Sex Differences in Cardiovascular Disease-Related Hospitalization and Mortality in Japan　- Analysis of Health Records From a Nationwide Claim-Based Database, the Japanese Registry of All Cardiac and Vascular Disease (JROAD).

BACKGROUND: The prevalence of cardiovascular disease (CVD) is rising in Japan with its aging population, but there is a lack of epidemiological data on sex differences in CVD, including acute coronary syndrome (ACS), acute heart failure (AHF), and acute aortic disease. METHODS AND RESULTS: This retrospective study analyzed data from 1,349,017 patients (January 2012-December 2020) using the Japanese Registry Of All Cardiac and Vascular Diseases database. ACS patients were youngest on average (70.5±12.9 years) and had the lowest female proportion (28.9%). AHF patients had the oldest mean age (79.7±12.0 years) and the highest proportion of females (48.0%). Acute aortic disease had the highest in-hospital mortality (26.1%), followed by AHF (11.5%) and ACS (8.9%). Sex-based mortality differences were notable in acute aortic disease, with higher male mortality in Stanford Type A acute aortic dissection (AAD) with surgery (males: 14.2% vs. females: 10.4%, P<0.001) and similar rates in Type B AAD (males: 6.2% vs. females: 7.9%, P=0.52). Aging was a universal risk factor for in-hospital mortality. Female sex was a risk factor for ACS and acute aortic disease but not for AHF or Types A and B AAD. CONCLUSIONS: Sex-based disparities in the CVD-related hospitalization and mortality within the Japanese national population have been highlighted for the first time, indicating the importance of sex-specific strategies in the management and understanding of these conditions.

Tumor size discrepancy between endoscopic and pathological evaluations in colorectal endoscopic submucosal dissection.

BACKGROUND: Tumor size impacts the technical difficulty and histological curability of colorectal endoscopic submucosal dissection (ESD); however, the preoperative evaluation of tumor size is often different from histological assessment. Analyzing influential factors on failure to obtain an accurate tumor size evaluation could help prepare optimal conditions for safer and more reliable ESD. AIM: To investigate the tumor size discrepancy between endoscopic and pathological evaluations and the influencing factors. METHODS: This was a retrospective study conducted at a single institution. A total of 377 lesions removed by colorectal ESD at our hospital between April 2018 and March 2022 were collected. We first assessed the difference in size with an absolute percentage of the scaling discrepancy. Subsequently, we compared the clinicopathological characteristics of the correct scaling group (> -33% and < 33%) with that of the incorrect scaling group (< -33% or > 33%), which was further subdivided into the underscaling group (-33% or less of the discrepancy) and overscaling group (33% or more of the discrepancy), respectively. As secondary outcome measures, parameters on size estimation were compared between the underscaling and correct scaling groups, as well as between the overscaling and correct scaling groups. Finally, multivariate analysis was performed in terms of the following relevant parameters on size estimation: Pathological size, location, and possible influential factors (P < 0.1) in the univariate analysis. RESULTS: The mean of absolute percentage in the scaling discordance was 21%, and 91 lesions were considered to be incorrectly estimated in size. The incorrect scaling was significantly remarkable in larger lesions (40 mm vs 28 mm; P < 0.001) and less experience (P < 0.001), and these two factors were influential on the underscaling (75 lesions; P < 0.001). Conversely, compared with the correct scaling group, 16 lesions in the overscaling group were significantly small (20 mm vs 28 mm; P < 0.001), and the small lesion size was influential on the overscaling (P = 0.002). CONCLUSION: Lesions indicated for colorectal ESD tended to be underestimated in large tumors, but overestimated in small ones. This discrepancy appears worth understanding for optimal procedural preparation.

Systemic THrombolysis Randomization IN Endovascular Stroke Therapy (SHRINE) Collaboration: a patient-level pooled analysis of the SKIP and DEVT Trials.

OBJECTIVE: To evaluate the non-inferiority of endovascular treatment (EVT) alone versus intravenous thrombolysis (IVT) followed by EVT and to assess its heterogeneity across prespecified subgroups. METHODS: We pooled data from two trials (SKIP in Japan; DEVT in China). Individual patient data were pooled to assess outcomes and heterogeneity of treatment effect. The primary outcome was functional independence (modified Rankin Scale score 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: We included 438 patients (217 EVT alone; 221 combined IVT+EVT). The meta-analysis failed to demonstrate the non-inferiority of EVT alone over combined IVT+EVT in achieving 90-day functional independence (56.7% vs 51.6%; adjusted common odds ratio (cOR)=1.27, 95% CI 0.84 to 1.92, pnon-inferiority=0.06). Effect sizes favoring EVT alone were present with stroke onset to puncture time longer than 180 min (cOR=2.28, 95% CI 1.18 to 4.38, pinteraction ≤180 vs >180 min=0.02) and intracranial internal carotid artery ICA occlusions (for ICA cOR=3.04, 95% CI 1.10 to 8.43, pinteraction ICA vs MCA=0.08). The rates of sICH (6.5% vs 9.0%; cOR=0.77, 95% CI 0.37 to 1.61) and 90-day mortality (12.9% vs 13.6%; cOR=1.05, 95% CI 0.58 to 1.89) were comparable. CONCLUSIONS: The cumulative data of these two recent Asian trials failed to unequivocally demonstrate the non-inferiority of EVT alone over combined IVT+EVT. However, our study suggests a potential role for more individualized decision-making. Specifically, Asian patients with stroke onset to EVT longer than 180 min, as well as those with intracranial ICA occlusions and those with atrial fibrillation might have better outcomes with EVT alone than with combined IVT+EVT.

Rationale and design of Non-antithrombotic Therapy After Transcatheter Aortic Valve Implantation (NAPT) Trial.

BACKGROUND: Despite the wide implementation of transcatheter aortic valve implantation (TAVI), the optimal antithrombotic therapy after TAVI has not been established yet. Owing to the accumulating evidence supporting the efficacy and safety of single antiplatelet therapy (SAPT) over dual antiplatelet therapy, the latest guideline recommends life-long SAPT. However, there is scarce evidence supporting SAPT compared with non-antithrombotic therapy. Given the vulnerability of patients undergoing TAVI in terms of high bleeding risk, the benefit of SAPT may be canceled out by its potential increased bleeding risk. STUDY DESIGN AND OBJECTIVES: Non-antithrombotic Therapy After Transcatheter Aortic Valve Implantation (NAPT) Trial is a prospective, randomized controlled, open-label blinded endpoint multicenter trial conducted in Japan, testing the non-inferiority of non-antithrombotic therapy compared with aspirin monotherapy in patients who underwent TAVI and had no indications for long-term oral anticoagulation therapy (OAC). Patients who successfully underwent trans-femoral TAVI for severe aortic stenosis with either balloon-expandable or self-expandable valves are eligible for inclusion. Key exclusion criteria are (i) occurrence of perioperative complications (ii) indications of taking antithrombotic drugs for other reasons; (iii) eGFR <30 ml/min/1.73 m2 or hemodialysis or peritoneal dialysis. A total of 360 patients will be randomized (1:1) to aspirin monotherapy vs. non-antithrombotic therapy. The primary outcome is a composite of all-cause mortality, myocardial infarction, stroke, and bleeding. All bleeding events based on the Valve Academic Research Consortium 3 are included as a component of the primary outcome. CONCLUSION: The NAPT trial will determine the non-inferiority of a non-antithrombotic therapy compared with aspirin monotherapy after TAVI.

Biweekly TAS-102 and bevacizumab as third-line chemotherapy for advanced or recurrent colorectal cancer: a phase II, multicenter, clinical trial (TAS-CC4 study).

BACKGROUND: TAS-102 improves overall survival (OS) of patients with refractory colorectal cancer (CRC), resulting in median progression-free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, a combination of TAS-102 and bevacizumab was shown to extend median PFS by 3.7 months. However, approximately half of these patients experience grade 3/4 neutropenia. In this study, we evaluated whether biweekly TAS-102 and bevacizumab therapy has efficacy equal to that of conventional TAS-102 and bevacizumab therapy and whether it reduces adverse hematological effects. METHODS: This phase II, investigator-initiated, open-label, single-arm, multicenter study was conducted in Japan. Eligible patients had previously received first- and second-line chemotherapy for metastatic CRC. TAS-102 (35 mg/m2) was given twice daily on days 1-5 and days 15-19 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion for 30 min every 2 weeks. The primary end point was progression-free survival (PFS), and secondary end points were time-to-treatment failure (TTF), response rate (RR), OS, and safety. RESULTS: 44 patients with metastatic colorectal cancer were enrolled in this study. Median PFS was 4.6 months (95% confidence interval [95% CI] 3.6-5.3) and median OS was 10.5 months (95% CI 9.6-11.4). A partial response was observed in 2 patients (4.5%, 95% CI 0.4-16.0%). The most common adverse event above grade 3 was neutropenia (7 patients, 15.9%, 95% CI 7.6-29.7%). CONCLUSIONS: Biweekly TAS-102 and bevacizumab therapy as third-line chemotherapy appears as effective as conventional TAS-102 and bevacizumab therapy, and this approach reduces adverse hematological effects.

Multicenter randomized study evaluating the outcome of ganglionated plexi ablation in maze procedure.

OBJECTIVE: The benefit of adding ganglionated plexi ablation to the maze procedure remains controversial. This study aims to compare the outcomes of the maze procedure with and without ganglionated plexi ablation. METHODS: This multicenter randomized study included 74 patients with atrial fibrillation associated with structural heart disease. Patients were randomly allocated to the ganglionated plexi ablation group (maze with ganglionated plexi ablation) or the maze group (maze without ganglionated plexi ablation). The lesion sets in the maze procedure were unified in all patients. High-frequency stimulation was applied to clearly identify and perform ganglionated plexi ablation. Patients were followed up for at least 6 months. The primary endpoint was a recurrence of atrial fibrillation. RESULTS: The intention-to-treat analysis included 69 patients (34 in the ganglionated plexi ablation group and 35 in the maze group). No surgical mortality was observed in either group. After a mean follow-up period of 16.3 ± 7.9 months, 86.8% of patients in the ganglionated plexi ablation group and 91.4% of those in the maze group did not experience atrial fibrillation recurrence. Kaplan-Meier atrial fibrillation-free curves showed no significant difference between the two groups (P = .685). Cox proportional hazards regression analysis indicated that left atrial dimension was the only risk factor for atrial fibrillation recurrence (hazard ratio: 1.106, 95% confidence interval 1.017-1.024, P = .019). CONCLUSION: The addition of ganglionated plexi ablation to the maze procedure does not improve early outcome when treating atrial fibrillation associated with structural heart disease.

Serial change in perfusion-metabolism mismatch after coronary artery bypass grafting.

OBJECTIVE: Myocardial ischemia is known to suppress fatty acid metabolism and favor glucose metabolism. However, changes in myocardial metabolism after coronary revascularization are not fully elucidated. METHODS: Thirty-eight patients with coronary artery disease were retrospectively enrolled. These patients had undergone stress perfusion single photon emission computed tomography (SPECT) and 123I-BMIPP SPECT in both the short-term (6.4 ± 4.7 months) and mid-term (29.9 ± 7.2 months) after isolated coronary artery bypass grafting. Tracer uptake was graded using a 17-segment, 5-point scoring model. Serial changes in SRS (summed rest score), SDS (summed difference score), the BMIPP score (total defect score of BMIPP), and the mismatch score (BMIPP score-SRS) were evaluated. In addition, persistent perfusion-metabolism mismatch (PM) was defined as mismatch score minus SDS of 3 or more during the mid-term postoperative period. The clinical parameters associated with PM were examined. RESULTS: From short- to mid-term postoperative period, the extent of infarcted myocardium (SRS) did not change significantly (7.8 ± 8.0 to 7.1 ± 7.0, P = 0.117). The extent of ischemic myocardium (SDS), the BMIPP score and the mismatch score, which reflects perfusion-metabolism mismatch, were significantly improved (2.0 ± 2.8 to 0.7 ± 1.0, P = 0.010; 12.2 ± 9.0 to 9.5 ± 7.9, P < 0.001; 4.4 ± 3.7 to 2.5 ± 2.6, P < 0.001; respectively). Remarkably, perfusion-metabolism mismatch persisted in 13 patients (34%) even in the mid-term postoperative period. eGFR and SYNTAX score were independent predictors of persistent perfusion-metabolic mismatch in multivariable analysis (OR = 0.951, 95% CI 0.898-0.985, P = 0.010 and OR = 1.126, 95% CI 1.011-1.254, P = 0.031, respectively). The mismatch score both in the short- and mid-term significantly correlated with SYNTAX score (r = 0.400 and r = 0.472, respectively). CONCLUSIONS: Fatty acid metabolism disturbance improved from short- to mid-term postoperative period in patients with successful reperfusion by coronary artery bypass grafting. However, in patients with severe atherosclerosis, impaired fatty acid metabolism was sustained until the mid-term postoperative period, even though ischemia had resolved.

Effect of holiday admission for acute aortic dissection on in-hospital mortality in Japan: A nationwide study.

BACKGROUND: Patients admitted on weekends have higher mortality than those admitted on weekdays. However, whether the "weekend effect" results in a higher mortality after admission for acute aortic dissection (AAD),-classified according to Stanford types-remains unclear. This study aimed to examine the association between admission day and in-hospital mortality in AAD Type A and B. METHODS: We used data from the Japanese registry of all Cardiac and Vascular Diseases Diagnostic Procedure Combination, a nationwide claim-based database with data from 953 certified hospitals, and enrolled in-patients with AAD admitted between April 1, 2012, and March 31, 2016. Based on the admission day, we stratified patients into groups (Weekdays, Saturdays, and Sundays/holidays). The influence of the admission day on in-hospital mortality was assessed via multi-level logistic regression analysis. We also performed a Stanford type-based stratified analysis. RESULTS: Among the included 25,641 patients, in-hospital mortality was 16.0%. The prevalence of patients admitted with AAD was relatively higher on weekdays. After adjustment for covariates, patients admitted on a Sunday/holiday showed an increased risk of in-hospital mortality (odds ratio [OR] 1.20; 95% confidence interval [CI] 1.07-1.33, p<0.001) than patients admitted on weekdays. Among patients admitted on a Sunday/holiday, only the subgroup of Stanford Type A showed a significantly increased risk of in-hospital mortality. (Stanford Type A, non-surgery vs. surgery groups: 95% CI 1.06-1.48 vs. 1.17-1.68, p<0.001 for both groups, OR 1.25 vs. 1.41, respectively, Stanford Type B, non-surgery vs. surgery groups: 95% CI 0.64-1.09 vs. 0.40-2.10; p = 0.182 vs. 0.846; OR 0.84 vs. 0.92). CONCLUSIONS: In conclusion, patients with AAD Type A admitted on a Sunday/holiday may have an increased in-hospital mortality risk.

Myocardial ultrastructure can augment genetic testing for sporadic dilated cardiomyopathy with initial heart failure.

AIMS: The aim of the present study was to consider whether the ultrastructural features of cardiomyocytes in dilated cardiomyopathy can be used to guide genetic testing. METHODS AND RESULTS: Endomyocardial biopsy and whole-exome sequencing were performed in 32 consecutive sporadic dilated cardiomyopathy patients [51.0 (40.0-64.0) years, 75% men] in initial phases of decompensated heart failure. The predicted pathogenicity of ultrarare (minor allele frequency ≤0.0005), non-synonymous variants was determined using the American College of Medical Genetics guidelines. Focusing on 75 cardiomyopathy-susceptibility and 41 arrhythmia-susceptibility genes, we identified 404 gene variants, of which 15 were considered pathogenic or likely pathogenic in 14 patients (44% of 32). There were five sarcomeric gene variants (29% of 17 variants) found in five patients (16% of 32), involving a variant of MYBPC3 and four variants of TTN. A patient with an MYBPC3 variant showed disorganized sarcomeres, three patients with TTN variants located in the region encoding the A-band domain showed sparse sarcomeres, and a patient with a TTN variant in encoding the I-band domain showed disrupted sarcomeres. The distribution of diffuse myofilament lysis depended on the causal genes; three patients with the same TMEM43 variant had diffuse myofilament lysis near nuclei (P = 0.011), while two patients with different DSP variants had lysis in the peripheral areas of cardiomyocytes (P = 0.033). CONCLUSIONS: Derangement patterns of myofilament and subcellular distribution of myofilament lysis might implicate causal genes. Large-scale studies are required to confirm whether these ultrastructural findings are related to the causative genes.

Four-dimensional flow analysis reveals mechanism and impact of turbulent flow in the dissected aorta.

OBJECTIVES: This study aimed to explore the flow dynamics factors affecting turbulence formation in the false lumen (FL) of aortic dissection using four-dimensional flow magnetic resonance imaging (4D flow MRI). This study also aimed to uncover risk factors affecting late complications of aortic dissection. METHODS: Thirty-three aortic dissection patients were examined using 4D flow MRI for quantitative flow dynamics (gross flow, velocity and regurgitant fraction) and turbulence visualization (helix and vortex with three-point visual grading) in the FL. The incidence of late complications (rupture or prophylactic intervention) was also obtained prospectively. RESULTS: The helix grade was correlated with FL gross flow (rS = 0.55, P < 0.001) and FL velocity (rS = 0.45, P = 0.008). The vortex grade was also correlated with FL gross flow (rS = 0.70, P < 0.001) and FL velocity (rS = 0.67, P < 0.001). Comparative analysis of patients with complications and stable patients revealed that patients with complications exhibited higher FL gross flow [41.7 (interquartile range, IQR 29.1-59.7) vs 17.7 (IQR 9.0-42.0) ml/s; P = 0.01], higher helix grade [2 (IQR 1.25-2) vs 0 (IQR 0-1); P = 0.001] and higher vortex grade [2 (IQR 1-2) vs 0 (IQR 0-2); P = 0.01]. CONCLUSIONS: Using 4D flow MRI analysis, we showed that turbulence formation depends on flow volume and velocity in the FL. Patients with high-volume turbulent flow in their FL are at higher risk of late complications; therefore, close follow-up and aggressive prophylactic intervention may improve their survival. CLINICAL TRIAL REGISTRATION NUMBER: Nippon Medical School Hospital Institutional Review Board approved this observational study in September 2018 (No. 30-08-986).

Combination of TAS-102 and bevacizumab as third-line treatment for metastatic colorectal cancer: TAS-CC3 study.

BACKGROUND: TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clinical impact beyond cytotoxic doublets. METHODS: This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRC patients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m2) was given orally twice daily on days 1-5 and 8-12 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion every 2 weeks. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety. RESULTS: Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 months; the median overall survival was 9.3 months. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematological adverse events above grade 3 and no treatment-related deaths occurred. CONCLUSIONS: This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC.

Left Ventricular Hypertrophy Is More Prevalent in Type B than Type A Aortic Dissection.

OBJECTIVES: Several factors determining differences between types A and B aortic dissection (AD) have been reported; however, little data exist examining their differences in left ventricular hypertrophy (LVH). We compared the prevalence of LVH in patients with types A and B AD. METHODS: We retrospectively analyzed 334 patients with acute AD (227 type A; 107 type B). Concentric hypertrophy (CH; increased left ventricular mass index [LVMI] and relative wall thickness [RWT]) is one of four types of left ventricular (LV) geometry thought to be most associated with hypertension. We compared LVMI and the prevalence of CH in patients with types A or B AD. Multivariate logistic regression analyses of variables associated with type B AD were performed. RESULTS: Comparing type A and B AD, LVMI (95 ± 26 vs.107 ± 28, p <0.001) and prevalence of CH (26% vs. 44%, p = 0.001) were higher in type B AD. In multivariate analysis, CH was an independent factor associated with type B AD (odds ratio: 2.62, confidence interval: 1.54-4.47, p <0.001). CONCLUSIONS: Our data suggested LVH was more prevalent in type B than in type A AD. Considering LVH usually results from hypertension, patients with type B AD may be more affected by hypertension than those with type A.

Clinical risk model for predicting 1-year mortality after transcatheter aortic valve replacement.

OBJECTIVES: Estimating 1-year life expectancy is an essential factor when evaluating appropriate indicators for transcatheter aortic valve replacement (TAVR). BACKGROUND: It is clinically useful in developing a reliable risk model for predicting 1-year mortality after TAVR. METHODS: We evaluated 2,588 patients who underwent TAVR using data from the Optimized CathEter vAlvular iNtervention (OCEAN) Japanese multicenter registry from October 2013 to May 2017. The 1-year clinical follow-up was achieved by 99.5% of the entire population (n = 2,575). Patients were randomly divided into two cohorts: the derivation cohort (n = 1,931, 75% of the study population) and the validation cohort (n = 644). Considerable clinical variables including individual patient's comorbidities and frailty markers were used for predicting 1-year mortality following TAVR. RESULTS: In the derivation cohort, a multivariate logistic regression analysis demonstrated that sex, body mass index, Clinical Frailty Scale, atrial fibrillation, peripheral artery disease, prior cardiac surgery, serum albumin, renal function as estimated glomerular filtration rate, and presence of pulmonary disease were independent predictors of 1-year mortality after TAVR. Using these variables, a risk prediction model was constructed to estimate the 1-year risk of mortality after TAVR. In the validation cohort, the risk prediction model revealed high discrimination ability and acceptable calibration with area under the curve of 0.763 (95% confidence interval, 0.728-0.795, p < .001) in the receiver operating characteristics curve analysis and a Hosmer-Lemeshow χ2 statistic of 5.96 (p = .65). CONCLUSIONS: This risk prediction model for 1-year mortality may be a reliable tool for risk stratification and identification of adequate candidates in patients undergoing TAVR.

A Trial Protocol of Biweekly TAS-102 and Bevacizumab as Third-Line Chemotherapy for Advanced/Recurrent Colorectal Cancer: A Phase II Multicenter Clinical Trial (The TAS-CC4 Study).

BACKGROUND: Treatment with TAS-102 has significantly improved the progression-free survival (PFS) and overall survival (OS) of patients with metastatic colorectal cancer (mCRC). Reportedly, the combination of TAS-102 plus bevacizumab extends the median PFS. The present study aimed to confirm the efficacy and safety of TAS-102 plus bevacizumab (biweekly administration) as third-line chemotherapy for patients with mCRC. METHODS/DESIGN: This is a single-arm, open-label, prospective, nonrandomized, multicenter phase II trial conducted in Japan. With a threshold and expected PFS of 2.1 and 3.5 months, respectively, the simulation results showed a sample size of 42 with α = 0.05 (both sides) for 90% power, based on the One-Arm Binomial test using the SWOG statistical tool. If the estimated dropout is 7%-8%, the target sample size is estimated to be 45. The TAS-CC4 study regimen comprised 28-day cycles with biweekly oral administration of TAS-102 (35 mg/m2 twice daily on days 1-5 and 15-19 of every 28-day cycle) and bevacizumab (5.0 mg/kg on days 1 and 15). The primary end point is the PFS; secondary end points include response rate (RR), OS, grade ≥3 neutropenia, and genetic alterations (KRAS/BRAF mutations) in the circulating cell-free DNA. DISCUSSION: The present study can contribute to the determination of the effective dosing interval of TAS-102 and bevacizumab in patients with mCRC and is thought to lead to prophylaxis of neutropenia and prolongation of the treatment period.

Is it safe to continue antithrombotic agents before prostate biopsy?

BACKGROUND: Whether antithrombotic agents should be stopped before prostate biopsy is unsettled. We investigated the impact of antithrombotic agents on bleeding complications after prostate biopsy. MATERIALS AND METHODS: Among the patients who underwent transrectal ultrasound-guided prostate biopsy from June 2006 to December 2013 at Ebina General Hospital, Kanagawa, Japan, 1817 cases were retrospectively assessed. Patients were divided into two groups: those not taking antithrombotic agents (control group) and those taking them (experimental group). The frequency and severity of bleeding complications after the procedure were compared. The severity of bleeding events was graded using the Common Terminology Criteria for Advanced Events vol. 4.0. RESULTS: Hemorrhagic complications were classified into grades 1 to 3. Patients with complications of Grade 2 and above needed treatment. As for the Grade 1 event, there were no differences between two groups. The frequency of more than Grade 2 bleeding events was 1.7% and 3.5% in the control and experimental group, respectively; the odds ratio was 2.18 (P = 0.039). Grade 3 events occurred in seven patients of the control group (0.5%) and four patients of the experimental group (1.2%). CONCLUSIONS: The present study showed that continuation of antithrombotic agents increased the frequency of hemorrhagic complications requiring intervention. It suggests that attention should be paid to the patients taking antithrombotic agents before prostate biopsy.

Risk Factors of Recurrence of Atrial Fibrillation (AF) After AF Surgery in Patients With AF and Mitral Valve Disease.

The purpose of this study was to determine the 22-year experience of the relationship between preoperative left atrial diameter (LAD) and atrial fibrillation (AF) recurrence after AF surgery. Between November 1993 and April 2015, 244 patients underwent AF surgery concomitant with mitral valve surgery, and were completely followed up in our institute. The full-maze procedure was performed in 231 patients and pulmonary vein isolation in 13. Three quartiles divided the list of sorted LAD data into 4 groups: group Q1: LAD = 40.5 ± 4.3 (n = 55), group Q2: LAD = 47.9 ± 2.0 (n = 61), group Q3: LAD = 54.2 ± 1.6 (n = 66), and group Q4: LAD = 64.2 ± 5.6 (n = 62). The AF cure rates for 22 years were verified between the groups. Although the AF cure rate of the full-maze procedure was 94%, 80%, 63%, and 51% at 1, 5, 10, and 20 years after AF surgery, respectively, it was 100% at 5 and 10 years after the pulmonary vein isolation (P = 0.088). Although there were no significant differences in the AF cure rate between groups Q1-Q3, the AF cure rate was significantly lower in group Q4 than the other groups (P < 0.001). A multivariate Cox proportional hazard model revealed that the preoperative LAD and cardiothoracic ratio were significant risk factors of AF recurrence (hazard ratio 1.063 per 1-mm increase, P = 0.003, and hazard ratio 1.064 per 1% increase, P = 0.043, respectively). AF surgery was effective for 22 years after surgery for AF concomitant with mitral valve disease. A preoperative LAD of ≥58.0 mm and the cardiothoracic ratio were risk factors of AF recurrence after AF surgery.

Relationship between swallowing function and breathing/phonation.

OBJECTIVE: Clarification of the association between the swallowing function and respiratory and phonatory functions. METHODS: The subjects were 30 patients with a chief complaint of swallowing disorder with clear consciousness capable of retaining a sitting position. Patients with organic and functional diseases of the larynx were excluded. Twenty-two and eight patients were male and female, respectively, and the mean age was 77.0±14.6years old. The chest expansion score was measured as an index of the respiratory function, and the maximum phonation time (MPT) was measured as an index of the phonatory function. The presence or absence of aspiration was judged using videoendoscopic swallowing study (VESS) and videofluoroscopic swallow studies (VFSS). The patients were divided into those with and without aspiration, and the chest expansion score and MPT were compared. In addition, the distance of laryngeal elevation was measured in the lateral view of VFSS, and its correlations with the chest expansion score and MPT were closely analyzed. To evaluate reliability of the test, the distance of laryngeal elevation and videoendoscopic score were compared between the presence and absence of aspiration. RESULTS: The distance of laryngeal elevation was significantly shortened and the videoendoscopic score was significantly higher in the group with aspiration, as previously reported. On comparison of the chest expansion score between the groups with and without aspiration, no significant difference was noted at the axillary or xiphoid process level, and shortening was significant only at the 10th rib level in the group with aspiration. On comparison of MPT, it was significantly shortened in the group with aspiration. In addition, a significant positive correlation with the distance of laryngeal elevation was noted in both chest expansion score and MPT. CONCLUSION: It was suggested that declines of the respiratory and phonatory functions are risk factors of aspiration through limiting laryngeal elevation, and the chest expansion score at the 10th rib level and MPT are useful for screening of aspiration.

Impact of frailty markers on outcomes after transcatheter aortic valve replacement: insights from a Japanese multicenter registry.

There are no standardized criteria for measuring patients' frailty. We examined prognosis based on four frailty markers [serum albumin level, grip strength, gait speed, and clinical frailty scale (CFS)] in patients who underwent transcatheter aortic valve replacement (TAVR) between October 2013 and April 2016 and were recorded in the Optimized CathEter vAlvular iNtervention (OCEAN) Japanese multicenter registry. Serum albumin level was assessed by dividing patients into two groups: hypoalbuminemia or non-hypoalbuminemia according to their serum albumin level. Clinical outcomes including all-cause, cardiovascular and non-cardiovascular mortality rates after TAVR were compared. During the follow-up period cumulative all-cause, cardiovascular and non-cardiovascular mortality rates were significantly higher in the hypoalbuminemia group than in the non-hypoalbuminemia group. This result remained unchanged even after a propensity-matched model was used in terms of cumulative all-cause and non-cardiovascular mortality; however, differences in cardiovascular mortality rates were attenuated. To consider the impact of grip strength patients were divided into a low or high peak grip strength group based on classification and regression tree (CART) survival analysis. The clinical outcomes for each sex were compared between the two groups. In both sexes the cumulative 1-year mortality rates were significantly different between the two groups. To investigate gait speed patients were classified into two gait speed groups (low or high gait speed group) based on CART survival analysis. Clinical outcomes were compared between the two groups. The cumulative 1-year mortality rate was significantly different between the two gait speed groups. The effect of CFS on prognosis after TAVR was assessed. Patients were categorized into five groups based on the following CFS scores: CFS1-3, CFS4, CFS5, CFS6, and CFS ≥7. We evaluated the relationship between the CFS score and other indicators of frailty markers. We also assessed the mid-term mortality among the five groups. The CFS score had a significant correlation with other frailty markers. The cumulative 1-year mortality increased with an increasing CFS score. In the Cox regression multivariable analysis, the CFS score was an independent predictive factor of an increased late cumulative mortality risk. In conclusion, the results suggest that serum albumin level, grip strength, gait speed, and CFS score are all useful indicators when considering the optimal indications and risk stratification for TAVR.

Impact of glucose control on early vein graft failure after coronary artery bypass grafting: one-month angiographic results.

Objectives: To identify factors that determine early saphenous vein graft failure (VGF) within 1 month after coronary artery bypass grafting (CABG). Methods: Seven hundred forty-nine consecutive patients underwent primary isolated CABG with saphenous vein grafts at three Japanese centres from 1 January 2005 to 31 December 2014. According to angiographic findings within 1 month of CABG surgery, 63 patients (8.4%) developed early VGF. We examined the relationships between variables and early VGF by using multivariable logistic regression analysis. Results: The preoperative clinical characteristics were similar between patients with and without early VGF, except for median preoperative haemoglobin A1c levels, which were significantly higher among patients with early VGF (6.7 vs 6.4%, P = 0.046). Additionally, anastomosis to the vessel with chronic total obstruction was performed more frequently among patients with early VGF (22/63 [34.9%] vs 140/686 [20.4%], P = 0.007), and myocardial infarction during the hospital admission occurred more frequently among patients with early VGF (4/63 [6.3%] vs 2/686 [0.3%], P < 0.0001). Results of multivariable analysis showed that the preoperative haemoglobin A1c level was associated with early VGF (odds ratio per unit increase, 1.30; 95% confidence interval, 1.06-1.60; P = 0.013). Conclusions: An increased preoperative haemoglobin A1c level was strongly associated with early VGF after CABG. Thus, VGF happened more frequently in patients with poorly controlled diabetes mellitus.

Dyslipidemia and the Risk of Developing Hypertension in a Working-Age Male Population.

BACKGROUND: Hypertension is one of the main comorbidities associated with dyslipidemia. This study aimed to examine the extent to which dyslipidemia increases the risk of developing hypertension in a Japanese working-age male population. METHODS AND RESULTS: We analyzed data from 14 215 nonhypertensive male workers (age 38±9 years) who underwent annual medical checkups. Subjects were followed up for a median of 4 years to determine new-onset hypertension, defined as blood pressure (BP) ≥140/90 mm Hg or use of antihypertensive medication. The associations between serum lipid levels and development of hypertension were examined. During the follow-up period, 1483 subjects developed hypertension. After adjusting for age, body mass index, impaired fasting glucose/diabetes, baseline BP category, alcohol intake, smoking, exercise, and parental history of hypertension, subjects with a total cholesterol (TC) level ≥222 mg/dL were at a significantly increased risk of developing hypertension (hazard ratio: 1.28; 95% CI: 1.06-1.56) compared to subjects with a TC level ≤167 mg/dL. Similar results were observed for subjects with high low-density lipoprotein cholesterol (LDLC) and non-high-density lipoprotein cholesterol (HDLC) levels. A U-shaped relationship was found between HDLC level and risk of hypertension; compared to the third quintile, the multiadjusted hazard ratio was 1.22 (95% CI: 1.03-1.43) in the lowest quintile and 1.34 (95% CI: 1.12-1.60) in the highest quintile. CONCLUSIONS: Elevated serum levels of TC, LDLC, and non-HDLC were associated with an increased risk of hypertension in working-age Japanese men. For HDLC, risk of hypertension was increased at both low and high levels.