Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
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Reviews
  • Albert Youngwoo Jang, Seung Hwan Han, Il Suk Sohn, Pyung Chun Oh, Kwan ...
    Type: REVIEW
    2020 Volume 84 Issue 6 Pages 867-874
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 24, 2020
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    Two decades ago, it was recognized that lipoprotein(a) (Lp(a)) concentrations were elevated in patients with cardiovascular disease (CVD). However, the importance of Lp(a) was not strongly established due to a lack of both Lp(a)-lowering therapy and evidence that reducing Lp(a) levels improves CVD risk. Recent advances in clinical and genetic research have revealed the crucial role of Lp(a) in the pathogenesis of CVD. Mendelian randomization studies have shown that Lp(a) concentrations are causal for different CVDs, including coronary artery disease, calcified aortic valve disease, stroke, and heart failure, despite optimal low-density lipoprotein cholesterol (LDL-C) management. Lp(a) consists of apolipoprotein (apo) B100 covalently bound to apoA. Thus, Lp(a) has atherothrombotic traits of both apoB (from LDL) and apoA (thrombo-inflammatory aspects). Although conventional pharmacological therapies, such as statin, niacin, and cholesteryl ester transfer protein, have failed to significantly reduce Lp(a) levels, emerging new therapeutic strategies using proprotein convertase subtilisin-kexin type 9 inhibitors or antisesnse oligonucleotide technology have shown promising results in effectively lowering Lp(a). In this review we discuss the revisited important role of L(a) and strategies to overcome residual risk in the statin era.

  • Bartosz Krzowski, Paweł Balsam, Michał Peller, Piotr Lodziński, Marcin ...
    Type: REVIEW
    2020 Volume 84 Issue 6 Pages 875-882
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 29, 2020
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    Supplementary material

    Catheter ablation (CA) is considered first-line treatment for many patients with symptomatic arrhythmias. Indications for CA are constantly increasing, as is the number of procedures. Although CA is nowadays regarded a safe procedure, there is a risk of complications, including both bleeding- and thrombosis-related events. Several factors contribute to periprocedural risk; of these, patient coagulation status is of considerable clinical relevance. In this context, even a simple procedure poses a considerable challenge in a patient with coagulation disorder. However, the level of evidence regarding CA in patients with coagulation disorders is very low. Neither experts’ recommendations nor clinical guidelines have been presented so far. The aim of this article is to analyze potential procedure-related risks and provide clinicians with useful information and practical suggestions regarding optimization of procedural safety in patients with coagulation disorders.

Editorials
Original Articles
Arrhythmia/Electrophysiology
  • Hiroyuki Inoue, Nobuaki Tanaka, Koji Tanaka, Yuichi Ninomiya, Yuko Hir ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2020 Volume 84 Issue 6 Pages 894-901
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: March 17, 2020
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    Background:Associations between characteristics of premature atrial contraction (PAC) 6 months after catheter ablation (CA) and later recurrence are not known. We investigated the effects of PAC characteristics on long-term outcomes of initially successful atrial fibrillation (AF) ablation.

    Methods and Results:In all, 378 patients (mean age 61 years, 21% female, 67% paroxysmal AF) who underwent initial radiofrequency CA for AF without recurrence up to 24-h Holter monitoring 6 months after the procedure were reviewed retrospectively. The calculated number of PAC/24 h and the length of the longest PAC run during Holter recording were analyzed. After 4.3±1.2 years (mean±SD) follow-up, 123 (32.5%) patients experienced late recurrence. Patients with recurrence had significantly more PAC/24 h (median [interquartile range] 110 [33–228] vs. 42 [16–210]; P<0.01) and a longer longest PAC run (5 [2–8] vs. 3 [1–5]; P<0.01) than those without. Receiver operating characteristic curve analysis indicated 58 PAC/24 h and a longest PAC run of 5 were optimal cut-off values for predicting recurrence. After adjusting for previously reported predictors of late recurrence, frequent PAC (≥58/24 h) and longest PAC run ≥5 were found to be independent predictors of late recurrence (hazard ratios [95% confidence intervals] 1.93 [1.24–3.02; P<0.01] and 1.81 [1.20–2.76; P<0.01], respectively).

    Conclusions:Six months after successful AF ablation, both frequent PAC and long PAC run are independent predictors of late recurrence.

  • Christian-Hendrik Heeger, Enida Rexha, Sabrina Maack, Laura Rottner, T ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2020 Volume 84 Issue 6 Pages 902-910
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 18, 2020
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    Background:The second-generation cryoballoon (CB2) has demonstrated high procedural efficacy and convincing clinical success rates for pulmonary vein isolation (PVI). Nevertheless, data on the impact of different ablations protocols on durability are limited. The aim was to comparing the durability of PVI following 3 different ablation strategies in patients with recurrence of atrial fibrillation or atrial tachycardia undergoing repeat procedures.

    Methods and Results:In 192 patients, a total of 751 PVs were identified. All PVs were successfully isolated during index PVI. Thirty-one out of 192 (16%) patients were treated with a bonus-freeze protocol (group 1), 67/192 (35%) patients with a no bonus-freeze protocol (group 2), and 94/192 (49%) patients with a time-to-effect-guided protocol (group 3). Persistent PVI was documented in 419/751 (55.8%) PVs, and in 41/192 (21%) patients, all PVs were persistently isolated. The total rate of PV reconnection was not significantly different between the groups (P=0.134) and the comparison of individual PVs revealed no differences (P-values for RSPV: 0.424, RIPV: 0.541, LSPV: 0.788, LIPV: 0.346, LCPV: 0.865). The procedure times were significantly reduced by omitting the bonus-freeze and applying individualized application times (group 1: 123.4±31.5 min, group 2: 112.9±39.8 min, group 3: 86.67±28.4 min, P<0.001).

    Conclusions:Comparing 3 common ablation protocols, no differences for durable PVI were detected. Procedure times were significantly reduced by omitting the bonus-freeze cycle and by applying individualized application times.

Cardiovascular Intervention
  • Amir Kh. M. Khalifa, Takashi Kubo, Yasushi Ino, Kosei Terada, Hiroki E ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2020 Volume 84 Issue 6 Pages 911-916
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 18, 2020
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    Background:Acute myocardial infarction (AMI) is caused by coronary plaque rupture (PR), plaque erosion (PE), or calcified nodule (CN). We used optical coherence tomography (OCT) to compare stent expansion immediately after primary percutaneous coronary intervention (PCI) in patients with AMI caused by PR, PE, or CN.

    Methods and Results:In all, 288 AMI patients were assessed by OCT before and immediately after PCI, performed with OCT guidance according to OPINION criteria for stent sizing and optimization. The frequency of OCT-identified PR (OCT-PR), OCT-PE, and OCT-CN was 172 (60%), 82 (28%), and 34 (12%), respectively. Minimum stent area was smallest in the OCT-CN group, followed by the OCT-PE and OCT-PR groups (mean [±SD] 5.20±1.77, 5.44±1.78, and 6.44±2.2 mm2, respectively; P<0.001), as was the stent expansion index (76±13%, 86±14%, and 87±16%, respectively; P=0.001). The frequency of stent malapposition was highest in the OCT-CN group, followed by the OCT-PR and OCT-PE groups (71%, 38%, and 27%, respectively; P<0.001), as was the frequency of stent edge dissection in the proximal reference (44%, 23%, and 10%, respectively; P<0.001). The frequency of tissue protrusion was highest in the OCT-PR group, followed by the OCT-PE and OCT-CN groups (95%, 88%, and 85%, respectively; P=0.036).

    Conclusions:Stent expansion was smallest in the OCT-CN group, followed by the OCT-PR and OCT-PE groups. Plaque morphology in AMI culprit lesions may affect stent expansion immediately after primary PCI.

  • Kazumasa Kurogi, Masanobu Ishii, Kenji Sakamoto, Soichi Komaki, Hiroak ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2020 Volume 84 Issue 6 Pages 917-925
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 29, 2020
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    Background:The excessive volume of contrast needed is a significant limitation of optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI). Low-molecular-weight dextran (LMWD) has been used for OCT image acquisition instead of contrast media. This study compared the effects of OCT-guided PCI using LMWD on renal function and clinical outcomes to those of intravascular ultrasound (IVUS)-guided PCI.

    Methods and Results:In all, 1,183 consecutive patients who underwent intracoronary imaging-guided PCI were enrolled in this single-center, retrospective, observational study. After propensity score matching, 133 pairs of patients were assigned to undergo either OCT-guided PCI using LMWD or IVUS-guided PCI. There was no significant change from baseline in the primary endpoint, serum creatinine concentrations, after the procedure in either group. There were no significant differences between the OCT and IVUS groups in the volume of contrast medium, the incidence of contrast-induced nephropathy (1.5% vs. 2.3%; P=0.65), and major adverse cardiovascular events (MACE) at 30 days (2.3% vs. 6.0%; P=0.12) and 12 months (2.3% vs. 3.0%; P=0.70) after the procedure. Kaplan-Meier analysis at the 12-month follow-up revealed no significant difference in the incidence of MACE between the 2 groups (P=0.75).

    Conclusions:OCT-guided PCI using LMWD did not negatively affect renal function and achieved similar short- and long-term clinical outcomes to IVUS-guided PCI.

Cardiovascular Surgery
  • Kazuma Handa, Daisuke Yoshioka, Koichi Toda, Jun-ya Yokoyama, Takaaki ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Surgery
    2020 Volume 84 Issue 6 Pages 926-934
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 14, 2020
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    Supplementary material

    Background:Infective endocarditis remains associated with substantial mortality and morbidity rates, and the presence of acute heart failure (AHF) compromises clinical results after valve surgery; however, little is known in cardiogenic shock (CGS) patients. This study evaluated the clinical results and risk of mortality in CGS patients after valve surgery.

    Methods and Results:This study enrolled 585 patients who underwent valve surgery for active endocarditis at 14 institutions between 2009 and 2017. Of these patients, 69 (12%) were in CGS, which was defined as systolic blood pressure <80 mmHg and severe pulmonary congestion, requiring mechanical ventilation and/or mechanical circulatory support, preoperatively. The predictors of CGS were analyzed, and clinical results of patients with non-CGS AHF (n=215) were evaluated and compared.Staphylococcus aureusinfection (odds ratio [OR] 2.19; P=0.044), double valve involvement (OR 3.37; P=0.003), and larger vegetation (OR 1.05; P=0.036) were risk factors for CGS. Hospital mortality occurred in 27 (13%) non-CGS AHF patients and in 15 (22%) CGS patients (P=0.079). Overall survival at 1 and 5 years in CGS patients was 76% and 69%, respectively, and there were no significant differences in overall survival compared with non-CGS AHF patients (P=1.000).

    Conclusions:Clinical results after valve surgery in CGS patients remain challenging; however, mid-term results were equivalent to those of non-CGS AHF patients.

Epidemiology
  • Keisuke Yamasaki, Jun Hata, Yoshihiko Furuta, Naoki Hirabayashi, Tomoy ...
    Type: ORIGINAL ARTICLE
    Subject area: Epidemiology
    2020 Volume 84 Issue 6 Pages 935-942
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 09, 2020
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    Supplementary material

    Background:Both chronic kidney disease and brain white matter hyperintensities (WMH) are known to be risk factors of dementia and mortality.

    Methods and Results:In 2012, 1,214 community-dwelling Japanese subjects aged ≥65 years underwent brain magnetic resonance imaging (MRI) scans and a comprehensive health examination. This study investigated associations of the urinary albumin : creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) with the WMH volume to intracranial volume (WMHV : ICV) ratio, and the association of the combination of UACR and the WMHV : ICV ratio with cognitive decline and mortality risk. The geometric mean of the WMHV : ICV ratio was 0.223% in the entire study population, and increased significantly with higher UACR levels after adjusting for potential confounding factors (0.213% for normoalbuminuria, 0.248% for microalbuminuria, and 0.332% for macroalbuminuria; Ptrend=0.01). In contrast, there was no clear association between eGFR and the WMHV : ICV ratio. Compared with subjects with normoalbuminuria and a smaller WMHV : ICV ratio (<0.257% [median]), subjects with albuminuria and a larger WMHV : ICV ratio (≥0.257%) had higher probabilities of cognitive decline at baseline and all-cause death during the follow-up.

    Conclusions:This study suggests that subjects with albuminuria have a greater risk of WMH enlargement and that the combination of albuminuria and WMH enlargement increases the risk of cognitive decline and all-cause mortality in an elderly Japanese population.

  • Naoyuki Takashima, Hisatomi Arima, Yoshikuni Kita, Takako Fujii, Sachi ...
    Type: ORIGINAL ARTICLE
    Subject area: Epidemiology
    2020 Volume 84 Issue 6 Pages 943-948
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 29, 2020
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    Background:Despite many effective strategies for the prevention of recurrent stroke, individuals who survive an initial stroke have been shown to be at high risk of recurrent stroke. The aim of this study was to investigate the current status of stroke recurrence after first-ever stroke using a population-based stroke registry in Japan.

    Methods and Results:As part of the Shiga Stroke and Heart Attack Registry, the Shiga Stroke Registry is an ongoing population-based stroke registry study that covers approximately 1.4 million residents of Shiga Prefecture, Japan. A total of 1,883 first-ever stroke survivors at 28 days was registered in 2011 and followed-up until the end of 2013. Recurrence was defined as any type of stroke after 28 days from the onset of an index event. Two-year cumulative recurrence rates were estimated using cumulative incidence function methods. Over a mean 2.1-year follow-up period, 120 patients experienced recurrent stroke and 389 patients died without recurrence. The 2-year cumulative recurrence rate was higher in patients with index ischemic stroke (6.8%) than in those with index hemorrhagic stroke (3.8%).

    Conclusions:Two-year cumulative recurrence rate after first-ever stroke remained high, particularly among patients with ischemic stroke, in the present population-based registry study in a real-world setting in Japan. Further intensive secondary prevention strategies are required for these high-risk individuals.

Heart Failure
  • Keiichiro Iwasaki, Osamu Seguchi, Shunsuke Murata, Kunihiro Nishimura, ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2020 Volume 84 Issue 6 Pages 949-957
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 08, 2020
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    Background:Sarcopenia is characterized by progressive loss of skeletal muscle and has frequently been associated with poor clinical outcomes in patients with advanced heart failure (HF). The urinary creatinine excretion rate (CER) index is an easily measured marker of muscle mass, but its predictive capacity for mortality and cerebrovascular events has not been investigated in patients with a continuous-flow implantable left ventricular assist device (CF-iLVAD).

    Methods and Results:We retrospectively reviewed 147 patients (mean [±SD] age 43.7±12.5 years, 106 male) who underwent CF-iLVAD implantation between April 2011 and June 2019. CER indices in 24-h urine samples before CF-iLVAD implantation were determined. Over a median follow-up of 2.3 years, there were 10 (6.8%) deaths and 43 (29.3%) cerebrovascular events. Patients were divided into 2 groups (low and high CER index) according to the median CER index in men and women (i.e., 13.71 and 12.06 mg·kg−1·day−1, respectively). Mortality and intracranial hemorrhage rates after CF-iLVAD implantation were significantly higher in the low than high CER index group (mortality 12.3% vs. 1.4% [P<0.01]; intracranial hemorrhage 23.3% vs. 8.1% [P=0.01]). Multivariate Cox proportional hazard models revealed that a low CER index was an independent predictor of intracranial hemorrhage in patients receiving a CF-iLVAD (hazard ratio 3.63; 95% confidence interval 1.43–9.24; P<0.01).

    Conclusions:A low preoperative CER index is an independent, non-invasive predictor of intracranial hemorrhage after CF-iLVAD implantation.

  • Mitsutoshi Oguri, Hideki Ishii, Kunihiko Takahara, Kenichiro Yasuda, T ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2020 Volume 84 Issue 6 Pages 958-964
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 21, 2020
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    Supplementary material

    Background:Clinical congestion is the most dominant feature in patients with acute decompensated heart failure (HF). However, uncertainty exists due to the permutations and combinations of congestion status and decongestion strategies. This study investigated the effect of congestion status and its improvement on 1-year mortality.

    Methods and Results:In all, 453 consecutive patients hospitalized for acute decompensated HF between July 2015 and March 2017 were prospectively included in the study. Congestion was evaluated using the congestion score. The 1-year mortality rate was 22.7%. The mean (±SD) congestion scores at admission, on Day 3, and at discharge were 10.7±3.9, 3.4±3.5, and 0.3±0.8, respectively. The improvement rate in congestion scores during the first 3 days was 78%; 46.6% of patients had residual congestion. The Day 3 congestion score and the improvement rate during the first 3 days were related to 1-year all-cause mortality and cardiovascular mortality. Combined predictive values were examined by calculating multivariable-adjusted hazard ratios for associations of residual congestion and improvement rate during the first 3 days, and prognostic variables identified by the Cox regression model. Residual congestion and lesser improvement (<64%) were associated with higher relative risk of 1-year all-cause mortality and cardiovascular mortality than residual congestion and higher improvement (≥64%) or resolved congestion.

    Conclusions:Rapid decongestion could be a prerequisite regardless of residual congestion in hospitalized acute decompensated HF patients.

  • Masanobu Yanase, Keiichiro Iwasaki, Takuya Watanabe, Osamu Seguchi, Se ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2020 Volume 84 Issue 6 Pages 965-974
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 29, 2020
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    Background:During these 2 decades (1999–2019), many therapeutic strategies have been developed in the field of heart transplant (HTx) to improve post-HTx outcomes. In the present study, 116 consecutive HTx adults between 1999 and 2019 were retrospectively reviewed to evaluate the influences of a therapeutic modification on post HTx outcomes.

    Methods and Results:Patient survival, functional status and hemodynamics after HTx and modification of therapeutic strategies were reviewed. The overall cumulative survival rate at 10 and 20 years post-HTx was 96.4 and 76.7%, respectively. There were no significant differences in survival rate or exercise tolerance after HTx between extracorporeal and implantable continuous flow-LVAD. Post-HTx patient survival in patients, irrespective of the donor risk factors such as donor age, low LVEF, history of cardiac arrest, was equivalent across cohorts, while longer TIT and higher inotrope dosage prior to procurement surgery were significant risk factors for survival. In 21 patients given everolimus (EVL) due to renal dysfunction, serum creatinine significantly decreased 1 year after initiation. In 22 patients given EVL due to transplant coronary vasculopathy (TCAV), maximum intimal thickness significantly decreased 3 years after initiation.

    Conclusions:The analysis of a 20-year single-center experience with HTx in Japan shows encouraging improved results when several therapeutic modifications were made; for example, proactive use of donor hearts declined by other centers and the use of EVL in patients with renal dysfunction and TCAV.

Ischemic Heart Disease
  • Shinnosuke Kikuchi, Kengo Tsukahara, Shinya Ichikawa, Takeru Abe, Yugo ...
    Type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2020 Volume 84 Issue 6 Pages 975-984
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: March 19, 2020
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    Supplementary material

    Background:Prompt and potent antiplatelet effects are important aspects of management of ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). We evaluated the association between platelet-derived thrombogenicity during PPCI and enzymatic infarct size in STEMI patients.

    Methods and Results:Platelet-derived thrombogenicity was assessed in 127 STEMI patients undergoing PPCI by: (1) the area under the flow-pressure curve for the PL-chip (PL18-AUC10) using the total thrombus-formation analysis system (T-TAS); and (2) P2Y12reaction units (PRU) using the VerifyNow system. Patients were divided into 2 groups (High and Low) based on median PL18-AUC10during PPCI. PRU levels during PPCI were suboptimal in both the High and Low PL18-AUC10groups (median [interquartile range] 266 [231–311] vs. 272 [217–317], respectively; P=0.95). The percentage of final Thrombolysis in Myocardial Infarction (TIMI) 3 flow was lower in the High PL18-AUC10group (75% vs. 90%; P=0.021), whereas corrected TIMI frame count (31.3±2.5 vs. 21.0±2.6; P=0.005) and the incidence of slow-flow/no-reflow phenomenon (31% vs. 11%, P=0.0055) were higher. The area under the curve for creatine kinase (AUCCK) was greater in the High PL18-AUC10group (95,231±7,275 IU/L h vs. 62,239±7,333 IU/L h; P=0.0018). Multivariate regression analysis identified high PL18-AUC10during PPCI (β=0.29, P=0.0006) and poor initial TIMI flow (β=0.37, P<0.0001) as independent determinants of AUCCK.

    Conclusions:T-TAS-based high platelet-derived thrombogenicity during PPCI was associated with enzymatic infarct size in patients with STEMI.

  • Jinxin Liu, Shanjie Wang, Jingbo Hou, Hengxuan Cai, Weili Pan, Haimeng ...
    Type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2020 Volume 84 Issue 6 Pages 985-993
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 29, 2020
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    Supplementary material

    Background:Plaque erosion (PE) has been considered a secondary pathogenesis of ST-segment elevated myocardial infarction (STEMI) following plaque rupture (PR). Previous studies demonstrated that they had different demographic and histology characteristics and need different treatment strategy. But there are few non-invasive plasma biomarkers for distinguishing them. The present study aimed to identify non-invasive predictive biomarkers for PE and PR in patients with STEMI.

    Methods and Results:A total 108 patients were recruited and grouped into a PE group (n=36), a PR group (n=36), and an unstable angina pectoris (UAP) (n=36) group for analysis. A 9-plex tandem mass tag (TMT)-based proteomics was used to compare plasma protein profiles of PE, PR, and UAP. In total, 36 significant differential proteins (DPs) were identified among groups, 10 of which were screened out using bio-information analysis and validated with enzyme-linked immunosorbent assay (ELISA). The relationship of angiography and optical coherence tomography (OCT) imaging data and the 10 target DPs was analyzed statistically. Logistic regression showed elevated collagen type VI α-2 chain (COL6A2) and insulin-like growth factor 1 (IGF1), and decreased fermitin family homolog 3 (FERMT3), were positively associated with PE. Multivariate analysis indicated IGF1, FERMT3, and COL6A2 had independent predictive ability for PE. IGF1 was inversely correlated with lumen stenosis and the lipid arc of the plaque.

    Conclusions:IGF1, COL6A2, and FERMT3 are potential predictive biomarkers of PE in STEMI patients. And IGF1 was negatively correlated with the developing of culprit plaque.

Metabolic Disorder
  • Koutaro Yokote, Kiyoshi Niwa, Tomomi Hakoda, Fumiki Oh, Yoshitaka Kaji ...
    Type: ORIGINAL ARTICLE
    Subject area: Metabolic Disorder
    2020 Volume 84 Issue 6 Pages 994-1003
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 11, 2020
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    Supplementary material

    Background:This study is the first to evaluate the short-term efficacy and long-term safety of AZD0585, a mixture of omega-3 free fatty acids, in Japanese patients with dyslipidemia.

    Methods and Results:In this randomized double-blind placebo-controlled Phase III study, 383 patients were randomized to 2 g AZD0585, 4 g AZD0585, or placebo once daily for 52 weeks. Eligible patients had low-density lipoprotein cholesterol (LDL-C) levels controlled regardless of statin use, and triglyceride levels between 150 and 499 mg/dL. The least-squares (LS) mean percentage changes in triglyceride concentrations from baseline to the 12-week endpoint (mean of measurements at Weeks 10 and 12) in the 2 and 4 g AZD0585 and placebo groups were −15.57%, −21.75%, and 11.15% respectively (P<0.0001 for both AZD0585 doses vs. placebo). No clinically significant changes from baseline to the 12-week endpoint in total cholesterol, LDL-C, and LDL-C/apolipoprotein (Apo) B were found with AZD0585. High-density lipoprotein cholesterol (HDL-C) was slightly increased and very low-density lipoprotein cholesterol, non-HDL-C, ApoC-II, and ApoC-III were decreased with AZD0585 compared with placebo at the 12-week endpoint. Lipid profiles up to Week 52 were consistent with those up to the 12-week endpoint. No clinically important safety concerns were raised.

    Conclusions:AZD0585 significantly decreased serum triglyceride levels compared with placebo at the 12-week endpoint and was generally safe and well tolerated in Japanese patients with dyslipidemia.

Renal Disease
  • Te-Hui Kuo, Chin-Li Lu, Ya-Hui Chang, Chung-Yi Li
    Type: ORIGINAL ARTICLE
    Subject area: Renal Disease
    2020 Volume 84 Issue 6 Pages 1004-1011
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 22, 2020
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    Supplementary material

    Background:An unconventional risk factor, “dysfunction of hemodialysis vascular access”, was demonstrated to be associated with subsequent major adverse cardiovascular events (MACE) in our previous study. However, applying this suggestion in a clinical scenario may be not intuitive. A group-based trajectory model was applied to further recognize those patients with the highest risks for MACE.

    Methods and Results:In a cohort of patients who received hemodialysis from 2001 to 2010, we identified 9,711 cases that developed MACE in the stage of stable maintenance dialysis, and 19,422 randomly selected controls matched to cases on age, gender and duration of dialysis. Events of vascular access dysfunction in the 6-month period before MACE for cases and index dates for controls were evaluated. By group-based trajectory modeling, patients according to their counts of vascular access dysfunction in each month over the 6-month period prior to MACE or index dates were categorized. There were 26,744 patients in group 1 (no dysfunction), 650 in group 2 (escalating dysfunction) and 1,739 in group 3 (persistent dysfunction). Logistic regression analysis indicated that patients in group 3 had the highest chance of subsequent MACE (odds ratio 2.47, in comparison with group 1) after controlling for all the available potential confounders.

    Conclusions:Uninterrupted clusters of vascular access dysfunction are associated with a higher risk of subsequent MACE.

Valvular Heart Disease
  • Kenichi Sasaki, Masaki Izumo, Shingo Kuwata, Yuki Ishibashi, Ryo Kamij ...
    Type: ORIGINAL ARTICLE
    Subject area: Valvular Heart Disease
    2020 Volume 84 Issue 6 Pages 1012-1019
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: March 27, 2020
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    Background:Although left bundle-branch block (LBBB) is a known conduction disorder that occurs after transcatheter aortic valve implantation (TAVI), its clinical impact in the Japanese population remains unclear.

    Methods and Results:Of the 298 consecutive patients who underwent TAVI from January 2016 to December 2018 in a high-volume center in Japan, 68 with prior or periprocedural permanent pacemaker implantation (PPI), pre-existing LBBB, death during hospitalization, aborted procedure, or incomplete data were excluded. Among the final cohort of 230 patients, new-onset LBBB occurred in 90 (39%) after TAVI and persisted at 1-month follow up in 29 patients (13%; persistent new-onset LBBB, PN-LBBB). On multivariable analysis, self-expandable valve (SEV) use was found to be the only predictor of PN-LBBB (odds ratio: 4.39, 95% confidence interval: 1.69–11.41, P=0.002). There were no differences between patients with and without PN-LBBB in terms of overall mortality (18.8% vs. 26.0%, log-rank P=0.90) or need for late PPI (4.0% vs. 3.5%, log-rank P=0.74), yet there was an increased re-admission rate for heart failure (HF) in the PN-LBBB group (15.6% vs. 8.0%, log-rank P=0.046) at a median follow up of 431 (interquartile range, 271–733) days.

    Conclusions:PN-LBBB following TAVI was not associated with mortality or late PPI, but with a higher incidence of HF-related re-hospitalization at the mid-term follow up.

  • Shinji Takahashi, Naoyuki Yokoyama, Yusuke Watanabe, Taiga Katayama, H ...
    Type: ORIGINAL ARTICLE
    Subject area: Valvular Heart Disease
    2020 Volume 84 Issue 6 Pages 1020-1027
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 25, 2020
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    Background:The frequency and predictors of thrombocytopenia after transcatheter aortic valve implantation (TAVI) are unclear.

    Methods and Results:This study enrolled 342 patients undergoing TAVI (245 with a percutaneous transfemoral approach, 65 with transfemoral surgical cutdown, and 32 with a non-transfemoral approach). Balloon-expandable and self-expanding valves were implanted in 235 and 107 patients, respectively. Platelet counts started to drop immediately, reaching a nadir 2–4 days after TAVI. Clinically significant thrombocytopenia (CSTP) was defined as a platelet count ≤50×109/L at the time of the nadir or both a platelet count between 80 and 51×109/L and a decrease in platelet count ≥50%. CSTP occurred in 16.7% patients. Approach site and TAVI valve selection significantly predicted CSTP. In multivariate analysis, independent predictors of CSTP were liver cirrhosis (odds ratio [OR] 7.22; 95% confidence interval [CI] 1.05–49.82), baseline platelet count ≤120×109/L (OR 2.98; 95% CI 1.20–7.38), multiple blood transfusions (OR 4.03; 95% CI 1.72–9.41), and the use of balloon-expandable valves (OR 2.38; 95% CI 1.04–5.46). Kaplan-Meier survival analysis with a generalized Wilcoxon test revealed that mid-term (2 years) mortality was greater for patients with than without CSTP (31.4% vs. 15.5%; P=0.008).

    Conclusions:TAVI-related CSTP was not rare and was associated with poor mid-term outcomes. CSTP was not only caused by patients’ comorbidities and TAVI complications, but also related to TAVI procedural factors.

Rapid Communications
  • Hiroko Deguchi, Masataka Ikeda, Tomomi Ide, Tomonori Tadokoro, Soichir ...
    Type: RAPID COMMUNICATION
    2020 Volume 84 Issue 6 Pages 1028-1033
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: March 24, 2020
    JOURNALS FREE ACCESS FULL-TEXT HTML

    Background:Ischemic preconditioning (IPC) is an effective procedure to protect against ischemia/reperfusion (I/R) injury. Hypoxia-inducible factor-1α (Hif-1α) is a key molecule in IPC, and roxadustat (RXD), a first-in-class prolyl hydroxylase domain-containing protein inhibitor, has been recently developed to treat anemia in patients with chronic kidney disease. Thus, we investigated whether RXD pretreatment protects against I/R injury.

    Methods and Results:RXD pretreatment markedly reduced the infarct size and suppressed plasma creatinine kinase activity in a murine I/R model. Analysis of oxygen metabolism showed that RXD could produce ischemic tolerance by shifting metabolism from aerobic to anaerobic respiration.

    Conclusions:RXD pretreatment may be a novel strategy against I/R injury.

  • Takayuki Warisawa, Christopher M. Cook, Henry Seligman, James P. Howar ...
    Type: RAPID COMMUNICATION
    2020 Volume 84 Issue 6 Pages 1034-1038
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 22, 2020
    JOURNALS FREE ACCESS FULL-TEXT HTML

    Background:The per-vessel level impact of physiological pattern of disease on the discordance between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) has not been clarified.

    Methods and Results:Using the AJIP registry, vessels with FFR/iFR discordance (133/671 [19.8%]) were analyzed. In the left anterior descending artery (LAD), physiologically diffuse disease, as assessed by pressure-wire pullback, was associated with FFR−/iFR+ (83.3% [40/48]), while physiologically focal disease was associated with FFR+/iFR− (57.4% [31/54]), significantly (P<0.0001). These differences were not significant in non-LAD (P=0.17).

    Conclusions:The impact of physiological pattern of disease on FFR/iFR discordance is more pronounced in the LAD.

  • Tadafumi Sugimoto, Atsushi Mizuno, Takuya Kishi, Naoya Ito, Chisa Mats ...
    Type: RAPID COMMUNICATION
    2020 Volume 84 Issue 6 Pages 1039-1043
    Published: May 25, 2020
    Released: May 25, 2020
    [Advance publication] Released: April 29, 2020
    JOURNALS FREE ACCESS FULL-TEXT HTML
    Supplementary material

    Background:Despite the rapidly increasing attention being given to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, more commonly known as coronavirus disease 2019 (COVID-19), the relationship between cardiovascular disease and COVID-19 has not been fully described.

    Methods and Results:A systematic review was undertaken to summarize the important aspects of COVID-19 for cardiologists. Protection both for patients and healthcare providers, indication for treatments, collaboration with other departments and hospitals, and regular update of information are essentials to front COVID-19 patients.

    Conclusions:Because the chief manifestations of COVID-19 infection are respiratory and acute respiratory distress syndrome, cardiologists do not see infected patients directly. Cardiologists need to be better prepared regarding standard disinfection procedures, and be aware of the indications for extracorporeal membrane oxygenation and its use in the critical care setting.

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