Joëlle Elias

Bioresorbable Scaffolds versus Metallic Stents in Routine PCI

BACKGROUND Bioresorbable vascular scaffolds were developed to overcome the shortcomings of drug‐eluting stents in percutaneous coronary intervention (PCI). We performed an investigator‐initiated, randomized trial to compare an everolimus‐eluting bioresorbable scaffold with an everolimus‐eluting metallic stent in the context of routine clinical practice. METHODS We randomly assigned 1845 patients undergoing PCI to receive either a bioresorbable vascular scaffold (924 patients) or a metallic stent (921 patients). The primary end point was target‐vessel failure (a composite of cardiac death, target‐vessel myocardial infarction, or target‐vessel revascularization). The data and safety monitoring board recommended early reporting of the study results because of safety concerns. This report provides descriptive information on end‐point events. RESULTS The median follow‐up was 707 days. Target‐vessel failure occurred in 105 patients in the scaffold group and in 94 patients in the stent group (2‐year cumulative event rates, 11.7% and 10.7%, respectively; hazard ratio, 1.12; 95% confidence interval [CI], 0.85 to 1.48; P=0.43); event rates were based on Kaplan–Meier estimates in time‐to‐event analyses. Cardiac death occurred in 18 patients in the scaffold group and in 23 patients in the stent group (2‐year cumulative event rates, 2.0% and 2.7%, respectively), target‐vessel myocardial infarction occurred in 48 patients in the scaffold group and in 30 patients in the stent group (2‐year cumulative event rates, 5.5% and 3.2%), and target‐vessel revascularization occurred in 76 patients in the scaffold group and in 65 patients in the stent group (2‐year cumulative event rates, 8.7% and 7.5%). Definite or probable device thrombosis occurred in 31 patients in the scaffold group as compared with 8 patients in the stent group (2‐year cumulative event rates, 3.5% vs. 0.9%; hazard ratio, 3.87; 95% CI, 1.78 to 8.42; P<0.001). CONCLUSIONS In this preliminary report of a trial involving patients undergoing PCI, there was no significant difference in the rate of target‐vessel failure between the patients who received a bioresorbable scaffold and the patients who received a metallic stent. The bioresorbable scaffold was associated with a higher incidence of device thrombosis than the metallic stent through 2 years of follow‐up. (Funded by Abbott Vascular; AIDA ClinicalTrials.gov number, NCT01858077.)

Meta-analysis on the impact of percutaneous coronary intervention of chronic total occlusions on left ventricular function and clinical outcome

BACKGROUND Percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs) may have a beneficial effect on survival through a better-preserved or improved LVEF. Current literature consists of small observational studies therefore we performed a weighted meta-analysis on the impact of revascularization of CTOs on left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV) and long-term mortality. METHODS We conducted a meta-analysis evaluating LVEF before and after CTO PCI and long-term mortality. No language or time restrictions were applied. References from the identified articles and reviews were examined to find additional relevant manuscripts. RESULTS Of the 812 citations, 34 studies performed between 1987-2014 in 2243 patients were eligible for LVEF and 27 studies performed between 1990-2013 in 11,085 patients with success and 4347 patients that failed CTO PCI were eligible for long-term mortality. After successful CTO PCI, LVEF increased with 4.44% (95% CI: 3.52-5.35, p<0.01) compared to baseline. In a small cohort of ~70 patients, no significant difference in LVEF was observed after non-successful CTO PCI or reocclusion. Additionally, 8 studies reported the change in left ventricular end-diastolic volume (LVEDV) in a total of 412 patients. LVEDV decreased with 6.14 ml/m(2) (95% CI: -9.31 to -2.97, p<0.01). Successful CTO PCI was also associated with reduced mortality in comparison with failed CTO PCI (OR: 0.52, 95% CI: 0.43-0.62, p-value<0.01). CONCLUSIONS The current meta-analysis revealed that successful recanalization of a CTO resulted in an overall improvement of 4.44% absolute LVEF points, reduced adverse remodeling and an improvement of survival (OR: 0.52).

The impact of the location of a chronic total occlusion in a non-infarct-related artery on long-term mortality in ST-elevation myocardial infarction patients

AIMS Several studies have evaluated the impact of a CTO on short- and long-term mortality in STEMI patients. It has been speculated that the adverse effect on prognosis could differ per coronary location. The purpose of this study was to evaluate whether the long-term prognosis of STEMI patients differs according to the coronary location of the CTO. METHODS AND RESULTS Between 2000 and 2012, a total of 480 STEMI patients with a CTO in a non-infarct-related artery were included. The primary outcome for the present analysis was three-year all-cause mortality, evaluating the impact of the coronary CTO and infarct location. Four hundred and thirteen patients had a single CTO in a non-infarct-related artery, whereas 67 patients had more than one CTO and in this group mortality was higher. In patients with a single CTO, the highest risk of mortality was observed when the culprit lesion was located in the LAD or proximal LCX or when the CTO lesion was located in the proximal LAD. CONCLUSIONS We previously reported that STEMI patients with a CTO have a worse prognosis than STEMI patients without a CTO. We now show that, in these patients, LAD or proximal LCX location for the culprit lesion, or proximal LAD location for the CTO lesion, is associated with the highest risk. As a result, almost all CTO patients are at increased risk for mortality due to the combination of the culprit and CTO artery location.

Long-term impact of chronic total occlusion recanalisation in patients with ST-elevation myocardial infarction

Background During primary percutaneous coronary intervention (PCI), a concurrent chronic total occlusion (CTO) is found in 10% of patients with ST-elevation myocardial infarction (STEMI). Long-term benefits of CTO-PCI have been suggested; however, randomised data are lacking. Our aim was to determine mid-term and long-term clinical outcome of CTO-PCI versus CTO-No PCI in patients with STEMI with a concurrent CTO. Methods The Evaluating Xience and left ventricular function in PCI on occlusiOns afteR STEMI (EXPLORE) was a multicentre randomised trial that included 302 patients with STEMI after successful primary PCI with a concurrent CTO. Patients were randomised to either CTO-PCI or CTO-No PCI. The primary end point of the current study was occurrence of major adverse cardiac events (MACE): cardiac death, coronary artery bypass grafting and MI. Other end points were 1-year left ventricular function (LVF); LV-ejection fraction and LV end-diastolic volume and angina status. Results The median long-term follow-up was 3.9 (2.1–5.0) years. MACE was not significantly different between both arms (13.5% vs 12.3%, HR 1.03, 95% CI 0.54 to 1.98; P=0.93). Cardiac death was more frequent in the CTO-PCI arm (6.0% vs 1.0%, P=0.02) with no difference in all-cause mortality (12.9% vs 6.2%, HR 2.07, 95% CI 0.84 to 5.14; P=0.11). One-year LVF did not differ between both arms. However, there were more patients with freedom of angina in the CTO-PCI arm at 1 year (94% vs 87%, P=0.03). Conclusions In this randomised trial involving patients with STEMI with a concurrent CTO, CTO-PCI was not associated with a reduction in long-term MACE compared to CTO-No PCI. One-year LVF was comparable between both treatment arms. The finding that there were more patients with freedom of angina after CTO-PCI at 1-year follow-up needs further investigation. Clinical trial registration EXPLORE trial number NTR1108 www.trialregister.nl.

Coronary Artery Vessel Healing Pattern, Short and Long Term, After Implantation of the Everolimus‐Eluting Bioresorbable Vascular Scaffold

Background Although the Absorb bioresorbable vascular scaffold is increasingly used in daily clinical practice for the treatment of coronary artery disease, the exact vascular healing pattern and the resorption process in humans is unknown because histological data are derived only from animal studies. Methods and Results We have obtained 4 autopsies (5 scaffolds) since August 2013. Duration of bioresorbable vascular scaffold implantation ranged from 3 to 501 days. All autopsies and histological assessments were performed by dedicated cardiovascular pathologists. At 1 week after bioresorbable vascular scaffold implantation, struts were covered with a fine layer of fibrin and platelets. At 113 days, the scaffold struts were fully covered with smooth muscle cells. Hyaline eosinophilic and proteoglycan material infiltrating the scaffold struts was observed at 501 days after implantation. At all time points, we observed the presence of multinuclear foreign body giant cells adjacent to the scaffold struts. Conclusions Resorption and healing processes after bioresorbable vascular scaffold implantation in human patients mirror those observed in porcine models. The presence of multinucleated foreign body giant cells at both short‐ and long‐term follow‐up needs further investigation and may be related to a low‐grade absorptive inflammatory response to the polymer.

Evaluation of the Impact of a Chronic Total Coronary Occlusion on Ventricular Arrhythmias and Long‐Term Mortality in Patients With Ischemic Cardiomyopathy and an Implantable Cardioverter‐Defibrillator (the eCTOpy‐in‐ICD Study)

Background Previous studies report conflicting results about a higher incidence of ventricular arrhythmias in patients with a chronic total coronary occlusion (CTO). We aimed to investigate this association in a large cohort of implantable cardioverter defibrillator patients with long‐term follow‐up. Methods and Results All consecutive patients from 1992 onwards who underwent implantable cardioverter defibrillator implantation for ischemic cardiomyopathy at the Leiden University Medical Center were evaluated. Coronary angiograms were reviewed for the presence of a CTO. The occurrence of ventricular arrhythmias and survival status at follow‐up were compared between patients with and patients without a CTO. A total of 722 patients constitute the study cohort (age 66±11 years; 84% males; 74% primary prevention, median left ventricular ejection fraction 30% [first–third quartile: 25–37], 44% received a cardiac resynchronization therapy defibrillator). At baseline, 240 patients (33%) had a CTO, and the CTOs were present for at least 44 (2–127) months. The median follow‐up duration was 4 (2–6) years. On long‐term follow‐up, CTO patients had a higher crude appropriate device therapy rate (37% versus 27%, P=0.010) and a lower crude survival rate (51% versus 67%, P<0.001) compared with patients without a CTO. Corrected for baseline characteristics including left ventricular ejection fraction, the presence of a CTO was an independent predictor for appropriate device therapy. Conclusions The presence of a CTO in implantable cardioverter defibrillator patients was associated with more appropriate device therapy and worse prognosis at long‐term follow‐up. Further investigation is warranted regarding a potential beneficial effect of CTO revascularization on the incidence of ventricular arrhythmias.

Complete two-year follow-up with formal non-inferiority testing on primary outcomes of the AIDA trial comparing the Absorb bioresorbable scaffold with the XIENCE drug-eluting metallic stent in routine PCI

AIMS The aim of this report of the AIDA trial is to provide full two-year outcomes for the primary endpoint of target vessel failure (TVF) and an update on device thrombosis. METHODS AND RESULTS AIDA was a single-blind, multicentre, investigator-initiated, non-inferiority, randomised (1:1) clinical trial. At complete two-year follow-up, the primary endpoint of TVF had occurred in 100 patients in the Absorb BVS arm versus 90 patients in the XIENCE EES arm (HR 1.12, 95% CI: 0.94-1.49; psuperiority=0.436). Estimated two-year Kaplan-Meier event rates of TVF were 11.0% and 9.9%, respectively (95% CI: -0.9%-3.0%; pnon-inferiority=0.003). Definite or probable device thrombosis at two years occurred in 30 patients in the Absorb BVS arm and in eight patients in the XIENCE EES arm. Kaplan-Meier estimates of device thrombosis were 3.3% in the Absorb BVS arm and 0.9% in the XIENCE EES arm (HR 5.22, 95% CI: 2.00-13.59; p<0.001). CONCLUSIONS AIDA formally met its criterion for non-inferiority of Absorb BVS versus XIENCE EES in terms of the combined endpoint of TVF. The Absorb BVS, however, was associated with higher rates of scaffold thrombosis and target vessel myocardial infarction at complete two-year follow-up.

Monocytic microRNA profile associated with coronary collateral artery function in chronic total occlusion patients

An expansive collateral artery network is correlated with improved survival in case of adverse cardiac episodes. We aimed to identify cellular microRNAs (miRNA; miR) important for collateral artery growth. Chronic total occlusion (CTO) patients (n = 26) were dichotomized using pressure-derived collateral flow index (CFIp) measurements; high collateral capacity (CFIp > 0.39; n = 14) and low collateral (CFIp < 0.39; n = 12) capacity. MiRNA profiling via next generation sequencing from various monocyte phenotypes (freshly isolated monocytes, monocytes cultured without stimulant, or stimulation with lipopolysaccharide, interleukin 4, transforming growth factor beta-1, or interferon gamma) revealed significantly different miRNA expression patterns between high versus low collateral capacity patients. Validation by real-time polymerase chain reaction demonstrated significantly decreased expression of miR339-5p in all stimulated monocyte phenotypes of low collateral capacity patients. MiR339-5p showed significant correlation with CFIp values in stimulated monocytes. Ingenuity pathway analysis of predicted gene targets of miR339-5p and differential gene expression data from high versus low CFIp patients (n = 20), revealed significant association with STAT3 pathway, and also suggested a possible regulatory role for this signaling pathway. These results identify a novel association between miR339-5p and coronary collateral function. Future work examining modulation of miR339-5p and downstream effects on the STAT3 pathway and subsequent collateral vessel growth are warranted.

The first generation ABSORB BVS scaffold; to be or not to be?

In the routine treatment of coronary artery disease, balloon angioplasty has been replaced by stents. The use of bare-metal stents resulted in lower rates of restenosis and repeat revascularisations. Drug-eluting stents (DES), designed with thinner struts and anti-proliferative drugs, have further enhanced the efficacy and safety of percutaneous coronary intervention. Nevertheless, the new generation of metallic DES are also limited by risks of neoatherosclerosis with late and very late stent thrombosis and a rigid metallic cage impairing vasomotion [1]. Bioabsorbable ‘stents’ were developed to restore coronary flow and temporary support the vessel with the advantage of dissolving completely over time, possibly overcoming abovementioned short-comings of metallic DES. The ABSORB (Abbot Vascular, Santa Clara, California, USA) bioabsorbable vascular scaffold (BVS), consisting of a poly-L-lactide backbone coated with a mixture of polyD,L-lactide and an everolimus-eluting drug, was the first bioresorbable device to receive CE (Conformité Européene) approval in 2010 and approval by the Food and Drug Administration in the United States in 2016. Studies performed in relative simple coronary lesions have shown reasonable short-term to mid-term results. Conversely, world-wide registries from clinical practice raised concerns regarding increased rates of scaffold thrombosis. Recently, longer-term follow-up randomised clinical data have become available. The ABSORB II trial is the first randomised trial reporting 3 years’ follow-up. This trial did not meet the co-primary endpoints: BVS compared with Xience

Impact of collateralisation to a concomitant chronic total occlusion in patients with ST-elevation myocardial infarction: a subanalysis of the EXPLORE randomised controlled trial

Objective The impact on cardiac function of collaterals towards a concomitant chronic total coronary occlusion (CTO) in patients with ST-elevation myocardial infarction (STEMI) has not been investigated yet. Therefore, we have evaluated the impact of well-developed collaterals compared with poorly developed collaterals to a concomitant CTO in STEMI. Methods and results In the EXPLORE trial, patients with STEMI and a concomitant CTO were randomised to either CTO percutaneous coronary intervention (PCI) or no-CTO PCI. Collateral grades were scored angiographically using the Rentrop grade classification. Left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume (LVEDV) at 4 months were measured using cardiac magnetic resonance imaging. Well-developed collaterals (Rentrop grades 2–3) to the CTO were present in 162 (54%) patients; these patients had a significantly higher LVEF at 4 months (46.2±11.4% vs 42.1±12.7%, p=0.004) as well as a trend for a lower LVEDV (208.2±55.7 mL vs 222.6±68.5 mL, p=0.054) when compared with patients with poorly developed collaterals to the CTO. There was no significant difference in the total amount of scar in the two groups. Event rates were statistically comparable between patients with well-developed collaterals and poorly developed collaterals to the CTO at long-term follow-up. Conclusions In patients with STEMI and a concomitant CTO, the presence of well-developed collaterals to a concomitant CTO is associated with a better LVEF at 4 months. However, this effect on LVEF did not translate into improvement in clinical outcome. Therefore, the presence of well-developed collaterals is important, but should not solely guide in the clinical decision-making process regarding any additional revascularisation of a concomitant CTO in patients with STEMI. Clinical trial registration NTR1108.