International Heart Journal
Online ISSN : 1349-3299
Print ISSN : 1349-2365
ISSN-L : 1349-2365
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Editorials
Review Articles
  • Toshiaki Isogai, Chizuko A. Kamiya
    2019 Volume 60 Issue 3 Pages 503-511
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 25, 2019
    JOURNALS FREE ACCESS

    Peripartum cardiomyopathy (PPCM) is a specific cardiomyopathy in which heart failure develops due to reduced myocardial contraction during pregnancy or in the postpartum period in women without a previous history of heart disease. The epidemiology of PPCM has been reported in various countries and areas, and the incidence of PPCM differed among these reports. The incidence was highest (1 in 102 deliveries) in Nigeria and lowest (1 in 15,533 births) in Japan. The incidence was higher in African-Americans than in other races in several reports from the United States, and was also high in African countries and Haiti, indicating that the risk for PPCM is highest in the black race. However, the study design and definition of PPCM differ among studies, and these differences may influence the incidence. Moreover, the incidence of PPCM and the maternal mortality rate were well correlated. Since maternal mortality reflects the level of perinatal health care and hygiene, this finding suggests that the extent of perinatal care is partly related to the incidence of PPCM, which reflects heart failure and cardiomyopathy of unknown cause in women.

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  • Zhi-Dong Ge, Qingquan Lian, Xiaowen Mao, Zhengyuan Xia
    2019 Volume 60 Issue 3 Pages 512-520
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 10, 2019
    JOURNALS FREE ACCESS

    Diabetic cardiomyopathy is one of the main causes of heart failure and death in patients with diabetes mellitus. Reactive oxygen species produced excessively in diabetes mellitus cause necrosis, apoptosis, ferroptosis, inflammation, and fibrosis of the myocardium as well as impair the cardiac structure and function. It is increasingly clear that oxidative stress is a principal cause of diabetic cardiomyopathy. The transcription factor nuclear factor-erythroid 2 p45-related factor 2 (NRF2) activates the transcription of more than 200 genes in the human genome. Most of the proteins translated from these genes possess anti-oxidant, anti-inflammatory, anti-apoptotic, anti-ferroptotic, and anti-fibrotic actions. There is a growing body of evidence indicating that NRF2 and its target genes are crucial in preventing high glucose-induced oxidative damage in diabetic cardiomyopathy. Recently, many natural and synthetic activators of NRF2 are shown to possess promising therapeutic effects on diabetic cardiomyopathy in animal models of diabetic cardiomyopathy. Targeting NRF2 signaling by pharmacological entities is a potential approach to ameliorating diabetic cardiomyopathy. However, the persistent high expression of NRF2 in cancer tissues also protects the growth of cancer cells. This "dark side" of NRF2 increases the challenges of using NRF2 activators to treat diabetic cardiomyopathy. In addition, some NRF2 activators were found to have off-target effects. In this review, we summarize the current status and challenges of NRF2 as a potential therapeutic target for diabetic cardiomyopathy.

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Clinical Studies
  • Shintaro Takamura, Nobuaki Suzuki, Ruri Ishibashi, Nozomu Yukimitsu, K ...
    2019 Volume 60 Issue 3 Pages 521-526
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    Prior research has revealed poorer clinical outcomes after drug-eluting stent (DES) implantation for hemodialysis patients. This study aims to investigate the long-term clinical and angiographic outcomes after new-generation DES implantation for hemodialysis patients.

    We retrospectively enrolled 91 consecutive patients (118 lesions) who underwent successful new-generation DES (everolimus-, zotarolimus-, and biolimus-eluting stents) implantation for the first time. We measured the serum calcium and phosphorus levels in the blood samples obtained just before hemodialysis. The follow-up period of clinical events was, at least, 1.5 years. In this study, major adverse cardiac and cerebrovascular events (MACCE) and clinically driven target lesion revascularization were reported in 36 (39.6%) and 11 (12.1%) patients, respectively. The prevalence of peripheral artery disease was significantly higher in the MACCE group (41.7% versus 14.5%, P = 0.006). The serum calcium level was significantly higher in the MACCE group (9.34 ± 0.92 mg/dL versus 8.77 ± 0.88 mg/dL; P = 0.004). The multivariate Cox proportional hazards model revealed that the serum calcium level (hazard ratio, 1.86; 95% confidence interval [CI]: 1.26-2.77; P = 0.002), suboptimal (over 55 mg2/dL2) calcium-phosphorus product (hazard ratio, 3.27; 95% CI: 1.41-7.61; P = 0.006) and the coexistence of peripheral artery disease (hazard ratio, 3.15; 95% CI: 1.49-6.65; P = 0.003) were independent predictors of MACCE.

    For hemodialysis patients, MACCE remains a frequent occurrence after new-generation DES implantation and is associated with calcium-phosphate metabolism and peripheral artery disease.

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  • Alireza Sepehri Shamloo, Boris Dinov, Livio Bertagnolli, Philipp Somme ...
    2019 Volume 60 Issue 3 Pages 527-538
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    Cardiogoniometry (CGM) has been proposed as a new diagnostic tool for coronary artery disease (CAD) in recent years. Although different studies have evaluated the diagnostic value of CGM in CAD diagnosis, no pooled analysis of its diagnostic accuracy has been performed so far. This study aimed to assess the value of CGM in diagnosing CAD in patients with suspected stable ischemic heart disease (SIHD).

    This was a systematic review and meta-analysis conducted on available literature until May 2018. Studies considered coronary angiography as the reference standard for CAD diagnosis and reported CGM diagnostic value parameters were included. No language and time restrictions for enrolling the studies were considered. Statistical analysis was performed using Meta-DiSc software.

    The findings of the 10 studies published in 9 articles were enrolled in the meta-analysis. Overall pooled sensitivity was 71.7% (69.1 to 74.1; Cochrane Q = 39.5; P < 0.00001; I2 = 77.3%), and pooled specificity was 78.8% (76.3 to 81.1; Cochrane Q = 37.39; P < 0.00001; I2 = 75.9%). Regarding Egger's regression test (P = 0.32), there was no published bias in the studies.

    It seems that CGM, as an easy-to-use and non-invasive modality, should be considered as a part of risk stratifying strategies for CAD in patients with SIHD, mainly in patients with contraindications for stress tests. However, further studies with a high quality of methodology are still needed to assess the diagnostic value of CGM for CAD in patients with suspected SIHD.

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  • Teruyoshi Nemoto, Yoshiyasu Minami, Minako Yamaoka-Tojo, Toshimitsu Sa ...
    2019 Volume 60 Issue 3 Pages 539-545
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 10, 2019
    JOURNALS FREE ACCESS

    The association between endothelial function, evaluated using flow-mediated dilatation (FMD), and the severity of coronary artery disease remains to be elucidated.

    A total of 245 consecutive patients with stable angina were prospectively enrolled. FMD was evaluated in the brachial artery before percutaneous coronary intervention. Patients were divided into 2 groups according to the FMD value (lower FMD group [FMD < 2.0], n = 82; higher FMD group [FMD ≥ 2.0], n = 163). The severity of coronary artery disease was evaluated using findings of angiography and optical coherence tomography, and compared between the 2 groups.

    The prevalence of left main (LM) disease was significantly higher in the lower FMD group than in the higher FMD group (8.5% versus 2.5%, P = 0.046), although the prevalence of multivessel disease was comparable between the groups. Lower FMD was independently associated with a higher prevalence of LM disease (odds ratio, 3.89; 95% confidence interval, 1.12-15.5; P = 0.033). A general linear model with multiple variables revealed that the minimal lumen area (MLA) in the culprit lesion was significantly smaller in patients with lower FMD than in those with higher FMD (regression coefficient b, −0.249 mm2; 95% confidence interval, −0.479-−0.018 mm2; P = 0.035). The prevalence ofvulnerable plaque characteristics was comparable between the 2 groups.

    Patients with lower FMD had a higher incidence of LM disease and a smaller MLA in the culprit lesion. FMD may be a useful, noninvasive indicator for identifying patients with severe coronary artery disease.

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  • Xiaofei Gao, Zhen Ge, Xiangquan Kong, Zhimei Wang, Guangfeng Zuo, Feng ...
    2019 Volume 60 Issue 3 Pages 546-553
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    Antithrombotic strategies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remain challenging. This study aims to explore the best antithrombotic strategy for AF patients after PCI based on a network meta-analysis. This study was registered in PROSPERO (CRD42018093928). The PubMed, Cochrane, and EMBASE databases were searched to identify clinical trials concerning antithrombotic therapy for AF patients with PCI from inception to April 2018. Pairwise and network meta-analysis were conducted to compare clinical outcomes of different antithrombotic therapy. The primary endpoint was major bleeding. Fifteen studies including 16,382 patients were identified with follow-up ranging from 3 to 12 months. Non-vitamin K oral anticoagulants (NOAC) plus P2Y12 inhibitor ranked first with a reduced risk of major bleeding compared with vitamin K antagonist (VKA) plus dual antiplatelet therapy (OR: 0.57, 95% CI: 0.43-0.75) but with no significant difference compared with VKA plus single platelet therapy (OR: 0.85, 95% CI: 0.62-1.16). Similar thrombotic events were evident among these groups. Subgroup analysis showed that VKA plus aspirin exhibited a similar risk of major bleeding compared with VKA plus clopidogrel (OR: 0.94, 95% CI: 0.73-1.23) but was associated with increased risks of ischaemic stroke (OR: 2.10, 95% CI: 1.33-3.32) and all-cause death (OR: 1.77, 95% CI: 1.15-2.74) versus VKA plus clopidogrel. In AF patients undergoing PCI, NOAC plus P2Y12 inhibitor and VKA plus clopidogrel, but not VKA plus aspirin, were associated with reduced risk of major bleeding compared with the recommended VKA-based triple therapy, while thrombotic events were similar among these treatments.

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  • Kazuhiro Nitta, Satoshi Kurisu, Yumiko Nakamoto, Yoji Sumimoto, Atsuhi ...
    2019 Volume 60 Issue 3 Pages 554-559
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    It has been shown in several studies that coronary artery calcium (CAC) burden or CAC progression is associated with heart failure. We tested the hypothesis that the extent of CAC is associated with left ventricular (LV) diastolic parameters derived from gated myocardial perfusion single-photon emission computed tomography (SPECT) in patients with no evidence of myocardial ischemia.

    157 patients undergoing coronary computed tomography (CT), gated SPECT, and transthoracic echocardiography (TTE) were enrolled in this study. The CAC score was calculated according to the Agatston method. The peak filling rate (PFR) and the one-third mean filling rate (1/3MFR) were obtained as LV diastolic parameters.

    There were 139 patients with CAC and 18 patients without. The CAC score ranged from 0 to 4,976. There were no significant differences in the LV end-diastolic volume (LVEDV) (61 ± 21 mL versus 62 ± 22 mL, P = 0.79) and LV ejection fraction (LVEF) (66 ± 9% versus 68 ± 9%, P = 0.43). Patients with CAC had lower PFR than those without (2.2 ± 0.5 EDV/s versus 2.6 ± 0.7 EDV/s, P = 0.03). Multivariate linear regression analysis showed that ln (CAC score + 1) was significantly associated with PFR (β = −0.20, P = 0.01) and 1/3MFR (β = −0.18, P = 0.049).

    Our data suggest that the extent of CAC is inversely associated with LV diastolic parameters derived from gated SPECT independent of myocardial ischemia.

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  • Masamitsu Noguchi, Kenichi Sakakura, Naoyuki Akashi, Yusuke Adachi, Yu ...
    2019 Volume 60 Issue 3 Pages 560-568
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    Right ventricular infarction (RVI) is a complication following inferior ST-elevation myocardial infarction (STEMI). The aim of the present study was to investigate the clinical outcomes of RVI in the contemporary primary percutaneous coronary intervention (PCI) era. The primary endpoint was in-hospital death, and the secondary endpoint was major adverse cardiac events (MACE), defined as the composite of cardiovascular death, re-hospitalization for heart failure, and non-fatal acute myocardial infarction (AMI). Event-free survival curves for MACE were constructed using the Kaplan-Meier method, and statistical differences between curves were assessed using the log-lank test. A total of 1354 patients with AMI were screened from January 2010 to December 2016. The final study population involved 315 patients with STEMI whose infarct related artery (IRA) was the right coronary artery (RCA). We categorized these 315 patients into the RVI group (n = 85) and the non-RVI group (n = 230). Median follow-up duration was 358 (IQR: 208-987) days. In-hospital deaths were more frequently observed in the RVI group (9.4%) than in the non-RVI group (3.0%) (P = 0.018). However, the incidence of MACE was not different between the groups (P = 0.537). In conclusion, in-hospital clinical outcomes were poorer in the RVI group than in the non-RVI group. However, mid-term MACE was not different between the two groups, suggesting the importance of aggressive acute treatment for STEMI patients with RVI.

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  • Tao Zhang, Gong Su, Shu-hua Mi, Hong-xia Yang, Wei Xin, Wen-long Dai, ...
    2019 Volume 60 Issue 3 Pages 569-576
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 25, 2019
    JOURNALS FREE ACCESS

    Blood glucose variability is considered to be one of the risk factors for coronary heart disease, and there is growing evidence that blood glucose fluctuation is closely related to the characteristics of plaques. The aim of the study was to investigate the influence of blood glucose variability on the vulnerability of culprit plaques in elderly non-ST segment elevation acute coronary syndrome (NSTE-ACS) patients.

    Coronary angiography and VH-IVUS were applied to evaluate the components of culprit plaque in NSTE-ACS patients. CGMS monitoring was performed for 72 hours and blood glucose variability was assessed by glycemic excursions (MAGE), absolute means of daily differences (MODD), postprandial glycemic excursions (PPGE), and the largest amplitude of glycemic excursions (LAGE). An oxidative stress indicator (urinary 8-iso-PGF) was also tested.

    Eighty two elderly NSTE-ACS patients were enrolled in this study. Higher glucose variability was associated with the increased culprit plaque instability. MODD was positively correlated with urinary 8-iso-PGF. PPGE and urinary 8-iso-PGF were independent risk factors for percent fibrous and necrotic volume in culprit plaques (PPGE: β = −0.340, P = 0.024; urinary 8-iso-PGF: β = −0.294, P = 0.013).

    Blood glucose variability is positively related to oxidative stress. With an increase in blood glucose variability, the instability of criminal plaques in elderly NSTE-ACS patients increased.

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  • Tien-Yu Chen, Wen-Jung Chung, Chien-Ho Lee, Po-Jui Wu, Shu-Kai Hsueh, ...
    2019 Volume 60 Issue 3 Pages 577-585
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 25, 2019
    JOURNALS FREE ACCESS

    We investigated the accuracy of various bleeding risk scores to estimate the bleeding risk in patients with acute myocardial infarction (AMI) managed with percutaneous coronary intervention (PCI) access via the radial artery.

    We retrospectively enrolled 1,651 patients who were definitively diagnosed with ST-elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI). We assessed the predictive validities of 30-day bleeding events in various scoring systems using receiver operating characteristic curves.

    Overall, ACUITY-HORIZONS exhibited the highest area under the curve to predict 30-day bleeding, followed by ACTION and CRUSADE; HAS-BLED displayed the lowest score. With a cut-off of 17, ACUITY-HORIZONS demonstrated the best discrimination for the Thrombolysis in Myocardial Infarction (TIMI) 30-day serious bleeding rate. We observed significant differences among all-cause death, cardiovascular death, and major adverse cardiac events between the ACUITY-HORIZONS groups with a score of ≤ 17 and > 17. ACUITY-HORIZONS score > 17, initial systolic blood pressure (SBP) < 90 mmHg, and Killip III and IV upon admission positively predicted the 30-day bleeding risk, whereas myocardial infarction (MI) and TIMI major bleeding within 30 days, heart failure at admission, and initial SBP < 90 mmHg positively predicted the 30-day mortality.

    Comparatively, ACUITY-HORIZON is the most reliable system in predicting 30-day bleeding for patients with AMI via transradial PCI. In the transradial scenario, bleeding and MI within 30 days are substantially related to 30-day mortality.

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  • Jing Shi, Yumeng Xing, Juying Qian, Hongbo Yang, Yan Yan, Qing Li, Lim ...
    2019 Volume 60 Issue 3 Pages 586-592
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 25, 2019
    JOURNALS FREE ACCESS

    Previous studies reported a controversial left ventricular (LV) function impairment and pathophysiology in patients with coronary slow flow (CSF). Greater arterial load has been shown to increase aortic impedance and endothelial shear stress, potentially affecting coronary anatomy and function. We investigated LV systolic function by a new layer-specific strain technology and assessed the association between pulsatile arterial load and contractility.

    A total of 70 patients with CSF and 50 controls with normal coronary angiography were included in the study. Layer-specific longitudinal and circumferential strains were assessed from endocardium, mid-myocardium, and epicardium (global longitudinal strain (GLS)-endo, GLS-mid, GLS-epi and GCS-endo, GCS-mid, GCS-epi) by two-dimensional speckle tracking imaging (2D-STI). Pulsatile arterial load was estimated by indexed arterial compliance (ACI). Layer-specific GLS showed a decreasing gradient from the endocardium to the epicardium in both the controls and CSF group. GLS-endo and GLS-mid in the CSF group were significantly lower than the control group (all P < 0.05). Layer-specific longitudinal strain showed a good correlation with the number of affected coronary arteries (all P < 0.05) and the mean thrombolysis in the myocardial infarction frame count (TFC) (all P < 0.05). ACI was lower in patients with CSF (P = 0.005), and ACI was correlated negatively with layer-specific GLS (all P < 0.05).

    Layer-specific evaluation of the LV provides an understanding of the layer-specific properties of the LV wall and the possible process of the LV impairment in patients with CSF. Greater pulsatile arterial load, as manifested by a lower ACI, is coupled with worse LV longitudinal function in patients with CSF.

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  • Do Jung Kim, Seung Hyun Lee, Hyun-Chel Joo, Kyung-Jong Yoo, Young-Nam ...
    2019 Volume 60 Issue 3 Pages 593-600
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 25, 2019
    JOURNALS FREE ACCESS

    Severe aortic atherosclerosis is a risk factor for stroke during coronary artery bypass grafting (CABG). The purpose of this study was to evaluate the incidence of postoperative neurologic complications after off-pump CABG (OPCAB) with a proximal seal system (Heartstring).

    From January 2011 to December 2014, 729 patients underwent isolated OPCAB. The cohort was divided into two groups (Heartstring [HS] and aortic no-touch [NT]). The severity of aortic atherosclerosis (Katz grade) was evaluated by intraoperative epiaortic ultrasonography (EUS). The primary endpoints were postoperative neurologic complications (early stroke and minor events (delirium, transient ischemic attack, and syncope) ), and the secondary endpoints were late major adverse cardiac and cerebrovascular events (MACCEs) and death.

    The mean age of all patients was 65.1 ± 9.5 years, and a severe Katz grade (IV or V) was demonstrated to be an independent risk factor of long-term mortality (HR 3.53; 95% CI 1.06-11.75; P = 0.04) and MACCEs (HR 2.41; 95% CI 1.19-4.92; P = 0.02), but no significant differences were found for early stroke (0.9% versus 1.7%; P = 0.53) and minor neurologic complications (14.6% versus 9.9%; P = 0.05) between the groups regardless of the Katz grade. The 5-year overall survival rate did not differ significantly between the groups (90.9% versus 87.6%; P = 0.61).

    Although a higher Katz grade was identified as an independent risk factor of death and MACCEs, the HS group was not inferior in terms of neurologic complications regardless of the Katz grade. Therefore, the Heartstring system might be safely and efficiently used with EUS to decrease the incidence of neurologic complications.

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  • Yoshinori Sanuki, Shinjo Sonoda, Yoshitaka Muraoka, Konosuke Inoue, Ko ...
    2019 Volume 60 Issue 3 Pages 601-607
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    Recent studies reported that cardiac troponin elevation after percutaneous coronary intervention is related to adverse cardiac events. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are often used to assess lesion characteristics in the coronary arteries. However, little is known about the trend of cardiac troponin elevation after diagnostic invasive intracoronary examination and the prognostic influence. We assessed the relationship between myocardial injury manifested by the high-sensitivity cardiac troponin T (hs-cTnT) level after invasive intracoronary examination and future adverse cardiac outcomes. We evaluated 115 patients with stable coronary artery disease who underwent IVUS or OCT for detailed coronary assessment during coronary angiography (CAG). Baseline and post-procedural (within 24 hours after examination) hs-cTnT were measured. In consequence, post-procedural hs-cTnT level and percentage increase were higher in patients with IVUS or OCT during CAG than in those without. Periprocedural myocardial injury (PMI, defined as post-procedural hs-cTnT with upper reference limit greater than five-fold) occurred in 10 (8.6%) patients. There were no significant differences in baseline characteristics between patients with and without PMI, except for left-ventricular diastolic dimension. Only two major adverse cardiac events (MACE, defined as cardiovascular death, nonfatal myocardial infarction, and target lesion revascularization) occurred in non-PMI during a mean observation period of 32 ± 18 months. On Kaplan-Meier analysis, MACE-free survival rate was similar between PMI and non-PMI. In conclusion, a few imperceptible PMI derived by hs-cTnT assay occurred after diagnostic invasive intracoronary examination. However, it was not associated with subsequent poor cardiac outcome.

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  • Yan Yi, Xue-Mei Zhao, Run-Ze Wu, Yun Wang, Mani Vembar, Zheng-Yu Jin, ...
    2019 Volume 60 Issue 3 Pages 608-617
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    The aim of the present study was to investigate the performance of low keV mono-energetic reconstructions in spectral coronary computed tomography angiography (CCTA) using spectral detector CT (SDCT) with reduced contrast media and radiation dose.

    Sixty patients were randomly assigned to Groups A and B (both n = 30) to undergo CCTA on a dual-layer SDCT with tube voltage 120 kVp and 100 kVp (average tube current: 108.5 and 73.8 mAs, respectively), with contrast media volume of 36 mL used in both groups. The mono-energetic 40-80 keV and conventional 120 kVp images in Group A and conventional 100 kVp images in Group B were reconstructed. Quantitative and qualitative image quality (IQ) were evaluated in the aortic root and distal segments of the coronary arteries.

    The patient characteristics were not significantly different between the two groups (all P≥ 0.47), nor was the effective radiation dose (1.5 ± 0.3 and 1.4 ± 0.3 mSv, P = 0.20). The quantitative IQ in aorta and coronary arteries of mono-energetic 40-60 keV was superior to conventional 120 kVp and 100 kVp images (all P < 0.05). The noise in spectral images was lower compared to conventional images (all P < 0.01). The subjective IQ score of 40-50 keV images was not significantly different from that of 100 kVp images (P > 0.8).

    The mono-energetic 40-50 keV reconstructions from spectral CCTA using SDCT provide improved IQ compared to conventional techniques while facilitating reduced radiation dose and contrast media.

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  • Shinsuke Miyazaki, Hiroaki Nakamura, Takatsugu Kajiyama, Tomonori Wata ...
    2019 Volume 60 Issue 3 Pages 618-623
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 10, 2019
    JOURNALS FREE ACCESS

    Radiofrequency energy applications immediately produce tissue edema. This study aimed to investigate the acute tissue reaction immediately after second-generation cryoballoon applications using 3-dimensional intracardiac echocardiography (ICE) imaging technology.

    This study consisted of 10 patients with paroxysmal atrial fibrillation who underwent pulmonary vein isolation (PVI) using second-generation cryoballoons. Ablation was performed with a single 3-minute freeze strategy and exclusively 28-mm balloons. The left atrial and right pulmonary vein (PV) antra geometries were created with 3-dimensional ICE technology before and immediately after the PVI.

    Out of 20 right PVs, 19 were isolated exclusively with cryoballoons, and one right inferior PV (RIPV) required touch-up ablation. All 10 right superior PVs (RSPVs) were isolated by single cryoballoon applications, and RIPVs were isolated by a mean of 1.2 ± 0.4 applications. The total application time was 171 ± 19 and 203 ± 71 seconds, and nadir balloon temperature was −56.0 ± 4.9 and −53.8 ± 5.4°C for the RSPVs and RIPVs, respectively. In all patients, diffuse wall thickening of the antra and ostium of the right PVs was observed as compared to baseline. The wall thickening was 0-0.25 mm in 3 patients, and 0.25-0.5 mm in the remaining 7. During the median follow-up of 13 [10.2-17.2] months, 8 (80%) patients were free from arrhythmia recurrences. Nine (90%) patients underwent repeat cardiac computed tomography at a median of 6.0 [4.5-12.0] months after the initial procedure, and no PV stenosis was observed in all.

    Tissue edema and wall thickening appeared in the human left atrium immediately after second-generation cryoballoon ablation.

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  • Hui Chen, Yuqing Deng, Shunhui Li
    2019 Volume 60 Issue 3 Pages 624-630
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    The aim of this study was to evaluate the association of the body mass index (BMI) categories with the risk of sudden cardiac death (SCD) in a systematic review and meta-analysis.

    We systematically searched the PubMed, Embase, and Cochrane Library databases up to February 2018 for all studies reporting an association between BMI and risk of SCD. Relative risks (RRs) and 95% confidence intervals (CIs) were extracted and pooled using a random effects model.

    A total of 10 studies involving 1,381,445 participants were included in the meta-analysis. Overall, compared with the risk level in normal-weight controls, being underweight was not associated with increased risk of SCD (RR = 1.20, 95% CI, 0.95-1.51; P = 0.13). In contrast, both being overweight (RR = 1.21, 95% CI, 1.08-1.35; P = 0.0008) and obesity (RR = 1.52, 95% CI, 1.31-1.77; P < 0.00001) were associated with increased risk of SCD. The association between the BMI categories and risk of SCD was stable in the sensitivity analysis in which individual studies were serially excluded.

    The findings from this meta-analysis indicate that excess weight is associated with an increased risk of SCD. Further research is required to explore the underlying mechanisms.

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  • Litao Zhang, Yanli Long, Hongyan Xiao, Jun Yang, Xiaohui Liu, Zhenlu Z ...
    2019 Volume 60 Issue 3 Pages 631-636
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 25, 2019
    JOURNALS FREE ACCESS

    Mechanical heart valve replacement (MHVR) entails lifetime oral anticoagulation to eliminate thrombosis. However, adverse events may still occur despite proper anticoagulation therapy. In this study, we investigated whether D-dimer can predict the clinical events in post-MHVR patients during oral anticoagulation therapy.

    This was a single-center, prospective study. In all, 772 patients who underwent MHVR in the Wuhan Asia Heart Hospital from January 2013 to May 2014 were screened. Patients were assigned to the abnormal D-dimer group and the normal D-dimer group according to the D-dimer levels measured 3 months after the beginning of the oral anticoagulation therapy regime. All patients were followed up for 24 months or until the observation of the endpoints, which included thrombotic events, bleeding events, and all-cause deaths.

    A total of 718 patients were included in the analysis: 91 had abnormal D-dimer levels, and 627 had normal D-dimer levels. In all, 53 events were observed during 24 months. Compared with the normal D-dimer group, patients with abnormal D-dimer levels had a higher incidence of thrombotic events (10 versus 14; hazard ratio (HR): 5.36; 95% confidence interval (CI): 2.38-12.1; P < 0.001), all-cause mortality (8 versus 13; HR: 4.65; 95% CI: 1.93-11.2; P < 0.001), and a higher incidence of total events (16 versus 37; HR: 3.26; 95% CI: 1.81-5.86; P < 0.001). No significant difference was observed in bleeding events (2 versus 21; HR: 0.72; 95% CI: 0.17-3.07; P = 0.66).

    D-dimer may be a useful marker to predict thrombotic events and all-cause deaths in post-MHVR patients during oral anticoagulation therapy (ClinicalTrials.gov; NCT01996657).

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  • Xinshuang Ren, Fei Li, Chuangshi Wang, Zhihui Hou, Yang Gao, Weihua Yi ...
    2019 Volume 60 Issue 3 Pages 637-642
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    Bicuspid aortic valve (BAV) is the most common congenital heart disease. Different distribution of valve dysfunction was found in patients with BAV in different age and sex groups, but related difference was not well established. The aim of our study is to investigate age- and sex-related clinical characteristics differences in patients with BAV.

    Six hundred twenty patients with BAV who had moderate or severe aortic valve dysfunction were included in the study. Basic clinical data and image data were recorded. Patients were classified into four different age groups: (A: ≤ 50 years old; B: 50-60 years old; C: 60-70 years old; D: > 70 years old). The sex-related clinical difference in different age groups was compared. Association between incidence of aortic valve dysfunction and age was evaluated.

    Male patients had more frequent aortic regurgitation (AR) in patients younger than 70 years old (A: 52.3% versus 20.0%, P = 0.012; B: 43.2% versus 17.8%, P < 0.001; C: 17.0 versus 2.6%, P = 0.002), whereas female patients were more likely to have aortic stenosis (AS) (A: 75.0% versus 34.1%, P = 0.001; B: 77.8% versus 37.0%, P < 0.001; C: 93.6% versus 69.8%, P < 0.001). Frequency of AR in male patients decreased with age, whereas frequency of AS increased. Trend test showed a significant difference in incidence of aortic valve dysfunction as age increased in male patients (AR, P < 0.001; AS, P < 0.001). No trend was found in female patients.

    Male patients with BAV present more often with moderate/severe AR at a young age, and the frequency of AR decreases with age. Female patients with BAV had more frequent AS at first presentation regardless of age.

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  • Hyue Mee Kim, Dae-Won Sohn, Jin Chul Paeng
    2019 Volume 60 Issue 3 Pages 643-647
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 25, 2019
    JOURNALS FREE ACCESS

    Senile or wild-type transthyretin (wtTTR) amyloidosis is an age-related disease caused by the deposition of wtTTR amyloid protein. In contrast to light chain amyloidosis, 99 mTc-DPD scintigraphy (DPD scan) is a useful diagnostic modality for wtTTR amyloidosis.

    We retrospectively analyzed patients older than 30 years who underwent DPD scanning for non-cardiac reasons at our hospital between June 2014 and March 2017 (n = 9,581). Transthoracic echocardiography was used to assess left ventricular hypertrophy (LVH), as well as systolic and diastolic function.

    A positive DPD scan was observed in only six patients (0.06%). All six of these patients were older than 70 years, and they constitute only 0.4% of patients in this age group (6/1652). Among the patients with a positive DPD scan, four showed concentric LVH and two showed a normal wall thickness. With respect to the severity of diastolic dysfunction and pulmonary artery pressure, patients with a positive DPD scan showed the expected E' and pulmonary artery systolic pressure for their age.

    Even considering the limited sensitivity of a positive DPD scan detecting wtTTR amyloidosis, the incidence of a positive DPD scan in non-cardiac patients indicated that wtTTR amyloid deposition does not seem to be a major cause for age-related diastolic dysfunction, nor does appear to have a high incidence in patients with heart failure with preserved EF in the elderly.

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  • Ying Zhou, Jiansong Yuan, Yong Wang, Shubin Qiao
    2019 Volume 60 Issue 3 Pages 648-655
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 25, 2019
    JOURNALS FREE ACCESS

    Apelin was proved to attenuate cardiac interstitial fibrosis. However, the association between apelin level and myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM) is still unclear.

    This study aims to determine whether apelin is associated with myocardial fibrosis in HCM and investigate the predictive values of apelin for myocardial fibrosis in HCM.

    One hundred sixteen patients with HCM were enrolled in this study. Plasma apelin-13 and high-sensitivity cardiac troponin I (cTNI) were measured. The cardiac systolic and diastolic functions were evaluated by echocardiography, and the presence and extent of cardiac fibrosis were assessed by cardiac magnetic resonance. All statistical data were analyzed by SPSS version 21.0.

    The percentage of late gadolinium enhancement (LGE) was negatively correlated with apelin and positively correlated with cTNI, maximum wall thickness (MWT), and left ventricular mass index in the overall patients with HCM and LGE. Apelin, cTNI, MWT, and left ventricular ejection fraction were independent predictors of the presence of LGE. The cutoff values of apelin, cTNI, and MWT were 1.24 pg/mL, 0.031 ng/mL, and 19 mm, respectively, for the prediction of LGE. The combined measurements of MWT ≥ 19 mm and/or apelin ≤ 1.24 pg/mL, as well as the combined measurements of MWT ≥ 19 mm and/or cTNI ≥ 0.031 ng/mL, obtained higher specificity and higher sensitivity, thus, indicating the presence of LGE.

    Plasma apelin and cTNI are independent predictors of myocardial fibrosis. The combined measurements of serum apelin and MWT, as well as cTNI and MWT, showed higher predictive values for predicting myocardial fibrosis in patients with HCM.

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  • Min Chen, Yu-Feng Jiang, Hua-Jia Yang, Nan-Nan Zhang, Qing Rui, Ya-Fen ...
    2019 Volume 60 Issue 3 Pages 656-664
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 25, 2019
    JOURNALS FREE ACCESS

    The issue that genetic polymorphism of tumor necrosis factor-α (TNF-α) is associated with dilated cardiomyopathy (DCM) is debatable. We sought to investigate the potential role of TNF-α gene polymorphism (G-308A) in the susceptibility to dilated cardiomyopathy.

    We retrieved PubMed, EMBASE, and CNKI to collect all articles which reported on the association between TNF-α G-308A polymorphism and dilated cardiomyopathy. Two authors used the Newcastle-Ottawa Scale (NOS) checklist to assess the quality of the included studies. The odds ratio (OR) with 95% confidence intervals (CI) were pooled in a specific genetic model to assess the association and Stata version 14.0 software was used.

    A total of 9 studies with 1338 patients and 1677 controls were included in this study. The results from this meta-analysis indicated that TNF-α G-308A polymorphism significantly increased the risk of dilated cardiomyopathy in heterozygous comparison (GA versus GG: OR = 1.87; 95%CI = 1.03-3.40; P < 0.05). The increased risk of DCM was also found in Asian populations using a dominant model and heterozygous comparison (GA+AA versus GG: OR = 2.00, 95%CI = 1.02-3.92, P < 0.05; GA versus GG: OR = 1.94, 95%CI = 1.23-3.06, P < 0.05).

    The current meta-analysis revealed that TNF-α gene polymorphism (G-308A) may be associated with the susceptibility to DCM.

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  • Yan Peng, Junjie Fang, Wei Huang, Shu Qin
    2019 Volume 60 Issue 3 Pages 665-670
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    Cognitive behavioral therapy has emerged as an important approach to alleviate the depression of patients with heart failure. However, the use of cognitive behavioral therapy for heart failure has not been well established. We conduct a systematic review and meta-analysis to evaluate the efficacy of cognitive behavioral therapy for alleviating depression for heart failure.

    PubMed, Embase, and the Cochrane Central Register of Controlled Trials are searched. Randomized controlled trials (RCTs) assessing the influence of cognitive behavioral therapy on heart failure are included. Two investigators independently have searched articles, extracted data, and assessed the quality of included studies. Meta-analysis is performed using the random-effect model.

    Eight RCTs involving 480 patients are included in the meta-analysis. Compared with control intervention for heart failure, cognitive behavioral therapy can substantially decrease depression scale (Std. MD = −0.27; 95% CI = −0.47 to −0.06; P = 0.01), but has no substantial influence on the quality of life (Std. MD = 0.21; 95% CI = −0.01 to 0.42; P = 0.06), self-care scores (Std. MD = 0.12; 95% CI = −0.18 to 0.42; P = 0.44), and 6-minute walk test distance (Std. MD = 0; 95% CI = −0.28 to 0.28; P = 0.99).

    Cognitive behavioral therapy is associated with significantly decreased depression scale, but with no substantial impact on the quality of life, self-care scores, and 6-minute walk test distance for heart failure.

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  • Yuko Matsuura, Masao Daimon, Yuuichi Notomi, Naoyuki Miyasaka, Yohei Y ...
    2019 Volume 60 Issue 3 Pages 671-678
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    In fetal echocardiography, conventional parameters for assessing cardiac function are limited because of limited echocardiographic windows or the fetus' position. We aimed to evaluate the feasibility and reproducibility of fetal left ventricular (LV) twist by two-dimensional, speckle-tracking echocardiography (2DSTE) in a Japanese population.

    We included 55 normal fetuses at gestational ages between 21 and 36 weeks. Subjects with adverse maternal health issues were excluded. LV twist was calculated as the net difference between LV basal and apical rotation at end-systole estimated with 2DSTE.

    We were able to analyze the 2DSTE images in 44 cases (80%). The mean (±SE) apical rotation, basal rotation, and LV twist were 7.88 ± 0.77, −3.68 ± 0.50, and 11.1 ± 0.75 degrees, respectively. We could not analyze 11 cases (20%) because of poor image quality due to fetal position in five cases (45.5%), failure to track the endocardium because of blurred images in five cases (45.5%), and failure to obtain images of the heart due to the presence of the placenta in front of the fetus in one case (9.1%). There were no significant differences in the demographic data between pregnant women in whom LV twist analysis was feasible and not feasible. The intra- and interobserver intraclass correlation coefficients were 0.67 and 0.64, respectively.

    LV twist analysis by 2DSTE in the fetus was feasible in a substantial population and may provide new insight into cardiac function during the prenatal period. On the other hand, its reproducibility was moderate and needs to be improved.

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  • Masato Narita, Masahiro Yamada, Michiko Tsushima, Natsumi Kudo, Tomo K ...
    2019 Volume 60 Issue 3 Pages 679-687
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 25, 2019
    JOURNALS FREE ACCESS

    Although there are several diagnostic criteria for left ventricular hypertrophy (LVH), their sensitivity remains low. A recent study reported that the sum of the amplitude of the deepest S wave in any lead (SD) and the S wave in lead V4 (SV4) (SD + SV4) improved sensitivity compared with commonly used criteria. To test whether this new formula improves sensitivity in the Japanese general population, we analyzed 12-lead electrocardiograms for Japanese residents participating in the Iwaki Health Promotion Project (n = 866). Left ventricular mass was calculated by echocardiography, indicating that 156 (18%) of the study population had LVH. In receiver operating characteristic analyses, the sum of the R wave in limb lead Ι (RLΙ) and the S wave in V4 (SV4) (RLΙ + SV4) showed a higher area under the curve (AUC = 0.76) than the Sokolow-Lyon voltage criteria (0.61) and the SD + SV4 criteria (0.63), and almost the same AUC as the Cornell voltage criteria (0.74) and the Cornell product criteria (0.76). The validation study also showed similar results. The cutoff values of RLΙ + SV4 criteria were ≥1.6 mV in men and ≥1.4 mV in women with a sensitivity of 39% and a specificity of 89%, whereas the sensitivity and specificity calculated based on SD + SV4 criteria were 21% and 94%, respectively. Thus, the diagnostic criterion of RLΙ + SV4 seems to be more useful than the previous criteria for diagnosing LVH in the Japanese general population.

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  • Ryoto Hourai, Hideki Ozawa, Koichi Sohmiya, Yoshinobu Hirose, Takahiro ...
    2019 Volume 60 Issue 3 Pages 688-694
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    The prevalence and extent of immunoglobulin G4 (IgG4)-positive cell infiltration were investigated in 282 surgical samples of aortic wall and aortic valve. Tissue infiltration of IgG4-positive cells was observed in 24 (17.3%) of 139 aortic valve samples and 46 (32%) of 143 aortic wall samples, and the condition of IgG4-positive cell infiltration > 30/hpf together with IgG4/CD138 ratio > 40% was observed in 2 (1.4%) of aortic valve samples and 14 (9.8%) of aortic wall samples. Among 275 patients, preoperative serum IgG4 level was available in 48 patients (50 samples), and it was > 135 mg/dL in only one patient. Of these 48 patients with serum IgG4 measurement, 29 patients had aortic valve stenosis and 12 had aortic aneurysm. Compared with 23 aortic stenosis patients without tissue infiltration of IgG4-positive cells in the aortic valve, six patients with IgG4-positive cell infiltration had a more prevalent smoking history (26% versus 83%) and borderline significantly higher serum IgG4 (median, 24.5 mg/dL versus 55.5 mg/dL), although either preoperative peak pressure gradient between left ventriculum and aorta or aortic valve area did not differ significantly between groups. Compared with six aortic aneurysm patients without tissue infiltration of IgG4-positive cells in the aortic wall, six patients with IgG4-positive cell infiltration had borderline significantly higher serum IgG4 (median, 28.9 mg/dL versus 68.2 mg/dL). The current study showed that tissue IgG4-positive infiltration is not a rare occurrence in the aortic stenosis and aortic aneurysm. Clinical significance of tissue IgG4-postive cell infiltration in these patients requires further investigation.

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  • Karam Nam, Eun Jin Jang, Ga Hee Kim, Hannah Lee, Dal Ho Kim, Ho Geol R ...
    2019 Volume 60 Issue 3 Pages 695-700
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 25, 2019
    JOURNALS FREE ACCESS

    The relationship between lower institutional case-volume and higher mortality after complex high-risk procedures has been shown. The aim of this study is to examine the effect of institutional volume on patient outcome after heart transplantation (HT) in the entire Korean population.

    We analyzed all adult HTs performed in Korea between 2007 and 2016 using data from the National Health Insurance Service. The association between case-volume and in-hospital mortality after HT was analyzed after categorizing hospitals performing HT into low-, medium-, or high-volume centers depending on the number of HTs performed. The effect of case-volume on long-term mortality was also assessed.

    A total of 833 adult HTs were performed in 17 centers. In-hospital mortality was 3.7% (13/356), 10.1% (38/375), and 18.6% (19/102) in high-, medium-, and low-volume centers, respectively. Medium-, and low-volume centers showed increased risk of in-hospital mortality (odds ratio [95% confidence interval]; 2.11 [1.42-3.13] and 3.68 [2.16-2.27], respectively.). Long-term survival of up to 10 years was worse in lower-volume centers compared to high-volume centers (P < 0.001).

    In conclusion, lower case-volume was associated with increased in-hospital mortality and long-term mortality after HT. A minimum case-volume mandate may be required for hospitals performing HT to ensure the best patient outcome and effective resource allocation.

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  • Cui-Ling Ji, Adnan Nomi, Bin Li, Cheng Shen, Bing-Chun Song, Jin-Guo Z ...
    2019 Volume 60 Issue 3 Pages 701-707
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 25, 2019
    JOURNALS FREE ACCESS

    Fractalkine has been reported to play an important role in the pathophysiology of various cardiovascular disorders. This research aims to study the change of soluble fractalkine (sFKN) in plasma level of patients with chronic heart failure (CHF) and evaluate its prognostic value.

    A total of 96 patients with CHF and 45 healthy subjects were included in this study. The plasma levels of sFKN, brain natriuretic peptide (BNP), and Interleukin-18 (IL-18) were determined by ELISA kits when they were first admitted to the hospital. Left ventricular ejection fraction (LVEF) was measured by echocardiogram. Rehospitalization status within 1 year after the first hospitalization was also recorded.

    The plasma levels of sFKN, BNP, and IL-18 in patients with CHF were significantly higher than in the control group (P < 0.05). The concentrations of sFKN and BNP were increased with the severity of heart failure classified by NYHA classification (P < 0.05). There were no statistical differences among all CHF subgroups classified by etiology (P > 0.05). Plasma sFKN level in CHF group was positively correlated with BNP (r = 0.441, P < 0.001) and IL-18 (r = 0.592, P < 0.001). Receiver operating characteristic curve analysis showed that area under the curve values of FKN, BNP, and IL-18 were 0.885 (95%CI: 0.810 to 0.960, P < 0.001), 0.889 (95%CI: 0.842 to 0.956, P < 0.001), and 0.878 (95%CI: 0.801-0.954, P < 0.001), respectively. The concentrations of sFKN and BNP were increased in patients readmitted more than once within 1 year (P < 0.05).

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  • Kwang Sun Ryu, Jang-Whan Bae, Myung Ho Jeong, Myeong-Chan Cho, Keun-Ho ...
    2019 Volume 60 Issue 3 Pages 708-714
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    Multivessel disease (MVD) is an independent risk factor for poor prognosis in acute myocardial infarction patients. Although several global risk scoring systems (RSS) are in use in clinical practice, there is no dedicated RSS for MVD in ST-segment elevation myocardial infarction (STEMI). The primary objective of this study is to develop a novel RSS to estimate the prognosis of patients with MVD in STEMI.

    We used the Korean Acute Myocardial Infarction Registry (KAMIR) to identify 2,030 STEMI patients with MVD who underwent appropriate percutaneous coronary intervention (PCI). Their data were analyzed to develop a new RSS. The prognostic power of this RSS was validated with 2,556 STEMI patients with MVD in the Korean Working Group on Myocardial Infarction Registry (KORMI).

    Six prognostic factors related to all-cause death in STEMI patients with MVD were age, serum creatinine, Killip Class, lower body weight, decrease in left ventricular ejection fraction, and history of cerebrovascular disease. The RSS for all-cause death was constructed using these risk factors and their statistical weight. The RSS had appropriate performance (c-index: 0.72) in the KORMI validation cohort.

    We developed a novel RSS that estimates all-cause death in the year following discharge for patients with MVD in STEMI appropriately treated by PCI. This novel RSS was transformed into a simple linear risk score to yield a simplified estimate prognosis of MVD among STEMI patients.

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Experimental Studies
  • Shin Yajima, Shigeru Miyagawa, Satsuki Fukushima, Kayako Isohashi, Tad ...
    2019 Volume 60 Issue 3 Pages 715-727
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    Occlusion of a major coronary artery induces myocardial infarction (MI), leading to left ventricle (LV) remodeling due to progressive microvasculature dysfunction. Irreversible impairment in microvascular function has been suggested to extend from the infarcted region into the infarct-border or remote regions, depending on the time to revascularization. Our aim was to determine whether the occlusion of a major coronary artery induces microvascular dysfunction in the adjacent area perfused by intact coronary arteries using a porcine model for chronic total occlusion of the left anterior descending artery (LAD). MI was induced via an ameroid constrictor ring around the LAD in adult Göttingen pigs (Sus scrofa domesticus, n = 5). Age-matched normal pigs were treated as controls (n = 3). Cardiac magnetic resonance showed reduced systolic regional wall motion in the left circumflex (LCx) and right coronary artery (RCA) territories, with a progressively worsening motion in the infarction-adjacent area over an eight-week period. On 13N-ammonia positron emission tomography (PET), myocardial blood flow (MBF) during hyperemia was significantly greater in the LCx and RCA territories (particularly in the infarction-adjacent area) compared to that in the LAD territory at four weeks after infarct induction. Subsequently, the flow significantly decreased, approaching that in the LAD territory at eight weeks after infarct induction. Fluoroscopy-guided pressure-wire studies showed significantly higher microvascular resistance in the LCx area at eight weeks compared to that in controls. Electron microscopy showed endothelium swelling and microvasculature disruption in areas adjacent to the LCx and RCA territories. Anterior MI caused coronary microvascular dysfunction in the adjacent area, associated with a reduced MBF and regional wall motion.

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  • Tomonari Kimura, Kazufumi Nakamura, Toru Miyoshi, Masashi Yoshida, Kao ...
    2019 Volume 60 Issue 3 Pages 728-735
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors are drugs for diabetes and might prevent heart failure. In this study, we investigated the effects of tofogliflozin, an SGLT2 inhibitor, on cardiac hypertrophy and metabolism in hypertensive rats fed a high-fat diet. Dahl salt-sensitive (DS) rats, hypertensive model rats, and Dahl salt-resistant (DR) rats, non-hypertensive model rats, were fed a high-salt and high-fat diet containing tofogliflozin (0.005%) for 9 weeks to examine the effects of this drug on cardiac hypertrophy and metabolism. Tofogliflozin tended to suppress a rise of the systolic blood pressure, relative to the control, throughout the treatment period in both DR and DS rats, and significantly suppress a rise of the systolic blood pressure, relative to the control, at the 9th week in DS rats. Tofogliflozin reduced cardiac hypertrophy (heart weight/body weight) not only in DS rats but also in DR rats. Histological analysis showed that tofogliflozin significantly decreased cardiomyocyte hypertrophy and perivascular fibrosis in both DS and DR rats. Tofogliflozin significantly decreased the expression levels of genes related to cardiac hypertrophy (encoding for natriuretic peptides A and B and interleukin-6), and to cardiac fibrosis (encoding for transforming growth factor-β1 and collagen type IV), in DS rats. Recent studies have shown that hypertrophied and failing hearts shift to oxidizing ketone bodies as a significant fuel source. We also performed metabolome analysis for ventricular myocardial tissue. Tofogliflozin reduced 3-hydroxybutyrate, a ketone body, and significantly decreased the expression levels of β-hydroxybutyrate dehydrogenase 1 and 3-oxoacid CoA-transferase, which are related to ketone oxidization. In conclusion, tofogliflozin ameliorated cardiac hypertrophy and fibrosis along with reduction of ketone usage in myocardial tissue.

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  • Tomoki Kokubun, Shu-ichi Saitoh, Shunsuke Miura, Takafumi Ishida, Yasu ...
    2019 Volume 60 Issue 3 Pages 736-745
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    Aging is not only a major risk factor for impaired collateral growth under ischemia but also shortens the telomere length, which is regulated by telomerase. We examined the role of telomerase activity during impaired collateral growth during aging in ischemic skeletal muscle. Unilateral hind limb ischemia was generated in old, young, and old mice chronically administered a telomerase activator. In old mice, blood flow recovery and capillary density development in ischemic hind limbs were reduced compared to those in young mice, and these changes were restored to equal levels by administration of TA-65, a telomerase activator. During the early phase of ischemic muscle changes in old mice, telomerase reverse transcriptase expression and telomerase activity were both low compared to those in young mice and old mice treated with TA-65. Levels of reactive oxygen species (ROS), DNA double-strand breaks, and expression of p53, p16, and Bax/Bcl-2 were all elevated in ischemic muscles of old mice compared to those in the muscles of young mice and old mice treated with TA-65 treatment; these factors were maintained at low levels equivalent to those seen in young mice during the experiment. Expression of HIF1α/vascular endothelial growth factor (VEGF) and PGC1α were decreased in old mice compared to those in young mice and old mice treated with TA-65. Collateral growth under ischemic conditions is impaired in aged animals due to low telomerase activity, increased ROS, resultant DNA damage, and expression of tumor suppressor and pro-apoptotic proteins. These data suggest that telomerase activation enhances collateral growth and rescues ischemic tissue in old individuals.

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  • Jun-Xiang Liu, Xiao Li, Wen-Jie Ji, Li-Fang Yan, Tan Li, Yu-Xiu Li, Zh ...
    2019 Volume 60 Issue 3 Pages 746-755
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 25, 2019
    JOURNALS FREE ACCESS

    To detect the development of monocytes and proliferative macrophages in atherosclerosis of ApoE−/− mice, we randomly assigned 84 ApoE−/− mice fed western diet or chow diet. On weeks 2, 4, 6, 8, 10, and 12 after fed high-fat diet or normal chow diet, animals were euthanized (n = 7 for each group at each time point). Flow cytometry methods were used to analyze the proportions of circulation monocyte subsets. The macrophage and proliferative macrophage accumulation within atherosclerotic plaques was estimated by confocal florescence microscopy. Plasma levels of total cholesterol and triglyceride were measured by ELISA kit. The plaques of aortic sinus were stained with Oil Red O. The percent of Ly6Chi circulation monocyte, the density of proliferation macrophage, the total plasma cholesterol and triglyceride levels, the lesion area of ApoE−/− mice were consistently elevated in chow diet throughout the trial. The total plasma cholesterol and triglyceride levels, the lesion area were elevated in western diet group with age, and they were always higher than the chow diet group. The Ly6Chi monocytes and proliferative macrophages reached a plateau at 8 weeks and 6 weeks; despite continued high-triglyceride high-cholesterol diet the percent did not significantly change. Interestingly, the density of macrophage did not change significantly over age in western and chow diet groups. Our results provide a dynamic view of Ly6Chi monocyte subset, the density of macrophage and proliferation macrophage change during the development and progression of atherosclerosis, which is relevant for designing new treatment strategies targeting mononuclear phagocytes in this model.

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Case Reports
  • Yoshiaki Kaneko, Tadashi Nakajima, Takashi Iizuka, Shuntaro Tamura, Ma ...
    2019 Volume 60 Issue 3 Pages 756-760
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    We report a case of atypical fast-slow atrioventricular nodal reentrant tachycardia (AVNRT) using a slow pathway variant extending to the superoanterior right atrium. The AVNRT diagnosis was confirmed by using standard electrophysiological criteria that exclude a diagnosis of atrial tachycardia and atrioventricular reentrant tachycardia. The earliest atrial activation during tachycardia was found in the superoanterior right atrium adjacent to the tricuspid annulus, where the first delivery of radiofrequency energy terminated and eliminated the inducibility of the tachycardia.

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  • Masato Okada, Koji Tanaka, Yasuharu Matsunaga-Lee, Yuichi Ninomiya, Yu ...
    2019 Volume 60 Issue 3 Pages 761-767
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: May 17, 2019
    JOURNALS FREE ACCESS

    A 70-year-old woman was admitted for treatment of supraventricular tachycardia. Ventriculoatrial conduction was revealed through programmed ventricular stimulation; the coronary sinus ostium (CSos) was the earliest atrial activation site. The fast-slow forms of atrioventricular nodal reentrant tachycardia (AVNRT) were induced by ventricular extra-stimuli. During tachycardia, the earliest atrial activation site was located at the bottom of CSos. Radiofrequency (RF) energy application to this site resulted in the delay of local electrical potential, prolongation of tachycardia cycle length, and a shift of the earliest retrograde activation site to the roof of CSos. Subsequent ablation induced a similar shift to the inferior tricuspid annulus and to the right posterior septum. Finally, RF energy application to the right posterior septum resulted in the termination of tachycardia, which was not induced afterward. Multiple shifts in the earliest retrograde atrial activation site along the tricuspid annulus after each slow pathway ablation suggested that annular tissue plays a substantial role as a substrate for AVNRT.

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  • Hiroyuki Kiriyama, Satoshi Kodera, Jiro Ando, Masao Daimon, Hiroyuki M ...
    2019 Volume 60 Issue 3 Pages 768-771
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 25, 2019
    JOURNALS FREE ACCESS

    A 91-year-old woman was admitted to our hospital for treatment of congestive heart failure with severe aortic stenosis. After admission, she developed a high fever due to pneumonia and worsened heart failure. We could not perform transcatheter aortic valve implantation (TAVI) because of active infection; therefore, retrograde balloon aortic valvuloplasty (BAV) was urgently performed. A complete atrioventricular block and severe functional mitral regurgitation appeared suddenly after BAV in the absence of mechanical disorders. Her condition improved after several days in our intensive care unit. Pacemaker implantation and TAVI were then performed, and the patient was discharged from our hospital. MR could sometimes exacerbate after BAV in clinical practice; therefore, we set out to report this case.

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  • Yasuo Tsuru, Mizuki Miura, Shinichi Shirai, Masaomi Hayashi, Kenji Tan ...
    2019 Volume 60 Issue 3 Pages 772-777
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 25, 2019
    JOURNALS FREE ACCESS

    Aortic complex rupture is one of the most critical complications associated with transcatheter aortic valve implantation (TAVI). Its incidence is rare, and its mechanism varies by case; therefore, it is difficult to identify the predictors of complex rupture. Herein, we report a clinical case series of aortic complex rupture. Within our cohort, the frequency of complex rupture was 0.8% (4/497 consecutive patients) with an in-hospital mortality of 0. Among these four patients with complex rupture, two underwent emergent thoracotomy and surgical hemostasis without a heart-lung machine and surgical aortic valve replacement, whereas the other two were conservatively managed. The case overview revealed the following similarities: all the patients were elderly, small women; balloon-expandable valves were used; the annulus area was small with heavily calcified leaflet; and aggressive treatment strategy was used (i.e., oversizing and post-dilatation). In such cases, TAVI should be performed with a careful strategy. Once aortic complex rupture occurs, damage can be minimized through cooperation with an institutional heart team and calm management.

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  • Juanjuan Liu, Xiaobing Wang, Dandan Sun, Jun Yang
    2019 Volume 60 Issue 3 Pages 778-783
    Published: May 30, 2019
    Released: May 30, 2019
    [Advance publication] Released: April 25, 2019
    JOURNALS FREE ACCESS

    Echocardiographic detection of abnormalities occurring medially and distally in coronary arteries is uncommon and is not well recognized. Herein, we describe an 87-year-old woman with two distinct aneurysms involving a branch of the left anterior descending coronary artery (LAD), one of which communicated with the pulmonary artery (PA). Initially determined via transthoracic echocardiography (TTE), these findings were subsequently validated by coronary computed tomography angiography (CTA). We also present a review of the published studies of multiple coronary artery aneurysms (CAAs) exceeding 20 mm in diameter, focusing on the location, etiology, symptoms, and common ultrasonic characteristics of 30 cases. Echocardiography is a valuable, noninvasive technique for initial detection, monitoring, and follow-up of CAAs, serving to direct further diagnostics.

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