Quantitative coronary angiography versus intravascular ultrasound guidance for drug-eluting stent implantation (GUIDE-DES): study protocol for a randomised controlled non-inferiority trial

IntroductionAngiography remains the gold standard for guiding percutaneous coronary intervention (PCI). However, it is prone to suboptimal stent results due to the visual estimation of coronary measurements. Although the benefit of intravascular ultrasound (IVUS)-guided PCI is becoming increasingly recognised, IVUS is not affordable for many catheterisation laboratories. Thus, a more practical and standardised angiography-based approach is necessary to support stent implantation.Methods and analysisThe Quantitative Coronary Angiography versus Intravascular Ultrasound Guidance for Drug-Eluting Stent Implantation trial is a randomised, investigator-initiated, multicentre, open-label, non-inferiority trial comparing the quantitative coronary angiography (QCA)-guided PCI strategy with IVUS-guided PCI in all-comer patients with significant coronary artery disease. A novel, standardised, QCA-based PCI protocol for the QCA-guided group will be provided to all participating operators, while the PCI optimisation criteria will be predefined for both strategies. A total of 1528 patients will be randomised to either group at a 1:1 ratio. The primary endpoint is the 12-month cumulative incidence of target-lesion failure defined as a composite of cardiac death, target-vessel myocardial infarction or ischaemia-driven target-lesion revascularisation. Clinical follow-up assessments are scheduled at 1, 6 and 12 months for all patients enrolled in the study.Ethics and disseminationEthics approval for this study was granted by the Institutional Review Board of Asan Medical Center (no. 2017-0060). Informed consent will be obtained from every participant. The study findings will be published in peer-reviewed journal articles and disseminated through public forums and academic conference presentations. Cost-effectiveness and secondary imaging analyses will be shared in secondary papers.Trial registration numberNCT02978456.

Comparison of Resting Full-Cycle Ratio and Fractional Flow Reserve in a German Real-World Cohort

Objective: The aim of this study was to evaluate non-hyperemic resting pressure ratios (NHPRs), especially the novel “resting full-cycle ratio” (RFR; lowest pressure distal to the stenosis/aortic pressure during the entire cardiac cycle), compared to the gold standard fractional flow reserve (FFR) in a “real-world” setting.Methods: The study included patients undergoing coronary pressure wire studies at one German University Hospital. No patients were excluded based on any baseline or procedural characteristics, except for insufficient quality of traces. The diagnostic performance of four NHPRs vs. FFR ≤ 0.80 was tested. Morphological characteristics of stenoses were analyzed by quantitative coronary angiography.Results: 617 patients with 712 coronary lesions were included. RFR showed a significant correlation with FFR (r = 0.766, p < 0.01). Diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of RFR were 78% (95% confidence interval = 75; 81), 72% (65; 78), 81% (77; 84), 63% (57; 69), and 86% (83; 89). Relevant predictors for discordance of RFR ≤ 0.89/FFR > 0.8 were LAD lesions, peripheral artery disease, age, female sex and non-focal stenoses. Predictors for discordance of RFR > 0.89/FFR ≤ 0.8 included non-LCX lesions, percent diameter stenosis and previous percutaneous coronary intervention in the target vessel. RFR and all other NHPRs were highly correlated with each other.Conclusion: All NHPRs have a similar correlation with the gold standard FFR and may facilitate the acceptance and implementation of physiological assessments of lesion severity. However, we found ~20% discordant results between NHPRs and FFR in our “all-comers” German cohort.

Development and Validation of a Nomogram for Predicting the Risk of Adverse Cardiovascular Events in Patients with Coronary Artery Ectasia

Coronary artery ectasia (CAE) is a rare finding and is associated with poor clinical outcomes. However, prognostic factors are not well studied and no prognostication tool is available. In a derivation set comprising 729 consecutive CAE patients between January 2009 and June 2014, a nomogram was developed using Cox regression. Total of 399 patients from July 2014 to December 2015 formed the validation set. The primary outcome was 5-year major adverse cardiovascular events (MACE), a component of cardiovascular death and nonfatal myocardial infarction. Besides the clinical factors, we used quantitative coronary angiography (QCA) and defined QCA classification of four types, according to max diameter (< or ≥5 mm) and max length ratio (ratio of lesion length to vessel length, < or ≥1/3) of the dilated lesion. A total of 27 cardiovascular deaths and 41 nonfatal myocardial infarctions occurred at 5-year follow-up. The nomogram effectively predicted 5-year MACE risk using predictors including age, prior PCI, high sensitivity C-reactive protein, N-terminal pro-brain natriuretic peptide, and QCA classification (area under curve [AUC] 0.75, 95% CI 0.68–0.82 in the derivation set; AUC 0.71, 95% CI 0.56–0.86 in the validation set). Patients were classified as high-risk if prognostic scores were ≥155 and the Kaplan–Meier curves were well separated (log-rank p < 0.001 in both sets). Calibration curve and Hosmer–Lemeshow test indicated similarity between predicted and actual 5-year MACE survival (p = 0.90 in the derivation and p = 0.47 in the validation set). This study developed and validated a simple-to-use method for assessing 5-year MACE risk in patients with CAE.

720 Angiography-derived index of microvascular resistance (IMR-angio) in Takotsubo syndrome

Aims Coronary microvascular dysfunction (CMD) has been proposed as a key driver in the etiopathogenesis of Takotsubo syndrome (TTS), likely related to an ‘adrenergic storm’ upon a susceptible microvascular circulation. The aim of our manuscript was to assess and quantify coronary microvascular disfunction in patients with TTS using the recently developed angiography-derived index of microcirculation (IMRangio) and evaluate its correlation with clinical and instrumental presentation. Methods and results 41 consecutive TTS patients were retrospectively analysed. Three different formulas for compute non-hyperemic IMRangio (NH-IMRangio) derived by 3D-Quantitative Coronary Angiography (3D-QCA) and Quantitative Flow Reserve (QFR) analysis were used according to each fluidodynamic mathematical expression as reported by respective authors. CMD was defined as an IMRangio ≥25. Moreover, correlation between NH-IMRangio and clinical presentation and a comparation between the three formulas were provided. Median age was 76 years, 85.7% were women and mean LVEF at first echocardiogram was 41.2%. All patients presented CMD with NH-IMRangio ≥25 in at least one territory. Mean NH-IMRangio was higher in Left Anterior Descending artery (LAD) than Circumflex artery (CX) and Right Coronary artery (RCA) with either Oxford-NH-IMRangio (52.7 ± 18.6 vs. 35.3 ± 13.6 vs. 41.4 ± 15.1, P-value &lt; 0.001), Madrid-NH-IMRangio (47.2 ± 17.3 vs. 31.8 ± 12.2 vs. 37.3 ± 13.7, P-value &lt;0.001) or Ferrara-NH-IMRangio (52.7 ± 19 vs. 36.1 ± 14.1 vs. 41.8 ± 16.1, P-value &lt; 0.001). Furthermore, the mean values of NH-IMRangio were not significantly different using the different equations (OXFvsMAD P-value = 0.1930; OXFvsFER P-value = 0.9609; MADvsFER P-value = 0.2144). NH-IMRangio in LAD territory was significantly higher in pts presenting with LVEF impairment (≤40%) than pts with preserved ventricular global function (mean NH-IMRangio LAD 59.3 ± 18.1 vs. 46.3 ± 16, P-value = 0.030). NH-IMRangio assessed in LAD territory showed a trend towards linear association with LVEF (Figure 1). 720 Figure Conclusions CMD, assessed with NH-IMRangio, is a common finding in TTS and it is associated with LVEF dysfunction and LVEF recovery. The validated formulas for NH-IMRangio computation have a superimposable diagnostic performance and accuracy.

Assessment of New Coronary Features on Quantitative Coronary Angiographic Images With Innovative Unsupervised Artificial Adaptive Systems: A Proof-of-Concept Study

Background and Purpose: The Active Connection Matrixes (ACMs) are unsupervised artificial adaptive systems able to extract from digital images features of interest (edges, tissue differentiation, etc.) unnoticeable with conventional systems. In this proof-of-concept study, we assessed the potentiality of ACMs to increase measurement precision of morphological structures (e.g., stenosis and lumen diameter) and to grasp morphological features (arterial walls) from quantitative coronary angiography (QCA), unnoticeable on the original images.Methods: Archive images of QCA and intravascular ultrasound (IVUS) of 10 patients (8 men, age 69.1 ± 9.7 years) who underwent both procedures for clinical reasons were retrospectively analyzed. Arterial features derived from “IVUS images,” “conventional QCA images,” and “ACM-reprocessed QCA images” were measured in 21 coronary segments. Portions of 1-mm length (263 for lumen and 526 for arterial walls) were head-to-head compared to assess quali-quantitative between-methods agreement.Results: When stenosis was calculated on “ACM-reprocessed QCA images,” the bias vs. IVUS (gold standard) did not improve, but the correlation coefficient of the QCA–IVUS relationship increased from 0.47 to 0.83. When IVUS-derived lumen diameters were compared with diameters obtained on ACM-reprocessed QCA images, the bias (−0.25 mm) was significantly smaller (p &lt; 0.01) than that observed with original QCA images (0.58 mm). ACMs were also able to extract arterial wall features from QCA. The bias between the measures of arterial walls obtained with IVUS and ACMs, although significant (p &lt; 0.01), was small [0.09 mm, 95% CI (0.03, 0.14)] and the correlation was fairly good (r = 0.63; p &lt; 0.0001).Conclusions: This study provides proof of concept that ACMs increase the measurement precision of coronary lumen diameter and allow extracting from QCA images hidden features that mirror well the arterial walls derived by IVUS.

Relationship of diabetes to atherosclerotic plaque characteristics of coronary artery lesions by differing angiographic stenosis severity

Background There is a strong relationship between atherosclerotic plaque characteristics (APCs) and major adverse cardiovascular events. However, whether APCs are different in obstructive vs. non-obstructive lesions, and whether diabetic status modifies this relationship is unknown. Purpose This study examines the relationship between APCs and angiographic stenosis severity in diabetic vs. non-diabetic patients. Methods We evaluated 303 subjects referred for invasive coronary angiography with coronary computed tomographic angiography and classified lesions as obstructive (&gt;50%) or non-obstructive using blinded quantitative coronary angiography. APCs, including plaque volume (PV), low density non-calcified plaque (LD-NCP), non-calcified plaque (NCP), calcified plaque (CP), lesion length, positive remodeling (PR), and high-risk plaque (HRP) were quantified and normalized for vessel volume. The relationship between APCs and angiographic stenosis severity was compared in diabetics vs. non-diabetics. Results Among 362 coronary lesions observed, 48.3% were obstructive, 51.7% were non-obstructive. In diabetics, NCP was significantly higher in obstructive vs. non-obstructive lesions (p=0.0033); however, in non-diabetics, no difference was observed (p=0.0525). In non-diabetics, PR was significantly higher in non-obstructive vs. obstructive lesions (p=0.0424); however, among diabetics, no difference was observed (p=0.7509). Comparing ACPs in obstructive lesions between diabetics and non-diabetics, diabetics had less NCP and HRP, more CP, PR and LD-NCP with comparable PV and lesion lengths. Comparing APCs in non-obstructive lesions, diabetics had greater PV, CP and PR with less LD-NCP, NCP, HRP, and shorter lesion lengths. Conclusion In diabetics, NCP is significantly higher in obstructive vs. non-obstructive lesions. Thus, measuring NCP may help identify high-grade stenotic lesions in this population. FUNDunding Acknowledgement Type of funding sources: None.

A novel vessel fraction flow reserve three-dimensional quantitative coronary angiography-based software. First case in Latin America

Fractional flow reserve has become the mainstay of functional hemodynamic assessment and is considered the gold standard to identify ischemic coronary stenoses. However, adopting the method into daily practice has been limited. Indeed, it requires the use of a costly pressure wire and the administration of a hyperemic agent. Vessel fractional flow reserve is a 3D-QCA based fractional flow reserve, using CAAS Workstation (version 8.4; Pie Medical Imaging, Maastricht, the Netherlands). It is a non-invasive method that does not require pressure wire or hyperemic agent; therefore it is time saving and easy to use. This is the first case performed in Brazil and demonstrates the correlation between fractional flow reserve and vessel fractional flow reserve performed in the same lesion, and the feasibility of calculation of vessel fractional flow reserve using 3D QCA-based software. We report the case of a 61-year-old male, who was admitted for typical chest pain. Coronary angiography revealed serial intermediate lesions in the mid- and distal left anterior descending. We evaluated left anterior descending lesions initially by fractional flow reserve then by vessel fractional flow reserve. Fractional flow reserve in distal left anterior descending was 0.65. Then, vessel fractional flow reserve value was calculated at 0.61. In our case, the correlation was adequate and the feasibility with offline calculation was excellent and fast. To the best of our knowledge, this is the first case of vessel fractional flow reserve performed in Latin America. Therefore, we expect vessel fractional flow reserve to be a game changer in management of coronary artery disease patients, particularly those with intermediate lesions.

AngioNet: a convolutional neural network for vessel segmentation in X-ray angiography

Coronary Artery Disease (CAD) is commonly diagnosed using X-ray angiography, in which images are taken as radio-opaque dye is flushed through the coronary vessels to visualize the severity of vessel narrowing, or stenosis. Cardiologists typically use visual estimation to approximate the percent diameter reduction of the stenosis, and this directs therapies like stent placement. A fully automatic method to segment the vessels would eliminate potential subjectivity and provide a quantitative and systematic measurement of diameter reduction. Here, we have designed a convolutional neural network, AngioNet, for vessel segmentation in X-ray angiography images. The main innovation in this network is the introduction of an Angiographic Processing Network (APN) which significantly improves segmentation performance on multiple network backbones, with the best performance using Deeplabv3+ (Dice score 0.864, pixel accuracy 0.983, sensitivity 0.918, specificity 0.987). The purpose of the APN is to create an end-to-end pipeline for image pre-processing and segmentation, learning the best possible pre-processing filters to improve segmentation. We have also demonstrated the interchangeability of our network in measuring vessel diameter with Quantitative Coronary Angiography. Our results indicate that AngioNet is a powerful tool for automatic angiographic vessel segmentation that could facilitate systematic anatomical assessment of coronary stenosis in the clinical workflow.