In vitro validation and comparison of different software packages or algorithms for coronary bifurcation analysis using calibrated phantoms: implications for clinical practice and research of bifurcation stenting.

BACKGROUND: The accuracy and precision of quantitative coronary angiography (QCA) software dedicated for bifurcation lesions compared with conventional single-vessel analysis remains unknown. Furthermore, comparison of different bifurcation analysis algorithms has not been performed. METHODS: Six plexiglas phantoms with 18 bifurcations were manufactured with a tolerance < 10 µm. The bifurcation angiograms were analyzed using Cardiovascular Angiography Analysis System (CAAS; Version 5.10, Pie Medical Imaging, Maastricht, The Netherlands) and QAngio XA (Version 7.3, Medis Medical Imaging System BV, Leiden, The Netherlands) software packages. RESULTS: Conventional single-vessel analysis underestimated the reference vessel diameter and percent diameter stenosis in the proximal main vessel while it overestimated these parameters in the distal main vessel and side branch. CAAS software showed better overall accuracy and precision than QAngio XA (with automatic Y- or T-shape bifurcation algorithm selection) for various phantom diameters including minimum lumen diameter (0.012 ± 0.103 mm vs. 0.041 ± 0.322 mm, P = 0.003), reference vessel diameter (-0.050 ± 0.043 mm vs. 0.116 ± 0.610 mm, P = 0.026), and % diameter stenosis (-0.94 ± 4.07 % vs. 1.74 ± 7.49 %, P = 0.041). QAngio XA demonstrated higher minimal lumen diameter, reference vessel diameter, and % diameter stenosis when compared to the actual phantom diameters; however, the accuracy of these parameters improved to a similar level as CAAS when the sole T-shape algorithm in the QAnxio XA was used. CONCLUSION: The use of the single-vessel QCA method is inaccurate in bifurcation lesions. Both CAAS and QAngio XA (when the T shape is systematically used) bifurcation software packages are suitable for quantitative assessment of bifurcations.

Comparison between two- and three-dimensional quantitative coronary angiography bifurcation analyses for the assessment of bifurcation lesions: A subanalysis of the TRYTON pivotal IDE coronary bifurcation trial.

BACKGROUND: Three-dimensional (3D) quantitative coronary angiography (QCA) provides more accurate measurements by minimizing inherent limitations of two-dimensional (2D) QCA. The aim of this study was to compare the measurements between 2D and 3D QCA analyses in bifurcation lesions. METHODS AND RESULTS: A total of 114 cases with non-left main bifurcation lesions in the TRYTON pivotal IDE Coronary Bifurcation Trial (ClinicalTrials.gov: NCT01258972) were analyzed using a validated bifurcation QCA software (CAAS 5.10, Pie Medical Imaging, Maastricht, the Netherlands). All cases were analyzed in matched projections between pre- and post-procedure. The 2D analysis was performed using one of two angiographic images used for 3D reconstruction showing a larger distal bifurcation angle. In the treated segments (stent and balloon), there were no differences in minimal luminal diameter (MLD) between 2D and 3D, while diameter stenosis (DS) was significantly higher in 2D compared to 3D both pre-procedure and post-procedure (53.9% for 2D vs. 52.1% for 3D pre-procedure, P < 0.01; 23.2% for 2D vs. 20.9% for 3D post-procedure, P = 0.01). In the sub-segment level analysis, lengths of proximal main branch, distal main branch, and side branch were consistently shorter in 2D compared to 3D both pre-procedure and post-procedure. Using 3D QCA, the anatomic location of the smallest MLD or the highest DS was relocated to a different bifurcation sub-segment in a considerable proportion of the patients compared to when 2D-QCA was used (kappa values: 0.50 for MLD, 0.55 for DS). CONCLUSIONS: Our data showed differences in addressing anatomical severity and location of coronary bifurcation lesions between in vivo 2D and 3D QCA analyses. More studies are needed to investigate potential clinical benefits in using 3D approach over 2D QCA for the assessment of bifurcation lesions.

A CT-based Medina classification in coronary bifurcations: does the lumen assessment provide sufficient information?

AIMS: To evaluate the distribution of atherosclerosis at bifurcations with computed tomography coronary angiography (CTCA) and propose a novel CT-Medina classification for bifurcation lesions. METHODS: In 26 patients (age 55 ± 10 years, 81% male) imaged with CTCA, 39 bifurcations were studied. The bifurcations analysis included the proximal main vessel, the distal main vessel and the side branch (SB). Plaque contours were manually traced on CTCA; the lumen, vessel and plaque area were measured, as well as plaque burden (%). The carina cross-sections were divided into four equal parts according to the expected wall shear stress (WSS) to assess circumferential plaque distribution. All the bifurcation lesions were classified using the Medina classification and a novel CT-Medina classification combining lumen narrowing and plaque burden ≥70%. RESULTS: Presence of severe plaque (plaque burden ≥70%) by CTCA was demonstrated in 12.8% (5/39) of the proximal segments, 15.4% (6/39) of the distal segments and 7.7% (3/39) of the SB segments. The thickest plaque was located more often in low WSS parts of the carina cross-sections, whereas the flow divider was rarely affected. Although in the majority of bifurcations plaque was present, based on the Medina classification 92% of the assessed bifurcations were identified as 0,0,0. Characterization of bifurcation lesions using the new CT-Medina classification provided additional information in seven cases (18%) compared to the Medina classification CONCLUSION: Atherosclerotic plaque is widely present in all bifurcation segments, even in the absence of coronary lumen stenosis. A CT-Medina classification combining lumen and plaque parameters is more informative than angiographic classification of bifurcation lesions and could potentially facilitate the decision-making on the treatment of these lesions.

Validity and variability in visual assessment of stenosis severity in phantom bifurcation lesions: a survey in experts during the fifth meeting of the European Bifurcation Club.

OBJECTIVES: To investigate the adequacy of visual estimate regarding the percent diameter stenosis (DS) in bifurcation lesions. BACKGROUND: Quantitative coronary angiography (QCA) is more accurate and precise compared to visual estimate in assessing stenosis severity in single-vessel lesions. METHODS: Thirty-six experts in the field of bifurcation PCI visually assessed the DS in cine images of five precision manufactured phantom bifurcation lesions, experts being blinded to the true values. Expert DS estimates were compared with the true values and they were also used to define the Medina class of each individual bifurcation. Results were pooled together both for proximal main vessel (PMV), distal main vessel (DMV) and side-branch (SB) segments and for vessel segments with similar DS values. RESULTS: Individual performance was highly variable among observers; pooled values and range of accuracy and precision were 2.79% (-6.67% to 17.33%) and 8.69% (4.31-16.25%), respectively. On average, DS was underestimated in the PMV (-1.08%, P = 0.10) and overestimated in the DMV (3.86% P < 0.01) and SB segments (5.58%, P < 0.01). Variability in visual estimates was significantly larger in lesions of medium severity compared to the clearly obstructive ones (P < 0.01); the latter were consistently overestimated. Inter-observer agreement was moderate (κ = 0.55) over the entire number of estimates. However, if the segments with true DS = 0% were excluded, agreement was diminished (κ = 0.27). Inter-observer agreement in Medina class was rather low (κ = 0.21). True bifurcation lesions were misclassified as non-true ones in 14/180 estimates. CONCLUSIONS: Visual assessment by experts is more variable and less precise in the analysis of bifurcation lesions compared to bifurcation QCA software.

Vascular compliance changes of the coronary vessel wall after bioresorbable vascular scaffold implantation in the treated and adjacent segments.

BACKGROUND: Implantation of a metallic prosthesis creates local stiffness with a subsequent mismatch in the compliance of the vessel wall, disturbances in flow and heterogeneous distribution of wall shear stress. Polymeric bioresorbable ABSORB scaffolds have less stiffness than metallic platform stents. We sought to analyze the mismatch in vascular compliance after ABSORB implantation and its long-term resolution with bioresorption. METHODS AND RESULTS: A total of 83 patients from the ABSORB trials underwent palpography investigations (30 and 53 patients from ABSORB Cohorts A and B, respectively) to measure the compliance of the scaffolded and adjacent segments at various time points (from pre-implantation up to 24 months). The mean of the maximum strain values was calculated per segment by utilizing the Rotterdam Classification (ROC) score and expressed as ROC/mm. Scaffold implantation lead to a significant decrease in vascular compliance (median [IQR]) at the scaffolded segment (from 0.37 [0.24-0.45] to 0.14 [0.09-0.23], P<0.001) with mismatch in compliance in a paired analysis between the scaffolded and adjacent segments (proximal: 0.23 [0.12-0.34], scaffold: 0.12 [0.07-0.19], distal: 0.15 [0.05-0.26], P=0.042). This reported compliance mismatch disappears at short- and mid-term follow-up. CONCLUSIONS: The ABSORB scaffold decreases vascular compliance at the site of scaffold implantation. A compliance mismatch is evident immediately post-implantation and in contrast to metallic stents disappears in the mid-term, likely leading to a normalization of the rheological behavior of the scaffolded segment.

SYNTAX score and Clinical SYNTAX score as predictors of very long-term clinical outcomes in patients undergoing percutaneous coronary interventions: a substudy of SIRolimus-eluting stent compared with pacliTAXel-eluting stent for coronary revascularization (SIRTAX) trial.

AIMS: To investigate the ability of SYNTAX score and Clinical SYNTAX score (CSS) to predict very long-term outcomes in an all-comers population receiving drug-eluting stents. METHODS AND RESULTS: The SYNTAX score was retrospectively calculated in 848 patients enrolled in the SIRolimus-eluting stent compared with pacliTAXel-Eluting Stent for coronary revascularization (SIRTAX) trial. The CSS was calculated using age, and baseline left ventricular ejection fraction and creatinine clearance. A stratified post hoc comparison was performed for all-cause mortality, cardiac death, myocardial infarction (MI), ischaemia-driven target lesion revascularization (TLR), definite stent thrombosis, and major adverse cardiac events (MACE) at 1- and 5-year follow-up. Tertiles for SYNTAX score and CSS were defined as SS(LOW) ≤ 7, 7< SS(MID) ≤ 14, SS(HIGH) >14 and CSS(LOW) ≤ 8.0, 8.0 17.0, respectively. Major adverse cardiac events rates were significantly higher in SS(HIGH) compared with SS(LOW) at 1- and 5-year follow-up, which was also seen at 5 years for all-cause mortality, cardiac death, MI, and TLR. Stratifying outcomes across CSS tertiles confirmed and augmented these results. Within CSS(HIGH), 5-year MACE increased with use of paclitaxel- compared with sirolimus-eluting stents (34.7 vs. 21.3%, P = 0.008). SYNTAX score and CSS were independent predictors of 5-year MACE; CSS was an independent predictor for 5-year mortality. Areas-under-the-curve for SYNTAX score and CSS for 5-year MACE were 0.61 (0.56-0.65) and 0.62 (0.57-0.67), for 5-year all-cause mortality 0.58 (0.51-0.65) and 0.66 (0.59-0.73) and for 5-year cardiac death 0.63 (0.54-0.72) and 0.72 (0.63-0.81), respectively. CONCLUSION: SYNTAX score and to a greater extent CSS were able to stratify risk for very long-term adverse clinical outcomes in an all-comers population receiving drug-eluting stents. Predictive accuracy for 5-year all-cause mortality was improved using CSS. TRIAL REGISTRATION NUMBER: NCT00297661.

Novel bifurcation phantoms for validation of quantitative coronary angiography algorithms.

BACKGROUND: Validation is lacking for two- and three-dimensional (2D and 3D) bifurcation quantitative coronary angiography (QCA) algorithms. METHODS: Six plexiglas phantoms were designed, each of them mimicking a coronary vessel with three successive bifurcations lesions, wherein at least one vessel segment had a percent diameter stenosis (DS) of ≥60%. The five most frequently occurring Medina classes (1,1,1), (1,1,0), (0,1,0), (0,1,1), and (1,0,0) were used in the design. Diameters of the daughter vessels in every bifurcation were dictated by the scaling law of Finet. Lesions were cosinus-shaped in longitudinal view and circular-shaped in cross-sectional view. At the level of the carina, lesions were becoming eccentric, favoring "plaque" at the outer bifurcation walls. Adjacent bifurcation lesions were kept distant by nontapering, stenosis-free segments of ≥10 mm length. The direction of the side branch relative to the main vessel was based on relevant literature. The phantoms were precision manufactured using computer-aided design and machining techniques. Because of the high drilling accuracy (within 10 µm), the 3D luminal surface description of the phantom could be used to determine the true lumen dimensions and bifurcation angle (BA) values of the final geometry. RESULTS: Our series of bifurcation phantoms comprised 33 narrowed and 21 stenosis-free vessel segments with a mean true minimal lumen diameter (MLD) value of 0.98 ± 0.40 mm (range, 0.53-1.96 mm) and 2.29 ± 0.74 mm (range, 1.40-4.00 mm), respectively. Overall, the mean true values for MLD, reference diameter, and DS were 1.49 ± 0.85 mm, 2.70 ± 0.71 mm, and 40.9% ± 34.2%. The mean true values for the proximal and the distal BA were 123.6° ± 19.0° and 69.6° ± 19.9°, respectively. CONCLUSIONS: Six plexiglas phantoms containing a total of 18 bifurcations lesions with variable anatomy and Medina class were designed and precision manufactured to facilitate the validation of bifurcation QCA algorithms.

Two-dimensional quantitative coronary angiographic models for bifurcation segmental analysis: in vitro validation of CAAS against precision manufactured plexiglas phantoms.

BACKGROUND: Quantitative coronary angiography (QCA) analysis for bifurcation lesions needs to be standardized. OBJECTIVES: In vitro validation of two models for bifurcation QCA segmental analysis. METHODS: In the latest edition of the Cardiovascular angiography analysis system (CAAS 5v8, Pie Medical Imaging, Maastricht, The Netherlands) a 6-segment model for two-dimensional coronary bifurcation analysis was implemented next to the currently available 11-segment model. Both models were validated against 6 precision manufactured plexiglas phantoms, each of them mimicking a vessel with three successive bifurcation lesions with variable anatomy and Medina class. The phantoms were filled with 100% contrast agent and imaged with a biplane gantry. Images acquired in antero-posterior (AP) direction by either C-arm and at 30° right and left anterior oblique angulation were analyzed by two independent analysts, blinded to the actual dimensions. Manual correction of the contours was not allowed. Measurements for minimal lumen diameter (MLD), reference vessel diameter (RVD), percent diameter stenosis (DS) and bifurcation angle (BA) were compared with the true phantom dimensions. RESULTS: In AP views the accuracy and precision (mean difference ± SD) of 11- and 6-segment model for MLD, RVD, and DS were 0.065 ± 0.128 mm vs. 0.058 ± 0.142 mm, -0.021 ± 0.032 mm vs. -0.022 ± 0.030 mm, and -2.45% ± 5.07% vs. -2.28% ± 5.29%, respectively. Phantom MLD values ≤ 0.7 mm were systematically overestimated; if excluded, MLD accuracy and precision became 0.015 ± 0.106 mm and 0.004 ± 0.125 mm for the 11- and 6-segment model, respectively. Accuracy and precision for BA were -2.2° ± 3.3°. Interobserver variability for MLD, RVD, DS, and BA for either model was ≤ 0.049 mm, ≤ 0.056 mm, ≤ 2.77%, and 1.6°, respectively. Agreement between models for MLD, RVD, and DS was ± 0.079 mm, ± 0.011 mm, and ± 2.07%. Accuracy and precision for diameter-derived parameters were slightly decreased in angulated projections; precision for BA measurements dropped to 6.1°. CONCLUSIONS: The results of both models are highly reproducible and for phantom MLD values >0.7 mm in excellent agreement with the true dimensions.

The SYNTAX score revisited: a reassessment of the SYNTAX score reproducibility.

OBJECTIVES: To reassess the reproducibility of the SYNTAX score. BACKGROUND: The SYNTAX score appears to have an important role to play in the evaluation of patients with complex coronary artery disease undergoing revascularisation. However, the calculation of the SYNTAX score relies on the subjective assessment of lesions using coronary angiography, and therefore is subject to intra-and inter-observer variability. METHODS: The SYNTAX score was calculated in 100 patients randomly selected from the SYNTAX trial, on two occasions 8 weeks apart, by a team made up of three interventional cardiologists. The weighted kappa values were compared with values obtained 1 year previously, when core lab analysts assessed the intra-observer reproducibility amongst the same patient cohort. RESULTS: The mean +/- standard deviation difference in SYNTAX score was 2.1 +/- 7.6. The respective weighted kappa values for the number of lesions, bifurcation lesions, ostial lesions, and total occlusions were 0.62, 0.36, 0.66, and 0.91 compared with 0.59, 0.41, 0.63, and 0.82 in the previous core lab assessment. The weighted kappa for the intra-observer reproducibility of the SYNTAX score grouped into deciles was 0.54, and according to the terciles < or = 22, >22-< or = 32, >32 was 0.51 both indicating a moderate level of agreement beyond the level of chance. In the previous assessment, the comparative kappa values were 0.45 and 0.53. CONCLUSIONS: The SYNTAX score has moderate intra-observer reproducibility when assessed by a team of three interventional cardiologists, which is consistent with a prior evaluation performed by core lab analysts. The scoring of bifurcation lesions remains the main source of inconsistency.

Bifurcation lesions: Functional assessment by fractional flow reserve vs. anatomical assessment using conventional and dedicated bifurcation quantitative coronary angiogram.

BACKGROUND: The purpose of this study was to compare the performance of both conventional quantitative coronary angiography (QCA) and the dedicated three branch QCA model for bifurcations in the prediction of a functionally significant lesion according to fractional flow reserve (FFR) in patients with bifurcation lesions. METHODS: Twenty patients with bifurcation lesions underwent coronary angiography together with a functional evaluation of both the main branch and side-branch using FFR. QCA was performed off-line with both conventional QCA software (CAASII, Pie Medical Imaging, Maastricht, The Netherlands) and three branch QCA software (CAAS5, Pie Medical Imaging, Maastricht, The Netherlands). A stenosis was considered hemodynamically significant when the FFR value was ≤ 0.80 and anatomically significant when the diameter stenosis was >50%. The QCA and FFR data were correlated by means of the Pearson correlation. RESULTS: Eighteen bifurcation lesions were suitable for the QCA analysis. In the main vessel, a significant inverse correlation with FFR was seen with both conventional QCA (Pearson r = 0.52 for the MV, P = 0.02), and the three branch QCA model (Pearson r = 0.67 for the MV, P = 0.002). Conversely, in the side-branch, the correlation between QCA and FFR was only significant with the three branch QCA model (Pearson r = 0.57, P = 0.02 for the SB). CONCLUSIONS: In bifurcation lesions the correlation between the anatomic severity of a coronary stenosis and its functional significance appears to be somewhat higher when QCA is performed using the three branch model. This is most notable for side-branch stenoses which can be overestimated when using conventional QCA.

Intravascular ultrasound and 3D angle measurements of coronary bifurcations.

OBJECTIVE: To standardize the intravascular ultrasound (IVUS) analysis of coronary bifurcations. BACKGROUND: Percutaneous treatment of bifurcation lesions is difficult particularly at the side branch ostium. Imaging techniques may improve our understanding of treatment options. There is no established IVUS methodology to assess the bifurcation. The present study aims to develop standards for bifurcation imaging. METHODS: Quantitative IVUS analysis and 3D bifurcation angle measurements were performed in 34 patients who were selected from the Washington Hospital Center Database. Patients were included if both left anterior descending (LAD) and first diagonal (DX) pullbacks in the same procedure were done. Angiograms were available in 27 patients to measure the 3D bifurcation angle using specialized software. Pullbacks were analyzed proximal and distal to the bifurcation, and at the bifurcation. RESULTS: Prox(LAD) versus Prox(LAD(DX)) were similar for vessel area (15.5 +/- 4.6 mm(2) vs. 15.9 +/- 4.0 mm(2), P = 0.19), lumen area (8.3 +/- 3.6 mm(2) vs. 8.6 +/- 3.3 mm(2), P = 0.25), and plaque area (7.2 +/- 2.0 mm(2) vs. 7.3 +/- 1.9 mm(2), P = 0.55). However, Bifurcation(LAD) was larger than Bifurcation(DX) for vessel area (17.3 +/- 4.0 mm(2) vs. 16.6 +/- 3.9 mm(2), P = 0.0083). The 3D angiographic bifurcation angle was 50 degrees +/- 13 degrees (range of 26 degrees -84 degrees), and did not affect the IVUS measurements. IVUS analysis showed that bifurcation lesions did obey Murray's Law, as Prox(LAD) lumen area measured 36.7 +/- 25.1 mm(3) versus Dist(LAD)/Dist(DX) measured 38.0 +/- 29.1 mm(3), P = 0.56. CONCLUSIONS: Two IVUS pullbacks should be performed for a complete assessment of the bifurcation and comparison with Murray's Law. The proposed IVUS analysis was not influenced by the bifurcation angle.

The effect of coronary bifurcation and haemodynamics in prediction of atherosclerotic plaque development: a serial computed tomographic coronary angiographic study.

AIMS: The aim of this study was to examine the effect of the daughter branches on the haemodynamics and the potential prediction of atherosclerotic plaque development as well as the best flow division model for accurate blood flow modelling. METHODS AND RESULTS: We analysed computed tomography coronary angiography retrospective data portraying 17 coronary artery bifurcations in 15 patients recruited into the PROSPECT MSCT study. Baseline and three-year follow-up imaging data were used to reconstruct coronary artery anatomy. In the baseline models blood flow simulations were performed using three flow division approaches: stress-free, Murray's law and Doriot's fit. Blood flow simulation was also performed omitting the daughter branch. The association between ESS estimated in models that incorporated the daughter branches and lumen reduction was higher than the cases where the side branch was omitted. Murray's law provides the most accurate results when comparing the different flow division models. More specifically, low ESS is a predictor of significant lumen reduction (p=0.007), plaque burden increase (p=0.0006) and necrotic core change (p=0.025). CONCLUSIONS: The ESS distribution in coronary models including the daughter branches and based on the calculations implementing Murray's law allows more accurate prediction of atherosclerotic evolution than ESS estimated in models including only the main vessel.

Prediction of atherosclerotic disease progression using LDL transport modelling: a serial computed tomographic coronary angiographic study.

AIM: To investigate the efficacy of low-density lipoprotein (LDL) transport simulation in reconstructed arteries derived from computed tomography coronary angiography (CTCA) to predict coronary segments that are prone to progress. METHODS AND RESULTS: Thirty-two patients admitted with an acute coronary event who underwent 64-slice CTCA after percutaneous coronary intervention and at 3-year follow-up were included in the analysis. The CTCA data were used to reconstruct the coronary anatomy of the untreated vessels at baseline and follow-up, and LDL transport simulation was performed in the baseline models. The computed endothelial shear stress (ESS), LDL concentration, and CTCA-derived plaque characteristics were used to identify predictors of substantial disease progression (defined as an increase in the plaque burden at follow-up higher than two standard deviations of the intra-observer variability of the expert who performed the analysis). Fifty-eight vessels were analysed. High LDL concentration [odds ratio (OR): 2.16; 95% confidence interval (CI): 1.64-2.84; P = 0.0054], plaque burden (OR: 1.40; 95% CI: 1.13-1.72; P = 0.0017), and plaque area (OR: 3.46; 95% CI: 2.20-5.44; P≤ 0.0001) were independent predictors of a substantial disease progression at follow-up. The ESS appears as a predictor of disease progression in univariate analysis but was not an independent predictor when the LDL concentration was entered into the multivariate model. The accuracy of the model that included the LDL concentration was higher than the accuracy of the model that included the ESS (65.1 vs. 62.5%). CONCLUSIONS: LDL transport modelling appears a better predictor of atherosclerotic disease progression than the ESS, and combined with the atheroma characteristics provided by CTCA is able to detect with a moderate accuracy segments that will exhibit a significant plaque burden increase at mid-term follow-up.

Differences between the left main and other bifurcations.

The left main is the largest bifurcation of the coronary tree and is, therefore, easier to access. Nevertheless, the risks of untoward consequences associated with the loss of the side branch are much higher. Although the usual technical strategies implemented in coronary bifurcations can generally be applied to left main lesions, several inherent characteristics (the ostial position of the main branch, the size of the side branch, the amount of calcification, the angle which is often in a T shape, the use of stents of variable suitability, the crucial role of POT) need to be taken into account in order to achieve optimal acute and long-term results.

The need for dedicated bifurcation quantitative coronary angiography (QCA) software algorithms to evaluate bifurcation lesions.

Single-vessel quantitative coronary angiography (QCA) software is inaccurate when used in bifurcation lesions due to the specific anatomical characteristics of bifurcations, including the natural step-down in diameters after every bifurcation. Dedicated bifurcation QCA software has been developed to overcome the limitations of single-vessel QCA in bifurcations. A phantom validation study has shown the superior accuracy of these bifurcation QCA algorithms compared to the single-vessel QCA software. These QCA software algorithms are currently highly recommended to assess bifurcation lesions.

Inter-core lab variability in analyzing quantitative coronary angiography for bifurcation lesions: a post-hoc analysis of a randomized trial.

OBJECTIVES: This study sought to evaluate inter-core lab variability in quantitative coronary angiography (QCA) analysis of bifurcation lesions. BACKGROUND: QCA of bifurcation lesions is challenging. To date there are no data available on the inter-core lab variability of bifurcation QCA analysis. METHODS: The randomized Tryton IDE (Tryton Pivotal IDE Coronary Bifurcation Trial) compared the Tryton Side Branch Stent (Tryton Medical, Durham, North Carolina) with balloon angioplasty as side branch treatment. QCA was performed in an angiographic subcohort (n = 326) at 9-month follow-up. Inter-core lab variability of QCA analysis between the Cardiovascular Research Foundation and the Cardialysis core labs was evaluated before and after alignment of the used QCA methodology using angiographic data derived from this angiographic follow-up cohort. RESULTS: In the original analysis, before alignment of QCA methodology, the mean difference between the core labs (bias) was large for all QCA parameters with wide 95% limits of agreement (1.96 × SD of the bias), indicating marked variability. The bias of the key angiographic endpoint of the Tryton trial, in-segment percentage diameter stenosis (%DS) of the side branch, was 5.5% (95% limits of agreement: -26.7% to 37.8%). After reanalysis, the bias of the in-segment %DS of the side branch reduced to 1.8% (95% limits of agreement: -16.7% to 20.4%). Importantly, after alignment of the 2 core labs, there was no longer a difference between both treatment groups (%DS of the side branch: treatment group A vs. group B: 34.4 ± 19.4% vs. 32.4 ± 16.1%, p = 0.340). CONCLUSIONS: Originally, a marked inter-core lab variability of bifurcation QCA analysis was found. After alignment of methodology, inter-core lab variability decreased considerably and impacted angiographic trial results. This latter finding emphasizes the importance of using the same methodology among different core labs worldwide. (Tryton Pivotal Prospective, Single Blind, Randomized Controlled Study to Evaluate the Safety & Effectiveness of the Tryton Side Branch Stent Used With DES in Treatment of de Novo Bifurcation Lesions in the Main Branch & Side Branch in Native Coronaries [TRYTON]; NCT01258972).

Acute coronary syndromes in patients with atrial fibrillation and heart failure. Could novel oral anticoagulants be the solution of the optimal antithrombotic therapy puzzle?

The patients experiencing an acute coronary event are exposed to increased risk of thromboembolic events. That risk becomes substantially greater when AF fibrillation and heart failure are present as well. Dual antiplatelet therapy remains the gold standard in the treatment of patients with ACS. The combination of an oral anticoagulant agent with dual antiplatelet therapy is proven to be more effective in prevention of further antithrombotic events but is followed by increased risks of clinically significant bleeding thus it is not suggested in the treatment of ACS. However, it has been proven beneficial in patients with AF who present with an acute coronary episode. NOACs have proved to be at least as effective as vitamin K antagonists in protecting patients with atrial fibrillation from thromboembolic events without increased risk of major bleeding. However, only data on the effectiveness of NOACS in patients with ACS and AF have been quite contradictory. Even more, the data on the effect of NOACS in patients with concomitant HF and AF who present with an acute coronary event is almost lacking from current bibliography. In this review, we attempt to describe the available data of the use of NOACS in patients with AF and HF who experience an ACS and to address the need for further studies in this area.

Acute epigastric and low back pain during amiodarone infusion; is it the drug or the vehicle to blame?

Amiodarone is a Class III antiarrhythmic agent used for cardioversion and prevention of recurrences of atrial fibrillation. However, its use is limited due to its side-effects resulting from the drug's long-term administration. We have described acute epigastric pain following treatment with intravenous amiodarone for atrial fibrillation in a previous report. Hereby, we describe a second patient who suffered acute epigastric pain, as well as one who suffered acute low back pain. Intravenous amiodarone has been related to a series of minor and major adverse reactions, indicating other constituents of the intravenous solution as the possible cause, possibly polysorbate-80. A possible correlation between acute epigastric and low back pain after intravenous amiodarone loading is unproven; however it is of crucial importance for clinicians to be aware of this phenomenon, and especially since an acute epigastric pain is implicated in the differential diagnosis of cardiac ischemia.

Accumulation of microvascular target organ damage in newly diagnosed hypertensive patients.

Early identification of hypertensive target organ damage (TOD) emerges as important for global cardiovascular risk assessment. Retinal vascular alterations, capillary rarefaction, and microalbuminuria represent different forms of microvascular TOD. However, data regarding their concomitant presence in the early stages of hypertension, the association of the number of affected organs with cardiovascular risk, and aldosterone effect on multiple TOD are lacking. We studied naïve, never-treated patients with recent duration of hypertension and healthy volunteers. Innovative software was developed to estimate retinal vascular diameters and capillary density. Biochemical parameters including microalbuminuria and serum aldosterone were derived. Framingham Risk Score was used to determine cardiovascular risk. In total 103 subjects, 66 hypertensives and 37 normotensives, were included. Hypertensive patients exhibited a greater number of affected target organs compared with normotensives (P = .014), with retinopathy and capillary rarefaction (40.9%) representing the most common TOD among hypertensives. The number of affected organs was linearly correlated with increased Framingham score and serum aldosterone, analyzed with univariate (P < .001 and P = .002) and multivariate analysis (P = .025 and P = .004), respectively. Physicians dealing with hypertensive patients should be aware of the possibility of diffuse microvascular impairment and seek multiple TOD even in the early stages of hypertension.

Advanced three-dimensional quantitative coronary angiographic assessment of bifurcation lesions: methodology and phantom validation.

AIMS: Validation of new three-dimensional (3-D) bifurcation quantitative coronary angiography (QCA) software. METHODS AND RESULTS: Cardiovascular Angiography Analysis System (CAAS 5v10) allows 3-D angiographic reconstructions based on two or more 2-D projection images. Measurements for minimal lumen diameter (MLD), reference vessel diameter (RVD), percent diameter stenosis (DS) and bifurcation angle (BA) were validated against precision manufactured phantom bifurcations. Length measurements were validated against angiographic measurement catheters inserted into a plexiglas bifurcation phantom. In 3-D reconstructions based on two 2-D images, acquired at variable rotation and angulation, accuracy and precision (mean difference ± SD) of the 11-segment model for MLD, RVD and DS were 0.013±0.131 mm, -0.052±0.039 mm and -1.08±5.13%, respectively; inter-observer variability was 0.141 mm, 0.058 mm and 5.42%, respectively. Adding the antero-posterior (optimal) projection to these basic reconstructions resulted in reduced variability (0.101 mm, 0.041 mm and 3.93% for MLD, RVD and DS, p<0.01 for all) and showed a trend towards improved precision (0.109 mm, 0.031 mm and 4.26%, respectively, p>0.05 for all). In basic reconstructions, accuracy and precision for BA was -1.3±5.0°, whereas inter-observer variability was 7.5°; respective measures for length were 0.15±0.26 mm and 0.54 mm. Adding the antero-posterior projection resulted in decreased precision (0.47 mm, p<0.01) and increased variability (1.03 mm, p<0.01) for length measurements; precision (5.4°) and variability (7.9°) for BA did not change significantly (p>0.30). CONCLUSIONS: Advances in the methodology of 3-D reconstruction and quantitative analysis for bifurcation lesions translated into highly accurate, precise and reproducible measures of diameter, length and BA.