Intravascular ultrasound appearance of scattered necrotic core as an index for deterioration of coronary flow during intervention in acute coronary syndrome

In acute coronary syndrome (ACS) patients with deterioration of coronary flow during percutaneous coronary intervention (PCI), a scattered necrotic core pattern (SNC) is observed by intravascular ultrasound virtual histology (VH-IVUS). The purpose of this study was to evaluate the impact of SNC on deterioration of coronary flow during PCI in ACS. A total of 38 ACS patients were imaged using VH-IVUS before PCI. In addition to conventional definitions of thin-cap fibroatheroma by VHIVUS (ID-TCFA), the SNC was defined as necrotic core foci with a maximum diameter of 50% plaque burden except in the ID-TCFA frame. Patients were divided into deterioration of coronary flow group (n = 15) and normal-reflow group (n = 23). The incidence of residual thrombus and plaque rupture, the external elastic membrane, plaque and fibrous volumes, the incidence of IDTCFA and the average number of SNC per frame was significantly greater in deterioration of coronary flow group than in normal-reflow group (all parameters P < 0.05). Multivariate analysis revealed that the average number of SNC per frame was independently associated with deterioration of coronary flow in ACS patients (odds ratio 1.18, P < 0.05). In conclusion, an increased number of SNC is associated with deterioration of coronary flow during PCI in ACS patients. © Springer 2011

Polymorphic ventricular tachycardia in a patient with hypertrophic cardiomyopathy and digitalis intoxication

SummaryWe report the case of a 74-year-old woman who presented with recurrent episodes of polymorphic ventricular tachycardia (PVT) with a normal QT interval due to digitalis intoxication (serum digoxin concentration, 5.0 ng/mL) and severe hyperkalemia (serum potassium level, 8.3 mEq/L). In addition, laboratory data showed elevated levels of blood urea nitrogen (54 mg/dL) and serum creatinine (1.57 mg/dL), suggesting dehydration. She had been treated with a combination of digoxin and eplerenone for atrial fibrillation and heart failure. The PVT resolved after treatment for hyperkalemia. Cardiac magnetic resonance imaging and left ventriculography showed left ventricular hypertrophy predominantly in the apex, suggesting apical hypertrophic cardiomyopathy (HCM). We presume that the presence of HCM was related to the occurrence of PVT in this patient with digitalis intoxication and hyperkalemia.<Learning objective: PVT with a normal QT interval caused by digitalis intoxication with hyperkalemia was observed in a patient with HCM treated with digoxin and eplerenone for atrial fibrillation and heart failure. The presence of HCM may be related to the occurrence of PVT. Combination therapy with digoxin and aldosterone receptor antagonist may predispose severe hyperkalemia, and monitoring of serum digitalis concentration and potassium level should be done strictly.

フィンランドにおける文芸振興政策と公共図書館 : 作家と図書館のための公的支援システムに焦点を当てて

本研究はフィンランドの作家と図書館のための公的支援システムに焦点を当てて，公共図書館と関連づけられた（1）図書館助成金制度（2）貸与補償制度（著作権補償制度）（3）資料購入・購読補助制度を，フィンランド文化政策全体を射程に入れて検討した。分析の結果，これらの助成制度の意義として，創作者側の文化創造を保障することで文芸の幅と厚みを担保し受取側の多様な文化へのアクセスを保障する基盤を創出していること，少数話者言語であるフィンランド語の文芸を活性化し保護する役割を担っていることの2点を導出した

Diagnostic Value of DCE-MRI for Differentiating Malignant Adnexal Masses Compared with Contrast-enhanced-T1WI

Purpose: To compare the diagnostic performance of dynamic contrast-enhanced-MR (DCE-MR) and delayed contrast-enhanced (CE)-MRI added to unenhanced MRI, including diffusion weighted image (DWI) for differentiating malignant adnexal tumors, conducting a retrospective blinded image interpretation study. Methods: Data of 80 patients suspected of having adnexal tumors by ultrasonography between April 2008 and August 2018 were used for the study. All patients had undergone preoperative MRI and surgical resection at our institution. Four radiologists (two specialized in gynecological radiology and two non-specialized) were enrolled for blinded review of the MR images. A 3-point scale was used: 0 = benign, 1 = indeterminate, and 2 = malignant. Three imaging sets were reviewed: Set A, unenhanced MRI including DWI; Set B, Set A and delayed CE-T1WI; and Set C, Set A and DCE-MRI. Imaging criteria for benign and malignant tumors were given in earlier reports. The diagnostic performance of the three imaging sets of the four readers was calculated. Their areas under the curve (AUCs) were compared using the DeLong method. Results: Accuracies of Set B were 81%–88%. Those of Set C were 81%–85%. The AUCs of Set B were 0.83 and 0.89. Those of Set C were 0.81–0.86. For two readers, Set A showed lower accuracy and AUC than Set B/Set C (less than 0.80), although those were equivalent in other readers. No significant difference in AUCs was found among the three sequence sets. Intrareader agreement was moderate to almost perfect in Sets A and B, and substantial to almost perfect in Set C. Conclusion: DCE-MR showed no superiority for differentiating malignant adnexal tumors from benign tumors compared to delayed CE-T1WI with conventional MR and DWI

The Hearing Outcomes of Cochlear Implantation in Waardenburg Syndrome

Objectives. This study aimed to determine the feasibility of cochlear implantation for sensorineural hearing loss in patients with Waardenburg syndrome. Method. A retrospective chart review was performed on patients who underwent cochlear implantation at the University of Tokyo Hospital. Clinical classification, genetic mutation, clinical course, preoperative hearing threshold, highresolution computed tomography of the temporal bone, and postoperative hearing outcome were assessed. Result. Five children with Waardenburg syndrome underwent cochlear implantation. The average age at implantation was 2 years 11 months (ranging from 1 year 9 months to 6 years 3 months). Four patients had congenital profound hearing loss and one patient had progressive hearing loss. Two patients had an inner ear malformation of cochlear incomplete partition type 2. No surgical complication or difficulty was seen in any patient. All patients showed good hearing outcome postoperatively. Conclusion. Cochlear implantation could be a good treatment option for Waardenburg syndrome

Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases

Aims The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines as well as evaluating the usefulness of functional studies for determining them. Methods and Results We performed WES of 23 probands diagnosed with early-onset (&amp;lt;65 years) CCSD and analyzed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. We focused on rare variants (minor allele frequency &amp;lt; 0.1%) that were absent from population databases. Five probands had protein truncating variants in EMD and LMNA which were classified as “pathogenic” by 2015 ACMG standards and guidelines. To evaluate the functional changes brought about by these variants, we generated a knock-out zebrafish with CRISPR-mediated insertions or deletions of the EMD or LMNA homologs in zebrafish. The mean heart rate and conduction velocities in the CRISPR/Cas9-injected embryos and F2 generation embryos with homozygous deletions were significantly decreased. Twenty-one variants of uncertain significance were identified in 11 probands. Cellular electrophysiological study and in vivo zebrafish cardiac assay showed that 2 variants in KCNH2 and SCN5A, 4 variants in SCN10A, and 1 variant in MYH6 damaged each gene, which resulted in the change of the clinical significance of them from “Uncertain significance” to “Likely pathogenic” in 6 probands. Conclusions Of 23 CCSD probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%). Functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants in patients with CCSD. SCN10A may be one of the major genes responsible for CCSD. Translational Perspective Whole-exome sequencing (WES) may be helpful in determining the causes of cardiac conduction system disease (CCSD), however, the identification of pathogenic variants remains a challenge. We performed WES of 23 probands diagnosed with early-onset CCSD, and identified 12 pathogenic or likely pathogenic variants in 11 of these probands (48%) according to the 2015 ACMG standards and guidelines. In this context, functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants, and SCN10A may be one of the major development factors in CCSD

Assessment of Coronary atherosclerosis in patients with familial hypercholesterolemia by coronary computed tomography angiography

The aims of this study were (1) to determine whether the accumulation of coronary plaque burden assessed with coronary computed tomography angiography (CCTA) can predict future events and (2) to estimate the onset and progression of coronary atherosclerosis in patients with familial hypercholesterolemia (FH). Consecutive 101 Japanese patients with heterozygous FH (men= 52, mean age 56 ± 16years, mean low-density lipoprotein cholesterol 264 ± 58mg/dl) who underwent 64-detector row CCTA without known coronary artery disease were retrospectively evaluated by assigning a score (0 to 5) to each of 17 coronary artery segments according to the Society of Cardiovascular Computed Tomography guidelines. Those scores were summed and subsequently natural log transformed. The periods to major adverse cardiac events (MACE) were estimated using multivariable Cox proportional hazards models. During the follow-up period (median 941days), 21 MACE had occurred. Receiver operating characteristic curve analyses identified a plaque burden score of 3.35 (raw score 28.5) as the optimal cutoff for predicting a worse prognosis. Multivariate Coxregression analysis identified the presence of a plaque score ≥3.35 as a significant independent predictor of MACE (hazard ratio= 3.65; 95% confidence interval 1.32 to 25.84, p<0.05). The regression equations were Y= 0.68. X- 15.6 (r= 0.54, p <0.05) in male and Y= 0.74. X- 24.8 (r= 0.69, p <0.05) in female patients with heterozygous FH. In conclusion, coronary plaque burden identified in a noninvasive, quantitative manner was significantly associated with future coronary events in Japanese patients with heterozygous FH and that coronary atherosclerosis may start to develop, on average, at age 23 and 34years in male and female patients with heterozygous FH, respectively

Impact of Distal Protection with Filter-Type Device on Long-term Outcome after Percutaneous Coronary Intervention for Acute Myocardial Infarction: Clinical Results with Filtrap®.

Aim: Although distal embolization during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) deteriorates cardiac function, whether distal protection (DP) can improve prognosis is still controversial. We investigated whether a filter-type DP device, Filtrap®, could improve long-term outcomes after PCI for AMI. Method: We studied 164 patients (130 men, mean age: 65.7 years) who underwent PCI. Patients were divided into two groups based on the use of Filtrap®. The occurrence of congestive heart failure (CHF) and major adverse cardiac events (MACE) defined as cardiac death, recurrent AMI, and target vessel revascularization were compared. Result: Between DP (n=53, 41 men, mean age: 65.5 years) and non-DP (n=111, 89 men, mean age: 65.8 years) groups, although there was significantly greater plaque area in the DP group than in the non-DP group, there were no significant differences in coronary reperfusion flow after PCI. Interestingly, patients with CHF in the non-DP group exhibited a higher CK level than those in the DP group. During a 2-year follow-up period, cumulative CHF was significantly lower in the DP group than in the non-DP group (log-rank p=0.018), and there was no significant difference in the MACE rate (log-rank p=0.238). The use of DP device could not predict MACE, but could predict CHF by multivariate analysis (odds ratio=0.099, 95% CI: 0.02–0.42, p=0.005). Conclusion: These results demonstrate that favorable clinical outcomes could be achieved by the filter-type DP device in AMI, particularly in patients with CHF.出版者照会後に全文公

Prediction of Post-Discharge Bleeding in Elderly Patients with Acute Coronary Syndromes: Insights from the BleeMACS Registry

Background A poor ability of recommended risk scores for predicting in-hospital bleeding has been reported in elderly patients with acute coronary syndromes (ACS). No study assessed the prediction of post-discharge bleeding in the elderly. The new BleeMACS score (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome), was designed to predict post-discharge bleeding in ACS patients. We aimed to assess the predictive ability of the BleeMACS score in elderly patients. Methods We assessed the incidence and characteristics of severe bleeding after discharge in ACS patients aged ≥ 75 years. Bleeding was defined as any intracranial bleeding or bleeding leading to hospitalization and/or red blood transfusion, occurring within the first year after discharge. We assessed the predictive ability of the BleeMACS score according to age by Fine-Gray proportional hazards regression analysis, calculating receiver-operating characteristic (ROC) curves and the area under the ROC curves (AUC). Results The BleeMACS registry included 15,401 patients of whom 3,376/15,401 (21.9%) were aged ≥ 75 years. Elderly patients were more commonly treated with clopidogrel and less often treated with ticagrelor or prasugrel. Of 3,376 elderly patients, 190 (5.6%) experienced post-discharge bleeding. The incidence of bleeding was moderately higher in elderly patients (hazard ratio [HR], 2.31, 95% confidence interval [CI], 1.92-2.77). The predictive ability of the BleeMACS score was moderately lower in elderly patients (AUC, 0.652 vs. 0.691, p = 0.001). Conclusion Elderly patients with ACS had a significantly higher incidence of post-discharge bleeding. Despite a lower predictive ability in older patients, the BleeMACS score exhibited an acceptable performance in these patients