Myocardial Blood Flow by Magnetic Resonance in Patients With Suspected Coronary Stenosis: Comparison to PET and Invasive Physiology.

BACKGROUND: Despite recent guideline recommendations, quantitative perfusion (QP) estimates of myocardial blood flow from cardiac magnetic resonance (CMR) have only been sparsely validated. Furthermore, the additional diagnostic value of utilizing QP in addition to the traditional visual expert interpretation of stress-perfusion CMR remains unknown. The aim was to investigate the correlation between myocardial blood flow measurements estimated by CMR, positron emission tomography, and invasive coronary thermodilution. The second aim is to investigate the diagnostic performance of CMR-QP to identify obstructive coronary artery disease (CAD). METHODS: Prospectively enrolled symptomatic patients with >50% diameter stenosis on computed tomography angiography underwent dual-bolus CMR and positron emission tomography with rest and adenosine-stress myocardial blood flow measurements. Subsequently, an invasive coronary angiography (ICA) with fractional flow reserve and thermodilution-based coronary flow reserve was performed. Obstructive CAD was defined as both anatomically severe (>70% diameter stenosis on quantitative coronary angiography) or hemodynamically obstructive (ICA with fractional flow reserve ≤0.80). RESULTS: About 359 patients completed all investigations. Myocardial blood flow and reserve measurements correlated weakly between estimates from CMR-QP, positron emission tomography, and ICA-coronary flow reserve (r<0.40 for all comparisons). In the diagnosis of anatomically severe CAD, the interpretation of CMR-QP by an expert reader improved the sensitivity in comparison to visual analysis alone (82% versus 88% [P=0.03]) without compromising specificity (77% versus 74% [P=0.28]). In the diagnosis of hemodynamically obstructive CAD, the accuracy was only moderate for a visual expert read and remained unchanged when additional CMR-QP measurements were interpreted. CONCLUSIONS: CMR-QP correlates weakly to myocardial blood flow measurements by other modalities but improves diagnosis of anatomically severe CAD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481712.

Two-year MRI-defined structural damage and patient-reported outcomes following surgery or exercise for meniscal tears in young adults.

OBJECTIVE: To investigate potential differences in structural knee joint damage assessed by MRI and patient-reported outcomes (PROMs) at 2-year follow-up between young adults randomised to early surgery or exercise and education with optional delayed surgery for a meniscal tear. METHODS: A secondary analysis of a multicentre randomised controlled trial including 121 patients (18-40 years) with an MRI-verified meniscal tear. For this study, only patients with 2-year follow-up were included. The main outcomes were the difference in worsening of structural knee damage, assessed by MRI using the Anterior Cruciate Ligament OsteoArthrits Score, and the difference in change in the mean score of four Knee Injury and Osteoarthritis Outcome Score (KOOS4) subscales covering pain, symptoms, function in sport and recreation, and quality of life, from baseline to 2 years. RESULTS: In total, 82/121 (68%) patients completed the 2-year follow-up (39 from the surgical group and 43 from the exercise group). MRI-defined cartilage damage had developed or progressed in seven (9.1%) patients and osteophytes developed in two (2.6%) patients. The worsening of structural damage from baseline to 2-year follow-up was similar between groups. The mean (95% CI) adjusted differences in change in KOOS4 between intervention groups from baseline to 2 years was -1.4 (-9.1, 6.2) points. The mean improvement in KOOS4 was 16.4 (10.4, 22.4) in the surgical group and 21.5 (15.0, 28.0) in the exercise group. No between group differences in improvement were found in the KOOS subscales. CONCLUSIONS: The 2-year worsening of MRI-defined structural damage was limited and similar in young adult patients with a meniscal tear treated with surgery or exercise with optional delayed surgery. Both groups had similar clinically relevant improvements in KOOS4, suggesting the choice of treatment strategy does not impact 2-year structural knee damage or PROMs. TRIAL REGISTRATION NUMBER: NCT02995551.

Implementation of ultrasound-guided carpal tunnel release.

INTRODUCTION: Ultra-minimally invasive ultrasound-guided carpal tunnel release is a surgical procedure for treatment of carpal tunnel syndrome that is associated with less surgery-related morbidity and faster recovery than open surgery. The objectives of this study were to describe how the surgical technique may be acquired and to report the results obtained after implementation in a clinical setting. METHODS: The study consisted of two parts: 1) description of the surgical skills needed to perform the procedure, and 2) evaluation of the procedure in the first ten consecutively operated patients after 12-month follow-up using questionnaires and magnetic resonance imaging (MRI). RESULTS: The procedure was performed on 29 cadaveric arms and assessed regarding surgical release success and signs of iatrogenic damage. Subsequently, the procedure was performed on ten patients with carpal tunnel syndrome. The results of the six-item Carpal Tunnel Symptoms Scale (1-5) improved from 3.3 ± 0.9 (mean ± standard deviation) preoperatively to 1.2 ± 0.3, p = 0.002, after 12 months. Quick Disabilities of the Arm, Shoulder and Hand (DASH) (0-100) results improved from 33.4 ± 14.8 to 2.3 ± 4.0, p = 0.002. There were no infections or iatrogenic damage to nerves or blood vessels. CONCLUSIONS: This study presents a way to safely acquire the skills needed to perform the procedure and implement it in an out-patient setting. The results were comparable to previous findings regarding both effectiveness and safety. MRI documented the surgical gap in the transverse carpal ligament, release length, cross-sectional area changes in the carpal tunnel and median nerve, and reactive changes in the carpal tunnel. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Diagnostic performance of clinical likelihood models of obstructive coronary artery disease to predict myocardial perfusion defects.

AIMS: Clinical likelihood (CL) models are designed based on a reference of coronary stenosis in patients with suspected obstructive coronary artery disease. However, a reference standard for myocardial perfusion defects (MPDs) could be more appropriate. We aimed to investigate the ability of the 2019 European Society of Cardiology pre-test probability (ESC-PTP), the risk-factor-weighted (RF-CL) model, and coronary artery calcium score-weighted (CACS-CL) model to diagnose MPDs. METHODS AND RESULTS: Symptomatic stable de novo chest pain patients (n = 3374) underwent coronary computed tomography angiography and subsequent myocardial perfusion imaging by single-photon emission computed tomography, positron emission tomography, or cardiac magnetic resonance. For all modalities, MPD was defined as coronary computed tomography angiography with suspected stenosis and stress-perfusion abnormality in ≥2 segments. The ESC-PTP was calculated based on age, sex, and symptom typicality, and the RF-CL and CACS-CL additionally included a number of risk factors and CACS. In total, 219/3374 (6.5%) patients had an MPD. Both the RF-CL and the CACS-CL classified substantially more patients to low CL (<5%) of obstructive coronary artery disease compared with the ESC-PTP (32.5 and 54.1 vs. 12.0%, P < 0.001) with preserved low prevalences of MPD (<2% for all models). Compared with the ESC-PTP [area under the receiver-operating characteristic curve (AUC) 0.74 (0.71-0.78)], the discrimination of having an MPD was higher for the CACS-CL model [AUC 0.88 (0.86-0.91), P < 0.001], while it was similar for the RF-CL model [AUC 0.73 (0.70-0.76), P = 0.32]. CONCLUSION: Compared with basic CL models, the RF-CL and CACS-CL models improve down classification of patients to a very low-risk group with a low prevalence of MPD.

Second-Line Myocardial Perfusion Imaging to Detect Obstructive Stenosis: Head-to-Head Comparison of CMR and PET.

BACKGROUND: Guidelines recommend verification of myocardial ischemia by selective second-line myocardial perfusion imaging (MPI) following a coronary computed tomography angiography (CTA) with suspected obstructive coronary artery disease (CAD). Head-to-head data on the diagnostic performance of different MPI modalities in this setting are sparse. OBJECTIVES: The authors sought to compare, head-to-head, the diagnostic performance of selective MPI by 3.0-T cardiac magnetic resonance (CMR) and 82rubidium positron emission tomography (RbPET) in patients with suspected obstructive stenosis at coronary CTA using invasive coronary angiography (ICA) with fractional flow reserve (FFR) as reference. METHODS: Consecutive patients (n = 1,732, mean age: 59.1 ± 9.5 years, 57.2% men) referred for coronary CTA with symptoms suggestive of obstructive CAD were included. Patients with suspected stenosis were referred for both CMR and RbPET and subsequently ICA. Obstructive CAD was defined as FFR ≤0.80 or >90% diameter stenosis by visual assessment. RESULTS: In total, 445 patients had suspected stenosis on coronary CTA. Of these, 372 patients completed both CMR, RbPET and subsequent ICA with FFR. Hemodynamically obstructive CAD was identified in 164 of 372 (44.1%) patients. Sensitivities for CMR and RbPET were 59% (95% CI: 51%-67%) and 64% (95% CI: 56%-71%); P = 0.21, respectively, and specificities 84% (95% CI: 78%-89%) and 89% (95% CI: 84%-93%]); P = 0.08, respectively. Overall accuracy was higher for RbPET compared with CMR (73% vs 78%; P = 0.03). CONCLUSIONS: In patients with suspected obstructive stenosis at coronary CTA, CMR, and RbPET show similar and moderate sensitivities but high specificities compared with ICA with FFR. This patient group represents a diagnostic challenge with frequent mismatch between advanced MPI tests and invasive measurements. (Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 2 [Dan-NICAD 2]; NCT03481712).

The clinical relevance of magnetic resonance imaging of the lower back.

Magnetic resonance imaging (MRI) is commonly used in the management of low back pain (LBP). This review provides an overview of the clinical relevance of degenerative MRI findings in the lumbar spine. The association between degenerative MRI findings and LBP is relatively consistent at population level, but very little research exists on the prognostic value of MRI findings and based on the current evidence, MRI cannot be used to guide treatment. Lumbar spine MRI is only recommended for patients with progressive neurological deficits, suspicion of specific pathology or in absence of progress of conservative treatment.

Colonic volume in patients with functional constipation or irritable bowel syndrome determined by magnetic resonance imaging.

BACKGROUND: Functional constipation (FC) and irritable bowel syndrome constipation type (IBS-C) share many similarities, and it remains unknown whether they are distinct entities or part of the same spectrum of disease. Magnetic resonance imaging (MRI) allows quantification of intraluminal fecal volume. We hypothesized that colonic volumes of patients with FC would be larger than those of patients with IBS-C, and that both patient groups would have larger colonic volumes than healthy controls (HC). METHODS: Based on validated questionnaires, three groups of participants were classified into FC (n = 13), IBS-C (n = 10), and HC (n = 19). The colonic volume of each subject was determined by MRI. Stool consistency was described by the Bristol stool scale and colonic transit times were assessed with radiopaque makers. KEY RESULTS: Overall, total colonic volumes were different in the three groups, HC (median 629 ml, interquartile range (IQR)(562-868)), FC (864 ml, IQR(742-940)), and IBS-C (520 ml IQR(489-593)) (p = 0.001). Patients with IBS-C had lower colonic volumes than patients with FC (p = 0.001) and HC (p = 0.019), but there was no difference between FC and HC (p = 0.10). Stool consistency was similar in the two patient groups, but patients with FC had longer colonic transit time than those with IBS-C (117.6 h versus 43.2 h, p = 0.019). CONCLUSION: Patients with IBS-C have lower total colonic volumes and shorter colonic transit times than patients with FC. Future studies are needed to confirm that colonic volume allows objective distinction between the two conditions.

Sex Differences in the Association Between Bone Mineral Density and Coronary Artery Disease in Patients Referred for Cardiac Computed Tomography.

Atherosclerosis and osteoporosis are both common and preventable diseases. Evidence supports a link between coronary artery disease (CAD) and low bone mineral density (BMD). This study aimed to assess the association between thoracic spine BMD and CAD in men and women with symptoms suggestive of CAD. This cross-sectional study included 1487 (mean age 57 years (range 40-80), 47% men) patients referred for cardiac computed tomography (CT). Agatston coronary artery calcium score (CACS), CAD severity (no, mild, moderate, and severe), vessel involvement (no, 1-, 2-, and 3/left main disease), and invasive measurements were evaluated. BMD of three thoracic vertebrae was measured using quantitative CT. We used the American college of radiology cut-off values for lumbar spine BMD to categorize patients into very low (<80 mg/cm3), low (80-120 mg/cm3), or normal BMD (>120 mg/cm3). BMD as a continuous variable was included in the linear regression analyses to assess associations between CACS (CACS=0, CACS 1- 399, and CACS ≥ 400) and BMD, and CAD severity and BMD. Significant lower BMD was present with increasing CACS and stenosis degree unadjusted. Multivariate linear regression analyses in women revealed a significant correlation between BMD and CACS groups (ß = -4.06, p<0.05), but no correlation between BMD and CAD severity (ß = -1.59, p = 0.14). No association was found between BMD and CACS (ß = -1.50, p = 0.36) and CAD severity (ß = 0.07, p = 0.94) in men. BMD is significantly correlated to CACS after adjusting for confounders in women, but not in men, suggesting a possible sex difference in pathophysiology.

One-step anatomic and function testing by cardiac CT versus second-line functional testing in symptomatic patients with coronary artery stenosis: head-to-head comparison of CT-derived fractional flow reserve and myocardial perfusion imaging.

BACKGROUND: CT-QFR is a novel coronary computed tomography angiography (CTA)-based method for on-site evaluation of patients with suspected obstructive coronary artery disease (CAD). AIMS: We aimed to compare the diagnostic performance of CT-QFR with myocardial perfusion scintigraphy (MPS) and cardiovascular magnetic resonance (CMR) as second-line tests in patients with suspected obstructive CAD after coronary CTA. METHODS: A paired analysis of CT-QFR and MPS or CMR, with an invasive FFR-based classification as reference standard was carried out. Symptomatic patients with >50% diameter stenosis on coronary CTA were randomised to MPS or CMR and referred for invasive coronary angiography. RESULTS: The rate of coronary CTA not feasible for CT-QFR analysis was 17%. Paired patient-level data were available for 118 patients in the MPS group and 113 in the CMR group. Patient-level diagnostic accuracy was better for CT-QFR than for both MPS (82.2% [95% CI: 75.2-89.2] vs 70.3% [95% CI: 62.0-78.7], p=0.029) and CMR (77.0% [95% CI: 69.1-84.9] vs 65.5% [95% CI: 56.6-74.4], p=0.047). Following a positive coronary CTA and with the intention to diagnose, CT-QFR, CMR and MPS were equally suitable as rule-in and rule-out modalities. CONCLUSIONS: The diagnostic performance of CT-QFR as a second-line test was at least similar to MPS and CMR for the evaluation of obstructive CAD in symptomatic patients presenting with ≥50% diameter stenosis on coronary CTA.

Thoracic Bone Mineral Density Derived from Cardiac CT Is Associated with Greater Fracture Rate.

Background Osteoporosis is a prevalent, under-diagnosed, and treatable disease associated with increased fracture risk. Bone mineral density (BMD) derived from cardiac CT may be used to determine fracture rate. Purpose To assess the association between fracture rate and thoracic BMD derived from cardiac CT. Materials and Methods This prospective cohort study included consecutive participants referred for cardiac CT for evaluation of ischemic heart disease between September 2014 and March 2016. End of follow-up was June 30, 2018. In all participants, volumetric BMD of three thoracic vertebrae was measured by using quantitative CT software. The primary and secondary outcomes were any incident fracture and any incident osteoporosis-related fracture registered in the National Patient Registry, respectively. Hazard ratios were assessed by using BMD categorized as very low (<80 mg/cm3), low (80-120 mg/cm3), or normal (>120 mg/cm3). The study is registered at ClinicalTrials.gov (identifier: NCT02264717). Results In total, 1487 participants (mean age, 57 years ± 9; age range, 40-80 years; 52.5% women) were included, of whom 179 (12.0%) had very low BMD. During follow-up (median follow-up, 3.1 years; interquartile range, 2.7-3.4 years; range, 0.2-3.8 years), 80 of 1487 (5.3%) participants were diagnosed with an incident fracture and in 31 of 80 participants, the fracture was osteoporosis related. In unadjusted Cox regressions analyses, very low BMD was association with a greater rate of any fracture (hazard ratio, 2.6; 95% confidence interval [CI]: 1.4, 4.7; P = .002) and any osteoporosis-related fracture (hazard ratio, 8.1; 95% CI: 2.4, 26.7; P = .001) compared with normal BMD. After adjusting for age and sex, very low BMD remained associated with any fracture (hazard ratio, 2.1; 95% CI: 1.1, 4.2) and any osteoporosis-related fracture (hazard ratio, 4.0; 95% CI: 1.1, 14.6). Conclusion Routine cardiac CT can be used to help measure thoracic bone mineral density (BMD) to identify individuals who have low BMD and a greater fracture rate. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Bredella in this issue.

Prediction of Coronary Revascularization in Stable Angina: Comparison of FFRCT With CMR Stress Perfusion Imaging.

OBJECTIVES: This study was designed to compare head-to-head fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) (FFRCT) and cardiac magnetic resonance (CMR) stress perfusion imaging for prediction of standard-of-care-guided coronary revascularization in patients with stable chest pain and obstructive coronary artery disease by coronary CTA. BACKGROUND: FFRCT is a novel modality for noninvasive functional testing. The clinical utility of FFRCT compared to CMR stress perfusion imaging in symptomatic patients with coronary artery disease is unknown. METHODS: Prospective study of patients (n = 110) with stable angina pectoris and 1 or more coronary stenosis ≥50% by coronary CTA. All patients underwent invasive coronary angiography. Revascularization was FFR-guided in stenoses ranging from 30% to 90%. FFRCT ≤0.80 in 1 or more coronary artery or a reversible perfusion defect (≥2 segments) by CMR categorized patients with ischemia. FFRCT and CMR were analyzed by core laboratories blinded for patient management. RESULTS: A total of 38 patients (35%) underwent revascularization. Per-patient diagnostic performance for identifying standard-of-care-guided revascularization, (95% confidence interval) yielded a sensitivity of 97% (86% to 100%) for FFRCT versus 47% (31% to 64%) for CMR, p < 0.001; corresponding specificity was 42% (30% to 54%) versus 88% (78% to 94%), p < 0.001; negative predictive value of 97% (91% to 100%) versus 76% (67% to 85%), p < 0.05; positive predictive value of 47% (36% to 58%) versus 67% (49% to 84%), p < 0.05; and accuracy of 61% (51% to 70%) versus 74% (64% to 82%), p > 0.05, respectively. CONCLUSIONS: In patients with stable chest pain referred to invasive coronary angiography based on coronary CTA, FFRCT and CMR yielded similar overall diagnostic accuracy. Sensitivity for prediction of revascularization was highest for FFRCT, whereas specificity was highest for CMR.

Comparison of quantitative flow ratio and fractional flow reserve with myocardial perfusion scintigraphy and cardiovascular magnetic resonance as reference standard. A Dan-NICAD substudy.

Quantitative flow ratio (QFR) and fractional flow reserve (FFR) have not yet been compared head to head with perfusion imaging as reference for myocardial ischemia. We aimed to compare the diagnostic accuracy of QFR and FFR with myocardial perfusion scintigraphy (MPS) or cardiovascular magnetic resonance (CMR) as reference. This study is a predefined post hoc analysis of the Dan-NICAD study (NCT02264717). Patients with suspected coronary artery disease by coronary computed tomography angiography (CCTA) were randomized 1:1 to MPS or CMR and were referred to invasive coronary angiography with FFR and predefined QFR assessment. Paired data with FFR, QFR and MPS or CMR were available for 232 vessels with stenosis in 176 patients. Perfusion defects were detected in 57 vessel territories (25%). For QFR and FFR the diagnostic accuracy was 61% and 57% (p = 0.18) and area under the receiver operating curve was 0.64 vs. 0.58 (p = 0.22). Stenoses with absolute indication for stenting due to diameter stenosis > 90% by visual estimate were not classified as significant by either QFR or MPS/CMR in 21% (7 of 34) of cases. The diagnostic performance of QFR and FFR was similar but modest with MPS or CMR as reference. Comparable performance levels for QFR and FFR are encouraging for this pressure wire-free diagnostic method.

Danish study of Non-Invasive testing in Coronary Artery Disease 2 (Dan-NICAD 2): Study design for a controlled study of diagnostic accuracy.

BACKGROUND: Coronary computed tomography angiography (CTA) is the preferred primary diagnostic modality when examining patients with low to intermediate pre-test probability of coronary artery disease (CAD). Only 20-30% of these have potentially obstructive CAD. Because of the relatively poor positive predictive value of coronary CTA, unnecessary invasive coronary angiographies (ICAs) are conducted with the costs and risks associated with the procedure. Hence, an optimized diagnostic CAD algorithm may reduce the numbers of ICAs not followed by revascularization. The Dan-NICAD 2 study has 3 equivalent main aims: (1) To examine the diagnostic precision of a sound-based diagnostic algorithm, The CADScor®System (Acarix A/S, Denmark), in patients with a low to intermediate pre-test risk of CAD referred to a primary examination by coronary CTA. We hypothesize that the CADScor®System provides better stratification prior to coronary CTA than clinical risk stratification scores alone. (2) To compare the diagnostic accuracy of 3T cardiac magnetic resonance imaging (3T CMRI), 82rubidium positron emission tomography (82Rb-PET), and CT-derived fractional flow reserve (FFRCT) in patients where obstructive CAD cannot be ruled out by coronary CTA using ICA fractional flow reserve (FFR) as reference standard. (3) To compare the diagnostic performance of quantitative flow ratio (QFR) and ICA-FFR in patients with low to intermediate pre-test probability of CAD using 82Rb-PET as reference standard. METHODS: Dan-NICAD 2 is a prospective, multicenter, cross-sectional study including approximately 2,000 patients with low to intermediate pre-test probability of CAD and without previous history of CAD. Patients are referred to coronary CTA because of symptoms suggestive of CAD, as evaluated by a cardiologist. Patient interviews, sound recordings, and blood samples are obtained in connection with the coronary CTA. If coronary CTA does not rule out obstructive CAD, patients will be examined by 3T CMRI 82Rb-PET, FFRCT, ICA, and FFR. Reference standard is ICA-FFR. Obstructive CAD is defined as an FFR ≤0.80 or as high-grade stenosis (>90% diameter stenosis) by visual assessment. Diagnostic performance will be evaluated as sensitivity, specificity, predictive values, likelihood ratios, calibration, and discrimination. Enrolment started January 2018 and is expected to be completed by June 2020. Patients are followed for 10 years after inclusion. DISCUSSION: The results of the Dan-NICAD 2 study are expected to contribute to the improvement of diagnostic strategies for patients suspected of CAD in 3 different steps: risk stratification prior to coronary CTA, diagnostic strategy after coronary CTA, and invasive wireless QFR analysis as an alternative to ICA-FFR.

Danish study of Non-Invasive testing in Coronary Artery Disease (Dan-NICAD): study protocol for a randomised controlled trial.

BACKGROUND: Coronary computed tomography angiography (CCTA) is an established method for ruling out coronary artery disease (CAD). Most patients referred for CCTA do not have CAD and only approximately 20-30 % of patients are subsequently referred to further testing by invasive coronary angiography (ICA) or non-invasive perfusion evaluation due to suspected obstructive CAD. In cases with severe calcifications, a discrepancy between CCTA and ICA often occurs, leading to the well-described, low-diagnostic specificity of CCTA. As ICA is cost consuming and involves a risk of complications, an optimized algorithm would be valuable and could decrease the number of ICAs that do not lead to revascularization. The primary objective of the Dan-NICAD study is to determine the diagnostic accuracy of cardiac magnetic resonance imaging (CMRI) and myocardial perfusion scintigraphy (MPS) as secondary tests after a primary CCTA where CAD could not be ruled out. The secondary objective includes an evaluation of the diagnostic precision of an acoustic technology that analyses the sound of coronary blood flow. It may potentially provide better stratification prior to CCTA than clinical risk stratification scores alone. METHODS/DESIGN: Dan-NICAD is a multi-centre, randomised, cross-sectional trial, which will include approximately 2,000 patients without known CAD, who were referred to CCTA due to a history of symptoms suggestive of CAD and a low-risk to intermediate-risk profile, as evaluated by a cardiologist. Patient interview, sound recordings, and blood samples are obtained in connection with the CCTA. All patients with suspected obstructive CAD by CCTA are randomised to either stress CMRI or stress MPS, followed by ICA with fractional flow reserve (FFR) measurements. Obstructive CAD is defined as an FFR below 0.80 or as high-grade stenosis (>90 % diameter stenosis) by visual assessment. Diagnostic performance is evaluated as sensitivity, specificity, predictive values, likelihood ratios, and C statistics. Enrolment commenced in September 2014 and is expected to be complete in May 2016. DISCUSSION: Dan-NICAD is designed to assess whether a secondary perfusion examination after CCTA could safely reduce the number of ICAs where revascularization is not required. The results are expected to add knowledge about the optimal algorithm for diagnosing CAD. TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT02264717 . Registered on 26 September 2014.

Coronary computed tomography angiography and calcium scoring in routine clinical practice for identification of patients who require revascularization.

BACKGROUND: The predictive value of CCTA to predict coronary artery disease is high in particular in the absence of coronary calcification. However, the consideration of both CCTA and the calcium score, in addition to the risk factors to determine the indication for coronary revascularization, has not been yet studied. MATERIALS AND METHODS: This study included 2302 patients (mean age: 60±9.8 years, 46% men), without known coronary artery disease (CAD), who underwent 320-row CCTA. Logistic regression, c-statistic and net reclassification improvement (NRI) were used to assess the role of coronary artery calcium score (CACS) in predicting revascularization after CCTA. RESULTS: The revascularization rates were 0.75% in patients with a CACS of 0, and there were no adverse events during the follow-up period. The revascularization rates were 3.3% in patients with a CACS of 1-99, 15.4% in patients with a CACS of 100-399, 25.6% in patients with a CACS of 400-999, and 42.4% in patients with a CACS≥1000. The crude and adjusted odds ratios (95% confidence interval) for revascularization per CACS group category were 2.89 (2.53-2.3) and 2.71 (2.33-3.15), respectively; the area under the ROC curve (AUC) was 0.85 (0.83-0.88). The addition of CACS to conventional risk factors improved the accuracy of risk prediction model for revascularization (AUC 0.74 vs 0.63, P=0.001), but it did not reclassify a substantial proportion of patients with positive CACS to risk categories (NRI=-0.023, P=0.66). CONCLUSIONS: The 320-row CCTA might rule out CAD in low- to intermediate-risk patients. However, its accuracy in identifying patients who require revascularization is limited. The CACS added to the conventional risk factors did not improve the identification of patients who require revascularization.

Single-centre cohort study of gender influence in coronary CT angiography in patients with a low to intermediate pretest probability of coronary heart disease.

BACKGROUND: In 'real-world' patient populations undergoing coronary CT angiography (CCTA), it is unclear whether a correlation exists between gender, coronary artery calcium (CAC) score and subsequent referral for invasive coronary angiography and coronary revascularisation. We therefore investigated the relationship between gender, CAC and use of subsequent invasive coronary angiography and coronary revascularisation in a cohort of patients with chest discomfort and low to intermediate pretest probability of coronary artery disease who underwent a CCTA at our diagnostic centre. METHODS: This is a cohort study that included patients examined between 2010 and 2013. Data were obtained from the Western Denmark Heart Registry. The follow-up ended 11 March 2014. RESULTS: A total of 3541 people (1621 men and 1920 women) were examined by CCTA. The rate of invasive coronary angiography during follow-up was 28.5% in men versus 18.3% in women (p<0.001). The rate of coronary revascularisation during follow-up was 11.4% in men versus 5.1% in women (p<0.001). The CAC-adjusted HR in women versus men was 0.98 (95% CI 0.85 to 1.13) for invasive coronary angiography and 0.73 (95% CI 0.57 to 0.93) for coronary revascularisation. Further adjustment for age and other risk factors did not change these estimates. CONCLUSIONS: Women had a lower CAC score than men and a corresponding lower rate of invasive coronary angiography. The risk of coronary revascularisation was modestly reduced in women, irrespective of CAC. This may reflect a gender-specific difference in coping with chest discomfort, gender-specific referral bias for CCTA, and/or a gender-specific difference in the balance between coronary calcification and obstructive coronary heart disease.

[Suddenly occurring pain in the shin due to solitary metastasis to bone from a non-recognised primary tumour]. / Nyopståede smerter i crus på baggrund af ossøs solitær metastase fra ikkeerkendt primærtumor.

A woman who had formerly had adequately treated breast cancer presented with symptoms of pain in the right shin. An X-ray of the punctum maximum for the pain showed a bone lesion. Biopsy revealed that it came from an adenocarcinoma of the lung, contrary to the first diagnosis of breast cancer meta-stasis. The lung lesion had been seen on a subsequent computed tomography. There were no presenting symptoms relating to lung cancer. This case is interesting as adenocarcinoma metastasis to bone rarely occurs in the tibia and below the knee.

CT coronary angiography in low- to intermediate-risk patients: less radiation, less invasive angiography, and less revascularisation.

OBJECTIVES: We investigated whether any change in the use of invasive coronary angiography and coronary revascularisation after CT coronary angiography in patients with a low to intermediate pre-test probability of coronary artery disease could be explained from alterations in patient characteristics. DESIGN: A cohort study based on data samples from the Western Denmark Heart Registry. Follow-up ended on 11 March 2014. RESULTS: A total of 3541 persons were examined during the period of January 2010-December 2013. The median radiation dose was reduced from 4.2 to 2.2 mSv (p < 0.001) due to improved technology. The immediate referral rate for subsequent myocardial perfusion scans was increased from 2.8% to 10.0% (p < 0.001), while the immediate referral rate for invasive coronary angiography decreased from 25.3% to 10.8% (p < 0.001). The revascularisation rate diminished from 10.4% to 6.3%. The multivariable adjusted hazard ratio (95% confidence interval) for invasive coronary angiography during follow-up after CT coronary angiography was 0.59 (0.47-0.74) and that for coronary revascularisation was 0.66 (0.45-0.97) in 2013 compared to that in 2010. CONCLUSIONS: The radiation dose diminished considerably. The reductions in the use of invasive coronary angiography and coronary revascularisation could not be explained by changes in patient characteristics but are driven by an increased use of perfusion scans in combination with increasing use of measurement of functional coronary flow reserve.

Sudden cardiac death in a young woman: tumor of the atrioventricular (AV) node or citalopram intoxication?

Atrioventricular (AV) node tumor is a very rare lesion of the cardiac conduction system. Clinically, it is associated with complete AV block and sudden cardiac death, often in apparently healthy young people. We report a case of a 24-year-old woman who developed ventricular fibrillation during sexual intercourse and died before admittance to the hospital. The woman had a medical history of depression and was treated with citalopram.At first, no macroscopic or microscopic pathologic changes were found. Toxicologic analysis showed a toxic level of citalopram in the blood. Further microscopic examination of the cardiac conduction system disclosed a tumor of the AV node. Immunohistochemical staining confirmed endodermal origin in accordance with the latest hypothesis of the pathogenesis of this tumor. It was concluded that this young woman died of cardiac arrhythmia due to the AV tumor and not from citalopram intoxication, as first suspected. This case emphasizes the importance of a microscopic examination of the cardiac conduction system in cases of sudden unexpected death, even in cases with a plausible cause and manner of death at first glance.