Cytoplasmic control of Rab family small GTPases through BAG6.

Rab family small GTPases are master regulators of distinct steps of intracellular vesicle trafficking in eukaryotic cells. GDP-bound cytoplasmic forms of Rab proteins are prone to aggregation due to the exposure of hydrophobic groups but the machinery that determines the fate of Rab species in the cytosol has not been elucidated in detail. In this study, we find that BAG6 (BAT3/Scythe) predominantly recognizes a cryptic portion of GDP-associated Rab8a, while its major GTP-bound active form is not recognized. The hydrophobic residues of the Switch I region of Rab8a are essential for its interaction with BAG6 and the degradation of GDP-Rab8a via the ubiquitin-proteasome system. BAG6 prevents the excess accumulation of inactive Rab8a, whose accumulation impairs intracellular membrane trafficking. BAG6 binds not only Rab8a but also a functionally distinct set of Rab family proteins, and is also required for the correct distribution of Golgi and endosomal markers. From these observations, we suggest that Rab proteins represent a novel set of substrates for BAG6, and the BAG6-mediated pathway is associated with the regulation of membrane vesicle trafficking events in mammalian cells.

Bilateral Internal Thoracic Artery Grafting Improves Survival for Severe Left Ventricular Dysfunction and Diabetes.

BACKGROUND: In patients with severe left ventricular (LV) dysfunction requiring coronary artery bypass grafting (CABG), the association between diabetic status and outcomes after surgery, as well as with survival benefit following bilateral internal thoracic artery (ITA) grafting, remain largely unknown.Methods and Results:Patients (n=188; mean [±SD] age 67±9 years) with LV ejection fraction ≤40% who underwent isolated initial CABG were classified into non-diabetic (n=64), non-insulin-dependent diabetic (NIDM; n=74), and insulin-dependent diabetic (IDM; n=50) groups. During follow-up (mean [±SD] 68±47 months), the 5-year survival rate was 84% and 65% among non-diabetic and diabetic patients, respectively (P=0.034). After adjusting for all covariates, both NIDM and IDM were associated with increased mortality, with hazard ratios (HRs) of 1.9 (95% confidence interval [CI] 1.0-3.7; P=0.049) and 2.4 (95% CI 1.2-4.8; P=0.016), respectively. Among non-diabetic patients, there was no difference in the 5-year survival rate between single and bilateral ITA grafting (86% vs. 80%, respectively; P=0.95), whereas bilateral ITA grafting increased survival among diabetic patients (57% vs. 81%; P=0.004). Multivariate analysis revealed that bilateral ITA was significantly associated with a decreased risk of mortality (HR 0.3; 95% CI 0.1-0.8; P=0.024). CONCLUSIONS: NIDM and IDM were significantly associated with worse long-term clinical outcome after CABG for severe LV dysfunction. Bilateral ITA grafting has the potential to improve survival in diabetic patients with severe LV dysfunction.

Which Patients Are Candidates for Minimally Invasive Mitral Valve Surgery?　- Establishment of Risk Calculators Using National Clinical Database.

BACKGROUND: Although minimally invasive mitral valve surgery via a right minithoracotomy (MICS-mitral) is widely performed, no tool to evaluate its risk has been reported. We sought to establish MICS-mitral risk calculators using a national clinical database for selection of appropriate patients.Methods and Results:Between 2008 and 2015, 3,240 patients (mean age 59±14 years, males 1,950) underwent a MICS-mitral procedure in Japan and were registered in a national clinical database. We examined mortality and composite outcome (operative mortality, stroke, reoperation for bleeding) using multivariate analysis, then developed a risk calculator for each using stepwise analysis. Operative mortality was 1.1% and the composite outcome rate was 5%. In multivariate analysis, risk factors for operative mortality were shown to be age, respiratory dysfunction, thoracic aortic disease, myocardial infarction, body mass index >30, NYHA class IV, moderate or severe aortic regurgitation, mitral valve replacement, multiple valve surgery, and annual cases <10. ROC curve analysis of our prediction formulas for mortality and composite outcome revealed an area under the curve for operative mortality of 0.877 (95% confidence interval: 0.82-0.94, P<0.01) and for composite outcome of 0.665 (95% confidence interval: 0.62-0.71, P<0.01). CONCLUSIONS: We developed risk calculator formulas using risk factors associated with both operative mortality and composite outcome. The present risk calculator formula is useful for patient selection and may influence future applications for this procedure.

[Postoperative Atrial Fibrillation in Patients who Underwent Thoracic Aortic Surgery].

PURPOSE: Postoperative atrial fibrillation (POAF) is a very common and important complication occurring after open heart surgery. Risk factors and prevention measure including ß blocker use have been reported mainly in regard to patients who underwent coronary artery bypass grafting, while little is known about POAF following thoracic aortic surgery. In the present study, we examined risk factors related to POAF and effective prevention of POAF in patients who underwent thoracic aortic surgery. PATIENTS AND METHODS: We evaluated 95 consecutive patients who underwent thoracic aortic surgery since 2010. We analyzed the relationship between perioperative factors and occurrence of POAF in the study cohort, as well as in 62 patients who had perioperative intravenous ß blocker (landiolol) administration. RESULTS: Following surgery, 21 (22%) of the patients had new onset POAF. The occurrence of POAF was related to that of stroke. Univariate analysis showed that age was a risk factor for POAF. In patients with landiolol, risk factors for POAF were age, arch aneurysm, and timing of landiolol administration. Six patients developed POAF during landiolol administration. However, of 56 patients who had not have POAF during landiolol administration, 8 developed POAF after stopping landiolol. CONCLUSION: Our findings show that the risk factor of POAF after thoracic aortic surgery is age, while perioperative administration of landiolol may reduce POAF incidence.

Recent Surgical Results for Active Endocarditis Complicated With Perivalvular Abscess.

BACKGROUND: Surgical treatment for endocarditis patients with a perivalvular abscess is still challenging.Methods and Results:From 2009 to 2016, 470 patients underwent surgery for active endocarditis at 11 hospitals. Of these, 226 patients underwent aortic valve surgery. We compared the clinical results of 162 patients without a perivalvular abscess, 37 patients who required patch reconstruction of the aortic annulus (PR group) and 27 who underwent aortic root replacement (ARR group). Patients with a perivalvular abscess had a greater number ofStaphylococcusspecies and prosthetic valve endocarditis, a greater level of inflammation at diagnosis and symptomatic heart failure before surgery, especially in the ARR group. Nevertheless, the duration between diagnosis and surgery was similar, because of a high prevalence of intracranial hemorrhage in the ARR group. Hospital death occurred in 13 (9%) patients without a perivalvular abscess, in 4 (12%) in the PR and in 7 (32%) in the ARR group. Postoperative inflammation and end-organ function were similar between the groups. Overall survival of patients without a perivalvular abscess and that of the PR group was similar, but was significantly worse in the ARR group (P=0.050, 0.026). Freedom from endocarditis recurrence was similar among all patients. CONCLUSIONS: Patients treated with patch reconstruction showed favorable clinical results. Early surgical intervention is necessary when a refractory invasive infection is suspected.

The efficacy of tolvaptan in the perioperative management of chronic kidney disease patients undergoing open-heart surgery.

PURPOSE: The perioperative management of chronic kidney disease (CKD) patients undergoing open-heart surgery is challenging. In this study, we evaluated the effects of tolvaptan in CKD patients after open-heart surgery. METHODS: Between 2010 to 2015, 731 patients underwent open-heart surgery in our hospital. We consecutively selected 71 patients with stage IIIa-IV CKD and divided them into two groups. Those who received tolvaptan postoperatively were defined as the "Tolvaptan group" (n = 25) and those who did not were defined as the "Non-tolvaptan group" (n = 46). We compared the urine volume of postoperative days (POD) 1 and 2, the number of days to return to preoperative body weight (BW), and the change in the postoperative estimated glomerular filtration rate (eGFR). RESULTS: In the tolvaptan group, the urine volume was significantly larger (P = .04) and the duration to preoperative BW tended to be shorter. Overall, the postoperative change in the eGFR tended to be better in the tolvaptan group (P = .008). In particular, we found a significantly better trend in CKD stage IV (P = .04) patients and in the patients, whose cardiopulmonary bypass (CPB) time was longer than 120 min (P = .03). CONCLUSIONS: Tolvaptan can safely be used for CKD patients undergoing open-heart surgery and can provide a feasible urine volume without leading to a deterioration of their renal function.

Factors that influence the pharmacokinetics of lamotrigine in Japanese patients with epilepsy.

PURPOSE: Lamotrigine (LTG) is used to treat epilepsy. The variability of LTG pharmacokinetics among individuals may be attributed to polymorphisms in the genes of uridine diphosphate glucuronosyltransferases (UGTs) 1A4 and UGT2B7 and/or combination with other drugs. In this study, we evaluated the association between LTG concentrations and patient characteristics such as genetic polymorphisms and the co-administration of antiepileptic drugs. METHODS: We recruited 122 patients with epilepsy. LTG concentrations were measured in blood samples from each patient under steady-state condition. We assessed the influence of multiple factors on LTG concentrations and derived a formula for predicting LTG concentrations using multiple linear regression analysis. RESULTS: We derived a formula to predict LTG concentrations that considers the daily dose of LTG, body weight, valproic acid concentration, phenytoin co-administration, and the co-administration of phenobarbital and/or carbamazepine as well as UGT1A4 142T>G and UGT2B7 -161C>T polymorphisms (adjusted coefficients of determination R (2) = 0.734). Furthermore, we used this formula to reveal a strong positive correlation between measured and predicted LTG concentrations (r (2) = 0.76, p < 0.001). CONCLUSION: We derived a formula that will be useful in clinical practice for predicting LTG concentrations in patients with epilepsy.

Influence of uridine diphosphate glucuronosyltransferase 2B7 -161C>T polymorphism on the concentration of valproic acid in pediatric epilepsy patients.

BACKGROUND: Valproic acid (VPA) is widely used to treat various types of epilepsy. Interindividual variability in VPA pharmacokinetics may arise from genetic polymorphisms of VPA-metabolizing enzymes. This study aimed to examine the relationships between plasma VPA concentrations and the -161C>T single nucleotide polymorphism in uridine diphosphate glucuronosyltransferase (UGT) 2B7 genes in pediatric epilepsy patients. METHODS: This study included 78 pediatric epilepsy patients carrying the cytochrome P450 (CYP) 2C9*1/*1 genotype and who were not treated with the enzyme inducers (phenytoin, phenobarbital, and carbamazepine), lamotrigine, and/or topiramate. CYP2C9*3 and UGT2B7 -161C>T polymorphisms were identified using methods based on polymerase chain reaction-restriction fragment length polymorphism. Blood samples were drawn from each patient under steady-state conditions, and plasma VPA concentrations were measured. RESULTS: Significant differences in adjusted plasma VPA concentrations were observed between carriers of CC, CT, and TT genotypes in the UGT2B7 -161C>T polymorphism (P = 0.039). Patients with the CC genotype had lower adjusted plasma VPA concentrations than those with CT or TT genotype (P = 0.028). CONCLUSIONS: These data suggest that the UGT2B7 -161C>T polymorphism in pediatric epilepsy patients carrying the CYP2C9*1/*1 genotype affects VPA concentration.

Impact of introducing endovascular aneurysm repair on treatment strategy for repair of abdominal aortic aneurysm--National Hospital Organization network study in Japan.

BACKGROUND: The objective of the present study was to assess the hypothesis that the introduction of endovascular aneurysm repair (EVAR) into Japan has expanded the indication of abdominal aortic aneurysm (AAA) repair without increasing surgical mortality. METHODS AND RESULTS: From 10 national hospitals, we registered a total of 2,154 consecutive patients (Open surgery [OS]: n=1,577, EVAR: n=577) over 8 years, divided into 4 time periods: Group I (2005-2006: n=522), Group II (2007-2008: n=475), Group III (2009-2010: n=551), Group IV, (2011-2012: n=606). Mean age increased over the 4 time periods (P<0.0001). The incidences of COPD, smoking history, history of abdominal surgery and concomitant malignancy significantly increased as well, while the numbers of patients with preoperative shock or high ASA status reduced over time. The proportion of EVAR in AAA repair increased from: 0% in Group I, 11.6% in Group II, 41.0% in Group III, to 48.8% in Group IV (P<0.0001). Early mortality was 0.8% in the EVAR and 3.4% in the OS (P<0.001) groups. Survival rates among the 4 groups free of all-cause death and aneurysm-related death at 1 year were 92.1-96.3% (P=0.1555) and 95.5-96.8% (P=0.9891), respectively. Multiple logistic regression analysis for surgical death failed to demonstrate survival advantage of EVAR over OS. CONCLUSIONS: Introduction of EVAR expanded the indication of AAA repair without increasing mortality, while high risk for anesthesia and emergency cases reduced over time. UMIN-CTR (UMIN000008345).

Protein quality control machinery supports primary ciliogenesis by eliminating GDP-bound Rab8-family GTPases.

The small GTPase Rab8 plays a vital role in the vesicular trafficking of cargo proteins from the trans-Golgi network to target membranes. Upon reaching its target destination, Rab8 is released from the vesicular membrane into the cytoplasm via guanosine triphosphate (GTP) hydrolysis. The fate of GDP-bound Rab8 released from the destination membranes, however, has not been investigated adequately. In this study, we found that GDP-bound Rab8 subfamily proteins are targeted for immediate degradation, and the pre-emptive quality control machinery is responsible for eliminating these proteins in a nucleotide-specific manner. We provide evidence that components of this quality control machinery have a critical role in vesicular trafficking events, including the formation of primary cilia, a process regulated by the Rab8 subfamily. These results suggest that the protein degradation machinery plays a critical role in the integrity of membrane trafficking by limiting the excessive accumulation of GDP-bound Rab8 subfamily proteins.

Impact of complete revascularization in coronary artery bypass grafting for ischemic cardiomyopathy.

Objective: In patients with ischemic cardiomyopathy, coronary artery bypass grafting ensures better survival than medical therapy. However, the long-term clinical impact of complete revascularization remains unclear. This observational study aimed to evaluate the effects of complete revascularization on long-term survival and left ventricular functional recovery in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting. Methods: We retrospectively reviewed outcomes of 498 patients with ischemic cardiomyopathy who underwent complete (n = 386) or incomplete (n = 112) myocardial revascularization between 1993 and 2015. The baseline characteristics were adjusted using inverse probability of treatment weighting to reduce the impact of treatment bias and potential confounding. The mean follow-up duration was 77.2 ± 42.8 months in survivors. Results: The overall 5-year survival rate (complete revascularization, 72.5% vs incomplete revascularization, 57.9%, P = .03) and freedom from all-cause death and/or readmission due to heart failure (54.5% vs 40.1%, P = .007) were significantly greater in patients with complete revascularization than those with incomplete revascularization. After adjustments using inverse probability of treatment weighting, the complete revascularization group demonstrated a lower risk of all-cause death (hazard ratio, 0.61; 95% confidence interval, 0.43-0.86; P = .005) and composite adverse events (hazard ratio, 0.59; 95% confidence interval, 0.44-0.79; P < .001) and a greater improvement in the left ventricular ejection fraction 1-year postoperatively (absolute change: 11.0 ± 11.9% vs 8.3 ± 11.4%, interaction effect P = .05) than the incomplete revascularization group. Conclusions: In patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting, complete revascularization was associated with better long-term outcomes and greater left ventricular functional recovery and should be encouraged whenever possible.

Total arch replacement for a subacute type A dissection in a patient with a terminal tracheostoma after total laryngectomy: report of a case.

Standard full median sternotomy for total arch replacement in tracheostomy patients may lead to mediastinitis and graft infection. Several approaches for typical cardiac surgery, including a T-shaped sternotomy, have been used in patients with both terminal and transient tracheostomas; however, these procedures offer inadequate surgical exposure of the arch vessels. We herein report the case of a 67-year-old man with a subacute type A aortic dissection with a terminal tracheostoma after total laryngectomy, who successfully underwent total arch replacement by a fourth intercostal thoracotomy performed using an anterior bilateral approach and the arch-first technique. To our knowledge, this is the first report of a case of total arch replacement in a patient with subacute aortic dissection and a terminal tracheostoma.

Cardiac calcified amorphous tumor with sustained ventricular tachycardia.

Cardiac calcified amorphous tumors are rare non-neoplastic intracavitary masses with unknown cause. A 60-year-old man presented with sustained ventricular tachycardia. Transthoracic echocardiography and contrast-enhanced angio-computed tomography demonstrated an expanding 73 × 40 mm sized calcified mass in the left ventricle. He underwent successful total removal of the mass and cryo-ablation at the normal myocardial border. Histopathological examination confirmed a diagnosis of cardiac calcified amorphous tumors. The postoperative course was uneventful, without ventricular tachycardia recurrence. To our knowledge, this is the first reported case of confirmed cardiac calcified amorphous tumors causing ventricular tachycardia and treated by surgical resection combined with cryo-ablation.

A reproducible swine model of a surgically created saccular thoracic aortic aneurysm.

A reproducible swine thoracic aortic aneurysm (TAA) model is useful for investigating new therapeutic interventions. We report a surgical method for creating a reproducible swine saccular TAA model. We used eight female swine weighing 20-25 kg (LWD; ternary species). All procedures were performed under general anesthesia and involved left thoracotomy. Following aortic cross-clamping, the thoracic aorta was surgically dissected and the media and intima were resected, and the dissection plane was extended by spreading the outer layer for aneurysmal space. Subsequently, only the adventitial layer of the aorta was sutured. At 2 weeks after these procedures, angiography and computed tomography were performed. After follow-up imaging, the model animals were euthanized. Macroscopic, histological, and immunohistological examinations were performed. All model animals survived, and a saccular TAA was confirmed by follow-up imaging in all cases. The mean length of the shorter and the longer aortic diameter after the procedure were 14.01 ± 1.0 mm and 18.35 ± 1.4 mm, respectively (P<0.001). The rate of increase in the aortic diameter was 131.7 ± 13.8%, and the mean length of aneurysmal change at thoracic aorta was 22.4 ± 1.9 mm. Histological examination revealed intimal tears and defects of elastic fibers in the media. Immunostaining revealed MMP-2 and MMP-9 expressions at the aneurysm site. We report our surgical method for creating a swine saccular TAA model. Our model animal may be useful to investigate new therapeutic interventions for aortic disease.

Surgical Ablation Concomitant With Nonmitral Valve Surgery for Persistent Atrial Fibrillation.

BACKGROUND: Consensus regarding an optimal atrial fibrillation (AF) ablation lesion set concomitant with aortic valve replacement (AVR) and/or coronary artery bypass grafting (CABG) has not been established. METHODS: We enrolled 125 consecutive patients (89 men; 70 ± 8 years old) with persistent AF who underwent radiofrequency-based pulmonary vein isolation (PVI) (PVI group, n = 53) or a Cox-Maze procedure (Maze group, n = 72) with AVR and/or CABG. To reduce the impact of treatment bias and potential confounding in the direct comparisons between patients who underwent Cox-Maze with and those who underwent PVI, we established weighted Cox proportional-hazards regression models with inverse probability of treatment weighting. Mean follow-up was 63 ± 34 months (maximum, 154 months). RESULTS: There was 1 in-hospital death in each group. Patients who underwent Cox-Maze showed a higher freedom from AF at all follow-up examinations. After the operation, there were 32 deaths, 13 thromboembolisms, 8 hemorrhagic events, and 22 heart failure readmissions. The Maze group had higher rates for 5-year survival (88% vs 64%, P = .013) and freedom from composite events (74% vs 42%, P < .001). After adjustment with inverse probability of treatment weighting, the Cox-Maze procedure still showed a lower risk of overall mortality (adjusted hazard ratio, 0.38; 95% confidence interval, 0.21-0.66; P = .001) and composite adverse events (adjusted hazard ratio, 0.52; 95% confidence interval, 0.35-0.76; P = .001). CONCLUSIONS: In patients with persistent AF indicated for nonmitral valve surgery, a concomitant Cox-Maze procedure resulted in superior AF- and event-free survival compared with PVI, without increased risk of early mortality. These findings may assist decision making for surgical management of persistent AF concomitant with AVR and/or CABG.

Incidence, determinants and clinical impact of left ventricular function recovery after surgical treatments for ischaemic cardiomyopathy.

OBJECTIVES: This retrospective study aimed to clarify the incidence, determinants and clinical impact of left ventricular (LV) function non-recovery after coronary artery bypass grafting (CABG) in patients with ischaemic cardiomyopathy. METHODS: A total of 490 patients with ischaemic cardiomyopathy (LV ejection fraction ≤ 40%) undergoing CABG were analysed. Follow-up echocardiography was performed at 1 month, 1 year, and annually thereafter. LV function recovery was defined as ejection fraction (EF) ≥40% at least once during follow-up. LV function non-recovery was defined as EF <40% at any follow-up. The primary and secondary end points were changes in LV function and all-cause mortality, respectively. Clinical follow-up was completed in 461 patients (94.1%; mean follow-up: 64.5 ± 45.5 months). RESULTS: During follow-up, echocardiographic assessments were performed 1863 times (mean, 3.8 ± 2.4), and 193 patients (39.4%) exhibiting LV function non-recovery were identified. Overall survival was significantly higher in the recovery group (53.9%) than in the non-recovery group (31.4%) at 10 years (P < 0.001). Independent predictors of LV function non-recovery were preoperative LV end-systolic diameter [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.04-1.10; P < 0.001] and bilateral internal thoracic artery grafting (OR 0.61, 95% CI 0.39-0.95; P = 0.028). In a multivariable Cox proportional hazards model, LV function non-recovery was significantly associated with all-cause mortality (hazard ratio 2.14, 95% CI 1.60-2.86; P < 0.001). CONCLUSIONS: Almost 40% of patients with ischaemic cardiomyopathy undergoing CABG did not achieve LV function recovery and were associated with poor prognosis. To achieve LV function recovery, CABG with bilateral internal thoracic artery may be recommended before excessive LV remodelling occurs. CLINICAL TRIAL REGISTRATION NUMBER: Institutional review board of Osaka University Hospital, number 16105.

Aortic angioscopy assisted thoracic endovascular repair for chronic type B aortic dissection.

BACKGROUND: Non-obstructive general angioscopy is a powerful modality for detecting areas in the aorta with vulnerable plaque, which are difficult to visualize using conventional diagnostic tools such as computed tomography (CT). The aim of the present study was to clarify the efficacy and usefulness of aortic angioscopy in patients with chronic type B aortic dissection scheduled for thoracic endovascular repair (TEVAR). METHODS: Ten patients with chronic type B aortic dissection who underwent elective TEVAR were enrolled. Before starting the stent graft procedure, the aortic intima was observed by use of non-obstructive general angioscopy. Based on those findings, the range of the stent graft position was confirmed. RESULTS: In all patients, observations of the aortic intima with non-obstructive general angioscopy from a point just proximal of the descending aorta to the iliac artery were successful. At the proximal site, an entry site or ulcer-like projection was detected in all patients, while a small intimal tear or entry, or an irregular intima surface with a salmon-pink color were seen in some cases. In contrast, preoperative CT did not detect any such findings in the same locations. After confirming the position of the abnormal intima, we determined the position of the distal end of the stent graft. No complications considered to be related to aortic angioscopy were noted. CONCLUSIONS: Non-obstructive general angioscopy is useful for observing the condition of the aortic intima, revealing abnormal conditions, and confirming a normal aortic intima in patients with chronic type B aortic dissection. This modality may play an important role in determining the precise position of a stent graft for a TEVAR procedure.

Restrictive mitral annuloplasty with or without coronary artery bypass grafting in ischemic mitral regurgitation.

AIMS: In patients with ischaemic mitral regurgitation (MR), the impact of mitral valve surgery with concomitant coronary artery bypass grafting (CABG) on post-operative survival and left ventricular (LV) reverse remodelling remains unknown. Therefore, we investigated these outcomes following restrictive mitral annuloplasty (RMA) with and without CABG in those patients. METHODS AND RESULTS: This study included 309 patients with chronic MR and ischaemic cardiomyopathy for whom concomitant CABG was indicated (n = 225) or not indicated (n = 84) with RMA. The primary endpoint was all cause mortality during the follow-up, and the secondary endpoint was defined as the composite of mortality and re-admission for heart failure. Linear mixed model was used to analyse serial echocardiographic changes in LV function. To reduce the impact of treatment bias and potential confounding in the direct comparisons between patients who underwent RMA with and those who underwent it without CABG, we established weighted Cox proportional-hazards regression models with inverse-probability-of-treatment weighting. Pre-operatively, there were no intergroup differences in age (RMA with CABG, 67 ± 9 vs. RMA without CABG, 68 ± 11, P = 0.409) and logistic EuroSCORE II (16 ± 14 vs. 15 ± 15%, P = 0.496). The 30-day mortalities were 2.7% and 3.6%, respectively (P = 0.67). During follow-up with a mean duration of 72 ± 37 months (range, 5.6-179), there were 157 deaths and 105 re-admissions for heart failure. Overall 1-year and 5-year survival rates were 83 ± 2% and 58 ± 3%, respectively. Patients who did not receive CABG with RMA had a significantly lower 5-year survival rate (45% vs. 63%, P = 0.049) and freedom from adverse events defined as mortality and/or admission for heart failure (19% vs. 43%, P < 0.001) than those who did. After adjustments for clinical covariates with inverse-probability-of-treatment weighting, concomitant CABG was identified as an independent protective factor for adverse events (hazard ratio: 0.53; 95% confidence interval: 0.44-0.64; P < 0.001). Along with significant MR reduction, LV function parameters changed over time after surgery in both groups, with greater improvements in patients who underwent RMA with CABG (time effect, P < 0.001; and interaction effect, P = 0.002). CONCLUSIONS: RMA can be performed with an acceptable operative mortality, irrespective of indications for CABG. Patients with ischaemic MR for whom CABG is indicated with RMA are more likely to show better long-term and event-free survival and greater improvements in LV systolic function. The optimal revascularization strategy should be discussed with a heart team whenever indicated in patients with ischaemic MR; otherwise, they may miss the opportunity to benefit from concomitant CABG during subsequent RMA.

Equations Estimating the Predissected Diameter of the Ascending Aorta for Acute Type A Aortic Dissection.

BACKGROUND: A successful endovascular treatment for acute type A dissection has been recently reported. However, there has been no consensus regarding the appropriate stent graft size based on the estimated predissected aortic diameter for this pathology. METHODS: We developed new equations for estimating the predissected ascending aorta and aortic arch by investigating computed tomography images that had been scanned less than 3 years before dissection. From 684 patients with type A AAD, 28 were matched for the study. We measured the predissected whole circumference length (pre-wCL), postdissected whole circumference length (post-wCL), postdissected true lumen circumference length (post-tCL), postdissected major diameter (post-Dma), and postdissected minor diameter (post-Dmi) of the acutely dissected aorta. This was followed by the calculation of (post-tCL + post-wCL)/2 and (post-Dma + post-Dmi)/2. Six equations (linear function) and modified equations were derived from each of the abovementioned parameters. RESULTS: Four equations (post-wCL, post-Dma, [post-tCL + post-wCL]/2, and [post-Dma + post-Dmi]/2) had nearly the same bias and accuracy (<9.42 mm). For clinical use, we also developed one modified equation using the post-wCL (y = 0.9x) among four parameters because of its simplicity and decreased the possibility of measurement error. The biases of circumference length and accuracy were 5.5 ± 4.9 mm and 84.6%, respectively, and they improved to 4.4 ± 3.3 mm and 93.4% in cases with a ratio of post-tCL/post-wCL of 0.66 or more. CONCLUSIONS: Our newly developed equation can be used to calculate the predissected ascending aortic diameter and aortic arch diameter in cases of acute type A dissection.

Surgery-first treatment improves clinical results in infective endocarditis complicated with disseminated intravascular coagulation†.

OBJECTIVES: Infective endocarditis (IE) is a critical infection with a high mortality rate, and it usually causes sepsis. Though disseminated intravascular coagulation (DIC) sometimes occurs in IE patients, no definitive treatment strategy for IE patients with DIC as a complication exists. Therefore, we evaluated the prevalence, surgical results and treatment strategy for IE complicated with DIC. METHODS: Between 2009 and 2017, a total of 585 patients undergoing valve surgery for active IE were enrolled at 14 institutions, of whom 116 (20%) had DIC as a complication. For further evaluation, we divided DIC patients into medical treatment-first (n = 45, group M) and valve surgery-first (n = 51, group S) groups after excluding 20 patients with intracranial haemorrhage. RESULTS: The overall survival rates at 1 and 5 years were 91% and 85% in the non-DIC group and 65% and 55% in the DIC group, respectively (P < 0.001). Recurrence-free survival rates at 1 and 5 years were 99% and 95% in the non-DIC group and 94% and 74% in the DIC group, respectively (P < 0.001). The overall survival rates at 1 and 5 years were 77% and 64% in group S and 51% and 46% in group M, respectively (P = 0.032). Multivariable analysis revealed that 'medical treatment first' was an exclusive independent risk factor [hazards ratio 2.26 (1.13-4.75), P = 0.024] for overall mortality. CONCLUSIONS: Mortality and IE recurrence were statistically significantly higher in DIC patients. Valve surgery should not be delayed because most patients proceeding with medical treatment eventually require emergency surgery and their clinical outcomes are worse than those of patients undergoing early surgery.