SYNTAX II and SYNTAX III trials: What is the take home message for surgeons?

Percutaneous coronary intervention (PCI) has evolved greatly in the last 40 years since its introduction by Andreas Grüntzig in 1977. Since then, we've observed an evolution in balloons, the development of stents, changes in stent structure, development of drug eluting stents, improvements in strut design, thickness and even their polymeric coating. Most recently we saw the rise and "fall" of bioabsorbable scaffolds for PCI. Trials with the most diverse devices for PCI and diagnostic techniques have been conducted. Two of the most recent trials were reported in the last year and deserve special attention-SYNTAX II and SYNTAX III. These trials are completely different in design but present valuable information for doctors managing coronary artery disease (CAD). Both trials take into account contemporary technology for assessing and treating CAD. The first uses so-called "state-of-the-art" PCI and compares the outcomes of that approach with the outcomes of the PCI arm of the pivotal SYNTAX trial. SYNTAX III Revolution on the other hand does not focus on clinical endpoints: it is a blinded trial that does not randomize patients but randomizes doctors ("the heart team") to make a decision on the best treatment for complex CAD. This decision was based either on multi-slice CT with physiological assessment using FFRCT or on conventional angiography. In this review we bring the most important aspects of those trials and the key messages for surgeons together; also, what the surgeon may expect in the future after the publication of these interesting concepts

Delineation of management zones using mobile measurements of soil apparent electrical conductivity and multivariate geostatistical techniques

Site-specific management promotes the identification and management of areas within the field, which represent subfield regions with homogeneous characteristics (management zones). However, determination of subfield areas is difficult because of the complex combination of factors which could affect crop yield. One possibility to capture yield variability is the use of soil physical properties to define the management zones as they are related to plant available water. With the aim of characterizing the spatial variability of the main soil physical variables and using this information to determine potential management zones, soil samples were taken from 70 locations in a 33-ha field in Badajoz, southwestern Spain. Firstly, accurate spatial distribution maps of the soil attributes were generated by using regression kriging as the most suitable algorithm in which exhaustive secondary information on soil apparent electrical conductivity (ECa) was incorporated. ECa measurements were carried out with a Veris 3100 operating in both shallow (0–30 cm), ECs, and deep (0–90 cm), ECd,mode. Clay, coarse sand and fine sand were the soil physical properties which exhibited higher correlation with ECa (positively correlated with the finer texture component, clay, and negatively correlated with the coarser ones, coarse and fine sands), particularly with ECs. Thus, this was the secondary variable used to obtain the kriged maps. Later, principal component analysis and fuzzy cluster classification were performed to delineate management zones, resulting in two subfields to be managed separately. This number of subfields was determined using the fuzzy performance index and normalized classification entropy as the way to optimize the classification algorithm

Anomalous septal perforator artery arising from the proximal right coronary artery

The interventricular septum is the most densely vascularized portion of the heart, containing important elements of the cardiac conduction system and providing mechanical support for both right and left ventricular function. The diagnosis and understanding of anomalies in coronary circulation are important when surgical or percutaneous myocardial revascularization is required. We report the case of a patient with an anomalous septal perforator artery arising from the proximal portion of the right coronary artery.O septo interventricular é uma das regiões mais vascularizadas do coração, contendo elementos importantes do sistema de condução cardíaco e fornecendo suporte mecânico para as funções ventriculares esquerda e direita. O diagnóstico e a compreensão das anomalias na circulação coronária são importantes quando a revascularização miocárdica, cirúrgica ou percutânea, é necessária. Descrevemos a seguir o caso de um paciente com artéria septal perfurante anômala originando-se da porção proximal da artéria coronária direita.939

Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus

BACKGROUND: The molecular mechanisms involved in the genesis of the adrenocortical lesions seen in MEN1 syndrome (ACL-MEN1) remain poorly understood; loss of heterozygosity at 11q13 and somatic mutations of MEN1 are not usually found in these lesions. Thus, additional genes must be involved in MEN1 adrenocortical disorders. Overexpression of the glucose-dependent insulinotropic peptide receptor has been shown to promote adrenocortical tumorigenesis in a mice model and has also been associated with ACTH-independent Cushing syndrome in humans. However, to our knowledge, the status of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions in MEN1 has not been previously investigated. OBJECTIVE: To evaluate glucose-dependent insulinotropic peptide receptor expression in adrenocortical hyperplasia associated with MEN1 syndrome. MATERIALS/METHODS: Three adrenocortical tissue samples were obtained from patients with previously known MEN1 germline mutations and in whom the presence of a second molecular event (a new MEN1 somatic mutation or an 11q13 loss of heterozygosity) had been excluded. The expression of the glucose-dependent insulinotropic peptide receptor was quantified by qPCR using the DDCT method, and b-actin was used as an endogenous control. RESULTS: The median of glucose-dependent insulinotropic peptide receptor expression in the adrenocortical lesions associated with MEN1 syndrome was 2.6-fold (range 1.2 to 4.8) higher than the normal adrenal controls (p = 0.02). CONCLUSION: The current study represents the first investigation of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions without 11q13 loss of heterozygosity in MEN1 syndrome patients. Although we studied a limited number of cases of MEN1 adrenocortical lesions retrospectively, our preliminary data suggest an involvement of glucose-dependent insulinotropic peptide receptor overexpression in the etiology of adrenocortical hyperplasia. New prospective studies will be able to clarify the exact role of the glucose-dependent insulinotropic peptide receptor in the molecular pathogenesis of MEN1 adrenocortical lesions

Impact of non-respect of SYNTAX score II recommendation for surgery in patients with left main coronary artery disease treated by percutaneous coronary intervention: an EXCEL substudy

OBJECTIVES: The SYNTAX score II (SSII) was developed from the SYNTAX trial to predict the 4-year all-cause mortality after left main or multivessel disease revascularization and to facilitate the decision-making process. The SSII provides the following treatment recommendations: (i) coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) (equipoise risk), (ii) CABG preferred (excessive risk for PCI) or (iii) PCI preferred (excessive risk for CABG). We sought to externally validate SSII and to investigate the impact of not abiding by the SSII recommendations in the randomized EXCEL trial of PCI versus CABG for left main disease. METHODS: The calibration plot of predicted versus observed 4-year mortality was constructed from individual values of SSII in EXCEL. To assess overestimation versus underestimation of predicted mortality risk, an optimal fit regression line with slope and intercept was determined. Prospective treatment recommendations based on SSII were compared with actual treatments and all-cause mortality at 4 years. RESULTS: SSII variables were available from EXCEL trial in 1807/1905 (95%) patients. For the entire cohort, discrimination was possibly helpful (C statistic = 0.670). SSII-predicted all-cause mortality at 4 years overestimated the observed mortality, particularly in the highest-risk percentiles, as confirmed by the fit regression line [intercept 2.37 (1.51-3.24), P = 0.003; slope 0.67 (0.61-0.74), P < 0.001]. When the SSII-recommended treatment was CABG, randomized EXCEL patients treated with PCI had a trend towards higher mortality compared with those treated with CABG (14.1% vs 5.3%, P = 0.07) in the as-treat population. In the intention-to-treat population, patients randomized to PCI had higher mortality compared with those randomized to CABG (15.1% vs 4.1%, P = 0.02), when SSII recommended CABG. CONCLUSIONS: In the EXCEL trial of patients with left main disease, the SSII-predicted 4-year mortality overestimated the 4-year observed mortality with a possibly helpful discrimination. Non-compliance with SSII CABG treatment recommendations (i.e. randomized to PCI) was associated with higher 4-year all-cause mortality

Validation of Prosthetic Mitral Regurgitation Quantification Using Novel Angiographic Platform by Mock Circulation.

This study aimed to validate a dedicated software for quantitative videodensitometric angiographic assessment of mitral regurgitation (QMR).Quantitative videodensitometric aortography of aortic regurgitation using the time-density principle is a well-documented technique, but the angiographic assessment of mitral regurgitation (MR) remains at best semi-quantitative and operator dependent.Fourteen sheep underwent surgical mitral valve replacement using 2 different prostheses. Pre-sacrifice left ventriculograms were used to assess MR fraction (MRF) using QMR and MR volume (MRV). In an independent core lab, the CAAS QMR 0.1 was used for QMR analysis. In vitro MRF and MRV were assessed in a mock circulation at a comparable cardiac output to the in vivo one by thermodilution. The correlations and agreements of in vitro and in vivo MRF, MRV, and interobserver reproducibility for QMR analysis were assessed using the averaged cardiac cycles (CCs).In vivo derived MRF by QMR strongly correlated with in vitro derived MRF, regardless of the number of the CCs analyzed (best correlation: 3 CCs y = 0.446 + 0.994x; R = 0.784; p =0.002). The mean absolute difference between in vitro derived MRF and in vivo derived MRF from 3 CCs was 0.01 ± 4.2% on Bland-Altman analysis. In vitro MRV and in vivo MRV from 3 CCs were very strongly correlated (y = 0.196 + 1.255x; R = 0.839; p 0.001). The mean absolute difference between in vitro MRV and in vivo MRV from 3 CCs was -1.4 ± 1.9 ml. There were very strong correlations of in vivo MRF between 2 independent analysts, regardless of the number of the CCs.In vivo MRF using the novel software is feasible, accurate, and highly reproducible. These promising results have led us to initiate the first human feasibility study comprising patients undergoing percutaneous mitral valve edge-to-edge repair

Impact of coronary calcification assessed by coronary CT angiography on treatment decision in patients with three-vessel CAD:insights from SYNTAX III trial

 : OBJECTIVES: The aim of this study was to determine Syntax scores based on coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) and to assess whether heavy coronary calcification significantly limits the CCTA evaluation and the impact of severe calcification on heart team’s treatment decision and procedural planning in patients with three-vessel coronary artery disease (CAD) with or without left main disease. METHODS: SYNTAX III was a multicentre, international study that included patients with three-vessel CAD with or without left main disease. The heart teams were randomized to either assess coronary arteries with coronary CCTA or ICA. We stratified the patients based on the presence of at least 1 lesion with heavy calcification defined as arc of calcium >180° within the lesion using CCTA. Agreement on the anatomical SYNTAX score and treatment decision was compared between patients with and without heavy calcifications. RESULTS: Overall, 222 patients with available CCTA and ICA were included in this trial subanalysis (104 with heavy calcification, 118 without heavy calcification). The mean difference in the anatomical SYNTAX score (CCTA derived—ICA derived) was lower in patients without heavy calcifications [mean (−1.96 SD; +1.96 SD) = 1.5 (−19.3; 22.4) vs 5.9 (−17.5; +29.3), P = 0.004]. The agreement on treatment decision did not differ between patients with (Cohen’s kappa 0.79) or without coronary calcifications (Cohen’s kappa 0.84). The agreement on the treatment planning did not differ between patients with (concordance 80.3%) or without coronary calcifications (concordance 82.8%). CONCLUSIONS: An overall good correlation between CCTA- and ICA-derived Syntax score was found. The presence of heavy coronary calcification moderately influenced the agreement between CCTA and ICA on the anatomical SYNTAX score. However, agreement on the treatment decision and planning was high and irrespective of the presence of calcified lesions

The impact of plaque type on strut embedment/protrusion and shear stress distribution in bioresorbable scaffold

AIMS: Scaffold design and plaque characteristics influence implantation outcomes and local flow dynamics in treated coronary segments. Our aim is to assess the impact of strut embedment/protrusion of bioresorbable scaffold on local shear stress distribution in different atherosclerotic plaque types. METHODS AND RESULTS: Fifteen Absorb everolimus-eluting Bioresorbable Vascular Scaffolds were implanted in human epicardial coronary arteries. Optical coherence tomography (OCT) was performed post-scaffold implantation and strut embedment/protrusion were analysed using a dedicated software. OCT data were fused with angiography to reconstruct 3D coronary anatomy. Blood flow simulation was performed and wall shear stress (WSS) was estimated in each scaffolded surface and the relationship between strut embedment/protrusion and WSS was evaluated. There were 9083 struts analysed. Ninety-seven percent of the struts (n = 8840) were well-apposed and 243 (3%) were malapposed. At cross-section level (n = 1289), strut embedment was significantly increased in fibroatheromatous plaques (76 ± 48 µm) and decreased in fibrocalcific plaques (35 ± 52 µm). Compatible with strut embedment, WSS was significantly higher in lipid-rich fibroatheromatous plaques (1.50 ± 0.81 Pa), whereas significantly decreased in fibrocalcified plaques (1.05 ± 0.91 Pa). After categorization of WSS as low (<1.0 Pa) and normal/high WSS (≥1.0 Pa), the percent of low WSS in the plaque subgroups were 30.1%, 31.1%, 25.4%, and 36.2% for non-diseased vessel wall, fibrous plaque, fibroatheromatous plaque, and fibrocalcific plaque, respectively (P-overall < 0.001). CONCLUSION: The composition of the underlying plaque influences strut embedment which seems to have effect on WSS. The struts deeply embedded in lipid-rich fibroatheromas plaques resulted in higher WSS compared with the other plaque types

Advances in IVUS/OCT and Future Clinical Perspective of Novel Hybrid Catheter System in Coronary Imaging

Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed and improved as both diagnostic and guidance tools for interventional procedures over the past three decades. IVUS has a resolution of 100µm with a high tissue penetration and capability of assessing the entire structure of a coronary artery including the external elastic membrane, whereas OCT has a higher resolution of 10–20µm to assess endoluminal structures with a limited tissue penetration compared to IVUS. Recently, two companies, CONAVI and TERUMO, integrated IVUS and OCT into a single catheter system. With their inherent strength and limitations, the combined IVUS and OCT probes are complementary and work synergistically to enable a comprehensive depiction of coronary artery. In this review, we summarize the performance of the two intracoronary imaging modalit