Background: Recent progress in surgical and intensive care has improved the prognosis of congenital heart disease (CHD) associated with heterotaxy syndrome. Less is known, however, about pulmonary vascular complications in these patients.

Methods and Results: We reviewed medical records of 236 patients who were diagnosed with polysplenia syndrome at 2 institutions for pediatric cardiology in Japan from 1978 to 2015. We selected and compared the clinical records of 16 patients with polysplenia who had incomplete atrioventricular septal defect (AVSD) as the polysplenia group, and 22 age-matched patients with incomplete AVSD without any syndromes including polysplenia as the control group. Although the severity of systemic to pulmonary shunt was not significantly different between the groups, mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance index (PVRI) were significantly higher in the polysplenia group than the control (mPAP, 37.3 vs. 19.1 mmHg, P=0.001; PVRI, 5.7 vs. 1.4 WU∙m², P=0.014) before surgical intervention. On regression analysis, polysplenia influenced the development of pulmonary hypertension (PH) regardless of age at evaluation or degree of systemic to pulmonary shunt in the patients with incomplete AVSD.

Conclusions: Polysplenia syndrome is an independent risk factor for CHD-associated PH. Earlier intervention may be required to adjust the pulmonary blood flow in polysplenia syndrome with CHD to avoid the progression of PH.

Background:Increased heart rate (HR) is an independent risk factor for cardiovascular outcomes in chronic heart failure (HF). Ivabradine, anI_finhibitor, improved outcomes in patients with HF and reduced ejection fraction (HFrEF) in the SHIFT study. We evaluated its efficacy and safety in Japanese HFrEF patients in a randomized, double-blind, placebo-controlled phase III study: the J-SHIFT study. The main objective was to confirm a hazard ratio of <1 in the primary composite endpoint of cardiovascular death or hospital admission for worsening HF.

Methods and Results:Patients with NYHA functional class II–IV, left ventricular EF ≤35%, and resting HR ≥75 beats/min in sinus rhythm under optimal medical therapy received ivabradine (n=127) or placebo (n=127). Mean reduction in resting HR was significantly greater in the ivabradine group (15.2 vs. 6.1 beats/min, P<0.0001). However, symptomatic bradycardia did not occur. A total of 26 (20.5%) patients in the ivabradine group and 37 (29.1%) patients in the placebo group had the primary endpoint event (hazard ratio 0.67, 95% CI 0.40–1.11, P=0.1179) during median follow-up of 589 days. Mild phosphenes were reported in 8 (6.3%) patients in the ivabradine group and 4 (3.1%) patients in the placebo group (P=0.3760).

Conclusions:The J-SHIFT study supported the efficacy and safety of ivabradine for Japanese HFrEF patients, in accord with the SHIFT study.

Background: To determine the impact of cardiac function and type of mitral valve (MV) surgery on blood flow and energy loss in the left ventricle (LV).

Methods and Results: This study enrolled patients with ejection fraction (EF) <35% or >50%; both groups had native (n=27 and n=16), repaired (n=19 and n=33), or prosthetic MVs (n=18 and n=19). They were examined by echocardiography-based vector flow mapping to assess the LV blood flow pattern and energy loss per heartbeat. Among patients with preserved EF, those with native MVs displayed a clockwise vortex and relatively low energy loss. In contrast, MV replacement induced a counterclockwise vortex producing higher energy loss than MV repair, which induced a normal clockwise vortex. This indicated the need for MV repair to minimize LV energy loss after surgery. Among the patients with reduced EF, those with native MVs showed a blood flow pattern similar to those with preserved EF and native MVs; furthermore, those with repaired MVs and half of the patients with prosthetic MVs displayed a clockwise vortex, resulting in no difference in energy loss between the 2 types of MV surgery.

Conclusions: Cardiac function and the type of MV surgery are factors affecting the postoperative LV blood flow pattern. MV replacement resulted in abnormal blood flow with normal cardiac function, whereas advanced cardiomyopathy modified the blood flow pattern post-MV replacement.

Background:Many studies show that dietary factors such as vegetables, fruit, and salt are associated with cardiovascular disease (CVD) risk. However, a risk assessment chart for CVD mortality according to combinations of dietary factors has not been established.

Methods and Results:Participants were 9,115 men and women aged 30–79 years enrolled in the National Nutritional Survey of Japan in 1980 with a 29-year follow-up. Dietary intake was assessed using a 3-day weighed dietary record at baseline. Cox regression models were used to estimate the hazard ratio (HR) of CVD mortality stratified by vegetables, fruit, fish, and salt consumption. HRs of CVD mortality according to combinations of dietary factors were color coded on an assessment chart. Higher intakes of vegetables, fruit, and fish, and lower salt intake were associated with lower CVD mortality risk. HRs calculated from combinations of dietary factors were displayed using 5 colors corresponding to the magnitude of the HR. People with the lowest intake of vegetables, fruit, and fish, and higher salt intake had a HR of 2.87 compared with those with the highest intake of vegetables, fruit, and fish, and lower salt intake.

Conclusions:Vegetables, fruit, fish, and salt intake were independently associated with CVD mortality risk. The assessment chart generated could be used in Japan as an educational tool for CVD prevention.

Background: Evidence from prospective cohort studies regarding the relationship between working hours and risk of cardiovascular disease is limited

Methods and Results: The Japan Public Health Center-Based Prospective Study Cohort II involved 15,277 men aged 40–59 years at the baseline survey in 1993. Respondents were followed up until 2012. During the median 20 years of follow up (257,229 person-years), we observed 212 cases of acute myocardial infarction and 745 stroke events. Cox proportional hazards models adjusted for sociodemographic factors, cardiovascular risk factors, and occupation showed that multivariable-adjusted hazard ratios (HRs) associated with overtime work of ≥11h/day were: 1.63 (95% confidence interval [CI] 1.01–2.63) for acute myocardial infarction and 0.83 (95% CI 0.60–1.13) for total stroke, as compared with the reference group (working 7 to <9 h/day). In the multivariable model, increased risk of acute myocardial infarction associated with overtime work of ≥11 h/day was more evident among salaried employees (HR 2.11, 95% CI 1.03–4.35) and men aged 50–59 years (HR 2.60, 95% CI 1.42–4.77).

Conclusions: Among middle-aged Japanese men, working overtime is associated with a higher risk of acute myocardial infarction.

Background: The rapid increase in the number of heart failure (HF) patients in parallel with the increase in the number of older people is receiving attention worldwide. HF not only increases mortality but decreases quality of life, creating medical and social problems. Thus, it is necessary to define molecular mechanisms underlying HF development and progression. HMGB2 is a member of the high-mobility group superfamily characterized as nuclear proteins that bind DNA to stabilize nucleosomes and promote transcription. A recent in vitro study revealed that HMGB2 loss in cardiomyocytes causes hypertrophy and increases HF-associated gene expression. However, it’s in vivo function in the heart has not been assessed.

Methods and Results: Western blotting analysis revealed increased HMGB2 expression in heart tissues undergoing pressure overload by transverse aorta constriction (TAC) in mice. Hmgb2 homozygous knockout (Hmgb2^−/−) mice showed cardiac dysfunction due to AKT inactivation and decreased sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA)2a activity. Compared to wild-type mice, Hmgb2^−/− mice had worsened cardiac dysfunction after TAC surgery, predisposing mice to HF development and progression.

Conclusions: This study demonstrates that upregulation of cardiac HMGB2 is an adaptive response to cardiac stress, and that loss of this response could accelerate cardiac dysfunction, suggesting that HMGB2 plays a cardioprotective role.

Background: The differential prognostic impact of β-blocker dose after acute myocardial infarction (AMI) has been under debate. The current study sought to compare clinical outcome after AMI according to β-blocker dose using the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH).

Methods and Results: Of the total population of 13,104 consecutive AMI patients enrolled in the KAMIR-NIH, the current study analyzed 11,909 patients. These patients were classified into 3 groups (no β-blocker; low-dose [<25% of target dose]; and high-dose [≥25% of target dose]). The primary outcome was cardiac death at 1 year. Compared with the no β-blocker group, both the low-dose and high-dose groups had significantly lower risk of cardiac death (HR, 0.435; 95% CI: 0.363–0.521, P<0.001; HR, 0.519; 95% CI: 0.350–0.772, P=0.001, respectively). The risk of cardiac death, however, was similar between the high- and low-dose groups (HR, 1.194; 95% CI: 0.789–1.808, P=0.402). On multivariable adjustment and inverse probability weighted analysis, the result was the same.

Conclusions: The use of β-blockers in post-AMI patients had significant survival benefit compared with no use of β-blockers. There was no significant additional benefit of high-dose β-blockers compared with low-dose β-blockers, however, in terms of 1-year risk of cardiac death.

Background: Left ventricular non-compaction (LVNC) is a cardiomyopathy morphologically characterized by 2-layered myocardium and numerous prominent trabeculations, and is often associated with dilated cardiomyopathy (DCM). Variants in the gene encoding tafazzin (TAZ) may change mitochondrial function and cause dysfunction of many organs, but they also contribute to the DCM phenotype in LVNC, and the clinical and echocardiographic features of children with this phenotype are poorly understood.

Methods and Results: We enrolled 92 DCM phenotype LVNC patients and performed next-generation sequencing to identify the genetic etiology. Ten TAZ variants were identified in 15 male patients (16.3%) of the 92 patients, including 3 novel missense substitutions. The patients with TAZ variants had a higher frequency of early onset of disease (92.3% vs. 62.3%, P=0.0182), positive family history (73.3% vs. 20.8%, P=0.0001), and higher LV posterior wall thickness Z-score (8.55±2.60 vs. 5.81±2.56, P=0.0103) than those without TAZ variants, although the mortality of both groups was similar.

Conclusions: This study provides new insight into the impact of DCM phenotype LVNC and emphasizes the clinical advantages available for LVNC patients with TAZ variants.

Background: Mutation in the lamin A/C gene (LMNA) is associated with several cardiac phenotypes, such as cardiac conduction disorders (CCD), atrial arrhythmia (AA), malignant ventricular arrhythmia (MVA) and left ventricular dysfunction (LVD), leading to sudden cardiac death (SCD) and/or end-stage heart failure. We investigated how these phenotypes are associated with each other and which of them are most important for total mortality.

Methods and Results: A multicenter registry included 110 LMNA mutation carriers (age, 43±15 years, male: 62%) from 60 families. After genetic diagnosis of LMNA mutation (missense: 27%, non-missense: 73%), patients or subjects were followed to evaluate the manifestations of their phenotypes and the risk of total mortality; 90 patients could be followed (median: 5 [0–35] years). Prevalence of the 4 clinical phenotypes was significantly increased during follow-up. Among these phenotypes, AA was significantly associated with MVA. CCD was significantly associated with LVD. LVD, meanwhile, was significantly associated with CCD and MVA. Male sex was significantly associated with MVA. Furthermore, during follow-up, 17 patients died: 12 end-stage heart failure, 4 SCD and 1 stroke. LVD was the only independent predictor for all-cause death (OR: 41.7, 95% CI: 4.1–422.3; P=0.0016).

Conclusions: Several cardiac phenotypes were age-dependently increased in LMNA mutation carriers, suggesting that ICD or CRT-D could suppress SCD after middle age; however, LVD leading to end-stage heart failure was the only independent predictor for total mortality.

Background: Dilatation of the ascending aorta affects those patients with bicuspid aortic valve (BAV), even after valvular surgery, possibly due to tissue fragility. The goal of the study was the molecular characterization of aorta with BAV compared to that with normal tricuspid aortic valve (TAV).

Methods and Results: The subjects were patients who underwent surgery for aortic valve stenosis in 2013 and 2014. Nine patients with BAV and 13 with TAV were examined. There was no difference in the clinical characteristics or grade of aortic valve stenosis, but the diameters of the ascending aorta were significantly higher in the BAV group. The ascending aortic specimens were subjected to transcriptome analyses, which revealed the changes in receptor tyrosine kinase (RTK) pathway-related genes between TAV and BAV samples. Immunohistochemical study revealed higher staining of phosphorylated AKT (pAKT) in the media of the ascending aorta in the BAV group, regardless of the size of ascending aorta, whereas total AKT did not show such a difference. Immunofluorescence staining revealed the AKT activation was mainly in the medial vascular smooth muscle cells.

Conclusions: The results showed that the RTK-AKT pathway in the medial layer of the ascending aorta is activated in aortae with BAV. Activation of this pathway may be associated with fragility and dilatation of the ascending aorta with BAV.

Background: Lipoprotein lipase (LPL) plays an important role in triglyceride metabolism. It is translocated across endothelial cells to reach the luminal surface of capillaries by glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1), where it hydrolyzes triglycerides in lipoproteins. MicroRNA 377 (miR-377) is highly associated with lipid levels. However, how miR-377 regulates triglyceride metabolism and whether it is involved in the development of atherosclerosis remain largely unexplored.

Methods and Results: The clinical examination displayed that miR-377 expression was markedly lower in plasma from patients with hypertriglyceridemia compared with non-hypertriglyceridemic subjects. Bioinformatics analyses and a luciferase reporter assay showed that DNA methyltransferase 1 (DNMT1) was a target gene of miR-377. Moreover, miR-377 increased LPL binding to GPIHBP1 by directly targeting DNMT1 in human umbilical vein endothelial cells (HUVECs) and apolipoprotein E (ApoE)-knockout (KO) mice aorta endothelial cells (MAECs). In vivo, hematoxylin-eosin (H&E), Oil Red O and Masson’s trichrome staining showed that ApoE-KO mice treated with miR-377 developed less atherosclerotic plaques, accompanied by reduced plasma triglyceride levels.

Conclusions: It is concluded that miR-377 upregulates GPIHBP1 expression, increases the LPL binding to GPIHBP1, and reduces plasma triglyceride levels, likely through targeting DNMT1, inhibiting atherosclerosis in ApoE-KO mice.

Background:Late gadolinium enhancement (LGE) pattern is a powerful imaging biomarker for prognosis of cardiac amyloidosis. It is unknown if the query amyloid late enhancement (QALE) score in light-chain (AL) amyloidosis could provide increased prognostic value compared with LGE pattern.

Methods and Results:Seventy-eight consecutive patients with AL amyloidosis underwent contrast-enhanced cardiovascular magnetic resonance imaging. Patients with cardiac involvement were grouped by LGE pattern and analyzed using QALE score. Receiver operating characteristic curve was used to identify the optimal cut-off for QALE score in predicting all-cause mortality. Survival of these patients was analyzed with the Kaplan-Meier method and multivariate Cox regression. During a median follow-up of 34 months, 53 of 78 patients died. The optimal cut-off for QALE score to predict mortality at 12-month follow-up was 9.0. On multivariate Cox analysis, QALE score ≥9 (HR, 5.997; 95% CI: 2.665–13.497; P<0.001) and log N-terminal pro-brain natriuretic peptide (HR, 1.525; 95% CI: 1.112–2.092; P=0.009) were the only 2 independent predictors of all-cause mortality. On Kaplan-Meier analysis, patients with subendocardial LGE can be further risk stratified using QALE score ≥9.

Conclusions:The QALE scoring system provides powerful independent prognostic value in AL cardiac amyloidosis. QALE score ≥9 has added value to differentiate prognosis in AL amyloidosis patients with a subendocardial LGE pattern.

Background:Clinical profiles of acute heart failure (AHF) complicating severe aortic stenosis (AS) remain unclear.

Methods and Results:From a Japanese multicenter registry enrolling consecutive patients with severe AS, 3,813 patients were categorized into the 3 groups according to the symptom of heart failure (HF); No HF (n=2,210), chronic HF (CHF) (n=813) and AHF defined as hospitalized HF at enrolment (n=790). Median follow-up was 1,123 days with 93% follow-up rate at 2 years. Risk factors for developing AHF included age, female sex, lower body mass index, untreated coronary artery stenosis, anemia, history of HF, left ventricular ejection fraction <50%, presence of any combined valvular disease, peak aortic jet velocity ≥5 m/s and tricuspid regurgitation pressure gradient ≥40 mmHg, and negative risk factors included dyslipidemia, history of percutaneous coronary intervention and hemodialysis. Respective cumulative 5-year incidences of all-cause death and HF hospitalization in No HF, CHF and AHF groups were 37.1%, 41.8% and 61.8% (P<0.001) and 20.7%, 33.8% and 52.3% (P<0.001). Even in the initial aortic valve replacement (AVR) stratum, AHF was associated with excess 5-year mortality risk relative to No HF and CHF (adjusted hazard ratio [HR] 1.64; 95% confidence interval [CI]: 1.14–2.36, P=0.008; adjusted HR 1.47; 95% CI: 1.03–2.11, P=0.03, respectively).

Conclusions:AHF complicating severe AS was associated with an extremely dismal prognosis, which could not be fully resolved by AVR. Careful management to avoid the development of AHF is crucial.

Background:Although hepatitis C virus (HCV) is a known risk factor for cardiovascular disease, whether antiviral therapy (AVT) can reduce heart failure (HF) hospitalizations is unknown.

Methods and Results:In this population-based cohort study, we used data from the Taiwan National Health Insurance Research Database to evaluate the effect of interferon-based therapy (IBT) on cardiovascular events in patients with chronic HCV infection. Clinical outcomes evaluated included HF hospitalizations; a composite of acute myocardial infarction, ischemic stroke, and peripheral artery disease; all-cause death; and cardiovascular death. Of 83,229 eligible patients with chronic HCV infection, we compared 16,284 patients who received IBT with untreated subjects after propensity score matching. Patients who received IBT were less likely to be hospitalized for HF compared with untreated subjects (incidence density.ID, 0.9 vs. 1.5 events per 10³person-years; hazard ratio.HR, 0.58; 95% confidence interval.CI, 0.42–0.79; P=0.001). Compared with untreated subjects, the treated group had significantly lower risk of composite vascular events (ID, 3.7 vs. 5.0 events per 10³person-years; P<0.001), all-cause death (ID, 5.6 vs. 17.2 events per 10³person-years; P<0.001), and cardiovascular death (ID, 0.2 vs. 0.6 events per 10³person-years; P=0.001).

Conclusions:AVT for chronic HCV infection might offer protection against HF hospitalizations, critical vascular events, and cardiovascular death beyond known beneficial effects.

Background:Coronary spastic angina (CSA) is common among East Asians and tobacco smoking (TS) is an established risk factor for CSA. Aldehyde dehydrogenase 2 (ALDH2) plays a key role in removing reactive toxic aldehydes and a deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. We examined the interaction between TS andALDH2*2as a risk factor for CSA to better understand the disease pathogenesis.

Methods and Results:The study subjects comprised 410 patients (258 men, 152 women; mean age, 66.3±11.5) in whom intracoronary injection of acetylcholine was performed on suspicion of CSA.ALDH2genotyping was performed by direct application of the Taqman polymerase chain reaction system. Of the study subjects, 244 had CSA proven and 166 were non-CSA. The frequencies of male sex,ALDH2*2, alcohol flushing syndrome, TS, coronary organic stenosis, and plasma levels of uric acid were higher (P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, and P=0.015, respectively) and that of high-density lipoprotein cholesterol lower (P=0.002) in the CSA than non-CSA group. Multivariable logistic regression analysis revealed thatALDH2*2and TS were significant risk factors for CSA (P<0.001 and P=0.002, respectively).ALDH2*2exacerbated TS risk for CSA more than the multiplicative effects of each.

Conclusions:ALDH2*2synergistically exacerbates TS risk for CSA, probably through aldehydes.

Background:In the EMPA-REG OUTCOME^®trial, empagliflozin added to standard of care reduced the risk of 3-point major adverse cardiovascular (CV) events (3-point MACE: composite of CV death, non-fatal myocardial infarction, or non-fatal stroke) by 14%, CV death by 38%, hospitalization for heart failure by 35%, and all-cause mortality by 32% in patients with type 2 diabetes (T2DM) and established CV disease. We investigated the effects of empagliflozin in patients of Asian race.

Methods and Results:Patients were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo. Of 7,020 patients treated, 1,517 (21.6%) were of Asian race. The reduction in 3-point MACE in Asian patients was consistent with the overall population: 3-point MACE occurred in 79/1,006 patients (7.9%) in the pooled empagliflozin group vs. 58/511 patients (11.4%) in the placebo group (hazard ratio: 0.68 [95% confidence interval: 0.48–0.95], P-value for treatment by race interaction (Asian, White, Black/African-American): 0.0872). The effects of empagliflozin on the components of MACE, all-cause mortality, and heart failure outcomes in Asian patients were consistent with the overall population (P-values for interaction by race >0.05). The adverse event profile of empagliflozin in Asian patients was similar to the overall trial population.

Conclusions:Reductions in the risk of CV outcomes and mortality with empagliflozin in Asian patients with T2DM and established CV disease were consistent with the overall trial population.

Background:An atrial fibrillation (AF) risk score for a non-Western general population has not been established.

Methods and Results:A total of 6,898 participants (30–79 years old) initially free of AF have been prospectively followed for incident AF since 1989. AF was diagnosed when AF or atrial flutter was present on ECG at a biannual health examination; was indicated as a current illness; or was in the medical records during follow-up. Cox proportional hazard ratios were analyzed after adjusting for cardiovascular risk factors at baseline. During the 95,180 person-years of follow-up, 311 incident AF events occurred. We developed a scoring system for each risk factor as follows: 0/−5, 3/0, 7/5, and 9/9 points for men/women in their 30 s–40 s, 50 s, 60 s, and 70 s, respectively; 2 points for systolic hypertension, overweight, excessive drinking, or coronary artery disease; 1 point for current smoking; −1 point for moderate non-high-density lipoprotein-cholesterol; 4 points for arrhythmia; and 8, 6, and 2 points for subjects with cardiac murmur in their 30 s–40 s, 50 s, and 60 s, respectively (C-statistic 0.749; 95% confidence interval, 0.724−0.774). Individuals with score ≤2, 10–11, or ≥16 points had, respectively, ≤1%, 9%, and 27% observed probability of developing AF in 10 years.

Conclusions:We developed a 10-year risk score for incident AF using traditional risk factors that are easily obtained in routine outpatient clinics/health examinations without ECG.

Background:Approximately 10–20% of Kawasaki disease (KD) patients are resistant to intravenous immunoglobulin (IVIG) treatment. Further, these patients are at a particularly high risk of having coronary artery abnormalities. The mechanisms of IVIG resistance in KD have been analyzed using patient leukocytes, but not patient vascular endothelial cells (ECs). The present study clarifies the mechanisms of IVIG resistance in KD using an induced pluripotent stem cell (iPSC) disease model.

Methods and Results:Dermal fibroblasts or peripheral blood mononuclear cells from 2 IVIG-resistant and 2 IVIG-responsive KD patients were reprogrammed by the episomal vector-mediated transduction of 6 reprogramming factors. KD patient-derived iPSCs were differentiated into ECs (iPSC-ECs). The gene expression profiles of iPSC-ECs generated from IVIG-resistant and IVIG-responsive KD patients were compared by RNA-sequencing analyses. We found that the expression ofCXCL12was significantly upregulated in iPSC-ECs from IVIG-resistant KD patients. Additionally, Gene Set Enrichment Analysis (GSEA) revealed that gene sets involved in interleukin (IL)-6 signaling were also upregulated.

Conclusions:The first iPSC-based model for KD is reported here. Our mechanistic analyses suggest thatCXCL12, which plays a role in leukocyte transmigration, is a key molecule candidate for IVIG resistance and KD severity. They also indicate that an upregulation of IL-6-related genes may be involved in this pathogenesis.

Background:Hematuria is a common and important complication in atrial fibrillation (AF) patients on oral anticoagulation therapy (OAT). This study evaluated the clinical significance of hematuria and its relationship with genitourinary disease in AF patients receiving OAT.

Methods and Results:Among 20,456 consecutive AF patients who visited a tertiary hospital from January 2005 to April 2015, 5,833 had hematuria. Of these 5,833 patients, 3,798 were on OAT (OAT(+) group) and 2,035 were not (OAT(–) group). A total of 1,785 patients from each group were then matched on propensity score analysis. The prevalence of cancer and other diseases in the genitourinary tract was evaluated. While there was no difference in the prevalence of genitourinary stones or urinary tract infection, genitourinary cancer was significantly more common in the OAT(+) group than in the OAT(–) group (1.6% vs. 0.7%, P=0.011). Bladder cancer was the most common genitourinary malignancy, and it was significantly more common in the OAT(+) group (1.2% vs. 0.5%, P=0.019). Subjects on warfarin were more likely to have bladder cancers of lower pathologic grade (63.6% vs. 33.3%, P=0.124).

Conclusions:OAT was associated with a higher prevalence and early detection of genitourinary cancer in AF patients with hematuria. Meticulous evaluation of the cause of hematuria is necessary in AF patients with hematuria receiving OAT.

Background:The MitraClip^®system is a transcatheter-based therapeutic option for patients with chronic mitral regurgitation (MR) who are at high risk for surgery. A prospective, multicenter, single-arm study was initiated to confirm the transferability of this system to Japan.

Methods and Results:Patients with symptomatic chronic moderate-to-severe (3+) or severe (4+) functional or degenerative MR with a Society of Thoracic Surgery (STS) score ≥8%, or the presence of 1 predefined risk factor were enrolled. Patients with left ventricular (LV) ejection fraction (EF) <30% were excluded. MR severity and LV function were assessed by an independent echocardiography core lab. Primary outcome included major adverse events (MAE) at 30 days and acute procedural success (APS). A total of 30 patients (age: 80±7 years; STS score: 10.3%±6.6%) were treated with the MitraClip^®. At baseline, all patients had MR 3+/4+ with 53%/47% patients with degenerative/functional etiology with mean LVEF of 50.2±12.8%, and 37% of patients were NYHA class III/IV. APS was achieved in 86.7% with no occurrence of MAE. At 30 days, 86.7% of patients had MR ≤2+ and 96.7% were NYHA class I/II.

Conclusions:The MitraClip^®procedure resulted in clinically meaningful improvements in MR severity, function and quality of life measures, and low MAE rates. These early results suggest the transferability of this therapy to appropriately selected Japanese patients. (Trial Registration: clinicaltrials.gov Identifier NCT02520310.)