Aim:Severe gastrointestinal bleeding sometimes occurs in patients with aortic stenosis (AS), known as Heyde's syndrome. This syndrome is thought to be caused by acquired von Willebrand syndrome and is characterized by reduced large von Willebrand factor (vWF) multimers. However, the relationship between the severity of AS and loss of large vWF multimers is unclear. Methods: We examined 31 consecutive patients with severe AS. Quantitative evaluation for loss of large vWF multimers was performed using the conventional large vWF ratio and novel large vWF multimer index. This novel index was defined as the ratio of large multimers of patients to those of controls. Results: Loss of large vWF multimers, defined as the large vWF multimer index 80%, was detected in 21 patients (67.7%). The large vWF multimer ratio and the large vWF multimer index were inversely correlated with the peak aortic gradient (R 0.58, p 0.0007, and R 0.64, p 0.0001, respectively). Anemia defined as hemoglobin 9.0 g/dl was observed in 12 patients (38.7%), who were regarded as Heyde's syndrome. Aortic valve replacement was performed in 7 of these patients, resulting in the improvement of anemia in all patients from a hemoglobin concentration of 7.5 1.0 g/dl preoperatively to 12.4 1.3 g/dl postoperatively (p 0.0001). Conclusions: Acquired von Willebrand syndrome may be a differential diagnosis in patients with AS with anemia. The prevalence of AS-associated acquired von Willebrand syndrome is higher than anticipated.

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a b s t r a c tBackground: Activated partial thromboplastin time (aPTT) is recommended for monitoring anticoagulant activity in dabigatran-treated patients; however, there are limited data in Japanese patients. To clarify the relationship between plasma dabigatran concentration and aPTT, we analyzed plasma dabigatran concentration and aPTT at various time points following administration of oral dabigatran in a Japanese hospital. Methods: We enrolled 149 patients (316 blood samples) with non-valvular atrial fibrillation (NVAF) who were taking dabigatran. Patients had a mean age of 66.67 10.0 years (range: 35-84) and 66% were men. Plasma dabigatran concentrations and aPTT were measured using the Hemoclot s direct thrombin inhibitor assay and Thrombocheck aPTT-SLA s , respectively. Samples were classified into eight groups according to elapsed times in hours since oral administration of dabigatran.Results: Significantly higher dabigatran concentrations were observed in samples obtained from patients with low creatinine clearance (CLCr) (CLCro 50 mL/min). Dabigatran concentrations and aPTT were highest in the 4-h post-administration range. Additionally, there was a significant correlation between plasma dabigatran concentrations and aPTT (y¼ 0.063xþ32.596, r 2 ¼ 0.648, po 0.001). However, when plasma dabigatran concentrations were 200 ng/mL or higher, the correlation was lower (y¼ 0.040xþ38.034 and r 2 ¼0.180); these results were evaluated by a quadratic curve, resulting in an increased correlation (r 2 ¼0.668).Conclusions: There was a significant correlation between plasma dabigatran concentrations and aPTT. Additionally, in daily clinical practice in Japan, plasma dabigatran concentrations and aPTT reached a peak in the 4-h post administration range. Considering the pharmacokinetics of dabigatran, aPTT can be used as an index for risk screening for excess dabigatran concentrations in Japanese patients with NVAF.

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Mutations in SCN5A have been reported to cause several types of hereditary arrhythmias (overlap syndrome). We herein report two patients with the overlapping phenotypes of juvenile sick sinus syndrome (SSS) and Brugada syndrome (BrS). The proband was a man who was in his twenties and had been diagnosed with both SSS and ventricular tachycardia (VT). A pilsicainide challenge test revealed a coved type ST segment elevation. His teenage brother also suffered from SSS, but no VT had been documented. A pilsicainide challenge failed to produce a Brugada-type ST elevation, but there was a marked prolongation of the His-ventricle interval. Their electrocardiograms at rest did not display any Brugada-type ST elevations. We identified a novel SCN5A (F1775Lfs*15) mutation in both patients, even though there was a phenotype discrepancy.