Validation of a Three-Dimensional Computed Tomography Reconstruction Tool for Aortic Valve Calcium Quantification.

Background: Aortic valve calcification correlates with the severity of aortic valve stenosis and a high calcium score is associated with conduction disturbances and paravalvular leakage after transcatheter aortic valve replacement. The 3mensio Structural Heart is a semiautomated software package to facilitate aortic root analysis by multislice computed tomography.The aim of the contemporary study is to validate a semiautomated calcium quantification scoring tool with a conventional manual calcium quantification tool. Methods: Fifty randomly selected patients who underwent multislice computed tomography for preprocedural planning were retrospectively selected to compare the semiautomated aortic valve Agatston calcium score by 3mensio with the manually obtained score using IntelliSpace Portal as standard reference. Results: Patients had a mean age of 76.7 ± 7.4 years and 60% were male. The median Agatston score was 3390 [interquartile range 1877-4509] with 3mensio and 3434 [interquartile range 1839-4620] with IntelliSpace.The mean difference was -0.18 [95% confidence interval (CI) -53.8 to 53.4]. The intraclass correlation coefficient between the Agatston scores using IntelliSpace and 3mensio showed an excellent correlation of 0.995 [95% CI 0.992-0.997], p ≤ 0.001. The interobserver and intraobserver variability was 0.993 ([95% CI 0.961-0.998], p ≤ 0.001) and 0.995([95%CI 0.981-0.999], p = <0.001), respectively. Conclusions: The semiautomated calcium quantification module in 3mensio Structural Heart highly correlated with a conventional manual calcium scoring tool.

Hospital implementation of minimally invasive autopsy: A prospective cohort study of clinical performance and costs.

OBJECTIVES: Autopsy rates worldwide have dropped significantly over the last decades and imaging-based autopsies are increasingly used as an alternative to conventional autopsy. Our aim was to evaluate the clinical performance and cost of minimally invasive autopsy. METHODS: This study was part of a prospective cohort study evaluating a newly implemented minimally invasive autopsy consisting of MRI, CT, and biopsies. We calculated diagnostic yield and clinical utility-defined as the percentage successfully answered clinical questions-of minimally invasive autopsy. We performed minimally invasive autopsy in 46 deceased (30 men, 16 women; mean age 62.9±17.5, min-max: 18-91). RESULTS: Ninety-six major diagnoses were found with the minimally invasive autopsy of which 47/96 (49.0%) were new diagnoses. CT found 65/96 (67.7%) major diagnoses and MRI found 82/96 (85.4%) major diagnoses. Eighty-four clinical questions were asked in all cases. Seventy-one (84.5%) of these questions could be answered with minimally invasive autopsy. CT successfully answered 34/84 (40.5%) clinical questions; in 23/84 (27.4%) without the need for biopsies, and in 11/84 (13.0%) a biopsy was required. MRI successfully answered 60/84 (71.4%) clinical questions, in 27/84 (32.1%) without the need for biopsies, and in 33/84 (39.8%) a biopsy was required. The mean cost of a minimally invasive autopsy was €1296 including brain biopsies and €1087 without brain biopsies. Mean cost of CT was €187 and of MRI €284. CONCLUSIONS: A minimally invasive autopsy, consisting of CT, MRI and CT-guided biopsies, performs well in answering clinical questions and detecting major diagnoses. However, the diagnostic yield and clinical utility were quite low for postmortem CT and MRI as standalone modalities.

Conventional Autopsy versus Minimally Invasive Autopsy with Postmortem MRI, CT, and CT-guided Biopsy: Comparison of Diagnostic Performance.

Purpose To compare the diagnostic performance of minimally invasive autopsy with that of conventional autopsy. Materials and Methods For this prospective, single-center, cross-sectional study in an academic hospital, 295 of 2197 adult cadavers (mean age: 65 years [range, 18-99 years]; age range of male cadavers: 18-99 years; age range of female cadavers: 18-98 years) who died from 2012 through 2014 underwent conventional autopsy. Family consent for minimally invasive autopsy was obtained for 139 of the 295 cadavers; 99 of those 139 cadavers were included in this study. Those involved in minimally invasive autopsy and conventional autopsy were blinded to each other's findings. The minimally invasive autopsy procedure combined postmortem MRI, CT, and CT-guided biopsy of main organs and pathologic lesions. The primary outcome measure was performance of minimally invasive autopsy and conventional autopsy in establishing immediate cause of death, as compared with consensus cause of death. The secondary outcome measures were diagnostic yield of minimally invasive autopsy and conventional autopsy for all, major, and grouped major diagnoses; frequency of clinically unsuspected findings; and percentage of answered clinical questions. Results Cause of death determined with minimally invasive autopsy and conventional autopsy agreed in 91 of the 99 cadavers (92%). Agreement with consensus cause of death occurred in 96 of 99 cadavers (97%) with minimally invasive autopsy and in 94 of 99 cadavers (95%) with conventional autopsy (P = .73). All 288 grouped major diagnoses were related to consensus cause of death. Minimally invasive autopsy enabled diagnosis of 259 of them (90%) and conventional autopsy 224 (78%); 200 (69%) were found with both methods. At clinical examination, the cause of death was not suspected in 17 of the 99 cadavers (17%), and 124 of 288 grouped major diagnoses (43%) were not established. There were 219 additional clinical questions; 189 (86%) were answered with minimally invasive autopsy and 182 (83%) were answered with conventional autopsy (P = .35). Conclusion The performance of minimally invasive autopsy in the detection of cause of death was similar to that of conventional autopsy; however, minimally invasive autopsy has a higher yield of diagnoses. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Krombach in this issue.

Diagnostic accuracy of postmortem computed tomography, magnetic resonance imaging, and computed tomography-guided biopsies for the detection of ischaemic heart disease in a hospital setting.

Aims: The autopsy rate worldwide is alarmingly low (0-15%). Mortality statistics are important, and it is, therefore, essential to perform autopsies in a sufficient proportion of deaths. The imaging autopsy, non-invasive, or minimally invasive autopsy (MIA) can be used as an alternative to the conventional autopsy in an attempt to improve postmortem diagnostics by increasing the number of postmortem procedures. The aim of this study was to determine the diagnostic accuracy of postmortem magnetic resonance imaging (MRI), computed tomography (CT), and CT-guided biopsy for the detection of acute and chronic myocardial ischaemia. Methods and results: We included 100 consecutive adult patients who died in hospital, and for whom next-of-kin gave permission to perform both conventional autopsy and MIA. The MIA consists of unenhanced total-body MRI and CT followed by CT-guided biopsies. Conventional autopsy was used as reference standard. We calculated sensitivity and specificity and receiver operating characteristics curves for CT and MRI as the stand-alone test or combined with biopsy for detection of acute and chronic myocardial infarction (MI). Sensitivity and specificity of MRI with biopsies for acute MI was 0.97 and 0.95, respectively and 0.90 and 0.75, respectively for chronic MI. MRI without biopsies showed a high specificity (acute: 0.92; chronic: 1.00), but low sensitivity (acute: 0.50; chronic: 0.35). CT (total Agatston calcium score) had a good diagnostic value for chronic MI [area under curve (AUC) 0.74, 95% confidence interval (CI) 0.64-0.84], but not for acute MI (AUC 0.60, 95% CI 0.48-0.72). Conclusion: We found that the combination of MRI with biopsies had high sensitivity and specificity for the detection of acute and chronic myocardial ischaemia.

Total-body CT and MR features of postmortem change in in-hospital deaths.

OBJECTIVES: To evaluate the frequency of total-body CT and MR features of postmortem change in in-hospital deaths. MATERIALS AND METHODS: In this prospective blinded cross-sectional study, in-hospital deceased adult patients underwent total-body postmortem CT and MR followed by image-guided biopsies. The presence of PMCT and PMMR features related to postmortem change was scored retrospectively and correlated with postmortem time interval, post-resuscitation status and intensive care unit (ICU) admittance. RESULTS: Intravascular air, pleural effusion, periportal edema, and distended intestines occurred more frequently in patients who were resuscitated compared to those who were not. Postmortem clotting was seen less often in resuscitated patients (p = 0.002). Distended intestines and loss of grey-white matter differentiation in the brain showed a significant correlation with postmortem time interval (p = 0.001, p<0.001). Hyperdense cerebral vessels, intravenous clotting, subcutaneous edema, fluid in the abdomen and internal livores of the liver were seen more in ICU patients. Longer postmortem time interval led to a significant increase in decomposition related changes (p = 0.026). CONCLUSIONS: There is a wide variety of imaging features of postmortem change in in-hospital deaths. These imaging features vary among clinical conditions, increase with longer postmortem time interval and must be distinguished from pathologic changes.

Autopsy rates in the Netherlands: 35 years of decline.

OBJECTIVE: Although the autopsy still is a valuable tool in health statistics, health care quality control, medical education, and biomedical research, autopsy rates have been declining worldwide. The aim of this study was to examine trends of overall, clinical and forensic autopsy rates among adults in the Netherlands over the last four decades, and trends per sex, age (groups), and hospital type. METHODS: We performed a retrospective study covering 35 years of Dutch national death counts (1977-2011), the number of in-hospital deceased patients, the number of deaths due to external causes, and the proportion of autopsies performed in these populations. The effects of sex, age and hospital category were analysed by linear and logistic regression and differences were evaluated by chi-square tests. RESULTS: Overall autopsy rates declined by 0.3% per calendar year, clinical autopsy rates by 0.7% per calendar year (from 31.4% to 7.7%), and forensic autopsy rates did not decline. Per calendar year the fraction of in-hospital deceased patients decreased by 0.2%. Autopsy rates were highest among men and younger patients; clinical autopsy rates were highest for patients dying in academic hospitals. CONCLUSIONS: In the Netherlands clinical autopsy rates have rapidly declined while at the same time the fraction of in-hospital deaths decreased, both contributing to the overall reduced absolute number of autopsies performed. It is important to improve awareness among both clinicians and general practitioners of the significance of the clinical autopsy.

Autopsy of Adult Patients Deceased in an Academic Hospital: Considerations of Doctors and Next-of-Kin in the Consent Process.

INTRODUCTION: Hospital autopsies, vanishing worldwide, need to be requested by clinicians and consented to by next-of-kin. The aim of this prospective observational study was to examine how often and why clinicians do not request an autopsy, and for what reasons next-of-kin allow, or refuse it. METHODS: Clinicians at the Erasmus University Medical Centre were asked to complete a questionnaire when an adult patient had died. Questionnaires on 1000 consecutive naturally deceased adults were collected. If possible, missing data in the questionnaires were retrieved from the electronic patient record. RESULTS: Data from 958 (96%) questionnaires was available for analysis. In 167/958 (17·4%) cases clinicians did not request an autopsy, and in 641/791 (81·0%) cases next-of-kin did not give consent. The most important reason for both clinicians (51·5%) and next-of-kin (51·0%) to not request or consent to an autopsy was an assumed known cause of death. Their second reason was that the deceased had gone through a long illness (9·6% and 29·5%). The third reason for next-of-kin was mutilation of the deceased's body by the autopsy procedure (16·1%). Autopsy rates were highest among patients aged 30-39 years, Europeans, suddenly and/or unexpectedly deceased patients, and tissue and/or organ donors. The intensive care and emergency units achieved the highest autopsy rates, and surgical wards the lowest. CONCLUSION: The main reason for not requesting or allowing an autopsy is the assumption that the cause of death is known. This is a dangerous premise, because it is a self-fulfilling prophecy. Clinicians should be aware, and communicate with the next of kin, that autopsies not infrequently disclose unexpected findings, which might have changed patient management. Mutilation of the deceased's body seems a minor consideration of next-of-kin, though how it really affects autopsy rates, should be studied by offering minimally or non-invasive autopsy methods.

Non-invasive or minimally invasive autopsy compared to conventional autopsy of suspected natural deaths in adults: a systematic review.

OBJECTIVES: Autopsies are used for healthcare quality control and improving medical knowledge. Because autopsy rates are declining worldwide, various non-invasive or minimally invasive autopsy methods are now being developed. To investigate whether these might replace the invasive autopsies conventionally performed in naturally deceased adults, we systematically reviewed original prospective validation studies. MATERIALS AND METHODS: We searched six databases. Two reviewers independently selected articles and extracted data. Methods and patient groups were too heterogeneous for meaningful meta-analysis of outcomes. RESULTS: Sixteen of 1538 articles met our inclusion criteria. Eight studies used a blinded comparison; ten included less than 30 appropriate cases. Thirteen studies used radiological imaging (seven dealt solely with non-invasive procedures), two thoracoscopy and laparoscopy, and one sampling without imaging. Combining CT and MR was the best non-invasive method (agreement for cause of death: 70 %, 95%CI: 62.6; 76.4), but minimally invasive methods surpassed non-invasive methods. The highest sensitivity for cause of death (90.9 %, 95%CI: 74.5; 97.6, suspected duplicates excluded) was achieved in recent studies combining CT, CT-angiography and biopsies. CONCLUSION: Minimally invasive autopsies including biopsies performed best. To establish a feasible alternative to conventional autopsy and to increase consent to post-mortem investigations, further research in larger study groups is needed. KEY POINTS: • Health care quality control benefits from clinical feedback provided by (alternative) autopsies. • So far, sixteen studies investigated alternative autopsy methods for naturally deceased adults. • Thirteen studies used radiological imaging modalities, eight tissue biopsies, and three CT-angiography. • Combined CT, CT-angiography and biopsies were most sensitive diagnosing cause of death.

Post-mortem tissue biopsies obtained at minimally invasive autopsy: an RNA-quality analysis.

INTRODUCTION: Bereaved relatives often refuse to give consent for post-mortem investigation of deceased cancer patients, mainly because of the mutilation due to conventional autopsy (CA). Minimally invasive autopsy (MIA) may be a more acceptable alternative and, if implemented in clinical practice, creates an opportunity to more often obtain post-mortem tissue samples of (recurred) primary tumors and metastases for molecular research. As a measure for tissue quality for molecular studies, we hereby present a feasibility study, comparing the RNA quality of MIA and CA samples, and fresh frozen samples as reference. MATERIALS AND METHODS: Tissue samples of heart, liver and kidney were prospectively collected from 24 MIAs followed by CA, and compared to corresponding archival fresh frozen tissue. After RNA isolation and RT-qPCR, RNA integrity numbers (RIN) and GAPDH expression (six amplicon sizes ranging from 71 to 530 base pairs) were measured. RIN values and GAPDH Cq values were analyzed and compared between all sample groups and post-mortem intervals (PMI). RESULTS: RIN values in MIA samples were significantly higher than those in CA samples. GAPDH was expressed significantly higher in MIA samples than in CA samples and 530 bp PCR products could be measured in all cases. GAPDH expression was significantly lower in samples with PMI >15 hours. As expected, the samples of the fresh frozen reference standard performed best in all analyses. CONCLUSION: MIA samples showed better RNA quality than CA samples, probably due to shorter PMI. Both had lower RNA quality and expression levels than fresh frozen tissue, however, remaining GAPDH RNA was still sufficiently intact. Therefore, other highly expressed genes are most likely also detectable. Gene array analysis should be performed to gain insight into the quality of entire post-mortem genomes. Reducing PMI will further improve the feasibility of demanding molecular research on post-mortem tissues, this is most likely more feasible with MIA than CA.

Diagnostic performance of computed tomography coronary angiography to detect and exclude left main and/or three-vessel coronary artery disease.

OBJECTIVES: To determine the diagnostic performance of CT coronary angiography (CTCA) in detecting and excluding left main (LM) and/or three-vessel CAD ("high-risk" CAD) in symptomatic patients and to compare its discriminatory value with the Duke risk score and calcium score. MATERIALS AND METHODS: Between 2004 and 2011, a total of 1,159 symptomatic patients (61 ± 11 years, 31 % women) with stable angina, without prior revascularisation underwent both invasive coronary angiography (ICA) and CTCA. All patients gave written informed consent for the additional CTCA. High-risk CAD was defined as LM and/or three-vessel obstructive CAD (≥50 % diameter stenosis). RESULTS: A total of 197 (17 %) patients had high-risk CAD as determined by ICA. The sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratios of CTCA were 95 % (95 % CI 91-97 %), 83 % (80-85 %), 53 % (48-58 %), 99 % (98-99 %), 5.47 and 0.06, respectively. CTCA provided incremental value (AUC 0.90, P < 0.001) in the discrimination of high-risk CAD compared with the Duke risk score and calcium score. CONCLUSIONS: CTCA accurately excludes high-risk CAD in symptomatic patients. The detection of high-risk CAD is suboptimal owing to the high percentage (47 %) of overestimation of high-risk CAD. CTCA provides incremental value in the discrimination of high-risk CAD compared with the Duke risk score and calcium score. KEY POINTS: • Computed tomography coronary angiography (CTCA) accurately excludes high-risk coronary artery disease. • CTCA overestimates high-risk coronary artery disease in 47 %. • CTCA discriminates high-risk CAD better than clinical evaluation and coronary calcification.

Restriction of the referral of patients with stable angina for CT coronary angiography by clinical evaluation and calcium score: impact on clinical decision making.

OBJECTIVE: To investigate the value of the calcium score (CaSc) plus clinical evaluation to restrict referral for CT coronary angiography (CTCA) by reducing the number of patients with an intermediate probability of coronary artery disease (CAD). METHODS: We retrospectively included 1,975 symptomatic stable patients who underwent clinical evaluation and CaSc calculation and CTCA or invasive coronary coronary angiography (ICA). The outcome was obstructive CAD (≥50 % diameter narrowing) assessed by ICA or CTCA in the absence of ICA. We investigated two models: (1) clinical evaluation consisting of chest pain typicality, gender, age, risk factors and ECG and (2) clinical evaluation with CaSc. Discrimination of the two models was compared. The stepwise reclassification of patients with an intermediate probability of CAD (10-90 %) after clinical evaluation followed by clinical evaluation with CaSc was assessed by clinical net reclassification improvement (NRI). RESULTS: Discrimination of CAD was significantly improved by adding CaSc to the clinical evaluation (AUC: 0.80 vs. 0.89, P < 0.001). CaSc and CTCA could be avoided in 9 % using model 1 and an additional 29 % of CTCAs could be avoided using model 2. Clinical NRI was 57 %. CONCLUSION: CaSc plus clinical evaluation may be useful in restricting further referral for CTCA by 38 % in symptomatic stable patients with suspected CAD. KEY POINTS: • CT calcium scores (CaSc) could proiritise referrals for CT coronary angiography (CTCA) • CaSc provides an incremental discriminatory value of CAD compared with clinical evaluation • Risk stratification is better when clinical evaluation is combined with CaSc • Appropriate use of clinical evaluation and CaSc helps avoid unnecessary CTCA referrals.

Vessel specific coronary artery calcium scoring: an automatic system.

RATIONALE AND OBJECTIVES: The aim of this study was to automatically detect and quantify calcium lesions for the whole heart as well as per coronary artery on non-contrast-enhanced cardiac computed tomographic images. MATERIALS AND METHODS: Imaging data from 366 patients were randomly selected from patients who underwent computed tomographic calcium scoring assessments between July 2004 and May 2009 at Erasmum MC, Rotterdam. These data included data sets with 1.5-mm and 3.0-mm slice spacing reconstructions and were acquired using four different scanners. The scores of manual observers, who annotated the data using commercially available software, served as ground truth. An automatic method for detecting and quantifying calcifications for each of the four main coronary arteries and the whole heart was trained on 209 data sets and tested on 157 data sets. Statistical testing included determining Pearson's correlation coefficients and Bland-Altman analysis to compare performance between the system and ground truth. Wilcoxon's signed-rank test was used to compare the interobserver variability to the system's performance. RESULTS: Automatic detection of calcified objects was achieved with sensitivity of 81.2% per calcified object in the 1.5-mm data set and sensitivity of 86.6% per calcified object in the 3.0-mm data set. The system made an average of 2.5 errors per patient in the 1.5-mm data set and 2.2 errors in the 3.0-mm data set. Pearson's correlation coefficients of 0.97 (P < .001) for both 1.5-mm and 3.0-mm scans with respect to the calcium volume score of the whole heart were found. The average R values over Agatston, mass, and volume scores for each of the arteries (left circumflex coronary artery, right coronary artery, and left main and left anterior descending coronary arteries) were 0.93, 0.96, and 0.99, respectively, for the 1.5-mm scans. Similarly, for 3.0-mm scans, R values were 0.94, 0.94, and 0.99, respectively. Risk category assignment was correct in 95% and 89% of the data sets in the 1.5-mm and 3-mm scans. CONCLUSIONS: An automatic vessel-specific coronary artery calcium scoring system was developed, and its feasibility for calcium scoring in individual vessels and risk category classification has been demonstrated.

Diagnostic accuracy of 128-slice dual-source CT coronary angiography: a randomized comparison of different acquisition protocols.

OBJECTIVES: To compare the diagnostic performance and radiation exposure of 128-slice dual-source CT coronary angiography (CTCA) protocols to detect coronary stenosis with more than 50 % lumen obstruction. METHODS: We prospectively included 459 symptomatic patients referred for CTCA. Patients were randomized between high-pitch spiral vs. narrow-window sequential CTCA protocols (heart rate below 65 bpm, group A), or between wide-window sequential vs. retrospective spiral protocols (heart rate above 65 bpm, group B). Diagnostic performance of CTCA was compared with quantitative coronary angiography in 267 patients. RESULTS: In group A (231 patients, 146 men, mean heart rate 58 ± 7 bpm), high-pitch spiral CTCA yielded a lower per-segment sensitivity compared to sequential CTCA (89 % vs. 97 %, P = 0.01). Specificity, PPV and NPV were comparable (95 %, 62 %, 99 % vs. 96 %, 73 %, 100 %, P > 0.05) but radiation dose was lower (1.16 ± 0.60 vs. 3.82 ± 1.65 mSv, P < 0.001). In group B (228 patients, 132 men, mean heart rate 75 ± 11 bpm), per-segment sensitivity, specificity, PPV and NPV were comparable (94 %, 95 %, 67 %, 99 % vs. 92 %, 95 %, 66 %, 99 %, P > 0.05). Radiation dose of sequential CTCA was lower compared to retrospective CTCA (6.12 ± 2.58 vs. 8.13 ± 4.52 mSv, P < 0.001). Diagnostic performance was comparable in both groups. CONCLUSION: Sequential CTCA should be used in patients with regular heart rates using 128-slice dual-source CT, providing optimal diagnostic accuracy with as low as reasonably achievable (ALARA) radiation dose.

Computed tomography coronary angiography accuracy in women and men at low to intermediate risk of coronary artery disease.

OBJECTIVES: To investigate the diagnostic accuracy of CT coronary angiography (CTCA) in women at low to intermediate pre-test probability of coronary artery disease (CAD) compared with men. METHODS: In this retrospective study we included symptomatic patients with low to intermediate risk who underwent both invasive coronary angiography and CTCA. Exclusion criteria were previous revascularisation or myocardial infarction. The pre-test probability of CAD was estimated using the Duke risk score. Thresholds of less than 30 % and 30-90 % were used for determining low and intermediate risk, respectively. The diagnostic accuracy of CTCA in detecting obstructive CAD (≥50 % lumen diameter narrowing) was calculated on patient level. P < 0.05 was considered significant. RESULTS: A total of 570 patients (46 % women [262/570]) were included and stratified as low (women 73 % [80/109]) and intermediate risk (women 39 % [182/461]). Sensitivity, specificity, PPV and NPV were not significantly different in and between women and men at low and intermediate risk. For women vs. men at low risk they were 97 % vs. 100 %, 79 % vs. 90 %, 80 % vs. 80 % and 97 % vs. 100 %, respectively. For intermediate risk they were 99 % vs. 99 %, 72 % vs. 83 %, 88 % vs. 93 % and 98 % vs. 99 %, respectively. CONCLUSION: CTCA has similar diagnostic accuracy in women and men at low and intermediate risk. KEY POINTS : • Coronary artery disease (CAD) is increasingly investigated by computed tomography angiography (CTCA). • CAD detection or exclusion by CTCA is not different between sexes. • CTCA diagnostic accuracy was similar between low and intermediate risk sex-specific-groups. • CTCA rarely misses obstructive CAD in low-intermediate risk women and men. • CAD yield by invasive coronary angiography after positive CTCA is similar between sex-risk-specific groups.

Major adverse cardiac events and the severity of coronary atherosclerosis assessed by computed tomography coronary angiography in an outpatient population with suspected or known coronary artery disease.

PURPOSE: To investigate the predictive value of 64-slice computed tomography coronary angiography (CTCA) for major adverse cardiac events (MACEs) in patients with suspected or known coronary artery disease (CAD). MATERIALS AND METHODS: Seven hundred and sixty-seven consecutive patients (496 men, age 62±11 y) with suspected or known heart disease referred to an outpatient clinic underwent 64-slice CTCA. The patients were followed for the occurrence of MACE (ie, cardiac death, nonfatal myocardial infarction, unstable angina). RESULTS: Eleven thousand five hundred and sixty-four coronary segments were assessed. Of these, 178 (1.5%) were not assessable because of insufficient image quality. Overall, CTCA revealed the absence of CAD in 219 (28.5%) patients, nonobstructive CAD (coronary plaque ≤50%) in 282 (36.8%) patients, and obstructive CAD in 266 (34.7%) patients. A total of 21 major cardiac events (4 cardiac deaths, 12 myocardial infarctions, and 5 unstable angina) occurred during a mean follow-up of 20 months. One noncardiac death occurred. Seventeen events occurred in the group of patients with obstructive CAD, and 4 events occurred in the group with nonobstructive CAD. The event rate was 0% among patients with normal coronary arteries at CTCA. In multivariate analysis, the presence of obstructive CAD and diabetes were the only independent predictors of MACE. CONCLUSIONS: Coronary plaque evaluation by CTCA provides an independent prognostic value for the prediction of MACE. Patients with normal CTCA findings have an excellent prognosis at follow-up.

Accelerated subclinical coronary atherosclerosis in patients with familial hypercholesterolemia.

OBJECTIVES: We determined the extent, severity, distribution and type of coronary plaques in cardiac asymptomatic patients with familial hypercholesterolemia (FH) using computed tomography (CT). BACKGROUND: FH patients have accelerated progression of coronary artery disease (CAD) with earlier major adverse cardiac events. Non-invasive CT coronary angiography (CTCA) allows assessing the coronary plaque burden in asymptomatic patients with FH. MATERIALS AND METHODS: A total of 140 asymptomatic statin treated FH patients (90 men; mean age 52 ± 8 years) underwent CT calcium scoring (Agatston) and CTCA using a Dual Source CT scanner with a clinical follow-up of 29 ± 8 months. The extent, severity (obstructive or non-obstructive plaque based on >50% or <50% lumen diameter reduction), distribution and type (calcified, non-calcified, or mixed) of coronary plaque were evaluated. RESULTS: The calcium score was 0 in 28 (21%) of the patients. In 16% of the patients there was no CT-evidence of any CAD while 24% had obstructive disease. In total 775 plaques were detected with CT coronary angiography, of which 11% were obstructive. Fifty four percent of all plaques were calcified, 25% non-calcified and 21% mixed. The CAD extent was related to gender, treated HDL-cholesterol and treated LDL-cholesterol levels. There was a low incidence of cardiac events and no cardiac death occurred during follow-up. CONCLUSION: Development of CAD is accelerated in intensively treated male and female FH patients. The extent of CAD is related to gender and cholesterol levels and ranges from absence of plaque in one out of 6 patients to extensive CAD with plaque causing >50% lumen obstruction in almost a quarter of patients with FH.

Image quality and radiation exposure using different low-dose scan protocols in dual-source CT coronary angiography: randomized study.

PURPOSE: To compare image quality, radiation dose, and their relationship with heart rate of computed tomographic (CT) coronary angiographic scan protocols by using a 128-section dual-source CT scanner. MATERIALS AND METHODS: Institutional review board approved the study; all patients gave informed consent. Two hundred seventy-two patients (175 men, 97 women; mean ages, 58 and 59 years, respectively) referred for CT coronary angiography were categorized according to heart rate: less than 65 beats per minute (group A) and 65 beats per minute or greater (group B). Patients were randomized to undergo prospective high-pitch spiral scanning and narrow-window prospective sequential scanning in group A (n = 160) or wide-window prospective sequential scanning and retrospective spiral scanning in group B (n = 112). Image quality was graded (1 = nondiagnostic; 2 = artifacts present, diagnostic; 3 = no artifacts) and compared (Mann-Whitney and Student t tests). RESULTS: In group A, mean image quality grade was significantly lower with high-pitch spiral versus sequential scanning (2.67 ± 0.38 [standard deviation] vs 2.86 ± 0.21; P < .001). In a subpopulation (heart rate, <55 beats per minute), mean image quality grade was similar (2.81 ± 0.30 vs 2.94 ± 0.08; P = .35). In group B, image quality grade was comparable between sequential and retrospective spiral scanning (2.81 ± 0.28 vs 2.80 ± 0.38; P = .54). Mean estimated radiation dose was significantly lower (high-pitch spiral vs sequential scanning) in group A (for 100 kV, 0.81 mSv ± 0.30 vs 2.74 mSv ± 1.14 [P < .001]; for 120 kV, 1.65 mSv ± 0.69 vs 4.21 mSv ± 1.20 [P < .001]) and in group B (sequential vs retrospective spiral scanning) (for 100 kV, 4.07 mSv ± 1.07 vs 5.54 mSv ± 1.76 [P = .02]; for 120 kV, 7.50 mSv ± 1.79 vs 9.83 mSv ± 3.49 [P = .1]). CONCLUSION: A high-pitch spiral CT coronary angiographic protocol should be applied in patients with regular and low (<55 beats per minute) heart rates; a sequential protocol is preferred in all others.

Non-invasive diagnostic workup of patients with suspected stable angina by combined computed tomography coronary angiography and magnetic resonance perfusion imaging.

BACKGROUND: To evaluate additional adenosine magnetic resonance perfusion (MRP) imaging in the diagnostic workup of patients with suspected stable angina with computed tomography coronary angiography (CTCA) as first-line diagnostic modality. METHODS AND RESULTS: Two hundred and thirty symptomatic patients (male, 52%; age, 56 year) with suspected stable angina underwent CTCA. In patients with a stenosis of >50% as visually assessed, MRP was performed and the quantitative myocardial perfusion reserve index (MPRI) was calculated. Coronary flow reserve (CFR) using invasive coronary flow measurements served as the standard of reference. CTCA showed non-significant CAD in 151/230 (66%) patients and significant CAD in 79/230 patients (34%), of whom 50 subsequently underwent MRP and CFR. MRP showed reduced perfusion in 32 patients (64%), which was confirmed by CFR in 27 (84%). All 18 cases of normal MRP (36%) were confirmed by CFR. The positive likelihood ratio of MRP for the presence of functional significant disease in patients with a lesion on CTCA was 4.49 (95% confidence interval [CI] 2.12-9.99). The negative likelihood ratio was 0.05 (95%CI 0.01-0.34). CONCLUSIONS: CTCA as first-line diagnostic modality excluded coronary artery disease in a high percentage of patients referred for diagnostic workup of suspected stable angina. MRP made a significant contribution to the detection of functional significant lesions in patients with a positive CTCA.

Is there a difference in the diagnostic accuracy of computed tomography coronary angiography between women and men?

OBJECTIVE: To assess the influence of sex on the diagnostic performance of computed tomography coronary angiography (CTCA). METHODS: A total of 916 symptomatic patients (30.5% women) without earlier history of coronary artery intervention underwent both CTCA and invasive coronary angiography. Descriptive diagnostic parameters, to detect obstructive coronary artery disease (CAD; ≥ 50% lumen diameter narrowing) on CTCA, were compared between women and men on a per-patient, per-vessel, and per-segment level. Adjusted values were calculated for clustered segments and differences in sex variables using logistic multivariate regression models in general estimated equations. RESULTS: Women were older, had less typical chest complaints, and had a lower prevalence, extent, and severity of CAD compared with men. Multivariate analysis on a per-patient level revealed no difference in sensitivity (98 vs. 99%, P=0.15), specificity (78 vs. 82%, P=0.65), positive predictive value (PPV; 87 vs. 95%, P=0.10), negative predictive value (NPV; 97 vs. 98%, P=0.63), and diagnostic odds ratio (DOR; 198 vs. 721, P=0.07). No difference was found on per-vessel level analysis (sensitivity 95 vs. 97%, P=0.14; specificity 89 vs. 87%, P=0.93; PPV 73 vs. 79%, P=0.06; NPV 98 vs. 98%, P=0.72; and DOR 143 vs. 240, P=0.08). Per-segment analysis revealed a lower sensitivity (88 vs. 94%, P<0.001) and DOR (163 vs. 302, P=0.002) in women compared with men, without a difference in specificity (96 vs. 95%, P=0.19), PPV (64 vs. 69%, P=0.07), and NPV (99 vs. 99%, P=0.08). CONCLUSION: CTCA can accurately rule out obstructive CAD in both women and men. CTCA is less accurate in women to detect individual obstructive disease.

CT coronary plaque burden in asymptomatic patients with familial hypercholesterolaemia.

OBJECTIVE: To determine the calcium score and coronary plaque burden in asymptomatic statin-treated patients with heterozygous familial hypercholesterolaemia (FH) compared with a control group of patients with low probability of coronary artery disease, having non-anginal chest pain, using CT. DESIGN, SETTING AND PATIENTS: 101 asymptomatic patients with FH (mean age 53 ± 7 years; 62 men) and 126 patients with non-anginal chest pain (mean age 56 ± 7 years; 80 men) underwent CT calcium scoring and CT coronary angiography. All patients with FH were treated with statins during a period of 10 ± 8 years before CT. The coronary calcium score and plaque burden were determined and compared between the two patient groups. RESULTS: The median total calcium score was significantly higher in patients with FH (Agatston score = 87, IQR 5-367) than in patients with non-anginal chest pain (Agatston score = 7, IQR 0-125; p < 0.001). The overall coronary plaque burden was significantly higher in patients with FH (p < 0.01). Male patients with FH, whose low-density lipoprotein cholesterol levels were reduced by statins below 3.0 mmol/l, had significantly less coronary calcium (p < 0.01) and plaque burden (p = 0.02). CONCLUSION: The coronary plaque burden is high in asymptomatic middle-aged patients with FH despite intense statin treatment.