Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 86, Issue 7
Displaying 1-20 of 20 articles from this issue
Focus on issue: Heart Failure and Cardiomyopathy
Reviews
  • Lillian Benck, Takuma Sato, Jon Kobashigawa
    Article type: REVIEW
    2022 Volume 86 Issue 7 Pages 1061-1067
    Published: June 24, 2022
    Released on J-STAGE: June 24, 2022
    Advance online publication: August 21, 2021
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    Despite the overall success of heart transplantation as a definitive treatment for endstage heart failure, cardiac allograft rejection remains an important cause of morbidity and mortality. Endomyocardial biopsy has been the standard of care for rejection monitoring, but is associated with several diagnostic limitations and serious procedural complications. The use of molecular diagnostics has emerged over the past decade as a tool to potentially circumvent some of these limitations. We present an update on novel molecular approaches to detecting transplant rejection, focusing on 4 categories: microarray technology, gene expression profiling, cell-free DNA and microRNA.

Original Articles
Worsening Heart Failure
  • Koichiro Kinugawa, Eisuke Nakata, Takahiro Hirano, Seongryul Kim
    Article type: ORIGINAL ARTICLE
    Subject area: Worsening Heart Failure
    2022 Volume 86 Issue 7 Pages 1068-1078
    Published: June 24, 2022
    Released on J-STAGE: June 24, 2022
    Advance online publication: March 10, 2022
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    Supplementary material

    Background: OPC-61815, a prodrug of tolvaptan, is an injectable aquaretic drug. This study evaluated the tolerability of OPC-61815 in patients with congestive heart failure (CHF) who had difficulty with, or were incapable of, oral intake in a multicenter, uncontrolled, open-label Phase III study.

    Methods and Results: Forty-five patients were enrolled at 30 Japanese sites. OPC-61815 infusion was administered once daily; the 8 mg initial dose could be increased to 16 mg if the dose escalation criteria were met. Patients were treated for up to 5 days. Thirty-eight patients maintained the 8-mg dose and 7 had a dose increase to 16 mg; 41 completed the trial (34 completed early). One patient had mild hypernatremia. No significant safety concerns were observed with OPC-61815 administration at a starting dose of 8 mg and with dose escalation in accordance with the protocol-specified criteria. Treatment resulted in weight decrease (−3.01 kg); improvement or disappearance rates for other CHF symptoms (including edema, dyspnea, orthopnea, pulmonary congestion, and rales) indicated that treatment was effective. Urine excretion was increased 0–1 h after OPC-61815 administration and reached a maximum level at 1–2 h.

    Conclusions: The tolerability of once daily (up to 5 days) intravenous OPC-61815 (8 mg or 16 mg) was confirmed in patients with CHF who had difficulty with, or were incapable of, oral intake.

  • Kotaro Nochioka
    Article type: EDITORIAL
    2022 Volume 86 Issue 7 Pages 1079-1080
    Published: June 24, 2022
    Released on J-STAGE: June 24, 2022
    Advance online publication: May 11, 2022
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  • Mika Sakoda, Hidetsugu Asanoi, Tomohito Ohtani, Kei Nakamoto, Daisuke ...
    Article type: ORIGINAL ARTICLE
    Subject area: Worsening Heart Failure
    2022 Volume 86 Issue 7 Pages 1081-1091
    Published: June 24, 2022
    Released on J-STAGE: June 24, 2022
    Advance online publication: December 11, 2021
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    Background: Early detection of worsening heart failure (HF) with a telemonitoring system crucially depends on monitoring parameters. The present study aimed to examine whether a serial follow up of all-night respiratory stability time (RST) built into a telemonitoring system could faithfully reflect ongoing deterioration in HF patients at home and detect early signs of worsening HF in a multicenter, prospective study.

    Methods and Results: Seventeen subjects with New York Heart Association class II or III were followed up for a mean of 9 months using a newly developed telemonitoring system equipped with non-attached sensor technologies and automatic RST analysis. Signals from the home sensor were transferred to a cloud server, where all-night RSTs were calculated every morning and traced by the monitoring center. During the follow up, 9 episodes of admission due to worsening HF and 1 episode of sudden death were preceded by progressive declines of RST. The receiver operating characteristic curve demonstrated that the progressive or sustained reduction of RST below 20 s during 28 days before hospital admission achieved the highest sensitivity of 90.0% and specificity of 81.7% to subsequent hospitalization, with an area under the curve of 0.85.

    Conclusions: RST could serve as a sensitive and specific indicator of worsening HF and allow the detection of an early sign of clinical deterioration in the telemedical management of HF.

Cardiomyopathy
  • Keiko Ohta-Ogo, Yasuo Sugano, Soshiro Ogata, Takafumi Nakayama, Takahi ...
    Article type: ORIGINAL ARTICLE
    Subject area: Cardiomyopathy
    2022 Volume 86 Issue 7 Pages 1092-1101
    Published: June 24, 2022
    Released on J-STAGE: June 24, 2022
    Advance online publication: March 10, 2022
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    Supplementary material

    Background: Dilated cardiomyopathy (DCM) associated with inflammation is diagnosed by endomyocardial biopsy; patients with this have a poorer prognosis than patients without inflammation. To date, standard diagnostic criteria have not been established.

    Methods and Results: This study analyzed clinical records and endomyocardial biopsy samples of 261 patients with DCM (201 males, median left ventricular ejection fraction; 28%) from 8 institutions in a multicenter retrospective study. Based on the European Society of Cardiology criteria and CD3 (T-lymphocytes) and CD68 (macrophages) immunohistochemistry, 48% of patients were categorized as having inflammatory DCM. For risk-stratification, we divided patients into 3 groups using Akaike Information Criterion/log-rank tests, which can determine multiple cut-off points: CD3+-Low, <13/mm2(n=178, 68%); CD3+-Moderate, 13–24/mm2(n=58, 22%); and CD3+-High, ≥24/mm2(n=25, 10%). The survival curves for cardiac death or left ventricular assist device implantation differed significantly among the 3 groups (10-year survival rates: CD3+-Low: 83.4%; CD3+-Moderate: 68.4%; CD3+-High: 21.1%; Log-rank P<0.001). Multivariate Cox analysis revealed CD3+count as a potent independent predictive factor for survival (fully adjusted hazard ratio: CD3+-High: 5.70, P<0.001; CD3+-Moderate: 2.64, P<0.01). CD3+-High was also associated with poor left ventricular functional and morphological recovery at short-term follow up.

    Conclusions: Myocardial CD3+T-lymphocyte infiltration has a significant prognostic impact in DCM and a 3-tiered risk-stratification model could be helpful to refine patient categorization.

    Editor's pick

    Circulation Journal Awards for the Year 2022
    Second Place in the Clinical Investigation Section

  • Naoki Shibata, Hiroaki Hiraiwa, Shingo Kazama, Yuki Kimura, Takashi Ar ...
    Article type: ORIGINAL ARTICLE
    Subject area: Cardiomyopathy
    2022 Volume 86 Issue 7 Pages 1102-1112
    Published: June 24, 2022
    Released on J-STAGE: June 24, 2022
    Advance online publication: January 27, 2022
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    Supplementary material

    Background: Many patients with dilated cardiomyopathy (DCM) progress to heart failure (HF), although some demonstrate left ventricular (LV) reverse remodeling (LVRR), which is associated with better outcomes. The pulmonary artery diameter (PAD) to ascending aortic diameter (AoD) ratio has been used as a prognostic predictor in patients with HF, although this tool’s usefulness in predicting LVRR remains unknown.

    Methods and Results: Data from a prospective observational study of 211 patients diagnosed in 2000–2020 with DCM were retrospectively analyzed. Sixty-nine patients with New York Heart Association class I or II HF were included. LVRR was observed in 23 patients (33.3%). The mean LV ejection fraction (29%) and LV end-diastolic dimension (64.5 mm) were similar in patients with and without LVRR. The PAD/AoD ratio was significantly lower in patients with LVRR than those without (81.4% vs. 92.4%, respectively; P=0.003). The optimal PAD/AoD cut-off value for detecting LVRR was 0.9 according to the receiver operating characteristic curve analysis. Multivariate analysis identified a PAD/AoD ratio ≥0.9 as an independent predictor of presence/absence of LVRR. Cardiac events were significantly more common in patients with a PAD/AoD ratio ≥0.9 than those with a ratio <0.9, after a median follow up of 2.5 years (log-rank, P=0.007).

    Conclusions: The PAD/AoD ratio can predict LVRR in patients with DCM.

  • Masato Nishi, Seiji Takashio, Mami Morioka, Akira Fujiyama, Naoya Naka ...
    Article type: ORIGINAL ARTICLE
    Subject area: Cardiomyopathy
    2022 Volume 86 Issue 7 Pages 1113-1120
    Published: June 24, 2022
    Released on J-STAGE: June 24, 2022
    Advance online publication: May 21, 2022
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    Supplementary material

    Background: The accurate sensitivity of amyloid deposition in extracardiac tissue (subcutaneous tissue and gastrointestinal tract) has not been evaluated in transthyretin amyloidosis cardiomyopathy (ATTR-CM) patients. This study aimed to evaluate the sensitivity of amyloid deposition in obtained endomyocardial and extracardiac biopsies.

    Methods and Results: This study retrospectively evaluated 175 consecutive ATTR-CM patients (wild-type [ATTRwt]: 134, hereditary [ATTRv]: 41) who had positive findings on 99 mTc-labeled pyrophosphate (99 mTc-PYP) scintigraphy and underwent tissue biopsy of at least one organ (subcutaneous tissue, gastrointestinal tract, and endomyocardium). Amyloid deposition was observed in the subcutaneous tissue of 57/150 patients (38%), gastrointestinal tract of 80/131 patients (61%), and endomyocardium of 108/109 patients (99%). Compared to patients with ATTRv, ATTRwt had significantly lower sensitivity in subcutaneous tissue (73% vs. 25%, P<0.01) and tended to be lower in the gastrointestinal tract (74% vs. 57%, P=0.08) biopsies. Among 124 patients who underwent both subcutaneous tissue and gastrointestinal tract biopsies, amyloid was detected in at least 1 specimen in 91 (73%) patients. The sensitivity of the combination of extracardiac biopsies was 66% and 94% in ATTRwt-CM and ATTRv-CM, respectively. Multivariate analysis reveals that ATTRv was the only significant predictor of amyloid deposition in the subcutaneous tissue.

    Conclusions: Subcutaneous tissue and gastrointestinal tract biopsy sensitivity are inadequate, especially in patients with ATTRwt; however, the combination of these extracardiac biopsies contributes to increased sensitivity in patients with positive 99 mTc-PYP scintigraphy findings.

  • Yuri Ochi, Toru Kubo, Yuichi Baba, Kenta Sugiura, Kazuya Miyagawa, Tat ...
    Article type: ORIGINAL ARTICLE
    Subject area: Cardiomyopathy
    2022 Volume 86 Issue 7 Pages 1121-1128
    Published: June 24, 2022
    Released on J-STAGE: June 24, 2022
    Advance online publication: May 21, 2022
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    Background: Tafamidis has emerged as an effective treatment for patients with wild-type transthyretin cardiac amyloidosis (ATTRwt CA). The early experience of tafamidis treatment for Japanese patients with ATTRwt CA is reported here.

    Methods and Results: Over the past 2 years, in 82 patients with ATTRwt CA (mean age of 81.7±6.0 years), tafamidis treatment was initiated for 38 patients. The remaining 44 patients were not administered tafamidis. The most frequent reason for non-administration of tafamidis was advanced heart failure and the second most reason was the patient’s frailty. In patients who received tafamidis treatment, there was no discontinuation of tafamidis due to adverse events, the rate of cardiovascular-related hospitalizations per year was 0.19, and the 1-year survival rate was 92%. In the patients who continued tafamidis for 12–18 months, there was no significant deterioration from baseline for high-sensitivity cardiac troponin T level, plasma B-type natriuretic peptide level, left ventricular ejection fraction, inter-ventricular septum wall thickness, or value of left ventricular longitudinal strain.

    Conclusions: Tafamidis treatment was introduced for approximately half of the study patients with ATTRwt CA in real-world practice. Tafamidis is likely to be safe and may maintain the status of disease severity in the short-term in selected Japanese patients with ATTRwt CA. Further research is needed to determine appropriate patient selection for tafamidis treatment and efficacy of tafamidis in the long term.

Population Science
  • Dae-Young Kim, Min Ji Kim, Jiwon Seo, Iksung Cho, Chi Young Shim, Geu- ...
    Article type: ORIGINAL ARTICLE
    Subject area: Population Science
    2022 Volume 86 Issue 7 Pages 1129-1136
    Published: June 24, 2022
    Released on J-STAGE: June 24, 2022
    Advance online publication: December 08, 2021
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    Supplementary material

    Background: Left atrial appendage occlusion (LAAO) plays an important role in preventing stroke in patients with atrial fibrillation. However, LAAO may interact unfavorably with left atrial (LA) compliance and reservoir function and thus increase the risk of heart failure (HF). The purpose of this study was to identify predictors of subsequent HF after successful LAAO.

    Methods and Results: A total of 98 patients (mean age 70±9 years, 68% male) who had undergone LAAO were included. The primary endpoint was unexpected HF admission after LAAO. During a mean period of 36±26 months, 16 of the 98 patients (16%) experienced hospital HF admission. In multivariate analysis, higher E/e’ (hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.02–1.20, P=0.014), higher left ventricular mass index (HR 1.02, 95% CI 1.00–1.03, P=0.023), history of HF (HR 4.78, 95% CI 1.55–14.7, P=0.006), and lower LA strain (HR 0.80, 95% CI 0.70–0.93, P=0.003) were independently associated with hospital HF admission. Patients with LAAO had a significantly higher incidence of subsequent HF than the control group after propensity score matching (P=0.046).

    Conclusions: LAAO increases the occurrence of HF, and it is not uncommon after successful LAAO. A previous history of HF, left ventricular mass index, E/e’, and abnormal LA strain are independently associated with the development of HF. These parameters should be considered before attempting LAAO.

Rapid Communications
  • Yugo Yamashita, Sen Yachi, Makoto Takeyama, Yuji Nishimoto, Ichizo Tsu ...
    Article type: RAPID COMMUNICATION
    2022 Volume 86 Issue 7 Pages 1137-1142
    Published: June 24, 2022
    Released on J-STAGE: June 24, 2022
    Advance online publication: June 03, 2022
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    Background: The potential benefit of therapeutic-dose anticoagulation for critically ill patients with coronavirus disease 2019 (COVID-19) is still controversial.

    Methods and Results: In the CLOT-COVID study, 225 patients with severe COVID-19 on admission requiring mechanical ventilation or extracorporeal membrane oxygenation were divided into patients with therapeutic-dose anticoagulation (N=110) and those with prophylactic-dose anticoagulation (N=115). There was no significant difference in the incidence of thrombosis between the groups (9.1% vs. 7.8%, P=0.73).

    Conclusions: Among a cohort of critically ill patients with COVID-19, approximately half received therapeutic-dose anticoagulation, although it did not show a potential benefit compared with prophylactic-dose anticoagulation.

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