Catherine Gebhard

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.

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.

Left ventricular non-compaction: prevalence in congenital heart disease.

INTRODUCTION Left ventricular non-compaction cardiomyopathy (LVNC) is a rare cardiomyopathy, originally described as an isolated disease without other structural cardiac abnormalities. The aim of this study was to explore the prevalence of LVNC among adults with different types of congenital heart disease. METHODS From our databases we identified adults with congenital heart disease who fulfilled diagnostic criteria for LVNC. We report frequencies of associated congenital cardiac defects and the prevalence of LVNC among patients with different congenital heart defects. RESULTS From a total of 202 patients with LVNC, 24 patients (12%; mean age 32 ± 11 years, 19 males) had additional congenital cardiac defects. Associated defects were left ventricular outflow tract abnormalities in 11 patients (46%), including 7 uni- or bicuspid aortic valves; two aortic coarctations; one diffuse aortic hypoplasia and one subaortic stenosis, Ebstein anomaly in 6 patients (25%), tetralogy of Fallot in two (8%), and double outlet right ventricle in one patient (4%). In our cohort, the prevalence of LVNC was highest among patients with Ebstein anomaly (6/40, 15%), followed by aortic coarctation (2/60, 3%), tetralogy of Fallot (3/129, 2%) and uni- or bicuspid aortic valves (7/963, 1%). CONCLUSION In adults, various forms of congenital heart disease are associated with LVNC, particularly stenotic lesions of the left ventricular outflow tract, Ebstein anomaly, and tetralogy of Fallot. In the future, studying these patients in more depth may provide a better understanding of the interplay between genetic and hemodynamic factors that lead to the phenotype of LVNC.

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.

Globotriaosylsphingosine Accumulation and Not Alpha-Galactosidase-A Deficiency Causes Endothelial Dysfunction in Fabry Disease

Background Fabry disease (FD) is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA) resulting in the accumulation of globotriaosylsphingosine (Gb3) in a variety of tissues. While GLA deficiency was always considered as the fulcrum of the disease, recent attention shifted towards studying the mechanisms through which Gb3 accumulation in vascular cells leads to endothelial dysfunction and eventually multiorgan failure. In addition to the well-described macrovascular disease, FD is also characterized by abnormalities of microvascular function, which have been demonstrated by measurements of myocardial blood flow and coronary flow reserve. To date, the relative importance of Gb3 accumulation versus GLA deficiency in causing endothelial dysfunction is not fully understood; furthermore, its differential effects on cardiac micro- and macrovascular endothelial cells are not known. Methods and Results In order to assess the effects of Gb3 accumulation versus GLA deficiency, human macro- and microvascular cardiac endothelial cells (ECs) were incubated with Gb3 or silenced by siRNA to GLA. Gb3 loading caused deregulation of several key endothelial pathways such as eNOS, iNOS, COX-1 and COX-2, while GLA silencing showed no effects. Cardiac microvascular ECs showed a greater susceptibility to Gb3 loading as compared to macrovascular ECs. Conclusions Deregulation of key endothelial pathways as observed in FD vasculopathy is likely caused by intracellular Gb3 accumulation rather than deficiency of GLA. Human microvascular ECs, as opposed to macrovascular ECs, seem to be affected earlier and more severely by Gb3 accumulation and this notion may prove fundamental for future progresses in early diagnosis and management of FD patients.

Guggulsterone, an anti-inflammatory phytosterol, inhibits tissue factor and arterial thrombosis

BackgroundThe phytosterol guggulsterone is a potent anti-inflammatory mediator with less side effects than classic steroids. This study assesses the impact of guggulsterone on tissue factor (TF) expression and thrombus formation.Methods and resultsGuggulsterone inhibited TNF-α-induced endothelial TF protein expression and surface activity in a concentration-dependent manner; in contrast, dexamethasone did not affect TNF-α-induced TF expression. Guggulsterone enhanced endothelial tissue factor pathway inhibitor and impaired plasminogen activator inhibitor-1 as well as vascular cell adhesion molecule-1 protein. Real-time polymerase chain reaction revealed that guggulsterone inhibited TNF-α-induced TF mRNA expression; moreover, it impaired activation of the MAP kinases JNK and p38, while that of ERK remained unaffected. In vivo, guggulsterone inhibited TF activity and photochemical injury induced thrombotic occlusion of mouse carotid artery. Guggulsterone also inhibited TF expression, proliferation, and migration of vascular smooth muscle cells in a concentration-dependent manner.ConclusionsGuggulsterone inhibits TF expression in vascular cells as well as thrombus formation in vivo; moreover, it impairs vascular smooth muscle cell activation. Hence, this phytosterol offers novel therapeutic options, in particular in inflammatory diseases associated with an increased risk of thrombosis.

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.

Downstream resource utilization following hybrid cardiac imaging with an integrated cadmium-zinc-telluride/64-slice CT device

PurposeLow yield of invasive coronary angiography and unnecessary coronary interventions have been identified as key cost drivers in cardiology for evaluation of coronary artery disease (CAD). This has fuelled the search for noninvasive techniques providing comprehensive functional and anatomical information on coronary lesions. We have evaluated the impact of implementation of a novel hybrid cadmium-zinc-telluride (CZT)/64-slice CT camera into the daily clinical routine on downstream resource utilization.MethodsSixty-two patients with known or suspected CAD were referred for same-day single-session hybrid evaluation with CZT myocardial perfusion imaging (MPI) and coronary CT angiography (CCTA). Hybrid MPI/CCTA images from the integrated CZT/CT camera served for decision-making towards conservative versus invasive management. Based on the hybrid images patients were classified into those with and those without matched findings. Matched findings were defined as the combination of MPI defect with a stenosis by CCTA in the coronary artery subtending the respective territory. All patients with normal MPI and CCTA as well as those with isolated MPI or CCTA finding or combined but unmatched findings were categorized as “no match”.ResultsAll 23 patients with a matched finding underwent invasive coronary angiography and 21 (91%) were revascularized. Of the 39 patients with no match, 5 (13%, p < 0.001 vs matched) underwent catheterization and 3 (8%, p < 0.001 vs matched) were revascularized.ConclusionCardiac hybrid imaging in CAD evaluation has a profound impact on patient management and may contribute to optimal downstream resource utilization.

Coronary artery stents: influence of adaptive statistical iterative reconstruction on image quality using 64-HDCT

OBJECTIVE The assessment of coronary stents with present-generation 64-detector row computed tomography (HDCT) scanners is limited by image noise and blooming artefacts. We evaluated the performance of adaptive statistical iterative reconstruction (ASIR) for noise reduction in coronary stent imaging with HDCT. METHODS AND RESULTS In 50 stents of 28 patients (mean age 64 ± 10 years) undergoing coronary CT angiography (CCTA) on an HDCT scanner the mean in-stent luminal diameter, stent length, image quality, in-stent contrast attenuation, and image noise were assessed. Studies were reconstructed using filtered back projection (FBP) and ASIR-FBP composites. ASIR resulted in reduced image noise vs. FBP (P < 0.0001). Two readers graded the CCTA stent image quality on a 4-point Likert scale and determined the proportion of interpretable stent segments. The best image quality for all clinical images was obtained with 40 and 60% ASIR with significantly larger luminal area visualization compared with FBP (+42.1 ± 5.4% with 100% ASIR vs. FBP alone; P < 0.0001) while the stent length was decreased (-4.7 ± 0.9%, <P = 0.002) and volume measurements were unaffected. CONCLUSION Reconstruction of CCTA from HDCT using 40 and 60% ASIR incrementally improves intra-stent luminal area, diameter visualization, and image quality compared with FBP reconstruction.

Myocardial perfusion imaging with 13N-Ammonia PET is a strong predictor for outcome☆

BACKGROUND/OBJECTIVES The aim of the present study was to assess the long-term predictive value of myocardial perfusion imaging (MPI) with (13)N-ammonia positron emission tomography (PET) in patients with suspected myocardial perfusion abnormality. At present, outcome data on the predictive value of MPI in (13)N-ammonia PET exist only for rather small patient populations. METHODS Cardiac perfusion was assessed in 943 consecutive patients using (13)N-ammonia PET, and follow-up was obtained in 698 (74%). 77 patients who underwent early revascularization (<60 days) were excluded and 621 patients were assigned to normal versus abnormal perfusion for outcome analysis. Hard events (cardiac death and non-fatal myocardial infarction) and major adverse cardiac events (MACE; hard events, hospitalization for cardiac reasons and late revascularization) were investigated using the Kaplan-Meier method. Independent predictors for various cardiac events were identified using Cox proportional hazard regression analysis. RESULTS During follow-up (5.7 ± 2.5 years), 275 patients had at least 1 cardiac event, including 102 cardiac deaths and 33 non-fatal myocardial infarction. Abnormal perfusion (n=469) was associated with a higher incidence of MACE (P<0.001) and hard events (P<0.001) throughout the 10-year follow-up period. CONCLUSIONS Cardiac perfusion findings in (13)N-ammonia PET are strong predictors of long-term outcome.