Fabian Plank

Prediction model to estimate presence of coronary artery disease: Retrospective pooled analysis of existing cohorts

Objectives To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations. Design Retrospective pooled analysis of individual patient data. Setting 18 hospitals in Europe and the United States. Participants Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively). Main outcome measures Obstructive coronary artery disease (≥50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined. Results We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory. Conclusions Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates.

Does coronary CT angiography improve risk stratification over coronary calcium scoring in symptomatic patients with suspected coronary artery disease? Results from the prospective multicenter international CONFIRM registry

AIMS The prognostic value of coronary artery calcium (CAC) scoring is well established and has been suggested for use to exclude significant coronary artery disease (CAD) for symptomatic individuals with CAD. Contrast-enhanced coronary computed tomographic angiography (CCTA) is an alternative modality that enables direct visualization of coronary stenosis severity, extent, and distribution. Whether CCTA findings of CAD add an incremental prognostic value over CAC in symptomatic individuals has not been extensively studied. METHODS AND RESULTS We prospectively identified symptomatic patients with suspected but without known CAD who underwent both CAC and CCTA. Symptoms were defined by the presence of chest pain or dyspnoea, and pre-test likelihood of obstructive CAD was assessed by the method of Diamond and Forrester (D-F). CAC was measured by the method of Agatston. CCTAs were graded for obstructive CAD (>70% stenosis); and CAD plaque burden, distribution, and location. Plaque burden was determined by a segment stenosis score (SSS), which reflects the number of coronary segments with plaque, weighted for stenosis severity. Plaque distribution was established by a segment-involvement score (SIS), which reflects the number of segments with plaque irrespective of stenosis severity. Finally, a modified Duke prognostic index-accounting for stenosis severity, plaque distribution, and plaque location-was calculated. Nested Cox proportional hazard models for a composite endpoint of all-cause mortality and non-fatal myocardial infarction (D/MI) were employed to assess the incremental prognostic value of CCTA over CAC. A total of 8627 symptomatic patients (50% men, age 56 ± 12 years) followed for 25 months (interquartile range 17-40 months) comprised the study cohort. By CAC, 4860 (56%) and 713 (8.3%) patients had no evident calcium or a score of >400, respectively. By CCTA, 4294 (49.8%) and 749 (8.7%) had normal coronary arteries or obstructive CAD, respectively. At follow-up, 150 patients experienced D/MI. CAC improved discrimination beyond D-F and clinical variables (area under the receiver-operator characteristic curve 0.781 vs. 0.788, P = 0.004). When added sequentially to D-F, clinical variables, and CAC, all CCTA measures of CAD improved discrimination of patients at risk for D/MI: obstructive CAD (0.82, P < 0.001), SSS (0.81, P < 0.001), SIS (0.81, P = 0.003), and Duke CAD prognostic index (0.82, P < 0.0001). CONCLUSION In symptomatic patients with suspected CAD, CCTA adds incremental discriminatory power over CAC for discrimination of individuals at risk of death or MI.

All-cause mortality benefit of coronary revascularization vs. medical therapy in patients without known coronary artery disease undergoing coronary computed tomographic angiography: results from CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter Registry)

AIMS To date, the therapeutic benefit of revascularization vs. medical therapy for stable individuals undergoing invasive coronary angiography (ICA) based upon coronary computed tomographic angiography (CCTA) findings has not been examined. METHODS AND RESULTS We examined 15 223 patients without known coronary artery disease (CAD) undergoing CCTA from eight sites and six countries who were followed for median 2.1 years (interquartile range 1.4-3.3 years) for an endpoint of all-cause mortality. Obstructive CAD by CCTA was defined as a ≥50% luminal diameter stenosis in a major coronary artery. Patients were categorized as having high-risk CAD vs. non-high-risk CAD, with the former including patients with at least obstructive two-vessel CAD with proximal left anterior descending artery involvement, three-vessel CAD, and left main CAD. Death occurred in 185 (1.2%) patients. Patients were categorized into two treatment groups: revascularization (n = 1103; 2.2% mortality) and medical therapy (n = 14 120, 1.1% mortality). To account for non-randomized referral to revascularization, we created a propensity score developed by logistic regression to identify variables that influenced the decision to refer to revascularization. Within this model (C index 0.92, χ2 = 1248, P < 0.0001), obstructive CAD was the most influential factor for referral, followed by an interaction of obstructive CAD with pre-test likelihood of CAD (P = 0.0344). Within CCTA CAD groups, rates of revascularization increased from 3.8% for non-high-risk CAD to 51.2% high-risk CAD. In multivariable models, when compared with medical therapy, revascularization was associated with a survival advantage for patients with high-risk CAD [hazards ratio (HR) 0.38, 95% confidence interval 0.18-0.83], with no difference in survival for patients with non-high-risk CAD (HR 3.24, 95% CI 0.76-13.89) (P-value for interaction = 0.03). CONCLUSION In an intermediate-term follow-up, coronary revascularization is associated with a survival benefit in patients with high-risk CAD by CCTA, with no apparent benefit of revascularization in patients with lesser forms of CAD.

Evaluation of myocardial CT perfusion in patients presenting with acute chest pain to the emergency department: comparison with SPECT-myocardial perfusion imaging

Objective To determine whether evaluation of resting myocardial CT perfusion (CTP) from coronary CT angiography (CTA) datasets in patients presenting with chest pain (CP) to the emergency department (ED), might have added value to coronary CTA. Design, setting 76 Patients (age 54.9 y±13; 32 (42%) women) presenting with CP to the ED underwent coronary 64-slice CTA. Myocardial perfusion defects were evaluated for CTP (American Heart Association 17-segment model) and compared with rest sestamibi single-photon emission CT myocardial perfusion imaging (SPECT-MPI). CTA was assessed for >50% stenosis per vessel. Results CTP demonstrated a sensitivity of 92% and 89%, specificity of 95% and 99%, positive predictive value (PPV) of 80% and 82% and negative predictive value (NPV) of 98% and 99% for each patient and for each segment, respectively. CTA showed an accuracy of 92%, sensitivity of 70.4%, specificity of 95.5%, PPV 67.8%, and NPV of 95% compared with SPECT-MPI. When CTP findings were added to CTA the PPV improved from 67% to 90.1%. Conclusions In patients presenting to the ED with CP, the evaluation of rest myocardial CTP demonstrates high diagnostic performance as compared with SPECT-MPI. Addition of CTP to CTA improves the accuracy of CTA, primarily by reducing rates of false-positive CTA.

The diagnostic and prognostic value of coronary CT angiography in asymptomatic high-risk patients: a cohort study

Objective To prospectively assess the value of coronary CT angiography (CTA) in asymptomatic patients with high ‘a priori’ risk of coronary artery disease (CAD). Methods 711 consecutive asymptomatic patients (61.8 years; 40.1% female) with high ‘a priori’ risk of CAD were prospectively examined with a coronary calcium score (CCS) and CTA. Coronary arteries were evaluated for atherosclerotic plaque (non-calcified and calcified) and stenosis (mild <50%, intermediate 50–70% or high-grade >70%). Coronary Segment Involvement Score (SIS, total number of segments with plaque) and nc (non-calcified) SIS were calculated. Primary end points were major adverse cardiac events (ST-elevation MI, non-ST-elevation MI and cardiac death); secondary end points were coronary revascularisation and >50% stenosis by invasive angiography. Results Of 711 patients, 28.3% were negative for CAD and 71.7% positive (CAD+) by CTA (15.6% had plaques without stenosis, 23.9% mild, 10.7% intermediate and 21.5% high-grade stenosis). CCS zero prevalence was 306 (43%), out of those 100 (32.7%) had non-calcified plaque only. Mean follow-up period was 2.65 years. MACE rate was 0% in CAD negative and higher (1.2%) in CAD positive by CTA. Coronary revascularisation rate was 5.5%. Patients with SIS ≥5 had an HR of 6.5 (95% CI 1.6 to 25.8, p<0.013) for MACE, patients with ncSIS ≥1 had an HR of 2.4 (95% CI 1.2 to 4.6, p<0.01) for secondary end point. The sensitivity of CTA for stenosis >50% compared with invasive angiography was 92.9% (95% CI 83.0% to 98.1%). Negative predictive value of CTA was 99.4% (95% CI 98.3% to 99.8%) for combined end points. Conclusions CAD prevalence by CTA in asymptomatic high-risk patients is high. CCS zero does not exclude CAD. CTA is highly accurate to exclude CAD. Total coronary plaque burden and nc plaques, even if only one segment is involved, are associated with an increased risk of adverse outcome.

Benefits of High-Pitch 128-Slice Dual-Source Computed Tomography for Planning of Transcatheter Aortic Valve Implantation

BACKGROUND Transcatheter aortic valve implantation (TAVI) has emerged as an alternative treatment for high-risk and inoperable patients. Advanced multimodality imaging, including computed tomography (CT), plays a key role for optimized planning of TAVI. METHODS Forty-nine patients (25 women; age, 82.3±8.8 year) with severe aortic stenosis scheduled for TAVI were examined with 128-slice high-pitch dual-source prospective aortoiliac CT angiography (CTA). The 3-coronary-sinus-alignment (3-CSA) plane, comprising left and right anterior oblique and craniocaudal projection, was defined from three-dimensional volume-rendered technique data sets and compared with the intraoperative angiographic plane (deployment plane) used for device implantation. A tolerance level of ±5-degree deviation was acceptable. Volume of intraoperative iodine contrast agent was compared before and after the implementation of the 3-CSA plane estimation by CT. RESULTS All 49 patients underwent TAVI, during which 6 CoreValves (Medtronic, Minneapolis, MN) and 43 Sapien valves (Edwards Lifesciences, Irvine, CA) were successfully implanted using transapical (n=29), transfemoral (n=17), and transaxillary access (n=4). No severe complications occurred. In 47 patients (96%), CTA correctly predicted the 3-CSA plane used for device implantation. Mean left anterior oblique by CTA was 5.3±6.5 degrees and craniocaudal was -1.3±10.1 degrees. Mean left anterior oblique deviation between CTA and the intraoperative projection was 2.1±2.7 degrees and craniocaudal was 1.7±3.0 degrees. Ostium heights of the right and left coronary arteries were 12±1.9 and 12.9±3.3 mm. No over-stenting occurred in left coronary artery ostia of 8 mm or more. Contrast volume was reduced from 81.8±25.6 to 59.4±40.2 mL (p=0.05) when using 3-CSA plane estimation by CT for final prosthesis implantation plane. CONCLUSIONS Aortoiliac high-pitch 128-slice dual-source CT contributes to TAVI planning, including reliable prediction of the 3-CSA valve deployment plane, which saves contrast volume during the procedure and may facilitate correct valve placement.

The high-risk criteria low-attenuation plaque <60 HU and the napkin-ring sign are the most powerful predictors of MACE: a long-term follow-up study

Aims To assess the prognostic value of coronary CT angiography (CTA) for prediction of major adverse cardiac events (MACE) over a long-term follow-up period. Methods and Results A total of 1469 low-to-intermediate-risk patients (65.9 years; 44.2% females) were included in our prospective cohort study. CTA was evaluated for (i) stenosis severity (minimal <10%; mild <50%; moderate 50–70%; severe >70%), (ii) plaque types (calcified, mixed dominantly calcified, mixed dominantly non-calcified, non-calcified), and (iii) high-risk plaque criteria [low-attenuation plaque (LAP) quantified by HU, napkin-ring (NR) sign, spotty calcification <3 mm, and remodelling index (RI)]. Over a follow-up of mean 7.8 years, MACE rate was 41 (2.8%) and 0% in patients with negative CTA. MACE rate increased along with stenosis severity by CTA (from 1.3 to 7.8%) (P < 0.001) and was higher in T3/T4 plaques than in T2/T1 (7.8 vs. 1.9%; P < 0.0001). LAP density was lower (35.2 HU ± 32 vs. 108.8 HU ± 53) (P < 0.001) and both NR-sign prevalence with n = 26 (63.4%) vs. n = 40 (28%) and LAP <30, <60, and <90 HU prevalence with 46.3–78% vs. 2.4–7% were higher in the MACE group (P < 0.001). On univariate and unadjusted multivariable proportional Hazards model, LAP <60 HU and NR were the strongest MACE predictors (HR 4.96; 95% CI: 2.0–12.2 and HR 3.85; 95% CI: 1.7–8.6) (P < 0.0001), while spotty calcification (HR 2.2; 95% CI: 1.1–4.3, P < 0.001), stenosis severity, and plaque type (HR 1.5; 95% CI: 1.1–2.3 and HR 1.7; 95% CI: 1.1–2.6) (P < 0.001) were less powerful. After adjusting for risk factors, CTA stenosis severity, and plaque type, LAP <60 HU and the NR sign remained significant (P < 0.001), while the effect of NR sign was even enhancing. HRP criteria were independent predictors from other risk factors. Conclusion Prognosis is excellent over a long-term period if CTA is negative and worsening with an increasing non-calcifying plaque component. LAP <60 HU and NR sign are the most powerful MACE predictors.

Detection of bioprosthetic valve infection by image fusion of (18)fluorodeoxyglucose-positron emission tomography and computed tomography.

A 63-year old male with prior bioprosthetic mitral valve replacement and coronary artery bypass graft surgery presented with dyspnea. C-reactive protein and white blood cells were elevated and serial blood cultures were negative. Transesophageal echocardiography showed a paravalvular leak and a thickened anterior leaflet of unclear either infective or degenerative origin. For differential diagnosis, cardiac 128-dual source computed tomography (CT) was performed. The CT image showed a thickened anterior leaflet and further revealed that the paravalvular leak was draining into a large wall thickened pseudoaneurysm with dense tissue adjacent suggestive for an abscess. Therefore, (18)fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) was appended and fused with the CT images. There was no tracer-uptake surrounding the leak excluding an abscess. However, an increased (18)FDG-tracer uptake at the thickened anterior leaflet indicated active inflammation. During the subsequent cardiac surgery, vegetations were identified on the anterior cusp of the bioprosthetic valve. Intraoperative biopsy was taken and the cell culture was positive for Staphylococcus aureus. The pseudoaneurysm was repaired and the valve was replaced with a bioprosthesis. The patient was discharged uneventfully from hospital on day 12 and antibiotic treatment was continued for 4 weeks. In conclusion, our case indicates that (18)FDG-PET with cardiac CT image fusion may be a useful tool in patients with unclear focus of inflammation and possible bioprosthesis infection.

Improved non-calcified plaque delineation on coronary CT angiography by sonogram-affirmed iterative reconstruction with different filter strength and relationship with BMI

PURPOSE To prospectively compare non-calcified plaque delineation and image quality of coronary computed tomography angiography (CCTA) obtained with sinogram-affirmed iterative reconstruction (IR) with different filter strengths and filtered back projection (FBP). METHODS A total of 57 patients [28.1% females; body mass index (BMI) 29.2±6.5 kg/m(2)] were investigated. CCTA was performed using 128-slice dual-source CT. Images were reconstructed with standard FBP and sinogram-affirmed IR using different filter strength (IR-2, IR-3, IR-4) (SAFIRE, Siemens, Germany). Image quality of CCTA and a non-calcified plaque outer border delineation score were evaluated by using a 5-scale score: from 1= poor to 5= excellent. Image noise, contrast-to-noise ratio (CNR) of aortic root, left main (LM) and right coronary artery, and the non-calcified plaque delineation were quantified and compared among the 4 image reconstructions, and were compared between different BMI groups (BMI <28 and ≥28). Statistical analyses included one-way analysis of variance (ANOVA), least significant difference (LSD) and Kruskal-Wallis test. RESULTS There were 71.9% patients in FBP, 96.5% in IR-2, 96.5% in IR-3 and 98.2% in IR-4 who had overall CCTA image quality ≥3, and there were statistical differences in CCTA exam image quality score among those groups, respectively (P<0.001). Sixty-one non-calcified plaques were detected by IR-2 to IR-4, out of those 11 (18%) were missed by FBP. Plaque delineation score increased constantly from FBP (2.7±0.4) to IR-2 (3.2±0.3), to IR-3 (3.5±0.3) up to IR-4 (4.0±0.4), while CNRs of the non-calcifying plaque increased and image noise decreased, respectively. Similarly, CNR of aortic root, LM and right coronary artery improved and image noise declined from FBP to IR-2, IR-3 and IR-4. There were no significant differences of image quality and plaque delineation score between low and high BMI groups within same reconstruction (all P>0.05). Significant differences in image quality and plaque delineation scores among different image reconstructions both in low and high BMI groups (all P<0.001) were found. I4f revealed the highest image quality and plaque delineation score. CONCLUSIONS IR offers improved image quality and non-calcified plaque delineation as compared with FBP, especially if BMI is increasing. Importantly, 18% of non-calcified plaques were missed with FBP. IR-4 shows the best image quality score and plaque delineation score among the different IR-filter strength.

Caseous calcification of the mitral annulus

A 61-year-old asymptomatic woman was referred for echocardiography to evaluate recently detected systolic murmur. Transthoracic echocardiography revealed an echodense obstructive mass in the left ventricular outflow tract of unclear origin. Subsequent transesophageal echo suggested an intracardiac calcified tumor and recommended surgical excision. Contrast-enhanced cardiac computed tomography (CT) confirmed a well-defined lobulated mass adherent to the anterior mitral valve leaflet, the non-enhanced scout view revealed marked hyper-attenuation confirming diffuse calcification. Caseous calcification was diagnosed and surgery was deferred. Caseous calcification is typically benign and most commonly involves the posterior mitral annulus. Our patient displayed an atypical location of exuberant mitral annular calcification.