Transendocardial autologous bone marrow in chronic myocardial infarction using a helical needle catheter

Abstracts / Cardiovascular Revascularization Medicine 9 (2008) 101–129 Experience with CoreValve aortic valve replacement in patients for surgical aortic valve replacement E Grube a, U Gerckens a, G Schuler b, A Linke b, R Bonan c, PW Serruys d, P Dejaegere d, J Kovacs e, P Den Heijer f, M Labinaz g, M Ruell g, M Mullen h, A Bosmans i, N Moat h, W Tymchak j, B Benit k a Helios Heart Center, Siegburg, Germany b Heart Center University, Leipzig, Germany c Montreal Heart Institute, Montreal, QC, Canada d Erasmus Thoraxcenter, Rotterdam, The Netherlands e University Hospitals, Leicester, United Kingdom f Amphia Hospital, Breda, The Netherlands g Heart Institute University, Ottawa, ON, Canada h Royal Brompton Hospital, Brompton London, United Kingdom i University Hospital, Antwerp, Belgium j University of Alberta, Edmonton, AB, Canada k Virga Jesse Heart Center, Hasselt, Belgium Background: Percutaneous aortic valve replacement (PAVR) is an emerging alternative to palliative medical therapy for high-risk (HR) and nonsurgical patients (pts) with severe aortic stenosis (AS). We report the global experience of PAVR with the CoreValve RevalvingTM systems (Irvine, Calif), 21F and 18F, which includes a self-expandable porcine pericardium bioprosthesis within in a multilevel nitinol frame. Methods: We enrolled HR pts with symptomatic, severe AS. From a multidisciplinary approach involving general anesthesia, surgical arterial access and femoral-femoral cardiopulmonary bypass, the implantation evolved to a standard percutaneous intervention without any surgical cutdowns or repair and without hemodynamic/cardiac support. Results: Since August 2005, 175 (112 18F system) consecutive HR pts with severe native aortic stenosis were included. The mean Logistic Euroscore was 24.2% (mean age, 81.6 years; 60% females; mean aortic valve area (AVA) 0.61 cm 2. Procedural success occurred in 161 pts—8 prostheses were misplaced; in 3 pts, the prosthesis was not implanted after balloon valvuloplasty (access problem with the 21F system); 2 aortic root and 1 left ventricle (wire) perforations happened. Thirty days of cumulative mortality happened in 26 pts (15%) with mean Logistic Euroscore of 31%. Successful implants showed a postprocedure mean AVA of 1.65 cm 2. In 22% pts, there were significant immediate paravalvular leaks (grade III-IV: only 2%). Cumulative free survival between 30 days and 2 years is over 82%. The 18F, third-generation device experience showed an evolution toward a complete percutaneous procedure with implantation done without any type of cardiac support or surgical cutdown/repair. Conclusions: These multicenter studies with 2 generations of catheters with decreasing size has evolved PAVR towards a pure “cath lab” procedure, showed a definitive learning curve, has lead to a better understanding of the anatomical requirements, provide positive follow-up without bioprosthetic or coronary complications, and provide safety and efficacy data for this selfexpanding PAVR system in this high-risk AS population. doi:10.1016/j.carrev.2008.02.034

Incidence of true clopidogrel resistance in high-risk percutaneous coronary intervention patients using VASP test M Bedossa a, V Letocart a, P Gueret b, G Leurent a, D Boulmier a, H Le Breton a a Department of Cardiology, Rennes, France b Department of Hemostasis, Rennes, France Background: Incidence of biologic clopidogrel resistance (or insufficient response) occurs in about 30% of patients using platelet aggregometry or flow cytometry to measure the quantitative VASP protein phosphorylation (VASP test). The influence of a new loading dose in resistant patients (Pts) is still unknown. Purpose: We used the VASP test (Platelet VASP-FCM, Biocytex/ Diagnostica stago, France) to determine prospectively clopidogrel resistance incidence in high risk percutaneous coronary intervention (PCI) procedures

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and to evaluate the benefit of a new 300-mg loading dose in so-called resistant Pts. Methods: Seventy-seven Pts were included between September 2005 and February 2006 (mean age, 65.1±11.4 years) all pretreated by clopidogrel. High-risk PCI concerned the followed situations: left main lesion, ostial left anterior descending lesion, 3-vessel disease, single-patent coronary vessel, terminal renal failure, previous stent thrombosis, and rotative atherectomy procedure. The first VASP test was performed before the procedure. Patients were defined as resistant when they had a platelet reactivity index (PRI) higher than 60%. In those cases, Pts received a new 300-mg loading dose. A second VASP test was performed at least 6 hours after. Results: Mean PRI was 48.2%±19.5% with a high interindividual variability from 6% to 88.9%. Twenty⁎six Pts (34%) were considered as resistant to clopidogrel (PRI=70.5%±7.5%; 60.4%-88.9%). A new 300-mg loading dose was administrated to 22 of them. A second test was performed 18±6.5 hours after the new loading dose. Sixteen Pts (73% of the resistant Pts) became sensitive to clopidogrel with a mean decrease of the PRI of 25.1%, whereas 6 Pts (27% of the resistant Pts) remained resistant with a decrease of only 3.7%. The 2 Pts admitted for stent thrombosis were resistant to clopidogrel (PRI=74% and 80%). No resistance predictive factor was identified. Conclusion: Using the VASP test, 34% of high-risk PCI patients showed an insufficient response to standard doses of clopidogrel. Seventy-three percent of them became sensitive after a new 300-mg loading dose, and 27% remained resistant, which represent only 8% of the global study population. doi:10.1016/j.carrev.2008.02.035

Transendocardial autologous bone marrow in chronic myocardial infarction using a helical needle catheter Two-year follow-up in an open-label, nonrandomized, pilot study (the TABMMI study): a first in man cell therapy trial with new delivery catheter technology L de la Fuente a, SH Stertzer b, E Penaloza c, J Argentieri a, J Miano c, B Koziner d, C Bilos a, L Battaglia d, G Lucero d, J Stertzer e, D Rouy e, PA Altman e a Institute of Diagnostic and Treatment, Buenos Aires, Argentina b Stanford University Medical Center, Stanford, CA, USA c Swiss Clinic, Buenos Aires, Argentina d Cell Prep SA, Buenos Aires, Argentina e Biocardia Inc, South San Francisco, CA, USA Background: Helical needle fixation has promise as a platform for intramyocardial cell therapy that is implemented by fluoroscopic guidance. The alteration of ejection fraction (EF) in patients treated by helical needle transendocardial delivery of autologous bone marrow (ABM) mononuclear cells around regions of hypo- or akinesia in chronic post–myocardial infarction (MI) was reported at 1 year. Two-year follow-up in this cohort is to be presented. Methods: Stable post-MI ischemic heart failure patients (n=17) with an EF below 40% were enrolled. Autologous bone marrow cells were aspirated from the iliac crest, washed, filtered, counted for CD34 + and CD133 + content, resuspended at a concentration of 100 million cells/mL, and delivered to the heart percutaneously from 5 to 10 approximate peri infarct sites with a transendocardial helical needle catheter and a steerable Morph guide catheter platform. Two-dimensional echocardiographic left ventricle EF measurements, 24-hour Holter, and exercise tolerance testing were performed at baseline; days 0 and 1; and 12 weeks, 6 months, 12, and 24 months. Results: An average of 92 million ABM mononuclear cells were injected into 8.1±2.9 sites around the infarct targeting the peri-infarct zones (n=17). There were no adverse events associated with the catheter based cell transplantation procedure in any of 17 patients treated to date. There has been no significant increase in the averaged number of ventricular events on 24-hour Holter. In patients reaching the 24-month follow-up (n=10), EF significantly increased over baseline (35.2%±4.6%) at each time point:

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Abstracts / Cardiovascular Revascularization Medicine 9 (2008) 101–129

6 months (40.8±4.5, P=.003), 12 months (42.3±5.1, P=.0001) and 24 months (42.3±6.1, P=.0001). The average end-diastolic ventricular volume and exercise tolerance trended toward benefit, but differences were not statistically significant. Conclusions: Autologous bone marrow cells delivered with the helical needle transendocardial catheter was safe in this study sample of patients with chronic MI. Increased ejection fraction and other positive data trends support continued development of this therapeutic strategy in larger randomized trials. doi:10.1016/j.carrev.2008.02.036

Quantification of adventitial neovascularization during atherosclerosis progression with contrast ultrasound: a histologic validation D Moguillansky, A Carson, X Leng, L Lavery, X Chen, A Schwartz, J Gretton, D Fischer, JJ Pacella, FS Villanueva University of Pittsburgh, Pittsburgh, PA, USA Background: The density of vasa vasorum (VV) within atherosclerotic plaque correlates with histologic features of plaque vulnerability in postmortem studies. A method to noninvasively detect VV in vivo would be clinically useful. Recently, contrast ultrasound (CUS) using intravenously injected gas-filled microspheres (microbubbles) has shown potential for detecting VV. However, image parameters that accurately quantify VV require further validation against a histologic standard. We tested the hypothesis that CUS can quantify VV during atherosclerosis progression. Methods: New Zealand white rabbits received a high-fat diet for 3 weeks. After 1 week on the diet, bilateral femoral artery stenosis was induced by balloon injury. Nonlinear CUS femoral imaging (10 MHz) was performed at 0, 2, 4, and 6 weeks post injury during microbubble injection using a previously described destruction-replenishment approach to quantify blood velocity (β) and volume (peak videointensity [VI]). Peak VI was measured in the adventitia and normalized to luminal VI. At 0 (n=4), 2 (n=6), 4 (n=4), and 6 (n=10) weeks post injury, both femorals were sectioned (total 24 vessels) and stained for hematoxylin and eosin and von-Willebrand factor. Adventitial VV were quantified by the total number of stained microvessels as well as the total cross sectional area. Plaque burden (% lumen area) was measured from histology. Results: Plaque burden progressed over time: 0 weeks, 0%±0%; 2 weeks, 466%±21%; 4 weeks, 61%±23%; 6 weeks, 92%±3% (analysis of variance Pb.001). In the rabbits with serial images during the entire 6 weeks, peak VI also progressed over time: 0 weeks, 0.04±0.02; 2 weeks, 0.07±0.02; 4 weeks, 0.10±0.03; 6 weeks, 0.22±0.02 (analysis of variance Pb.001). There was a linear correlation between peak VI by CUS and both histologic VV CSA (Pb.001, R 2=0.75) and number of VV (Pb.001, R 2=0.55). β did not predict VV density. Conclusions: Histology confirms that the progression of atherosclerotic plaque is paralleled by proliferation of adventitial VV. Peak VI by CUS predicts the extent of neovascularization. This is the first report of serial in vivo imaging and mapping of pathologic evolution of VV with progressive atherosclerosis and provides proof of concept for a quantitative approach to imaging VV. doi:10.1016/j.carrev.2008.02.037

Prevalence and predictors of renal artery stenosis in patients with coronary artery disease M Bedossa, R Ollivier, D Boulmier, G Leurent, H Le Breton Department of Cardiology, Rennes, France Background: Renal artery stenosis (RAS) remains underrecognized owing to nonspecific clinical symptoms. Little is known about its real prevalence including in a specific high-risk population such as patients with coronary artery disease (CAD).

Aims: Determine the exact prevalence and the predictors of RAS in a population of CAD patients undergoing coronary angiography with simultaneous selective renal angiography. Methods: During a 24-month period, all consecutive patients with proven CAD at coronary angiography had simultaneous selective renal angiography. Renal artery stenoses above 50% were considered significant. Clinical history, cardiovascular risk factors, renal function, peripheral vascular disease and the number of coronary artery lesions were entered into a predictive statistical model. Results: Six hundred fifty-one consecutive patients were included. Renal angiography was interpretable in all but 1 patient. Ninety-four patients (14.5%) had significant RAS, including 20 (3.1%) with bilateral lesions. At univariate analysis, peripheral vascular disease (Pb.001), age above 70 years (Pb.05), number of coronary artery lesions (Pb.001) (Fig), hypertension (P=.01), and creatinine clearance b60 mL/min (Pb.001) were associated with an increased risk for RAS. At multivariate analysis, male sex (Pb.05), number of coronary artery lesions (Pb.01), hypertension (P=.01), and renal insufficiency (Pb.001) were predictive of the presence of RAS. Conclusions: The present study allowed us to identify clinical predictors of RAS in CAD patients, mainly history of hypertension, renal insufficiency, and multivessel disease. These findings could help at defining a high risk subpopulation in which RAS has to be investigated extensively.

doi:10.1016/j.carrev.2008.02.038

New treatment option for patients with end-stage coronary artery disease by extracorporeal shockwave myocardial revascularization therapy G Hakim a, CK Naber b, R Erbel b a Medispec Ltd., Germantown, MD, USA b Department of Cardiology, West German Heart Center Essen, University of Essen, Essen, Germany Background: Treating myocardial ischemia symptoms in patients with endstage coronary artery disease can be a challenge. The number of patients in this condition increases rapidly because of improved revascularization techniques. In vitro and animal data show an increase of angiogenic factors after treatment of low-intensity shock waves. The following demonstrates a new noninvasive therapy using focused, low-intensity shock waves to induce local angiogenesis at myocardial ischemic areas not treatable by conventional methods. Methods: The treatment is performed using a shock wave generator system (Cardiospec, Medispec) designed to address the clinical-anatomical requirements of the chest cavity. A cardiac ultrasound imaging system is used to locate the treatment area. Shock waves are then delivered via a special applicator through the anatomical acoustic window to the treatment area under electrocardiographic R-wave gating. Patients (n=25) with refractory angina due to 3-vessel disease or total occlusion of 1 epicardial vessel were treated. All had to have proven reversible ischemia in at least 1 myocardial area using