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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 21  |  Issue : 4  |  Page : 239-244  

Coronary computed tomographic angiography imaging as a prognostic indicator for coronary artery disease: Data from a lebanese tertiary center


1 Department of Internal Medicine, American University of Beirut-Medical Center, Beirut, Lebanon
2 Department of Anaesthesiology, Lebanese University, Beirut, Lebanon
3 Department of Internal Medicine, Lebanese University, Beirut, Lebanon
4 Department of Surgery, Division of Urology, American University of Beirut-Medical Center, Beirut, Lebanon
5 Department of Radiology, Saint Joseph University, Beirut, Lebanon

Date of Submission19-May-2020
Date of Acceptance27-Oct-2020
Date of Web Publication14-Jan-2021

Correspondence Address:
Dr. Antoine Haddad
Hôtel-Dieu de France Hospital, Blvd Alfred Naccache, Pierre Madet Bldg, Ground Floor, Beirut
Lebanon
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/HEARTVIEWS.HEARTVIEWS_87_20

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   Abstract 


Background: Coronary artery disease (CAD) is a major cause of death and disability worldwide. Coronary computed tomographic angiography (CCTA) is a noninvasive imaging technique with a high negative predictive value (NPV). Most studies were done in developed countries, where the prevalence of CAD does not reflect the actual disease burden in developing countries, such as Lebanon.
Methods: We retrospectively evaluated the prognostic value of CCTA in predicting acute myocardial events (AMEs) in 200 Lebanese patients. We determined if specific medical and radiological characteristics are linked with AME and looked for any association between the patient's medical risk factors and the type/location of detected atheromatous plaques. Patients' records were reviewed, and the follow-up period of 5–8 years ensued. Chi-square/Fisher test and Student's t-test were used, in addition to multinomial logistic regression to adjust for the confounding variables. P<0.05 was considered statistically significant.
Results: Our study showed that CCTA had a NPV that reaches 97.9% in asymptomatic patients, a positive predictive value (PPV) of 76.4% for symptomatic patients, a sensitivity of 88.9%, and a specificity of 52.5%. AMEs were significantly increased in patients with a mixed plaque type and/or a moderate-to-severe lumen reduction on CCTA.
Conclusions: CCTA is a sensitive modality for plaque detection and is found to have a remarkably high NPV for asymptomatic patients. A CCTA, along with a low pretest clinical probability of CAD, can be sufficient to rule out an AME for up to 8 years.

Keywords: Computed tomography angiography, coronary artery disease, Lebanon, myocardial infarction, prognosis


How to cite this article:
Koubaissi SA, Kamar Z, El Ankouni M, Degheili JA, Haddad A. Coronary computed tomographic angiography imaging as a prognostic indicator for coronary artery disease: Data from a lebanese tertiary center. Heart Views 2020;21:239-44

How to cite this URL:
Koubaissi SA, Kamar Z, El Ankouni M, Degheili JA, Haddad A. Coronary computed tomographic angiography imaging as a prognostic indicator for coronary artery disease: Data from a lebanese tertiary center. Heart Views [serial online] 2020 [cited 2021 Mar 3];21:239-44. Available from: https://www.heartviews.org/text.asp?2020/21/4/239/307043




   Introduction Top


Coronary artery disease (CAD) is a major cause of death and disability worldwide, causing nearly one-third of deaths in individuals over the age of 35 years. Both CAD mortality and predisposing risk factors continue to increase,[1] with an occurrence at an earlier age in developing countries, as compared to the rest of the world.[2],[3]

Invasive coronary angiography (ICA) is considered the “gold standard” for assessment of coronary artery lumen and degree of blood flow reduction.[4] Coronary computed tomographic angiography (CCTA) imaging is a noninvasive and cost-effective emerging tool for the evaluation of atypical chest pain. It visualizes atherosclerotic plaque burden, along with their composition and location. It also helps in diagnosing fatal causes of chest pain such as aortic dissection and pulmonary embolism.[5]

We herein studied the prognostic value of CCTA in a developing country, in terms of clinical myocardial infarction, and aimed to determine if any association between patient's risk factors and type/location of atheromatous plaques exists.


   Methods Top


Study design

A total of 200 patients who performed CCTA between the years 2009 and 2012 at Hotel Dieu De France Hospital in Lebanon, for various clinical indications, were retrospectively analyzed. A case–control study design was adopted and consisted of two parts:

Age, gender, body mass index (BMI), smoking status, history of personal cardiovascular risk factors or familial cardiovascular disease, initial imaging indication (asymptomatic vs. symptomatic chest pain), CCTA results, and clinical outcome in terms of acute myocardial event (AME) were extracted from the recruited patients' medical records. A follow-up period of 5–8 years ensued, depending on the imaging date and year of the last visit note with each patient's cardiologist. AME was defined as the occurrence of chest pain requiring coronarography intervention, followed by either percutaneous transluminal coronary angioplasty or, in cases of mild CAD, medical treatment alone.

Based on the abovementioned data, patients were then divided into two groups: a case group and a control group, reflecting the presence or absence of plaques on CCTA, respectively.

Risk factors and coronary computed tomographic angiography parameters

Risk factors studied were derived from the Framingham Coronary Heart Disease (CHD) Risk Score established in 1998[6],[7] and included age, gender, smoking status, exercise, hypertension (HTN), measured systolic blood pressure (SBP) (less, equal, or higher than 140 mmHg), diabetes mellitus (DM), dyslipidemia (DL), and personal or family history of cardiovascular disease (CVD).

Regarding CCTA results, three main findings were noted. First, the plaque location is classified into left main, three-vessel disease, two-vessel disease, predominantly left anterior descending (LAD), right coronary artery (RCA), or left circumflex (LCx) for the case group versus no plaques for the controls. Both three- and two-vessel diseases included, respectively, any three or two concomitant diseased major vessels of the following: LAD, RCX, or LCx.

The second studied parameter was the plaque type, divided into predominantly calcified, noncalcified, or mixed. The calcified type was defined as plaques with an attenuation value ≥ 100 Hounsfield units on CCTA; the noncalcified type represents a vessel wall structure that is mainly fibrofatty, with a homogeneously low density detected on CCTA, and that is lower than the coronary lumen contrast. The mixed type was regarded as a plaque read by CCTA to be predominately fibrocalcified but demonstrating calcification in ≤ 50% of the plaque area. Finally, the grade of coronary artery lumen reduction as detected by CCTA was also reported and divided into four different groups: no stenosis, mild (<50%), moderate (50%–70%), and severe reduction (>70%).[8]

Patients younger than 18 years old, lost to follow-up, refused to consent, or those with prior coronary artery bypass graft were excluded from the study. The presence of a technical imaging problem (respiratory artifacts on CCTA, movement, and morbid obesity) was also an exclusion criterion.

Coronary computed tomographic angiography technique

A 64-slice, multidetector, volume computed tomography scanner with 350 ms or millisecond rotation time was used.

Statistical analysis

Data analysis was performed using IBM SPSS statistics, version 23 (SPSS Inc.). Categorical variables were compared using Chi-square or Fisher's exact test and summarized as frequencies and percentages. The means of quantitative variables were compared using Student's t-test and presented as means and standard deviation. Multinomial logistic regression was used to adjust for the different variables in relation to the different categorical outcomes in question (AME, plaque type, and location). All tests are two-sided, and P < 0.05 was considered to be statistically significant.


   Results Top


Patient characteristics

Of 200 total patients, 176 (88%) were males. The mean age was 54.2 ± 10.8 years, and 94 (47%) of them actively smoked. The mean population BMI was 28.6 ± 4.4 kg/m2. The reported comorbidities were DM in 32 patients (16%), HTN in 83 patients (41.5%), and DL in 96 patients (48%).

The majority of the patients (153 patients, 76.5%) had a normal to high-normal measured SBP (<140 mmHg). Nineteen (9.5%) had a personal history of CVD and 81 (40.5%) had a family history of CVD. One hundred and sixty-five patients (82.5%) had at least one risk factor for CAD [Table 1].
Table 1: Differences in baseline patients' demographics and characteristics

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General coronary computed tomographic angiography findings

Seventy-nine patients (39.5%) did not have any plaques on CCTA and were considered as “control,” and 121 patients (60.5%) had a detected plaque and were classified as “case.”

Compared to controls, patients with any detected plaque on CCTA (cases) had significantly higher age (mean age of 57 years), and more than half of them were active smokers (53.3%), more commonly suffered from DL, or had at least one of the following risk factors: DM, HTN, DL, and personal and family history of CVD [Table 1].

The majority of plaque location was found to be in the LAD artery (25%), followed by either left main or three-vessel involvement (16%). As for the detected plaque type, the majority was mixed (40.7%), followed by noncalcified (12.4%) and calcified (6.2%). Among patients with detected plaques, 29.7% had a mild lumen reduction, 15.7% had a moderate reduction, and 11.9% had a severe reduction on CCTA [Table 2].
Table 2: General coronary computed tomography angiography findings

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Coronary computed tomographic angiography prognostic value in terms of acute myocardial event

Of the total 200 patients, 45 patients were excluded from the CCTA prognostic analysis due to loss of follow-up.

During the follow-up period of 5–8 years after performing CCTA, 55 patients (55/155; 35.5%) had an AME compared to 100 patients (64.5%) who were free of events. Patients who suffered an AME after 5-8 years of follow up were significantly older (mean difference of 6 years), and more frequently had DL or an old history personal CVD (P = 0.001, 0.051, and 0.031, respectively). No significant difference was found between both the groups in terms of gender, BMI, smoking status, regular exercise, HTN, DM, or presence of a family history of CVD [Table 3].
Table 3: Patients' demographics, risk factors, and occurrence of acute myocardial events upon follow-up

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Regarding CCTA findings, having a mixed plaque type, left main, three- or two-vessel involvement, and a moderate-to-severe lumen reduction were all found to be significantly associated with a higher risk of AME, compared to controls (P = 0.001). Patients with AME on follow-up were predominantly symptomatic when CCTA was initially done, as compared to those who remained event free [Table 4].
Table 4: Coronary computed tomographic angiography findings and occurrence of acute myocardial events upon follow-up

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Sensitivity, specificity, negative predictive value, and positive predictive value of coronary computed tomographic angiography

Regarding CCTA sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for AME, they were found to be 88.9%, 52.5%, 89.8%, and 50%, respectively, for the whole group of patients.

For asymptomatic patients, the CCTA sensitivity, specificity, NPV, and PPV for AME were found to be 85.7%, 57.8%, 97.9%, and 14.6%, respectively. On the contrary, the CCTA sensitivity, specificity, NPV, and PPV for AME in symptomatic patients were found to be 89.4%, 27.8%, 50%, and 76.4%, respectively [Table 5].
Table 5: Sensitivity, specificity, negative predictive value, and positive predictive value of coronary computed tomographic angiography for predicting acute myocardial events after 5-8 years

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Risk factors and location/type of plaques on coronary computed tomographic angiography

After adjusting for age, gender, BMI, smoking status, exercise, DM, HTN, DL, and personal or familial CVD, the following results regarding predominant plaque location involvement as per CCTA results are highlighted:

Old age (above 55 years) and male gender significantly increase the odds of having left main or triple-vessel involvement on CCTA, as compared to middle-aged individuals (36–55 years old) (adjusted odds ratio [AOR] =34.5, confidence interval [CI]: 9.7–125) or being a female (AOR = 15.3, CI = 2.4–96.8), respectively. No other risk factors were found to be significantly associated with a similar increased risk.

Regarding plaques detected on CCTA imaging in two different main coronary arteries, similar results of significantly increased involvement were found in older adults, males, and in addition, in active smokers as compared to middle-aged adults (AOR = 9.7, CI = 3–31.3), females (AOR: 7.7, CI = 1.2–49.8), and nonactive smokers (AOR = 6.4, CI = 2.2–18.9), respectively.

With respect to isolated LAD, a similarly increased involvement in older adults, males, and active smokers as compared to middle-aged (AOR = 4.7, CI = 1.8–12.3), younger adults aged 18–35 years (AOR = 14.3, CI = 1.1–166.7), females (AOR = 4.4, CI = 1.1–17.2), and nonsmokers (AOR = 2.4, CI = 1.1–5.3), respectively. Unpredictably, those who are overweight (defined as having a BMI ranging from 25 to 29.9 kg/m2) were found to have significantly more isolated LAD involvement as compared to those who are obese (BMI ≥ 30 kg/m2) with an AOR = 2.6 (CI = 1.1–6.5). Concerning either isolated RCA or LCx involvement, no significant results were concluded.

After adjusting for age, gender, BMI, smoking status, exercise, DM, HTN, DL, and personal or familial CVD, the following results are concluded:

Regarding mixed plaques identified on CCTA, a significantly higher involvement was found in older adults, males, and active smokers as compared to middle-aged (AOR = 9.5, CI = 3.9–23.3) and younger adults (AOR = 25, CI = 2.1–333.3), females (AOR = 7.7, CI = 2.1–28.5), and nonactive smokers (AOR = 2.7, CI = 1.3–5.8), respectively. With reference to noncalcified plaques, only having an older age was found to have a significantly higher association as compared to middle-aged individuals (AOR = 4.1, CI = 1.3–13.2). As for the calcified type, the least commonly detected plaque, a significantly higher association was found in older adults and those who actively smoke compared to middle-aged individuals (AOR = 5.1, CI = 1.1–23.3) and nonsmokers (AOR = 4.6, CI = 1.1–18.9), respectively.

In conclusion, having either left main or three-vessel disease involvement was found to be significantly associated with older age and male gender; having two concomitant vessel involvement or isolated LAD plaques with a mixed type and being older, male, or an active smoker; having mainly noncalcified plaques and being older; and finally, having predominantly calcified plaques and being older or active smoker. With respect to the remaining studied risk factors (exercise, DM, HTN, DL, and personal or familial CVD), there was no significant association with a specific location or plaque type.


   Discussion Top


The current study showed that CCTA has the best PPV (76.4%) in patients who underwent the procedure following symptomatic chest pain. However, for the general population, PPV was found to be only 50%. This PPV goes in the same average of a wide range of PPV values present in the literature (35%–97%).[9],[10],[11] This relatively low PPV can be explained by the overestimation of the coronary artery narrowing detected by CCTA, secondary to blurring artifacts.

With respect to our NPV, its lower result as compared to others (97%–100%)[11],[12] can be explained by the difference in the sample size studied, ethnicity, and the longer follow-up period (5–8 years in our study compared to a mean of 2 years in other studies).

In addition, the sensitivity of CCTA in our study is high reaching 88.9% and is almost similar to other studies. However, we noted a discrepancy in our specificity (52.5%) compared to other studies (90%–95%),[10],[12] except for the one conducted by Hoffmann et al. (54%–87%).[9] This is also due to the overdetection of the coronary artery plaques by CCTA due to calcified plaques.

Zhang et al.[13] found that diabetic patients had more diffuse vessel disease, with more than one vessel involved compared to nondiabetics; however, in our study, we did not reach any significance for the association between classical CAD risk factors such as HTN, DM, or DL and a specific plaque location on CCTA. A probable explanation is our small sample size. On the contrary, it was not surprising to find that older men and active smokers are most vulnerable for left main, triple-vessel, and/or LAD plaque involvement.

Concerning the smoking status, our study showed a significant association between older age group and active smoking with the predominance of calcified plaque detected on CCTA. Add to this, it showed that having an older age was significantly linked with the detection of noncalcified plaques. Going in parallel with our results, a study conducted by North et al. similarly highlighted the role of smoking in the pathogenesis of “calcified” coronary plaque,[14] whereas Lehman et al. reported in the ROMICAT trial that smoking was independently associated with coronary atherosclerotic plaque burden progression on CCTA in patients with acute chest pain over 2 years of follow-up, and the rate of this progression was dependent on plaque composition, being higher for “noncalcified,” when compared to “calcified” plaques.[15]

Apart from smoking, male gender and older age, we did not find any significant association between other classical CAD risk factors such as HTN, DM, DL, personal or familial CVD, and a specific plaque type detected by CCTA. Although these risk factors are all included in the Framingham CHD Risk Score,[6],[7] a score for CHD risk estimation, the latter also being increased by noncalcified plaque type, as mentioned above in the ROMICAT trial.[15] Many studies were conducted in the same context and revealed contradictory associations, both not shown in our study. Rivera et al.[16] showed that noncalcified coronary plaques were particularly associated with DM, while Zhang et al.[13] found that calcified plaques were significantly more detected in diabetic compared to nondiabetics. These contradictory results can be again explained by our small studied sample size.


   Conclusions Top


In this study, CCTA is proven to be sensitive for coronary plaque detection regardless of symptomatology and has a high NPV for excluding CAD, reaching 97.9% in asymptomatic patients. Using this test alone, along with a low pretest clinical probability (absence of risk factors for CAD), is sufficient to rule out any AME for up to 8 years.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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Hoffmann U, Bamberg F, Chae CU, Nichols JH, Rogers IS, Seneviratne SK, et al. Coronary computed tomography angiography for early triage of patients with acute chest pain: The ROMICAT (Rule Out Myocardial Infarction using Computer Assisted Tomography) trial. J Am Coll Cardiol 2009;53:1642-50.  Back to cited text no. 9
    
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Qi L, Tang LJ, Xu Y, Zhu XM, Zhang YD, Shi HB, et al. The diagnostic performance of coronary CT angiography for the assessment of coronary stenosis in calcified plaque. PLoS One 2016;11:e0154852.  Back to cited text no. 12
    
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Zhang J, Lv Z, Zhao D, Liu L, Wan Y, Fan T, et al. coronary plaque characteristics assessed by 256 slice coronary ct angiography and association with high sensitivity c reactive protein in symptomatic patients with type 2 diabetes. J Diabetes Res 2016;2016:1-6.  Back to cited text no. 13
    
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Lehman SJ, Schlett CL, Bamberg F, Lee H, Donnelly P, Shturman L, et al. Assessment of coronary plaque progression in coronary computed tomography angiography using a semiquantitative score. JACC Cardiovasc Imaging 2009;2:1262-70.  Back to cited text no. 15
    
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Rivera JJ, Nasir K, Cox PR, Choi EK, Yoon Y, Cho I, et al. Association of traditional cardiovascular risk factors with coronary plaque sub-types assessed by 64-slice computed tomography angiography in a large cohort of asymptomatic subjects. Atherosclerosis 2009;206:451-7.  Back to cited text no. 16
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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