Insights from 2D and 3D Quantitative Angiographic Assessment of Bioresorbable Everolimus-Eluting Vascular Scaffolds.

BACKGROUND: Bioresorbable vascular scaffold (BVS) is a promising technology that potentially offers several advantages over contemporary coronary drug-eluting stents (DES). Crucial to BVS implantation is the correct choice of scaffold size (diameter and length) in order to avoid "geographic miss" in length, provide the maximal support to the vessel wall, and avoid leaving "free-floating" foreign material in the coronary vasculature. OBJECTIVES: To assess the optimal method for measuring coronary stenosis prior to BVS implantation. METHODS: We compared the performance of two quantitative coronary angiography assessment (QCA) techniques: two dimensional real-time QCA (2D-QCA) and offline 3D QCA (3D-QCA) for the evaluation of coronary lesions in patients enrolled in a multicenter randomized controlled trial of BVS vs. metallic stents, by calculating the weighted kappa value for agreement regarding optimal BVS size with the reference method - CoreLab offline 2D-QCA measurements..In addition, we collected 2 year clinical outcomes (death/myocardial infarction/repeat revascularization/scaffold thrombosis) in BVS-implanted patients. RESULTS: In 17 patients with available CoreLab data, the weighted kappa for agreement for 3D-QCA was significantly better than for 2D-QCA (0.90, 95%CI 0.72-1.00 vs. 0.439, 95%CI 0.16-0.77). The rate of clinical events at 2 years was low (9.5%). CONCLUSIONS: Initial experience in a small group of carefully selected patients at our institution, suggests that the use of BVS for coronary revascularization is associated with a low rate of adverse events in suitable patients. 3D-QCA may be superior to 2D-QCA analysis in terms of reproducibility, and results in more patients receiving optimal size BVS.

The incremental impact of residual SYNTAX score on long-term clinical outcomes in patients with multivessel coronary artery disease treated by percutaneous coronary interventions.

OBJECTIVE: To broaden the data supporting the use of the residual SYNTAX score (rSS) to define "reasonable" incomplete coronary revascularization (ICR) in order to improve the allocation of patients with severe coronary artery disease (CAD) to surgical/percutaneous revascularization and long-term clinical outcomes. INTRODUCTION: ICR is associated with a worse prognosis in patients with severe CAD, yet no consensus exists regarding its definition. METHODS: We studied 148 consecutive patients with triple vessel/left main (3VD/LM) CVD treated by percutaneous coronary interventions (PCI). Clinical outcomes at 3 years were collected; the SS and rSS were calculated. We used various definitions of "reasonable" ICR:no post-PCI total occlusion, single vs. mutivessel residual post-PCI disease, and the rSS at a cutoff value determined according to ROC curve fitted for 3 years major adverse cardiovascular and cerebrovascular adverse events (MACCE) in order to determine which definition has the strongest correlation with long-term outcomes. RESULTS: rSS ≤ 8 was associated with significant reductions in 3 year MACCE (19.4 vs. 51.1%, HR = 3.62, P = 0.014) Death/MI/CVA (13.7 vs. 28.8%, HR = 6.01, P = 0.030) and repeat revascularization (8.6 vs. 28.9%, HR = 3.44, P = 0.033) using a Cox proportional hazard ratio model adjusted to baseline characteristics, whereas single vessel residual disease and absence of total occlusion were not. CONCLUSIONS: "Reasonable" ICR as determined by rSS carries better long-term prognosis in terms of clinical outcomes vs. more extensive residual coronary disease in patients with 3VD/LM coronary artery disease treated by PCI. The rSS may improve the allocation of coronary patients to the optimal mode of revascularization.

C-THV measures of self-expandable valve positioning and correlation with implant outcomes.

BACKGROUND: Accurate positioning of the valve device during transcutaneous aortic valve implantation (TAVI) is of crucial importance. The Paieon C-THV navigation system has been designed to correctly guide device deployment during TAVI. OBJECTIVES: Using this navigation system we aimed to determine the correlation between the anatomic measures of the native aortic valve and the deployed self-expandable valve positioning and to explore the impact upon procedural outcomes. METHODS: We analyzed data of 68 patients with severe symptomatic aortic stenosis undergoing TAVI, using the catheter-based Medtronic-CoreValve self-expandable system. Patients were subdivided into two groups according to whether the C-THV system was used (50) or not (18) during the implantation process. Analysis of geometrical outcomes vs. clinical outcomes including postprocedural electrical conduction defect and/or para-valvular leaks was performed. RESULTS: Taking the target implantation line as a reference; relatively lower vs. higher implantations correlated with a higher frequency of any new onset electrical conduction defect (ECD). The mean corresponding distance from valve inferior edge below the virtual aortic annulus line was 3.0 ± 1.6 mm vs. 1.2 ± 1.3 mm in patients with (38.5%) vs. without any new onset ECD, respectively (P = 0.05). The use of C-THV navigation seemed to correlate with higher valve implants but it had no impact on the occurrence of postprocedural paravalvular leaks. CONCLUSIONS: Self-expandable valve implants guided by C-THV navigation seems to be associated with more precise implants and lower risk for postprocedural electrical conduction defects, due to higher location in relation to the target line.

Intracoronary monocyte chemoattractant protein 1 and vascular endothelial growth factor levels are associated with necrotic core, calcium and fibrous tissue atherosclerotic plaque components: an intracoronary ultrasound radiofrequency study.

AIMS: To investigate the relationship between various serum biomarkers and coronary atherosclerotic plaque composition obtained by intravascular ultrasound virtual histology (IVUS-VH). METHODS: Using ELISA, we measured the serum levels of CD40 ligand, C-reactive protein, monocyte chemoattractant protein 1 (MCP-1), metalloproteinase 9, P-selectin and vascular endothelial growth factor (VEGF) in 40 patients with manifested coronary artery disease. RESULTS: Correlation analysis between biomarkers levels, IVUS grayscale parameters and VH-defined necrotic core (NC), calcium, fibrous and fibrofatty components was performed. MCP-1 and VEGF levels correlated with the severity of area stenosis (r = 0.35, p = 0.03 and r = 0.38, p = 0.017, respectively) and inversely correlated with the remodeling index (r = -0.35, p = 0.03 and r = 0.35, p = 0.02, respectively). Higher levels of MCP-1 were associated with increased calcium (r = 0.47, p = 0.004), NC (r = 0.38, p = 0.02) and less fibrous tissue components (r = -0.34, p = 0.03), whereas VEGF had an inverse correlation with both calcium components (r = -0.37, p = 0.02) and NC (r = -0.34, p = 0.036) but was strongly associated with increased fibrous components (r = 0.47, p = 0.003). No significant correlation was noted for any of the other biomarkers. CONCLUSIONS: MCP-1 and VEGF serum levels in patients with ischemic heart disease are correlated with coronary artery plaque burden and composition.

Online Angiography Image-Based FFR Assessment During Coronary Catheterization: A Single-Center Study.

OBJECTIVES: To assess the diagnostic performance of angiography-derived fractional flow reserve (FFRangio) measurements in patients with stable coronary artery disease when used online in the catheterization laboratory during routine coronary angiography. BACKGROUND: FFR, an index of the hemodynamic severity of coronary stenosis, is derived from invasive measurements using a pressure-monitoring guidewire and hyperemic stimulus. While FFR is the gold standard, it remains under-utilized. FFRangio may have several advantages owing to the reduced operator time, no wire-related or procedural complications, and no need for administration of vasodilators. METHODS: FFRangio is a novel technology that uses a patient's hemodynamic data and routine angiograms to generate FFR values at each point along the coronary tree. We present the online application of the system where FFRangio was successfully used in the catheterization laboratory during routine coronary angiography and compared to invasive FFR. Fifty-three patients (79% men) and 60 coronary lesions were analyzed. RESULTS: Values derived using FFRangio ranged from 0.58-0.96 and correlated closely (Pearson's correlation coefficient, r=0.91; P<.001) with the invasive FFR measurements (range, 0.52-0.97). The 95% limits of agreement between invasive and non-invasive FFR ranged from -0.065 to 0.07 using Bland-Altman analysis. For an FFR cut-off value of 0.80, the sensitivity, specificity, and diagnostic accuracy of FFRangio were 86%, 100%, and 95%, respectively. CONCLUSIONS: This is the first report of using the online application of the FFRangio system. In this single-center experience, FFRangio values showed high correlation rates to invasive FFR.

Validation Study of Image-Based Fractional Flow Reserve During Coronary Angiography.

BACKGROUND: Fractional flow reserve (FFR), an index of the hemodynamic severity of coronary stenoses, is derived from invasive measurements and requires a pressure-monitoring guidewire and hyperemic stimulus. Angiography-derived FFR measurements (FFRangio) may have several advantages. The aim of this study is to assess the diagnostic performance and interobserver reproducibility of FFRangio in patients with stable coronary artery disease. METHODS AND RESULTS: FFRangio is a computational method based on rapid flow analysis for the assessment of FFR. FFRangio uses the patient's hemodynamic data and routine angiograms to generate a complete 3-dimensional coronary tree with color-coded FFR values at any epicardial location. Hyperemic flow ratio is derived from an automatic resistance-based lumped model of the entire coronary tree. A total of 203 lesions were analyzed in 184 patients from 4 centers. Values derived using FFRangio ranged from 0.5 to 0.97 (median 0.85) and correlated closely (Spearman ρ=0.90; P<0.001) with the invasive FFR measurements, which ranged from 0.5 to 1 (median 0.84). In Bland-Altman analyses, the 95% limits of agreement between these methods ranged from -0.096 to 0.112. Using an FFR cutoff value of 0.80, the sensitivity, specificity, and diagnostic accuracy of FFRangio were 88%, 95%, and 93%, respectively. The intraclass coefficient between 2 blinded operators was 0.962 with a 95% confidence interval from 0.950 to 0.971, P<0.001. CONCLUSIONS: There is a high concordance between FFRangio and invasive FFR. The color-coded display of FFR values during coronary angiography facilitates the integration of physiology and anatomy for decision making on revascularization in patients with stable coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03005028.

Effect of coronary artery disease severity and revascularization completeness on 2-year clinical outcomes in patients undergoing transcatether aortic valve replacement.

AIMS: To evaluate the effect of coronary artery disease (CAD) severity and completeness of revascularization on clinical outcomes following transcatheter aortic valve replacement (TAVR) using the SYNTAX score (SS), clinical SYNTAX score (cSS), and residual SYNTAX score (rSS). METHODS AND RESULTS: We studied 287 consecutive patients undergoing TAVR at our institution. Patients were classified as having CAD or no CAD and coronary patients were stratified according to SS and cSS. The completeness of revascularization was stratified using the rSS. We compared the 2-year outcomes according to SS/cSS/rSS. Forty-nine patients (17.1%) had CAD and sustained a higher rate of the primary endpoint at 2 years (28.3 vs. 16.1%, P=0.026). Stratified by CAD severity, the difference was driven by the high-severity groups (75.0 vs. 16.1%, P=0.002 for SS>22 and 41.2 vs. 16.1%, P=0.001 for cSS>63). Low-severity CAD patients did not have worse outcomes versus no CAD. When evaluating the effect of revascularization, patients with a rSS less than 8 did not have worse outcomes versus patients who did not have CAD. CONCLUSION: In patients undergoing TAVR, it is the severity of CAD (as assessed by the SS/cSS) that is associated with worse prognosis and not the mere presence of CAD. More complete revascularization attenuates the effect of CAD on clinical outcomes.

Medical iPad use in the cardiac catheterization and echo laboratories.

The present study aims to describe a dedicated cardiac imaging application on a tablet and to assess the accuracy and reproducibility of this novel application for measurement on angiography and echocardiography data sets. Tablet devices have recently been used in radiological image interpretation and enable transfer of images. It allows the clinician to look up clinical information, search the Internet and communicate with colleagues and family. The study group consisted of 30 patients who had both echocardiographic and angiographic examinations. For each patient, a few measurements (i.e. length, area and angle) were performed using the iPad, and compared to the McKesson workstation, which is routinely used in the hospital. In order to show the equivalence between these two methods, a linear regression was fitted and the distribution of differences between measurements was examined. In addition, the variability of the measurements was compared between two different reviewers (inter-observer test) and between the measurements of the same reviewer at two different time settings (intra-observer test) by calculating the intraclass correlation coefficient (ICC). In all comparisons, the linear regression showed high correlation coefficient (r > 0.9), and the distribution of differences was around zero, implying that the two methods lead to equivalent results. The absolute mean difference between the two different observers demonstrated high agreement between the two observers' repeated measurements. The same conclusions can be deduced from the same observer's repeated measurements. The ICC indicates the resemblance between the two sets, and could be considered almost perfect (ICC > 0.968 for all cases). The newly developed cardiology iPad application offers the opportunity to accurately present the cardiac procedure in a visual, clear and professional manner.

Long-term outcomes of patients with complex coronary artery disease according to agreement between the SYNTAX score and revascularization procedure in contemporary practice.

AIMS: The SYNTAX score (SS) has been shown to identify subgroups of patients with left main or triple-vessel coronary artery disease (LM/3VCAD) that can be treated with a percutaneous coronary intervention (PCI) with equal clinical outcomes as coronary artery bypass surgery (CABG).We sought to assess the adequacy of referral to PCI/CABG of patients with LM/3VCAD at our institution. PATIENTS AND METHODS: We retrospectively matched all patients with LM/3VCAD referred to CABG (n=145) to patients referred to PCI in our institution during 2009-2010. We calculated the SS and clinical SS (cSS) according to the European Society of Cardiology guidelines and compared the agreement rates between the revascularization modality and the SS as well as clinical outcomes at the 3-year follow-up. RESULTS: The overall agreement rates between the revascularization procedure and the SS was 67%, for example the rate was higher in patients referred to PCI compared with CABG (78 vs. 49%) and patients with 3VCAD compared with patients with LMCAD (68 vs. 51%). Patients without agreement between the revascularization modality and the SS had higher rates of combined adverse cardiac events (42.6 vs. 27% P=0.008). Similar results were observed when using the cSS at different cutoff levels. CONCLUSION: At our institution, there was considerable disagreement between a clinical judgment-based coronary revascularization and the SS/cSS-based allocation process as to the preferred revascularization modality for patients with complex CAD. Our results suggest that integrating the SS/cSS into the decision-making process for assigning patients to revascularization would yield better clinical outcomes.

Transcatheter aortic valve implantation of a CoreValve device using novel real-time imaging guidance.

Thorough imaging of the aortic valve and related structures is highly important before and during transcatheter aortic-valve implantation. However, conventional aortography is limited for guiding precise valve placement and depends on contrast injections. A real-time imaging system capable of guiding the operator during Edwards-SPAIEN valve procedures has been introduced (C-THV, Paieon, Inc.). We describe the first application of the novel C-THV system during CoreValve implantation in a very challenging clinical scenario that required precise high implantation using minimal contrast.

Biomechanical factors in coronary vulnerable plaque risk of rupture: intravascular ultrasound-based patient-specific fluid-structure interaction studies.

OBJECTIVES: The aim of this study was to elucidate the mechanisms and underlying biomechanical factors that may play a role in the risk of rupture of vulnerable plaques (VPs) by studying patient-based geometries of coronary arteries reconstructed from intravascular ultrasound (IVUS) imaging utilizing fluid-structure interaction (FSI) numerical simulations. BACKGROUND: According to recent estimates, coronary artery disease is responsible for one in six deaths in the USA, and causes about one million heart attacks each year. Among these, the rupture of coronary VPs followed by luminal blockage is widely recognized as a major cause of sudden heart attacks; most importantly, the patients may appear as asymptomatic under routine screening before the occurrence of the index event. MATERIALS AND METHODS: FSI simulations of patient-based geometries of coronary arteries reconstructed from IVUS imaging were performed to establish the dependence of the risk of rupture of coronary VP on biomechanical factors, such as the fibrous cap thickness, presence of microcalcification in the fibrous cap, arterial anisotropy, and hypertension. RESULTS: Parametric FSI simulations indicated that mechanical stresses (von Mises stresses) increase exponentially with the thinning of the fibrous cap as well as with increasing levels of hypertension. The inclusion of a microcalcification in the fibrous cap considerably increases the risk of rupture of VP , with an ∼two-fold stress increase in the VP stress burden. Furthermore, the stress-driven reorientation and biochemical degradation of the collagen fibers in the vessel wall because of atherosclerosis (studied with an anisotropic fibrous cap 65° fiber reorientation angle) results in a 30% increase in the stress levels as compared with simulations with isotropic material models, clearly indicating that the latter, which are commonly used in such studies, underestimate the risk of rupture of VP. CONCLUSION: The results indicate that IVUS-based patient-specific FSI simulations for mapping the wall stresses, followed by analysis of the biomechanical risk factors, may be used as an additional diagnostic tool for clinicians to estimate the plaque burden and determine the proper treatment and intervention.

Multicenter evaluation of Edwards SAPIEN positioning during transcatheter aortic valve implantation with correlates for device movement during final deployment.

OBJECTIVES: This study sought to evaluate the exact location of Edwards SAPIEN (Edwards Lifesciences, Irvine, California) devices in different stages of implantation and to quantify possible operator-independent device movement during final deployment. BACKGROUND: Accurate device positioning during transcatheter aortic valve implantation is crucial in order to achieve optimal results. METHODS: This multicenter study consisted of 68 procedures with reliable pacemaker capture. Device positions were assessed using fluoroscopic images and the C-THV system (Paieon Medical, Rosh Ha'Ayin, Israel). RESULTS: The location after implantation was significantly higher than in the final stage of rapid pacing: 16.7 ± 16.3% of device height below the plane of the lower sinus border versus 32.6 ± 13.8%, p < 0.0001. Operator-independent device-center upper movement during final deployment was 2 ± 1.43 mm, range: -1.3 to 4.6 mm. Device movement was asymmetrical, occurring more in the lower part of the device than in its upper part (3.2 ± 1.4 mm vs. 0.75 ± 1.5 mm, p < 0.001), resulting in device shortening. Multivariate analysis revealed that moderate and severe aortic valve calcification had 49% higher upward movement than mild calcification (p = 0.03), and aortic sinus volume was negatively correlated with movement size (r = -0.35, p = 0.005). This movement was independent of device version (SAPIEN vs. SAPIEN XT), procedural access (transfemoral vs. transapical), and interventricular septum width. CONCLUSIONS: The final Edwards SAPIEN position is mostly aortic in relation to the lower sinus border. There is an operator-independent upward movement of the device center during the final stage of implantation. Anticipated upward movement of the device should influence its positioning before final deployment.

Necrotic core and thin cap fibrous atheroma distribution in native coronary artery lesion-containing segments: a virtual histology intravascular ultrasound study.

OBJECTIVES: The aim of this study was to assess the longitudinal topographical relationships between minimal luminal area (MLA) sites and plaques with the most vulnerable characteristics using radiofrequency-based virtual histology intravascular ultrasound analysis. METHODS: We analyzed 69 native coronary artery segments with de-novo lesions (>50% stenosis) obtained from 50 patients with ischemic coronary artery disease. Maximal necrotic core (maxNC) was defined as a virtual histology intravascular ultrasound frame with the maxNC area and virtual histology-characterized thin cap fibrous atheroma was defined as a cross-section, which contained a plaque burden of more than 40%, relative necrotic core area of 10% or more, and a narrow band encircling the lumen containing relative necrotic core area of more than 10%, in three consecutive frames. RESULTS: MaxNC was present at the MLA site in only 17.4% of the segments, proximal in 52.2% (by 5.0 ± 5.4 mm), and distal to MLA in 30.4% (by 4.0 ± 5.1 mm). Non-MLA sites with maxNC (n=57) compared with MLA sites had reduced plaque burden (64.5 ± 11.2% vs. 76.0 ± 10.5%, P<0.001), increased remodeling index (1.04 ± 0.17 vs. 0.89 ± 0.15, P<0.001), less fibrotic tissue (47.7 ± 13.4% vs. 54.8 ± 13.8%, P<0.001), and higher dense calcium deposition (15.3 ± 10.8% vs. 11.9 ± 10.3%, P<0.001). Plaques containing maxNC and virtual histology-characterized thin cap fibrous atheroma were found in 23 of the non-MLA sites compared with two of the MLA sites (P<0.0001). CONCLUSIONS: In coronary artery segments with intermediate-to-severe stenosis, plaques containing maxNC are mostly located away from the MLA site and more often comprise virtual histology-characterized thin cap fibrous atheroma. Such data may carry practical implications for coronary revascularization procedures.

Role of parenting style in achieving metabolic control in adolescents with type 1 diabetes.

OBJECTIVE: To examine the role of parenting style in achieving metabolic control and treatment adherence in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: Parents of 100 adolescents with type 1 diabetes completed assessments of their parenting style and sense of helplessness. Parents and patients rated patient adherence to the treatment regimen. Glycemic control was evaluated by HbA(1c) values. RESULTS: An authoritative paternal parenting style predicted better glycemic control and adherence in the child; a permissive maternal parenting style predicted poor adherence. A higher sense of helplessness in both parents predicted worse glycemic control and lesser adherence to treatment. Parental sense of helplessness was a significant predictor of diabetes control after correcting for other confounders (patient age, sex, and treatment method). CONCLUSIONS: An authoritative nonhelpless parenting style is associated with better diabetes control in adolescents. Paternal involvement is important in adolescent diabetes management. These results have implications for psychological interventions.