Background: Current guidelines give a class I recommendation to use of embolic protection devices (EPD) for saphenous vein graft (SVG) intervention; however, studies have shown conflicting results. The objective of this meta-analysis is to compare all-cause mortality, major adverse cardiovascular events, myocardial infarction (MI), or target vessel revascularization in SVG intervention with and without EPD. Methods and Results: Literature was searched through October 2016. Eight studies (n=52 893) comparing SVG intervention performed with EPD (n=11 506) and without EPD (n=41 387) were included. There was no significant difference in all-cause mortality (odds ratio [OR], 0.79; confidence interval [CI], 0.55–1.12; P=0.19), major adverse cardiovascular events (OR, 0.73, CI, 0.51–1.05; P=0.09), target vessel revascularization (OR, 1.0; CI, 0.95–1.05; P=0.94), periprocedural MI (OR, 1.12; CI, 0.65–1.90, P=0.69), and late MI (OR, 0.80; CI, 0.52–1.23; P=0.30) between the 2 groups. Sensitivity analysis excluding CathPCI Registry study showed no difference in periprocedural MI, late MI, and target vessel revascularization; however, it favored EPD use in all-cause mortality and major adverse cardiovascular events. Further sensitivity analysis including only observational studies revealed no difference in all-cause mortality, major adverse cardiovascular events, target vessel revascularization, and late MI. Additional analysis after excluding CathPCI Registry study revealed no difference in outcomes. Conclusions: This study including 52 893 patients suggests no apparent benefit in routine use of EPD during SVG intervention in the contemporary real-world practice. Further randomized clinical trials are needed in current era to evaluate long-term outcomes in routine use of EPD, and meanwhile, current guideline recommendations on EPD use should be revisited.

The final publication is available at http://dx.doi.org/10.1016/j.jtcvs.2013.11.054. Motoaki Ohnaka, Akira Marui, Kenichi Yamahara, Kenji Minakata, Kazuhiro Yamazaki, Motoyuki Kumagai, Hidetoshi Masumoto, Shiro Tanaka, Tadashi Ikeda, Ryuzo Sakata, Effect of microRNA-145 to prevent vein graft disease in rabbits by regulation of smooth muscle cell phenotype, The Journal of Thoracic and Cardiovascular Surgery, Volume 148, Issue 2, August 2014, Pages 676-682.e2, ISSN 0022-5223. / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18544号 / 医博第3937号 / 新制||医||1006(附属図書館) / 31444 / 京都大学大学院医学研究科医学専攻 / (主査)教授 木村 剛, 教授 野田 亮, 教授 瀬原 淳子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Yes / Type 2 diabetes (T2DM) confers increased risk of endothelial dysfunction, coronary heart disease, and vulnerability to vein graft failure after bypass grafting, despite glycaemic control. This study explored the concept that endothelial cells (EC) cultured from T2DM and nondiabetic (ND) patients are phenotypically and functionally distinct. Cultured human saphenous vein- (SV-) EC were compared between T2DM and ND patients in parallel. Proliferation, migration, and in vitro angiogenesis assays were performed; western blotting was used to quantify phosphorylation of Akt, ERK, and eNOS. The ability of diabetic stimuli (hyperglycaemia, TNF-α, and palmitate) to modulate angiogenic potential of ND-EC was also explored. T2DM-EC displayed reduced migration (~30%) and angiogenesis (~40%) compared with ND-EC and a modest, nonsignificant trend to reduced proliferation. Significant inhibition of Akt and eNOS, but not ERK phosphorylation, was observed in T2DM cells. Hyperglycaemia did not modify ND-EC function, but TNF-α and palmitate significantly reduced angiogenic capacity (by 27% and 43%, resp.), effects mimicked by Akt inhibition. Aberrancies of EC function may help to explain the increased risk of SV graft failure in T2DM patients. This study highlights the importance of other potentially contributing factors in addition to hyperglycaemia that may inflict injury and long-term dysfunction to the homeostatic capacity of the endothelium.

Background: Drug eluting stents (DES) are preferred over bare metal stents (BMS) for native coronary artery revascularization unless contraindicated. However, the preferred stent choice for saphenous venous graft (SVG) percutaneous coronary interventions (PCI) is unclear due to conflicting results. Methods: PubMed, Clinical trials registry and the Cochrane Center Register of Controlled Trials were searched through June 2018. Seven studies (n = 1639) comparing DES versus BMS in SVG-PCI were included. Endpoints were major adverse cardiac events (MACE), cardiovascular mortality, all-cause mortality, myocardial infarction (MI), target vessel revascularization (TVR), target lesion revascularization (TLR), in-stent thrombosis, binary in-stent restenosis, and late lumen loss (LLL). Results: Overall, during a mean follow up of 32.1 months, there was no significant difference in the risk of MACE, cardiovascular mortality, all-cause mortality, MI, stent thrombosis, TVR and TLR between DES and BMS. However, short-term follow up (mean 11 months) showed lower rate of MACE (OR 0.66 [0.51, 0.85]; p = 0.002), TVR (OR 0.47 [0.23, 0.97]; p = 0.04) and binary in-stent restenosis (OR 0.14 [0.06, 0.37]; p < 0.0001) in DES as compared with BMS. This benefit was lost on long-term follow up with a mean follow up 35.5 months. Conclusion: In this meta-analysis of SVG-PCI, DES use was associated with similar MACE, cardiovascular mortality, all-cause mortality, MI, in-stent thrombosis, TVR and TLR compared with BMS during long-term follow up. There was high incidence of MACE noted in both DES and BMS suggesting a need for exploring novel strategies to treat SVG disease to improve clinical outcomes.

Στο συγκεκριμένο ερευνητικό πρωτόκολλο μελετήθηκαν οι πιθανές ένοχες βλάβες σε φλεβικά μοσχεύματα ασθενών με οξέα στεφανιαία σύνδρομα με τη μέθοδο της Οπτικής Συνεκτικής Τομογραφίας (OCT). • Οι αθηροσκληρωτικές βλάβες των φλεβικών μοσχευμάτων έχουν μελετηθεί in vivo με τη μέθοδο της αγγειοσκόπησης και της ενδαγγειακής υπερηχογραφίας (IVUS). Απεναντίας, η απεικόνιση των μοσχευμάτων με τη μέθοδο της OCT, η οποία χαρακτηρίζεται από σημαντικά μεγαλύτερη διακριτική ικανότητα σε σχέση με το IVUS και βελτιωμένη διεισδυτική ικανότητα συγκρινόμενη με την αγγειοσκόπηση, δεν έχει μελετηθεί συστηματικά. • Μέθοδος: Η απεικόνιση των ένοχων βλαβών των μοσχευμάτων πραγματοποιήθηκε, κατόπιν αγγειογραφίας τους, με τη μέθοδο χωρίς απόφραξη της OCT σε ασθενείς με ασταθή στηθάγχη (UA), έμφραγμα μυοκαρδίου με ανάσπαση του διαστήματος ST (STEMI) και έμφραγμα μυοκαρδίου χωρίς ανάσπαση του διαστήματος ST (non-STEMI). Ο ινώδης ιστός, ο λιπώδης ιστός, οι εναποθέσεις ασβεστίου, ο θρόμβος και η ρήξη της πλάκας ορίστηκαν σύμφωνα με τα κριτήρια απεικόνισης στοιχείων για την OCT, όπως περιγράφηκαν και στο γενικό μέρος. • Αποτελέσματα: Απεικονίστηκαν 28 φλεβικά μοσχεύματα (μέσης ηλικίας 14.6 ετών) σε 26 ασθενείς. Οι βλάβες χαρακτηρίστηκαν ως σύμπλοκες αγγειογραφικά σε ποσοστό 96.4%, ενώ εμφάνιζαν εξέλκωση σε ποσοστό 32.1% και θρόμβο σε ποσοστό 21.4%. Η OCT αποκάλυψε ινολιπώδη σύσταση σε όλες τις βλάβες, εναπόθεση ασβεστίου στο 32.1% των βλαβών, ρήξη πλάκας σε ποσοστό 60.7% και παρουσία θρόμβου σε ποσοστό 46.4%. Η παρουσία του θρόμβου ήταν προοδευτικά συχνότερη ανάμεσα στις ομάδες ανάλογα με το κλινικό τους σύνδρομο (UA έως STEMI, p=0.003, UA έναντι εμφράγματος μυοκαρδίου, p=0.006). Η λεπτή ινώδης κάψα καταγράφηκε οριακά συχνότερα στους ασθενείς με οξύ έμφραγμα μυοκαρδίου (UA έναντι εμφράγματος μυοκαρδίου, p=0.06, STEMI 100% έναντι non-STEMI 53.3% έναντι UA 20%, p=0.03). Βλάβες με στοιχεία ευθρυπτότητας, όπως απεικονίζονταν στην OCT παρουσιάζονταν σε ποσοστό 67.9%, χωρίς όμως συσχέτιση με την κλινική εικόνα. • Συμπέρασμα: Οι ένοχες βλάβες φλεβικών μοσχευμάτων μεγάλης ηλικίας ασθενών με οξέα στεφανιαία σύνδρομα, όπως αυτές απεικονίζονται στην OCT, εμφανίζουν ινολιπώδη σύσταση, σχετικά λεπτή ινώδη κάψα, ρήξη πλάκας και θρόμβο που συσχετίζονται με το κλινικό φάσμα των οξέων στεφανιαίων συνδρόμων. Αυτά οδηγούν στο συμπέρασμα ότι οι ίδιοι μηχανισμοί αθηροσκλήρωσης που οδηγούν στην εμφάνιση οξέων στεφανιαίων συνδρόμων στα γηγενή στεφανιαία αγγεία, είναι πιθανόν να ενέχονται και στην πρόκληση οξέων στεφανιαίων συνδρόμων λόγω αποτυχίας των φλεβικών μοσχευμάτων. / This study sought to assess, with optical coherence tomography (OCT), presumably culprit atherosclerotic lesions of saphenous vein grafts (SVGs) in patients with acute coronary syndromes (ACS). Background: Atherosclerotic lesions of SVGs have been studied in vivo with angioscopy and intravascular ultrasound. However, imaging with OCT, which has a higher resolution than intravascular ultrasound and better penetration than angioscopy, has not been conducted systematically. Methods Using a nonocclusive OCT technique, we performed angiography and OCT of culprit SVG lesions in patients with unstable angina (UA), ST-segment elevation myocardial infarction (STEMI), and non-STEMI. Fibrous and fatty tissue, calcification, thrombus, and plaque rupture were defined according to OCT objective criteria. Results: Twenty-eight SVGs (average age 14.6 years) in 26 patients were imaged. Lesions on angiography were complex (96.4%), with ulceration in 32.1% and thrombus in 21.4%. OCT disclosed a fibrofatty composition in all lesions, calcification in 32.1%, plaque rupture in 60.7%, and thrombus in 46.4%. Thrombus was progressively more frequent across groups (UA to STEMI, p=0.003; UA vs. myocardial infarction, p=0.006). A thin fibrous cap was marginally more frequent in myocardial infarction patients (UA vs. myocardial infarction, p=0.06; STEMI 100% vs. non-STEMI 53.3% vs. UA 20%, p=0.03). OCT features of friability were present in 67.9% of SVGs not correlating with clinical presentation. Conclusions: OCT of culprit lesions of old SVGs in patients with ACS demonstrates fibrofatty composition, relatively thin fibrous cap, plaque rupture, and thrombus, which correlate with the clinical spectrum of ACS. This suggests that similar mechanisms with native vessels’ atherosclerosis may be involved in SVG-related ACS.