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OBJECTIVES We aimed to evaluate early and late outcomes by comparing open total arch repair and endovascular arch repair using proximal landing zone analysis in a multicentre cohort. METHODS From 2008 to 2019, patients treated surgically for aortic arch disease at 6 centres were included, excluding cases with type A aortic dissection, additional aortic root replacement and extensive aortic aneurysm. In all patients and populations with proximal landing zones 0/1 (N  = 144) and 2 (N  = 187), early and late outcomes were compared using propensity score matching. RESULTS A total of 1052 patients, including 331 (31%) and 721 (69%) patients undergoing endovascular arch repair and open total arch repair, respectively, were enrolled. After propensity score match (endovascular arch repair, 295; open total arch repair, 566), no significant difference was observed in in-hospital mortality rate (endovascular arch repair, 6.8%; open total arch repair, 6.2%; P  = 0.716). Open total arch repair was associated with a lower risk of all-cause death [log-rank test; P  = 0.010, hazard ratio (HR) 1.41 (95% confidence interval 1.17–1.71)]. The incidence of aorta-related death was higher in endovascular arch repair [Gray's test; P  = 0.030, HR; 1.44 (95% confidence interval 1.20–1.73)]. When compared to endovascular arch repair with proximal landing zone 0/1, open total arch repair was associated with lower risks of all-cause death [log-rank test; P  < 0.001, HR 2.04 (95% confidence interval 1.43–2.90)] and aorta-related death [Gray's test; P  = 0.002, HR 1.67 (95% confidence interval; 1.25–2.24)]. There was no difference in the risk of all-cause death [log-rank test; P  = 0.961, HR 0.99 (95% confidence interval 0.67–1.46)] and aorta-related death [Gray's test; P  = 0.55, HR 1.31 (95% confidence interval 1.03–1.67)] between endovascular arch repair with proximal landing zone 2 and open total arch repair. CONCLUSIONS Open total arch repair was considered the 1st choice based on early and late results; however, endovascular arch repair may be a useful option if the proximal landing zone is limited to zone 2. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the incidence and risk factors of postoperative acute pancreatitis (PAP) following thoracic aortic surgery with circulatory arrest. Methods: One hundred fifty-two patients who underwent thoracic aortic surgery with circulatory arrest between February 2015 and March 2023 were retrospectively reviewed. Postoperative acute pancreatitis was defined as the presence of two or more of the following criteria: (1) abdominal pain, (2) postoperative amylase or lipase levels greater than three times the upper limit of normal, and (3) evidence of pancreatitis on postoperative computed tomography (CT) scan. Univariate and multivariate analyses were performed to find risk factors for PAP. Results: Nine patients (5.9%) developed PAP without mortality. All of the nine patients had elevated pancreatic enzymes and evidence of pancreatitis on CT. They improved with conservative therapy. In multivariate analysis, only cross-clamp time was found to be a significant risk factor for PAP (adjusted odds ratio, 1.04; 95% confidence interval, 1–1.08; p = 0.042). Conclusion: The incidence of PAP after thoracic aortic surgery with circulatory arrest was 5.9%, and cross-clamp time is an independent risk factor for PAP. [ABSTRACT FROM AUTHOR]

Background Valve-sparing root replacement (VSRR) is an established therapy for aortic root pathology. However, late aortic valve dysfunction requiring reoperation remains a primary concern of this procedure. This study examines risk factors for late aortic insufficiency (AI) and aortic stenosis (AS) after David V VSRR. Methods A retrospective review from 2005 to 2015 at a US academic center identified 282 patients who underwent VSRR. Cox proportional hazards regression analysis was used to identify risk factors for late AI and AS after VSRR. Results The mean age was 46.4 years. Sixty-four patients (22.7%) had bicuspid valves, and 41 patients (14.5%) had Marfan syndrome. The incidence of reoperations was 27 (9.6%), and 42 cases (14.9%) presented with acute type A dissection. Operative mortality was 8 (2.8%). Seven-year survival was 90.9%. Seven-year cumulative incidence of reoperation, greater than 2+ AI and greater than moderate AS were 3.1%, 2.2%, and 0.8%, respectively. Multivariable analysis showed aortic root size 55 mm or larger (hazard ratio 3.44, 95% confidence interval: 1.27 to 9.29, p = 0.01) to be a risk factor for late AI whereas bicuspid valve (hazard ratio 16.07, 95% confidence interval: 3.12 to 82.68, p = 0.001) and cusp repair were found to be risk factors (hazard ratio 5.91, 95% confidence interval: 1.17 to 29.86, p = 0.03) for late AS. Conclusions Valve-sparing root replacement can be performed with low operative risk and good overall long-term survival even in complex clinical settings. Durable valve function can be expected; however, aortic root size 55 cm or more, bicuspid valve anatomy, and cusp repair represent independent risk factors for late aortic valve dysfunction after these procedures. [ABSTRACT FROM AUTHOR]

Background Valve-sparing root replacement (VSRR) is an established therapy for aortic root pathology. Limited insight exists when the results of VSRR are compared with those of conventional root replacement with use of a bioprosthetic composite conduit (BIO). This study compares the operative and midterm results of VSRR and BIO. Methods A retrospective review from 2002 to 2015 at a United States academic center identified 282 patients who underwent VSRR and 425 patients who underwent BIO. Propensity-score matching was performed based on 20 preoperative characteristics, and 123 matched pairs were identified. Results The mean age (VSRR 53.5 ± 11.1, BIO 53.0 ± 13.0; p = 0.74) and left ventricular ejection fraction (VSRR 54.5 ± 9.2%, BIO 54.4 ± 9.4%; p = 0.99) were equivalent in both groups. The incidence of bicuspid valves (VSRR 26.0%, BIO 27.6%; p = 0.77), Marfan syndrome (VSRR 6.5%, BIO 4.9%; p = 0.58), type A dissection (VSRR 13.0%, BIO 13.0%; p = 0.99), reoperation (VSRR 15.4%, BIO 20.3%; p = 0.32) and arch replacement (VSRR 60.2%, BIO 63.4%; p = 0.60) were similar between the groups. Operative mortality was 5.7% in VSRR and 0.8% in BIO ( p = 0.07). There were no significant differences in postoperative renal failure (VSRR 0.8%, BIO 0.0%; p = 0.99) or stroke (VSRR 3.3%, BIO 0.8%; p = 0.37) between the groups. The 7-year survival (VSSR 82.4%, BIO 83.0%; p = 0.53), 7-year freedom from reoperation (VSRR 97.4%, BIO 95.8%; p = 0.48), and 7-year freedom from greater than moderate aortic insufficiency (AI) (VSRR 98.1%, BIO 100.0%; p = 0.47) were similar between groups. Conclusions VSRR and BIO result in equivalent operative mortality and morbidity with similar midterm survival and valve durability. VSRR is an effective alternative to BIO for aortic root pathologic conditions; however, careful patient selection is paramount. [ABSTRACT FROM AUTHOR]

Background Valve-sparing root replacement (VSRR) is an attractive therapy for aortic root aneurysms; however, there is a paucity of data comparing VSRR with conventional root replacement using a mechanical valve-conduit (MECH). This study evaluates and compares outcomes of VSRR and MECH. Methods A retrospective review from 2002 to 2015 at a US academic center identified 444 patients who underwent VSRR (282 patients) or MECH (162 patients). Propensity score matching was performed, based on 22 preoperative and intraoperative characteristics, and 87 matched pairs were identified. Results There was no difference in mean age between the groups (VSRR 45.0 years, MECH 44.2 years, p = 0.59). The incidence of Marfan syndrome (VSRR 10.3%, MECH 12.6%, p = 0.63), type A acute aortic dissection (VSRR 25.3%, MECH 27.6%, p = 0.73), reoperation (VSRR 23.0%, MECH 21.8%, p = 0.86), and arch replacement (VSRR 54.0%, MECH 52.9%, p = 0.88) were similar in both groups. Ejection fraction was similar (VSRR 52.8% ± 10.9%, MECH 52.4% ± 11.7%, p = 0.83). Operative mortality was 2.3% with VSRR and 8.0% with MECH ( p = 0.10). There were no significant differences in renal failure requiring dialysis (VSRR 1.1%, MECH 4.6%, p = 0.24), permanent neurologic dysfunction (VSRR 2.3%, MECH 6.9%, p = 0.16), and pacemaker implantation (VSRR 1.1%, MECH 1.1%, p = 0.99) between the groups. Survival at 7 years was significantly improved in patients who underwent VSSR (VSRR 85.5%, MECH 73.6%, p = 0.03). Conclusions In comparison with patients undergoing MECH, there is improved midterm survival among patients undergoing VSRR, with similar operative mortality and morbidity. For appropriately selected patients, VSRR provides an attractive and potentially superior alternative to MECH. [ABSTRACT FROM AUTHOR]

Background: Bilateral internal thoracic artery grafting in coronary artery bypass surgery has a better long-term outcome than single internal thoracic artery grafting. However, the efficacy of gastroepiploic artery (GEA) grafting in addition to bilateral internal thoracic artery grafting is still not well-established. Methods: From 1989 to 1999, 311 patients underwent coronary artery bypass grafting using in situ bilateral internal thoracic arteries anastomosed to the left coronary arteries and either an in situ GEA or a saphenous vein graft (SVG) anastomosed to the right coronary artery. Ninety-nine patients using the in situ GEA (GEA group) were compared with 212 patients using the SVG (SVG group) anastomsed to the right coronary artery. Young patients and patients with hyperlipidemia were more prevalent in the GEA group. Results: The seven-year survival rate in the GEA group and the SVG group were 94.7% and 87.2%, respectively (p = 0.068). In a multivariate analysis, the age, renal failure, and a low ejection fraction (<0.40) were all significant predictors of survival. The GEA was not a significant predictor. The seven-year freedom rates from cardiac events were similar in both groups (GEA group, 76.5%; SVG group, 78.6%; p = 0.455). The seven-year freedom rates from recurrent angina were also similar between the groups (GEA group, 85.3%; SVG group, 88.8%; p = 0.700). Conclusions: In comparison with SVG grafting, GEA grafting to the right coronary artery did not significantly improve the late outcomes in patients with bilateral internal thoracic artery grafting. [Copyright &y& Elsevier]

Aims: There is a scarcity of studies comparing percutaneous coronary intervention (PCI) using new-generation drug-eluting stents (DES) with coronary artery bypass grafting (CABG) in patients with multi-vessel coronary artery disease., Methods and Results: The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who underwent first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. The current study population consisted of 2464 patients who underwent multi-vessel coronary revascularization including revascularization of left anterior descending coronary artery (LAD) either with PCI using new-generation DES (N = 1565), or with CABG (N = 899). Patients in the PCI group were older and more often had severe frailty, but had less complex coronary anatomy, and less complete revascularization than those in the CABG group. Cumulative 5-year incidence of a composite of all-cause death, myocardial infarction or stroke was not significantly different between the 2 groups (25.0% versus 21.5%, P = 0.15). However, after adjusting confounders, the excess risk of PCI relative to CABG turned to be significant for the composite endpoint (HR 1.27, 95%CI 1.04-1.55, P = 0.02). PCI as compared with CABG was associated with comparable adjusted risk for all-cause death (HR 1.22, 95%CI 0.96-1.55, P = 0.11), and stroke (HR 1.17, 95%CI 0.79-1.73, P = 0.44), but with excess adjusted risk for myocardial infarction (HR 1.58, 95%CI 1.05-2.39, P = 0.03), and any coronary revascularization (HR 2.66, 95%CI 2.06-3.43, P<0.0001)., Conclusions: In this observational study, PCI with new-generation DES as compared with CABG was associated with excess long-term risk for major cardiovascular events in patients who underwent multi-vessel coronary revascularization including LAD., Competing Interests: The authors have declared that no competing interests exist.

Background: Diabetes is a well-known risk factor for adverse outcomes after coronary revascularization., Objectives: This study sought to determine high-risk subgroups in whom the excess risks of diabetes relative to nondiabetes are particularly prominent and thus may benefit from more aggressive interventions., Methods: The study population consisted of 39,427 patients (diabetes: n = 15,561; nondiabetes: n = 23,866) who underwent first percutaneous coronary intervention (n = 33,144) or coronary artery bypass graft (n = 6,283) in the pooled CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Graft) registry. The primary outcome measure was major adverse cardiovascular and cerebral endpoints (MACCE), which was defined as a composite of all-cause death, myocardial infarction, and stroke., Results: With median follow-up of 5.6 years, diabetes was associated with significantly higher adjusted risks for MACCE. The excess adjusted risks of diabetes relative to nondiabetes for MACCE increased with younger age (≤64 years: adjusted HR: 1.30; 95% CI: 1.19-1.41; P  < 0.001; 64-73 years: adjusted HR: 1.24; 95% CI: 1.16-1.33; P  < 0.001; >73 years: adjusted HR: 1.17; 95% CI: 1.10-1.23; P  < 0.001; P interaction  < 0.001), mainly driven by greater excess adjusted mortality risk of diabetes relative to nondiabetes in younger tertile. No significant interaction was observed between adjusted risk of diabetes relative to nondiabetes for MACCE and other subgroups such as sex, mode of revascularization, and clinical presentation of acute myocardial infarction., Conclusions: The excess risk of diabetes relative to nondiabetes for MACCE was profound in the younger population. This observation suggests more aggressive interventions for secondary prevention in patients with diabetes might be particularly relevant in younger patients., Competing Interests: This study was supported by an educational grant from the Research Institute for Production Development (Kyoto, Japan). Dr Yamaji has received a research grant from Abbott Vascular. Dr Shiomi has received honoraria from Abbott Vascular and Boston Scientific. Dr Morimoto has received lecturer's fees from Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray; manuscript fees from Bristol-Myers Squibb and Kowa; and has served on the Advisory Board of Sanofi. Dr Ehara has received honoraria from Abbott Vascular, Bayer, Boston Scientific, Medtronic, and Terumo. Dr Furukawa has received honoraria from Bayer, Kowa, and Sanofi. Dr Nakagawa has received research grants from Abbott Vascular and Boston Scientific; and honoraria from Abbott Vascular, Bayer, and Boston Scientific. Dr Kimura has received a research grant from Abbott Vascular; and honoraria from Astellas, AstraZeneca, Bayer, Boston Scientific, Kowa, and Sanofi. All the other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Aims: Tricuspid regurgitation (TR) has been reported to be associated with worse survival in various heart diseases, but there are few data in aortic stenosis (AS)., Methods and Results: In the Contemporary Outcomes after Surgery and Medical Treatment in Patients with Severe Aortic Stenosis (CURRENT AS) Registry enrolling 3815 consecutive patients with severe AS, there were 628 patients with moderate or severe TR (TR group) and 3187 patients with no or mild TR (no TR group). The study patients were subdivided into the initial aortic valve replacement (AVR) stratum (n = 1197) and the conservative stratum (n = 2618) according to treatment strategy. The primary outcome measure was a composite of aortic valve-related death or hospitalization due to heart failure. The 5-year freedom rate from the primary outcome measure was significantly lower in the TR group than in the no TR group (49.1% vs. 67.3%, P < 0.001). Even after adjusting for confounders, the excess risk of TR relative to no TR for the primary outcome measure remained significant [hazard ratio (HR): 1.25, 95% confidence interval (CI): 1.06-1.48; P = 0.008]. The trend for the excess adjusted risk in the TR group was consistent in the initial AVR and the conservative strata (HR 1.55, 95% CI: 0.97-2.48; P = 0.07; HR 1.22, 95% CI: 1.02-1.46; P = 0.03, respectively). In the initial AVR stratum, the 5-year freedom rate from the primary outcome measure was not different between the two groups with (n = 56) or without (n = 91) concomitant tricuspid annuloplasty (61.5% vs. 72.1%, P = 0.48)., Conclusion: The presence of clinically significant TR concomitant with severe AS is associated with a poor long-term outcome, regardless of the initial treatment strategy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background: There is no large-scale study comparing postoperative mortality after aortic valve replacement (AVR) for asymptomatic severe aortic stenosis (AS) between initial treatment with AVR vs. eventual AVR after conservative management., Methods and results: We analyzed data from a multicenter registry enrolling 3,815 consecutive patients with severe AS. Of 1,808 asymptomatic patients, 286 patients initially underwent AVR (initial AVR group), and 377 patients were initially managed conservatively and eventually underwent AVR (AVR after watchful waiting group). Mortality after AVR was compared between the 2 groups. Subgroup analysis according to peak aortic jet velocity (Vmax) at diagnosis was also conducted. There was no significant difference between the 2 groups in 5-year overall survival (OS; 86.0% vs. 84.1%, P=0.34) or cardiovascular death-free survival (DFS; 91.3% vs. 91.1%, P=0.61), but on subgroup analysis of patients with Vmax ≥4.5 m/s at diagnosis, the initial AVR group was superior to the AVR after watchful waiting group in both 5-year OS (88.4% vs. 70.6%, P=0.003) and cardiovascular DFS (91.9% vs. 81.7%, P=0.023)., Conclusions: Asymptomatic severe AS patients who underwent AVR after watchful waiting had a postoperative survival rate similar to those who initially underwent AVR. In a subgroup of patients with Vmax ≥4.5 m/s at diagnosis, however, the AVR after watchful waiting group had worse postoperative survival rate than the initial AVR group.

Background: Although intravenous administration of prostaglandin E(1) (PGE(1)) is commonly used in the treatment of peripheral arterial disease, it rapidly becomes inactivated in the lung. Whether local administration of sustained-release (SR) PGE(1) enhances neovascularization in murine hindlimb ischemia was investigated., Methods and Results: Poly lactide-co-glycolide (PLGA) microspheres were the 4-week SR carrier of PGE(1). C57BL/6 mice with unilateral hindlimb ischemia were randomly treated as follows: no treatment (Group N); single administration of 100 microg/kg PGE(1) solution (Group L) into the ischemic muscles; daily systemic administration of PGE(1) for 2 weeks at a total dose 100 microg/kg (Group S); and single administration of PGE(1)-100 microg/kg-loaded PLGA (Group P100) into the ischemic muscles. The blood perfusion in Group P100 was higher than in Groups N, L and S (ischemic/nonischemic blood perfusion ratio 88 +/-11% vs 73 +/-11% (P<0.01), 77 +/-9% (P<0.05), 79 +/-11% (P<0.05), respectively). Vascular density and alphaSMA-positive-vessel density in Group P100 were higher than in Groups N, L and S (vascular density (vessels/m(2)): 241 +/-39 vs 169 +/-49 (P<0.01), 169 +/-54 (P<0.01), 201 +/-42 (P<0.05), respectively; alphaSMA-positive-vessel density (vessels/m(2)): 34 +/-10 vs 18 +/-6 (P<0.01), 21 +/-11 (P<0.01), 22 +/-10 (P<0.01), respectively), Conclusions: Local administration of a single dose of SR PGE(1) enhances neovascularization in mice hindlimb ischemia more efficiently than daily systemic administration.

Background: Basic fibroblast growth factor (bFGF) is a potent mitogen; however, diabetes mellitus might impair its angiogenic property. Prostaglandin E1 (PGE1) is a potent vasodilator and improves endothelial function. Thus, PGE1 could potentiate the angiogenic properties of bFGF in patients with diabetes mellitus., Methods and Results: Streptozotocin-induced diabetic mice with unilateral hindlimb ischemia were randomly treated as follows: no treatment, 0.2 microg of PGE1, 10 microg of bFGF, and combined administration of PGE1 and bFGF. Blood perfusion was evaluated by the ratio of ischemic-to normal-limb blood perfusion. Four weeks after the treatment, the combined administration of bFGF and PGE1 increased the blood perfusion ratio as compared with single bFGF or PGE1 (77+/-10% vs 56+/-10% and 58+/-10%; p < 0.05, respectively). A histological evaluation showed that vascular density in the combined therapy was higher than single bFGF or PGE1 (418+/-59 vs 306+/-69 and 283+/-71 vessels/mm2; p < 0.01, respectively); the maturity in combined therapy was also higher than single bFGF or PGE1 (46+/-14 vs 30+/-14 and 28+/-6 vessels/mm2; p < 0.01, respectively)., Conclusions: PGE1 potentiated the impaired angiogenic properties of bFGF in diabetic murine hindlimb ischemia. This new strategy might contribute to more effective therapeutic angiogenesis for ischemic limb in patients with diabetes.

Background: The combined treatment of sustained-release basic fibroblast growth factor (Sr-bFGF) and a 5-hydroxytryptamine(2A) blocker, sarpogrelate, was evaluated to see whether it reversed the impaired collateral circulation in diabetic (DM) mouse hindlimb ischemia., Method and Results: Diabetic and normal mice with ischemic hindlimb were randomly assigned to 1 of 5 experimental groups (no treatment, sarpogrelate 50 mg . kg(-1) . day(-1), 20 microg or 50 microg Sr-bFGF and a combined treatment of 20 microg Sr-bFGF and sarpogrelate), and treated for 4 weeks. Tissue blood perfusion (TBP), vascular density (angiogenesis) and the number of mature vessels (arteriogenesis) were checked by the use of standard methods. Although angiogenesis was comparable (161+/-14 vs 154+/-12 vessels/mm(2)), the laser Doppler perfusion image index (LDPII) (0.43+/-0.11 (SD) vs 0.63+/-0.08, p<0.05) and arteriogenesis (8+/-3 vs 12+/-4 vessels/mm(2), p<0.05) were significantly lower in DM mice than those in normal mice. The dose of Sr-bFGF for the sufficient number of mature vessels (>or=45 vessels/mm(2)) and LDPII (>or=0.9) was 20 microg for the normal mice, and 50 microg for the DM mice, which was reduced with the aid of sarpogrelate. Conclusions A combined therapy of Sr-bFGF and sarpogrelate is effective for neovascularization to reverse the impaired arteriogenesis and TBP in DM mice.

Worldwide, there is a growing number of patients with myocardial ischemia and limb ischemia associated with the aging population and an increased prevalence of atherosclerotic diseases. Medical therapy, percutaneous angioplasty and surgical revascularization are the present treatments of choice, but such treatments are not feasible for some patients with severe atherosclerosis. Therapeutic angiogenesis using growth factors or progenitor cells has drawn great attention as a favorable alternative treatment for such patients. This review discusses clinical trials using angiogenic growth factors for myocardial ischemia and limb ischemia, and also introduces a novel controlled release system for growth factors using a gelatin hydrogel.