Gabriel P. Krestin

High-Resolution Spiral Computed Tomography Coronary Angiography in Patients Referred for Diagnostic Conventional Coronary Angiography

Background— The diagnostic performance of the latest 64-slice CT scanner, with increased temporal (165 ms) and spatial (0.4 mm3) resolution, to detect significant stenoses in the clinically relevant coronary tree is unknown. Methods and Results— We studied 52 patients (34 men; mean age, 59.6±12.1 years) with atypical chest pain, stable or unstable angina pectoris, or non–ST-segment elevation myocardial infarction scheduled for diagnostic conventional coronary angiography. All patients had stable sinus rhythm. Patients with initial heart rates ≥70 bpm received &bgr;-blockers. Mean scan time was 13.3±0.9 seconds. The CT scans were analyzed by 2 observers unaware of the results of invasive coronary angiography, which was used as the standard of reference. All available coronary segments, regardless of size, were included in the evaluation. Lesions with ≥50 luminal narrowing were considered significant stenoses. Invasive coronary angiography demonstrated the absence of significant disease in 25% (13 of 52), single-vessel disease in 31% (16 of 52), and multivessel disease in 45% (23 of 52) of patients. One unsuccessful CT scan was classified as inconclusive. Ninety-four significant stenoses were present in the remaining 51 patients. Sensitivity, specificity, and positive and negative predictive values of CT for detecting significant stenoses on a segment-by-segment analysis were 99% (93 of 94; 95% CI, 94 to 99), 95% (601 of 631; 95% CI, 93 to 96), 76% (93 of 123; 95% CI, 67 to 89), and 99% (601 of 602; 95% CI, 99 to 100), respectively. Conclusions— Noninvasive 64-slice CT coronary angiography accurately detects coronary stenoses in patients in sinus rhythm and presenting with atypical chest pain, stable or unstable angina, or non–ST-segment elevation myocardial infarction.

Diagnostic accuracy of 64-slice computed tomography coronary angiography: a prospective, multicenter, multivendor study.

OBJECTIVES This study sought to determine the diagnostic accuracy of 64-slice computed tomographic coronary angiography (CTCA) to detect or rule out significant coronary artery disease (CAD). BACKGROUND CTCA is emerging as a noninvasive technique to detect coronary atherosclerosis. METHODS We conducted a prospective, multicenter, multivendor study involving 360 symptomatic patients with acute and stable anginal syndromes who were between 50 and 70 years of age and were referred for diagnostic conventional coronary angiography (CCA) from September 2004 through June 2006. All patients underwent a nonenhanced calcium scan and a CTCA, which was compared with CCA. No patients or segments were excluded because of impaired image quality attributable to either coronary motion or calcifications. Patient-, vessel-, and segment-based sensitivities and specificities were calculated to detect or rule out significant CAD, defined as >or=50% lumen diameter reduction. RESULTS The prevalence among patients of having at least 1 significant stenosis was 68%. In a patient-based analysis, the sensitivity for detecting patients with significant CAD was 99% (95% confidence interval [CI]: 98% to 100%), specificity was 64% (95% CI: 55% to 73%), positive predictive value was 86% (95% CI: 82% to 90%), and negative predictive value was 97% (95% CI: 94% to 100%). In a segment-based analysis, the sensitivity was 88% (95% CI: 85% to 91%), specificity was 90% (95% CI: 89% to 92%), positive predictive value was 47% (95% CI: 44% to 51%), and negative predictive value was 99% (95% CI: 98% to 99%). CONCLUSIONS Among patients in whom a decision had already been made to obtain CCA, 64-slice CTCA was reliable for ruling out significant CAD in patients with stable and unstable anginal syndromes. A positive 64-slice CTCA scan often overestimates the severity of atherosclerotic obstructions and requires further testing to guide patient management.

Prevalence and risk factors of cerebral microbleeds: The Rotterdam Scan Study

Background: Cerebral microbleeds are focal deposits of hemosiderin that can be visualized with MRI. Little is known on their prevalence in the general population and on their etiology. It has been suggested that, in analogy to spontaneous intracranial hemorrhage, the etiology of microbleeds differs according to their location in the brain, with lobar microbleeds being caused by cerebral amyloid angiopathy and deep or infratentorial microbleeds resulting from hypertension and atherosclerosis. We investigated the prevalence of and risk factors for microbleeds in the general population aged 60 years and older. Methods: This study is based on 1,062 persons (mean age 69.6 years) from the population-based Rotterdam Scan Study. MRI was performed at 1.5 T and included a sequence optimized to increase the conspicuity of microbleeds. We assessed the relation of APOE genotype, cardiovascular risk factors, and markers of small vessel disease to the presence and location of microbleeds with multiple logistic regression. Results: Overall prevalence of cerebral microbleeds was high and increased with age from 17.8% in persons aged 60-69 years to 38.3% in those over 80 years. APOE ε4 carriers had significantly more often strictly lobar microbleeds than noncarriers. In contrast, cardiovascular risk factors and presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial location but not in a lobar location. Conclusion: The prevalence of cerebral microbleeds is high. Our data support the hypothesis that strictly lobar microbleeds are related to cerebral amyloid angiopathy, whereas microbleeds in a deep or infratentorial location result from hypertensive or atherosclerotic microangiopathy.

Comprehensive Assessment of Coronary Artery Stenoses: Computed Tomography Coronary Angiography Versus Conventional Coronary Angiography and Correlation With Fractional Flow Reserve in Patients With Stable Angina

OBJECTIVES We sought to determine the diagnostic accuracy of noninvasive visual (computed tomography coronary angiography [CTCA]) and quantitative computed tomography coronary angiography (QCT) to predict the hemodynamic significance of a coronary stenosis, using intracoronary fractional flow reserve (FFR) as the reference standard. BACKGROUND It has been demonstrated that CTCA provides excellent diagnostic sensitivity for identifying coronary stenoses, but may lack accurate delineation of the hemodynamic significance. METHODS We investigated 79 patients with stable angina pectoris who underwent both 64-slice or dual-source CTCA and FFR measurement of discrete coronary stenoses. CTCA and conventional coronary angiography (CCA), and QCT and quantitative coronary angiography (QCA), were performed to determine the severity of a stenosis that was compared with FFR measurements. A significant anatomical or functional stenosis was defined as >/=50% diameter stenosis or an FFR <0.75. Stented segments and bypass grafts were not included in the analysis. RESULTS A total of 89 stenoses were evaluated of which 18% (16 of 89) had an FFR <0.75. The diagnostic accuracy of CTCA, QCT, CCA, and QCA to detect a hemodynamically significant coronary lesion was 49%, 71%, 61%, and 67%, respectively. Correlation between QCT and QCA with FFR measurement was weak (R values of -0.32 and -0.30, respectively). Correlation between QCT and QCA was significant, but only moderate (R = 0.53; p < 0.0001). CONCLUSIONS The anatomical assessment of the hemodynamic significance of coronary stenoses determined by visual CTCA, CCA, or QCT or QCA does not correlate well with the functional assessment of FFR. Determining the hemodynamic significance of an angiographically intermediate stenosis remains relevant before referral for revascularization treatment.

Prevalence and Risk Factors of Cerebral Microbleeds An Update of the Rotterdam Scan Study

Background and Purpose— We previously reported on the high prevalence of cerebral microbleeds (CMBs) in community-dwelling people aged 60 years and older. Moreover, we found that their spatial distribution likely reflects differences in underlying etiology. We have since almost quadrupled the number of participants in our study and expanded it to include persons of 45 years and older. We examined the prevalence and determinants of microbleeds in this larger and younger cohort from the general population. Methods— In 3979 persons (mean age, 60.3 years), we performed brain MRI at 1.5T, including a sequence optimized for visualization of CMBs. Associations between APOE genotype, cardiovascular risk factors, and markers of cerebrovascular disease with the presence and location of CMBs were assessed by multiple logistic regression adjusted for age, sex, and relevant confounders. Results— Microbleed prevalence gradually increased with age, from 6.5% in persons aged 45 to 50 years to 35.7% in participants of 80 years and older. Overall, 15.3% of all subjects had at least 1 CMB. Cardiovascular risk factors and presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial region, whereas APOE ϵ4 and diastolic blood pressure were related to microbleeds in a strictly lobar location. Conclusions— Findings in this larger population are in line with our previous results and, more importantly, extend these to a younger age group. CMBs are already present at middle age, and prevalence rises strongly with increasing age. We confirmed that determinants of the presence of cerebral microbleeds differ according to their location in the brain.

Evaluation of newer risk markers for coronary heart disease risk classification: a cohort study.

BACKGROUND Whether newer risk markers for coronary heart disease (CHD) improve CHD risk prediction remains unclear. OBJECTIVE To assess whether newer risk markers for CHD risk prediction and stratification improve Framingham risk score (FRS) predictions. DESIGN Prospective population-based study. SETTING The Rotterdam Study, Rotterdam, the Netherlands. PARTICIPANTS 5933 asymptomatic, community-dwelling participants (mean age, 69.1 years [SD, 8.5]). MEASUREMENTS Traditional CHD risk factors used in the FRS (age, sex, systolic blood pressure, treatment of hypertension, total and high-density lipoprotein cholesterol levels, smoking, and diabetes) and newer CHD risk factors (N-terminal fragment of prohormone B-type natriuretic peptide levels, von Willebrand factor antigen levels, fibrinogen levels, chronic kidney disease, leukocyte count, C-reactive protein levels, homocysteine levels, uric acid levels, coronary artery calcium [CAC] scores, carotid intima-media thickness, peripheral arterial disease, and pulse wave velocity). RESULTS Adding CAC scores to the FRS improved the accuracy of risk predictions (c-statistic increase, 0.05 [95% CI, 0.02 to 0.06]; net reclassification index, 19.3% overall [39.3% in those at intermediate risk, by FRS]). Levels of N-terminal fragment of prohormone B-type natriuretic peptide also improved risk predictions but to a lesser extent (c-statistic increase, 0.02 [CI, 0.01 to 0.04]; net reclassification index, 7.6% overall [33.0% in those at intermediate risk, by FRS]). Improvements in predictions with other newer markers were marginal. LIMITATION The findings may not be generalizable to younger or nonwhite populations. CONCLUSION Among 12 CHD risk markers, improvements in FRS predictions were most statistically and clinically significant with the addition of CAC scores. Further investigation is needed to assess whether risk refinements using CAC scores lead to a meaningful change in clinical outcome. Whether to use CAC score screening as a more routine test for risk prediction requires full consideration of the financial and clinical costs of performing versus not performing the test for both persons and health systems. PRIMARY FUNDING SOURCE Netherlands Organization for Health Research and Development (ZonMw).

A clinical prediction rule for the diagnosis of coronary artery disease: validation, updating, and extension

AIMS The aim was to validate, update, and extend the Diamond-Forrester model for estimating the probability of obstructive coronary artery disease (CAD) in a contemporary cohort. METHODS AND RESULTS Prospectively collected data from 14 hospitals on patients with chest pain without a history of CAD and referred for conventional coronary angiography (CCA) were used. Primary outcome was obstructive CAD, defined as ≥ 50% stenosis in one or more vessels on CCA. The validity of the Diamond-Forrester model was assessed using calibration plots, calibration-in-the-large, and recalibration in logistic regression. The model was subsequently updated and extended by revising the predictive value of age, sex, and type of chest pain. Diagnostic performance was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) and reclassification was determined. We included 2260 patients, of whom 1319 had obstructive CAD on CCA. Validation demonstrated an overestimation of the CAD probability, especially in women. The updated and extended models demonstrated a c-statistic of 0.79 (95% CI 0.77-0.81) and 0.82 (95% CI 0.80-0.84), respectively. Sixteen per cent of men and 64% of women were correctly reclassified. The predicted probability of obstructive CAD ranged from 10% for 50-year-old females with non-specific chest pain to 91% for 80-year-old males with typical chest pain. Predictions varied across hospitals due to differences in disease prevalence. CONCLUSION Our results suggest that the Diamond-Forrester model overestimates the probability of CAD especially in women. We updated the predictive effects of age, sex, type of chest pain, and hospital setting which improved model performance and we extended it to include patients of 70 years and older.

Non-invasive coronary angiography with multislice spiral computed tomography: impact of heart rate

Objective: To evaluate the impact of heart rate on the diagnostic accuracy of coronary angiography by multislice spiral computed tomography (MSCT). Design: Prospective observational study. Patients: 78 patients who underwent both conventional and MSCT coronary angiography for suspicion of de novo coronary artery disease (n=53) or recurrent coronary artery disease after percutaneous intervention (n=25). Setting: Tertiary referral centre. Methods: Intravenously contrast enhanced MSCT coronary angiography was done during a single breath hold, and ECG synchronised images were reconstructed retrospectively. All coronary segments of ≥ 2.0 mm without stents were evaluated by two investigators and compared with quantitative coronary angiography. Patients were classified according to the average heart rate (mean (SD)) into three equally sized groups: group 1, 55.8 (4.1) beats/min; group 2, 66.6 (2.8) beats/min; group 3, 81.7 (8.8) beats/min. Results: Image quality was sufficient for analysis in 78% of the coronary segments in patients in group 1, 73% in group 2, and 54% in group 3 (p < 0.01). The sensitivity and specificity for detecting significant stenoses (≥ 50% lumen reduction) in these assessable segments were: 97% (95% confidence interval (CI) 84% to 100%) and 96% in group 1; 74% (52% to 89%) and 94% in group 2; and 67% (33% to 90%) and 94% in group 3 (p < 0.05). Accounting for all segments of ≥ 2.0 mm, including lesions in non-assessable segments as false negatives, the sensitivity decreased to 82% (28/34 lesions, 95% CI 69% to 91%), 61% (14/23 lesions, 42% to 77%), and 32% (6/19 lesions, 15% to 50%), respectively (p < 0.01). Conclusions: MSCT allows reliable coronary angiography in patients with low heart rates.

Standardized evaluation methodology and reference database for evaluating coronary artery centerline extraction algorithms.

Efficiently obtaining a reliable coronary artery centerline from computed tomography angiography data is relevant in clinical practice. Whereas numerous methods have been presented for this purpose, up to now no standardized evaluation methodology has been published to reliably evaluate and compare the performance of the existing or newly developed coronary artery centerline extraction algorithms. This paper describes a standardized evaluation methodology and reference database for the quantitative evaluation of coronary artery centerline extraction algorithms. The contribution of this work is fourfold: (1) a method is described to create a consensus centerline with multiple observers, (2) well-defined measures are presented for the evaluation of coronary artery centerline extraction algorithms, (3) a database containing 32 cardiac CTA datasets with corresponding reference standard is described and made available, and (4) 13 coronary artery centerline extraction algorithms, implemented by different research groups, are quantitatively evaluated and compared. The presented evaluation framework is made available to the medical imaging community for benchmarking existing or newly developed coronary centerline extraction algorithms.

Usefulness of multislice computed tomography for detecting obstructive coronary artery disease

The latest generation of multislice spiral computed tomography (MSCT) scanners is capable of noninvasive coronary angiography. We evaluated its diagnostic accuracy to detect stenotic coronary artery disease (CAD). In 53 patients with suspected CAD, contrast-enhanced MSCT and conventional angiography were performed. The CT data were acquired within a single breathhold, and isocardiophasic slices were reconstructed by means of retrospective electrocardiographic gating. Coronary segments of > or = 2 mm in diameter, measured by quantitative angiography, were evaluated. In 70% of the 358 available segments, image quality was regarded as adequate for assessment. The overall sensitivity, specificity, and positive and negative predictive values to detect > or = 50% stenotic lesions in the assessable segments were 82% (42 of 51 lesions), 93% (285 of 307 nonstenotic segments), and 66% and 97%, respectively, regarding conventional quantitative angiography as the gold standard. Proximal segments were assessable in 92%, and distal segments and side branches in 71% and 50%, respectively. Including the undetected lesions in non-assessable segments, overall sensitivity decreased to 61% but remained 82% for lesions in proximal coronary segments. MSCT correctly predicted absent, single, or multiple lesions in 55% of patients. Thus, despite potentially high image quality, current MSCT protocols offer only reasonable diagnostic accuracy in an unselected patient group with a high prevalence of CAD.