J. Tobias Kühl

Left Atrial Function and Mortality in Patients With NSTEMI: An MDCT Study

OBJECTIVES We sought to test the hypothesis that measures of left atrial (LA) function are independent predictors of mortality in patients with acute myocardial infarction. BACKGROUND Left atrial maximal volume (LAmax) is known to predict mortality in patients with acute myocardial infarction. In a previous pilot study, however, we found that LA function in terms of fractional change and left atrial ejection fraction (LAEF) assessed by multidetector computed tomography (MDCT) is more closely related to clinical heart failure than LAmax. METHODS We prospectively included 384 patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) who underwent retrospectively gated, 64-slice MDCT coronary angiography and subsequent measurements of LA size and function. All patients were treated according to the current guidelines based on invasive coronary angiography. Patients were followed for a minimum of 2 years. The study endpoint was all-cause mortality. RESULTS The median follow-up time was 36 months (range 10 to 1,551 days). During follow-up, 35 (9%) patients died. Overall, 1- and 2-year survival in the study cohort was 97% and 94%. LA size and mechanical function was obtained in all patients: mean LAmax was 55 ± 11 ml/m(2), LA minimal volume 31 ± 11 ml/m(2), fractional change 45 ± 9%, and LAEF 32 ± 9%. Using a Cox proportional hazards model with adjustments for age, number of diseased coronary vessels, left ventricular ejection fraction (LVEF), and Killip class, both fractional change (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.45 to 0.94) and LAEF (HR: 0.63; 95% CI: 0.44 to 0.91) remained independent predictors of mortality. In contrast to this, LAmax was not significantly associated with an increased risk of mortality in this population. CONCLUSIONS In a low-risk group of patients with NSTEMI, reduced LA function is an independent predictor of mortality and provides prognostic value incremental to that of LAmax.

Normal values of left ventricular mass and cardiac chamber volumes assessed by 320-detector computed tomography angiography in the Copenhagen General Population Study

AIMS Normal values of left ventricular mass (LVM) and cardiac chamber sizes are prerequisites for the diagnosis of individuals with heart disease. LVM and cardiac chamber sizes may be recorded during cardiac computed tomography angiography (CCTA), and thus modality specific normal values are needed. METHODS AND RESULTS We studied 569 healthy subjects undergoing 320-detector CCTA as a part of the Copenhagen General Population Study. LVM as well as ventricular and atrial volumes was assessed with semi-automated software stratified by gender and age decades and indexed by body surface area (BSA). Mean age was 55 (range: 40-84) years, and 188 (33%) were men. BSA-indexed 97.5th percentile cut-off values: LVM = 80 and 65 gr/m(2), left ventricular volume = 97 and 83 mL/m(2), right ventricular volume = 120 and 102 mL/m(2), left atrial volume = 60 and 57 mL/m(2), and right atrial volume = 85 and 73 mL/m(2) for men and women, respectively. Men had greater absolute and indexed LVM and chamber volumes than women. For both genders, indexed ventricular volumes declined, whereas indexed atrial volumes increased in advancing age groups. For men, indexed LVM declined in advancing age groups. In multivariate analyses, gender, BSA, systolic blood pressure, and hard physical activity accounted for 63% of variance in LVM. CONCLUSION In this cross-sectional general population study, men have greater indexed LVM and chamber volumes than women, and cardiac indexed volumes vary between age groups in both genders. These findings demonstrate the need for age- and gender-specific normal values for clinical diagnostic purposes.

The Transmural Extent and Severity of Myocardial Hypoperfusion Predicts Long-Term Outcome in NSTEMI: An MDCT Study

OBJECTIVES The objective of this study was to test the hypothesis that the extent and severity of left ventricular myocardial hypoperfusion at rest, in addition to signs of left ventricular myocardial scar, are related to adverse long-term outcome in patients with non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND Multidetector computed tomography (MDCT) is a noninvasive test with a spatial resolution that allows for the assessment of transmural myocardial perfusion. In patients with suspected NSTEMI, the assessment of myocardial hypoperfusion could be clinically useful. METHODS MDCT was performed at rest before invasive treatment in 396 patients with NSTEMI. The transmural involvement of left ventricular hypoperfusion, the presence of intramyocardial fat or calcification, a summed defect score adding the extent of left ventricular myocardial hypoperfusion (0 to 64 point scale), and the transmural attenuation ratio between the subendocardial and the subepicardial myocardium were assessed. The study endpoint was a combination of death and hospitalization due to heart failure. RESULTS The median follow-up time of the study was 50 months, and the study endpoint was reached in 56 (15%) of the patients. In a Cox proportional hazards survival model with adjustments for known risk factors, both the summed defect score and transmural attenuation ratio were independently associated with adverse outcome (hazard ratio [HR]: 1.07; 95% confidence interval [CI]: 1.02 to 1.11; p = 0.004 and HR: 0.61; 95% CI: 0.44 to 0.85; p = 0.003, respectively). The presence of intramyocardial fat or calcification was also associated with adverse outcome (HR: 3.5; 95% CI: 1.2 to 10.7; p = 0.03) when compared with patients without any perfusion defect. CONCLUSIONS The extent and severity of left ventricular myocardial hypoperfusion at rest and signs of left ventricular myocardial scar assessed with MDCT before invasive treatment is strongly linked to adverse long-term outcome in patients with NSTEMI.

Coronary CT angiography in clinical triage of patients at high risk of coronary artery disease

Abstract Objectives. To test if cardiac computed tomography angiography (CCTA) can be used in the triage of patients at high risk of coronary artery disease. Design. The diagnostic value of 64-detector CCTA was evaluated in 400 patients presenting with non-ST segment elevation myocardial infarction using invasive coronary angiography (ICA) as the reference method. The relation between the severity of disease by CCTA and a combined endpoint of death, re-hospitalization due to new myocardial infarction, or symptom-driven coronary revascularization was assessed. Results. CCTA detects significant (>50%) coronary artery diameter stenosis with a sensitivity, specificity, and positive and negative predictive value of 99%, 81%, 96% and 95%, respectively. CCTA was used to triage patients into guideline defined treatment groups of “no or medical treatment”, “referral to percutaneous coronary intervention” or to “coronary artery bypass graft surgery” and was compared to the index ICA. CCTA correctly triaged patients in 86% of cases. During a median follow-up of 50 months, the presence of an occluded artery by CCTA was associated with adverse outcome. Conclusion. CCTA has high diagnostic and prognostic value in patients with high likelihood of coronary artery disease and could, in theory, be used to triage high risk patients. As many obstacles remain, including logistical and safety issues, our study does not support the use of CCTA as an additional diagnostic test before ICA in an all-comer NSTEMI population.

Assessment of coronary calcification using calibrated mass score with two different multidetector computed tomography scanners in the Copenhagen General Population Study

OBJECTIVE Population studies have shown coronary calcium score to improve risk stratification in subjects suspected for cardiovascular disease. The aim of this work was to assess the validity of multidetector computed tomography (MDCT) for measurement of calibrated mass scores (MS) in a phantom study, and to investigate inter-scanner variability for MS and Agaston score (AS) recorded in a population study on two different high-end MDCT scanners. MATERIALS AND METHODS A calcium phantom was scanned by a first (A) and second (B) generation 320-MDCT. MS was measured for each calcium deposit from repeated measurements in each scanner and compared to known physical phantom mass. Random samples of human subjects from the Copenhagen General Population Study were scanned with scanner A (N=254) and scanner B (N=253) where MS and AS distributions of these two groups were compared. RESULTS The mean total MS of the phantom was 32.9±0.8mg and 33.1±0.9mg (p=0.43) assessed by scanner A and B respectively - the physical calcium mass was 34.0mg. Correlation between measured MS and physical calcium mass was R2=0.99 in both scanners. In the population study the median total MS was 16.8mg (interquartile range (IQR): 3.5-81.1) and 15.8mg (IQR: 3.8-63.4) in scanner A and B (p=0.88). The corresponding median total AS were 92 (IQR: 23-471) and 89 (IQR: 40-384) (p=0.64). CONCLUSION Calibrated calcium mass score may be assessed with very high accuracy in a calcium phantom by different generations of 320-MDCT scanners. In population studies, it appears acceptable to pool calcium scores acquired on different 320-MDCT scanners.

Myocardial perfusion 320-row multidetector computed tomography–guided treatment strategy for the clinical management of patients with recent acute-onset chest pain: Design of the CArdiac cT in the treatment of acute CHest pain (CATCH)-2 randomized controlled trial

AIMS Patients admitted with chest pain are a diagnostic challenge because the majority does not have coronary artery disease (CAD). Assessment of CAD with coronary computed tomography angiography (CCTA) is safe, cost-effective, and accurate, albeit with a modest specificity. Stress myocardial computed tomography perfusion (CTP) has been shown to increase the specificity when added to CCTA, without lowering the sensitivity. This article describes the design of a randomized controlled trial, CATCH-2, comparing a clinical diagnostic management strategy of CCTA alone against CCTA in combination with CTP. METHODS Patients with acute-onset chest pain older than 50 years and with at least one cardiovascular risk factor for CAD are being prospectively enrolled to this study from 6 different clinical sites since October 2013. A total of 600 patients will be included. Patients are randomized 1:1 to clinical management based on CCTA or on CCTA in combination with CTP, determining the need for further testing with invasive coronary angiography including measurement of the fractional flow reserve in vessels with coronary artery lesions. Patients are scanned with a 320-row multidetector computed tomography scanner. Decisions to revascularize the patients are taken by the invasive cardiologist independently of the study allocation. The primary end point is the frequency of revascularization. Secondary end points of clinical outcome are also recorded. DISCUSSION The CATCH-2 will determine whether CCTA in combination with CTP is diagnostically superior to CCTA alone in the management of patients with acute-onset chest pain.

Four-dimensional image processing of myocardial CT perfusion for improved image quality and noise reduction

BACKGROUND Image noise and multiple sources of artifact may affect the accurate interpretation of myocardial CT perfusion (CTP) studies. Although artifact within the image is often time dependent, tissue characteristics remain unchanged irrespective of cardiac phase. OBJECTIVE We assessed a new technique of 4-dimensional, spatiotemporal analysis, using redundant time domain information within additional phase acquisitions to reduce CTP image noise. METHODS Four-dimensional analysis was assessed in a static phantom and in 10 CTP studies with invasive fractional flow reserve (FFR) correlation. For each voxel within the CTP study the distribution of local Hounsfield values was measured in both time and space with the use of a customized program within MATLAB software. These values were filtered to eliminate those likely to represent noise or rapidly changing beam hardening artifact. All CTP images were acquired within a single heartbeat with 320 detector-row CT. Image noise was quantified as the SD of voxel values within myocardial segments. Contrast was measured between normal and abnormal vascular territories as assessed by FFR. RESULTS The mean image noise within the unprocessed CTP images was 30 HU (range, 23-42 HU). After 4-dimensional filtering the mean image noise was 22 HU (range, 15-29 HU). The mean reduction in image noise was 28% (P < 0.001). The mean contrast between normally perfused and ischemic segments was not significantly changed. The mean increase in contrast-to-noise ratio between ischemic territories and the myocardial average was 52% (P < 0.001). CONCLUSION Four-dimensional analysis of CTP significantly reduces image noise and may assist in the assessment of myocardial perfusion studies.

Accurate, fully-automated registration of coronary arteries for volumetric CT digital subtraction angiography

Diagnosis of coronary artery disease with Coronary Computed Tomography Angiography (CCTA) is complicated by the presence of signi cant calci cation or stents. Volumetric CT Digital Subtraction Angiography (CTDSA) has recently been shown to be e ective at overcoming these limitations. Precise registration of structures is essential as any misalignment can produce artifacts potentially inhibiting clinical interpretation of the data. The fully-automated registration method described in this paper addresses the problem by combining a dense deformation eld with rigid-body transformations where calci cations/stents are present. The method contains non-rigid and rigid components. Non-rigid registration recovers the majority of motion artifacts and produces a dense deformation eld valid over the entire scan domain. Discrete domains are identi ed in which rigid registrations very accurately align each calci cation/stent. These rigid-body transformations are combined within the immediate area of the deformation eld using a distance transform to minimize distortion of the surrounding tissue. A recent interim analysis of a clinical feasibility study evaluated reader con dence and diagnostic accuracy in conventional CCTA and CTDSA registered using this method. Conventional invasive coronary angiography was used as the reference. The study included 27 patients scanned with a second-generation 320-row CT detector in which 41 lesions were identi ed. Compared to conventional CCTA, CTDSA improved reader con dence in 13/36 (36%) of segments with severe calci cation and 3/5 (60%) of segments with coronary stents. Also, the false positive rate of CTDSA was reduced compared to conventional CCTA from 18% (24/130) to 14% (19/130).

Subtraction CT angiography improves evaluation of significant coronary artery disease in patients with severe calcifications or stents—the C-Sub 320 multicenter trial

ObjectivesDiagnostic accuracy of conventional coronary CT angiography (CCTAconv) may be compromised by blooming artifacts from calcifications or stents. Blooming artifacts may be reduced by subtraction coronary CT angiography (CCTAsub) in which non-contrast and contrast CT data sets are subtracted digitally. We tested whether CCTAsub in patients with severe coronary calcification or stents reduces the number of false-positive stenosis evaluations compared with CCTAconv.MethodsIn this study, 180 symptomatic patients scheduled for invasive coronary angiography (ICA) were prospectively enrolled and CT scanned (2013-2016) at three international centers. CCTAconv, and CCTAsub data sets were reconstructed. Target segments were defined as motion-free coronary segments with a suspected stenosis (> 50% of lumen) potentially due to blooming of either calcium or stents. Target segments were evaluated with respect to misregistration artifacts from the CCTAsub reconstruction process, in which case evaluation was omitted. CCTAsub and CCTAconv were compared with ICA. Primary outcome measure was the frequency of false positives by CCTAconv versus CCTAsub to identify > 50% coronary stenosis by ICA on a per-segment level.ResultsAfter exclusion of 76 patients, 104 (14% females) with mean age 67 years and median Agatston score 852 were included. There were 136 target segments with misregistration and 121 target segments without. Accuracy calculations in target segments without misregistration showed a reduction of the false positives from 72% [95% confidence interval (CI): 63-80%] in CCTAconv to 33% (CI:25-42%) in CCTAsub, at the expense of 7% (CI:3-14%) false negatives in CCTAsub.ConclusionsIn severely calcified coronary arteries or stents, CCTAsub reduces the false-positive rate in well-aligned, calcified or stent segments suspected of significant stenosis on CCTAconv. Nevertheless, misregistration artifacts are frequent in CCTAsub.Key Points• A high calcium-score reduces the diagnostic accuracy in patients scanned with cardiac CT.• These patients would normally need an invasive angiogram for diagnosis.• In this prospective, multicenter study, subtraction CT, when evaluable, reduces false-positive stenosis evaluations.• Subtraction coronary CT angiography may, when evaluable, reduce excessive downstream testing.

Relationship between patient presentation and morphology of coronary atherosclerosis by quantitative multidetector computed tomography

Aims Quantitative computed tomography (QCT) allows assessment of morphological features of coronary atherosclerosis. We aimed to test the hypothesis that clinical patient presentation is associated with distinct morphological features of coronary atherosclerosis. Methods and results A total of 1652 participants, representing a spectrum of clinical risk profiles [787 asymptomatic individuals from the general population, 468 patients with acute chest pain without acute coronary syndrome (ACS), and 397 patients with acute chest pain and ACS], underwent multidetector computed tomography. Of these, 274 asymptomatic individuals, 254 patients with acute chest pain without ACS, and 327 patients with acute chest pain and ACS underwent QCT to assess coronary plaque volumes and proportions of dense calcium (DC), fibrous, fibro fatty (FF), and necrotic core (NC) tissue. Furthermore, the presence of vulnerable plaques, defined by plaque volume and tissue composition, was examined. Coronary plaque volume increased significantly with worsening clinical risk profile [geometric mean (95% confidence interval): 148 (129-166) mm3, 257 (224-295) mm3, and 407 (363-457) mm3, respectively, P < 0.001]. Plaque composition differed significantly across cohorts, P < 0.0001. The proportion of DC decreased, whereas FF and NC increased with worsening clinical risk profile (mean proportions DC: 33%, 23%, 23%; FF: 50%, 61%, 57%; and NC: 17%, 17%, 20%, respectively). Significant differences in plaque composition persisted after multivariable adjustment for age, gender, body surface area, hypertension, statin use at baseline, diabetes, smoking, family history of ischaemic heart disease, total plaque volume, and tube voltage, P < 0.01. Conclusion Coronary atherosclerotic plaque volume and composition are strongly associated to clinical presentation.