Julia Stehli

Detection of significant coronary artery disease by noninvasive anatomical and functional imaging.

Background—The choice of imaging techniques in patients with suspected coronary artery disease (CAD) varies between countries, regions, and hospitals. This prospective, multicenter, comparative effectiveness study was designed to assess the relative accuracy of commonly used imaging techniques for identifying patients with significant CAD. Methods and Results—A total of 475 patients with stable chest pain and intermediate likelihood of CAD underwent coronary computed tomographic angiography and stress myocardial perfusion imaging by single photon emission computed tomography or positron emission tomography, and ventricular wall motion imaging by stress echocardiography or cardiac magnetic resonance. If ≥1 test was abnormal, patients underwent invasive coronary angiography. Significant CAD was defined by invasive coronary angiography as >50% stenosis of the left main stem, >70% stenosis in a major coronary vessel, or 30% to 70% stenosis with fractional flow reserve ⩽0.8. Significant CAD was present in 29% of patients. In a patient-based analysis, coronary computed tomographic angiography had the highest diagnostic accuracy, the area under the receiver operating characteristics curve being 0.91 (95% confidence interval, 0.88–0.94), sensitivity being 91%, and specificity being 92%. Myocardial perfusion imaging had good diagnostic accuracy (area under the curve, 0.74; confidence interval, 0.69–0.78), sensitivity 74%, and specificity 73%. Wall motion imaging had similar accuracy (area under the curve, 0.70; confidence interval, 0.65–0.75) but lower sensitivity (49%, P<0.001) and higher specificity (92%, P<0.001). The diagnostic accuracy of myocardial perfusion imaging and wall motion imaging were lower than that of coronary computed tomographic angiography (P<0.001). Conclusions—In a multicenter European population of patients with stable chest pain and low prevalence of CAD, coronary computed tomographic angiography is more accurate than noninvasive functional testing for detecting significant CAD defined invasively. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979199.

Coronary computed tomography angiography with model-based iterative reconstruction using a radiation exposure similar to chest X-ray examination

Aims To evaluate the feasibility and image quality of coronary computed tomography angiography (CCTA) acquisition with a submillisievert fraction of effective radiation dose using model-based iterative reconstruction (MBIR) for noise reduction. Methods and results In 42 patients undergoing standard low-dose (100–120 kV; 450–700 mA) and additional ultra-low-dose CCTA (80–100 kV; 150–210 mA) reconstructed with MBIR, segmental image quality was graded on a four-point scale [(i): non-evaluative, (ii): good, (iii): adequate, and (iv): excellent]. Signal-to-noise ratio (SNR) was calculated dividing left main artery (LMA) and right coronary artery (RCA) attenuation by the aortic root noise. Over a wide range of body mass index (18–40 kg/m2), the estimated median radiation dose exposure was 1.19 mSv [interquartile range (IQR): 1.07–1.30 mSv] for standard and 0.21 mSv (IQR: 0.18–0.23 mSv) for ultra-low-dose CCTA (P < 0.001). The median image quality score per segment was 3.5 (IQR: 3.0–4.0) in standard CCTA vs. 3.5 (IQR: 2.5–4.0) in ultra-low dose with MBIR (P = 0.29). Diagnostic image quality (scores 2–4) was found in 98.7 vs. 97.8% coronary segments (P = 0.36). Introduction of MBIR for ultra-low-dose CCTA resulted in a significant increase in SNR (P < 0.001) for LMA (from 15 ± 5 to 29 ± 7) and RCA (from 14 ± 4 to 27 ± 6) despite 82% dose reduction. Conclusion Coronary computed tomography angiography acquisition with diagnostic image quality is feasible at an ultra-low radiation dose of 0.21 mSv, e.g. in the range reported for a postero-anterior and lateral chest X-ray.

Machine learning for prediction of all-cause mortality in patients with suspected coronary artery disease: a 5-year multicentre prospective registry analysis

Aims Traditional prognostic risk assessment in patients undergoing non-invasive imaging is based upon a limited selection of clinical and imaging findings. Machine learning (ML) can consider a greater number and complexity of variables. Therefore, we investigated the feasibility and accuracy of ML to predict 5-year all-cause mortality (ACM) in patients undergoing coronary computed tomographic angiography (CCTA), and compared the performance to existing clinical or CCTA metrics. Methods and results The analysis included 10 030 patients with suspected coronary artery disease and 5-year follow-up from the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry. All patients underwent CCTA as their standard of care. Twenty-five clinical and 44 CCTA parameters were evaluated, including segment stenosis score (SSS), segment involvement score (SIS), modified Duke index (DI), number of segments with non-calcified, mixed or calcified plaques, age, sex, gender, standard cardiovascular risk factors, and Framingham risk score (FRS). Machine learning involved automated feature selection by information gain ranking, model building with a boosted ensemble algorithm, and 10-fold stratified cross-validation. Seven hundred and forty-five patients died during 5-year follow-up. Machine learning exhibited a higher area-under-curve compared with the FRS or CCTA severity scores alone (SSS, SIS, DI) for predicting all-cause mortality (ML: 0.79 vs. FRS: 0.61, SSS: 0.64, SIS: 0.64, DI: 0.62; P< 0.001). Conclusions Machine learning combining clinical and CCTA data was found to predict 5-year ACM significantly better than existing clinical or CCTA metrics alone.

Impact of cardiac magnetic resonance imaging on human lymphocyte DNA integrity.

Aims Magnetic resonance (MR) imaging is widely used for diagnostic imaging in medicine as it is considered a safe alternative to ionizing radiation-based techniques. Recent reports on potential genotoxic effects of strong and fast switching electromagnetic gradients such as used in cardiac MR (CMR) have raised safety concerns. The aim of this study was to analyse DNA double-strand breaks (DSBs) in human blood lymphocytes before and after CMR examination. Methods and results In 20 prospectively enrolled patients, peripheral venous blood was drawn before and after 1.5 T CMR scanning. After density gradient cell separation of blood samples, DNA DSBs in lymphocytes were quantified using immunofluorescence microscopy and flow cytometric analysis. Wilcoxon signed-rank testing was used for statistical analysis. Immunofluorescence microscopic and flow cytometric analysis revealed a significant increase in median numbers of DNA DSBs in lymphocytes induced by routine 1.5 T CMR examination. Conclusion The present findings indicate that CMR should be used with caution and that similar restrictions may apply as for X-ray-based and nuclear imaging techniques in order to avoid unnecessary damage of DNA integrity with potential carcinogenic effect.

Coronary artery calcium scoring: Influence of adaptive statistical iterative reconstruction using 64-MDCT

OBJECTIVE Assessment of coronary artery calcification is increasingly used for cardiovascular risk stratification. We evaluated the reliability of calcium-scoring results using a novel iterative reconstruction algorithm (ASIR) on a high-definition 64-slice CT scanner, as such data is lacking. METHODS AND RESULTS In 50 consecutive patients Agatston scores, calcium mass and volume score were assessed. Comparisons were performed between groups using filtered back projection (FBP) and 20-100% ASIR algorithms. Calcium score was measured in the coronary arteries, signal and noise were measured in the aortic root and left ventricle. In comparison with FBP, use of 20%, 40%, 60%, 80%, and 100% ASIR resulted in reduced image noise between groups (7.7%, 18.8%, 27.9%, 39.86%, and 48.56%, respectively; p<0.001) without difference in signal (p=0.60). With ASIR algorithms Agatston coronary calcium scoring significantly decreased compared with FBP algorithms (837.3 ± 130.3; 802.2 ± 124.9, 771.5 ± 120.7; 744.7 ± 116.8, 724.5 ± 114.2, and 709.2 ± 112.3 for 0%, 20%, 40%, 60%, 80%, and 100% ASIR, respectively, p<0.001). Volumetric score decreased in a similar manner (p<0.001) while calcium mass remained unchanged. Mean effective radiation dose was 0.81 ± 0.08 mSv. CONCLUSION ASIR results in image noise reduction. However, ASIR image reconstruction techniques for HDCT scans decrease Agatston coronary calcium scores. Thus, one needs to be aware of significant changes of the scoring results caused by different reconstruction methods.

Cadmium-Zinc-Telluride Myocardial Perfusion Imaging in Obese Patients

We have evaluated the impact of increased body mass on the quality of myocardial perfusion imaging using a latest-generation γ-camera with cadmium-zinc-telluride semiconductor detectors in patients with high (≥40 kg/m2) or very high (≥45 kg/m2) body mass index (BMI). Methods: We enrolled 81 patients, including 18 with no obesity (BMI < 30 kg/m2), 17 in World Health Organization obese class I (BMI, 30–34.9 kg/m2), 15 in class II (BMI, 35–39.9 kg/m2), and 31 in class III (BMI ≥ 40 kg/m2), including 15 with BMI ≥ 45 kg/m2. Image quality was scored as poor (1), moderate (2), good (3), or excellent (4). Patients with BMI ≥ 45 kg/m2 and nondiagnostic image quality (≤2) were rescanned after repositioning to better center the heart in the field of view. Receiver-operating-curve analysis was applied to determine the BMI cutoff required to obtain diagnostic image quality (≥3). Results: Receiver-operating-curve analysis resulted in a cutoff BMI of 39 kg/m2 (P < 0.001) for diagnostic image quality. In patients with BMI ≥ 40 kg/m2, image quality was nondiagnostic in 81%; after CT-based attenuation correction this decreased to 55%. Repositioning further improved image quality. Rescanning on a conventional SPECT camera resulted in diagnostic image quality in all patients with BMI ≥ 45 kg/m2. Conclusion: Patients with BMI ≥ 40 kg/m2 should be scheduled for myocardial perfusion imaging on a conventional SPECT camera, as it is difficult to obtain diagnostic image quality on a cadmium-zinc-telluride camera.

Multicentre multi-device hybrid imaging study of coronary artery disease: results from the EValuation of INtegrated Cardiac Imaging for the Detection and Characterization of Ischaemic Heart Disease (EVINCI) hybrid imaging population

AIMS Hybrid imaging provides a non-invasive assessment of coronary anatomy and myocardial perfusion. We sought to evaluate the added clinical value of hybrid imaging in a multi-centre multi-vendor setting. METHODS AND RESULTS Fourteen centres enrolled 252 patients with stable angina and intermediate (20-90%) pre-test likelihood of coronary artery disease (CAD) who underwent myocardial perfusion scintigraphy (MPS), CT coronary angiography (CTCA), and quantitative coronary angiography (QCA) with fractional flow reserve (FFR). Hybrid MPS/CTCA images were obtained by 3D image fusion. Blinded core-lab analyses were performed for CTCA, MPS, QCA and hybrid datasets. Hemodynamically significant CAD was ruled-in non-invasively in the presence of a matched finding (myocardial perfusion defect co-localized with stenosed coronary artery) and ruled-out with normal findings (both CTCA and MPS normal). Overall prevalence of significant CAD on QCA (>70% stenosis or 30-70% with FFR≤0.80) was 37%. Of 1004 pathological myocardial segments on MPS, 246 (25%) were reclassified from their standard coronary distribution to another territory by hybrid imaging. In this respect, in 45/252 (18%) patients, hybrid imaging reassigned an entire perfusion defect to another coronary territory, changing the final diagnosis in 42% of the cases. Hybrid imaging allowed non-invasive CAD rule-out in 41%, and rule-in in 24% of patients, with a negative and positive predictive value of 88% and 87%, respectively. CONCLUSION In patients at intermediate risk of CAD, hybrid imaging allows non-invasive co-localization of myocardial perfusion defects and subtending coronary arteries, impacting clinical decision-making in almost one every five subjects.

Absolute Myocardial Blood Flow and Flow Reserve Assessed by Gated SPECT with Cadmium-Zinc-Telluride Detectors Using 99mTc-Tetrofosmin: Head to Head Comparison with 13N-Ammonia PET

Recent advances in SPECT technology including cadmium–zinc–telluride (CZT) semiconductor detector material may pave the way for absolute myocardial blood flow (MBF) measurements by SPECT. The aim of the present study was to compare K1 uptake rate constants as surrogates of absolute MBF and myocardial flow reserve index (MFRi) in humans as assessed with a CZT SPECT camera versus PET. Methods: Absolute MBF was assessed in 28 consecutive patients undergoing adenosine stress–rest myocardial perfusion imaging (MPI) by 99mTc-tetrofosmin CZT SPECT and 13N-ammonia PET, and MFR was calculated as a ratio of hyperemic over resting MBF. Results from both MPI methods were compared, and correlation coefficients were calculated. The diagnostic accuracy of CZT MFRi to predict an abnormal MFR defined as PET MFR less than 2 was assessed using a receiver-operator-characteristic curve. Results: Median MBF at rest was comparable between CZT and PET (0.89 [interquartile range (IQR), 0.77–1.00] vs. 0.92 [IQR, 0.78–1.06] mL/g/min; P = not significant) whereas it was significantly lower at stress in CZT than PET (1.11 [IQR, 1.00–1.26] vs. 2.06 [IQR, 1.48–2.56] mL/g/min; P < 0.001). This resulted in median MFRi values of 1.32 (IQR, 1.13–1.52) by CZT and 2.36 (IQR, 1.57–2.71) by PET (P < 0.001). The receiver-operator-characteristic curve revealed a cutoff for CZT MFRi at 1.26 to predict an abnormal PET MFR yielding an accuracy of 75%. Conclusion: The estimation of absolute MBF index values by CZT SPECT MPI with 99mTc-tetrofosmin is technically feasible, although hyperemic values are significantly lower than from PET with 13N-ammonia, resulting in a substantial underestimation of MFR. Nevertheless, CZT MFRi may confer diagnostic value.

Impact of a new motion-correction algorithm on image quality of low-dose coronary CT angiography in patients with insufficient heart rate control.

RATIONALE AND OBJECTIVES Prospective electrocardiogram (ECG) triggering allows coronary computed tomography angiography (CCTA) scanning with low radiation dose but requires heart rates below 63 beats/min. We assessed the impact of a novel vendor-specific motion-correction algorithm on image quality and interpretability of low-dose CCTA acquired despite insufficient heart rate control. MATERIALS AND METHODS In 40 patients undergoing CCTA for the assessment of known or suspected coronary artery disease who did not reach the target heart rate below 63 beats/min despite β-blockade before prospective low-dose scanning, the temporal acquisition window was increased (80 ms additional padding). The new algorithm detects and integrates vessel path and velocity from adjacent cardiac phases for motion correction. Two blinded observers assessed image quality on a 4-point Likert scale (1, nonevaluative; 2, reduced but evaluative; 3, good; and 4, excellent) and the fraction of interpretable segments (score 2 or more) using motion correction versus standard reconstruction. RESULTS Image reconstruction with motion correction resulted in an increased median coronary artery image quality score (excellent interobserver agreement, κ = 0.85) compared to standard reconstruction (3.4 vs. 3.0, P < .001). Consequently, motion-corrected reconstruction significantly improved the overall interpretability of coronary arteries (from 78% to 88%, P < .001). Estimated mean effective radiation dose was 2.3 ± 0.8 mSv. CONCLUSIONS A novel, vendor-specific, motion-corrected, reconstruction algorithm improves image quality and interpretability of prospectively ECG-triggered low-dose CCTA despite insufficient heart rate control.

Age-related normal structural and functional ventricular values in cardiac function assessed by magnetic resonance

BackgroundThe heart is subject to structural and functional changes with advancing age. However, the magnitude of cardiac age-dependent transformation has not been conclusively elucidated.MethodsThis retrospective cardiac magnetic resonance (CMR) study included 183 subjects with normal structural and functional ventricular values. End systolic volume (ESV), end diastolic volume (EDV), and ejection fraction (EF) were obtained from the left and the right ventricle in breath-hold cine CMR. Patients were classified into four age groups (20–29, 30–49, 50–69, and ≥70 years) and cardiac measurements were compared using Pearson’s rank correlation over the four different groups.ResultsWith advanced age a slight but significant decrease in ESV (r=−0.41 for both ventricles, P<0.001) and EDV (r=−0.39 for left ventricle, r=−0.35 for right ventricle, P<0.001) were observed associated with a significant increase in left (r=0.28, P<0.001) and right (r=0.27, P<0.01) ventricular EF reaching a maximal increase in EF of +8.4% (P<0.001) for the left and +6.1% (P<0.01) for the right ventricle in the oldest compared to the youngest patient group. Left ventricular myocardial mass significantly decreased over the four different age groups (P<0.05).ConclusionsThe aging process is associated with significant changes in left and right ventricular EF, ESV and EDV in subjects with no cardiac functional and structural abnormalities. These findings underline the importance of using age adapted values as standard of reference when evaluating CMR studies.