Júlia Karády

Assessing genetic and environmental influences on epicardial and abdominal adipose tissue quantities: A classical twin study

Background/Objectives:Various adipose tissue compartments play an important role in the development of cardiometabolic diseases. The quantity of different fat compartments is influenced by genetic and environmental factors. The aim of our study was to evaluate the magnitude of genetic and environmental effects on epicardial, subcutaneous and visceral adipose tissue (EAT, SAT and VAT) quantities in a cohort of adult twin pairs.Subjects/Methods:In this cross-sectional study we investigated adult twins (57 monozygotic (MZ) and 33 dizygotic (DZ) same-gender twin pairs; 180 twin subjects). We measured EAT volume using electrocardiogram-gated native computed tomography (CT) scan of the heart, and abdominal SAT and VAT areas were quantified between the third and fourth lumbar vertebra on native CT images. We calculated genetic and environmental impact on the size of various adipose tissue compartments by analyzing co-twin correlations in MZ and DZ pairs separately, and furthermore by using genetic structural equation models.Results:In co-twin analysis, MZ twins had stronger correlations than DZ twins for EAT (rMZ=0.81, rDZ=0.32), similar to SAT and VAT quantities (rMZ=0.80, rDZ=0.68 and rMZ=0.79, rDZ=0.48, respectively). In multi-trait model fitting analysis, the overall contribution of genetic factors to EAT, SAT and VAT volumes were 80%, 78% and 70%, whereas environmental factors were 20%, 22% and 30%, respectively. Common pathway model analyses indicated that none of the EAT, SAT and VAT phenotypes was independent of the other two.Conclusions:Genetic factors have substantial influence, while environmental factors have only a modest impact on EAT volume, abdominal SAT and VAT quantities. There is a considerable amount of common genetic background influencing the quantities of all three adipose tissue compartments.

Transcatheter mitral valve replacement in mitral annulus calcification – “The art of computer simulation”

There is considerable interest in transcatheter prosthetic valve treatment for mitral valve disease in high-risk individuals. Although the presence of mitral annular calcium (MAC) may provide an anchoring zone for such devices, results to date have been modest with reported technical failure rates approaching 30% in specialist centers. This in part relates to the risk of left ventricular outflow tract obstruction and device dislodgment but also to the lack of specific imaging guidelines to plan for such procedures. We present the use of finite element analysis and computer simulation based on cardiac CT in three patients with severe MAC in whom transcatheter devices were considered. In the first two cases, the computer simulations were performed after the clinical procedure and were concordant with the clinical outcome. For the third case, computer simulation was performed prior to the clinical procedure. This indicated unsuitability for transcatheter device deployment and a subsequent medical management was adopted. Overall, our initial results suggest that computer simulation may have the potential to improve patient selection for transcatheter mitral valve replacement in the presence of significant MAC.

Iterative model reconstruction reduces calcified plaque volume in coronary CT angiography

OBJECTIVE To assess the impact of iterative model reconstruction (IMR) on calcified plaque quantification as compared to filtered back projection reconstruction (FBP) and hybrid iterative reconstruction (HIR) in coronary computed tomography angiography (CTA). METHODS Raw image data of 52 patients who underwent 256-slice CTA were reconstructed with IMR, HIR and FBP. We evaluated qualitative, quantitative image quality parameters and quantified calcified and partially calcified plaque volumes using automated software. RESULTS Overall qualitative image quality significantly improved with HIR as compared to FBP, and further improved with IMR (p<0.01 all). Contrast-to-noise ratios were improved with IMR, compared to HIR and FBP (51.0 [43.5-59.9], 20.3 [16.2-25.9] and 14.0 [11.2-17.7], respectively, all p<0.01) Overall plaque volumes were lowest with IMR and highest with FBP (121.7 [79.3-168.4], 138.7 [90.6-191.7], 147.0 [100.7-183.6]). Similarly, calcified volumes (>130 HU) were decreased with IMR as compared to HIR and FBP (105.9 [62.1-144.6], 110.2 [63.8-166.6], 115.9 [81.7-164.2], respectively, p<0.05 all). High-attenuation non-calcified volumes (90-129 HU) yielded similar values with FBP and HIR (p=0.81), however it was lower with IMR (p < 0.05 both). Intermediate- (30-89 HU) and low-attenuation (<30 HU) non-calcified volumes showed no significant difference (p=0.22 and p=0.67, respectively). CONCLUSIONS IMR improves image quality of coronary CTA and decreases calcified plaque volumes.

Measurement of the Red Blood Cell Distribution Width Improves the Risk Prediction in Cardiac Resynchronization Therapy

Objectives. Increases in red blood cell distribution width (RDW) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) predict the mortality of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT). It was hypothesized that RDW is independent of and possibly even superior to NT-proBNP from the aspect of long-term mortality prediction. Design. The blood counts and serum NT-proBNP levels of 134 patients undergoing CRT were measured. Multivariable Cox regression models were applied and reclassification analyses were performed. Results. After separate adjustment to the basic model of left bundle branch block, beta blocker therapy, and serum creatinine, both the RDW > 13.35% and NT-proBNP > 1975 pg/mL predicted the 5-year mortality (n = 57). In the final model including all variables, the RDW [HR = 2.49 (1.27–4.86); p = 0.008] remained a significant predictor, whereas the NT-proBNP [HR = 1.18 (0.93–3.51); p = 0.07] lost its predictive value. On addition of the RDW measurement, a 64% net reclassification improvement and a 3% integrated discrimination improvement were achieved over the NT-proBNP-adjusted basic model. Conclusions. Increased RDW levels accurately predict the long-term mortality of CRT patients independently of NT-proBNP. Reclassification analysis revealed that the RDW improves the risk stratification and could enhance the optimal patient selection for CRT.

Computational fluid dynamic modelling to determine the hemodynamic effects of implanting a transcatheter mitral valve within the left ventricle

An 85-year-old man presented with increasing dyspnea. Echocardiography demonstrated severe aortic stenosis, severe mitral regurgitation (MR) and a left ventricular ejection fraction of 32%. He subsequently underwent transcatheter aortic valve replacement (TAVR) with a SAPIEN 3 valve (Edwards Lifesciences, Irvine, CA, USA). Given the residual severe MR a transcatheter mitral valve replacement (TMVR) was considered. This was associated with concerns as to introducing left ventricular outflow tract (LVOT) obstruction in the context of an existing TAVR [1]. Multiphase ECG-gated cardiac CT was therefore performed for geometric (Fig. 1) and computational flow evaluation. Two computational fluid-dynamic models were created. The first described the pre-procedural haemodynamic state whilst the second, the simulated haemodynamic state with proposed TMVR in situ (Fig. 2, Mov. 1). To drive the flow simulation the Doppler echocardiographic data for flow velocity assessment and endocardial wall motion tracking from CT dataset were incorporated into the model. The haemodynamic simulations suggested a < 6% reduction of the LVOT area following TMVR with a peak LVOT pressure gradient of 6.8 mmHg and a mean pressure gradient of 2.95 mmHg. Given these findings, TMVR with a Medtronic Intrepid valve (Medtronic Inc., Minneapolis, MN, USA) was performed. At 6-months the patient reported an improvement in symptoms with the echocardiogram showing good agreement with computational modelling. The post-procedural CT scan confirmed an absence of LVOT obstruction (9% LVOT area reduction) (Fig. 3). Although advanced imaging techniques can provide a quantitative description of the current pathophysiological state of a patient [1, 2]. they are unable to predict the ventricular response to TMVR. The current report demonstrates the utility of integrating imaging data with personalized Computational Fluid Dynamics models to simulate ventricular hemodynamics into a new clinical workstream. It is anticipated that as applications for cardiac CT expand, a further harmonisation with basic science with occur to enable solutions and personalised patient specific care to otherwise complex clinical problems.

Radiomic Features Are Superior to Conventional Quantitative Computed Tomographic Metrics to Identify Coronary Plaques With Napkin-Ring SignCLINICAL PERSPECTIVE

Background— Napkin-ring sign (NRS) is an independent prognostic imaging marker of major adverse cardiac events. However, identification of NRS is challenging because of its qualitative nature. Radiomics is the process of extracting thousands of quantitative parameters from medical images to create big-data data sets that can identify distinct patterns in radiological images. Therefore, we sought to determine whether radiomic analysis improves the identification of NRS plaques. Methods and Results— From 2674 patients referred to coronary computed tomographic angiography caused by stable chest pain, expert readers identified 30 patients with NRS plaques and matched these with 30 non-NRS plaques with similar degree of calcification, luminal obstruction, localization, and imaging parameters. All plaques were segmented manually, and image data information was analyzed using Radiomics Image Analysis package for the presence of 8 conventional and 4440 radiomic parameters. We used the permutation test of symmetry to assess differences between NRS and non-NRS plaques, whereas we calculated receiver-operating characteristics’ area under the curve values to evaluate diagnostic accuracy. Bonferroni-corrected P<0.0012 was considered significant. None of the conventional quantitative parameters but 20.6% (916/4440) of radiomic features were significantly different between NRS and non-NRS plaques. Almost half of these (418/916) reached an area under the curve value >0.80. Short- and long-run low gray-level emphasis and surface ratio of high attenuation voxels to total surface had the highest area under the curve values (0.918; 0.894 and 0.890, respectively). Conclusions— A large number of radiomic features are different between NRS and non-NRS plaques and exhibit excellent discriminatory value.

Inverse association between hyperthymic affective temperament and coronary atherosclerosis: A coronary computed tomography angiography study

OBJECTIVE A bidirectional relationship exists between psychiatric disorders and cardiovascular diseases, however less is known with regards to personality traits. Accumulating data suggest that affective temperaments are both associated with psychiatric and somatic diseases. The aim of our study was to evaluate the associations between different affective temperaments and the presence of coronary atherosclerosis. METHODS 200 consecutive patients referred to coronary computed tomography angiography (CCTA) due to suspected coronary artery disease (CAD) were included in our study. Medical history and demographic parameters were recorded and all patients completed the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) and the Beck Depression Inventory (BDI). The presence of coronary artery disease was evaluated based on the CCTA images. RESULTS 39 patients were free of any coronary atherosclerosis (CCTA-) and 161 had coronary atherosclerosis (CCTA+). Hyperthymic affective temperament score was higher in CCTA- subjects as compared to CCTA+ (13.1±3.0 vs 11.5±4.6, p=0.010, respectively). Hyperthymic affective temperament score showed a significant independent, inverse relationship with coronary atherosclerosis (OR: 0.91 CI: 0.82-0.99, p=0.04). CONCLUSION Our results suggest that hyperthymic affective temperament is independently associated with the absence of CAD. It requires further research to delineate the mechanism mediating the effect of hyperthymia on better coronary artery health and establishing potential biochemical or behavioral factors, both of which could be exploited for prevention and treatment purposes. But it is plausible, that the evaluation of affective temperaments have importance both in relation with psychiatric and cardiovascular disorders.

Editorial. The Closer We Get, The Further Apart We Become

Coronary computed tomography angiography (CTA) became a powerful tool in the detection of coronary artery disease (CAD) as it allows the visualization of the luminal stenosis and the vessel wall simultaneously. Detecting the presence of coronary atherosclerosis and stenosis alone does not provide sufficient prognostic information on future events. It has been shown that plaques with high risk features, such as positive remodeling, low attenuation, napkin ring sign, and spotty calcification, are associated with subsequent coronary events.1 Moreover, recent studies suggested that plaques with high risk features have a higher likelihood to cause ischemia independent of the degree of stenosis. Ischemia-guided revascularization compared to revascularization based on stenosis severity shows prognostic benefit.2–4 Therefore, to define the functional significance of atherosclerotic lesions, it is of utmost importance to be able to provide appropriate conservative or invasive therapy. Invasive fractional flow reserve (FFR) is the gold standard technique to detect lesion-specific ischemia. However, due to the technical advances that cardiac CT underwent during the past decade, noninvasive ischemia assessment has become feasible. Isotropic resolution and high-quality image datasets allow for advanced functional assessments and computational simulations. With the application of computational fluid dynamic modeling to cardiac CT datasets flow simulation and pressure estimation became feasible allowing the calculation of FFR values noninvasively. The simulation does not require any extra image acquisition or special medication, which eases the implementation of FFR-CT into the daily routine. All major studies aiming to assess the diagnostic performance of FFR-CT have been conducted with HeartFlow FFRCT (HeartFlow Inc, Redwood City, California, USA), which is a vendor-independent application.5 The main disadvantage of HeartFlow FFRCT however, is that it only provides off-site analysis, which takes 12–24 hours and requires data transfer. Other vendors have developed on-site FFR simulation algorithms; however, these still have to be validated. Transluminal attenuation gradient (TAG) quantifies the contrast material attenuation change along the vessel, which refers to flow circumstances within coronaries.6 TAG shows a consistent decrease and marks maximal stenosis with a significant attenuation drop. This technique can be applied on single heart beat-acquired CTA images, and similarly to the FFR-CT application, the regular CTA protocols do not need to be extended. Additionally, with the implementation of corrected contrast opacification, the inhomogeneous attenuation can be adjusted for in datasets acquired in more than one step. Initial validation studies confirmed diagnostic improvement if TAG was combined with conventional coronary CTA as compared to CTA only.7 However, probably due to the differences in scanners, reconstruction techniques, and contrast material injection protocols, there is currently no uniform cutoff value for TAG. It is of high clinical importance to understand the association of ischemia with the presence of high-risk plaque features. In two articles published in two consecutive issues of JCE, Orzan et al. demonstrated that TAG shows a good correlation with invasive FFR values. Furthermore, they showed that increased TAG values are associated with high-risk plaque characteristics, which

5 Real world experience of a novel on-site coronary ct derived fractional flow reserve algorithm for the assessment of intermediate stenoses

Objective Fractional flow reserve derived from coronary CT angiography (FFR-CT) is a novel tool for assessing the significance of coronary artery stenosis. The primary aim of this prospective study was to evaluate the diagnostic performance of a novel on-site rapid FFR-CT algorithm as compared to invasive FFR as the gold standard in a real world workflow. Our secondary aim was to determine whether the FFR-CT diagnostic performance was affected by inter-observer variations in lumen segmentation. Methods We enrolled 44 consecutive patients (64.6 ±8.9 years, 34% female) with 60 coronary atherosclerotic lesions who underwent coronary computed tomography angiography (CTA) and were referred for invasive coronary angiography (ICA) in two European centres. ICA with FFR measurements were performed within 60 days after coronary CTA in all lesions. An FFR value of ≤0.8 was considered significant. Coronary CTA scans were evaluated by two expert readers, who determined the effective diameter stenosis (EDS) and manually adjusted the semi-automated coronary lumen segmentations. All extracted vessels were evaluated by an on-site FFR simulator to calculate the FFR-CT values. Results The mean FFR-CT value was 0.77 ±0.15 and the average coronary CTA based EDS was 43.6±16.9%. On-site lumen segmentation, manual adjustment and FFR-CT simulations were performed in an average of 9 minutes, (range: 3–25 min). The sensitivity, specificity, positive predictive value and negative predictive value of FFR-CT vs. EDS with a cut-off of 50% were the following: 90.5%, 71.8%, 63.3% and 93.3% vs. 52.4%, 87.2%, 68.8% and 77.3%. FFR-CT demonstrated significantly better diagnostic performance as compared to EDS (AUC: 0.89 vs. 0.74 respectively; p<0.001). The FFR-CT AUCs of the two readers did not show any significant difference (0.89 vs. 0.88; p=0.74). Conclusion On-site FFR-CT simulation is feasible and has better diagnostic performance than anatomical stenosis assessment. The diagnostic performance of the FFR-CT simulation algorithm does not depend on the readers who adjust the semi-automated lumen segmentation adjustments.

The Doppler paradox

Obstructive prosthetic valve thrombosis (PVT) is a rare but severe complication that usually occurs in the presence of suboptimal anticoagulation. Although fluoroscopy is commonly used to detect abnormal leaflet motion as a surrogate marker for PVT, its inability to directly visualize adjacent tissue and valve physiology leaves it susceptible to miss clinically important PVT. In this manuscript, we report the case of a 54‐year‐old woman with a mechanical mitral valve who was admitted to our institute with exertional dyspnea. Although valve fluoroscopy was normal, subsequent 3D echocardiography and ECG‐gated multiphase computed tomography confirmed the presence of PVT that was subsequently treated successfully with surgical replacement. Our case demonstrates the utility of multimodality imaging in establishing PVT in patients with abnormal prosthetic valve physiology and progressive symptoms.