Background: The prospective observational Nippon Storm Study aggregated clinical data from Japanese patients receiving implantable cardioverter-defibrillator (ICD) therapy. This study investigated ...the usefulness of prophylactic ICD therapy in patients with non-ischemic heart failure (NIHF) enrolled in the study.Methods and Results: We analyzed 540 NIHF patients with systolic dysfunction (left ventricular ejection fraction <50%). Propensity score matching was used to select patient subgroups for comparison; 126 patients were analyzed in each of the primary (PP) and secondary (SP) prophylaxis groups. The incidence of appropriate ICD therapy during follow-up in the PP and SP groups was 21.4% and 31.7%, respectively (P=0.044). The incidence of electrical storm (ES) was higher in SP than PP patients (P=0.024). Cox proportional hazard analysis revealed that increased serum creatinine in SP patients (hazard ratio HR 1.18; 95% confidence interval CI 1.02–1.33; P=0.013) and anemia in PP patients (HR 0.92; 95% CI 0.86–0.98; P=0.008) increased the likelihood of appropriate ICD therapy, whereas long-lasting atrial fibrillation in PP patients (HR, 0.64 95% CI, 0.45–0.91, P=0.013) decreased that likelihood.Conclusions: In propensity score-matched Japanese NIHF patients, the incidence of appropriate ICD therapy and ES was significantly higher in SP than PP patients. Impaired renal function in SP patients and anemia in PP patients increased the likelihood of appropriate ICD therapy, whereas long-lasting atrial fibrillation reduced that likelihood in PP patients.
Background: In 2016, the DANISH study reported negative results regarding the efficacy of implantable cardioverter-defibrillators (ICDs) in patients with non-ischemic cardiomyopathy (NICM) and ...reduced left ventricular ejection fraction (LVEF). In this study we determined the efficacy of using ICDs for primary prophylaxis in patients with NICM.Methods and Results: We selected 1,274 patients with underlying cardiac disease who were enrolled in the Nippon Storm Study. We analyzed the data of 451 patients with LVEF ≤35% due to NICM or ischemic cardiomyopathy (ICM) who underwent ICD implantation for primary prophylaxis (men, 78%; age, 65±12 years; LVEF, 25±6.4%; cardiac resynchronization therapy, 73%; ICM, 33%). After propensity score matching, we compared the baseline covariates between groups: NICM (132 patients) and ICM (132 patients). The 2-year appropriate ICD therapy risks were 27.7% and 12.2% in the NICM and ICM groups, respectively (hazard ratio, 0.390 95% confidence interval, 0.218–0.701; P=0.002).Conclusions: This subanalysis of propensity score-matched patients from the Nippon Storm Study revealed that the risk of appropriate ICD therapy was significantly higher in patients with NICM than in those with ICM.
Background: Optimal periprocedural oral anticoagulant (OAC) therapy before catheter ablation (CA) for atrial fibrillation (AF) and the safety profile of OAC discontinuation during the remote period ...(from 31 days and up to 1 year after CA) have not been well defined.Methods and Results: The RYOUMA registry is a prospective multicenter observational study of Japanese patients who underwent CA for AF in 2017–2018. Of the 3,072 patients, 82.3% received minimally interrupted direct-acting OACs (DOACs) and 10.2% received uninterrupted DOACs. Both uninterrupted and minimally interrupted DOACs were associated with an extremely low thromboembolic event rate. Female, long-standing persistent AF, low creatinine clearance, hepatic disorder, and high intraprocedural heparin dose were independent factors associated with periprocedural major bleeding. At 1 year after CA, DOAC was continued in 55.9% of patients and warfarin in 56.4%. The incidence of thromboembolic and major bleeding events for 1 year was 0.3% and 1.2%, respectively. Age ≥73 years, dementia, and AF recurrence were independently associated with major bleeding events. Univariate analyses revealed that warfarin continuation and off-label overdose of DOACs were risk factors for major bleeding after CA.Conclusions: High intraprocedural dose of heparin was associated with periprocedural major bleeding events. At 1 year after CA, over half of the patients had continued OAC therapy. Thromboembolic events were extremely low; however, major bleeding occurred in 1.2%. Age ≥73 years, dementia, and AF recurrence were independently associated with major bleeding after CA.
MicroRNAs are associated with pivotal post-transcriptional gene regulation in bone formation. Human differentiated embryonic chondrocyte expressed gene 1 (Dec1) is also involved in regulating ...osteoblastogenesis. In the present study, we aimed to investigate the distinctive role of miR-21–5p and Dec1 in osteoblast function and to determine their biological functions. MC3T3-E1 pre-osteoblastic cells were used for in vitro analyses. miR-21–5p knockout (KO) mice, Dec1KO mice and age-matched wild-type (WT) mice were used to characterize the influence of miR-21–5p and Dec1 deficiencies on bone formation. Morphological analyses micro-computed tomography (micro-CT) were performed, and measurements were collected to validate miR-21-5pKO mice. Histopathological changes in mouse femur tissues were assessed by H-E staining, Azan staining, Masson's Trichrome staining, and Toluidine Blue staining. Quantitative real-time RT-PCR, western blotting and immunohistochemical staining were used to characterize the expression levels of Alkaline Phosphatase, Runx2, Osterix, Osteopontin, Dec1 and miR-21–5p. Bioinformatics analyses and dual-luciferase reporter assays were performed to confirm Dec1 as a target of miR-21–5p. Dec1 expression was gradually increased from day 7 of osteoblast induction, while miR-21–5p showed a peak at day 21. In non-induced osteoblasts, a mechanistically gain-of-function transfection study with a miR-21–5p mimic enhanced Runx2 and Osterix expression but suppressed Dec1. miR-21-5pKO mice had reduced bone growth. Dec1-deficient mice showed advanced bone formation at the age of 12 weeks compared to WT mice. The Dec1 deficiency upregulated Runx2 and Osterix expression in Dec1KO mouse femurs. Those changes, however, were reversed in miR-21-5pKO mouse femurs compared to WT mouse femurs. Dual-luciferase reporter assays showed that Dec1 is a possible downstream target of miR-21–5p. These findings showed that the reduced osteogenic potential due to a miR-21–5p deficiency is achieved by enhanced Dec1 expression and that the miR-21–5p/Dec1 axis is involved in regulating osteoblast function.
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•miR-21–5p induced osteoblast differentiation.•Dec1 inhibited osteoblast differentiation via downregulating Runx2 and Osx.•miR-21–5p antagonized Dec1 expression by binding to the 3′UTR region.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Prevention of sudden cardiac death (SCD) has become an important issue in today’s cardiovascular field, together with various developments in secondary prevention of basic cardiac diseases. The ...importance of the implantable cardioverter defibrillator (ICD) is now widely accepted because it has exhibited significant improvement in patients’ prognoses in ischemic and non-ischemic cardiovascular diseases. However, there is an unignorable gap between the ICD indication in the guidelines and real-world high-risk patients for SCD, especially in the acute recovery phase of cardiac injury. Although various studies have demonstrated a clinical benefit of defibrillation devices, the studies of immediate ICD use in the acute recovery phase have failed to exhibit a benefit in patients from the point of the view of a decrease in total deaths. To bridge this gap, the wearable cardioverter defibrillator (WCD) provides a safer observation period in the acute phase and eliminates inappropriate overuse of ICD in the subacute phase. Here, we discuss the usefulness of the WCD and current understanding of its indications based on various clinical data. In conclusion, WCD is a feasible bridge to therapy and/or safe observation for patients at high risk of SCD, especially in the acute recovery phase of cardiac diseases.
A 42-year-old man exhibiting hypoxia was diagnosed with coronavirus disease 2019. He had medical histories of type 2 diabetes, hyperlipidemia, hyperuricemia, and gout attack. He received favipiravir ...for compassionate use for 14 days. Subsequently, he showed increased uric acid levels and developed acute gouty arthritis. Favipiravir may induce not only hyperuricemia but also acute gouty arthritis. It should therefore be used with caution in patients with a history of gout and those with hyperuricemia, especially when used at a higher dose and for a longer duration than is typical.
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