Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 85, Issue 11
Displaying 1-41 of 41 articles from this issue
Focus on issue: Ischemic Heart Disease
Reviews
  • Shun Kohsaka, Kenji Fukushima, Ippei Watanabe, Susumu Manabe, Nozomi N ...
    Article type: REVIEW
    2021 Volume 85 Issue 11 Pages 1919-1927
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: June 18, 2021
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    Supplementary material

    Coronary artery disease (CAD) remains a leading cause of mortality and morbidity in developed countries. Although urgent revascularization is the cornerstone of management of acute coronary syndrome (ACS), for patients with stable CAD recent large-scale clinical trials indicate that a mechanical ‘fix’ of a narrowed artery is not obviously beneficial; ACS and stable CAD are increasingly recognized as different clinical entities. We review the perspectives on (1) modifying the diagnostic pathway of stable CAD with the incorporation of modern estimates of pretest probability, (2) non-imaging evaluations based on their availability, (3) the optimal timing of invasive coronary angiography and revascularization, and (4) the implementation of medical therapy during the work-up.

Original Articles
Coronary Intervention
  • Masahiro Natsuaki, Takeshi Morimoto, Hiroki Shiomi, Kazushige Kadota, ...
    Article type: ORIGINAL ARTICLE
    Subject area: Coronary Intervention
    2021 Volume 85 Issue 11 Pages 1928-1941
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: April 27, 2021
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    Supplementary material

    Background:Data evaluating the effects of acute coronary syndrome (ACS) relative to stable coronary artery disease (CAD) on bleeding risk after percutaneous coronary intervention (PCI) are scarce.

    Methods and Results:From the CREDO-Kyoto Registry Cohort-3, 13,258 patients undergoing first PCI (5,521 ACS; 7,737 stable CAD) were identified. Patients were further stratified according to ACS presentation and Academic Research Consortium High Bleeding Risk (HBR): ACS/HBR: n=2,502; ACS/no-HBR: n=3,019; stable CAD/HBR: n=3,905; and stable CAD/no-HBR: n=3,832. The primary bleeding endpoint was Bleeding Academic Research Consortium 3/5 bleeding, whereas the primary ischemic endpoint was myocardial infarction (MI)/ischemic stroke. Compared with stable CAD, ACS was associated with a significantly higher adjusted risk for bleeding (hazard ratio [HR] 1.85; 95% confidence interval [CI] 1.68–2.03; P<0.0001), with a markedly higher risk within 30 days (HR 4.24; 95% CI 3.56–5.06; P<0.0001). Compared with the stable CAD/no-HBR group, the ACS/HBR, no-ACS/HBR, and ACS/no-HBR groups were associated with significantly higher adjusted risks for bleeding, with HRs of 3.05 (95% CI 2.64–3.54; P<0.0001), 1.89 (95% CI 1.66–2.15; P<0.0001), and 1.69 (95% CI 1.45–1.98; P<0.0001), respectively. There was no excess adjusted risk of the ACS relative to stable CAD group for MI/ischemic stroke (HR 1.07; 95% CI 0.94–1.22; P=0.33).

    Conclusions:Bleeding risk after PCI depended on both ACS presentation and HBR, with a significant effect of ACS within 30 days.

  • Raisuke Iijima, Masato Nakamura
    Article type: EDITORIAL
    2021 Volume 85 Issue 11 Pages 1942-1943
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: May 22, 2021
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  • Jeehoon Kang, Jung-Kyu Han, Han-Mo Yang, Kyung Woo Park, Hyun-Jae Kang ...
    Article type: ORIGINAL ARTICLE
    Subject area: Coronary Intervention
    2021 Volume 85 Issue 11 Pages 1944-1955
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: June 02, 2021
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    Supplementary material

    Background:It has not been determined which specific 2-stenting strategy is the best for bifurcation lesions. Our aim was to investigate the clinical outcomes of various 2-stenting strategies in the era of 2nd-generation drug-eluting stents (2G-DES).

    Methods and Results:We analyzed 454 patients who finally underwent 2-stenting for a bifurcation lesion, from among 2,648 patients enrolled in the COBIS III registry. The primary outcome was target lesion failure (TLF). Patients were analyzed according to stenting sequence (provisional [main vessel stenting first] vs. systemic [side branch stenting first]) and stenting technique (crush vs. T vs. culotte vs. kissing/V stenting). Overall, 4.4 years’ TLF after 2-stenting treatment for bifurcation lesion was excellent: TLF 11.2% and stent thrombosis 1.3%. There was no difference in TLF according to 2-stenting strategy (11.1% vs. 10.5%, P=0.990 for provisional and systemic sequence; 8.6% vs. 14.4% vs. 12.9% vs. 12.2%, P=0.326 for crush, T, culotte, kissing/V technique, respectively). Only left main (LM) disease and a shorter duration of dual antiplatelet therapy (DAPT) were associated with TLF. The distribution of DAPT duration differed between patients with and without TLF, and the time-point of intersection was 2.5 years. Also, the side branch was the most common site of restenosis.

    Conclusions:The stenting sequence or technique did not affect clinical outcomes, but LM disease and shorter DAPT were associated with TLF, in patients with bifurcation lesions undergoing 2-stenting with 2G-DES.

  • Yoshinobu Murasato
    Article type: EDITORIAL
    2021 Volume 85 Issue 11 Pages 1956-1958
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: June 17, 2021
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  • Takahiro Jimba, Masayasu Ikutomi, Atsuko Tsukamoto, Masashiro Matsushi ...
    Article type: ORIGINAL ARTICLE
    Subject area: Coronary Intervention
    2021 Volume 85 Issue 11 Pages 1959-1968
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: July 07, 2021
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    Supplementary material

    Background:Stent edge-related restenosis (SER) remains a potential limitation of drug-eluting stent (DES). Hinge motion at the stent edge could lead to mechanical stress and contribute to incidents of SER. We investigated the effect of hinge motion on SER after implantation of current-generation DES in the right coronary artery (RCA), where excessive vessel movement is commonly observed.

    Methods and Results:Of 647 consecutive lesions in the RCA treated with second-generation or later DESs, 426 with follow-up angiography were included in this study. Intravascular imaging analysis was performed for 584 stent edges and reference segments. Binary restenosis occurred in 42 lesions (9.9%), and 55% were SERs. The hinge angle was significantly larger in the SER group than in the other restenosis or the no-restenosis group (17.9° vs. 11.6° and 10.6°, respectively; P<0.001). Lesions with an excessive hinge angle (>11.5°) had an increased rate of target lesion revascularization (19.1% vs. 7.2%; P<0.001) during the median follow-up period of 1,578 days. In per-edge analysis, hinge angle and residual plaque burden were independent predictors of SER. The coexistence of excessive hinge motion and residual plaque burden had a synergistic effect on stenotic progression in quantitative angiographic analysis (Pinteraction<0.001) at follow-up angiography.

    Conclusions:Substantial stress determined by angulation at a stent edge and its interaction with residual plaque can be considered as one plausible mechanism for SER.

  • Hiromasa Otake
    Article type: EDITORIAL
    2021 Volume 85 Issue 11 Pages 1969-1971
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: August 04, 2021
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  • Koya Okabe, Masanobu Ohya, Akihiro Ikuta, Makoto Takamatsu, Kohei Osak ...
    Article type: ORIGINAL ARTICLE
    Subject area: Coronary Intervention
    2021 Volume 85 Issue 11 Pages 1972-1980
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: August 03, 2021
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    Supplementary material

    Background:Percutaneous coronary intervention (PCI) for coronary bifurcation lesions using the 2-stent strategy remains a challenging procedure for interventionalists because of the higher incidence of in-stent restenosis (ISR) and adverse events. ISR predictors in patients treated with newer-generation everolimus-eluting stents (EES) and the 2-stent strategy remain unknown. Hence, we aimed to evaluate the 1-year clinical and angiographic outcomes of non-left main trunk (LMT) bifurcation lesions treated with the 2-stent strategy using newer-generation EES.

    Methods and Results:The study sample consisted of 262 non-LMT bifurcation lesions treated using culotte or T-stenting with EES between 2010 and 2018. One-year post-procedural angiographic and clinical examinations were conducted in 208 (79.4%) and 260 (99.2%) lesions, respectively. The primary outcome measure was the 1-year post-procedural ISR rate, which was found to be 15.9%. Independent predictors of 1-year post-procedural ISR were long side branch lesions (adjusted odds ratio [aOR] 2.31; 95% confidence interval [CI] 1.02–5.23; P=0.04) and 3-link EES implantation (aOR 2.45; 95% CI 1.07–5.61; P=0.03). The 1-year cumulative incidence of target lesion revascularization was 3.5%.

    Conclusions:The 1-year clinical outcomes of non-LMT bifurcation lesions treated with the 2-stent strategy using EES were acceptable. Long side branch lesions and lesions treated with 3-link EES were independent predictors of 1-year post-procedural ISR.

  • Hiroyuki Okura
    Article type: EDITORIAL
    2021 Volume 85 Issue 11 Pages 1981-1982
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: September 15, 2021
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  • Eline H Ploumen, Rosaly A Buiten, Paolo Zocca, Carine JM Doggen, Adel ...
    Article type: ORIGINAL ARTICLE
    Subject area: Coronary Intervention
    2021 Volume 85 Issue 11 Pages 1983-1990
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: July 13, 2021
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    Supplementary material

    Background:At 1 year, the international randomized BIONYX trial (ClinicalTrials.gov:NCT02508714) established non-inferiority regarding safety and efficacy of the novel Resolute Onyx zotarolimus-eluting stent (RO-ZES) vs. the Orsiro sirolimus-eluting stent (O-SES). Although the RO-ZES is used in daily practice, no clinical results have been published beyond 2 years.

    Methods and Results:We assessed 3-year clinical outcomes of 2,488 all-comers after percutaneous coronary intervention (PCI) with RO-ZES vs. O-SES. The main endpoint was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction (MI), or target vessel revascularization. Time-to-endpoints was assessed by Kaplan-Meier methods and between-group comparisons by log-rank tests. Follow-up was available in 2,433/2,488 (97.8%) patients. There was no significant between-stent difference in TVF (RO-ZES 112/1,243 [9.2%] vs. O-SES 109/1,245 [8.9%], hazard ratio [HR]: 1.03, 95% confidence interval [CI] 0.79–1.34; Plog-rank=0.85) and its individual components. The all-cause mortality was significantly lower after PCI with RO-ZES (3.7% vs.5.4%, HR: 0.67, 95% CI 0.46–0.97; Plog-rank=0.034), but cardiac mortality did not differ significantly (1.1% vs.1.9%, HR: 0.56, 95% CI 0.28–1.11; Plog-rank=0.09). Definite-or-probable stent thrombosis rates were low for both groups (0.6% vs.1.2%, HR: 0.46, 95% CI 0.19–1.14; Plog-rank=0.09).

    Conclusions:This first 3-year randomized assessment of the RO-ZES showed a favorable rate of TVF that matched the outcomes of patients treated with O-SES. We observed a lower rate of all-cause death in the RO-ZES group, but long-term clinical follow-up is of interest.

Surgery
  • Satoshi Kainuma, Koichi Toda, Takashi Daimon, Shigeru Miyagawa, Yasush ...
    Article type: ORIGINAL ARTICLE
    Subject area: Surgery
    2021 Volume 85 Issue 11 Pages 1991-2001
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: April 07, 2021
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    Supplementary material

    Background:In patients with severe left ventricular (LV) dysfunction requiring coronary artery bypass grafting (CABG), the association between diabetic status and outcomes after surgery, as well as with survival benefit following bilateral internal thoracic artery (ITA) grafting, remain largely unknown.

    Methods and Results:Patients (n=188; mean [±SD] age 67±9 years) with LV ejection fraction ≤40% who underwent isolated initial CABG were classified into non-diabetic (n=64), non-insulin-dependent diabetic (NIDM; n=74), and insulin-dependent diabetic (IDM; n=50) groups. During follow-up (mean [±SD] 68±47 months), the 5-year survival rate was 84% and 65% among non-diabetic and diabetic patients, respectively (P=0.034). After adjusting for all covariates, both NIDM and IDM were associated with increased mortality, with hazard ratios (HRs) of 1.9 (95% confidence interval [CI] 1.0–3.7; P=0.049) and 2.4 (95% CI 1.2–4.8; P=0.016), respectively. Among non-diabetic patients, there was no difference in the 5-year survival rate between single and bilateral ITA grafting (86% vs. 80%, respectively; P=0.95), whereas bilateral ITA grafting increased survival among diabetic patients (57% vs. 81%; P=0.004). Multivariate analysis revealed that bilateral ITA was significantly associated with a decreased risk of mortality (HR 0.3; 95% CI 0.1–0.8; P=0.024).

    Conclusions:NIDM and IDM were significantly associated with worse long-term clinical outcome after CABG for severe LV dysfunction. Bilateral ITA grafting has the potential to improve survival in diabetic patients with severe LV dysfunction.

  • Satoru Wakasa, Yoshiro Matsui
    Article type: EDITORIAL
    2021 Volume 85 Issue 11 Pages 2002-2003
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: May 14, 2021
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  • Kohei Hachiro, Takeshi Kinoshita, Tomoaki Suzuki, Tohru Asai
    Article type: ORIGINAL ARTICLE
    Subject area: Surgery
    2021 Volume 85 Issue 11 Pages 2004-2010
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: June 25, 2021
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    Background:We compared postoperative outcomes in hemodialysis (HD) patients who underwent isolated coronary artery bypass grafting (CABG) for multivessel disease using either bilateral or single skeletonized internal thoracic artery.

    Methods and Results:Among 1,486 patients who underwent isolated CABG between 2002 and 2020, 145 HD patients were retrospectively analyzed. After inverse probability of treatment weighting, there were no significant differences in the preoperative characteristics. No significant differences in 30-day mortality (P=0.551) or postoperative deep sternal wound infection (P=0.778) were observed. However, the bilateral internal thoracic artery grafting group had a lower postoperative stroke rate (0% vs. 4.0%, P=0.019). No significant differences in freedom from all-cause death (P=0.760) and cardiac death (P=0.863) were found. In the multivariate Cox proportional hazards models, bilateral internal thoracic artery grafting was not associated with all-cause death (P=0.246) or cardiac death (P=0.435).

    Conclusions:Bilateral internal thoracic artery grafting in HD patients did not improve mid-term outcomes, but it was also not associated with worse postoperative outcomes. Use of the bilateral internal thoracic artery may be an important option in patients with limited conduits to prevent postoperative complications.

  • Hirofumi Takemura
    Article type: EDITORIAL
    2021 Volume 85 Issue 11 Pages 2011-2013
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: August 21, 2021
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  • Hiroyuki Tsukihara, Noboru Motomura, Shinichi Takamoto
    Article type: ORIGINAL ARTICLE
    Subject area: Surgery
    2021 Volume 85 Issue 11 Pages 2014-2018
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: August 21, 2021
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    Background:The Japan Cardiovascular Surgery Database (JCVSD) is a nationwide registry of patients undergoing cardiovascular surgery in Japan. To investigate and improve data quality, we have been conducting on-site institutional audits since 2004. This study aimed to investigate the accuracy of the registered data by comparing it to site visit data.

    Methods and Results:The subjects of this study were the 95 facilities at which a site visit was conducted. The case registration accuracy was 98.74%. Furthermore, we confirmed high data input accuracy of >90% for almost all fields. Approximately 99% of cases had been correctly entered for diabetes, aortic stenosis, and mortality. We also discovered which fields were more likely to be incorrectly captured and the causes thereof, as well as problems regarding some definitions and the input system itself.

    Conclusions:We were able to confirm high registration accuracy in the JCVSD. Appropriately resourced, focused site visits as part of a national audit are capable of accurate data collection on which continual nationwide quality control can be based. Continued work and development to further improve the quality of the database are mandatory to maintain a high standard of cardiovascular surgery in Japan.

Imaging
  • Saki Iwai, Makoto Watanabe, Akihiko Okamura, Atsushi Kyodo, Kazutaka N ...
    Article type: ORIGINAL ARTICLE
    Subject area: Imaging
    2021 Volume 85 Issue 11 Pages 2019-2028
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: May 27, 2021
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    Supplementary material

    Background:Optical coherence tomography (OCT) has the potential to characterize the detailed morphology of calcified coronary plaques. This study examined the prognostic impact of calcified plaque morphology in patients with coronary artery calcification (CAC) who underwent newer-generation drug-eluting stent (DES) implantation.

    Methods and Results:In all, 251 patients with moderate to severe CAC who underwent OCT-guided DES implantation were reviewed retrospectively and divided into 3 groups according to OCT findings of the target lesion: 25 patients (10.0%) with calcified nodules (CN), 69 patients (27.5%) with calcified protrusion (CP) without CN, and 157 patients (62.5%) with superficial calcific sheet (SC) without CN and CP. The primary endpoint was major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, and target lesion revascularization (TLR). Kaplan-Meier survival analysis revealed that, among the 3 groups, the rates of MACE-free survival (log-rank test, P=0.0117), myocardial infarction (log-rank test, P=0.0103), and TLR (log-rank test, P=0.0455) were significantly worse in patients with CN. Multivariate Cox proportional hazards analysis demonstrated that CN was an independent predictor of MACE (hazard ratio 4.41; 95% confidence interval 1.63–10.8; P=0.0047).

    Conclusions:Target lesion CN was associated with higher cardiac event rates in patients who underwent newer-generation DES implantation for lesions with moderate to severe CAC.

  • Hiromasa Otake, Tomoyo Hamana
    Article type: EDITORIAL
    2021 Volume 85 Issue 11 Pages 2029-2031
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: June 25, 2021
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  • Daigo Hiraya, Akira Sato, Tomoya Hoshi, Shunsuke Sakai, Hiroaki Watabe ...
    Article type: ORIGINAL ARTICLE
    Subject area: Imaging
    2021 Volume 85 Issue 11 Pages 2032-2039
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: July 17, 2021
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    Supplementary material

    Background:Although elevated levels of oxidized low-density lipoprotein (LDL) could play a critical role in vulnerable plaque, there are no studies that have compared coronary high-intensity plaque (HIP) and circulating malondialdehyde-modified (MDA)-LDL levels for the prediction of cardiac events.

    Methods and Results:A total of 139 patients with coronary artery stenosis (>70%) were examined with non-contrast T1-weighted magnetic resonance imaging (MRI) (HIP: n=64, non-HIP: n=75). Scheduled percutaneous coronary intervention (PCI) for culprit lesions was performed within 48 h after MRI. HIP was defined as a signal intensity of coronary plaque to cardiac muscle ratio (PMR) ≥1.4. We evaluated the subsequent major adverse cardiac events (MACE) during the follow-up period (5.6±1.3 years). MDA-LDL levels were independently associated with the presence of HIP (P<0.0001). The incidence of MACE was 15%, and it was significantly higher in patients with HIP (27%) than in those without HIP (5%; P=0.011). Cox proportional hazard analysis showed MDA-LDL levels (P=0.007) and PMR (P=0.016) were significantly associated with MACE. For MACE prediction, C-statistic values for MDA-LDL, PMR, and PMR+MDA-LDL were 0.724, 0.791, and 0.800, respectively. Compared with MDA-LDL alone, the addition of PMR to MDA-LDL increased net reclassification improvement by 0.78 (P=0.012).

    Conclusions:MDA-LDL levels might be associated with the presence of HIP in patients with coronary artery disease. Furthermore, adding PMR to MDA-LDL levels markedly improved prediction of subsequent MACE after PCI.

  • Tomohiro Kawasaki
    Article type: EDITORIAL
    2021 Volume 85 Issue 11 Pages 2040-2042
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: September 04, 2021
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  • Itta Kawamura, Toru Tanigaki, Hiroyuki Omori, Takuya Mizukami, Tetsuo ...
    Article type: ORIGINAL ARTICLE
    Subject area: Imaging
    2021 Volume 85 Issue 11 Pages 2043-2049
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: June 18, 2021
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    Supplementary material

    Background:Myocardial perfusion imaging (MPI) and fractional flow reserve (FFR) are established approaches to the assessment of myocardial ischemia. Recently, various FFR cutoff values were proposed, but the diagnostic accuracy of MPI in identifying positive FFR using various cutoff values is not well established.

    Methods and Results:We retrospectively studied 273 patients who underwent stress MPI and FFR within a 3-month period. Results for FFR were obtained from 218 left anterior descending artery (LAD) lesions and 207 non-LAD lesions. Stress MPI and FFR demonstrated a good correlation in the detection of myocardial ischemia. However, the positive predictive value (PPV) of FFR for detecting MPI-positive lesions at the optimal FFR thresholds was insufficient (44% for LAD and 65% for non-LAD lesions). This was caused by a sharp drop in PPV at an FFR threshold of 0.7 or more. Notably, 41% of the lesions with normal MPI demonstrated FFRs <0.80. However, MPI-negative lesions had an extremely low lesion rate with FFR <0.65 (6%). Conversely, 78% and 41% of MPI-positive lesions had FFR <0.80 and <0.65, respectively.

    Conclusions:The data confirmed that decisions based on MPI are reasonable because MPI-negative patients have an extremely low rate of lesions with a FFR below the cutoff point for a hard event, and MPI-positive lesions include many lesions with FFR <0.65.

  • Nobuhiro Tanaka
    Article type: EDITORIAL
    2021 Volume 85 Issue 11 Pages 2050-2052
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: July 17, 2021
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  • Matthew Sibbald, Natalia Pinilla-Echeverri, Mognee Alameer, Jorge Chav ...
    Article type: ORIGINAL ARTICLE
    Subject area: Imaging
    2021 Volume 85 Issue 11 Pages 2053-2062
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: July 22, 2021
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    Background:Optical coherence tomographic (OCT) imaging has enabled identification of lipid, with increasing interest in how it may affect coronary interventions and clinical outcomes. This review summarizes the available evidence around OCT identification of lipid and its effect on interventions, clinical events, and the natural history of coronary disease.

    Methods and Results:We conducted a scoping review using the Medline, HealthStar, and Embase databases for articles published between 1996 and 2021. We screened 1,194 articles and identified 51 for inclusion in this study, summarizing the key findings. The literature supports a common OCT definition of lipid as low-signal regions with diffuse borders, validated against histology and other imaging modalities with acceptable intra- and inter-rater reliability. There is evidence that OCT-identified lipid at the site of stent implantation increases the risk of edge dissection, incomplete stent apposition, in-stent tissue protrusion, decreased coronary flow after stenting, side branch occlusion, and post-procedural cardiac biomarker increases. In mostly retrospective studies, lipid indices measured at non-stented sites are associated with plaque progression and the development of recurrent ischemic events.

    Conclusions:There is extensive literature supporting the ability of OCT to identify lipid and demonstrating a substantial impact of lipid on percutaneous coronary intervention outcomes. Future work to prospectively evaluate the effect of the characteristics of lipid-rich plaques on long-term clinical outcomes is needed.

Population Science
  • Anthony C. Keech, Kazuma Oyama, Peter S. Sever, Minao Tang, Sabina A. ...
    Article type: ORIGINAL ARTICLE
    Subject area: Population Science
    2021 Volume 85 Issue 11 Pages 2063-2070
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: May 12, 2021
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    Supplementary material

    Background:There are concerns that Asian patients respond differently to some medications. This study evaluated the efficacy and safety of evolocumab among Asian vs. other subjects in the FOURIER trial, which randomized stable atherosclerosis patients to receive either evolocumab or placebo.

    Methods and Results:Effects of adding evolocumab vs. placebo to background statin therapy on low-density lipoprotein cholesterol (LDL-C) reductions, cardiovascular outcomes, and adverse events were compared among 27,564 participants with atherosclerotic disease, according to self-reported Asian (n=2,723) vs. other (n=24,841) races followed for a median of 2.2 years in the FOURIER trial. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. At randomization, Asians had slightly lower LDL-C (median 89 [IQR 78–104] mg/dL vs. 92 [80–109] mg/dL; P<0.001) and were much less likely to be on a high-intensity statin (33.3% vs. 73.3%; P<0.001). Evolocumab lowered LDL-C more in Asians than in others (66% vs. 58%; P<0.001). The effect of evolocumab on the primary endpoint was similar in Asians (HR, 0.79; 95% CI, 0.61–1.03) and others (HR, 0.86; 95% CI, 0.79–0.93; P interaction=0.55). There was no excess of serious adverse events with evolocumab among Asians over others.

    Conclusions:Use of evolocumab robustly lowers LDL-C and is equally efficacious in lowering the risk of cardiovascular events and safe in Asians as it is in others.

  • Masaaki Miyata
    Article type: EDITORIAL
    2021 Volume 85 Issue 11 Pages 2071-2072
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: May 13, 2021
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  • Hayato Tada, Hirofumi Okada, Atsushi Nohara, Masakazu Yamagishi, Masay ...
    Article type: ORIGINAL ARTICLE
    Subject area: Population Science
    2021 Volume 85 Issue 11 Pages 2073-2078
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: May 20, 2021
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    Supplementary material

    Background:Recent studies suggest that cumulative exposure to low-density lipoprotein-cholesterol (LDL-C) leads to the development of atherosclerotic cardiovascular disease (ASCVD). However, few studies have investigated whether this link extends to individuals with familial hypercholesterolemia (FH), a relevant patient population.

    Methods and Results:We retrospectively investigated the health records of 1,050 patients with clinical FH diagnosis between April 1990 and March 2019. We used Cox proportional hazards models adjusted for established ASCVD risk factors to assess the association between cholesterol-year-score and major adverse cardiovascular events (MACEs), including death from any cause or hospitalization due to ASCVD events. Cholesterol-year-score was calculated as LDL-C max × [age at diagnosis/statin initiation] + LDL-C at inclusion × [age at inclusion − age at diagnosis/statin initiation]. The median follow-up period for MACE evaluation was 12.3 (interquartile range, 9.1–17.5) years, and 177 patients experienced MACEs during the observation period. Cholesterol-year-score was significantly associated with MACEs (hazard ratio, 1.35; 95% confidence interval, 1.07–1.53; P=0.0034, per 1,000 mg-year/dL), independent of other traditional risk factors including age and LDL-C, based on cross-sectional assessment. Cholesterol-year-score improved the discrimination ability of other traditional risk factors for ASCVD events (C-index, 0.901 vs. 0.889; P=0.00473).

    Conclusions:Cumulative LDL-C exposure was strongly associated with MACEs in Japanese patients with FH, warranting early diagnosis and treatment initiation in these patients.

  • Hirotoshi Ohmura
    Article type: EDITORIAL
    2021 Volume 85 Issue 11 Pages 2079-2080
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: July 02, 2021
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  • Jungchan Park, Ji-hye Kwon, Seung-Hwa Lee, Jong-Hwan Lee, Jeong Jin Mi ...
    Article type: ORIGINAL ARTICLE
    Subject area: Population Science
    2021 Volume 85 Issue 11 Pages 2081-2088
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: May 12, 2021
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    Supplementary material

    Background:This study compared myocardial injury after non-cardiac surgery (MINS) and mortalities between patients under and over the age of 45 years.

    Methods and Results:From January 2010 and June 2019, patients with cardiac troponin measurement within 30 days after non-cardiac surgery were enrolled and divided into groups according to age: >45 (≥45 years) and <45 (<45 years). Further analyses were conducted only in patients who were diagnosed with MINS. The outcomes were MINS and 30-day mortality. Of the 35,223 patients, 31,161 (88.5%) patients were in the >45-year group and 4,062 (11.5%) were in the <45-year group. After adjustment with inverse probability of weighting, the <45-years group showed a lower incidence of MINS and cardiovascular mortality (16.6% vs. 11.7%; odds ratio, 0.77; 95% confidence interval [CI], 0.69–0.84; P<0.001 and 0.4% vs. 0.2%; hazard ratio [HR], 0.41; 95% CI, 0.19–0.88; P=0.02, respectively). In a comparison of only the <45-years group, MINS was associated with increased 30-day mortality (0.7% vs. 10.3%; HR, 10.48; 95% CI, 6.18–17.78; P<0.001), but the mortalities of patients with MINS did not differ according to age.

    Conclusions:MINS has a comparable prognostic impact in patients aged under and over 45 years; therefore, future studies need to also consider patients aged <45 years regarding risk factors of MINS and screening of perioperative troponin elevation.

  • Shunsuke Kawamoto
    Article type: EDITORIAL
    2021 Volume 85 Issue 11 Pages 2089-2091
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: June 12, 2021
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  • Yoshihiro Tanaka, Satoko Matsuyama, Hayato Tada, Kenshi Hayashi, Masay ...
    Article type: ORIGINAL ARTICLE
    Subject area: Population Science
    2021 Volume 85 Issue 11 Pages 2092-2099
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: July 03, 2021
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    Supplementary material

    Background:Because it is unclear whether lower urinary tract symptoms (LUTS) are associated with cardiovascular disease (CVD) in the Japanese population, we explored the association in general Japanese men aged 55–75 years.

    Methods and Results:The cross-sectional study included male participants who had both national health checkup data and the International Prostate Symptom Score (IPSS) in the same calendar year between 2009 and 2017. LUTS severity was evaluated by IPSS. A robust Poisson regression model was used to assess the association between LUTS severity and the composite CVD outcome [coronary artery disease (CAD), stroke, or atrial fibrillation (AF)] and each component of the composite outcome. Prevalence ratio (PR) was adjusted for conventional cardiovascular risk factors. Of 16,781 male participants (mean age, 67±5 years), mild LUTS were observed in 9,243 (55.1%); moderate, 6,445 (38.4%); and severe, 1,093 (6.5%). Compared with the mild LUTS group, moderate LUTS [PR 1.18, 95% confidence interval (CI) 1.10–1.25, P<0.001] and severe LUTS (PR 1.38, 95% CI 1.24–1.53, P<0.001) were significantly associated with a higher prevalence of CVD. LUTS severity was associated with higher prevalence of CAD and stroke, but not AF.

    Conclusions:The severity of LUTS was associated with a higher prevalence of CVD, especially CAD and stroke, independent of conventional CVD risk factors.

  • Tetsuya Ohira
    Article type: EDITORIAL
    2021 Volume 85 Issue 11 Pages 2100-2101
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: September 17, 2021
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Basic Science
  • Hiroshi Wakabayashi, Junichi Taki, Hiroshi Mori, Tomo Hiromasa, Norihi ...
    Article type: ORIGINAL ARTICLE
    Subject area: Basic Science
    2021 Volume 85 Issue 11 Pages 2102-2108
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: June 26, 2021
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    Background:This study chronologically evaluated the expression of the intensity and distribution of the sigma-1 receptor (σ1R) demonstrated by radiolabeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) in a rat model of myocardial ischemia and reperfusion.

    Methods and Results:The left coronary artery was occluded for 30 min, followed by reperfusion. Dual-tracer autoradiography with 125I-OI5V and 99 mTc-MIBI was performed to assess the spatiotemporal changes in 125I-OI5V uptake (n=5–6). Significant and peaked 125I-OI5V uptake in the ischemic area was observed at 3 days after reperfusion, and the 125I-OI5V uptake ratio of ischemic area to normally perfused left ventricular area decreased gradually from 3 to 28 days (mean value±SD; 0.90±0.12 at 1 day, 1.89±0.19 at 3 days, 1.52±0.17 at 7 days, 1.34±0.13 at 14 days, and 1.16±0.14 at 28 days, respectively). Triple-tracer autoradiography with 125I-OI5V, 99 mTc-MIBI, and 201TlCl was performed to evaluate 125I-OI5V uptake in the ischemic area in relation to the residual perfusion at 7 days (n=4). The 125I-OI5V uptake ratio of the non-salvaged area was higher compared to that of the salvaged area in the ischemic area. 123I-OI5V and 99 mTc-MIBI SPECT/CT was performed 3 days after reperfusion (n=3), and the in vivo images showed clear uptake of 123I-OI5V in the perfusion defect area.

    Conclusions:The present study confirmed the spatiotemporal expression pattern of σ1R expression. Non-invasive σ1R imaging with 123I or 125I-OI5V was feasible to monitor the expression of σ1R after myocardial ischemia and reperfusion.

  • Kazuya Takehana
    Article type: EDITORIAL
    2021 Volume 85 Issue 11 Pages 2109-2110
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: August 28, 2021
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Rapid Communications
  • Tomoyuki Yamada, Taku Ogawa, Kenta Minami, Yusuke Kusaka, Masaaki Hosh ...
    Article type: RAPID COMMUNICATION
    2021 Volume 85 Issue 11 Pages 2111-2115
    Published: October 25, 2021
    Released on J-STAGE: October 25, 2021
    Advance online publication: September 22, 2021
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    Supplementary material

    Background:This study aimed to determine whether disease severity varied according to whether coronavirus disease 2019 (COVID-19) patients had multiple or single cardiovascular diseases and risk factors (CVDRFs).

    Methods and Results:COVID-19 patients with single (n=281) or multiple (n=412) CVDRFs were included retrospectively. Multivariable logistic regression showed no significant difference in the risk of in-hospital death between groups, but patients with multiple CVDRFs had a significantly higher risk of acute respiratory distress syndrome (odds ratio: 1.75, 95% confidence interval: 1.09–2.81).

    Conclusions:COVID-19 patients with multiple CVDRFs have a higher risk of complications than those with a single CDVRF.

Images in Cardiovascular Medicine
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