Background:The impact of chronic kidney disease (CKD) on long-term outcomes following acute myocardial infarction (AMI) in the era of modern primary PCI with optimal medical therapy is still in ...debate.Methods and Results:A total of 3,281 patients with AMI were enrolled in the J-MINUET registry, with primary PCI of 93.1% in STEMI. CKD stage on admission was classified into: no CKD (eGFR ≥60 mL/min/1.73 m2); moderate CKD (60>eGFR≥30 mL/min/1.73 m2); and severe CKD (eGFR <30 mL/min/1.73 m2). While the primary endpoint was all-cause mortality, the secondary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause death, cardiac failure, myocardial infarction (MI) and stroke. Of the 3,281 patients, 1,878 had no CKD, 1,073 had moderate CKD and 330 had severe CKD. Pre-person-days age- and sex-adjusted in-hospital mortality significantly increased from 0.014% in no CKD through 0.042% in moderate CKD to 0.084% in severe CKD (P<0.0001). Three-year mortality and MACE significantly deteriorated from 5.09% and 15.8% in no CKD through 16.3% and 38.2% in moderate CKD to 36.7% and 57.9% in severe CKD, respectively (P<0.0001). C-index significantly increased from the basic model of 0.815 (0.788–0.841) to 0.831 (0.806–0.857), as well as 0.731 (0.708–0.755) to 0.740 (0.717–0.764) when adding CKD stage to the basic model in predicting 3-year mortality (P=0.013; net reclassification improvement NRI 0.486, P<0.0001) and MACE (P=0.046; NRI 0.331, P<0.0001) respectively.Conclusions:CKD remains a useful predictor of in-hospital and 3-year mortality as well as MACE after AMI in the modern PCI and optimal medical therapy era.
Atrioventricular Block (AVB) is one of the common manifestations in cardiac sarcoidosis (CS). Although pacemaker implantation is generally recommended in patients with CS complicated by symptomatic ...AVB, some case reports have shown that they can be managed by steroid therapy without pacemaker implantation. The aim of this study was to evaluate the feasibility and effectiveness of steroid therapy without pacemaker implantation in patients with CS complicated by symptomatic AVB. We performed medical record review of consecutive ten CS patients who admitted Nippon Medical School Hospital for symptomatic second or third degree AVB between April 2015 and March 2021. Of the studied population, steroid therapy before pacemaker implantation was feasible in three patients with second degree AVB. Two of them showed subsequent recovery of atrioventricular conduction to 1:1, and they were managed by steroid therapy without pacemaker. The remaining one patient showed no improvement of atrioventricular conduction and required pacemaker implantation. Seven patients with third degree AVB required device implantation (pacemaker;
n
= 7, cardiac resynchronization therapy defibrillator;
n
= 1) before steroid therapy mainly because of hemodynamic instability. Steroid therapy without pacemaker implantation might be feasible, and possibly be effective in patients with CS presenting second degree AVB. However, the feasibility is limited in patients with third degree AVB.
Limited data exists on ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) managed by a well-organized cardiac care network in a metropolitan area. We analyzed the Tokyo CCU ...network database in 2009–2010. Of 4329 acute myocardial infarction (AMI) patients including STEMI (
n
= 3202) and NSTEMI (
n
= 1127), percutaneous coronary intervention (PCI) was performed in 88.8 % of STEMI and 70.4 % of NSTEMI patients. Mean onset-to-door and door-to-balloon times in STEMI patients were shorter than those in NSTEMI patients (167 vs 233 and 60 vs 145 min, respectively,
p
< 0.001). Coronary artery bypass graft surgery was performed in 4.2 % of STEMI and 11.4 % of NSTEMI patients. In-hospital mortality was significantly higher in STEMI patients than NSTEMI patients (7.7 vs 5.1 %,
p
< 0.007). Independent correlates of in-hospital mortality were advanced age, low blood pressure, and high Killip classification, statin-treated dyslipidemia and PCI within 24 h were favorable predictors for STEMI. High Killip classification, high heart rate, and hemodialysis were significant predictors of in-hospital mortality, whereas statin-treated dyslipidemia was the only favorable predictor for NSTEMI. In conclusion, patients with MI received PCI frequently (83.5 %) and promptly (door-to-balloon time; 66 min), and had favorable in-hospital prognosis (in-hospital mortality; 7.0 %). In addition to traditional predictors of in-hospital death, statin-treated dyslipidemia was a favorable predictor of in-hospital mortality for STEMI and NSTEMI patients, whereas hemodialysis was the strongest predictor for NSTEMI patients.
Background
Abnormal dynamics of QT intervals in response to sympathetic nervous system stimulation are used to diagnose long‐QT syndrome (LQTS). We hypothesized that parasympathetic stimulation with ...cold‐water face immersion following exercise would influence QT dynamics in patients with LQTS type 3 (LQT3).
Methods
Study participants (n = 42; mean age = 11.2 years) comprised 20 genotyped LQTS children and 22 healthy children. The LQTS group was divided into LQT3 (n = 12) and non‐LQT3 (n = 8) subgroups. Provocative testing for assessing QT dynamics comprised a treadmill exercise followed by cold‐water face immersion. The QT intervals were automatically measured at rest and during exercise, recovery, and cold‐water face immersion. The QT/heart rate (HR) relationship was visualized by plotting beat‐to‐beat confluence of the data.
Results
The QT/HR slopes, determined by linear regression analysis, were steeper in the LQTS group than in the control group during exercise and immersion tests: −2.16 ± 0.63 versus −1.21 ± 0.28, P < 0.0001, and −2.02 ± 0.76 vs −0.75 ± 0.24, P < 0.0001, respectively. The LQT3 patients had steeper slopes in the immersion test than did non‐LQT3 and control individuals: −2.42 ± 0.52 vs −1.40 ± 0.65, P < 0.0001, and vs −0.75 ± 0.24, P < 0.0001.
Conclusions
The QT dynamics of LQT3 patients differ from those of other LQTS subtypes during the post‐exercise cold‐water face immersion test in this study. Abnormal QT dynamics during the parasympathetic provocative test are concordant with the fact that cardiac events occur when HRs are lower or during sleep in LQT3 patients.
Adverse drug reactions (ADRs) during real-world osimertinib use were investigated in Japan.
Patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer treated ...with second-line or later oral osimertinib per the Japanese package insert (80 mg once daily) were included. Data were collected between 28 March 2016 and 31 August 2018.
The median observation period in the safety analysis population (n = 3578) was 343.0 days. ADRs (defined as adverse events whose causality to osimertinib could not be denied by the attending physicians or manufacturer) were reported in 58.1% (2079/3578) of patients. ADRs of interstitial lung disease events were reported in 6.8% (245/3578; Grade ≥ 3, 2.9% 104/3578) of patients, of whom 29 (11.8%) died (0.8% of patients overall). ADRs of QT interval prolonged, liver disorder and haematotoxicity were reported in 1.3% (45/3578; Grade ≥ 3, 0.1% 5/3578), 5.9% (212/3578; Grade ≥ 3, 1.0% 35/3578) and 11.4% (409/3578; Grade ≥ 3, 2.9% 104/3578) of patients, respectively. In the efficacy analysis population (n = 3563), 119 (3.3%) patients had complete responses, 2373 (66.6%) had partial responses and 598 (16.8%) had stable disease. The objective response rate was 69.9%; disease control rate was 86.7%; and median progression-free survival (PFS) was 12.3 months. At 6 and 12 months, PFS rates were 77.4% (95% confidence interval CI, 75.9-78.9) and 53.2% (95% CI, 51.3-55.1) and overall survival rates were 88.3% (95% CI, 87.2-89.4) and 75.4% (95% CI, 73.8-77.0), respectively.
These data support the currently established benefit-risk assessment of osimertinib in this patient population.
Abstract
Aims
The prognostic value of genetic variants for predicting lethal arrhythmic events (LAEs) in Brugada syndrome (BrS) remains controversial. We investigated whether the functional curation ...of SCN5A variations improves prognostic predictability.
Methods and results
Using a heterologous expression system and whole-cell patch clamping, we functionally characterized 22 variants of unknown significance (VUSs) among 55 SCN5A mutations previously curated using in silico prediction algorithms in the Japanese BrS registry (n = 415). According to the loss-of-function (LOF) properties, SCN5A mutation carriers (n = 60) were divided into two groups: LOF-SCN5A mutations and non-LOF SCN5A variations. Functionally proven LOF-SCN5A mutation carriers (n = 45) showed significantly severer electrocardiographic conduction abnormalities and worse prognosis associated with earlier manifestations of LAEs (7.9%/year) than in silico algorithm-predicted SCN5A carriers (5.1%/year) or all BrS probands (2.5%/year). Notably, non-LOF SCN5A variation carriers (n = 15) exhibited no LAEs during the follow-up period. Multivariate analysis demonstrated that only LOF-SCN5A mutations and a history of aborted cardiac arrest were significant predictors of LAEs. Gene-based association studies using whole-exome sequencing data on another independent SCN5A mutation-negative BrS cohort (n = 288) showed no significant enrichment of rare variants in 16 985 genes including 22 non-SCN5A BrS-associated genes as compared with controls (n = 372). Furthermore, rare variations of non-SCN5A BrS-associated genes did not affect LAE-free survival curves.
Conclusion
In vitro functional validation is key to classifying the pathogenicity of SCN5A VUSs and for risk stratification of genetic predictors of LAEs. Functionally proven LOF-SCN5A mutations are genetic burdens of sudden death in BrS, but evidence for other BrS-associated genes is elusive.
Graphical Abstract
Among currently recognized genetic and non-genetic risk factors for Brugada syndrome, functionally validated loss-of-function SCN5A mutations are associated with worse prognosis with earlier manifestation of lethal arrhythmic events (7.9%/year) than in silico algorithm-predicted SCN5A rare variations (5.1%/year) or Brugada-type ECG (2.5%/year).
Background: This All Nippon AF in the Elderly (ANAFIE) Registry sub-analysis evaluated the impact of polypharmacy on 2-year outcomes in a large, elderly (aged ≥75 years) Japanese population with ...non-valvular atrial fibrillation (NVAF).Methods and Results: The ANAFIE Registry was a multicenter, prospective, observational study with a 24-month follow-up period. Of 32,275 enrolled NVAF patients, 31,419 were grouped by the number of prescribed concomitant medications (other than oral anticoagulants OACs): 0–4 38.8%, 5–8 43.3%, and ≥9 17.9%). Patients receiving more concomitant medications were older, had poor renal function, and suffered more comorbidities than those receiving fewer concomitant medications. Several patient background factors, including diabetes mellitus, myocardial infarction, and chronic kidney disease, were significantly correlated with an increased number of concomitant medications. With increasing medications, OAC prescription rates decreased, but the warfarin prescription rate increased, and the cumulative incidence rates of stroke/systemic embolic events (SEE), major bleeding, gastrointestinal bleeding, fracture/falls, cardiovascular events, cardiovascular death, and all-cause death significantly increased (each, P<0.05). In multivariate analysis, increasing medications was independently associated with increases in these events, except for stroke/SEE. There were no significant interactions between the number of medications and anticoagulant treatment with direct OAC or warfarin concerning the incidence of these events.Conclusions: Polypharmacy was frequent among elderly patients with NVAF who were older with more comorbidities, and was independently associated with a higher incidence of extracranial events.
Diverse accelerated first-order methods have recently received considerable attention for solving large-scale convex optimization problems. This short paper shows that an exiting accelerated proximal ...gradient method for solving quasi-static incremental elastoplastic problems with the von Mises yield criterion can be naturally extended to the Tresca yield criterion.
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