Vasim Farooq

Anatomical and clinical characteristics to guide decision making between coronary artery bypass surgery and percutaneous coronary intervention for individual patients: development and validation of SYNTAX score II

BACKGROUND The anatomical SYNTAX score is advocated in European and US guidelines as an instrument to help clinicians decide the optimum revascularisation method in patients with complex coronary artery disease. The absence of an individualised approach and of clinical variables to guide decision making between coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) are limitations of the SYNTAX score. SYNTAX score II aimed to overcome these limitations. METHODS SYNTAX score II was developed by applying a Cox proportional hazards model to results of the randomised all comers SYNTAX trial (n=1800). Baseline features with strong associations to 4-year mortality in either the CABG or the PCI settings (interactions), or in both (predictive accuracy), were added to the anatomical SYNTAX score. Comparisons of 4-year mortality predictions between CABG and PCI were made for each patient. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. External validation was done in the multinational all comers DELTA registry (n=2891), a heterogeneous population that included patients with three-vessel disease (26%) or complex coronary artery disease (anatomical SYNTAX score ≥33, 30%) who underwent CABG or PCI. The SYNTAX trial is registered with ClinicalTrials.gov, number NCT00114972. FINDINGS SYNTAX score II contained eight predictors: anatomical SYNTAX score, age, creatinine clearance, left ventricular ejection fraction (LVEF), presence of unprotected left main coronary artery (ULMCA) disease, peripheral vascular disease, female sex, and chronic obstructive pulmonary disease (COPD). SYNTAX score II significantly predicted a difference in 4-year mortality between patients undergoing CABG and those undergoing PCI (p(interaction) 0·0037). To achieve similar 4-year mortality after CABG or PCI, younger patients, women, and patients with reduced LVEF required lower anatomical SYNTAX scores, whereas older patients, patients with ULMCA disease, and those with COPD, required higher anatomical SYNTAX scores. Presence of diabetes was not important for decision making between CABG and PCI (p(interaction) 0·67). SYNTAX score II discriminated well in all patients who underwent CABG or PCI, with concordance indices for internal (SYNTAX trial) validation of 0·725 and for external (DELTA registry) validation of 0·716, which were substantially higher than for the anatomical SYNTAX score alone (concordance indices of 0·567 and 0·612, respectively). A nomogram was constructed that allowed for an accurate individualised prediction of 4-year mortality in patients proposing to undergo CABG or PCI. INTERPRETATION Long-term (4-year) mortality in patients with complex coronary artery disease can be well predicted by a combination of anatomical and clinical factors in SYNTAX score II. SYNTAX score II can better guide decision making between CABG and PCI than the original anatomical SYNTAX score. FUNDING Boston Scientific Corporation.

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.

Endothelial-dependent vasomotion in a coronary segment treated by ABSORB everolimus-eluting bioresorbable vascular scaffold system is related to plaque composition at the time of bioresorption of the polymer: indirect finding of vascular reparative therapy?

AIMS To analyse the vasoreactivity of a coronary segment, previously scaffolded by the ABSORB bioresorbable vascular scaffold (BVS) device, in relationship to its intravascular ultrasound-virtual histology (IVUS-VH) composition and reduction in greyscale echogenicity of the struts. Coronary segments, transiently scaffolded by a polymeric device, may in the long-term recover a normal vasomotor tone. Recovery of a normal endothelial-dependent vasomotion may be enabled by scaffold bioresorption, composition of the underlying tissue, or a combination of both mechanisms. METHODS AND RESULTS All patients from the ABSORB Cohort A and B trials, who underwent a vasomotion test and IVUS-VH investigation at 12 and 24 months, were included. Acetylcholine (Ach) and nitroglycerin were used to test either the endothelial-dependent or -independent vasomotion of the treated segment. Changes in polymeric strut echogenicity-a surrogate for bioresorption-IVUS-VH composition of the tissue underneath the scaffold and their relationship with the pharmacologically induced vasomotion were all evaluated. Overall, 26 patients underwent the vasomotion test (18 at 12 and 8 at 24 months). Vasodilatory response to Ach was quantitatively associated with larger reductions over time in polymeric strut echogenicity (y= -0.159x- 6.85; r= -0.781, P< 0.001). Scaffolded segments with vasoconstriction to Ach had larger vessel areas (14.37 ± 2.50 vs. 11.85 ± 2.54 mm(2), P= 0.030), larger plaque burden (57.31 ± 5.96 vs. 49.09 ± 9.10%, P= 0.018), and larger necrotic core (NC) areas [1.39 (+1.14, +1.74) vs. 0.78 mm(2) (+0.20, +0.98), P= 0.006] compared with those with vasodilation. CONCLUSION Vasodilatory response to Ach, in coronary segments scaffolded by the ABSORB BVS device, is associated with a reduction in echogenicity of the scaffold over time, and a low amount of NC. In particular, the latter finding resembles the behaviour of a native coronary artery not caged by an intracoronary device.

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.

Restenosis Delineating the Numerous Causes of Drug-Eluting Stent Restenosis

In the past decade, tremendous progress has been made in reducing the incidence of restenosis with the advent of the drug-eluting stent (DES). With “plain old balloon angioplasty,” rates of acute and chronic vessel occlusion were unacceptably high at ≈30% to 60%, secondary to acute and chronic recoil and constrictive remodeling. The advent of bare-metal stents (BMS) appeared to eliminate the issue of acute and chronic recoil but introduced a new entity, neointimal hyperplasia (NIH), with classical papers unequivocally demonstrating a strong and linear relationship between NIH formation and late lumen loss (LLL). The restenosis rates with BMS were reported to be between 16% and 44%, with higher rates of stenosis attributable to several risk factors, in particular, long lesion length and small vessel caliber.1 DES were thus conceived as the next step in tackling this iatrogenic entity of NIH, with large-scale reductions in restenosis rates reported at 0% in highly selective lesions and up to 16% in a broader range of patients and lesions with first-generation DES.1 In contrast to plain old balloon angioplasty and BMS, in which an almost classical gaussian distribution of LLL is seen postprocedurally, the LLL after DES implantation appears to follow a bimodal pattern of distribution (Figure 1).2 Figure 1. The bimodal distribution of LLL (A, B) and percentage diameter stenosis (C, D) after Cypher (left) and Taxus (right) implantation. LLL indicates late lumen loss. Reproduced with permission from Byrne et al.2 Despite the significant advances in the technology to reduce DES restenosis, conservative estimates still suggest that the incidence of in-stent restenosis (ISR) requiring target vessel revascularization (TVR), so-called DES failure, to be ≈5% to 10%, with one estimate suggesting ≈200 000 repeat revascularizations in the United States alone.3 Whereas the pattern of restenosis in BMS has been shown …

Circumferential evaluation of the neointima by optical coherence tomography after ABSORB bioresorbable vascular scaffold implantation: can the scaffold cap the plaque?

OBJECTIVE To quantify the circumferential healing process at 6 and 12 months following scaffold implantation. BACKGROUND The healing process following stent implantation consists of tissue growing on the top of and in the space between each strut. With the ABSORB bioresorbable vascular scaffold (BVS), the outer circumference of the scaffold is detectable by optical coherence tomography (OCT), allowing a more accurate and complete evaluation of the intra-scaffold neointima. METHODS A total of 58 patients (59 lesions), who received an ABSORB BVS 1.1 implantation and a subsequent OCT investigation at 6 (n=28 patients/lesions) or 12 (n=30 patients with 31 lesions) months follow-up were included in the analysis. The thickness of the neointima was calculated circumferentially in the area between the abluminal side of the scaffold and the lumen by means of an automated detection algorithm. The symmetry of the neointima thickness in each cross section was evaluated as the ratio between minimum and maximum thickness. RESULTS The neointima area was not different between 6 and 12 months follow-up (1.57±0.42 mm(2) vs. 1.64±0.77 mm(2); p=0.691). No difference was also found in the mean thickness of the neointima (median [IQR]) between the two follow-up time points (210 μm [180-260]) vs. 220 μm [150-260]; p=0.904). However, the symmetry of the neointima thickness was higher at 12 than at 6 months follow-up (0.23 [0.13-0.28] vs. 0.16 [0.08-0.21], p=0.019). CONCLUSIONS A circumferential evaluation of the healing process following ABSORB implantation is feasible, showing the formation of a neointima layer, that resembles a thick fibrous cap, known for its contribution to plaque stability.

ABSORB II randomized controlled trial. A clinical evaluation to compare the safety, efficacy, and performance of the Absorb everolimus-eluting bioresorbable vascular scaffold system against the XIENCE everolimus-eluting coronary stent system in the treatment of subjects with ischemic heart disease caused by de novo native coronary artery lesions: Rationale and study design

BACKGROUND Currently, no data are available on the direct comparison between the Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) and conventional metallic drug-eluting stents. METHODS The ABSORB II study is a randomized, active-controlled, single-blinded, multicenter clinical trial aiming to compare the second-generation Absorb BVS with the XIENCE everolimus-eluting metallic stent. Approximately 501 subjects will be enrolled on a 2:1 randomization basis (Absorb BVS/XIENCE stent) in approximately 40 investigational sites across Europe and New Zealand. Treated lesions will be up to 2 de novo native coronary artery lesions, each located in different major epicardial vessels, all with an angiographic maximal luminal diameter between 2.25 and 3.8 mm as estimated by online quantitative coronary angiography (QCA) and a lesion length of ≤48 mm. Clinical follow-up is planned at 30 and 180 days and at 1, 2, and 3 years. All subjects will undergo coronary angiography, intravascular ultrasound (IVUS) and IVUS-virtual histology at baseline (pre-device and post-device implantation) and at 2-year angiographic follow-up. The primary end point is superiority of the Absorb BVS vs XIENCE stent in terms of vasomotor reactivity of the treated segment at 2 years, defined as the QCA quantified change in the mean lumen diameter prenitrate and postnitrate administration. The coprimary end point is the noninferiority (reflex to superiority) of the QCA-derived minimum lumen diameter at 2 years postnitrate minus minimum lumen diameter postprocedure postnitrate by QCA. In addition, all subjects allocated to the Absorb BVS group will undergo multislice computed tomography imaging at 3 years. CONCLUSIONS The ABSORB II randomized controlled trial (ClinicalTrials.gov NCT01425281) is designed to compare the safety, efficacy, and performance of Absorb BVS against the XIENCE everolimus-eluting stent in the treatment of de novo native coronary artery lesions.

Combined anatomical and clinical factors for the long-term risk stratification of patients undergoing percutaneous coronary intervention: the Logistic Clinical SYNTAX score

BACKGROUND The SYNTAX score (SXscore), an anatomical-based scoring tool reflecting the complexity of coronary anatomy, has established itself as an important long-term prognostic factor in patients undergoing percutaneous coronary intervention (PCI). The incorporation of clinical factors may further augment the utility of the SXscore to longer-term risk stratify the individual patient for clinical outcomes. METHODS AND RESULTS Patient-level merged data from >6000 patients in seven contemporary coronary stent trials was used to develop a logistic regression model-the Logistic Clinical SXscore-to predict 1-year risk for all-cause death and major adverse cardiac events (MACE). A core model (composed of the SXscore, age, creatinine clearance, and left ventricular ejection fraction) and an extended model [incorporating the core model and six additional (best performing) clinical variables] were developed and validated in a cross-validation procedure. The core model demonstrated a substantial improvement in predictive ability for 1-year all-cause death compared with the SXscore in isolation [area under the receiver operator curve (AUC): core model: 0.753, SXscore: 0.660]. A minor incremental benefit of the extended model was shown (AUC: 0.791). Consequently the core model alone was retained in the final the Logistic Clinical SXscore model. Validation plots confirmed the model predictions to be well calibrated. For 1-year MACE, the addition of clinical variables did not improve the predictive ability of the SXscore, secondary to the SXscore being the predominant determinant of all-cause revascularization. CONCLUSION The Logistic Clinical SXscore substantially enhances the prediction of 1-year mortality after PCI compared with the SXscore, and allows for an accurate personalized assessment of patient risk.

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.

Contemporary and evolving risk scoring algorithms for percutaneous coronary intervention

Risk stratification is an essential part of appropriately informing patients electing to undergo percutaneous coronary intervention (PCI). This process is also an integral part of the SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery)-pioneered heart team approach in determining the most appropriate revascularisation modality for patients with complex coronary artery disease. The SYNTAX score was pioneered as an anatomical-based risk score to aid in this decision-making process; the lack of clinical variables in this score has, however, been its main limitation. This review examines the important established and evolving contemporary risk models used to aid this risk-stratification process. Risk scores based on clinical and anatomical variables alone and in combination—the latter of which is the subject of continuing research—are all explored. Other areas of discussion include risk scores based on the completeness of revascularisation and emerging concepts such as functional anatomical risk scores and the patient-empowered risk-benefit trade-off between PCI and coronary artery bypass grafting, to help personalise the choice of revascularisation modality.