International Journal of Cardiology 176 (2014) 1244–1246

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International Journal of Cardiology

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Letter to the Editor

Long term prognostic value of Coronary Computed TomographyAngiography in suspected coronary artery disease: A 62 month medianfollow-up study

Mouaz H. Al-Mallah a,b,c,⁎,1, Waqas Qureshi d, Milan Pantelic a, Khaled Nour a

a 2799 W. Grand Blvd., Henry Ford Hospital/Wayne State University, Detroit, MI, 48202 USAb 540 E Canfield St., Wayne State University, Detroit, MI 48201 USAc King Abdul-Aziz Cardiac Center, National Guard Health Affairs, Riyadh, Saudi Arabiad Wake Forest University School of Medicine, Winston Salem, NC 27157, USA

Abbreviations: CCTA, Coronary Computed Tomographartery disease; SCCT, Society of Cardiovascular ComputedArtery Bypass Grafting; PCI, Percutaneous Coronary Interv⁎ Corresponding author at: Cardiac Imaging, King

King Abdul-Aziz Medical City (Riyadh), National Guard HCode: 1413, P.O. Box 22490, Riyadh 11426, Kingdom118011111x16594; fax: +966 118011111x16700.

1 Associate Professor of Medicine, Wayne State Univers

http://dx.doi.org/10.1016/j.ijcard.2014.07.2030167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved

a r t i c l e i n f o

Article history:

Received 26 June 2014Accepted 27 July 2014Available online 4 August 2014

Keywords:All-cause mortalityOutcomesCoronary Computed Tomography Angiography

workstation in the same setting. Coronary segments were visuallyscored for the presence of coronary plaque using a 16-segment coronaryartery model based on Society of Cardiovascular Computed Tomogra-phy (SCCT) guidelines [7]. Plaque Stenosis severity was visually classi-fied into three groups based on 1) no CAD defined as no coronaryplaque, 2) non-obstructive CAD defined as luminal stenosis between 1

In recent years, Coronary Computed Tomography Angiography(CCTA) has emerged as a novel tool for the non-invasive detection ofCAD [1,2]. Its prognostic value has been well demonstrated over shortfollow-up duration (median follow-up duration of nearly two years)[3–5]. However, there is limited data regarding the long termprognosticvalue of CCTA [6]. We evaluated five year prognosis of normal or non-obstructive CAD on CCTA. We also determined the prognostic value ofplaque burden and plaque morphology based on their calcificationpattern.

Consecutive patients (n = 454) without known CAD whounderwent CCTA at a single tertiary care center between 2006 and2008 were included. Patients with known CAD, systolic left ventricularfailure and renal disease were excluded. The study was approved bythe Institutional Review Board of the study hospital. All CCTA scanswere performedwith a 64-multidetector row scanner (General Electric,Milwaukee, WI) using retrospective gating. Each CCTA was interpretedby a cardiologist and a radiologist on a 3-dimensional image analysis

y Angiography; CAD, coronaryTomography; CABG, Coronaryention; HR, hazard ratio.Abdul-Aziz Cardiac Center,

ealth Affairs, Department Mailof Saudi Arabia. Tel.: +966

ity, Detroit, MI, USA.

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and 49% and 3) obstructive CAD was defined as luminal stenosis≥50%. A ≥50% stenosis in the LMwas considered to be two-vessel dis-ease in the LAD and LCx. In each coronary artery segment, plaques wereclassified as non-calcified, mixed, or calcified by visual inspection. Non-calcified plaque was defined as a tissue structure N1 mm [1] that couldbe clearly discriminated from the vessel lumen and surrounding tissuewith a density below the contrast-enhanced blood pool. Plaques meet-ing this definition and in addition showing calcified areas of any extentwere classified as mixed plaques. Coronary artery plaque scores werecalculated for overall plaque burden by extent and severity of CADusing a segment stenosis score (SSS) and segment-involvement score(SIS). As a measure of CAD distribution, SIS was calculated based onjust the presence of plaque within a segment, irrespective of the degreeof luminal stenosis within each segment (min = 0; max = 16) [4]. Inaddition, calcified segment involvement score, mixed segment involve-ment score, and non-calcified segment involvement score (per segmentinvolved) were calculated. SSS was used as a measure of overall coro-nary artery plaque extent. Each individual coronary segment was grad-ed as having no to severe plaque (scores from 0 to 4) based on theextent of luminal stenosis (0 = none, 1 = 1%–25%, 2 = 26–49%, 3 =50–74% and4≥ 75%). Then the sumscores of all 16 individual segmentswere summed to yield a total score ranging from 0 to 64.

Patients were followed using extensive medical records and clinicvisit evaluation search up to six years to assess major adverse cardiacevents post CCTA. Major adverse cardiac events (MACE) were definedas all-cause mortality, myocardial infarction and late revascularizationmore than 90 days after the index CCTA using Percutaneous CoronaryIntervention (PCI) or Coronary Artery Bypass Grafting (CABG). Alevents were adjudicated by two physicians who were blinded to theCCTA results and disagreement was resolved by consensus.

Table 1Cumulative incidence of 5-year major cardiovascular adverse outcomes.

Variables Normal Non-obstructiveCAD

ObstructiveCAD

p value

N 194 (42%) 197 (44%) 63 (14%)Death 6 (3.1%) 13 (6.6%) 7 (11.1%) 0.046Myocardial infarction 3 (1.5%) 2 (1.0%) 1 (1.6%) 0.882Late revascularization 0 4 (2.0%) 5 (7.9%) b0.001Major adverse cardiac events 9 (4.6%) 17 (8.6%) 12 (19.0%) 0.002

CAD: coronary artery disease.

1245M.H. Al-Mallah et al. / International Journal of Cardiology 176 (2014) 1244–1246

Time to MACE events was calculated using unvariable Cox propor-tional hazards models. Multivariable Cox proportional hazards modelswere used to examine the relationship between CCTA findings andMACE after adjusting for confounders (i.e. age, sex, race, hypertension,diabetes, dyslipidemia, family history of premature coronary disease,smoking, ejection fraction). Statistical analysis was done using SPSSv19(Chicago, IL).

The average age was 56 ± 13 years and 53% were male. CCTAshowed normal coronaries in 194 (42%), non-obstructive CAD (stenosisb50%) in 197 (44%) and 63 (14%) had obstructive CAD. Among patientswith obstructive CAD, 41 (65%) had one-vessel, 13 (20%) two-vessel,and 9 (14%) three-vessel disease.

Fig. 1. Kaplan Meier curves of major adverse cardiac events (MACE) free survival. The presencassociated with worsening outcomes over a median follow-up duration of 62 months.

Table 2Association of various findings on coronary computed tomography angiogram with major adv

Variables UnadjustHR (95%

Any severe stenosis 4.3 (1.8Two or three vessels obstructive CAD 6.1 (2.7Segment stenosis score (per segment involved) 1.10 (1.0Segment involvement score (per segment involved) 1.21 (1.1Calcified segment involvement score (per segment involved) 1.31 (1.1Mixed segment involvement score (per segment involved) 1.22 (1.0Non-calcified segment involvement score (per segment involved) 1.17 (0.8

a Analysis adjusted for age, sex, diabetes, hypertension, dyslipidemia, ejection fraction, smok

After a median follow-up of 62 months (25th–75th interquartilerange 51–69 months), 26 patients died, 6 patients experiencedmyocardi-al infarction and 9 patients had late revascularization. MACE occurred in38 (8.4%) patients (Table 1). A graded increase in the risk of MACE wasseen in the presence of obstructive CAD by CCTA (Fig. 1, p = 0.002).The annual event rate for patients with normal coronaries, non-obstructive CAD and obstructive CADwas 0.9%, 1.7% and 3.7% respectively(p = 0.002). After adjusting for potential confounders, the presence ofany obstructive lesions, SSS, SIS as well SIS for calcified plaquewere inde-pendently associated with increased events (Table 2).

Our analysis confirms the excellent prognostic value of CCTA. Amongpatients with normal CCTA, the annual event rate is low up to 5 yearsof follow-up. On the other hand, patients with obstructive CAD haveworse long term prognosis. The short and intermediate term prognosticvalues of CCTA have been well demonstrated. The CONFIRM registryevaluated a consecutive cohort of 24,775 patients undergoing ≥64-detector row CCTA. After a 2.3 ± 1.1-year follow-up, obstructive andnon-obstructive CAD conferred increased independent risk of mortalitycompared with patients without evident CAD. In addition, the absenceof CAD was associated with a very favorable prognosis. In a meta-analysis of 18 studies that evaluated 9592 patients with a medianfollow-up of 20 month, adverse cardiovascular events among patientswith normal findings on CCTA were rare. Our analysis confirms these

e of obstructive coronary artery disease on coronary computed tomography angiogram is

erse cardiovascular outcomes.

edCI)

p value Adjusteda

HR (95% CI)p value

–10.1) b0.001 3.0 (1.1–7.7) 0.026–14.1) 0.001 4.7 (1.9–11.5) 0.0025–1.15) b0.001 1.08 (1.03–1.13) 0.0020–1.34) b0.001 1.13 (1.04–1.36) 0.0104–1.50) b0.001 1.22 (1.04–1.43) 0.0143–1.45) 0.021 1.14 (0.94–1.38) 0.0198–1.55) 0.29 1.12 (0.85–1.50) 0.464

ing and family history of premature coronary artery disease (CAD).

1246 M.H. Al-Mallah et al. / International Journal of Cardiology 176 (2014) 1244–1246

findings and extends the follow-up duration to more than 62 months.Patients with normal CCTA continued to have a low event rate com-pared to those with obstructive and non-obstructive CAD.

We found that calcified segment involvement score was associatedwithworse outcomes. Such a relationwas not demonstrated among pa-tients with non-calcified plaque or mixed plaque. Long term prognosticvalue by plaque morphology is not well established.

In conclusion, the absence of coronary artery plaque on CCTA has anexcellent 5 year prognostic value.

Disclosures

There are no financial disclosures to disclose. All authors have madesubstantial contributions to the research and manuscript development.All authors have approved the final manuscript.

Acknowledgments

WQureshi is funded by Ruth L. Kirsch stein NRSA Institutional Train-ing Grant 5T32HL076132-10.

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