Subacute Stent Thrombosis in a Clopidogrel Resistant Octogenarian

Tel: 2610 999281, e-mail: [email protected]: An octogenarian on double clopidogrel maintenance dose (150 mg qd), due to clopidogrel resistance determined with a point-of-care assay, was subjected to percutaneous intervention (PCI) of the left anterior descending artery with two drug eluting stents. Twenty-four hours latter the patient sustained sub acute stent thrombosis manifesting as an anterior ST-elevation myocardial infarction with cardiogenic shock. Optical coherence tomography disclosed thrombus inside the stent without malapposition. Thrombus aspiration and balloon inflation of the thrombosed stent restored vessel patency. The issue of clopidogrel resistance and methods to overcome it are discussed

Effect of Aging on Human Mesenchymal Stem Cell Therapy in Ischemic Cardiomyopathy Patients

AbstractBackgroundThe role of patient age in the efficacy of mesenchymal stem cell (MSC) therapy in ischemic cardiomyopathy (ICM) is controversial.ObjectivesThis study sought to determine whether the therapeutic effect of culture-expanded MSCs persists, even in older subjects.MethodsPatients with ICM who received MSCs via transendocardial stem cell injection (TESI) as part of the TAC-HFT (Transendocardial Autologous Cells in Ischemic Heart Failure) (n = 19) and POSEIDON (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis) (n = 30) clinical trials were divided into 2 age groups: younger than 60 and 60 years of age and older. Functional capacity was measured by 6-min walk distance (6MWD) and quality of life using the Minnesota Living With Heart Failure Questionnaire (MLHFQ) score, measured at baseline, 6 months, and 1 year post-TESI. Various cardiac imaging parameters, including absolute scar size, were compared at baseline and 1 year post-TESI.ResultsThe mean 6MWD was similar at baseline and increased at 1 year post-TESI in both groups: 48.5 ± 14.6 m (p = 0.001) for the younger and 35.9 ± 18.3 m (p = 0.038) for the older participants (p = NS between groups). The older group exhibited a significant reduction in MLHFQ score (−7.04 ± 3.54; p = 0.022), whereas the younger than 60 age group had a borderline significant reduction (−11.22 ± 5.24; p = 0.058) from baseline (p = NS between groups). Although there were significant reductions in absolute scar size from baseline to 1 year post-TESI, the effect did not differ by age.ConclusionsMSC therapy with TESI in ICM patients improves 6MWD and MLHFQ score and reduces myocardial infarction size. Importantly, older individuals did not have an impaired response to MSC therapy

Mechanisms of non-fatal stent-related myocardial infarction late following coronary stenting with drug-eluting stents and bare metal stents-insights from optical coherence tomography

Acute myocardial infarction (MI) occurring late following stenting may be related to either the stent or disease progression at the same or other coronary arteries.1 Stent-related MI involves stent thrombosis, with or without restenosis. Pathologic and intravascular ultrasoundstudies have shown that delayed healing with incomplete neointimal tissue strut coverage, vessel remodeling, and inflammation constitutes the most frequent substrate of late and verylate drug-eluting stent (DES) thrombosis (LST). Prospective angioscopic and optical coherence tomography (OCT) studies have shown that features possibly associated with DES-LST, such as uncovered stent struts, may be found very frequently, even late post-stenting, depending on the type of DES. However, the reported rate of clinical LST is much lower thanthe reported rate of uncovered DES struts, underlining the fact that this phenomenon is multifactorial and questioning the relevance of the abovementioned OCT findings in prospective studies without clinical events.On the other hand, LST also happens following bare metal stent (BMS) implantation and may have different chronology and mechanisms, as delayed healing is not an issue with thesestents. Very recently, some case series and studies using intracoronary imaging in patients with late clinical events following BMS implantation are suggesting that developmentof new atherosclerotic lesions inside the BMS may be a possible mechanism explaining late events. More intriguing is the fact that features possibly indicative of neointimal“atherosclerotic transformation” have been found also inside DES and questions exist regarding its possible role in LSTΗ στεφανιαία αγγειογραφία είναι σήμερα η βασική τεχνική για την εκτίμηση της νόσου των στεφανιαίων αρτηριών. Ωστόσο, αυτή η τεχνική περιορίζεται σε μία δισδιάστατη αναπαράσταση του περιγράμματος του αυλού , χωρίς να παρέχει πληροφορίες σχετικά με το τοίχωμα του αγγείου, το οποίο είναι το υπόστρωμα της αθηροσκλήρωσης. Αυτός ο περιορισμός οδήγησε στην ανάπτυξη νέων τεχνικών ενδοστεφανιαίας άμεσης απεικόνισης της αθηρωματικής πλάκας. Η ανάπτυξη της ενδαγγειακής υπερηχογραφίας (IVUS), επέτρεψε την πολύ πιο λεπτομερή αξιολόγηση της στεφανιαίας αθηροσκλήρωσης , αλλά η περιορισμένη ανάλυση (150-200 μm) απέκλειε την πιο ακριβή απεικόνιση ορισμένων μικροδομών.Η οπτική συνεκτική τομογραφία (OCT) είναι μια βασισμένη στο υπέρυθρο φως απεικονιστική τεχνολογία που παρέχει την δυνατότητα εικόνων in vivo υψηλής ανάλυσης (10-20 μm) της στεφανιαίας αρτηρίας δέκα φορές υψηλότερες από ό, τι η IVUS , αλλά με μια διείσδυση στο αγγειακό τοίχωμα που περιορίζεται σε 1,5-2 mm.Το οξύ έμφραγμα του μυοκαρδίου (ΟΕΜ) που συμβαίνει καθυστερημένα μετά από την εμφύτευση ενδοστεφανιαίας ενδοπρόθεσης μπορεί να σχετίζεται είτε με την ενδοπρόθεση ή την εξέλιξης της αθηρωματικής νόσου στην ίδια ή άλλη στεφανιαία αρτηρία. ΟΕΜ που σχετίζονται με ενδοπρόθεση περιλαμβάνουν θρόμβωση ενδοπρόθεσης με ή χωρίς επαναστένωση. Ιστολογικές και ενδαγγειακές απεικονιστικές μελέτες υπερήχων έδειξαν ότι η καθυστερημένη επούλωση με ελλιπή επικάλυψη του ερείσματος (strut) της ενδοπρόθεσης με νέο έσω χιτώνα, αναδιαμόρφωση αγγείων και η φλεγμονή αποτελούν το πιο συχνό υπόστρωμα της καθυστερημένης και πολύ καθυστερημένης θρόμβωσης ενδοστεφανιαίας ενδοπρόθεσης που εκλύει φάρμακο (DES). Προοπτικές αγγειογραφικές και απεικονιστικες μελέτες με τη χρήση της οπτικής συνεκτικής τομογραφίας (OCT) έχουν δείξει ότι ευρήματα που ενδεχομένως συνδέονται με καθυστερημένη θρόμβωση DES, όπως μη κεκαλυμμένα strut, μπορεί να είναι παρόντα πολύ συχνά, ακόμη και αργά μετά την εμφύτευση της ενδοπρόθεσης , ανάλογα με τον τύπο του DES. Ωστόσο, το δημοσιευμένο ποσοστό των κλινικών καθυστερημένων θρομβώσεων ενδοπροθέσεων είναι πολύ χαμηλότερο από το αναφερόμενο ποσοστό των ακάλυπτων strut των DES. Το γεγονός αυτό υποδεικνύει ότι το φαινόμενο είναι πολυπαραγοντικό και αμφισβητεί την σημασία των ανωτέρω ευρημάτων των προοπτικών μελετών χωρίς κλινικές εκδηλώσεις .Από την άλλη πλευρά, καθυστερημένη θρόμβωση συμβαίνει επίσης μετά από εμφύτευση απλής ενδοστεφανιαίας πρόθεσης (BMS) και μπορεί να έχει διαφορετική χρονολογία και μηχανισμό, καθώς η καθυστερημένη επούλωση δεν είναι συχνή με αυτές τις ενδοπροθέσεις. Πολύ πρόσφατα , ορισμένες αναφορές και μελέτες που χρησιμοποιούν ενδοστεφανιαία απεικόνιση σε ασθενείς με καθυστερημένα κλινικά συμβάματα μετά από εμφύτευση BMS προτείνουν ότι η ανάπτυξη νέων αθηρωματικών βλαβών στο εσωτερικό του BMS μπορεί να είναι ένας πιθανός μηχανισμός που να εξηγεί αυτά τα καθυστερημένα κλινικά συμβάματα. Ενδιαφέρον είναι το γεγονός ότι ευρήματα που πιθανώς είναι ενδεικτικά " αθηρωματικής μεταμόρφωσης » του νέου έσω χιτώνα έχουν βρεθεί επίσης στο εσωτερικό DES και υπάρχουν ερωτήματα σχετικά με τον πιθανό ρόλο της στην καθυστερημένη θρόμβωση

Clinical research skills development program in cell-based regenerative medicine

Cell-based therapy aimed at restoring organ function is one of the most exciting and promising areas of medical research. However, a novel intervention like cell-based therapy requires physician education and training. An increasing number of physicians untrained in regenerative medicine are using cell-based therapy to treat patients for a wide variety of chronic illnesses. The current lack of training for physicians in this area combined with the sharply increasing practice of regenerative medicine is concerning for a number of reasons, namely potential harm to patients and avoidable conflicts between governmental regulatory agencies and physicians. Academic medical fellowship training programs are needed that specifically prepare physicians for treating patients with cell-based therapies for various organ systems and chronic diseases. The National Heart, Lung, and Blood Institute established the Cardiovascular Cell Therapy Network to design and conduct clinical trials that advance the field of cell-based therapy for patients with cardiovascular disease. As part of the network, a two-year Clinical Research Skills Development Program was supported at two centers with the goal of training early career investigators in cell-based clinical and translational research. In this review, we describe the implementation of this training program at our institution with the purpose of promoting the further development of academic fellowship programs in cell-based regenerative medicine

Cell-based therapy for prevention and reversal of myocardial remodeling

Although pharmacological and interventional advances have reduced the morbidity and mortality of ischemic heart disease, there is an ongoing need for novel therapeutic strategies that prevent or reverse progressive ventricular remodeling following myocardial infarction, the process that forms the substrate for ventricular failure. The development of cell-based therapy as a strategy to repair or regenerate injured tissue offers extraordinary promise for a powerful anti-remodeling therapy. In this regard, the field of cell therapy has made major advancements in the past decade. Accumulating data from preclinical studies have provided novel insights into stem cell engraftment, differentiation, and interactions with host cellular elements, as well as the effectiveness of various methods of cell delivery and accuracy of diverse imaging modalities to assess therapeutic efficacy. These findings have in turn guided rationally designed translational clinical investigations. Collectively, there is a growing understanding of the parameters that underlie successful cell-based approaches for improving heart structure and function in ischemic and other cardiomyopathies

Mechanisms of Non-Fatal Stent-Related Myocardial Infarction Late Following Coronary Stenting With Drug-Eluting Stents and Bare Metal Stents - Insights From Optical Coherence Tomography

Background: A prospective observational study using optical coherence tomography (OCT) of patients with myocardial infarction (MI), late following drug-eluting (DES) or bare metal stent (BMS) implantation, when the stented segment was considered culprit. Methods and Results: Seventeen patients (58.9 +/- 8.3 years; 7 DES, 10 BMS) with MI at 50 (3-180) months post-stenting. Patients with BMS sustained a MI later than patients with DES (95 (3-180) vs. 8(3-62) months, P=0.01]; 5 (71.4%) of the DES patients demonstrated binary angiographic restenosis, in contrast to 8 (80%) with BMS (P=1.0). DES had significantly less thickness of the neointimal hyperplasia compared with BMS (0.08 +/- 0.04 vs. 0.36 +/- 0.2 mm, P=0.003). None of the DES was totally covered with neointimal tissue. The overall percentage of uncovered and malapposed struts (ANCOVA), was significantly higher in DES than BMS (1.96, 95% confidence interval (CI) 1.5-2.4 vs. 0.25, 95%CI 0.1-0.6, P<0.001, and 0.66, 95%CI 0.29-1.03 vs. 0.11, 95%CI 0.19-0.4, P=0.03, respectively). OCT features of atherosclerosis (lipid, neovascularization, or calcification) and possible neointimal rupture were found only in patients with BMS. Thrombus detection was not different between the 2 groups. Conclusions: Stent-related, non-fatal, late acute MI following stent implantation occurs later in patients with a BMS compared with those with a DES, and the mechanism includes delayed healing (mainly DES), and neointimal hyperplasia with atherosclerotic transformation and subsequent rupture (mainly BMS). (Circ J 2011; 75: 2789 2797

Abstract 246: Transendocardial Injections of Allogeneic Mesenchymal Stem Cells Demonstrate Reversal of Left Ventricular Remodeling to Baseline

Background: Mesenchymal stem cells (MSCs) improve ventricular function post MI Hypothesis: Transendocardial stem cell injections (TESI) reverse remodeling in a swine model of chronic ischemic cardiomyopathy (CIC). Methods: Gottingen swine (n=12), underwent a closed-chest, LAD occlusion-reperfusion model to create chronic ischemic cardiomyopathy. Three months post-MI, transendocardial injections of allogeneic MSCs (n=6) or sham injection (control group, n=6) were administered to the infarct and border zones. Cardiac MRI and pressure volume loops were obtained at baseline, during injection, and 6 months post injection. The three dimensional sphericity index (SI) was determined using the formula, SI= (π x LVLA3)/6, where LVLA is the left ventricle long axis length as measured in a 4-chamber long axis cardiac MRI end diastolic frame perpendicular to the line from the annulus of the mitral valve to the apex. Results: The sphericity index increased in both groups 3 months after MI, from 0.268 ± 0.054 to 0.348 ± 0.050 in the sham injection group and 0.277 ± 0.051 to 0.380 ± 0.059 in the TESI group. In the sham injection group, SI remained stable 9 months post sham injections indicative of irreversible remodeling post MI. In contrast, the injection group SI continued to decrease from 0.380 ± 0.059 to 0.346 ± 0.064 and 0.280 ± 0.50 at 3 and 6 months post TESI, respectively. Conclusions: Measurements of SI show that transendocardial stem cell injections of allogeneic MSCs demonstrate the potential to reverse left ventricular remodeling in CIC patients to geometric configurations comparable to their pre-MI shapes