Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 82, Issue 12
Displaying 1-39 of 39 articles from this issue
Reviews
  • Teruhiko Imamura, Koichiro Kinugawa, Nir Uriel
    Article type: REVIEW
    2018 Volume 82 Issue 12 Pages 2931-2938
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: October 27, 2018
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    Left ventricular assist device (LVAD) technology has improved the survival of advanced heart failure patients. However, readmission rates following LVAD implantation remain high and are an unsolved matter. Currently, gastrointestinal bleeding is one of the major causes of readmission and has recently been demonstrated to mainly result from increased angiogenesis. In addition to the conventional therapeutic strategies, including a reduction in antiplatelet and anticoagulation therapies and blood products administration, several therapeutic tools have recently been proposed: octreotide, thalidomide, hemodynamic optimization by the ramp test, and fish oil therapy. This review will update the therapeutic strategy for gastrointestinal bleeding in LVAD patients.

Editorials
Late Breaking Clinical Trials (JCS 2018)
  • Kazutaka Aonuma, Hiro Yamasaki, Masato Nakamura, Tatsushi Ootomo, Mori ...
    Article type: LATE BREAKING CLINICAL TRIAL (JCS 2018)
    2018 Volume 82 Issue 12 Pages 2946-2953
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: October 11, 2018
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    Supplementary material

    Background: The PROTECT AF and PREVAIL trials demonstrated that the WATCHMAN left atrial appendage (LAA) closure device is a reasonable alternative to warfarin therapy for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) in the USA and Europe. We conducted the SALUTE trial to confirm the safety and efficacy of the LAA closure therapy for patients with NVAF in Japan.

    Methods and Results: A total of 54 subjects (including 12 Roll-in) with NVAF who had a CHA2DS2-VASc score ≥2 were enrolled. All subjects were successfully implanted with the LAA closure device. No serious adverse events related to the primary procedure-safety endpoint occurred. The 2nd co-primary endpoint was a composite of all stroke, systemic embolism and cardiovascular/unexplained death. One ischemic stroke (1/42) occurred during the 6-month follow-up. The effective LAA closure rate defined as the 3rd co-primary endpoint was 100% (42/42) at both 45-day and 6-month follow-up.

    Conclusions: The procedural safety and 6-month results from the SALUTE trial demonstrated that the LAA closure device was safe and effective, similar to the results of large-scale randomized clinical trials, and provides a novel perspective of LAA closure for Japanese patients with NVAF in need of an alternative to long-term oral-anticoagulation. (Trial Registration: clinicaltrials.gov Identifier NCT 03033134)

Original Articles
Aortic Disease
  • Pawel Szulc, Ez Zoubir Amri, Annie Varennes, Patricia Panaia-Ferrari, ...
    Article type: ORIGINAL ARTICLE
    Subject area: Aortic Disease
    2018 Volume 82 Issue 12 Pages 2954-2961
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: October 03, 2018
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    Supplementary material

    Background: Severe abdominal aortic calcification (AAC) points to high cardiovascular risk and leptin stimulates arterial calcification; however, clinical data on their association are scarce. We studied the link between serum leptin and AAC severity and progression, and the effect of smoking and lipid levels, on this association in men.

    Methods and Results: At baseline, 548 community-dwelling men aged 50–85 years underwent blood collection and lateral lumbar spine radiography. In 448 men, X-ray was repeated after 3 and 7.5 years. AAC was assessed using Kauppila’s semiquantitative score. In multivariable models, high leptin was associated with higher odds of severe AAC (odds ratio [OR]=1.71 per SD, 95% confidence interval [CI]: 1.22–2.40). The odds of severe AAC were the highest in men who had elevated leptin levels and either were ever-smokers (OR=9.22, 95% CI: 3.43–24.78) or had hypertriglyceridemia (vs. men without these characteristics). Higher leptin was associated with greater AAC progression (OR=1.34 per SD, 95% CI: 1.04–1.74). The risk of AAC progression was the highest in men who had elevated leptin levels and either were current smokers or had high low-density lipoprotein-cholesterol levels (OR=5.91, 95% CI: 2.46–14.16 vs. men without these characteristics). These links remained significant after adjustment for baseline AAC and in subgroups defined according to smoking and low-density lipoprotein-cholesterol levels.

    Conclusions: In older men, high leptin levels are associated with greater severity and rapid progression of AAC independent of smoking, low-density lipoprotein-cholesterol or triglycerides.

Arrhythmia/Electrophysiology
  • In-Jung Kim, Pil-Sung Yang, Tae-Hoon Kim, Jae-Sun Uhm, Hui-Nam Pak, Mo ...
    Article type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2018 Volume 82 Issue 12 Pages 2962-2969
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: September 26, 2018
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    Supplementary material

    Background: The relationship between anemia and sudden cardiac arrest (SCA) is unclear in the general population, so we assessed it in a nationwide cohort.

    Methods and Results: We studied 494,948 subjects (mean age, 47.8 years; 245,333 men [49.6%]) with national health check-up data from the Korean National Health Insurance Database Cohort. During a mean follow-up period of 5.4 years, SCA occurred in 616 participants (396 men, 220 women). The incidence rates of SCA increased across the 4 anemia groups in both men (0.3, 1.5, 5.3, and 4.5 per 1,000 person-years) and women (0.2, 0.5, 0.5, and 1.2 per 1,000 person-years). The SCA risk per 1-unit decrease in hemoglobin (Hb) increased by 21% and 24%, respectively, in multivariable models adjusted for cardiovascular factors, in men (95% confidence interval [CI], 13–29%; P<0.001) and women (95% CI, 13–37%; P<0.001). A negative correlation between QTc interval and Hb level was observed in men, and a trend was observed in women.

    Conclusions: Anemia was associated with an increased risk of SCA even after accounting for concomitant conditions in a South Korean nationwide cohort. The correlation between anemia and SCA might be explained by an increase in arrhythmic risks, such as QTc prolongation.

  • Myung-Jin Cha, Youngjin Cho, Il-Young Oh, Eue-Keun Choi, Seil Oh
    Article type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2018 Volume 82 Issue 12 Pages 2970-2975
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: October 04, 2018
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    Supplementary material

    Background: There is little evidence that focuses on the ethnic variability of clinical risk factors for thromboembolism (TE) in atrial fibrillation (AF). We aimed to investigate the effect of each traditional risk factor in the Korean AF population.

    Methods and Results: Medical records of 12,876 consecutive patients (aged >18 years) newly diagnosed and followed up with non-valvular AF from 2000 to 2013 were reviewed. TE events, including ischemic stroke and systemic embolism, were investigated for risk factor validation. Among the total of 12,876 patients, 1,390 (10.8%) had TE events. In univariate/multivariate analysis adjusting for clinical factors and antithrombotic medications, traditional risk factors included in the CHA2DS2-VASc scheme showed statistical significance, except for female sex, which was not a predictor of events. Additionally, chronic kidney disease (CKD; hazard ratio 1.62, P<0.001) was shown to be an independent predictor of TE events. Based on the analysis, we developed a novel stratification system, CHA2DS2-VAK, omitting the female sex category and adding CKD. The new scoring system showed greater discrimination in event rates between score 0 and 1 patients.

    Conclusions: Female sex was not associated with TE events in a Korean non-valvular AF population. The novel CHA2DS2-VAK scoring system, with substitution of CKD for female sex, might be more appropriate for the Korean population.

  • Achim Leo Burger, Stefan Stojkovic, Herwig Schmidinger, Robin Ristl, T ...
    Article type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2018 Volume 82 Issue 12 Pages 2976-2982
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: September 29, 2018
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    Background: Careful device programming is necessary to reduce inappropriate antitachycardia pacing (ATP) and shock therapy in recipients of implantable cardioverter-defibrillators (ICD). This retrospective study investigated the safety and efficacy of a therapy-reducing programming strategy in comparison with conventional strategies in consecutive ICD recipients of a university cardiac center.

    Methods and Results: All 1,471 ICD recipients from 2000 to 2015 were analyzed. Individual ICD programming (IND) was used from 2000 to 2005 followed by standard-three-zone programming (STD) until 2010. From 2010 to 2015 therapy-reducing long detection time programming (RED) was established. The mean follow-up was 2.4±1.6, 2.3±1.6 and 1.7±1.2 years in the IND, STD and RED groups, respectively. Switchover from IND to STD revealed a significant reduction in inappropriate ATP (P=0.024) and shock therapy (P<0.001). Further reduction of 58% (RR=0.42, 95% confidence interval [CI]: 0.17–1.04; P=0.061) in inappropriate ATP and 29% (RR=0.71, 95% CI: 0.29–1.72; P=0.452) in inappropriate shock therapy was achieved by switchover from STD to RED. Kaplan-Meier analysis revealed a significant difference in time until first inappropriate ATP and shock therapy among the 3 groups, being lowest in the RED group (P≤0.001). There was no difference in overall mortality (P=0.416).

    Conclusions: Defensive ICD programming with prolonged detection times is safe and significantly reduced inappropriate ICD therapies.

  • Nobutoyo Masunaga, Mitsuru Abe, Hisashi Ogawa, Yuya Aono, Syuhei Ikeda ...
    Article type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2018 Volume 82 Issue 12 Pages 2983-2991
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: October 31, 2018
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    Supplementary material

    Background: The combination of oral anticoagulant (OAC) and antiplatelet drug (APD) increases the bleeding risk in atrial fibrillation (AF). Non-vitamin K antagonist OAC (NOAC) have been increasingly used since 2011. We investigated current status, time trends and outcomes of AF patients using combination therapy in 2011–2017.

    Methods and Results: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. Of 2,378 patients with OAC at enrollment, 521 (22%) received combination therapy, while 1,857 (78%) received OAC alone. When compared with OAC alone, combination therapy patients had more comorbidities, but approximately 30% had no atherosclerotic disease. From 2011 to 2017, the prevalence of combination therapy decreased from 26% to 14%. The prevalence of NOAC increased in those on combination therapy. Off-label under-dosing of NOAC increased year by year, especially in combination therapy. During follow-up, the incidence of major bleeding (hazard ratio [HR], 1.42; 95% CI: 1.03–1.95) and stroke/systemic embolism (HR, 1.48; 95% CI: 1.09–2.00) was higher in the combination therapy than in the OAC alone group.

    Conclusions: In Japanese AF patients receiving OAC, the prevalence of combination therapy decreased, with the proportion of NOAC use increasing in 2011–2017. Many patients, however, received off-label NOAC under-dosing, especially in the combination therapy group. Patients with combination therapy had higher incidences of major bleeding as well as stroke/systemic embolism, compared with OAC monotherapy.

  • Takakatsu Yoshitake, Masahiko Goya, Takeshi Sasaki, Shinya Shiohira, M ...
    Article type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2018 Volume 82 Issue 12 Pages 2992-2997
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: October 12, 2018
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    Background: Transvenous lead extractions have been performed using 40-Hz laser sheaths. Recently, a new 80-Hz laser sheath became available, but only a few reports have compared the effectiveness of the 40- and 80-Hz laser sheaths.

    Methods and Results: This study included 215 patients. Lead extractions using only laser sheaths were analyzed. The clinical characteristics, extraction parameters, and extraction tools were evaluated. The procedures were performed with 40-Hz sheaths in 150 patients (group 1: 270 leads) and 80-Hz sheaths in 65 (group 2: 99 leads). No statistically significant differences were observed in the clinical parameters except for sex. The mean implant duration was 95.3±86.0 and 78.2±56.8 months in groups 1 and 2, respectively (P=0.07). The respective mean laser time and number of laser pulses were 48.5±52.1 and 48.1±56.1 s (P=0.96) and 2,035.0±2,384.0 and 3,955.1±2,339.3 pulses (P<0.0001). Complete removal was achieved for 97.4% of the leads and in 98.0% in both groups (P=0.38). Major complications occurred in 2.0% and 3.1% of the patients in groups 1 and 2, respectively (P=0.94).

    Conclusions: Transvenous lead extraction using high-frequency laser sheaths was as highly successful as with low-frequency laser sheaths in Japanese patients.

Cardiovascular Surgery
  • Sachie Terazawa, Hideki Oshima, Yuji Narita, Kazuro Fujimoto, Masato M ...
    Article type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Surgery
    2018 Volume 82 Issue 12 Pages 2998-3004
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: September 27, 2018
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    Background: The strategy for cardiovascular surgery in dementia patients is controversial, so we aimed to investigate whether preoperative dementia and its severity might affect the outcomes of cardiovascular surgery by evaluating with the Mini-Mental State Examination (MMSE).

    Methods and Results: The study group comprised 490 patients undergoing cardiovascular surgery. Their preoperative cognitive status was evaluated using the MMSE, and analysis was performed to compare the patients with MMSE score <24 (dementia group, n=51) or MMSE score 24–30 (non-dementia group, n=439). Furthermore, the effect of the severity of dementia was analyzed with a cut-off MMSE score of 19/20. Risk factors for surgical outcomes were explored using multivariate logistic regression analysis. Hospital mortality was 11.8% in the dementia group and 2.1% in the non-dementia group (P=0.002). Regarding the postoperative morbidities, the incidence of cerebrovascular disorder (P=0.001), pneumonia (P=0.039), delirium (P=0.004), and infection (P=0.006) was more frequent in dementia group. Among the patients with MMSE <20, hospital mortality was as high as 25%, and the rate of delirium was 58%. Multivariate logistic regression analysis revealed that MMSE score <24 (P=0.003), lower serum albumin (P=0.023) and aortic surgery (P=0.036) were independent risk factors for hospital death.

    Conclusions: Preoperative dementia affects the outcomes of cardiovascular surgery with regard to hospital death and delirium. The surgical indication for patients with MMSE <20 might be difficult, but surgery with an appropriate strategy should be considered for patients with MMSE <24.

Epidemiology
  • Shamima Akter, Tohru Nakagawa, Toru Honda, Shuichiro Yamamoto, Keisuke ...
    Article type: ORIGINAL ARTICLE
    Subject area: Epidemiology
    2018 Volume 82 Issue 12 Pages 3005-3012
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: September 12, 2018
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    Background: The effect of smoking on mortality in working-age adults remains unclear. Accordingly, we compared the effects of cigarette smoking and smoking cessation on total and cause-specific mortality in a Japanese working population.

    Methods and Results: This study included 79,114 Japanese workers aged 20–85 years who participated in the Japan Epidemiology Collaboration on Occupational Health Study. Deaths and causes of death were identified from death certificates, sick leave documents, family confirmation, and other sources. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated via Cox proportional hazards regression. During a maximum 6-year follow-up, there were 252 deaths in total. Multivariable-adjusted HRs (95% CIs) for total mortality, cardiovascular disease (CVD) mortality, and tobacco-related cancer mortality were 1.49 (1.10–2.01), 1.79 (0.99–3.24), and 1.80 (1.02–3.19), respectively, in current vs. never smokers. Among current smokers, the risks of total, tobacco-related cancer, and CVD mortality increased with increasing cigarette consumption (Ptrend<0.05 for all). Compared with never smokers, former smokers who quit <5 and ≥5 years before baseline had HRs (95% CIs) for total mortality of 1.80 (1.00–3.25) and 1.02 (0.57–1.82), respectively.

    Conclusions: In this cohort of workers, cigarette smoking was associated with increased risk of death from all and specific causes (including CVD and tobacco-related cancer), although these risks diminished 5 years after smoking cessation.

  • Choy-Lye Chei, Kazumasa Yamagishi, Akihiko Kitamura, Masahiko Kiyama, ...
    Article type: ORIGINAL ARTICLE
    Subject area: Epidemiology
    2018 Volume 82 Issue 12 Pages 3013-3020
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: October 13, 2018
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    Background: Few prospective studies have explored the association between fatty acids (FA) and risk of CAD. Understanding of the role of each individual serum FA as a coronary risk or protective factor is still limited. The aim was to investigate which serum FA are associated with the incidence of CAD in Japanese subjects.

    Methods and Results: A prospective nested case-control study of 40–85-year-old Japanese subjects was undertaken using frozen serum samples collected from 12,840 participants who participated in cardiovascular risk surveys from 1984 to 1998 for 1 community and 1989–1997 for 2 other communities. Three control subjects per case were matched by sex, age, community, year of serum storage and fasting status. By 2005 we had identified 152 incident cases of CAD. Mean n-3-polyunsaturated and saturated FA did not differ between cases and controls, while mean n-6-polyunsaturated FA was higher in controls compared with cases. The multivariable OR of CAD for the highest vs. lowest quartiles of miristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16:1), and linoleic acid (18:2) were 2.8 (95% CI: 1.5–5.2), 2.7 (95% CI: 1.4–5.5), 3.2 (95% CI: 1.7–6.1) and 0.4 (95% CI: 0.2–0.7), respectively.

    Conclusions: High serum miristic acid, palmitic acid and palmitoleic acid have an adverse effect, and high serum linoleic acid had a protective effect, on the risk of CAD.

Heart Failure
  • Yuki Kimura, Osamu Seguchi, Keiichiro Iwasaki, Koichi Toda, Noriko Kik ...
    Article type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2018 Volume 82 Issue 12 Pages 3021-3028
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: September 29, 2018
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    Background: Coronary artery disease (CAD) after heart transplantation (HTx) develops as a combination of donor-transmitted coronary atherosclerosis (DTCA) and cardiac allograft vasculopathy. Assessing donor CAD before procurement is important. Because coronary artery calcification (CAC) is a predictor for CAD, donor-heart CAC is usually evaluated to estimate the risk of donor CAD. The usefulness of CAC for predicting DTCA, however, is not known.

    Methods and Results: Sixty-four HTx recipients whose donor underwent chest computed tomography before procurement or ≤2 weeks after HTx and who underwent coronary angiography and intravascular ultrasound (IVUS) ≤3 months after HTx were enrolled. Eight patients had CAC (CAC group) and 56 patients did not have CAC (no-CAC group). Patients in the CAC group were significantly older and had a higher prevalence of maximum intimal thickness (MIT) of the coronary artery ≥0.5 mm at initial IVUS than patients in the no-CAC group (100% vs. 55%, P=0.02). Adverse cardiac events and death were not significantly different. Everolimus tended to be used more often in the CAC group.

    Conclusions: Donor-heart CAC is a significant predictor for MIT of the coronary artery ≥0.5 mm after HTx. The presence of CAC, however, is not associated with future cardiac events. The higher prevalence of everolimus use in the CAC group may have affected the results.

Imaging
  • Masanori Kawasaki, Ryuhei Tanaka, Akihiro Yoshida, Maki Nagaya, Shingo ...
    Article type: ORIGINAL ARTICLE
    Subject area: Imaging
    2018 Volume 82 Issue 12 Pages 3029-3036
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: October 16, 2018
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    Background: Although new-onset atrial fibrillation (AF) increases with ageing, the prediction of new-onset AF is complicated. We previously reported that pulmonary capillary wedge pressure (ePCWP) estimated by the combination of left atrial volume index (LAVI) and active left atrial emptying function (aLAEF) had a strong relationship with PCWP on catheterization (r=0.92): ePCWP=10.8−12.4×log (aLAEF/minimum LAVI). We sought to determine the usefulness of ePCWP to predict new-onset AF.

    Methods and Results: We measured LAVI, aLAEF and ePCWP on speckle tracking echocardiography (STE) in 566 consecutive elderly patients (72±6 years) without a history of AF. A total of 63 patients (73±6 years) developed electrocardiographically confirmed AF during a mean follow-up period of 50 months. Baseline aLAEF was significantly lower in patients with than without new-onset AF (17.9±6.5 vs. 28.2±7.5%), whereas ePCWP was significantly higher (14.8±3.7 vs. 10.3±3.1 mmHg). In multivariate logistic regression analysis, ePCWP and aLAEF were strong independent predictors of AF. Using ePCWP >13 mmHg or aLAEF ≤22% on univariate Cox regression analysis, the HR for new-onset AF were 3.53 (95% CI: 1.68–7.44, P<0.001) and 4.06 (95% CI: 1.90–8.65, P<0.001), respectively. By combining these 2 criteria (>13 mmHg and ≤22%), the HR increased to 11.84 (95% CI: 6.85–20.5, P<0.001).

    Conclusions: ePCWP and aLAEF measured on STE are useful predictors of new-onset AF. ePCWP provides added value for risk stratification of new-onset AF.

Ischemic Heart Disease
  • Toshiki Takano, Komei Tanaka, Kazuyuki Ozaki, Akinori Sato, Kenichi Ii ...
    Article type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2018 Volume 82 Issue 12 Pages 3037-3043
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: October 11, 2018
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    Background: The implantable cardioverter defibrillator (ICD) is a standard prevention therapy for patients at high risk for sudden cardiac death (SCD) due to life-threatening ventricular arrhythmia (VA), that is, ventricular fibrillation and ventricular tachycardia. However, clinical predictors of recurrent VA in secondary prevention ICD recipients with coronary artery disease (CAD) remain unknown.

    Methods and Results: We followed up 96 consecutive patients with CAD undergoing ICD implantation for secondary prevention of SCD. Long-term rates and clinical predictors of appropriate ICD therapy (ICD-Tx) for VA were analyzed. Appropriate ICD-Tx occurred in 41 (42.7%) patients during a median follow-up of 2.4 years (interquartile range, 0.9-6.1). These patients had significantly greater left ventricular end-diastolic diameter (62.3±1.3 vs. 54.6±1.1 mm, P<0.001), lower left ventricular ejection fraction (LVEF; 36.3±2.0% vs. 45.7±1.8%, P<0.001), and more incomplete revascularization (ICR; 70.7% vs. 45.5%, P=0.014) than those without appropriate ICD-Tx. Multivariable analysis showed that LVEF (hazards ratio [HR], 0.950; 95% CI: 0.925–0.975; P<0.001) and ICR (HR, 2.293; 95% CI: 1.133–4.637; P=0.021) were significant predictors of appropriate ICD-Tx for VA.

    Conclusions: Lower LVEF and ICR were independent predictors of recurrent VA in secondary prevention ICD recipients with CAD.

  • Takashi Kubo, Masahiro Takahata, Kosei Terada, Kazuya Mori, Yu Arita, ...
    Article type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2018 Volume 82 Issue 12 Pages 3044-3051
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: October 13, 2018
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    Background: A fractional flow reserve (FFR) between 0.75 and 0.80 constitutes a “gray zone” for clinical decision-making in coronary artery disease. We compared long-term outcomes of percutaneous coronary intervention (PCI) using drug-eluting stents vs. medical therapy for coronary stenosis with gray zone FFR.

    Methods and Results: We retrospectively investigated the clinical outcomes of 263 patients with gray zone FFR: 78 patients in the PCI group and 185 patients in the medical therapy group. During a median follow-up of 3.7 years, the frequency of target vessel failure (TVF, defined as a composite of cardiac death, myocardial infarction [MI], or ischemia-driven target vessel revascularization [TVR]) was significantly lower in the PCI group compared with the medical therapy group (6% vs. 19%, hazard ratio [HR]:0.33, 95% confidence interval [CI]: 0.13–0.84, P=0.008). The frequency of a composite of cardiac death or MI was not different between the 2 groups (1% vs. 2%, HR: 0.61, 95% CI: 0.07–5.49, P=0.645). The frequency of ischemia-driven TVR was significantly lower in the PCI group compared with the medical therapy group (5% vs. 18%, HR: 0.28, 95% CI: 0.10–0.79, P=0.005).

    Conclusions: In patients with gray zone FFR, compared with medical therapy, PCI decreased the frequency of TVF, which was mainly driven by a reduction in the frequency of angina or myocardial ischemia without any difference in the frequency of cardiac death or MI.

Metabolic Disorder
  • Shin Kawasoe, Kazuki Ide, Tomoko Usui, Takuro Kubozono, Shiro Yoshifuk ...
    Article type: ORIGINAL ARTICLE
    Subject area: Metabolic Disorder
    2018 Volume 82 Issue 12 Pages 3052-3057
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: September 27, 2018
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    Background: The independent role of serum triglyceride (TG) levels as a cardiovascular risk factor is still not elucidated. We aimed to investigate if the effect of TG on arterial stiffness is influenced by the serum level of low-density lipoprotein cholesterol (LDL-C).

    Methods and Results: We studied 11,640 subjects who underwent health checkups. They were stratified into 4 groups according to LDL-C level (≤79, 80–119, 120–159, and ≥160 mg/dL). Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). In each group, univariate and multivariete logistic regression analyses were performed to investigate the association between high TG (≥150 mg/dL) and high baPWV (>1,400 cm/s). In the univarite analysis, high TG was significantly associated with high baPWV in LDL-C <79 mg/dL (OR, 3.611, 95% CI, 2.475–5.337; P<0.0001) and 80–119 mg/dL (OR, 1.881; 95% CI, 1.602–2.210; P<0.0001), but not in LDL-C 120–159 mg/dL and ≥160 mg/dL. In the multivariate analysis, high TG was significantly associated with high baPWV in LDL-C ≤79 mg/dL (OR, 2.558; 95% CI, 1.348–4.914; P=0.0040) and LDL-C 80–119 mg/dL (OR, 1.677; 95% CI, 1.315–2.140; P<0.0001), but not in LDL-C 120–159 mg/dL and ≥160 mg/dL.

    Conclusions: High TG and increased arterial stiffness showed an independent relationship in a Japanese general population with LDL-C ≤119 mg/dL. TG-lowering therapy might be an additional therapeutic consideration in these subjects.

  • Hiroki Katsuta, Kazuya Tsuboi, Hiroshi Yamamoto, Hiromi Goto
    Article type: ORIGINAL ARTICLE
    Subject area: Metabolic Disorder
    2018 Volume 82 Issue 12 Pages 3058-3063
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: October 03, 2018
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    Supplementary material

    Background: Fabry disease is an X-linked lysosomal storage disorder and shows globotriosylceramide (Gb3) accumulation in multiple organs, resulting from a deficiency of α-galactosidase. In patients with Fabry disease, cardiovascular disease occurs at an early age. Previous studies have shown that serum levels of high-density lipoprotein-cholesterol (HDL-C) increase in this disease, yet its clinical significance for cardiovascular disease remains unclear.

    Methods and Results: In order to determine why the serum HDL-cholesterol is high in various cardiovascular diseases of Fabry disease patients, we evaluated the serum lipid profiles, ocular vascular lesions, and levels of serum vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 in 69 patients with Fabry disease diagnosed by genetic examination. The serum HDL-C/total cholesterol (T-Chol) ratio was significantly high, especially in male patients (41.5±1.7%) regardless of body mass index. Ocular vascular lesions were more likely to occur in female patients with a high HDL-C/T-Chol ratio compared with most male patients. Female patients with a high HDL-C/T-Chol ratio also presented a high serum VEGF level, suggesting that vascular endothelium dysfunction and arteriosclerotic changes progress more severely than in patients with a normal HDL-C/T-Chol ratio. In most patients, enzyme replacement therapy improved serum Gb3 and lyso-Gb3 levels, but these Gb3 and lyso-Gb3 still remained higher than in healthy controls, which appears to result in continuous vascular arteriosclerotic changes.

    Conclusions: We concluded that increased low-density lipoprotein-cholesterol uptake to the vascular wall caused by endothelial dysfunction is likely to contribute to the high HDL-C/T-Chol ratio observed in Fabry disease patients.

Pediatric Cardiology and Adult Congenital Heart Disease
  • Jae Gun Kwak, Woong-Han Kim, Eung Re Kim, Jae Hong Lim, Jooncheol Min
    Article type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2018 Volume 82 Issue 12 Pages 3064-3068
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: October 05, 2018
    JOURNAL FREE ACCESS FULL-TEXT HTML

    Background: We reviewed our revised surgical strategy for tetralogy of Fallot (TOF) total correction to minimize early exposure to significant pulmonary regurgitation (PR) and to avoid right ventriculotomy (RV-tomy).

    Methods and Results: Since February 2016, we have tried to preserve, first, pulmonary valve (PV) function to minimize PR by extensive commissurotomy with annulus saving; and second, RV infundibular function by avoiding RV-tomy. With this strategy, we performed total correction for 50 consecutive patients with TOF until May 2018. We reviewed the early outcomes of 27 of 50 patients who received follow-up for ≥3 months. Mean patient age at operation was 10.2±5.0 months, and mean body weight was 8.8±1.2 kg. The preoperative pressure gradient at the RV outflow tract and the PV z-score were improved at most recent echocardiography from 82.0±7.1 to 26.8±6.4 mmHg, and from −2.35±0.49 to −0.55±0.54, respectively, during 11.1±1.6 months of follow-up after operation. One patient required re-intervention for residual pulmonary stenosis. Twenty-two patients had less than moderate PR (none, 1; trivial, 8; mild, 13), and 5 patients had moderate PR. There was no free or severe PR.

    Conclusions: At 1-year follow-up, the patients who underwent total TOF correction with our revised surgical strategy had acceptable results in terms of PV function. The preserved PV had a tendency to grow on short-term follow-up.

Peripheral Vascular Disease
  • Takayuki Sugai, Tetsu Watanabe, Yoichiro Otaki, Jun Goto, Ken Watanabe ...
    Article type: ORIGINAL ARTICLE
    Subject area: Peripheral Vascular Disease
    2018 Volume 82 Issue 12 Pages 3069-3075
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: September 29, 2018
    JOURNAL FREE ACCESS FULL-TEXT HTML
    Supplementary material

    Background: The prognosis of peripheral artery disease (PAD) and comorbid sarcopenia is poor. Some reports indicate that the computed tomography (CT) value of skeletal muscle, which reflects intramuscular fat deposition as well as skeletal muscle mass, is considered a marker of sarcopenia. However, it remains unclear if skeletal muscle area and CT value are associated with poor outcomes in patients with PAD.

    Methods and Results: Psoas muscle area and CT value were measured by manual trace at the level of the third lumbar vertebral body in 327 consecutive patients with PAD undergoing endovascular therapy (EVT). The endpoint was major adverse cardiovascular and limb events (MACLE). There were 60 MACLE during the follow-up period. Patients with MACLE had lower mean psoas muscle CT value than those without. However, there was no significant difference in total psoas muscle area between patients with and without MACLE. Kaplan-Meier analysis demonstrated that the lowest tertile of psoas muscle CT value was associated with the highest risk of MACLE. Multivariate Cox hazard analysis revealed that psoas muscle CT value was associated with MACLE after adjustment for Fontaine class, previous ischemic heart disease, prevalence of diabetes mellitus, brain natriuretic peptide, and serum albumin.

    Conclusions: Psoas muscle CT value is a feasible predictor of MACLE in patients with PAD.

Pulmonary Circulation
  • Mika Nagaoka, Ayumi Goda, Kaori Takeuchi, Hanako Kikuchi, Mayumi Finge ...
    Article type: ORIGINAL ARTICLE
    Subject area: Pulmonary Circulation
    2018 Volume 82 Issue 12 Pages 3076-3081
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: October 16, 2018
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    Background: Sleep apnea (SA) can cause repeated nocturnal arterial oxygen desaturation and result in acute increase in pulmonary arterial pressure (PAP). The presence of SA is associated with a poor prognosis in patients with chronic left-sided heart failure, but little is known for patients with pulmonary arterial hypertension (PAH).

    Methods and Results: We enrolled 151 patients with PAH (44±16 years old, male/female=37/114). They were all in the Nice Classification group 1 (idiopathic PAH/associated PAH=52/48%, mean PAP of 46±16 mmHg). They underwent right-heart catheterization and a sleep study with simplified polysomnography. Averaged percutaneous oxygen saturation (SpO2) during sleep was measured and an apnea-hypopnea index >5 was defined as SA. SA was noted in 58 patients (obstructive SA/central SA: 29/29). Over an average follow-up of 1,170±763 days, 32 patients died. By Kaplan-Meier analysis, there was no significant difference in deaths of patients with and without SA (χ2=2.82, P=0.093). On the other hand, the mortality in patients with lower averaged SpO2 was significantly higher than in those with higher averaged SpO22=14.7, P<0.001) and that was the only independent variable related to death in multivariate Cox proportional hazards analysis.

    Conclusions: SA in patients with PAH was not associated with worse prognosis, unlike left ventricular heart failure, but nocturnal hypoxemia was related to poor prognosis.

Valvular Heart Disease
  • Taishi Okuno, Keita Koseki, Toru Nakanishi, Kai Ninomiya, Daijiro Tomi ...
    Article type: ORIGINAL ARTICLE
    Subject area: Valvular Heart Disease
    2018 Volume 82 Issue 12 Pages 3082-3089
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: October 05, 2018
    JOURNAL FREE ACCESS FULL-TEXT HTML

    Background: Obesity has previously been identified as an indicator of good prognosis in patients undergoing transcatheter aortic valve implantation (TAVI), an association known as the “obesity paradox”. We investigated whether abdominal total fat area (TFA), visceral fat area (VFA), or subcutaneous fat area (SFA) are prognostic indicators of long-term clinical outcome in patients undergoing TAVI.

    Methods and Results: We retrospectively analyzed 100 consecutive patients who underwent TAVI between December 2013 and April 2017. TFA, VFA, and SFA were measured from routine pre-procedural computed tomography (CT). Patients were divided into 2 groups according to median TFA, VFA, or SFA, and we investigated the association of abdominal fat area with adverse clinical events, including all-cause death and re-hospitalization due to worsening heart failure. At a median follow-up of 665 days, patients with higher SFA had significantly lower incidence of the composite outcome and all-cause death compared with patients with lower SFA (15.0% vs. 37.7%, P=0.025; and 8.9% vs. 23.7%, P=0.047, respectively). In contrast, patients with higher TFA or VFA did not show significant reduction in the incidences of the composite outcome or all-cause mortality.

    Conclusions: CT-derived SFA had prognostic value in patients undergoing TAVI.

  • Kizuku Yamashita, Tomoyuki Fujita, Satsuki Fukushima, Yusuke Shimahara ...
    Article type: ORIGINAL ARTICLE
    Subject area: Valvular Heart Disease
    2018 Volume 82 Issue 12 Pages 3090-3099
    Published: November 24, 2018
    Released on J-STAGE: November 24, 2018
    Advance online publication: October 05, 2018
    JOURNAL FREE ACCESS FULL-TEXT HTML
    Supplementary material

    Background: In patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS), a sigmoid septum, characterized by subaortic interventricular hypertrophy, often results in the need for new pacemaker implantation (PMI). In this study, we reviewed the feasibility and treatment efficacy of TAVR for AS in patients with a sigmoid septum.

    Methods and Results: Between 2011 and 2016, 48 patients (25.4%; mean age 84.9±5.4 years; 9 males) with a sigmoid septum and 141 (74.6%; mean age 82.9±5.5 years; 61 males) without underwent TAVR. Their operative outcomes, echocardiographic and electrocardiographic findings, and long-term outcomes were retrospectively compared. Second TAVR because of valve malposition was performed in 3 patients with a sigmoid septum (6.3%) and in 2 patients without a sigmoid septum (1.4%), with no significant difference between the 2 groups. Although there was no significant difference in valve hemodynamics between the 2 groups, sigmoid septum and deep implantation (implantation depth ≥10 mm) were independent predictors of new PMI following TAVR.

    Conclusions: Although a sigmoid septum did not preclude the feasibility, safety, or efficacy of TAVR for severe AS, its presence was associated with new PMI. Our approach to TAVR in patients with a sigmoid septum may contribute to clinical outcomes comparable to those of patients without this pathology.

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