina pectoris, symptom typicality was classified as asymptomatic, nonanginal, atypical, and typical. Multivariable Cox proportional hazards models were used to assess the risk of major adverse cardiac events (MACE), comprising all-cause mortality, myocardial infarction, unstable angina, and late revascularization, according to symptom typicality. Mean patient age was 57.0 +/- 12.0years (54.9% male). During a median follow-up of 5.3years (interquartile range, 4.6-5.9years), MACE were reported in 312 (7.4%) patients. Among patients with nonobstructive CAD, there was an association between symptom typicality and MACE (P for interaction=0.05), driven by increased risk of MACE among those with typical angina and nonobstructive CAD (hazard ratio: 1.62, 95% confidence interval: 1.06-2.48, P=0.03). No consistent relationship was found between symptom typicality and MACE among patients without any CAD (hazard ratio: 0.73, 95% confidence interval: 0.34-1.57, P=0.08). In the CONFIRM registry, patients who presented with concomitant typical angina and nonobstructive CAD had a higher rate of MACE than did asymptomatic patients with nonobstructive CAD. However, the presence of typical angina did not appear to portend worse prognosis in patients with no CAD.</P>

Predictive Value of Age- and Sex-Specific Nomograms of Global Plaque Burden on Coronary Computed Tomography Angiography for Major Cardiac Events

Naoum, Christopher,Berman, Daniel S.,Ahmadi, Amir,Blanke, Philipp,Gransar, Heidi,Narula, Jagat,Shaw, Leslee J.,Kritharides, Leonard,Achenbach, Stephan,Al-Mallah, Mouaz H.,Andreini, Daniele,Budoff, Mat Ovid Technologies Wolters Kluwer -American Heart A 2017 Circulation. Cardiovascular imaging Vol.10 No.3

Diagnostic Performance of Hybrid Cardiac Imaging Methods for Assessment of Obstructive Coronary Artery Disease Compared With Stand-Alone Coronary Computed Tomography Angiography : A Meta-Analysis

Rizvi, Asim,Han, Donghee,Danad, Ibrahim,Ó,Hartaigh, Brí,ain,Lee, Ji Hyun,Gransar, Heidi,Stuijfzand, Wijnand J.,Roudsari, Hadi Mirhedayati,Park, Mahn Won,Szymonifka, Jackie,Chang, Hyuk-Jae Elsevier 2018 JACC CARDIOVASCULAR IMAGING Vol.11 No.4

<P><B>Abstract</B></P> <P><B>Objectives</B></P> <P>The current meta-analysis aimed to evaluate the diagnostic performance of hybrid cardiac imaging techniques compared with stand-alone coronary computed tomography angiography (CTA) for assessment of obstructive coronary artery disease (CAD).</P> <P><B>Background</B></P> <P>The usefulness of coronary CTA for detecting obstructive CAD remains suboptimal at present. Myocardial perfusion imaging encompasses positron emission tomography, single-photon emission computed tomography, and cardiac magnetic resonance, which permit the identification of myocardial perfusion defects to detect significant CAD. A hybrid approach comprising myocardial perfusion imaging and coronary CTA may improve diagnostic performance for detecting obstructive CAD.</P> <P><B>Methods</B></P> <P>PubMed and Web of Knowledge were searched for relevant publications between January 1, 2000 and December 31, 2015. Studies using coronary CTA and hybrid imaging for diagnosis of obstructive CAD (a luminal diameter reduction of >50% or >70% by invasive coronary angiography) were included. In total, 12 articles comprising 951 patients and 1,973 vessels were identified, and a meta-analysis was performed to determine pooled sensitivity, specificity, and summary receiver-operating characteristic curves.</P> <P><B>Results</B></P> <P>On a per-patient basis, the pooled sensitivity of hybrid imaging was comparable to that of coronary CTA (91% vs. 90%; p = 0.28). However, specificity was higher for hybrid imaging versus coronary CTA (93% vs. 66%; p < 0.001). On a per-vessel basis, sensitivity for hybrid imaging against coronary CTA was comparable (84% vs. 89%; p = 0.29). Notably, hybrid imaging yielded a specificity of 95% versus 83% for coronary CTA (p < 0.001). Summary receiver-operating characteristic curves displayed improved discrimination for hybrid imaging beyond coronary CTA alone, on a per-vessel basis (area under the curve: 0.97 vs. 0.93; p = 0.047), although not on a per-patient level (area under the curve: 0.97 vs. 0.93; p = 0.132).</P> <P><B>Conclusions</B></P> <P>Hybrid cardiac imaging demonstrated improved diagnostic specificity for detection of obstructive CAD compared with stand-alone coronary CTA, yet improvement in overall diagnostic performance was relatively limited.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>