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Red cell distribution width (RDW) is known to be associated with anemia and mortality in cardiovascular diseases, while anemia itself is related to increased mortality. RDW may also be related to cytokine activation. We investigated the potential of RDW to predict anemia-adjusted mortality in patients with adult congenital heart disease (ACHD) and we evaluated the relationships among RDW, anemia, and interleukin-6 (IL-6).This was a single-center, retrospective cohort study. Blood RDW and IL-6 levels were measured in 144 patients with ACHD (median age [interquartile range (IQR)], 28 [22-36] years), 84% in New York Heart Association class I/II. During a mean 4.8-year follow-up, 21 (15%) patients died of cardiovascular causes. Elevated RDW (15.0%) correlated significantly with mortality risk in a univariate analysis (RDW hazard ratio [HR]: 1.570; 95% confidence interval [CI]: 1.208-2.040 per 1 standard deviation increase; P=0.001). Elevated RDW levels correlated significantly with increased anemia-adjusted mortality (adjusted RDW HR: 1.912; 95% CI: 1.369-2.670; P0.001). The high RDW group had significantly elevated serum IL-6 levels (RDW15%, median [IQR], 3.7 [0.9-13.9] pg/ml vs. RDW ≤15%, 1.4 [0.8-2.5 pg/ml]; P=0.001), as did patients with anemia (anemia, 1.9 [0.9-5.2] pg/ml vs. no anemia, 1.4 [0.8-2.5 pg/ml]; P=0.021).Elevation of RDW may be related with increased IL-6 and anemia-adjusted cardiovascular mortality in patients with ACHD.

BACKGROUND Although the survival rate for repaired Tetralogy of Fallot (TOF) is dramatically improving, anatomical and functional residua and sequelae followed by arrhythmias and sudden death are still challenging issues to be resolved. Reoperation can reduce the incidence of arrhythmias and sudden death, but there is no consensus on the indications of reoperation for patients with TOF, especially in Japan. METHODS AND RESULTS A cross-sectional questionnaire survey of reoperation indications in patients with TOF was performed through a Japanese multicenter study. The questionnaire, which focused on the number of repaired TOF patients aged >15 years old, reoperation indications and management, was sent to the institutions belonging to Japanese Society for Adult Congenital Heart Disease. In total, 41.5% (78/188) of the institutions replied. The total number of repaired TOF patients was 4,010, and sudden cardiac death was observed in 45.236/4,010 (5.9%) experienced reoperation. Pulmonary stenosis (32%) and pulmonary regurgitation (29%) were the most common reasons for reoperation. There were only 2 implantable cardioverter defibrillator or resynchronization therapy defibrillator implantations. The physiological/anatomical indications of reoperation differed among the hospitals. CONCLUSIONS Approximately 1.1% of patients suffered sudden death and 6% of repaired TOF patients had reoperation. The indications of reoperation, however, varied among the institutions. Therefore, detailed information for each case of sudden death or reoperation should be collected and analyzed in order to establish guidelines for reoperation.

Background: Mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene, the activin receptor-like kinase 1 (ALK1) gene, and SMAD8 gene have been reported in heritable pulmonary arterial hypertension (HPAH) and in idiopathic pulmonary arterial hypertension (IPAH). However, almost 30% of HPAH cases and 60–90% of IPAH cases have no mutations in those genes. This suggests that there remain unidentified genes associated with HPAH and IPAH. Methods and Results: This study screened for mutations in endoglin, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6, SMAD7, bone morphogenetic protein receptor type 1A (BMPR1A) and bone morphogenetic protein receptor type 1B (BMPR1B) genes in 43 IPAH patients who had no mutations in BMPR2, ALK1 and SMAD8. Two missense mutations (c.479 G>A S160N, c.1176 C>A F392L) in BMPR1B were each identified in 2 IPAH patients. Immunoblot analysis revealed that the BMPR1B F392L protein promoted SMAD8 phosphorylation. The response to BMP was analyzed using promoter-reporter activities. The transcriptional activation of the BMPR1B F392L protein with SMAD8 increased above that of wild-type BMPR1B with SMAD8, and those of BMPR1B S160N and F392L with SMAD8 and SMAD4 were each increased above those of the wild-type BMPR1B with SMAD8 and SMAD4. Conclusions: We identified 2 novel mutations in BMPR1B in 2 patients with IPAH. Our study suggests that BMPR1B mutations are associated with the pathogenesis of IPAH. (Circ J 2012; 76: 1501 – 1508)