Inflammation plays a significant role in a wide range of cardiovascular diseases (CVDs). The numerous implications of inflammation in all steps of CVDs, including initiation, progression and complications, have prompted the emergence of noninvasive imaging modalities as diagnostic, prognostic and monitoring tools. In this review, we first synthesize the existing evidence on the role of inflammation in vascular and cardiac diseases, in order to identify the main targets used in noninvasive imaging. We chose to focus on positron emission tomographic (PET) and magnetic resonance imaging (MRI) studies, which offer the greatest potential of translation and clinical application. We detail the main preclinical and clinical studies in the following CVDs: coronary and vascular atherosclerosis, abdominal aortic aneurysms, myocardial infarction, myocarditis, and acute heart transplant rejection. We highlight the potential complementary roles of these imaging modalities, which are currently being studied in the emerging technology of PET/MRI. Finally, we provide a perspective on innovations and future applications of noninvasive imaging of cardiovascular inflammation. (Circ J 2016; 80: 1269–1277)

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Antioxidants are expected to improve cardiovascular disease (CVD) by eliminating oxidative stress, but clinical trials have not shown promising results in chronic CVD. Animal studies have revealed that reactive oxygen species (ROS) exacerbate acute CVDs in which high levels of ROS are observed. However, ROS are also necessary for angiogenesis after ischemia, because ROS not only damage cells but also stimulate the cell signaling required for angiogenesis. ROS affect signaling by protein modifications, especially of cysteine amino acid thiols. Although there are several cysteine modifications, S-glutathionylation (GSH adducts; -SSG), a reversible cysteine modification by glutathione (GSH), plays an important role in angiogenic signal transduction by ROS. Glutaredoxin-1 (Glrx) is an enzyme that specifically removes GSH adducts in vivo. Overexpression of Glrx inhibits, whereas deletion of Glrx improves revascularization after mouse hindlimb ischemia. These studies indicate that increased levels of GSH adducts in ischemic muscle are beneficial in promoting angiogenesis. The underlying mechanism can be explained by multiple targets of S-gluathionylation, which mediate the angiogenic effects in ischemia. Increments in the master angiogenic transcriptional factor, HIF-1α, reduction of the anti-angiogenic factor sFlt1, activation of the endoplasmic reticulum Ca²⁺pump, SERCA, and inhibition of phosphatases may occur as a consequence of enhanced S-glutathionylation in ischemic tissue. In summary, inducing S-glutathionylation by inhibiting Glrx may be a therapeutic strategy to improve ischemic angiogenesis in CVD. (Circ J 2016; 80: 1278–1284)

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Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac arrhythmia disorder that is characterized by emotion- and exercise-induced polymorphic ventricular arrhythmias and may lead to sudden cardiac death (SCD). CPVT plays an important role in SCD in the young and therefore recognition and adequate treatment of the disease are of vital importance. In the past years tremendous improvements have been made in the diagnostic methods and treatment of the disease. In this review, we summarize the clinical characteristics, genetics, and diagnostic and therapeutic strategies of CPVT and describe the most recent advances and some of the current challenges. (Circ J 2016; 80: 1285–1291)

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Cardiac arrest, though not common during coronary angiography, is increasingly occurring in the catheterization laboratory because of the expanding complexity of percutaneous interventions (PCI) and the patient population being treated. Manual chest compression in the cath lab is not easily performed, often interrupted, and can result in the provider experiencing excessive radiation exposure. Mechanical cardiopulmonary resuscitation (CPR) provides unique advantages over manual performance of chest compression for treating cardiac arrest in the cardiac cath lab. Such advantages include the potential for uninterrupted chest compressions, less radiation exposure, better quality chest compressions, and less crowded conditions around the catheterization table, allowing more attention to ongoing PCI efforts during CPR. Out-of-hospital cardiac arrest patients not responding to standard ACLS therapy can be transported to the hospital while mechanical CPR is being performed to provide safe and continuous chest compressions en route. Once at the hospital, advanced circulatory support can be instituted during ongoing mechanical CPR. This article summarizes the epidemiology, pathophysiology and nature of cardiac arrest in the cardiac cath lab and discusses the mechanics of CPR and defibrillation in that setting. It also reviews the various types of mechanical CPR and their potential roles in and on the way to the laboratory. (Circ J 2016; 80: 1292–1299)

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Myocardial fibrosis is common in patients with congenital heart disease (CHD) and has been associated with arrhythmias, decreased functional status, and adverse ventricular mechanics. There are multiple types of myocardial fibrosis that occur in response to different pathophysiologic stimuli. Recent advances in imaging technology have made detection and quantification of the types of myocardial fibrosis possible. In this review, we describe the pathophysiology of myocardial fibrosis, examine the imaging techniques used to evaluate fibrosis, and discuss the relationship between myocardial fibrosis and clinical outcomes in CHD. (Circ J 2016; 80: 1300–1307)

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The 65^thAnnual Scientific Sessions of the American College of Cardiology (ACC) were held at McCormick Place, Chicago, from April 2–4, 2016. The ACC Scientific Sessions are one of the 2 major scientific cardiology meetings in the USA and one of the major scientific meetings of cardiology in the world. It had an attendance of 18,769 and over 2,000 oral and poster abstracts, including 8 late-breaking clinical trials. This report presents the key presentations and the highlights from the ACC Scientific Sessions 2016 in Chicago. (Circ J 2016; 80: 1308–1313)

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Background:The subcutaneous implantable cardioverter defibrillator (S-ICD) provides an attractive option for patients with congenital heart disease (CHD) in whom a transvenous defibrillator is contraindicated. Given the unusual cardiac anatomy and repolarization strain, the surface electrocardiogram (ECG) is frequently abnormal, potentially increasing the screen failure rate.Methods and Results:We prospectively screened 100 adult CHD patients regardless of the presence of clinical indication for ICD utilizing a standard left sternal lead placement, as well as a right parasternal position. Baseline patient and 12-lead ECG characteristics were examined to assess for predictors of screen failure. Average patient age was 48±14 years, average QRS duration was 134±37 ms, and 13 patients were pacemaker dependent. Using the standard left parasternal electrode position, 21 patients failed screening. Of these 21 patients with screen failure, 9 passed screening with the use of right parasternal electrode positioning, reducing screening failure rate from 21% to 12%. QT interval and inverted T wave anywhere in V2–V6 leads were found to be independent predictors of left parasternal screening failure (P=0.01 and P=0.04, respectively).Conclusions:Utilization of both left and right parasternal screening should be used in evaluation of CHD patients for S-ICD eligibility. ECG repolarization characteristics were also identified as novel predictors of screening failure in this group. (Circ J 2016; 80: 1328–1335)

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Background:Beat-to-beat variability in ventricular repolarization (BVR) associates with increased arrhythmic risk. Proarrhythmic remodeling in the dog with chronic AV-block (CAVB) compromises repolarization reserve and associates with increased BVR, which further increases upon dofetilide infusion and correlates with Torsade de Pointes (TdP) arrhythmias. It was hypothesized that these pro-arrhythmia-associated increases in BVR are induced by beat-to-beat variability in preload.Methods and Results:Left ventricular monophasic action potential duration (LVMAPD) was recorded in acute (AAVB) and CAVB dogs, before and after dofetilide infusion. BVR was quantified as short-term variability of LVMAPD. The PQ-interval was controlled by pacing: either a constant or an alternating preload pattern was established, verified by PV-loop. The effect of the stretch-activated channel blocker, streptomycin, on BVR was evaluated in a second CAVB group. At alternating preload only, BVR was increased after proarrhythmic remodeling (0.45±0.14 ms AAVB vs. 2.2±1.1 ms CAVB, P<0.01). At CAVB, but not at AAVB, dofetilide induced significant proarrhythmia. Preload variability augmented the dofetilide-induced BVR increase at CAVB (+1.5±0.8 ms vs. +0.9±0.9 ms, P=0.058). In the second group, the increase in baseline BVR by alternating preload (0.3±0.03 ms to 1.0±0.8 ms, P<0.01) was abolished by streptomycin (0.5±0.2 ms, P<0.05).Conclusions:In CAVB dogs, the inverse relation between BVR and repolarization reserve originates from an augmented sensitivity of ventricular repolarization to beat-to-beat preload changes. Stretch-activated channels appear to be involved in the mechanism of BVR. (Circ J 2016; 80: 1336–1345)

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Background:Atrial fibrillation (AF) begets AF in part due to atrial remodeling, the molecular mechanisms of which have not been completely elucidated. This study was conducted to identify microRNA(s) responsible for electrical remodeling in AF.Methods and Results:The expression profiles of 1205 microRNAs, in cardiomyocytes from patients with persistent AF and from age-, gender-, and cardiac function-matched control patients with normal sinus rhythm, were examined by use of a microRNA microarray platform. Thirty-nine microRNAs differentially expressed in AF patients’ atria were identified, including miR-30d, as a candidate responsible for ion channel remodeling by in silico analysis. MiR-30d was significantly upregulated in cardiomyocytes from AF patients, whereas the mRNA and protein levels ofCACNA1C/Cav1.2 andKCNJ3/Kir3.1, postulated targets of miR-30d, were markedly reduced.KCNJ3/Kir3.1 expression was downregulated by transfection of the miR-30 precursor, concomitant with a reduction of the acetylcholine-sensitive inward-rectifier K⁺current (I_K.ACh).KCNJ3/Kir3.1 (but notCACNA1C/Cav1.2) expression was enhanced by the knockdown of miR-30d. The Ca²⁺ionophore, A23187, induced a dose-dependent upregulation of miR-30d, followed by the suppression ofKCNJ3mRNA expression. Blockade of protein kinase C signaling blunted the [Ca²⁺]_i-dependent downregulation of Kir3.1 via miR-30d.Conclusions:The downward remodeling ofI_K.AChis attributed, at least in part, to deranged Ca²⁺handling, leading to the upregulation of miR-30d in human AF, revealing a novel post-transcriptional regulation ofI_K.ACh. (Circ J 2016; 80: 1346–1355)

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Background:The aim of this study was to assess the risk factors for dilatation of the aorta over time in Japanese patients with bicuspid aortic valve (BAV) undergoing aortic valve replacement (AVR), focusing on the possible impact of valve fusion phenotype.Methods and Results:Of 167 BAV patients undergoing AVR (24% of overall AVR patients, n=702), 135 patients in whom surgical intervention for the aorta was not undertaken were focused on (74 had right-left fusion and 61 non-right-left fusion type). During a mean follow up of 5.2 years, aortic growth rate (mm/year) of the ascending aorta was similar between the valve phenotype. In multivariate logistic regression, the presence of aortic regurgitation > moderate was significantly associated with a rapid dilatation of the ascending aorta, defined as >0.7 mm/year (odds ratio 2.1, 95% confidence interval 1.2–3.7, P=0.03). Independent predictors of dilatation of the aorta up to more than 45 mm were: a diameter of the ascending aorta >40 mm at the time of surgery (odds ratio 3.7, 95% confidence interval 1.2–11.4, P=0.02) and length of follow up (odds ratio 1.3-increase per year, 95% confidence interval 1.0–1.5, P=0.04).Conclusions:The presence of aortic regurgitation and the ascending aorta of >40 mm at the time of surgery emerged as significant predictors of dilatation of the aorta after AVR but valve fusion phenotype was not. (Circ J 2016; 80: 1356–1361)

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Background:Significant tricuspid valve regurgitation (TR) is considered a poor prognosis factor for patients with hypoplastic left heart syndrome (HLHS). Performing a tricuspid valve plasty (TVP) during Norwood Stage I palliation (S1P) has rarely been reported. We report mid-term results of performing TVP during Norwood S1P.Methods and Results:Between December 2004 and July 2013, 48 patients with HLHS or variants underwent Norwood S1P and of them 11 (23%) with TR of a moderate degree or above underwent TVP. The estimated 1- and 5-year survival rates for Norwood S1P were 61% and 54%, respectively. Among the 11 patients with TVP, there were 2 early deaths. Nine patients had a Stage II operation and 3 of them died late. Four patients completed a Fontan operation, and 2 were waiting. Using Cox regression analysis, lower body weight, presence of intact atrial septum, and preoperative cardiopulmonary resuscitation were factors associated with increased risk for death. Patients with significant TR and undergoing TVP during Norwood S1P had a similar survival curve to those without significant TR.Conclusions:Our results for TVP performed during Norwood S1P were encouraging. They suggested that aggressive TVP is warranted in Norwood S1P when primary heart transplantation is not available. Further study is required to determine if the strategy does improve the results for patients with HLHS and TR initially. (Circ J 2016; 80: 1362–1370)

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Background:Continuous-flow left ventricular assist devices (CF-LVAD) may induce pathological changes to the aortic wall and aortic valve. We assessed histological changes in the relevant anatomic structures exposed to continuous flow over time and compared the histological results with clinical features in patients supported with CF-LVAD.Methods and Results:A retrospective histological analysis was performed of 38 explanted hearts supported with CF-LVAD from patients who received heart transplantation between July 2003 and February 2014. Sections of formalin-fixed paraffin-embedded tissue showing the continuity of aortic wall and left-sided valves were examined histologically. Thickness of aorta, aortic root and aortic valve as well as 3 layers of the aortic cusps were measured individually on Elastica van Gieson-stained slides using specific software. Clinical parameters concerning aortic valve dysfunction were evaluated and validated against the histology. The aortic valve spongiosa and fibrosa layers showed no significant differences in thickness with regard to support duration or occurrence of aortic insufficiency. Longer CF-LVAD support duration correlated with a thinner aortic valve ventricularis layer (r_S=–0.496).Conclusions:Long-term CF-LVAD support appears to cause involution of the ventricularis layer of the aortic valve cusp, consistent with more pronounced degenerative change with longer LVAD exposure, which may be explained by continuous coaptation of the cusps. (Circ J 2016; 80: 1371–1377)

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Background:Home oxygen therapy (HOT) is used to adapt patients to the bidirectional Glenn (BDG) physiology. However, the precise cardiovascular effect of oxygen inhalation is still unknown. We used phase-contrast MRI to evaluate the cardiovascular effects of oxygen inhalation in young patients with BDG physiology.Methods and Results:The 56 sessions of cardiac MRI were performed in 36 patients with BDG circulation. Oxygen saturation (SpO₂) and heart rate (HR) were monitored under both room air and nasal 100% oxygen inhalation, and the blood flow volumes of the ascending aorta (AA), superior vena cava (SVC), and inferior vena cava (IVC) were measured by phase-contrast MRI. Systemic-to-pulmonary collateral flow (SPCF) volumes were calculated by subtracting the sum of flow volumes through the SVC and IVC from the flow volume through the AA, and used for further comparative examination. Under nasal oxygen inhalation, SpO₂significantly increased from 82% to 89%, while HR decreased from 115 to 110 beats/min. AA (5.0 vs. 4.9 L·min^–1·m^–2), SVC (1.85 vs. 1.77 L·min^–1·m^–2), and systemic blood flow volume (=SVC+IVC) significantly decreased (3.60 vs. 3.46 L·min^–1·m^–2). In contrast, SPCF and the pulmonary-to-systemic blood flow ratio (Qp/Qs) remained unchanged.Conclusions:Oxygen inhalation improved arterial blood oxygenation and lowered HR in patients with BDG circulation without an increase in Qp/Qs. HOT would be protective of the cardiovascular system in patients with BDG circulation. (Circ J 2016; 80: 1378–1385)

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Background:Global risk assessment for the prevention of atherosclerotic cardiovascular diseases helps guide the intensity of behavioral and pharmacological interventions.Methods and Results:The Japan Public Health Center-based prospective (JPHC) Study Cohort II (age range: 40–69 years at baseline in 1993–1994, n=15,672) was used to derive the risk equations for coronary artery disease (CAD) and ischemic stroke incidence via hazard regression. The model discrimination was evaluated by the area under the receiver-operating curve (AUC), and model goodness-of-fit by the Grønnesby-Borgan chi-squared statistic. During a mean of 16.4 years of follow up, 192 incident CAD cases and 552 ischemic stroke cases occurred. Variables selected for the CAD equation were age, sex, current smoking, systolic blood pressure, antihypertensive medication use, diabetes, and high-density lipoprotein cholesterol (HDLC) and non-HDLC. The same variables, except non-HDLC, were selected for the ischemic stroke equation. The equations discriminated incidence reasonably well (AUC: 0.81 for CAD, 0.78 for ischemic stroke). The AUC of the equation applied externally to Cohort I (n=11,598) was also good: 0.77 and 0.76 for CAD and ischemic stroke, respectively. Risk calculator application and color charts to visualize estimated risk according to the combinations of risk factors were prepared.Conclusions:Risk equations were developed to estimate the 10-year probability of CAD and ischemic stroke in Japanese people, using variables that are routinely obtained. (Circ J 2016; 80: 1386–1395)

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Background:It remains to be elucidated whether addition of renin-angiotensin-aldosterone system (RAAS) inhibitors and/or β-blockers to loop diuretics has a beneficial prognostic impact on chronic heart failure (CHF) patients.Methods and Results:From the Chronic Heart failure Analysis and Registry in the Tohoku district 2 (CHART-2) Study (n=10,219), we enrolled 4,134 consecutive patients with symptomatic stage C/D CHF (mean age, 69.3 years, 67.7% male). We constructed Cox models for composite of death, myocardial infarction, stroke and HF admission. On multivariate inverse probability of treatment weighted (IPTW) Cox modeling, loop diuretics use was associated with worse prognosis with hazard ratio (HR) 1.28 (P<0001). Furthermore, on IPTW multivariate Cox modeling for multiple treatments, both low-dose (<40 mg/day) and high-dose (≥40 mg/day) loop diuretics were associated with worse prognosis with HR 1.32 and 1.56, respectively (both P<0.001). Triple blockade with RAS inhibitor(s), mineral corticoid (aldosterone) receptor antagonist(s) (MRA), and β-blocker(s) was significantly associated with better prognosis in those on low-dose but not on high-dose loop diuretics.Conclusions:Chronic use of loop diuretics is significantly associated with worse prognosis in CHF patients in a dose-dependent manner, whereas the triple combination of RAAS inhibitor(s), MRA, and β-blocker(s) is associated with better prognosis when combined with low-dose loop diuretics. (Circ J 2016; 80: 1396–1403)

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Background:Obstructive sleep apnea (OSA) is associated with activation of the sympathetic nervous system, and patients with this condition often experience elevated blood pressure (BP), increased BP variability, and nocturnal BP surges.Methods and Results:The SYMPLICITY HTN-3 trial was a large prospective, randomized, blinded, sham-controlled trial of renal denervation for treatment of uncontrolled, apparently treatment-resistant hypertension. In a post hoc analysis, we examined the effect of renal denervation vs. sham control on office and ambulatory (including nocturnal) systolic BP in patients with and without OSA. 26% (94/364) of renal denervation subjects and 32% (54/171) of sham control subjects had OSA. Baseline office and nighttime systolic BP values were similar in both arms, including in subjects with and without OSA. Compared with sham control, renal denervation reduced the 6-month office systolic BP in subjects with (−17.0±22.4 vs. −6.3±26.1 mmHg, P=0.01) but not in subjects without OSA (−14.7±24.5 vs. −13.4±26.4 mmHg, P=0.64), P=0.07 for the interaction between treatment arm and OSA status. In those with sleep apnea, renal denervation was also associated with a reduction in maximum (−4.8±21.8 vs. 4.5±24.6 mmHg, P=0.03) and average peak (−5.6±20.4 vs. 3.2±22.4 mmHg, P=0.02) nighttime systolic BP.Conclusions:OSA subjects appeared to be responsive to renal denervation therapy. However, this hypothesis requires prospective testing. (Circ J 2016; 80: 1404–1412)

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Background:Target lesion calcification is known to influence percutaneous coronary intervention. We evaluated the effects of rotational atherectomy (RA) and subsequent balloon angioplasty on calcified coronary lesions using optical coherence tomography (OCT).Methods and Results:Thirty-seven calcified lesions in 36 patients were treated with RA followed by balloon angioplasty and stent implantation. In all patients, serial OCT images obtained after RA, after balloon angioplasty, and after stent implantation were analyzed at 1-mm intervals. The arc and thickness of the calcium component were measured after RA. The formation of calcium cracks was assessed after balloon angioplasty. A total of 625 segments were analyzed. The formation of calcium crack after balloon angioplasty was associated with greater stent cross-sectional area (7.38±1.92 vs. 7.13±1.68 mm², P=0.035) as well as greater lumen gain (3.89±1.53 vs. 3.40±1.46 mm², P<0.001). Segments with calcium cracks after angioplasty had a larger median calcium arc (360°, IQR, 246–360° vs. 147°, IQR, 118–199°, P<0.001) and a thinner calcium thickness (0.53±0.28 vs. 1.02±0.42 mm, P<0.001) than those without. The optimal thresholds of calcium arc and calcium thickness for the prediction of cracks were 227° and 0.67 mm, respectively.Conclusions:Larger calcium arc and thinner calcium thickness were associated with formation of calcium crack. Presence of calcium crack was the important determinant of optimal stent expansion. (Circ J 2016; 80: 1413–1419)

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Background:We hypothesized the cardio-ankle vascular stiffness index (CAVI) could predict future cardiovascular events.Methods and Results:We enrolled 288 consecutive patients with acute coronary syndrome (ACS) who underwent CAVI measurement soon after the onset of ACS. Exclusion criteria were as follows: unable to detect significant stenosis by coronary angiography, severe aortic insufficiency, peripheral artery disease, atrial fibrillation (AF), informed consent was not given. We divided the patients into 2 groups according to the cutoff value of CAVI determined by receiver-operating characteristics curve for the prediction of cardiovascular events: low CAVI group, 135 patients with CAVI ≤8.325; high CAVI group, 153 patients with CAVI >8.325. Patients were followed up for a median period of 15 months. The primary and secondary endpoints were the incidence of cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke), and nonfatal ischemic stroke. Of the 288 patients, cardiovascular events occurred in 19 patients (6.6%). The Kaplan-Meier estimate of the event-free rate revealed cardiovascular events occurred more frequently in the high CAVI group than in the low CAVI group (log-rank, P<0.001). Multiple adjusted Cox proportional hazards analysis, including age, indicated the high CAVI group was an independent predictor of cardiovascular events (hazard ratio [HR] 18.00, P=0.005), and nonfatal ischemic stroke (HR 9.371, P=0.034).Conclusions:High CAVI is an independent predictor of cardiovascular events and nonfatal ischemic stroke in patients with ACS. (Circ J 2016; 80: 1420–1426)

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Background:The Korea Acute Myocardial Infarction Registry (KAMIR)-National Institutes of Health (NIH) registry has the aim of evaluating the clinical characteristics, management, and long-term outcomes of patients with acute myocardial infarction (AMI) in Korea.Methods and Results:Patients hospitalized for AMI in 20 tertiary university hospitals in Korea have been enrolled since November 2011. The study is expected to complete the scheduled enrollment of approximately 13,000 patients in October 2015, and follow-up duration is up to 5 years for each patient. As of October 2015, an interim analysis of 13,623 subjects was performed to understand the baseline clinical profiles of the study population. The mean age was 64.1 years; 73.5% were male; and 48.2% were diagnosed with ST-segment elevation AMI. Hypertension is a leading cause of AMI in Korea (51.2%), followed by smoking (38.5%) and diabetes mellitus (28.6%). Percutaneous coronary intervention was performed in 87.4% and its success rate was very high (99.4%). In-hospital, 1-year, and 2-year mortality rates were 3.9%, 4.3%, and 8.6%, respectively. The rates of major adverse cardiac events at 1 and 2 years were 9.6% and 18.8%, respectively.Conclusions:This analysis demonstrated the clinical characteristics of Korean AMI patients in comparison with those of other countries. It is necessary to develop guidelines for Asian populations to further improve their prognosis. (Circ J 2016; 80: 1427–1436)

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Background:Total bilirubin (TB) concentration is inversely associated with stable coronary artery disease, but there have been few studies on initial TB in patients with ST-segment elevation myocardial infarction (STEMI).Methods and Results:A total of 1,111 consecutive patients with STEMI undergoing primary percutaneous coronary intervention (PCI) with drug-eluting stents (DES) were divided into a high TB group (n=295) and a low TB group (n=816) according to the optimal cut-off 0.79 mg/dl. The high TB group had a higher rate of in-hospital major adverse cardiac events (MACE), a composite of cardiac death, non-fatal MI, and definite/probable stent thrombosis (14.2% vs. 4.2%, P<0.001) and cardiac death (13.9% vs. 3.9%, P<0.001) compared with the low TB group. The 30-day MACE-free survival rate was also significantly different between the groups (P<0.001, log-rank test). On multivariate Cox regression, initial high TB was a significant predictor of in-hospital MACE (HR, 2.69; 95% CI: 1.67–4.34, P=0.010) and of cardiac death (HR 2.72, 95% CI: 1.67–4.44, P=0.012). Adding initial TB to TIMI risk score significantly improved prediction for in-hospital MACE according to net reclassification improvement (NRI=5.2%, P=0.040) and integrated discrimination improvement (IDI=0.027, P=0.006).Conclusions:Initial TB is a powerful prognostic marker, and inclusion of this can improve prediction of in-hospital MACE in patients with STEMI undergoing primary PCI with DES. (Circ J 2016; 80: 1437–1444)

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Background:There is no definite consensus regarding the management of symptomatic isolated celiac artery dissection (ICAD), and the effect of conservative medical treatment has never been evaluated.Methods and Results:We enrolled 13 consecutive symptomatic ICAD patients without signs of arterial rupture between 2006 and 2015. All patients received noninvasive conservative medical treatment. The epidemiology, radiological findings and prognostic effect of conservative medical treatment on outcomes were retrospectively assessed. ICAD usually developed in middle-aged men around 50 years old who had a history of smoking. The patients typically presented with acute continuous epigastric pain at rest and with abdominal tenderness on physical examination. On enhanced computed tomography at presentation, the false lumen was found to be double-barreled in 2 patients (15.4%), partially thrombosed in 1 (7.7%), and completely thrombosed in 10 (76.9%). Dissection of associated branches was found in the left gastric artery in 1 patient (7.7%), common hepatic artery in 5 (38.5%), and splenic artery in 7 patients (53.8%). Malperfusion was not found in the stomach or liver but was found in the spleen in 4 patients (30.8%). During a median follow-up period of 376 (165–602) days, all patients were alive without any antiplatelet, anticoagulant, endovascular or surgical treatment.Conclusions:Symptomatic ICAD without arterial rupture can be safely treated with conservative medical therapy over the short term. (Circ J 2016; 80: 1445–1451)

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Background:Spontaneous isolated superior mesenteric artery (SMA) dissection is a rare condition, and its clinical and angiographic courses are poorly defined. We aimed to monitor the morphological characteristics of spontaneous isolated SMA dissection using computed tomography (CT) over 2 years of follow-up, including the recovery process via vascular remodeling, and identify the factors that affect vascular remodeling using univariate analysis.Methods and Results:We retrospectively reviewed the medical records and morphological findings of 59 consecutive patients with spontaneous isolated SMA dissection between October 2007 and July 2014, which included 36 symptomatic and 23 asymptomatic patients. Surgical intervention with open laparotomy was required in 3 patients during the follow-up period; 41 patients who received conservative treatment were followed up over 2 years with regular CT. Complete remodeling was achieved in 16 of 25 symptomatic patients who were treated conservatively (64.0%). A patent false lumen and aneurysmal formation on an initial CT scan were identified as negative factors that affected remodeling in patients with spontaneous isolated SMA dissection.Conclusions:Conservative management of spontaneous isolated SMA dissection is associated with a good prognosis, both clinically and morphologically. Surgical intervention is only required in patients with severe intestinal ischemia or rapid aneurysmal enlargement. (Circ J 2016; 80: 1452–1459)

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Background:There is currently no positive opinion regarding infrapopliteal revascularization for intermittent claudication (IC) in any guidelines. The aim of this study was to analyze the outcomes of infragenicular bypass and verify the adequacy of tibial artery bypass for IC.Methods and Results:Over a 21-year period, 58 below-knee popliteal artery (BKPOP) bypasses and 35 tibial artery bypasses were performed for IC caused by arteriosclerosis obliterans. Graft patency and major amputation (MA) were examined as primary endpoints and the predictor of each outcome was estimated by multivariate analysis. The primary patency (PP), secondary patency (SP), and freedom from MA (ffMA) rates of a prosthetic/vein graft in all cases at 5 years were 19/68%, 22/86%, and 78/100% (P<0.01 in all). Limited to vein graft cases, PP and SP rates of popliteal/tibial bypass at 5 years were 73/62% (P=0.32) and 92/80% (P=0.22), respectively. In tibial artery bypass with a vein graft, the PP and SP rates of a single saphenous vein/spliced vein graft at 5 years were 71/46% (P=0.11) and 89/61% (P=0.03). A prosthetic graft was a common negative predictor for graft patency and MA by multivariate analysis.Conclusions:Tibial artery bypass is an acceptable treatment option for IC when a single saphenous vein can be harvested as a graft conduit. (Circ J 2016; 80: 1460–1469)

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Background:It remains to be determined whether balloon pulmonary angioplasty (BPA) improves biventricular cardiac functions and pulmonary flow in patients with chronic thromboembolic pulmonary hypertension (CTEPH).Methods and Results:We enrolled 30 consecutive patients with inoperable CTEPH who underwent BPA, and carried out serial cardiac magnetic resonance imaging (CMR; M/F, 9/21; median age, 65.2 years). No patient died during the treatment or follow-up period. BPA significantly improved WHO functional class (III/IV, 83.0 to 4.0%), 6-min walking distance (330.2±168.7 to 467.3±114.4 m), mean pulmonary artery pressure (40.8±10.7 to 23.2±4.94 mmHg), pulmonary vascular resistance (9.26±4.19 to 3.35±1.40 WU) and cardiac index (2.19±0.64 to 2.50±0.57 L·min·m²; all P<0.01). CMR also showed improvement of right ventricular (RV) ejection fraction (EF; 41.3±12.4 to 50.7±8.64%), left ventricular (LV) end-diastolic volume index (72.1±14.0 to 81.6±18.6 ml/m²) and LV stroke volume index (41.0±9.25 to 47.8±12.3 ml/m²; all P<0.01). There was a significant correlation between change in RVEF and LVEF (Pearson’s r=0.45, P=0.01). Average velocity in the main pulmonary artery was also significantly improved (7.50±2.43 to 9.79±2.92 cm/s, P<0.01).Conclusions:BPA improves biventricular functions and pulmonary flow in patients with inoperable CTEPH. (Circ J 2016; 80: 1470–1477)

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Background:Macitentan is a novel, dual endothelin receptor antagonist with sustained receptor binding, used for the long-term treatment of pulmonary arterial hypertension (PAH). In the present study, we assessed the efficacy and safety of macitentan in Japanese patients with PAH.Methods and Results:Macitentan was administered at a once-daily dose of 10 mg in 30 patients. The primary endpoint was change in pulmonary vascular resistance (PVR) from baseline to week 24. Change to week 24 in the other hemodynamic parameters, 6-min walk distance (6MWD), World Health Organization (WHO) functional class, and plasmaN-terminal pro-brain natriuretic peptide (NT-pro-BNP), as well as time to clinical deterioration up to week 52 were also assessed as secondary endpoints. In the 28 patients on per-protocol analysis, PVR decreased from 667±293 to 417±214 dyn·sec·cm^–5(P<0.0001). 6MWD increased from 427±128 to 494±116 m (P<0.0001). WHO functional class improved in 13 patients (46.4%) and was maintained in 15 patients (53.6%), and NT-pro-BNP was reduced by 18% (P<0.0001). The favorable treatment effect on PVR was apparent regardless of concomitant therapy for PAH.Conclusions:Macitentan was efficacious and well tolerated and improved the hemodynamic parameters, exercise capacity, symptoms, and clinical biomarkers in Japanese PAH patients. Macitentan can be a valuable therapeutic option for Japanese patients with PAH. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-121986].) (Circ J 2016; 80: 1478–1483)

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