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Original Contribution

Accuracy and Potential Benefit of Ultraselective Invasive Coronary Angiography Guided by Computed Tomographic Coronary Angiography

Konrad A.J. van Beek, BSc1,2; Anouk G.W. de Lepper, MD1; Marcel van’t Veer, PhD1; Sjoerd Bouwmeester, MD1; Luuk C. Otterspoor, MD, PhD1; Pim A.L. Tonino, MD, PhD1; Jeroen Lammers, MD3; Mark Winkens, MD, PhD4; Lokien X. van Nunen, MD, PhD1

May 2022
1557-2501
J INVASIVE CARDIOL 2022;34(5):E390-E396. doi: 10.25270/jic/21.00271. Epub 2022 April 22.

Abstract

Objectives. It is unknown whether computed tomographic coronary angiography (CTCA) can be used to perform ultraselective invasive coronary angiography (ICA) by only visualizing the abnormal coronary artery on CTCA and defer visualization of the normal contralateral coronary artery. This study assessed the accuracy of CTCA in patients with coronary artery disease (CAD) on CTCA limited to either the left (LCA) or right coronary artery (RCA) in predicting a contralateral coronary artery without abnormalities on CTCA determined to be normal by ICA. Methods. This retrospective analysis included patients with CAD limited to the LCA or RCA on CTCA. Primary endpoint was the accuracy of CTCA to predict a contralateral coronary artery without abnormalities on CTCA to be normal by ICA. Secondary endpoints were potential reductions in procedure time and radiation exposure if an ultraselective ICA approach would be used compared to standard ICA. Results. In total, 202 patients were included. CTCA was correct in predicting a normal contralateral coronary artery in 201 of the 202 patients (99.5%). Deferring ICA of the normal contralateral coronary artery on CTCA resulted in a potential reduction in procedure time and dose area product of 4.22 ± 2.67 minutes (61 ± 16% reduction) and 1501 ± 1304 mGy•cm2 (29 ± 13% reduction). Conclusions. In this retrospective study, CTCA was extremely accurate in predicting a normal contralateral coronary artery in patients with LCA- or RCA-limited CAD on CTCA. A potential CTCA-guided ultraselective ICA approach was feasible and would have led to a considerable decrease in procedure time and radiation exposure.

J INVASIVE CARDIOL 2022;34(5):E390-E396. Epub 2022 April 22.

Key words: computed tomographic coronary angiography, coronary angiography, coronary artery disease, radiation exposure


Patients presenting with stable angina can be evaluated with multiple noninvasive tests.1,2 In the recent guidelines by the European Society of Cardiology, anatomical noninvasive imaging by computed tomographic coronary angiography (CTCA) plays an important role in analyzing the presence of coronary artery disease (CAD) in patients without a history of CAD and a low to intermediate likelihood of CAD.1 Timely diagnosis of the presence and extent of CAD is critical for the determination of an adequate treatment strategy. CTCA provides high accuracy in the detection of CAD by visualizing the coronary artery lumen using intravenous contrast agent.3 However, to determine the hemodynamic significance of CTCA-identified stenosis, invasive coronary angiography (ICA) with or without functional testing is still required, with the option to perform ad hoc percutaneous coronary intervention (PCI).4 During ICA, as per protocol, the complete epicardial coronary artery system is visualized by using specific catheters, contrast agent, and radiation.

van Beek Coronary Angiography Figure 1
Figure 1. Case example of the potential benefit of CTCA-guided ultraselective invasive coronary angiography. CTCA of a 58-year-old man presenting with chest pain, showing a mixed plaque (up to 70% stenosis) in the mid LAD (B, red arrow) and no plaques or wall abnormalities in the RCA and RCX (A, C). On ICA, a stenosis of 70%-99% was confirmed in the mid LAD (E, red arrow). ICA confirmed the contralateral RCA (D) to be normal. A CTCA-guided ultraselective invasive coronary angiography, solely visualizing the LCA, would result in a reduction in procedure time and radiation exposure of 3.5 minutes (70%) and 1001 mGy•cm2 (27%), respectively. CTCA = computed tomographic coronary angiography; DAP = dose-area product; ICA = invasive coronary angiography; LAD = left anterior descending; LCX = left circumflex; RCA = right coronary artery.

While the excellent negative predictive value in patients with no or minimal obstructive CAD on CTCA is widely proven,5-7 the efficacy of CTCA in assessing the contralateral coronary artery in patients with obstructive isolated left (LCA) or right coronary artery (RCA) disease on CTCA is unknown. In these patients, with abnormalities on CTCA in only 1 coronary artery (ie, the LCA or RCA), ICA might be simplified by “ultraselectively” visualizing only the coronary artery of interest and refraining from angiographic visualization of the contralateral coronary artery without abnormalities on CTCA. This approach is only feasible if CTCA accuracy proves to be vessel specific, which is investigated as the primary endpoint of this study. Subsequently, such an ultraselective strategy will reduce procedure time, usage of catheters, complication risk, amount of contrast agent, and radiation exposure (Figure 1).

The aim of this retrospective study was therefore to determine the diagnostic accuracy of CTCA in predicting a normal contralateral coronary artery without abnormalities on CTCA to be normal by ICA in patients with CAD limited to either the LCA or RCA. Second, we investigated the potential benefit of a CTCA-guided ultraselective ICA approach of focusing solely on visualizing the coronary artery of interest on CTCA and deferring visualization of the normal contralateral coronary artery.


Methods

Study design and patient population. This retrospective, multicenter study took place at 3 hospitals in the Netherlands. All centers received approval by their local ethics committees with waiver of informed consent. All patients who underwent ICA within 90 days after CTCA during a 5-year period (January 1, 2015 to January 1, 2020) were included in this analysis. Only patients with CAD limited to either the LCA or RCA were included in this study. Patients with 2-vessel disease could be included if the coronary artery stenoses were limited to the LCA, ie, the left main (LM), left anterior descending (LAD), and/or left circumflex (LCX). The temporal interval of 90 days was chosen to prevent possible aggravation of CAD between both examinations. There were no exclusion criteria.

Image acquisition, image reconstruction, and interpretation of CTCA. Patients were analyzed using 2 multidetector computed tomography tests (coronary calcium scoring and angiography). All examinations were performed using a 256-slice system. Prospectively electrocardiogram-triggered sequential CTCA with automated tube-current modulation and tube-potential selection is the standard of care in order to keep radiation dose as low as possible. In every patient with a heart rate above 65 bpm and absence of contraindications, a beta-blocker (metoprolol tartrate) was administered intravenously in fractions up to a maximum dose of 20 mg to stabilize and reduce the heart rate. The scan range extended from the carina to just below the bottom of the heart as detected on the thoracic anterior-posterior scout scan. Contrast agent (iomeprol) was administered via a patent venous cannula at a flow rate of 5 mL/s. A test bolus of 12 mL of contrast and 30 mL of sodium chloride was used to determine the individual scan delay time. The injection protocol was as follows: (1) a 60 mL bolus of pure iodinated contrast material; (2) a mixed bolus with 65 mL of a 30% contrast agent and 70% saline solution; and (3) 40 mL of pure  sodium chloride bolus.

Images were processed using a soft tissue and medium sharp reconstruction kernel with filtered back projection with a slice thickness of 0.75 mm and an increment of 0.4 mm. Atherosclerotic plaque was graded by visual estimation of stenosis in a standard way: normal (absence of plaque and no luminal stenosis); minimal (plaque with <25% luminal stenosis); mild (25%-49% luminal stenosis); moderate (50%-69% luminal stenosis); severe (70%-99% luminal stenosis); or occluded (100% luminal stenosis). Only vessels with a minimal diameter of 1.5 mm were evaluated. In this study, a coronary artery was defined without atherosclerosis (“normal”) in case of an Agatston score of <10 and no lumen loss on contrast admission.

Image acquisition of coronary angiograms. ICA was performed using a standard cardiology fluoroscopy device. Angiograms were obtained in pulsed fluoroscopy mode at a standard frame rate of 15 frames/s. Dose reports were automatically generated and archived after the end of an examination with display of tube settings and dose-area product (DAP) for every single acquired series of the examination. The interventional cardiologist interpreted the images visually during the procedure. The severity of coronary artery stenosis was defined as <30%, 30%-49%, 50%-69%, 70%-99%, and 100%. Therapy decision was made based upon clinical presentation and other available test results, such as stress electrocardiogram, echocardiography, and myocardial perfusion scintigraphy. As appropriate, conservative medical treatment, physiologic testing, or PCI was performed. With regard to this study, a coronary artery was defined as “normal” on ICA in cases of coronary atherosclerosis <30%, ie, wall abnormalities.

Outcome measures. The primary endpoint of this study was defined as the accuracy of CTCA in predicting a normal contralateral coronary artery on CTCA to be indeed normal on ICA in patients with CAD limited to the LCA or RCA. As described above, this was defined as follows: the absence of CAD in a coronary artery on CTCA was defined as an Agatston score <10 and no lumen loss on contrast admission; the absence of CAD on ICA was defined as coronary atherosclerosis <30%, ie, wall abnormalities. So, CTCA was defined to be accurate in predicting a normal contralateral coronary artery if that contralateral coronary artery showed <30% coronary atherosclerosis (and no further functional testing and/or PCI was performed in that contralateral coronary artery).

van Beek Coronary Angiography Figure 2
Figure 2. Definitions of total procedure time and potential superfluous procedure time. The logged procedure time starts at the time of the first acquired coronary angiography cine run (preparation and advancement to coronary ostium are unknown due to the retrospective nature of the study) and ends after the last coronary angiography cine run. The potential superfluous procedure time used for visualization of the coronary artery without abnormalities on CTCA is defined as the time used to change catheters and acquisition of coronary angiography cine runs of the normal coronary artery (A, B, hashed section). This time period is dependent on which coronary artery is visualized first. CTCA = computed tomographic coronary angiography.

Secondary endpoints were defined as the potential benefit of a CTCA-guided ultraselective ICA approach, deferring visualization of the contralateral coronary artery and solely focusing on the coronary artery with abnormalities on CTCA. Potential benefits in this study were defined as the reduction in procedure time and radiation exposure. To retrospectively assess this potential benefit, we compared the procedure time and DAP of the standard ICA procedure with the hypothetical ultraselective ICA procedure deferring visualization of the contralateral coronary artery (Figure 2). Depending on which coronary artery is visualized first, the potential benefit in procedure time was defined as the time used to change catheters and visualize the contralateral coronary artery without abnormalities on CTCA (Figure 2). This potentially superfluous time interval was deducted from the total procedure time, resulting in a hypothetical procedure time of a CTCA-guided ultraselective ICA. This was used to calculate the potential benefit in terms of procedure time. To adequately assess this endpoint, we defined time intervals as follows: start of the procedure was the time of the first cine run of the diagnostic part of the coronary angiogram, while the end of the procedure was defined as the time of the last cine run of the diagnostic part of the coronary angiogram.

A similar approach was used to assess potential benefit in radiation exposure. We studied the structured dose reports provided by the fluoroscopy system and analyzed the DAP (expressed in mGy•cm2) used for the RCA and LCA, respectively. By deducting the DAP used to visualize the contralateral normal coronary artery on CTCA from the total DAP, the hypothetical DAP of an ultraselective ICA approach was calculated and used to calculate the potential benefit of ultraselective ICA in terms of radiation exposure.

van Beek Coronary Angiography Table 1
Table 1. Baseline characteristics of the study population.

Statistical analysis. Patient characteristics are reported as percentages for discrete variables, while continuous variables are presented as mean ± standard deviation. Values for the absolute and relative potential reduction of procedure time, number of acquired coronary angiograms, and DAP are presented as mean ± standard deviation.

Since the potential benefits of an ultraselective approach are statistically significant per definition (due to the paired nature of these values), we performed no statistical analysis of the potential benefit in terms of procedure time or DAP. We used 1-way analysis of variance (ANOVA) to detect potential differences in procedure time and DAP between the 3 participating hospitals. The acquired data were analyzed using IBM Statistical Package for Social Sciences (SPSS) for Windows, version 25 (IBM Corporation).


Results

Baseline characteristics. All patients undergoing ICA within 90 days after CTCA were screened (n = 885). A total of 202 patients (23%) with CAD limited to the LCA or RCA were included. Baseline characteristics are presented in Table 1. Mean age in the patient population was 59 ± 10 years, 51% were male, mean height was 172 ± 10 cm, and mean body weight was 80 ± 15 kg. Most patients had one or more risk factors for CAD and 16% had diabetes mellitus. One patient had previous myocardial infarction and none of the patients underwent a previous PCI.

van Beek Coronary Angiography Table 2
Table 2. Computed tomographic coronary angiography and invasive coronary angiography variables.

Angiographic variables. All angiographic variables of CTCA and ICA are displayed in Table 2. In the patient population, CTCA showed 261 coronary artery stenoses. A total of 143 patients had single-vessel disease on CTCA, while 2-vessel disease limited to the LCA was present in 59 patients. The coronary artery stenoses were located in the LM, LAD, LCX, or RCA in 32 (12%), 180 (69%), 44 (17%), and 5 (2%), respectively. Mean time between CTCA and ICA was 39 ± 36 days. Mean procedure time was 7.05 ± 3.62 minutes. Procedure time was not different between the 3 participating centers (P=.07). DAP was available in 118 patients (58%). For the complete standard ICA, mean DAP was 5289 ± 3478 mGy•cm2. There was a significant difference between the hospitals in terms of mean DAP (P=.01). Mean number of procedural coronary angiography cine runs acquired was 7 ± 1 runs.

van Beek Coronary Angiography Figure 3
Figure 3. Potential benefit of CTCA-guided ultraselective invasive coronary angiography. (A) The potential benefit of CTCA-guided ultraselective ICA focusing solely on the coronary artery with abnormalities on CTCA in terms of procedure time (7.05 ± 3.62 minutes vs 2.82 ± 2.62 minutes) and (B) dose-area product (5288 ± 3478 mGy•cm2 vs 3787 ± 2707 mGy•cm2). CTCA = computed tomographic coronary angiography; ICA = invasive coronary angiography.

Accuracy of CTCA and potential benefit of CTCA-guided ultraselective ICA. CTCA was accurate in predicting a normal contralateral coronary artery on CTCA to be indeed normal on ICA in 201 patients (99.5%) with CAD limited to the LCA or RCA. In only 1 patient (0.5%), ICA revealed a nonsignificant coronary artery stenosis (30%-50%) in the contralateral coronary artery, not needing further evaluation or intervention. Therefore, in all patients included in this study, a CTCA-guided ultraselective ICA approach would be feasible and could have led to a decrease in procedure time and radiation exposure (Figure 3 and Table 3). If this ultraselective ICA had been used, the mean decrease in procedure time would have been 4.22 ± 2.67 minutes (61 ± 16%). Mean values for potential DAP reduction were 1501 ± 1304 mGy•cm2 (29 ± 13%).


Discussion

van Beek Coronary Angiography Table 3
Table 3. Potential reduction in procedure time and dose-area product of CTCA-guided ultraselective ICA.

In this largest, most comprehensive retrospective study of ­patients with CAD limited to the LCA or RCA, CTCA is extremely accurate in predicting a normal contralateral coronary artery on ICA. Therefore, a CTCA-guided ultraselective ICA strategy solely directed to visualizing the atherosclerotic coronary artery as identified on CTCA and deferring visualization of the normal contralateral coronary artery is potentially safe and leads to benefits in terms of procedure time, radiation exposure, and amount of contrast agent used, ultimately resulting in reduction in procedure costs. In this study, ultraselective ICA would have led to a reduction in procedure time (on average, 61%) and radiation exposure (on average, 29%). This shows the potential of an ultraselective ICA approach guided by CTCA in patients with CAD limited to the LCA or RCA on CTCA.

The need to reassure that a normal or mildly abnormal vessel on CTCA is indeed normal on ICA seems superfluous based on the results presented in this study. In current daily practice in the catheterization laboratory, the abnormal CTCA is merely used as risk stratification justifying ICA while discarding all further anatomical information that can easily be used to guide ICA, being aware of the excellent prognosis of a coronary artery without visual lumen loss or calcification on CTCA.8 While the benefits of this CTCA-guided ICA approach might be perceived as relatively modest at first, the new workflow of introducing preprocedural planning by CTCA in the catheterization laboratory postulated here might be the start of a paradigm shift. The utilization of CTCA in the catheterization laboratory could shift from preprocedural risk stratification to an integrated part of the ICA procedure guiding the interventional cardiologist. Preprocedural planning using CT angiography is standard of care in many non-cardiac vascular interventional procedures and may well be extended into ICA.9

Numerous studies have demonstrated the high sensitivity of CTCA for the detection of significant stenosis from 95% to 100%.5-7 More often there is an overestimation of degree of stenosis due to the blooming effect of calcified plaques, leading to a lower specificity and positive predictive value.10,11 So, if anything, CTCA seems to overestimate the severity of CAD when compared with the gold standard of ICA. Furthermore, it should be noted that in this study, there were no exclusion criteria for the CTCA based on image quality, body mass index, or presence of artifact, precluding any form of selection bias.

To the best of our knowledge, there is only 1 other study reporting DAP reduction of CTCA guidance corroborating the results found in this study in a smaller study population.12

The potential benefits of a CTCA-guided ultraselective ICA are numerous. First, the potential benefits in procedure time and radiation exposure have already been described above. The effect on procedure time will lead to cost reduction, which will be increased by the use of fewer diagnostic catheters. The decrease in radiation exposure will serve the patient as well as the interventional cardiologist. Long-term radiation exposure is known to be a risk for several diseases, including cataract, skin lesions, early atherosclerosis, and various malignancies.13-15 Interventional cardiologists are particularly at risk, as they are exposed to the most radiation of all health professionals.16,17 Since the complexity and number of interventions is only increasing, more attention has to be focused on reducing periprocedural radiation doses and minimizing the accompanied risks, in line with the “as low as reasonably achievable” radiation safety principle.18,19 The most effective measure to reduce radiation dose is to avoid unnecessary exposure, as is the case by visualizing the coronary artery without abnormalities on CTCA as described in this study.

Besides the benefits, potential complications of ICA can be minimized by avoiding additional manipulation, change of catheters, and intubation of the contralateral coronary artery. These complications are rare, but can have serious consequences.20 Moreover, the use of CTCA-guided ultraselective ICA will most likely lead to a reduction in contrast agent. Higher amounts of contrast are associated with a higher risk of developing contrast-induced nephropathy,21 which is related to prolonged hospitalization and increased morbidity and mortality. In order to reduce the risk, the contrast media should be limited to the minimum amount necessary. The use of CTCA-guided ultraselective ICA will further reduce the use of contrast agent during diagnostic ICA.

Finally, with the expected increase in CTCA use due to the major role in the recent guidelines of the European Society of Cardiology on chronic coronary syndromes, the use of CTCA is only expected to rise in the upcoming decade. This emphasizes the importance of these first retrospective findings and encourages further prospective studies to better investigate the potential of CTCA-guided ultraselective ICA.

Study limitations. The current study has multiple limitations. Most importantly, due to its retrospective nature, the potential benefit in terms of procedure time is only estimated using procedure logs. Therefore, this potential benefit might be overestimated due to the fact that initial preparations are not included in the procedure time by the definitions used in this study. However, it should be clearly noted that the potential benefit of CTCA-guided ultraselective ICA was not the primary goal of this study. Primarily, this study set out to investigate the accuracy of CTCA to predict a normal contralateral coronary artery in patients with isolated LCA or RCA disease. A recently started prospective registry (NCT04907786) will answer the questions regarding the potential benefits of this ultraselective approach. This is also the case with regard to the effect on catheter use, amount of contrast agent, incidence of iatrogenic dissection, and/or kidney injury.

Another limitation of this study is the lack of clinical endpoints. Most importantly, information regarding major adverse cardiac events due to missing important disease by CTCA-guided ultraselective ICA on the one hand, or procedural complications due to visualizing a coronary artery without CAD on CTCA on the other hand, are not available. Nonetheless, taking into account the average complication rate of ICA20 and the chance of missing important disease when focusing on the primary outcome of this study (CTCA was correct in identifying a normal contralateral coronary artery in 99.5%), the number of patients needed to investigate these benefits or disadvantages would be enormous.

Third, the magnitude of the potential reduction of radiation exposure as found in this study varied between the 3 hospitals. This is most likely due to different interventional cardiology teams, their experience and protocols, fluoroscopic equipment, and patient anatomy.

Last, in this study, very few patients were included with abnormalities on CTCA limited to the RCA. This might be due to the low pretest probability of CAD limited only to the RCA based on the CTCA definition of an Agatston score <10. It is therefore unknown whether the results of this study can safely be extrapolated to patients with suspected CAD on CTCA restricted to the RCA, but we have no reasons to believe otherwise.


Conclusion

In this retrospective study in patients with CAD in the LCA or RCA as found on CTCA, the use of CTCA was extremely accurate in predicting the contralateral coronary artery to be normal on ICA. Visualization of the contralateral coronary artery by ICA was superfluous in all patients. The use of CTCA-guided ultraselective ICA solely focused on visualizing the coronary artery of interest could lead to a considerable decrease in procedure time as well as radiation exposure. A prospective, multicenter study was recently started to further investigate the potential of CTCA-guided ultraselective ICA (NCT04907786) and to further reconsider the standard of care in ICA for the visualization of the entire coronary system after CTCA in every patient.


Affiliations and Disclosures

From the 1Heart Center, Catharina Hospital Eindhoven, The Netherlands; 2University of Maastricht, Maastricht, The Netherlands; 3Department of Cardiology, Elkerliek Hospital, The Netherlands; 4Department of Cardiology, Elisabeth-TweeSteden Hospital, The Netherlands.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

The authors report that patient consent was provided for publication of the images used herein.

Manuscript accepted August 18, 2021.

Address for correspondence: Lokien X. van Nunen, MD, PhD, Catharina Hospital Eindhoven, Department of Cardiology, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands. Email: lokien.v.nunen@catharinaziekenhuis.nl


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