Per-patient Diagnostic Accuracy Research Articles

Non-contrast computed tomography findings for identification of chronically occluded coronary artery bypass grafts.

Detecting occlusions of coronary artery bypass grafts using non-contrast computed tomography (CT) series is understudied and underestimated. To evaluate morphological findings for the diagnosis of chronic coronary artery bypass graft occlusion on non-contrast CT and investigate performance statistics for potential use cases. Seventy-three patients with coronary artery bypass grafts who had CT angiography of the chest (non-contrast and arterial phases) were retrospectively included. Two readers applied pre-set morphologic findings to assess the patency of a bypass graft on non-contrast series. These findings included vessel shape (linear-band like), collapsed lumen and surgical graft marker without a visible vessel. Performance was tested using the simultaneously acquired arterial phase series as the ground truth. The per-patient diagnostic accuracy for occlusion was 0.890 (95% confidence interval=0.795-0.951). Venous grafts overall had an 88% accuracy. None of the left internal mammary artery to left anterior descending artery arterial graft occlusions were detected. The negative likelihood ratio for an occluded graft that is truly patent was 0.121, demonstrating a true post-test probability of 97% for identifying a patent graft as truly patent given a prevalence of 20% occlusion at a median 8.4 years post-surgery. Neither years post-surgery, nor number of vessels was associated with a significant decrease in reader accuracy. Evaluation of coronary bypass grafts for chronic occlusion on non-contrast CT based off vessel morphology is feasible and accurate for venous grafts. Potential use cases include low-intermediate risk patients with chest pain or shortness of breath for whom non-contrast CT was ordered, or administration of iodine-based contrast is contraindicated.

Intravascular Ultrasound-Guided Transvenous Biopsy of Abdominal and Pelvic Targets Difficult to Access by Percutaneous Needle Biopsy: Technique and Initial Clinical Experience

PurposeTo report initial clinical experience with intravascular ultrasound (US)-guided transvenous biopsy (TVB) for perivascular target lesions in the abdomen and pelvis using side-viewing phased-array intracardiac echocardiography catheters. Materials and MethodsIn this single-institution, retrospective study, 48 patients underwent 50 intravascular US-guided TVB procedures for targets close to the inferior vena cava or iliac veins deemed difficult to access by conventional percutaneous needle biopsy (PNB). In all procedures, side-viewing phased-array intracardiac echocardiography intravascular US catheters and transjugular liver biopsy sets were inserted through separate jugular or femoral vein access sheaths, and 18-gauge core needle biopsy specimens were obtained under real-time intravascular US guidance. Diagnostic yield, diagnostic accuracy, and complications were analyzed. ResultsIntravascular US-guided TVB was diagnostic of malignancy in 40 of 50 procedures for a diagnostic yield of 80%. There were 5 procedures in which biopsy was correctly negative for malignancy, with a per-procedure diagnostic accuracy of 90% (45/50). Among the 5 false negatives, 2 patients underwent repeat intravascular US-guided TVB, which was diagnostic of malignancy for a per-patient diagnostic accuracy of 94% (45/48). There were 1 (2%) mild, 2 (4%) moderate, and 1 (2%) severe adverse events, with 1 moderate severity adverse event (venous thrombosis) directly attributable to the intravascular US-guided TVB technique. ConclusionsIntravascular US-guided TVB performed on difficult-to-approach perivascular targets in the abdomen and pelvis resulted in a high diagnostic accuracy, similar to accepted thresholds for PNB. Complication rates may be slightly higher but should be weighed relative to the risks of difficult PNB, surgical biopsy, or clinical management without biopsy.

Impact of heart rate on diagnostic accuracy of second generation 320-detector computed tomography coronary angiography.

To assess the impact of elevated heart rate (HR) on the diagnostic accuracy and image quality of second-generation 320-detector computed tomography coronary angiography (320-CTCA). Consecutive patients with suspected coronary disease referred for invasive coronary angiography (ICA) were prospectively recruited and underwent 320-CTCA. Pre-scan beta-blockers were administered if native HR>80 bpm and post-scan cohorts stratified by traditional (HR ≤60 bpm) and elevated HR (61-80 bpm). A wider phase window was used for the elevated HR group (30-80%). 320-CTCA and ICA were analyzed by independent readers blinded to other data. Significant disease was defined as ≥50% visual stenosis on ICA. Uninterpretable segments by 320-CTCA were considered to be significant on an intention-to-diagnose principle. Image quality was assessed by 5-point Likert score. Of 107 patients studied (1,662 segments), there was no significant difference in sensitivity, specificity, positive and negative predictive value between patients with HR ≤60 bpm (n=55) vs. HR 61-80 bpm (n=52): 97%, 88%, 95%, 94% vs. 100%, 88%, 95%, 100%; Receiver operator characteristic-area under the curve 0.93 vs. 0.94, P=0.82). Overall per-patient diagnostic accuracy was 96% in both groups with no significant difference in interpretable segments (Likert ≥2) or median radiation dose (2.4 mSv vs. 2.7 mSv, P=0.35). Only 4/1,662 (0.2%) segments were uninterpretable by motion artefact in the whole cohort. In patients with HR >60 and up to 80bpm, second generation 320-CTCA provides comparably adequate diagnostic accuracy to HR ≤60 without significantly impacting upon overall segmental evaluability.

Fractional flow reserve derived from coronary computed tomography angiography: diagnostic performance in hypertensive and diabetic patients.

Fractional flow reserve (FFR) derived from coronary computed tomography (FFRCT) has high diagnostic performance in stable coronary artery disease (CAD). The diagnostic performance of FFRCT in patients with hypertension (HTN) and diabetes (DM), who are at risk of microvascular impairment, is not known. We analysed the diagnostic performance of FFRCT, in patients (vessels) with DM (n = 16), HTN (n = 186), DM + HTN (n = 58) vs. controls (n = 107) with or with suspected CAD. Patients (vessels) were further divided according to left ventricular mass index (LVMI) tertiles. Reference standard was invasively measured FFR ≤0.80. Per-patient diagnostic accuracy (95% CI) in control patients was 71.7% (61.6-81.8) vs. 79.3 (74.0-85.0) (P = 0.12), 75.0% (47.6-92.7) (P = 0.52), and 75.9% (62.8-86.1) (P = 0.39) in patients with HTN, DM, and HTM + DM, respectively. There was no difference in discrimination of ischaemia by FFRCT between groups. On a per-vessel level, there was no significant difference in diagnostic performance or discrimination of ischaemia by FFRCT between groups. There was a decline in both per-patient and -vessel diagnostic specificity of FFRCT in the upper LVMI tertile when compared with lower tertiles; however, discrimination of ischaemia by FFRCT was unaltered across LVMI tertiles. The diagnostic performance of FFRCT is independent of the presence of HTN and DM. FFRCT is a robust method in a broad stable CAD population, including patients at high risk for microvascular disease.

Diagnostic accuracy and discrimination of ischemia by fractional flow reserve CT using a clinical use rule: Results from the Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography study

BackgroundFractional flow reserve (FFR) is the gold standard for determining lesion-specific ischemia. Computed FFRCT derived from coronary CT angiography (coronary CTA) correlates well with invasive FFR and accurately differentiates between ischemia-producing and nonischemic lesions. The diagnostic performance of FFRCT when applied in a clinically relevant way to all vessels ≥ 2 mm in diameter stratified by sex and age has not been previously examined. MethodsTwo hundred fifty-two patients and 407 vessels underwent coronary CTA, FFRCT, invasive coronary angiography, and invasive FFR. FFRCT and FFR ≤0.80 were considered ischemic, whereas CT stenosis ≥50% was considered obstructive. The diagnostic performance of FFRCT was assessed following a prespecified clinical use rule which included all vessels ≥2 mm in diameter, not just those assessed by invasive FFR measurements. Stenoses <30% were assigned an FFR of 0.90, and stenoses >90% were assigned an FFR of 0.50. Diagnostic performance of FFRCT was stratified by vessel diameter, sex, and age. ResultsBy FFR, ischemia was identified in 129 of 252 patients (51%) and in 151 of 407 vessels (31%). Mean age (±standard deviation) was 62.9 ± 9 years, and women were older (65.5 vs 61.9 years; P = .003). Per-patient diagnostic accuracy (83% vs 72%; P < .005) and specificity (54% vs 82%, P < .001) improved significantly after application of the clinical use tool. These were significantly improved over standard coronary CTA values before application of the clinical use rule. Discriminatory power of FFRCT also increased compared with baseline (area under the receiver operating characteristics curve [AUC]: 0.93 vs 0.81, P < .001). Diagnostic performance improved in both sexes with no significant differences between the sexes (AUC: 0.93 vs 0.90, P = .43). There were no differences in the discrimination of FFRCT after application of the clinical use rule when stratified by age ≥65 or <65 years (AUC: 0.95 vs 0.90, P = .10). ConclusionsThe diagnostic accuracy and discriminatory power of FFRCT improve significantly after the application of a clinical use rule which includes all clinically relevant vessels >2 mm in diameter. FFRCT has similar diagnostic accuracy and discriminatory power for ischemia detection in men and women irrespective of age using a cut point of 65 years.

Letter by Fan et al Regarding Article, “Additive Value of Magnetic Resonance Coronary Angiography in a Comprehensive Cardiac Magnetic Resonance Stress-Rest Protocol for Detection of Functionally Significant Coronary Artery Disease: A Pilot Study”

We took great interest in the pilot study by Bettencourt et al1 about evaluating the additive diagnostic value of a three-dimensional (3D) whole-heart magnetic resonance coronary angiography (MRCA) integration into 1.5T Cardiovascular Magnetic Resonance–Myocardial Perfusion Imaging (MPI)/late-gadolinium–enhancement protocol for the detection of functionally significant coronary artery disease (CAD). However, the data, in spite of the limited number of patients, revealed that the integration of whole-heart noncontrast-enhanced MRCA nonsignificantly improves per-patient diagnostic accuracy. Maybe we could take another way to couple anatomic data with functional parameters to detect functionally significant CAD. Fractional flow reserve (FFR) is an invasive, lesion-specific, and well-validated index to evaluate the severity of coronary artery stenosis. With the speed …

Additive Value of Magnetic Resonance Coronary Angiography in a Comprehensive Cardiac Magnetic Resonance Stress-Rest Protocol for Detection of Functionally Significant Coronary Artery Disease

Cardiovascular magnetic resonance (CMR) myocardial perfusion imaging (MPI) is a state-of-the-art noninvasive modality for detection of myocardial ischemia and coronary artery disease. Magnetic resonance coronary angiography (MRCA) allows visualization of the coronary tree, but its incremental value as part of a CMR protocol including MPI and late gadolinium enhancement (LGE) is not well established. We aimed to evaluate the additive diagnostic value of a 3-dimensional whole-heart MRCA integration into a 1.5T CMR-MPI/LGE protocol for the detection of functionally significant coronary artery disease. Forty-three symptomatic patients (61 ± 8.3 years; 65% men) with suspected coronary artery disease and intermediate/high-pretest probability underwent CMR (including CMR-MPI, MRCA, and LGE) and x-ray invasive coronary angiography (XA) with fractional flow reserve evaluation. Diagnostic performances of MRCA, CMR-MPI/LGE, and MRCA+CMR-MPI/LGE integration were determined having XA+fractional flow reserve as standard for coronary artery disease (≥90% stenosis/occlusion or fractional flow reserve ≤ 0.80 in vessels>2 mm). MRCA inclusion into the CMR protocol was associated with a mean increase of 7.9 ± 4.69 (0-17.7) minutes in total examination duration (14%). On patient-based analysis, MRCA had 96% sensitivity, 68% specificity, positive predictive value of 79%, and negative predictive value of 93%. CMR-MPI/LGE had 79% sensitivity, 95% specificity, positive predictive value of 95%, and negative predictive value of 78%. Integration of MRCA with CMR-MPI/LGE further improved CMR performance to 96% sensitivity, 89% specificity, positive predictive value of 92%, and negative predictive value of 94%, with a global accuracy of 93%. In this intermediate/high-pretest population, integration of noncontrast-enhanced whole-heart MRCA nonsignificantly improved per-patient diagnostic accuracy of a comprehensive 1.5-T stress-rest CMR-MPI/LGE protocol at a cost of longer scanning times.

Computed Tomography Angiography and Myocardial Computed Tomography Perfusion in Patients With Coronary Stents: Prospective Intraindividual Comparison With Conventional Coronary Angiography

This study sought to determine whether adding myocardial computed tomography perfusion (CTP) to computed tomography angiography (CTA) improves diagnostic performance for coronary stents. CTA of coronary stents has been limited by nondiagnostic studies caused by metallic stent material and coronary motion. CTA and CTP were performed in 91 consecutive patients with stents before quantitative coronary angiography, the reference standard for obstructive stenosis (≥50%). If a coronary stent or vessel was nondiagnostic on CTA, adenosine stress CTP in the corresponding myocardial territory was read for combined CTA/CTP. Patients had an average of 2.5 ± 1.8 coronary stents (1 to 10), with a diameter of 3.0 ± 0.5 mm. Significantly more patients were nondiagnostic for stent assessment by CTA (22%; mainly due to metal artifacts [75%] or motion [25%]) versus CTP (1%; p < 0.001; severe angina precluded CTP in 1 case). The per-patient diagnostic accuracy of CTA/CTP for stents (87%, 95% confidence interval [CI]: 78% to 93%) was significantly higher than that of CTA alone (71%, 95% CI: 61% to 80%; p < 0.001), mainly because nondiagnostic examinations were significantly reduced (p < 0.001). In the analysis of any coronary artery disease, diagnostic accuracy and nondiagnostic rate were also significantly improved by the addition of CTP (p < 0.001). CTA/CTP (7.9 ± 2.8 mSv) had a significantly lower effective radiation dose than angiography (9.5 ± 5.1 mSv; p = 0.005). The area under the receiver-operating characteristic curve for CTA/CTP (0.82, 95% CI: 0.69 to 0.95) was superior to that for CTA (0.69, 95% CI: 0.57 to 0.82; p < 0.001) in identifying patients requiring stent revascularization. Combined coronary CTA and myocardial CTP improves diagnosis of CAD and in-stent restenosis in patients with stents compared with CTA alone. (Coronary Artery Stent Evaluation With 320-Slice Computed Tomography-The CArS 320 Study [CARS-320]; NCT00967876).

Rationale and design of the ViCTORY (Validation of an Intracycle CT Motion CORrection Algorithm for Diagnostic AccuracY) trial

BackgroundCoronary CT angiography (CTA) has emerged as an effective noninvasive method for direct visualization of the coronary arteries, with high diagnostic performance compared with invasive coronary angiography (ICA). However, coronary CTA is prone to artifacts, including coronary motion, which may reduce its diagnostic performance. Intracycle motion compensation algorithms (MCAs) from a combination of software and hardware techniques now allow for correction of coronary motion, but the diagnostic performance of MCAs compared with traditional coronary CTA reconstruction methods remains unexplored. MethodsViCTORY (Validation of an Intracycle CT Motion CORrection Algorithm for Diagnostic AccuracY) is a prospective international multicenter trial of 218 patients which is designed to evaluate the performance of MCAs for the diagnosis of anatomically obstructive coronary artery disease (CAD) compared with an ICA reference standard, on a per-patient, per-vessel, and per-segment basis. Patients enrolled into ViCTORY will undergo investigational coronary CTA and clinically indicated ICA and will not receive heart rate-lowering medications before coronary CTA. Coronary CTA images will be reconstructed by conventional standard methods as well as by MCAs. Blinded core laboratory interpretation will be performed for coronary CTA and ICA in an intent-to-diagnose fashion. ResultsThe primary end point of ViCTORY is the per-patient diagnostic accuracy of MCAs for the diagnosis of anatomically obstructive CAD compared with ICA. Secondary end points will include other per-patient, per-vessel, and per-segment diagnostic performance characteristics, including accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. Other key secondary end points will include diagnostic interpretability, image quality, the upper heart rate threshold of utility of MCAs, and the additive value of MCAs to traditionally reconstructed coronary CTA. ConclusionViCTORY will determine whether MCAs improve the diagnosis of obstructive CAD in patients undergoing coronary CTA who are not receiving heart rate-lowering medications.

Diagnostic Accuracy of Fractional Flow Reserve From Anatomic CT Angiography

Coronary computed tomographic (CT) angiography is a noninvasive anatomic test for diagnosis of coronary stenosis that does not determine whether a stenosis causes ischemia. In contrast, fractional flow reserve (FFR) is a physiologic measure of coronary stenosis expressing the amount of coronary flow still attainable despite the presence of a stenosis, but it requires an invasive procedure. Noninvasive FFR computed from CT (FFR(CT)) is a novel method for determining the physiologic significance of coronary artery disease (CAD), but its ability to identify ischemia has not been adequately examined to date. To assess the diagnostic performance of FFR(CT) plus CT for diagnosis of hemodynamically significant coronary stenosis. Multicenter diagnostic performance study involving 252 stable patients with suspected or known CAD from 17 centers in 5 countries who underwent CT, invasive coronary angiography (ICA), FFR, and FFR(CT) between October 2010 and October 2011. Computed tomography, ICA, FFR, and FFR(CT) were interpreted in blinded fashion by independent core laboratories. Accuracy of FFR(CT) plus CT for diagnosis of ischemia was compared with an invasive FFR reference standard. Ischemia was defined by an FFR or FFR(CT) of 0.80 or less, while anatomically obstructive CAD was defined by a stenosis of 50% or larger on CT and ICA. The primary study outcome assessed whether FFR(CT) plus CT could improve the per-patient diagnostic accuracy such that the lower boundary of the 1-sided 95% confidence interval of this estimate exceeded 70%. Among study participants, 137 (54.4%) had an abnormal FFR determined by ICA. On a per-patient basis, diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of FFR(CT) plus CT were 73% (95% CI, 67%-78%), 90% (95% CI, 84%-95%), 54% (95% CI, 46%-83%), 67% (95% CI, 60%-74%), and 84% (95% CI, 74%-90%), respectively. Compared with obstructive CAD diagnosed by CT alone (area under the receiver operating characteristic curve [AUC], 0.68; 95% CI, 0.62-0.74), FFR(CT) was associated with improved discrimination (AUC, 0.81; 95% CI, 0.75-0.86; P < .001). Although the study did not achieve its prespecified primary outcome goal for the level of per-patient diagnostic accuracy, use of noninvasive FFR(CT) plus CT among stable patients with suspected or known CAD was associated with improved diagnostic accuracy and discrimination vs CT alone for the diagnosis of hemodynamically significant CAD when FFR determined at the time of ICA was the reference standard.

Detecting Obstructive Coronary Disease With CT Angiography and Noninvasive Fractional Flow Reserve

PHYSICIANS COMMONLY ENCOUNTER PATIENTS REPORTing chest discomfort. In these cases, the physician needs to determine whether the patient has obstructive coronary artery disease (CAD), and if so, whether the patient is at increased risk of future cardiovascular events. The ultimate goal of this evaluation is to direct optimal medical therapy and potentially lead to ischemiadriven coronary revascularization. The fractional flow reserve (FFR) performed during invasive coronary angiography has been shown to provide lesion-specific data on ischemia, which, when used to direct revascularization, leads to improved clinical outcomes. Fractional flow reserve is the ratio of the mean coronary artery pressure distal to an obstructive coronary lesion relative to the mean aortic pressure during maximal coronary blood flow and represents a physiologic measure of coronary stenosis. Current guidelines recommend that this evaluation should be differential based on patient pretest risk assessment. Lowrisk patients should receive only expectant management, intermediate-risk patients should be referred for noninvasive testing, and high-risk patients should undergo invasive cardiac catheterization. To date, noninvasive tests have performed this evaluation by taking either an anatomic approach such as computed tomographic (CT) angiography to identify obstructive CAD or a functional approach to determine ischemia by perfusion or wall motion function via a variety of stress and imaging modes. Therefore, technologies that provide both a highly sensitive anatomic evaluation for obstructive disease and a highly specific physiologic evaluation for ischemia represent the “holy grail” for noninvasive imaging for CAD. It is with this background that Min et al report the findings of the DeFACTO study in this issue of JAMA evaluating CT angiography with a novel noninvasive FFR computed from CT (FFRCT) compared with the reference standard of invasive FFR determined by conventional coronary angiography. The investigators performed a multicenter (17 centers in 5 countries) diagnostic performance study involving 288 stable patients with known or suspected CAD, of whom 252 patients had evaluable images that were compared with invasive FFR. The study’s prespecified aim was to determine if FFRCT plus CT could improve the per-patient diagnostic accuracy such that the lower boundary of the 95% confidence interval exceeded 70%. The investigators went to great lengths to ensure blinding, such as using core laboratories for CT angiography evaluation, FFRCT evaluation, and invasive coronary angiography as well as an integration core laboratory that helped register the images and identify locations for FFRCT vs reference FFR analysis. The investigators report that 137 patients (54.4%) had an abnormal FFR based on invasive angiography. In the perpatient analysis, FFRCT had an accuracy of 73% (95% CI, 67%-78%) arising from a sensitivity of 90% (95% CI, 84%95%) and specificity of 54% (95% CI, 46%-83%). However, this level of diagnostic accuracy did not meet the prespecified primary end point because the lower bound of the 95% CI for accuracy was 67%. For lesions of 50% or greater, CT angiography had an accuracy of 64% (95% CI, 58%70%) with a sensitivity of 84% (95% CI, 77%-90%) and a specificity of 42% (95% CI, 34%-51%). The investigators rightly conclude that FFRCT plus CT was associated with improved diagnostic accuracy and discrimination compared with CT angiography alone. This well-conducted multicenter study provides important data about the performance both of FFRCT plus CT and CT angiography. Additionally, beyond the sheer novelty of the FFRCT technology, the investigators raise the bar by comparing this diagnostic technology with a reference standard of both invasive angiography and invasive FFR. This change in reference standard may in part explain some of the accuracy findings. So how should these findings be considered with regard to current clinical evaluation for chest pain?

Diagnostic performance of combined noninvasive coronary angiography and myocardial perfusion imaging using 320 row detector computed tomography: design and implementation of the CORE320 multicenter, multinational diagnostic study

Multidetector coronary computed tomography angiography (CTA) is a promising modality for widespread clinical application because of its noninvasive nature and high diagnostic accuracy as found in previous studies using 64 to 320 simultaneous detector rows. It is, however, limited in its ability to detect myocardial ischemia. In this article, we describe the design of the CORE320 study (“Combined coronary atherosclerosis and myocardial perfusion evaluation using 320 detector row computed tomography”). This prospective, multicenter, multinational study is unique in that it is designed to assess the diagnostic performance of combined 320-row CTA and myocardial CT perfusion imaging (CTP) in comparison with the combination of invasive coronary angiography and single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). The trial is being performed at 16 medical centers located in 8 countries worldwide. CT has the potential to assess both anatomy and physiology in a single imaging session. The co-primary aim of the CORE320 study is to define the per-patient diagnostic accuracy of the combination of coronary CTA and myocardial CTP to detect physiologically significant coronary artery disease compared with (1) the combination of conventional coronary angiography and SPECT-MPI and (2) conventional coronary angiography alone. If successful, the technology could revolutionize the management of patients with symptomatic CAD.

Influence of heart rate on diagnostic accuracy and image quality of 16-slice CT coronary angiography: comparison of multisegment and halfscan reconstruction approaches

The lower the heart rate the better image quality in multislice computed tomography (MSCT) coronary angiography. We prospectively assessed the influence of heart rate on per-patient diagnostic accuracy and image quality of MSCT coronary angiography and compared adaptive multisegment and standard halfscan reconstruction. A consecutive cohort of 126 patients scheduled to undergo conventional coronary angiography was examined with 16-slice CT. For all heart rate groups, per-patient diagnostic accuracy was significantly higher for multisegment than halfscan reconstruction with values of 95 vs. 79% (p < 0.05, <65 bpm, 38 patients), 85 vs. 66% (p < 0.05, 65-74 bpm, 47 patients), and 78% vs. 41% (p < 0.001, >74 bpm, 41 patients). Differences in diagnostic accuracy between adjacent heart rate groups were only significant for halfscan reconstruction for the comparison between the 65-74 and >74 bpm group (p < 0.05). The vessel lengths free of motion artifacts were significantly longer with multisegment reconstruction in all heart rate groups and for all coronary arteries (p < 0.005). For noninvasive MSCT coronary angiography, both per-patient diagnostic accuracy and image quality decline with increasing heart rate, and multisegment reconstruction at high heart rates yields similar results as standard halfscan reconstruction at low heart rates.