Circulating PCSK9 levels in acute coronary syndrome: Results from the PC-SCA-9 prospective study.

BACKGROUND: Serum proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations have been shown to be positively associated with LDL cholesterol (LDL-C), but the relationship between PCSK9 and coronary atherosclerosis lesions remains unclear. OBJECTIVE: This study aims to investigate the correlation between serum PCSK9 levels and coronary damage severity in patients hospitalized for acute coronary syndrome (ACS). METHODS: In this prospective proof-of-concept study, coronary lesions were assessed using SYNTAX scores. Serum PCSK9 concentrations were measured on admission (Day 0) for ACS by Elisa, and on every day of hospitalization. Spearman's correlations were used to determine the association between PCSK9 levels, SYNTAX score and metabolic parameters. RESULTS: A total of 174 patients (mean age: 59±14 years, 79% male) with ACS (on Day 0, 119 patients were not taking statins, but 55 were) were included. After initiation of high-intensity statin therapy, serum PCSK9 concentrations increased significantly, reaching maximum levels on Day 2 (+31% vs. Day 0), and remained stable up to Day 4 (P<0.001, by mixed model). Serum PCSK9 on Day 0 was associated with LDL-C (rho=0.226, P=0.017) and apolipoprotein B (rho=0.282, P=0.005) in the statin-naïve group only, and with triglycerides and non-HDL-C in all groups. More important, PCSK9 levels on Day 0 were positively associated with SYNTAX scores in the statin-naïve group (rho=0.239, P=0.009), but not in the statin-treated group (P=NS). This association was maintained after adjusting for LDL-C (P=0.014) and major CV risk factors (P=0.008). CONCLUSION: Serum PCSK9 levels are positively associated with severity of coronary artery lesions independently of LDL-C concentrations in patients hospitalized for ACS. This reinforces the potential importance of PCSK9 inhibition in the management of ACS.

Femoropopliteal In-stent Restenosis Repair: Midterm Outcomes After Paclitaxel Eluting Balloon Use (PLAISIR Trial).

OBJECTIVE: The aim was to assess 18 month outcomes of the paclitaxel eluting balloon (PEB) in patients with femoropopliteal (FP) in-stent restenosis (ISR). METHODS: In a national prospective and multicentre cohort study, symptomatic patients with femoropopliteal in-stent restenosis were included from January 2012 to June 2013. Patients were treated by paclitaxel eluting balloon angioplasty (In Pact Admiral, Medtronic, Santa Rosa, CA, USA). Clinical and duplex scan follow-up evaluations were performed at 1, 3, 6, 9, 12, and 18 months. The primary endpoint was freedom from target lesion revascularisation (TLR) at 12 months. Secondary endpoints were major adverse cardiovascular events (MACE), Target extremity revascularisation (TER), primary and secondary sustained clinical improvement, recurrent restenosis rate, primary and secondary patency, quality of life assessed by EQ-5D questionnaire, technical success, clinical success, and length of stay RESULTS: A total of 53 patients were enrolled. After a blinded review, 10 patients were defined as protocol violation because restenosis occurred more than 2 years after stent implantation. Procedures were performed in 55 limbs, 48 (87%) for claudication and 7 (13%) for critical limb ischaemia. The mean diameter and length of PEB were 6 ± 0.57 mm and 86 mm ± 32 mm, follow-up was 17 months (range 1-19). At 1 year, the survival rate was 96 ± 2.7% and freedom from TLR and TER were 90.2 ± 4.2% and 85 ± 5%, respectively. Sustained primary and secondary clinical improvements were 78.6 ± 5.7% and 92.0 ± 3.8%, respectively. At 1 year, the primary patency rate was 83.7 ± 5.0%. Prior to the procedure, the mean EQ-5D score was 66 ± 14 and 74 ± 16 at 1 year (p = .10). Two patients died during follow-up; one patient died 33 days after the procedure because of limb ischaemia. CONCLUSION: PEB for the treatment of FP ISR is associated with a low rate of re-interventions and restenosis. Clinical improvement is maintained at 18 months.

Bone Like Arterial Calcification in Femoral Atherosclerotic Lesions: Prevalence and Role of Osteoprotegerin and Pericytes.

OBJECTIVE/BACKGROUND: Arterial calcification, a process that mimics bone formation, is an independent risk factor of cardiovascular morbidity and mortality, and has a significant impact on surgical and endovascular procedures and outcomes. Research efforts have focused mainly on the coronary arteries, while data regarding the femoral territory remain scarce. METHODS: Femoral endarterectomy specimens, clinical data, and plasma from a cohort of patients were collected prospectively. Histological analysis was performed to characterize the cellular populations present in the atherosclerotic lesions, and that were potentially involved in the formation of bone like arterial calcification known as osteoid metaplasia (OM). Enzyme linked immunosorbent assays and cell culture assays were conducted in order to understand the cellular and molecular mechanisms underlying the formation of OM in the lesions. RESULTS: Twenty-eight of the 43 femoral plaques (65%) displayed OM. OM included osteoblast and osteoclast like cells, but very few of the latter exhibited the functional ability to resorb mineral tissue. As in bone, osteoprotegerin (OPG) was significantly associated with the presence of OM (p = .04). Likewise, a high plasma OPG/receptor activator for the nuclear factor kappa B ligand (RANKL) ratio was significantly associated with the presence of OM (p = .03). At the cellular level, there was a greater presence of pericytes in OM+ compared with OM- lesions (5.59 ± 1.09 vs. 2.42 ± 0.58, percentage of area staining [region of interest]; p = .04); in vitro, pericytes were able to inhibit the osteoblastic differentiation of human mesenchymal stem cells, suggesting that they are involved in regulating arterial calcification. CONCLUSION: These results suggest that bone like arterial calcification (OM) is highly prevalent at femoral level. Pericyte cells and the OPG/RANK/RANKL triad seem to be critical to the formation of this ectopic osteoid tissue and represent interesting potential therapeutic targets to reduce the clinical impact of arterial calcification.

Treatment of TASC C and D Femoropoliteal Lesions with Paclitaxel eluting Stents: 12 month Results of the STELLA-PTX Registry.

OBJECTIVE: The aim was to evaluate the safety and the efficacy of primary stenting with paclitaxel eluting stents for TASC C and D femoropopliteal lesions. METHODS: Patients with TASC C/D de novo femoropopliteal lesions were treated by implanting paclitaxel eluting stents. Patients were included in a single center registry and prospectively followed by clinical and ultrasound evaluation. X-ray of the stented zone was systematically performed 12 months after implantation. The primary endpoint was primary sustained clinical improvement after 12 months. RESULTS: A total of 45 patients (48 limbs) suffering from claudication (25 limbs) or CLI (23 limbs) were enrolled. Lesions were either TASC C (28 limbs) or TASC D (20 limbs). The mean length of the treated segment was 252 ± 90 mm. The mean number of stents was 2.9 ± 1 (2-5). Mean follow up was 12.7 months. No patient was lost to follow up. At 1 year post procedure, primary and secondary sustained clinical improvements were 56.3 ± 7.4% and 80.1 ± 5.9% respectively. Freedom from target lesion and target extremity revascularization were 63.6% and 90.1%, respectively. Primary and secondary patency rates were 52.5% and 79.6%. One year primary sustained clinical improvement rates for TASC C/D were 63.3 ± 9.2% and 45.6 ± 11.7%, respectively (p = .34). One year primary sustained clinical improvement rates for claudication/CLI patients were 68 ± 9.3% and 41.6 ± 11.1%, respectively (p = .13). The incidence of in stent re-stenosis and in stent thrombosis were 25% and 14%, respectively. The incidence of stent fracture was 12.5% on a limb basis and 9% on a per stent basis. CONCLUSIONS: The paclitaxel eluting stent did not achieve its goal in terms of prevention of in stent re-stenosis for TASC C/D femoropopliteal lesions. It requires frequent re-interventions during the first year to maintain satisfactory clinical results.

Susceptibility Vessel Sign on MRI Predicts Favorable Clinical Outcome in Patients with Anterior Circulation Acute Stroke Treated with Mechanical Thrombectomy.

BACKGROUND AND PURPOSE: The susceptibility vessel sign on MR imaging has been reported to indicate acute occlusion from erythrocyte-rich thrombus. The purpose of this study was to evaluate the influence of the susceptibility vessel sign seen on MR imaging before treatment on the clinical outcome after mechanical thrombectomy for anterior circulation acute stroke. MATERIALS AND METHODS: We retrospectively included 73 consecutive patients who were treated for anterior circulation acute stroke by mechanical thrombectomy from December 2009 to September 2013. Each patient underwent MR imaging before mechanical thrombectomy. The presence (susceptibility vessel sign+) or absence of the susceptibility vessel sign (susceptibility vessel sign-) was recorded. Mechanical thrombectomy was performed either alone or in association with IV tPA according to the site and time after occlusion. Good functional outcome was defined by an mRS ≤ 2 at 3 months in susceptibility vessel sign+ and susceptibility vessel sign- groups. Patient clinical characteristics, initial NIHSS score and ASPECTS, site of occlusion, time between onset to groin puncture, TICI after mechanical thrombectomy, NIHSS score at day 1, and spontaneous hyperattenuation on CT at day 1 were also analyzed. RESULTS: Fifty-three patients with susceptibility vessel sign+ and 20 with susceptibility vessel sign- were included in our study. mRS ≤ 2 at 3 months occurred in 65% patients in the susceptibility vessel sign+ group and 26% in the susceptibility vessel sign- group (P = .004). On multivariate analysis, the susceptibility vessel sign was the only parameter before treatment that could predict mRS ≤ 2 at 3 months (OR, 8.7; 95% CI, 1.1-69.4; P = .04). CONCLUSIONS: Our study strongly suggests that the susceptibility vessel sign on MR imaging before treatment is predictive of favorable clinical outcome for patients presenting with anterior circulation acute stroke and treated with mechanical thrombectomy.

Incidence and the clinical impact of stent fractures after primary stenting for TASC C and D femoropopliteal lesions at 1 year.

BACKGROUND: The clinical impact of stent fractures is still controversial. This study analyzed the incidence and the clinical impact of stent fractures after stenting of long femoropopliteal lesions. METHODS: From November 2008 to October 2009, 58 patients (62 limbs) were treated in a single center with a primary nitinol self-expanding stent for Trans-Atlantic Inter-Consensus (TASC) C and D de novo femoropopliteal lesions. Patients were prospectively followed by medical and duplex scan examinations. Stent fractures were assessed by biplane X-rays at 12 months. Logistic regression analysis was performed. RESULTS: At 1 year a complete follow-up was obtained in 42 limbs/90 stents. The median length of the stented segment was 240 ± 180 cm with a mean of 2.1 (1-4) stents per patient. Sixteen stents (17.8%) were fractured: one type I (asymptomatic); seven type II (2 restenosis); five type III (asymptomatic), and three type IV stent fractures (1 restenosis). Stent diameter (p = .04) and stent implantation in the distal part of the superficial femoral artery (p = .05) were positively associated with stent fractures. Stent fracture had no influence on restenosis. CONCLUSION: This study suggests that the high stent fracture rate associated with endovascular treatment of long femoropopliteal lesions should be balanced with its low clinical impact.

One-year clinical outcome after primary stenting for Trans-Atlantic Inter-Society Consensus (TASC) C and D femoropopliteal lesions (the STELLA "STEnting Long de L'Artère fémorale superficielle" cohort).

OBJECTIVE: The study aims to evaluate the safety and the efficacy of primary stenting for Trans-Atlantic Inter-Society Consensus Document II on Management of Peripheral Arterial Disease (TASC) C and D femoropopliteal lesions. DESIGN: Prospective cohort study. METHODS: Patients with TASC C and D de novo femoropopliteal lesions were treated with the same endovascular technique by implanting a primary nitinol self-expanding stent (LifeStent(®), Bard Peripheral Vascular, Tempe, AZ, USA). Patients were included in a single-centre registry and prospectively followed up. The primary end point was primary sustained clinical improvement after 12 months. Secondary end points were secondary sustained clinical improvement, primary and secondary patency rates, freedom from target lesion revascularisation (TLR), freedom from target extremity revascularisation (TER) and stent fracture rate. RESULTS: We enrolled 58 patients (62 limbs) suffering from either claudication (40.3%) or critical limb ischaemia (59.7%). Lesions were either TASC C (62.9%) or TASC D (37.1%). Median length of the treated segment was 220 ± 160 mm. The mean number of stents was 2.2. Mean follow-up was 17 months, with one patient lost to follow-up. At 1 year, the primary end point was 68.6% while secondary sustained clinical improvement was 82.6%. Freedom from TLR and TER rates were 81.1% and 96.3%. Primary and secondary patencies were 66% and 80.9%. One-year primary and secondary sustained clinical improvement rates were 76.7% ± 7.2 for TASC C and 46.3% ± 11.1 for TASC D (p = 0.03) and 87.6% ± 5.9 for TASC C and 67.3% ± 11.3 for TASC D (p = 0.09), respectively. The ankle-brachial pressure index increased from 0.58 to 0.94 (p = 0.001) at 1 year and the incidence of in-stent restenosis (ISR) was 19.3%. Stent fracture and disconnection rate was 17.7%. CONCLUSIONS: Primary stenting of TASC C and D lesions appears to be safe and efficient given the high-sustained clinical improvement and the low rate of ISR observed in our study. Endovascular treatment of such long and severe lesions exposes to high rate of stent fractures, which should not be a concern given their low clinical impact.

Endovascular repair of common femoral artery and concomitant arterial lesions.

OBJECTIVE: The common femoral artery (CFA) is an unusual location for endovascular repair (ER). We report the early results after ER of the CFA in a single centre. DESIGN: This is a cohort study. MATERIALS/METHODS: From 2006 to 2008, ER of the CFA was proposed to 36 patients (mean age 67.9, range 51-92). CFA lesions were classified into four types: in type I, lesions were located at the iliac external artery and were extended to the CFA; in type II, lesions were limited to the CFA; in type III, lesions were located at the CFA and its bifurcation; type IV represents restenosis bypass anastomosis. All patients were treated by stenting. RESULTS: Indications for ER of the CFA included 25 patients (70%) for claudication and 11 patients (30%) for critical limb ischaemia. Forty-three stents were implanted. The mean follow-up was 22 months (range, 12-42). At 1 year, primary and secondary sustained clinical improvements were 80% and 90%; target lesion revascularisation and target extremity revascularisation free cumulative survival were 85% and 80%, respectively, and in-stent restenosis rate was 20%. One stent fracture was noted. CONCLUSIONS: ER of CFA and concomitant arterial lesions seems to be a safe technique with acceptable clinical outcome at 1 year.