Hans Scheffel

Sirolimus and Kidney Growth in Autosomal Dominant Polycystic Kidney Disease

BACKGROUND In autosomal dominant polycystic kidney disease (ADPKD), aberrant activation of the mammalian target of rapamycin (mTOR) pathway is associated with progressive kidney enlargement. The drug sirolimus suppresses mTOR signaling. METHODS In this 18-month, open-label, randomized, controlled trial, we sought to determine whether sirolimus halts the growth in kidney volume among patients with ADPKD. We randomly assigned 100 patients between the ages of 18 and 40 years to receive either sirolimus (target dose, 2 mg daily) or standard care. All patients had an estimated creatinine clearance of at least 70 ml per minute. Serial magnetic resonance imaging was performed to measure the volume of polycystic kidneys. The primary outcome was total kidney volume at 18 months on blinded assessment. Secondary outcomes were the glomerular filtration rate and urinary albumin excretion rate at 18 months. RESULTS At randomization, the median total kidney volume was 907 cm3 (interquartile range, 577 to 1330) in the sirolimus group and 1003 cm3 (interquartile range, 574 to 1422) in the control group. The median increase over the 18-month period was 99 cm3 (interquartile range, 43 to 173) in the sirolimus group and 97 cm3 (interquartile range, 37 to 181) in the control group. At 18 months, the median total kidney volume in the sirolimus group was 102% of that in the control group (95% confidence interval, 99 to 105; P=0.26). The glomerular filtration rate did not differ significantly between the two groups; however, the urinary albumin excretion rate was higher in the sirolimus group. CONCLUSIONS In adults with ADPKD and early chronic kidney disease, 18 months of treatment with sirolimus did not halt polycystic kidney growth. (Funded by Wyeth and others; ClinicalTrials.gov number, NCT00346918.)

Low-Dose CT Coronary Angiography in the Step-and-Shoot Mode: Diagnostic Performance

Objective: To investigate the performance of low-dose, dual-source computed tomography (DSCT) coronary angiography in the step-and-shoot (SAS) mode for the diagnosis of significant coronary artery stenoses in comparison with conventional coronary angiography (CCA). Design, setting and patients: Prospective, single-centre study conducted in a referral centre enrolling 120 patients (71 men, mean (SD) age 68 (9) years, mean (SD) body mass index 26.2 (3.2) kg/m2). All study participants underwent DSCT in the SAS mode and CCA within 14 days. Twenty-seven patients were given intravenous β blockers for heart rate reduction before CT. Patients were excluded if a target heart rate ⩽70 bpm could not be achieved by β blockers or when the patients were in non-sinus rhythm. Two blinded readers independently evaluated coronary artery segments for assessability and for the presence of significant (>50%) stenoses. Sensitivity, specificity, negative (NPV) and positive predictive values (PPV) were determined, with CCA being the standard of reference. Radiation dose values were calculated. Results: DSCT coronary angiography in the SAS mode was successfully performed in all 120 patients. Mean (SD) heart rate during scanning was 59 (6) bpm (range 44–69). 1773/1803 coronary segments (98%) were depicted with a diagnostic image quality in 109/120 patients (91%). The overall patient-based sensitivity, specificity, PPV and NPV for the diagnosis of significant stenoses were 100%, 93%, 94% and 100%, respectively. The mean (SD) effective dose of the CT protocol was 2.5 (0.8) mSv (range 1.2–4.4). Conclusions: DSCT coronary angiography in the SAS mode allows, in selected patients with a regular heart rate, the accurate diagnosis of significant coronary stenoses at a low radiation dose.

Dual-source CT in step-and-shoot mode: noninvasive coronary angiography with low radiation dose.

PURPOSE To prospectively investigate computed tomographic (CT) image quality parameters by using different protocols and to calculate radiation dose estimates for noninvasive coronary angiography performed with dual-source CT in the step-and-shoot (SAS) mode. MATERIALS AND METHODS This study was local ethics board approved; written informed consent was obtained from all patients. In the preliminary portion of the study, 40 patients underwent CT coronary angiography in the SAS mode: at 100 kV (protocol A) in 22 patients with a body mass index (BMI) of less than 25 kg/m(2) and at 120 kV (protocol B) in 18 patients with a BMI of 25-30 kg/m(2). Both protocols involved use of an attenuation-based tube current and 1 mL of contrast material per kilogram of body weight. The final portion of the study involved 50 additional patients: 21 patients with a BMI of 25-30 kg/cm(2) assigned to protocol B and 29 patients with a BMI of less than 25 kg/cm(2) assigned to protocol C, which was performed with 100 kV, an attenuation-based tube current, and a reduced contrast material dose of 0.8 mL/kg. Image quality was independently assessed. Attenuation in the aorta and coronary arteries and image noise were measured. Radiation dose was estimated. RESULTS Mean image noise was similar with protocols A and B. Mean attenuation in the aorta and coronary arteries with protocol A (444 HU) was significantly (P < .001) higher than that with protocol B (358 HU). The reduced contrast material dose in protocol C yielded attenuation similar to that with protocol B. Diagnostic image quality was achieved with all protocols in 1237 (97.9%) of 1264 coronary segments. No significant differences in image quality between the 100- and 120-kV protocols were found. Mean heart rate had a significant effect on motion artifacts (area under receiver operating characteristic curve [AUC] = 0.818; 95% confidence interval [CI]: 0.723, 0.892; P < .001), whereas heart rate variability had a significant effect on stair-step artifacts (AUC = 0.79; 95% CI: 0.687, 0.865; P < .001). The mean estimated effective dose was 1.2 mSv +/- 0.2 for protocols A and C and 2.6 mSv +/- 0.5 for protocol B. CONCLUSION Dual-source SAS-mode CT coronary angiography yielded diagnostic image quality for 97.9% of coronary segments at a low radiation dose.

Multislice Computed Tomography in Infective Endocarditis Comparison With Transesophageal Echocardiography and Intraoperative Findings

OBJECTIVES The aim of this study was to assess the value of multislice computed tomography (CT) for the assessment of valvular abnormalities in patients with infective endocarditis (IE) in comparison with transesophageal echocardiography (TEE) and intraoperative findings. BACKGROUND Multislice CT has recently shown promising data regarding valvular imaging in a 4-dimensional fashion. METHODS Thirty-seven consecutive patients with clinically suspected IE were examined with TEE and 64-slice CT or dual-source CT. Twenty-nine patients had definite IE and underwent surgery. RESULTS The diagnostic performance of CT for the detection of evident valvular abnormalities for IE compared with TEE was: sensitivity 97%, specificity 88%, positive predictive value (PPV) 97%, and negative predictive value (NPV) 88% on a per-patient basis (n = 37; excellent intermodality agreement kappa = 0.84). CT correctly identified 26 of 27 (96%) patients with valvular vegetations and 9 of 9 (100%) patients with abscesses/pseudoaneurysms compared with the intraoperative specimen. On a per-valve-based analysis, diagnostic accuracy for the detection of vegetations and abscesses/pseudoaneurysms compared with surgery was: sensitivity 96%, specificity 97%, PPV 96%, NPV 97%, and sensitivity 100%, specificity 100%, PPV 100%, NPV 100%, respectively, without significant differences as compared with TEE. Vegetation size measurements by CT correlated (r = 0.95; p <0.001) with TEE (mean 7.6 +/- 5.6 mm). The mobility of vegetations was accurately diagnosed in 21 of 22 (96%) patients with CT, but all of 4 leaflet perforations (<or=2 mm) were missed. CT provided more accurate anatomic information regarding perivalvular extent of abscess/pseudoaneurysms than TEE. CONCLUSIONS Multislice CT shows good results in detecting valvular abnormalities in IE and could be applied in pre-operative planning and exclusion of coronary artery disease before surgery.

Cardiac Image Fusion from Stand-Alone SPECT and CT: Clinical Experience

Myocardial perfusion imaging with SPECT (SPECT-MPI) and 64-slice CT angiography (CTA) are both established techniques for the noninvasive evaluation of coronary artery disease (CAD). Three-dimensional (3D) SPECT/CT image fusion may offer an incremental diagnostic value by integrating both sets of information. We report our first clinical experiences with fused 3D SPECT/CT in CAD patients. Methods: Thirty-eight consecutive patients with at least 1 perfusion defect on SPECT-MPI (1-d adenosine stress/rest SPECT with 99mTc-tetrofosmin) and 64-slice CTA were included. 3D volume-rendered fused SPECT/CT images were generated and compared with the findings from the side-by-side analysis with regard to coronary lesion interpretation by assigning the perfusion defects to their corresponding coronary lesion. Results: The fused SPECT/CT images added information on pathophysiologic lesion severity in 27 coronary stenoses (22%) of 12 patients (29%) (P < 0.001). Among 40 equivocal lesions on side-by-side analysis, the fused interpretation confirmed hemodynamic significance in 14 lesions and excluded functional relevance in 10 lesions. In 3 lesions, assignment of perfusion defect and coronary lesion appeared to be reliable on side-by-side analysis but proved to be inaccurate on fused interpretation. Added diagnostic information by SPECT/CT was more commonly found in patients with stenoses of small vessels (P = 0.004) and involvement of diagonal branches (P = 0.01). Conclusion: In addition to being intuitively convincing, 3D SPECT/CT fusion images in CAD may provide added diagnostic information on the functional relevance of coronary artery lesions.

Functionally Relevant Coronary Artery Disease: Comparison of 64-Section CT Angiography with Myocardial Perfusion SPECT

PURPOSE To prospectively determine the accuracy of 64-section computed tomographic (CT) angiography for the depiction of coronary artery disease (CAD) that induces perfusion defects at myocardial perfusion imaging with single photon emission computed tomography (SPECT), by using myocardial perfusion imaging as the reference standard. MATERIALS AND METHODS All patients gave written informed consent after the study details, including radiation exposure, were explained. The study protocol was approved by the local institutional review board. In patients referred for elective conventional coronary angiography, an additional 64-section CT angiography study and a myocardial perfusion imaging study (1-day adenosine stress-rest protocol) with technetium 99m-tetrofosmin SPECT were performed before conventional angiography. Coronary artery diameter narrowing of 50% or greater at CT angiography was defined as stenosis and was compared with the myocardial perfusion imaging findings. Quantitative coronary angiography served as a reference standard for CT angiography. RESULTS A total of 1093 coronary segments in 310 coronary arteries in 78 patients (mean age, 65 years +/- 9 [standard deviation]; 35 women) were analyzed. CT angiography revealed stenoses in 137 segments (13%) corresponding to 91 arteries (29%) in 46 patients (59%). SPECT revealed 14 reversible, 13 fixed, and six partially reversible defects in 31 patients (40%). Sensitivity, specificity, and negative and positive predictive values, respectively, of CT angiography in the detection of reversible myocardial perfusion imaging defects were 95%, 53%, 94%, and 58% on a per-patient basis and 95%, 75%, 96%, and 72% on a per-artery basis. Agreement between CT and conventional angiography was very good (96% and kappa = 0.92 for patient-based analysis, 93% and kappa = 0.84 for vessel-based analysis). CONCLUSION Sixty-four-section CT angiography can help rule out hemodynamically relevant CAD in patients with intermediate to high pretest likelihood, although an abnormal CT angiography study is a poor predictor of ischemia.

Dual-Source CT Coronary Angiography: Image Quality, Mean Heart Rate, and Heart Rate Variability

OBJECTIVE The purpose of this study was to evaluate the effect of mean heart rate and heart rate variability on the image quality of dual-source CT coronary angiography. SUBJECTS AND METHODS Eighty patients underwent dual-source CT coronary angiography. Thirteen data sets were reconstructed in 5% steps from 20-80% of the R-R interval. Heart rate variability was calculated as SD of mean heart rate. Two independent blinded reviewers assessed the image quality of each segment. RESULTS Mean heart rate was 65.3 +/- 13.9 (SD) beats per minute (bpm) (range, 35-99 bpm) with a variability of 3.4 +/- 4.1 bpm (range, 0.4-17.5 bpm). Image quality was sufficient for diagnosis for 97.8% (1,043/1,066) of arterial segments. No significant correlation was found between mean heart rate and image quality in any segment or any coronary artery. No significant correlation was found between heart rate variability and image quality in any segment, the right coronary artery, or the left anterior descending artery, but there was a significant (p < 0.05) correlation in the left circumflex artery. A significant correlation (p < 0.05) between overall image quality was found for mean and variability of heart rate as shared predictors, the latter having a greater contribution. CONCLUSION The overall image quality of dual-source CT coronary angiography is sufficient for diagnosis within a wide range of mean heart rates and variability of heart rates. Only heart rates that are both high and variable significantly deteriorate image quality, but the quality remains adequate for diagnosis.

Endoleaks after endovascular abdominal aortic aneurysm repair: detection with dual-energy dual-source CT.

PURPOSE To assess the diagnostic performance of dual-energy dual-source computed tomography (CT) in the detection of endoleaks after endovascular abdominal aortic aneurysm (AAA) repair. MATERIALS AND METHODS This study was local ethics board approved, and written informed consent was obtained from all patients. One hundred eighteen patients (21 women, 97 men; mean age, 74 years +/- 8 [standard deviation]) underwent follow-up dual-energy dual-source CT during the nonenhanced, arterial, and delayed phases after AAA repair. Delayed phase CT images were acquired in the dual-energy mode for reconstruction of virtual nonenhanced images. Two blinded and independent readers evaluated the data for the presence or absence of endoleaks during three reading sessions: Standard nonenhanced, arterial phase, and delayed phase images were read during session A; virtual nonenhanced, arterial phase, and delayed phase images, during session B; and virtual nonenhanced and delayed phase images, during session C. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were calculated, with the session A image data set as the reference standard. Radiation dose parameters were estimated. RESULTS Reading session A revealed that 52 (44%) of 118 patients had endoleaks. Overall sensitivity, specificity, NPV, and PPV for CT endoleak detection during sessions B and C were identical: 100%, 97%, 100%, and 96%, respectively. The accuracy of the session B and session C readings was not significantly different from that of the session A reading (P = .50). The effective radiation dose in the image acquisition protocol involving one dual-energy scan was significantly (P < .001) lower than the effective doses in the protocols involving standard triple-phase scanning (mean difference, 61%) and standard nonenhanced and delayed phase scanning (mean difference, 41%). CONCLUSION Compared with standard protocols, one dual-energy dual-source CT scan performed during the delayed phase with reconstruction of virtual nonenhanced images enables detection of endoleaks after endovascular AAA repair with high accuracy and a considerably lower radiation dose.

Image quality and reconstruction intervals of dual-source CT coronary angiography: recommendations for ECG-pulsing windowing.

Purpose:To evaluate reconstruction intervals and image quality in dual-source computed tomography (DSCT) coronary angiography for optimal placement of the ECG-pulsing window. Materials and Methods:DSCT coronary angiography was performed in 60 patients. Thirteen datasets were reconstructed in 5% increments from 20–80%. Two readers independently assessed image quality of each segment in each percentage-interval, using scores ranging from 1 (no motion artifacts) to 4 (nonevaluable). Results:Mean heart rate (HR) was 69.0 ± 18.9 beats per minute (bpm) (range, 35–117 bpm). Diagnostic image quality (scores 1–3) was found in 97.8% of all segments (763 of 780). The 70% RR-interval provided best image quality in all patients and all HRs. The narrowest reconstruction window providing diagnostic image quality was 60–70% for HR <60 bpm, 60–80% for 60–70 bpm, 55–80% for 70–80 bpm, and 30–80% for HR >80 bpm. Conclusions:DSCT coronary angiography provides best image quality for various HRs at 70%. The ECG-pulsing window can be adapted according to the HR while maintaining diagnostic image quality.

Dual-source computed tomography coronary angiography: influence of obesity, calcium load, and heart rate on diagnostic accuracy

AIMS To prospectively investigate the diagnostic accuracy of dual-source computed tomography coronary angiography (CTCA) to diagnose coronary stenoses in relation to body mass index (BMI), Agatston score (AS), and heart rate (HR) as compared with catheter coronary angiography (CCA). METHODS AND RESULTS Hundred and fifty consecutive patients (47 female, mean age 62.9 +/- 12.1 years) underwent dual-source CTCA without HR control. Patients were divided into subgroups depending on the median of their BMI (26.0 kg/m2), AS (194), and HR (66 b.p.m.). CCA was considered the standard of reference. Mean BMI was 26.5 +/- 4.2 kg/m2 (range 18.3-39.1 kg/m2), mean AS was 309 +/- 408 (range 0-4387), and HR was 68.5 +/- 12.6 b.p.m. (range 35-102 b.p.m.). Diagnostic image quality was found in 98.1% of all segments (2020/2059). Considering not-evaluative segments at CTCA as false-positive, overall per-patient sensitivity, specificity, positive, and negative predictive value were 96.6%, 86.8%, 82.6%, and 97.5%, respectively. High HR did not deteriorate diagnostic accuracy of CTCA. High BMI and AS were associated with a decrease in per-patient specificity to 84.1% and 77.8%, respectively, while sensitivity and negative predictive value remained high. CONCLUSION Dual-source CTCA provides high diagnostic accuracy irrespective of the HR and serves as a modality to rule-out coronary artery stenoses even in patients with high BMI and AS.