Neointima and neoatherosclerotic characteristics in bare metal and first- and second-generation drug-eluting stents in patients admitted with cardiovascular events attributed to stent failure: an optical coherence tomography study.

AIMS: The aim of this study was to assess neoatherosclerotic plaque morphology in bare metal (BMS) and first- and second-generation drug-eluting stents (DES) in patients presenting with an event attributed to stent failure. METHODS AND RESULTS: Thirty-five patients (11 implanted with BMS, 13 with a first-generation and 11 with a second-generation DES) admitted with an event due to stent failure who had neoatherosclerotic lesions on optical coherence tomography were included in the analysis. The lumen and stent borders were detected and the lipid and calcific tissue were identified in the neointima and their burden was estimated. The neointima attenuation and backscatter indices were computed and compared between the different stent types. Although there were no differences in the neointima burden, the BMS group exhibited thinner fibrous caps (p<0.001), and a numerically increased incidence of lipid-rich plaques (p=0.052) and macrophage accumulation (p=0.012). Neointima discontinuities (p=0.009) and thrombus (p=0.032) were seen more often in first-generation DES. In all stent types, neoatherosclerosis had focal manifestations. In neoatherosclerotic lesions the attenuation and backscatter indices were increased in BMS (p=0.031 and p=0.018, respectively) compared to DES; however, there were no differences between stents in the attenuation indices in subsegments located distally to neoatherosclerotic lesions which had low values in all stent types. CONCLUSIONS: Although there are differences in lipid burden and neointima characteristics in different stent types, in all stents neoatherosclerosis has focal manifestations indicating that, irrespective of the stent type, focal triggers are involved in the generation of vulnerable neolesions.

Implications of the local hemodynamic forces on the formation and destabilization of neoatherosclerotic lesions.

OBJECTIVE: To examine the implications of endothelial shear stress (ESS) distribution in the formation of neoatherosclerotic lesions. METHODS: Thirty six patients with neoatherosclerotic lesions on optical coherence tomography (OCT) were included in this study. The OCT data were used to reconstruct coronary anatomy. Blood flow simulation was performed in the models reconstructed from the stent borders which it was assumed that represented the lumen surface at baseline, immediate after stent implantation, and the estimated ESS was associated with the neointima burden, neoatherosclerotic burden and neointima characteristics. In segments with neointima rupture blood flow simulation was also performed in the model representing the lumen surface before rupture and the ESS was estimated at the ruptured site. RESULTS: An inverse association was noted between baseline ESS and the incidence and the burden of neoatherosclerotic (ß = -0.60, P < 0.001, and ß = -4.05, P < 0.001, respectively) and lipid-rich neoatherosclerotic tissue (ß = -0.54, P < 0.001, and ß = -3.60, P < 0.001, respectively). Segments exposed to low ESS (<1 Pa) were more likely to exhibit macrophages accumulation (28.2% vs 10.9%, P < 0.001), thrombus (11.0% vs 2.6%, P < 0.001) and evidence of neointima discontinuities (8.1% vs 0.9%, P < 0.001) compared to those exposed to normal or high ESS. In segments with neointima rupture the ESS was high at the rupture site compared to the average ESS over the culprit lesion (4.00 ±â€¯3.65 Pa vs 3.14 ±â€¯2.90 Pa, P < 0.001). CONCLUSIONS: Local EES is associated with neoatherosclerotic lesion characteristics, which suggests involvement of ESS in the formation of vulnerable plaques in stented segments.

An exploratory randomized control study of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with ischaemic cardiomyopathy: the REGENERATE-IHD clinical trial.

AIMS: The effect of combined cytokine and cell therapy in ischaemic cardiomyopathy is unknown. Meta-analyses suggest improved cardiac function with cell therapy. The optimal cell delivery route remains unclear. We investigated whether granulocyte colony-stimulating factor (G-CSF) alone or in combination with intracoronary (i.c.) or intramyocardial (i.m.) injection of autologous bone marrow-derived cells (BMCs) improves cardiac function. METHODS AND RESULTS: Ninety patients with symptomatic ischaemic cardiomyopathy and no further treatment options were enrolled in the randomized, placebo-controlled, single-centre REGENERATE-IHD study. Randomization was to one of three arms: peripheral, i.c., or i.m. In each arm, patients were randomized to active treatment or placebo. All patients, apart from the peripheral placebo group (saline only) received G-CSF for 5 days. The i.c. and i.m. arms received either BMCs or serum (placebo). The primary endpoint was change in LVEF at 1 year assessed by cardiac magnetic resonance imaging/computed tomography. The i.m. BMC group showed a significant improvement in LVEF of 4.99% (95% confidence interval 0.33-9.6%; P = 0.038) at 1 year. This group also showed a reduction in NYHA class at 1 year and NT-proBNP at 6 months. No other group showed a significant change in LVEF. This finding is supported by post-hoc between-group comparisons. CONCLUSION: We have shown that G-CSF combined with autologous i.m. BMCs has a beneficial effect on cardiac function and symptoms. However, this result should be considered preliminary in support of a clinical benefit of i.m. stem cell infusion in 'no option' patients and needs further exploration in a larger study.

Drug-eluting stents appear superior to bare metal stents for vein-graft PCI in vessels up to a stent diameter of 4 mm.

BACKGROUND: Research trials have shown improved short-term outcome with drug-eluting stents (DES) over bare metal stents (BMS) in saphenous vein graft (SVG) percutaneous coronary intervention (PCI), primarily by reducing target vessel revascularization (TVR) for in-stent restenosis. We compared the outcomes in patients undergoing SVG stent implantation treated with DES or BMS. In exploratory analyses we investigated the influence of stent generation and diameter. METHODS: Data were obtained from a prospective database of 657 patients who underwent PCI for SVG lesions between 2003 and 2011. A total of 344 patients had PCI with BMS and 313 with DES. Propensity scores were developed based on 15 observed baseline covariates in a logistic regression model with stent type as the dependent variable. The nearest-neighbour-matching algorithm with Greedy 5-1 Digit Matching was used to produce two patient cohorts of 313 patients each. We assessed major adverse cardiac events (MACE) out to a median of 3.3 years (interquartile range: 2.1-4.1). MACE was defined as all-cause mortality, myocardial infarction (MI), TVR and stroke. RESULTS: There was a significant difference in MACE between the two groups in favour of DES (17.9% DES vs. 31.2% BMS group; p = 0.0017) over the 5-year follow-up period. MACE was driven by increased TVR in the BMS group. There was no difference in death, MI or stroke. Adjusted Cox analysis confirmed a decreased risk of MACE for DES compared with BMS 0.75 (95% confidence interval (CI) 0.52-0.94), with no difference in the hazard of all-cause mortality (hazard ratio: 1.08; 95% CI: 0.77-1.68). However, when looking at stent diameters greater than 4 mm, no difference was seen in MACE rates between BMS and DES. CONCLUSIONS: Overall in our cohort of patients who had PCI for SVG disease, DES use resulted in lower MACE rates compared with BMS over a 5-year follow-up period; however, for stent diameters over 4 mm no difference in MACE rates was seen.