Carlos M. Campos

Bioresorbable Drug-Eluting Magnesium-Alloy Scaffold for Treatment of Coronary Artery Disease

The introduction of metallic drug-eluting stents has reduced the risk of restenosis and widened the indications of percutaneous coronary intervention in treatment of coronary artery disease. However, this medical device can induce hypersensitive reaction that interferes with the endothelialization and healing process resulting in late persistent or acquired malapposition of the permanent metallic implant. Delayed endotheliaization and malapposition may lead to late and very late stent thrombosis. Bioresorbable scaffolds (BRS) have been introduced to potentially overcome these limitations, as they provide temporary scaffolding and then disappear, liberating the treated vessel from its cage. Magnesium is an essential mineral needed for a variety of physiological functions in the human body and its bioresorbable alloy has the strength-to-weight ratio comparable with that of strong aluminum alloys and alloy steels. The aim of this review is to present the new developments in Magnesium BRS technology, to describe its clinical application and to discuss the future prospects of this innovative therapy.

Long-term forecasting and comparison of mortality in the Evaluation of the Xience Everolimus Eluting Stent vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial: prospective validation of the SYNTAX Score II

AIMS To prospectively validate the SYNTAX Score II and forecast the outcomes of the randomized Evaluation of the Xience Everolimus-Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) Trial. METHODS AND RESULTS Evaluation of the Xience Everolimus Eluting Stent vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization is a prospective, randomized multicenter trial designed to establish the efficacy and safety of percutaneous coronary intervention (PCI) with the everolimus-eluting stent compared with coronary artery bypass graft (CABG) surgery in subjects with unprotected left-main coronary artery (ULMCA) disease and low-intermediate anatomical SYNTAX scores (<33). After completion of patient recruitment in EXCEL, the SYNTAX Score II was prospectively applied to predict 4-year mortality in the CABG and PCI arms. The 95% prediction intervals (PIs) for mortality were computed using simulation with bootstrap resampling (10 000 times). For the entire study cohort, the 4-year predicted mortalities were 8.5 and 10.5% in the PCI and CABG arms, respectively [odds ratios (OR) 0.79; 95% PI 0.43-1.50). In subjects with low (≤22) anatomical SYNTAX scores, the predicted OR was 0.69 (95% PI 0.34-1.45); in intermediate anatomical SYNTAX scores (23-32), the predicted OR was 0.93 (95% PI 0.53-1.62). Based on 4-year mortality predictions in EXCEL, clinical characteristics shifted long-term mortality predictions either in favour of PCI (older age, male gender and COPD) or CABG (younger age, lower creatinine clearance, female gender, reduced left ventricular ejection fraction). CONCLUSION The SYNTAX Score II indicates at least an equipoise for long-term mortality between CABG and PCI in subjects with ULMCA disease up to an intermediate anatomical complexity. Both anatomical and clinical characteristics had a clear impact on long-term mortality predictions and decision making between CABG and PCI.

Assessing Bioresorbable Coronary Devices : Methods and Parameters

Bioresorbable vascular scaffolds (BRS) represent a novel approach to provide transient vessel support to drug-delivery capability without the long-term limitations of metallic drug-eluting stents (DES). The technology has the potential to overcome many of the safety concerns associated with metallic DES and possibly even convey further clinical benefit. In particular, the BRS are designed to provide short-term lumen support, and after being completely bioresorbed, eliminate the permanent caging typical of metallic DES. However, this technology has required new imaging modalities and methodologies for its assessment because the design, degradation rate, loss of mechanical property, and drug deliverability may affect its safety and efficacy. We provide an overview of all existing methods for assessing bioresorbable devices, from noninvasive to invasive, from light to sound based, and from morphological to functional parameters.

Long-term prognostic effect of coronary atherosclerotic burden validation of the computed tomography-leaman score

Background— Computed tomography–adapted Leaman score (CT-LeSc) was developed to quantify coronary CT angiography information about atherosclerotic burden (lesion localization, stenosis degree, and plaque composition). The objective of the study is to evaluate CT-LeSc long-term prognostic value in patients with suspected coronary artery disease (CAD). Methods and Results— Single-center prospective registry including 1304 consecutive patients undergoing coronary CT angiography for suspected CAD. High CT-LeSc was defined by upper tertile (score, >5) cutoff. Segment involvement score and segment stenosis score were also evaluated. Hard cardiac events (cardiac death and nonfatal acute coronary syndromes) were considered for analysis. Different Cox regression models were used to identify independent event predictors. Kaplan–Meier event-free survival was evaluated in 4 patient subgroups stratified by obstructive (≥50% stenosis) versus nonobstructive CAD and a high (>5) versus a low (≤5) CT-LeSc. Of 1196 patients included in the final analysis (mean follow-up of 52±22 months), 125 patients experienced 136 hard events (18 cardiac deaths and 118 nonfatal myocardial infarction). All atherosclerotic burden scores were independent predictors of cardiac events (hazard ratios of 3.09 for segment involvement score, 4.42 for segment stenosis score, and 5.39 for CT-LeSc). Cumulative event-free survival was 76.8% with a high CT-LeSc and 96.0% with a low CT-LeSc. Event-free survival in nonobstructive CAD with high CT-LeSc (78.6%) was similar to obstructive CAD with high CT-LeSc (76.5%) but lower than obstructive CAD with low CT-LeSc (80.7%). Conclusions— CT-LeSc is an independent long-term predictor of hard cardiac events. Patients with nonobstructive CAD and high CT-LeSc had hard event-free survival similar to patients with obstructive CAD.Background—Computed tomography–adapted Leaman score (CT-LeSc) was developed to quantify coronary CT angiography information about atherosclerotic burden (lesion localization, stenosis degree, and plaque composition). The objective of the study is to evaluate CT-LeSc long-term prognostic value in patients with suspected coronary artery disease (CAD). Methods and Results—Single-center prospective registry including 1304 consecutive patients undergoing coronary CT angiography for suspected CAD. High CT-LeSc was defined by upper tertile (score, >5) cutoff. Segment involvement score and segment stenosis score were also evaluated. Hard cardiac events (cardiac death and nonfatal acute coronary syndromes) were considered for analysis. Different Cox regression models were used to identify independent event predictors. Kaplan–Meier event-free survival was evaluated in 4 patient subgroups stratified by obstructive (≥50% stenosis) versus nonobstructive CAD and a high (>5) versus a low (⩽5) CT-LeSc. Of 1196 patients included in the final analysis (mean follow-up of 52±22 months), 125 patients experienced 136 hard events (18 cardiac deaths and 118 nonfatal myocardial infarction). All atherosclerotic burden scores were independent predictors of cardiac events (hazard ratios of 3.09 for segment involvement score, 4.42 for segment stenosis score, and 5.39 for CT-LeSc). Cumulative event-free survival was 76.8% with a high CT-LeSc and 96.0% with a low CT-LeSc. Event-free survival in nonobstructive CAD with high CT-LeSc (78.6%) was similar to obstructive CAD with high CT-LeSc (76.5%) but lower than obstructive CAD with low CT-LeSc (80.7%). Conclusions—CT-LeSc is an independent long-term predictor of hard cardiac events. Patients with nonobstructive CAD and high CT-LeSc had hard event-free survival similar to patients with obstructive CAD.

Intravascular Ultrasound Guidance to Minimize the Use of Iodine Contrast in Percutaneous Coronary Intervention: The MOZART (Minimizing cOntrast utiliZation With IVUS Guidance in coRonary angioplasTy) Randomized Controlled Trial

Objective To evaluate the impact of IVUS guidance on the final volume of contrast agent utilized in patients undergoing PCI.

Predicting 3-Year Mortality After Percutaneous Coronary Intervention Updated Logistic Clinical SYNTAX Score Based on Patient-Level Data From 7 Contemporary Stent Trials

OBJECTIVES This study aimed to update the Logistic Clinical SYNTAX score to predict 3-year survival after percutaneous coronary intervention (PCI) and compare the performance with the SYNTAX score alone. BACKGROUND The SYNTAX score is a well-established angiographic tool to predict long-term outcomes after PCI. The Logistic Clinical SYNTAX score, developed by combining clinical variables with the anatomic SYNTAX score, has been shown to perform better than the SYNTAX score alone in predicting 1-year outcomes after PCI. However, the ability of this score to predict long-term survival is unknown. METHODS Patient-level data (N = 6,304, 399 deaths within 3 years) from 7 contemporary PCI trials were analyzed. We revised the overall risk and the predictor effects in the core model (SYNTAX score, age, creatinine clearance, and left ventricular ejection fraction) using Cox regression analysis to predict mortality at 3 years. We also updated the extended model by combining the core model with additional independent predictors of 3-year mortality (i.e., diabetes mellitus, peripheral vascular disease, and body mass index). RESULTS The revised Logistic Clinical SYNTAX models showed better discriminative ability than the anatomic SYNTAX score for the prediction of 3-year mortality after PCI (c-index: SYNTAX score, 0.61; core model, 0.71; and extended model, 0.73 in a cross-validation procedure). The extended model in particular performed better in differentiating low- and intermediate-risk groups. CONCLUSIONS Risk scores combining clinical characteristics with the anatomic SYNTAX score substantially better predict 3-year mortality than the SYNTAX score alone and should be used for long-term risk stratification of patients undergoing PCI.

Scaffold and Edge Vascular Response Following Implantation of Everolimus-Eluting Bioresorbable Vascular Scaffold: A 3-Year Serial Optical Coherence Tomography Study

OBJECTIVES This study sought to investigate the in-scaffold vascular response (SVR) and edge vascular response (EVR) after implantation of an everolimus-eluting bioresorbable scaffold (BRS) using serial optical coherence tomography (OCT) imaging. BACKGROUND Although studies using intravascular ultrasound have evaluated the EVR in metal stents and BRSs, there is a lack of OCT-based SVR and EVR assessment after BRS implantation. METHODS In the ABSORB Cohort B (ABSORB Clinical Investigation, Cohort B) study, 23 patients (23 lesions) in Cohort B1 and 17 patients (18 lesions) in Cohort B2 underwent truly serial OCT examinations at 3 different time points (Cohort B1: post-procedure, 6 months, and 2 years; B2: post-procedure, 1 year, and 3 years) after implantation of an 18-mm scaffold. A frame-by-frame OCT analysis was performed at the 5-mm proximal, 5-mm distal edge, and 2-mm in-scaffold margins, whereas the middle 14-mm in-scaffold segment was analyzed at 1-mm intervals. RESULTS The in-scaffold mean luminal area significantly decreased from baseline to 6 months or 1 year (7.22 ± 1.24 mm(2) vs. 6.05 ± 1.38 mm(2) and 7.64 ± 1.19 mm(2) vs. 5.72 ± 0.89 mm(2), respectively; both p < 0.01), but remained unchanged from then onward. In Cohort B1, a significant increase in mean luminal area of the distal edge was observed (5.42 ± 1.81 mm(2) vs. 5.58 ± 1.53 mm(2); p < 0.01), whereas the mean luminal area of the proximal edge remained unchanged at 6 months. In Cohort B2, the mean luminal areas of the proximal and distal edges were significantly smaller than post-procedure measurements at 3 years. The mean luminal area loss at both edges was significantly less than the mean luminal area loss of the in-scaffold segment at both 6-month and 2-year follow-up in Cohort B1 or at 1 year and 3 years in Cohort B2. CONCLUSIONS This OCT-based serial EVR and SVR evaluation of the Absorb Bioresorbable Vascular Scaffold (Abbott Vascular, Santa Clara, California) showed less luminal loss at the edges than luminal loss within the scaffold. The luminal reduction of both edges is not a nosologic entity, but an EVR in continuity with the SVR, extending from the in-scaffold margin to both edges. (ABSORB Clinical Investigation, Cohort B [ABSORB B]; NCT00856856).

First-in-man randomised comparison of a novel sirolimus- eluting stent with abluminal biodegradable polymer and thin- strut cobalt-chromium alloy: INSPIRON-I trial

AIMS The INSPIRON-I trial is a first-in-man evaluation of the safety and efficacy of the Inspiron drug-eluting stent, a sirolimus-eluting stent with abluminal biodegradable polymer coating and thin cobalt-chromium alloy. METHODS AND RESULTS This is a randomised, multicentre comparison between Inspiron and a stent with the same metallic structure but without polymer coating or drug elution (Cronus). The primary objective was to evaluate the in-segment late loss (LLL) at six months. Secondary endpoints included percent in-stent obstruction as measured by intravascular ultrasound (IVUS) at six months and major adverse cardiac events (MACE). Fifty-eight patients were enrolled (60 lesions), 39 for Inspiron and 19 for Cronus. Baseline clinical and angiographic characteristics of both groups were similar. At six months, the in-segment LLL was reduced in the Inspiron group compared to the control group (0.19±0.16 mm vs. 0.58±0.4 mm, respectively; p<0.001), as well as the percent neointimal obstruction (7.8±7.1% vs. 26.5±11.4%; p<0.001). At two-year follow-up, incidence of MACE was similar between groups (7.9 vs. 21.1%, respectively; p=0.20), with lower target lesion revascularisation for Inspiron (0 vs. 21.1%, respectively; p=0.01) and no stent thrombosis. CONCLUSIONS Sirolimus eluted from an abluminal biodegradable polymer on a cobalt-chromium alloy proved effective in reducing restenosis at six months.

The EXCEL and NOBLE trials: similarities, contrasts and future perspectives for left main revascularisation.

Unprotected left main coronary artery (ULMCA) stenosis has relatively high prevalence and exposes patients to a high risk for adverse cardiovascular events. The optimal revascularisation strategy (coronary artery bypass surgery [CABG] or percutaneous coronary intervention [PCI]) for patients with complex coronary artery disease is a topic of continuing debate. The introduction of the newer-generation drug-eluting stents (DES) -with documented improvements in both safety and efficacy- has prompted the interventional community to design two new dedicated randomised trials comparing CABG and PCI: the NOBLE (Coronary Artery Bypass Grafting Vs Drug Eluting Stent Percutaneous Coronary Angioplasty in the Treatment of Unprotected Left Main Stenosis) and EXCEL (Evaluation of XIENCE Everolimus Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trials. The aims of the present review are to describe the similarities and contrasts between these two trials as well to explore their future implications in ULMCA treatment.

Differential impact of five coronary devices on plaque size: Insights from the ABSORB and SPIRIT trials

BACKGROUND Coronary plaque size modification, by either local (device) or systemic treatments, has been the target for many years. METHODS From ABSORB Cohort A (Absorb BVS 1.0), ABSORB Cohort B (Absorb BVS 1.1), SPIRIT FIRST (Multi-Link Vision vs. Xience V) & SPIRIT II (Xience V vs. Taxus), we calculated the total plaque area (vessel minus lumen area - thus it comprises both compartments - the plaque behind struts and the neointima.) changes by IVUS. RESULTS A total of 313 patients were included. Comparison-at-6-month follow-up: All devices induced an increase in the total plaque area. The largest increase occurred with Vision and Taxus stents as compared to other devices [Absorb BVS (1.0 and 1.1) and Xience V], (p=0.0002). Comparison-at-2-year follow-up: Absorb BVS 1.1 had a larger increase from post procedure in total plaque compared to Absorb BVS 1.0, Xience V and Taxus (p=0.0499). However, in Absorb BVS 1.1 total plaque showed a reduction of 2.2% from 1 to 3 years. Specifically, the total plaque in the sequential cohorts of Absorb BVS 1.1 increased 16.2% from baseline to 2 years (Cohort B1) while at 3 years this increase is only 5% compared to baseline (Cohort B2). CONCLUSIONS Local devices affect coronary plaque size differently and it depends on the platform (metallic vs. polymeric) and on whether it is a bare - or drug eluting stent. Coronary scaffolds appear to be a promising alternative to metallic stents since they allow plaque regression at long-term follow-up.