Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 83 , Issue 3
Showing 1-34 articles out of 34 articles from the selected issue
Message From the Editor-in-Chief
Reviews
  • Sang-Hyun Ihm, George Bakris, Ichiro Sakuma, Il Suk Sohn, Kwang Kon Ko ...
    Type: REVIEW
    2019 Volume 83 Issue 3 Pages 504-510
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: December 29, 2018
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    Until the 2017 ACC/AHA Hypertension Guidelines were released, the target blood pressure (BP) for adults with hypertension (HTN) was 140/90 mmHg in most of the guidelines. The new 2018 ESC/ESH, Canadian, Korean, Japan, and Latin American hypertension guidelines have maintained the <140/90 mmHg for the primary target in the general population and encourage reduction to <130/80 if higher risk. This is more in keeping with the 2018 American Diabetes Association guidelines. However, the 2017 ACC/AHA guidelines classify HTN as BP ≥130/80 mmHg and generally recommend target BP levels below 130/80 mmHg for hypertensive patients independently of comorbid disease or age. Although the new guidelines mean that more people (nearly 50% of adults) will be diagnosed with HTN, the cornerstone of therapy is still lifestyle management unless BP cannot be lowered to this level; thus, more people will require BP-lowering medications. To date, there have been many controversies about the definition of HTN and the target BP. Targeting an intensive systolic BP goal can increase the adverse effects of multiple medications and the cardiovascular disease risk by excessively lowering diastolic BP, especially in patients with high risk, including those with diabetes, chronic kidney disease, heart failure, and coronary artery disease, and the elderly. In this review, we discuss these issues, particularly regarding the optimal target BP.

Editorials
Original Articles
Aortic Disease
  • Shi-Lin Tang, Zhen-Wang Zhao, Shang-Ming Liu, Gang Wang, Xiao-Hua Yu, ...
    Type: ORIGINAL ARTICLE
    Subject area: Aortic Disease
    2019 Volume 83 Issue 3 Pages 515-523
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: January 18, 2019
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    Supplementary material

    Background: Recent studies have suggested that pregnancy-associated plasma protein-A (PAPP-A) is involved in the pathogenesis of atherosclerosis. This study aim is to investigate the role and mechanisms of PAPP-A in reverse cholesterol transport (RCT) and inflammation during the development of atherosclerosis.

    Methods and Results: PAPP-A was silenced in apolipoprotein E (apoE−/−) mice with administration of PAPP-A shRNA. Oil Red O staining of the whole aorta root revealed that PAPP-A knockdown reduced lipid accumulation in aortas. Oil Red O, hematoxylin and eosin (HE) and Masson staining of aortic sinus further showed that PAPP-A knockdown alleviated the formation of atherosclerotic lesions. It was found that PAPP-A knockdown reduced the insulin-like growth factor 1 (IGF-1) levels and repressed the PI3K/Akt pathway in both aorta and peritoneal macrophages. The expression levels of LXRα, ABCA1, ABCG1, and SR-B1 were increased in the aorta and peritoneal macrophages from apoE−/−mice administered with PAPP-A shRNA. Furthermore, PAPP-A knockdown promoted RCT from macrophages to plasma, the liver, and feces in apoE−/−mice. In addition, PAPP-A knockdown elevated the expression and secretion of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), tumor necrosis factor-α, and interleukin-1β through the nuclear factor kappa-B (NF-κB) pathway.

    Conclusions: The present study results suggest that PAPP-A promotes the development of atherosclerosis in apoE−/−mice through reducing RCT capacity and activating an inflammatory response.

Arrhythmia/Electrophysiology
  • Eitaro Kodani, Tomohiro Kaneko, Hitomi Fujii, Hiroyuki Nakamura, Hajim ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2019 Volume 83 Issue 3 Pages 524-531
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: January 11, 2019
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    Supplementary material

    Background: Although National Health Insurance special health checkups have been useful for the diagnosis of metabolic syndrome, they are insufficient to identify atrial fibrillation (AF). In Tama City in Tokyo, 12-lead electrocardiogram has been included as an essential examination in special health checkups to diagnose AF since 2008.

    Methods and Results: In subjects aged 40–74 years at entry, prevalence of AF was 0.8% (men, 1.7%; women, 0.2%) in 2008 and 1.4% (men, 2.9%; women, 0.4%) in 2015. Of 10,430 subjects without AF in 2008 (mean age, 64.9±7.1 years; men, 40.4%), AF developed in 133 between 2008 and 2015. The incidence rate of new-onset AF was 2.5/1,000 person-years during an observation period of 52,707 person-years. On multivariate Cox regression analysis in subjects without a history of cardiac disease, hypertension (HR, 1.58; 95% CI: 1.01–2.47, P=0.045) and body mass index (BMI; /1-kg/m2increase; HR, 1.07; 95% CI: 1.00–1.12, P=0.049) were significant risk factors for new-onset AF in addition to age and male sex.

    Conclusions: Prevalence of AF increased between 2008 and 2015. Age, male sex, hypertension, and BMI were significant predictors for future incidence of AF in the general population without overt cardiac disease. Controlling hypertension and BMI may prevent new-onset AF in the general population.

  • Tomomi Nagayama, Satoshi Nagase, Tsukasa Kamakura, Mitsuru Wada, Kohei ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2019 Volume 83 Issue 3 Pages 532-539
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: January 12, 2019
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    Background: Spontaneous type 1 electrocardiogram (ECG) in the right precordial lead is a dominant predictor of ventricular fibrillation (VF) in Brugada syndrome (BrS). In some BrS patients with VF, however, spontaneous type 1 ECG is undetectable, even in repeated ECG and immediately after VF. This study investigated differences between BrS patients with spontaneous or drug-induced type 1 ECG.

    Methods and Results: We evaluated 15 BrS patients with drug-induced (D-BrS) and 29 with spontaneous type 1 ECG (SP-BrS). All patients had had a previous VF episode. In each D-BrS patient, ECG was recorded more than 15 times (mean, 46±34) during 7.2±5.1 years of follow-up. Age and family history were comparable between groups. Inferolateral early repolarization (ER) was observed in 13 D-BrS (87%) at least once but in only 3 SP-BrS (10%, P<0.01). Immediately after VF, inferolateral ER was accentuated in 9 of 10 D-BrS, while type 1 ECG was accentuated in 12 of 16 SP-BrS. Fragmented QRS in the right precordial lead and aVR sign were absent in D-BrS but present in 20 (69%, P<0.01) and 11 (38%, P<0.01) SP-BrS, respectively. There was no prognostic difference between groups.

    Conclusions: Although having similar clinical profiles, there are obvious ECG differences between VF-positive BrS patients with spontaneous or drug-induced type 1 ECG. The inferolateral lead rather than the right precordial lead on ECG may be particularly crucial in some BrS patients.

  • Paula Tiili, Jukka Putaala, Juha Mehtälä, Houssem Khanfir, Jussi Niira ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2019 Volume 83 Issue 3 Pages 540-547
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: January 25, 2019
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    Supplementary material

    Background: Intracranial hemorrhage (ICH) is a devastating complication of oral anticoagulation. The aim of this study was to describe the spectrum of ICH and to evaluate the association of warfarin control with the risk of ICH in a nationwide cohort of unselected atrial fibrillation (AF) patients.

    Methods and Results: The FinWAF is a retrospective registry-linkage study. Data were collected from several nationwide Finnish health-care registers and laboratory databases. The primary outcome was any ICH (traumatic or non-traumatic). The quality of warfarin therapy was assessed continuously by calculating the time in therapeutic range in a 60-day window (TTR60). Adjusted Cox proportional hazard models were used. A total of 53,953 patients were included (53% men; mean age, 73 years; mean follow-up, 2.94 years; mean TTR, 63%). In 129,684 patient-years, 1,196 patients had ICH (non-traumatic, 53.5%; traumatic, 43.6%; traumatic subdural, 38.6%); crude annual rate, 0.92%; 95% CI: 0.87–0.98). A lower TTR60 was significantly associated with higher risk of ICH (TTR60 ≤40% vs. TTR60 >80%; adjusted hazard ratio, 2.16; 95% CI: 1.83–2.54). Other variables independently associated with ICH included age >65 years, previous stroke, male sex, low hemoglobin, thrombocytopenia, elevated alanine aminotransferase, and previous bleeding other than ICH.

    Conclusions: Poor control of warfarin treatment was associated with elevated risk of ICH. Approximately half of the ICH were traumatic, mainly subdural.

  • Nobuaki Tanaka, Koji Tanaka, Yuichi Ninomiya, Yuko Hirao, Takafumi Oka ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2019 Volume 83 Issue 3 Pages 548-555
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: February 06, 2019
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    Background: Automated ablation lesion annotation with optimal settings for parameters including contact force (CF) and catheter stability may be effective for achieving durable pulmonary vein isolation.

    Methods and Results: We retrospectively examined 131 consecutive patients who underwent initial catheter ablation (CA) for paroxysmal atrial fibrillation (PAF) by automatic annotation system (VISITAG module)-guided radiofrequency CA (RFCA) (n=61) and 2nd-generation cryoballoon ablation (CBA) (n=70) in terms of safety and long-term efficacy. The automatic annotation criteria for the RFCA group were as follows: catheter stability range of motion ≤1.5 mm, duration ≥5 s, and CF ≥5 g. We ablated for >20 s with a force-time integral >150 gs at each site, before moving to the next site. Each interlesion distance was <6 mm. Procedural complications were more frequent in the CBA group (1.6% vs. 10.0%, P=0.034). Across a median follow-up of 2.98 years, 88.5% and 70.0% of patients in the RFCA and CBA groups, respectively, were free from recurrence (log-rank test, P=0.0039). There was also a significant difference in favor of RFCA with respect to repeat ablations (3.3% vs. 24.3%, log-rank test, P=0.0003).

    Conclusions: RF ablation guided by an automated algorithm that includes CF and catheter stability parameters showed better long-term outcomes than CBA in the treatment of patients with PAF without increasing complications.

Cardiovascular Intervention
  • Taku Asano, Jarkko Hytönen, Ply Chichareon, Jouni Taavitsainen, Norihi ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2019 Volume 83 Issue 3 Pages 556-566
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: January 31, 2019
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    Supplementary material

    Background: Little is known about serial changes in lumen and device dimensions after bioresorbable scaffold implantation in a growing animal model.

    Methods and Results: ABSORB (n=14) or bare metal stents (ICROS amg [Abbott Vascular, Santa Clara, CA, USA], Winsen-Luhe, Germany; n=15) were implanted in the coronary arteries of domestic swine (a hybrid of Finnish-Norwegian Landrace swine) weighing 30–35 kg. Angiography and optical coherence tomography (OCT) were performed immediately after implantation and repeated at 7 days, 1, 3, 6 and 12 months after the index procedure. One month after implantation, mean lumen area decreased relative to baseline in both groups (relative area change from baseline, −41.4±15.6% for ABSORB vs. −20.9±18.6% for ICROS) while mean device area decreased only in the ABSORB group (relative area change: −11.1±9.4% vs. +0.14±7.95%, respectively). At 12 months, mean lumen area increased relative to baseline in both groups (relative area change from baseline, +55.6±22.4% vs. +32.3±83.6%, respectively) in accordance with the swine growth weighing up to 260–300 kg. Mean device area in the ICROS group remained stable whereas that in the ABSORB group began to increase between 3 and 6 months along with the vessel growth (relative area change: +107.8±25.7% vs. +0.14±7.95%).

    Conclusions: In the growing porcine model, ABSORB was associated with greater extent of recoil 1 month after implantation compared with ICROS but demonstrated substantial adaptability to vessel growth in late phase.

Cardiovascular Surgery
  • Naoko Ikeda, Hiroki Yamaguchi, Masami Takagaki, Shinichi Mitsuyama, Mi ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Surgery
    2019 Volume 83 Issue 3 Pages 567-575
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: February 09, 2019
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    Background: The ideal surgical technique for ischemic mitral regurgitation (MR) is controversial. We introduced an extended posterior mitral leaflet (PML) augmentation technique for functional MR with severe tethering, which detached the PML from the annulus almost completely and augmented it with a large 3×6-cm oval pericardial patch.

    Methods and Results: A total of 17 mitral repairs using the new technique were performed for ischemic MR with no 30-day mortality and 2 hospital deaths. The NYHA class was III in 47% and IV in 13%. The EuroSCORE II was 9.7±4.9. The ring size was 32±1.4 mm. Concomitant coronary bypass was performed in 67% and left ventricular repair in 28%. The mechanism of leaflet closure was evaluated using transthoracic echocardiography in 15 survivors. MR decreased to none or trivial with a significant increase in coaptation length (Pre: 4.6±0.8 mm vs. Post: 9.8±2.5 mm; P<0.001). The PML flexibly moved forward and tightly contacted as if “snuggling up” to the anterior leaflet. There were no late deaths, heart failure readmissions or MR recurrences during follow-up (850±181 days). All patients remained in NYHA I or II.

    Conclusions: Extended PML augmentation for ischemic MR showed excellent early results with deep leaflet coaptation through a “snuggling up” phenomenon, which would help prevent late MR recurrence.

Heart Failure
  • Satoshi Yamaguchi, Masami Abe, Tomohiro Arakaki, Osamu Arasaki, Michio ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2019 Volume 83 Issue 3 Pages 576-583
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: December 29, 2018
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    Supplementary material

    Background: Acute heart failure (AHF) triggers platelet aggregation and platelet markers are associated with the severity of AHF. The present study aimed to investigate the prognostic value of platelet count (PLT) in patients with AHF.

    Methods and Results: This single-center retrospective observational study analyzed 425 consecutive patients with AHF. The patients were divided into groups based on tertiles of PLT: low (PLT1 <170,000/μL), intermediate (170,000/μL≤PLT<230,000/μL), and high (PLT3 ≥230,000/μL). The endpoint was all-cause death with a composite endpoint of all-cause death and HF rehospitalization. Survival analysis was performed, and Cox proportional hazard models adjusted by an established risk score (Get With The Guidelines score) were generated. The PLT1 group had the worst survival for all-cause death (log-rank, P=0.003) and the composite endpoint (P=0.009). A significant trend of increasing survival was observed for all-cause death (log-rank trend, P<0.001) and the composite endpoint (P=0.002) in the following order: PLT1, PLT2, and PLT3. Adjusted Cox proportional hazard models demonstrated that low PLT was a risk factor of all-cause death and the composite endpoint.

    Conclusions: Low PLT was associated with risk for all-cause death and HF rehospitalization in patients with AHF.

  • Masayoshi Yamamoto, Yoshihiro Seo, Tomoko Ishizu, Isao Nishi, Yoshie H ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2019 Volume 83 Issue 3 Pages 584-594
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: January 23, 2019
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    Supplementary material

    Background: Left ventricular ejection fraction (LVEF) can dramatically change when the patient has acute decompensated heart failure (ADHF). We investigated the impact of LVEF and subsequent changes on prognosis in patients with ADHF through a prospective study.

    Methods and Results: A total of 516 hospitalized patients with ADHF were evaluated. Echocardiography was performed on admission, prior to discharge, and 1 year after discharge. The primary endpoint was a composite of cardiovascular death and hospitalization. In heart failure with reduced EF (HFrEF; LVEF <40%), LVEF did not significantly improve during hospitalization (P=0.348); however, it improved after discharge (P<0.001). In contrast, LVEF improved during hospitalization (P<0.001) in HF with preserved EF (HFpEF; LVEF ≥50%). In HF with mid-range EF (HFmrEF; LVEF 40–49%), LVEF consistently improved throughout the observation period (P<0.001). A multivariable Cox model showed that improved LVEF after discharge was associated with a better outcome in HFrEF (hazard ratio [HR]: 0.951; 95% confidence interval [CI]: 0.928–0.974; P<0.001), while improved LVEF during hospitalization was associated with a better outcome in HFpEF (HR: 0.969; 95% CI: 0.940–0.998; P=0.038).

    Conclusions: Improved LVEF after discharge in HFrEF and during hospitalization in HFpEF was associated with a better prognosis in patients with ADHF. Longitudinal improvements in LVEF had different prognostic impact, depending on the HF type by LVEF measurement.

  • Mohamed Rady, Stefan Ulbrich, Felix Heidrich, Stefanie Jellinghaus, Ka ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2019 Volume 83 Issue 3 Pages 595-603
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: January 20, 2019
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    Supplementary material

    Background: Left ventricular (LV) torsion is a key parameter in cardiac function and predicts functional capacity (FC) more appropriately than LV ejection fraction (EF). We sought to investigate LV torsion as a marker of hospitalization for worsening heart failure (HF) in non-ischemic dilated cardiomyopathy (DCM) patients.

    Methods and Results: The 91 outpatients with newly diagnosed DCM (53±13 years, 20% female) were evaluated with 3D speckle-tracking imaging and followed up for 12 months; 43 healthy sex- and age-matched volunteers served as controls. LV torsion, LVEF, right ventricular function, LV global longitudinal (GLS) and circumferential (GCS) strain values, peak oxygen uptake (peak V̇O2) from FC and B-type natriuretic peptide levels were measured at baseline. Peak V̇O2correlated successively with LV torsion, diastolic filling and GCS (r=0.70, −0.52 and −0.41, P<0.01) disclosing the central role of LV torsion. During follow-up (median 272 days), 24 (26%) cardiac events occurred. A reduced LV torsion (<0.59 degrees/cm) predicted cardiac events similar to a reduced peak V̇O2(<19 mL/kg/min) (unadjusted hazard ratio 6.41 and 5.90, P<0.001). LV torsion provided a significant incremental value over right ventricular function and peak V̇O2(C-index: 0.85, P=0.02).

    Conclusions: The results demonstrated a clear relation between LV torsion and disease severity, suggesting that LV torsion has additional prognostic relevance in DCM patients.

  • Yuta Seko, Takao Kato, Yusuke Morita, Yuhei Yamaji, Yoshizumi Haruna, ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2019 Volume 83 Issue 3 Pages 604-613
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: January 30, 2019
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    Supplementary material

    Background: Using the normal values for the East Asian population, we evaluated age- and body size-adjusted left ventricular end-diastolic dimension (LVEDD) and its prognostic impact in a hospital-based population in Japan.

    Methods and Results: We retrospectively analyzed data obtained from 4,444 consecutive patients who had undergone both transthoracic echocardiography and electrocardiography at Kitano Hospital in 2013. Those who presented with a history of previous episodes of myocardial infarction and severe or moderate valvular disease or with low ejection fraction (<50%) were excluded from the analysis. We calculated LVEDD adjusted by age and body surface area. A total of 3,474 patients were categorized into 3 groups: 401 with large adjusted LVEDD, 2,829 with normal adjusted LVEDD, and 244 with small adjusted LVEDD. Mean patient age in the large, normal, and small adjusted LVEDD groups was 66.6±18.4, 65.6±15.7, and 62.1±15.5 years, respectively (P<0.001). After adjusting for confounding factors, the excess adjusted 3-year risk of primary outcome of large adjusted LVEDD relative to normal LVEDD was significant (HR, 1.40; 95% CI: 1.08–1.78). The risk for primary outcomes of small adjusted LVEDD relative to normal adjusted LVEDD was significantly lower (HR, 0.55; 95% CI: 0.34–0.85).

    Conclusions: Adjusted large LVEDD has a deleterious impact on long-term mortality, whereas small LVEDD carried a significantly lower risk.

  • Hiroki Nakano, Kazunori Omote, Toshiyuki Nagai, Michikazu Nakai, Kunih ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2019 Volume 83 Issue 3 Pages 614-621
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: January 31, 2019
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    Supplementary material

    Background: The ideal mortality prediction model (MPM) for acute heart failure (AHF) patients would have sufficient and stable predictive ability for long-term as well as short-term mortality. However, published MPMs for AHF predominantly predict short-term mortality up to 90 days, and their prognostic performance for long-term mortality remains unclear.

    Methods and Results: We analyzed 609 AHF patients in a prospective registry from January 2013 to May 2016. We compared the prognostic performance for long-term mortality among 8 systematically identified MPMs for AHF that predict short-term mortality up to 90 days from admission. The PROTECT 7-day model showed the highest c-index for long-term as well as short-term mortality among the studied MPMs. Sensitivity analyses revealed serum albumin and total cholesterol to be the most important variables, as dropping these variables resulted in a significant decline in c-index, when compared with other variables specific to the PROTECT 7-day model. Furthermore, significant improvements in c-index and net reclassification were observed when serum albumin or serum albumin plus total cholesterol was added to the studied MPMs, other than the PROTECT 7-day model.

    Conclusions: The PROTECT 7-day model demonstrated the highest predictive performance for long-term as well as short-term mortality in AHF patients among the published MPMs. Our findings indicate the importance of accounting for nutritional status such as serum albumin and total cholesterol in AHF patients when developing a MPM.

Hypertension and Circulatory Control
  • Kazuomi Kario, Eiichiro Yamamoto, Hirofumi Tomita, Takafumi Okura, Shi ...
    Type: ORIGINAL ARTICLE
    Subject area: Hypertension and Circulatory Control
    2019 Volume 83 Issue 3 Pages 622-629
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: February 13, 2019
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    Supplementary material

    Background: SYMPLICITY HTN-Japan is a prospective, randomized, controlled trial comparing renal denervation (RDN) with standard pharmacologic therapy for treatment of uncontrolled hypertension (HTN).

    Methods and Results: Patients enrolled had uncontrolled HTN, defined as office systolic blood pressure (SBP) ≥160 mmHg and 24-h ambulatory SBP ≥135 mmHg, on ≥3 antihypertensive drugs of maximally tolerated dose for at least 6 weeks prior to enrollment. Randomization was 1:1 to RDN or maintenance of current medical therapy (control). Patients were followed every 6 months post-randomization for up to 36 months. There were 22 patients randomized to RDN and 19 to control, and 11 patients were crossed over and received RDN at 6 months post-randomization. For the RDN group (n=22), office SBP reduction was −32.8±20.1 mmHg and office DBP reduction was −15.8±12.6 mmHg at 36 months post-procedure, both P<0.001. For the combined RDN and crossover group (n=33), office SBP reduction was −26.7±18.9 mmHg and office DBP reduction was −12.7±11.8 mmHg at 30 months post-procedure, both P<0.001. There were no procedural-, device- or treatment-related safety events through 36 months.

    Conclusions: SYMPLICITY HTN-Japan is the first randomized controlled trial to evaluate RDN in an Asian population. Despite the small number of enrollments, results show patients who received RDN therapy maintained SBP reduction out to 36 months.

Ischemic Heart Disease
  • Hirohisa Endo, Tomotaka Dohi, Takehiro Funamizu, Jun Shitara, Hideki W ...
    Type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2019 Volume 83 Issue 3 Pages 630-636
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: December 12, 2018
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    Supplementary material

    Background: High-sensitivity C-reactive protein (hs-CRP) is a well known risk factor for the development of cardiovascular disease and cancer. We investigated the long-term impact of hs-CRP on cancer mortality in patients with stable coronary artery disease (CAD).

    Methods and Results: This study was a retrospective analysis of 2,867 consecutive patients who underwent percutaneous coronary intervention for stable CAD from 2000 to 2016. The patients were divided into 2 groups according to median hs-CRP. We then evaluated the association between baseline hs-CRP and both all-cause and cancer deaths. Median hs-CRP was 0.10 mg/dL (IQR, 0.04–0.27 mg/dL). The median follow-up period was 5.8 years (IQR, 2.3–10.0 years). There were 416 deaths (14.5%), including 149 cardiovascular deaths (5.2%) and 115 (4.0%) cancer deaths. On Kaplan-Meier analysis the higher hs-CRP group had a significantly higher incidence of both all-cause and cancer death (log-rank, P<0.001 and P=0.001, respectively). On multivariable analysis higher hs-CRP was significantly associated with higher risk of cancer death (HR, 1.74; 95% CI: 1.18–2.61, P=0.005).

    Conclusions: Elevated baseline hs-CRP was significantly associated with cancer mortality in patients with stable CAD. Hs-CRP measurement may be useful for the identification of subjects with an increased risk of cancer death.

  • Masato Nakamura, Ken Kozuma, Takanari Kitazono, Tomoko Iizuka, Toru Se ...
    Type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2019 Volume 83 Issue 3 Pages 637-646
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: January 24, 2019
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    Supplementary material

    Background: A unique dose of prasugrel has been approved exclusively for Japanese patients, but real-world data for prasugrel at that dose in patients with ischemic heart disease (IHD) are limited. Therefore, large-scale, real-world data are needed.

    Methods and Results: A 2-year observational study of Japanese patients with IHD undergoing percutaneous coronary intervention and being treated with prasugrel to evaluate safety and effectiveness. This report is an interim analysis of data from case report forms (CRFs) after 3 months. CRFs were collected from 4,270 patients, 4,157 of whom were eligible for the safety and effectiveness analysis sets (mean age, 68.3 years; male, 76.5%). The median treatment period was 112 days, and 92.3% of patients continued treatment with prasugrel. The incidence of non-coronary artery bypass grafting-related bleeding adverse events (AEs) was 3.1%, of which Thrombolysis in Myocardial Infarction (TIMI) major and minor bleeding accounted for 0.5% and 0.6%, respectively. The most common bleeding AEs were gastrointestinal disorders, which accounted for 43.2% of the sum of “TIMI major and minor bleeding AEs”. The incidence of major adverse cardiovascular events (MACE) was 1.0%, and the cumulative incidence of MACE was 1.4%. The incidence of stent thrombosis was 0.2%.

    Conclusions: Interim study results indicated that prasugrel was safe and effective during the early phase of treatment in Japanese patients with IHD in real-world clinical settings.

Pediatric Cardiology and Adult Congenital Heart Disease
  • Fengpu He, Yiping Jiao, Kai Ma, Zhongdong Hua, Hao Zhang, Jun Yan, Kem ...
    Type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2019 Volume 83 Issue 3 Pages 647-653
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: February 09, 2019
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    Supplementary material

    Background: Common atrioventricular valve (CAVV) repair in patients with a single ventricle remains a great challenge and a refractory issue for pediatric cardiac surgeons.

    Methods and Results: From January 2007 to April 2018, 37 consecutive patients with a single ventricle who underwent CAVV repair were included in the study group. Patients were divided into 2 groups based on the repair technique: patients in Group A were treated using the bivalvation technique, and patients in Group B underwent conventional repair techniques; baseline data were similar between groups. The inhospital and follow-up mortality were 5.4% (2/37) and 11.4% (4/35), respectively. After a follow-up of 65.5±29.3 months, the estimated 1-, 5-, and 10-year overall survival rates were 94.6%, 83.4%, and 77.0%, respectively. The rates of freedom from CAVV failure were 94.3%, 72.7%, and 62.9% after 1, 5, and 10 years, respectively. In the multivariate analysis, the independent factors for CAVV repair failure were repair technique (P=0.004) and heterotaxy syndrome (P=0.003). A total of 30 patients (81.1%) completed total cavopulmonary connection (TCPC); 3 patients required re-intervention; 24 of 31 patients (77.4%) were in New York Heart Association classes II and I at the latest follow-up.

    Conclusions: Outcomes of CAVV repair in patients palliated by single-ventricular surgery are acceptable. The bivalvation technique is a simple and effective technique.

  • Takahiro Kemmotsu, Utako Yokoyama, Junichi Saito, Satoko Ito, Azusa Uo ...
    Type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2019 Volume 83 Issue 3 Pages 654-661
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: February 07, 2019
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    Background: Antenatal betamethasone (BMZ) is a standard therapy for reducing respiratory distress syndrome in preterm infants. Recently, some reports have indicated that BMZ promotes ductus arteriosus (DA) closure. DA closure requires morphological remodeling; that is, intimal thickening (IT) formation; however, the role of BMZ in IT formation has not yet been reported.

    Methods and Results: First, DNA microarray analysis using smooth muscle cells (SMCs) of rat preterm DA on gestational day 20 (pDASMCs) stimulated with BMZ was performed. Among 58,717 probe sets, ADP-ribosyltransferase 3 (Art3) was markedly increased by BMZ stimulation. Quantitative reverse transcription polymerase chain reaction (RT-PCR) confirmed the BMZ-induced increase of Art3 in pDASMCs, but not in aortic SMCs. Immunocytochemistry showed that BMZ stimulation increased lamellipodia formation. BMZ significantly increased total paxillin protein expression and the ratio of phosphorylated to total paxillin. A scratch assay demonstrated that BMZ stimulation promoted pDASMC migration, which was attenuated byArt3-targeted siRNAs transfection. pDASMC proliferation was not promoted by BMZ, which was analyzed by a 5’-bromo-2’-deoxyuridine (BrdU) assay. Whether BMZ increased IT formation in vivo was examined. BMZ or saline was administered intravenously to maternal rats on gestational days 18 and 19, and DA tissues were obtained on gestational day 20. The ratio of IT to tunica media was significantly higher in the BMZ-treated group.

    Conclusions: These data suggest that antenatal BMZ administration promotes DA IT through Art3-mediated DASMC migration.

Peripheral Vascular Disease
  • Keisuke Shoji, Kenji Yanishi, Ryusuke Yoshimi, Naoki Hamada, Kazuhisa ...
    Type: ORIGINAL ARTICLE
    Subject area: Peripheral Vascular Disease
    2019 Volume 83 Issue 3 Pages 662-671
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: February 07, 2019
    JOURNALS FREE ACCESS FULL-TEXT HTML

    Background: Many patients with collagen disease (CD), particularly scleroderma (SSc), develop critical limb ischemia (CLI), which leads to limb amputation. However, conventional therapies, including revascularization via surgical bypass, showed poor outcomes in CLI patients with CD. Many CLI patients with SSc showed poor responses to combination therapies including intravenous iloprost, PDE-5 inhibitors, and bosentan. Therefore, new methods of improving the peripheral circulation for limb salvage are required. This study was a subanalysis of the long-term clinical outcomes after autologous bone marrow-derived mononuclear cells (BM-MNC) in CLI patients with SSc.

    Methods and Results: We assessed no-option CLI patients with CD who underwent BM-MNC implantation at 10 institutes; 69 patients (39 with SSc-related diseases (SSc group) and 30 with other CDs (non-SSc group)), were included. The median follow-up duration was 36.5 months. The 10-year overall survival rate was 59.1% in the SSc group and 82.4% in the non-SSc group. The 10-year major amputation-free rates were 97.4% and 82.6%, respectively. The number of major or minor amputations in the SSc group trended to be less than that in the non-SSc group. Significant improvements in visual analog scale scores were observed in both groups.

    Conclusions: The BM-MNC implantation may be feasible in no-option CLI patients with CD. In the SSc group, limb salvage rate tended to be higher than in the non-SSc group.

Valvular Heart Disease
  • Masaki Miyasaka, Sung-Han Yoon, Rahul P. Sharma, Yoshio Maeno, Sandhu ...
    Type: ORIGINAL ARTICLE
    Subject area: Valvular Heart Disease
    2019 Volume 83 Issue 3 Pages 672-680
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: January 30, 2019
    JOURNALS FREE ACCESS FULL-TEXT HTML
    Supplementary material

    Background: Patients with severe aortic stenosis (AS) and an extra-large annulus (ELA) area (>683 mm2) can rarely be treated by transcatheter aortic valve replacement (TAVR) because of the size limitation of the transcatheter heart valves. This study aimed to evaluate the feasibility of TAVR using a 29-mm SAPIEN3 (S3) valve in patients with ELA and S3-dimensions by post-procedural computed tomography (post-CT).

    Methods and Results: We included 261 patients undergoing TAVR using a 29-mm S3: 30 patients with ELA and 231 with non-ELA were identified. S3-dimensions were evaluated at the S3 inflow and annulus level by post-CT in 129 patients. The ELA group had a greater aortic annulus area measured by pre-procedural CT (737.3±54.7 vs. 578.4±41.9 mm2, P<0.0001), higher balloon inflation volume (36 vs. 33 mL, P<0.0001), a larger S3 area at inflow by post-CT (729.6±42.2 vs. 682.2±35.0 mm2, P<0.001), and a correlation between the inflation volume and S3 area (r=0.71, P=0.0005). No differences were observed between groups in paravalvular aortic regurgitation (PAR) ≥mild (43.3% vs. 27.6%, P=0.09), PAR ≥moderate (3.3% vs. 1.3%, P=0.39) or 1-year mortality (10.0% vs. 9.1%, P=0.87).

    Conclusions: TAVR using a 29-mm S3 with extra inflation of the delivery balloon can be considered as a treatment option for patients with severe AS and ELA.

Rapid Communications
  • Shinichi Nunoda, Taro Sasaoka, Yasushi Sakata, Minoru Ono, Yoshiki Saw ...
    Type: RAPID COMMUNICATION
    2019 Volume 83 Issue 3 Pages 681-683
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: December 27, 2018
    JOURNALS FREE ACCESS FULL-TEXT HTML
    Supplementary material

    Background: In Japan, there are more patients waiting for heart transplants (HTXs) than available organs.

    Methods and Results: Since July 2010, 68 pediatric and 366 adult patients aged <60 years applied for HTX candidacy with the Japanese Circulation Society’s HTX Committee. No significant differences in freedom from death or HTX were observed between pediatric Status 1 and Status 2 patients. More adult Status 1 patients reached the endpoint of death or HTX than adult Status 2 patients. Pediatric patients (Status 1 and 2) did not have better survival than adult Status 1 or Status 2 patients.

    Conclusions: Pediatric patients should be prioritized over adult patients for HTX.

  • Osamu Seguchi, Kensuke Kuroda, Tomoyuki Fujita, Yuto Kumai, Seiko Naka ...
    Type: RAPID COMMUNICATION
    2019 Volume 83 Issue 3 Pages 684-686
    Published: February 25, 2019
    Released: February 25, 2019
    [Advance publication] Released: January 26, 2019
    JOURNALS FREE ACCESS FULL-TEXT HTML
    Supplementary material

    Background: Heart transplantation (HTx) is reported to have a comparable effect on the prognosis of heart failure patients without muscular disease and for those with muscular dystrophy (MD). However, little is known about the changes in muscular diseases in patients with MD after HTx.

    Methods and Results: We assessed the ambulatory capacity of 9 patients with MD who underwent HTx. All patients demonstrated improvement in ambulation to varying degrees and 1 patient successfully climbed Mount Fuji 3.8 years after HTx.

    Conclusions: HTx potentially improves not only the prognosis but also the ambulatory capacity of patients with MD.

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