Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 83 , Issue 11
Showing 1-28 articles out of 28 articles from the selected issue
In Memoriam
Reviews
  • Yuji Okura, Kazuyuki Ozaki, Hiroshi Tanaka, Tatsuya Takenouchi, Nobuak ...
    Type: REVIEW
    2019 Volume 83 Issue 11 Pages 2191-2202
    Published: October 25, 2019
    Released: October 25, 2019
    [Advance publication] Released: September 18, 2019
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    Onco-cardiology, a new academic field, aims to improve the quality of life and prognosis of cancer patients and survivors with cardiovascular diseases (CVD). With the aging of the population, an epidemic of cancer with CVD is emerging in developed countries. Cancer and CVD share risk factors, pathophysiology, treatments, and preventive and rehabilitative measures. A multidisciplinary team-based approach is needed to support cancer treatment to maximize its effectiveness and minimize its cardiotoxic potential. Basic and clinical onco-cardiology are already being practiced harmoniously. However, systematization in academia and clinical practice and accumulation of evidence have just started. In this review, we present the epidemiology, common risk factors between cancer and CVD, future epidemic of CVD in patients with cancer, and the necessity for an onco-cardiological approach to managing the burden of CVD in cancer patients and survivors.

Editorials
Original Articles
Cardiovascular Intervention
  • Joo Myung Lee, Tae-Min Rhee, Ki Hong Choi, Jonghanne Park, Doyeon Hwan ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2019 Volume 83 Issue 11 Pages 2210-2221
    Published: October 25, 2019
    Released: October 25, 2019
    [Advance publication] Released: September 04, 2019
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    Supplementary material

    Background:We evaluated the 2-year clinical outcomes of deferred lesions with discordant results between resting and hyperemic pressure-derived physiologic indices, including resting distal to aortic coronary pressure (resting Pd/Pa), instantaneous wave-free ratio (iFR), resting full-cycle ratio (RFR), diastolic pressure ratio (dPR), and fractional flow reserve (FFR).

    Methods and Results:The 2-year clinical outcomes of 1,024 vessels (435 patients) with available resting Pd/Pa, iFR, RFR, dPR, and FFR data were analyzed according to a 4-group classification using known cutoff values (resting Pd/Pa ≤0.92, iFR/RFR/dPR ≤0.89, and FFR ≤0.80): Group 1 (concordant normal), Group 2 (high resting index and low FFR), Group 3 (low resting index and high FFR), and Group 4 (concordance abnormal). The primary outcome was vessel-oriented composite outcomes (VOCO) in deferred vessels at 2 years. In the comparison of VOCO risk among 4 groups classified according to FFR and 4 resting physiologic indices, Group 4 consistently showed a significantly higher risk of VOCO than Group 1. Comparison of VOCO risk among 4 groups classified according to iFR and other resting physiologic indices also showed the same results. The presence of discordance, either between hyperemic and resting indices or among resting indices, was not an independent predictor for VOCO.

    Conclusions:Discordant results between resting physiologic indices and FFR and among the resting indices were not associated with increased risk of VOCO in deferred lesions.

Cardiovascular Surgery
  • Keigo Yamashita, Takehisa Abe, Yoshihiro Hayata, Tomoaki Hirose, Shige ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Surgery
    2019 Volume 83 Issue 11 Pages 2222-2228
    Published: October 25, 2019
    Released: October 25, 2019
    [Advance publication] Released: September 05, 2019
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    Background:Pulmonary arterial capacitance (PAC) is a determinant of right ventricular afterload and a strong independent predictor of unfavorable outcomes in advanced heart failure (HF) with pulmonary hypertension (PH). We aimed to test the hypothesis that preoperative PAC may affect postoperative clinical outcomes in patients undergoing aortic valve replacement (AVR) for severe aortic valve stenosis (AS), even in the absence of PH.

    Methods and Results:We studied 116 patients who underwent AVR for severe AS between January 2005 and December 2017. Right heart catheterization was performed for all patients prior to surgery. PAC and pulmonary vascular resistance (PVR) fit well to a hyperbolic relationship (PAC=0.23/PVR, R2=0.73). PAC also showed an inverse relationship with pulmonary capillary wedge pressure (PCWP) (r=−0.15) and mean pulmonary arterial pressure (r=−0.29) and provided a stronger prediction of death or HF admission than PCWP or PVR (area under the ROC curve of 0.74 vs. 0.40 and 0.41, respectively, P=0.002). During a median follow-up of 36 months, PAC (hazard ratio, 0.48; 95% confidence interval, 0.30–0.78; P=0.003) was an independent predictor of death or hospitalization for HF.

    Conclusions:In these patients undergoing AVR for severe AS, even in the absence of PH, preoperative reduced PAC was independently associated with adverse surgical outcomes. It seems that preoperative PAC has potential as an independent predictor of long-term prognosis after AVR for severe AS.

  • Genichi Sakaguchi, Hiroaki Miyata, Noboru Motomura, Chikara Ueki, Erik ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Surgery
    2019 Volume 83 Issue 11 Pages 2229-2235
    Published: October 25, 2019
    Released: October 25, 2019
    [Advance publication] Released: September 11, 2019
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    Background:Ventricular septal defect (VSD) after myocardial infarction (MI) is a rare but fatal complication. We report patients’ characteristics and operative outcomes after surgical repair of post-MI VSD using a national database of Japan.

    Methods and Results:This was a retrospective review of the Japan Adult Cardiovascular Surgery Database (JCVSD) to identify adults (age ≥18 years) who underwent surgical repair of post-MI VSD between 2008 and 2014. The primary outcome was operative death. We identified 1,397 patients (671 male [48%], 74.1±9.3 years old) undergoing surgical repair of post-MI VSD among 288,736 patients undergoing cardiac surgery enrolled in the JCVSD during the same period. Of these, 1,075 (77.0%) were supported preoperatively with an intra-aortic balloon pump. Surgical status was urgent in 391 (28.0%) and emergency/salvage in 731 (52.3%). Concomitant coronary artery bypass grafting was performed in 475 (34.0%). Overall 30-day and operative mortalities were 24.3% and 33.0%, respectively. Operative mortality varied according to surgical status: 15.6% in elective, 30.9% in urgent, and 40.6% in emergency/salvage cases. Multivariable analysis identified advanced age and emergency/salvage status as being strongly associated with increased odds of operative death.

    Conclusions:Post-MI VSD remains a devastating complication in Japan as well as in the USA and Europe.

Epidemiology
  • Sung Keun Park, Ju Young Jung, Jeong Gyu Kang, Pil-Wook Chung, Jae-Hon ...
    Type: ORIGINAL ARTICLE
    Subject area: Epidemiology
    2019 Volume 83 Issue 11 Pages 2236-2241
    Published: October 25, 2019
    Released: October 25, 2019
    [Advance publication] Released: September 07, 2019
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    Background:It is believed that left ventricular (LV) geometry change contributes to the elevated cardiovascular risk in patients with chronic kidney disease. However, data are less available on the association between LV geometry change and mildly decreased renal function within estimated glomerular filtration rate (eGFR) from 60 to 89 (mL/min/1.73 m2).

    Methods and Results:In a cohort of 47,730 Koreans undergoing echocardiography as part of a health check-up, we evaluated the association of LV hypertrophy (LVH) and abnormal relative wall thickness (RWT) with 4 levels and 3 levels of eGFR in men (≥90, 89.99–80, 79.99–70, 69.99–60) and women (≥90, 89.99–80, 79.99–60), respectively. Multivariate logistic regression analysis was used to calculate the odds ratios (OR) and 95% confidence intervals (CI) for LVH and abnormal RWT, adjusting for conventional cardiovascular risk factors (adjusted OR [95% CI]). In the fully adjustment model, men did not show a significant association between LVH and levels of eGFR between 60 and 89. However, abnormal RWT was significantly associated with the levels of eGFR between 60 and 89. Women did not show a significant association of LVH and abnormal RWT with levels of eGFR between 60 and 89.

    Conclusions:Men with mildly decreased renal function (eGFR between 60 and 89 mL/min/1.73 m2) had increased probability of LV geometry change represented by abnormal RWT.

Ischemic Heart Disease
  • Katsuya Miura, Takenobu Shimada, Masanobu Ohya, Ryosuke Murai, Hidewo ...
    Type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2019 Volume 83 Issue 11 Pages 2242-2249
    Published: October 25, 2019
    Released: October 25, 2019
    [Advance publication] Released: September 07, 2019
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    Supplementary material

    Background:To date, the long-term incidence and details of major bleeding (MB) and coronary thrombotic events (CTE) in patients with everolimus-eluting stent (EES) implantation have not been made clear.

    Methods and Results:The study population comprised 1,193 patients treated with EES without in-hospital events between 2010 and 2011. MB was defined as the occurrence of a Bleeding Academic Research Consortium type 3 or 5 bleeding event. The mean follow-up period was 2,996±433 days. Cumulative rate of MB was 7.4% and 10.8% at 5 and 8 years, respectively. Of 46 patients with intracranial bleeding, 20 had trauma-related intracranial bleeding. Cumulative rates of definite stent thrombosis and CTE at 8 years were 0.4% and 5.9%, respectively. Multivariate analysis revealed low body mass index (<23) (hazard ratio (HR), 1.57; 95% confidence interval (CI), 1.03–2.36; P=0.03) and concomitant use of oral anticoagulants (HR, 2.17; 95% CI, 1.30–3.50; P=0.004) as independent risk factors of MB and previous PCI (HR, 2.47; 95% CI, 1.29–1.00; P=0.006) as the factor for CTE.

    Conclusions:MB is not uncommon and is a long-term hazard, but the occurrence of stent thrombosis is very low after EES implantation. Approximately half of the cases involving intracranial bleeding were associated with trauma.

  • Manabu Kashiwagi, Toshio Imanishi, Yuichi Ozaki, Akira Taruya, Tsuyosh ...
    Type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2019 Volume 83 Issue 11 Pages 2250-2256
    Published: October 25, 2019
    Released: October 25, 2019
    [Advance publication] Released: September 11, 2019
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    Background:Monocytes in human peripheral blood are heterogeneous and can be divided into 2 groups, inflammatory and pro-inflammatory, according to the differential expression of CD14 and CD16. Pro-inflammatory monocytes (CD14+CD16+) seem to contribute to the development of coronary artery disease. This study aimed to investigate the involvement of specific human peripheral monocyte subsets in the development of future coronary events.

    Methods and Results:We enrolled 271 patients who were suspected to have either stable angina pectoris or silent myocardial ischemia and underwent coronary angiography (CAG). Two monocyte subsets (CD14+CD16and CD14+CD16+) were measured by flow cytometry. Patients who did not undergo coronary artery revascularization at initial CAG were followed as the medical therapy group, which included 136 patients among whom 15 had future coronary events. The frequency of CD14+CD16+monocytes was significantly higher in patients who had future coronary events than in those who did not (P<0.01). Furthermore, the frequencies of CD14+CD16+monocyte were not significantly different between patients who had future coronary events and those who underwent coronary revascularization at initial CAG (P<0.33). Multivariate analysis revealed that the frequency of CD14+CD16+monocytes was an independent predictor for future coronary events (P<0.01).

    Conclusions:An increase in the abundance of human peripheral pro-inflammatory monocytes is related to the development of future coronary events.

Pediatric Cardiology and Adult Congenital Heart Disease
  • Keiko Yamasaki, Hiroyuki Sawatari, Nao Konagai, Chizuko A. Kamiya, Jun ...
    Type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2019 Volume 83 Issue 11 Pages 2257-2264
    Published: October 25, 2019
    Released: October 25, 2019
    [Advance publication] Released: August 29, 2019
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    Background:The average maternal age at delivery, and thus the associated maternal risk are increasing including in women with congenital heart disease (CHD). A comprehensive management approach is therefore required for pregnant women with CHD. The present study aimed to investigate the factors determining peripartum safety in women with CHD.

    Methods and Results:We retrospectively collected multicenter data for 217 pregnant women with CHD (age at delivery: 31.4±5.6 years; NYHA classifications I and II: 88.9% and 7.4%, respectively). CHD severity was classified according to the American College of Cardiology/American Heart Association guidelines as simple (n=116), moderate complexity (n=69), or great complexity (n=32). Cardiovascular (CV) events (heart failure: n=24, arrhythmia: n=9) occurred in 30 women during the peripartum period. Moderate or great complexity CHD was associated with more CV events during gestation than simple CHD. CV events occurred earlier in women with moderate or great complexity compared with simple CHD. Number of deliveries (multiparity), NYHA functional class, and severity of CHD were predictors of CV events.

    Conclusions:This study identified not only the severity of CHD according to the ACC/AHA and NYHA classifications, but also the number of deliveries, as important predictive factors of CV events in women with CHD. This information should be made available to women with CHD and medical personnel to promote safe deliveries.

  • Yuki Kimura, Takao Kato, Hiromi Miyata, Issei Sasaki, Eri Minamino-Mut ...
    Type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2019 Volume 83 Issue 11 Pages 2265-2270
    Published: October 25, 2019
    Released: October 25, 2019
    [Advance publication] Released: September 22, 2019
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    Background:Because cardiovascular function and hemodynamics markedly change during pregnancy, our aim was to elucidate left ventricular (LV) diastolic function in pregnant women.

    Methods and Results:We prospectively collected the data of 397 pregnant women treated between 2012 and 2013. We evaluated their LV systolic and diastolic functions via echocardiography during the 3rd trimester (28–30 weeks’ gestation) and within 4 days of delivery. Additionally, we analyzed the cardiac geometry: relative wall thickness and LV mass index (LVMI). Diastolic dysfunction was defined as early diastolic mitral annulus velocity (e’) <7 cm/s and peak early filling velocity (E)/e’ ratio >15. The pregnant women were 33.7±5.0 years old and the prevalence of hypertensive disorders in pregnancy (HDP) was 4.0%. LV systolic function was preserved in all pregnant women. However, diastolic function significantly decreased after delivery (mean e’: 12.6 vs. 11.6 cm/s, P<0.0001; median E/e’ ratio: 6.4 vs. 7.3, P<0.0001). Diastolic function after delivery was associated with the prevalence of HDP (P=0.035) and was correlated with age (R=−0.17, P=0.0009) and LVMI (R=−0.30, P<0.0001). However, these changes in diastolic function remained within the normal range and only 1 woman (1/397, 0.3%) had LV diastolic dysfunction after delivery.

    Conclusions:LV diastolic function decreased after delivery in pregnant women but was within the normal range.

Pulmonary Circulation
  • Jiro Sakamoto, Yugo Yamashita, Takeshi Morimoto, Hidewo Amano, Toru Ta ...
    Type: ORIGINAL ARTICLE
    Subject area: Pulmonary Circulation
    2019 Volume 83 Issue 11 Pages 2271-2281
    Published: October 25, 2019
    Released: October 25, 2019
    [Advance publication] Released: September 20, 2019
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    Supplementary material

    Background:There is a paucity of data on the management and prognosis of cancer-associated venous thromboembolism (VTE), leading to uncertainty about optimal management strategies.

    Methods and Results:The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive acute symptomatic VTE patients in Japan between 2010 and 2014. We divided the entire cohort into 3 groups: active cancer (n=695, 23%), history of cancer (n=243, 8%), and no history of cancer (n=2089, 69%). The rate of anticoagulation discontinuation was higher in patients with active cancer (43.5%, 27.0%, and 27.0%, respectively, at 1 year, P<0.001). The cumulative 5-year incidences of recurrent VTE, major bleeding, and all-cause death were higher in patients with active cancer (recurrent VTE: 17.7%, 10.2%, and 8.6%, P<0.001; major bleeding: 26.6%, 8.8%, and 9.3%, P<0.001; all-cause death: 73.1%, 28.6%, 14.6%, P<0.001). Among the 4 groups classified according to active cancer status, the cumulative 1-year incidence of recurrent VTE was higher in the metastasis group (terminal stage group: 6.4%, metastasis group: 22.1%, under chemotherapy group: 10.8%, and other group: 5.8%, P<0.001).

    Conclusions:In a current real-world VTE registry, patients with active cancer had higher risk for VTE recurrence, bleeding, and death, with variations according to cancer status, than patients without active cancer. Anticoagulation therapy was frequently discontinued prematurely in patients with active cancer in discordance with current guideline recommendations.

Regenerative Medicine
  • Maya Adachi, Mai Watanabe, Yasutaka Kurata, Yumiko Inoue, Tomomi Notsu ...
    Type: ORIGINAL ARTICLE
    Subject area: Regenerative Medicine
    2019 Volume 83 Issue 11 Pages 2282-2291
    Published: October 25, 2019
    Released: October 25, 2019
    [Advance publication] Released: September 13, 2019
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    Supplementary material

    Background:Treatment of myocardial infarction (MI) includes inhibition of the sympathetic nervous system (SNS). Cell-based therapy using adipose-derived stem cells (ASCs) has emerged as a novel therapeutic approach to treat heart failure in MI. The purpose of this study was to determine whether a combination of ASC transplantation and SNS inhibition synergistically improves cardiac functions after MI.

    Methods and Results:ASCs were isolated from fat tissues of Lewis rats. In in vitro studies using cultured ASC cells, mRNA levels of angiogenic factors under normoxia or hypoxia, and the effects of norepinephrine and a β-blocker, carvedilol, on the mRNA levels were determined. Hypoxia increased vascular endothelial growth factor (VEGF) mRNA in ASCs. Norepinephrine further increased VEGF mRNA; this effect was unaffected by carvedilol. VEGF promoted VEGF receptor phosphorylation and tube formation of human umbilical vein endothelial cells, which were inhibited by carvedilol. In in vivo studies using a rat MI model, transplanted ASC sheets improved contractile functions of MI hearts; they also facilitated neovascularization and suppressed fibrosis after MI. These beneficial effects of ASC sheets were abolished by carvedilol. The effects of ASC sheets and carvedilol on MI heart functions were confirmed by Langendorff perfusion experiments using isolated hearts.

    Conclusions:ASC sheets prevented cardiac dysfunctions and remodeling after MI in a rat model via VEGF secretion. Inhibition of VEGF effects by carvedilol abolished their beneficial effects.

Stroke
  • Ataru Nishimura, Kunihiro Nishimura, Daisuke Onozuka, Ryu Matsuo, Akik ...
    Type: ORIGINAL ARTICLE
    Subject area: Stroke
    2019 Volume 83 Issue 11 Pages 2292-2302
    Published: October 25, 2019
    Released: October 25, 2019
    [Advance publication] Released: September 26, 2019
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    Supplementary material

    Background:We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing Diagnosis Procedure Combination (DPC) database.

    Methods and Results:We conducted a systematic review of domestic and international studies using the modified Delphi method. Feasibility of measuring the QI adherence rates was examined using a DPC-based nationwide stroke database (396,350 patients admitted during 2013–2015 to 558 hospitals participating in the J-ASPECT study). Associations between adherence rates of these QIs and hospital characteristics were analyzed using hierarchical logistic regression analysis. We developed 17 and 12 measures as QIs for primary and comprehensive stroke care, respectively. We found that measurement of the adherence rates of the developed QIs using the existing DPC database was feasible for the 6 QIs (primary stroke care: early and discharge antithrombotic drugs, mean 54.6% and 58.7%; discharge anticoagulation for atrial fibrillation, 64.4%; discharge antihypertensive agents, 51.7%; comprehensive stroke care: fasudil hydrochloride or ozagrel sodium for vasospasm prevention, 86.9%; death complications of diagnostic neuroangiography, 0.4%). We found wide inter-hospital variation in QI adherence rates based on hospital characteristics.

    Conclusions:We developed QIs for primary and comprehensive stroke care. The DPC database may allow efficient data collection at low cost and decreased burden to evaluate the developed QIs.

  • Bizhong Che, Chongke Zhong, Jinzhuo Ge, Ruyi Li, Zhengbao Zhu, Xiaoqin ...
    Type: ORIGINAL ARTICLE
    Subject area: Stroke
    2019 Volume 83 Issue 11 Pages 2303-2311
    Published: October 25, 2019
    Released: October 25, 2019
    [Advance publication] Released: September 27, 2019
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    Supplementary material

    Background:Matrix metalloproteinase-9 (MMP-9), a key determinant of extracellular matrix degradation, might cause cerebral damage after stroke and be involved in the development of depressive symptoms. This study aimed to evaluate the association of serum MMP-9 levels and post-stroke depression (PSD).

    Methods and Results:Serum MMP-9 levels were determined in 558 acute ischemic stroke patients from 7 hospitals comprising the China Antihypertensive Trial in Acute Ischemic Stroke. We assessed depression status using the 24-item Hamilton Depression Rating Scale and defined PSD as a cutoff score of 8. Logistic regression was performed to estimate the risk of PSD associated with serum MMP-9. Discrimination and reclassification for PSD by MMP-9 were analyzed. A total of 222 (39.8%) stroke patients were categorized as PSD within 3 months. Serum MMP-9 concentrations were higher among PSD patients than those without PSD (658.8 vs. 485.7 ng/mL; P<0.001). The multiple-adjusted odds ratio (95% confidence interval) for the highest MMP-9 quartile compared with the lowest quartile was 4.36 (2.49–7.65) for PSD, and 1 standard deviation higher log-MMP-9 was associated with 68% (37–106%) increased odds of PSD. Adding MMP-9 to the conventional risk factors model substantially improved discrimination and reclassification for PSD (all P<0.05).

    Conclusions:Elevated serum MMP-9 levels in the acute phase of ischemic stroke were associated with increased risk of PSD, suggesting an important prognostic role of MMP-9 for PSD.

Valvular Heart Disease
  • Hiroki Takada, Hidekazu Tanaka, Shun Yokota, Jun Mukai, Makiko Suto, F ...
    Type: ORIGINAL ARTICLE
    Subject area: Valvular Heart Disease
    2019 Volume 83 Issue 11 Pages 2312-2319
    Published: October 25, 2019
    Released: October 25, 2019
    [Advance publication] Released: September 13, 2019
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    Background:The underlying mechanism of mitral regurgitation (MR) in atrial fibrillation (AF) is an isolated annulus dilation caused by left atrial (LA) remodeling. However, the association of mitral valve (MV) geometry with MR in AF patients remains unclear.

    Methods and Results:We studied 96 AF patients with preserved left ventricular ejection fraction (LVEF). MV geometry was evaluated with 3-dimensional transesophageal echocardiography (3D-TEE). Mitral annulus area of the MR group (n=11, ≥ moderate) was significantly larger (10.6±1.8 vs. 8.2±1.5 cm2, P<0.0001), and relative posterior mitral leaflet (PML) area (PML area / mitral annulus area) was significantly smaller (0.51±0.06 vs. 0.57±0.01, P=0.002) than in the non-MR group (n=85, <moderate). Multivariate logistic regression analysis showed that, in addition to LA volume index (LAVI), a relative PML area was independently associated with MR. For sequential logistic regression models to determine the association of MR, clinical variables including age, gender and LVEF were improved by the addition of LAVI (P<0.001) and was improved by addition of mitral annulus area (P=0.01), and further improved by addition of relative PML area (P<0.001).

    Conclusions:A relatively short PML plays an important role in the development of MR in AF patients. Assessment of MV geometry by 3D-TEE may thus have clinical implications for better surgical management of AF patients with significant MR.

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