Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 78 , Issue 9
Showing 1-43 articles out of 43 articles from the selected issue
Message From the Editor-in-Chief
Reviews
  • Fernando Alfonso, Teresa Bastante, Fernando Rivero, Javier Cuesta, Amp ...
    Type: REVIEW
    2014 Volume 78 Issue 9 Pages 2099-2110
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: August 13, 2014
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    Spontaneous coronary artery dissection (SCAD) is a rare but challenging clinical entity of unknown etiology. From a pathophysiological standpoint, SCAD may occur in patients with a coronary intimal tear (presenting with the classic angiographic “flap” and multiple lumens), but also in patients without an intimal rupture (presenting as an intramural hematoma). Until now, available information on SCAD was largely based on multiple, small case-series studies but, recently, data from relatively large registries have cast a new light on this disease. Classically, SCAD was thought to present in young females without traditional atherosclerotic risk factors but recent reports suggest a broader clinical spectrum encompassing older patients with associated coronary artery disease. In this review, we concentrate on 3 main aspects of this unique disease: (1) the value of intracoronary diagnostic techniques (intravascular ultrasound and optical coherence tomography) to complement coronary angiography and to provide novel diagnostic insights on this elusive clinical condition; (2) the growing clinical evidence suggesting an association and potential causation between fibromuscular dysplasia and SCAD; and (3) the challenges of coronary revascularization in this adverse anatomic setting, together with recent data suggesting that a initial, conservative medical management may be preferable for the majority of patients with SCAD. (Circ J 2014; 78: 2099 – 2110)
  • Larry A. Barr, John W. Calvert
    Type: REVIEW
    2014 Volume 78 Issue 9 Pages 2111-2118
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: August 12, 2014
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    Hydrogen sulfide (H2S) is an endogenously produced gaseous signaling molecule that elicits a number of cytoprotective effects in mammalian species. H2S was originally considered toxic at elevated levels, but 15 years ago the labile molecule was discovered in mammalian tissue and termed a gasotransmitter, thus opening the door for research aimed towards understanding its physiologic nature. Since then, novel findings have depicted the beneficial aspects of H2S therapy, such as vasodilation, antioxidant upregulation, inflammation inhibition, and activation of anti-apoptotic pathways. These cytoprotective alterations effectively treat multiple forms of cardiac injury at the preclinical level of research. The field has progressed towards instituting novel H2S donors that prove more effective at activating the subsequent cardioprotective enhancements over longer time periods. As more findings explore the efficacy of H2S, research focused on detection of sulfhydrated targets is on the rise. Understanding the molecular mechanisms that stem from H2S treatment may lead the field towards powerful therapeutics in the clinical setting. This review will discuss the cytoprotective and cardioprotective effects of H2S therapy, provide analysis on the molecular alterations that lead to these enhancements, and explore recently developed therapeutics that may bring this gasotransmitter into the clinic in the near future. (Circ J2014;78:2111–2118)
Focus Issue on Takotsubo Cardiomyopathy
  • Scott W. Sharkey, Barry J. Maron
    Type: Focus Issue on Takotsubo Cardiomyopathy
    2014 Volume 78 Issue 9 Pages 2119-2128
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: August 05, 2014
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    First described in Japan over 2 decades ago, takotsubo cardiomyopathy (TTC) has emerged as a unique cardiomyopathy with world-wide recognition, mimicking acute coronary syndrome. In early TTC experience, typical patients were older women, with a triggering emotional event, ST-segment elevation, and apical ballooning left ventricular (LV) contraction pattern. However, TTC is now more heterogeneous, occurring in males and younger individuals, without ST-segment elevation, as a spontaneous event in the absence of a trigger, and with diverse LV contraction patterns. Furthermore, TTC is more common than initially thought, now constituting 10% of women with suspected acute coronary syndrome. TTC is also associated with a broader range of psychological or physical triggers, including presentation during outpatient medical evaluations or hospitalization for acute illness. Although TTC has been considered a benign condition, it now carries a small but important risk for adverse outcomes, including cardiac arrest in 5%. Hemodynamic instability requiring intervention with vasopressor drugs or intra-aortic balloon pump is necessary in 15% and in-hospital mortality is approximately 5%, largely because of refractory cardiogenic shock or irreversible major comorbid conditions. Although complete cardiac recovery usually occurs rapidly, post-hospital survival may be less than the general population of similar age, largely because of concomitant illnesses. TTC may reoccur in up to 10% of patients, but β-blocking drugs are not absolutely preventive for initial or subsequent events. (Circ J2014;78:2119–2128)
  • Dawn C Scantlebury, Abhiram Prasad
    Type: Focus Issue on Takotsubo Cardiomyopathy
    2014 Volume 78 Issue 9 Pages 2129-2139
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: August 13, 2014
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    Takotsubo cardiomyopathy, also known as left ventricular apical ballooning syndrome and stress-induced cardiomyopathy, is typically characterized by transient systolic dysfunction of the apical and mid-segments of the left ventricle, in the absence of obstructive coronary artery lesions. Patients may present with symptoms and signs of acute coronary syndrome, and the provider is challenged to differentiate between these conditions. In this review, we guide the reader through the diagnostic pathway, focusing on differential diagnoses and diagnostic criteria for takotsubo cardiomyopathy. (Circ J 2014; 78: 2129–2139)
2014 JCS Report
  • Masafumi Watanabe
    Type: 2014 JCS REPORT
    2014 Volume 78 Issue 9 Pages 2140-2145
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: August 08, 2014
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    The 78thAnnual Scientific Meeting of the Japanese Circulation Society was held in Tokyo on March 21–23, 2014. The main theme was “Cardiology in the Information Era: From Bench to Community”. Because of technological advancements, including computer networking, a vast amount of information from basic and clinical research is being generated in a short time period. This information has great potential to contribute to human health, and some of the results are presented. However, we must remain vigilant, for there are many risks inherent in information generation. To ensure high-quality information, we need to obtain enough knowledge to focus on not only the medicine, but also ethics, and methodology. Moreover, we need to train the specialists, establish economic support, and create a regulatory framework. More than 15,000 people, including paramedical specialists, attended this meeting. The most popular sessions included those on “Transcatheter Aortic Valve Implantation for Aortic Stenosis”, “Diabetes Mellitus”, “Atrial Fibrillation”, “Pulmonary Hypertension”, and “Diuretics To Treat Heart Failure”. Even in rather small sessions, attendees participated in discussion, identified opportunities to expand or start research, and were able to update their clinical knowledge. The meeting was successfully completed with a discussion of the future of cardiology. (Circ J2014;78:2140–2145)
Editorials
Original Articles
Arrhythmia/Electrophysiology
  • Masaharu Akao, Yeong-Hwa Chun, Masahiro Esato, Mitsuru Abe, Hikari Tsu ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2014 Volume 78 Issue 9 Pages 2166-2172
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: June 27, 2014
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    Background:Atrial fibrillation (AF) is a common arrhythmic disorder among the elderly, and increases the risk of stroke. Oral anticoagulants (OAC) are highly effective in preventing stroke, and there are evidence-based guidelines for the optimal use of OAC in patients with AF.Methods and Results:The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, a typical urban community in Japan with a total population of 283,000. Of the 3,282 patients enrolled by October 2012, 1-year follow-up was completed for 2,914 patients. OAC, mainly warfarin, were given to 1,546 patients (53.1%); overused for low-risk patients, and underused for patients at risk, based on the guidelines. Moreover, warfarin was sometimes given at a sub-therapeutic dose; only 54.4% of patients were within the optimal therapeutic range. The 1-year outcomes revealed that the incidences of both stroke and major bleeding were equivalent between patients taking OAC and those without; major clinical events were as follows: (OAC vs. non-OAC) stroke 2.7% vs. 2.8%, ischemic stroke 2.1% vs. 2.0% and major bleeding 1.4% vs. 1.5% (NS for all).Conclusions:The Fushimi AF Registry provides a unique snapshot of current AF management in an urban community in Japan. The present study reveals inappropriate use of OAC for patients with AF, indicating discordance between guideline recommendations and real-world clinical practice. (Circ J2014;78:2166–2172)
  • Shinya Takahashi, Mai Fujiwara, Keisuke Watadani, Takahiro Taguchi, Ke ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2014 Volume 78 Issue 9 Pages 2173-2181
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: July 15, 2014
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    Background:Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery and may result in stroke or heart failure and poor prognosis. This study aimed to evaluate a novel index of total atrial conduction time derived from the P-wave onset (lead II) to the peak A’ wave on tissue Doppler imaging (PA-TDI duration). The PA-TDI duration was compared with previously reported predictors of POAF, and the optimal cutoff value of PA-DTI was calculated in patients undergoing aortic valve replacement (AVR) for AV stenosis (AS).Methods and Results:We enrolled 63 patients undergoing isolated AVR. They underwent transthoracic echocardiography with TDI preoperatively and were monitored postoperatively with continuous electrocardiographic telemetry for 7 days. The hospital stay was significantly longer in the 41 patients with POAF than in the 22 without POAF (33.8±19.7 vs. 24.1±8.1 days, P=0.03). Multivariate analysis revealed that PA-TDI duration (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.02–1.13; P=0.0072) and age (OR, 1.14; CI, 1.03–1.28; P=0.016) were significant independent predictors of POAF. Receiver-operating characteristic curve analysis showed the optimal cutoff values of PA-TDI duration and age were 147.3 ms and 74 years, respectively.Conclusions:The PA-TDI duration was an independent predictor of POAF after AVR for AS. Patients with PA-TDI duration >147 ms should be considered high risk and treated appropriately to improve outcomes. (Circ J 2014; 78: 2173–2181)
  • Tze-Fan Chao, Chia-Jen Liu, Su-Jung Chen, Kang-Ling Wang, Yenn-Jiang L ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2014 Volume 78 Issue 9 Pages 2182-2187
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: July 23, 2014
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    Background:Although the link between sleep-disordered breathing (SDB) and atrial fibrillation (AF) has been reported, a population-based longitudinal cohort study was lacking. The goal of the present study was to investigate the AF risk carried by SDB, using the National Health Insurance Research Database in Taiwan.Methods and Results:From 2000 to 2001, a total of 579,521 patients who had no history of cardiac arrhythmias or significant comorbidities were identified. Among them, 4,082 subjects with the diagnosis of SDB were selected as the study group, and the remaining 575,439 subjects constituted the control group. The study endpoint was the occurrence of new-onset AF. During a follow-up of 9.2±2.0 years, there were 4,023 patients (0.7%) experiencing new-onset AF. The occurrence rate of AF was higher in patients with SDB compared to those without it (1.3% vs. 0.7%, P<0.001). The AF incidences were 1.38 and 0.76 per 1,000 person-years for patients with and without SDB, respectively. After anadjustment for age and sex, SDB was a significant risk factor of AF with a hazard ratio of 1.536. The AF risk increased with increasing clinical severity of SDB, represented by the requirement of continuous positive airway pressure use.Conclusions:SDB itself, without the coexistence of other systemic diseases, was a risk factor of AF. (Circ J2014;78:2182–2187)
Cardiovascular Intervention
  • Masamichi Iwasaki, Hiromasa Otake, Toshiro Shinke, Masayuki Nakagawa, ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2014 Volume 78 Issue 9 Pages 2188-2196
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: July 14, 2014
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    Background:Previous reports have shown potential disadvantages of limus-derivative drugs for the stenting treatment of patients with diabetes mellitus (DM).Methods and Results:We studied 159 coronary artery lesions (DM: n=72, non-DM: n=87) in 123 patients treated with everolimus-eluting stent (EES) and who underwent scheduled 9-month follow-up angiography with optical coherence tomography (OCT) regardless of symptoms. In addition to standard OCT variables, neointimal unevenness score (maximum/average neointimal thickness) and stent eccentricity index (minimum/maximum stent diameter) were calculated for each cross-section. To investigate a potential baseline difference between DM and non-DM lesions, pre- and post-interventional intravascular ultrasound (IVUS) images were also evaluated as an IVUS subgroup analysis. The average neointimal thickness and neointimal coverage did not differ between DM and non-DM patients. DM patients had, however, greater asymmetric stent expansion and variability of neointimal thickness than non-DM patients. There was a weak, but significant association between average stent eccentricity index and neointimal unevenness score. The IVUS substudy showed that the culprit plaque volume and plaque eccentricity in DM patients were significantly greater than in non-DM patients.Conclusions:Although EES provided a similar level of average neointimal thickness and coverage both in the presence and absence of DM, uneven neointimal suppression occurred in DM patients. A larger plaque volume of the culprit lesion may hamper symmetric stent expansion, possibly explaining the non-uniform neointimal suppression in DM patients. (Circ J2014;78:2188–2196)
  • Zhen-fei Fang, Yi-yuan Huang, Liang Tang, Xin-qun Hu, Xiang-qian Shen, ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2014 Volume 78 Issue 9 Pages 2197-2202
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: July 16, 2014
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    Background:Transcatheter closure (TCC) of ruptured sinus of Valsalva aneurysm (RSVA) is an alternative strategy to surgery, but there is a lack of long-term outcome data.Methods and Results:From 2004 to 2012, 17 patients (8 males, 9 females) were treated with patent ductus arteriosus (PDA) occluders by antegrade venous approach and were followed for 18–102 months. Of the 17 patients, transthoracic echocardiography revealed rupture of the right coronary sinus into the right ventricle in 9 and into the right atrium in 4, and noncoronary sinus rupture into the right ventricle in 3 and into the right atrium in 1. Most (10/17) were in New York Heart Association (NYHA) functional class III or IV. Aortography showed that the size of the defect was 7.71±2.84 mm (4–15 mm). TCC was attempted using PDA occluders 2–5 mm larger than the aortic end of the defects. The device sizes ranged from 8/6 to 18/16 mm (median, 10/8 mm). The procedure was successful in 16 (94.1%), and all of them had complete occlusion at discharge. On a median follow-up of 42 months, 14 patients were in NYHA class I and 2 were in class II, and there was no residual shunt, device embolization, infective endocarditis, or aortic regurgitation.Conclusions:TCC of RSVA is a safe and effective alternative to surgery with favorable long-term follow-up results. (Circ J2014;78:2197–2202)
  • Mayu Nishio, Yasunori Ueda, Koshi Matsuo, Masahiko Tsujimoto, Hiroyuki ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2014 Volume 78 Issue 9 Pages 2203-2208
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: July 04, 2014
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    Background:Theslow-flow or no re-flow phenomenon has been associated with distal embolization, especially of plaque debris, and with unfavorable clinical outcomes. Therefore, we examined the association between the coronary computed tomography angiography (CCTA) findings of the target lesion and distal embolization during percutaneous coronary intervention (PCI).Methods and Results:Consecutive patients (n=55: 18 unstable angina, 19 stable effort angina, 18 silent ischemia) who underwent PCI with a filter-type distal protection device after evaluation of the target lesion by CCTA were analyzed. CCTA examined low-attenuation plaque (LAP), positive remodeling (PR), and ring-like enhancement of the target lesion. Distal embolization of thrombus and plaque debris was evaluated by pathological examination of material collected in the filter.Any distal embolization and distal embolization of plaque debris were respectively detected in 75% and 0% of patients with LAP or PR alone, in 95% and 17% of patients with both LAP and PR, and in 100% and 27% of patients with all of LAP, PR and ring-like enhancement. The sensitivity and specificity to predict plaque debris embolization by having both findings of LAP and PR was 100% and 46%, respectively.Conclusions:The CCTA findings of the target lesion were associated with distal embolization and were very sensitive for predicting plaque debris embolization. (Circ J2014;78:2203–2208)
  • Yuhei Kobayashi, Hiroyuki Okura, Teruyoshi Kume, Ryotaro Yamada, Yukar ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2014 Volume 78 Issue 9 Pages 2209-2214
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: July 14, 2014
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    Background:Stent underexpansion remains a concern as a cause of drug-eluting stent (DES) failure. Although coronary calcification is considered to be a contributing factor in stent underexpansion, previous intravascular ultrasound studies have failed to demonstrate this relationship. We investigated whether stent expansion could be predicted by coronary calcification as assessed by optical coherence tomography (OCT).Methods and Results:We enrolled 51 de novo native coronary artery lesions treated by a single 2nd-generation DES (3 types). Prior to stent deployment, the arc and area of calcium at the target lesion were measured using OCT. After successful stent implantation, OCT imaging was repeated to assess minimal stent diameter and area (MSD and MSA). Stent expansion was defined as MSD (or MSA) divided by the values predicted by the manufacturers’ compliance charts. Patients were divided into 4 groups according to the median values of the arc and area of calcium. Mean stent expansion was 73.3±8.7% for MSD and 65.2±12.0% for MSA. Stent expansion defined by MSD was significantly different among the 4 groups (P=0.02). A similar trend was observed for stent expansion defined by MSA (P=0.16).Conclusions:The extent of target lesion calcification as assessed by OCT may be an important determinant of the expansion of 2nd-generation DES. (Circ J 2014; 78: 2209–2214)
  • Wei-Hsian Yin, Jeng Wei, Shen Kou Tsai, Ming C. Hsiung, Yung-Tsai Lee, ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2014 Volume 78 Issue 9 Pages 2215-2218
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: July 16, 2014
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    Background:Ascending aortic pseudoaneurysm (PsA) is an uncommon but surgically challenging problem with high morbidity and mortality. Herein we describe the efficacy and safety of the different approaches to transcatheter intervention for repair of ascending PsA and assess the selection of occluder devices using real-time 3-dimensional (RT 3D) color Doppler transesophageal echocardiography (TEE).Methods and Results:Three patients with complex ascending PsA after cardiac or aortic root surgery were treated with transcatheter intervention due to high risk for redo surgery. Perioperative RT 3D-TEE combined with fluoroscopy was used for monitoring. All ascending PsA were successfully occluded with different devices using the transcatheter technique either with the transapical, transarterial approach, or transvenous combined with hybrid process depending on lesion anatomy.Conclusions:Treatment of complex ascending PsA with transcatheter or combined hybrid intervention with cautious planning based on patient presentation and well-coordinated teamwork was successful. RT 3D color Doppler TEE provided precise information for the selection of appropriate occluder device, and also facilitated the procedure by guiding the catheter through difficult anatomy. (Circ J 2014; 78: 2215–2218)
Cardiovascular Surgery
  • Katsuyuki Hoshina, Masaru Nemoto, Kunihiro Shigematsu, Ayako Nishiyama ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Surgery
    2014 Volume 78 Issue 9 Pages 2219-2224
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: July 04, 2014
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    Background:Renal insufficiency is the most frequent complication of surgeries that involve suprarenal aortic cross-clamping. Although some studies have assessed the risk of intraoperative renal ischemia by comparing juxtarenal abdominal aortic aneurysms (AAAs) and infrarenal AAAs, a critical limitation is the difference in these patients’ clinical backgrounds and aneurysmal features. The present study evaluated the effect of suprarenal aortic clamping by comparing a juxtarenal AAA group with a subgroup of infrarenal AAAs (ie, short and/or large neck).Methods and Results:Among patients who underwent open surgery for AAA, the 2 types of AAA were selected and compared: juxtarenal AAA (JR group: n=35) and infrarenal AAA with short (<15 mm) and/or large (>28 mm) aneurysmal neck that only required infrarenal aortic clamping (SL group: n=26). Postoperative renal function was evaluated using the RIFLE classification. There were no significant differences between groups in baseline characteristics, comorbidities, and intraoperative variables. There were no adverse events leading directly to in-hospital mortality in either group. The rate of postoperative renal insufficiency (estimated glomerular filtration rate decrease ≥–25%) was not significantly different between groups.Conclusions:The outcomes of the 2 groups were similar, indicating that intraoperative renal ischemia with no specific intraoperative protection would not adversely affect postoperative outcomes. (Circ J 2014; 78: 2219–2224)
  • Kenji Minakata, Ko Bando, Shiro Tanaka, Shuichiro Takanashi, Hiroaki K ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Surgery
    2014 Volume 78 Issue 9 Pages 2225-2231
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: July 25, 2014
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    Background:The aim of this study was to determine the influence of preoperative kidney dysfunction (ie, chronic kidney disease (CKD)) on postoperative cardiovascular events, infection, acute kidney injury and hospital mortality in patients undergoing coronary artery bypass grafting (CABG).Methods and Results:A multi-institutional retrospective study was performed at 14 hospitals of adult patients undergoing isolated CABG from 2007 to 2008 (n=1,522). We classified CKD level according to preoperative estimated glomerular filtration rate (eGFR): normal, eGFR >90 ml·min–1·1.73 m–2; mild, eGFR 60–90 ml·min–1·1.73 m–2; moderate, eGFR 30–59 ml·min–1·1.73 m–2; and severe, eGFR <30 ml·min–1·1.73 m–2, and assessed postoperative outcome. Preoperative CKD distribution was as follows: normal, n=121 (8%); mild, n=713 (47%); moderate, n=515 (34%); and severe, n=169 (11%). Risk of infection was strongly correlated with CKD level (normal, 3.3%; mild, 7.0%; moderate, 8.3%; severe, 17.0%; P<0.01). The risk of in-hospital death was also strongly correlated with CKD level (normal, 1.7%; mild, 1.0%; moderate, 1.6%; severe, 5.9%; P<0.01). On multivariate logistic regression analysis, CKD level was identified as a significant risk factor for postoperative infection, acute kidney injury, and in-hospital death.Conclusions:Advanced preoperative CKD is a strong predictor of postoperative infection, acute kidney injury and in-hospital death after CABG. (Circ J 2014; 78: 2225–2231)
Heart Failure
  • Roberto Rordorf, Simone Savastano, Antonio Sanzo, Carla Spazzolini, Ma ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2014 Volume 78 Issue 9 Pages 2232-2239
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: June 20, 2014
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    Background:Pro-inflammatory cytokines contribute to the pathophysiology of heart failure (HF) and are up-regulated in affected patients. We investigated whether pro-inflammatory cytokines might predict the response to cardiac resynchronization therapy (CRT).Methods and Results:Plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 were assessed in 91 patients before CRT. Response to CRT was defined as a decrease ≥15% in left ventricular end-systolic volume (LVESV) at 6 months. Baseline TNF-α did correlate with LVESV reduction (P=0.001) after CRT. The subject group was divided according to tertiles of TNF-α. From the lower to the upper tertile LVESV (–31±28%, –17±17%, –9±22%) and LV end-diastolic volume (–23±25%, –14±16%, –4±18%) were progressively less reduced after CRT (P<0.001). The proportion of responders to CRT was 70%, 42% and 33%, according to the lower, intermediate and upper tertile of TNF-α distribution (P=0.01). Serious cardiac events (cardiac death, HF hospitalization or urgent heart transplantation) occurred in 63% of patients in the upper tertile vs. 32% and 17% in the intermediate and lower tertiles, respectively, during a median follow-up of 47 months (P<0.001).Conclusions:Circulating TNF-α predicts the degree of LV reverse remodeling after CRT and may contribute to the early identification of those patients at higher risk of events after device implantation. (Circ J 2014; 78: 2232–2239)
  • Teruhiko Imamura, Koichiro Kinugawa, Takeo Fujino, Toshiro Inaba, Hisa ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2014 Volume 78 Issue 9 Pages 2240-2249
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: June 20, 2014
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    Background:Preserved function of the renal collecting duct may be essential for response to the vasopressin V2receptor antagonist, tolvaptan (TLV), but the predictors of response to TLV are unknown.Methods and Results:Sixty consecutive patients with stage D decompensated heart failure (HF) who had received TLV on a de novo basis were retrospectively enrolled (TLV(+) group). Among them, 41 patients were responders defined according to urine volume (UV) increase after TLV initiation. In the UV-defined responders, plasma arginine vasopressin (P-AVP) had a close correlation with urine aquaporin-2 (U-AQP2; 5.42±3.54 ng/ml; r=0.843, P<0.001). In contrast, 19 were UV-defined non-responders, and they had extremely low U-AQP2 (0.76±0.59 ng/ml, P<0.001 vs. responders) regardless of P-AVP level. On receiver operating characteristic analysis, U-AQP2/P-AVP ≥0.5×103clearly separated the UV-defined responders from the non-responders. We then identified AQP-defined responders as having U-AQP2/P-AVP ≥0.5×103. Sixty propensity score-matched HF patients without TLV treatment were examined, and exactly the same number of patients as that of the AQP-defined responders (n=41) was selected. These patients had a poorer survival without TLV than the TLV-treated responders during a 2-year observation period (73.8% vs. 94.8%, P=0.034).Conclusions:U-AQP2/P-AVP is a novel predictor of response to TLV in patients with decompensated HF. AQP-defined responders may have a better prognosis on TLV treatment. (Circ J 2014; 78: 2240–2249)
  • Yasuhide Mochizuki, Hidekazu Tanaka, Kazuhiro Tatsumi, Kensuke Matsumo ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2014 Volume 78 Issue 9 Pages 2250-2258
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: July 04, 2014
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    Background:Left ventricular (LV) dyssynchrony has emerged as an important mechanism contributing to the patient’s response to cardiac resynchronization therapy (CRT), but other potential factors, especially LV myocardial viability, are also influential.Methods and Results:We studied 132 patients undergoing CRT. LV dyssynchrony was determined by anteroseptal-to-posterior wall delay on the mid-LV short-axis view using 2-dimensional speckle-tracking radial strain (≥130 ms as significant). Global circumferential strain (GCS), considered as a parameter of LV intrinsic myocardial function, was also determined as the peak GCS from the same view. Long-term follow-up was tracked over 40 months. Kaplan-Meier analysis indicated that patients with GCS >3.9% experienced fewer cardiovascular events overall (log-rank P=0.034). Similarly, patients with GCS >3.9% and ≥6.6% experienced fewer cardiovascular events than those with GCS ≤3.9% and <6.6% among patients with and without LV dyssynchrony (log-rank P=0.025 and P=0.029, respectively). An important finding from multivariate Cox proportional hazards analysis was that LV dyssynchrony and GCS were independently associated with cardiovascular events. Of note, only 2±1 min per patient were needed to analyze both LV dyssynchrony and GCS from the same routine mid-LV short-axis view.Conclusions:This easy-to-use combined assessment of LV dyssynchrony and myocardial function using speckle-tracking strain from the same mid-LV short-axis view may well have clinical implications for CRT. (Circ J 2014; 78: 2250–2258)
  • Teruhiko Imamura, Koichiro Kinugawa, Masaru Hatano, Takeo Fujino, Tosh ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2014 Volume 78 Issue 9 Pages 2259-2267
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: July 10, 2014
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    Background:Depressed hemodynamics stimulates arginine vasopressin (AVP) release, but the relationship between plasma AVP levels (P-AVP) and cardiac parameters, especially in patients with stage D heart failure (HF) receiving guideline-directed medical therapy, has not examined.Methods and Results:Data including P-AVP were obtained from 162 in-hospital patients with stage D HF and from 80 patients receiving ventricular assist device (VAD, n=46) or heart transplantation (HTx, n=34) at 3 months after surgery. In the HF group, considerably high P-AVP (5.9±6.1 pg/ml) negatively correlated with serum sodium concentration (S-Na, 135.3±5.8 mEq/L, r=–0.548 [P<0.01]) and cardiac index (CI, 2.2±0.5 L·min–1·m–2, r=–0.458 [P<0.01]). After VAD/HTx treatment, improvement in the CI (2.7±0.5 L·min–1·m–2[P<0.01] vs. HF) was accompanied by normalization of serum sodium concentration (S-Na; 138.2±2.0 mEq/L [P<0.01] vs. HF) and suppressed release of AVP (1.7±3.4 pg/ml [P<0.01] vs. HF). P-AVP positively correlated with only S-Na (r=0.454 [P<0.01]), whereas no correlation was observed with CI after VAD/HTx treatment. P-AVP ≥5.3 pg/ml well predicted poor 2-year survival in HF group (60% [P<0.01] vs. 90%).Conclusions:Low cardiac output stimulates AVP release via a non-osmotic process that results in hyponatremia and poor prognosis in patients with stage D HF. After sufficient recovery of cardiac output by cardiac replacement therapy, AVP release is suppressed and is mainly regulated by serum osmolality. (Circ J 2014; 78: 2259–2267)
  • Michio Nakanishi, Hiroshi Takaki, Reon Kumasaka, Tetsuo Arakawa, Teruo ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2014 Volume 78 Issue 9 Pages 2268-2275
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: July 23, 2014
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    Background:Peak oxygen uptake (V̇O2) and ventilatory efficiency (V̇E/V̇CO2slope) measured on cardiopulmonary exercise testing (CPX) are prognostic indicators in heart failure (HF) patients, but peak V̇O2is influenced by patient effort. In CPX targeting a peak respiratory exchange ratio (pRER; an objective index of effort adequacy) higher than the commonly recommended level, we assessed the safety and prognostic value of CPX parameters compared with non-CPX parameters.Methods and Results:We studied 283 consecutive HF patients with left ventricular ejection fraction (LVEF) ≤45% (mean, 26.3%) who underwent CPX targeting pRER >1.20. The attained pRER (mean, 1.26) was consistently high irrespective of LVEF, and there was no major exercise-related adverse event. The composite of all-cause death or HF hospitalization occurred in 111 patients (39%) during a median follow-up of 47 months. Among well-known prognostic markers, peak V̇O2was the most powerful predictor of outcome as both a continuous and an optimal dichotomous variable, followed by V̇E/V̇CO2slope. On multivariate analysis, peak V̇O2was a significant independent predictor, whereas V̇E/V̇CO2slope, B-type natriuretic peptide, and LVEF were not.Conclusions:In CPX targeting pRER >1.20 for HF patients, peak V̇O2is the most powerful among well-known predictors, without an increased risk of exercise-related events. These findings advocate a high target pRER in CPX even in advanced HF. (Circ J 2014; 78: 2268–2275)
  • Masanobu Miura, Yasuhiko Sakata, Kotaro Nochioka, Tsuyoshi Takada, Soi ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2014 Volume 78 Issue 9 Pages 2276-2283
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: July 23, 2014
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    Background:Although the need for nursing care (NC) in heart failure (HF) patients is recognized, detailed information on the current status in Japan is lacking.Methods and Results:In the CHART-2 Study, we obtained information on daily life, physical ability, nutrition and mental status for 4,174 patients (mean age, 67.1±10.8 years; 73.3% male) out of 10,219 patients. We examined the prevalence, baseline characteristics and clinical outcomes of stage B and C/D HF patients requiring NC. The prevalence of HF requiring NC was significantly higher in stage C/D (38.6%) than in stage B (30.4%; P<0.001). Among the reasons for requiring NC, physical dysfunction was most prevalent in both stage B (20.6%) and C/D (29.0%). Compared with the non-NC group, the NC group was characterized by higher age, higher prevalence of female gender and cerebrovascular disease, and increased plasma brain natriuretic peptide regardless of HF stage. During a median follow-up of 12.7 months after the survey, the NC group had a significantly higher mortality compared with the non-NC group (9.6% vs. 3.6%, P<0.001). On multivariate logistic analysis depressive mental status (hazard ratio [HR], 3.61; P<0.001) and dementia (HR, 2.70; P<0.001) were significantly associated with NC need.Conclusions:In HF patients, NC need is considerably high and is associated with increased mortality regardless of HF stage in Japan. (Circ J 2014; 78: 2276–2283)
Hypertension and Circulatory Control
  • Yuji Aoki, Hisashi Kai, Hidemi Kajimoto, Hiroshi Kudo, Narimasa Takaya ...
    Type: ORIGINAL ARTICLE
    Subject area: Hypertension and Circulatory Control
    2014 Volume 78 Issue 9 Pages 2284-2291
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: June 30, 2014
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    Background:It has been shown that increased short-term blood pressure (BP) variability (BPV) aggravates hypertensive cardiac remodeling in spontaneously hypertensive rats (SHRs) through a cardiac angiotensin II (angII) system. However, little was known about the renal damage induced by large BPV. Thus, histological changes in the kidney were investigated and candesartan, an angII type 1 receptor blocker (ARB), was also examined to see whether it would prevent renal damage in SHRs with large BPV.Methods and Results:Bilateral sinoaortic denervation (SAD) was performed in SHRs to create a model of a combination of hypertension and large BPV. SAD increased BPV without changing mean BP. Seven weeks later, SAD induced patchy, wedge-shaped, focal sclerotic lesions accompanied by interstitial fibrosis and ischemic changes of glomeruli and tubules in the cortex. The pre-glomerular arterioles adjacent to the sclerotic lesions showed arteriolosclerotic changes associated with vascular smooth muscle cell proliferation and extracellular matrix deposition, leading to the luminal narrowing and occlusion. Chronic treatment with a subdepressor dose of candesartan prevented not only arteriolosclerotic changes but also cortical sclerotic lesions in SHRs with SAD without changing BPV.Conclusions:Large BPV aggravates pre-glomerular arteriolosclerosis, which results in the cortical sclerotic changes in SHRs through a local angII-mediated mechanism. This study raised the possibility that ARB is useful for renal protection in patients who have a combination of hypertension and increased BPV. (Circ J 2014; 78: 2284–2291)
Myocardial Disease
  • Hyelim Park, Hyewon Park, Dajeong Lee, Sujung Oh, Jisoo Lim, Hye jin H ...
    Type: ORIGINAL ARTICLE
    Subject area: Myocardial Disease
    2014 Volume 78 Issue 9 Pages 2292-2301
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: July 24, 2014
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    Background:Because fatal arrhythmia is an important cause of death in patients with myocarditis, we investigated the proarrhythmic mechanisms of experimental autoimmune myocarditis.Methods and Results:Myocarditis was induced by injection of 2 mg porcine cardiac myosin into the footpads of adult Lewis rats on days 1 and 8 (Myo, n=15) and the results compared with Control rats (Control, n=15). In an additional 15 rats, 6 mg/kg prednisolone was injected into the gluteus muscle before the injection of porcine cardiac myosin on days 1 and 8 (MyoS, n=15). Hearts with myocarditis had longer action potential duration (APD), slower conduction velocity (CV; P<0.01 vs. Control), higher CV heterogeneity, greater fibrosis, higher levels of immunoblotting of high-mobility group protein B1, interleukin 6 and tumor necrosis factor-α proteins. Steroid treatment partially reversed the translations for myocarditis, CV heterogeneity, reduced APD at 90% recovery to baseline, increased CV (P<0.01), and reversed fibrosis (P<0.05). Programmed stimulation triggered sustained ventricular tachycardia in Myo rats (n=4/5), but not in controls (n=0/5) or Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor (KN93) treated Myo rats (n=0/5, P=0.01). CaMKII autophosphorylation at Thr287 (201%), and RyR2 phosphorylation at Ser2808 (protein kinase A/CaMKII site, 126%) and Ser2814 (CaMKII site, 21%) were increased in rats with myocarditis and reversed by steroid.Conclusions:The myocarditis group had an increased incidence of arrhythmia caused by increased phosphorylation of Ca2+handling proteins. These changes were partially reversed by an antiinflammatory treatment and CaMKII inhibition. (Circ J 2014; 78: 2292–2301)
Pediatric Cardiology and Adult Congenital Heart Disease
  • Satoru Iwashima, Takamichi Ishikawa
    Type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2014 Volume 78 Issue 9 Pages 2302-2308
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: July 09, 2014
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    Background:We evaluated the hemodynamic status of patent ductus arteriosus (PDA) by measuring vena contracta width (VCW) and effective shunt orifice area (ESOA) using proximal isovelocity surface area (PISA) on color Doppler imaging.Methods and Results:Study subjects were 21 patients with PDA (mean age, 3.6 years). We measured VCW (mm/m2) and ESOA (cm2) by the PISA method using echocardiography. Color images were obtained from parasternal long-axis views. VCW (mm/m2) was measured at the narrowest region of PDA flow. ESOA by PISA (PDA-ESOA) was defined on color Doppler flow imaging as a hemispheric area of laminar flow with aliased velocities [PDA-ESOA (cm2)=2π[PDA radius (cm)]^2×aligning velocity (cm/s)/PDA peak velocity (cm/s)]. Upon examining the relationships with catheterization parameters by univariate analysis, VCW correlated with diastolic blood pressure (DBP), % left ventricular end-diastolic volume (%LVEDV), pulmonary blood flow index, pulmonary blood flow/systemic blood flow ratio (Qp/Qs), left-right (LR) shunt ratio, left atrial to aortic root ratio (LA/AO), chest-thoracic ratio and N-terminal pro-brain natriuretic peptide (NTproBNP); and PDA-ESOA correlated with DBP, Qp/Qs, average pulmonary artery pressure, pulmonary/systemic pressure ratio, %LVEDV, LR shunt ratio, LA/AO and NTproBNP. When stepwise multiple linear regression analysis was performed with the correlations that were significant on univariate analysis, significant correlations with Qp/Qs were noted (VCW; R2=0.836, β=0.914, P<0.001, PDA-ESOA; R2=0.621, β=0.788, P<0.001).Conclusions:Measurement of VCW and PDA-ESOA by the PISA method can noninvasively evaluate the hemodynamic status of PDA. (Circ J 2014; 78: 2302–2308)
Preventive Medicine
  • Kyoung-bok Min, Jin-young Min
    Type: ORIGINAL ARTICLE
    Subject area: Preventive Medicine
    2014 Volume 78 Issue 9 Pages 2309-2316
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: June 30, 2014
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    Background:We explored whether reduced lung function is a predictor of mortality due to cardiovascular or coronary artery disease (CVD or CAD), and, if this hypothesis is correct, whether C-reactive protein (CRP), a systemic inflammatory marker, is responsible for this association in a general population-based cohort.Methods and Results:We used the Third Nutrition and Health Examination Survey (NHANES III) database and the NHANES III Linked Mortality File. A total of 13,310 participants ≥20 years of age who completed a spirometric test at baseline examination were included. On comparison of the participants in the lowest forced vital capacity percent predicted (FVC% pred) quartile with those in the highest quartile, the hazard ratio (HR) was 2.1 (95% CI: 1.7–2.6) for cardiovascular mortality and 2.2 (95% CI: 1.6–3.2) for coronary mortality. A similar association was observed for forced expiratory volume in 1 s percent predicted (FEV1% pred). When the participants with the highest FVC% pred or FEV1% pred (Q4) and low CRP (≤0.22 mg/dl) were defined as the reference group, the adjusted HR for cardiovascular mortality was significantly increased in the individuals with the lowest spirometric volume (Q1), and the risk was prominent in individuals with high CRP (>0.22 mg/dl).Conclusions:There is a significant association between lung function parameters and death from CVD and CAD in the general population. (Circ J 2014; 78: 2309–2316)
Regenerative Medicine
  • Tatsuya Noguchi, Yoshihiko Kakinuma, Mikihiko Arikawa, Kayo Okazaki, E ...
    Type: ORIGINAL ARTICLE
    Subject area: Regenerative Medicine
    2014 Volume 78 Issue 9 Pages 2317-2324
    Published: August 25, 2014
    Released: August 25, 2014
    [Advance publication] Released: July 25, 2014
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    Background:Saving more limbs of patients with peripheral arterial disease (PAD) from amputation by accelerating angiogenesis in affected limbs has been anticipated for years. We hypothesized that an anti-Alzheimer drug, donepezil (DPZ), can activate angiomyogenic properties of satellite cells, myogenic progenitors, and thus be an additional pharmacological therapy against PAD.Methods and Results:In a murine hindlimb ischemia model, we investigated the angiogenic effects of a clinical dose of DPZ (0.2 mg·kg–1·day–1) and its combination with cilostazol, a platelet aggregation inhibitor and a conventional therapeutic drug against PAD. The combination therapy most effectively improved skin coldness and most effectively upregulated vascular endothelial growth factor (VEGF)-producing satellite cells in ischemic hindlimbs. Computed tomography revealed that DPZ remarkably attenuated ischemic muscle atrophy and induced super-restoration in affected hindlimbs. The in vitro study with human aortic endothelial cells showed that DPZ or its combination with cilostazol effectively upregulated the expression of pAkt, hypoxia inducible factor-1α, and VEGF protein. Likewise, in primary cultured satellite cells, DPZ, alone or in combination, upregulated the expression of VEGF, interleukin-1β, and fibroblast growth factor 2 protein.Conclusions:The present results suggest that a clinical dosage of DPZ accelerates angiomyogenesis by directly acting on both endothelial and satellite cells. Therefore, DPZ is a potential additional choice for conventional drug therapy against PAD. (Circ J 2014; 78: 2317–2324)
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