Christos V. Bourantas

Quantification of Incomplete Revascularization and its Association With Five-Year Mortality in the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) Trial Validation of the Residual SYNTAX Score

Background— The residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) Score is an objective measure of the degree and complexity of residual stenosis after percutaneous coronary intervention (PCI). Methods and Results— In the randomized PCI cohort of the SYNTAX Trial (n=903), the baseline and residual SYNTAX Scores were calculated. Subjects with a residual SYNTAX Score of 0 were defined as having undergone complete revascularization (CR), and a residual SYNTAX Score >0 as incomplete revascularization (ICR). Five-year clinical outcomes were stratified by CR and ICR (tertiles of the residual SYNTAX Score: >0–4, >4–8, and >8). In the PCI cohort, the mean baseline and residual SYNTAX Scores were 28.4±11.5 and 4.5±6.9, respectively. The mean &Dgr; SYNTAX Score (representative of the burden of disease removed by PCI) was 23.8±10.9. The residual SYNTAX Score was distributed as follows: CR, 0 (n=386, 42.7%); ICR, >0 to 4 (n=184, 20.4%), >4 to 8 (n=167, 18.5%), >8 (n=153, 16.9%). A progressively higher residual SYNTAX Score was shown to be a surrogate marker of increasing clinical comorbidity and anatomic complexity. Subjects with CR or residual SYNTAX Scores ⩽8 had comparable 5-year mortality (CR, 8.5%; residual SYNTAX Score >0–4, 8.7%; >4–8, 11.4%; P=0.60). A residual SYNTAX Score >8 was associated with 35.3% all-cause mortality at 5-years (P<0.001). Stratified analyses in the predefined medical treated diabetic and left main subgroups yielded similar results. Conclusions— The residual SYNTAX Score was shown to be a powerful indicator of 5-year mortality in the SYNTAX Trial. The residual SYNTAX Score may aid in determining a reasonable level of revascularization. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00114972.

Comparison of intravascular ultrasound versus angiography-guided drug-eluting stent implantation: a meta-analysis of one randomised trial and ten observational studies involving 19,619 patients.

AIMS The impact of intravascular ultrasound (IVUS) guided coronary drug-eluting stent (DES) implantation on clinical outcomes remains controversial. A meta-analysis of the currently available clinical trials investigating IVUS-guided DES implantation was undertaken. METHODS AND RESULTS We searched Medline, the Cochrane Library and other internet sources, without language or date restrictions, for published articles comparing clinical outcomes between IVUS-guided and angiography-guided DES implantation. Clinical studies with both adjusted and unadjusted data were included. Eleven studies were identified (one randomised controlled trial and 10 registries) and included in the meta-analysis with a weighted follow-up time of 20.7±11.5 months. Compared with angiography guidance, IVUS-guided DES implantation was associated with a reduced incidence of death (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.48-0.73, p<0.001), major adverse cardiac events (HR: 0.87, 95% CI: 0.78-0.96, p=0.008) and stent thrombosis (HR: 0.58, 95% CI: 0.44-0.77, p<0.001). The incidence of myocardial infarction (HR: 0.82, 95% CI: 0.63-1.06, p=0.126), target lesion (HR: 0.90, 95% CI: 0.73-1.11, p=0.316) and target vessel (HR: 0.90, 95% CI: 0.77-1.05, p=0.195) revascularisation was comparable between the angiography and IVUS-guided arms. A repeat meta-analysis of propensity-matched studies only (six studies, n=5,300) yielded broadly similar results in terms of clinical outcomes. CONCLUSIONS IVUS-guided coronary DES implantation is associated with a significant reduction in death, MACE and stent thrombosis compared to angiography guidance. Appropriately powered randomised trials are necessary to confirm the findings from this meta-analysis.

Incomplete Stent Apposition Causes High Shear Flow Disturbances and Delay in Neointimal Coverage as a Function of Strut to Wall Detachment Distance Implications for the Management of Incomplete Stent Apposition

Background—Lack of re-endothelialization and neointimal coverage on stent struts has been put forward as the main underlying mechanism leading to late stent thrombosis. Incomplete stent apposition (ISA) has been observed frequently in patients with very late stent thrombosis after drug eluting stent implantation, suggesting a role of ISA in the pathogenesis of this adverse event. The aim of this study was to evaluate the impact of different degrees of ISA severity on abnormal shear rate and healing response with coverage, because of its potential implications for stent optimization in clinical practice. Methods and Results—We characterized flow profile and shear distribution in different cases of ISA with increasing strut-wall detachment distance (ranging from 100 to 500 &mgr;m). Protruding strut and strut malapposed with moderate detachment (ISA detachment distance <100 &mgr;m) have minimal disturbance to blood flow as compared with floating strut that has more significant ISA distance. In vivo impact on strut coverage was assessed retrospectively using optical coherence tomography evaluation on 72 stents (48 patients) sequentially at baseline and after 6-month follow-up. Analysis of coverage revealed an important impact of baseline strut-wall ISA distance on the risk of incomplete strut coverage at follow-up. Malapposed segments with an ISA detachment <100 &mgr;m at baseline showed complete strut coverage at follow-up, whereas segments with a maximal ISA detachment distance of 100 to 300 &mgr;m and >300 &mgr;m had 6.1% and 15.7% of their struts still uncovered at follow-up, respectively (P<0.001). Conclusions—Flow disturbances and risk of delayed strut coverage both increase with ISA detachment distance. Insights from this study are important for understanding malapposition as a quantitative, rather than binary phenomenon (present or absent) and to define the threshold of ISA detachment that might benefit from optimization during stent implantation.

Clinical and intravascular imaging outcomes at 1 and 2 years after implantation of absorb everolimus eluting bioresorbable vascular scaffolds in small vessels. Late lumen enlargement: does bioresorption matter with small vessel size? Insight from the ABSORB cohort B trial

Background The long-term results after second generation everolimus eluting bioresorbable vascular scaffold (Absorb BVS) placement in small vessels are unknown. Therefore, we investigated the impact of vessel size on long-term outcomes, after Absorb BVS implantation. Methods In ABSORB Cohort B Trial, out of the total study population (101 patients), 45 patients were assigned to undergo 6-month and 2-year angiographic follow-up (Cohort B1) and 56 patients to have angiographic follow-up at 1-year (Cohort B2). The pre-reference vessel diameter (RVD) was <2.5 mm (small-vessel group) in 41 patients (41 lesions) and ≥2.5 mm (large-vessel group) in 60 patients (61 lesions). Outcomes were compared according to pre-RVD. Results At 2-year angiographic follow-up no differences in late lumen loss (0.29±0.16 mm vs 0.25±0.22 mm, p=0.4391), and in-segment binary restenosis (5.3% vs 5.3% p=1.0000) were demonstrated between groups. In the small-vessel group, intravascular ultrasound analysis showed a significant increase in vessel area (12.25±3.47 mm2 vs 13.09±3.38 mm2 p=0.0015), scaffold area (5.76±0.96 mm2 vs 6.41±1.30 mm2 p=0.0008) and lumen area (5.71±0.98 mm2 vs 6.20±1.27 mm2 p=0.0155) between 6-months and 2-year follow-up. No differences in plaque composition were reported between groups at either time point. At 2-year clinical follow-up, no differences in ischaemia-driven major adverse cardiac events (7.3% vs 10.2%, p=0.7335), myocardial infarction (4.9% vs 1.7%, p=0.5662) or ischaemia-driven target lesion revascularisation (2.4% vs 8.5%, p=0.3962) were reported between small and large vessels. No deaths or scaffold thrombosis were observed. Conclusions Similar clinical and angiographic outcomes at 2-year follow-up were reported in small and large vessel groups. A significant late lumen enlargement and positive vessel remodelling were observed in small vessels.

The Effect of Shear Stress on Neointimal Response Following Sirolimus- and Paclitaxel-Eluting Stent Implantation Compared With Bare-Metal Stents in Humans

OBJECTIVES We aimed to explore the relationship of neointimal thickness (NT) to shear stress (SS) after implantation of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) compared with bare-metal stents (BMS). We then tested the hypothesis that drug elution attenuates the SS effect. BACKGROUND Neointimal thickness after BMS implantation has been associated with SS; pertinent data for drug-eluting stents (DES) are limited. METHODS Three-dimensional coronary artery and stent reconstruction was performed in 30 patients at 6-month follow-up after SES (n = 10), PES (n = 10), or BMS (n = 10) implantation. Baseline SS at the stent surface was calculated using computational fluid dynamics and NT at follow-up was computed in 3-dimensional space. RESULTS Neointimal thickness was lower in DES versus BMS (0.03 ± 0.07 mm vs. 0.16 ± 0.08 mm, p < 0.001) and maximum NT was reduced in SES versus PES (0.33 ± 0.13 mm vs. 0.46 ± 0.13 mm, p = 0.025). In the total population, both SS (slope: -0.05 mm/Pa, p < 0.001) and DES (coefficient for DES vs. BMS: -0.17 mm, p = 0.003) were independent predictors of NT. Subgroup analysis demonstrated a significant negative relationship of NT to SS in PES (slope: -0.05 mm/Pa, p = 0.016) and BMS (slope: -0.05 mm/Pa, p = 0.001). Sirolimus elution significantly attenuated the effect of SS on NT (interaction coefficient for SES vs. BMS: 0.04 mm/Pa, p = 0.023), whereas the SS effect remained unchanged in PES (interaction coefficient for PES vs. BMS: 0.01 mm/Pa, p = 0.71). CONCLUSIONS Neointimal thickness is significantly correlated (inversely) to SS in PES as in BMS. Sirolimus elution abrogates the SS effect on the neointimal response following stent implantation, whereas the SS effect is unchanged in PES.

New concepts in the design of drug-eluting coronary stents

Drug-eluting stents (DES) have revolutionized the practice of interventional cardiology over the past decade. Although their efficacy has never been called into question, concerns have been raised regarding their safety, particularly with respect to very late stent thrombosis. These valid concerns have prompted extensive research into improving stent safety, with particular interest in modifying the permanent polymer used on first-generation DES. Subsequently, various new types of coronary stent have been developed, including DES with biocompatible polymers, DES with biodegradable polymers, polymer-free DES, and completely bioresorbable scaffolds. Some of these new DES are already available in clinical practice, and others are currently undergoing clinical evaluation. Improvements in stent performance have made detecting statistically robust and clinically relevant differences between contemporary devices difficult. The wide array of available stents enables the choice of device to be tailored to the individual patient.

Prognostic implications of coronary calcification in patients with obstructive coronary artery disease treated by percutaneous coronary intervention: a patient-level pooled analysis of 7 contemporary stent trials

Objective To investigate the long-term prognostic implications of coronary calcification in patients undergoing percutaneous coronary intervention for obstructive coronary artery disease. Methods Patient-level data from 6296 patients enrolled in seven clinical drug-eluting stents trials were analysed to identify in angiographic images the presence of severe coronary calcification by an independent academic research organisation (Cardialysis, Rotterdam, The Netherlands). Clinical outcomes at 3-years follow-up including all-cause mortality, death—myocardial infarction (MI), and the composite end-point of all-cause death—MI—any revascularisation were compared between patients with and without severe calcification. Results Severe calcification was detected in 20% of the studied population. Patients with severe lesion calcification were less likely to have undergone complete revascularisation (48% vs 55.6%, p<0.001) and had an increased mortality compared with those without severely calcified arteries (10.8% vs 4.4%, p<0.001). The event rate was also high in patients with severely calcified lesions for the combined end-point death—MI (22.9% vs 10.9%; p<0.001) and death—MI— any revascularisation (31.8% vs 22.4%; p<0.001). On multivariate Cox regression analysis, including the Syntax score, the presence of severe coronary calcification was an independent predictor of poor prognosis (HR: 1.33 95% CI 1.00 to 1.77, p=0.047 for death; 1.23, 95% CI 1.02 to 1.49, p=0.031 for death—MI, and 1.18, 95% CI 1.01 to 1.39, p=0.042 for death—MI— any revascularisation), but it was not associated with an increased risk of stent thrombosis. Conclusions Patients with severely calcified lesions have worse clinical outcomes compared to those without severe coronary calcification. Severe coronary calcification appears as an independent predictor of worse prognosis, and should be considered as a marker of advanced atherosclerosis.

Relationship between right ventricular volumes measured by cardiac magnetic resonance imaging and prognosis in patients with chronic heart failure.

The aim of this study was to investigate the prognostic impact of right ventricular (RV) size in patients with chronic heart failure.

Left atrial function measured by cardiac magnetic resonance imaging in patients with heart failure: clinical associations and prognostic value

BACKGROUND Left atrial (LA) volume is an important marker of cardiac dysfunction and cardiovascular outcome in heart failure (HF), but LA function is rarely measured. METHODS Left atrial emptying function (LAEF), its clinical associations and prognostic value was studied in outpatients referred with suspected HF who were in sinus rhythm and had cardiac magnetic resonance imaging (CMRI). Heart failure was defined as relevant symptoms and signs with either a left ventricular ejection fraction (LVEF) <50% or amino-terminal pro-B-type natriuretic peptide (NTproBNP) >400 pg/mL (or >125 pg/mL if taking loop diuretics). RESULTS Of 982 patients, 664 fulfilled the HF criteria and were in sinus rhythm. The median (interquartile range, IQR) LAEF was 42 (31-51)% and 55 (48-61)% in patients with and without HF (P < 0.001). Patients with HF in the lowest quartile of LAEF (23%; IQR: 17-28%) had lower LV and right ventricular (RV) EF, and greater LV and RV mass and higher plasma NTproBNP than those in the highest quartile of LAEF (56%; IQR: 53-61%). Log[LAEF] and log[NTproBNP] were inversely correlated (r = -0.410, P < 0.001). During a median follow-up of 883 (IQR: 469-1626) days, 394 (59%) patients with HF died or were admitted with HF and 101 (15%) developed atrial fibrillation (AF). In a multivariable Cox model, increasing LAEF, but not LVEF, was independently associated with survival (HR for 10% change: 0.81 (95%CI: 0.73-0.90), P = <0.001). Increasing age and decreasing LAEF predicted incident AF. CONCLUSIONS In patients with HF, LAEF predicts adverse outcome independently of other measures of cardiac dysfunction.

Hybrid intravascular imaging: current applications and prospective potential in the study of coronary atherosclerosis.

The miniaturization of medical devices and the progress in image processing have allowed the development of a multitude of intravascular imaging modalities that permit more meticulous examination of coronary pathology. However, these techniques have significant inherent limitations that do not allow a complete and thorough assessment of coronary anatomy. To overcome these drawbacks, fusion of different invasive and noninvasive imaging modalities has been proposed. This integration has provided models that give a more detailed understanding of coronary artery pathology and have proved useful in the study of the atherosclerotic process. In this review, the authors describe the currently available hybrid imaging approaches, discuss the technological innovations and efficient algorithms that have been developed to integrate information provided by different invasive techniques, and stress the advantages of the obtained models and their potential in the study of coronary atherosclerosis.