小林 欣夫

Percutaneous coronary intervention has become a standard-of-care procedure in patients with acute and chronic coronary syndromes, in which coronary stent technology is commonly used. In this mini-review article, we summarize the characteristics of contemporary coronary drug-eluting and coated stents.

The management of acute decompensated heart failure often requires intensive care. However, the effects of early intensive care unit/coronary care unit admission on activities of daily living (ADL) in acute decompensated heart failure patients have not been precisely evaluated. Thus, we retrospectively assessed the association between early intensive care unit admission and post-discharge ADL performance in these patients. Acute decompensated heart failure patients (New York Heart Association I-III) admitted on emergency between April 1, 2014, and December 31, 2018, were selected from the Diagnosis Procedure Combination database and divided into intensive care unit/coronary care unit (ICU) and general ward (GW) groups according to the hospitalization type on admission day 1. The propensity score was calculated to create matched cohorts where admission style (intensive care unit/coronary care unit admission) was independent of measured baseline confounding factors, including ADL at admission. The primary outcome was ADL performance level at discharge (post-ADL) defined according to the Barthel index. Secondary outcomes included length of stay and total hospitalization cost (expense). Overall, 12231 patients were eligible, and propensity score matching created 2985 pairs. After matching, post-ADL was significantly higher in the ICU group than in the GW group [mean (standard deviation), GW vs. ICU: 71.5 (35.3) vs. 78.2 (31.2) points, P<0.001; mean difference: 6.7 (95% confidence interval, 5.1-8.4) points]. After matching, length of stay was significantly shorter and expenses were significantly higher in the ICU group than in the GW group. Stratified analysis showed that the patients with low ADL at admission (Barthel index score <60) were the most benefited from early intensive care unit/coronary care unit admission. Thus, early intensive care unit/coronary care unit admission was associated with improved post-ADL in patients with emergency acute decompensated heart failure admission.

Previous studies have shown that the sudden cardiac death (SCD) prediction model proposed by the 2014 European Society of Cardiology (ESC) guideline (5-Year Risk-SCD) was validated in European patients with hypertrophic cardiomyopathy (HCM). However, there are limited data on Asian patients with HCM. We assessed the validity of the estimated 5-Year Risk-SCD in Japanese HCM patients with an implantable cardioverter-defibrillator (ICD) using the2014 ESC guidelines. We retrospectively examined data of 492 consecutive Japanese patients with an ICD. Sixty-two Japanese HCM patients with an ICD were enrolled in this study, and 50 patients (81%) were followed up for ≥ 5 years. We analyzed the characteristics and outcomes of these 50 patients. We investigated the incidence of appropriate ICD therapy as categorized by the ESC guideline and compared the 5-Year Risk-SCD with the 5-year rate of appropriate shock therapies. Based on the 2012 Japanese Circulation Society guideline and the 2011guidelines of the American Heart Association and American College of Cardiology Foundation, 10 and 40 patients met classes I and IIa of the ICD recommendation, respectively. However, only 18 (36%) patients were classified into class I or IIa of the ESC guideline. Among 50 patients followed up for ≥ 5 years after ICD implantation, the incidences of appropriate ICD therapies for classes I, IIa, IIb, and III indications based on the 2014 ESC guideline were 50%, 38%, 17%, and 0%, respectively. Risk stratification for SCD using 5-Year Risk-SCD is valid in Japanese HCM patients with an ICD, and the 2014 ESC guideline might be useful for the indication of ICD implantation in Japan.

Coronary artery fistulas are abnormal vascular conduits, rarely related to atrioventricular conduction abnormalities. We report the case of a 52-year-old woman who presented with dyspnoea on exertion. Her ECG revealed advanced atrioventricular block and left bundle branch block. CT scans confirmed two fistulas, from the conus branch of right coronary artery and from the left anterior descending coronary artery, into the pulmonary artery. The patient underwent pacemaker implantation. To date, only nine patients with different degrees of heart blocks associated with coronary artery fistulas have been reported. Herein, we review and summarise previously reported cases of different degrees of heart blocks associated with coronary artery fistulas.

背景:肥大型心筋症(HCM)患者では心臓突然死のリスクが高く、植込み型除細動器(ICD)による治療が広く行われている。心尖部肥大型心筋症(Apical HCM)の予後を検討した報告は少ない。目的:Apical HCMとその他のHCM患者のICD植え込み症例において、予後に差があるかを調べることである。方法:当院のデータベースより2006年10月から2016年7月までにICD植え込み術を施行しているHCM症例を抽出した。Apical HCMとその他のHCM患者に分けて、患者背景、採血データ、診断時の左室駆出率、最大左室壁厚、ICDの適切作動率、心疾患による入院の有無、死亡等について解析を行い、比較した。結果:2006年10月〜2016年7月にICD植え込み術を施行したHCM患者は53例(平均年齢67±15歳、男性45例(85%)、一次予防46例(87%)、フォローアップ期間85±25ヵ月、診断時左室駆出率57±12%)であり、Apical HCMは13例、その他のHCMは40例であった。2群間で年齢や性別、左室駆出率など患者背景において、有意差は認めなかった。イベントについては、Apical HCM患者はICD適切作動を13症例中5例(38%)認め、40症例中4例(10%)であったその他のHCM患者より、ICD適切作動が有意に多かった。また、2群間で心不全入院や死亡率に有意差は認めなかった。結語:ICD植え込み術後のHCM症例において、Apical HCMは、その他のHCM症例と比較し、ICD適切作動が有意に多かった。しかし、心不全による入院や死亡については、Apical HCMとその他のHCMでは有意差を認めなかった。(著者抄録)

OBJECTIVES: We investigated the medical or mechanical therapy, and the present knowledge of Japanese cardiologists about aborted sudden cardiac death (ASCD) due to coronary spasm. METHODS: A questionnaire was developed regarding the number of cases of ASCD, implantable cardioverter-defibrillator (ICD), and medical therapy in ASCD patients due to coronary spasm. The questionnaire was sent to the Japanese general institutions at random in 204 cardiology hospitals. RESULTS: The completed surveys were returned from 34 hospitals, giving a response rate of 16.7%. All SCD during the 5 years was observed in 5726 patients. SCD possibly due to coronary spasm was found in 808 patients (14.0%) and ASCD due to coronary spasm was observed in 169 patients (20.9%). In 169 patients with ASCD due to coronary spasm, one or two coronary vasodilators was administered in two-thirds of patients [113 patients (66.9%)], while more than 3 coronary vasodilators were found in 56 patients (33.1%). ICD was implanted in 117 patients with ASCD due to coronary spasm among these periods including 35 cases with subcutaneous ICD. Majority of cause of ASCD was ventricular fibrillation, whereas pulseless electrical activity was observed in 18 patients and complete atrioventricular block was recognized in 7 patients. Mean coronary vasodilator number in ASCD patients with ICD was significantly lower than that in those without ICD (2.1 ± 0.9 vs. 2.6 ± 1.0, p < 0.001). Although 16 institutions thought that the spasm provocation tests under the medications had some clinical usefulness of suppressing the next fatal arrhythmias, spasm provocation tests under the medication were performed in just 4 institutions. CONCLUSIONS: In the real world, there was no fundamental strategy for patients with ASCD due to coronary spasm. Each institution has each strategy for these patients. Cardiologists should have the same strategy and the same knowledge about ASCD patients due to coronary spasm in the future.

We treated a man with co-incident Marfan-like connective tissue disease with morphologic left ventricular non-compaction (LVNC). He underwent valve-sparing aortic root replacement because of aortic root dilation at 43 years old. Pathological findings of the aorta revealed cystic medio-necrosis, consistent with Marfan syndrome. He developed congestive heart failure caused by LVNC at 47 years old. His daughter had scoliosis, and he had several physical characteristics suggestive of Marfan syndrome. We herein report a rare case of a patient who had Marfan-like connective disease with an LVNC appearance.

Some cancers are related to atherosclerotic diseases; therefore, these two types of disease may share some antibody biomarkers in common. To investigate this, a first screening of sera was performed from patients with esophageal squamous cell carcinoma (ESCC) or acute ischemic stroke (AIS) for serological identification of antigens using recombinant cDNA expression cloning (SEREX). The amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) method, which incorporates glutathione donor beads and anti-human IgG acceptor beads, was used to evaluate serum antibody levels. SEREX screening identified low-density lipoprotein receptor-related protein-associated protein 1 (LRPAP1) as a target antigen of serum IgG antibodies in the sera of patients with ESCC or AIS. Antigens, including recombinant glutathione S-transferase-fused LRPAP1 protein, were prepared to examine serum antibody levels. AlphaLISA revealed significantly higher antibody levels against the LRPAP1 protein in patients with solid cancers such as ESCC and colorectal carcinoma and some atherosclerosis-related diseases such as AIS and diabetes mellitus compared with healthy donors. Correlation analysis revealed that the elevated serum antibody levels against LRPAP1 were associated with smoking, a well-known risk factor for both cancer and atherosclerosis. Serum LRPAP1 antibody is therefore a common marker for the early diagnosis of some cancers and atherosclerotic diseases and may reflect diseases caused by habitual smoking.

植込み型除細動器(implantable cardioverter-defibrillator:ICD)は心室細動(ventricular fibrillation;VF)などの致死的不整脈に対する有効な治療法であるが、ICDによる不適切作動が生命予後の悪化につながるという報告がされている。不適切作動の原因として心房細動(atrial fibrillation;AF)が知られているが、AFの心拍数や持続時間を用いて、VF検出のための設定心拍数(VF検出ゾーン)の設定を考慮することに注目した報告はない。今回、ICD症例においてAFによる不適切作動のリスク因子について検討した。当院で遠隔モニタリングシステムを利用している403人を対象に、AFが記録された80人(19.8%)をAFによる不適切作動あり群となし群に分けて比較した。AFによる不適切作動あり群では、左房径が大きく、以前に12誘導心電図でAFが記録された症例やシングルチャンバーICDの症例が多かった。デバイスで記録されたAFの最大心拍数や平均心拍数、AF時間の割合は不適切作動あり群で高く、またデバイスにおけるVF検出レートとAFの最大心拍数との差であるminimum marginおよび平均心拍数との差であるaverage marginは、不適切作動あり群で小さかった。多変量解析を行うと、シングルチャンバーICDとaverage marginは、AFによる不適切作動の独立したリスク因子であった。さらに、average marginはカットオフ値を21bpmとすることで、リスク層別化が可能であった。AFによる不適切作動のリスク因子として、average marginは有用な指標であり、21bpm以下となる場合には積極的なAF治療を検討する必要がある。(著者抄録)

BACKGROUND: Autonomic nerve system and endothelial function play important roles in vasospastic angina. Elevated heart rate (HR), blood pressure (BP), and double product (DP) can increase endothelial-dependent coronary artery dilation and blood flow. However, the impact of HR, BP, and DP on occurrence and severity of VSA in the clinical setting is unclear. METHOD: A total of 170 patients undergoing intracoronary acetylcholine (ACh) provocation test during hospitalisation was included. Resting HR, BP, and DP were measured at least four times, and their variabilities were evaluated by standard deviations (SD) and coefficient of variations (CVs). Angiographic coronary artery vasospasm was defined as total or subtotal occlusion induced by ACh provocation. RESULTS: Mean±SD HR (65.7±9.1 vs 69.6±7.9 beats per minute; p=0.003), systolic BP (122.3±13.4 vs 127.7±14.6 mmHg; p=0.01), and DP (8,001±1,229 vs 8,903±1,495; p<0.001) were significantly lower in patients with a positive ACh test than the counterpart, whereas SD and CV of both HR and systolic BP were not significantly different between the two groups. Mean HR, BP, and DP progressively decreased with increase in the number of vessels with angiographic vasospasm. Multivariate analysis showed current smoking and lower DP as independent predictors of the greater number of vessels with provoked angiographic vasospasm. CONCLUSIONS: Resting HR, BP, and DP were lower in patients with vasospastic angina, especially in those with severe vasospasm.

In the original publication of the article, author group affiliation was published incorrectly. The correct affiliation for author group is given in this correction.

We report the case of a 70-year-old woman with hypertrophic obstructive cardiomyopathy, who was admitted because of severe heart failure and cardiogenic shock and mechanical support requiring extracorporeal membrane oxygenation. She recovered well by percutaneous transluminal septal myocardial ablation under the extracorporeal membrane oxygenation support and was discharged without complications. (Level of Difficulty: Advanced.).

PURPOSE: The classification using QRS morphology of V1 lead is a useful simple predictor of accessory pathway location (type A, R or Rs pattern; type B, rS pattern; type C, QS or Qr pattern), but often leads to misdiagnosis of accessory pathway location, especially in types B and C. The synthesized 18-lead electrocardiography (ECG) derived from standard 12-lead ECG can provide virtual waveforms of right-sided chest leads. This study aimed to evaluate the usefulness of the right-sided chest lead ECG for prediction of accessory pathway location. METHODS: This retrospective study included 44 patients in whom successful ablation of manifest Wolff-Parkinson-White (WPW) syndrome was performed. Synthesized ECG waveforms were automatically generated, and ECG data obtained before the procedure. RESULTS: There were 26, 4, and 14 patients with left, right, and septal accessory pathways, respectively. All left accessory pathway cases have type A in V1 and syn-V4R leads. Of the 4 right accessory pathway cases, 2 have type B in V1 and syn-V4R leads. Other 2 of 4 cases have type C. In V1 lead, 5 of 14 septal accessory pathway cases have type C, 7 of 14 cases have type B, and 2 of 14cases have type A. In syn-V4R lead, all 14 septal accessory pathway cases have type C. The QRS morphology of V1 and syn-V4 leads could predict the site of accessory pathway with overall accuracy of 79% and 95%, respectively. CONCLUSIONS: QRS morphology of syn-V4R lead may be useful for predicting accessory pathway location of manifest WPW syndrome.

AIMS: Takotsubo syndrome (TTS) is an acute heart failure syndrome, which shares many features with acute coronary syndrome (ACS). Although TTS was initially described with angiographically normal coronary arteries, smaller studies recently indicated a potential coexistence of coronary artery disease (CAD) in TTS patients. This study aimed to determine the coexistence, features, and prognostic role of CAD in a large cohort of patients with TTS. METHODS AND RESULTS: Coronary anatomy and CAD were studied in patients diagnosed with TTS. Inclusion criteria were compliance with the International Takotsubo Diagnostic Criteria for TTS, and availability of original coronary angiographies with ventriculography performed during the acute phase. Exclusion criteria were missing views, poor quality of angiography loops, and angiography without ventriculography. A total of 1016 TTS patients were studied. Of those, 23.0% had obstructive CAD, 41.2% had non-obstructive CAD, and 35.7% had angiographically normal coronary arteries. A total of 47 patients (4.6%) underwent percutaneous coronary intervention, and 3 patients had acute and 8 had chronic coronary artery occlusion concomitant with TTS, respectively. The presence of CAD was associated with increased incidence of shock, ventilation, and death from any cause. After adjusting for confounders, the presence of obstructive CAD was associated with mortality at 30 days. Takotsubo syndrome patients with obstructive CAD were at comparable risk for shock and death and nearly at twice the risk for ventilation compared to an age- and sex-matched ACS cohort. CONCLUSIONS: Coronary artery disease frequently coexists in TTS patients, presents with the whole spectrum of coronary pathology including acute coronary occlusion, and is associated with adverse outcome. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01947621.

Objective Forward-projected Model-based Iterative Reconstruction SoluTion (FIRST) is a novel reconstruction method. We investigated the improvement in the diagnostic performance for the detection of abnormal late enhancement (LE) in left ventricular myocardium (LVM) using a new-generation 320-slice computed tomography (CT) device with FIRST. Methods This is a retrospective study that included 100 adult patients who underwent cardiac CT including a late phase scan and magnetic resonance imaging (MRI) within 3 months. The first 50 consecutive patients (first-generation group) underwent first-generation 320-slice CT without FIRST, and the next 50 consecutive patients (second-generation group) underwent second-generation 320-slice CT with FIRST. We compared the diagnostic performance of the first- and second-generation 320-slice CT with FIRST with MRI as a reference standard to detect LE in LVM. Results In the patient-based analysis, the sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of detection of LE on CT were 79%, 90%, 92%, 76%, and 84%, respectively, in the first-generation group and 97%, 84%, 91%, 94%, and 92%, respectively, in the second-generation group. The sensitivity was significantly higher in the second-generation group than in the first-generation group (p=0.049). In the segment-based analysis, the sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of detection of LE on CT were 69%, 96%, 83%, 92%, and 90%, respectively, in the first-generation group and 87%, 94%, 84%, 95%, and 92%, respectively, in the second-generation group. The sensitivity and negative predictive value were significantly higher in the second-generation group than in the first-generation group (p<0.001 and p=0.016). The contrast-noise ratio was significantly higher in the second-generation group than in the first-generation group (5.6±1.7 vs. 2.8±1.1, p<0.001), and the radiation dose for the assessment of LE on CT was significantly higher in the first-generation group than in the second-generation group (4.7±2.7 mSv vs. 2.3±0.1 mSv, p<0.001). Conclusion The diagnostic performance for the detection of LE in LVM significantly improved with the use of second-generation 320-slice CT and FIRST.

BACKGROUND: Previous studies showed the relation of mental distress such as anxiety and depression to coronary vasoconstriction and myocardial ischemia. However, the mental health status of patients suspected to have vasospastic angina is unclear. METHODS: A total of 99 patients underwent intracoronary acetylcholine (ACh) provocation tests for the diagnosis of vasospastic angina and mental health assessment using the 12-item General Health Questionnaire (GHQ-12) and State-Trait Anxiety Inventory Form Y (STAI Y-2). Patients with binary GHQ-12 ≥ 4 were defined as having poor mental health. RESULTS: Median GHQ-12 and STAI Y-2 were 3 [1, 6] and 44 [36, 50]. Forty-one (41%) patients had binary GHQ-12 ≥ 4, and 48 (48%) had positive ACh provocation tests. The number of provoked vasospasms and rate of electrocardiographic change and chest pain during ACh tests were not significantly different between patients with and without GHQ-12 ≥ 4. The incidence of positive ACh provocation test was similar between the two groups (49% vs. 48%, p = 1.00). The multivariable analysis indicated that younger age, no history of percutaneous coronary intervention and no diabetes mellitus were factors associated with higher GHQ-12 and/or STAI Y-2 scores. CONCLUSIONS: More than 40% of patients who underwent ACh provocation tests had poor mental condition. No impact of mental distress on positive ACh tests was found in this study.

Background: Despite the growing knowledge regarding optimal treatments for critical limb ischemia (CLI), there are still a considerable number of patients who have to undergo major limb amputation. Intramuscular injection of autologous adipose-derived regenerative cells (ADRCs) in these patients has shown therapeutic potential in improving tissue ischemia, in both preclinical and initial pilot studies. Here, we present a clinical protocol for ADRCs use in a multicenter trial. Methods and Results: The TACT-ADRC multicenter trial is a prospective, interventional, single-arm, open-labeled study at 8 hospitals in Japan, investigating the safety and feasibility of intramuscular injections of ADRCs and testing the hypothesis that this treatment promotes neovascularization and improves major amputation-free survival rates in patients with CLI who have no other treatment option. 40 patients with CLI will be enrolled and followed up from November 2015 to November 2020. Freshly isolated autologous ADRCs will be injected into the target ischemic limbs. Survival rate, adverse events, major limb amputation, ulcer size, 6-min walking distance, numerical rating scale, ankle-brachial pressure index, skin perfusion pressure and digital subtraction angiography will be evaluated at baseline and during 6 months' follow-up. Conclusions: This trial will demonstrate whether implantation of autologous ADRCs is a safe and effective method for therapeutic angiogenesis, resulting in an improvement in major amputation-free survival rates in patients with CLI.

BACKGROUND: Leads are often considered the weakest link in implantable cardioverter-defibrillator (ICD) systems, and lead dysfunction is a major concern for ICD recipients. The aim of this study was to compare the lead performance from three different manufacturers. METHODS: We retrospectively reviewed consecutive patients who underwent ICD system implantation at Chiba University Hospital, Japan, between March 2008 and September 2017. The following leads were implanted in our center: Durata (St. Jude Medical, St. Paul, MN, USA, now Abbott) (n = 105), Linox and LinoxSmart (Biotronik, Berlin, Germany) (n = 66), and Sprint Quattro (Medtronic, Minneapolis, MN, USA) (n = 126). RESULTS: A total of 297 ICD leads were analyzed. Failure rates for Durata, Linox/LinoxSmart, and Sprint Quattro were 0.20%/patient year, 0.95%/patient year, and 1.84%/patient year, respectively, during a mean follow-up of 4.8, 6.4, and 3.0 years, respectively. The cumulative ICD lead survival probability was 98.9%, 100%, and 87.5%, after 5 years, respectively. The survival probability over the entire follow-up time as measured by the log-rank test was lower for Sprint Quattro leads than for either Durata (p = 0.011) or Linox/LinoxSmart (p = 0.028). The difference between Durata and Linox/LinoxSmart was not significant (p = 0.393). CONCLUSIONS: In this single-center retrospective study, the performance of Sprint Quattro was lower than the performance of Linox/LinoxSmart and Durata leads. Large-scale, multi-center studies or manufacturer-independent registries may be necessary to confirm or reject self-reported survival probabilities from manufacturers' product performance reports.

The aim of the present study was to identify novel antibody markers for the early diagnosis of atherosclerosis in order to improve the prognosis of patients at risk for acute ischemic stroke (AIS) and acute myocardial infarction (AMI). A first screening involved the serological identification of antigens by recombinant cDNA expression cloning and identified additional sex combs‑like 2 (ASXL2) as a target antigen recognized by serum IgG antibodies in the sera of patients with atherosclerosis. Antigens, including the recombinant glutathione S‑transferase‑fused ASXL2 protein and its synthetic peptide were then prepared to examine serum antibody levels. Amplified luminescence proximity homogeneous assay‑linked immunosorbent assay, which incorporates glutathione‑donor beads and anti‑human‑IgG‑acceptor beads, revealed significantly higher serum antibody levels against the ASXL2 protein and its peptide in the patients with AIS, diabetes mellitus, AMI, chronic kidney disease, esophageal squamous cell carcinoma, or colorectal carcinoma compared with those in healthy donors. The ASXL2 antibody levels were well associated with hypertension complication, but not with sex, body mass index, habitual smoking, or alcohol intake. These results suggest that the serum ASXL2 antibody marker can discriminate between hypertension‑induced atherosclerotic AIS and AMI, as well as a number of digestive organ cancers.

• Congenital leaflet prolapse and absent chordae of tricuspid valve (TV) is rare. • Congenital TV abnormalities were difficult to evaluate with echocardiography. • Three-dimensional transesophageal echocardiography revealed this TV abnormality.

BACKGROUND: Tendon xanthoma, represented as Achilles tendon xanthoma (ATX), is one of the important diagnostic criteria for familial hypercholesterolemia (FH). However, there are some cases with ATX who do not meet these criteria. This study aimed to investigate the severity of coronary artery disease (CAD) in patients with ATX. METHODS: A total of 394 patients with CAD undergoing percutaneous coronary intervention (PCI) at Chiba University Hospital between June 2016 and February 2018 were enrolled. Soft X-ray radiography of Achilles tendon was performed, and a maximum thickness of 9 mm or more was regarded as ATX. Heterozygous FH was diagnosed according to the diagnostic criteria proposed by the Japan Atherosclerosis Society in 2017. CAD severity was assessed by SYNTAX score before the first PCI during the study period. RESULTS: There were 43 (10.9%) patients with ATX, and 16 (4.1%) were diagnosed as FH (15 with ATX and 1 without ATX). The ATX group showed greater body mass index, lower high-density lipoprotein cholesterol level, and the higher prevalence of FH, diabetes, prior myocardial infarction, acute coronary syndrome, multivessel disease, hemodialysis, and prior statin administration. SYNTAX score and the rate of SYNTAX score ≥23 were significantly higher in the ATX group compared with the non-ATX group (p < 0.001 for each). When patients were divided into quartiles according to Achilles tendon thickness, SYNTAX score and the prevalence of SYNTAX score ≥23 were progressively increased in favor of greater Achilles tendon thickness (p < 0.001 for each). Multivariate analysis determined male, diabetes, and ATX as independent predictors for higher SYNTAX score. CONCLUSIONS: In CAD patients undergoing PCI, ATX was independently associated with severity of CAD. Detecting ATX may be useful not only for diagnosing FH, but also for identifying patients with advanced CAD.

A 32-year-old male received catheter ablation of frequent ventricular extrasystoles (VEs). His electrocardiogram showed monomorphic VEs with an inferior axis and early precordial transitional zone. During electrophysiological testing, a 10-pole catheter positioned in the left ventricular outflow tract recorded sharp pre-potentials just before the ventricular activation during VEs as well as sinus beats. Three-dimensional mapping was performed by annotating the sharp pre-potentials to reveal that the earliest activation site was deemed to be close to the left anterior fascicle. A cryoablation catheter was introduced into the left ventricle and freezing for 240 seconds successfully eliminated the clinical VEs without any complications.

AIMS: To investigate the predictive capability of insulin resistance surrogate markers for insulin resistance and arterial stiffness based on sex. METHODS: We assessed the association of triglyceride glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), visceral adiposity index (VAI), and lipid accumulation product (LAP) with homeostasis model assessment-insulin resistance (HOMA-IR) and brachial-ankle pulse wave velocity (baPWV) in both sexes. RESULTS: A total of 1720 men and 1098 women were evaluated. HOMA-IR showed good correlation with the TyG index (men: r = 0.47, women: r = 0.45), TG/HDL-C (men: r = 0.45, women: r = 0.41), VAI (men: r = 0.51, women: r = 0.48), and LAP (men: r = 0.55, women r = 0.49) (all p-values < 0.001). These markers positively correlated with increased baPWV in both sexes. The standardized partial regression coefficients were 0.11 and 0.14 for the TyG index, 0.13 and 0.16 for TG/HDL-C, 0.14 and 0.19 for VAI, and 0.12 and 0.17 for LAP in men and women, respectively (all p-values < 0.01; all p-values for sex interaction < 0.05). CONCLUSIONS: All insulin surrogate markers showed good correlation with HOMA-IR in both sexes. These indices were also associated with increased baPWV and the associations were stronger in women than in men.

BACKGROUND: Ticagrelor and prasugrel are novel and potent P2Y12 inhibitors. Ticagrelor 90mg or 60mg twice daily is known to reduce ischemic events but be associated with an increased risk of bleeding in patients with prior myocardial infarction in Western countries. Although ticagrelor 90mg twice daily was tested in a randomized clinical trial in East Asia, the clinical significance of ticagrelor 60mg twice daily is unclear. This study aimed to evaluate platelet inhibition of low-dose ticagrelor compared to prasugrel in Japanese patients. METHODS: A total of 33 patients with prior myocardial infarction (>3 months) who received aspirin and prasugrel 3.75mg once daily were enrolled. Prasugrel was switched to ticagrelor 60mg twice daily. Platelet inhibition was assessed by VerifyNow assay (Accumetrics, San Diego, CA, USA) at baseline and 14 days after switching to ticagrelor. P2Y12 reaction unit (PRU) ≤95 was defined as low on-treatment platelet reactivity (LPR) and PRU≥262 as high on-treatment platelet reactivity. RESULTS: Ticagrelor treatment resulted in significantly lower PRU [10 (7-39) vs. 143 (102-201), p<0.001] and a higher rate of LPR (94% vs. 24%, p<0.001), compared to prasugrel treatment. Neither patients treated with ticagrelor nor prasugrel had high on-treatment platelet reactivity. During 2-week follow-up on ticagrelor therapy, no major bleeding occurred in both groups, while four minor bleeding events were observed. CONCLUSION: In Japanese patients with prior myocardial infarction, significantly lower PRU and a higher rate of LPR were observed on ticagrelor 60mg twice daily compared to prasugrel 3.75mg once daily.

BACKGROUND: Takotsubo syndrome (TTS) occurs predominantly in post-menopausal women but is also found in younger patients. OBJECTIVES: This study aimed to investigate age-related differences in TTS. METHODS: Patients diagnosed with TTS and enrolled in the International Takotsubo Registry between January 2011 and February 2017 were included in this analysis and were stratified by age (younger: ≤50 years, middle-age: 51 to 74 years, elderly: ≥75 years). Baseline characteristics, hospital course, as well as short- and long-term mortality were compared among groups. RESULTS: Of 2,098 TTS patients, 242 (11.5%) patients were ≤50 years of age, 1,194 (56.9%) were 51 to 74 years of age, and 662 (31.6%) were ≥75 years of age. Younger patients were more often men (12.4% vs. 10.9% vs. 6.3%; p = 0.002) and had an increased prevalence of acute neurological (16.3% vs. 8.4% vs. 8.8%; p = 0.001) or psychiatric disorders (14.1% vs. 10.3% vs. 5.6%; p < 0.001) compared with middle-aged and elderly TTS patients. Furthermore, younger patients had more often cardiogenic shock (15.3% vs. 9.1% vs. 8.1%; p = 0.004) and had a numerically higher in-hospital mortality (6.6% vs. 3.6% vs. 5.1%; p = 0.07). At multivariable analysis, younger (odds ratio: 1.60; 95% confidence interval: 0.86 to 3.01; p = 0.14) and older age (odds ratio: 1.09; 95% confidence interval: 0.66 to 1.80; p = 0.75) were not independently associated with in-hospital mortality using the middle-aged group as a reference. There were no differences in 60-day mortality rates among groups. CONCLUSIONS: A substantial proportion of TTS patients are younger than 50 years of age. TTS is associated with severe complications requiring intensive care, particularly in younger patients.

Previous studies reported that elevated serum uric acid level was associated with greater coronary lipid plaque. Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine metabolism and is believed to play important roles in coronary atherosclerosis. However, the relation between XOR and coronary lipid plaque is unclear. Patients with stable coronary artery disease who underwent elective percutaneous coronary intervention under near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) guidance were prospectively included. They were divided into 3 groups according to plasma XOR activities based on a previous report: low, normal, and high. Quantitative coronary angiography and gray-scale IVUS were analyzed. The primary end point was coronary lipid plaques in a nontarget vessel assessed by NIRS-IVUS with lipid core burden index (LCBI) and maximum LCBI in 4 mm (maxLCBI4mm). Out of 68 patients, 26, 31, and 11 patients were classified as low, normal, and high XOR activity groups. Quantitative coronary angiography demonstrated that the high XOR activity group had longer lesion length, smaller minimum lumen diameter, and higher percentage of diameter stenosis in a nontarget vessel among the 3 groups. Gray-scale IVUS analysis also showed smaller lumen area in the high XOR activity group than the others. LCBI (102.1 ± 56.5 vs 65.6 ± 48.5 vs 55.6 ± 37.8, p = 0.04) and maxLCBI4mm (474.4 ± 171.6 vs 347.4 ± 181.6, 294.0 ± 155.9, p = 0.04) in a nontarget vessel were significantly higher in the high XOR group than in the normal and low groups. In conclusion, elevated XOR activity was associated with coronary lipid-rich plaque in a nontarget vessel in patients with stable coronary artery disease.

BACKGROUND: Left ventricular reverse remodeling (LVRR) has been detected in non-ischemic dilated cardiomyopathy (NIDCM) patients following optimal treatment. However, its prediction with only conventional modalities is often difficult. This study sought to examine whether RNA sequencing (RNA-seq) of myocardium tissue samples could predict LVRR in NIDCM. METHODS: A total of 17 advanced NIDCM patients with left ventricular ejection fraction (LVEF) below 30% who underwent cardiac biopsy from Left ventricle (LV) were prospectively recruited. They received optimal treatment and followed with echocardiogram every 6 months. Based on LVRR status after 12 months of treatment, patients were divided into the reverse remodeling (RR) or non-RR group. Tissue samples were analyzed by RNA-seq, and a functional analysis of differentially expressed genes was carried out. RESULTS: There were eight and nine patients in the RR and non-RR groups, respectively. No difference was found in age, sex, disease duration, LV end-diastolic diameter, and LVEF between the two groups. There were 155 genes that were differentially expressed between the two groups. Nicotinamide adenine dinucleotide ubiquinone oxidoreductase subunit (NDUF)S5 and Growth arrest and DNA-damage-inducible protein (GADD)45G, along with several genes related to the mitochondrial respiratory chain and ribosome, were significantly downregulated in the RR as compared to the non-RR group. CONCLUSION: GADD45G and NDUFS5 are potential biomarkers for LVRR in patients with advanced NIDCM.

植込み型除細動器(ICD)や両心室ペーシング機能付き植込み型除細動器(CRT-D)は薬物療法と比較して、心臓突然死を予防し生命予後を改善することが知られているが、その一方で心房細動(AF)を含む上室頻拍(SVT)に対する不適切作動も懸念されている。今回われわれは、不適切作動の原因となる頻拍の特性を明らかにするため、当院でICD/CRT-Dを植込んだ患者400人を対象に解析を行った。平均フォローアップ期間43±28ヵ月で、36人(9.0%)に不適切作動を認め、合計83件の不適切作動エピソードがあった。不適切作動の原因の93%(77件)がSVTであり、そのうちAFが原因であった群(AF群、45件)とAF以外のSVTが原因であった群(non-AF群、32件)に分けて比較したところ、頻拍レートは両群で差はなかったが(AF群 vs. non-AF群;202±22bpm vs. 210±21bpm、p=0.191)、ショック作動前の抗頻拍ペーシング(ATP)による頻拍停止はnon-AF群で多く認められた(AF群 vs. non-AF群;0% vs. 72%、p<0.001)。これらの結果から、ICD/CRT-D患者における不適切作動の多くはSVTが原因であり、AF以外のSVTにはATPが有効なことから、ショック作動前のATP治療を積極的に設定することで不適切なショック作動を避けられる可能性が示唆された。(著者抄録)

A 40-year-old male visited our institute complaining of transient loss of consciousness. He had been implanted with an implantable cardioverter defibrillator (ICD) due to idiopathic ventricular fibrillation for secondary prevention. His past genetic screening detected a single nucleotide SCN5A mutation (pR18Q), while neither QT prolongation nor ST segment elevation in the right precordial leads was observed. An interrogation of the ICD revealed that a shock therapy successfully terminated ventricular fibrillation at the time syncope occurred. His electrocardiogram revealed ventricular premature contractions (VPCs) with a short coupling interval of 250 ms. Since the spontaneous occurrence of non-sustained polymorphic ventricular tachycardia following the same VPCs was observed after admission, he was diagnosed with a short-coupled variant of Torsades de Pointes (ScTdP). Contact mapping on the basal inferior right ventricular free wall, exhibiting the earliest activation, revealed pre-potentials preceding the QRS by 30 ms during the VPCs. Radiofrequency ablation was performed to reduce the triggering VPCs. To the best of our knowledge, this is the first report describing a case of ScTdP harboring an SCN5A mutation. The present N-terminally mutated SCN5A was originally reported in relation to Brugada syndrome, whereas the detailed mechanism remains to be elucidated. 〈: Learning objective: The fundamental genetic disorders of short-coupled variant of Torsades de Pointes (ScTdP) are not clear. The present case harboring a mutation of SCN5A exhibited no long-QT or Brugada syndrome, which may implicate an unknown mechanism of the development of ScTdP.〉.