Small- and large-conductance Ca²⁺-activated K⁺channels (SKCa and BKCa, respectively) may be important targets for therapeutic interventions in a variety of cardiac conditions. In cardiomyocytes, BKCa channels are localized to mitochondria where they beneficially modulate reactive oxygen species, mitochondrial Ca²⁺, and respiration. In vascular smooth muscle cells, BKCa channels regulate vascular tone and promote vasodilation. Activation of BKCa channels has demonstrated significant cardioprotection following ischemic injury, including improved function and reduced infarct size. SKCa channels are expressed in both the membrane and mitochondria of cardiomyocytes. Modulation of cardiomyocyte SKCa channels may be beneficial for arrhythmia, heart failure, and ischemia. Mitochondrial SKCa channels may provide similar benefit to BKCa channels. In addition, activation of SKCa channels on the endothelium promotes vasodilation. This mini-review focuses on the modulation of cardiomyocyte BKCa and SKCa channels for cardioprotection and briefly address associated potential therapeutic benefits in the coronary circulation. (Circ J 2015; 79: 455–462)

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Soluble guanylyl cyclase (sGC) is the physiological receptor for nitric oxide (NO) and NO-releasing drugs, and is a key enzyme in several cardiovascular signaling pathways. Its activation induces the synthesis of the second messenger cGMP. cGMP regulates the activity of various downstream proteins, including cGMP-dependent protein kinase G, cGMP-dependent phosphodiesterases and cyclic nucleotide gated ion channels leading to vascular relaxation, inhibition of platelet aggregation, and modified neurotransmission. Diminished sGC function contributes to a number of disorders, including cardiovascular diseases. Knowledge of its regulation is a prerequisite for understanding the pathophysiology of deficient sGC signaling. In this review we consolidate the available information on sGC signaling, including the molecular biology and genetics of sGC transcription, translation and function, including the effect of rare variants, and present possible new targets for the development of personalized medicine in vascular diseases. (Circ J 2015; 79: 463–469)

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Despite the growing number of patients affected, the understanding of diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) is still poor. Clinical trials, largely based on successful treatments for systolic heart failure, have been disappointing, suggesting that HFpEF has a different pathology to that of systolic dysfunction. In this review, general concepts, epidemiology, diagnosis, and treatment of diastolic dysfunction are summarized, with an emphasis on new experiments suggesting that oxidative stress plays a crucial role in the pathogenesis of at least some forms of the disease. This observation has lead to potential new diagnostics and therapeutics for diastolic dysfunction and heart failure caused by diastolic dysfunction. (Circ J 2015; 79: 470–477)

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Mechanical circulatory support devices, including ventricular assist devices (VADs) and the total artificial heart, have evolved to become accepted therapeutic options for patients with severe congestive heart failure. Continuous-flow left VADs are the most prevalent option for mechanical circulatory assistance and reliably provide years of support. However, problems related to acute and chronic right heart failure in patients with left VADs continue to cause important mortality and morbidity. This review discusses the assessment and management of right ventricular failure in left VAD patients. The goal is to summarize current knowledge and suggest new approaches to managing this problem. (Circ J 2015; 79: 478–486)

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Cardiovascular magnetic resonance is a well-established tool for the quantification of focal fibrosis. With the introduction of T1 mapping, diffuse myocardial processes can be detected and quantified. In particular, infiltration and storage disorders with large disease-related changes, and diffuse fibrosis where measurement is harder but the potential impact larger. This has added a new dimension to the understanding and assessment of various myocardial diseases. T1 mapping promises to detect early disease, quantify disease severity and provide prognostic insights into certain conditions. It also has the potential to be a robust surrogate marker in drug development trials to monitor therapeutic response and be a prognostic marker in certain diseases. T1 mapping is an evolving field and numerous factors currently preclude its standardization. In this review, we describe the current status of T1 mapping and its potential promises and pitfalls. (Circ J 2015; 79: 487–494)

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Atrial fibrillation (AF) is the most common clinically relevant arrhythmia, but the methods available for treating AF and its complications (of which the most important is thrombogenesis), as well as for assessing AF risk and underlying pathophysiology, are largely limited. Emerging evidence suggests a significant role of inflammation in the pathogenesis of AF. That evidence includes elevated serum levels of inflammatory biomarkers in AF subjects, the expression of inflammatory markers in cardiac tissues of AF patients and animal models of AF, and beneficial effects of anti-inflammatory drugs in experimental AF paradigms. Inflammation is suggested to be linked to various pathological processes, such as oxidative stress, apoptosis, and fibrosis, that promote AF substrate formation. Inflammation has also been associated with endothelial dysfunction, platelet activation, and coagulation cascade activation, leading to thrombogenesis. Thus, inflammation may contribute to both the occurrence/maintenance of AF and its thromboembolic complications. Here, we review the evidence for a role of inflammation and inflammatory biomarkers in the risk management and treatment of AF. We also summarize the current knowledge of inflammation-dependent cellular and molecular mechanisms in AF pathophysiology and their potential as therapeutic targets. (Circ J 2015; 79: 495–502)

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Background:Physical examination as an initial screening tool to diagnose abdominal aortic aneurysm (AAA) has lost favor over the past 20 years. This multicenter cohort study aimed to determine the prevalence of AAA in elderly Japanese patients with hypertension (HT) and to clarify the diagnostic accuracy of physical examination using a pocket-sized ultrasound imaging device (the “pocket-echo”).Methods and Results:A total of 1,731 patients with HT aged >60 years from 20 collaborating institutions were enrolled in this study. Abdominal palpation was performed on physical examination, and the pocket-echo was used to confirm the diagnosis of AAA. The abdominal aorta was well visualized in 1,692 patients (98%). AAA was discovered in 69 patients (4.1%), with advanced age and male sex identified as independent risk factors. The prevalence of AAA increased according to age regardless of sex, and reached 9.2% and 5.7%, respectively, in males and females ≥80 years. Overall, 33 cases of AAA were missed on abdominal palpation (sensitivity, 52%), whereas for AAAs >40 mm, the sensitivity was 75%.Conclusions:We assessed the utility of the pocket-echo and physical examination for diagnosing AAA in Japanese patients with HT aged over 60 years. Our findings highlight the importance of AAA screening programs in high-risk Japanese populations, and confirm the ability of physical examination to detect large, but not small, AAAs. (Circ J 2015; 79: 524–529)

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Background:Papaverine is useful for evaluating the functional status of a coronary artery, but it may provoke malignant ventricular arrhythmia (VA). The aim of this study was to investigate the incidence, and clinical and ECG characteristics of patients with papaverine-induced VAs.Methods and Results:The 182 consecutive patients underwent fractional flow reserve (FFR) measurement of 277 lesions. FFR was determined after intracoronary papaverine administration by standard procedures. The clinical and ECG characteristics were compared between patients with and without ventricular tachycardia (VT: ≥3 successive premature ventricular beats (PVBs), or ventricular fibrillation (VF)). After papaverine administration, the QTc interval, QTUc interval, and T-peak to U-end interval were prolonged significantly. Single PVBs on the T-wave or U-wave type developed in 29 patients (15.9%). Polymorphic VT (torsade de pointes) occurred in 5 patients (2.8%), and of those, VF developed in 3 patients (1.7%). No clinical and baseline ECG parameters were predictors for VT or VF except for sex and administration of papaverine into the left coronary artery. Excessive prolongation of QT (or QTU), T-peak to U-end intervals and giant T-U waves were found immediately prior to the ventricular tachyarrhythmias (VTAs), which were unpredictable from the baseline data.Conclusions:Intracoronary administration of papaverine induced fatal VTAs, although the incidence is rare. Excessive prolongation of the QT (and QTU) interval appeared prior to VTAs; however, they were unpredictable. (Circ J 2015; 79: 530–536)

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Background:This study investigated the safety and outcome of endovascular therapy for steno-occlusive subclavian or innominate artery disease at a single center over a long period of more than 2 decades.Methods and Results:We retrospectively analyzed all endovascular procedures of stenosis or occlusion of the subclavian or innominate artery between January 1990 and October 2013. During the observation period, a total of 130 procedures were attempted in 127 mostly symptomatic patients with stenosis (n=108; 83%) or occlusion (n=22; 17%) of the subclavian (n=119; 92%) and innominate (n=11; 8%) artery. The overall technical success rate was 97.7% (n=127/130). Accounting for the type of lesion, the success rate for stenosis was 100% (n=108/108) and for total occlusion, 86% (n=19/22). The periprocedural complication rate was low and included stroke, transient ischemic attack, and access site complications of 0.8%, 1.5%, and 3.8%, respectively. During a mean follow-up of 28 months the rate of restenosis (>70%) was 12%. Due to the overall low event rate no significant lesion or procedural risk factor for the development of restenosis could be identified.Conclusions:Stenosis and occlusion of the subclavian and innominate artery can be treated safely and successfully by endovascular therapy with excellent long-term patency. (Circ J 2015; 79: 537–543)

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Background:There are limited data on the relative efficacy of 1st- vs. 2nd-generation limus-eluting stents in bifurcation lesions.Methods and Results:Our analysis of a Korean multicenter registry for bifurcated coronary lesions enrolled 1,762 patients treated with 2nd-generation everolimus-eluting stent (EES, n=348) or 1st-generation sirolimus-eluting stents (SES, n=1,414). In the overall population, EES was comparable to SES regarding major adverse cardiac events (MACE: composite of cardiac death, nonfatal myocardial infarction, and target vessel revascularization (TVR)), cardiac death, and TVR rates within a 2-year follow-up. In 1:3 propensity score-matched populations, EES showed a significantly lower MACE rate compared with SES (HR [95% CI], 0.53 [0.29–0.97]; P=0.039), mainly through a reduction in repeat revascularization (HR [95% CI], 0.47 [0.24–0.92]; P=0.027). EES was superior to SES in reducing TVR in patients with left main (LM) lesions (HR [95% CI], 0.21 [0.06–0.67]; P=0.008) or in patients treated with 2-stent technique PCI (HR [95% CI], 0.28 [0.09–0.91]; P=0.035). There was no difference in clinical outcomes between 2 stents in a non-LM bifurcation lesion or in patients treated with a 1-stent technique.Conclusions:At 2-year follow-up, 1st- and 2nd-generation limus-eluting stents showed comparable clinical outcomes in general bifurcation lesions. EES was superior to SES after matching by propensity score, especially in patients with LM bifurcation or in those treated by a 2-stent technique. (Circ J 2015; 79: 544–552)

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Background:We conducted in vivo examinations of a newly designed stentless mitral valve (SMV), formed by suturing 2 leaflets with the “legs” serving as chorda tendinea, made from bovine pericardium, to a flexible ring.Methods and Results:Seven pigs underwent implantation of the SMV constructed with a 23-mm (n=5) or 25-mm (n=2) Duran ring. Baseline echocardiography examinations were used to evaluate the annular anteroposterior diameter, and distance between the mitral annulus (MA) and papillary muscles (PMs) to determine SMV-leg length. After removing the native valve, the SMV-legs were fixed to the anterior and posterior PMs, followed by fixation of the ring to the native MA. Immediately after surgery, all animals presented none or trivial mitral regurgitation, with mean and peak trans-SMV pressure gradient values of 1.9±0.8 and 6.0±3.1 mmHg, respectively. The mean length of the SMV-leg was 19.4±3.9 mm, which correlated with the distance between anterior and posterior MA-PM (r=0.96 and 0.94, respectively, P<0.01 for both). The discrepancy between the anteroposterior diameter of the ring (outside diameter) and that of the native valve was 1.0±2.9 mm, which correlated with the trans-SMV pressure gradient (r=0.81, P=0.025).Conclusions:In our preliminary study, the SMV demonstrated excellent diastolic inflow dynamics and closing function in vivo. Preoperative precise assessment of MV configuration may serve as a basis for selection of appropriate ring size and SMV-leg length. (Circ J 2015; 79: 553–559)

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Background:Although cardiopulmonary exercise (CPX) testing is an established tool for predicting survival in patients with heart failure (HF), its prognostic impact on explantation of left ventricular assist device (LVAD) was unknown.Methods and Results:We enrolled 33 patients who had undergone implantation of extracorporeal pulsatile flow LVAD and symptom-limited CPX testing at 3 months after operation, and who were followed between 2005 and 2014. Patients who received conversion to continuous flow LVAD were excluded. On Cox regression analysis, E1 (maximum load ≥51W; HR, 27.55), E2 (minute ventilation/carbon dioxide output [V̇E/V̇CO₂] slope ≤34; HR, 16.86), and E3 (peak oxygen consumption [PV̇O₂] ≥12.8 ml·kg^–1·min^–1; HR, 18.35) significantly predicted explantation expectancy during 2 years after LVAD implantation (P<0.05 for all). Explantation score, the sum of positive E1–3, significantly stratified 2-year cumulative explantation rate into low (0 points), intermediate (1–2 points), and high (3 points) expectancy groups (0%, 29%, and 86%, respectively, P<0.001). When the scoring system was used for 45 patients with continuous flow LVAD, the 2 patients who had explantation were assigned to the high expectancy group.Conclusions:Explantation score, calculated simply from 3 postoperative symptom-limited CPX testing parameters, is a novel tool to predict explantation expectancy of LVAD and to select good candidates for the weaning test. (Circ J 2015; 79: 560–566)

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Background:In practice, patients with acute aortic dissection (AAD) are generally divided into 2 groups according to the status of the false lumen: non-communicating or communicating. The similarities and differences between the 2 groups, however, have not been fully determined in a large population.Methods and Results:We studied 502 patients with Stanford type B AAD. Clinical background at symptom onset was compared, and similarities and differences characterized, for patients with non-communicating (NC group, n=288) vs. communicating (C group, n=214) false lumens. Time of day (00.00–06.00 hours, 06.00–12.00 hours, 12.00–18.00 hours, and 18.00–24.00 hours) and extent of physical activity (extreme exertion, slight exertion, at rest, and sleeping) at symptom onset were similar between groups. Patients in the NC group were older (mean age, 71±11 years vs. 64±14 years, P<0.01) and had lower prevalence of distally extended aortic dissection (26% vs. 8%, P<0.01) and deaths in hospital (2% vs. 7%, P=0.011) than those in the C group.Conclusions:At symptom onset, clinical circumstances and physical activity were similar between the groups, and old age and a background of DeBakey IIIa aortic dissection may be associated with determination of false lumen status. The outcome in the NC group was better than in the C group. (Circ J 2015; 79: 567–573)

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Background:The effectiveness of statins remains to be examined in patients with heart failure (HF) with preserved ejection fraction (EF).Methods and Results:Among 4,544 consecutive HF patients registered in the Chronic Heart Failure Registry and Analysis in the Tohoku district-2 (CHART-2) between 2006 and 2010, 3,124 had EF ≥50% (HFpEF; mean age 69 years; male 65%) and 1,420 had EF <50% (HF with reduced EF (HFrEF); mean age 67 years; male 75%). The median follow-up was 3.4 years. The 3-year mortality in HFpEF patients was lower in patients receiving statins [8.7% vs. 14.5%, adjusted hazard ratio (HR) 0.74; 95% confidence interval (CI), 0.58–0.94; P<0.001], which was confirmed in the propensity score-matched cohort (HR, 0.72; 95% CI, 0.49–0.99; P=0.044). The inverse probability of treatment weighted further confirmed that statin use was associated with reduced incidence of all-cause death (HR, 0.71; 95% CI, 0.62–0.82, P<0.001) and noncardiovascular death (HR, 0.53; 95% CI, 0.43–0.66, P<0.001), specifically reduction of sudden death (HR, 0.59; 95% CI, 0.36–0.98, P=0.041) and infection death (HR, 0.53; 95% CI, 0.35–0.77, P=0.001) in HFpEF. In the HFrEF cohort, statin use was not associated with mortality (HR, 0.87; 95% CI, 0.73–1.04, P=0.12), suggesting a lack of statin benefit in HFrEF patients.Conclusions:These results suggest that statin use is associated with improved mortality rates in HFpEF patients, mainly attributable to reductions in sudden death and noncardiovascular death. (Circ J 2015; 79: 574–582)

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Background:Chronic kidney disease is associated with sympathetic activation and muscle abnormalities, which may contribute to decreased exercise capacity. We investigated the correlation of renal function with peak exercise oxygen consumption (V̇O₂) in heart failure (HF) patients.Methods and Results:We recruited 2,938 systolic HF patients who underwent clinical, laboratory, echocardiographic and cardiopulmonary exercise testing. The patients were stratified according to estimated glomerular filtration rate (eGFR). Mean follow-up was 3.7 years. The primary outcome was a composite of cardiovascular death and urgent heart transplantation at 3 years. On multivariable regression, eGFR was predictor of peakV̇O₂(P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, B-type natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakV̇O₂<12 ml·kg⁻¹·min⁻¹was 1.75 (95% confidence interval (CI): 1.06–2.91; P=0.0292) in patients with eGFR ≥60, 1.77 (0.87–3.61; P=0.1141) in those with eGFR of 45–59, and 2.72 (1.01–7.37; P=0.0489) in those with eGFR <45 ml·min⁻¹·1.73 m⁻². The area under the receiver-operating characteristic curve for peakV̇O₂<12 ml·kg⁻¹·min⁻¹was 0.63 (95% CI: 0.54–0.71), 0.67 (0.56–0.78), and 0.57 (0.47–0.69), respectively. Testing for interaction was not significant.Conclusions:Renal dysfunction is correlated with peakV̇O₂. A peakV̇O₂cutoff of 12 ml·kg^–1·min^–1offers limited prognostic information in HF patients with more severely impaired renal function. (Circ J 2015; 79: 583–591)

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Background:There is ongoing controversy over whether neural or peripheral factors are the predominant cause of hypertension. The closed-loop negative feedback operation of the arterial baroreflex hampers understanding of how arterial pressure (AP) is determined through the interaction between neural and peripheral factors.Methods and Results:A novel analysis of an isolated open-loop baroreceptor preparation to examine sympathetic nervous activity (SNA) and AP responses to changes in carotid sinus pressure (CSP) in adult spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) was conducted. In the neural arc (CSP-SNA relationship), the midpoint pressure (128.9±3.8 vs. 157.9±8.1 mmHg, P<0.001) and the response range of SNA to CSP (90.5±3.7 vs. 115.4±7.6%/mmHg, P=0.011) were higher in SHR. In the peripheral arc (SNA-AP relationship), slope and intercept did not differ. A baroreflex equilibrium diagram was obtained by depicting neural and peripheral arcs in a pressure-SNA plane with rescaled SNA (% in WKY). The operating-point AP (111.3±4.4 vs. 145.9±5.2 mmHg, P<0.001) and SNA (90.8±3.2 vs. 125.1±6.9% in WKY, P<0.001) were shifted towards a higher level in SHR.Conclusions:The shift of the neural arc towards a higher SNA range indicated a predominant contribution to baroreflex resetting in SHR. Notwithstanding the resetting, the carotid sinus baroreflex in SHR preserved an ability to reduce AP if activated with a high enough pressure. (Circ J 2015; 79: 592–599)

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Background:The aim of the present study was to evaluate the feasibility of optical coherence tomography (OCT) for measurement of vessel area in coronary arteries with lipid-rich plaque as compared with intravascular ultrasound (IVUS).Methods and Results:We investigated 80 coronary artery segments with lipid-rich plaque on OCT and non-attenuated plaque on IVUS. According to the lipid arc on OCT, the plaques were classified into 4 groups: group 1, lipid arc ≤90°; group 2, 90°<lipid arc≤180°; group 3, 180°<lipid arc≤270°; group 4, lipid arc >270°. Vessel circular arcs that could not be identified due to OCT signal attenuation were interpolated using an approximating algorithm. OCT-measured vessel area was well-correlated with IVUS-measured vessel area (R=0.834, P<0.001). On Bland-Altman plot, there was a good agreement between OCT-measured vessel area and IVUS-measured vessel area, although mean difference and limits of agreement increased with increase of lipid arc (mean difference in groups 1–4: –0.21, –0.31, –1.02, and –2.13 mm²; lower limit: –1.49, –3.22, –5.24, and –9.25 mm²; and upper limit: 1.07, 2.60, 3.20, and 4.99 mm²). Intra-observer (R=0.97–0.99, P<0.001) and inter-observer (R=0.97–0.99, P<0.001) reproducibility for OCT measurement of vessel area was excellent.Conclusions:Like IVUS, OCT can be used to measure vessel area in coronary arteries with lipid-rich plaque. (Circ J 2015; 79: 600–606)

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Background:Coronary arterial segments distal to the severely stenotic lesion sometimes shrink as a result of decreased coronary flow. Pathological studies have shown that vessel shrinkage is accompanied by folding of the internal elastic membrane (IEM). A peri-medial high-echoic band (PHB) by intravascular ultrasound (IVUS) may represent folding of the IEM and therefore detect chronically shrunken coronary segments that have potential to enlarge subsequently.Methods and Results:IVUS imaging of the distal reference segments was performed in 27 patients after stenting. PHB was defined as a high-echoic band observed at the luminal side of the media. Serial (baseline and 9 months) changes in minimal lumen diameter (LD) were compared between those with (PHB group) and without PHB (non-PHB group). During follow-up, LD increased significantly in PHB group (1.2±0.3 vs. 1.7±0.5 mm, P=0.001) but not in the non-PHB group (2.0±0.7 vs. 2.1±0.7 mm, P=NS). Late lumen gain (LLG) was observed in 16 of the 27 (59%) lesions. Lesions with LLG showed a trend toward smaller baseline lumen cross-sectional area and significantly higher prevalence of PHB (88% vs. 18%, P=0.007). By multivariable logistic regression analysis, PHB was the only IVUS predictor of LLG.Conclusions:Presence of PHB on IVUS predicts chronic enlargement of the coronary segments distal to the stented lesion. (Circ J 2015; 79: 607–612)

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Background:We sought to identify the feasibility of speckle tracking echocardiography (STE) to predict cardiac resynchronization therapy (CRT) responders in a prospective multicenter study.Methods and Results:Patients who were newly implanted with a CRT device were enrolled. Time (T) from QRS to maximum peak radial and circumferential strain (CS) in 6 segments on the left ventricular (LV) short-axis plane, and to the maximum peak of longitudinal strain in 18 segments on 3 apical LV planes was measured (T_max). In segments with multiple peaks on the time-strain curves, time to the first peak (T_first) was also assessed. Difference in T between the earliest and latest segment and standard deviation (SD) of T in each strain component were assessed. CRT responders were defined as having LV end-systolic volume reduction >15% at 6 months after CRT. Clinical outcomes were assessed with a composite endpoint of death from cardiac causes or unplanned hospitalization for heart failure. Among 180 patients, 109 patients were identified as responders. T_first-SD of CS >116 ms was selected as the best independent predictor of CRT responders (P<0.001, hazard ratio=9.83, 95% confidence interval 3.78–25.6). In addition, T_first-SD of CS was associated with the clinical endpoints.Conclusions:This prospective multicenter study revealed the high feasibility of dyssynchrony assessment by STE, which may improve the ability to predict CRT responders. (Circ J 2015; 79: 613–622)

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Background:Myocardial perfusion imaging (MPI) may fail to detect balanced ischemia. We evaluated myocardial perfusion reserve (MPR) using Tl dynamic single-photon emission computed tomography (SPECT) and a novel cadmium zinc telluride (CZT) camera for predicting 3-vessel or left main coronary artery disease (CAD).Methods and Results:A total of 55 consecutive patients with suspected CAD underwent SPECT-MPI and coronary angiography. The MPR index was calculated using the standard 2-compartment kinetic model. We analyzed the utility of MPR index, other SPECT findings, and various clinical variables. On multivariate analysis, MPR index and history of previous myocardial infarction (MI) predicted left main and 3-vessel disease. The area under the receiver operating characteristic curve was 0.81 for MPR index, 0.699 for history of previous MI, and 0.86 for MPR index plus history of previous MI. MPR index ≤1.5 yielded the highest diagnostic accuracy. Sensitivity, specificity, and accuracy were 86%, 78%, and 80%, respectively, for MPR index, 64%, 76%, 73% for previous MI, and 57%, 93%, and 84% for MPR index plus history of previous MI.Conclusions:Quantification of MPR using dynamic SPECT and a novel CZT camera may identify balanced ischemia in patients with left main or 3-vessel disease. (Circ J 2015; 79: 623–631)

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Background:Benefit of β-blockers (BB) and angiotensin-converting-enzyme inhibitors (ACEI) on mortality following acute myocardial infarction (MI) is well demonstrated. This study assessed the impact of BB and ACEI doses administered following ST-elevation MI on mortality and outcome up to 1 year.Methods and Results:The French prospective observational cohort “RIMA” included 1,461 MI patients. Dosing of BB and ACEI given at 24 h and at time of discharge was assessed as follows: no treatment; <50% of target dose; or ≥50% of target dose. For in-hospital mortality, after MI, the use of BB in the first 24 h, but not ACEI, was associated with significantly lower event rate on multivariate analysis (OR, 5.78; 95% CI: 2.62–12.76, P<0.001). In contrast at 1 year, use of higher doses of ACEI, but not BB, was associated with significantly lower CV mortality, readmission for heart failure and the composite of CV mortality and readmission for heart failure (HR, 2.65; 95% CI: 1.32–5.31, P=0.006 for absence of ACEI at discharge).Conclusions:Prescription of BB in the first 24 h was independently associated with a lower in-hospital mortality following MI. There appeared to be a significant dose effect on outcome with regard to <50% vs. ≥50% of target dose, which requires confirmation in further large-scale clinical studies. (Circ J 2015; 79: 632–640)

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Background:Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) level is a reliable prognostic biomarker in acute coronary syndrome. However, it is unclear whether its plasma level at acute phase is related to the long-term prognosis in patients with ST-segment elevation acute myocardial infarction (STEMI).Methods and Results:We prospectively examined the relation between plasma sLOX-1 level on admission and prognosis in 153 consecutive STEMI patients admitted within 24 h of onset. Primary percutaneous coronary intervention was performed in 144 patients. The patients were divided into 2 groups by the median value (71 pg/ml) of plasma sLOX-1 level on admission [sLOX-1 level ≤71 pg/ml (n=77) and >71 pg/ml (n=76)], and were followed for median of 1,156 days. All-cause mortality and the combined endpoints of major adverse cardiovascular events (MACE) defined as cardiovascular mortality and recurrent MI were both significantly higher in patients with sLOX-1 values above median than in those below median (25.0% vs. 3.9%, P<0.001, and 19.4% vs. 6.5%, P=0.019 by log-rank test, respectively). Even after adjustment for confounders, a level of sLOX-1 above median was an independent predictor for all-cause mortality (hazard ratio (HR): 5.893; 95% confidence interval (CI): 1.665–20.854, P=0.006) and MACE (HR: 3.457; 95% CI: 1.164–10.270, P=0.030).Conclusions:Elevated plasma sLOX-1 level on admission independently predicts long-term all-cause mortality and MACE after STEMI. (Circ J 2015; 79: 641–648)

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Background:Cardiac resynchronization therapy (CRT) can result in functional improvement and reduced mortality in patients with medically refractory heart failure. Although CRT is reportedly effective in patients with congenital heart disease (CHD), it is still controversial in patients who have systemic right ventricle.Methods and Results:Twenty CHD patients treated with CRT since 2006 were divided into 3 groups based on systemic ventricular (sysV) morphology (7 with left ventricle [sLV], 7 with right ventricle [sRV], and 6 with unbalanced 2 ventricles as a single-ventricular physiology [sBV]). The acute effects of CRT on hemodynamics and sysV function before device implantation was retrospectively evaluated and the chronic (≥6 months) effects of CRT on late outcomes was assessed. In our CHD populations, sysV volume index was reduced from 139±41 to 118±33 ml/m²(P=0.04) after CRT, and there was significant improvement in B-type natriuretic peptide levels (from 341±384 to 160±152 pg/ml, P=0.01) and New York Heart Association (NYHA) functional class (from 2.1±0.6 to 1.8±0.7, P=0.02) on a late outcome. The sRV group did not show a late sysV volume reduction despite significant QRS shortening, and an increase of sysV peak dP/dt in the acute study differed from that of other groups.Conclusions:CRT improves late hemodynamic and functional status in sLV and sBV CHD patients with a dyssynchronized sysV. However, an acute CRT effect cannot guarantee long-term benefit in sRV patients. (Circ J 2015; 79: 649–655)

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Background:We prospectively investigated the prognostic value of the combined use of cardiac troponin T (TnT), B-type natriuretic peptide (BNP), and high-sensitivity C-reactive protein (CRP) for long-term mortality in hemodialysis (HD) patients.Methods and Results:Baseline measurements of TnT, BNP, and CRP were performed in 516 patients on chronic HD. Patients were followed up for 10 years. Using the Cox multivariate model with these 3 biomarkers as variables categorized into tertiles for mortality, a simplified score was obtained by underscoring individual biomarkers based on the adjusted hazard ratio (HR). The multimarker score was defined as the sum of these points. TnT, BNP, and CRP levels were individually independent predictors for mortality (P<0.05). Among low-risk (multimarker score <4), intermediate-risk (multimarker score 4–7), and high-risk (multimarker score ≥7) groups, 10-year survival rates were 83.3%, 54.3%, and 27.2% (P<0.0001), respectively. After adjusting for other confounders, the multimarker score had strong predictive power for mortality (HR: 4.26; P<0.0001 for high-risk vs. low-risk group). Furthermore, adding the multimarker score to a baseline model with established risk factors improved the C-index (P<0.01), net reclassification improvement (P<0.0001), and integrated discrimination improvement (P<0.0001) greater than that of any single biomarker or baseline model alone.Conclusions:The multimarker approach (ie, simultaneous assessment of TnT, BNP, and CRP, which individually independently predict prognosis) may improve the prediction of long-term mortality in HD patients. (Circ J 2015; 79: 656–663)

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Background:We examined the prevalence, predictors and prognostic impact of post-traumatic stress disorder (PTSD) after the Great East Japan Earthquake in patients with cardiovascular disease (CVD) in the CHART-2 study.Methods and Results:The prevalence of PTSD was 14.7% at 6 months after the Earthquake. Female sex, experiencing the Tsunami, property loss, poverty, and insomnia medication use were associated with PTSD. The patients with PTSD more frequently experienced a composite of death, acute myocardial infarction, stroke and heart failure (18.5% vs. 15.0%, P=0.035).Conclusions:PTSD was frequent in CVD patients after the Earthquake and had an adverse prognostic impact. (Circ J 2015; 79: 664–667)

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