Looking Outside the Box of the Heart: Non-Cardiac Findings Encountered During Coronary CT Angiography

Francesca Pugliese, MD, PhD and Simon PG Padley, FRCP FRCR
Address for correspondence:
Dr Simon Padley
Radiology Department
Chelsea and Westminster Hospital
369 Fulham Road
London SW10 9NH
United Kingdom



Abstract
Although the purpose of most cardiac gated computed tomography (CT) studies is the assessment of cardiac structures, incidental findings are common. These may be detected within the small field of view images of the heart but increase in number when larger field of view reconstructions, to include the whole thorax within the scan range, are examined. Most of these findings will turn out to be unimportant, but it is often not possible to provide definitive guidance based on a single examination. Many patients will go on for further investigation, often requiring additional irradiation which is associated with uncertainty and anxiety. It has been suggested that one solution to these collateral findings is to confine the report to cardiac structures in question, but this seems to run against the grain of current radiological practice. This article examines the frequency of these incidental findings and discusses some of the issues they raise.

Introduction
Coronary computed tomography (CT), originally used for the detection and quantification of coronary calcium, is now considered a robust cardiovascular imaging modality for the non-invasive visualisation of coronary arteries using electrocardiography (ECG)-gated multi-detector CT angiography[1-7]. The field of view (FOV) for assessment of cardiac structures may be as small as 15 cm and at this size will exclude much of the lungs. However, it is possible to reconstruct the same raw data using a larger FOV to demonstrate all of the included thoracic structures. The study may also include a portion of the upper abdomen. Therefore, it is common practice to review a second set of images that are reconstructed with a larger FOV to evaluate these structures at no additional radiation burden to the patient.

This practice is not universal and has given rise to debate amongst radiologists and cardiologists over whether the lungs and chest should be routinely reviewed. The ability to detect incidental relevant disease such as a small, and presumably curable, early stage lung cancer is cited as an argument to support this view. Also, non-cardiac pathology delineated by CT (e.g., lung infiltrates, pleural effusion, dissecting aorta/aneurysm) may explain symptoms in the absence of coronary artery disease[8, 9].

Figure 1
Figure 1. Scan range of a normal coronary CT angiography scan. The lung apices are generally not included in the scan.
On the other hand, not all non-cardiac incidental findings are clinically relevant. Full diagnostic characterisation and/or follow-up of unimportant lesions invokes additional irradiation, further cost and psychological stress. Also, only a portion of the lung parenchyma is imaged during a normal cardiac acquisition (the superior and inferior borders of the heart serve as landmarks to the acquisition) (Figure 1). Therefore, coronary CT angiography cannot detect or rule out relevant disease in the apices of the lungs, which could result in a false reassurance to the patient and the physician. Based on these considerations it can be argued that it might be preferable to confine the examination to the coronary tree and not specifically to reconstruct and read coronary CT angiography studies for extra-cardiac pathology[10]. This can of course be countered by the suggestion that choosing to overlook significant non-cardiac pathology incidentally included in a cardiac CT study would not be defensible in the eyes of the law.

This article will review the available data on the frequency of incidental non-cardiac findings on coronary CT angiography, their significance and the evidence on whether their detection is associated with improved outcomes.

Frequency and significance of extra-cardiac findings
Table 1

Several studies have evaluated the frequency, nature and clinical significance of extra-cardiac findings detected on CT scans of the heart (Table 1). A few of these studies[11-14] have evaluated the frequency of non-cardiac incidental findings in asymptomatic populations screened for coronary calcium with electron-beam computed tomography (EBCT). Similar scan protocols were used in these studies (single breath hold, 3-mm slice thickness, electrocardiographically gated), and reconstructions at maximum FOV for the evaluation of the chest were obtained in addition to reconstructions aimed at the measurement of coronary calcium.

Other studies[8, 15-19] have evaluated the occurrence of extra-cardiac findings in patients undergoing coronary CT angiography. Most of these studies[8, 16-19] were performed in patients with suspected coronary artery disease; 1 study[15] was conducted in asymptomatic self-referred subjects. Sixteen, 40- and 64-slice scanners were used. Scan parameters were peak tube voltage 120 to 140 kV, tube current 400 to 800 mA, table feed 2.8 to 3.8 mm/rotation. Additional data sets were reconstructed with a large FOV to include the entire chest with a slice thickness of 1 mm[15, 16, 19], 3 mm[18] or 5 mm[8]. Images were reviewed by experienced radiologists using at least 2 different window settings (mediastinal window 400W/40C and lung window 1700W/-500C)[8, 15-19].

Most of the available reports[8, 12-15] made a distinction between clinically non-significant and clinically significant findings. A clinically non-significant finding was defined as a finding lacking proven clinical and/or prognostic significance and therefore not requiring follow-up (e.g., degenerative changes of the spine)[20]. A clinically significant finding was defined as an imaging abnormality that required further diagnostic work-up[20].

The total percentage of patients with at least 1 incidental finding varied from 8.0 to 79.4% across the studies (Table 1). The percentage of patients with at least 1 clinically significant incidental finding also varied widely between studies ranging between 2.8 to 45.6%. Similarly, if findings were considered individually according to their location and nature (e.g., lung nodules), there was wide variation in the percentage of findings qualified as clinically significant (Table 1).

These variations between studies are in part explained by the differing definition of a clinically significant finding. If a clinically significant finding is defined as ‘an imaging abnormality requiring further diagnostic work-up’, this category will include not only findings with ‘immediate’ therapeutic consequences (e.g., newly diagnosed cancer or pulmonary embolism) or with ‘unquestionable’ clinical relevance (e.g., large pulmonary consolidation), but also findings with ‘possible’ clinical and/or prognostic relevance suggesting the need for follow-up (e.g., indeterminate pulmonary nodules)[20]. Moreover, although these studies used the same definition of a clinically significant finding, the actual decision to recommend a follow-up investigation was not standardised and may have differed substantially from centre to centre.

Lung nodules
Figure 2

Figure 2
Figure 2. 70-year-old male asymptomatic patient with hyperlipidemia and history of premature coronary artery disease. Patient never smoked. Coronary CT angiography ruled out the presence of obstructive coronary artery disease. However a 10-mm nodule (arrows) was noted in the right upper lobe. The nodule was surgically resected at the insistence of the patient. Histology revealed a focus of granulomatous vasculitis.
Although there were a number of non-cardiac findings detected during cardiac CT (pneumonia, interstitial lung disease, lymphadenopathy, hiatus hernia etc.) the largest proportion of incidental abnormalities requiring follow-up consisted of small non-calcified pulmonary nodules (Table 1). It is accepted that small lung nodules may represent an early stage lung cancer. The ability to detect disease at a curable stage is obviously very appealing. Therefore individuals with an incidental pulmonary nodule during coronary calcium screening or coronary CT angiography were the category most often referred for further testing[8, 15, 17].

However it also is known from previous studies such as the Mayo CT screening study[21], that if CT is carried out in individuals with a low prior chance of serious lung disease (e.g., screening), findings will rarely be of clinical relevance. From this it follows that many lesions will have to be followed up to detect one genuine lung cancer. Amongst those individuals without important disease, caught up in the follow-up regimen, there may be a number of unquantifiable undesirable effects. These include patient anxiety, further irradiation and unnecessary treatments and interventions (Figure 2). Swensen reported one such prospective cohort study of 1520 asymptomatic individuals with cigarette smoking history who were screened for lung cancer using low-radiation-dose spiral CT and sputum cytology[22]. One year after baseline scanning, 2244 non calcified lung nodules were identified in 1000 participants (66%). Twenty-five cases of lung cancer were diagnosed (1.6%). Twelve (57%) of the 21 non-small cell cancers detected were stage IA at diagnosis. Although 22 patients underwent curative surgical resection, 7 benign nodules were resected. This study highlights the pros and cons of CT in the detection and management of lung nodules; although CT can detect early-stage lung cancers in a population of asymptomatic smokers, the rate of benign nodule detection is high[22].

Figure 3

Figure 3
Figure 3. 61-year-old male patient (ex-smoker) with recent onset of exertional angina. Patient had history of oesophageal carcinoma treated surgically. Coronary CT angiography showed heavy coronary calcifications and obstructive plaque. A 9-mm nodule (arrows) was also noted in the left upper lobe. CT-guided biopsy revealed secondary lesion.
The frequency of lung nodules detected in asymptomatic individuals undergoing screening for coronary calcium was reported to be in the range 0.44 to 4.9% (Table 1)[11-14]. In symptomatic patients undergoing coronary CT angiography on the suspicion of coronary artery disease the frequency of lung nodules reported has been higher, in the range 3.7 to 20.2%[8, 15]. Thus despite some degree of overlap, there appears to be a difference in the frequency of significant incidental findings between patients who had coronary CT angiography and individuals who were screened for coronary calcium. This higher prevalence is perhaps not surprising. First, coronary CT angiography is not indicated as a screening test and usually is part of the work-up in a patient with symptoms that are of possible cardiovascular origin, or be undertaken to clarify results of other investigations, typically myocardial perfusion scanning or exercise testing. Other conditions may produce symptoms similar to those associated with cardiac disease and these include aortic pathology or pulmonary vascular pathology (dissecting aorta/aneurysm, pneumonia, pleural effusions, pulmonary hypertension, pulmonary oedema). One study has shown[8] that in 32 of 201 (16%) patients in whom coronary disease was ruled out, non-cardiac findings delineated by CT were considered sufficient to explain the patients’ symptoms. Second, the risk factors for coronary artery disease, particularly smoking, are associated with lung diseases such as cancer and chronic obstructive pulmonary disease. Whereas the risk of coronary artery disease decreases promptly after smoking cessation, the risk of lung cancer does not[23]. Onuma et al[8]. identified and confirmed newly diagnosed malignancies in 4/503 patients (0.8%) undergoing coronary CT angiography for symptoms suggestive of coronary artery disease. It is self evident that risk factors such as asbestos exposure, or a specific clinical context such as a known malignancy will increase the probability of detecting lung lesions with therapeutic or prognostic consequences (e.g., primary or secondary lesions) in an individual patient (Figure 3).

When the rates of lung nodules and lung malignancies from the available coronary CT angiography series[8, 15-19] are compared to the study by Swensen et al[22]. in a lung cancer screening population, lower rates of patients with lung nodules (≤20.2% vs. 66%) and lung malignancies (≤1.2% vs. 1.6%) are seen. The partial inclusion of the lung in routine coronary CT angiography may account for this difference (with all lung above the carina being routinely excluded. Also, whereas all subjects undergoing lung cancer screening were smokers or ex-smokers, the proportions of patients with smoking history among those included in the coronary CT angiography studies were much lower (Table 1).

Table 2. Recommendations for follow-up and management of nodules smaller than 8 mm detected incidentally at non-screening CT (reproduced with permission[24])

Nodule size (mm) a

Low-Risk Patient b

<4

No follow-up needed d

4-6

Follow-up CT at 12 mo; if unchanged, no further follow-up

6-8

Initial follow-up CT at 6–12 mo then at 18–24 mo if no change

>8

Follow-up CT at around 3, 9, and 24 mo, dynamic contrast-enhanced CT, PET, and/or biopsy

 

Note - Newly detected indeterminate nodule in persons 35 years of age or older.
a Average of length and width.
b Minimal or absent history of smoking and of other known risk factors.
c History of smoking or of other known risk factors.
d The risk of malignancy in this category (<1%) is substantially less than that in a baseline CT scan of an asymptomatic smoker.
e Nonsolid (ground-glass) or partly solid nodules may require longer follow-up to exclude indolent adenocarcinoma.

The Fleischner Society’s recommendations[24] for follow-up and management of pulmonary nodules detected incidentally on CT do not suggest follow-up of nodules smaller than 4 mm in non-smokers and in patients with a low risk of lung cancer (Table 2). Nodules greater than 8 mm or with suspicious features may benefit from formal thoracic CT for characterisation and detection of possible concurrent nodules, assessment of lymph nodes or other pulmonary disease. An initial 3-month follow-up is usually recommended in these cases (Table 2)[24].

Extended examinations
Figure 4

Figure 4
Figure 4. 76-year-old male patient referred for aortic valve replacement for severe aortic stenosis. CT angiography revealed aortic atheroma and mild calcifications at the level of the femoral arteries. Incidentally, a 20-mm mass (arrows) suggestive of renal cell carcinoma was seen at the lower pole of the left kidney. Left renal vein and inferior vena cava did not show signs of invasion. Patient underwent uneventful aortic valvuloplasty and subsequently underwent renal surgery. Diagnosis of renal cell carcinoma (T1) was confirmed.
There is no shortage of incidental pathology to be detected in the short range included when the heart alone is examined. It follows that the greater the range of anatomy examined, the more numerous the incidental findings will be. Furthermore there are an increasing number of cardiac examinations that employ an extended scan range. The follow-up of patients with coronary artery bypass grafts (CABG) and the planning of retrograde trans-femoral aortic valve implantation (TAVI) (Figure 4) are 2 such examples[25].

In the instance of previous CABG, especially in patients with internal mammary artery grafts, the scan range will include the entire course of the graft from its origin from the subclavian artery to anastomosis. Therefore, almost the entire lungs will be included in the scan, resulting in an increased frequency of incidental lung nodules as well as detection of abnormalities of the supra-aortic vessels, mediastinal nodes and the thyroid gland.

Whole body CT angiography is part of the routine work-up in patients proposed for TAVI to evaluate the vascular tree and assess access via the thoraco-abdominal aorta and femoral arteries. Data on the frequency of incidental findings at CT of the abdomen are available from the literature relating to CT colonography. In one such study of 1233 asymptomatic subjects screened for colon cancer, Pickhardt et al[26]. detected unsuspected extra-colonic cancers in 5 (0.4%) subjects (1 with renal cell carcinoma, 1 with lymphoma, 1 with ovarian carcinoma and 2 with bronchogenic carcinoma). In another community-based screening program in asymptomatic subjects, Chin et al[27]. detected extra-colonic findings in 118 (27%) of 432 subjects. Thirty-two (7%) subjects required further investigation, and 9 subjects (2.1%) had findings of major clinical importance that made an impact on outcome. The latter group included 1 subject diagnosed with an unsuspected renal cell cancer, 7 potentially life-threatening abdominal aortic aneurysms and 1 splenic artery aneurysm. Findings which were further investigated but did not derive a clinical benefit to the patient were benign adrenal adenomas, renal and ovarian cysts of uncertain nature, liver hemangiomas and benign lung nodules. Simple cysts in the kidneys and liver, renal calculi, cholelithiasis, diverticulosis and uterine leiomyomas accounted for the findings which were not further investigated[27].

Other studies have found a higher prevalence of extra-colonic abnormalities[28-29]. In a population with known colorectal cancer or undergoing surveillance for colorectal neoplasia, Gluecker et al[28]. described incidental extra-colonic findings in 470 (69%) of 681 patients examined and 68 (10%) required further investigation.

Limitations
All the studies evaluating extra-cardiac findings CT of the heart had limitations. First the duration of clinical follow-up, when performed[8], was relatively short. The only way to make sure that a pulmonary nodule is benign, short of a tissue diagnosis, is to follow it up to demonstrate stability over at least 2 years. Therefore the significance of non-cardiac findings might have been underestimated. Second, none of these studies evaluated the implications of incidental findings in formal cost-effectiveness analyses.

Conclusions
Available data indicate that only a small percentage of incidental findings on coronary CT angiography are potentially serious and carry risks and/or benefits that have importance for the patient.

Although it is logical to keep the FOV as small as possible for optimal visualisation of coronary arteries, information regarding the peripheral area of the chest is available within the raw data and confining the reporting process to the coronaries eliminates the opportunity to act upon what might be important additional findings. How ethical it is to ignore or overlook these non-targeted anatomical regions is a controversy highlighting the core abilities and interests of cardiologists as opposed to radiologists. The accurate and appropriate reporting of incidental abnormalities is clearly desirable but the exhaustive investigation of every tiny nodule is clearly of no benefit in the vast majority of individuals. The required studies, to determine if there is an improved outcome associated with the detection and management non-cardiac findings, have yet to be published.

Therefore, it is acknowledged that there is a lack of concrete evidence that the detection of incidental pathology in an individual has any overall benefit when measured against the harm of over-investigation in the majority. Nevertheless, in the current climate of blame and compensation it seems unavoidable that potentially important findings should be reported. Having the expertise to do this accurately and in accordance with published guidelines is clearly desirable and this can only realistically be undertaken by a diagnostic radiologist with appropriate training and accreditation, who encounters these findings on a daily basis.

The cardiac component of the interpretation of these studies is already undertaken by a radiologist alone in the majority of institutions in the United States and probably in the United Kingdom[30]. Ideally these studies are later reviewed at a joint clinical radiological conference. Perhaps the ideal practice is combined radiological/cardiological reporting. This works well in those centres that follow this model, with a final co-signed report being issued that will address all the cardiac and non-cardiac observations and define a plan for appropriate further investigation.

Inevitably a small incidental early stage lung cancer will be detected from time to time in patients undergoing cardiac CT. The reporting practitioners who do not detect or report these non-cardiac findings do so at their peril.

Key Learning
  • Cardiac CT studies may detect incidental abnormalities in surrounding structures.
  • These abnormalities are usually of no importance, but frequently this can be established only after further investigation or potentially lengthy follow-up.
  • The necessity to accurately and appropriately report these findings has been the subject of some debate amongst radiologists and cardiologists undertaking these studies.
  • At present it remains imperative to identify these collateral findings so that appropriate observation or intervention can be planned.
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    31. JB3826