Sinisa Markovic

Prospective randomised trial evaluating a paclitaxel-coated balloon in patients treated with endothelial progenitor cell capturing stents for de novo coronary artery disease

Background Percutaneous coronary intervention with stent implantation is limited by the occurrence of re-stenosis and the risk of stent thromboses. Objective To define the impact of paclitaxel-coated balloon angioplasty plus endothelial progenitor cell capturing (EPC) stent implantation in de novo coronary artery disease. This combination may reduce neointimal proliferation within the EPC stent and address the risk of stent thrombosis by facilitating rapid endothelialisation. Methods In this prospective single-blind multicentre randomised trial, 120 patients with a de novo lesion in a native coronary artery were randomly assigned to undergo treatment with paclitaxel-coated balloon plus EPC stent or EPC stent alone. Dual antiplatelet therapy was prescribed for 3 months. Angiographic follow-up was scheduled at 6 months. The primary endpoint was in-stent late lumen loss. The secondary clinical endpoint was a composite of death from a cardiac cause, myocardial infarction attributed to the target vessel or target lesion revascularisation. Results There was no difference in patient baseline characteristics or procedural results. The angiographic follow-up rate was 96%. Treatment with paclitaxel-coated balloon plus EPC stent was superior to EPC stent alone, with an in-stent late loss of 0.34±0.45 mm versus 0.88±0.48 mm (p<0.001). The re-stenosis rate was reduced from 23.2% to 5.1% (p=0.006) and the clinical endpoint was reduced from 17.2% to 4.8% (p=0.039). There was no definite or probable stent thrombosis. Conclusions Paclitaxel-coated balloon plus EPC stent implantation is superior to EPC stent implantation alone for treatment of de novo coronary artery disease. Trial registration NCT00732953.

Transfemoral aortic valve implantation with the repositionable Lotus valve compared with the balloon-expandable Edwards Sapien 3 valve

BACKGROUND The rate of paravalvular aortic insufficiency (AI) with transcatheter aortic valve implantation (TAVI) with first generation devices was higher compared with surgical replacement. Residual AI after TAVI has been linked to an increased mortality rate. We compared two second generation TAVI devices - the repositionable Lotus valve with the balloon-expandable Edwards Sapien 3 valve - regarding procedural and 30 day outcome. METHODS AND RESULTS In 78 patients with severe aortic stenosis undergoing transfemoral TAVI we evaluated post-procedural paravalvular AI, device success and early safety according to VARC criteria. Valve size was based on a 256-multislice computed tomography. Patients were followed for 30 days. The Lotus valve (N = 26) and the Edwards Sapien 3 valve (N = 52) were implanted under fluoroscopic guidance. Baseline characteristics were similar between groups. Perimeter derived annulus diameter did not differ with 25.7 ± 1.6mm for Lotus and 25.2 ± 2.1mm for Edwards Sapien 3 patients. After TAVI aortography and transthoracic echocardiography revealed no moderate or severe AI. The rate of mild AI was 12% for Lotus and 15% for Edwards Sapien 3 (p = 0.62). There were no deaths, stroke, annulus rupture or coronary obstruction. Device success was 96% and 98% (p = 0.61), early safety according to VARC 11.5% in both groups (p = 1.0) and the need for pacemaker implantation 27% and 4% (p < 0.003), respectively. CONCLUSIONS TAVI with second-generation devices was associated with no moderate or severe AI and a low rate of mild AI. Device success was high for Lotus and Edwards Sapien 3 while the need for permanent pacemaker was significantly higher with the Lotus valve.

Standardized radial approach reduces access site complications: a prospective observational registry.

ObjectivesThe aim of this study was to evaluate the occurrence of complications by Doppler sonography after radial access for cardiac catheterization in a prospective observational registry. BackgroundThe radial approach for cardiac catheterization is being used with increasing frequency. In randomized trials, the risk of bleeding was lower with radial access compared with femoral access. However, there are still concerns in terms of the radial access because of reported high rates of radial artery occlusion (RAO) up to 30%. Materials and methodsIn this prospective observational registry, a total of 369 procedures were performed using a standardized radial approach in terms of sheath size, anticoagulation, and postinterventional hemostasis. The rates of RAO, hematoma, and vascular complications were assessed the day after catheterization. ResultsA diagnostic procedure was performed in 25.7% and a coronary intervention in 74.3% of patients. Sheath size was 5 Fr in 12.2% (N=45) or 6 Fr in 87.8% (N=324). Doppler sonography showed RAO in 3.8% (N=14/369), with no difference between the 5- and the 6-Fr sheath (2.2 vs. 4.0%, P=0.56). A hematoma of 5 cm or more was documented after two (0.5%) procedures. There was no need for any blood transfusion or surgery. A small hematoma (every hematoma <5 cm) was observed in 16.0% (N=59). There was no statistical difference in the frequency of RAO, hematoma, or vascular complications between procedures performed with 5-Fr or less or 6-Fr sheaths and the use of dual antiplatelet therapy or oral anticoagulation. ConclusionRadial access for coronary catheterization is effective and safe. With a standardized approach, the rates of bleeding events and RAOs are low.

Efficacy of different devices for transcatheter closure of patent foramen ovale assessed by serial transoesophageal echocardiography and rates of recurrent cerebrovascular events in a long-term follow-up.

AIMS Closure of patent foramen ovale (PFO) is non-inferior to medical treatment for patients with cryptogenic stroke. Results in randomised trials might be based on the different types of used occluders. We determined residual shunting with serial contrast transoesophageal echocardiography (cTEE) and evaluated rates of recurrent cerebrovascular events in a long-term follow-up. METHODS AND RESULTS cTEE was repeated three and 12 months after PFO closure using AMPLATZER (n=109), BioSTAR (n=68), Cardia (n=104) or Premere (n=54) occluders. Closure was demonstrated in 91.6% and 95.9% of patients after three and 12 months. Closure rates were not different among groups (p=0.58; p=0.94). The PFO diameter was a risk factor for residual shunting (p=0.02), but not the prevalence of an atrial septal aneurysm (ASA). During follow-up, including 1,815 patient-years (PY), eight patients suffered a stroke (0.44/100 PY) and seven patients a transient ischaemic attack (0.39/100 PY). Rates of recurrent cerebrovascular events were similar among the four groups. CONCLUSIONS Closure at three or 12 months (as measured by cTEE) and rates of recurrent cerebrovascular events were similar among occluder groups. PFO diameter was a risk factor for residual shunting, but not the presence of ASA. The rate of recurrent cerebral ischaemic events was low.

Everolimus-eluting stents compared with paclitaxel-eluting stents for treatment of coronary in-stent restenoses

BACKGROUND Everolimus-eluting stent (EES) implantation was superior to paclitaxel-eluting stent (PES) implantation for treatment of de-novo coronary artery disease. We evaluated the outcome of EES compared with PES for treatment of restenosis in bare-metal and drug-eluting stents (DES). METHODS AND MATERIALS In a prospective observational study patients with in-stent restenosis (ISR) were treated with EES (N=91) or PES (N=107). Dual antiplatelet therapy was given for 6 months. Patients were scheduled for 6 months angiographic follow-up and 24 months clinical follow-up. Primary outcome measure was the occurrence of major adverse cardiac events (MACE) defined as a composite of cardiac death, any myocardial infarction and target lesion revascularization (TLR). RESULTS Baseline data showed some differences between groups including frequency of DES restenosis, length of stented segment and reference vessel diameter. For EES versus PES occurrence of MACE (18.7% vs. 15.0%, p=0.48) and need for TLR did not differ (13.2% vs. 9.3%, p=0.39). In-stent late loss was similar with 0.20±0.39 mm for EES and 0.18±0.31mm for PES (p=0.34). Binary angiographic restenosis rate for the total segment was 18.0% and 16.7% (p=0.85), respectively. In multivariable analysis the stented length (p=0.014), minimal lumen diameter post stenting (p<0.01) and repeated restenosis (p<0.001) were risk factors for a higher late loss but not type of DES or presence of diabetes mellitus. CONCLUSIONS In this observational registry treatment of DES and BMS restenosis with EES versus PES implantation resulted in similar clinical and angiographic outcome.

Improvement of regional and global left ventricular function in magnetic resonance imaging after recanalization of true coronary chronic total occlusions

BACKGROUND Successful recanalization of true chronic total occlusion (CTO) has been linked to a decrease in cardiac mortality. We evaluated the effect of CTO recanalization on LVEF and regional wall motion using paired cardiac magnetic resonance imaging (cMRI) studies. METHODS AND RESULTS 43 patients underwent contrast enhanced cMRI prior to and 9 months after successful recanalization of a true CTO defined as thrombolysis in myocardial infarction flow 0 and duration of occlusion of more than 3 months. Regional wall motion was analyzed using the AHA model. For each segment the wall thickness (WT) was measured over the duration of one heart cycle and segmental wall thickening (SWT) was calculated. Left ventricular ejection fraction (LVEF) and volumes were measured. LVEF significantly increased by 2.4 ± 6.0% (p = 0.01). The increase was confined to patients with baseline LVEF below the median of 49.3% (4.1 ± 7.0%, p = 0.01) compared to 0.6 ± 4.0 (p = 0.48) in patients with baseline LVEF higher than the median. Segmental wall motion analysis was performed in 706 myocardial segments. SWT significantly increased in segments within the perfusion territory of the CTO vessel (5.1 ± 30.4%, p = 0.01), especially in dysfunctional segments at baseline with SWT(init) <45% (13.3 ± 24.3%, p < 0.001). In addition, SWT significantly increased in segments of non-CTO vessels (4.1 ± 32.1%, p < 0.01). CONCLUSIONS In conclusion, in patients with successful recanalization of CTO left ventricular ejection fraction and regional wall motion are significantly improved, especially in patients with decreased LVEF and in dysfunctional segments.

Bioresorbable polymer sirolimus-eluting coronary stent compared with permanent polymer everolimus-eluting coronary stent implantation for treatment of small vessel coronary artery disease: CENTURY II trial

AIMS CENTURY II is a prospective, multicentre, randomised, single-blind trial comparing the bioresorbable polymer sirolimus-eluting Ultimaster® stent (BP-SES) with the permanent polymer everolimus-eluting XIENCE stent (PP-EES). Here we present a pre-specified analysis of safety and efficacy outcomes in a subgroup of patients with small vessel coronary artery disease. METHODS AND RESULTS CENTURY II included 525 patients with lesions of reference diameter ≤2.5 mm. Treatment was randomly assigned: 277 patients received BP-SES (399 lesions) and 248 patients received PP-EES (377 lesions). The primary outcome was target lesion failure (TLF), which is a composite of cardiac death, target vessel-related myocardial infarction (MI) and target lesion revascularisation (TLR). There was no significant difference between treatment groups in baseline or procedural data. Mean pre-procedural reference diameter was similar (BP-SES 2.30±0.40 mm, PP-EES 2.31±0.42 mm, p=0.59). Stented length was 24.0±11.7 mm for BP-SES and 23.5±11.5 mm for PP-EES (p=0.45). At 12 months, there was no significant difference between the BP-SES and PP-EES groups in TLF (6.9% vs. 7.7%; p=0.72), cardiac death (1.1% vs. 1.2%; p=0.90), target vessel MI (1.8% vs. 3.2%; p=0.30), TLR (4.0% vs. 5.7%; p=0.37), or definite or probable stent thrombosis (0.7% vs. 1.2%; p=0.57). CONCLUSIONS In the large-scale, randomised CENTURY II trial, use of BP-SES and PP-EES for the treatment of small vessel coronary artery disease resulted in similar outcomes at 12 months.

Paclitaxel-coated balloon plus bare-metal stent for de-novo coronary artery disease: final 5-year results of a randomized prospective multicenter trial.

BackgroundThe PERfECT Stent Study compared paclitaxel-coated balloon (PCB) angioplasty plus bare-metal stent (BMS) implantation with BMS alone in de-novo lesions in native coronary artery disease. Angiographic follow-up after 6 months showed the superiority of the additional PCB. We evaluated a potential late catch-up phenomenon with the use of PCB. Methods and resultsIn the prospective, multicenter, single-blind, randomized PERfECT Stent trial, 120 patients were assigned to either PCB angioplasty plus BMS implantation or BMS alone. For BMS, the endothelial progenitor cell capturing stent was used. Dual antiplatelet therapy was recommended for 3 months. The clinical endpoint for 5-year follow-up was a composite of cardiac death, myocardial infarction attributed to the target vessel, or target lesion revascularization. The follow-up rate after 5 years was 97%. Baseline and procedural characteristics did not differ. At the 5-year follow-up, clinically driven target lesion revascularization was 23.2% in the BMS group versus 15% with PCB plus BMS (P=0.26). The clinical endpoint (major adverse cardiac event) was 30.4% with BMS and with 23.5% lower with PCB plus BMS. No definite or probable stent thrombosis was found in either group with a dual antiplatelet therapy for 3 months for the total period. ConclusionPCB angioplasty plus BMS was superior to BMS alone for the treatment of de-novo lesions. The combined clinical endpoint was lower with PCB plus BMS at 6 months and remained lower after 5 years. There was no late catch-up phenomenon (http://www.clinicaltrials.gov; NCT 00732953).

Angiographic patterns of drug-eluting stent restenosis after treatment with drug-coated balloon versus balloon angioplasty: Late lumen loss subgroup analyses of the PEPCAD-DES study.

This report provides the results of additional late lumen loss (LLL) analyses the predefined subgroup of diabetics and post hoc analyses of selected lesion morphologies to further elucidate the efficacy of paclitaxel coated balloon (PCB) angioplasty (clinical trials identifier NCT00998439).

Long‐term clinical results of bioresorbable absorb scaffolds using the PSP‐technique in patients with and without diabetes

OBJECTIVES We evaluated clinical results up to 36 months after implantation of Absorb BVS using PSP-technique and compared the outcome of patients with and without diabetes mellitus. BACKGROUND Absorb II demonstrated that interventional treatment of coronary artery disease with bioresorbable vascular scaffolds (BVS) without proper PSP-technique (pre-dilation, proper sizing, and post-dilation) is associated with an increased thrombotic risk, even in simple lesions. METHODS In this prospective study 319 patients with 420 lesions were enrolled and treated with the Absorb BVS. Pre-dilation was mandatory and post-dilation with a high-pressure balloon was performed in patients with a scaffold length >12 mm. Patients were clinically followed up to 3 years. Primary outcome measure was the device-oriented endpoint (DoCE) defined as cardiac death, myocardial infarction not clearly related to a non-target vessel and target lesion revascularization. RESULTS DoCE was 5.0%, 7.1%, and 10.0% after 12, 24, and 36 months for the total population. Rate of scaffold thrombosis was 0.5%, 0.8%, and 1.4% after 12, 24, and 36 months. Rate of DoCE was higher in the diabetic subgroup with 9.1%, 12.6%, and 12.9% after 12, 24, and 36 months compared with 4.0% (P = 0.13), 5.6% (P = 0.05), and 9.9% (P = 0.20) in patients without diabetes mellitus. CONCLUSIONS Patients treated with the Absorb BVS using the PSP-technique show good results up to 3 years with a low rate of scaffold thrombosis. Patients suffering from diabetes mellitus have an increased rate of DoCE compared with non-diabetic patients. CLINICAL TRIAL REGISTRATION clinicaltrials.gov_NCT02162056.