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.)

Background:We explored the usefulness of myocardial strain analysis on cardiac magnetic resonance imaging (CMR) scans for the identification of cardiac amyloidosis.

Methods and Results:The 61 patients with systemic amyloidosis underwent 3.0-T CMR, including CMR tagging and late-gadolinium enhanced (LGE) imaging. The circumferential strain (CS) of LGE-positive and LGE-negative patients was measured on midventricular short-axis images and compared. Logistic regression modeling of CMR parameters was performed to detect patients with LGE-positive cardiac amyloidosis. Of the 61 patients with systemic amyloidosis 48 were LGE-positive and 13 were LGE-negative. The peak CS was significantly lower in the LGE-positive than in the LGE-negative patients (−9.5±2.3 vs. −13.3±1.4%, P<0.01). The variability in the peak CS time was significantly greater in the LGE-positive than in the LGE-negative patients (46.1±24.5 vs. 21.2±20.1 ms, P<0.01). The peak CS significantly correlated with clinical biomarkers. The sensitivity, specificity, and accuracy of the diagnostic model using CS parameters for the identification of LGE-positive amyloidosis were 93.8%, 76.9%, and 90.2%, respectively.

Conclusions:Myocardial strain analysis by CMR helped detect LGE-positive amyloidosis without the need for contrast medium. The peak CS and variability in the peak CS time may correlate with the severity of cardiac amyloid deposition and may be more sensitive than LGE imaging for the detection of early cardiac disease in patients with amyloidosis.

Background:Pressure overload induces cardiac hypertrophy, which often ends in heart failure. Afadin is an adaptor protein that is ubiquitously expressed and, in the heart, it localizes at intercalated disks. The current study aimed to examine the afadin-mediated cardiac phenotype in mice exposed to different types of pressure overload: transverse aortic constriction (TAC) burden and angiotensin II (Ang II) stimulation.

Methods and Results:Conditional knockout mice with selective deletion of afadin (afadin cKO) in cardiomyocytes were generated. TAC-operated and Ang II-infused mice at 4 weeks had a similar degree of pressure overload and cardiac hypertrophy in the heart. In afadin cKO mice, TAC operation caused progressive left ventricular dysfunction and heart failure, while Ang II infusion did not deteriorate cardiac function. Furthermore, TAC operation produced more fibrosis and apoptosis in the heart than Ang II infusion, and the expression of growth differentiation factor 15, which can promote apoptosis, in the afadin cKO heart was higher in TAC-operated mice than Ang II-infused ones.

Conclusions:In the 2 pressure overload models, myocardial afadin is involved in mechanical stress-induced, but not pharmacological Ang II-related, compensated cardiac hypertrophy.

Background:Predicting tachycardia-induced cardiomyopathy (TIC) in patients presenting with left ventricular (LV) dysfunction and tachyarrhythmias remains challenging. We assessed the diagnostic value of early right ventricular (RV) dysfunction to predict TIC using cardiac magnetic resonance (CMR) imaging.

Methods and Results:A total of 102 consecutive patients with newly diagnosed LV dysfunction and atrial tachyarrhythmias were examined. Patients whose LV ejection fraction (EF) improved to ≥50% during a 1-year follow-up were diagnosed with TIC, and with dilated cardiomyopathy (DCM) in those whose did not improve. CMR was performed at a median of 23 days after admission, and the TIC and DCM patients exhibited different distributions of EF and end-diastolic volume (EDV) between the LV and RV (both P<0.001, ANCOVA). TIC patients had significantly lower RVEF/LVEF ratio (1.01±0.23 vs. 1.36±0.31, P<0.001) and higher RVEDV/LVEDV ratio (0.96±0.21 vs. 0.73±0.19, P<0.001) compared with DCM patients, suggesting that RV systolic dysfunction and RV dilatation were observed in TIC. In the multivariate analysis, age, RVEF/LVEF ratio, and RVEDV/LVEDV ratio were significant predictors of TIC, and RVEF/LVEF ratio of <1.05 most highly predicted TIC with a sensitivity of 69.1% and specificity of 91.5% (area under the curve 0.860).

Conclusions:Among patients with newly diagnosed LV dysfunction and atrial tachyarrhythmias, age and coexistence of RV dysfunction was a strong predictor of TIC. (Circ J 2016; 80: 2141–2148)

Background:Depressive symptoms and memory impairment are prevalent in patients with chronic heart failure (CHF). Although the mechanisms remain to be elucidated, the hippocampus (an important brain area for emotion and memory) may be a possible neural substrate for these symptoms.

Methods and Results:We prospectively enrolled 40 Stage C patients, who had past or current CHF symptoms, and as controls 40 Stage B patients, who had structural heart disease but had never had CHF symptoms, in Brain Assessment and Investigation in Heart Failure Trial (B-HeFT) (UMIN000008584). As the primary index, we measured cerebral blood flow (CBF) in the 4 anterior-posterior segments of the hippocampus, using brain MRI analysis. Depressive symptoms, immediate memory (IM) and delayed memory (DM) were assessed using Geriatric Depression Scale (GDS), and Wechsler Memory Scale-revised (WMS-R), respectively. Hippocampus CBF in the most posterior segment was significantly lower in Stage C than in Stage B group (P=0.029 adjusted for Holm’s method). Multiple regression analysis identified significant association between hippocampus CBF and GDS or DM score in Stage C group (all P<0.05). GDS score was significantly higher, and IM and DM scores were lower in Stage C patients with hippocampus CBF below the median than those with hippocampus CBF above the median (all P<0.05).

Conclusions:Hippocampus abnormalities are associated with depressive symptoms and cognitive impairment in CHF patients. (Circ J 2016; 80: 1773–1780)

Background:Some disagreements surround the effects of calcium-channel blockers (CCBs) on the risk of dementia. The purpose of this study was to investigate the protective effects of CCBs on dementia among elderly hypertensive Koreans.

Methods and Results:We conducted a large population-based cohort study using the senior cohort database of the Korean National Health Insurance Service (2002–2013). Subjects were elderly hypertensive Koreans older than 60 years of age. A total of 18,423 patients (CCB user group: 13,692 patients; non-CCB antihypertensive user group: 4,731 patients) were statistically analyzed using the Cox proportional hazard regression model to estimate the adjusted hazard ratio (aHR) and confidence intervals (CIs) of dementia associated with CCB use. There were 2,881 cases (21.0%) of dementia in the CCB user group and 1,124 cases (23.8%) in the non-user group. CCB use significantly reduced the risk of total dementia (aHR 0.81, 95% CI 0.75–0.87, P<0.0001), Alzheimer’s dementia (aHR 0.80, 95% CI 0.72–0.88, P<0.0001), and vascular dementia (aHR 0.81, 95% CI 0.70–0.94, P=0.0067).

Conclusions:CCB use had a protective effect on the risk of dementia among elderly hypertensive Koreans. (Circ J 2016; 80: 2336–2342)