Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 84, Issue 10
Displaying 1-34 of 34 articles from this issue
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Reviews
  • Yu-Feng Hu, Wen-Han Cheng, Yuan Hung, Wen-Yu Lin, Tze-Fan Chao, Jo-Nan ...
    Article type: REVIEW
    2020 Volume 84 Issue 10 Pages 1679-1685
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: September 09, 2020
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    The health crisis due to coronavirus disease 2019 (COVID-19) has shocked the world, with more than 1 million infections and casualties. COVID-19 can present from mild illness to multi-organ involvement, but especially acute respiratory distress syndrome. Cardiac injury and arrhythmias, including atrial fibrillation (AF), are not uncommon in COVID-19. COVID-19 is highly contagious, and therapy against the virus remains premature and largely unknown, which makes the management of AF patients during the pandemic particularly challenging. We describe a possible pathophysiological link between COVID-19 and AF, and therapeutic considerations for AF patients during this pandemic.

Editorials
Original Articles
Arrhythmia/Electrophysiology
  • Eitaro Kodani, Tomohiro Kaneko, Hitomi Fujii, Hiroyuki Nakamura, Hajim ...
    Article type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2020 Volume 84 Issue 10 Pages 1693-1700
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: August 22, 2020
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    Supplementary material

    Background:Atrial fibrillation (AF) and chronic kidney disease (CKD) are known risk factors for each other. In Tama City in Tokyo, 12-lead ECG and serum creatinine concentration have been included as essential examinations in specific health checkups to diagnose AF and CKD. In the present study, we investigated the impact of CKD classification on new-onset AF in the general population.

    Methods and Results:Among 13,478 subjects aged 40–74 years at entry (age, 65.6±7.8 years; men, 42.0%), renal impairment with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2and proteinuria were found in 15.5% and 4.6%, respectively. CKD severity in individual subjects was classified according to a heatmap of the Japanese Society of Nephrology as 81.3% in the green, 15.1% in the yellow, 2.5% in the orange, and 0.9% in the red. Of those without AF in 2012, it had developed in 115 up to 2017; thus, the new-onset AF incidence rate was 2.6/1,000 person-years. Hazard ratios and 95% confidence intervals for new-onset AF in each CKD classification were 1.50 (0.93–2.41, P=0.097) in the yellow, 2.53 (1.03–6.23, P=0.044) in the orange, and 4.65 (1.47–14.70, P=0.009) in the red compared with the green as a reference.

    Conclusions:CKD classification was significantly associated with new-onset AF in the general population. Thus, it would be useful for risk stratification of new-onset AF. Renal function evaluation is recommended in health checkups.

  • Mitsunori Oida, Shinya Suzuki, Takuto Arita, Naoharu Yagi, Takayuki Ot ...
    Article type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2020 Volume 84 Issue 10 Pages 1701-1708
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: August 28, 2020
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    Supplementary material

    Background:Ischemic stroke (IS) and major bleeding, which are serious adverse events in patients with atrial fibrillation (AF), could have seasonal variations, but there are few reports.

    Methods and Results:In the Shinken Database 2004–2016 (n=22,018), 3,581 AF patients (average age, 63.5 years; 2,656 men, 74.2%; 1,388 persistent AF, 38.8%) were identified. Median CHADS2and HAS-BLED scores were both 1 point. Oral anticoagulants were prescribed for 2,082 (58.1%) patients (warfarin, 1,214; direct oral anticoagulants [DOACs], 868). Incidence and observation period (maximum 3 years) of IS, extracranial hemorrhage (ECH), and intracranial hemorrhage (ICH) were counted separately for the northern hemisphere seasons. During the mean follow-up period of 2.4 years, there were totals of 90 IS, 73 ECH, and 33 ICH cases. The respective incidence rates per 1,000 patient-years in spring, summer, autumn, and winter were 8.5, 8.8, 7.5, and 16.8 for IS, 7.2, 9.7, 3.8, and 13.1 for ECH, and 2.7, 1.9, 3.8, and 7.0 for ICH. The number of patients with DOACs relatively increased among those with ECH in summer.

    Conclusions:Significant seasonal variations were observed for IS, ECH, and ICH events in AF patients, and were consistently the highest in winter. A small peak of ECH was observed in summer, which seemed, in part, to be related to increased DOAC use.

  • Long Peng, Zexiong Li, Yanting Luo, Xixiang Tang, Xing Shui, Xujing Xi ...
    Article type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2020 Volume 84 Issue 10 Pages 1709-1717
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: September 03, 2020
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    Background:Atrial fibrillation (AF) recurrence remains a tricky problem in patients undergoing ablation. This meta-analysis aimed to summarize the current literature to clarify whether renin-angiotensin system inhibitors (RASIs) prevent AF recurrence after ablation.

    Methods and Results:Relevant studies were searched on Pubmed and EMBASE through December 2019. Pooled relative risk (RR) of AF recurrence was calculated. Subgroup analyses according to study design, race, and follow-up duration were further performed. A total of 15 studies examining 4,300 patients were included, with 3 randomized controlled trials and 12 cohort studies. Overall analysis showed that RASIs significantly reduced AF recurrence after ablation (RR=0.83; 95% confidence interval (CI) 0.70–0.98, P=0.028; I2=68.9%). Subgroup analysis further indicated that positive results were found in randomized controlled trials (RR=0.51, 95% CI 0.37–0.70, P<0.001; I2=4%), studies conducted in Asia (RR=0.59, 95% CI 0.46–0.76, P<0.001; I2=30.7%), and studies with follow-up duration ≥1 year (RR=0.82, 95% CI 0.70–0.95, P=0.01; I2=59.1%); negative results were found in cohort studies, studies conducted in Europe or the USA, and studies with follow-up duration <1 year.

    Conclusions:RASIs can potentially prevent AF recurrence after ablation under selected conditions. However, more studies are required to confirm this finding due to the variation in current evidence.

Cardiovascular Intervention
  • Sida Jia, Ce Zhang, Lin Jiang, Lianjun Xu, Jian Tian, Xueyan Zhao, Xin ...
    Article type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2020 Volume 84 Issue 10 Pages 1718-1727
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: August 26, 2020
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    Supplementary material

    Background:The aim of this study is to compare the long-term prognosis of non-ST elevation acute coronary syndrome (NSTE-ACS) patients with 3-vessel disease (3VD) who underwent percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or medical therapy (MT).

    Methods and Results:Overall, 3,928 NSTE-ACS patients with 3VD were consecutively enrolled from April 2004 to February 2011 at Fu Wai Hospital. Patients were followed up for a median of 7.5 years, and were divided into PCI, CABG or MT groups according to their treatment. Compared with patients undergoing PCI, CABG patients had lower rates of myocardial infarction (MI), unplanned revascularization, major adverse cardiovascular and cerebrovascular events (MACCE) and a higher rate of stroke (all P<0.05). Compared with MT, PCI and CABG had lower incidences of all adverse outcomes (all P<0.05), except for a similar rate of stroke between PCI and MT. Kaplan-Meier analysis showed similar results. After adjusting for confounders, CABG was independently associated with a lower risk of cardiac death, revascularization and MACCE compared with PCI (all P<0.05). Compared with MT, PCI reduced long-term risk of death, whereas CABG reduced long-term risk of death, revascularization and MACCE events (all P<0.05).

    Conclusions:In NSTE-ACS patients with 3VD, CABG is independently associated with a lower risk of long-term cardiac death, revascularization and MACCE compared with PCI. Patients who received MT alone had the highest risk of long-term MACCE.

    Editor's pick

    Circulation Journal Awards for the Year 2020
    Circulation Journal Asian Award

  • Peng-fei Chen, Jun-lin Yi, Jun-yu Pei, Liang Tang, Zhen-fei Fang, Shen ...
    Article type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2020 Volume 84 Issue 10 Pages 1728-1733
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: August 26, 2020
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    Background:Patients with anterior acute myocardial infarction (AMI) and left ventricular (LV) dysfunction have an increased risk of LV thrombus (LVT). In the thrombolytic era, short-term anticoagulation using low-molecular-weight heparin during hospitalization proved to significantly reduce LVT formation, but, the effect of this prophylactic approach remains unclear in the current era. Therefore, we conducted a study to evaluate the effects of post-procedural anticoagulation (PPAC) using enoxaparin in addition to dual antiplatelet therapy (DAPT) after primary percutaneous coronary intervention (PCI) in such patients.

    Methods and Results:A total of 426 anterior AMI patients with LV ejection fraction ≤40% were retrospectively enrolled and classified into 2 groups based on whether they received PPAC (enoxaparin SC for at least 7 days). All patients received primary PCI and DAPT. The primary endpoint was definite LVT at 30 days diagnosed by echocardiography. The secondary endpoints were 30-day mortality, embolic events, and major bleeding events. PPAC was independently associated with a lower incidence of LVT (odds ratio 0.139, 95% confidence interval 0.032−0.606, P=0.009). The 30-day mortality, embolic events, and major bleeding events were not statistically different between groups.

    Conclusions:Short-term PPAC using enoxaparin after primary PCI may be an effective and safe way to prevent LVT in patients with anterior AMI and LV dysfunction.

  • Ko Yamamoto, Masahiro Natsuaki, Yusuke Yoshikawa, Takeshi Morimoto, Hi ...
    Article type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2020 Volume 84 Issue 10 Pages 1734-1745
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: September 05, 2020
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    Supplementary material

    Background:The effect of body weight (BW) on bleeding and ischemic events has not been adequately evaluated in real-world percutaneous coronary intervention (PCI) practice.

    Methods and Results:12,690 consecutive patients undergoing first PCI in the CREDO-Kyoto registry cohort-2 were divided into 3 groups according to tertiles of BW stratified by sex (male; Tertile 1 [<60.0 kg], 2 [60.0–68.0 kg], and 3 [>68.0 kg], and female; Tertile 1 [<47.9 kg], 2 [47.9–55.8 kg], and 3 [>55.8 kg]). Cumulative 5-year incidences of the primary bleeding (GUSTO moderate/severe) and ischemic (myocardial infarction/ischemic stroke) endpoints increased incrementally with decrease in BW in both strata (male Tertiles 1, 2, and 3: 13.7%, 10.3%, and 8.0%, P<0.001, and 13.9%, 11.3%, and 10.2%, P<0.001; female Tertiles 1, 2, and 3: 17.9%, 12.9%, and 10.1%, P<0.001, and 17.9%, 12.9%, and 10.1%, P<0.001). Compared with Tertile 3, the adjusted risks of Tertile 1 for the primary bleeding and ischemic endpoints remained significant in the female stratum (hazard ratio (HR): 1.45, 95% confidence interval (CI): 1.14–1.87, P=0.003, and HR:1.49, 95% CI:1.13–1.95, P=0.004), but not in the male stratum (HR:1.10, 95% CI:0.92–1.32, P=0.31, and HR:1.06, 95% CI:0.90–1.27, P=0.47).

    Conclusions:Cumulative incidences of bleeding and ischemic events increased incrementally as BW decreased in both men and women. The adjusted risks of underweight relative to overweight for bleeding and ischemic events were significant only in women.

  • Hidewo Amano, Shunsuke Kubo, Kohei Osakada, Katsuya Miura, Masanobu Oh ...
    Article type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2020 Volume 84 Issue 10 Pages 1746-1753
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: September 04, 2020
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    Background:Guide catheter-induced iatrogenic coronary artery dissection is a rare but feared complication. When it occurs, bailout stenting is widely performed; however, its prognosis and the impact of stent type remains unclear.

    Methods and Results:The study population consisted of 77,257 consecutive patients (coronary angiography, 55,864; percutaneous coronary intervention, 21,393) between 2000 and 2015. We investigated the incidence, clinical outcomes, and angiographic results after bailout stenting and compared by stent type: bare-metal stent (BMS) and drug-eluting stent (DES). Iatrogenic coronary artery dissection occurred in 105 patients (incidence rate, 0.14%). All cases of iatrogenic coronary artery dissection that were recognized as requiring bailout procedure could be managed by stent implantation, and no patients died during bailout procedure. The 5-year cumulative incidences of cardiac death, target lesion revascularization, and major adverse cardiac events were 11.3%, 10.3%, and 21.0%, respectively. The binary restenosis rate was 10.4%, and it was not significantly different between BMS and DES implantation. In lesions with preprocedural stenosis, however, it was significantly lower in the DES group than in the BMS group. On the other hand, coronary artery dissection recurred in 8 patients, which was observed only after DES implantation.

    Conclusions:The immediate and long-term outcomes of bailout stenting for iatrogenic coronary artery dissection were acceptable. Although DES may be favorable for stenotic lesions, coronary artery dissection can recur after DES implantation.

  • Sylwia Sławek-Szmyt, Aleksander Araszkiewicz, Marek Grygier, Krzysztof ...
    Article type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2020 Volume 84 Issue 10 Pages 1754-1763
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: September 05, 2020
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    Background:Cardiac implantable electronic device-related infections (CDI) are of increasing importance and involve substantial healthcare resources. This study aimed to evaluate potential CDI risk factors and the utility of the novel PADIT and PACE DRAP scores to predict CDI.

    Methods and Results:The study group included 1,000 consecutive patients undergoing implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy (CRT) surgery. Patients’ and procedural characteristics were collected. CDI occurrence was assessed during 1-year follow-up. Moreover, if periprocedural significant pocket hematoma (SPH) occurred, the maximal volume was calculated based on ultrasonographic measurements and ABC/2 formula. The overall incidence of CDI was 1.8%. In the multivariable regression analysis independent CDI risk factors were: age >75 years (odds ratio [OR]: 5.93; 95% confidence interval [CI]: 1.77–19.84), system upgrade procedure (OR: 6.46; CI: 1.94–21.44), procedure duration >1 h (OR: 13.96; CI: 4.40–44.25), presence of SPH (OR: 4.95; CI: 1.62–15.13) and reintervention within 1 month (OR: 16.29; CI: 3.14–84.50). The PACE DRAP score had higher discrimination of CDI incidence (area under curve [AUC] 0.72) as compared with the PADIT score (AUC 0.63).

    Conclusions:We identified 5 independent risk factors of CDI development. Our study also showed that the PACE DRAP score was better able to identify patients at high risk of CDI than the PADIT score.

Cardiovascular Surgery
  • Naoki Fujimura, Tomohiro Imazuru, Hitoshi Matsumura, Tsuyoshi Shibata, ...
    Article type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Surgery
    2020 Volume 84 Issue 10 Pages 1764-1770
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: August 05, 2020
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    Background:Limited data is available on the use of a polyester graft limb with a helical stent configuration deployed in the external iliac artery (EIA) during endovascular aneurysm repair (EVAR), so we prospectively analyzed the efficacy of the Zenith Spiral-Z limb deployed in the EIA.

    Methods and Results:Patients undergoing EVAR using a Zenith stent-graft and Spiral-Z limb deployed in the EIA were prospectively registered in 24 Japanese institutions from June 2017 to November 2017. In total, 65 patients (74 limbs) (mean age: 77.1±8.0 years, 87.7% men, mean abdominal aortic aneurysm (AAA) diameter: 51.9±7.2 mm, mean iliac artery aneurysm (IAA) diameter: 38.3±10.0 mm) were registered and followed up. The most common reason for deployment in the EIA was a common IAA (43 limbs, 58.1%), and 8 limbs (10.8%) had a bare nitinol stent placed at the Spiral-Z limb. A total of 61 patients (70 limbs) completed a 24-month follow-up. There were 2 Spiral-Z limb stenoses and 1 occlusion, leading to a primary patency of 95.5% and a secondary patency of 100%, at 24 months. Buttock claudication occurred in 24.3% of the limbs treated at 1 month but decreased to 4.3% at 24 months.

    Conclusions:Our multicenter prospective study showed that Spiral-Z limb deployed in the EIA was associated with satisfactory results and seems to be a durable option, even in the era of iliac branch devices.

Epidemiology
  • Hidehiro Kaneko, Hidetaka Itoh, Haruki Yotsumoto, Hiroyuki Kiriyama, T ...
    Article type: ORIGINAL ARTICLE
    Subject area: Epidemiology
    2020 Volume 84 Issue 10 Pages 1771-1778
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: September 12, 2020
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    Supplementary material

    Background:The complex clinical status of heart failure (HF) patients with concomitant cancer is gaining clinical interest. This study sought to explore the prevalence of cancer in patients with HF and its effect on outcomes using a nationwide inpatient database.

    Methods and Results:In total, 447,818 HF patients who were admitted and discharged between January 2010 and March 2018 were studied and included in the Diagnosis Procedure Combination (DPC) database. The median age was 81 years; 238,192 patients (53.2%) were men and 25,951 (5.8%) had concomitant cancer. The prevalence of cancer peaked in patients aged in their 70 s and 80 s and increased with time. Patients with cancer were older and more likely to be male. Cigarette smoking was more common in patients with cancer. Patients with cancer more frequently had infectious complications during hospitalization. Advanced medical procedures were less frequently performed for patients with cancer. In-hospital mortality was higher in patients with cancer than those without (10.0% vs. 6.7%, P<0.001). Among patients with cancer, in-hospital mortality was higher in patients with metastasis than those without (18.9% vs. 9.4%, P<0.001). Multivariable logistic regression analysis, fitted with a generalized estimating equation, indicated cancer is associated with higher in-hospital mortality (odds ratio 1.51, 95% confidential interval 1.43–1.59, P<0.001).

    Conclusions:Cancer was frequently observed in patients hospitalized for worsened HF, and its prevalence increased with time. The presence of cancer increased the risk of in-hospital death. Further studies are warranted to establish the optimal management strategy for HF patients with cancer in the field of cardio-oncology.

  • Lenka Eremiasova, Jaroslav A Hubacek, Vilém Danzig, Věra Adamkova, Len ...
    Article type: ORIGINAL ARTICLE
    Subject area: Epidemiology
    2020 Volume 84 Issue 10 Pages 1779-1785
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: August 26, 2020
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    Background:The potential antiatherogenic role of bilirubin is generally acknowledged, so the aim of this study was to determine serum bilirubin concentrations and the prevalence of Gilbert syndrome (GS) in the Czech general population with particular reference to its relationship to the risk of myocardial infarction (MI).

    Methods and Results:Biochemical markers were analyzed in 2 independent Czech post-MONICA studies (in total, n=3,311), and in 741 male MI patients. TheUGT1A1promoter gene variant (rs81753472) was analyzed in these MI patients and in the first control population cohort (n=717). Medians of serum bilirubin concentrations in the 2 Czech general population cohorts were 9.6 and 9.8 μmol/L (10.7 and 11.3 μmol/L in males, and 8.3 and 8.8 μmol/L in females; P<0.01). The prevalence of GS was 8.9%, twice as high in males compared with females (11.6 vs. 6.1%; P<0.01). TheUGT1A1(TA)7/7promoter repeats significantly influenced serum bilirubin concentrations in the controls, but not in the MI patients. Serum bilirubin concentrations were significantly lower in MI patients (7.7 vs. 10.7 μmol/L; P<0.01), with almost 5-fold lower prevalence of GS.

    Conclusions:Serum bilirubin concentrations and the prevalence of GS were determined in the Czech general population. Significantly lower serum bilirubin concentrations were observed in male MI patients.

  • Yoshiko Watanabe, Tetsuro Miyata, Kunihiro Shigematsu, Kazuo Tanemoto, ...
    Article type: ORIGINAL ARTICLE
    Subject area: Epidemiology
    2020 Volume 84 Issue 10 Pages 1786-1796
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: September 01, 2020
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    Background:The epidemiology and clinical features of thromboangiitis obliterans (TAO) in Japan have not been updated extensively.

    Methods and Results:This retrospective study used the Japanese Ministry of Health, Labour and Welfare (JMHLW) medical support system database and associated health insurance data. The number of medical financial support recipients registered as TAO patients and estimated prevalence of TAO decreased from fiscal year (FY) 2000 (10,089 and 7.95 [95% confidence interval, CI: 7.79–8.10] per 100,000 population) to FY 2010 (7,147 and 5.58 [95% Cl: 5.45–5.71] per 100,000) and leveled off until 2014. The prevalence of TAO among patients with peripheral arterial occlusive diseases declined from 7.15% (95% Cl: 7.00–7.31) in FY 2008 to 6.12% (95% Cl: 5.98–6.26) in FY 2014. Clinicodemographic features were obtained from 89 new recipients in FY 2013 and 2014: 12 (13%) women, 36 (40%) aged ≥50 years, 26 (29%) had probable onset age ≥50 years, 7 (8%) were non-smokers, and 12 (13%) had arteriosclerosis-related comorbidities. The symptoms were similar regardless of registration age, smoking history, or sex. Although 40 (45%) had digit ulcers, only 12 (13%) fulfilled Shionoya’s criteria. They rarely had infrapopliteal lesions combined with upper extremity involvement or phlebitis.

    Conclusions:The prevalence of TAO has decreased in Japan. In the current diagnosis of TAO, various clinical characteristics including late onset, arteriosclerotic factors, non-smoking, or mild symptoms should be considered.

Heart Failure
  • Yu Wang, Meng-Xi Yang, Qiang Tu, Li-Yuan Tao, Gang Liu, Hui An, Hu Zha ...
    Article type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2020 Volume 84 Issue 10 Pages 1797-1806
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: September 04, 2020
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    Supplementary material

    Background:Whether ischemic stroke per se, rather than older age or additional comorbidities, accounts for the adverse prognosis of heart failure (HF) is uncertain. The present study examineed the intrinsic association of ischemic stroke with outcomes in a propensity-matched cohort.

    Methods and Results:Of 1,351 patients hospitalized with HF, 388 (28.7%) had prior ischemic stroke. Using propensity score for prior ischemic stroke, estimated for each patient, a matched cohort of 379 pairs of HF patients with and without prior ischemic stroke, balanced on 32 baseline characteristics was assembled. At 30 days, prior ischemic stroke was associated with significantly higher risks of the combined endpoint of all-cause death or readmission (hazard ratio [HR]: 1.91; 95% confidence interval [CI]: 1.38 to 2.65; P<0.001), all-cause death (HR: 2.08; 95% CI: 1.28 to 3.38; P=0.003), all-cause readmission (HR: 2.67; 95% CI: 1.78 to 4.01; P<0.001), and HF readmission (HR: 2.11; 95% CI: 1.19 to 3.72; P=0.010). Prior ischemic stroke was associated with a significantly higher risk of all 4 outcomes at both 6 months and 1 year.

    Conclusions:Prior ischemic stroke was a potent and persistent risk predictor of death and readmission among patients with HF after accounting for clinical characteristics.

  • Hiroyuki Kayano, Shinji Koba, Tsutomu Hirano, Taiju Matsui, Hiroto Fuk ...
    Article type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2020 Volume 84 Issue 10 Pages 1807-1817
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: September 12, 2020
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    Supplementary material

    Background:This prospective randomized multicenter open-label trial evaluated whether sodium-glucose cotransporter-2 inhibitor (SGLT2-i) improves left ventricular (LV) pump function and suppresses elevation of LV filling pressure (LVFP) and right ventricular systolic pressure (RVSP) during exercise in type 2 diabetes mellitus (T2DM) patients.

    Methods and Results:Based on HbA1c and LV ejection fraction, 78 patients with poorly controlled T2DM were randomly assigned to D-group (dapagliflozin 5 mg/day add-on) or C-group (conventional therapy add-on). Physical examination, home and office blood pressure examination, blood tests, and echocardiography at rest and during ergometer exercise were performed at baseline and at 1.5 and 6 months after treatment. The primary endpoint was defined as the change in RVSP (mmHg) between baseline and 6-month follow up. The secondary endpoints were changes in LVFP (ratio), stroke volume index (SVi; mL/m2), and cardiac index (CI; L/min/m2). Both RVSP and LVFP during exercise significantly decreased from baseline to 6 months after starting treatment in the D-group (P<0.001). No changes to either parameter was observed in the C-group. The SVi and CI did not improve in either group. Both home and office blood pressure significantly decreased in the D-group. Decreases in HbA1c were somewhat greater in the C-group.

    Conclusions:Dapagliflozin significantly improved RVSP and LVFP during exercise in patients with T2DM and cardiovascular risk, which may contribute to favorable effects on heart failure.

Imaging
  • Yasuyuki Suzuki, Naoya Matsumoto, Ayano Makita, Tadashi Ashida, Keiich ...
    Article type: ORIGINAL ARTICLE
    Subject area: Imaging
    2020 Volume 84 Issue 10 Pages 1818-1825
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: September 05, 2020
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    Background:Sequential assessment using CT coronary angiography (coronary CT) and nuclear myocardial perfusion imaging (MPI) is considered an anatomical and functional evaluation of coronary artery disease (CAD). However, there can be unexpected radiation exposure. Hybrid MPI with stress-only nuclear MPI and rest CT-MPI using coronary CT may contribute to reducing the radiation dose in sequential assessment with nuclear MPI after coronary CT. We analyzed the diagnostic performance and total radiation dose of hybrid MPI for detection of significant CAD compared with sequential assessment using nuclear MPI after coronary CT.

    Methods and Results:The results for 101 patients who underwent coronary CT, nuclear MPI and invasive coronary angiography within 3 months of all imaging were analyzed. We calculated the summed difference score (SDS) from standard nuclear MPI and hybrid SDS from hybrid MPI, which revealed myocardial ischemia. The diagnostic performance of SDS and hybrid SDS for detecting significant CAD was analyzed using receiver-operating characteristic (ROC) curve analysis. We also compared the total radiation dose of both methods. The area under the ROC curve was not different between SDS and hybrid SDS (0.901 and 0.815, P=0.079). Total radiation dose of hybrid MPI was significantly lower than standard nuclear MPI with CT angiography (4.62 mSv vs. 9.72 mSv, P<0.0001).

    Conclusions:Hybrid MPI showed a precise diagnostic accuracy for significant CAD detection.

  • Yoichiro Sugizaki, Hiromasa Otake, Koji Kuroda, Hiroyuki Kawamori, Tak ...
    Article type: ORIGINAL ARTICLE
    Subject area: Imaging
    2020 Volume 84 Issue 10 Pages 1826-1836
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: August 05, 2020
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    Supplementary material

    Background:In-stent neoatherosclerosis (NA) is a risk for future cardiovascular events through atherosclerotic progression in non-stented lesions. Using optical coherence tomography, this study assessed the efficacy of intensive therapy with 10 mg/day rosuvastatin plus 1,800 mg/day eicosapentaenoic acid (EPA) vs. standard 2.5 mg/day rosuvastatin therapy on native coronary plaques in patients with NA.

    Methods and Results:This was a subgroup analysis of the randomized LINK-IT trial, which was designed to compare changes in the lipid index in NA between intensive and standard therapy for 12 months. In all, 42 patients with native coronary plaques and NA were assessed. Compared with standard therapy, intensive therapy resulted in greater decreases in serum low-density lipoprotein cholesterol concentrations and greater increases in serum 18-hydroxyeicosapentaenoic acid concentrations, with significantly greater decreases in the lipid index and macrophage grade in both NA (−24 vs. 217 [P<0.001] and −15 vs. 24 [P<0.001], respectively) and native coronary plaques (−112 vs. 29 [P<0.001] and −17 vs. 1 [P<0.001], respectively) following intensive therapy. Although there was a greater increase in the macrophage grade in NA than in native coronary plaques in the standard therapy group, in the intensive therapy group there were comparable reductions in macrophage grade between NA and native coronary plaques.

    Conclusions:Compared with standard therapy, intensive therapy prevented atherosclerotic progression more effectively in native coronary plaques in patients with NA.

Ischemic Heart Disease
  • Masashi Yokoi, Tsuyoshi Ito, Hiroshi Fujita, Tomonori Sugiura, Yoshihi ...
    Article type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2020 Volume 84 Issue 10 Pages 1837-1845
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: August 28, 2020
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    Background:Cardiac events can occur after drug-eluting stent (DES) implantation due to coronary plaque progression at non-stented sites. Malondialdehyde-modified low-density lipoprotein (MDA-LDL) is suggested to be an atherogenic marker. This study investigated the relationship between serum MDA-LDL and angiographic progression after DES implantation.

    Methods and Results:In total, 207 patients who underwent percutaneous coronary intervention (PCI) using DES and follow-up coronary angiography were retrospectively analyzed. MDA-LDL was serially measured before PCI and at follow up. Persistent high MDA-LDL was defined as a MDA-LDL level more than the median value both before PCI and at follow up. Angiographic progression was assessed by serial analysis of quantitative coronary angiography. Angiographic progression occurred in 35 patients (16.9%). MDA-LDL before PCI was significantly higher in the progression group than the non-progression group in all patients (143.4±35.8 U/L vs. 103.0±33.5U/L, P<0.001) and in patients with controlled LDL-cholesterol (LDL-C <100 mg/dL both before PCI and at follow up; 121.8±32.7 U/L vs. 84.9±24.9 U/L, P<0.001). There were positive correlations between % diameter stenosis changes and serum MDA-LDL before PCI in all patients (r=0.33, P<0.01) and those with controlled LDL-C (r=0.23, P=0.04). In multivariate logistic regression analysis, persistent high MDA-LDL was an independent predictor of plaque progression.

    Conclusions:Increased serum MDA-LDL was associated with angiographic progression after DES implantation.

Myocardial Disease
  • Yasuteru Nakashima, Toru Kubo, Kenta Sugiura, Yuri Ochi, Asa Takahashi ...
    Article type: ORIGINAL ARTICLE
    Subject area: Myocardial Disease
    2020 Volume 84 Issue 10 Pages 1846-1853
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: August 22, 2020
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    Supplementary material

    Background:Hypertrophic cardiomyopathy (HCM) is mainly caused by mutations in sarcomere genes. Regarding the clinical implications of genetic information, little is known about the lifelong clinical effect of sarcomere mutations in Japanese HCM patients.

    Methods and Results:We studied 211 consecutive Japanese patients with HCM who had agreed to genetic testing between 2003 and 2013. Genetic analyses were performed by direct DNA sequencing in the 6 common sarcomere genes (MYH7,MYBPC3,TNNT2,TNNI3,TPM1,ACTC). Through variant filtering, 21 mutations were identified in 67 patients. After excluding 8 patients whose variants were determined as having uncertain significance, finally 203 patients (130 men, age at study entry: 61.8±14.1 years) were investigated for clinical presentation and course. At the time of study entry, patients with mutations were younger, had more frequent non-sustained ventricular tachycardia, had greater interventricular wall thickness, were more frequently in the dilated phase and less frequently had apical HCM. Through their lifetimes, a total of 98 HCM-related morbid events occurred in 72 patients. Survival analysis revealed that patients with sarcomere gene mutations experienced those morbid events significantly more frequently, and this tendency was more prominent for lethal arrhythmic events.

    Conclusions:In our HCM cohort, patients with sarcomere gene mutations had poorer lifelong outcome. Genetic information is considered important for better management of HCM.

Peripheral Vascular Disease
  • Kojiro Miki, Takamasa Tanaka, Koji Yanaka, Nagataka Yoshihara, Toshio ...
    Article type: ORIGINAL ARTICLE
    Subject area: Peripheral Vascular Disease
    2020 Volume 84 Issue 10 Pages 1854-1861
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: August 08, 2020
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    Background:Although self-expanding drug-eluting stents (DES) have recently shown superior outcomes for superficial femoral artery (SFA) lesions, optimal sizing of DES diameter in SFA intervention is unclear.

    Methods and Results:A total of 40 de novo SFA lesions were randomized 1:1 to receive self-expanding DES with either a 1-mm or 2-mm larger diameter than the reference vessel diameter. Follow-up optical coherence tomography (OCT) was scheduled 6 months after DES implantation to evaluate the vascular response to the stents. Volume index (VI) was defined as volume divided by stent length. The primary endpoint was neointimal VI at 6 months. Baseline reference vessel diameter was similar between the 1-mm larger diameter group and the 2-mm larger diameter group (5.0±0.8 mm vs. 4.7±0.9 mm, P=0.35). Stent diameter was 6.3±0.6 mm in the 1-mm larger group and 7.1±0.6 mm in the 2-mm larger group (P<0.0001), and stent to reference vessel diameter ratio (SV ratio) was 1.3±0.2 and 1.5±0.2 (P<0.0001), respectively. At 6-month, neointimal VI was greater in the 2-mm larger diameter group (5.5±1.5 mm2vs. 9.6±3.4 mm2, P<0.001). The correlation analysis revealed that degree of neointimal VI was positively correlated with SV ratio (r=0.43, P<0.01).

    Conclusions:Implantation of self-expanding DES with a considerably high SV ratio resulted in neointimal hyperplasia in SFA lesions.

  • Shunichiro Fujioka, Hirotoki Ohkubo, Tadashi Kitamura, Toshiaki Mishim ...
    Article type: ORIGINAL ARTICLE
    Subject area: Peripheral Vascular Disease
    2020 Volume 84 Issue 10 Pages 1862-1865
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: August 20, 2020
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    Background:There is insufficient evidence regarding the optimal treatment method for distal deep vein thrombosis (DVT), including indications for anticoagulation therapy. Treatment results of patients with distal DVT were evaluated to clarify the risk factors that result in extension of distal DVT to the proximal vein and indications for anticoagulation therapy.

    Methods and Results:Among 430 patients with DVT between January 2018 and December 2019, 253 were diagnosed with distal DVT; 41 patients who had already started anticoagulation therapy were excluded, and the remaining 212 were included as study subjects. Anticoagulation therapy was not started immediately; conservative treatment with compression stockings was performed. Ultrasonography after 2 weeks revealed thrombus disappearance in 39 patients (21%), and thrombus reduction in 38 patients (20%). In contrast, extension of thrombus to the proximal vein was noted in 12 patients (6.3%) and anticoagulation therapy was commenced. After 3 months, the thrombus had disappeared in 75 patients (52%). No patient developed pulmonary thromboembolism during follow-up. With respect to the risk factors for extension to proximal vein during conservative treatment, active cancer (P=0.03), prolonged bed rest (P<0.01), and D-dimer level >8µg/mL (P=0.01) were identified.

    Conclusions:It is reasonable to consider anticoagulation therapy in distal DVT patients with active cancer, prolonged bed rest or high D-dimer level.

Pulmonary Circulation
  • Nobuhiro Tanabe, Keiichi Fukuda, Hiromi Matsubara, Norifumi Nakanishi, ...
    Article type: ORIGINAL ARTICLE
    Subject area: Pulmonary Circulation
    2020 Volume 84 Issue 10 Pages 1866-1874
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: September 03, 2020
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    Background:Selexipag is an oral prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. This study examined its efficacy and safety in Japanese patients with non-operated or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH).

    Methods and Results:This Phase II study was a randomized, double-blind, placebo-controlled parallel-group comparison. The primary endpoint was a change in pulmonary vascular resistance (PVR) from baseline to week 17. The main analysis involved a per-protocol set group of 28 subjects. The change in PVR (mean±SD) after 17 weeks of treatment in the selexipag group was −104±191 dyn·s/cm5, whereas that in the placebo group was 26±180 dyn·s/cm5. Thus, the treatment effect after 17 weeks of selexipag treatment was calculated as −130±189 dyn·s/cm5(P=0.1553). Although the primary endpoint was not met, for the group not concomitantly using a pulmonary vasodilator the PVR in the selexipag group was significantly decreased compared with placebo group (P=0.0364). The selexipag group also showed improvement in total pulmonary resistance and cardiac index.

    Conclusions:Selexipag treatment improved pulmonary hemodynamics in Japanese patients with CTEPH, but PVR did not show a significant difference between the selexipag and placebo groups. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-111667])

Valvular Heart Disease
  • Kensuke Matsushita, Mohamad Kanso, Mickael Ohana, Benjamin Marchandot, ...
    Article type: ORIGINAL ARTICLE
    Subject area: Valvular Heart Disease
    2020 Volume 84 Issue 10 Pages 1875-1883
    Published: September 25, 2020
    Released on J-STAGE: September 25, 2020
    Advance online publication: September 01, 2020
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    Supplementary material

    Background:New-onset conduction abnormalities (CAs) following transcatheter aortic valve replacement (TAVR) are associated with hospital rehospitalization and long-term mortality, but available predictors are sparse. This study sought to determine clinical predictors of new-onset left bundle branch block (LBBB) and new permanent pacemaker (PPM) implantation in patients undergoing TAVR.

    Methods and Results:We enrolled 290 patients who received SAPIEN 3 (Edwards Lifesciences, Irvine, CA, USA; n=217) or Evolut R (Medtronic, Minneapolis, MN, USA; n=73) from a prospective registry at Nouvel Hôpital Civil, Strasbourg, France between September 2014 and February 2018. Of 242 patients without pre-existing LBBB, 114 (47%) experienced new-onset LBBB and/or new PPM implantation. A difference between membranous septal length and implantation depth (∆MSID) was the only predictor of CAs for both types of valves. In the multivariate analysis, PR interval and ∆MSID remained as sole predictors of CAs. The risk for adverse clinical events, including all-cause death, myocardial infarction, stroke, and heart failure hospitalization, was higher for patients with CAs as compared with patients without CAs (hazard ratio: 2.10; 95% confidence interval: 1.26 to 3.57; P=0.004).

    Conclusions:Computed tomography assessment of membranous septal anatomy and implantation depth predicted CAs after TAVR with new-generation valves. Future studies are required to identify whether adjustment of the implantation depth can reduce the risk of CAs and adverse clinical outcomes.

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