Michael Fiechter

Diagnostic Value of 13N-Ammonia Myocardial Perfusion PET: Added Value of Myocardial Flow Reserve

The ability to obtain quantitative values of flow and myocardial flow reserve (MFR) has been perceived as an important advantage of PET over conventional nuclear myocardial perfusion imaging (MPI). We evaluated the added diagnostic value of MFR over MPI alone as assessed with 13N-ammonia and PET/CT to predict angiographic coronary artery disease (CAD). Methods: Seventy-three patients underwent 1-d adenosine stress–rest 13N-ammonia PET/CT MPI, and MFR was calculated. The added value of MFR as an adjunct to MPI for predicting CAD (luminal narrowing ≥ 50%) was evaluated using invasive coronary angiography as a standard of reference. Results: Per patient, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MPI for detecting significant CAD were 79%, 80%, 91%, 59%, and 79%, respectively. Adding a cutoff of less than 2.0 for global MFR to MPI findings improved the values to 96% (P < 0.005), 80%, 93%, 89% (P < 0.005), and 92% (P < 0.005), respectively. Conclusion: The quantification of MFR in 13N-ammonia PET/CT MPI provides a substantial added diagnostic value for detection of CAD. Particularly in patients with normal MPI results, quantification of MFR helps to unmask clinically significant CAD.

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.

Prognostic value of cardiac hybrid imaging integrating single-photon emission computed tomography with coronary computed tomography angiography

Aims Although cardiac hybrid imaging, fusing single-photon emission computed tomography (SPECT) myocardial perfusion imaging with coronary computed tomography angiography (CCTA), provides important complementary diagnostic information for coronary artery disease (CAD) assessment, no prognostic data exist on the predictive value of cardiac hybrid imaging. Hence, the aim of this study was to assess the prognostic value of hybrid SPECT/CCTA images. Methods and results Of 335 consecutive patients undergoing a 1-day stress/rest (99m)Tc-tetrofosmin SPECT and a CCTA, acquired on stand-alone scanners and fused to obtain cardiac hybrid images, follow-up was obtained in 324 patients (97%). Survival free of all-cause death or non-fatal myocardial infarction (MI) and free of major adverse cardiac events (MACE: death, MI, unstable angina requiring hospitalization, coronary revascularizations) was determined using the Kaplan-Meier method for the following groups: (i) stenosis by CCTA and matching reversible SPECT defect; (ii) unmatched CCTA and SPECT finding; and (iii) normal finding by CCTA and SPECT. Coxs proportional hazard regression was used to identify independent predictors for cardiac events. At a median follow-up of 2.8 years (25th-75th percentile: 1.9-3.6), 69 MACE occurred in 47 patients, including 20 death/MI. A corresponding matched hybrid image finding was associated with a significantly higher death/MI incidence (P < 0.005) and proved to be an independent predictor for MACE. The annual death/MI rate was 6.0, 2.8, and 1.3% for patients with matched, unmatched, and normal findings. Conclusion Cardiac hybrid imaging allows risk stratification in patients with known or suspected CAD. A matched defect on hybrid image is a strong predictor of MACE.

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.

Semiconductor Detectors Allow Low-Dose–Low-Dose 1-Day SPECT Myocardial Perfusion Imaging

Cadmium zinc telluride (CZT) detectors with linear counting rate response enable count subtraction in sequential scanning. We evaluated whether count subtraction eliminated the need for higher activity doses in the second part of the 1-d stress–rest myocardial perfusion imaging (MPI) protocol. Methods: For 50 patients (mean age ± SD, 66 ± 12 y) with visually abnormal (n = 42) or equivocal (n = 8) adenosine-stress MPI (320 MBq of 99mTc-tetrofosmin) on a CZT camera, rest MPI was performed with a low dose (320 MBq) and repeated after injection of an additional 640 MBq of 99mTc-tetrofosmin to achieve a standard 3-fold increased dose at rest (960 MBq), compared with stress (320 MBq). Low-dose rest myocardial perfusion images were reconstructed after subtracting the background activity of the preceding stress scan. Segmental percentage tracer uptake of the 2 rest myocardial perfusion images (320 vs. 960 MBq) was compared using intraclass correlation and Bland–Altman limits of agreement. Patient- and coronary territory–based clinical agreement was assessed. Results: The standard protocol revealed ischemia in 34 (68%) and a fixed defect in 8 (16%) patients, of whom 33 (97%) and 8 (100%) were correctly identified by low-dose MPI (clinical agreement, 98%). Segmental uptake correlated well between low- and standard-dose rest scans (r = 0.94, P < 0.001; Bland–Altman limits of agreement, −11 to +11%). Defect extent was 14.4% (low-dose) versus 13.1% (standard-dose) at rest (P = not statistically significant) and 26.6% at stress (P < 0.001 vs. rest scans). Conclusion: These promising results suggest that accurate assessment of ischemic myocardial disease is feasible with a low-dose–low-dose 1-d SPECT MPI protocol using a CZT device.

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.

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.