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Erschienen in: European Radiology 8/2022

Open Access 22.02.2022 | Cardiac

Diagnostic accuracy of coronary computed tomography angiography for the evaluation of obstructive coronary artery disease in patients referred for transcatheter aortic valve implantation: a systematic review and meta-analysis

verfasst von: Marco Gatti, Guglielmo Gallone, Vittoria Poggi, Francesco Bruno, Alessandro Serafini, Alessandro Depaoli, Ovidio De Filippo, Federico Conrotto, Fatemeh Darvizeh, Riccardo Faletti, Gaetano Maria De Ferrari, Paolo Fonio, Fabrizio D’Ascenzo

Erschienen in: European Radiology | Ausgabe 8/2022

Abstract

Objective

To evaluate the diagnostic accuracy of coronary computed tomography angiography (CCTA) for the evaluation of obstructive coronary artery disease (CAD) in patients referred for transcatheter aortic valve implantation (TAVI).

Methods

EMBASE, PubMed/MEDLINE, and CENTRAL were searched for studies reporting accuracy of CCTA for the evaluation of obstructive CAD compared with invasive coronary angiography (ICA) as the reference standard. QUADAS-2 tool was used to assess the risk of bias. A bivariate random effects model was used to analyze, pool, and plot the diagnostic performance measurements across studies. Pooled sensitivity, specificity, positive ( + LR) and negative (−LR) likelihood ratio, diagnostic odds ratio (DOR), and hierarchical summary ROC curve (HSROC) were evaluated. Prospero registration number: CRD42021252527.

Results

Fourteen studies (2533 patients) were included. In the intention-to-diagnose patient-level analysis, sensitivity and specificity for CCTA were 97% (95% CI: 94–98%) and 68% (95% CI: 56–68%), respectively, and + LR and −LR were 3.0 (95% CI: 2.1–4.3) and 0.05 (95% CI: 0.03 – 0.09), with DOR equal to 60 (95% CI: 30–121). The area under the HSROC curve was 0.96 (95% CI: 0.94–0.98). No significant difference in sensitivity was found between single-heartbeat and other CT scanners (96% (95% CI: 90 – 99%) vs. 97% (95% CI: 94–98%) respectively; p = 0.37), whereas the specificity of single-heartbeat scanners was higher (82% (95% CI: 66–92%) vs. 60% (95% CI: 46 – 72%) respectively; p < 0.0001). Routine CCTA in the pre-TAVI workup could save 41% (95% CI: 34 – 47%) of ICAs if a disease prevalence of 40% is assumed.

Conclusions

CCTA proved an excellent diagnostic accuracy for assessing obstructive CAD in patients referred for TAVI; the use of single-heartbeat CT scanners can further improve these findings.

Key Points

CCTA proved to have an excellent diagnostic accuracy for assessing obstructive CAD in patients referred for TAVI.
Routine CCTA in the pre-TAVI workup could save more than 40% of ICAs.
Single-heartbeat CT scanners had higher specificity than others in the assessment of obstructive CAD in patients referred for TAVI.
Begleitmaterial
Hinweise

Supplementary Information

The online version contains supplementary material available at https://​doi.​org/​10.​1007/​s00330-022-08603-y.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Abkürzungen
CAD
Coronary artery disease
CCTA
Coronary computed tomography angiography
CTA
Computed tomography angiography
DOR
Diagnostic odds ratio
HSROC
Hierarchical summary receiver operating characteristic curve
ICA
Invasive coronary angiography
−LR
Negative likelihood ratio
+ LR
Positive likelihood ratio
PCI
Percutaneous coronary intervention
PTP
Post-test probability
TAVI
Transcatheter aortic valve implantation

Introduction

Transcatheter aortic valve implantation (TAVI) represents the gold standard for treatment of severe aortic stenosis in patients at high and intermediate surgical risk [1]. Candidates for TAVI are an elderly and frail population with a high prevalence (up to 60%) of coronary artery disease (CAD).
Current guidelines recommend pre-procedural screening for CAD before valvular intervention [1]. Computed tomography angiography (CTA) has become the standard imaging method for pre-procedural TAVI assessment because it can evaluate non-invasively both the aortic arch and the peripheral vessels [1, 2]. Coronary computed tomography angiography (CCTA) has been recommended as an initial test in patients with low clinical likelihood of CAD due to its very high negative predictive value in this population [2], but the clinical value of this approach in the TAVI setting is still under evaluation. Indeed, patients with severe aortic stenosis have a high pre-test probability of obstructive CAD and present specific technical challenges to CCTA interpretation, including extensive coronary calcifications, frequent abnormal cardiac rhythm, and contraindication to nitrate administration [1].
To the best of our knowledge, only two meta-analyses [3, 4] have evaluated the diagnostic accuracy of CCTA in patients with aortic stenosis referred for aortic valve replacement (surgical or transcatheter). In the last few years, technological advances in CT scanners have resulted in improved image quality, allowing accurate assessment of coronary anatomy even in difficult technical settings [5, 6]; this aspect was not assessed by the two abovementioned meta-analyses, both published in 2018. Moreover, indications to TAVI are progressively extending to low-surgical-risk patients with lower pre-test probability of CAD [7, 8].
In this framework, the incorporation of coronary artery assessment into pre-TAVI CT evaluation has the potential to reduce the need for unnecessary ICA and total amount of contrast medium applied, making pre-procedural evaluation safer and faster with reduced cost [9, 10].
The aim of this systematic review and meta-analysis is to provide an updated overview of the diagnostic accuracy of CCTA for the evaluation of obstructive CAD among patients referred for TAVI.

Materials and methods

Protocol and registration

This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) extension for Diagnostic Test Accuracy (DTA) Studies [11]. The protocol was prospectively registered in the PROSPERO International register of systematic reviews with the ID number CRD42021252527.

Eligibility criteria

The primary aim of this study was to evaluate the diagnostic accuracy of CCTA for obstructive coronary stenosis among patients referred for TAVI. Studies reporting data on CCTA for the evaluation of obstructive CAD were deemed eligible if all the following inclusion criteria were respected: (1) CCTA performed with at least a 64-slice CT scanner; (2) ICA performed in all patients and used as the reference standard; (3) sensitivity and specificity were reported or assessed by the published data. Obstructive CAD was defined in the meta-analysis as a narrowing of the coronary lumen by more than 50% on CCTA and a lumen diameter reduction of more than 50% on ICA.

Study endpoints

The primary endpoint was the patient-level accuracy of CCTA to identify obstructive CAD. For the purpose of this analysis, non-evaluable segments were considered positive based on an intention to diagnose approach [12]. Secondary analyses included the evaluation of the accuracy of CCTA for obstructive CAD at the patient level, excluding patients with non-evaluable segments, at the vessel and at the segment level, evaluating also coronary artery bypass grafting (CABG) and stented coronary artery segments. Sensitivity was analyzed according to the risk of bias and applicability. Subgroup analysis was performed based on CT scanner characteristics. We identified three main CT scanner subgroups: (1) whole-heart coverage CT scanner—scanners with extensive detector coverage on the z-axis (i.e., the 160-mm scanners); (2) high temporal resolution CT scanners (i.e., dual-source scanners); (3) single-heartbeat CT scanners—scanner capable of acquiring the entire heart volume in a single beat, including both whole-heart CT scanners and high temporal resolution scanners with a large number of detectors (e.g., Somatom Force, Siemens Healthineers). In particular, we conducted three subgroup analyses to determine the effect of these technical CT parameters on diagnostic accuracy: (1) whole-heart coverage CT scanner vs. other CT scanners; (2) high temporal resolution CT scanners (i.e., dual-source CTs) vs. other CT scanners, and (3) single-heartbeat CT scanners vs. other CT scanners.

Search strategy

Excerpta Medica dataBASE (EMBASE), Medical Literature Analysis and Retrieval System Online (PubMed/MEDLINE), and Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to May 1, 2021. The string used is reported in the Supplementary Material. The reference lists of selected articles were also searched manually to identify additional eligible studies.

Data collection, data extraction, and risk of bias and applicability

Two researchers (F.B. and A.S.) independently searched for studies fulfilling the inclusion criteria in a two-stage process: first by using title and abstract of the papers and then the full text. The reasons for excluding studies in this second phase were recorded. The results from both searches were compared and the discrepancies were discussed. In some cases of disagreement, the decision was reached by consultation with a third researcher (G.G.). All selected articles were automatically downloaded, imported, and de-duplicated in Microsoft Excel (Microsoft).
General characteristics included total number of patients, age, sex, body mass index, cardiovascular risk factor (i.e., diabetes, hypercholesterolemia, smoking, history, hypertension), known CAD, previous percutaneous coronary intervention or CABG and atrial fibrillation. Moreover, main CT scanner characteristics were recorded: number of detector rows, dual-energy techniques, tube voltage tube current, contrast media concentration, contrast media volume, heart rate during acquisition, and mean dose-to-length product.
The quality assessment of diagnostic accuracy studies 2 (QUADAS-2) tool [13] was used to assess the risk of bias of included studies (reported in Supplementary Material).

Statistical analysis

Two-by-two contingency tables were extracted from each study and used to calculate sensitivity, specificity, positive (+LR) and negative (−LR) likelihood ratio, and diagnostic odds ratio (DOR) with 95% confidence interval (CI) of CCTA for the detection of significant coronary artery stenosis (in general, + LR > 10 and −LR < 0.1 demonstrates a satisfactory diagnostic performance [14]). A bivariate random effects model was used to analyze, pool, and plot the diagnostic performance measurements across studies. Derived logit estimates of sensitivity, specificity, and respective variances were used to construct a hierarchical summary ROC curve (HSROC). Heterogeneity between studies was evaluated utilizing Cochran’s Q and Higgins I2 statistics. Deeks’ funnel plot was used to assess publication bias. The patient-level clinical accuracy of CCTA was evaluated using the likelihood ratios to calculate post-test probability based on Bayes’ theorem with the use of Fagan’s nomograms, Likelihood ratio scattergram, and probability modifying plot.
The analyses were performed with STATA (version 16.1, Stata Corp LP) using the MIDAS module [15] and MetaDTA (Diagnostic Test Accuracy Meta-Analysis v2.01) [16]. A p value of less than 0.05 was considered statistically significant.

Results

Literature search and study characteristics

The PRISMA 2020 flow diagram [17] for systematic reviews is reported in Figure 1. Fourteen studies with a total of 2533 patients were included in the analysis. Tables 1 and 2 report the baseline characteristic of the included patients and of the CT scanner used.
Table 1
Baseline characteristics of the study population
Author
Publication date
N
Age
Men
BMI
DM
HC
Smoke
AF
Sinus rhythm
HT
CAD
PCI
CABG
Year
No.
Years
%
%
%
%
%
%
%
%
%
%
%
Pontone et al [26]
2011
60
80
36.6
25
13
40
25
0
100
67
37
24
16
Andreini [30]
2014
325
81.1
40.6
25.6
30
53
20
0
100
74
28
15
13
Hamdan et al [28]
2015
115
81.4
43.5
NR
30
70
36.5
7.8
92.2
85
52.2
29
20
Harris et al [12]
2015
100
79.6
61
NR
24
72
59
36
74
92
57
16
41
Opolsky et al [27]
2015
475
82
41
27.5
32
48
NR
19
75
95
67
48
19
Matsumoto et al [25]
2016
60
84.4
28.3
22.2
NR
NR
NR
NR
NR
NR
13
10
3.3
Rossi et al [19]
2017
140
82.3
48.6
27.1
21
59
19
0
100
75
0
0
0
Annoni et al [22]
2018
115
82.3
55.7
26.7
18
69
7
13
87
71
20.8
15
6.1
Hachulla [24]
2019
84
84.65
48.1
26.9
NR
NR
NR
NR
NR
NR
NR
NR
NR
Strong et al [20]
2019
200
83.4
40
26.6
28
74
21.5
34
76.5
93
0
0
0
Schicchi et al [29]
2020
223
79.2
NR
NR
NR
NR
NR
NR
NR
NR
51.6
35
16.6
Gohmann et al [21]
2020
388
79.6
50.8
29.2
13
59
8
NR
64.7
89
41.4
29
0
Shuai et al [23]
2020
121
73.3
47.1
22.6
26
12
25
27
73.8
37
NR
0
0
Meier et al [18]
2021
127
82.3
38.6
26.5
28
54
NR
NR
NR
77
38.6
17
0
N number, BMI body mass index, DM diabetes mellitus, HC hypercholesterolemia, AF atrial fibrillation, HT hypertension, CAD coronary artery disease, PCI percutaneous coronary intervention, CABG coronary artery bypass graft, NR not reported
Table 2
Baseline characteristics of the CT scanner used
Author
Publication date
CT scanner
X-ray source
Detector rows
Detector element z-dimension
Total detector z-axis coverage
Dual energy
rotation time
Intrinsic temporal resolution
Single-heart beat CT scanner
Tube voltage
Tube current
 
Year
 
Detector design
Slices
mm
mm
In the present study
ms/rot
ms
Yes/no
Mean kVp
Mean mA
Pontone et al [26]
2011
LightSpeed VCT XT Scanner (GE Healthcare)
Single
64
0.625
40
No
350
175
No
120
650
Andreini [30]
2014
LightSpeed VCT XT Scanner (GE Healthcare)
Single
64
0.625
40
No
350
175
No
105
575
Hamdan et al [28]
2015
Brilliance iCT Elite (Philips Healthcare)
Single
128
0.625
80
No
270
135
No
100
485
Harris et al [12]
2015
Somatom Definition Flash Stellar (Siemens Healthcare)
Dual
64
0.6
38.4
No
285
75
No
NR
NR
Opolsky et al [27]
2015
Somatom Definition (Siemens Healthcare)
Dual
64
0.6
38.4
No
330
83
No
120
360
Matsumoto et al [25]
2016
Aquilion ONE Vision (Toshiba Medical Systems)
Single
320
0.5
160
No
275
137
Yes
100
382.5
Rossi et al [19]
2017
Somatom Definition Flash Stellar (Siemens Healthcare)
Dual
64
0.6
38.4
No
280
75
No
100
363.3
Annoni et al [22]
2018
Revolution CT (GE Healthcare)
Single
256
0.625
160
No
280
140
Yes
100
583.3
Hachulla [24]
2019
Somatom Definition Flash Stellar (Siemens Healthcare)
Dual
64
0.6
38.4
No
280
75
No
120
NR
Strong et al [20]
2019
Somatom Definition Flash Stellar (Siemens Healthcare)
Dual
64
0.6
38.4
No
280
75
No
110
NR
Schicchi et al [29]
2020
Somatom Force (Siemens Healthineers)
Dual
96
0.6
57.6
No
250
66
Yes
120
NR
Gohmann et al [21]
2020
Somatom Definition Flash Stellar (Siemens Healthcare)
Dual
64
0.6
38.4
No
280
75
No
86.7
NR
Shuai et al [23]
2020
Revolution CT (GE Healthcare)
Single
256
0.625
160
No
280
140
Yes
100
400
Meier et al [18]
2021
LightSpeed VCT XT; Revolution CT (GE Healthcare)
Single; single
64; 256
0.625
40; 160
No; no
350; 280
175; 140
No; yes
110
500

Assessment of study quality

The QUADAS-2 Domain assessment is reported in Figure 2. The supplementary material contains the details of this analysis.

Diagnostic accuracy: primary endpoint

A total of 2228 patients were included in the analysis. For the purpose of this analysis, performed at the patient level, non-evaluable segments were considered positive based on an intention-to-diagnose approach. The pooled sensitivity and specificity for CCTA were 97% (94–98%) and 68% (56–68%), respectively, and the + LR and −LR were 3.0 (2.1–4.3) and 0.05 (0.03–0.09), with a DOR of 60 (30–121). The HSROC had an AUC = 0.96 (0.94–0.98). Table 3 shows sensitivity and specificity with % (95% CI) derived from each study included in the analysis. The summary forest plot and HSROC plot are reported in Figure 3.
Table 3
Summary sensitivities and specificities of CCTA for the identification of patients with obstructive coronary artery considering non-evaluable segments as positive
Author
Publication date
N
TP
FN
FP
TN
Se
Sp
Year
No.
No.
No.
No.
No.
% (CI 95%)
% (CI 95%)
Pontone et al [26]
2011
60
23
3
4
30
88.5 (69.9 – 97.6)
88.2 (72.6 – 96.7)
Hamdan et al [28]
2015
115
47
2
18
48
95.9 (86.0 – 99.5)
72.7 (60.4 – 83.0)
Harris et al [12]
2015
100
73
1
11
15
98.7 (92.7 – 99.9)
57.7 (28.1 – 63.7)
Opolsky et al [27]
2015
475
265
5
129
76
98.2 (95.7 – 99.4)
37.1 (30.5 – 44.1)
Matsumoto et al [25]
2016
66
22
2
21
21
91.7 (73.0 – 99.0)
50.0 (34.2 – 65.8)
Rossi et al [19]
2017
145
58
5
37
45
92.1 (82.4 – 97.4)
54.9 (43.5 – 65.9)
Annoni et al [22]
2018
115
22
1
12
80
95.7 (78.1 – 99.9)
87.0 (78.3 – 93.1)
Strong et al [20]
2019
200
69
0
76
55
100.0 (94.8 – 100.0)
42.0 (33.4 – 50.9)
Schicchi et al [29]
2020
223
44
1
20
158
97.8 (88.2 – 99.9)
88.8 (61.9 – 82.9)
Gohmann et al [21]
2020
388
135
3
137
113
97.8 (93.8 – 99.6)
45.2 (32.9 – 51.6)
Shuai et al [23]
2020
130
28
1
11
90
96.6 (82.2 – 99.9)
89.1 (81.4 – 94.4)
Meier et al [18]
2021
127
43
6
33
45
87.8 (75.2 – 95.4)
57.7 (46.0 – 68.8)
N number of patients, TP true positive, FP false positive, FN false negative, TN true negative, Se sensitivity, Sp specificity
The per-patient analysis revealed a + LR of 3.03 (2.12–4.33) and a −LR of 0.05 (0.03–0.09) (i.e., with an estimated pre-test probability of CAD of 40%, a positive CCTA could increase the post-test probability to 67% and a negative CCTA can decrease the post-test probability to 3%, whereas in a hypothetical population with pre-test probability of 15%, the post-test probability can reduce to less than 1%).
Fagan’s nomograms, with estimated pretest probability of 40% and 15%, Likelihood ratio scattergram and probability modifying plot are reported in Figure 4. In summary, estimating a disease prevalence of 40% in a population of 1000 patients, the study of coronary arteries with CCTA before the TAVI procedure would correctly avoid 409 (95% CI 335–470) ICAs (Figure 5).
Table 4 provides a summary of the CCTA diagnostic performance for the evaluation of obstructive CAD among patients referred for TAVI at a patient, vessel, and segment level. The secondary analysis is reported in the Supplementary Material.
Table 4
CCTA diagnostic performance for the evaluation of obstructive coronary artery disease in patients referred for TAVI
Analysis
N
TP
FP
FN
TN
Se
Sp
+ LR
− LR
DOR
No.
No.
No.
No.
No.
% (CI 95%)
% (CI 95%)
% (CI 95%)
% (CI 95%)
n (CI 95%)
Patient level 1a)
2228
872
518
30
808
97 (94 – 98)
68 (56 – 78)
3.0 (2.1 – 4.3)
0.05 (0.03 – 0.09)
60 (30 – 121)
Patient level 1b)
794
252
123
16
403
94 (89 – 97)
80 (64 – 90)
4.6 (2.4 – 8.8)
0.08 (0.04 – 0.14)
59 (23 – 149)
Vessel level
6865
1307
1529
102
3927
92 (88 – 95)
79 (70 – 86)
4.4 (3.1 – 6.3)
0.10 (0.07 – 0.15)
42 (25 – 74)
Segment level
13525
1379
1408
81
10657
95 (89 – 98)
91 (83 – 95)
10.6 (5.6 – 20.4)
0.06 (0.03 – 0.12)
189 (61 – 583)
1a) Considering as positive the nonvaluable segments; 1b) including only patients with all segments evaluable
N number of cases included, TP true positive, FP false positive, FN false negative, TN true negative, Se sensitivity, Sp specificity, + LR positive likelihood ratio, − LR negative likelihood ratio, DOR diagnostic odds ratio

Sub-analysis: sensitivity and subgroup analysis

We found a high value for Cochran’s Q and I2, which indicates the presence of heterogeneity in the studies. As a result, we visually assessed the forest plot and HSROC and a significant heterogeneity in specificity was found, particularly in the forest plot (Figure 4a), where some studies fell outside the combined 95% CI.
For the purpose of the sub-analysis, performed at the patient level, non-evaluable segments were considered positive based on an intention-to-diagnose approach.
A sensitivity analysis including only five studies [23, 2629] without high or unclear risk of bias or concerns regarding applicability showed similar results to the analysis containing all studies: a total of 1003 patients were included, the pooled sensitivity and specificity for CCTA were 96% (92 – 98%) and 79% (59 – 91%) respectively, and the + LR and −LR were 4.6 (2.2 – 9.7) and 0.05 (0.03 – 0.09), with a DOR of 94 (39–227). The HSROC had AUC = 0.97 (0.95 – 0.98).
The results of the subgroup analysis based the various CT scanner features are summarized in Table 5.
Table 5
CCTA diagnostic performance (comparison between single-heartbeat CT scanner vs. others) for the evaluation of obstructive coronary artery disease in patients referred for TAVI
CT scanner feature
Present
N
TP
FP
FN
TN
Se
Sp
+ LR
− LR
DOR
HSROC
 
No.
No.
No.
No.
No.
% (CI 95%)
% (CI 95%)
% (CI 95%)
% (CI 95%)
n (CI 95%)
AUC
Whole-heart coverage CT scanner
Yes
311
72
44
4
191
95 (86 – 98)
80 (57 – 92)
4.6 (1.9 – 11.2)
0.06 (0.02 – 0.20)
73 (12 – 454)
0.96 (0.94 – 0.97)
No
1790
757
441
20
572
97 (95 – 98)
65 (50 – 77)
2.8 (1.9 – 4.1)
0.04 (0.02 – 0.08)
64 (31 – 130)
0.97 (0.95 – 0.98)
High temporal resolution CT scanners
Yes
1615
687
419
15
494
98 (96 – 99)
59 (43 – 74)
2.4 (1.6 – 3.6)
0.03 (0.01 – 0.08)
73 (26 – 206)
0.97 (0.95 – 0.98)
No
486
142
66
9
269
94 (89 – 97)
80 (66 – 89)
4.7 (2.6 – 8.5)
0.07 (0.04 – 0.14)
64 (23 – 179)
0.95 (0.92 – 0.96)
Single-heartbeat CT scanner
Yes
1567
713
421
19
414
96 (90 – 99)
82 (66 – 92)
5.4 (2.6 – 11.3)
0.05 (0.02 – 0.14)
112 (23 – 548)
0.97 (0.95 – 0.98)
No
534
116
64
5
349
97 (94 – 98)
60 (46 – 72)
2.4 (1.7 – 3.3)
0.05 (0.03 – 0.09)
47 (25 – 91)
0.95 (0.93 – 0.97)
N number of cases included, TP true positive, FP false positive, FN false negative, TN true negative, Se sensitivity, Sp specificity, + LR positive likelihood ratio, − LR negative likelihood ratio, DOR diagnostic odds ratio
In summary, the use of a whole-heart coverage CT increased specificity (p < 0.001) but did not affect sensitivity (p = 0.26); the use of high temporal resolution scanners increased sensitivity (p = 0.02) but decreased specificity (p < 0.001); and the use of single-heartbeat scanners increased specificity (p < 0.001) with no effect on sensitivity (p = 0.37).
To translate our findings into clinical practice, we estimated a disease prevalence of 40% in a 1000-patient population and evaluated coronary arteries with different CT scanners: a whole-heart coverage CT scanner could correctly avoid 477 (95% CI 340–552) ICAs, a high temporal resolution CT scanner could correctly avoid 357 (95% CI 259–444) ICAs, and a single-heartbeat CT scanner could correctly avoid 494 (95% CI 398–550) ICAs (Figure 6).
Furthermore, the percentage of non-evaluable patients with a whole-heart coverage CT scanner or a single-heartbeat CT scanner was 21.7% (13/60) compared to 37.1% (438/1180) with other CTs (p = 0.019). The percentage of non-evaluable patients using high temporal resolution CT scanners was 45.1% (368/815) compared to 19.5% (83/425) using other CTs (p = 0.001).

Discussion

In this systematic review and meta-analysis, we investigated the diagnostic accuracy of CCTA for the assessment of obstructive CAD among patients referred for TAVI. Overall, CCTA prior to TAVI procedure provides high sensitivity (97%) with a good −LR (0.05).
This result highlights the effectiveness of CCTA to rule out significant CAD and to reduce unnecessary ICA procedures by 40.9%, aspiring its potential role as a gatekeeper test in this subgroup of patients. Furthermore, the use of new CT scanners, particularly single-heartbeat CT, has the potential to save the number of ICAs by up to 49.4%.
A recent meta-analysis on the same topic by van den Boogert et al [3] with included seven studies on a total of 1275 patients (all of these studies/patients were also incorporated into our meta-analysis) reported sensitivity, specificity, positive predictive value, and negative predictive value of 95.3% (93.3–96.9%), 65.3% (61.6–68.9%), 70.8% (68.6–72.9%), and 94.0% (91.6–95.8%) respectively. These results are very similar to our findings, despite the fact that the authors did not use a bivariate random effects model to summarize sensitivity, specificity, and their 95%, but rather a fixed effects model. In addition, they did not estimate +LR, −LR, and DOR.
Another meta-analysis on the performance of CCTA in patients with aortic stenosis undergoing surgery or transcatheter intervention by Chaikriangkrai et al [4] was performed. It included thirteen studies with a total of 1498 patients (6 of these studies, for a total of 1135 patients, were also incorporated into our meta-analysis); the results showed sensitivity = 95% (93–97%), specificity= 79% (68–86%), +LR = 4.48 (2.96–6.78), −LR = 0.06 (0.04–0.09) and AUC= 0.96 (0.95–0.98). The obtained specificity is slightly higher than our finding. This may be partially due to the population included in their study: in fact, in the subgroup analysis comparing patients who underwent surgery with those who underwent percutaneous intervention, the latter group showed a lower specificity (albeit not significant) (83% (77–87%) vs. 74% (51–88%)). This difference would be further increased by removing the study of Andreini et al [30] from their meta-analysis, thus increasing the specificity in the percutaneous intervention group even if it excluded non-evaluable patients. Another explanation could be the difference in disease prevalence between the two groups (48% in transcatheter vs. 29% in surgical): subjects who underwent transcatheter replacement were typically more fragile and at higher risk than those who underwent surgery, and this may increase the number of non-evaluable segments, thus reducing specificity.
In accordance with the European Society of Cardiology (ESC) guidelines [1], CCTA with its high negative predictive value is considered useful to exclude CAD in patients undergoing TAVI who are at low risk for atherosclerosis. This is in perfect agreement with our findings: a patient with a pre-test probability of 15% has a post-test probability of less than 1%, if the CCTA is negative.
However, our data seem to support a slightly broader usefulness and feasibility of CCTA even for patients with intermediate risk of CAD. In fact, on the basis of our findings, a patient with a pre-test probability of 40% (i.e., the prevalence of the disease in our population = 40%), in case of CCTA negativity, has a post-test probability of about 3%. This last finding is supported by a recent meta-analysis [31] of prospective studies comparing CCTA with coronary angiography as the reference standard. It highlighted the role of CCTA in patients with a low-to-intermediate pretest probability of CAD, emphasizing how this population could benefit the most from CCTA to rule in and rule out significant CAD.
The European Society of Cardiovascular Radiology (ESCR) consensus document [32] recently reported that CCTA should not be used routinely for pre-procedural assessment of CAD; however, they also added that, as technology evolves, CCTA can be used on a “case-by-case” basis, according to local expertise and available equipment and primarily to exclude significant coronary stenosis. This last statement was one of the starting points for our subgroup analyses. Technological advances in CT scanners were notable in recent years: the ideal CT scanner for cardiac imaging has high spatial and temporal resolution, covers the entire cardiac volume in a single rotation, and is ALARP (as low as reasonably practicable) compliant [33].
The abovementioned meta-analyses on a similar population [3, 4], published in 2018, did not analyze this aspect: (a) Regarding the high temporal resolution CT scanners, only three studies [12, 19, 27] analyzing 100, 475, and 145 patients, respectively, were included. (b) Concerning whole heart and single-heartbeat CT scanner, only one study [25] containing 66 patients was included.
In the period between those meta-analyses and our study, seven more papers using these technologies were published [18, 2024, 29]. Therefore, we planned a sub-group analysis to explore the benefits of high intrinsic TR obtained by dual-source CT scanner, whole-heart coverage CT scanner, and single-heartbeat CT scanner. According to our findings, the use of CT scanners with high temporal resolution seems to improve sensitivity with lower specificity, whereas the use of whole-heart coverage and single-heartbeat CT scanners resulted in a higher specificity.
Single-heartbeat CT scanners in the evaluation of obstructive CAD prior to TAVI could correctly avoid up to 49.4% of ICAs. This data may be at least partially related to the increased number of segments, which allows accurate assessment of coronary arteries even in challenging population. The non-assessable segments were considered positive, leading to higher sensitivity and lower specificity in case of a high number of non-assessable segments. Our results confirm in a larger population the findings of Meier et al [18], who reported that the use of a 64-row scanner (compared to a 256-row scanner) for evaluating CAD in a pre-TAVI population was the only parameter in a multivariate analysis to be associated with a high risk of unanalyzable images. Our findings are consistent also with the meta-analysis of Haase et al [31], who reported that using a CT scanner with more than 64 detector rows led to higher sensitivity (93.4% vs 86.5%, p = 0.002) and specificity (84.4% vs 72.6%, p = 0.001) in ruling out or confirming CAD patients with a pretest probability of CAD ranging from 7 to 67%.
From a clinical point of view, it has been reported that patients with a large area of myocardium at ischemic risk may benefit the most from revascularization intervention prior to TAVI, and the proximal segment stenosis is prognostically more important than distal [34]. Unfortunately, the only study included in this meta-analysis that allows this type of analysis is that of Andreini et al [30], where the exclusion of non-assessable segments gives a boost to the specificity of CCTA, which appears superior even in the study of distal vs. proximal segments [35, 36].
Further studies are needed to evaluate the real impact of CCTA in clinical practice; a randomized controlled trial could be proposed to evaluate the prognostic impact of patients undergoing CCTA pre-TAVI vs. a group not undergoing CCTA; also, the actual potential of CCTA in the study of proximal segments in such a selected population remains to be explored.
This meta-analysis has some limitations. First of all, a relatively low number of studies met the selection criteria. Unfortunately, only a fraction of the studies reported the analyses at patient level, either by considering non-analyzable segments as positive or by excluding them, and therefore it was not possible to create 3 × 2 tables [37]. Moreover, despite relevance from a clinical point of view, we were not able to compare performance among high vs. low calcium and arrhythmic and vs. non-arrhythmic patients. Almost all studies included are retrospective cohorts; only one is prospective and none a randomized controlled study. In addition, many of the included studies are small in size. The studies’ overall quality was however adequate for analysis according to the QUADAS-2 evaluation, despite the presence of some unclear or high-risk items.
In conclusion, CCTA proved to have excellent diagnostic accuracy for assessing obstructive CAD in patients referred for TAVI. Routine CCTA assessment of coronary arteries as part of the pre-TAVI workup could save more than 40% of ICAs. The use of single-heartbeat CT scanners, which provide higher specificity, can further improve these findings.

Declarations

Guarantor

The scientific guarantor of this publication is Prof. Paolo Fonio, chief of Diagnostic and Interventional Radiology at the University of Turin.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

Dott. Marco Gatti, one of the authors, kindly provided statistical advice for this manuscript.
The protocol was prospectively registered in the PROSPERO International register of systematic reviews with the ID number CRD42021252527.

Ethical approval

Institutional Review Board approval was obtained.

Methodology

• Meta-analysis
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://​creativecommons.​org/​licenses/​by/​4.​0/​.

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Supplementary Information

Literatur
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Zurück zum Zitat Dwamena B (2007) MIDAS: Stata module for meta-analytical integration of diagnostic test accuracy studies. Statistical Software Components S456880, Boston College Department of Economics. Revised 05 Feb 2009 Dwamena B (2007) MIDAS: Stata module for meta-analytical integration of diagnostic test accuracy studies. Statistical Software Components S456880, Boston College Department of Economics. Revised 05 Feb 2009
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Zurück zum Zitat Francone M, Budde RPJ, Bremerich J et al (2020) CT and MR imaging prior to transcatheter aortic valve implantation: standardisation of scanning protocols, measurements and reporting—a consensus document by the European Society of Cardiovascular Radiology (ESCR). Eur Radiol 30:2627–2650. https://doi.org/10.1007/s00330-019-06357-8CrossRefPubMed Francone M, Budde RPJ, Bremerich J et al (2020) CT and MR imaging prior to transcatheter aortic valve implantation: standardisation of scanning protocols, measurements and reporting—a consensus document by the European Society of Cardiovascular Radiology (ESCR). Eur Radiol 30:2627–2650. https://​doi.​org/​10.​1007/​s00330-019-06357-8CrossRefPubMed
Metadaten
Titel
Diagnostic accuracy of coronary computed tomography angiography for the evaluation of obstructive coronary artery disease in patients referred for transcatheter aortic valve implantation: a systematic review and meta-analysis
verfasst von
Marco Gatti
Guglielmo Gallone
Vittoria Poggi
Francesco Bruno
Alessandro Serafini
Alessandro Depaoli
Ovidio De Filippo
Federico Conrotto
Fatemeh Darvizeh
Riccardo Faletti
Gaetano Maria De Ferrari
Paolo Fonio
Fabrizio D’Ascenzo
Publikationsdatum
22.02.2022
Verlag
Springer Berlin Heidelberg
Erschienen in
European Radiology / Ausgabe 8/2022
Print ISSN: 0938-7994
Elektronische ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-022-08603-y

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