Author + information
- Received February 13, 2017
- Revision received September 26, 2017
- Accepted October 6, 2017
- Published online November 5, 2018.
- Marisa Lubbers, MDa,b,∗ (, )
- Adriaan Coenen, MDa,b,
- Marcel Kofflard, MD, PhDc,
- Tobias Bruning, MD, PhDd,
- Bas Kietselaer, MD, PhDe,
- Tjebbe Galema, MD, PhDa,
- Marc Kock, MD, PhDf,
- Andre Niezen, MD, PhDg,
- Marco Das, MD, PhDh,
- Marco van Gent, MDc,
- Ewout-Jan van den Bos, MD, PhDc,
- Leon van Woerkens, MD, PhDc,
- Paul Musters, MANPa,
- Suze Kooij, BScf,
- Fay Nous, MDb,
- Ricardo Budde, MD, PhDb,
- Miriam Hunink, MD, PhDb and
- Koen Nieman, MD, PhDa,b,i
- aDepartment of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands
- bDepartment of Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands
- cDepartment of Cardiology, Albert Schweitzer Ziekenhuis, Dordrecht, the Netherlands
- dDepartment of Cardiology, Maasstad Ziekenhuis, Rotterdam, the Netherlands
- eDepartment of Cardiology, Maastricht University Medical Center, Maastricht, the Netherlands
- fDepartment of Radiology, Albert Schweitzer Ziekenhuis, Dordrecht, the Netherlands
- gDepartment of Radiology, Maasstad Ziekenhuis, Rotterdam, the Netherlands
- hDepartment of Radiology, Maastricht University Medical Center, Maastricht, the Netherlands
- iStanford Cardiovascular Institute, Stanford University, Palo Alto, California
- ↵∗Address for correspondence:
Dr. Marisa Lubbers, Department of Cardiology, Erasmus Medical Center, 's-Gravendijkwal 230, Room Ca-207a, 3015 CE Rotterdam, the Netherlands.
Objectives This study sought to assess the effectiveness, efficiency, and safety of a tiered, comprehensive cardiac computed tomography (CT) protocol in comparison with functional testing.
Background Although CT angiography accurately rules out coronary artery disease (CAD), incorporation of CT myocardial perfusion imaging as part of a tiered diagnostic approach could improve the clinical value and efficiency of cardiac CT in the diagnostic work-up of patients with angina pectoris.
Methods Between July 2013 and November 2015, 268 patients (mean age 58 years; 49% female) with stable angina (mean pre-test probability 54%) were prospectively randomized between cardiac CT and standard guideline-directed functional testing (95% exercise electrocardiography). The tiered cardiac CT protocol included a calcium scan, followed by CT angiography if calcium was detected. Patients with ≥50% stenosis on CT angiography underwent CT myocardial perfusion imaging.
Results By 6 months, the primary endpoint, the rate of invasive coronary angiograms without a European Society of Cardiology class I indication for revascularization, was lower in the CT group than in the functional testing group (2 of 130 [1.5%] vs. 10 of 138 [7.2%]; p = 0.035), whereas the proportion of invasive angiograms with a revascularization indication was higher (88% vs. 50%; p = 0.017). The median duration until the final diagnosis was 0 (0 of 0) days in the CT group and 0 (0 of 17) in the functional testing group (p < 0.001). Overall, 13% of patients randomized to CT required further testing, compared with 37% in the functional testing group (p < 0.001). The adverse event rate was similar (3% vs. 3%; p = 1.000), although the median cumulative radiation dose was higher for the CT group (3.1 mSv [interquartile range: 1.6 to 7.8] vs. 0 mSv [interquartile range: 0.0 to 7.1]; p < 0.001).
Conclusions In patients with suspected stable CAD, a tiered cardiac CT protocol with dynamic perfusion imaging offers a fast and efficient alternative to functional testing. (Comprehensive Cardiac CT Versus Exercise Testing in Suspected Coronary Artery Disease 2 [CRESCENT2]; NCT02291484)
- coronary CT angiography
- CT calcium scan
- CT myocardial perfusion imaging
- diagnostic testing
- functional testing
- stable angina
Coronary computed tomography angiography (CTA) (1) has become an established, reliable diagnostic test in the management of coronary artery disease (CAD). Two large randomized studies demonstrated that coronary CTA performs at least equally as well as functional tests for the evaluation of stable angina (2,3). In the CRESCENT-I (Comprehensive Cardiac CT Versus Exercise Testing in Suspected Coronary Artery Disease I) trial we found that incorporation of a calcium scan in a tiered CT strategy is safe and effective (4). Although coronary CTA effectively rules out coronary disease, it is limited in its ability to assess the hemodynamic importance of angiographic lesions. Because anatomic lesion severity is a poor predictor of hemodynamic significance, functional evaluation of intermediate stenoses is recommended for therapeutic decision making (5,6). The performance of myocardial perfusion imaging (MPI) by computed tomography (CT) has been validated in a large number of studies (6–11). A comprehensive cardiac CT examination, combining CTA and CT-MPI, could provide all the essential information for clinical decision making in CAD and could avoid invasive coronary angiography in patients without hemodynamically significant CAD (7–9,12).
In the CRESCENT-II randomized controlled trial we assessed the effectiveness, efficiency, and safety of a tiered cardiac CT protocol consisting of a calcium scan with selective performance of CTA and CT-MPI, in comparison with functional testing.
The CRESCENT-II trial is a pragmatic randomized controlled trial comparing the effectiveness, efficiency, and safety of a comprehensive, tiered cardiac CT approach with a standard diagnostic work-up using functional testing. At 4 hospitals in the Netherlands, 268 patients referred with stable chest pain and suspected CAD were prospectively enrolled in the study. Medical ethics committees at each of the sites approved the study. The CRESCENT-II trial is registered at the U.S. National Institutes of Health (NCT02291484).
Patients ≥18 years of age with chest pain symptoms suggestive of obstructive CAD and CAD probability >10% were eligible for inclusion in the study (13). Exclusion criteria were prior myocardial infarction or revascularization procedure, renal failure (estimated glomerular filtration rate <60 ml/min/1.73m2), iodine allergy, contraindications to adenosine, or known pregnancy.
After an outpatient clinic assessment, participants provided written informed consent and were randomly assigned to either the CT group or the functional testing group. All participants filled out the Seattle Angina Questionnaire (SAQ), the EuroQol-5D-5L questionnaire (EQ-5D), and the Short-Form-36 (SF-36) for quality-of-life assessment, as well as a cost questionnaire. All testing was performed at the recruiting center. For ascertainment of trial endpoints at 6 months, results of downstream diagnostic and therapeutic procedures were collected from the medical records, and patients again completed the questionnaires for ascertainment of angina complaints, quality of life, and health status.
Cardiac CT strategy
In the CT group all patients first underwent a non–contrast-enhanced calcium scan (Somatom Definition Flash and Force, Siemens Healthineers, Forchheim, Germany). In patients with a low to intermediate probability of CAD (10% to 80% according to Diamond and Forrester ), the absence of calcium excluded obstructive CAD and obviated the need for further testing. Patients with a 0 calcium score but a >80% pre-test probability and all patients with a positive calcium score (>0) underwent contrast-enhanced coronary CTA.
All patients received sublingual nitroglycerin before CTA studies. If indicated (heart rate >65/min) and clinically acceptable, beta-blockers were administrated. The prospective electrocardiographically triggered axial scan mode was used, with an exposure window during diastole and/or systole depending on the heart rate. Tube current and tube voltage were selected semiautomatically on the basis of body size. A test bolus acquisition was performed using 15 ml of contrast medium followed by a 40 ml saline chaser. For CTA, a contrast bolus of 50 to 60 ml (depending on iodine concentration) was injected to achieve an iodine delivery rate of 2.2 g/s, followed by a 40-ml saline bolus chaser. Images were reconstructed with a medium-smooth kernel (B26, Bv40), a slice thickness of 0.5 mm, and an increment of 0.3 mm. The CTA was immediately assessed, and all patients with >50% stenosis underwent an adenosine-stress dynamic CT-MPI scan during the same session. All recruiting sites had previous cardiac CT experience.
Dynamic CT myocardial perfusion imaging
Detailed descriptions of the dynamic MPI protocol were published previously (8,11). In brief, CT perfusion started 10 min after CTA for wash-out of contrast media. Myocardial hyperemia was achieved by adenosine infusion (≥3 min; 140 μg/kg/min) over a second shielded intravenous catheter. To avoid interference with adenosine, patients abstained from caffeine-containing beverages 24 h before their appointment. A 50-ml contrast bolus (Ultravist, 370 mgI/ml, Bayer, Germany) and 40 ml saline were injected at 6 ml/s. Using an alternating table positions (shuttle mode) for complete myocardial coverage, systolic images were acquired every second heart cycle while the patient maintained a 35-s inspiratory breath hold.
The following scan parameters were used for the second-generation dual-source scanner: 2 × 64 × 0.6 mm collimation, 280-ms gantry rotation time, 75-ms temporal resolution, 100-kV and 300-mA or 80-kV and 370-mA tube voltage and current per rotation, and shuttle-mode with 73-mm total z-axis coverage; for the third-generation dual-source scanner: 2 × 96 × 0.6 mm collimation, 250-ms gantry rotation time, 66-ms temporal resolution, 80-kV tube voltage and 300-mA current (Care-kV as a reference), and 102-mm shuttle-mode z-axis coverage.
From a series of 12 to 15 consecutive datasets, myocardial attenuation was plotted against time. A parametric deconvolution technique with a 2-compartment model as its basis was used to fit the time-attenuation curves (Volume Perfusion CT body, Siemens). Myocardial blood flow (MBF) (ml/100 ml/min) was computed by dividing the convoluted maximal slope of the myocardial time-attenuation curve by the maximum arterial input function (aorta). By calculating MBF on a per-voxel basis, 3-dimensional MBF maps were reconstructed with a slice thickness of 3.0 mm and an increment of 1.5 mm; these maps were used for interpretation of hypoperfusion in relation to angiographic obstructions (Figures 1A to 1I). Patients without (substantial) myocardial ischemia were treated medically. Patients with substantial myocardial ischemia (visually ≥10% left ventricle) were referred for invasive angiography, in accordance with international guidelines (5).
Functional test strategy
The functional testing strategy was selected by the treating physicians in accordance with international guidelines (5). Most patients underwent a symptom-limited exercise ECG, with a target heart rate defined as 85% of the age-defined maximum predicted heart rate. The main diagnostic ECG criterion for ischemia consists of a horizontal or down-sloping ST-segment depression ≥0.1 mV, persisting for at least 0.06 to 0.08 s after the J-point, in 1 or more ECG leads. Single-photon emission computed tomography (SPECT) MPI or stress echocardiography was performed in case of contraindications to exercise ECG or in patients with noninterpretable or equivocal results. Criteria for the presence of ischemia were reversible perfusion defects on SPECT-MPI (≥10% ischemia, on the basis of a segment difference score of 7 or higher) or the presence of new wall motion abnormalities on echocardiography. All functional imaging tests were interpreted for the presence of inducible ischemia and risk of adverse outcome, by applying established criteria for each respective test (14,15).
Interpretation of CT and functional test results, using all available clinical data, as well as subsequent clinical management decisions, was performed by local physicians. Patients considered to be at high risk on the basis of on test results and clinical interpretation, or patients with refractory symptoms despite optimal medical treatment, were generally referred for invasive coronary angiography.
The primary outcome was the negative invasive angiography rate, defined as the number of angiograms without a Class I indication for revascularization on the basis of European Society of Cardiology guidelines (16), as a proportion of the total number of patients. Class I indication for revascularization were as follows: left main coronary artery >50% with objective ischemia; proximal left anterior descending coronary artery >50% with ischemia; 2- or 3-vessel disease with impaired left ventricular function and ischemia; proven large area of ischemia (>10% left ventricle); and >50% stenosis with limiting angina unresponsive to optimal medical treatment (16). An external, independent reviewer reassessed revascularization criteria, irrespective of clinical decisions by the treating physician.
Pre-specified secondary outcomes included the positive yield of invasive coronary angiography: the proportion of invasive angiograms leading to a Class I revascularization indication. Clinical effectiveness was defined by persistent or recurrent anginal symptoms and quality of life at 6 months. Efficiency outcomes included time to diagnosis from first outpatient visit until the first test that led to the final diagnosis or the final test that ruled out obstructive CAD. Downstream testing included all noninvasive tests and invasive angiography to diagnose CAD after the initial test. Diagnostic costs included all tests to diagnose CAD over the first 6 months. Costs per test were determined on the basis of previously published cost analyses (17).
Major adverse events included death, nonfatal myocardial infarction, unstable angina, urgent revascularization, and stroke. For the survival analysis, events were counted once for each patient in the hierarchical order listed earlier. The cumulative effective radiation dose (mSv) included all tests and interventions applying radiation. For cardiac CT, a conversion factor of 0.017 was used. For SPECT and invasive angiography, conversion factors of 0.0085 mSv/mBq and 0.24 mSv/Gy × cm2 were used (18,19).
On the basis of registry data, rates of angiography without a Class I indication for revascularization of 1.2% in the CT group and 10.9% in the control group were predicted (20). For 80% power at a 2-sided p value of 0.05, at least 250 patients were required to detect a similar difference in invasive angiograms without a Class I revascularization indication. Continuous data are presented as mean ± SD or medians with interquartile ranges. Groups were compared by independent sample Student t test or Mann-Whitney U test for continuous variables and by chi-square or Fisher exact test for categorical variables. The invasive angiography without Class I indication for revascularization rate was compared using a Fisher exact test. The event-free survival probability was estimated by Kaplan-Meier survival analysis and log-rank statistic. A Cox proportional hazards model was employed to estimate the relative hazard of events by randomized test strategy, thus deriving hazard ratios and 95% confidence intervals. A 2-sided p value of <0.05 was considered statistically significant. Statistical analyses were performed using SPSS software version 21 (IBM Corp., Armonk New York), according to the intention-to-treat principle.
Between July 2013 and November 2015, out of 352 potential candidates, 268 patients (age 58 ± 11 years, 49% women) could be enrolled and randomized between cardiac CT (n = 130) and functional testing (n = 138) (Table 1, Figure 2). All patients were included in the intention-to-treat analysis. Pre-test CAD probability was 54 ± 30% according to Diamond and Forrester (13). Invasive angiography demonstrated >50% CAD in 28 patients (8%). At 6-month follow-up, original records of hospital visits and events were available for 266 of the 268 (99%) patients.
In the functional testing group the first test was exercise ECG in 131 (95%) and nuclear imaging in 7 patients (5%), with a result interpreted as positive in 12 (9%), negative in 77 (56%), and inconclusive in 47/138 (34%); 2 patients did not undergo their scheduled examinations. Additional testing, and multiple tests in some patients, included the following: SPECT-MPI (n = 24); stress echocardiography (n = 4); cardiac CT (n = 11); exercise ECG (n = 1); and invasive angiography (n = 20) (Figure 3). Of 20 patients undergoing invasive angiograms, 10 required revascularization.
In the CT group, the median calcium score was 5 (0 to 146), and 50 (39%) patients had no detectable calcium. CTA was performed in 79 (61%) patients with a positive calcium scan result and in 5 patients with a 0 calcium score but a >80% pre-test probability. Of 29 patients with >50% stenosis, 19 (66%) showed myocardial ischemia on perfusion imaging (Figure 3). Concordant ischemia was demonstrated by CT-MPI in 7 of 12 (58%) vessels of patients with 3-vessel disease (n = 4), in 3 of 4 (75%) with left main or proximal left anterior descending coronary disease, and in 13 of 25 (52%) vessels of patients with other 1- or 2-vessel disease (n = 21) by CTA. Concordant ischemia was demonstrated by CT-MPI in 11 of 12 (92%) patients with >70% maximum stenosis and in 8 of 17 (47%) patients with 50% to 70% maximum stenosis by CTA. Of 19 patients with myocardial ischemia, 14 underwent invasive angiography, and 13 underwent revascularization procedures. Two patients with a normal CT-MPI result later underwent percutaneous coronary intervention because of insufficient symptomatic relief, 1 patient in the setting of unstable angina.
Fewer invasive angiograms without a Class I indication for revascularization were observed in the CT group (2 of 130; 1.5%), compared with the functional testing group (10 of 138; 7.2%; p = 0.035) (Table 2). At a comparable rate of invasive angiograms (p = 0.860), the positive yield was higher after CT (15 of 17; 88%) compared with functional testing (10 of 20; 50%; p = 0.017). The independently assigned Class I revascularization indications were concordant with the clinically performed revascularization procedures.
In both groups the majority of patients reached the final clinical diagnosis the same day at the outpatient clinic, although most frequently in the cardiac CT group (87% vs. 64% of functional testing group; p < 0.001) (Figure 4). Further testing was needed in 13% of patients randomized to CT, compared with 37% after functional testing (p < 0.001) (Figure 5). Although index testing costs were higher for CT, the mean cumulative diagnostic expenses were comparable for CT (€435; range €64 to €2439) and for functional testing (€450; range €106 to €2015) (p = 0.827).
Anginal symptoms and quality of life
After 6 months 38% of patients in the CT group reported absent anginal symptoms, in comparison with 28% in the functional testing group (p = 0.118). In both groups comparable improvements in Seattle Angina Questionnaire subscales were observed (Online Table 1). Quality-of-life improvement as determined by the EuroQol-5D-5L questionnaire did not differ (p = 0.245) (Online Table 2). The improvement in the quality of life visual analog (QoL-VAS) scale for CT was from 66.8 to 73.7 (p < 0.001) compared with 68.9 to 72.4 (p = 0.042) for functional testing; this numeric difference failed to reach statistical significance (p = 0.168) (Online Table 3).
After an average follow-up of 250 ± 95 days (8 ± 3 months), 3 noncardiac deaths, 4 nonfatal infarctions, and 1 case of unstable angina requiring revascularization were observed in 266 patients (CT 4 vs. functional testing 4 events; p = 1.000). Event-free survival was similar (CT 96.9% vs. functional testing 97.1%; p = 0.929), with an adverse event hazard ratio of 1.07 (95% confidence interval: 0.27 to 4.26) for CT compared with standard care (p = 0.929).
No adverse events occurred in the 45 patients (35%) with CAD ruled out on the basis of a 0 calcium score. One patient later presented with acute chest pain and ECG changes, although biomarkers were negative and invasive angiography revealed no abnormalities. Among the 5 patients without calcium but a >80% pre-test probability, CTA revealed single-vessel CAD with ischemia on CT-MPI in 1 case.
In the functional test group only 51 patients (37%) were exposed to radiation, which resulted in a lower median cumulative dose (CT 3.1 mSv [interquartile range: 1.6 to 7.8 mSv] vs. 0 mSv [interquartile range: 0.0 to 7.1 mSv]; p < 0.001). The mean dose of the cardiac CT examination was 5.6 ± 6.3 mSv. The mean dose was 1.3 ± 0.7 mSv for the calcium scan, 3.5 ± 3.0 mSv for CTA, and 10.6 ± 6.3 mSv for CT-MPI.
In this multicenter randomized clinical trial, a comprehensive cardiac CT examination that involved a stepwise performance of a calcium scan, CTA, and CT-MPI was compared with the current standard of functional testing for suspected CAD. The main findings are that a tiered cardiac CT protocol improves the efficiency of invasive angiography without increasing overall catheterization rates. The combined CT protocol achieved a diagnosis faster, and it removed the need for additional noninvasive testing.
Diagnostic management of stable angina
There are many noninvasive techniques for diagnosing CAD, but the low diagnostic yield of invasive angiography suggests a lack of effectiveness by current diagnostic practices (21). Although stress imaging is more sensitive to the detection of angiographic CAD, without evident clinical outcome benefit (22), the American College of Cardiology/American Heart Association guidelines maintain that exercise ECG is the first choice in suitable patients with a low to intermediate CAD probability (23). CTA is a newer diagnostic option with a high sensitivity for the detection of CAD. In a very large cohort the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial demonstrated equivalent clinical outcomes for CTA and stress testing (2). Meta-analyses, however, indicate that CTA may increase catheterization and revascularization rates, of which clinical benefit remains yet unproven (24,25). Functional tests can differentiate patients more likely to benefit from revascularization, although the prospective evidence for this is stronger for fractional flow reserve (FFR) than noninvasive functional tests. In SCOT-HEART (Scottish Computed Tomography of the Heart trial), which demonstrated improved outcomes from CTA, cardiac CT was combined with exercise ECG in the majority of patients (3,26). This finding supports the idea that both anatomic information and functional information are required for therapeutic decisions that affect clinical outcome. Another observation from these trials is the low, but often overestimated, CAD prevalence, as well as a low adverse event rate in real-world populations with stable chest pain (2–4), thus fueling a paradoxical debate on the value of extensive testing in low-risk populations (27).
Comprehensive cardiac CT protocol
The objective of the CRESCENT-II trial was to test a tiered comprehensive cardiac CT protocol that would allow safe exclusion of CAD by relatively simple means while at the same time incorporating functional measures of CAD for well-informed decisions and avoidance of premature invasive procedures. Calcium imaging in symptomatic patients is controversial because of the possibility of noncalcified obstructions. Supported by CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) and other registries in real-world populations (28–32), and the low CAD prevalence in recent trials (2–4), we concluded that triage by calcium imaging in lower-risk patients would be a safe opportunity to reduce radiation exposure and save resources. Similar to CRESCENT, the present study suggests an uneventful intermediate-term outcome when CAD is excluded on the basis of a negative calcium scan (4). Restriction to patients with detectable calcium or a high CAD probability increased the positive yield of CTA to more than one-third.
Although there are multiple, more established stress imaging techniques, CT-MPI may have practical advantages because it can be performed in conjunction with CTA, and it allows for a comprehensive assessment of anatomy and function. Contrary to CRESCENT (4), the addition of CT-MPI virtually removed the need for a separate functional test after CT (1% in CRESCENT-II vs. 16% in CRESCENT).
Overall, cardiac CT increased the diagnostic yield of invasive angiography (88% vs. 50%; p = 0.017), but without affecting the overall catheterization rate. All except 1 patient referred for invasive angiography after a positive CTA result and CT-MPI (19 of 29) required revascularization. CRESCENT-II was not large enough to assess differences in adverse events, or in a statistically significant manner reproduce the symptomatic relief after CT, as observed in the previous trial (4).
Although anatomic imaging as the first step appears to be most efficient in our cohort with a low prevalence of CAD and no history of CAD, this may be different in patients with a history or a truly high prevalence of CAD.
The use of contemporary CT technology, and restricting CT-MPI to the highest-risk patients, resulted in a median overall effective dose of 3.1 mSv (including diagnostic tests after cardiac CT), compared with a median cumulative dose of 10.0 mSv in PROMISE and a 4.1 mSv median dose for CTA alone in SCOT-HEART.
In patients with a low CAD probability, often younger and female, calcium imaging and newer CT technology lowered doses in those patients most vulnerable to radiation exposure. However, radiation exposure was lowest in the functional testing group; most of these patients underwent exercise testing without nuclear imaging.
As scanner and data processing technology develop further, the comfort of use and radiation exposure of dynamic CT-MPI will likely improve. Apart from dynamic CT-MPI, and well-known established functional modalities, several other CT-based functional assessment techniques have emerged. Static MPI (7,12,33), potentially with dual-energy protocols, or hybrid systems that combine CT with positron emission tomography or SPECT, also offer functional interpretation in conjunction with CTA. CTA-based FFR (CT-FFR) computes coronary flow parameters from conventional CTA (34,35). Although CT-FFR is not a direct physiological measurement, and it relies on sufficient CT quality, the lack of additional testing and the radiation exposure are obvious advantages. The PLATFORM study (Prospective LongitudinAl Trial of FFRct: Outcome and Resource IMpacts) demonstrated how CTA combined with CT-FFR can improve the diagnostic yield of invasive angiography (36). The few direct comparisons published to date suggest a comparable and partially complementary performance of CT-MPI and CT-FFR (37–39).
Although this study allowed several relevant observations, the cohort size does not permit conclusive results in terms of clinical outcome. Similar to other pragmatic diagnostic trials, the CRESCENT-II trial did not apply a predefined management protocol. Although blinding of caregivers and patients was not possible, participants were treated by multiple physicians without direct involvement in the study. We designed a specific CT algorithm and compared performance with a control group that mostly underwent exercise ECG. Although the use of exercise ECG is supported by guidelines and is part of standard practice in many parts of the world, extrapolation of the results may not be possible to settings with substantially different diagnostic and therapeutic practices. More stress imaging would be expected to improve diagnostic accuracy, but it could also increase cost (22). Dynamic CT-MPI was validated in multiple studies, but the technique requires specific CT equipment and is not yet widely practiced. Implementation of the tiered algorithm requires scheduling flexibility and immediate reading, which can pose practical challenges.
In patients with stable angina and a typically low CAD prevalence, the challenge is to rule out CAD accurately in the majority by relative simple means while comprehensively assessing those patients who may benefit from revascularization. A tiered, comprehensive cardiac CT protocol, including dynamic perfusion imaging, appears to be a fast and efficient alternative to standard functional testing in these patients.
COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: The use of cardiac CT for noninvasive angiographic assessment of CAD is rapidly expanding, but it may not provide sufficient information for clinical decisions. A tiered cardiac CT protocol, combining calcium imaging, CTA, and dynamic CT-MPI, offers a fast and efficient alternative to standard diagnostic care by functional testing.
TRANSLATIONAL OUTLOOK: The present findings suggest a promising role for a tiered, comprehensive cardiac CT protocol. However, this is a small trial, and our findings need to be confirmed in larger populations and compared with other diagnostic strategies. Because dynamic CT-MPI is a relatively new technique in a state of ongoing technical development, performance by the most recent technology is currently ongoing.
The authors are grateful to all participating patients, as well as the medical teams at each of the participating centers, who made this study possible.
This work was supported by the Erasmus University Medical Center and ZonMW. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Lubbers is supported by a grant from the Dutch Heart Foundation (NHS 2014T061). Dr. Coenen is supported by a grant from the Dutch Heart Foundation (NHS 2014T061). Dr. Das has received institutional grant support from and has been a speaker for Siemens, Bayer, Philips, and Cook. Dr. Nieman is supported by a grant from the Dutch Heart Foundation (NHS 2014T061); has received institutional research support from Siemens, General Electric Healthcare, Bayer, and HeartFlow; and has received speaker fees from Siemens. Dr. Hunink has received personal research support from Cambridge University Press; has received grants and nonfinancial support from the European Society of Radiology; and has received nonfinancial support from the European Institute for Biomedical Imaging Research, outside the submitted work. Dr. Kietselaer has received institutional research support from AstraZeneca and Bayer; was supported by internal research grants from Maastricht University Medical Center; and has received speaker fees from Astellas and Amgen. All other authors have reported that they have relationships relevant to this paper to disclose.
- Abbreviations and Acronyms
- computed tomography
- computed tomography angiography
- fractional flow reserve
- myocardial blood flow
- myocardial perfusion imaging
- single-photon emission computed tomography
- Received February 13, 2017.
- Revision received September 26, 2017.
- Accepted October 6, 2017.
- 2018 American College of Cardiology Foundation
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