Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
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Reviews
  • William K. Sietsema, Atsuhiko Kawamoto, Hiroshi Takagi, Douglas W. Los ...
    Type: REVIEW
    2019 Volume 83 Issue 7 Pages 1422-1430
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: June 07, 2019
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    In 1997, the seminal manuscript by Asahara, Murohara, Isner et al outlined the evidence for the existence of circulating, bone marrow-derived cells capable of stimulating and contributing to the formation of new blood vessels. Consistent with the paradigm shift that this work represented, it triggered much scientific debate and controversy, some of which persists 2 decades later. In contrast, the clinical application of autologous CD34 cell therapy has been marked by a track record of consistent safety and clinical benefit in multiple ischemic conditions. In this review, we summarize the preclinical and clinical evidence from over 700 patients in clinical trials of CD34 cell therapy.

  • Rajib Neupane, Xiongjie Jin, Takeshi Sasaki, Xiang Li, Toyoaki Murohar ...
    Type: REVIEW
    2019 Volume 83 Issue 7 Pages 1431-1438
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: May 16, 2019
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    Atherosclerotic cardiovascular disease (ACVD) is an inflammatory phenomenon that leads to structural abnormality in the vascular lumen due to the formation of atheroma by the deposition of lipid particles and inflammatory cytokines. There is a close interaction between innate immune cells (neutrophils, monocyte, macrophages, dendritic cells) and adaptive immune cells (T and B lymphocytes) in the initiation and progression of atherosclerosis. According to novel insights into the role of adaptive immunity in atherosclerosis, the activation of CD4+T cells in response to oxidized low-density lipoprotein-antigen initiates the formation and facilitates the propagation of atheroma, whereas CD8+T cells cause the rupture of a developed atheroma by their cytotoxic nature. Peripheral CD4+and CD8+T-cell counts were altered in patients with other cardiovascular risk factors. Furthermore, on evaluation of the feasibility of immune cells as a diagnostic tool, the blood CD4+(helper), CD8+(cytotoxic), and CD4+CD25+Foxp3+(regulatory) T cells and the ratio of CD4 to CD8 cells hold promise as biomarkers of coronary artery disease and their subtypes. T cells also could be a therapeutic target for cardiovascular diseases. The goal of this review was therefore to summarize the available information regarding immune disorders in ACVD with a special focus on the clinical implications of circulating T-cell subsets as biomarkers.

Editorials
Original Articles
Arrhythmia/Electrophysiology
  • Kuo-Li Pan, Ya-Wen Hsiao, Yenn-Jiang Lin, Li-Wei Lo, Yu-Feng Hu, Fa-Po ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2019 Volume 83 Issue 7 Pages 1449-1455
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: May 23, 2019
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    Background:Telomere length is a biologic aging marker. This study investigated leukocyte telomere length (LTL) as a new biomarker to predict recurrence after paroxysmal atrial fibrillation (PAF) ablation.

    Methods and Results:A total of 131 participants (26 healthy individuals and 105 symptomatic PAF patients) were enrolled. PAF patients (54.1±10.8 years) who received catheter ablation therapy were divided into 2 groups: recurrent AF (n=25) and no recurrent AF after catheter ablation (n=80). Peripheral blood mononuclear cells were collected from all subjects to measure LTL. Under 50 years old, LTL in healthy individuals (n=17) was longer than in PAF patients (n=31; 7.34±0.58 kbp vs. 6.44±0.91 kbp, P=0.01). In PAF patients, LTL was positively correlated with left atrial bipolar voltage (R=0.497, P<0.001), and negatively correlated with biatrial scar area (R=−0.570, P<0.001) and left atrial diameter (R=−0.214, P=0.028). LTL was shorter in the patients with recurrent AF than in those without recurrent AF after catheter ablation (5.68±0.82 kbp vs. 6.66±0.71 kbp; P<0.001). On receiver operating characteristic curve analysis, LTL cut-off <6.14 kbp had a specificity of 0.68 and sensitivity of 0.79 to predict recurrent AF after catheter ablation.

    Conclusions:Young PAF patients (≤50 years) had shorter LTL. Shorter LTL was associated with a degenerative atrial substrate and recurrence after catheter ablation in younger PAF patients.

  • Takanori Ikeda, Tsuyoshi Shiga, Wataru Shimizu, Koichiro Kinugawa, Ats ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2019 Volume 83 Issue 7 Pages 1456-1462
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: May 23, 2019
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    Background:We aimed to investigate the efficacy and safety of landiolol in Japanese patients with recurrent hemodynamically unstable ventricular tachycardia or recurrent ventricular fibrillation (recurrent VT/VF).

    Methods and Results:This was an open-label, uncontrolled, multicenter study. Patients with hemodynamically unstable VT or VF 24 h prior to providing informed consent, and who were refractory to class III antiarrhythmic drugs, were enrolled. Landiolol was started at a dose of 1 μg/kg/min, after VT/VF was suppressed with electrical defibrillation. Landiolol was titrated up to 10 μg/kg/min in 1 h and adjusted between 1 and 40 μg/kg/min for the efficacy assessment (1–49 h). The primary efficacy endpoint was the proportion of patients free from recurrent VT/VF. Secondary efficacy endpoints included the number of recurrent VT/VF events and the survival rate 30 days after the start of landiolol treatment. Adverse events (AEs) were assessed for safety; 27 and 29 patients were analyzed for efficacy and safety, respectively. The proportion of patients free from recurrent VT/VF was 77.8% (95% CI 57.1–89.3). The mean (±standard deviation) number of recurrent VT/VF events was 9.3±7.9. The survival rate was 96.3%. The overall incidence of AEs and of serious AEs was 72.4% and 6.9%, respectively.

    Conclusions:Landiolol may be useful for Japanese patients with recurrent VT/VF who do not respond to class III antiarrhythmic drugs.

  • Qiqi Wang, Chengui Zhuo, Yunpeng Shang, Jianqiang Zhao, Nan Chen, Ning ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2019 Volume 83 Issue 7 Pages 1463-1471
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: June 08, 2019
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    Background:The larger the left atrium anteroposterior dimension (LAD) and left atrium volume (LAV), the stronger the association with recurrent atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA). Patients with a smaller left atrium (LA) size, however, also have increased AF recurrence.

    Methods and Results:In 521 patients, routine 48-h Holter electrocardiogram and echocardiography were obtained at each outpatient visit every 3 months for 12 months. On multivariate analysis, AF type, LAD, and LAV calculated using the ellipsoid model/body surface area (LAVe/BSA) were independent predictors of AF recurrence. Patients were divided into 7 groups at 0.4-cm increments of LAD: ≤3 cm, LAD≤3 cm, 3.0<LAD≤3.4 cm, 3.4<LAD≤3.8 cm, 3.8<LAD≤4.2 cm, 4.2<LAD≤4.6 cm, 4.6<LAD≤5.0 cm; and LAD>5.0 cm. Compared with the 3.4–3.8-cm group, the adjusted HR were 3.88 (95% CI: 2.02–7.46, P<0.001), 1.03 (95% CI: 0.50–2.12, P=0.939), 0.96 (95% CI: 0.52–1.77, P=0.901), 1.36 (95% CI: 0.72–2.57, P=0.347), 3.04 (95% CI: 1.67–5.53, P<0.001), and 4.07 (95% CI: 1.93–8.60, P<0.001), respectively. Similarly, we divided LAVe/BSA into 8 groups and also observed a U-shaped curve for AF recurrence.

    Conclusions:Both larger and smaller LAD and LAVe/BSA were associated with a higher risk of AF recurrence 1 year after RFCA. The association of LA size and AF recurrence after RFCA is represented by a U-shaped curve.

Biomedical Engineering
  • Xinke Yao, Zhengze Dai, Xu Zhang, Jie Gao, Gelin Xu, Yan Cai, Zhiyong ...
    Type: ORIGINAL ARTICLE
    Subject area: Biomedical Engineering
    2019 Volume 83 Issue 7 Pages 1472-1479
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: April 26, 2019
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    Background:Carotid angioplasty and stenting (CAS) is emerging as an alternative treatment for carotid stenosis, but neointimal hyperplasia (NIH) remains a drawback of this treatment strategy. This study aimed to evaluate the effect of variations of carotid bifurcation geometry on local hemodynamics and NIH.

    Methods and Results:Hemodynamic and geometric effects on NIH were compared between 2 groups, by performing computational fluid dynamics (CFD) simulations both on synthetic models and patient-specific models. In the idealized models, multiple regression analysis revealed a significant negative relationship between internal carotid artery (ICA) angle and the local hemodynamics. In the patient-derived models, which were reconstructed from digital subtraction angiography (DSA) of 25 patients with bilateral CAS, a low time-average wall shear stress (TAWSS) and a high oscillatory shear index (OSI) were often found at the location of NIH. Larger difference values of the OSI percentage area (10.56±20.798% vs. −5.87±18.259%, P=0.048) and ECA/CCA diameter ratio (5.64±12.751% vs. −3.59±8.697%, P=0.047) were detected in the NIH-asymmetric group than in the NIH-symmetric group.

    Conclusions:Changes in carotid bifurcation geometry can make apparent differences in hemodynamic distribution and lead to bilateral NIH asymmetry. It may therefore be reasonable to consider certain geometric variations as potential local risk factors for NIH.

Cardiovascular Intervention
  • Yuichi Ozaki, Hector M. Garcia-Garcia, Solomon S. Beyene, Alexandre Hi ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2019 Volume 83 Issue 7 Pages 1480-1488
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: May 22, 2019
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    Background:Statin therapy has been shown to result in coronary plaque regression, but the relationship between statin use and stabilization of coronary plaque has not been elucidated. We conducted a systematic review and meta-analysis to evaluate the effect of statin therapy on fibrous cap thickness (FCT) on optical coherence tomography (OCT).

    Methods and Results:Nine OCT studies (6 randomized controlled trials and 3 observational studies) were enrolled with a total of 341 patients (390 lesions). Arms of the studies were grouped according to statin type and/or dose. Random effects meta-analysis was used to estimate a pooled mean change in FCT from baseline to follow-up. The overall effect mean FCT change was 67.7 µm (95% CI: 51.4–84.1, I2=95.0%, P<0.001). All statin groups had an increase in FCT, but the magnitude of the increase differed according to the statin. Two homogeneous subgroups with I2=0 were identified: mean FCT change was 27.8 µm (for subgroup atorvastatin 5 mg and rosuvastatin), and 61.9 µm (for subgroup atorvastatin 20 mg, fluvastatin 30 mg, and pitavastatin 4 mg). On meta-regression modeling, statin therapy alone explained most of the change in FCT.

    Conclusions:Statin therapy induced a significant increase in FCT as assessed on OCT, independent of coronary risk factors and other medications.

  • Chee Hae Kim, Kyung Woo Park, Jeehoon Kang, Byoung-Eun Park, Kwang Soo ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2019 Volume 83 Issue 7 Pages 1489-1497
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: May 31, 2019
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    Background:There are limited data on the long-term outcome of platinum chromium-based everolimus-eluting stents (PtCr-EES) vs. cobalt chromium-based zotarolimus-eluting stents (CoCr-ZES).

    Methods and Results:A total of 3,755 patients undergoing percutaneous coronary intervention (PCI) were randomized 2:1 to PtCr-EES or CoCr-ZES, and 96.0% of patients completed the 3-year clinical follow-up. The primary outcome was target lesion failure (TLF), defined as a composite of cardiac death, target vessel-related myocardial infarction (MI), and clinically-driven target lesion revascularization (TLR). At 3 years, TLF occurred in 5.3% and in 5.4% of the PtCr-EES and CoCr-ZES groups, respectively (hazard ratio 0.978; 95% confidence interval 0.730–1.310, P=0.919). There were no significant differences in the individual components of TLF. Routine angiographic follow-up was performed in 38.9% of the total patients. In a landmark analysis of the subgroup that had follow-up angiography, the clinically-driven TLR rate of CoCr-ZES was significantly higher than PtCr-EES group during the angiography follow-up period (P=0.009). Overall definite and probable stent thrombosis rates were very low in both groups (0.5% vs. 0.6%, P=0.677).

    Conclusions:PtCr-EES and CoCr-ZES had similar and excellent long-term outcomes in both efficacy and safety after PCI in an all-comer population.

  • Satoshi Kodera, Hiroyuki Morita, Arihiro Kiyosue, Jiro Ando, Issei Kom ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2019 Volume 83 Issue 7 Pages 1498-1505
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: June 05, 2019
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    Background:The cost-effectiveness of percutaneous coronary intervention (PCI) for ischemic heart disease is undetermined in Japan. The aim of this study was to analyze the cost-effectiveness of PCI compared with medical therapy for ST-elevation myocardial infarction (STEMI) and angina pectoris (AP) in Japan.

    Methods and Results:We used Markov models for STEMI and AP to assess the costs and benefits associated with PCI or medical therapy from a health system perspective. We estimated the incremental cost-effectiveness ratio (ICER), expressed as quality-adjusted life-years (QALY), and ICER <¥5 m per QALY gained was judged to be cost-effective. The impact of PCI on cardiovascular events was based on previous publications. In STEMI patients, the ICER of PCI over medical treatment was ¥0.97 m per QALY gained. The cost-effectiveness probability of PCI was 99.9%. In AP patients, the ICER of fractional flow reserve (FFR)-guided PCI over medical treatment was ¥4.63 m per QALY gained. The cost-effectiveness probability of PCI was 50.4%. The ICER of FFR-guided PCI for asymptomatic patients was ¥23 m per QALY gained.

    Conclusions:In STEMI patients, PCI was cost-effective compared with medical therapy. In AP patients, FFR-guided PCI for symptomatic patients could be cost-effective compared with medical therapy. FFR-guided PCI for asymptomatic patients with myocardial ischemia was not cost-effective.

Epidemiology
  • Nagako Okuda, Aya Kadota, Nobuo Nishi, Katsuyuki Miura, Takayoshi Ohku ...
    Type: ORIGINAL ARTICLE
    Subject area: Epidemiology
    2019 Volume 83 Issue 7 Pages 1506-1513
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: May 16, 2019
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    Background:Several cohort studies have demonstrated an association between socioeconomic status (SES) and health outcomes in Japan. As long-term employment is common in Japan, the size of the company may be related to cardiovascular disease (CVD) mortality risk. We examined the association of employment conditions with CVD mortality risk among working-age Japanese men (30–59 years, n=2,091).

    Methods and Results:We used 20-year follow-up data from NIPPON DATA90, for which baseline data were obtained from the 4th National Survey on Circulatory Disorders in 1990. Participants were classified into 4 groups: 3 strata for indefinite-term employees according to company size (large company/public office, moderate-sized, or small), and the self-employed/administrator group. Multivariable-adjusted hazard ratios (HRs) were adjusted for age, lifestyle, and CVD risk factors. Smokers were more common, habitual exercise was less common, and the average systolic blood pressure was higher among indefinite-term employees of small companies compared with employees at large companies/public offices. There was no significant difference in the total CVD mortality risk between indefinite-term employees and self-employed/administrator participants. The age-adjusted HR (95% confidence interval) for total CVD using indefinite-term employees of large companies/public office as a reference was 2.53 (1.12, 5.69) for employees of small companies.

    Conclusions:Working as an indefinite-term employee at a small company in Japan was significantly associated with elevated risk of CVD mortality among Japanese men.

Heart Failure
  • Yi-Lin Tsai, Ruey-Hsing Chou, Chin-Sung Kuo, Chun-Chin Chang, Cheng-Hs ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2019 Volume 83 Issue 7 Pages 1514-1519
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: May 14, 2019
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    Background:Diastolic dysfunction (DD) is a characteristic of heart failure with preserved ejection fraction (HFpEF), which is thought to be caused by cardiac hypertrophy or fibrosis. Activin A is involved in the inflammatory response and myocardial fibrosis, but the relationship between the activin A level and DD remains unclear.

    Methods and Results:A total of 209 patients with stable angina were enrolled. Serum activin A levels were assessed, and echocardiography and cross-sectional analysis were performed. Among the subjects (65% male; mean age, 70±13 years), 84 (40%) subjects had DD. The subjects were divided into tertiles based on activin A levels. Patients in the high activin A group had enhanced left ventricular mass indexes, medial E/e’ ratios, left atrial diameter, and right ventricular systolic pressure compared with those in the lower activin A groups (all P<0.001). Prevalence of DD (P=0.001), HFpEF at enrollment (P=0.007), and the composite endpoints including new-onset heart failure (HF) or death within 3 years (P<0.001) correlated positively with high activin A levels. After adjusting for confounding factors, high activin A levels remained significantly associated with DD (P=0.036) and the composite endpoints (P=0.012).

    Conclusions:Enhanced serum activin A levels were associated with the incidence of DD and development of HF.

  • Koichiro Kinugawa, Naoki Sato, Takayuki Inomata, Moriyoshi Yasuda, Tos ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2019 Volume 83 Issue 7 Pages 1520-1527
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: May 22, 2019
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    Background:In Japan, tolvaptan is indicated for patients with heart failure and volume overload who have inadequate response to other diuretics. In contrast to the USA and Europe, tolvaptan can be used in Japan in patients with normal sodium levels.

    Methods and Results:In this multicenter, non-interventional, post-marketing surveillance study, prospective data from 3,349 patients treated with tolvaptan over a 5-year period were analyzed to identify benefits and risks. By Day 2 of treatment, 76.9% of evaluable patients had an increase in baseline 24-h urine volume (tolvaptan responders). Mean change in body weight was similar between 7.5 mg and 15 mg dosage groups (−3.6±3.9 kg and −3.7±4.0 kg, respectively). Improvement or disappearance rates for congestive symptoms from baseline to Day 14 ranged from 77.7% for lower limb edema to 51.1% for 3rd sound. Adverse drug reactions were reported in 18.1% of patients, most frequently thirst (8.4%). No case of central pontine myelinolysis was reported. All-cause mortality was significantly lower in patients with improved sodium concentration and increased 24-h urine volume.

    Conclusions:The effectiveness and safety of tolvaptan in real-world clinical settings was confirmed in this large-scale analysis. The 7.5-mg dose was equally as effective as the 15-mg dose and had a better safety profile. Improvements in all-cause mortality were suggested in tolvaptan responders.

  • Michio Nakanishi, Hiroyuki Miura, Kazuhiro Nakao, Masashi Fujino, Tets ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2019 Volume 83 Issue 7 Pages 1528-1537
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: May 30, 2019
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    Background:Although peak oxygen uptake (pV̇O2) is a well-established powerful prognostic predictor in heart failure (HF) patients, implementation of cardiopulmonary exercise testing (CPX) is limited by its complex analysis. We aimed to develop a new bivariate predictor obtained without respiratory gas measurement, comparable to pV̇O2.

    Methods and Results:We studied 560 consecutive HF patients with ejection fraction (EF) <45% who underwent CPX. During a median follow-up of 49.0 months, the composite of all-cause death or HF hospitalization occurred in 228 patients (40.7%) and all-cause death in 111 (19.8%). pV̇O2was the strongest single predictor of the composite outcome (chi-square, 99.3). Among the bivariate non-spirometry parameters, the ratio of systolic blood pressure at peak exercise to left atrial diameter (pSBP/LAD) was the strongest predictor (chi-square, 112.4). Patients with pSBP/LAD <2.8 mmHg/mm, compared with those with pSBP/LAD ≥2.8 mmHg/mm, had a hazard ratio of 3.84 (95% confidence interval, 2.95–5.04) for the composite outcome and 3.66 (2.50–5.37) for all-cause death. In the subgroup with pV̇O2<14 mL/kg/min (n=149), where pV̇O2had no further predictive value, pSBP was the strongest single predictor, and the predictive power of pSBP/LAD was more enhanced.

    Conclusions:pSBP/LAD was a new powerful predictor of HF hospitalization and death, comparable to pV̇O2, in HF with reduced EF. Because of its simplicity and high availability, this index has the potential for more widespread use than pV̇O2.

  • Yukihiro Koretsune, Takeshi Yamashita, Masaharu Akao, Hirotsugu Ataras ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2019 Volume 83 Issue 7 Pages 1538-1545
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: June 05, 2019
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    Background:Despite the well-established benefits in patients with nonvalvular atrial fibrillation (NVAF), anticoagulants have been underused in elderly patients. The All Nippon AF In the Elderly (ANAFIE) Registry is a multicenter, prospective, observational study with 2-year follow-up of Japanese patients aged ≥75 years with a definitive diagnosis of NVAF, aiming to collect detailed information on clinical status and therapeutic challenges in this patient population.

    Methods and Results:Patients were enrolled from October 2016 to January 2018. A total of 32,726 patients (57.2% male) were included. The average age, CHADS2score, and creatinine clearance were 81.5±4.8 years (26.2% of patients were aged ≥85 years), 2.9±1.2, and 48.4±21.8 mL/min, respectively. Paroxysmal AF was the most common clinical AF type (42.0%), and most patients (97.2%) had comorbidities. Most patients (91.9%) were receiving anticoagulant therapy; of these, 27.8% and 72.2% were treated with warfarin and direct oral anticoagulants, respectively. The average number of concomitant drugs used was 6.6±3.2, including anticoagulants.

    Conclusions:The ANAFIE Registry is the largest prospective registry study of elderly Japanese patients with NVAF to date. Baseline data indicate that patients in this age group are treated in a manner similar to their younger counterparts.

  • Kentaro Kamiya, Takanobu Yamamoto, Miyuki Tsuchihashi-Makaya, Toshimi ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2019 Volume 83 Issue 7 Pages 1546-1552
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: June 11, 2019
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    Background:The purpose of this study was to clarify the implementation rate of multidisciplinary heart failure (HF) care and cardiac rehabilitation (CR) in Japan, as well as the relationship between implementation rates and characteristics of the facility.

    Methods and Results:Survey participants were cardiologists who are members of the Japan Heart Failure Society and belonged to 1 of 845 medical institutions that are members of the Japan Heart Failure Society, as of April 2016. A total of 288 institutions (34.1%) returned the questionnaire. The percentages of hospitals implementing multidisciplinary HF care were 78.5% for inpatients and 32.6% for outpatients with HF. Inpatient and outpatient CR for HF had implementation rates of 80.4% and 56.5%, respectively. In addition, very few HF patients (7.3%, 3,741/51,323 patients) received outpatient CR. Both the presence of nurses certified in chronic HF care and registered CR instructors on staff were consistently associated with implementation of multidisciplinary HF care, and Japanese Circulation Society training hospitals, lower number of hospital beds, and presence of registered CR instructors on staff were consistently associated with implementation of CR.

    Conclusions:This first nationwide survey demonstrated that the implementation rates of multidisciplinary care and CR for HF, especially for outpatients, are low in Japan. Skilled healthcare professionals are expected to play important roles in the widespread implementation of this type of HF care in Japan.

Imaging
  • Enver Tahir, Jitka Starekova, Kai Muellerleile, Eric Freiwald, Alexand ...
    Type: ORIGINAL ARTICLE
    Subject area: Imaging
    2019 Volume 83 Issue 7 Pages 1553-1562
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: May 11, 2019
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    Background:To analyze the effect of myocardial fibrosis on left ventricular (LV) function evaluated by feature-tracking strain analysis by cine cardiac magnetic resonance (CMR) in competitive male triathletes with normal ejection fraction (EF).

    Methods and Results:78 asymptomatic male triathletes with >10 weekly training hours (43±11 years) and 28 male age-matched controls were studied by late gadolinium enhancement (LGE) and cine CMR. Global and segmental radial, longitudinal and circumferential strains were analyzed using feature-tracking cine CMR. Focal non-ischemic LGE was observed in 15 of 78 triathletes (19%, LGE+) with predominance in the basal inferolateral segments. LVEF was normal in LGE+ (62±6%) and LGE− triathletes (62±5%, P=0.958). In contrast, global radial strain was lower in LGE+ triathletes at 40±7% compared with LGE− triathletes (45±7%, P<0.05). Reduced segmental radial strain occurred either in LGE+ segments or in directly adjacent segments. Strain analysis revealed regional differences in controls, with the highest radial and longitudinal strain in the inferolateral segments, which were typically affected by fibrosis in LGE+ triathletes.

    Conclusions:Reduced global and regional radial strain suggests a negative effect of myocardial fibrosis on LV function in LGE+ triathletes with normal EF. The observed regional differences in controls with the highest radial and longitudinal strain in the inferolateral segments may explain the typical occurrence of fibrosis in this myocardial region in triathletes.

  • Akira Kurata, Naoki Fukuyama, Kuniaki Hirai, Naoto Kawaguchi, Yuki Tan ...
    Type: ORIGINAL ARTICLE
    Subject area: Imaging
    2019 Volume 83 Issue 7 Pages 1563-1571
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: June 08, 2019
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    Background:This study evaluated the diagnostic capability of on-site coronary computed tomography-derived computational fractional flow reserve (CT-FFR) determinations for detecting coronary artery disease (CAD), as assessed by invasive fractional flow reserve (FFR).

    Methods and Results:Seventy-four patients with coronary artery calcium scores <1,500 who underwent coronary CT angiography (CTA) and invasive FFR measurements within 90 days were retrospectively reviewed. CT-FFR was computed using a prototype machine-learning (ML) algorithm in 91 vessels; 47 vessels of 42 patients were determined to have significant CAD (FFR ≤0.8). Correlation between CT-FFR and FFR was good (r=0.786, P<0.001). Per-vessel area under the curve was significantly larger for CT-FFR (0.907, 95% confidence interval: 0.828–0.958) than for CTA stenosis ≥50% (0.595, 0.487–0.697) or ≥70% (0.603, 0.495–0.705) (both P<0.001). Standard coronary CTA classifications recommended further functional tests in 57 patients with moderate or worse stenosis on CTA. CT-FFR analysis (mean analysis time: 16.4±7.5 min) corrected the standard coronary CTA classification in 18 of 74 patients and confirmed it in 45 of 74 patients. Thus, the per-patient diagnostic accuracy of the classifications was improved from 66% (54–77%) to 85% (75–92%).

    Conclusions:On-site CT-FFR based on a ML algorithm can provide good diagnostic performance for detecting hemodynamically significant CAD, suggesting the high value of coronary CTA for selected patients in clinical practice.

Ischemic Heart Disease
  • Wonsuk Choi, Hyoung Woo Chang, Si-Hyuck Kang, Chang-Hwan Yoon, Young-S ...
    Type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2019 Volume 83 Issue 7 Pages 1572-1580
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: May 24, 2019
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    Background:Some studies comparing minimally invasive direct coronary artery bypass (MIDCAB) and percutaneous coronary intervention (PCI) have reported MIDCAB’s superiority, but they did not investigate contemporary PCI with newer generation drug-eluting stents (DES). We compared clinical outcomes after MIDCAB with previously reported outcomes after PCI with second-generation DES.

    Methods and Results:We retrospectively reviewed the records of patients treated with MIDCAB. Baseline characteristics and clinical outcomes after MIDCAB were compared with those for left anterior descending artery disease treated via PCI. The primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE), a composite of cardiovascular death, non-fatal myocardial infarction, ischemic stroke, and target vessel revascularization (TVR). A propensity score-matching (PSM) analysis was conducted to adjust for between-group differences in baseline characteristics. We analyzed 77 patients treated with MIDCAB and 2,206 treated with PCI. The MIDCAB group was older and had more severe coronary disease and a higher incidence of left ventricular dysfunction. Over a 3-year follow-up, the PCI group had favorable MACCE outcomes. After PSM, there were no between-group differences in MACCE (MIDCAB, 15.6% vs. PCI, 23.4%; hazard ratio [HR], 0.80; 95% CI: 0.38–1.68, P=0.548) or TVR (MIDCAB, 2.6% vs. PCI, 5.2%; HR, 0.51; 95% CI: 0.10–3.09, P=0.509).

    Conclusions:Clinical outcomes were similar between MIDCAB and PCI using second-generation DES over 3 years of follow-up.

Peripheral Vascular Disease
  • Yusuke Yoshikawa, Yugo Yamashita, Takeshi Morimoto, Hidewo Amano, Toru ...
    Type: ORIGINAL ARTICLE
    Subject area: Peripheral Vascular Disease
    2019 Volume 83 Issue 7 Pages 1581-1589
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: May 28, 2019
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    Background:It remains controversial whether sex category is a risk for recurrent venous thromboembolism (VTE) and major bleeding among VTE patients.

    Methods and Results:The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive acute symptomatic VTE patients from 29 centers in Japan between January 2010 and August 2014. We compared the clinical characteristics and outcomes of men and women. Men accounted for 1,169 (39%) and women 1,858 (61%). Compared with women, men were younger (64.9±14.7 vs. 68.6±15.6 years old, P<0.001), more often had prior VTE (7.2% vs. 5.1%, P=0.02), and less often had transient risk factors for VTE (30% vs. 40%, P<0.001). The proportions of active cancer and pulmonary embolism were comparable between men and women (24% vs. 22%, P=0.26; 56% vs. 57%, P=0.48, respectively). The cumulative 3-year incidences of recurrent VTE, major bleeding, and all-cause death were not significantly different between men and women (7.0% vs. 8.6%, P=0.47; 10.6% vs. 9.2%, P=0.25; 25.2% vs. 23.4%, P=0.35, respectively). The adjusted risks of men relative to women for recurrent VTE and for major bleeding remained insignificant (HR 0.83, 95% CI 0.63–1.09, P=0.17; HR 1.15, 95% CI 0.90–1.47, P=0.25, respectively).

    Conclusions:In real-world VTE patients, the clinical characteristics differed between men and women, but there was not a large sex-related difference in the risks for recurrent VTE or major bleeding.

Regenerative Medicine
  • Takeshi Yagyu, Satoshi Yasuda, Noritoshi Nagaya, Kaori Doi, Takeshi Na ...
    Type: ORIGINAL ARTICLE
    Subject area: Regenerative Medicine
    2019 Volume 83 Issue 7 Pages 1590-1599
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: May 17, 2019
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    Background:Mesenchymal stem cells (MSCs), which have the potential to differentiate into cardiomyocytes or vascular endothelial cells, have been used clinically as therapy for cardiomyopathy. In this study, we aimed to evaluate the long-term follow-up results.

    Methods and Results:We studied 8 patients with symptomatic heart failure (HF) on guideline-directed therapy (ischemic cardiomyopathy, n=3; nonischemic cardiomyopathy, n=5) who underwent intracardiac MSC transplantation using a catheter-based injection method between May 2004 and April 2006. Major adverse events and hospitalizations were investigated up to 10 years afterward. Compared with baseline, there were no significant differences in B-type natriuretic peptide (BNP) (from 211 to 173 pg/mL), left ventricular ejection fraction (LVEF) (from 24% to 26%), and peak oxygen uptake (from 16.5 to 19.2 mL/min/kg) at 2 months. During the follow-up period, no patients experienced serious adverse events such as arrhythmias. Three patients died of pneumonia in the 1st year, liver cancer in the 6th year, and HF in the 7th year. Of the remaining 5 patients, 3 patients were hospitalized for exacerbated HF, 1 of whom required heart transplantation in the 2nd year; 2 patients survived for 10 years without worsening HF.

    Conclusions:The results of this exploratory study of intracardiac MSCs administration suggest further research regarding the feasibility and efficacy is warranted.

Valvular Heart Disease
  • Koichi Maeda, Toru Kuratani, Isamu Mizote, Kazuo Shimamura, Yasuhiro I ...
    Type: ORIGINAL ARTICLE
    Subject area: Valvular Heart Disease
    2019 Volume 83 Issue 7 Pages 1600-1606
    Published: June 25, 2019
    Released: June 25, 2019
    [Advance publication] Released: May 23, 2019
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    Background:Little is known about late outcomes after transcatheter aortic valve replacement (TAVR) in dialysis patients.

    Methods and Results:We enrolled 25 dialysis patients (mean age 76.5 years; mean STS score 14.7%; men 60.0%) with aortic valve stenosis undergoing TAVR at our institute. Cardiovascular mortality and stroke were defined according to the VARC-2 criteria, and major adverse cardiac and cerebrovascular events (MACCE) were investigated. Twenty-three patients (92.0%) were discharged, and the median hospital stay after TAVR was 9 days (IQR, 7.5–11 days). Mortality at 30 days was not observed. The overall survival rate at 1 and 3 years were 80.0% and 55.7%, respectively (follow-up period, 879±493 days; range, 40–1,826 days). At 1 and 3 years, rates of freedom from cardiovascular mortality, disabling stroke, and MACCE were 100% and 83.0%, 91.2% and 84.7%, and 69.8% and 39.9%, respectively. Three patients required redo-TAVR for valve dysfunction at 23, 36, and 38 months after the first TAVR, respectively (The rate of freedom from severe structural valve deterioration at 1 and 3 years was 100% and 85.9%, respectively).

    Conclusions:Satisfactory in-hospital outcomes were achieved in dialysis patients after TAVR. Various problems, however, such as complications particular to dialysis patients and valve durability, remained at midterm follow-up. Further studies are recommended to solve these problems, and prudent preoperative assessments should be mandatory.

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