Progression of coronary artery disease with Coronary CT
asymptomatic patients in low-to-moderate risk
PABLO A BAYOL, JORGE I PARRAS, ERIKA C BOSCH, SILVIA A HAK, BRENDA A, SALVATIERRA,
MARÍA C SCARPINO, MARÍA L BURGOS
Instituto de Cardiología de CORRIENTES “Juana Francisca Cabral”.
(3400) Corrientes, Argentina. E-mail
Recibido 17-AGO-19 – ACEPTADO después de revisión el 21-SETIEMBRE-2019.
There are no conflicts of interest to disclose.
Objective: To evaluate the long-term progression of coronary disease, in asymptomatic patients in low to moderate risk. Materials and methods: There were 33 patients with low to moderate risk of coronary disease, previously studied between 2006-2008, with Coronary Computed Tomography Angiography (CCTA), with an average follow-up of 116 months, between 2011 and 2018, who were reevaluated by random sampling for convenience at the Instituto de Cardiología de Corrientes.
The following was evaluated: detection of new plaques, their morphology, location, degree of stenosis and calcium score. Patients were followed taking into account their classification in low-moderate risk. Results: Follow-up was achieved in 33 patients (81% males, mean age 60 ± 10 years) in an average of 9.67 years. Patients with coronary stenosis were initially 39% (n=13), with an increase of 78% (n=26) (p=0.000) to a predominance of non-significant stenosis. There was a progression of proximal plaques (p=0.001), both calcified and noncalcified (p=0.021) and mixed (p=0.039). There was also an increase in calcium score; a previous average of 80 was calculated, and a current average of 281; and given the distribution of this variable, the median value was also taken into account, which initially was 0, and currently 33. Conclusions: There was progression of coronary atherosclerosis as determined by CCTA, in asymptomatic long-term patients with low to moderate risk, demonstrated by the increase in the number of lesions, the degree of stenosis generated and the calcification of the coronary tree.
For some decades now, the medical community has pressured the technological community on the need to develop a noninvasive way to explore coronary anatomy . Computed tomography coronary angiogram (CTCA) by volumetric multislice 64-detector computed tomography (VCT) is emerging as a tool capable of achieving this goal. There is great heterogeneity between atherosclerotic lesions in the human anatomy, with plaques that could be composed of calcium, as well as cholesterol esters, constituting the so-called soft or noncalcified plaques, also called vulnerable or high-risk plaques, that could be responsible for plaque ruptures that will constitute Acute Coronary Syndromes [3,4]. There are hypotheses that discuss the existence of vulnerable patients, considering that extraluminal plaques, i.e. nonstenotic plaques, are invisible to the methods that only show arterial lumen. Because of this, the vulnerability of patents is determined by the probability of plaque rupture rather than by the degree of lumen occlusion. In asymptomatic patients, the prevalence of atherosclerotic plaques is not well established, given the invasiveness of the current gold-standard method, conventional coronary angiography . There are certain patients that, in spite of being asymptomatic, present CAD in CTCA, and although it is often a mild CAD, this doesn’t rule out the risk of progression of the disease. In patients in low risk according to traditional scores like Framingham, the risk is often underestimated , having found evidence of new risk factors that are indicators of subclinical atherosclerotic disease, such as coronary calcium score . The finding of atherosclerotic plaques in patients in low traditional risk would allow to reclassify them into a likely higher risk ; mainly if the so-called “high-risk” plaques are visualized, because of their characteristics compatible with those found in acute coronary syndromes .
With a long-term follow-up, progression of atherosclerotic CAD will be found in patients, even in spite of the low-to-moderate risk and of being asymptomatic at the time of the study.
To evaluate the progression of CAD in asymptomatic patients, in low risk, over a long term.
Materials and methods
Prospective, observational, cross-sectional study.
Thirty-three patients were reevaluated by random convenience sampling. They presented low-to-moderate risk of CAD, previously studied in the 2006-2008 term, with an average follow-up of 116 months, in the 2011-2018 term, at the Instituto de Cardiología de Corrientes, by CTCA in 64-slice VCT. Vascular analysis was conducted with 2D and 3D reconstructions by CardiacIQ software of vascular analysis.
Asymptomatic patients, in low-to-moderate risk, studied by CTCA from 2006 to 2008, who could be studied again from 2011 to 2018.
Patients not having been studied from 2006 to 2008.
Patients who died within those years due to causes unrelated to CAD.
Patients who refused to participate in the study.
Patients unable to move to the Cardiology Institute.
Patients allergic to iodine, with renal failure, or any other clinical situation in which Computed Tomography with IV contrast injection could be harmful.
The procedure was explained to the patients and their relatives, who signed an informed consent.
A follow-up of 33 patients (6 women and 27 men), older than 42 years of age, was conducted over an average period of 116 months, who presented low-to-moderate risk of CAD, according to the European Society scale. Between the risk factors, the following were taking into account: hypertension (HTN), smoking (SM), diabetes (DBT), dyslipidemia (DLP) and obesity. HTN was defined as documented history of high blood pressure or treatment with antihypertensive medications. DBT was defined by its diagnosis made previously by a physician and/or use of insulin or oral hypoglycemic agents. DLP was defined as known but untreated DLP, or current treatment with lipid-lowering medications. A history of positive SM was defined as current SM or having ceased within the last 3 months after the test. None of them presented history of previous cardiovascular event.
Protocol of image acquisition
Pre-medication was made with oral beta blockers, Nebivolol 7.5 mg, and IV Propranolol if the required heart rate was not reached (<65 beats per minute).
The Parameters of Image Acquisition were: kilovolts (kv): 120; milliamperes (mA): 500 to 800; Slice: 0.625 mm; tube rotation: 0.35 seconds; Field of View (FOV): 25 cm; Time of Acquisition: 5 to 7 seconds.
Vascular access was obtained by abbocath 16 to 18 in left elbow antecubital vein. A dual-head injection pump was used, by Bolus Timing and S-Segment techniques for acquisition. Initially, an acquisition was made without IV contrast, with a protocol called Smart Score, which later allows to estimate calcium score according to Agatston; and later, an exploration protocol called Smart Prep to be able to visualize the contrast arriving, at the height of the valve plane. A 50 to 70 ml bolus (up to 2 ml per kg) of IV iodinated contrast was injected, followed by saline bolus (10% of the contrast) to improve its compaction and obtaining a greater concentration in the cardiac chambers.
The acquisition of images was made with a cardiac protocol in a retrospective manner, with the patient connected to a cardiac monitor.
All patients presented a normal heart rate (<65 beats per minute) and were capable of maintaining the required respiration.
Post-processing was made in a GE (General Electric), Advantage 4.3 work station with vascular analysis by CardiacIQ Express. The diagnosis of progression of CAD was based on the Min parameters (10) (modified for practical reasons, for this study); taking into account the detection of new plaques (noncalcified, calcified or mixed), their location in vessels (proximal or distal), and the degree of stenosis they generate (mild, moderate or severe), change in size or morphology, increase in calcium score, need for revascularization, or the development of cardiovascular event. Coronary segmentation was used according to the AHA (American Heart Association) classification.
The degree of stenosis was quantified by visual estimation, and divided into nonsignificant and mild (<50% of vessel lumen), significant and moderate (50-69%) and severe (>70%). Calcium score was evaluated according to the Agatston scale.
The analysis of CTCA data was conducted by a specialist cardiologist.
In the statistical analysis, frequencies or percentages were used to describe categorical variables; means and standard deviations for quantitative variables; and McNemar test to evaluate the significant associations between categories.
There was a total of 33 patients evaluated; 18% were female (n=6) and 81% male (n=27) with an average age of 60 years of age (range from 42 to 83 years), asymptomatic, who presented low-to-moderate risk of presenting CAD, over a follow-up term of 116 months (9.67 years); and their results were compared to those obtained previously. The most frequent risk factor between the patients was HTN present in 45% (n=15), followed by DLP in 27% (n=9), obesity 21% (n=7), SM 12% (n=4), and finally DBT as the least frequent in 3% of patients (n=1).
As to the data analysis, taking into account the location of vascular lesions, an increase was observed in those of proximal location, initially in 36% of patients (n=12) and currently 75% (n=25) (p=0.001). about the distal position of lesions, they were observed in 24% of patients (n=8) comparatively with the previous 6% (n=2) (p=0.70) (Figure 1).
Figure 1. Comparative graph of the percentage of patients with plaques according to their location (proximal and distal) in the previous study (grey color) and the current one (yellow color). There is evidence of increase in the percentage of lesions currently, with predominance of those with a distal location in comparison to previous studies.
About the morphology of lesions, noncalcified plaques went from being present in 30% of patients (n=10) to 60% of them (n=20) (p=0.021). The calcified plaques had a similar increase, initially in 30% of patients (n=10), and currently in 54% (n=18) (p=0.021). Finally, the mixed plaques were the least frequent ones; they were present in 9% (n=3) of patients initially, and currently there was an increase, as they were detected in 30% of patients (n=10) (p=0.039) (Figure 2).
Figure 2. Percentage of lesions according to morphology, in the previous studies (grey color) versus current studies (yellow color). As to the morphology of the lesions, noncalcified plaques went from presenting in 30% of patients (n=10) to 60% of them (n=20) (p=0.021). Calcified plaques showed a similar increase; initially in 30% of patients (10%), and currently in 54% (n=18) (p=0.021). Finally, plaques of the mixed type were the least frequent ones, presenting in 9% (n=3) of patients initially; and currently there was an increase, as they were detected in 30% of patients (n=10) (p=0.039).
Taking into account the calcium score according to Agatston, a previous average of 80 and a current of 281 was estimated; given the distribution of this variable, the mean value was also taken into account, which was 0 initially, and 33 currently.
In regard to vascular stenosis, on the one hand the presence or absence of it was taken into account; and on the other, the degree of stenosis. Patients with coronary stenosis were initially 39% (n=13), with an increase at 78% (n=26) (p=0.000), with predominance of nonsignificant or mild ones. These were present in 33% of patients (n=11), increasing to 57% (n=19); on the other hand, significant stenosis was taken into account, that were grouped into moderate and severe (>50 of vessel lumen), that were present in 21% (n=7) of patients, comparatively to the previous study, where they were found in just 6% (n=2) (p=0.063) (Figure 3).
Figure 3. Percentage of lesions divided according to the degree of stenosis they generate (mild or nonsignificant and moderate-severe or significant). The patients with coronary stenosis were initially 39% (n=13), with an increase to 78% (n=26) (p=0.000) and a predominance of nonsignificant or mild ones. They were in 33% of patients (n=11) (grey color), increasing to 57% (n=19) (yellow color); on the other hand, significant stenosis was taken into account, where moderate to severe stenosis were grouped (>50% of vessel lumen), that were present in 21% (n=7) of patients, in comparison to the previous study, where they were only in 6% (n=2) (p=0.063).
The findings show CAD progression at the expense of new vascular lesions with predominantly proximal location above the distal lesions, by increase of noncalcified and calcified plaques.
It is important to emphasize that this progression mainly occurs by lesions that generate mild stenosis; a finding that could be due to working with patients in low-to-moderate risk, asymptomatic, and with no history of previous cardiovascular events; several of which presented normal studies initially. However, 21% (n=7) presented new lesions with moderate to severe stenosis, and also a significant increase both in the number of proximal lesions and coronary calcium score; that is to say, the plaque load (Figures 4 and 5). The progression of CAD in this group is evident.
Figure 4. Curved multiplanar reconstruction of CTCA, where the anterior descending artery (ADA) is observed: (a) in the previous study (2012); where two calcified plaques were observed in the proximal third of the vessel and a third mixed plaque in its distal third, that generated mild stenosis. (c) ADA is visualized in the current study (2017) with an increase in the number of atheromatous plaques, most of them calcified, in the proximal and middle third of the vessel (b and d). Orthogonal view at the proximal level of the ADA; (b) in the previous study (2012), where the vessel lumen is observed, with a small calcified plaque in its inferior border, generating mild stenosis. (d) In the current study (2017), where a decrease is observed in vascular lumen at the expense of an increase in the number of calcified atheromatous plaques, compromising the vessel in an almost circumferential fashion; in correlation with image (c).
Figure 5. (a and c) Curved multiplanar reconstruction of CTCA, where the right coronary artery (RCA) is visualized; (a) in the previous study (2012); where two atheromatous plaques are observed in the proximal third of the vessel; the first noncalcified (plaque 1) and the second calcified (plaque 2). (c) RCA is visualized in the recent study (2017) with plaque 1 currently of the mixed type. (b and d) Orthogonal view in the proximal region of the RCA, at the level of plaque 1. (b) In the previous study (2012), where the vessel lumen is observed with moderate stenosis. (d) Current study (2017), where compromise of more than 50% of the vessel is observed in the area of plaque 1, with decrease in vascular lumen at said level (moderate-severe stenosis); in correlation with image (c).
Another datum to mention is the fact that all patients were receiving treatment for the pathologies included within the risk factors (except two of them untreated for dyslipidemia [DLP]). This could point out the fact that there is progression of the disease in spite of the established treatment. The patients that presented more progression of the disease were those that in the initial study presented a greater number of lesions and calcium score.
Min et al, indicate that in patients with chest pain, computed tomography coronary angiography (CTCA) identifies patients in higher risk of death by all causes. It is important to highlight that a negative CTCA foreshadows an extremely low risk of death . Noninvasive cardiac images of CTCA, with multislice or electron beam technology, is highly specific and sensitive in the diagnosis of CAD .
Limitations of the study
This study was conducted in a single center, which makes the applicability of the results uncertain for other populations. The sample was also small, which prevents evaluating the relation between disease progression and other subgroups that constitute risk factors.
By CTCA, it is possible to evaluate the progression of CAD, both for the increase in the number of atherosclerotic lesions and the degree of stenosis, also increasing the coronary tree calcification in the long term. Such findings could be the starting point for the re-stratification of patients considered to be in low risk by conventional scores.
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