Ulrich Gerckens

TAXUS I Six- and Twelve-Month Results From a Randomized, Double-Blind Trial on a Slow-Release Paclitaxel-Eluting Stent for De Novo Coronary Lesions

Background—The TAXUS NIRx stent (Boston Scientific Corp) provides local delivery of paclitaxel via a slow-release polymer coating. The TAXUS I trial was the first in-human experience evaluating safety and feasibility of the TAXUS NIRx stent system compared with bare NIR stents (control) (Boston Scientific Corp) for treatment of coronary lesions. Methods and Results—The TAXUS I trial was a prospective, double-blind, three-center study randomizing 61 patients with de novo or restenotic lesions (≤12 mm) to receive a TAXUS (n=31) versus control (n=30) stent (diameter 3.0 or 3.5 mm). Demographics, lesion characteristics, clinical outcomes were comparable between the groups. The 30-day major adverse cardiac event (MACE) rate was 0% in both groups (P =NS). No stent thromboses were reported at 1, 6, 9, or 12 months. At 12 months, the MACE rate was 3% (1 event) in the TAXUS group and 10% (4 events in 3 patients) in the control group (P =NS). Six-month angiographic restenosis rates were 0% for TAXUS versus 10% for control (P =NS) patients. There were significant improvements in minimal lumen diameter (2.60±0.49 versus 2.19±0.65 mm), diameter stenosis (13.56±11.77 versus 27.23±16.69), and late lumen loss (0.36±0.48 versus 0.71±0.48 mm) in the TAXUS group (all P <0.01). No evidence of edge restenosis was seen in either group. Intravascular ultrasound analysis showed significant improvements in normalized neointimal hyperplasia in the TAXUS (14.8 mm3) group compared with the control group (21.6 mm3) (P <0.05). Conclusions—In this feasibility trial, the TAXUS slow-release stent was well tolerated and showed promise for treatment of coronary lesions, with significant reductions in angiographic and intravascular ultrasound measures of restenosis.

Percutaneous Implantation of the CoreValve Self-Expanding Valve Prosthesis in High-Risk Patients With Aortic Valve Disease The Siegburg First-in-Man Study

Background— The morbidity and mortality of surgical aortic valve replacement are increased in elderly patients with multiple high-risk comorbid conditions. Therefore, a prospective, single-center, nonrandomized study was performed in high-risk patients with aortic valve disease to evaluate the feasibility and safety of percutaneous implantation of a novel self-expanding aortic valve bioprosthesis (CoreValve). Methods and Results— Symptomatic high-risk patients with an aortic valve area <1 cm2 were considered for enrollment. CoreValve implantation was performed under general anesthesia with extracorporeal support using the retrograde approach. Clinical follow-up and transthoracic echocardiography were performed after the procedure and at days 15 and 30 after device implantation to evaluate short-term patient and device outcomes. A total of 25 patients with symptomatic aortic valve stenosis (mean gradient before implantation, 44.2±10.8 mm Hg) and multiple comorbidities (median logistic EuroScore, 11.0%) were enrolled. Device success and procedural success were achieved in 22 (88%) and 21 (84%) patients, respectively. Successful device implantation resulted in a marked reduction in the aortic valve gradients (mean gradient after implantation, 12.4±3.0 mm Hg; P<0.0001). The mean aortic regurgitation grade was unchanged. Major in-hospital cardiovascular and cerebral events occurred in 8 patients (32%), including mortality in 5 patients (20%). Among 18 patients with device success surviving to discharge, no adverse events occurred within 30 days after leaving the hospital. Conclusions— Percutaneous implantation of the self-expanding CoreValve aortic valve prosthesis in high-risk patients with aortic stenosis with or without aortic regurgitation is feasible and, when successful, results in marked hemodynamic and clinical improvement.

Procedural and 30-day outcomes following transcatheter aortic valve implantation using the third generation (18 Fr) corevalve revalving system: results from the multicentre, expanded evaluation registry 1-year following CE mark approval

AIMS To describe the procedural performance and 30-day outcomes following implantation using the 18 Fr CoreValve Revalving System (CRS) as part of the multicentre, expanded evaluation registry, 1-year after obtaining CE mark approval. METHODS AND RESULTS Patients with symptomatic severe aortic stenosis and logistic Euroscore > or =15%, or age > or =75 years, or age > or =65 years associated with pre-defined risk factors, and for whom a physician proctor and a clinical specialist were in attendance during the implantation and who collected the clinical data, were included. From April 2007, to April 2008, 646 patients with a mean age of 81 +/- 6.6 years, mean aortic valve area 0.6 +/- 0.2 cm2, and logistic EuroSCORE of 23.1 +/- 13.8% were recruited. After valve implantation, the mean transaortic valve gradient decreased from 49.4 +/- 13.9 to 3 +/- 2 mmHg. All patients had paravalvular aortic regurgitation < or = grade 2. The rate of procedural success was 97%. The procedural mortality rate was 1.5%. At 30 days, the all-cause mortality rate (i.e, including procedural) was 8% and the combined rate of death, stroke and myocardial infarction was 9.3%. CONCLUSIONS The results of this study demonstrate the high rate of procedural success and a low 30-day mortality in a large cohort of high-risk patients undergoing transcatheter aortic valve implantation (TAVI) with the CRS.

Transcatheter aortic valve implantation: first results from a multi-centre real-world registry

AIMS Treatment of elderly symptomatic patients with severe aortic stenosis and co-morbidities is challenging. Transcatheter aortic valve interventions [balloon valvuloplasty and transcatheter aortic valve implantation (TAVI)] are evolving as alternative treatment options to surgical valve replacement. We report the first results of the prospective multi-centre German Transcatheter Aortic Valve Interventions-Registry. METHODS AND RESULTS Between January 2009 and December 2009, a total of 697 patients (81.4 ± 6.3 years, 44.2% males, and logistic EuroScore 20.5 ± 13.2%) underwent TAVI. Pre-operative aortic valve area was 0.6 ± 0.2 cm² with a mean transvalvular gradient of 48.7 ± 17.2 mmHg. Transcatheter aortic valve implantation was performed percutaneously in the majority of patients [666 (95.6%)]. Only 31 (4.4%) procedures were done surgically: 26 (3.7%) transapically and 5 (0.7%) transaortically. The Medtronic CoreValve™ prosthesis was used in 84.4%, whereas the Sapien Edwards™ prosthesis was used in the remaining cases. Technical success was achieved in 98.4% with a post-operative mean transaortic pressure gradient of 5.4 ± 6.2 mmHg. Any residual aortic regurgitation was observed in 72.4% of patients, with a significant aortic insufficiency (≥Grade III) in only 16 patients (2.3%). Complications included pericardial tamponade in 1.8% and stroke in 2.8% of patients. Permanent pacemaker implantation after TAVI became necessary in 39.3% of patients. In-hospital death rate was 8.2%, and the 30-day death rate 12.4%. CONCLUSION In this real-world registry of high-risk patients with aortic stenosis, TAVI had a high success rate and was associated with moderate in-hospital complications. However, careful patient selection and continued hospital selection seem crucial to maintain these results.

Incidence and Predictors of Drug-Eluting Stent Thrombosis During and After Discontinuation of Thienopyridine Treatment

Background— The need for prolonged aspirin and thienopyridine therapy and the risk of stent thrombosis (ST) remain as drawbacks associated with drug-eluting stents. Methods and Results— A prospective observational cohort study was conducted between June 2002 and January 2004 on 3021 patients consecutively and successfully treated in 5389 lesions with drug-eluting stents. Detailed patient information was collected on antiplatelet therapy. We analyzed the incidence of ST throughout the 18-month follow-up period and its relationship with thienopyridine therapy. ST occurred in 58 patients (1.9%) at 18 months. Forty-two patients (1.4%) experienced the event within 6 months of stent implantation. Acute myocardial infarction (fatal or nonfatal) occurred in 46 patients (79%) and death in 23 patients (39%) with ST. The median interval from discontinuation of thienopyridine therapy to ST was 13.5 days (interquartile range 5.2 to 25.7 days) for the first 6 months and 90 days (interquartile range 30 to 365 days) between 6 and 18 months. On multivariable analysis, the strongest predictor for ST within 6 months of stenting was discontinuation of thienopyridine therapy (hazard ratio, 13.74; 95% CI, 4.04 to 46.68; P<0.001). Thienopyridine discontinuation after 6 months did not predict the occurrence of ST (hazard ratio, 0.94; 95% CI, 0.30 to 2.98; P=0.92). Conclusions— Discontinuation of thienopyridine therapy was the major determinant of ST within the first 6 months, but insufficient information is available to determine whether there is benefit in continuing a thienopyridine beyond 6 months.

Aortic regurgitation after transcatheter aortic valve implantation: incidence and early outcome. Results from the German transcatheter aortic valve interventions registry

Background Significant aortic regurgitation (AR) is rare following surgical aortic valve replacement and has been associated with worse outcome. Following transcatheter aortic valve implantation (TAVI), AR is common, but little is known about its determinants and its effect on clinical outcome. Objective To evaluate early outcome and risk factors possibly associated with AR after TAVI. Methods Data were analysed from 690 patients with severe aortic stenosis treated with TAVI enrolled in the prospective multicentre German transcatheter aortic valve interventions registry. The occurrence of AR was evaluated angiographically after device deployment and removal of the catheter and guidewire. Significant AR was defined as AR≥2/4. Results The study populations mean age was 81.4±6.3 years and men represented 44%. The mean logistic Euroscore was 20.4±13.1%. Overall, 84% of patients received the Medtronic CoreValve system and 16% received the Edwards Sapien valve. Significant AR occurred in 119 patients (17.2%). Factors independently associated with significant AR were aortic valve area (adjusted OR=0.10), annulus measurement by transoesophageal echocardiography (adjusted OR=1.94), male gender (adjusted OR=1.80), cardiogenic shock (adjusted OR=1.94) and renal failure (adjusted OR=0.53). In-hospital death rates were significantly higher in patients with significant AR than in those with no/mild AR (15.1% vs 6.7%, OR=2.50, 95% CI 1.37 to 4.55), as were rates of low cardiac output (20% vs 4.4%) and respiratory failure (16.5% vs 7.1%). Using multivariate analysis, the presence of post-procedural AR≥2/4 remained a strong independent predictor of in-hospital death (adjusted OR=2.43, 95% CI 1.22 to 4.85). Conclusion Significant AR after TAVI is common and is associated with increased in-hospital mortality. Long-term follow-up is critical to further define the impact of residual AR on clinical outcome. Until these data become available, every effort should be made to prevent and treat this complication.

Progress and Current Status of Percutaneous Aortic Valve Replacement: Results of Three Device Generations of the CoreValve Revalving System

Background—Percutaneous aortic valve replacement is a new emerging technology for interventional treatment of severe aortic valve stenosis in surgical high-risk patients. This study was intended to provide a summary of the development and current safety and efficacy status of the self-expanding CoreValve Revalving prosthesis. Method and Results—Between 2005 and 2008, we have enrolled 136 consecutive patients with percutaneous aortic valve replacement using the CoreValve prosthesis. In this prospective nonrandomized, single-center trial, we analyzed procedural outcome, complications and clinical status up to 1 year. First, second, and third generation of the CoreValve prosthesis were implanted in 10, 24, and 102 consecutive high-risk patients (logistic EuroScore: 23.1±15.0%) with severe symptomatic aortic valve stenosis. Mean transvalvular pressure gradient was 41.5±16.7 mm Hg. The procedural success rate increased from generation 1/2 to 3 from 70.0%/70.8% to 91.2% (P=0.003). The 30-day combined rate of death/stroke/myocardial infarction was 40.0%/20.8%/14.7% (P=0.11) for generation 1, 2, and 3, with no procedural death in generation 3. Pressure gradients improved significantly with a final mean gradient of 8.1±3.8 mm Hg. Overall functional status assessed by New York Heart Association class improved from 3.3±0.5 (pre) to 1.7±0.7 (post) (P<0.001) and remained stable in the follow-up. Conclusion—In experienced hands, percutaneous aortic valve replacement with the CoreValve system for selected patients with severe aortic valve stenosis has a high acute success rate associated with a low periprocedural mortality/stroke rate as well as remarkable clinical and hemodynamic improvements, which persist over time. Additional studies are now required to confirm these findings, particularly head-to-head comparisons with surgical valve replacement in different risk populations.

First report on a human percutaneous transluminal implantation of a self-expanding valve prosthesis for interventional treatment of aortic valve stenosis.

Background: Percutaneous aortic valve replacement is a new technology for the treatment of patients with significant aortic valve stenosis. We present the first report on a human implantation of a self‐expanding aortic valve prosthesis, which is composed of three bovine pericardial leaflets inserted within a self‐expanding nitinol stent. The 73‐year‐old woman presented with severe symptomatic aortic valve stenosis (mean transvalvular gradient of 45 mmHg; valve area of 0.7 cm2). Surgical valve replacement had been declined for the patient because of comorbidities, including previous bypass surgery. Method and Results: A retrograde approach via the common iliac artery was used for valve deployment. The contralateral femoral vessels were used for a temporary extracorporal circulation, unloading the left ventricle during the actual stent expansion. Clinical, hemodynamic, and echocardiographic outcomes were assessed serially during the procedure. Clinical and echocardiographic follow‐up at day 1, 2, and 14 post procedure was performed to evaluate the short‐term outcome. The prosthesis was successfully deployed within the native aortic valve, with accurate and stable positioning and with no impairment of the coronary artery or vein graft blood flow. 2D and doppler echo immediately after device deployment showed a significant reduction in transaortic mean pressure gradient (from 45 to 8 mmHg) without evidence of aortic or mitral valve insufficiency. The clinical status has then significantly improved. These results remained unchanged up to the day 14 follow‐up. Conclusion: This case report demonstrates a successful percutaneous implantation of a self‐expanding aortic valve prosthesis with remarkable functional and clinical improvements in the acute and short‐term outcome.

2-Year Follow-Up of Patients Undergoing Transcatheter Aortic Valve Implantation Using a Self-Expanding Valve Prosthesis

OBJECTIVES The purpose of this study was to evaluate the safety, device performance, and clinical outcome up to 2 years for patients undergoing transcatheter aortic valve implantation (TAVI). BACKGROUND The role of TAVI in the treatment of calcific aortic stenosis evolves rapidly, but mid- and long-term results are scarce. METHODS We conducted a prospective, multicenter, single-arm study with symptomatic patients undergoing TAVI for treatment of severe aortic valve stenosis using the 18-F Medtronic CoreValve (Medtronic, Minneapolis, Minnesota) prosthesis. RESULTS In all, 126 patients (mean age 82 years, 42.9% male, mean logistic European System for Cardiac Operative Risk Evaluation score 23.4%) with severe aortic valve stenosis (mean gradient 46.8 mm Hg) underwent the TAVI procedure. Access was transfemoral in all but 2 cases with subclavian access. Retrospective risk stratification classified 54 patients as moderate surgical risk, 51 patients as high-risk operable, and 21 patients as high-risk inoperable. The overall technical success rate was 83.1%. Thirty-day all-cause mortality was 15.2%, without significant differences in the subgroups. At 2 years, all-cause mortality was 38.1%, with a significant difference between the moderate-risk group and the combined high-risk groups (27.8% vs. 45.8%, p = 0.04). This difference was mainly attributable to an increased risk of noncardiac mortality among patients constituting the high-risk groups. Hemodynamic results remained unchanged during follow-up (mean gradient: 8.5 ± 2.5 mm Hg at 30 days and 9.0 ± 3.4 mm Hg at 2 years). Functional class improved in 80% of patients and remained stable over time. There was no incidence of structural valve deterioration. CONCLUSIONS The TAVI procedure provides sustained clinical and hemodynamic benefits for as long as 2 years for patients with symptomatic severe aortic stenosis at increased risk for surgery.

Six- and Twelve-Month Results From First Human Experience Using Everolimus-Eluting Stents With Bioabsorbable Polymer

Background—Everolimus, an active immunosuppressive and antiproliferative agent of the same family as sirolimus (rapamycin), has demonstrated significant reduction of neointimal proliferation in animal studies. The First Use To Underscore restenosis Reduction with Everolimus (FUTURE) I trial was the first in-human experience to evaluate the safety and efficacy of everolimus-eluting stents (EES), coated with a bioabsorbable polymer, compared with bare metal stents (BMS). Methods and Results—FUTURE I was a prospective, single-blind, randomized trial that enrolled 42 patients with de novo coronary lesions (EES 27, BMS 15). Patient and lesion characteristics were comparable between the groups. Major adverse cardiac event rates were low at 30 days and 6 months, without any early or late stent thrombosis for either group (P =NS). Between 6 and 12 months, there were no additional reports of major adverse cardiac events. The 6-month angiographic in-stent restenosis rate was 0% versus 9.1% (1 patient) (P =NS), with an associated late loss of 0.11 mm versus 0.85 mm (P <0.001), and the in-segment restenosis rate was 4% (1 patient) and 9.1% (1 patient) (P =NS) for EES and BMS, respectively. Intravascular ultrasound analysis revealed a significant reduction of percent neointimal volume in EES compared with BMS (2.9±1.9 mm3 /mm versus 22.4±9.4 mm3 /mm, P <0.001). There was no late stent malapposition in either group. The safety and efficacy of the EES appeared to be sustained at 12 months. Conclusions—In this initial clinical experience, EES with bioabsorbable polymer demonstrated a safe and efficacious method to reduce in-stent neointimal hyperplasia and restenosis.