Objectives To evaluate to what extent treatment decisions for patients with stable angina pectoris can be made based on hybrid myocardial perfusion single-photon emission CT (SPECT) and CT coronary angiography (CCTA). It has been shown that hybrid SPECT/CCTA has good performance in the diagnosis of significant coronary artery disease (CAD). The question remains whether these imaging results lead to similar treatment decisions as compared to standalone SPECT and invasive coronary angiography (CA).
Methods We prospectively included 107 patients (mean age 62.8±10.0 years, 69% male) with stable anginal complaints and an intermediate to high pre-test likelihood for CAD. Hybrid SPECT/CCTA was performed prior to CA in all patients. The study outcome was the treatment decision categorised as: no revascularisation, percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Treatment decisions were made by two interventional cardiologists and one cardiothoracic surgeon in two steps: first, based on the results of hybrid SPECT/CCTA; second, based on SPECT and CA.
Results Revascularisation (PCI or CABG) was indicated in 54 (50%) patients based on SPECT and CA. Percentage agreement of treatment decisions in all patients based on hybrid SPECT/CCTA versus SPECT and CA on the necessity of revascularisation was 92%. Percentage agreement of treatment decisions in patients with matched, unmatched and normal hybrid SPECT/CCTA findings was 95%, 84% and 100%, respectively.
Conclusions Panel evaluation shows that patients could be accurately indicated for and deferred from revascularisation based on hybrid SPECT/CCTA.
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Current guidelines on the management of patients with stable chest pain syndromes recommend revascularisation in patients with persistent limiting symptoms, high risk anatomy or significant ischaemic territory (>10% of the myocardium).1 ,2 Since intervention of functionally irrelevant lesions is associated with the risks but not the benefits of revascularisation, (non-)invasive evidence of the functional significance of each lesion is preferable.1 ,3 ,4 As such, myocardial perfusion imaging with single-photon emission CT (SPECT) has been suggested as a non-invasive gatekeeper for invasive coronary angiography (CA).5 ,6 Also, with the advent of CT coronary angiography (CCTA), reliable non-invasive anatomical information on the coronary arteries can now be obtained.7 Like CA however, standalone CCTA lacks functional information on lesion severity and thereby is unsuitable for therapeutic decision making.8 ,9 The availability of hybrid SPECT/CCTA as an anatomical and functional imaging technique generated the interest in non-invasive imaging as a tool to guide therapeutic decision making, for example to decide on necessity of revascularisation or even the choice of the method of revascularisation.10–13
Hybrid SPECT/CCTA has good diagnostic performance in patients who are evaluated for the presence of coronary artery disease (CAD) when compared to CA.10 ,11 ,14–16 The value of hybrid imaging lies not only in the correlation of perfusion abnormalities on SPECT with coronary stenosis on CCTA. Rather, complementary results of hybrid imaging may compensate for the respective diagnostic pitfalls of each technique as a stand-alone imaging procedure.10 ,17 Recently, prognosis and effect on choice of treatment strategy in subgroups of patients with matched, unmatched and normal hybrid SPECT/CCTA findings have been analysed.12 ,13 However, a direct comparison of the effect of hybrid SPECT/CCTA versus traditional work-up using SPECT and CA on the choice of treatment strategy is lacking.
For several decades, cardiologists and cardiothoracic surgeons have been meeting in ‘heart teams’ to decide on the necessity of coronary revascularisation based on CA and (non-)invasive evidence of myocardial ischaemia.1 ,2 With the demonstrated reliability of hybrid SPECT/CCTA, we hypothesised that in a similar setting, treatment decisions can be made for patients with stable angina pectoris using hybrid SPECT/CCTA just as good as with SPECT and CA. Also, we evaluated the reliability of these treatment decisions in groups of patients with matched, unmatched and normal hybrid SPECT/CCTA findings.
Patients with an intermediate to high pre-test likelihood of CAD were prospectively enrolled in this study from September 2010 until December 2011. Pre-test likelihood was calculated according to Diamond and Forrester criteria.18 Exclusion criteria were a history of surgical revascularisation coronary artery bypass grafting (CABG), stent implantation percutaneous coronary intervention (PCI), an unstable cardiac condition or a cardiac rhythm other than sinus rhythm. After acquisition of all imaging data each case was evaluated during a routine heart team meeting. Additionally, as we discuss below in more detail, a panel evaluation took place on a separate occasion. The study conformed to the principles outlined in the declaration of Helsinki and was approved by the local ethics committee. Written informed consent was obtained from all patients.
Imaging procedure and interpretation
Gated SPECT and CCTA data were acquired on a hybrid SPECT/CT system, CardioMD gamma camera and Brilliance 64-slice CT scanner (Philips Medical Systems, Best, The Netherlands). On the first imaging day stress SPECT and CCTA data were acquired. Patients started with exercise (82 patients, 77%) or pharmacological (25 patients, 23%) stress, after which stress SPECT was acquired. For stress and rest SPECT a weight adjusted dose of 400–600 MBq99mTc-sestamibi was used. Attenuation correction was performed on all images using a non-enhanced CT scan. Directly following stress SPECT acquisition, all patients underwent prospectively ECG-triggered axial CCTA according to the guidelines provided by the Society of Cardiovascular Computed Angiography.19 All participants presenting with baseline heart rates over 60 bpm received 100 mg oral metoprolol tartrate at the start of the stress test preceding SPECT imaging. Patients with an initial heart rate below 60 bpm received 50 mg metoprolol tartrate. CA was scheduled within 14 days from the first image acquisition, preceded by rest SPECT image acquisition on the same day, only in those patients with an abnormal stress SPECT. As part of the prospective study, CA was performed in all patients, including those with normal non-invasive test results. CA was acquired on Allura (Philips Medical Systems) catheterisation equipment via femoral or radial artery access. Biplane views were acquired from all major coronary arteries. Fractional flow reserve measurements (FFR) were performed at the discretion of the performing operator and available in 72 (67%) patients.
Hybrid SPECT/CCTA data were interpreted with regard to functional relevance of coronary stenosis, in consensus by two experienced physicians blinded for other imaging procedures using dedicated software (Intellispace Portal 5.0, Philips, Best, The Netherlands). Stress and rest SPECT images were interpreted as previously described according to a 17-segment model and scored for perfusion defects using a five-point scoring system (0=normal to 4=absence of tracer uptake).20–22 CCTA images were read according to a 16-segment model and five categories of luminal loss: no CAD (0% luminal loss), mild lesion severity (luminal loss 0–50%), intermediate lesion severity (luminal loss 50–70%), severe lesions (luminal loss 70–99%), and total occlusion. Significant disease was defined as the presence of >50% luminal loss on CCTA.
Similar to a previous study on the impact of hybrid SPECT/CCTA on choice of treatment strategy,12 we assessed the panel decisions and the frequency of revascularisation in patients with normal, unmatched and matched hybrid imaging findings. A matched hybrid finding was defined as a reversible defect on SPECT in a myocardial territory subtended by a stenotic coronary artery with a lesion exceeding 50% luminal loss. An ischaemic finding on SPECT was defined as an summed difference score (SDS) of ≥1 in a myocardial territory corresponding to one supplying coronary artery. An unmatched hybrid finding was defined as an ischaemic SPECT finding without a lesion with >50% luminal loss in the corresponding coronary artery, or as a lesion with >50% luminal loss in a coronary artery on CCTA, without an ischaemic finding in the corresponding myocardial territory on SPECT. If no stenosis was present on CCTA and SPECT was normal, the hybrid finding was regarded as normal. Subsequently, patients were assigned to one of the following three categories: matched, unmatched or normal hybrid SPECT/CCTA findings.
To quantify the percentage agreement of treatment decisions between the new work-up including hybrid SPECT/CCTA imaging and the traditional diagnostic work-up using SPECT and CA, a design of two panel evaluations was chosen (figure 1). The treatment decision consisted of three categories: no revascularisation, PCI or CABG. The panel consisted of one cardiothoracic surgeon (TdK) and two interventional cardiologists (BR and JVdH). First, the panel decided on the choice of treatment based on hybrid SPECT/CCTA findings. These sessions consisted of the evaluation of all available images and were chaired by two experienced readers (JS and FV). The choice for revascularisation was made in the presence of clear significant CAD, which could be an unmatched or matched hybrid SPECT/CCTA finding (figures 2 and 3). All panel members were unaware of the CA results. Second, on another occasion at least 4 weeks later, treatment decisions were based on the evaluation of SPECT and CA images, which served as the reference method. The choice for revascularisation was made in the presence of significant disease defined as >50% luminal loss on CA with evidence of myocardial ischaemia (FFR <0.80 or ischaemic SPECT findings). During both sessions the panel members were supplied with anonymous baseline clinical characteristics of the patient: medical history, medication use, clinical symptoms, physical examination, risk factors and baseline ECG. The results of exercise stress ECGs were disclosed when available, prior to evaluation of the imaging data.
The primary outcome was defined as the percentage agreement on the necessity of revascularisation (no revascularisation vs revascularisation) between the new diagnostic strategy using hybrid SPECT/CCTA versus conventional SPECT and CA. Secondary outcome was defined as the percentage agreement of decisions on the method of revascularisation, PCI versus CABG, in patients referred for revascularisation based on hybrid SPECT/CCTA. Primary and secondary outcomes were calculated for all patients combined and for the subgroups of patients with matched, unmatched and normal hybrid SPECT/CCTA findings. The χ2 test was used to compare rates of indicated revascularisations based on SPECT and CA in the three patient groups with matched, unmatched and normal hybrid SPECT/CCTA findings. A p value of <0.05 was considered statistically significant. Statistical analyses were performed with SPSS V.18.0.
In total 107 patients (mean age 62.8±10.0 years, 69% male) with stable anginal complaints and median pre-test likelihood of CAD of 87% (range 22–95%) were included. Complete characteristics of the study population are shown in table 1.
Hybrid SPECT/CCTA imaging findings
SPECT revealed reversible perfusion defects in myocardial segments subtended by one coronary artery in 61 (57%) patients. At least one stenosis of >50% in a coronary segment on CCTA was observed in 63 patients (59%). Forty patients (37%) showed at least one matched SPECT and CCTA finding, only unmatched findings were present in 44 patients (41%), and normal findings on both SPECT and CCTA in the remainder.
Radiation dose analysis
Average effective dose of CCTA was 4.2±1.0 mSv.23 Average effective dose of SPECT was 6.8±2.4 mSv.24 The average effective dose for hybrid SPECT/CCTA was 11.1±2.8 mSv. The average effective dose of CA was 10.5±4.9 mSv.24 Mean total effective dose was 21.7±6.4 mSv per patient.
Treatment decisions in all patients
The overall percentage agreement of treatment decisions based on hybrid SPECT/CCTA versus SPECT and CA was 92% (95% CI 85 to 96) for the primary outcome measure (no revascularisation versus revascularisation) (table 2A). Overall percentage agreement for the secondary outcome measure on method of revascularisation (PCI versus CABG) was 74% (95% CI 60 to 84) (table 2B).
The percentage of patients with matched, unmatched and normal hybrid findings indicated for revascularisation based on SPECT and CA is shown in figure 4.
Treatment decisions in patients with matched hybrid SPECT/CCTA findings
In patients with matched findings on SPECT and CCTA, the overall percentage agreement of decisions based on hybrid SPECT/CCTA versus SPECT and CA was 95% (95% CI 83 to 99) for the primary outcome measure (table 3A). Two patients with a matched hybrid SPECT/CCTA result were indicated for PCI based on the hybrid findings and optimal medical treatment based on SPECT and CA. One patient had a difficult-to-interpret CCTA (CCS 877) and ischaemia on SPECT (SDS of 6) that turned out to be a false-positive finding. The second patient showed total occlusion of the proximal RCA both on CCTA and CA. Based on hybrid SPECT/CCTA the panel opted for PCI, however based on CA this segment was regarded as unsuitable for revascularisation.
The percentage agreement for the used method of revascularisation, PCI or CABG, in patients with matched findings was 72% (95% CI 56 to 84) (table 3B).
Treatment decisions in patients with unmatched hybrid SPECT/CCTA findings
In patients with unmatched findings on SPECT and CCTA the overall percentage agreement of decisions based on hybrid SPECT/CCTA versus SPECT and CA was 84% (95% CI 71 to 92). (table 3A)
All three patients that would have been treated with PCI based on hybrid findings had challenging CCTAs; two as a result of high CCS and one with a motion artefact. Of four cases that would have been treated conservatively based on hybrid SPECT/CCTA and revascularised based on SPECT and CA, three patients showed a normal SPECT, probably as a result of balanced ischaemia. The fourth patient suffered from very diffuse CAD resulting in very small coronary arteries; revascularisation for this patient was almost impossible despite severe ischaemia on SPECT (SDS=11). The panel gave this patient the benefit of the doubt, indicating him for PCI based on SPECT and CA.
The overall percentage agreement for the used method of revascularisation, PCI or CABG, in patients with unmatched findings was 79% (95% CI 52 to92) (table 3B).
Treatment decisions in patients with normal hybrid SPECT/CCTA findings
No patients with normal non-invasive imaging findings were proven to have significant CAD (N=23). Panel decisions based on hybrid SPECT/CCTA findings were in complete agreement with decisions made based on SPECT and CA (table 3A,B).
The current study is the first to show that similar treatment decisions can be made by a non-invasive work-up using hybrid SPECT/CCTA when compared to a traditional work-up using SPECT and CA. Our primary outcome measure evaluating decisions on the necessity of revascularisation showed a high overall agreement (92%). Our unique study design of panel decisions on treatment strategy resembles the routine work-up of patients in so-called heart team meetings. As such it allows for conclusions on the clinical value in therapeutic decision making of this imaging procedure compared to the conventional imaging procedure including CA commonly used in clinical practice.
Specific attention should be paid to patients with unmatched hybrid SPECT/CCTA findings. Compared to the percentage agreement on treatment decisions in the matched and normal group (95% and 100%, respectively) the percentage agreement of 84% in this group was low. Unmatched findings predominantly arise in patients with minor ischaemic findings on SPECT. In these patients the high negative predictive value of CCTA should be of added value.25 Conversely, only in patients with definite high grade stenosis on CCTA, could normal or equivocal SPECT findings be overruled. As such, the combination of a negative or equivocal SPECT and a non-conclusive CCTA (eg, 50–70% luminal loss or high CCS) will remain most problematic. In these instances possible high risk CAD (eg, left main or proximal LAD disease on CCTA) should be treated with great caution when evaluated on the basis of hybrid SPECT/CCTA alone. These patients should be referred for CA. Further research should explore how to reduce the incidence of unmatched hybrid SPECT/CCTA findings.
The incremental value of hybrid SPECT/CCTA in the assessment of the prognosis and impact on choice of treatment strategy in patients under the evaluation of CAD has been described recently.12 ,13 The authors demonstrated an increased incidence of revascularisation procedures and adverse cardiac events in patients with matched abnormalities on SPECT and CCTA versus patients with unmatched abnormalities or normal scans. They described a patient population with an intermediate pre-test likelihood of CAD referred for hybrid SPECT/CCTA imaging. CA data were not available from all patients. Reasons for referral to or deference from CA were not described. A significantly lower number of revascularisation procedures was observed in the group of patients with unmatched findings compared to the group of patients with a matched perfusion defect and anatomic abnormality on CCTA. These findings are consistent with our results. However, for a technique with excellent diagnostic performance it could be argued that the percentage of revascularisation procedures, 41%, in the matched group is rather low. According to our analysis in the group of patients with matched findings on SPECT and CCTA, the revascularisation rate is high, up to 90%. Despite the different characteristics of our patient population, the reason for this difference remains unexplained. This should lead to further comparison of the results of hybrid SPECT/CCTA.
Several limitations to our study should be noted. The panel of two cardiologists and one thoracic surgeon are very experienced members of routine clinical heart teams, but less experienced with making treatment decisions based on hybrid SPECT/CCTA imaging. The performance of SPECT or CCTA as standalone procedure in the process of clinical decision making was not addressed in this analysis. It is reasonable to assume that in patients with normal findings on standalone SPECT or CCTA, the decisions would be in high agreement with decisions based on SPECT and CA. We chose an SDS ≥1 in myocardial territory subtended by one coronary artery as threshold for significant ischaemia on SPECT when evaluating the three groups of matched, unmatched and normal findings by SPECT and CCTA. This threshold is lower and different from the chosen threshold by Pazhenkottil et al.12 ,13 In our opinion a threshold of a summed stress score (SSS) ≥4 with a summed rest score (SRS) ≤1 is correct for a patient based analysis. However, since matching of a reversible perfusion defect and its anatomical substrate is performed at a per vessel level, a different threshold is needed. We chose the lowest possible level for reversible perfusion defect to match with coronary stenosis on CCTA. This could cause high numbers of false positive results and subsequently unnecessary referral for revascularisation. However, this is not reflected in our analysis; a high percentage of patients with matched hybrid SPECT/CCTA findings was referred for revascularisation based on SPECT and CA. Current healthcare policies advocate a stepwise imaging protocol in the diagnostic work-up of patients, for radiation dose saving purposes and a cost effective use of diagnostic modalities. As such, a hybrid imaging approach should not be the primary imaging strategy for all patients presenting with angina pectoris. Patients with non-conclusive SPECT or CCTA results could be referred for either CCTA or SPECT respectively. Subsequent hybrid depiction of coronary anatomy and myocardial perfusion should lead to an adequate therapeutic decision, which is demonstrated by the current report. However, it is to be expected that only in very specific cases will the surgeon plan surgery solely based on these non-invasive imaging data.17 Scientific proof that reliable depiction of functional relevance of CAD is feasible and CT myocardial perfusion imaging is growing.26–28 The availability of anatomic and functional information on CAD from one imaging modality obviously has great advantages. Data on clinical benefit of hybrid SPECT/CCTA cannot be obtained from this patient subset since actual therapy was instituted after routine heart team evaluation of all clinical cases after acquisition of the CA. Randomisation to different imaging strategies would be needed to address this subject.
Overall, our study is the first to show that with a work-up including hybrid SPECT/CCTA, similar treatment decisions can be reached as compared to a traditional work-up including invasive CA. We show in a large prospectively acquired population that patients with an intermediate to high pre-test likelihood could be accurately deferred from, or indicated for revascularisation based on hybrid SPECT/CCTA. In selected cases percutaneous and possibly surgical revascularisation could even be instituted on the basis of the findings by hybrid SPECT/CCTA.
Contributors All authors were involved in reporting the results of this study, and all approved the final version of the submitted manuscript. JS, BR, KM and JV contributed in the conception, design and planning of the study. JS, JdG, KN, WB, MB, MP, JVH, TdK, BR, KM and JV conducted the study, and were involved in the analysis and interpretation of the data. JV is responsible for the overall content and serves as guarantor.
Competing interests None.
Ethics approval Ethics Committee of the St Antonius Hospital.
Provenance and peer review Not commissioned; externally peer reviewed.
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