Peter den Heijer

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.

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.

Left Bundle-Branch Block Induced by Transcatheter Aortic Valve Implantation Increases Risk of Death

Background— Transcatheter aortic valve implantation (TAVI) is a novel therapy for treatment of severe aortic stenosis. Although 30% to 50% of patients develop new left bundle-branch block (LBBB), its effect on clinical outcome is unclear. Methods and Results— Data were collected in a multicenter registry encompassing TAVI patients from 2005 until 2010. The all-cause mortality rate at follow-up was compared between patients who did and did not develop new LBBB. Of 679 patients analyzed, 387 (57.0%) underwent TAVI with the Medtronic CoreValve System and 292 (43.0%) with the Edwards SAPIEN valve. A total of 233 patients (34.3%) developed new LBBB. Median follow-up was 449.5 (interquartile range, 174–834) days in patients with and 450 (interquartile range, 253–725) days in patients without LBBB (P=0.90). All-cause mortality was 37.8% (n=88) in patients with LBBB and 24.0% (n=107) in patients without LBBB (P=0.002). By multivariate regression analysis, independent predictors of all-cause mortality were TAVI-induced LBBB (hazard ratio [HR], 1.54; confidence interval [CI], 1.12–2.10), chronic obstructive lung disease (HR, 1.56; CI, 1.15–2.10), female sex (HR, 1.39; CI, 1.04–1.85), left ventricular ejection fraction ⩽50% (HR, 1.38; CI, 1.02–1.86), and baseline creatinine (HR, 1.32; CI, 1.19–1.43). LBBB was more frequent after implantation of the Medtronic CoreValve System than after Edwards SAPIEN implantation (51.1% and 12.0%, respectively; P<0.001), but device type did not influence the mortality risk of TAVI-induced LBBB. Conclusions— All-cause mortality after TAVI is higher in patients who develop LBBB than in patients who do not. TAVI-induced LBBB is an independent predictor of mortality.

Quality of Life after PCI with Drug-Eluting Stents or Coronary-Artery Bypass Surgery

BACKGROUND Previous studies have shown that among patients undergoing multivessel revascularization, coronary-artery bypass grafting (CABG), as compared with percutaneous coronary intervention (PCI) either by means of balloon angioplasty or with the use of bare-metal stents, results in greater relief from angina and improved quality of life. The effect of PCI with the use of drug-eluting stents on these outcomes is unknown. METHODS In a large, randomized trial, we assigned 1800 patients with three-vessel or left main coronary artery disease to undergo either CABG (897 patients) or PCI with paclitaxel-eluting stents (903 patients). Health-related quality of life was assessed at baseline and at 1, 6, and 12 months with the use of the Seattle Angina Questionnaire (SAQ) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The primary end point was the score on the angina-frequency subscale of the SAQ (on which scores range from 0 to 100, with higher scores indicating better health status). RESULTS The scores on each of the SAQ and SF-36 subscales were significantly higher at 6 and 12 months than at baseline in both groups. The score on the angina-frequency subscale of the SAQ increased to a greater extent with CABG than with PCI at both 6 and 12 months (P=0.04 and P=0.03, respectively), but the between-group differences were small (mean treatment effect of 1.7 points at both time points). The proportion of patients who were free from angina was similar in the two groups at 1 month and 6 months and was higher in the CABG group than in the PCI group at 12 months (76.3% vs. 71.6%, P=0.05). Scores on all the other SAQ and SF-36 subscales were either higher in the PCI group (mainly at 1 month) or were similar in the two groups throughout the follow-up period. CONCLUSIONS Among patients with three-vessel or left main coronary artery disease, there was greater relief from angina after CABG than after PCI at 6 and 12 months, although the extent of the benefit was small. (Funded by Boston Scientific; ClinicalTrials.gov number, NCT00114972.).

Accelerated vascular repair following percutaneous coronary intervention by capture of endothelial progenitor cells promotes regression of neointimal growth at long term follow-up: final results of the Healing II trial using an endothelial progenitor cell capturing stent (Genous R stent).

AIMS The study sought to define the long-term angiographic and clinical outcome of a bio-engineered stent, able to sequester endothelial progenitor cells (EPC) to the stent to promote the post-stenting vascular repair response. METHODS AND RESULTS The HEALING-II was a multicentre, prospective registry, including 63 patients treated with the implantation of a Genous EPC capture stent. Serial quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) analysis was performed at 6 and 18 month. The 18 month composite MACE rate was 7.9%, whereas 6.3% clinically justified target lesion revascularisations were observed. Although patients received one month of clopidogrel, no (sub)acute or late angiographic stent thrombosis occurred. At 6 month follow-up, in-stent late luminal loss was 0.78+/-0.39 mm and percent in-stent volume obstruction was 22.9+/-13.7% (mean+/-sd). Serial angiographic and IVUS analyses were available in 30 event-free patients at post-procedure, 6 months and 18 months. From 6 months to 18 months follow-up, a significant late regression of neointimal hyperplasia was observed on QCA (late luminal loss 0.59+/-0.31, 24.4% reduction or 16.9% by matched serial analysis) and IVUS (percent in-stent volume obstruction 20.3+/-14.3%, 11.4% reduction or 9.6% by matched serial analysis). The relative increase in circulating EPC titers at long-term follow-up correlated with neointimal compaction in individual patients, suggestive of an EPC-mediated vascular repair response. CONCLUSIONS The HEALING II study suggests that the EPC capture stent, aimed to stimulate the coronary vascular repair response, significantly promotes late regression of neointimal hyperplasia up to 18 months after stent implantation.

Angioscopic versus angiographic detection of intimal dissection and intracoronary thrombus

OBJECTIVES This study was undertaken to compare coronary angioscopy with angiography for the detection of intimal dissection and intracoronary thrombus. BACKGROUND It has been demonstrated previously that coronary angioscopy provides more intravascular detail than cineangiography. Both imaging methods have to be compared directly to assess the additional diagnostic value of angioscopy. METHODS The angiograms and videotapes of 52 patients who had undergone angioscopy were reviewed independently by two observers unaware of other findings. Classic angiographic definitions were used for dissection and thrombus. Angioscopic dissection was defined as visible cracks or fissures on the lumen surface or mobile protruding structures that are contiguous with the vessel wall. Angioscopic thrombus was defined as a red, white or mixed red and white intraluminal mass. RESULTS Angiography and angioscopy were in agreement in 40.4% of cases in the absence of thrombus and in 11.5% in the presence of thrombus. No fewer than 25 (48.1%) angioscopically observed thrombi remained undetected at angiography. With angioscopy as the standard, although the specificity of angiography for thrombus was 100%, sensitivity was very low at 19%. Angioscopic dissection was present in 40 patients (76.9%) versus angiographic dissection in 15 patients (28.8%). With regard to dissection, there was no correlation between the two imaging methods (r phi = 0.15, p = 0.29). CONCLUSIONS Coronary angiography underestimates the presence of intracoronary thrombus. Angioscopy and angiography are complementary techniques for detecting and grading intimal dissections.

Evaluation of a weight-adjusted single-bolus plasminogen activator in patients with myocardial infarction: A double-blind, randomized angiographic trial of lanoteplase versus alteplase

BACKGROUND Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. METHODS AND RESULTS InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double-blind, randomized, double-placebo angiographic trial, evaluated the dose-response relationship and safety of single-bolus, weight-adjusted lanoteplase. Patients (n=602) presenting within 6 hours of acute myocardial infarction were randomized and treated with either a single-bolus injection of lanoteplase (15, 30, 60, or 120 kU/kg) or accelerated alteplase. The primary objective was to determine TIMI grade flow at 60 minutes. Angiographic assessments were also performed at 90 minutes and on days 3 to 5. Follow-up was continued for 30 days. Lanoteplase achieved its primary objective, demonstrating a dose-response in TIMI grade 3 flow at 60 minutes (23.6% to 47.1% of subjects, P<0. 001). Similar results were observed at 90 minutes (26.1% to 57.1%, P<0.001). At 90 minutes, coronary patency (TIMI 2 or 3) increased across the dose range up to 83% of subjects at 120 kU/kg lanoteplase compared with 71.4% with alteplase. Thus, at this dose, lanoteplase was superior to alteplase in restoring coronary patency (difference, 12%; 95% CI, 1% to 23%). The early safety experience in this study suggests that lanoteplase was well tolerated at all doses with safety comparable to that of alteplase. CONCLUSIONS Lanoteplase, a single-bolus, weight-adjusted agent, increased coronary patency at 60 and 90 minutes in a dose-dependent fashion. Coronary patency at 90 minutes was achieved more frequently with 120 kU/kg lanoteplase than alteplase. In this study, safety with lanoteplase and alteplase was comparable. InTIME-II, a worldwide mortality trial, will evaluate efficacy and safety with this promising new agent.

Coronary blood flow dynamics during transcutaneous electrical nerve stimulation for stable angina pectoris associated with severe narrowing of one major coronary artery

To study the effect of transcutaneous electrical nerve stimulation (TENS) on coronary vasomotion, patients with New York Heart Association class III angina pectoris and significant single-vessel left coronary artery disease and who were also scheduled for elective percutaneous transluminal coronary angioplasty, were allocated to a study group (precordial actual TENS, n = 10) and a control group (precordial simulated TENS, n = 5, and TENS on the back, n = 3). Coronary volumetric flow was assessed in the stenotic and nonstenotic coronary artery before and after neurostimulation. The diameter (in millimeters) of the stenotic coronary artery was reduced in the study group after actual TENS (from 2.73 +/- 0.55 by 0.12 +/- 0.11; p = 0.008). In the nonstenotic coronary artery, the diameter increased in the study group (from 2.64 +/- 0.43 by 0.24 +/- 0.15; p = 0.01). In both the stenotic and nonstenotic coronary arteries, no effect was shown on the average peak velocity (centimeters per second) in the study group. The coronary volumetric flow (milliliters per minute) was reduced in the stenotic artery of the study group (from 62 +/- 18 by 8 +/- 7; p = 0.007). In the nonstenotic coronary artery, volumetric flow increased in the study group (from 57 +/- 18 by 11 +/- 10; p = 0.007). In the control group, simulated TENS and TENS on the back had no effect on the diameter of the artery, average peak velocity, or volumetric flow. In addition, in all patients, TENS had no effect on the total volumetric flow of the left coronary artery and hemodynamic variables during the study period. This observation suggests that TENS modulates regional coronary vasomotion in patients with coronary artery disease.

Randomized study to compare balloon angioplasty and elective stent implantation in venous bypass grafts: The Venestent Study

The aim of the study was to compare acute and long‐term angiographic and clinical outcome of balloon angioplasty and elective stenting in de novo lesions in the body of a saphenous vein graft (SVG). A total of 150 patients, with de novo lesions in SVG, were randomly assigned to balloon angioplasty or elective Wiktor I stent implantation. The angiographic restenosis rate at 6‐month follow‐up was 32.8% in the balloon group and 19.1% in the stent group (P = 0.069). At 1‐year follow‐up, target vessel revascularization rate was 31.4% vs. 14.5% (P < 0.05), and event‐free survival was 60.0% vs. 76.3% (P < 0.05) for the balloon and stent group, respectively. Elective stent implantation in de novo SVG lesions is associated with a significant lower target vessel revascularization rate and a significant higher event‐free survival at 1‐year follow‐up as compared to balloon angioplasty. Catheter Cardiovasc Interv 2003;60:452–457.

Clinical outcomes in patients with ST-segment elevation myocardial infarction treated with everolimus-eluting stents versus bare-metal stents (EXAMINATION): 5-year results of a randomised trial

BACKGROUND Data for the safety and efficacy of new-generation drug-eluting stents at long-term follow-up, and specifically in patients with ST-segment elevation myocardial infarction, are scarce. In the EXAMINATION trial, we compared everolimus-eluting stents (EES) with bare-metal stents (BMS) in an all-comer population with ST-segment elevation myocardial infarction. In this study, we assessed the 5-year outcomes of the population in the EXAMINATION trial. METHODS In the multicentre EXAMINATION trial, done in Italy, Spain, and the Netherlands, patients with ST-segment elevation myocardial infarction were randomly assigned in a 1:1 ratio to receive EES or BMS. The random allocation schedule was computer-generated and central randomisation (by telephone) was used to allocate patients in blocks of four or six, stratified by centre. Patients were masked to treatment assignment. At 5 years, we assessed the combined patient-oriented outcome of all-cause death, any myocardial infarction, or any revascularisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00828087. FINDINGS 1498 patients were randomly assigned to receive either EES (n=751) or BMS (n=747). At 5 years, complete clinical follow-up data were obtained for 731 patients treated with EES and 727 treated with BMS (97% of both groups). The patient-oriented endpoint occurred in 159 (21%) patients in the EES group versus 192 (26%) in the BMS group (hazard ratio 0·80, 95% CI 0·65-0·98; p=0·033). This difference was mainly driven by a reduced rate of all-cause mortality (65 [9%] vs 88 [12%]; 0·72, 0·52-0·10; p=0·047). INTERPRETATION Our findings should be taken as a point of reference for the assessment of new bioresorbable polymer-based metallic stents or bioresorbable scaffolds in patients with ST-segment elevation myocardial infarction. FUNDING Spanish Heart Foundation.