Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 79 , Issue 6
Showing 1-42 articles out of 42 articles from the selected issue
Message From the Editor-in-Chief
Reviews
  • Siobhan M. Craige, Shashi Kant, John F. Keaney Jr
    Type: REVIEW
    2015 Volume 79 Issue 6 Pages 1145-1155
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: May 18, 2015
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    Endothelial function is largely dictated by its ability to rapidly sense environmental cues and adapt to these stimuli through changes in vascular tone, inflammation/immune recruitment, and angiogenesis. When any one of these abilities is compromised, the endothelium becomes dysfunctional, which ultimately leads to disease. Reactive oxygen species (ROS) have been established at the forefront of endothelial dysfunction; however, more careful examination has demonstrated that ROS are fundamental to each of the sensing/signaling roles of the endothelium. The purpose of this review is to document endothelial ROS production in both disease and physiological adaptation. Through understanding new endothelial signaling paradigms, we will gain insight into more targeted therapeutic strategies for vascular diseases. (Circ J 2015; 79: 1145–1155)
  • Karl B Kern
    Type: REVIEW
    2015 Volume 79 Issue 6 Pages 1156-1163
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: April 16, 2015
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    The post-cardiac arrest syndrome is a complex, multisystems response to the global ischemia and reperfusion injury that occurs with the onset of cardiac arrest, its treatment (cardiopulmonary resuscitation) and the re-establishment of spontaneous circulation. Regionalization of post-cardiac arrest care, utilizing specified cardiac arrest centers (CACs), has been proposed as the best solution to providing optimal care for those successfully resuscitated after out-of-hospital cardiac arrest. A multidisciplinary team of intensive care specialists, including critical care/pulmonologists, cardiologists (general, interventional, and electrophysiology), neurologists, and physical medicine/rehabilitation experts, is crucial for such centers. Particular attention to the timely initiation of targeted temperature management and early coronary angiography/percutaneous coronary intervention is best provided by such CACs. A State-wide program of CACs was started in Arizona in 2007. This is a voluntary program, whereby medical centers agree to provide all resuscitated cardiac arrest patients brought to their facility with state-of-the-art post-resuscitation care, including targeted temperature management for comatose patients and strong consideration for emergent coronary angiography for all patients with a likely cardiac etiology for their cardiac arrest. Survival improved by more than 50% at facilities that became CACs with a commitment to provide aggressive post-resuscitation care to all such patients. Providing aggressive, post-resuscitation care is the next real opportunity to increase long-term survival for cardiac arrest patients. (Circ J 2015; 79: 1156–1163)
  • Carmelo Grasso, Davide Capodanno, Corrado Tamburino, Yohei Ohno
    Type: REVIEW
    2015 Volume 79 Issue 6 Pages 1164-1171
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: May 01, 2015
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    Transcatheter mitral valve intervention has emerged as an effective treatment option for symptomatic severe mitral regurgitation in patients considered to be inoperable or at high operative risk for surgical mitral valve surgery. Most transcatheter approaches are modifications of existing surgical approaches. Transcatheter edge-to-edge mitral valve repair with the MitraClip system has the largest clinical experience to date, as it offers a sustained clinical benefit in selected patients. This review aims to provide an up-to-date overview of transcatheter mitral valve interventions, including leaflet repair, annuloplasty, and mitral valve implantation. (Circ J 2015; 79: 1164–1171)
  • Sukhjinder S Nijjer, Sayan Sen, Ricardo Petraco, Justin ER Davies
    Type: REVIEW
    2015 Volume 79 Issue 6 Pages 1172-1184
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: April 13, 2015
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    Pressure-wire technology, most typically fractional flow reserve (FFR), has provided interventional cardiologists with a means of determining the physiological importance of a stenosis during angiography. There has been renewed interest in coronary physiology in the light of guideline recognition, ongoing clinical research and new technologies changing the paradigm of how assessment is performed in the catheter laboratory. We reflect on FFR, with regards the potential effects of changing hemodynamics on FFR and the latest evidence with regards to outcomes. We also review the instantaneous wave-free ratio (iFR), a new pressure-only index, measured at rest, that is under active evaluation in several international randomized controlled trials. We review the accumulated evidence and discuss the important physiological concepts between pressure and flow that underlie the approach to using resting indices. Finally we investigate future developments, including physiological mapping with iFR-Pullback and the potential to predict the hemodynamic effect of stenting. (Circ J 2015; 79: 1172–1184)
  • Tadashi Nakajima, Yoshiaki Kaneko, Masahiko Kurabayashi
    Type: REVIEW
    2015 Volume 79 Issue 6 Pages 1185-1192
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: April 30, 2015
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    Patients with inherited arrhythmia syndromes, such as long QT syndrome, Brugada syndrome, early repolarization syndrome, catecholaminergic polymorphic ventricular tachycardia, and their latent forms, are at risk for fatal arrhythmias. These diseases are typically associated with genetic mutations that perturb cardiac ionic currents. The analysis of cardiac events by genotype-phenotype correlation studies has revealed that fatal arrhythmias in some genotypes are triggered by physical or emotional stress, and those in the others are more likely to occur during sleep or at rest. Thus, the risk stratification and management of affected patients differ strikingly according to the genetic variant of the inherited arrhythmia syndrome. Risk stratification may be further refined by considering the precipitating factors, such as drugs, bradycardia, electrolyte disturbances, fever, and cardiac memory. Moreover, an increasing number of studies imply that the susceptibility of fatal arrhythmias in patients with acute coronary syndrome or takotsubo cardiomyopathy is at least partly ascribed to the genetic variants causing inherited arrhythmia syndromes. In this article, we review the recent advances in the understanding of the molecular genetics and genotype-phenotype correlations in inherited arrhythmia syndromes and consider the triggers and precipitating factors for fatal arrhythmias in these disorders. Further studies to explore the triggers and precipitating factors specific to the genotypes and diseases are needed for better clinical management. (Circ J 2015; 79: 1185–1192)
2015 ACC Report
  • Toyoaki Murohara
    Type: 2015 ACC REPORT
    2015 Volume 79 Issue 6 Pages 1193-1198
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: May 11, 2015
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    The 64thAnnual Scientific Sessions and Exposition of the American College of Cardiology (ACC) were held at the San Diego Convention Center from March 14–16, 2015. The ACC Scientific Sessions are 1 of 2 major scientific cardiology meetings in the United States, with nearly 20,000 attendees, including 15,000 cardiovascular professionals. There were over 2,100 oral and poster abstracts, and more than 15 late-breaking clinical trials (LBCTs) abstructs. This report presents the highlights and several key presentations, especially the LBCTs, from the ACC Scientific Sessions 2015. I hope this review will help cardiologists update to the latest information. (Circ J 2015; 79: 1193–1198)
Editorials
Late Breaking Clinical Trials (JCS 2015)
  • Kazuomi Kario, Hisao Ogawa, Ken Okumura, Takafumi Okura, Shigeru Saito ...
    Type: LATE BREAKING CLINICAL TRIAL (JCS 2015)
    2015 Volume 79 Issue 6 Pages 1222-1229
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: April 24, 2015
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    Background:SYMPLICITY HTN-Japan is a prospective, randomized, controlled trial comparing renal artery denervation (RDN) with standard pharmacotherapy for treatment of resistant hypertension (systolic blood pressure [SBP] ≥160 mmHg on ≥3 anti-hypertensive drugs including a diuretic for ≥6 weeks). When SYMPLICITY HTN-3 failed to meet the primary efficacy endpoint, the HTN-Japan enrollment was discontinued before completion.Methods and Results:The 6-month change in office and 24-h ambulatory SBP were compared between RDN (n=22) and control (n=19) subjects. Mean baseline office SBP was 181.0±18.0 mmHg and 178.7±17.8 mmHg for the RDN and control groups, respectively. The 6-month office SBP change was –16.6±18.5 mmHg for RDN subjects (P<0.001) and –7.9±21.0 mmHg for control subjects (P=0.117); the difference between the 6-month change in RDN and control subjects was –8.64 (95% CI: –21.12 to 3.84, P=0.169). Mean 24-h SBP was 164.7±18.3 (RDN group) and 163.3±17.2 mmHg (control group). The 24-h 6-month SBP change for the RDN group was –7.52±11.98 mmHg (P=0.008) and –1.38±10.2 mmHg (P=0.563) for control subjects; the between-group difference in SBP change was –6.15 (95% CI: –13.23 to 0.94, P=0.087). No major adverse events were reported.Conclusions:SYMPLICITY HTN-Japan, the first randomized controlled trial of RDN in an Asian population, was underpowered for the primary endpoint analysis and did not demonstrate a significant difference in 6-month BP change between RDN and control subjects. (Circ J 2015; 79: 1222–1229)
  • Mashio Nakamura, Masakatsu Nishikawa, Issei Komuro, Isao Kitajima, Yos ...
    Type: LATE BREAKING CLINICAL TRIAL (JCS 2015)
    2015 Volume 79 Issue 6 Pages 1230-1236
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: April 24, 2015
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    Supplementary material
    Background:Anticoagulation is recommended as standard of care for venous thromboembolism (VTE) (pulmonary embolism [PE]/deep vein thrombosis [DVT]), for which unfractionated heparin (UFH) and warfarin are used in Japan. In the multi-regional AMPLIFY study, a fixed-dose regimen of apixaban alone was non-inferior to conventional therapy for treatment of PE/DVT and was associated with significantly fewer bleeding events.Methods and Results:Japan phase 3 study (AMPLIFY-J), randomized, active-controlled, open-label study in Japanese subjects with acute PE/DVT, was designed based on AMPLIFY. Key objectives were to investigate safety and efficacy of apixaban in symptomatic PE/DVT subjects during 24-week treatment. UFH/warfarin was used as control treatment. Apixaban was initiated at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 23 weeks. All endpoints and imaging for thrombotic burden were assessed by an event adjudication committee. Eighty subjects were randomized, 33 subjects (41.3%) were aged <65 years. Proportion of major/clinically relevant non-major bleeding was lower in apixaban (7.5%) compared with well-controlled UFH/warfarin (28.2%; median TTR, 70.1%). Recurrent VTE occurred in no subjects in apixaban and in 1 subject in UFH/warfarin. Thrombotic burden results were similar in both groups. Proportions of subjects with adverse events was generally similar in both groups.Conclusions:Apixaban was well-tolerated and had a favorable safety profile. No clinically important efficacy difference compared with UFH/warfarin was observed. (Circ J 2015; 79: 1230–1236)
  • Naoki Sato, Wataru Takahashi, Atsushi Hirayama, Masayoshi Ajioka, Naot ...
    Type: LATE BREAKING CLINICAL TRIAL (JCS 2015)
    2015 Volume 79 Issue 6 Pages 1237-1247
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: April 24, 2015
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    Supplementary material
    Background:Serelaxin, a recombinant form of human relaxin-2, is in development for treating acute heart failure (AHF) and a Phase II study in Japanese AHF patients was conducted.Methods and Results:A randomized, double-blind, placebo-controlled study of serelaxin at 10 and 30 µg·kg–1·day–1continuous intravenous infusion for up to 48 h, added to standard care for Japanese AHF patients. Primary endpoints were adverse events (AEs) through Day 5, serious AEs (SAEs) through Day 14, and serelaxin pharmacokinetics. Secondary endpoints included changes in systolic blood pressure (SBP) and cardiorenal biomarkers. A total of 46 patients received the study drug and were followed for 60 days. The observed AE profile was comparable between the groups, with no AEs of concern. Dose-dependent increase in the serum concentration of serelaxin was observed across the 2 dose rates of serelaxin. A greater reduction in SBP was observed with serelaxin 30 µg·kg–1·day–1vs. placebo (–7.7 [–16.4, 1.0] mmHg). A greater reduction in NT-proBNP was noted with serelaxin (–50.8% and –54.9% for 10 and 30 µg·kg–1·day–1, respectively at Day 2).Conclusions:Serelaxin was well tolerated in this study with Japanese AHF patients, with no AEs of concern and favorable beneficial trends on efficacy. These findings support further evaluation of serelaxin 30 µg·kg–1·day–1in this patient population. (Circ J 2015; 79: 1237–1247)
  • Young Seok Lee, Cai De Jin, Moo Hyun Kim, Long Zhe Guo, Young-Rak Cho, ...
    Type: LATE BREAKING CLINICAL TRIAL (JCS 2015)
    2015 Volume 79 Issue 6 Pages 1248-1254
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: May 11, 2015
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    Background:There is insufficient data on the efficacy of prasugrel and ticagrelor in Korean patients with ST-segment elevation myocardial infarction (STEMI).Methods and Results:In the current double-blind, prospective pilot study, 39 patients with STEMI undergoing primary percutaneous coronary intervention were randomized to receive prasugrel 60 mg loading dose (LD) followed by 10 mg daily maintenance dose (n=19), or ticagrelor 180 mg LD followed by 90 mg twice daily maintenance dose (n=20). We assessed platelet reactivity with the VerifyNow and Vasodilator-Stimulated Phosphoprotein (VASP) P2Y12 assays. Compared to baseline platelet reactivity, both prasugrel and ticagrelor groups achieved similar and significantly lower P2Y12 reaction units (PRU) (259 [IQR: 230 to 281] vs. 28 [12 to 55] for prasugrel; 261 [196 to 286] vs. 43 [11 to 61] for ticagrelor), and platelet reactivity indexes (PRI) (51.2% [39.3 to 61.3] vs. 8.1% [6.1 to 14.7] for prasugrel; 47.5% [38.4 to 50.4] vs. 11.2% [7.1 to 15.5] for ticagrelor, all P values <0.001) at 48 h post-LD. Most patients had low platelet reactivity with 95% PRU values <85 and 82% with PRI <16%.Conclusions:Both prasugrel and ticagrelor were effective for platelet inhibition in Korean STEMI patients with almost no patients exhibiting high platelet reactivity at 48 h after the LD. Our finding of a high number of patients with very low platelet reactivity deserves further studies to assess the safety of the drugs (Prasugrel and Ticagrelor in ST-segment Elevation Myocardial Infarction Study, NCT02075125). (Circ J 2015; 79: 1248–1254)
Late Breaking Cohort Studies (JCS 2015)
  • Masaharu Ishihara, Masashi Fujino, Hisao Ogawa, Satoshi Yasuda, Teruo ...
    Type: LATE BREAKING COHORT STUDY (JCS 2015)
    2015 Volume 79 Issue 6 Pages 1255-1262
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: April 24, 2015
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    Background:New criteria for diagnosis of acute myocardial infarction (AMI) were proposed in 2000 as a universal definition, in which cardiac troponin (cTn) was the preferred biomarker. A large number of patients formerly classified by creatine kinase (CK) as unstable angina are now ruled-in by cTn as non-ST-elevation myocardial infarction (NSTEMI).Methods and Results:The Japanese registry of acute Myocardial INfarction diagnosed by Universal dEfiniTion (J-MINUET) is a prospective and multicenter registry conducted in 28 institutions. We enrolled 3,283 consecutive patients with AMI diagnosed by cTn-based criteria who were admitted to participating institutions within 48 h of symptom onset. There were 2,262 patients (68.9%) with STEMI and 1,021 (31.1%) with NSTEMI. CK was not elevated more than twice the upper limit of normal in 458 patients (44.9%) with NSTEMI (NSTEMI-CK). Although there was no significant difference in the in-hospital mortality of STEMI and NSTEMI with CK elevation (NSTEMI+CK) patients (7.1% vs. 7.8%, P=0.57), it was significantly lower in patients with NSTEMI-CK than in those with STEMI or NSTEMI+CK (1.7%, P<0.001 for each).Conclusions:J-MINUET revealed the clinical presentation, management and outcomes of Japanese patients with AMI in the current cTn era. We should be aware of the difference between AMI diagnosed by CK-based criteria and AMI diagnosed by cTn-based criteria when using universal definitions for the diagnosis of AMI. (Circ J 2015; 79: 1255–1262)
Original Articles
Arrhythmia/Electrophysiology
  • Junya Hosoda, Toshiyuki Ishikawa, Shinichi Sumita, Kohei Matsushita, K ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2015 Volume 79 Issue 6 Pages 1263-1268
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: March 05, 2015
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    Background:The incidence of atrioventricular block (AVB) in pacemaker patients with sick sinus syndrome (SSS) is not yet known. The aim of this study was to analyze AVB episodes in SafeR mode based on stored electrograms (EGM), and determine the occurrence rate and risk factors for advanced AVB in a pacemaker population with SSS.Methods and Results:The study included 50 consecutive patients with SSS without a history of advanced AVB who had a dual-chamber pacemaker programmed in SafeR mode. A total of 377 EGM stored in the pacemakers as AVB episodes fulfilling the second- or third-degree criterion were analyzed. Of 377 EGM, 73 EGM (19.4%) were appropriate episodes, whereas the other EGM did not show actual AVB, and showed atrial tachyarrhythmia, ventricular event in the blanking period, or premature atrial contractions with block. On EGM analysis, advanced AVB occurred in 9 patients (18%), and the occurrence rate was 11.7% per year. Moreover, on multivariate analysis β-blocker use was an independent risk factor for advanced AVB (OR, 9.10; P=0.004).Conclusions:The occurrence rate of advanced AVB in patients with SSS is much higher than previously reported, and β-blocker use is an independent risk factor for advanced AVB. SafeR is useful to detect latent AVB. Stored EGM, however, sometimes include inaccurately classified events. (Circ J 2015; 79: 1263–1268)
Cardiovascular Intervention
  • Seiji Hokimoto, Kenji Sakamoto, Tomonori Akasaka, Koichi Kaikita, Osam ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2015 Volume 79 Issue 6 Pages 1269-1276
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: March 17, 2015
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    Background:Cardiovascular disease is a major cause of mortality in hemodialysis patients. The aim was to assess the relationship of various invasive cardiovascular procedures (ICP) to clinical outcome in hemodialysis patients.Methods and Results:A total of 5,813 patients at 76 facilities were on maintenance hemodialysis in Kumamoto Prefecture. Of these, 4,807 patients at 58 institutions were enrolled. Of 4,807 patients, 212 ICP (4.4%) were performed for various cardiovascular diseases in 189 patients (3.9%). ICP included PCI (n=80), endovascular treatment (n=59), radiofrequency catheter ablation (n=8), implantation of permanent pacemaker (n=15) and ICD (n=5), thoracotomy for valvular diseases (n=16), CABG (n=14), bypass surgery for peripheral artery disease (PAD; n=8), and artificial vessel replacement for aneurysm or aortic dissection (n=7). The overall mortality rate was 10.1% (19/189 patients). The mortality rate was highest in patients who underwent ICP for PAD, compared with other ICP (PAD, 18.2%; non-PAD, 6.7%, P=0.017). Infection and PAD were significant predictors of mortality (infection: OR, 8.30; 95% CI: 1.29–65.13, P=0.027; PAD: OR, 3.76; 95% CI: 1.35–10.48, P=0.012). The presence of inflammation/malnutrition factors was associated with high mortality (OR, 15.49; 95% CI: 3.22–74.12, P=0.0006).Conclusions:In this community-based registry study of 4,807 hemodialysis patients, the mortality rate of PAD patients was high despite ICP. (Circ J 2015; 79: 1269–1276)
  • Sosei Kuma, Koichi Morisaki, Akio Kodama, Atsushi Guntani, Ryota Fukun ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2015 Volume 79 Issue 6 Pages 1277-1281
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: March 20, 2015
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    Background:The efficacy and safety of ultrasound-guided thrombin injection (UGTI) for the treatment of post-catheterization femoral and brachial artery pseudoaneurysms (PSA) is unclear in Japan.Methods and Results:A retrospective study of 32 consecutive patients undergoing percutaneous UGTI of post-catheterization PSA between February 2011 and February 2014 was performed. There were 23 femoral PSA and 9 brachial PSA treated with UGTI. The prevalence of CAD and smoking history were higher in the brachial PSA patients, but there were no statistically significant differences in other patient demographic factors or in the preprocedural antiplatelet therapy between the femoral and brachial PSA patients. The median dose of thrombin injected was 200 U (range, 100–600 U). The initial success rate, early recurrence rate and surgical conversion rate were 91%, 0% and 4% in the femoral PSA, and 89%, 11% and 11% in the brachial PSA, respectively. There were 2 cases of medial nerve compression in the brachial PSA group, but there were no complications in the femoral PSA group (P=0.0198). On outpatient clinical follow-up in the successfully treated patients, there were no recurrences after an average follow-up of 16 months.Conclusions:UGTI is a feasible, safe and effective less-invasive treatment for post-catheterization PSA. Brachial PSA, however, might require additional attention because of their tendency toward higher recurrence and complications. (Circ J 2015; 79: 1277–1281)
  • Hiroki Shiomi, Takeshi Morimoto, Yutaka Furukawa, Yoshihisa Nakagawa, ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2015 Volume 79 Issue 6 Pages 1282-1289
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: March 30, 2015
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    Supplementary material
    Background:Studies evaluating long-term (≥5 years) outcome of percutaneous coronary intervention (PCI) compared with coronary artery bypass grafting (CABG) in patients with unprotected left main coronary artery disease (ULMCAD) are still limited, despite concerns for late adverse events after drug-eluting stents implantation.Methods and Results:We identified 1,004 patients with ULMCAD (PCI: n=364, CABG: n=640) among 15,939 patients with first coronary revascularization enrolled in the CREDO-Kyoto PCI/CABG registry cohort-2. The primary outcome measure in the current analysis was a composite of death, myocardial infarction, and stroke (death/MI/stroke). The cumulative 5-year incidence of and the adjusted risk for death/MI/stroke were significantly higher in the PCI group than in the CABG group (34.5% vs. 24.1%, log-rank P<0.001, adjusted hazard ratio (HR): 1.48 [95% confidence interval (CI): 1.07–2.05, P=0.02]). The adjusted risks for all-cause death was not significantly different between the 2 groups. Regarding the stratified analysis by the SYNTAX score, the adjusted risk for death/MI/stroke was not significantly different between the 2 groups in patients with low (<23) or intermediate (23–33) SYNTAX score, whereas it was significantly higher in the PCI group than in the CABG group in patients with high (≤33) SYNTAX score.Conclusions:CABG as compared with PCI was associated with better long-term outcome in patients with ULMCAD, especially those with high anatomical complexity. (Circ J 2015; 79: 1282–1289)
Cardiac Rehabilitation
  • Naonori Tashiro, Shinya Takahashi, Taiichi Takasaki, Keijiro Katayama, ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiac Rehabilitation
    2015 Volume 79 Issue 6 Pages 1290-1298
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: March 13, 2015
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    Background:Postoperative complications after cardiac surgery increase mortality. This study aimed to evaluate the efficacy of cardiopulmonary rehabilitation with adaptive servo-ventilation (ASV) in patients undergoing off-pump coronary artery bypass grafting (OPCAB).Methods and Results:A total of 66 patients undergoing OPCAB were enrolled and divided into 2 groups according to the use of ASV (ASV group, 30 patients; non-ASV group, 36 patients). During the perioperative period, all patients undertook cardiopulmonary rehabilitation. ASV was used from postoperative day (POD) 1 to POD5. Hemodynamics showed a different pattern in the 2 groups. Blood pressure (BP) on POD6 in the ASV group was significantly lower than that in the non-ASV group (systolic BP, 112.9±12.6 vs. 126.2±15.8 mmHg, P=0.0006; diastolic BP, 62.3±9.1 vs. 67.6±9.3 mmHg, P=0.0277). The incidence of postoperative atrial fibrillation (POAF) was lower in the ASV group than in the non-ASV group (10% vs. 33%, P=0.0377). The duration of oxygen inhalation in the ASV group was significantly shorter than that in the non-ASV group (5.1±2.2 vs. 7.6±6.0 days, P=0.0238). The duration of postoperative hospitalization was significantly shorter in the ASV group than in the non-ASV group (23.5±6.6 vs. 29.0±13.1 days, P=0.0392).Conclusions:Cardiopulmonary rehabilitation with ASV after OPCAB reduces both POAF occurrence and the duration of hospitalization. (Circ J 2015; 79: 1290–1298)
Cardiovascular Surgery
  • Naoto Fukunaga, Yukikatsu Okada, Yasunobu Konishi, Takashi Murashita, ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Surgery
    2015 Volume 79 Issue 6 Pages 1299-1306
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: March 03, 2015
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    Background:We assessed late outcome after tricuspid annuloplasty (TAP) using a flexible band or ring for functional tricuspid regurgitation (FTR).Methods and Results:We reviewed 220 consecutive patients (mean age, 65.4±11.4 years) who underwent TAP for FTR during mitral valve surgery between January 2000 and December 2010. Indications for TAP included the following: (1) TR grade greater than mild; (2) history of right heart failure; (3) atrial fibrillation; and (4) systolic pulmonary artery pressure (SPAP) ≥50 mmHg. The mean follow-up period was 4.4±2.6 years. Overall hospital mortality was 5.5% (12/220). The 5- and 10-year survival rates were 90.2±2.1% and 82.4±5.6%, respectively. Freedom from recurrent TR at 8 years was 78.0±6.6%. Twenty patients had a greater than mild TR grade at final follow-up. Elevated SPAP was a predictor of recurrent TR (hazard ratio, 1.091; P=0.0003), which was associated with advanced age, atrial fibrillation, rheumatic etiology and preoperative TR grade. There was a significant difference in freedom from valve-related events between residual TR greater than mild and less than moderate (log-rank test, P=0.0464). Factors affecting residual TR were preoperative TR grade (OR, 7.368; P=0.0267) and mitral valve replacement (OR, 4.369; P=0.0402).Conclusions:Late outcome of TAP in the present series was acceptable. Late outcome can be improved by performing TAP before deterioration of TR. (Circ J 2015; 79: 1299–1306)
Heart Failure
  • Tomoya Ueda, Rika Kawakami, Taku Nishida, Kenji Onoue, Tsunenari Soeda ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2015 Volume 79 Issue 6 Pages 1307-1314
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: March 03, 2015
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    Supplementary material
    Background:The renin-angiotensin system (RAS) is activated in heart failure (HF) as a compensatory mechanism, being related to cardiac remodeling and poor prognosis. Although RAS inhibitors are used as first-line drugs for HF, plasma renin activity (PRA) is upregulated by RAS inhibitors via a negative feedback mechanism. The clinical significance of PRA during RAS inhibitor therapy is poorly understood in acute decompensated HF (ADHF). Therefore we examined the impact of PRA in HF patients already receiving RAS inhibitors.Methods and Results:Of 611 consecutive patients with ADHF and emergency admission to hospital, we studied the impact of PRA on the prognosis of ADHF in 293 patients already receiving RAS inhibitors before admission. The patients were divided into 2 groups according to median PRA (≥ vs. <3.4 ng·ml−1·h−1). During a mean follow-up of 29.0 months, there were 124 deaths from all causes. Kaplan-Meier analysis showed that all-cause and cardiovascular mortality were significantly higher in patients with high PRA than low PRA (log-rank P=0.0002 and P<0.0001, respectively). Log PRA was an independent predictor of all-cause and cardiovascular death (HR, 1.194; 95% CI: 1.378–2.678, P<0.0001; and HR, 2.559; 95% CI: 1.610–4.144, P<0.0001, respectively).Conclusions:PRA was associated with an increased risk of all-cause and cardiovascular mortality in ADHF patients already receiving RAS inhibitors, suggesting that PRA would be a useful biomarker during ADHF treatment. (Circ J 2015; 79: 1307–1314)
  • Nobuhiro Nishii, Motoki Kubo, Yoji Okamoto, Satoki Fujii, Atsuyuki Wat ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2015 Volume 79 Issue 6 Pages 1315-1322
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: March 17, 2015
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    Background:Ambulatory measurement of intrathoracic impedance (ITI) with an implanted device may detect increases in pulmonary fluid retention early, but the clinical utility of this method is not well established. The goal of this study was to test whether conventional ITI-derived parameters can diagnose fluid retention that may cause early stage heart failure (HF).Methods and Results:HF patients implanted with high-energy devices with OptiVol (Medtronic) monitoring were enrolled in this study. Patients were monitored remotely. At both baseline and OptiVol alert, patients were assessed on standard examinations, including analysis of serum brain natriuretic peptide (BNP). From April 2010 to August 2011, 195 patients from 12 institutes were enrolled. There were 154 primary OptiVol alert events. BNP level at the alerts was not significantly different from that at baseline. Given that ITI was inversely correlated with log BNP, we added a criterion specifying that the OptiVol alert is triggered only when ITI decreases by ≥4% from baseline. This change improved the diagnostic potential of increase in BNP at OptiVol alert (sensitivity, 75%; specificity, 88%).Conclusions:BNP increase could not be identified based on OptiVol alert. Decrease in ITI ≥4% compared with baseline, in addition to the alert, however, may be a useful marker for the likelihood of HF (Clinical trial info: UMIN000003351). (Circ J 2015; 79: 1315–1322)
Imaging
  • Kensuke Nishimiya, Yasuharu Matsumoto, Hironori Uzuka, Kazuma Oyama, A ...
    Type: ORIGINAL ARTICLE
    Subject area: Imaging
    2015 Volume 79 Issue 6 Pages 1323-1331
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: April 03, 2015
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    Supplementary material
    Background:Coronary adventitia harbors a wide variety of components, such as inflammatory cells and vasa vasorum (VV). Adventitial VV initiates the development of coronary artery diseases as an outside-in supply route of inflammation. We have recently demonstrated that drug-eluting stent implantation causes the enhancement of VV formation, with extending to the stent edges in the porcine coronary arteries, and also that optical frequency domain imaging (OFDI) is capable of visualizing VV in humans in vivo. However, it remains to be fully validated whether OFDI enables the precise measurement of VV formation in pigs and humans.Methods and Results:In the pig protocol, a total of 6 bare-metal stents and 12 drug-eluting stents were implanted into the coronary arteries, and at 1 month, the stented coronary arteries were imaged by OFDI ex vivo. OFDI data including the measurement of VV area at the stent edge portions were compared with histological data. There was a significant positive correlation between VV area on OFDI and that on histology (R=0.91, P<0.01). In the human protocol, OFDI enabled the measurement of the VV area at the stent edges after coronary stent implantation in vivo.Conclusions:These results provide the first direct evidence that OFDI enables the precise measurement of the VV area in coronary arteries after stent implantation in pigs and humans. (Circ J 2015; 79: 1323–1331)
Myocardial Disease
  • Ryoichi Ushigome, Yasuhiko Sakata, Kotaro Nochioka, Satoshi Miyata, Ma ...
    Type: ORIGINAL ARTICLE
    Subject area: Myocardial Disease
    2015 Volume 79 Issue 6 Pages 1332-1341
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: April 02, 2015
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    Supplementary material
    Background:Recent trends in the clinical characteristics, management and prognosis of dilated cardiomyopathy (DCM) remain to be examined in Japan.Methods and Results:We compared 306 and 710 DCM patients in the Chronic Heart Failure Analysis and Registry in the Tohoku District (CHART)-1 (2000–2005, n=1,278) and the CHART-2 (2006–present, n=10,219) Studies, respectively. Between the 2 groups of DCM patients, there were no significant differences in baseline characteristics. The prevalence of hypertension, dyslipidemia and diabetes mellitus were all significantly increased from the CHART-1 to the CHART-2 Study. The use of β-blockers and aldosterone antagonists was significantly increased, while that of loop diuretics and digitalis was significantly decreased in the CHART-2 Study. The 3-year mortality rate was significantly improved from 14% in the CHART-1 to 9% in the CHART-2 Study (adjusted HR, 0.60; 95% CI: 0.49–0.81; P=0.001). In particular, 3-year incidence of cardiovascular death was significantly decreased (adjusted HR, 0.26; 95% CI: 0.14–0.50, P<0.001), while that of HF admission was not (adjusted HR, 0.90; 95% CI: 0.59–1.37, P=0.632). The prognostic improvement was noted in patients with BNP <220 pg/ml, LVEF>40%, β-blocker use and aldosterone antagonist use.Conclusions:Long-term prognosis of DCM patients has been improved, along with the implementation of evidence-based medication in Japan. (Circ J 2015; 79: 1332–1341)
Pediatric Cardiology and Adult Congenital Heart Disease
  • Jia-wang Xiao, Xian-yang Zhu, Qi-guang Wang, Duan-zhen Zhang, Chun-She ...
    Type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2015 Volume 79 Issue 6 Pages 1342-1348
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: March 23, 2015
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    Background:We investigated the acute vasodilator effects of i.v. fasudil, a specific Rho-kinase inhibitor, on pulmonary circulation in patients with congenital heart defects (CHD) and severe pulmonary arterial hypertension (PAH).Methods and Results:Thirty-five patients (34.23±12.10 years old) with CHD and severe PAH were consecutively enrolled. All patients underwent heart catheterization. At baseline and 30 min after initiation of i.v. fasudil, the following hemodynamic parameters were measured and calculated: right atrial pressure, pulmonary and systemic artery pressure (PAP and SAP), pulmonary and systemic vascular resistance, pulmonary-to-systemic blood pressure ratio (Pp/Ps), pulmonary-to-systemic blood flow ratio (Qp/Qs), cardiac index (CI) and artery oxygen saturation (SaO2). After fasudil treatment, marked decrease in mean PAP (mPAP), pulmonary vascular resistance (PVR), total pulmonary resistance, pulmonary-to-systemic vascular resistance ratio (Rp/Rs) and mean Pp/Ps (mPp/Ps) was found, while Qp/Qs increased significantly without affecting CI and SAP. mPAP, PVR, Rp/Rs and Qp/Qs tended to be improved more significantly in the post-tricuspid shunt group compared with the pre-tricuspid shunt group.Conclusions:Fasudil was well tolerated in patients with CHD and severe PAH, and significantly reduced PAP and PVR without affecting CI, SAP or SaO2. (Circ J 2015; 79: 1342–1348)
  • Kentaro Ueno, Yuichi Nomura, Yasuko Morita, Taisuke Eguchi, Kiminori M ...
    Type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2015 Volume 79 Issue 6 Pages 1349-1356
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: March 19, 2015
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    Background:Circulating platelet-neutrophil aggregates play a crucial role in amplifying acute inflammation and could promote adverse effects involving vascular injury. The aim of this study was to evaluate the role of platelet-neutrophil aggregates in Kawasaki disease (KD).Methods and Results:Forty patients with KD (30 intravenous immunoglobulin [IVIG] responders and 10 IVIG non-responders), 7 febrile patients with bacterial infections, and 9 normal volunteers were analyzed. Thirty-three patients with KD were treated with IVIG, and 7 were treated with IVIG plus prednisolone. We evaluated the rate of platelet-neutrophil aggregates and measured the platelet factor 4 (PF4) and β-thromboglobulin (β-TG) levels. The rate of platelet-neutrophil aggregates was significantly higher in patients with KD than those with bacterial infection and normal volunteers. The rate of platelet-neutrophil aggregates was significantly higher in patients with coronary artery abnormalities (CAA) than in those without CAA, and was correlated with PF4 and β-TG levels in patients with KD. Comparing time-course analysis, the rate of platelet-neutrophil aggregates was significantly decreased in patients treated with IVIG plus prednisolone than in those treated with IVIG alone.Conclusions:The findings demonstrate that platelet-neutrophil aggregates are significantly present in higher rates and are closely related to pathological developments of CAA in KD. Additional prednisolone treatment for patients in the acute phase of KD could suppress platelet-neutrophil aggregates, indicating that platelet-neutrophil aggregates would inhibit amplified reciprocal vascular inflammatory activation. (Circ J 2015; 79: 1349–1356)
Peripheral Vascular Disease
  • Hiroaki Tanaka, Shinji Katsuragi, Kazuhiro Osato, Junichi Hasegawa, Ma ...
    Type: ORIGINAL ARTICLE
    Subject area: Peripheral Vascular Disease
    2015 Volume 79 Issue 6 Pages 1357-1362
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: March 11, 2015
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    Background:The aim of the present work was to understand the current circumstances of maternal-death-related venous thromboembolism (MD-VTE) in Japan. We retrospectively investigated the characteristics of cases of MD-VTE, and compared past and present rates of occurrence.Methods and Results:We examined the Japanese data for MD-VTE in 2010–2013, and compared it with that from 1991–1992. MD-VTE occurred in 17 women in 1991–1992, and in 13 women in 2010–2013. The maternal mortality ratio of MD-VTE was 0.7 per 100,000 in 1991–1992 and 0.4 per 100,000 in 2010–2013. Both the maternal mortality ratio and rate of MD-VTE in 2010–2013 deceased significantly compared with 1991–1992 (P<0.05). However, the number of cases of MD-VTE during pregnancy was 6 among 13 women (41%) in 2010–2013, but 1 in 17 women (6%) in 1991–1992, showing an increase (P<0.05). In the present study, cesarean delivery was more frequently associated with MD-VTE.Conclusions:MD-VTE overall has decreased within the past 20 years in Japan. But, MD-VTE during pregnancy in 2010–2013 increased relative to 1991–1992. Future guidelines for prevention of VTE may need to extend beyond the perioperative period to decrease the incidence of MD-VTE. (Circ J 2015; 79: 1357–1362)
Regenerative Medicine
  • Motoki Matsuki, Maki Kabara, Yukihiro Saito, Kohei Shimamura, Akiho Mi ...
    Type: ORIGINAL ARTICLE
    Subject area: Regenerative Medicine
    2015 Volume 79 Issue 6 Pages 1363-1371
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: March 11, 2015
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    Supplementary material
    Background:Capillary pericytes (cPCs), the mural cells of microvessels, play an important role in the formation and maintenance of microvessels; however, little is known about the mechanisms of how cPCs regulate angiogenesis. To identify factors that modulate cPC function, genes whose levels were altered in cPCs during neovessel formation were identified through a microarray screen.Methods and Results:Ninjurin1 (nerve injury-induced protein, Ninj1) was selected as a candidate factor for angiogenesis regulation. Ninj1 was expressed in capillary cells including endothelial cells (cECs) and was expressed at a higher level in cPCs. Hypoxia induced the gene expression of Ninj1 in addition of vascular endothelial growth factor (VEGF) in cPCs. When cPCs were co-incubated with a thoracic aorta in a three-dimensional Matrigel system, the length of the EC-tubes sprouting from the aorta was increased. Small interfering RNA-mediated downregulation of Ninj1 in cPCs enhanced these cPCs-mediated angiogenic effects, whereas overexpression of Ninj1 attenuated their effects. The production of angiogenic growth factors, such as VEGF and angiopoietin 1, by cPCs was enhanced by the downregulation of Ninj1, and reduced by the overexpression of Ninj1.Conclusions:Ninj1 is a novel regulator for the angiogenic effect of PCs. Specifically, Ninj1 negatively regulates the formation of neovessels, that is, the EC-tube, by reducing the trophic effects of cPCs. (Circ J 2015; 79: 1363–1371)
Vascular Biology and Vascular Medicine
  • Sebastião D. Silva Jr., Thais T. Zampieri, Adriana Ruggeri, Alexandre ...
    Type: ORIGINAL ARTICLE
    Subject area: Vascular Biology and Vascular Medicine
    2015 Volume 79 Issue 6 Pages 1372-1380
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: March 25, 2015
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    Background:Hyperactivity of the renin-angiotensin system (RAS) and functional deficits in hypertension are reduced after exercise training. We evaluate in arteries, kidney and plasma of hypertensive rats the sequential effects of training on vascular angiotensinogen, Ang II and Ang (1-7) content.Methods and Results:Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were trained or kept sedentary (S) for 3 months. After hemodynamic measurements (weeks 0, 1, 2, 4, 8 and 12), blood, arteries and kidneys were obtained to quantify the angiotensin content (HPLC) and angiotensinogen expression (Western Blotting). SHR-S vs. WKY-S exhibited elevated pressure, increased angiotensinogen and angiotensins’ content in the renal artery with a high Ang II/Ang (1-7) ratio (~5-fold higher than in the femoral artery, kidney and plasma, and 14-fold higher than in the aorta). Training promptly reduced angiotensinogen expression and downregulated the RAS in the renal SHR artery (1st–12thweek), with a specific reduction of the vasoconstrictor axis; significant reduction of the AngII/Ang (1-7) ratio (36%, T4-T8) occurred simultaneously with significant pressure fall (5%). In other SHR arteries, plasma and kidneys and in all WKY tissues, T-induced AngII and Ang (1-7) reductions were proportional, maintaining the AngII/Ang (1-7) ratio.Conclusions:Vascular RAS is not equally expressed in vessels, having crucial importance in the renal artery. In the renal SHR artery, training downregulates the vasoconstrictor and preserves the vasodilator axis while in other tissues and plasma training reduces both RAS axes, thus maintaining the vasoconstriction/vasodilatation balance in a lower level. (Circ J 2015; 79: 1372–1380)
  • Masanori Azuma, Yuichi Chihara, Chikara Yoshimura, Kimihiko Murase, Sa ...
    Type: ORIGINAL ARTICLE
    Subject area: Vascular Biology and Vascular Medicine
    2015 Volume 79 Issue 6 Pages 1381-1389
    Published: May 25, 2015
    Released: May 25, 2015
    [Advance publication] Released: March 25, 2015
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    Supplementary material
    Background:Visceral obesity, low adiponectin, and severe obstructive sleep apnea (OSA) are associated with cardiovascular diseases, but the interactions among these factors on endothelial dysfunction are not well known.Methods and Results:Endothelial function in 133 patients after polysomnography was evaluated as reactive hyperemia index (RHI) on reactive hyperemia peripheral arterial tonometry. Visceral obesity was defined as visceral fat area ≥100 cm2on computed tomography. RHI was significantly correlated with apnea hypopnea index (AHI), visceral fat area, and serum adiponectin (r=–0.24, P=0.0055, r=–0.19, P=0.031, and r=0.20, P=0.019, respectively). RHI in patients with visceral obesity was significantly decreased in the presence of severe OSA (AHI ≥30; P=0.042). On multivariate regression analysis, only severe OSA remained as an independent predictive factor of RHI (P=0.024, R2=5.4%). RHI in patients with severe OSA (n=44) was significantly improved after 3 months of continuous positive airway pressure (CPAP) treatment (1.78±0.40 before CPAP vs. 2.00±0.53 after CPAP, P=0.013), similarly to those with AHI <30 (P=0.45).Conclusions:Severe OSA, but not visceral fat area or serum adiponectin, was independently associated with endothelial function according to RHI. In addition, impaired endothelial function was reversible following 3 months of CPAP treatment. (Circ J 2015; 79: 1381–1389)
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