Impact of virtual monoenergetic levels on coronary plaque volume components using photon-counting computed tomography.

OBJECTIVES: Virtual monoenergetic images (VMIs) from photon-counting CT (PCCT) may change quantitative coronary plaque volumes. We aimed to assess how plaque component volumes change with respect to VMIs. METHODS: Coronary CT angiography (CTA) images were acquired using a dual-source PCCT and VMIs were reconstructed between 40 and 180 keV in 10-keV increments. Polychromatic images at 120 kVp (T3D) were used as reference. Quantitative plaque analysis was performed on T3D images and segmentation masks were copied to VMI reconstructions. Calcified plaque (CP; > 350 Hounsfield units, HU), non-calcified plaque (NCP; 30 to 350 HU), and low-attenuation NCP (LAP; - 100 to 30 HU) volumes were calculated using fixed thresholds. RESULTS: We analyzed 51 plaques from 51 patients (67% male, mean age 65 ± 12 years). Average attenuation and contrast-to-noise ratio (CNR) decreased significantly with increasing keV levels, with similar values observed between T3D and 70 keV images (299 ± 209 vs. 303 ± 225 HU, p = 0.15 for mean HU; 15.5 ± 3.7 vs. 15.8 ± 3.5, p = 0.32 for CNR). Mean NCP volume was comparable between T3D and 100-180-keV reconstructions. There was a monotonic decrease in mean CP volume, with a significant difference between all VMIs and T3D (p < 0.05). LAP volume increased with increasing keV levels and all VMIs showed a significant difference compared to T3D, except for 50 keV (28.0 ± 30.8 mm3 and 28.6 ± 30.1 mm3, respectively, p = 0.63). CONCLUSIONS: Estimated coronary plaque volumes significantly differ between VMIs. Normalization protocols are needed to have comparable results between future studies, especially for LAP volume which is currently defined using a fixed HU threshold. CLINICAL RELEVANCE STATEMENT: Different virtual monoenergetic images from photon-counting CT alter attenuation values and therefore corresponding plaque component volumes. New clinical standards and protocols are required to determine the optimal thresholds to derive plaque volumes from photon-counting CT. KEY POINTS: • Utilizing different VMI energy levels from photon-counting CT for the analysis of coronary artery plaques leads to substantial changes in attenuation values and corresponding plaque component volumes. • Low-energy images (40-70 keV) improved contrast-to-noise ratio, however also increased image noise. • Normalization protocols are needed to have comparable results between future studies, especially for low-attenuation plaque volume which is currently defined using a fixed HU threshold.

Microstructural alterations measured by diffusion tensor imaging following transcatheter aortic valve replacement and their association with cerebral ischemic injury and cognitive function - a prospective study.

PURPOSE: We assessed diffusion tensor imaging (DTI) metric changes of the corpus callosum and cingulum correlated to postprocedural ischemic lesion load (ILL) and cognitive performance in transcatheter aortic valve replacement (TAVR). METHODS: TAVR subjects had DTI post-TAVR (≤ 8 days) and at 6 months (78 participants, males 56%, age 78.8 years ± 6.3) and four neurocognitive tests (pre-TAVR, post-TAVR, 6 months, 1 year). DTI metrics (fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD)) were calculated for 7 regions: corpus callosum (genu, body, splenium) and cingulum (cingulate gyrus, parahippocampal cingulum bilaterally). DTI metrics post-TAVR and at 6 months were compared with Student's t-test (p < 0.0071) and ANOVA covarying for sex, ILL (p < 0.05) with post hoc analysis of ILL groups (p < 0.0167). Repeated-measures linear mixed-effect model (p < 0.05) was performed to investigate the effect of time and ILL on cognition. RESULTS: At 6 months, significant decrease of the following DTI metrics was detected: AD (genu, body, splenium, right parahippocampal cingulum: p ≤ 0.0046); MD (body, both cingulate gyri: p ≤ 0.0050); RD (left cingulate gyrus: p = 0.0021); FA (splenium: p < 0.0001). ANOVA confirmed significant effect of female sex on AD + MD reduction (body, right cingulate gyrus) and AD reduction (left cingulate gyrus) (p ≤ 0.0254). Significant negative effect of ILL on some DTI metric changes was found (AD + MD-body: p ≤ 0.0050; MD-left cingulate gyrus: p = 0.0087). Cognitive performance remained stable with significant negative correlation of ILL and retrograde memory and visual scores (p ≤ 0.0483). CONCLUSION: Significant effect of TAVR on cerebral microstructural integrity was found with reduced diffusivities opposite to the trends reported in various neurodegenerative conditions/ageing, notably in women and lower ILL, and with preserved/improved cognition. TRIAL REGISTRATION NUMBER: NCT02826200 at ClinicalTrials.gov; date of registration: 07. July 2016.

Association of Hepatic Steatosis With Major Adverse Cardiovascular Events, Independent of Coronary Artery Disease.

BACKGROUND & AIMS: Hepatic steatosis has been associated with increased risk of major adverse cardiovascular events (MACE) but it is not clear whether steatosis is independently associated with risk of MACE. We investigated whether steatosis is associated with risk of MACE independently of the presence and extent of baseline coronary artery disease, assessed by comprehensive contrast-enhanced computed tomography angiography (CTA). METHODS: We conducted a nested cohort study of 3756 subjects (mean age, 60.6 years; 48.4% men) who underwent coronary CTA at 193 sites in North America, from July 2010 through September 2013, as part of the PROMISE study, which included noninvasive cardiovascular analyses of symptomatic outpatients without coronary artery disease. Independent core laboratory readers measured hepatic and splenic attenuation, using non-contrast computed tomography images to identify steatosis, and evaluated coronary plaques and stenosis in coronary CTA images. We collected data on participants' cardiovascular risk factors, presence of metabolic syndrome, and body mass index. The primary endpoint was an adjudicated composite of MACE (death, myocardial infarction, or unstable angina) during a median follow-up time of 25 months. RESULTS: Among the 959 subjects who had steatosis (25.5% of the cohort), 42 had MACE (4.4%), whereas among the 2797 subjects without steatosis, 73 had MACE (2.6%) (hazard ratio [HR] for MACE in subjects with steatosis, 1.69; 95% CI, 1.16-2.48; P = .006 for MACE in subjects with vs without steatosis). This association remained after adjustment for atherosclerotic cardiovascular disease risk scores, significant stenosis, and metabolic syndrome (adjusted HR, 1.72; 95% CI, 1.16-2.54; P = .007) or obesity (adjusted HR, 1.75; 95% CI, 1.19-2.59; P = .005). Steatosis remained independently associated with MACE after adjustment for all CTA measures of plaques and stenosis. CONCLUSIONS: Hepatic steatosis is associated with MACE independently of other cardiovascular risk factors or extent of coronary artery disease. Strategies to reduce steatosis might reduce risk of MACE. ClinicalTrials.gov no: NCT01174550.

Novel anti-inflammatory therapies to reduce cardiovascular burden of psoriasis.

Psoriasis mainly affects the skin and joints and has serious impacts on the physical, emotional, and financial life of patients. Recent studies have demonstrated that other comorbidities are frequently detected in psoriatic patients. A strong association with the development of cardiovascular diseases, such as hypertension, myocardial infarction, and stroke is responsible for the shortened (by 4.5-5 years) life expectancy of severe psoriatic patients. Systemic inflammation plays an important role in the interrelationship between psoriasis and atherosclerotic plaque formation, which is a common immunopathogenic pathway that explains the multiorgan involvement in psoriasis. As far life-threatening cardiovascular diseases are very often symptom-free, the treating dermatologist's responsibility is to initiate interdisciplinary holistic patient care, which may lead to directly saved patients' lives. Holistic care of severe psoriatic patients should include regular cardiac monitoring using cardiovascular imaging modalities and functional testing to detect even subclinical coronary artery disease. Effective anti-inflammatory treatment with biologic therapies may have beneficial effects on the cardiovascular state and may reduce the incidence of cardiac events. The authors review the latest findings on the shared immunopathogenic background of psoriasis and cardiovascular diseases and discuss the available data about the cardiovascular responses to the currently used biologic treatments.

Patients with Moderate Non-Culprit Coronary Lesions of Recent Acute Coronary Syndrome.

Fractional flow reserve (FFR) measurement was compared to dobutamine stress echocardiography (DSE) instable angina (SA) with stable coronary lesion (s) (SCL (s) ) in a few trials; however, similar comparisons in patients with acute coronary syndrome (ACS) with non-culprit lesion (s) (NCL (s) ) are lacking. Our objectives were to prospectively evaluate the diagnostic performance of FFR with two different cutoff values (< 0.80 and < 0.75) relative to DSE in moderate (30%-70% diameter stenosis) NCLs (ACS group) and to compare these observations with those measured in SCLs (SA group). One hundred seventy-five consecutive patients with SA (n = 86) and ACS (n = 89) with 225 coronary lesions (109 SCLs and 116 NCLs) were enrolled. In contrast to the ACS cohort in SA patients, normal DSE was associated with higher FFR values compared to those with abnormal DSE (P = 0.051 versus P = 0.006). In addition, in the SA group, a significant correlation was observed between DSE (regional wall motion score index at peak stress) and FFR (r = -0.290; P = 0.002), whereas a similar association was absent (r = -0.029; P = 0.760) among ACS patients. In the SA group, decreasing the FFR cutoff value (< 0.80 versus < 0.75) improved the concordance of FFR with DSE (70.6% versus 81.7%) without altering its discriminatory power (area under the curve; 0.68 versus 0.63; P = 0.369), whereas in the ACS group, concordance remained similar (69.0% versus 71.6%) and discriminatory power decreased (0.62 versus 0.51; P = 0.049), respectively. In conclusion, lesion-specific FFR assessment may have different relevance in patients with moderate NCLs than in patients with SCLs.

Left Ventricular Systolic Function Has Strong Independent Genetic Background from Diastolic Function: A Classical Twin Study.

Background and Objectives: No data are available on whether the heritability of left ventricle (LV) systolic and diastolic parameters are independent of each other. Therefore, our aim was to assess the magnitude of common and independent genetic and environmental factors defining LV systolic and diastolic function. Materials and Methods: We analyzed 184 asymptomatic twins (65% female, mean age: 56 ± 9 years). Transthoracic echocardiography was performed to measure LV systolic (global longitudinal and circumferential strain; basal and apical rotation) and diastolic (early diastolic velocity of mitral inflow and lateral mitral annulus tissue; deceleration time and early diastolic strain rate) parameters using conventional and speckle-tracking echocardiography. Genetic structural equation models were evaluated to quantify the proportion of common and specific genetic (Ac, As) and environmental factors (Ec, Es) contributing to the phenotypes. Results: LV systolic parameters had no common genetic or environmental heritability (Ac range: 0-0%; Ec range: 0-0%; As range: 57-77%; Es range: 24-43%). Diastolic LV parameters were mainly determined by common genetic and environmental effects (Ac range: 9-40%; Ec range: 11-49%; As range: 0-29%; Es range: 0-51%). Systolic parameters had no common genetic or environmental factors (Ac = 0%; Ec = 0%) with diastolic metrics. Conclusions: Systolic LV parameters have a strong genetic predisposition to any impact. They share no common genetic or environmental factors with each other or with diastolic parameters, indicating that they may deteriorate specifically to given effects. However, diastolic functional parameters are mainly affected by common environmental influences, suggesting that pathological conditions may deteriorate them equally. Estimation of the genetic and environmental influence and interdependence on systolic and diastolic LV function may help the understanding of the pathomechanism of different heart failure classification types.

Calcium scoring: a personalized probability assessment predicts the need for additional or alternative testing to coronary CT angiography.

OBJECTIVE: To assess whether anthropometrics, clinical risk factors, and coronary artery calcium score (CACS) can predict the need of further testing after coronary CT angiography (CTA) due to non-diagnostic image quality and/or the presence of significant stenosis. METHODS: Consecutive patients who underwent coronary CTA due to suspected coronary artery disease (CAD) were included in our retrospective analysis. We used multivariate logistic regression and receiver operating characteristics analysis containing anthropometric factors: body mass index, heart rate, and rhythm irregularity (model 1); and parameters used for pre-test likelihood estimation: age, sex, and type of angina (model 2); and also added total calcium score (model 3) to predict downstream testing. RESULTS: We analyzed 4120 (45.7% female, 57.9 ± 12.1 years) patients. Model 3 significantly outperformed models 1 and 2 (area under the curve, 0.84 [95% CI 0.83-0.86] vs. 0.56 [95% CI 0.54-0.58] and 0.72 [95% CI 0.70-0.74], p < 0.001). For patients with sinus rhythm of 50 bpm, in case of non-specific angina, CACS above 435, 756, and 944; in atypical angina CACS above 381, 702, and 890; and in typical angina CACS above 316, 636, and 824 correspond to 50%, 80%, and 90% probability of further testing, respectively. However, higher heart rates and arrhythmias significantly decrease these cutoffs (p < 0.001). CONCLUSION: CACS significantly increases the ability to identify patients in whom deferral from coronary CTA may be advised as CTA does not lead to a final decision regarding CAD management. Our results provide individualized cutoff values for given probabilities of the need of additional testing, which may facilitate personalized decision-making to perform or defer coronary CTA. KEY POINTS: • Anthropometric parameters on their own are insufficient predictors of downstream testing. Adding parameters of the Diamond and Forrester pre-test likelihood test significantly increases the power of prediction. • Total CACS is the most important independent predictor to identify patients in whom coronary CTA may not be recommended as CTA does not lead to a final decision regarding CAD management. • We determined specific CACS cutoff values based on the probability of downstream testing by angina-, arrhythmia-, and heart rate-based groups of patients to help individualize patient management.

CAD-RADS - a new clinical decision support tool for coronary computed tomography angiography.

Coronary computed tomography angiography (CTA) has been established as an accurate method to non-invasively assess coronary artery disease (CAD). The proposed 'Coronary Artery Disease Reporting and Data System' (CAD-RADS) may enable standardised reporting of the broad spectrum of coronary CTA findings related to the presence, extent and composition of coronary atherosclerosis. The CAD-RADS classification is a comprehensive tool for summarising findings on a per-patient-basis dependent on the highest-grade coronary artery lesion, ranging from CAD-RADS 0 (absence of CAD) to CAD-RADS 5 (total occlusion of a coronary artery). In addition, it provides suggestions for clinical management for each classification, including further testing and therapeutic options. Despite some limitations, CAD-RADS may facilitate improved communication between imagers and patient caregivers. As such, CAD-RADS may enable a more efficient use of coronary CTA leading to more accurate utilisation of invasive coronary angiograms. Furthermore, widespread use of CAD-RADS may facilitate registry-based research of diagnostic and prognostic aspects of CTA. KEY POINTS: • CAD-RADS is a tool for standardising coronary CTA reports. • CAD-RADS includes clinical treatment recommendations based on CTA findings. • CAD-RADS has the potential to reduce variability of CTA reports.

Image Quality of Prospectively ECG-Triggered Coronary CT Angiography in Heart Transplant Recipients.

OBJECTIVE: Cardiac allograft vasculopathy (CAV) is among the top causes of death 1 year after heart transplantation (HTx). Coronary CT angiography (CTA) is a potential alternative to invasive imaging in the diagnosis of CAV. However, the higher heart rate (HR) of HTx recipients prompts the use of retrospective ECG-gating, which is associated with higher radiation dose, a major concern in this patient population. Therefore, we sought to evaluate the feasibility and image quality of low-radiation-dose prospectively ECG-triggered coronary CTA in HTx recipients. MATERIALS AND METHODS: In total, 1270 coronary segments were evaluated in 50 HTx recipients and 50 matched control subjects who did not undergo HTx. The control subjects were selected from our clinical database and were matched for age, sex, body mass index, HR, and coronary dominance. Scans were performed using 256-MDCT with prospective ECG-triggering. The degree of motion artifacts was evaluated on a per-segment basis on a 4-point Likert-type scale. RESULTS: The median HR was 74.0 beats/min (interquartile range [IQR], 67.8-79.3 beats/min) in the HTx group and 73.0 beats/min (IQR, 68.5-80.0 beats/min) in the matched control group (p = 0.58). In the HTx group, more segments had diagnostic image quality compared with the control group (624/662 [94.3%] vs 504/608 [82.9%]; p < 0.001). The mean effective radiation dose was low in both groups (3.7 mSv [IQR, 2.4-4.3 mSv] in the HTx group vs 4.3 mSv [IQR, 2.6-4.3 mSv] in the control group; p = 0.24). CONCLUSION: Prospectively ECG-triggered coronary CTA examinations of HTx recipients yielded diagnostic image quality with low radiation dose. Coronary CTA is a promising noninvasive alternative to routine catheterization during follow-up of HTx recipients to diagnose CAV.

The effect of four-phasic versus three-phasic contrast media injection protocols on extravasation rate in coronary CT angiography: a randomized controlled trial.

OBJECTIVES: Contrast media (CM) extravasation is a well-known complication of CT angiography (CTA). Our prospective randomized control study aimed to assess whether a four-phasic CM administration protocol reduces the risk of extravasation compared to the routinely used three-phasic protocol in coronary CTA. METHODS: Patients referred to coronary CTA due to suspected coronary artery disease were included in the study. All patients received 400 mg/ml iomeprol CM injected with dual-syringe automated injector. Patients were randomized into a three-phasic injection-protocol group, with a CM bolus of 85 ml followed by 40 ml of 75%:25% saline/CM mixture and 30 ml saline chaser bolus; and a four-phasic injection-protocol group, with a saline pacer bolus of 10 ml injected at a lower flow rate before the three-phasic protocol. RESULTS: 2,445 consecutive patients were enrolled (mean age 60.6 ± 12.1 years; females 43.6%). Overall rate of extravasation was 0.9% (23/2,445): 1.4% (17/1,229) in the three-phasic group and 0.5% (6/1,216) in the four-phasic group (p = 0.034). CONCLUSIONS: Four-phasic CM administration protocol is easy to implement in the clinical routine at no extra cost. The extravasation rate is reduced by 65% with the application of the four-phasic protocol compared to the three-phasic protocol in coronary CTA. KEY POINTS: • Four-phasic CM injection-protocol reduces extravasation rate by 65% compared to three-phasic. • The saline pacer bolus substantially reduces the risk of CM extravasation. • The implementation of four-phasic injection-protocol is at no cost.

Aortic root dimensions are predominantly determined by genetic factors: a classical twin study.

OBJECTIVES: Previous studies using transthoracic echocardiography (TTE) observed moderate heritability of aortic root dimensions. Computed tomography angiography (CTA) might provide more accurate heritability estimates. Our primary aim was to assess the heritability of the aortic root with CTA. Our secondary aim was to derive TTE-based heritability and compare this with the CTA-based results. METHODS: In the BUDAPEST-GLOBAL study 198 twin subjects (118 monozygotic, 80 dizygotic; age 56.1 ± 9.4 years; 126 female) underwent CTA and TTE. We assessed the diameter of the left ventricular outflow tract (LVOT), annulus, sinus of Valsalva, sinotubular junction and ascending aorta. Heritability was assessed using ACDE model (A additive genetic, C common environmental, D dominant genetic, E unique environmental factors). RESULTS: Based on CTA, additive genetic effects were dominant (LVOT: A = 0.67, E = 0.33; annulus: A = 0.76, E = 0.24; sinus of Valsalva: A = 0.83, E = 0.17; sinotubular junction: A = 0.82, E = 0.18; ascending aorta: A = 0.75, E = 0.25). TTE-derived measurements showed moderate to no genetic influence (LVOT: A = 0.38, E = 0.62; annulus: C = 0.47, E = 0.53; sinus of Valsalva: C = 0.63, E = 0.37; sinotubular junction: C = 0.45, E = 0.55; ascending aorta: A = 0.67, E = 0.33). CONCLUSION: CTA-based assessment suggests that aortic root dimensions are predominantly determined by genetic factors. TTE-based measurements showed moderate to no genetic influence. The choice of measurement method has substantial impact on heritability estimates. KEY POINTS: • Aortic root dimensions are determined by genetic and environmental effects. • Transthoracic echocardiography (TTE) demonstrated moderate to no genetic effects on aortic root dimensions. • Computed tomography angiography might provide more accurate heritability estimates compared to TTE. • Three-dimensional imaging techniques are needed to reliably quantify aortic root dimensions.

Thoracic aortic strain can affect endograft sizing in young patients.

OBJECTIVE: Aortic computed tomography angiography (CTA) examination with electrocardiography gating is becoming the clinical routine image acquisition protocol for diagnosis and intervention planning. To minimize motion artifact, the images are reconstructed in the diastolic phase of the cardiac cycle. The aim of our study was to quantify aortic strain in an elderly nonaneurysmatic patient cohort and to identify the phases of the R-R cycle that correspond to the minimal and maximal aortic diameters. The quantification of aortic strain may enable the improvement of intervention planning and the introduction of more effective dose-saving protocols for CTA scans. METHODS: We assessed CTA images of 28 patients (14 men; mean age, 74 years). Aortic calcium score was calculated on native images. Angiography images were reconstructed in equally spaced 10 phases of the R-R cycle. After semiautomatic centerline analysis, we measured the cross-sectional areas in each of the 10 phases at 9 specific segments between the ascending aorta and the common iliac bifurcation representing the attachment sites of thoracic and abdominal stent grafts. Area-derived effective diameter, pulsatility (Amax - Amin), and strain [(Amax - Amin)/Amin] were calculated. Repeated measurements were taken to evaluate inter-reader and intrareader reproducibility (10-10 patients each). RESULTS: A total of 4320 measurements were performed. We found significant difference between diastolic and systolic diameters (DD,Z0 = 33.2, DS,Z0 = 34.4; P < .001). Pulsatility values of the vessel diameters were 1.0 to 1.1 mm in the thoracic aorta, 0.7 to 0.9 mm in the abdominal aorta, and 0.5 to 0.6 mm in the common iliac arteries. Negative, moderate correlations were found between aortic strain and age (r = -0.586; P = .001), aortic strain and plaque area (r = -0.429; P = .026), and age and body mass index (r = -0.412; P = .029). We found positive, moderate correlation between age and plaque area (r = 0.594; P = .001). The aortic pulsatility curve has a positive extreme at 30% and a negative extreme at 90% of the R-R cycle throughout the aorta. Lin concordance coefficients were 0.987 for inter-reader and 0.994 for intrareader correlations. CONCLUSIONS: Aortic strain can be reliably quantified on electrocardiography-gated CTA images. Pulsatility of the aorta can be substantial in the thoracic aortic segments of young patients; therefore, the routine use of systolic images is not recommended. In addition, we demonstrated that images at 30% of the heart cycle correspond to the largest diameter of the aorta.

Clinical predictors of mortality following rotational atherectomy and stent implantation in high-risk patients: A single center experience.

OBJECTIVES: Our aim was to assess the procedural success and determine the clinical predictors of postprocedure mortality, following rotational atherectomy (RA) and stenting in high-risk patients. BACKGROUND: RA is mainly used to facilitate stenting in complex lesions. Outcomes involving RA and stenting have been investigated, yet high-risk patients have not been adequately described. METHODS: Data of 218 consecutive patients who underwent RA were evaluated in a prospective register. Primary endpoints were the angiographic success and long-term mortality. Secondary endpoints were procedural success, consumption of the angioplasty equipment, and periprocedural major adverse cardiac events. The impact of the relevant angiographic and clinical characteristics on long-term mortality was analyzed using uni- and multivariate Cox regression analysis. RESULTS: Mean age of the patients was 70 ± 8.2 years, diabetes was present in 44%, and chronic renal failure in 29%. Prior myocardial infarction and three-vessel disease amounted to 42.2% and 32.6%, respectively. Altogether, 52.8% of patients underwent RA after a failed, non-RA intervention attempt, and 30.7% of cases presented as acute coronary syndromes. Angiographic success was 100%, and all patients received stents after RA. Periprocedural major adverse cardiac events occurred in five (2.3%) patients. Postprocedural death was investigated, with a mean follow-up of 36 months. Mortality amounted to 37.2%. Multivariate analysis revealed that left ventricular ejection fraction < 50%, glomerular filtration rate < 60 ml/min, cardiogenic shock, and diabetes were the only independent mortality predictors. CONCLUSIONS: We have found that RA and stenting is feasible and viable in an elderly high-risk population, with exceptional procedural success and acceptable long-term results.

Possible extracardiac predictors of aortic dissection in Marfan syndrome.

BACKGROUND: According to previous studies, aortic diameter alone seems to be insufficient to predict the event of aortic dissection in Marfan syndrome (MFS). Determining the optimal schedule for preventive aortic root replacement (ARR) aortic growth rate is of importance, as well as family history, however, none of them appear to be decisive. Thus, the aim of this study was to search for potential predictors of aortic dissection in MFS. METHODS: A Marfan Biobank consisting of 79 MFS patients was established. Thirty-nine MFS patients who underwent ARR were assigned into three groups based on the indication for surgery (dissection, annuloaortic ectasia and prophylactic surgery). The prophylactic surgery group was excluded from the study. Transforming growth factor-ß (TGF-ß) serum levels were measured by ELISA, relative expression of c-Fos, matrix metalloproteinase 3 and 9 (MMP-3 and -9) were assessed by RT-PCR. Clinical parameters, including anthropometric variables - based on the original Ghent criteria were also analyzed. RESULTS: Among patients with aortic dissection, TGF-ß serum level was elevated (43.78 ± 6.51 vs. 31.64 ± 4.99 ng/l, p < 0.0001), MMP-3 was up-regulated (Ln2α = 1.87, p = 0.062) and striae atrophicae were more common (92% vs. 41% p = 0.027) compared to the annuloaortic ectasia group. CONCLUSIONS: We found three easily measurable parameters (striae atrophicae, TGF-ß serum level, MMP-3) that may help to predict the risk of aortic dissection in MFS. Based on these findings a new classification of MFS, that is benign or malignant is also proposed, which could be taken into consideration in determining the timing of prophylactic ARR.

Low-attenuation coronary plaque burden and troponin release in chronic coronary syndrome: A mediation analysis.

BACKGROUND: Coronary low-attenuation plaque (LAP) burden is a strong predictor of myocardial infarction in patients with stable chest pain. We aimed to assess the relationship between LAP burden and circulating levels of high-sensitivity cardiac troponin T (hs-cTnT), and to explore the potential underlying etiology in patients undergoing clinically indicated coronary CT angiography (CCTA). METHODS: A comprehensive metabolic and lipid panel, as well as C-reactive protein (CRP) and hs-cTnT tests were obtained from consecutive patients with stable chest pain at the time of CCTA. Qualitative and quantitative coronary plaque analysis, CT-derived fractional flow reserve (FFR) calculation, and pericoronary adipose tissue (PCAT) attenuation measurement around the right coronary artery were performed on CCTA images. Linear regression analyses were performed to identify independent associations with hs-cTnT concentration and mediation analysis was used to assess whether ischemia or markers of inflammation mediate hs-cTnT elevation. RESULTS: In total, 114 patients (56.3 â€‹± â€‹10.6 years, 44.7 â€‹% female) were enrolled. In multivariable analysis, age (ߠ​= â€‹0.04 [95%CI: 0.02; 0.06], p â€‹< â€‹0.001), female sex (ߠ​= â€‹-0.77 [95%CI: -1.20; 0.33], p â€‹< â€‹0.001), and LAP burden (ߠ​= â€‹0.03 [95%CI: 0.001; 0.06], p â€‹= â€‹0.04) were independently associated with hs-cTnT levels. Mediation analysis, on the other hand, did not identify a significant mediating effect of lesion-specific ischemia based on CT-FFR, circulating CRP levels, or PCAT values between LAP burden and hs-cTnT levels (all p â€‹> â€‹0.05). CONCLUSION: Although ischemia and inflammation have previously been proposed to mediate the association between LAP burden and hs-cTnT levels, our results did not confirm the role of these pathophysiological pathways in patients with stable chest pain.

Truncated titin is structurally integrated into the human dilated cardiomyopathic sarcomere.

Heterozygous (HET) truncating variant mutations in the TTN gene (TTNtvs), encoding the giant titin protein, are the most common genetic cause of dilated cardiomyopathy (DCM). However, the molecular mechanisms by which TTNtv mutations induce DCM are controversial. Here, we studied 127 clinically identified DCM human cardiac samples with next-generation sequencing (NGS), high-resolution gel electrophoresis, Western blot analysis, and super-resolution microscopy in order to dissect the structural and functional consequences of TTNtv mutations. The occurrence of TTNtv was found to be 15% in the DCM cohort. Truncated titin proteins matching, by molecular weight, the gene sequence predictions were detected in the majority of the TTNtv+ samples. Full-length titin was reduced in TTNtv+ compared with TTNtv- samples. Proteomics analysis of washed myofibrils and stimulated emission depletion (STED) super-resolution microscopy of myocardial sarcomeres labeled with sequence-specific anti-titin antibodies revealed that truncated titin was structurally integrated into the sarcomere. Sarcomere length-dependent anti-titin epitope position, shape, and intensity analyses pointed at possible structural defects in the I/A junction and the M-band of TTNtv+ sarcomeres, which probably contribute, possibly via faulty mechanosensor function, to the development of manifest DCM.

Ultra-high resolution coronary CT angiography on photon-counting detector CT: bi-centre study on the impact of quantum iterative reconstruction on image quality and accuracy of stenosis measurements.

PURPOSE: To assess the impact of different quantum iterative reconstruction (QIR) levels on objective and subjective image quality of ultra-high resolution (UHR) coronary CT angiography (CCTA) images and to determine the effect of strength levels on stenosis quantification using photon-counting detector (PCD)-CT. METHOD: A dynamic vessel phantom containing two calcified lesions (25 % and 50 % stenosis) was scanned at heart rates of 60, 80 and 100 beats per minute with a PCD-CT system. In vivo CCTA examinations were performed in 102 patients. All scans were acquired in UHR mode (slice thickness0.2 mm) and reconstructed with four different QIR levels (1-4) using a sharp vascular kernel (Bv64). Image noise, signal-to-noise ratio (SNR), sharpness, and percent diameter stenosis (PDS) were quantified in the phantom, while noise, SNR, contrast-to-noise ratio (CNR), sharpness, and subjective quality metrics (noise, sharpness, overall image quality) were assessed in patient scans. RESULTS: Increasing QIR levels resulted in significantly lower objective image noise (in vitro and in vivo: both p < 0.001), higher SNR (both p < 0.001) and CNR (both p < 0.001). Sharpness and PDS values did not differ significantly among QIRs (all pairwise p > 0.008). Subjective noise of in vivo images significantly decreased with increasing QIR levels, resulting in significantly higher image quality scores at increasing QIR levels (all pairwise p < 0.001). Qualitative sharpness, on the other hand, did not differ across different levels of QIR (p = 0.15). CONCLUSIONS: The QIR algorithm may enhance the image quality of CCTA datasets without compromising image sharpness or accurate stenosis measurements, with the most prominent benefits at the highest strength level.

Comparison of Two Contemporary Quantitative Atherosclerotic Plaque Assessment Tools for Coronary Computed Tomography Angiography: Single-Center Analysis and Multi-Center Patient Cohort Validation.

BACKGROUND: Coronary computed tomography angiography (CCTA) provides non-invasive quantitative assessments of plaque burden and composition. The quantitative assessment of plaque components requires the use of analysis software that provides reproducible semi-automated plaque detection and analysis. However, commercially available plaque analysis software can vary widely in the degree of automation, resulting in differences in terms of reproducibility and time spent. AIM: To compare the reproducibility and time spent of two CCTA analysis software tools using different algorithms for the quantitative assessment of coronary plaque volumes and composition in two independent patient cohorts. METHODS: The study population included 100 patients from two different cohorts: 50 patients from a single-center (Siemens Healthineers, SOMATOM Force (DSCT)) and another 50 patients from a multi-center study (5 different > 64 slice CT scanner types). Quantitative measurements of total calcified and non-calcified plaque volume of the right coronary artery (RCA), left anterior descending (LAD), and left circumflex coronary artery (LCX) were performed on a total of 300 coronaries by two independent readers, using two different CCTA analysis software tools (Tool #1: Siemens Healthineers, syngo.via Frontier CT Coronary Plaque Analysis and Tool #2: Siemens Healthineers, successor CT Coronary Plaque Analysis prototype). In addition, the total time spent for the analysis was recorded with both programs. RESULTS: The patients in cohorts 1 and 2 were 62.8 ± 10.2 and 70.9 ± 11.7 years old, respectively, 10 (20.0%) and 35 (70.0%) were female and 34 (68.0%) and 20 (40.0%), respectively, had hyperlipidemia. In Cohort #1, the inter- and intra-observer variabilities for the assessment of plaque volumes per patient for Tool #1 versus Tool #2 were 22.8%, 22.0%, and 26.0% versus 2.3%, 3.9%, and 2.5% and 19.7%, 21.4%, and 22.1% versus 0.2%, 0.1%, and 0.3%, respectively, for total, noncalcified, and calcified lesions (p < 0.001 for all between Tools #1 and 2 both for inter- and intra-observer). The inter- and intra-observer variabilities using Tool #2 remained low at 2.9%, 2.7%, and 3.0% and 3.8%, 3.7%, and 4.0%, respectively, for total, non-calcified, and calcified lesions in Cohort #2. For each dataset, the median processing time was higher for Tool #1 versus Tool #2 (459.5 s IQR = 348.0-627.0 versus 208.5 s; IQR = 198.0-216.0) (p < 0.001). CONCLUSION: The plaque analysis Tool #2 (CT-guided PCI) encompassing a higher degree of automated support required less manual editing, was more time-efficient, and showed a higher intra- and inter-observer reproducibility for the quantitative assessment of plaque volumes both in a representative single-center and in a multi-center validation cohort.

Photon-counting detector CT reduces the rate of referrals to invasive coronary angiography as compared to CT with whole heart coverage energy-integrating detector.

BACKGROUND: We sought to compare the degree of maximal stenosis and the rate of invasive coronary angiography (ICA) recommendations in patients who underwent coronary CT angiography (CCTA) with photon-counting detector CT (PCD-CT) versus those who underwent CCTA with whole heart coverage energy-integrating detector CT (EID-CT). METHODS: In our retrospective single-center study, we included consecutive patients with suspected CAD who underwent CCTA performed with either PCD-CT or a 280-slice EID-CT. The degree of coronary stenosis was classified as no CAD, minimal (1-24 â€‹%), mild (25-49 â€‹%), moderate (50-69 â€‹%), severe stenosis (70-99 â€‹%), or occlusion. RESULTS: A total of 812 consecutive patients were included in the analysis, 401 patients scanned with EID-CT and 411 patients with PCD-CT (mean age: 58.4 â€‹± â€‹12.4 years, 45.4 â€‹% female). Despite the higher total coronary artery calcium score (CACS) in the PCD-CT group (10 [interquartile range (IQR) â€‹= â€‹0-152.8] vs 1 [IQR â€‹= â€‹0-94], p â€‹< â€‹0.001), obstructive CAD was more frequently reported in the EID-CT vs PCD-CT group (no CAD: 28.7 â€‹% vs 26.0 â€‹%, minimal: 23.2 â€‹% vs 30.9 â€‹%, mild: 19.7 â€‹% vs 23.4 â€‹%, moderate: 14.5 â€‹% vs 9.7 â€‹%, severe: 11.5 â€‹% vs 8.5 â€‹% and occlusion: 2.5 â€‹% vs 1.5 â€‹%, respectively, p â€‹= â€‹0.025). EID-CT was independently associated with downstream ICA (OR â€‹= â€‹2.76 [95%CI â€‹= â€‹1.58-4.97] p â€‹< â€‹0.001) in the overall patient population, in patients with CACS<400 (OR â€‹= â€‹2.18 [95%CI â€‹= â€‹1.13-4.39] p â€‹= â€‹0.024) and in patients with CACS≥400 (OR â€‹= â€‹3.83 [95%CI â€‹= â€‹1.42-11.05] p â€‹= â€‹0.010). CONCLUSION: In patients who underwent CCTA with PCD-CT the number of subsequent ICAs was lower as compared to patients who were scanned with EID-CT. This difference was greater in patients with extensive coronary calcification.

Qualitative and quantitative image quality of coronary CT angiography using photon-counting computed tomography: Standard and Ultra-high resolution protocols.

PURPOSE: We aimed to identify the optimal reconstruction settings based on qualitative and quantitative image quality parameters on standard and ultra-high resolution (UHR) images using photon-counting CT (PCCT). METHOD: We analysed 45 patients, 29 with standard and 16 with UHR acquisition, applying both smoother and sharper kernel settings. Coronary CT angiography images were performed on a dual-source PCCT system using standard (0.4/0.6 mm slice thickness, Bv40/Bv44 kernels, QIR levels 0-4) or UHR acquisition (0.2/0.4 mm slice thickness, Bv44/Bv56 kernels, QIR levels 0-4). Qualitative image quality was assessed using a 4-point Likert scale. Image noise (SD), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated in both the proximal and distal segments. RESULTS: On standard resolution, larger slice thickness resulted in an average increase of 12.5 % in CNR, whereas sharper kernel led to an average 8.7 % decrease in CNR. Highest CNR was measured on 0.6 mm, Bv40, QIR4 images and lowest on 0.4 mm, Bv44, QIR0 images: 25.8 ± 4.1vs.8.3 ± 1.6 (p < 0.001). On UHR images, highest CNR was observed on 0.4 mm, Bv40, QIR4 and lowest on 0.2 mm, Bv56 and QIR0 images: 21.5 ± 3.9vs.3.6 ± 0.8 (p < 0.001). Highest qualitative image quality was found on images with Bv44 kernel and QIR level 3/4 with both slice thicknesses on standard reconstruction. Additionally, Bv56 with QIR4 on 0.2 mm slice thickness images showed highest subjective image quality. Preserved distal vessel visualization was detected using QIR 2-4, Bv56 and 0.2 mm slice thickness. CONCLUSIONS: Photon-counting CT demonstrated high qualitative and quantitative image quality for the assessment of coronaries and stents.