Thyroid storm after mitral valve repair in a patient with Becker muscular dystrophy.

A 40-year-old male with Becker muscular dystrophy presented with severe mitral regurgitation and underwent mitral valve repair. Following the surgery, the patient became tachycardic and developed a continuous high-grade fever and hyperbilirubinemia. The patient's condition worsened and we eventually tested his thyroid levels and discovered abnormally high thyroid levels. After diagnosing a severe thyroid storm, the patient was treated with oral administration of Lugol's iodine and thiamazole, as well as an intravenous steroid, which led to an immediate improvement of symptoms. The incidence of thyroid storm after open-heart surgery is extremely rare but highly life-threatening if unrecognized.

Surgical Ineligibility and Long-Term Outcomes in Patients With Severe Coronary Artery Disease.

BACKGROUND: In patients with severe coronary artery disease (CAD) requiring coronary revascularization, the prevalence of surgical ineligibility and its clinical effect on long-term outcomes remain unclear.Methods and Results:Among 15,939 patients with first coronary revascularization in the CREDO-Kyoto percutaneous coronary intervention (PCI)/coronary artery bypass grafting (CABG) registry cohort-2, we identified 3,982 patients with triple-vessel or left main disease (PCI: n=2,188, and CABG: n=1,794). Surgical ineligibility as documented in hospital charts was present in 142 (6.5%) of 2,188 PCI-patients, which was mainly related to comorbidities and advanced age. The cumulative 5-year incidence of the primary outcome measure (all-cause death/myocardial infarction/stroke) was much higher in PCI-patients with surgical ineligibility than in PCI-patients without surgical ineligibility and in CABG-patients (52.5%, 27.6%, and 24.0%, respectively, log-rank P<0.001). After adjusting for confounders, the excess risk of PCI-patients with surgical ineligibility relative to CABG-patients was substantial (hazard ratio [HR] 1.97, 95% CI 1.51-2.58, P<0.001), while the excess risk of PCI-patients without surgical ineligibility relative to CABG-patients was modest, but remained significant (HR 1.37, 95% CI 1.19-1.59, P<0.001). CONCLUSIONS: Among patients with severe CAD, PCI-patients with surgical ineligibility had worse long-term outcomes as compared with those without surgical ineligibility and CABG-patients.

Therapeutic angiogenesis by local sustained release of microRNA-126 using poly lactic-co-glycolic acid nanoparticles in murine hindlimb ischemia.

OBJECTIVE: Recent studies demonstrate that microRNAs show promising potential, including angiogenesis, in therapeutic intervention. MicroRNA-126 (miR-126) is reported to regulate angiogenesis by blocking Sprouty-related EVH1 domain-containing protein 1 (SPRED1), an endogenous inhibitor of vascular endothelial cell growth factor. In this study, we investigated the angiogenic effects of the sustained release of miR-126 loaded with poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) in a murine hindlimb ischemia model. METHODS: We induced mice hindlimb ischemia through femoral artery excision. We randomly assigned the mice to two groups and performed an intramuscular injection of miR-126-loaded PLGA NPs (miR-126) or scrambled miR-loaded PLGA NPs (control) shortly after induction of ischemia. RESULTS: The miR-126 expression levels in the ischemic limb at 3 days after treatment were significantly higher in mice treated with miR-126-loaded PLGA NPs than in those with scrambled miR, indicating the fair efficiency of local miR transduction (control vs miR-126: 0.33 ± 0.12 vs 0.74 ± 0.42; P < .05; n = 6). Laser Doppler perfusion imaging revealed that limb blood flow in mice treated with miR-126-loaded PLGA NPs was significantly higher at 14 days after treatment (sham vs control vs miR-126: 0.62 ± 0.09 vs 0.58 ± 0.05 vs 0.72 ± 0.07; P < .001; n = 12). Immunohistochemical analysis indicated that CD31-positive cell density and α-smooth muscle actin-positive vessel density were significantly higher in miR-126-treated mice (control vs miR-126: 0.33 ± 0.12 vs 0.74 ± 0.42; P < .05; n = 6). SPRED1 messenger RNA expression levels were significantly lower in miR-126-treated mice (control vs miR-126: 1.00 ± 0.05 vs 0.81 ± 0.07; P < .05; n = 6). Western blotting indicated that protein levels of pERK/ERK mediated by SPRED1 were significantly higher in miR-126-treated mice (control vs miR-126: 0.29 ± 0.10 vs 0.54 ± 0.21; P < .05; n = 6). CONCLUSIONS: This study suggests that sustained release of miR-126-loaded PLGA NPs might be an effective method in therapeutic angiogenesis for hindlimb ischemia.

A therapeutic angiogenesis of sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel sheets in a canine chronic myocardial infarction model.

This study investigated the safety and efficacy of a sustained release of basic fibroblast growth factor (bFGF) with biodegradable gelatin hydrogel sheets as therapeutic angiogenesis in canine chronic myocardial infarction (MI) models. Canine chronic MI model was induced by ligating the left anterior descending coronary artery and its diagonal branches. At 4 week post-induction, we applied either saline (Control group, n = 5) or 200 µg of bFGF (Treatment group, n = 6) soaked gelatin hydrogel sheets on the ischemic area of the left ventricular (LV) wall. At 6 weeks after the procedure, we evaluated the efficacy by echocardiography and immunohistochemical study. There were no procedure-related adverse events or deaths. The serum bFGF level was under detectable levels in all animals at any sampling points. In terms of efficacy, echocardiographic evaluation demonstrated that fractional shortening was significantly improved in the treatment group. In addition, immunohistochemical study showed that the capillary density in the border zone of the MI area, as well as the MI area, significantly increased in the treatment group. Therapeutic angiogenesis by bFGF using biodegradable gelatin hydrogel sheets was safe, increased the capillary density, and improved LV function in canine chronic MI models.

Short- and long-term outcomes following redo valvular surgery.

AIM: We reviewed our experience in redo valvular surgery to evaluate trends in short- and long-term outcomes. METHODS: We reviewed 414 patients (mean age, 62.8 ± 13.6 years) who underwent redo valvular surgery in the past 25 years. A total of 301 patients (54.2%) underwent first-time redo valvular surgeries; 178 (32.1%) were second redos, 60 (10.8%) were third redos, and 16 were fourth redos (2.9%). The mean follow-up period was 6.8 ± 6.3 years. RESULTS: Hospital mortality was 5.8%. New York Heart Association (NYHA) class III/IV (P = 0.0007, odds ratio = 4.403) and hemodialysis (P = 0.0383, odds ratio = 7.196) were risk factors for hospital death. Long-term survival rates at 15 and 20 years were 64.7% ± 4.3% and 59.1% ± 5.0%, respectively. Predictors of late death were first time redo (P = 0.0076, hazard ratio = 0.422) and age younger than 61 years (P = 0.0005, hazard ratio = 0.229). There were significant differences in long-term survival between NYHA classes I/II and III/IV (log-rank test, P = 0.0419) and between the time from redo surgery (log-rank test, P = 0.0189) and age (log-rank test, P = 0.0001). CONCLUSIONS: The hospital mortality rate for redo valve surgery has improved. Early referral for redo surgery can contribute to improving early and late outcomes.

Effects of Age and Sex on Clinical Outcomes After Percutaneous Coronary Intervention Relative to Coronary Artery Bypass Grafting in Patients With Triple-Vessel Coronary Artery Disease.

BACKGROUND: Age and sex are important considerations in the choice between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in daily clinical practice. METHODS AND RESULTS: Of 25 816 patients enrolled in the multicenter Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto; Cohort-1, n=9877; Cohort-2, n=15 939), the present study population consisted of 5651 patients (men, n=3998; women, n=1653) with triple-vessel coronary artery disease who were considered to be pertinent in comparisons of PCI with CABG (PCI, n=3165; CABG, n=2486). Patients were divided into 3 groups according to the tertiles of age: ≤65 years (n=1972), 66 to 73 years (n=1820), and ≥74 years (n=1859). The excess adjusted mortality risk of PCI relative to CABG was significant in patients ≥74 years of age (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.10-1.79; P=0.006), whereas the risks were neutral in patients ≤65 years of age (HR, 1.05; 95% CI, 0.73-1.53; P=0.78) and in patients 66 to 73 years of age (HR, 1.03; 95% CI, 0.78-1.36; P=0.85; interaction P=0.003). The excess mortality risk of PCI relative to CABG was significant in men (HR, 1.24; 95% CI, 1.03-1.50; P=0.02) and trended to be significant in women (HR, 1.34; 95% CI, 0.98-1.84; P=0.07) without significant interaction between sex and the mortality risk of PCI relative to CABG (interaction P=0.40). CONCLUSIONS: There was a significant association between age and the mortality risk of PCI relative to CABG with excess risk in patients ≥74 years of age and neutral risk in younger patients. There was no significant sex-related difference in the mortality risk of PCI relative to CABG.

Prevention of abdominal aortic aneurysm progression by oral administration of green tea polyphenol in a rat model.

OBJECTIVE: Inflammation-mediated elastin destruction in the aortic medial layer is related to progression of abdominal aortic aneurysm (AAA). Epigallocatechin-3-gallate (EGCG), a major component of green tea polyphenols, reportedly increases elastin synthesis in vitro and may possess anti-inflammatory effects. We used a rat model to investigate whether EGCG could prevent AAA progression. METHODS: AAA was induced with administration of intraluminal elastase and extraluminal CaCl2 in male rats. Rats were randomly divided into a control group (n = 30) and an EGCG group (n = 30). In the EGCG group, an EGCG solution (20 mg/d) was administered orally to each rat from 2 weeks before AAA induction and continued 4 weeks beyond induction. RESULTS: The abdominal aortic diameter was significantly smaller in the EGCG group than in the control group on day 28 (2.9 ± 0.2 vs 2.3 ± 0.1 mm; P < .0001). The medial layer wall thickness and elastin content were significantly greater in the EGCG group than in the control group on day 28 (68.4 ± 13.6 vs 46.7 ± 13.4 µm [P < .001] and 20.3 ± 4.6 vs 9.5 ± 3.6% [P < .0001], respectively). Gene expression levels of tropoelastin and lysyl oxidase were significantly higher in the EGCG group immediately before AAA induction, indicating promoted elastoregeneration by EGCG administration (tropoelastin: 0.59 ± 0.36 control vs 1.24 ± 0.36 EGCG [P < .05], lysyl oxidase: 0.77 ± 0.45 control vs 1.34 ± 0.4 EGCG [P < .05]) (fold increase). Gene expression levels of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1ß, were significantly downregulated in the EGCG group (1.82 ± 0.71 vs 0.97 ± 0.59 [P < .05] and 3.91 ± 3.24 vs 0.89 ± 0.59 [P < .05], respectively). On day 7, gene expression levels and gelatinolytic activity of matrix metalloproteinase 9 were significantly lower in the EGCG group (1.41 ± 0.86 vs 0.51 ± 0.42 [P < .05] and 1.00 ± 0.17 vs 0.29 ± 0.12 [P < .0001], respectively), whereas gene expression levels of tissue inhibitors of metalloproteinase-1 were significantly higher in the EGCG group (0.96 ± 0.11 vs 1.14 ± 0.09; P < .05). CONCLUSIONS: EGCG attenuated AAA progression in a rat model by preserving the aortic thickness and elastin content of the medial layer through regeneration of elastin, as mediated by anti-inflammatory effects, and subsequent reduction of matrix metalloproteinase activity.

Comparison of the Long-Term Outcomes of Mechanical and Bioprosthetic Aortic Valves　- A Propensity Score Analysis.

BACKGROUND: The aim of this study was to assess the long-term outcomes of aortic valve replacement (AVR) with either mechanical or bioprosthetic valves according to age at operation.Methods and Results:A total of 1,002 patients (527 mechanical valves and 475 bioprosthetic valves) undergoing first-time AVR were categorized according to age at operation: group Y, age <60 years; group M, age 60-69 years; and group O, age ≥70 years). Outcomes were compared on propensity score analysis (adjusted for 28 variables). Hazard ratio (HR) was calculated using the Cox regression model with adjustment for propensity score with bioprosthetic valve as a reference (HR=1). There were no significant differences in overall mortality between mechanical and bioprosthetic valves for all age groups. Valve-related mortality was significantly higher for mechanical valves in group O (HR, 2.53; P=0.02). Reoperation rate was significantly lower for mechanical valves in group Y (HR, 0.16; P<0.01) and group M (no events for mechanical valves). Although the rate of thromboembolic events was higher in mechanical valves in group Y (no events for tissue valves) and group M (HR, 9.05; P=0.03), there were no significant differences in bleeding events between all age groups. CONCLUSIONS: The type of prosthetic valve used in AVR does not significantly influence overall mortality.

Five-Year Clinical Outcome of Asymptomatic vs. Symptomatic Severe Aortic Stenosis After Aortic Valve Replacement.

BACKGROUND: There is discordance regarding the effect of symptom status before aortic valve replacement (AVR) on long-term outcome after AVR in severe aortic stenosis (AS).Methods and Results:The CURRENT AS registry is a multicenter retrospective registry enrolling 3,815 consecutive patients with severe AS. Among 1,196 patients managed with the initial AVR strategy, long-term clinical outcomes were compared between the symptomatic patients (n=905), and asymptomatic patients (n=291). Median follow-up interval was 1337 days with a 91% follow-up rate at 2 years. AVR was performed in 886 patients (98%) in the symptomatic group and in 287 patients (99%) in the asymptomatic group. Symptomatic patients were older and more often had comorbidities than asymptomatic patients with similar echocardiographic AS severity. The cumulative 5-year incidences of all-cause death and heart failure (HF) hospitalization were significantly higher in symptomatic patients than in asymptomatic patients (25.6% vs. 15.4%, P=0.001, and 14.2% vs. 3.8%, P<0.001, respectively). On landmark analysis at 30 days after AVR, the differences in mortality and HF hospitalization between the 2 groups were mainly observed beyond 30 days. CONCLUSIONS: When managed with the initial AVR strategy, the long-term outcomes of symptomatic severe AS were worse than those of asymptomatic severe AS. Early AVR strategy might be recommended in some selected asymptomatic severe AS patients with reasonable operative risk.

[Dehiscence of the Pericardial Patch, after Surgical Treatment of Active Infective Aortic Valve Endocarditis with Reconstruction of the Aortic Annulus Using a Glutaraldehyde-treated Autologous Pericardium].

A 50-year-old man was admitted with fever and chill sensation 6 months ago. Transthoracic echocardiography (TTE) showed left and right coronary cusp prolapses and a thickened tissue of the aortic curtain. Congestive heart failure due to active infective aortic valve endocarditis was diagnosed, and he underwent aortic valve replacement. The aortic annulus was reconstructed using a glutaraldehydetreated autologous pericardium. Six months after surgery, TTE showed severe aortic regurgitation and saccular change in the aortic annulus. Transesophageal echocargiography showed some echo free space from left to noncoronary cusp and abnormal movement of the prosthetic valve annulus. Intraoperative examination showed dehiscence of the pericardial patch from the aortic wall, but no finding of infection. Aortic valve rereplacement was performed with reconstruction of the aortic annulus using a bovine pericardium. To prevent the dehiscence of the pericardial patch from the aortic wall, sutures fixing the prosthetic valve were passed from outside of the aortic wall.

Favorable Clinical Outcomes of Transcatheter Aortic Valve Implantation in Japanese Patients　- First Report From the Post-Approval K-TAVI Registry.

BACKGROUND: Very limited data exist on the outcomes of transcatheter aortic valve implantation (TAVI) since Japanese marketing approval of the first TAVI device.Methods and Results:The Kyoto University-related hospital Transcatheter Aortic Valve Implantation (K-TAVI) registry includes prospectively collected data from 6 participating hospitals in Japan. We included 302 patients with severe aortic stenosis who underwent TAVI using the SAPIEN XT balloon-expandable valve via transfemoral (TF; n=203, 67%) or transapical (TA; n=99, 33%) approach between October 2013 and September 2015. Device success rate, based on the Valve Academic Research Consortium-2 criteria, was very high in the TF (97.0%) and TA (99.0%) groups. The 30-day mortality rates were 1.5% and 1.0% in the TF and TA groups, respectively. Major complications included stroke (transient or persistent: 2.3%), annulus rupture (1.0%), coronary intervention (1.0%), major vascular complications (1.7%), and permanent pacemaker implantation (5.4%). The procedure times of the post-proctoring period (n=210) were decreased compared with those of the proctoring period (n=89) without affecting the clinical outcomes. The survival rates at 6 and 12 months were 96.9% and 92.5% in the TF group, and 93.9% and 91.8% in the TA group, respectively. CONCLUSIONS: The K-TAVI registry data revealed that the early outcomes of TAVI using the SAPIEN XT were favorable in real-world Japanese patients.

Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia.

As a form of therapeutic angiogenesis, we sought to investigate the safety and efficacy of a sustained-release system of basic fibroblast growth factor (bFGF) using biodegradable gelatin hydrogel in patients with critical limb ischemia (CLI). We conducted a phase I-IIa study that analyzed 10 CLI patients following a 200-µg intramuscular injection of bFGF-incorporated gelatin hydrogel microspheres into the ischemic limb. Primary endpoints were safety and transcutaneous oxygen pressure (TcO2) at 4 and 24 weeks after treatment. During the follow-up, there was no death or serious procedure-related adverse event. After 24 weeks, TcO2 (28.4 ± 8.4 vs. 46.2 ± 13.0 mmHg for pretreatment vs after 24 weeks, p < 0.01) showed significant improvement. Regarding secondary endpoints, the distance walked in 6 min (255 ± 105 vs. 318 ± 127 m, p = 0.02), the Rutherford classification (4.4 ± 0.5 vs. 3.1 ± 1.4, p = 0.02), the rest pain scale (1.7 ± 1.0 vs. 1.2 ± 1.3, p = 0.03), and the cyanotic scale (2.0 ± 1.1 vs. 0.9 ± 0.9, p < 0.01) also showed improvement. The blood levels of bFGF were within the normal range in all patients. A subanalysis of patients with arteriosclerosis obliterans (n = 7) or thromboangiitis obliterans (Buerger's disease) (n = 3) revealed that TcO2 had significantly improved in both subgroups. TcO2 did not differ between patients with or without chronic kidney disease. The sustained release of bFGF from biodegradable gelatin hydrogel may offer a safe and effective form of angiogenesis for patients with CLI.

Comparison of Percutaneous Coronary Intervention With Coronary Artery Bypass Grafting in Unprotected Left Main Coronary Artery Disease - 5-Year Outcome From CREDO-Kyoto PCI/CABG Registry Cohort-2 - .

BACKGROUND: Studies evaluating long-term (≥5 years) outcome of percutaneous coronary intervention (PCI) compared with coronary artery bypass grafting (CABG) in patients with unprotected left main coronary artery disease (ULMCAD) are still limited, despite concerns for late adverse events after drug-eluting stents implantation. METHODS AND RESULTS: We identified 1,004 patients with ULMCAD (PCI: n=364, CABG: n=640) among 15,939 patients with first coronary revascularization enrolled in the CREDO-Kyoto PCI/CABG registry cohort-2. The primary outcome measure in the current analysis was a composite of death, myocardial infarction, and stroke (death/MI/stroke). The cumulative 5-year incidence of and the adjusted risk for death/MI/stroke were significantly higher in the PCI group than in the CABG group (34.5% vs. 24.1%, log-rank P<0.001, adjusted hazard ratio (HR): 1.48 [95% confidence interval (CI): 1.07-2.05, P=0.02]). The adjusted risks for all-cause death was not significantly different between the 2 groups. Regarding the stratified analysis by the SYNTAX score, the adjusted risk for death/MI/stroke was not significantly different between the 2 groups in patients with low (<23) or intermediate (23-33) SYNTAX score, whereas it was significantly higher in the PCI group than in the CABG group in patients with high (≤33) SYNTAX score. CONCLUSIONS: CABG as compared with PCI was associated with better long-term outcome in patients with ULMCAD, especially those with high anatomical complexity.

Twenty-year outcome of aortic valve replacement with St. Jude Medical mechanical valves in Japanese patients.

BACKGROUND: Bioprostheses have become increasingly popular for aortic valve replacement (AVR) in recent years, but mechanical valves are still the standard choice, especially for younger patients. The aim of this study was to assess the very long-term outcomes in Japanese patients who underwent AVR with St. Jude Medical (SJM) mechanical valves. METHODS AND RESULTS: From 1991 to 2001, a total of 816 patients underwent AVR with SJM mechanical valves in 5 hospitals. Of these, 801 patients (mean age, 58.3±11.7 years) were analyzed in this study. There were 24 in-hospital deaths (3.0%). Mean follow-up duration was 11.6±6.7 years and the 10-year follow-up rate was 84.1%. Freedom from valve-related death at 5, 10, 15, and 20 years was 96.2%, 92.7%, 88.8%, and 86.6%, respectively. The linearized ratio of major bleeding events and thromboembolic events was 1.1% per patient-year and 1.0% per patient-year, respectively. Freedom from reoperation for the aortic prosthesis was 98.0% and 94.8% at 10 and 20 years, respectively. CONCLUSIONS: The SJM mechanical valve provided excellent long-term freedom from valve-related death and reoperation in patients undergoing AVR. Therefore, this valve should be recommended to younger patients who wish to avoid reoperation.

Long-term durability of pericardial valves in the aortic position in younger patients: when does reoperation become necessary?

BACKGROUND: We sought to assess the long-term durability of pericardial valves in patients at age <65 years undergoing aortic valve replacement (AVR), and to determine the timing of redo operations due to structural valve deterioration (SVD). METHODS: From 1986 to 2001, a total of 574 adult patients underwent AVR with pericardial valves in nine hospitals in Japan. Of these, 53 patients were at age <65 years (group Y). These patients were compared with those of age ≥ 65 (group O, n = 521). RESULTS: The mean follow-up duration was 9.5 years in group Y and 8.1 years in group O. Freedom from reoperation due to SVD was 100% at five years, 90.8% at 10 years, and 47.2% at 15 years in group Y, and 99.3% at five years, 97.4% at 10 years, and 94.4% at 15 years in group O (log-rank test, p < 0.01). In those who required redo AVR in group Y (n = 12), the mean time from initial operation to reoperation was 12.1 years. The reoperation-free survival curve started to decline after eight years postoperation in group Y. CONCLUSIONS: Redo AVR started to become necessary eight years after surgery in the patients who underwent AVR with pericardial valve at age <65 years. In addition, approximately half of those patients required reoperation due to SVD by 15 years postoperatively.

Impact of statin therapy on patients with coronary heart disease and aortic aneurysm or dissection.

OBJECTIVE: The impact of statin therapy on cardiovascular outcome in coronary artery disease (CAD) patients with aortic aneurysm or dissection (AD) is still unclear. The aim of this study was to elucidate the effect of statins at discharge to improve outcomes in CAD patients with AD. METHODS: Among 14,834 consecutive patients who underwent first coronary revascularization in the CREDO-Kyoto PCI/CABG registry, we identified 699 patients (4.7%) with AD. The primary outcome measure was defined as a composite of all-cause death, myocardial infarction, and stroke. The effect of statin therapy was assessed by a Cox proportional hazards model incorporating clinically relevant factors. RESULTS: The risk for the primary outcome measure was significantly higher in patients with AD (adjusted hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.23-1.66; P < .0001). In patients with AD, 215 patients (31%) had already undergone aneurysm repair, and only 274 patients (39%) were treated with statins at discharge. Patients treated with statins were younger, had higher body mass index, and were more often treated with percutaneous coronary intervention. Heart failure, anemia, and hemodialysis were more prevalent in patients treated without statins. In patients without AD, 7014 patients (50%) were treated with statins. Patients treated with statins were younger and had higher body mass index, and more patients were treated for CAD due to myocardial infarction. Heart failure, prior stroke, hemodialysis, anemia, and malignant disease were more prevalent in patients treated without statins. The use of statins was associated with lower risk for the primary outcome measure in patients with AD (adjusted HR, 0.71; 95% CI, 0.51-0.99; P = .045) as well as in patients without AD (adjusted HR, 0.79; 95% CI, 0.73-0.85; P < .0001). The effect size of statin use was similar between the patients with AD and those without AD (P interaction = .69). CONCLUSIONS: CAD patients with AD had significantly higher long-term risk for cardiovascular events. Statin therapy was associated with lower risk for cardiovascular events in patients with CAD with AD as well as in patients without AD.

Long-term outcome of the carpentier-edwards pericardial valve in the aortic position in Japanese patients.

BACKGROUND: According to the Japanese Circulation Society guidelines, a bioprosthesis is recommended for aortic valve replacement (AVR) in patients aged ≥65 years who have no risk factors for thromboembolism. There are few data, however, regarding the actual durability of bioprosthetic valves in Japanese patients. The purpose of this study was to assess the long-term durability of Carpentier-Edwards pericardial (CEP) valves in Japanese AVR patients, and to assess the risk factors for reoperation due to structural valve deterioration (SVD). METHODS AND RESULTS: From 1986 to 2001, a total of 591 patients underwent AVR with CEP valves in 9 hospitals. Of these, 574 patients (mean age, 71.9±8.5 years) were analyzed in this study. There were 26 in-hospital deaths (4.5%). The 10-year follow-up rate was 82.6% and the median follow-up time was 9.2 years. Freedom from reoperation due to SVD was 99.5%, 96.7%, and 87.5% at 5, 10, and 15 years, respectively. Factors that raised the risk of reoperation due to SVD included younger age at operation and history of prior operation. In patients aged ≥65 years, freedom from reoperation due to SVD was 94.4% at 15 years. CONCLUSIONS: The durability of CEP valves in patients with AVR was excellent, especially in elderly patients. Thus, it seems appropriate to follow the current Japanese Circulation Society recommendations for the use of bioprosthetic valves.

Preoperative chronic kidney disease as a strong predictor of postoperative infection and mortality after coronary artery bypass grafting.

BACKGROUND: The aim of this study was to determine the influence of preoperative kidney dysfunction (ie, chronic kidney disease (CKD)) on postoperative cardiovascular events, infection, acute kidney injury and hospital mortality in patients undergoing coronary artery bypass grafting (CABG). METHODS AND RESULTS: A multi-institutional retrospective study was performed at 14 hospitals of adult patients undergoing isolated CABG from 2007 to 2008 (n=1,522). We classified CKD level according to preoperative estimated glomerular filtration rate (eGFR): normal, eGFR >90 ml·min(-1)·1.73 m(-2); mild, eGFR 60-90 ml·min(-1)·1.73 m(-2); moderate, eGFR 30-59 ml·min(-1)·1.73 m(-2); and severe, eGFR <30 ml·min(-1)·1.73 m(-2), and assessed postoperative outcome. Preoperative CKD distribution was as follows: normal, n=121 (8%); mild, n=713 (47%); moderate, n=515 (34%); and severe, n=169 (11%). Risk of infection was strongly correlated with CKD level (normal, 3.3%; mild, 7.0%; moderate, 8.3%; severe, 17.0%; P<0.01). The risk of in-hospital death was also strongly correlated with CKD level (normal, 1.7%; mild, 1.0%; moderate, 1.6%; severe, 5.9%; P<0.01). On multivariate logistic regression analysis, CKD level was identified as a significant risk factor for postoperative infection, acute kidney injury, and in-hospital death. CONCLUSIONS: Advanced preoperative CKD is a strong predictor of postoperative infection, acute kidney injury and in-hospital death after CABG.

Optimal dose-setting study of curcumin for improvement of left ventricular systolic function after myocardial infarction in rats.

A natural p300-specific histone acetyltransferase inhibitor, curcumin, may have a therapeutic potential for heart failure. However, a study of curcumin to identify an appropriate dose for heart failure has yet to be performed. Rats were subjected to a left coronary artery ligation. One week later, rats with a moderate severity of myocardial infarction (MI) were randomly assigned to 4 groups receiving the following: a solvent as a control, a low dose of curcumin (0.5 mg∙kg(-1)∙day(-1)), a medium dose of curcumin (5 mg∙kg(-1)∙day(-1)), or a high dose of curcumin (50 mg∙kg(-1)∙day(-1)). Daily oral treatment was continued for 6 weeks. After treatment, left ventricular (LV) fractional shortening was dose-dependently improved in the high-dose (25.2% ± 1.6%, P < 0.001 vs. vehicle) and medium-dose (19.6% ± 2.4%) groups, but not in the low-dose group (15.5% ± 1.4%) compared with the vehicle group (15.1% ± 0.8%). The histological cardiomyocyte diameter and perivascular fibrosis as well as echocardiographic LV posterior wall thickness dose-dependently decreased in the groups receiving high and medium doses. The beneficial effects of oral curcumin on the post-MI LV systolic function are lower at 5 compared to 50 mg∙kg(-1)∙day(-1) and disappear at 0.5 mg∙kg(-1)∙day(-1). To clinically apply curcumin therapy for heart failure patients, a precise, optimal dose-setting study is required.

Benefits of off-pump coronary artery bypass grafting in high-risk patients.

BACKGROUND: The benefits of off-pump coronary artery bypass graft (OPCAB) compared with conventional on-pump coronary artery bypass graft (CCAB) remain controversial. Thus, it is important to investigate which patient subgroups may benefit the most from OPCAB rather than CCAB. METHODS AND RESULTS: Among the patients undergoing first coronary revascularization enrolled in the CREDO-Kyoto Registry (a registry of first-time percutaneous coronary intervention and coronary artery bypass graft patients in Japan), 2468 patients undergoing coronary artery bypass graft were entered into the study (mean age, 67 ± 9 years). Predicted risk of operative mortality (PROM) of each patient was calculated by logistic EuroSCORE. Patients were divided into tertile based on their PROM. Mortality rates and the incidences of cardiovascular events were compared between CCAB and OPCAB within each PROM tertile using propensity score analysis. A total of 1377 patients received CCAB whereas 1091 received OPCAB. Adjusted 30-day mortality was not significantly different between CCAB and OPCAB patients regardless of their PROM range. However, the odds ratio of 30-day stroke in CCAB compared with OPCAB in the high-risk tertile was 8.30 (95% confidence interval, 2.25-30.7; P<0.01). Regarding long-term outcomes, hazard ratio of stroke in CCAB compared with OPCAB in the high-risk tertile was 1.80 (95% confidence interval, 1.07-3.02; P=0.03). Nevertheless, hazard ratio of overall mortality in the high-risk tertile was 1.44 (95% confidence interval, 0.98-2.11; P=0.06), indicating no statistically significant difference between the 2 procedures. CONCLUSIONS: OPCAB as opposed to CCAB is associated with short-term and long-term benefits in stroke prevention in patients at higher risk as estimated by EuroSCORE. No survival benefit of OPCAB was shown regardless of preoperative risk level.