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INTRODUCTION Gender-based differences in atrial fibrillation have been identified, but limited data exist for patients undergoing left atrial appendage occluder (LAAO) implantation. This study reports gender-related periprocedural and 1-year outcomes of the prospective, multicenter German left atrial appendage occlusion registry (LAARGE). METHODS LAARGE enrolled 641 patients who were scheduled for LAAO implantation from July 2014 to January 2016 in 38 hospitals in Germany. The data collected included demographics, clinical characteristics, details of implantation, and outcome. Efficacy and safety at 1-year follow-up were assessed by the occurrence of thrombembolic and bleeding events, as well as mortality. RESULTS Of 638 patients undergoing LAAO implantation 38.9% were female and 61.1% male. Females were older (76.4 ± 8.2 [females] vs. 75.6 ± 7.7 [males], p = .042) and had a higher stroke risk (CHA2 DS2 -VASc score: 4.9 ± 1.5 vs. 4.3 ± 1.5, p

Background: Transcatheter left atrial appendage closure (LAAC) is performed either in conscious sedation (CS) or general anesthesia (GA), and limited data exist regarding clinical outcomes for the two approaches. The aim of the study was to analyze the effect of CS versus GA on acute outcomes in a large patient cohort undergoing LAAC with a Watchman occluder. Methods: A cohort of 521 consecutive patients underwent LAAC with Watchman occluders at two centers (REGIOMED hospitals, Germany) between 2012 and 2018. One site performed 303 consecutive LAAC procedures in GA, and the other site performed 218 consecutive procedures in CS. The safety endpoint was a composite of major periprocedural complications and postoperative pneumonia. The efficacy endpoint was defined as device success. Results: After a 1:1 propensity score matching, 196 (CS) vs. 115 (GA) patients could be compared. In 5 (2.6%) cases CS was converted to GA. The primary safety endpoint (3.5% [CS] vs. 7.0% [GA], p = 0.18) and its components (major periprocedural complications: 2.5% vs. 3.5%, p = 0.73; postoperative pneumonia: 2.6% vs. 4.3%, p = 0.51) did not differ between the groups. Also, device success was comparable (96.9% vs. 93.9%, p = 0.24). Conclusions: In patients undergoing LAAC with the Watchman device, conscious sedation and general anesthesia showed comparable device success rates and safety outcomes. The type of anesthesia for LAAC may therefore be tailored to patient comorbidities, operator experience, and hospital logistics.

OBJECTIVES To investigate periprocedural and long-term outcome of left atrial appendage closure (LAAC) using Amplatzer occluders with respect to individual pre-procedural stroke risk. BACKGROUND LAAC is a proven strategy for prevention from stroke and bleeding in patients with nonvalvular atrial fibrillation not amenable to oral anticoagulation. Whether individual pre-procedural stroke risk may affect procedural and long-term clinical outcome after LAAC is unclear. METHODS Multicenter study of consecutive patients who underwent Amplatzer-LAAC. Using pre-procedural CHADS$_{2}$ score, outcomes were compared between a low (0-2 points) and a high stroke risk group (3-6 points). RESULTS Five hundred consecutive patients (73.9 ± 10.1 years) who underwent Amplatzer-LAAC. Two hundred and forty eight had preprocedural CHADS$_{2}$ score ≤ 2 points (low-risk group) and the remaining 252 patients had 3-6 points (high-risk group). Periprocedural complication rates (6.0% vs. 5.6%, p = .85), procedural success (LAAC without major periprocedural or device-related complications or major para-device leaks: 89.4% vs. 87.9%, p = .74), and 30-day-mortality (2.4% vs. 2.6%, p = .77) were comparable. After 1,346 patient-years (PY), the long-term composite efficacy endpoint (stroke, systemic embolism, cardiovascular, and unexplained death) was reached in 23/653 (3.5/100 PY) versus 52/693 (7.5/100 PY); HR = 2.13; 95%-CI, 1.28-3.65, p = .002) with stroke rates 67% and 68% lower than anticipated by preprocedural CHADS$_{2}$ score. Combined safety endpoint (major periprocedural complications and major, life-threatening or fatal bleedings) occurred in 22/653 (3.4/100 PY) versus 28/693 (4.0/100 PY); HR = 1.20; 95%-CI, 0.66-2.20, p = .52). CONCLUSIONS Compared with patients at low risk of stroke, LAAC with Amplatzer devices is associated with similar safety and efficacy in high-risk patients in our study.

OBJECTIVES This study compares procedural and late clinical outcomes of left atrial appendage closure (LAAC) with Amplatzer devices as a single versus a combined procedure with other structural or coronary interventions. BACKGROUND Multiple cardiac conditions are frequent among elderly patients and invite simultaneous treatment to ensure a favorable patient outcomes. METHODS 559 consecutive patients (73.3��������11.1���years) underwent LAAC with Amplatzer devices at two centres (Bern and Zurich university hospitals, Switzerland) either as a single procedure or combined with other interventions. The primary safety endpoint was a composite of major peri-procedural complications and major bleeding at follow-up, the primary efficacy endpoint included stroke, systemic embolism, and cardiovascular/unexplained death. All event rates are reported per 100 patient-years. RESULTS In 263 single and 296 combined procedures with percutaneous coronary interventions (47.6%), closure of an atrial septal defect (8.4%) or a patent foramen ovale (36.5%), transcatheter aortic valve implantation (10.1%), mitral clipping (4.1%), atrial fibrillation ablation (8.8%), or another procedure (3.0%) were analyzed. Device success (96.6% [single] vs. 99.0% [combined], p��=��.08) did not differ between the groups. After a mean follow-up of 2.6��������1.5 vs. 2.5��������1.5���years and a total of 1,422 patient-years, the primary efficacy (40/677, 5.9% [single] vs. 37/745, 5.0% [combined]; HR, 1.2, 95% CI, 0.8-1.9, p��=��.44), as well as the primary safety endpoint (25/677, 3.7% vs 28/745, 3.8%; HR, 1.0, 95% CI, 0.6-1.8, p��=��.89) were comparable. CONCLUSIONS LAAC with Amplatzer devices combined with structural, coronary, and electrophysiological procedures offers procedural feasibility and safety, as well as long-term efficacy.

Atrial fibrillation (AF) is associated with an increased risk of stroke, morbidity and overall mortality. So far, oral anticoagulation (OAC) is the standard of care for stroke prevention, either with vitamin K antagonists or with non-vitamin K oral anticoagulants (NOACs). The left atrial appendage (LAA) can be eliminated by epicardial or endocardial exclusion. Left atrial appendage closure (LAAC) represents a mechanical thromboprophylaxis - which has also been termed mechanical vaccination - against stroke, bleeding and death.Studies show that LAAC provides stroke prevention comparable to (N)OAC. Additionally, a notable reduction of bleeding events and its associated mortality is achieved by LAAC. With accruing experience and advances in patient selection, procedural planning, implantation techniques and devices, contemporary LAAC registries report high rates of success and low rates of complications.The decision to provide the most appropriate stroke prevention for patients with AF (OAC, NOAC or LAAC) needs to be individualized to patients' thromboembolic and bleeding risk and life expectancy. This review on LAAC provides an update on contemporary devices and techniques, as well as recommendations for patient selection and management.

Aims Left atrial appendage closure (LAAC) with AMPLATZER occluders is used for stroke prevention in atrial fibrillation (AF). Net clinical benefit compared to medical therapy has not been tested. The aim of this study was to test whether long-term clinical outcome after LAAC with AMPLATZER occluders may be similar to medical therapy. Methods and results Five hundred consecutive patients who underwent LAAC with AMPLATZER occluders were compared to 500 patients with medical therapy by propensity score matching. The primary efficacy endpoint was a composite of stroke, systemic embolism and cardiovascular/unexplained death. The primary safety endpoint consisted of major procedural adverse events and major bleedings. For assessment of net clinical benefit, all of the above-mentioned hazards were combined. After 2,645 patient-years at a mean follow-up of 2.7±1.5 years, the primary efficacy endpoint was reached by 75/1,342, 5.6% in the LAAC group versus 102/1,303, 7.8% per 100 patient-years (hazard ratio [HR] 0.70, 95% confidence interval [CI]: 0.53-0.95, p=0.026). The primary safety endpoint occurred in 48/1,342, 3.6% versus 60/1,303, 4.6% per 100 patient-years (HR 0.80, 95% CI: 0.55-1.18, p=0.21), and the combined hazard endpoint in 109/1,342, 8.1% versus 142/1,303, 10.9% per 100 patient-years (HR 0.76, 95% CI: 0.60-0.97, p=0.018). Patients receiving LAAC demonstrated lower rates of both all-cause and cardiovascular mortality (111/1,342, 8.3% vs 151/1,303, 11.6% per 100 patient-years [HR 0.72, 95% CI: 0.56-0.92, p=0.005] and 54/1,342, 4.0% vs 84/1,303, 6.5% per 100 patient-years [HR 0.64, 95% CI: 0.46-0.89, p=0.007]). Conclusions LAAC with AMPLATZER devices showed a net clinical benefit over medical therapy by superior efficacy, similar safety and a benefit in all-cause and cardiovascular mortality.

AIMS Acute kidney injury (AKI) remains a frequent complication after cardiac interventions, such as left atrial appendage closure (LAAC), yet limited data are available on the incidence and clinical implication of AKI in this setting. We sought to assess incidence, predictors and relevance of AKI after LAAC. METHODS AND RESULTS We retrospectively analyzed 95 LAAC patients in three European centers. AKI was defined according to the Acute Kidney Injury Network (AKIN) classification. The incidence of AKI was 13.7% with mild AKI in 92.3% and AKI stage > II in 7.7%. Total contrast volume was not linked to the occurrence of AKI (AKI: 127 ± 83 vs. no AKI: 109 ± 92 ml, p = 0.41), however increasing contrast volume (CV) to glomerular filtration rate (GFR) ratio (CV/GFR ratio) was associated with an increased risk of AKI (OR, per unit increase: 1.24, 95% CI 0.97-1.58, p = 0.08). ROC-analysis revealed a moderate predictive value of CV/GFR ratio for the prediction of AKI (AUC: 0.67, 95% CI 0.50-0.84, p = 0.05). Furthermore, AKI was associated with significantly increased mortality 6 months and 1 year after LAAC. No significant difference in the incidence of AKI was observed between patients with mere fluoroscopic and additional echocardiographic guidance (16.3% vs. 11.5%, p = 0.56). CONCLUSION Whereas mild AKI is common in patients after LAAC, severe AKI is rare. AKI after LAAC is associated with poor baseline renal function, increased doses of contrast (CV/GFR ratio) and impaired outcome. Future studies will be needed to elaborate the benefit of reducing or avoiding contrast volume regarding this endpoint.

Background Optimal antithrombotic therapy following left atrial appendage closure (LAAC) with the Watchman occluder remains uncertain. This study retrospectively compared clinical outcomes of a 3-month dual antiplatelet therapy (DAPT group) and a protocol of anticoagulation plus aspirin for 45 days followed by DAPT for 6 months (ACT group) after LAAC with the Watchman device. Methods Of two Watchman registries (Coburg and Lichtenfels hospitals, Germany), 220 and 304 consecutive patients with successful LAAC were included. Patients in Coburg hospital received DAPT while they received ACT in Lichtenfels. After a 1:1 propensity score matching, 174 (DAPT) versus 174 (ACT) patients were compared by use of the primary efficacy endpoint of thromboembolic events and cardiovascular/unexplained death, the primary safety endpoint of nonprocedural related major bleeding events at follow-up, and the combined hazard endpoint, a composite of all above-mentioned hazards. Results The mean age 77.5 ± 7.2 (DAPT) versus 77.3 ± 7.1 (ACT) years, CHA2 DS2 -VASc score 4.6 ± 1.5 versus 4.7 ± 1.6, and HAS-BLED score 3.3 ± 0.8 versus 3.3 ± 0.8 were similar. After 12 months, the clinical efficacy (13/174, 7.4% [DAPT] vs 11/174, 6.3% [ACT]; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.38-1.86; P = .66) and safety (6/174, 3.4% vs 8/174, 4.5%; HR, 0.86; 95% CI, 0.29-2.56; P = .79) as well as the combined hazard endpoint (18/174, 10.3% vs 18/174, 10.3%; HR,1.01; 95% CI, 0.53-1.95; P = .97) were comparable. Conclusions This study suggests comparable efficacy and safety of 3-month DAPT versus 6 weeks ACT plus aspirin following LAAC with the Watchman.

Background Due the wide variability of left atrial appendage morphology left atrial appendage occlusion (LAAO) remains a challenging procedure. The steerable FuStar delivery sheath was designed to allow both, transseptal access and delivery of percutaneous devices. We here report the first-in-human experience of LAAO with the FuStar sheath. Methods Twenty patients (76.6 ± 8.4 years; 12 (60%) males; CHA2 DS2 -VASc score: 5.0 ± 2) with non-valvular fibrillation and contraindications to oral anticoagulation underwent LAAO with the LAmbre device using the FuStar steerable sheath (Lifetech Scientific Corp., Shenzhen, China) at two german centers. Results Successful device implantation was achieved in all patients (100%). No periprocedural complications were observed. Procedure time, fluoroscopy time, contrast media, and radiation dose were 23.4 min ± 9.2, 11.9 min ± 4.1, 96.2 mL ± 45.7, and 2718.4 cG*cm2 ± 3835.3, respectively. Conclusion This study demonstrates the feasibility and safety of the steerable FuStar sheath for LAAO.

Introduction The LAmbre (LifeTech Scientific, Shenzhen, China) is a novel occluder for left atrial appendage closure (LAAC) in patients with atrial fibrillation. This study compares late clinical outcomes of LAmbre and the established Amplatzer devices (Abbott, St Paul, MN). Methods Between 2012 and 2018, 265 consecutive patients underwent LAAC with LAmbre and Amplatzer devices at a single center. After a 3:1 propensity score matching, 40 (LAmbre) vs 107 (Amplatzer) patients were compared by the primary efficacy endpoint of all-cause stroke, systemic embolism and cardiovascular/unexplained death, the primary safety endpoint of major periprocedural complications and major bleeding events at follow-up, and the combined hazard endpoint, a composite of all the above-mentioned hazards. Results The mean age 75.6 ± 8.9 (LAmbre) vs 75.5 ± 9.0 (Amplatzer) years, CHA2 DS2 -VASc score 4.8 ± 1.7 vs 4.8 ± 1.7 and HAS-BLED score 3.1 ± 0.9 vs 3.2 ± 0.8 were similar. After 3.6 ± 1.9 vs 2.5 ± 1.4 years, the clinical efficacy (12/146, 8.2% [LAmbre] vs 28/266, 10.5% [Amplatzer]; hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.38-1.40; P = .34) and safety (5/146, 3.4% vs 14/266, 5.3%; HR, 0.47; 95% CI, 0.14-1.6; P = .22), as well as the combined hazard endpoint (15/146, 10.3% vs 36/266, 13.6%; HR, 0.67; 95% CI, 0.36-1.25; P = .21) were comparable. Conclusion In the presented report, in patients with nonvalvular atrial fibrillation, the LAmbre offered similar long-term efficacy and safety in comparison to Amplatzer devices.

OBJECTIVES To compare long-term clinical outcomes after left atrial appendage closure with the Amplatzer Cardiac Plug (ACP) and Amulet. BACKGROUND The Amulet was designed to improve clinical outcomes of first-generation ACP. METHODS Three Amplatzer registries (Bern, Coburg, Zurich), with enrollment of patients from 2009 to 2018, were retrospectively analyzed. The primary safety endpoint was a composite of major peri-procedural complications and major bleedings, the primary efficacy endpoint included stroke, systemic embolism, and cardiovascular/unexplained death. The net clinical benefit was a combination of all above-mentioned hazards. RESULTS A total of consecutive 563 patients (344 ACP vs. 219 Amulet) with a mean follow-up of 2.9 ± 1.6 and 1.9 ± 0.9 years were included. Mean age (74.4 ± 9.9 [ACP] vs. 74.4 ± 9.1 [Amulet] years), stroke (CHA2 DS2 -VASc score 4.4 ± 1.6 vs. 4.6 ± 1.7), and bleeding risk (HAS-BLED score 3.2 ± 1.1 vs. 3.2 ± 0.9) were comparable. The primary endpoints of efficacy (72/998, 7.2% [ACP] vs. 43/417, 10.3% [Amulet]; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.44-1.02, p = .062), safety (40/998, 4.0% vs. 18/417, 4.3%; HR, 1.15; 95% CI, 0.53-2.51, p = .72), and the net clinical benefit (101/998, 10.1% vs. 55/417, 13.4%; HR, 0.73; 95% CI, 0.49-1.07, p = .11) were similar. CONCLUSION In the long term, left atrial appendage closure with first and second-generation Amplatzer devices provided similar efficacy, safety, and net clinical benefit. Clinical outcomes may be rather determined by implantation technique and hemodynamics, but not by the design modifications of the Amulet.

Aims The aim of this study was to compare the periprocedural and late clinical outcomes of left atrial appendage closure (LAAC) with AMPLATZER devices by access through transseptal puncture (TSP) versus a patent foramen ovale (PFO) or an atrial septal defect (ASD). Methods and results Between 2009 and 2018, 578 consecutive patients underwent LAAC via TSP or PFO/ASD access in three centres. After a 3:1 propensity score matching, 246 (TSP) versus 91 (PFO/ASD) patients were compared using the primary efficacy endpoint of all-cause stroke, systemic embolism and cardiovascular/unexplained death and the primary safety endpoint of major periprocedural complications and major bleedings at follow-up. Mean age was 75.2±8.7 (TSP) vs 74.4±10.9 (PFO/ASD) years, CHA2DS2-VASc score 4.5±1.6 vs 4.3±1.4 and HAS-BLED score 3.3±1.0 vs 3.3±0.9. Device success (97.6% vs 97.8%, p=0.90) was similar. After 2.5±1.4 vs 2.6±1.6 years, clinical efficacy (46/603, 7.6% [TSP] vs 21/233, 9.0% [PFO/ASD], hazard ratio [HR] 1.2; 95% confidence interval [CI]: 0.69-0.85, p=0.54) and safety (24/603, 4.0% vs 11/233, 4.7%; HR 1.4; 95% CI: 0.52-3.6, p=0.49) did not differ. Conclusions Use of a PFO/ASD access for LAAC with AMPLATZER devices offers similar periprocedural and late clinical outcomes to TSP. Simultaneous PFO/ASD closure for an additional protective benefit does not increase risk.

Aims This study compares clinical outcomes of Watchman vs. Amplatzer devices for left atrial appendage closure (LAAC). Methods and results Of two real-world registries, the Watchman registry Lichtenfels, Germany, and the Amplatzer registry Bern-Zurich, Switzerland, 303 and 333 consecutive patients, respectively, were included. After a 1:1 propensity score matching, 266 vs. 266 patients were compared by use of the predefined primary efficacy endpoint of stroke, systemic embolism and cardiovascular/unexplained death, the primary safety endpoint of major peri-procedural complications and major bleeding events at follow-up, and the combined hazard endpoint, a composite of all above-mentioned hazards. Mean age was 75.3 ± 7.8 (Watchman) vs. 75.1 ± 9.9 (Amplatzer) years, CHA2DS2-VASc score 4.5 ± 1.7 vs. 4.5 ± 1.5, and HAS-BLED score 3.2 ± 1.0 vs. 3.2 ± 1.0. At a mean follow-up of 2.4 ± 1.3 vs. 2.5 ± 1.5 years and 1.322 patient-years, the primary endpoints of efficacy [40/646, 6.2% [Watchman] vs. 43/676, 6.4% [Amplatzer]; hazard ratio (HR), 1.02; 95% confidence interval (CI), 0.66–1.58; P = 0.92] and safety (33/646, 5.1% vs. 30/676, 4.4%; HR, 0.57; 95% CI, 0.29–1.11; P = 0.10), as well as the combined hazard endpoint (69/646, 10.7% vs. 66/676, 9.8%; HR, 0.80; 95% CI, 0.55–1.12; P = 0.26) were similar for both groups. Conclusion This study suggests comparable efficacy and safety of the Watchman and Amplatzer devices.

Left Atrial Appendage Closure With the New Occlutech® DeviceAims Percutaneous left atrial appendage closure (LAAC) is a valuable treatment option for stroke prevention in patients with atrial fibrillation and a HAS-BLED-Score ≥3. Determinants of procedural safety events and neurological outcome of the patients with the Occlutech device (OD) are not established yet. Methods and Results Between 2012 and 2016, 30 patients underwent LAAC using the OD. This is a prospective study. Neurological examination and transesophageal echocardiography was performed directly before and after the procedure and after 1, 3, and 12 months. The OC was successfully implanted in 28 of the 30 enrolled patients (93%). Two patients presented a hemodynamic relevant pericardial effusion. A leak

We here report the first European experience with the novel LAmbre left atrial appendage (LAA) occluder, a self-expanding device consisting of an umbrella and a cover connected by a central waist.A total of 60 patients (74.4 ± 8.3 years; 66.7% men; CHA2DS2-VASc: 4.0 ± 1.6, HAS-BLED score: 3.2 ± 1.3) with atrial fibrillation and contraindications to oral anticoagulation underwent left atrial appendage occlusion (LAAO) with the LAmbre device at two German centers between November 2013 and September 2015. Device success defined as correct placement of the device was achieved in all patients (100%). Resizing of the device was necessary in 3 (5%) patients. Device-related complications included 2 (3.3%) pericardial effusions on day 8 and 33 after the index procedure requiring pericardiocentesis. Transesophageal echocardiography at 6 months showed complete sealing of the LAA (residual jet flow of5 mm) in 51/54 (94.4%) patients. No device-related thrombus was documented. At 12 months transient ischemic attack was observed in 1 patient (1.6%) and minor bleeding in 3 patients (5%).Although minimizing procedure-related complications remains challenging, LAAO with the LAmbre showed high device success and good mid-term performance regarding prevention of stroke and bleeding.

Background: The Amplatzer Amulet (St. Jude Medical, Minneapolis, MN, USA) is a second gen­eration Amplatzer device for left atrial appendage (LAA) occlusion (LAAO) for stroke prophylaxis in patients with atrial fibrillation. This research sought to assess the clinical performance of the Amplatzer Amulet device and in follow up for 12 months. Methods: In this single-center registry patients with atrial fibrillation and contraindication to oral anticoagulation underwent LAAO with the Amplatzer Amulet device. Follow-up was performed before discharge, by transesophageal echocardiography (TEE) after 6 weeks and telephone interview after 3, 6 and 12 months. Results: Between October 2014 and August 2015 50 patients (76.1 ± 8.3 years; 30 male) were en­rolled. Procedural success was achieved in 49 (98%) patients. Major periprocedural adverse events were observed in 4 (8%) of patients: 1 device embolization, 2 pericardial effusions requiring pericardiocente­sis and 1 prolonged hospital stay due to retropharyngeal hematoma from the TEE probe. Follow-up TEE was available in 38 of 50 patients showing complete LAA sealing in all. 2 device-related thrombi were also documented. At 12-month follow-up 7 patients had died unrelated to the device. Ischemic stroke occurred in 3 patients. According to neurological examination two were classified as microangiopathic and not cardio-embolic. The other one could not be classified. Bleeding complications (5 minor, 3 major) were documented in 8 patients. Conclusions: Although minimizing procedure-related complications remains challenging, LAAO with the Amplatzer Amulet device showed high procedural success and excellent LAA sealing. (Cardiol J 2017; 24, 2: 131–138)

Aims The best strategy for stenting in bifurcations remains unclear. Szabo et al described a technique for accurate stent placement in bifurcations 010-001 or in aorto-ostial lesions. Its feasibility has been validated in animal models and small clinical series, but its safety and procedural results have never been compared to conventional positioning. Methods and results In a retrospective search, 257 out of 2,596 intervened lesions corresponded to Medina 010 (108, 42.0%)/001 (66, 25.7%) bifurcations or aorto-ostial lesions (83, 32.3%). Szabo was the initial choice in 78. Crude analysis showed significant differences between groups in several control variables, that disappeared after propensity score matching. Cross-over occurred in nine (11.7%) Szabo cases vs. no case in the conventional group. Two independent blinded investigators evaluated the angiographic result immediately after stent deployment. Szabo reduced the incidence of stent malpositioning (6.4% vs. 41.0%, p=0.000001), protrusion in the non-stented vessel/aorta (6.4% vs. 34.6%, p=0.00003) and incomplete scaffolding of the plaque (0.0% vs. 7.7%, p=NA). No significant differences regarding complications, procedural success or procedural complexity were observed after 30 days follow-up. Conclusions The Szabo technique reduces the incidence of angiographic malpositioning in Medina 010/001 bifurcations and aorto-ostial lesions, without increasing procedural complications.

AIMS Endothelial destruction and calcification primarily occur at the aortic side of the calcified aortic valves (AVs). This study investigated whether degenerative AV stenosis (AS) is associated with the presence of valvular endothelial senescence and a reduction in the number and function of endothelial progenitor cells (EPCs). METHODS AND RESULTS Fifteen patients with severe AS and 18 age-matched control subjects were enrolled. Senescence-associated beta-galactosidase activity was mostly localized on the valvular endothelial cells (ECs) of the explanted AVs and highly coincided with the calcified lesion at the aortic side. The number (9.3 +/- 8.3 vs. 20.5 +/- 9.0 cells per 10(6) mononuclear cells; P < 0.01) and the migratory capacity (107.8 +/- 54.6 vs. 185.0 +/- 68.8 cells per 1000 cells; P < 0.01) of EPCs evaluated by FACS analysis or migration assay were significantly reduced in AS when compared with control. As possible mechanisms of alterations in EPCs, caspase-3 activity was significantly increased, whereas telomere-repeating factor-2 expression quantified by western blot was significantly reduced in EPCs from AS when compared with control. CONCLUSION Reduced regenerative capacity of valvular ECs due to senescence and decreased levels of EPCs might be, at least in part, a pathological link for the destruction of valvular ECs, resulting in progression of degenerative AS.