Swee Yaw Tan

Computed tomography angiography and perfusion to assess coronary artery stenosis causing perfusion defects by single photon emission computed tomography: the CORE320 study

AIMS To evaluate the diagnostic power of integrating the results of computed tomography angiography (CTA) and CT myocardial perfusion (CTP) to identify coronary artery disease (CAD) defined as a flow limiting coronary artery stenosis causing a perfusion defect by single photon emission computed tomography (SPECT). METHODS AND RESULTS We conducted a multicentre study to evaluate the accuracy of integrated CTA-CTP for the identification of patients with flow-limiting CAD defined by ≥50% stenosis by invasive coronary angiography (ICA) with a corresponding perfusion deficit on stress single photon emission computed tomography (SPECT/MPI). Sixteen centres enroled 381 patients who underwent combined CTA-CTP and SPECT/MPI prior to conventional coronary angiography. All four image modalities were analysed in blinded independent core laboratories. The prevalence of obstructive CAD defined by combined ICA-SPECT/MPI and ICA alone was 38 and 59%, respectively. The patient-based diagnostic accuracy defined by the area under the receiver operating characteristic curve (AUC) of integrated CTA-CTP for detecting or excluding flow-limiting CAD was 0.87 [95% confidence interval (CI): 0.84-0.91]. In patients without prior myocardial infarction, the AUC was 0.90 (95% CI: 0.87-0.94) and in patients without prior CAD the AUC for combined CTA-CTP was 0.93 (95% CI: 0.89-0.97). For the combination of a CTA stenosis ≥50% stenosis and a CTP perfusion deficit, the sensitivity, specificity, positive predictive, and negative predicative values (95% CI) were 80% (72-86), 74% (68-80), 65% (58-72), and 86% (80-90), respectively. For flow-limiting disease defined by ICA-SPECT/MPI, the accuracy of CTA was significantly increased by the addition of CTP at both the patient and vessel levels. CONCLUSIONS The combination of CTA and perfusion correctly identifies patients with flow limiting CAD defined as ≥50 stenosis by ICA causing a perfusion defect by SPECT/MPI.

Simplified Models of Non-Invasive Fractional Flow Reserve Based on CT Images.

Invasive fractional flow reserve (FFR) is the gold standard to assess the functional coronary stenosis. The non-invasive assessment of diameter stenosis (DS) using coronary computed tomography angiography (CTA) has high false positive rate in contrast to FFR. Combining CTA with computational fluid dynamics (CFD), recent studies have shown promising predictions of FFRCT for superior assessment of lesion severity over CTA alone. The CFD models tend to be computationally expensive, however, and require several hours for completing analysis. Here, we introduce simplified models to predict noninvasive FFR at substantially less computational time. In this retrospective pilot study, 21 patients received coronary CTA. Subsequently a total of 32 vessels underwent invasive FFR measurement. For each vessel, FFR based on steady-state and analytical models (FFRSS and FFRAM, respectively) were calculated non-invasively based on CTA and compared with FFR. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value were 90.6% (87.5%), 80.0% (80.0%), 95.5% (90.9%), 88.9% (80.0%) and 91.3% (90.9%) respectively for FFRSS (and FFRAM) on a per-vessel basis, and were 75.0%, 50.0%, 86.4%, 62.5% and 79.2% respectively for DS. The area under the receiver operating characteristic curve (AUC) was 0.963, 0.954 and 0.741 for FFRSS, FFRAM and DS respectively, on a per-patient level. The results suggest that the CTA-derived FFRSS performed well in contrast to invasive FFR and they had better diagnostic performance than DS from CTA in the identification of functionally significant lesions. In contrast to FFRCT, FFRSS requires much less computational time.

Incremental diagnostic accuracy of computed tomography myocardial perfusion imaging over coronary angiography stratified by pre-test probability of coronary artery disease and severity of coronary artery calcification: The CORE320 study.

BACKGROUND Myocardial CT perfusion (CTP) has been validated as an incremental diagnostic predictor over coronary computed tomography angiography (CTA) in assessing hemodynamically significant stenosis. OBJECTIVES To assess the diagnostic performance of CTA and CTP alone versus combined CTA-CTP stratified by Morises pre-test probability and coronary artery calcium (CAC, Agatston) score. METHODS 381 individuals (153 low/intermediate-risk for CAD, 83 high-risk, 145 known CAD) were further stratified based on CAC score cut-offs of 1-399 and ≥400. Area under the curve for receiver operating characteristics (AUC) was calculated to assess the diagnostic performance. Reference standards were QCA≥50% stenosis+corresponding SPECT summed stress score ≥1. RESULTS In both pre-test risk groups with an Agatston score of 1-399, AUCs of CTA-CTP were not significantly different than that from CTA alone. In the low/intermediate-risk group with CAC score 1-399, AUC for CTA-CTP (89) was higher than that for CTP (76, p=0.003) alone. In the same group with CAC score ≥400, AUCs were higher for CTA-CTP (97) than that for CTA (88, p=0.030) and CTP (83, p=0.033). In high risk/known CAD patients with CAC 1-399, diagnostic performance for CTA-CTP (77) was superior to CTP (71, p=0.037) alone. In the high risk/known CAD group with CAC score ≥400, AUCs for combined imaging were higher (86) than that for CTA (75, p<0.001) as well as CTP (78, p=0.020). CONCLUSIONS The incremental diagnostic accuracy of CTP over CTA persists in patients across severity spectra of pre-test probability of CAD and coronary artery calcification. In patients with severe coronary calcification (CAC score≥400), combined CTA-CTP has better diagnostic accuracy than CTA and CTP alone.

Hemodynamic analysis of patient‐specific coronary artery tree

Local hemodynamic parameters, such as wall shear stress (WSS), oscillatory shear index and relative resident time (RRT), have been linked to coronary plaque initiation and progression. In this study, a left coronary artery tree model was reconstructed from computed tomography angiography images of a patient with multiple stenoses. The geometry of the coronary artery tree model was virtually restored by eliminating the lesions, essentially re-creating the virtually healthy artery anatomy. Using numerical simulations, flow characteristics and hemodynamic parameter distributions in the stenosed and virtually healthy models were investigated. In the virtually healthy artery model, disturbed flows were found at four locations, prone to initialization of plaque formation. Low WSS and high RRT were exhibited in three of the four locations, and high WSS and low RRT were exhibited in the fourth. These findings suggest that coronary plaque is more likely to form in locations with disturbed flow conditions characterized by low WSS and high RRT or high WSS and low RRT. In addition, clinical index of fractional flow reserve was found to significantly correlate with blood flow rate, rather than anatomic parameters, such as diameter stenosis, which implied the importance of hemodynamic environment in stenosis formation.

Iliofemoral anatomy among Asians: Implications for transcatheter aortic valve implantation

BACKGROUND/OBJECTIVES This study aims to examine iliofemoral anatomy and predictors of vessel size and tortuosity in Asian patients as transfemoral transcatheter aortic valve implantation (TAVI) may be limited by the smaller Asian physique. METHODS Characteristics and vessel dimensions of 549 patients undergoing ultrasonography were reviewed. The minimal luminal diameter (MLD) along the iliofemoral vasculature of each side was identified and the larger of the two sides was used to determine suitability for transfemoral TAVI. RESULTS The mean age was 66 ± 11 years (68% males). Mean iliac MLD was 7.6 ± 1.7 mm, females smaller than males (7.2 ± 1.7 vs 7.8 ± 1.7, p<0.001). Mean iliac MLD decreased with age: 7.9 ± 1.7 mm, 7.4 ± 1.9 mm and 7.3 ± 1.6mm for ages <70 years, 70-79 years and ≥ 80 years respectively (p=0.038). Mean femoral MLD was 7.0 ± 1.7 mm, females smaller than males (6.3 ± 1.5mm vs 7.3 ± 1.8mm, p<0.001). Females were more likely than males to have iliac and femoral MLD <6mm (20% vs 12%, p=0.019 and 34% vs 21%, p=0.001). Independent predictors of smaller iliofemoral dimensions were female gender, lower body surface area, diabetes mellitus, dyslipidemia and smoking history. Significant iliac tortuosity was present in 11.8%, more frequent in males than females (15% vs 6%, p=0.005), and in those with logistic EuroSCORE ≥ 15 than <15 (27% vs 10%, p=0.001). CONCLUSIONS This study establishes the mean iliac and femoral artery diameters in a cohort of relatively young Asian patients. Age and female gender were associated with smaller vessel dimension and several independent predictors of smaller vasculature and tortuosity were identified. These results have implications for TF TAVI in Asia.

Coronary artery segmentation via Hessian filter and curve-skeleton extraction

Precise coronary artery segmentation is a prerequisite for quantitatively assessing the severity of coronary artery stenosis. Extracting the centre line of the 3D volumetric coronary artery tree, also named as 3D skeletonization, plays an important role in identify the variations of cross-sectional profile. Typically there are three skeletonization methods, viz. distance transformation, Voronoi method and topological thinning method. All these three skeletonization methods were applied in this study to extract the curve-skeleton of coronary arteries, after segmenting the coronary artery tree with Hessin filter. Among them, topological thinning method is recommended, as it produces reliable and accurate curve-skeleton for vessels with varying size. This will facilitate quantitative assessment of the severity of coronary artery stenosis, help clinical diagnosis and treatment planning of coronary artery disease.

Area stenosis associated with non-invasive fractional flow reserve obtained from coronary CT images

Fractional flow reserve (FFR) determined by invasive angiography is the gold standard to assess the severity of coronary artery disease (CAD). FFRCT can be obtained non-invasively by combining computed tomography (CT) images and Computational Fluid Dynamics (CFD) method. In this study, FFRCT was computed for 6 models of patient-specific left coronary artery trees reconstructed from CT images. A total of 12 stenoses were observed. FFR values obtained for 7 of the 12 stenoses during invasive angiography were used as the gold standard for comparison. On a per-stenosis basis, the sensitivity, specificity, positive predictive value and negative predictive value were 50%, 100%, 100% and 83.3% respectively for FFRCT. A weak correlation was found between percent lumen diameter stenosis and FFRCT (r=0.431; p>0.05). However, the correlation between percent lumen area stenosis and FFRCT was significant (r=0.853; p<;0.05). Therefore, non-invasive FFRCT appears to be a promising index to assess the severity of CAD and lumen area has distinct advantages over diameter measurement in terms of anatomy assessment.

Percutaneous transcatheter aortic valve implantation for degenerated surgical bioprostheses: the first case series in Asia with one-year follow-up.

INTRODUCTION Percutaneous transcatheter aortic valve implantation (TAVI) has become an established therapy for inoperable and high-surgical-risk patients with severe aortic stenosis. Although TAVI in patients with degenerated surgical aortic bioprostheses (i.e. valve-in-valve TAVI) is increasingly reported in Western studies, such data is lacking in Asian patients. We describe the initial experience of valve-in-valve TAVI in Asia. METHODS Eight patients who underwent valve-in-valve TAVI due to degenerated aortic bioprostheses were enrolled. The mechanism of bioprosthetic valve failure was stenotic, regurgitation or mixed. All procedures were performed via transfemoral arterial access, using the self-expanding CoreValve prosthesis or balloon-expandable SAPIEN XT prosthesis. RESULTS The mean age of the patients was 71.6 ± 13.2 years and five were male. Mean duration to surgical bioprosthesis degeneration was 10.2 ± 4.1 years. Valve-in-valve TAVI was successfully performed in all patients. CoreValve and SAPIEN XT prostheses were used in six and two patients, respectively. There were no deaths, strokes or permanent pacemaker requirement at 30 days, with one noncardiac mortality at one year. All patients experienced New York Heart Association functional class improvement. Post-procedure mean pressure gradients were 20 ± 11 mmHg and 22 ± 8 mmHg at 30 days and one year, respectively. Residual aortic regurgitation (AR) of more than mild severity occurred in one patient at 30 days. At one year, only one patient had mild residual AR. CONCLUSION In our experience of valve-in-valve TAVI, procedural success was achieved in all patients without adverse events at 30 days. Good clinical and haemodynamic outcomes were sustained at one year.

Diagnosis of anomalous origin and course of coronary arteries using non-contrast cardiac CT scan and detection features

BACKGROUND Anomalous origin and course of coronary arteries (AOCA) is a potential cause of sudden cardiac death. Coronary CT angiography (coronary CTA) enables detailed 3-dimensional visualization of AOCA. Data are limited about the diagnostic performance of noncontrast cardiac CT obtained during coronary calcium scan for detecting AOCA. OBJECTIVE We assessed the feasibility of using noncontrast cardiac CT for detecting AOCA. METHODS Participants had noncontrast cardiac CT and coronary CTA performed (2005-2010). Cases had AOCA as diagnosed with coronary CTA. Controls were without AOCA. Noncontrast cardiac CT images were independently evaluated for AOCA by a cardiologist and a radiologist blinded to prior AOCA diagnosis. Detection features to assist AOCA diagnosis on noncontrast cardiac CT were evaluated. RESULTS The study enrolled 54 cases and 155 controls. Sensitivity and specificity for detecting AOCA were 82% (95% CI, 69%-90%) and 90% (95% CI, 85%-94%) for observer 1, respectively, and 82% (95% CI, 69%-90%) and 85% (95% CI, 79%-90%) for observer 2, respectively. Average sensitivity and specificity were 82% and 88%, respectively. Interobserver agreement (Cohen κ) was κ = 0.65 (95% CI, 0.53-0.76). Inability to visualize the right coronary artery (RCA) origin at the right sinus significantly predicted RCA anomaly. Inability to visualize the left main coronary artery branching point into the left anterior descending coronary artery and the left circumflex coronary artery significantly predicted left coronary artery anomaly. CONCLUSION Noncontrast cardiac CT in conjunction with detection features has the potential for use in the diagnosis of AOCA. A prospective study is needed for validation and to determine the modalitys accuracy for detecting AOCA.

Beyond fitness tracking: The use of consumer-grade wearable data from normal volunteers in cardiovascular and lipidomics research

The use of consumer-grade wearables for purposes beyond fitness tracking has not been comprehensively explored. We generated and analyzed multidimensional data from 233 normal volunteers, integrating wearable data, lifestyle questionnaires, cardiac imaging, sphingolipid profiling, and multiple clinical-grade cardiovascular and metabolic disease markers. We show that subjects can be stratified into distinct clusters based on daily activity patterns and that these clusters are marked by distinct demographic and behavioral patterns. While resting heart rates (RHRs) performed better than step counts in being associated with cardiovascular and metabolic disease markers, step counts identified relationships between physical activity and cardiac remodeling, suggesting that wearable data may play a role in reducing overdiagnosis of cardiac hypertrophy or dilatation in active individuals. Wearable-derived activity levels can be used to identify known and novel activity-modulated sphingolipids that are in turn associated with insulin sensitivity. Our findings demonstrate the potential for wearables in biomedical research and personalized health.