The members of the nebulin protein family, including nebulin, nebulette, LASP-1, LASP-2, and N-RAP, contain various numbers of nebulin repeats and bind to actin, but are otherwise heterogeneous with regard to size, expression pattern, and function. This review focuses on the roles of nebulin family members in the heart. Nebulin is the largest member predominantly expressed in skeletal muscle, where it stretches along the thin filament. In heart, nebulin is detectable only at low levels and its absence has no apparent effects. Nebulette is similar in structure to the nebulin C-terminal Z-line region and specifically expressed in heart. Nebulette gene mutations have been identified in dilated cardiomyopathy patients and transgenic mice overexpressing nebulette mutants partially recapitulate the human pathology. In contrast, nebulette knockout mice show no functional phenotype, but exhibit Z-line widening. LASP-2 is an isoform of nebulette expressed in multiple tissues, including the heart. It is present in the Z-line and intercalated disc and able to bind and cross-link filamentous actin. LASP-1 is similar in structure to LASP-2, but expressed only in non-muscle tissue. N-RAP is present in myofibril precursors during myofibrillogenesis and thought to be involved in myofibril assembly, while it is localized at the intercalated disc in adult heart. Additional in vivo models are required to provide further insights into the functions of nebulin family members in the heart. (Circ J 2015; 79: 2081–2087)

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Uremic toxins have been increasingly recognized as a crucial missing link in the cardiorenal syndrome. Advances in dialysis technologies have contributed to an enormous improvement in uremic toxin removal, but removal of protein-bound uremic toxins (PBUTs) by current conventional dialysis remains problematic because of their protein-binding capacity. Most PBUTs that have been implicated in cardiorenal toxicity have been demonstrated to be derived from a colonic microbiota metabolism pathway using dietary amino acids as a substrate. Currently, indoxyl sulfate and p-cresyl sulfate are the most extensively investigated gut-derived PBUTs. Strong evidence of adverse clinical outcomes, as well as biological toxicity on the kidney and cardiovascular system attributable to these toxins, has been increasingly reported. Regarding their site of origin, the colon has become a potential target for treatment of cardiorenal syndrome induced by gut-derived PBUTs. (Circ J 2015; 79: 2088–2097)

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Background:Brugada syndrome (BrS) is an inheritable cardiac disease associated with syncope, malignant ventricular arrhythmias and sudden cardiac death. The largest proportion of mutations in BrS is found in theSCN5Agene encoding the α-subunit of cardiac sodium channels (Nav1.5). CausalSCN5Amutations are present in 18–30% of BrS patients. The additional genetic diagnostic yield of variants in cardiac sodium channel β-subunits in BrS patients was explored and functional studies on 3 novel candidate variants were performed.Methods and Results:TheSCN1B-SCN4Bgenes were screened, which encode the 5 sodium channel β-subunits, in aSCN5Anegative BrS population (n=74). Five novel variants were detected; in silico pathogenicity prediction classified 4 variants as possibly disease causing. Three variants were selected for functional study. These variants caused only limited alterations of Nav1.5 function. Next generation sequencing of a panel of 88 arrhythmia genes could not identify other major causal mutations.Conclusions:It was hypothesized that the studied variants are not the primary cause of BrS in these patients. However, because small functional effects of these β-subunit variants can be discriminated, they might contribute to the BrS phenotype and be considered a risk factor. The existence of these risk factors can give an explanation to the reduced penetrance and variable expressivity seen in this syndrome. We therefore recommend including theSCN1-4Bgenes in a next generation sequencing-based gene panel. (Circ J 2015; 79: 2118–2129)

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Background:Few reports are available on the characteristics of electrical storms of ventricular tachycardia (VT storm) refractory to intravenous (IV) amiodarone.Methods and Results:IV-amiodarone was administered to 60 patients with ventricular tachyarrhythmia between 2007 and 2012. VT storms, defined as 3 or more episodes of VT within 24 h, occurred in 30 patients (68±12 years, 7 female), with 12 having ischemic and 18 non-ischemic heart disease. We compared the clinical and electrocardiographic characteristics of the patients with VT storms suppressed by IV-amiodarone (Effective group) to those of patients not affected by the treatment (Refractory group). IV-amiodarone could not control recurrence of VT in 9 patients (30%). The Refractory group comprised 5 patients with acute myocardial infarctions. Although there was no difference in the VT cycle length, the QRS duration of both the VT and premature ventricular contractions (PVCs) followed by VT was narrower in the Refractory group than in the Effective group (140±30 vs. 178±25 ms, P<0.01; 121±14 vs. 179±22 ms, P<0.01). In the Refractory group, additional administration of IV-mexiletine and/or Purkinje potential-guided catheter ablation was effective.Conclusions:IV-amiodarone-refractory VT exhibited a relatively narrow QRS tachycardia. The narrow triggering PVCs, suggesting a Purkinje fiber origin, may be treated by additional IV-mexiletine and endocardial catheter ablation. (Circ J 2015; 79: 2130–2137)

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Background:In Asian patients in RE-LY, dabigatran etexilate (DE) was as effective as warfarin, with a significantly lower bleeding risk. We evaluated the relationship between baseline renal function or CHADS₂score and efficacy or safety outcomes in these patients.Methods and Results:Asian patients (n=2,782) were categorized according to baseline renal function or CHADS₂score, and efficacy and safety outcomes were analyzed for DE (110 mg and 150 mg b.i.d.) vs. warfarin. There was an increase in the rates of stroke/systemic embolism and major bleeding with worsening renal function and CHADS₂score. For stroke/systemic embolism (primary efficacy endpoint), there was no treatment interaction for dabigatran at either 110 or 150 mg b.i.d. compared with warfarin related to patients’ baseline renal function (P_interaction=0.56 for DE 110 mg and 0.62 for DE 150 mg vs. warfarin) or CHADS₂score (P_interaction=0.68 for DE 110 mg and 0.31 for DE 150 mg vs. warfarin). For major bleeding, there was no treatment interaction by creatinine clearance category observed for either dose (P_interaction=0.60 and 0.62 for DE 110 mg and DE 150 mg, respectively). Baseline CHADS₂score had no significant effect on bleeding event rates with DE vs. warfarin.Conclusions:Bleeding and stroke rates in Asian patients varied according to renal function and CHADS₂score, but the relative benefits of DE over warfarin were preserved when analyzed by subcategories. (Circ J 2015; 79: 2138–2147)

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Background:This study sought to evaluate whether a poor increase in inferior P-wave amplitude during sympathetic stimulation might be a helpful diagnostic tool for sick sinus syndrome (SSS).Methods and Results:Three-dimensional electroanatomic mapping of the right atrium, inferior P-wave amplitude and conventional corrected sinus node recovery time (CSNRT) were compared in 112 consecutive atrial fibrillation (AF) patients with (n=21) and without SSS (n=91). The significant cranial shift of earliest activation site (EAS) (the distance from the superior vena cava to the EAS: 11.1 vs. 5.9 mm, P<0.001) and the increases of inferior P-wave amplitudes during isoproterenol infusion (all P<0.001) were observed in patients without SSS. However, cranial shift of EAS (16.5 vs. 14.2 mm, P=0.375) and P-wave amplitude increases were not observed in those with SSS. Although CSNRT >550 ms showed a sensitivity of 50% and specificity of 84% for diagnosing SSS, poor increases of P-waves amplitude in lead aVF (<0.1 mV) during isoproterenol infusion showed an improved sensitivity of 71% and specificity of 89%. Finally, the combined algorithm using CSNRT >550 ms and poor increase of P-waves amplitude in lead aVF showed more improved diagnostic accuracy (sensitivity 89%, specificity 75%).Conclusions:A combined algorithm using inferior P-wave amplitude showed improved performance for the diagnosis of SSS compared with CSNRT >550 ms alone. (Circ J 2015; 79: 2148–2156)

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Background:The aim of this study was to identify anatomical variations in coronary artery orifices among high-risk patients with a small aortic root undergoing bioprosthetic aortic valve replacement (BAVR) and transcatheter aortic valve replacement (TAVR) in order to prevent coronary orifice obstruction perioperatively.Methods and Results:Coronary orifice and root structure were identified in 400 patients using aortic multidetector-row computed tomography (MDCT). We measured the aortic root diameter; intercommissural distances; and distance from coronary orifice to valve annulus, commissure, and sinotubular junction. We examined positional relationships between the coronary orifice and stent post, or sewing cuff of the bioprosthetic valve and leaflet of the transcatheter aortic valve. Most left coronary artery orifices were distributed near the center of the non-left and left-right commissures; right ones were relatively distributed on the non-right commissural side. Thirty-four patients (8.5%) with BAVR (coronary orifice near the commissure: 31, 7.8%; low takeoff: 5, 1.3%; and both: 2) and 39 (9.8%) with TAVR were at risk for coronary orifice obstruction. During BAVR, one-stitch rotation of the stent and one-stitch rotation with intra-annular implantation were used in near-commissure and low takeoff cases, respectively. During TAVR, percutaneous coronary intervention may be required in the height of the coronary orifice was ≤10 mm from the base of the ventricle aortic junction.Conclusions:Potential coronary complications during BAVR and TAVR in high-risk patients for coronary obstruction were identified using preoperative aortic MDCT. Choice of appropriate surgical technique or valve is essential. (Circ J 2015; 79: 2157–2161)

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Background:Transcatheter closure is a well-established therapy for patients with perimembranous ventricular septal defects (VSDs), but with limited experience in intracristal VSDs (IVSDs) with aortic cusp prolapse (ACP).Methods and Results:From 2012 to 2014, we reviewed 38 patients with IVSDs complicated with mild ACP who underwent device closure, and, in light of the findings, assessed the effect of transcatheter intervention on preoperative mild ACP. The zero eccentric VSD occluder was chosen for closure (Shanghai Shape Memory Alloy Ltd, Shanghai, China). The mean defect was 4.8±1.6 mm (range, 2–8) as measured by transthoracic echocardiography and the mean device size was 10.1±2.1 mm (range, 4–14). Placement of the device was successful in 35 patients (92.1%). In the remaining 3 patients (7.9%), major complications occurred and they were converted to surgical intervention: severe aortic regurgitation (AR) in 2 patients and occluder dislodgement in 1 patient. During the follow-up (median 14.2 months; range, 3–24), no deaths, residual shunt, late-onset AR, heart block, or device failure occurred.Conclusions:The mid-term prognostic results of high success rate and low complications rate in this study are inspiring. Transcatheter closure of IVSD with mild ACP can be performed safely and effectively as an alternative to surgery in selected patients. (Circ J 2015; 79: 2162–2168)

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Background:Hemodialysis (HD) patients are reported to show poor clinical outcomes after percutaneous coronary intervention (PCI) with sirolimus-eluting stent (SES) compared with non-HD patients and their long-term prognosis remains unclear.Methods and Results:We prospectively enrolled 489 consecutive patients undergoing PCI with SES and performed a retrospective analysis focusing on HD patients. Median follow-up was 7.0 years (interquartile range, 4.2–7.9) and the follow-up rate was 100%. At the 7-year follow-up, the cumulative incidences of all-cause death, target lesion revascularization (TLR) and major adverse cardiac events (MACE) were significantly higher in HD patients than in non-HD patients (HD vs. non-HD=34.7% vs. 9.6%, 42.6% vs. 10.2% and 75.3% vs. 24.4%, respectively; log-rank P<0.001). Cox-proportional hazard analysis revealed that independent predictors of all-cause death were HD (hazard ratio [HR] 2.88, 95% confidence interval [CI]: 1.39–6.00), insulin-treated diabetes mellitus (HR 2.19, 95% CI: 1.17–4.11), heart failure (HR 2.58, 95% CI: 1.25–5.32) and older age (HR 1.06/1-age, 95% CI: 1.02–1.10). Moreover, HD was an independent predictor of TLR (HR 3.63, 95% CI: 1.85–7.11) and MACE (HR 3.54, 95% CI: 2.19–5.73).Conclusions:In the present study, Japanese HD patients undergoing PCI with SES showed poorer long-term clinical outcomes than non-HD patients. HD was a strong predictor of long-term adverse events after SES implantation. (Circ J 2015; 79: 2169–2176)

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Background:To investigate the relationship between age and both short- and long-term outcomes of off-pump coronary bypass grafting (OPCAB).Methods and Results:The 780 patients undergoing OPCAB were divided into 3 groups: 262 aged <65 years (young), 329 aged 65–74 years (early elderly), and 189 aged >75 years (late elderly), and retrospectively analyzed. Thefollow-up rate was 94.9%, and mean follow-up period was 5.6±3.4 years. In-hospital mortality rates were similar among the groups (0.8% in young, 1.2% in early elderly, and 1.1% in late elderly; P=0.862). In logistic regression analysis, the risk factor for predicting major complications was the New York Heart Association (NYHA) classification (odds ratio: 1.555, P=0.001), and not age. The 10-year estimated rates free from cardiac death (89.6±3.2, 95.0±2.1, and 96.5±2.1%, log rank, P=0.16) and cardiac events (71.8±3.8, 66.8±4.3, and 59.9±7.7%, P=0.61) were not significantly different among the groups. In multivariate Cox models, independent risk factors predicting cardiac events were the NYHA classification (hazard ratio (HR): 1.265, P=0.009), and ejection fraction (HR: 0.986, P=0.016), but not age (young HR: 1.0, early elderly HR: 1.276; P=0.210, late elderly HR: 0.910; P=0.707).Conclusions:Both short- and long-term cardiac outcomes of OPCAB are not influenced by age at operation. (Circ J 2015; 79: 2177–2185)

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Background:Improving quality of life (QOL) has become an important goal in left ventricular assist device (LVAD) therapy. We aimed (1) to assess the effect of an implantable LVAD on patients’ QOL, (2) to compare LVAD patients’ QOL to that of patients in different stages of heart failure (HF), and (3) to identify factors associated with patients’ QOL.Methods and Results:The QOL of 33 Japanese implantable LVAD patients was assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and Short-form 8 (SF-8), before and at 3 and 6 months afterwards. After LVAD implantation, QOL significantly improved [MLHFQ, SF-8 physical component score (PCS), SF-8 mental component score (MCS), all P<0.05]. Implanted LVAD patients had a better QOL than extracorporeal LVAD patients (n=33, 32.1±21.9 vs. n=17, 47.6±18.2), and Stage D HF patients (n=32, 51.1±17.3), but the score was comparable to that of patients who had undergone a heart transplant (n=13). In multiple regression analyses, postoperative lower albumin concentration and right ventricular failure were independently associated with poorer PCS. Female sex and postoperative anxiety were 2 of the independent factors for poorer MCS (all P<0.05).Conclusions:Having an implantable LVAD improves patients’ QOL, which is better than that of patients with an extracorporeal LVAD. Both clinical and psychological factors are influence QOL after LVAD implantation. (Circ J 2015; 79: 2186–2192)

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Background:The long-term results achieved with aortic St. Jude Medical (SJM) mechanical prostheses in various age groups of Japanese patients have not been previously compared or reported.Methods and Results:Since 1981, a total of 240 SJM valves were implanted in 79 patients using the Standard model, in 58 patients with the Hemodynamic Plus model, and in 103 patients with the Regent model for aortic valve replacement (AVR). Follow-up was completed for 2,397 patient-years in 97.5% of the patients, among whom the effect of age was compared, and the subjects were divided into younger (<65 years) and older (≥65 years) groups. Hospital mortality rate was 2.5%. No structural valve deterioration was observed during the follow-up period. In addition, no significant differences were observed in long-term survival between the 3 models. In contrast, significantly better rates of freedom from all-cause death (P<0.0001), valve-related death (P=0.0018) and valve-related morbidity (P=0.0021), including bleeding events (P=0.0007), were observed in the younger group (n=157, 50.6±1.0 years old) than in the older group (n=83, 72.5±0.7 years old).Conclusions:All types of SJM valve used for single AVR achieved satisfactory early and long-term results in each age group even 25 years after surgery. When selecting this prosthesis for elderly patients, however, relatively worse performance may be expected compared with that observed in younger patients. (Circ J 2015; 79: 2193–2200)

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Background:Because the initial (on admission) Glasgow Coma Scale (GCS) examination has not been fully evaluated in comatose survivors of cardiac arrest (CA) who receive therapeutic hypothermia (TH), the aim of the present study was to determine any association between the admission GCS motor score and neurologic outcomes in patients with out-of-hospital CA who receive TH.Methods and Results:In the J-PULSE-HYPO study registry, patients with bystander-witnessed CA were eligible for inclusion. Patients were divided into 3 groups based on GCS motor score (1, 2–3, and 4–5) to assess various effects on neurologic outcome. Univariate and multivariate analyses were performed to identify independent predictors of good neurologic outcome at 90 days. Of 452 patients, 302 were enrolled. There was a significant difference among the 3 patient groups with regard to neurologic outcome at 90 days in the univariate analysis. Multiple logistic regression analyses showed that the GCS motor score on admission, age >65 years, bystander cardiopulmonary resuscitation, the time from collapse to return of spontaneous circulation, and pupil size <4 mm were independent predictors of a good neurologic outcome at 90 days in cases of CA (GCS motor score, 4–5: odds ratio, 8.18; 95% confidence interval: 1.90–60.28; P<0.01).Conclusions:GCS motor score is an independent predictor of good neurologic outcome at 90 days in patients sustaining out-of-hospital CA who receive TH. (Circ J 2015; 79: 2201–2208)

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Background:Heart failure (HF) with preserved (HFpEF) left ventricular ejection fraction (LVEF) is a syndrome with complex pathophysiology. Little is known about changes in LVEF that occur over time in HFpEF patients. A fundamental clinical question about HFpEF is whether HFpEF is an early manifestation of HF with reduced LVEF (HFrEF). If so, which patients with HFpEF are likely to show a decline in LVEF to less than 50%? The aim of the present study was to examine longitudinal changes in LVEF in patients with HFpEF.Methods and Results:Among 279 consecutive HFpEF patients admitted as emergencies, we examined 100 who underwent echocardiography at least 1 year after discharge. EF >50% was used as the definition of HFpEF. During a mean duration from hospitalization to follow-up echocardiography of 31.5 months, 11% of patients had LVEF ≤50% (mildly reduced LVEF), known as mildly reduced (HFmrEF). The utility of LVEF during hospitalization to predict HFmrEF was assessed with receiver-operating characteristic curve analysis. A cutoff value of 55% had sensitivity of 90.9% and specificity of 97.7%. Logistic regression analysis indicated that LVEF ≤55% and ischemic etiology were strong predictors of progression from HFpEF to HFmrEF (odds ratio [OR] 435, 95% confidence interval [CI] 52.65–10,614, P<0.0001 and OR 10.9, 95% CI 2.60–74.80, P=0.0007, respectively).Conclusions:The present study suggests that HFpEF patients with LVEF ≤55% may progress to HFmrEF in the future. (Circ J 2015; 79: 2209–2215)

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Background:Syncope is a common occurrence. The presence of J-wave, also known as early repolarization, on electrocardiogram is often seen in the general population, but the relationship between syncope and J-wave is unclear.Methods and Results:After excluding 67 patients with structural heart disease from 326 with syncope, we classified 259 patients according to the presence or absence of J-wave (≥1 mm) in at least 2 inferior or lateral leads. Head-up tilt test (HUT) was performed for 30 min. If no syncope or presyncope occurred, HUT was repeated after drug loading. Before tilt, 97/259 (37%) had J-wave (57 male, 47.6±22.5 years) and 162 patients had no remarkable change (89 male, 51.1±21.2 years). HUT-positive rate was higher in patients with J-wave, compared with patients without (P<0.0001). The combination of J-wave and descending/horizontal ST segment in the inferior leads was more strongly associated with positive HUT than J-wave with ascending ST segment (odds ratio, 3.23).Conclusions:Prevalence of J-wave in the inferior or lateral leads was high in patients with syncope and was associated with HUT-induced neurally mediated reflex syncope (NMRS). Furthermore, the combination of J-wave and descending/horizontal ST segment in the inferior leads could be associated with a much higher risk of NMRS. (Circ J 2015; 79: 2216–2223)

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Background:We performed an ex vivo study to investigate optical coherence tomography (OCT) imaging for differentiating several types of neointimal tissue during the later phases after bare-metal stent (BMS) implantation as compared with histologic results.Methods and Results:OCT imaging was performed in 6 autopsy hearts for 10 BMS with implant duration >4 years. OCT qualitative neointimal tissue characterization was based on tissue structure and classified as homogeneous pattern, heterogeneous pattern with visible struts, or heterogeneous pattern with invisible struts. Corresponding histological analyses of each 2-mm cross-section of the entire BMS were performed. Of 81 cross-sections, histological analysis revealed that the homogeneous pattern of neointima on OCT (n=39) contained smooth muscle cells with collagen, indicating high neointimal maturity. The heterogeneous patterns with visible struts (n=35) contained different tissues, including a proteoglycan-rich myxomatous matrix or dense calcified plate deposition. The heterogeneous patterns with invisible struts (n=7) included neointimal lipid/necrotic core formation, accumulation of foam cells, or microcalcification scattering. Of the 66 cross-sections containing large microvessels within the neointima on histology, only 6 (9%) were visualized by OCT.Conclusions:The present study confirmed the potential use of OCT in differentiating several types of neointima after BMS implantation. The image interpretation of OCT, based on visualization of stent struts, enables identification of several types of neointimal tissues, including in-stent fibroatheroma formation, more accurately. (Circ J 2015; 79: 2224–2230)

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Background:The ability of iMap-intravascular ultrasound (IVUS) tissue characterization to detect thin-cap fibroatheroma (TCFA) identified on optical coherence tomography (OCT) has not yet been fully elucidated.Methods and Results:We evaluated 86 coronary lesions from 73 patients with stable angina pectoris using iMap-IVUS and OCT. We defined OCT-derived TCFA (OCT-TCFA) as lipid-rich plaque with a <65-μm-thick fibrous cap. The external elastic membrane (EEM) cross-sectional area (CSA), lumen CSA, plaque plus media (P+M) CSA, plaque burden and remodeling index were measured on gray-scale IVUS. Plaque components categorized on iMap-IVUS as fibrotic, lipidic, necrotic or calcified are presented as absolute area and proportion (%) of total plaque area. OCT-TCFA (22 lesions) had significantly greater EEM CSA, P+M CSA, plaque burden and remodeling index than non-TCFA (64 lesions). Significantly larger %necrotic area, absolute lipidic and necrotic areas and smaller %fibrotic areas were found in OCT-TCFA than in non-TCFA. On multivariate analysis, absolute necrotic area was an independent predictor of OCT-TCFA. The area under the ROC curve for absolute necrotic area required to identify OCT-TCFA was 0.86. The sensitivity, specificity, positive and negative predictive values of absolute necrotic area ≥7.3 mm²for identifying OCT-TCFA were 77%, 88%, 68% and 92%, respectively.Conclusions:Coronary lesions with greater iMap-IVUS absolute necrotic area were closely associated with OCT-TCFA. (Circ J 2015; 79: 2231–2237)

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Background:The dysregulation of systemic blood pressure (BP) variation or cardiac neuroadrenergic dysfunction is associated with adverse cardiovascular events. We aimed to clarify the prognostic significance of neuroadrenergic dysfunction for cardiovascular events in patients with acute myocardial infarction (AMI).Methods and Results:We enrolled 63 AMI patients (mean age, 67±12 years) underwent ambulatory BP monitoring (ABPM) and cardiac iodine-¹²³metaiodobenzylguanidine (MIBG) imaging within 4 weeks after AMI onset. We analyzed the circadian BP pattern and heart-to-mediastinum (H/M) MIBG uptake ratio. All the patients were followed for 2 years. The study endpoint was a composite of major adverse cardiovascular events, including all-cause death, MI, coronary revascularization except for the MI culprit lesion, and stroke. Patients with a non-dipper pattern (n=29) or an H/M ratio <1.96 (n=28) had a worse prognosis than those with either a dipper pattern (n=34) or an H/M ratio ≥1.96 (n=35; log-rank, P=0.013 and 0.010, respectively). Patients with both a non-dipper pattern and an H/M ratio <1.96 (n=12) had a significantly worse prognosis than did the other patients (P=0.0020).Conclusions:Dysregulation of BP variation and cardiac MIBG uptake were associated with cardiovascular events following AMI. Examining ABPM with MIBG imaging may potentially improve risk stratification in these patients. (Circ J 2015; 79: 2238–2245)

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Background:Although rapid progression (RP) of coronary artery disease (CAD) has been shown to be a powerful predictor of cardiovascular events, predictors of RP are not fully understood in patients with acute coronary syndrome (ACS).Methods and Results:We prospectively investigated the clinical impact of glycemic variability (GV), as determined on continuous glucose monitoring system (CGMS), on RP of non-culprit lesions in 88 patients with ACS. RP was defined as ≥10% diameter reduction in a pre-existing stenosis ≥50%; ≥30% diameter reduction in a stenosis <50%; development of a new stenosis ≥30% in a previously normal segment; or progression of any stenosis to total occlusion. Patients were classified into 2 groups according to the presence (progressor, n=20) or absence (non-progressor, n=68) of RP. All patients were equipped with a CGMS during the stable phase, and mean amplitude of glycemic excursion (MAGE) was calculated as a marker of GV. Mean MAGE was significantly higher in progressors than in non-progressors (55±19 mg/dl vs. 37±18 mg/dl, P<0.01). On multiple logistic regression analysis, MAGE was an independent predictor of RP (odds ratio, 1.06 per 1 mg/dl; P<0.01).Conclusions:MAGE early after the onset of ACS is a predictor of RP of non-culprit lesions. (Circ J 2015; 79: 2246–2254)

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Background:Although dobutamine stress echocardiography (DSE) is frequently associated with dynamic left ventricular outflow tract obstruction (DLVOTO), little is known about its clinical significance in women with suspected coronary artery disease (CAD).Methods and Results:One hundred and two female patients (57±10 years) who underwent DSE as part of the Korean women’s chest pain registry study were included. Doppler echocardiography was performed during DSE to assess the presence of DLVOTO. Patients with DLVOTO (n=52) were older than those without DLVOTO (n=50; P=0.001). Hypertension was more prevalent in patients with DLVOTO (P=0.02). Patients with DLVOTO had smaller LV diameter, but higher LV mass index and relative wall thickness (P<0.05 for all). LV diastolic function (as reflected by late diastolic velocity, deceleration time of early diastolic velocity [E], and ratio of E velocity to early diastolic mitral annular velocity), was worse in patients with DLVOTO (P<0.05 for all). Patients with DLVOTO had shorter exercise time (P=0.02) and lower amount of work (P=0.04) than patients without DLVOTO. DSE-provoked DLVOTO was not related to the presence of CAD in these patients.Conclusions:In Korean women with suspected CAD, DSE-provoked DLVOTO is correlated with LV concentric remodeling and LV diastolic dysfunction, and may be associated with limited exercise tolerance and symptoms of chest pain. (Circ J 2015; 79: 2255–2262)

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Background:Estimated glomerular filtration rate (eGFR) and proteinuria are both important determinants of the risk of cardiovascular disease and mortality. The aim of the present study was to investigate the independent and combined effects of eGFR and proteinuria on tissue characterization of the coronary plaques of culprit lesions.Methods and Results:Conventional intravascular ultrasound and 3-D integrated backscatter intravascular ultrasound (IB-IVUS) were performed in 555 patients undergoing elective percutaneous coronary intervention. They were divided into 2 groups according to the absence or presence of proteinuria (dipstick result ≥1+). Patients with proteinuria had coronary plaque with significantly greater percentage lipid volume compared with those without (43.6±14.8% vs. 48.6±16.1%, P=0.005). Combined analysis was done using eGFR and absence or presence of proteinuria. Subjects with eGFR 45–59 ml/min/1.73 m²and proteinuria were significantly more likely to have higher percent lipid volume compared with those with eGFR >60 ml/min/1.73 m²without proteinuria. After multivariate adjustment for confounders, the presence of proteinuria proved to be an independent predictor for lipid-rich plaque (OR, 1.85; 95% CI: 1.12–3.06, P=0.016).Conclusions:The addition of proteinuria to eGFR level may be of value in the risk stratification of patients with coronary artery disease. (Circ J 2015; 79: 2263–2270)

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Background:We successfully performed totally endoscopic atrial septal defect (ASD) repair via 2 ports, and we named this procedure two-port robotic cardiac surgery (TROCS).Methods and Results:A 51-year-old woman with secundum ASD underwent robot-assisted ASD repair under ventricle fibrillation without aortic cross-clamping. Two ports were placed in the right side of the chest, and 1 port was for the robotic endoscope. Two robotic instruments were inserted through another port and crossed while preventing them from colliding.Conclusions:TROCS ASD repair using a cross-arm technique was achieved safely with good clinical results and excellent cosmetic results. (Circ J 2015; 79: 2271–2273)

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Background:The association between ABO blood type and the activated partial thromboplastin time (aPTT) under dabigatran therapy in nonvalvular atrial fibrillation (NVAF) patients is unclear.Methods and Results:Between 2011 March and 2015 May, data on ABO blood type and aPTT under dabigatran were obtained for 396 NVAF patients (baseline aPTT, 166). The prevalence of blood type O tended to increase or significantly increase according to baseline aPTT, aPTT under dabigatran, and their difference (∆aPTT) (P=0.054, 0.001, and 0.012, respectively).Conclusions:In these NVAF patients, a high aPTT value under dabigatran therapy was associated with blood type O. (Circ J 2015; 79: 2274–2277)

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