Evaluation of computed tomography coronary angiography in patients with a high heart rate using 16-slice spiral computed tomography with 0.37-s gantry rotation time

The aim of our study is to evaluate computed tomography (CT) coronary angiography in patients with a high heart rate using 16-slice spiral CT with 0.37-s gantry rotation time. We compare the image quality of patients whose heart rates were over 70 beats per minute (bpm) with that of patients whose heart rates were 70 bpm or less. Sixty patients with various heart rates underwent retrospectively ECG-gated multislice spiral CT (MSCT) coronary angiography. Two experienced observers who were blind to the heart rates of the patients evaluated all the MSCT coronary angiographic images and calculated the assessable segments. A total of 620 out of 891 (69.6%) segments were satisfactorily visualized. On average, 10.3 coronary artery segments per patient could be evaluated. In 36 patients whose heart rates were below 70 bpm [mean 62.2 bpm±5.32 (standard deviation, SD)], the number of assessable segments was 10.72±2.02 (SD). In the other 24 patients whose heart rates were above 70 bpm [mean 78.6 bpm±8.24 (SD)], the corresponding number was 9.75±1.74 (SD). No statistically significant difference was found in these two subgroups t test, P>0.05. The new generation of 16-slice spiral CT with 0.37-s rotation time can satisfactorily evaluate the coronary arteries of patients with high heart rates (above 70 bpm, up to 102 bpm).     

Evaluation of the Ostium in Anomalous Origin of the Right Coronary Artery with an Interarterial Course Using Dynamic Cardiac CT and Implications of Ostial Findings

ObjectiveWe aimed to evaluate the ostium of right coronary artery of anomalous origin from the left coronary sinus (AORL) with an interarterial course throughout the cardiac cycle on CT and analyze the clinical significance of the ostial findings.Materials and MethodsFrom January 2011 to December 2015, 68 patients (41 male, 57.3 ± 12.1 years) with AORL with an interarterial course and retrospective cardiac CT data were included. AORL was classified as high or low ostial location based on the pulmonary annulus in the diastolic and systolic phases on cardiac CT. In addition, the height, width, height/width ratio, area, and angle of the ostium were measured in both cardiac phases. After cardiac CT, patients were followed until December 31, 2020 for major adverse cardiac events (MACE). Clinical and CT characteristics associated with MACE were explored using Cox regression analysis.ResultsDuring a median follow-up period of 2071 days (interquartile range, 1180.5–2747.3 days), 13 patients experienced MACE (19.1%, 13/68). Seven (10.3%, 7/68) had the ostial location change from high in the diastolic phase to low in the systolic phase. In the univariable analysis, younger age (hazard ratio [HR] = 0.918, p < 0.001), high ostial location (HR = 4.008, p = 0.036), larger height/width ratio (HR = 5.621, p = 0.049), and smaller ostial angle (HR = 0.846, p = 0.048) in the systolic phase were significant predictors of MACE. In multivariable cox regression analysis, younger age (adjusted HR = 0.917, p = 0.002) and high ostial location in the systolic phase (adjusted HR = 4.345, p = 0.026) were independent predictors of MACE.ConclusionThe ostial location of AORL with an interarterial course can change during the cardiac cycle, and high ostial location in the systolic phase was an independent predictor of MACE.     

电子束CT冠状动脉钙化积分与冠状动脉病变严重程度的相关研究

目的　探讨冠状动脉钙化 (CAC)程度与冠状动脉病变严重性之间的关系。材料与方法　 95例同期行冠状动脉造影(CAG)及电子束 CT(EBCT)检查者 ,根据 CAG血管狭窄程度和病变累及支数 ,分成正常 /轻微病变组 (n=42 ,A/ B组 )和显著病变组 (n=5 3,F组 ) ,并细分为正常血管 (n=2 4,A组 ) ,轻微病变 ((n=18,B组 ) ,单支病变 (n=2 1,C组 ) ,2支病变 (n=15 ,D组 )和 3支病变 (n=17,E组 )各亚组。根据管腔狭窄百分比再进一步分出 95 0个血管段 ,逐个血管段与 EBCT进行对比分析。其中无狭窄血管段 735个 ,狭窄介于 0～ 5 0 %之间者 79段 ,5 0 %～ 75 %者 34段 ,狭窄≥ 75 %者 10 2段。结果　 (1)血管病变支数与 CAC积分之间的关系 :A/ B组 CAC积分值明显低于 F组 (45 .1± 16 5 .1vs35 9.4± 5 0 5 .3,P<0 .0 0 0 1) ;A/ B组 CAC积分的平方根值 (3.33± 5 .91)也明显低于 C组 (9.33± 9.2 1)、D组 (12 .97± 9.16 )、E组 (2 2 .5 2± 14.17) ,P均 <0 .0 5 ,E组与 C组、D组之间也存在差别 ,但 C组和 D组之间无差别 (P>0 .0 5 ) ;A组 CAC积分的平方根值 (1.2 7± 1.2 5 )与 C组、D组、E组之间均有显著差别 (P<0 .0 5 ) ,但与 B组 (6 .0 8± 8.2 5 )之间无差别 (P>0 .0 5 )。 (2 )冠状动脉血管段狭窄程度与 CAC积分之间     

Longitudinal assessment of coronary plaque volume change related to glycemic status using serial coronary computed tomography angiography: A PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging) substudy

BackgroundData on the impact of glycemic status on coronary plaque progression have been limited. This study evaluated the association between glycemic status and coronary plaque volume change (PVC) using coronary computed tomography angiography (CCTA).MethodsA total of 1296 subjects (61 ± 9, 56.9% male) who underwent serial CCTA with available glycemic status were enrolled and analyzed from the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. The median inter-scan period was 3.2 (2.6–4.4) years. Quantitative assessment of coronary plaques was performed at both scans. All participants were categorized into the following groups according to glycemic status: normal, pre-diabetes (pre-DM), and diabetes mellitus (DM).ResultsDuring the follow-up, significant differences in PVC (normal: 51.3 ± 83.3 mm³ vs. pre-DM: 51.0 ± 84.3 mm³ vs. DM: 72.6 ± 95.0 mm³; p < 0.001) and annualized PVC (normal: 14.9 ± 24.9 mm³ vs. pre-DM: 15.7 ± 23.8 mm³ vs. DM: 21.0 ± 27.7 mm³; p = 0.001) were observed among the 3 groups. Compared with normal individuals, individuals with pre-DM showed no significant differences in the adjusted odds ratio (OR) for plaque progression (PP) (1.338, 95% confidence interval [CI] 0.967–1.853; p = 0.079). However, the adjusted OR for PP was higher in DM individuals than in normal individuals (1.635, 95% CI 1.126–2.375; p = 0.010).ConclusionDM had an incremental impact on coronary PP, but pre-DM appeared to have no significant association with an increased risk of coronary PP after adjusting for confounding factors.Clinical trial registrationClinicalTrials.gov NCT02803411.     

Evaluation of in-stent restenosis in proximal coronary arteries with multidetector computed tomography (MDCT)

The purpose of this study was to assess the ability of 16-slice computed tomography (CT) to detect in-stent restenosis of proximal coronary arteries. From November 2002 to April 2004, 134 consecutive patients with proximal stents (3.25 ± 0.47 mm) were prospectively studied. Multidetector CT (MDCT) was performed 24 h (baseline) and 6 months after angioplasty and analysed by two radiologists blinded to the results of the coronary angiography. Sensitivity, specificity, positive and negative predictive values for in-stent restenosis were compared with conventional quantitative coronary angiography (QCA). Stenosis with a diameter ≥50% was considered diagnostic of in-stent restenosis. The CT analysis was performed in 131 and 114 patients at baseline and 6 months, respectively. The in-stent lumen was evaluable in 111 (121 stents) and 99 patients (108 stents) at baseline and 6 months, respectively. The prevalence of in-stent restenosis was 22.5%. Restenoses were correctly identified in 91.7 and 87.5% by the two radiologists. The sensitivity, specificity, positive and negative predictive values for the assessment of significant in-stent restenosis were 92, 67, 43, 97% and 87, 66, 41, 95% for the radiologists, respectively. MDCT is a potential non-invasive technique for the screening of in-stent restenosis of proximal coronary arteries that needs further improvements.     

Accuracy of dual-source CT coronary angiography: first experience in a high pre-test probability population without heart rate control

The aim of this study was to assess the diagnostic accuracy of dual-source computed tomography (DSCT) for evaluation of coronary artery disease (CAD) in a population with extensive coronary calcifications without heart rate control. Thirty patients (24 male, 6 female, mean age 63.1±11.3 years) with a high pre-test probability of CAD underwent DSCT coronary angiography and invasive coronary angiography (ICA) within 14±9 days. No beta-blockers were administered prior to the scan. Two readers independently assessed image quality of all coronary segments with a diameter ≥1.5 mm using a four-point score (1: excellent to 4: not assessable) and qualitatively assessed significant stenoses as narrowing of the luminal diameter >50%. Causes of false-positive (FP) and false-negative (FN) ratings were assigned to calcifications or motion artifacts. ICA was considered the standard of reference. Mean body mass index was 28.3±3.9 kg/m² (range 22.4–36.3 kg/m²), mean heart rate during CT was 70.3±14.2 bpm (range 47–102 bpm), and mean Agatston score was 821±904 (range 0–3,110). Image quality was diagnostic (scores 1–3) in 98.6% (414/420) of segments (mean image quality score 1.68±0.75); six segments in three patients were considered not assessable (1.4%). DSCT correctly identified 54 of 56 significant coronary stenoses. Severe calcifications accounted for false ratings in nine segments (eight FP/one FN) and motion artifacts in two segments (one FP/one FN). Overall sensitivity, specificity, positive and negative predictive value for evaluating CAD were 96.4, 97.5, 85.7, and 99.4%, respectively. First experience indicates that DSCT coronary angiography provides high diagnostic accuracy for assessment of CAD in a high pre-test probability population with extensive coronary calcifications and without heart rate control.     

Cardiac computed tomography-derived coronary artery volume to myocardial mass

In the absence of disease impacting the coronary arteries or myocardium, there exists a linear relationship between vessel volume and myocardial mass to ensure balanced distribution of blood supply. This balance may be disturbed in diseases of either the coronary artery tree, the myocardium, or both. However, in contemporary evaluation the coronary artery anatomy and myocardium are assessed separately. Recently the coronary lumen volume to myocardial mass ratio (V/M), measured noninvasively using coronary computed tomography angiography (CTCA), has emerged as an integrated measure of myocardial blood supply and demand in vivo. This has the potential to yield new insights into diseases where this balance is altered, thus impacting clinical diagnoses and management.In this review, we outline the scientific methodology underpinning CTCA-derived measurement of V/M. We describe recent studies describing alterations in V/M across a range of cardiovascular conditions, including coronary artery disease, cardiomyopathies and coronary microvascular dysfunction. Lastly, we highlight areas of unmet research need and future directions, where V/M may further enhance our understanding of the pathophysiology of cardiovascular disease.     

The Diagnostic Accuracy, Image Quality and Radiation Dose of 64-Slice Dual-Source CT in Daily Practice: a Single Institution's Experience

Objective

We wanted to evaluate the image quality, diagnostic accuracy and radiation exposure of 64-slice dual-source CT (DSCT) coronary angiography according to the heart rate in symptomatic patients during daily clinical practice.

Materials and Methods

We performed a retrospective search for the DSCT coronary angiography reports of 729 consecutive symptomatic patients. For the 131 patients who underwent invasive coronary angiography, the image quality, the diagnostic performance (sensitivity, specificity, positive predictive value [PPV] and negative predictive value [NPV] for detecting significant stenosis ≥ 50% diameter) and the radiation exposure were evaluated. These values were compared between the groups with differing heart rates (HR): mean HR < 65 or ≥ 65 and HR variability (HRV) < 15 or ≥ 15.

Results

Among the 729 patients, the CT reports showed no stenosis or insignificant coronary artery stenosis in 72%, significant stenosis in 26% and non-diagnostic in 2%. For the 131 patients who underwent invasive coronary angiography, 95% of the patients and 97% of the segments were evaluable, and the overall per-patient/per-segment sensitivity, the perpatient/per-segment specificity, the per-patient/per-segment PPV and the per-patient/per-segment NPV were 100%/90%, 71%/98%, 95%/88% and 100%/97%, respectively. The image quality was better in the HR < 65 group than in the HR ≥ 65 group (p = 0.001), but there was no difference in diagnostic performance between the two groups. The mean effective radiation doses were lower in the HR < 65 or HRV < 15 group (p < 0.0001): 5.5 versus 6.7 mSv for the mean HR groups and 5.3 versus 9.3 mSv for the HRV groups.

Conclusion

Dual-source CT coronary angiography is a highly accurate modality in the clinical setting. Better image quality and a significant radiation reduction are being rendered in the lower HR group.     

Effect of Heart Rate and Coronary Calcification on the Diagnostic Accuracy of the Dual-Source CT Coronary Angiography in Patients with Suspected Coronary Artery Disease

Objective

To evaluate the diagnostic accuracy of a dual-source computed tomography (DSCT) coronary angiography, with a particular focus on the effect of heart rate and calcifications.

Materials and Methods

One hundred and nine patients with suspected coronary disease were divided into 2 groups according to a mean heart rate (< 70 bpm and ≥ 70 bpm) and into 3 groups according to the mean Agatston calcium scores (≤ 100, 101-400, and > 400). Next, the effect of heart rate and calcification on the accuracy of coronary artery stenosis detection was analyzed by using an invasive coronary angiography as a reference standard. Coronary segments of less than 1.5 mm in diameter in an American Heart Association (AHA) 15-segment model were independently assessed.

Results

The mean heart rate during the scan was 71.8 bpm, whereas the mean Agatston score was 226.5. Of the 1,588 segments examined, 1,533 (97%) were assessable. A total of 17 patients had calcium scores above 400 Agatston U, whereas 50 had heart rates ≥ 70 bpm. Overall the sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) for significant stenoses were: 95%, 91%, 65%, and 99% (by segment), respectively and 97%, 90%, 81%, and 91% (by artery), respectively (n = 475). Heart rate showed no significant impact on lesion detection; however, vessel calcification did show a significant impact on accuracy of assessment for coronary segments. The specificity, PPV and accuracy were 96%, 80%, and 96% (by segment), respectively for an Agatston score less than 100% and 99%, 96% and 98% (by artery). For an Agatston score of greater to or equal to 400 the specificity, PPV and accuracy were reduced to 79%, 55%, and 83% (by segment), respectively and to 79%, 69%, and 85% (by artery), respectively.

Conclusion

The DSCT provides a high rate of accuracy for the detection of significant coronary artery disease, even in patients with high heart rates and evidence of coronary calcification. However, patients with severe coronary calcification (> 400 U) remain a challenge to diagnose.     

Impact of scan quality on the diagnostic performance of CCTA,SPECT, and PET for diagnosing myocardial ischemia defined by fractional flow reserve

BackgroundScan quality can have a significant effect on the diagnostic performance of non-invasive imaging techniques. However, the extent of its influence has scarcely been investigated in a head-to-head manner.MethodsTwo-hundred and eight patients underwent CCTA, SPECT, and PET prior to invasive fractional flow reserve measurements. Scan quality was classified as either good, moderate, or poor.ResultsDistribution of good, moderate, and poor quality scans was; CCTA; 66%, 22%, 13%; SPECT; 52%, 38%, 9%; PET; 86%, 13%, 1%. Good quality CCTA scans possessed a higher specificity (75% vs. 31%, p = 0.001), positive predictive value (PPV, 71% vs. 51%, p = 0.050), and accuracy (80% vs. 60%, p = 0.009) compared to moderate quality scans, while sensitivity (94%) and negative predictive value (NPV, 88%) were similar to moderate and poor quality scans. Sensitivity (76%), NPV (84%), and accuracy (85%) of good quality SPECT scans was superior to those of moderate (41% p = 0.001, 56% p = 0.010, 70% p = 0.010) and poor quality (30% p = 0.003, 65% p = 0.069, 63% p = 0.038). Specificity (92%) and PPV (87%) of good quality SPECT scans did not differ from scans of diminished quality. Good quality PET scans exhibited high sensitivity (84%), specificity (86%), NPV (88%), PPV (81%) and accuracy (85%), which was comparable to scans of lesser quality. Good quality CCTA, SPECT, and PET scans demonstrated a similar diagnostic accuracy (p = 0.247).ConclusionDiagnostic performance of CCTA, and SPECT is hampered by scan quality, while the diagnostic value of PET is not affected. Good quality CCTA, SPECT, and PET scans possess a high diagnostic accuracy.     

Role of cardiac computed tomography in patients with suspected coronary artery disease: interaction with nuclear cardiology

Coronary computed tomography (CT) angiography (CTA) and myocardial perfusion single photon emission CT (SPECT, or MPS) provide complementary information on vascular structure and myocardial perfusion. In patients with coronary artery disease (CAD), the combination of both methods is helpful for disease detection and therapeutic strategy planning. This article addresses the utility of coronary CTA with current 64-row multidetector CT instruments, MPS, and the combination of these methods in the evaluation of CAD.     

Optimized interpretation of fractional flow reserve derived from computed tomography: Comparison of three interpretation methods

BackgroundAn optimal system for interpreting fractional flow reserve (FFR) values derived from CT (FFRCT) is lacking. We sought to evaluate performance of three FFR_CT measurements in detecting ischemia by comparing them with invasive FFR.MethodsFor 73 vessels in 50 patients who underwent coronary CT angiography (CCTA) and FFR_CT analysis followed by invasive FFR, the greatest diameter stenosis on CCTA, FFR_CT difference between distal and proximal to the stenosis (ΔFFR_CT), FFR_CT 2 cm distal to the stenosis (lesion-specific FFR_CT), and the lowest FFR_CT in distal vessel tip were calculated. Significant obstruction (≥50% diameter stenosis) and ischemia (lesion-specific FFR_CT ≤0.80, the lowest FFR_CT ≤0.80, or ΔFFR_CT ≥0.12 based on the greatest Youden index) were compared with invasive FFR (≤0.80).ResultsForty (55%) vessels demonstrated ischemia during invasive FFR. On multivariable generalized estimating equations, ΔFFR_CT (odds ratio [OR] 10.2, p < 0.01) remained a predictor of ischemia over CCTA (OR 2.9), lesion-specific FFR_CT (OR 3.1), and the lowest FFR_CT (OR 0.9) (p > 0.05 for all). Area under the curve (AUC) of ΔFFR_CT (0.86) was higher than CCTA (0.66), lesion-specific FFR_CT (0.71), and the lowest FFR_CT (0.65) (p < 0.01 for all). Addition of each FFR_CT measure to CCTA showed improvement of AUC and significant net reclassification improvement (NRI): ΔFFR_CT (AUC 0.84, NRI 1.24); lesion-specific FFR_CT (AUC 0.77, NRI 0.83); and the lowest FFR_CT (AUC 0.76, NRI 0.59) (p < 0.01 for all).ConclusionsCompared with diameter stenosis, ΔFFR_CT, lesion-specific FFR_CT, and the lowest FFR_CT improved ischemia discrimination and reclassification, with ΔFFR_CT being superior in identifying and discriminating ischemia.     

Relation of coronary vasoreactivity and coronary calcification in asymptomatic subjects with a family history of premature coronary artery disease

Electron-beam computed tomography (EBCT) allows non-invasive imaging of coronary calcification and has been promoted as a screening tool for coronary artery disease (CAD) in asymptomatic high-risk subjects. This study assessed the relation of coronary calcifications to alterations in coronary vascular reactivity by means of positron emission tomography (PET) in asymptomatic subjects with a familial history of premature CAD. Twenty-one subjects (mean age 51±10 years) underwent EBCT imaging for coronary calcifications expressed as the coronary calcium score (CCS according to Agatston) and rest/adenosine-stress nitrogen-13 ammonia PET with quantification of myocardial blood flow (MBF) and coronary flow reserve (CFR). The mean CCS was 237±256 (median 146, range 0–915). The CCS was <100 in eight subjects and >100 units in 13. As defined by age-related thresholds, 15 subjects had an increased CCS (>75th percentile). Overall mean resting and stress MBF and CFR were 71±16 ml 100 g^–1 min^–1, 218±54 ml 100 g^–1 min^–1 and 3.20±0.77, respectively. Three subjects with CCS ranging from 114 to 451 units had an abnormal CFR (<2.5). There was no relation between CCS and resting or stress MBF or CFR (r=0.17, 0.18 and 0.10, respectively). In asymptomatic subjects a pathological CCS was five times more prevalent than an abnormal CFR. The absence of any close relationship between CCS and CFR reflects the fact that quantitative myocardial perfusion imaging with PET characterises the dynamic process of vascular reactivity while EBCT is a measure of more stable calcified lesions in the arterial wall whose presence is closely related to age.     

Diagnostic accuracy of non-invasive 64-slice CT coronary angiography in patients with stable angina pectoris

Multislice computed tomography (CT) is an emerging technique for the non-invasive detection of coronary stenoses. While the diagnostic accuracy of 4-slice scanners was limited, 16-slice CT imagers showed promising results due to increased temporal and spatial resolution. These technical advances prompted us to evaluate the diagnostic performance of 64-slice CT coronary angiography in the detection of significant stenoses (defined as ≥ 50% luminal diameter reduction) versus invasive quantitative coronary angiography (QCA). Thirty-five patients with stable angina pectoris underwent CT coronary angiography performed with a 64-slice scanner (gantry rotation time 330 ms, individual detector width 0.6 mm) prior to conventional coronary angiography. Patients with heart rates >70 beats/min received 100 mg metoprolol orally. One hundred millilitres of contrast agent with an iodine concentration of 400 mgl/ml were injected at a rate of 5 ml/s into the antecubital vein. The CT scan was triggered with the bolus tracking technique. The sensitivity, specificity and the positive and negative predictive values of 64-slice CT were 99%, 96%, 78% and 99%, respectively, on a per-segment basis. The values obtained on a per-patient basis were 100%, 90%, 96% and 100%, respectively. When referral to catheterisation is questionable, CT coronary angiography may identify subjects with normal angiograms and consistently decrease the number of unnecessary invasive procedures.     

心电编辑技术在改善双源CT冠状动脉成像质量中的应用

目的探讨心电编辑技术在改善双源CT冠状动脉成像中的作用。方法对316例接受双源冠状动脉造影的患者图像进行回顾性分析,其中20例因在扫描过程中出现心律不齐而导致伪影并进行心电编辑。冠状动脉图像质量分为5级,Ⅰ～Ⅲ级为合格图像,Ⅳ和Ⅴ级为不合格图像。结果进行心电编辑者包括窦性心律不齐11例,室性早搏6例,心电起搏心率2例,房颤1例;其中Ⅲ级图像3例,Ⅲ级以下图像17例。经心电编辑处理后,17例Ⅲ级以下图像中16例达到Ⅲ级（94％）。结论心电编辑技术为改善心律不齐或心律失常患者双源CT冠脉成像质量提供了一项有效可靠的手段。     

Incidental Non-Cardiac Findings of a Coronary Angiography with a 128-Slice Multi-Detector CT Scanner: Should We Only Concentrate on the Heart?

Objective

To evaluate the spectrum, prevalence, and significance of incidental non-cardiac findings (INCF) in patients referred for a non-invasive coronary angiography using a 128-slice multi-detector CT (MDCT).

Materials and Methods

The study subjects included 1,044 patients; 774 males (mean age, 59.9 years) and 270 females (mean age, 63 years), referred for a coronary CT angiography on a 128-slice MDCT scanner. The scans were acquired from the level of the carina to just below the diaphragm. To evaluate INCFs, images were reconstructed with a large field of view (> 300 mm) covering the entire thorax. Images were reviewed in the axial, coronal, and sagittal planes, using the mediastinal, lung, and bone windows. The INCFs were classified as severe, indeterminate, and mild, based on their clinical importance, and as thoracic or abdominal based on their locations.

Results

Incidental non-cardiac findings were detected in 56% of patients (588 of 1,044), including 435 males (mean age, 65.6 years) and 153 females (mean age, 67.9 years). A total of 729 INCFs were observed: 459 (63%) mild (58% thoracic, 43% abdominal), 96 (13%) indeterminate (95% thoracic, 5% abdominal), and 174 (24%) severe (87% thoracic, 13% abdominal). The prevalence of severe INCFs was 15%. Two severe INCFs were histologically verified as lung cancers.

Conclusion

The 128-slice MDCT coronary angiography, in addition to cardiac imaging, can provide important information on the pathology of the chest and upper abdomen. The presence of severe INCFs is not rare, especially in the thorax. Therefore, all organs in the scan should be thoroughly evaluated in daily clinical practice.