Lutz Buellesfeld

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.

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.

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.

Percutaneous aortic valve replacement for severe aortic regurgitation in degenerated bioprosthesis: the first valve in valve procedure using the Corevalve Revalving system.

Percutaneous valve replacement for severe aortic stenosis has shown to be an alternative treatment option for non‐surgical candidates. We report on the first successful valve in valve procedure in an 80‐year‐old patient with a severe regurgitation of a degenerated aortic bioprosthesis using the Corevalve Revalving system.

Feasibility of Transcatheter Aortic Valve Implantation Without Balloon Pre-Dilation: A Pilot Study

OBJECTIVES The purpose of this pilot study was to evaluate the feasibility and safety of transcatheter aortic valve implantation (TAVI) without balloon pre-dilation. BACKGROUND Balloon pre-dilation of the stenosed aortic valve is currently believed to be a necessary step for valve preparation before device placement in patients undergoing TAVI and, therefore, is considered an obligatory part of the procedure. However, clear evidence supporting this policy is lacking. In contrast, pre-dilation might be responsible in part for distal embolizations as well as atrioventricular conduction disturbances seen during TAVI procedures. METHODS A total of 60 consecutive patients (mean age 80.1 ± 6.4 years, 53% female, mean logistic EuroScore 23.3 ± 15.2%) undergoing TAVI using the self-expanding Medtronic CoreValve prosthesis (Medtronic, Minneapolis, Minnesota) have been prospectively enrolled at 13 international centers. RESULTS Pre-procedural mean transaortic valve gradient was 47.8 ± 15.5 mm Hg, mean effective orifice area was 0.67 ± 0.15 cm(2). Technical success rate was 96.7% (58 of 60) of patients. Post-dilation was performed in 16.7% (10 of 60) of patients. Post-procedural mean valve gradient was 4.4 ± 2.0 mm Hg. Circular and noncircular valve configuration was present in 41 and 19 cases (68.3% vs. 31.7%), respectively, with similar effective orifice areas (1.74 ± 0.10 cm(2) vs. 1.71 ± 0.22 cm(2), p = NS). In-hospital mortality, myocardial infarction, stroke, and major vascular complications occurred in 6.7% (4 of 60), 0%, 5%, and 10% of patients. There was no valve embolization. New permanent pacing was needed in 11.7% (7 of 60) of patients. CONCLUSIONS Transcatheter aortic valve implantation without balloon pre-dilation is feasible and safe, resulting in similar acute safety and efficacy as the current standard approach of TAVI with pre-dilation.

Impact of permanent pacemaker implantation on clinical outcome among patients undergoing transcatheter aortic valve implantation.

OBJECTIVES This study sought to assess the impact of permanent pacemaker (PPM) implantation on clinical outcomes among patients undergoing transfemoral transcatheter aortic valve implantation (TAVI). BACKGROUND TAVI is associated with atrioventricular-conduction abnormalities requiring PPM implantation in up to 40% among patients treated with self-expanding prostheses. METHODS Between 2007 and 2010, 353 consecutive patients (mean age: 82.6 ± 6.1 years, log EuroSCORE: 25.0 ± 15.0%) with severe aortic stenosis underwent transfemoral TAVI at 2 institutions. Clinical outcomes were compared among 3 groups: (1) patients requiring PPM implantation after TAVI (PPM after TAVI), (2) patients without PPM before or after TAVI (no PPM), and (3) patients with PPM before TAVI (PPM before TAVI). The primary endpoint was all-cause mortality at 12 months, and an age-, sex-, and origin-matched standardized population served as controls. RESULTS Of 353 patients, 98 patients (27.8%) belonged to the PPM after TAVI group, 48 patients (13.6%) belonged to the PPM before TAVI group, and 207 patients (58.6%) belonged to the no PPM group. The PPM before TAVI patients had a significantly higher baseline risk compared with the PPM after TAVI and no PPM patients (coronary artery disease: 77.1% vs. 52.7% and 58.2%, respectively, p = 0.009; atrial fibrillation: 43.8% vs. 22.7% and 20.4%, respectively, p = 0.005). At 12 months of follow-up, all-cause mortality was similar in all 3 groups (PPM after TAVI group: 19.4%, PPM before TAVI group: 22.9%, no PPM group: 18.0%) in unadjusted analyses (p = 0.77) and adjusted analyses (p = 0.90). Compared with the standardized population, adjusted hazard ratios for death were 2.37 (95% confidence interval [CI]: 1.51 to 3.72) for the PPM after TAVI group, 2.75 (95% CI: 1.52 to 4.97) for the PPM before TAVI group, and 2.24 (95% CI: 1.62 to 3.09) for the no PPM group. CONCLUSIONS Although prognosis remains impaired compared with an age-, sex-, and origin-matched standardized population, periprocedural PPM implantation does not seem to affect clinical outcomes adversely among patients undergoing transfemoral TAVI.

Correlation of peripheral-blood gene expression with the extent of coronary artery stenosis.

Background—The molecular pathophysiology of coronary artery disease (CAD) includes cytokine release and a localized inflammatory response within the vessel wall. The extent to which CAD and its severity is reflected by gene expression in circulating cells is unknown. Methods and Results—From an initial coronary catheterization cohort we identified 41 patients, comprising 27 cases with angiographically significant CAD and 14 controls without coronary stenosis. Whole-genome microarray analysis performed on peripheral-blood mononuclear cells yielded 526 genes with >1.3-fold differential expression (P<0.05) between cases and controls. Real-time polymerase chain reaction on 106 genes (the 50 most significant microarray genes and 56 additional literature genes) in an independent subset of 95 patients (63 cases, 32 controls) from the same cohort yielded 14 genes (P<0.05) that independently discriminated CAD state in a multivariable analysis that included clinical and demographic factors. From an independent second catheterization cohort, 215 patients were selected for real-time polymerase chain reaction–based replication. A case:control subset of 107 patients (86 cases, 21 controls) replicated 11 of the 14 multivariably significant genes from the first cohort. An analysis of the 14 genes in the entire set of 215 patients demonstrated that gene expression was proportional to maximal coronary artery stenosis (P<0.001 by ANOVA). Conclusions—Gene expression in peripheral-blood cells reflects the presence and extent of CAD in patients undergoing angiography.