International Heart Journal
Online ISSN : 1349-3299
Print ISSN : 1349-2365
ISSN-L : 1349-2365
Volume 63, Issue 1
Displaying 1-30 of 30 articles from this issue
Review Article
  • Tsutomu Sunayama, Yuya Matsue, Taishi Dotare, Daichi Maeda, Takashi Is ...
    2022 Volume 63 Issue 1 Pages 1-7
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    Heart failure and frailty share aging as a strong risk factor. The prevalence of frailty has been shown to be particularly high in elderly patients with heart failure. Moreover, it is important not to confine frailty to physical aspects. Rather, it should be considered to consist of multiple domains, including physical disability, psychiatric disorders, cognitive impairment, depression, and social disconnection. Development of interventions that can improve frailty domains are not well established, although observational studies have evaluated the association of various frailty domains and their prognostic impact. Some interventions, including resistance exercise, functional exercise, and respiratory muscle training have been demonstrated to hold potential for improving physical frailty. In terms of cognitive dysfunction, previous studies have demonstrated that exercise therapy is also effective for cognitive dysfunction. The social domain of frailty is one of the least investigated domains, particularly in patients with heart failure. However, heart failure is also strongly associated with physical frailty and cognitive impairment and has a poor prognosis in old patients. The prevalence of social frailty in elderly patients who need hospitalization due to heart failure is higher than previously thought. Very few studies have tested interventions targeting social frailty. Frailty and heart failure affect each other, and both are becoming increasingly important in society. In this article, we review the physical, cognitive, and social domains of frailty and the possible interventions to improve them in patients with heart failure.

    Editor's pick

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Clinical Studies
  • Xiangdong Meng, Mingming Fu, Jianjie Wang, Hui Xu
    2022 Volume 63 Issue 1 Pages 8-14
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    Acute pulmonary embolism (PE) remains a significant cause of cardiovascular morbidity and mortality worldwide. Brain natriuretic peptide (BNP) combined with catheter-directed therapy (CDT) may improve right ventricular (RV) dysfunction and stabilize hemodynamics in acute PE.

    We retrospectively studied 159 patients with confirmed acute PE who were treated with CDT and admitted to the intensive care unit of our department between September 2016 and May 2020. The patients were divided into the control group and the rhBNP group based on whether to receive recombinant human BNP treatment (rhBNP) or not. The basic characteristics of the patients between the control group and the rhBNP group was systematically compared during admission and follow-up. Risk factors for all-cause mortality within 30 days were determined using multivariate logistic regression analysis.

    Respiratory rate was found to be significantly lower in the rhBNP group than in the control group. Patients in the rhBNP group had significantly lower levels of white blood cell, C-reactive protein (CRP), D-dimers, troponin I, creatinine, and N-terminal (NT) -proBNP compared with those in the control group. Levels of tricuspid annular plane systolic excursion were significantly higher in the rhBNP group than in the control group. The percentage of patients with rehospitalization readmission due to PE differed significantly between the control group and the rhBNP group. On the basis of the multivariate regression analysis, CRP, creatinine, troponin I, and NT-proBNP were independent factors of all-cause mortality in 30 days.

    rhBNP is effective in the treatment of patients with RV dysfunction caused by acute PE who underwent CDT, which may be an alternative treatment option for improving clinical prognosis.

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  • Joh Akama, Takeshi Shimizu, Takuya Ando, Fumiya Anzai, Yuuki Muto, Yus ...
    2022 Volume 63 Issue 1 Pages 15-22
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS
    Supplementary material

    The Patterns of non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) bleeding risk score has been proposed to predict the risk of bleeding events after percutaneous coronary intervention (PCI). However, the prognostic value of the PARIS bleeding risk score for long term all-cause mortality, cardiac mortality and hospitalization due to heart failure has not yet been evaluated. Therefore, the aim of the present study was to evaluate the prognostic value of the PARIS bleeding risk score for all-cause and cardiac mortalities and hospitalization due to heart failure after PCI. Consecutive 1061 patients who had undergone PCI were divided into 3 groups based on the PARIS bleeding risk score; low (n = 112), intermediate (n = 419) and high-risk groups (n = 530). We prospectively followed up the 3 groups for all-cause and cardiac mortalities and hospitalization due to heart failure. Kaplan-Meier analysis revealed that all of the outcomes were highest in the high-risk group among the 3 groups (P < 0.001, P < 0.001 and P < 0.001 respectively). Multivariable Cox proportional hazard analysis, adjusted for confounding factors, revealed that all-cause mortality of the intermediate or high-risk groups was higher than those of the low-risk group (adjusted hazard ratio 6.06 and 12.50, P = 0.013 and P < 0.001, respectively). The PARIS bleeding risk score is a significant indicator of prognosis for all-cause mortality in patients after PCI.

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  • One-Year Outcomes of the First-in-Man Study
    Yuliang Long, Wenzhi Pan, Cuizhen Pan, Wei Li, Lai Wei, Yongjian Wu, Y ...
    2022 Volume 63 Issue 1 Pages 23-29
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    The ValveClamp system is a novel edge-to-edge mitral valve repair system that is designed for ease of operation. We aimed to report the 1-year outcomes of the early feasibility study of this system.

    Patients with severe degenerative mitral regurgitation (MR) at higher surgical risk and who received transapical ValveClamp implantation were followed for 1 year for clinical and echocardiographic outcomes.

    Twelve patients (mean age, 76.5 ± 6.3 years; mean Society of Thoracic Surgery score, 6.9 ± 1.9%) were enrolled at three sites in China. At 1 year, no patient died, received reoperation, or had long-term complications. Of the 12 patients with MR of 3+ or 4+ at baseline, 11 patients (91.67%) remained with MR ≤ 2+ at 1 year, and no patient had mitral stenosis. Significant reductions in maximum MR area (from 15.1 ± 6.51 cm2 to 4.45 ± 1.85 cm2, P < 0.001), effective orifice area (from 4.34 ± 0.34 cm2 to 2.38 ± 0.45 cm2, P < 0.001), and vena contracta width (from 8.03 ± 1.11 to 3.38 ± 2.11 mm, P < 0.001) were observed. The left cardiac dimensions were decreased, especially the mitral valve annulus diameter (from 34.79 ± 4.27 mm to 31.42 ± 2.81 mm, P < 0.05). Of the 12 patients with baseline New York Heart Association functional class III/IV, all patients experienced an improvement of at least one class (P < 0.05).

    Our study provides evidence that transapical ValveClamp implantation in high-risk patients with severe degenerative MR is safe and feasible, with good efficacy in the mid-long term.

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  • Yuntao Lu, Ye Yang, Huan Liu, Wenshuo Wang, Jinmiao Chen, Shun Liu, Li ...
    2022 Volume 63 Issue 1 Pages 30-35
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    Patients with aortic stenosis and low left ventricular ejection fraction (LVEF) would benefit from transcatheter aortic valve replacement. However, the safety and efficacy of transcatheter aortic valve replacement in patients with aortic regurgitation and left ventricular dysfunction remains unknown.

    We defined LVEF < 50% as left ventricular dysfunction. A total of 27 symptomatic patients with aortic regurgitation and ejection fraction < 50% underwent transcatheter aortic valve replacement using the J-Valve™ system (JieCheng Medical Technology Co, Ltd, Suzhou, China) in Zhongshan Hospital, Fudan University, from May 2014 to June 2019. Procedural and postoperative clinical outcomes were analyzed according to Valve Academic Research Consortium-2 (VARC-2) criteria.

    All patients (eight females; 70.6 ± 7.1 years) were considered to be at least intermediate surgical risk and/or severe comorbidity precluding for surgical aortic valve replacement (logistic European System for Cardiac Operative Risk Evaluation, 16.8 ± 9.5%, range 4.6% to 37.9%) by a multidisciplinary heart team. Transapical implantations were successful in 26 (96.3%) patients. All-cause mortality was 3.7% in the latest follow-up (25-590 days, median 369 days). Significant improvements in LVEF, left ventricular end-diastolic, and systolic dimensions were observed after procedure (from 40.3 ± 6.7% to 50.8 ± 10.5%, P < 0.001; from 65.1 ± 8.9 mm to 56.0 ± 9.6 mm, P = 0.002; from 52.2 ± 9.8 mm to 35.9 ± 13.4 mm, P < 0.001, respectively). No patient had aortic stenosis and paravalvular leak more than moderate and heart function improvement was obtained in the majority of patients at 1-year follow-up.

    Transcatheter aortic valve replacement using the J-Valve™ system is a reasonable alternative for patients with aortic regurgitation and left ventricular dysfunction regarding promising short-term outcomes.

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  • A Systematic Review and Meta-analysis
    Chuyan Long, Xiao Liu, Qinmei Xiong, YuHao Su, Kui Hong
    2022 Volume 63 Issue 1 Pages 36-42
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS
    Supplementary material

    Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy, and it often has a poor outcome. Sex differences in the prognosis of patients with DCM remain controversial. The present meta-analysis aimed to investigate whether sex plays a role in the outcome of patients with DCM and to provide real-world information on these potential sex differences for physicians and patients.

    We searched the PubMed, Cochrane, and EMBASE databases for published cohort studies up to February 16, 2020 that reported sex-specific prognostic outcomes (e.g., all-cause mortality; sudden cardiac death (SCD) ) in patients with DCM.

    Finally, 5 clinical cohort studies with a total of 5,709 patients were included. The results showed that males with DCM had a higher risk of all-cause mortality than females (HR: 1.61, 95% CI: 1.36~1.90; P < 0.00001). Next, the included studies were divided into short-term (< 5 years) and long-term (≥ 5 years) outcome groups by follow-up duration. Males showed a higher risk of all-cause mortality in both subgroups (< 5 years, HR: 1.59, 95% CI: 1.13~2.23; P = 0.008; ≥ 5 years, HR: 1.65, 95% CI: 1.33~2.05; P < 0.00001). In addition, the risks of SCD (HR: 1.80, 95% CI: 1.63~2.61; P = 0.002) and cardiovascular mortality in males (HR: 1.67, 95% CI: 1.25~2.23; P = 0.0005) were higher than those in females.

    The evidence from the published studies suggested that compared with females, males with DCM had an increased risk of all-cause mortality, cardiovascular mortality, and SCD.

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  • Teruhiko Imamura, Masakazu Hori, Nikhil Narang, Stephanie Besser, Koic ...
    2022 Volume 63 Issue 1 Pages 43-48
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    The prognostic impact of mitral inflow wave overlap during ivabradine therapy in patients with heart failure with reduced ejection fraction (HFrEF) remains to be unknown. Thus, in this study, we have retrospectively examined consecutive inpatients with HFrEF admitted with decompensated heart failure who continued ivabradine following the index discharge. Ideal heart rate (HR), at which echocardiographic mitral inflow wave overlap is theoretically 0, was retrospectively calculated as follows: 96 - 0.13 × (deceleration time [msec]). HR difference was then calculated as follows: actual HR - ideal HR. The association between the HR difference at index discharge and a composite outcome of cardiovascular death and heart failure readmissions was investigated. In total, 16 patients (68 [47, 75] years old, 11 men, median left ventricular ejection fraction 28% [22%, 35%]) were included in this study for analysis. Baseline actual HR was determined to be 88 (81, 93) bpm, whereas the ideal HR was calculated as 75 (73, 76) bpm. Following the initiation of ivabradine, actual HR at index discharge was 75 (64, 84) bpm. Patients with optimal HR (actual HR - ideal HR < ± 10 bpm; n = 9) were found to have experienced a lower incidence of the composite endpoint (40% versus 100%, P = 0.013) compared with those with sub-optimal HR (n = 7) with a hazard ratio of 0.10 (95% confidence interval 0.01-0.91) adjusted for actual HR at index discharge. In conclusion, HR modulation therapy using ivabradine may improve outcomes in patients with HFrEF if individualized ideal HR was achieved.

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  • Evidence from a Cohort of 77 Cardiac Biopsy Cases
    Kanae Hasegawa, Hiroyasu Uzui, Yoshitomo Fukuoka, Dai Miyanaga, Yuichi ...
    2022 Volume 63 Issue 1 Pages 49-55
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    The diagnosis of cardiac amyloidosis is frequently delayed because histological confirmation is often challenging. Few studies have attempted to clarify the utility and safety of abdominal fat pad fine-needle aspiration (FPFNA) for an initial screening test in patients with suspected cardiac amyloidosis.

    This study included 77 consecutive patients with suspected non-ischemic cardiomyopathy who had left ventricular dysfunction and/or hypertrophy. All patients underwent abdominal FPFNA and an endomyocardial biopsy. In all patients, the abdominal FPFNA could be performed within less than 5 minutes with no complications; however, in 1 patient (1.3%), the obtained specimen was too small to evaluate. Among the remaining 76 patients, 5 (6.6%) were positive for amyloid (FPFNA[+]) and 7 (9.2%), including the 5 FPFNA[+], were diagnosed with cardiac amyloidosis (AL = 1, ATTR = 6) by endomyocardial biopsy. Positive abdominal FPFNAs indicated cardiac amyloidosis with high accuracy (sensitivity, 71.4%; specificity, 100%).

    Positive abdominal FPFNAs are directly linked to diagnoses of cardiac amyloidosis. Abdominal FPFNA is simple and useful for the initial screening test for cardiac amyloidosis in patients with non-ischemic cardiomyopathy.

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  • Teruhiko Imamura, Koichiro Kinugawa, Nikhil Narang, Hidefumi Nishida, ...
    2022 Volume 63 Issue 1 Pages 56-61
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    Optimal heart rate (HR) is a promising therapeutic target in patients with heart failure with reduced ejection fraction. Nevertheless, the implication of optimal HR in patients with left ventricular assist devices (LVAD) remains unknown. The cohort included consecutive patients with sinus rhythm undergoing LVAD implantation between 2014 and 2018. Ideal HR was calculated as follows: 93 − 0.13 × (deceleration time [msec]). The impact of "HR difference," defined as an HR difference between the actual HR at discharge and the calculated ideal HR, on the 1-year mortality and heart failure readmissions was investigated. A total of 143 patients (55 years old, 101 men) was identified and tertiled considering their HR differences: (1) the optimal HR group (n = 49; HR difference < 27 bpm), (2) the suboptimal HR group (n = 47; HR difference = 27-42 bpm), and (3) the nonoptimal HR group; HR difference (n = 47; HR difference > 43 bpm). The nonoptimal HR group had a significantly higher 1-year cumulative incidence of the primary endpoint compared with the optimal HR group (38% versus 16%, P = 0.029) with a hazard ratio of 1.69 (95% confidence interval 1.02-2.57) adjusted for 6 potential confounders. In conclusion, nonoptimized HR negatively affected clinical outcomes in LVAD patients. The implication of deceleration time-guided HR optimization in LVAD patients should be further investigated.

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  • Shou Ogawa, Yuji Nagatomo, Makoto Takei, Mike Saji, Ayumi Goda, Takash ...
    2022 Volume 63 Issue 1 Pages 62-72
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    Although heart failure with preserved ejection fraction (HFpEF) has a highly variable phenotype, heterogeneity in left ventricular chamber size (LVCS) and its association with long-term outcome have not been thoroughly investigated. The present study sought to determine the impact of LVCS on clinical outcome in HFpEF.

    A total of 1505 consecutive HFpEF patients admitted to hospitals in the multicenter WET-HF Registry for acute decompensated HF (ADHF) between 2006 and 2017 were analyzed. The patients (age: 80 [73-86], male: 48%) were divided into larger (L) or smaller (S) LV end-diastolic diameter (LVEDD) groups by the median value 45 mm.

    Younger age, male sex, higher body mass index, more favorable nutritional status, valvular etiology, and lower LVEF were associated with larger LVEDD. After propensity matching (399 pairs), the L group showed a larger left atrial diameter, E/e', and tricuspid regurgitation pressure gradient and greater severity of mitral regurgitation. The L group had a higher rate of composite endpoint of all-cause death and ADHF re-admission (P = 0.021) and was an independent predictor. On the other hand, in the pre-matched cohort, the S group rather showed higher in-hospital (4% versus 2%. P = 0.004) and post-discharge mortality (P = 0.009).

    In HFpEF, LVCS was affected by demographic and cardiac parameters. After adjustment for demographic parameters, larger LVCS was associated with worse clinical outcome. Higher mortality in the S group in the pre-matched cohort might be related to the demographic factors suggesting frailty and/or sarcopenia.

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  • Masakazu Hori, Teruhiko Imamura, Atsuko Fukuo, Takuya Fukui, Takatosh ...
    2022 Volume 63 Issue 1 Pages 73-76
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    Remote dielectric sensing (ReDS) is a recently introduced non-invasive electromagnetic-based device used to quantify lung fluid levels. Nevertheless, its inter-rater and intra-rater reliability remain uncertain. In 10 healthy volunteers, ReDS values were measured three times successively by the officially trained expert examiner to validate intra-rater reliability. Similar measures were performed by a total of three examiners to validate inter-rater reliability. Intra-class correlation (ICC) was applied to validate each reliability. Ten healthy volunteers [median 34 (32, 40) years old, 10 men, body mass index 23.0 (21.2, 23.9) ] were included. Median ReDS value was 28% (25%, 31%). For the intra-rater reliability, ICC (1, 1) and ICC (1, 3) were 0.966 and 0.988, respectively (P < 0.001). For the inter-rater reliability, ICC (2, 1) and ICC (2, 3) were 0.683 and 0.866, respectively (P < 0.001). Given almost perfect intra-rater reliability, an examiner does not need to repeat ReDS measurement. Given substantial inter-rater reliability, ReDS measurements had better be measured by multiple examiners if possible.

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  • Akihiro Hirashiki, Atsuya Shimizu, Noriyuki Suzuki, Kenichiro Nomoto, ...
    2022 Volume 63 Issue 1 Pages 77-84
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    Cerebral white matter hyperintensity (WMH) is highly prevalent among older adults. There is little information about the relationship among WMH extent, frailty status, and exercise capacity in older adults with cardiovascular disease (CVD). We assessed the association of WMH with frailty and exercise capacity in CVD patients.

    Seventy-eight stable older adults with CVD were evaluated for WMH, the Kihon Checklist (KCL), short physical performance battery score (SPPB), and cardiopulmonary exercise testing. WMH volume was quantified on brain magnetic resonance imaging. Patients were classified into 3 groups (using tertiles of 0.52% and 1.05%) according to WMH as a percentage of intracranial volume (ICV), and their KCL scores and exercise capacities were compared. The 3 WMH/ICV groups were mild (n = 26, 0.26% ± 0.14% of intracranial volume), moderate (n = 26, 0.70% ± 0.15%), and severe (n = 26, 1.75% ± 0.67%). Peak VO2 was 15.2 ± 3.7 mL kg−1 minute−1 (mild group), 12.9 ± 3.5 mL kg−1 min−1 (moderate), and 11.4 ± 2.3 mL kg−1 minute−1 (severe) (mild versus moderate, P = 0.049; mild versus severe, P = 0.001). Multivariate regression analysis showed significant associations of severe WMH/ICV with peak VO2 and SPPB. Cerebral WMH was strongly negatively associated with SPPB and peak VO2. WMH volume may be related to exercise capacity and frailty in stable older adult patients with CVD.

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  • AURORA Study
    Masami Nishino, Akihiro Tanaka, Shodai Kawanami, Hiroki Sugae, Kohei U ...
    2022 Volume 63 Issue 1 Pages 85-90
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    The short-term effectiveness of tolvaptan (TLV) for heart failure (HF) has been established, but the long-term effects are controversial. We investigated HF patients who could not discontinue both loop diuretics and TLV at discharge from AURORA (Acute Heart Failure Registry in Osaka Rosai Hospital). We compared the following factors at discharge between the RH group, consisting of patients with rehospitalizations due to worsening HF within 1 year after discharge (RH group), and non-RH group: age, gender, blood pressure, history of HF admission, electrocardiogram and echocardiographic parameters, atherosclerotic risk factors, laboratory data, and medications. Furthermore, we compared the effects of long-term low-dose TLV (≤ 7.5 mg/day) and high-dose TLV on HF rehospitalizations. The RH group consisted of 81 patients (58.7%). A multivariate analysis revealed that a history of HF admission and the TLV dose were independently and significantly associated with 1-year HF rehospitalizations. A receiver operating characteristic curve revealed that 7.5 mg of TLV was a suitable cutoff value for 1-year HF rehospitalizations. The Kaplan-Meier curves demonstrated that the HF rehospitalization free ratio was significantly higher in the low-dose TLV group (≤ 7.5 mg/day) than in high-dose TLV group over 1 year.

    In conclusion, the TLV dose, in addition to a history of HF admission, was associated with 1-year HF rehospitalizations in diuretic-dependent HF patients. In these patients, long-term low-dose TLV (≤ 7.5 mg/day) may be favorable for reducing HF rehospitalizations.

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  • Takashi Oka, Rine Nakanishi, Takayuki Kabuki, Hidenobu Hashimoto, Taka ...
    2022 Volume 63 Issue 1 Pages 91-98
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    Balloon pulmonary angioplasty (BPA) is a robust treatment and has been performed among patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). A lung perfusion scan (LPS) is required for inspection in deciding the curative effect judgment and treatment lesion of BPA. Nevertheless, the impact of BPA in the improvement of right heart system function is not well known. We investigated whether BPA improves right heart function alongside other parameters.

    We studied 20 patients with CTEPH (mean age 63.6 ± 15.9 years, male 30.0%) who underwent BPA. All study sets including right heart catheter, pulmonary angiography, 6-minute walk test (6MWT), blood gas analysis, and LPS were performed before BPA treatment. All parameters using right heart catheter and oxygenation level were measured at room air temperature. Regarding LPS, right ventricular ejection fraction (RVEF) was calculated using the first-pass method. These parameters before BPA were compared with those after BPA.

    In total, 120 BPAs were performed (mean number of procedures/patient; 6.0 ± 2.4 sessions). Per BPA session, 6.0 ± 2.4 areas and 10.0 ± 4.3 lesions were treated with a volume of 181.3 ± 53.5 mL of contrast media. No complication required an invasive procedure. World Health Organization functional class, 6MWT, pulmonary artery pressure, pulmonary vascular resistance, and oxygenation level were significantly improved after BPA. RVEF via LPS was also significantly improved after BPA (45.0 ± 6.2% to 50.6 ± 2.9%, P < 0.001).

    In the present study, we found that RVEF via LPS was improved through appropriate BPA alongside the other parameters. It would be useful to be able to evaluate right heart function.

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  • Masaru Hatano, Kohtaro Abe, George Koike, Tomohiko Takahashi, Grant Tu ...
    2022 Volume 63 Issue 1 Pages 99-105
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    The AMBITION study (NCT01178073) provided the first long-term clinical evidence for initial combination therapy with ambrisentan and tadalafil in patients with pulmonary arterial hypertension (PAH). Nevertheless, predictors of treatment response were not assessed.

    To identify predictors for response to initial combination therapy, we examined data from 302 patients with PAH (World Health Organization Functional Class II or III) who received initial combination therapy from the modified intention-to-treat population of the AMBITION study (n = 605). A responder was defined as not having undergone a clinical failure event. Univariate and multivariate analyses were performed. Multivariate logistic regression with interactive backward selection was used to assess the independent association of potential predictors with response.

    Treatment responders were younger, more often female, and less likely to have comorbidities or a requirement for oxygen therapy, compared with nonresponders. At multivariate analysis, female sex (odds ratio [OR] 2.67; 95% confidence interval [CI] 1.29, 5.52; P = 0.0081), longer 6-minute walk distance (OR 1.01; 95% CI 1.00, 1.01; P = 0.0039), lower baseline log N-terminal-prohormone of brain natriuretic peptide (OR 0.70; 95% CI 0.52, 0.94; P = 0.0190), and aldosterone antagonist use (OR 2.54; 95% CI 1.03, 6.26; P = 0.0436) independently predicted response to initial combination therapy.

    Besides demographic factors, the absence of comorbidities and less severe disease state, and the use of aldosterone antagonist therapy identified patients with PAH most likely to respond to initial combination therapy with ambrisentan and tadalafil. Further study to evaluate the role of aldosterone antagonist therapy in PAH is warranted.

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  • Lingyu Lin, Yanjuan Lin, Yanchun Peng, Xizhen Huang, Xuecui Zhang, Lia ...
    2022 Volume 63 Issue 1 Pages 106-112
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    Advance online publication: January 14, 2022
    JOURNAL FREE ACCESS

    Previous studies have demonstrated that admission hyperglycemia is a predictor of mortality and poor prognosis in patients with cardiovascular diseases, such as acute myocardial infarction. However, the prognostic value of admission hyperglycemia in patients with acute type A aortic dissection (AAAD) has never been explored. To clarify the association between hyperglycemia and in-hospital outcomes, we retrospectively analyzed 734 patients with AAAD. The interest endpoints were in-hospital mortality rate, the duration of intensive care unit and hospital stays, the occurrence of prolonged mechanical ventilation (PMV), and other complications. All patients were divided into the normal blood glucose group (≤ 140 mg/dL) and hyperglycemia group (> 140 mg/dL), to compare the in-hospital outcomes rate in the two groups. There were 531 (72.3%) patients with normal blood glucose levels and 203 (27.7%) patients with hyperglycemia. The in-hospital mortality rate was 21.1%, and no statistically significant differences were found between the two groups (20.3% versus 23.2%, P = 0.403). PMV is the most frequent postoperative complication, the incidence of which was significantly higher in the hyperglycemia group than in the normal blood glucose group (59.6% versus 50.8%, P = 0.040). The logistic regression analysis revealed that hyperglycemia (odds ratio (OR): 1.492; 95% CI: 1.014 to 2.197; P = 0.042) was an independent risk factor for PMV after adjusting for confounding factors. Age (OR: 1.021; 95% CI: 1.006-1.037; P = 0.007) and body mass index (OR: 1.101; 95% CI: 1.051-1.153; P < 0.001) were also associated with PMV. In conclusion, our study showed for the first time that a strong correlation between admission hyperglycemia and increased postoperative PMV in patients with AAAD, but not with in-hospital mortality rate.

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Experimental Studies
  • Haijie Jiang, Yueyan Zhao, Panyang Feng, Yan Liu
    2022 Volume 63 Issue 1 Pages 113-121
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    Advance online publication: January 14, 2022
    JOURNAL FREE ACCESS
    Supplementary material

    Sulfiredoxin1 (Srxn1), an endogenous antioxidant protein, is involved in cardiovascular diseases. In this study, we aimed to investigate the role of Srxn1 in VSMCs and its molecular mechanism. The murine vascular smooth muscle cells MOVAS were treated with different doses of platelet-derived growth factor-BB (PDGF-BB); then, Srxn1 expression was detected using reverse transcription-quantitative polymerase chain reaction and western blot analysis. MTT and wound healing assay were used to examine the effect of Srxn1 on MOVAS cell proliferation and migration. Reactive oxygen species (ROS) production, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity in MOVAS cells were detected using corresponding commercial kits. Moreover, the expression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP-2), and nuclear factor erythroid-2-related factor 2 (Nrf2) /antioxidant response element (ARE) signaling-related proteins was detected using western blot analysis. In our study, PDGF-BB dose-dependently increased Srxn1 expression in MOVAS cells, and Srxn1 expression was increased with time dependence in PDGF-BB-treated MOVAS cells. The knockdown of Srxn1 increased PDGF-BB-induced the proliferation, migration, ROS production, MDA level, and the protein expression of PCNA and MMP-2, as well as decreased SOD activity and the expression of Nrf2/ARE signaling-related proteins in PDGF-BB-stimulated MOVAS cells. However, the overexpression of Srxn1 showed the opposite results to those of knockdown of Srxn1. Moreover, the inhibitory effects of Srxn1 overexpression on PDGF-BB induced proliferation, migration, ROS production, and MDA level and the promotion of Srxn1 overexpression on PDGF-BB induced SOD activity were partially reversed by the knockdown of Nrf2. Srxn1 inhibited PDGF-BB-induced proliferation, migration, and oxidative stress through activating Nrf2/ARE signaling.

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  • Feasibility Study in a Swine Model
    Katsunari Terakawa, Haruo Yamauchi, Yangsin Lee, Minoru Ono
    2022 Volume 63 Issue 1 Pages 122-130
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    Polytetrafluoroethylene (PTFE) is widely used in cardiovascular surgeries; however, postoperative complications such as thrombosis, calcification, and neointimal hyperplasia are yet to be resolved in patients. We developed two types of novel knitted PTFE patches and evaluated them using a swine model. Both patches were composed of knitted PTFE impregnated with micro-PTFE particles, and one of them was pressed after PTFE impregnation. Twenty micromini pigs were used in this study. After left lateral thoracotomy, the new patches (n = 8 for each type of patch) were implanted into the descending aorta and left atrium for the high- and low-pressure models, respectively. Clinically used expanded PTFE (ePTFE) patches were used as the control material (n = 4). The patches were explanted and histopathologically examined at 4, 12, and 24 weeks after implantation. A tensile test was also applied to the high-pressure model at 12 and 24 weeks. As a result, there was no significant difference noted in the tensile test, intimal hyperplasia thickness, or endothelialization among the three patches. In contrast, the degree of macrophage infiltration into the patches and the degree of macrophage, lymphocyte, and granulocyte infiltration outside the patches were lower in the new patches than in the control ePTFE. The degree of cellular infiltration outside new patches decreased over time. There were no significant differences between the two new patch types in these results. In conclusion, our novel knitted PTFE patch showed noninferiority in durability and intensity and less inflammatory responses than a clinically used ePTFE patch.

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  • Yang Cao, Jianting Yao, Weiwei Gao, Zhengyu Cao, Kamal Diabakte, Linxi ...
    2022 Volume 63 Issue 1 Pages 131-140
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    Advance online publication: January 14, 2022
    JOURNAL FREE ACCESS
    Supplementary material

    Atherosclerotic cerebrocardiovascular disease is the major cause of acute ischemic diseases in humans. Impaired efferocytosis contributes to the progression of atherosclerosis. Pathological and apoptotic cells fail to undergo effective phagocytic clearance, leading to increased inflammation and necrotic core formation. Previously, we reported that 5-aminolevulinic acid-mediated sonodynamic therapy (SDT) promotes apoptotic cell efferocytosis via ATP release in atherosclerotic plaques. However, the exact signaling molecule involved in this process is still unknown. In the present study, sinoporphyrin sodium-mediated SDT (DVDMS-SDT) was applied to balloon-denuded rabbits in vivo to observe changes in the composition of atherosclerotic lesions. Cultured human THP-1-derived and mouse peritoneal macrophage-derived foam cells were used for in vitro mechanistic studies. Three days after DVDMS-SDT treatment, macrophage efferocytosis was significantly enhanced whereas local inflammation was attenuated in rabbit atherosclerotic lesions. At days 7 and 28, the histopathological analysis showed that DVDMS-SDT inhibited the progression of atherosclerosis, reduced the macrophage content, and increased the smooth muscle cell content in a time-dependent manner. Mechanistically, DVDMS-SDT activated mitochondria-caspase apoptosis in foam cells. Interestingly, activated by DVDMS-SDT, caspase-3 a key factor of apoptosis, reduced the expression of the anti-phagocytic molecule CD47 in foam cells. Of great importance, the promotion of macrophage efferocytosis by DVDMS-SDT can be eliminated by the overexpression of CD47. Overall, these results demonstrated that DVDMS-SDT effectively boosted efferocytosis via deactivation of CD47 expression, thereby reducing inflammation in advanced atherosclerotic plaques.

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  • Additive Effects to Atrial Fibrillation
    Yu-ki Iwasaki, Akiko Sekiguchi, Reiko Makabe, Takeshi Kato, Takeshi Ya ...
    2022 Volume 63 Issue 1 Pages 141-146
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    We have previously reported that atrial endocardial remodeling is induced by atrial fibrillation (AF), and the endocardial dysfunction may be partly responsible for the thrombus formation in the left atrium associated with AF. However, the relationship between the endocardial dysfunction and the epidemiologically determined risk factors of AF-related strokes, including aging, hypertension, and diabetes mellitus, is yet to be elucidated.

    To test the hypothesis that aging, hypertension, and diabetes mellitus individually impair the atrial endocardial function in conjunction with AF, we have analyzed the expression of the tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) in the atrial endocardium in 30-week-old Wister-Kyoto (WKY), 60-week-old WKY, 30-week-old spontaneously hypertensive rats (SHR), and 30-week Goto-Kakizaki (GK) rats during normal sinus rhythm and after rapid atrial pacing at 1200 bpm for 8 hours, using Western blotting and immunohistochemical analysis. Even during sinus rhythm, the TFPI and TM expressions were noted to be remarkably downregulated in the atrial endocardium among 60-week-old WKY rats. In contrast, in SHR rats, only the TFPI expression has significantly decreased, while TM was preserved to the same level of control 30-week-old WKY rats. Rapid atrial pacing significantly reduced the TM and TFPI expression similarly in each model, thereby augmenting the endocardial dysfunction during normal sinus rhythm individually induced by the risk factors themselves prior to AF.

    Aging and hypertension, both of which are epidemiologically well-known risk factors for strokes in AF, have been associated with a specific atrial endocardial impairment prior to AF that could additionally disturb the antithrombotic function of the atrial endocardium.

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Case Reports
  • A Case Report
    Hidesato Fujito, Daisuke Fukamachi, Naotaka Akutsu, Yuki Saito, Yasuo ...
    2022 Volume 63 Issue 1 Pages 147-152
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    Advance online publication: January 14, 2022
    JOURNAL FREE ACCESS

    Instantaneous wave-free ratio (iFR) is a non-hyperemic coronary physiological index measured during the diastolic wave-free period. Although atrial fibrillation (AF) with beat-to-beat fluctuations can occur during diastole, the feasibility of iFR measurements during AF has previously been demonstrated. However, the effects of coronary circulation during AF on iFR measurements remain unknown. In addition, the pathophysiology of ischemia due to AF tachycardia requires further elucidation. We report a unique case of myocardial ischemia due to rapid AF, as indicated by the iFR pullback measurement and beat-to-beat analysis. When planning revascularization in patients with rapid AF, the ability of iFR to reflect ischemic stress due to AF tachycardia should be considered.

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  • Yumiko Haraguchi, Kohki Nakamura, Mitsuho Inoue, Takehito Sasaki, Kent ...
    2022 Volume 63 Issue 1 Pages 153-158
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    We report a case of an ischemic stroke after a successful catheter ablation of atrial fibrillation (AF) and continuous oral anticoagulation therapy with direct oral anticoagulants (DOACs), which was the trigger for diagnosing antiphospholipid syndrome (APS). A 68-year-old woman underwent catheter ablation of persistent AF and continued oral anticoagulation with edoxaban at a dose of 30 mg once daily after the ablation procedure. An asymptomatic intracerebral hemorrhage was detected by brain computed tomography and magnetic resonance imaging one month post-ablation. Oral anticoagulation with dabigatran at 110 mg twice daily was continued thereafter due to a high stroke risk profile of a CHA2D2-VASc score of 3. Eight months after the procedure, the patient had multiple acute cerebral infarctions despite no apparent recurrence of atrial tachyarrhythmias and continuation of the DOAC. A blood examination revealed the presence of anti-cardiolipin-beta2-glycoproteion complex antibodies and lupus anticoagulants, and the patient was diagnosed with primary APS. The DOAC was changed to warfarin. The patient has remained free from any ischemic or hemorrhagic cerebral events for 11 months after the oral anticoagulants were changed. The ischemic stroke in the present case appeared to be associated with APS rather than AF. A diagnosis of APS may be extremely crucial in AF patients who have new-onset ischemic strokes under continuous administration of DOACs, because vitamin K antagonists are more effective for the prevention of APS-related ischemic strokes than DOACs.

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  • A Case Report
    Takatsugu Hiramatsu, Yoshiaki Mizutani, Satoshi Yanagisawa, Tomomi Sug ...
    2022 Volume 63 Issue 1 Pages 159-162
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    We report here the case of a 92-year-old woman with atrial fibrillation bradycardia in which leadless pacemaker implantation was performed with a difficult delivery of the catheter sheath due to an extremely large right atrium. Using a snare technique with correction of the direction of the force on the catheter toward the right ventricle (RV) can result in successful delivery of the pacemaker catheter and stable placement of the pacemaker system in the RV septum. This specific snare technique has the potential to facilitate leadless pacemaker implantation safely in a severely dilated chamber of the heart, making this technique effective to use in clinical practice.

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  • Naoto Hashimoto, Harutoshi Tamura, Yoichiro Otaki, Aoi Takahata, Hayat ...
    2022 Volume 63 Issue 1 Pages 163-167
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    The incidence of acute coronary obstruction during transcatheter aortic valve implantation (TAVI) is low (< 1.0%); however, it is associated with high mortality. An 83-year-old female with a history of chest pain and syncope was diagnosed with severe aortic stenosis. Computed tomography showed severely calcified aortic leaflets with a low left coronary ostial height of 7.8 mm, which indicates a high risk of coronary obstruction. TAVI was performed using the right femoral artery approach under general anesthesia. To prevent coronary obstruction and minimize coronary flow obstruction, coronary protection of the left main tract (LMT) via the left radial artery was established with a perfusion balloon. We crossed a 23 mm Sapien 3 transcatheter heart valve and settled it at an appropriate position on the aortic valve. After inflation of the perfusion balloon at the LMT, we started rapid ventricular pacing, and deployed the Sapien 3 using the KBI technique. Hemodynamics were stable and aortography showed excellent coronary flow with no stenosis of the LMT ostium. This strategy may serve as a useful method to prevent coronary obstruction and minimize coronary ischemia.

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  • Case Series and Review of the Literature
    Nobutaka Nagano, Atsuko Muranaka, Ryo Nishikawa, Wataru Ohwada, Hidemi ...
    2022 Volume 63 Issue 1 Pages 168-175
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    Diagnostic strategies for symptomatic transthyretin (ATTR) cardiac amyloidosis showing typical morphological features such as increased ventricular wall thickness and myocardial injury such as an elevation in serum troponin T level have been established, but those for subclinical cardiac amyloidosis are limited. In the era when effective therapies to suppress/delay progression of ATTR cardiac amyloidosis are available, early detection of cardiac involvement plays a crucial role in appropriate decision-making for treatment in TTR mutation carriers who have a family history of heart failure and death due to ATTR amyloidosis. Findings of three cases with known pathogenic transthyretin (TTR) mutations (p.Ser70Arg, p.Phe53Val, and p.Val50Met) and family histories of death for amyloidosis were presented. Two cases were asymptomatic, and a case carrying p.Phe53Val had gastrointestinal symptoms and autonomic neuropathy. Levels of plasma N-terminal fragment of pro-B-type natriuretic peptide and troponin T were within normal ranges in all cases, but results of cardiac magnetic resonance (CMR) and bone scintigraphy clearly revealed the presence of cardiac involvement in all cases, even in a case without echocardiographic abnormalities including left ventricular hypertrophy and relative apical sparing of longitudinal strain shown by two-dimensional speckle-tracking echocardiography. Electrocardiography revealed modest abnormalities including reduced R wave amplitude in V2 and a trend toward left axis deviation in all cases. In conclusion, CMR, bone scintigraphy, and electrocardiography are useful for early detection of ATTR cardiac amyloidosis in TTR mutation carriers. The role of comprehensive cardiac assessment in the early detection of cardiac amyloidosis in TTR mutation carriers is discussed.

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  • Seisuke Sayama, Takayuki Iriyama, Norifumi Takeda, Haruo Yamauchi, Mas ...
    2022 Volume 63 Issue 1 Pages 176-179
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    Loeys-Dietz syndrome (LDS) is a connective tissue disorder with a high incidence of aortic dissection (AD). After treating two previously reported cases of postpartum AD in women with LDS following prophylactic aortic root replacement (ARR), we succeeded in managing a 30-year-old primigravida with no AD during her peripartum period. On the basis of the patient's stated desire to conceive during preconception counseling, a multidisciplinary team was assembled. She conceived naturally after receiving prophylactic ARR and beta-blocker treatment. Multidisciplinary patient care included precise blood pressure management, continuation of beta-blocker treatment, cardiovascular assessment with echocardiogram, regional anesthesia during labor, prevention of lactation, and resumption of angiotensin II receptor blocker therapy immediately after delivery. On the basis of our assessment of three cases, including this case, and a literature review, we propose a peripartum management strategy for patients with LDS following prophylactic ARR.

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  • Akito Shindo, Masataka Yamasaki, Keita Uchino, Masao Yamasaki
    2022 Volume 63 Issue 1 Pages 180-183
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    Although myocarditis following immune checkpoint inhibitor (ICI) therapy is rarely reported, it is considered clinically important because of its high mortality rate. Although various tests may be used for early diagnosis, abnormalities suggestive of myocarditis may not be detected. We report a case of ICI-induced myositis and concurrent asymptomatic myocarditis with mild cardiac marker elevation following nivolumab therapy in a 79-year-old man with metastatic gastric cancer. In this case, cardiac magnetic resonance imaging was useful for diagnosis. Treatment with oral prednisolone rapidly improved the patient's symptoms and creatine kinase levels. Follow-up examination revealed no flare-up of myositis and exacerbation of myocarditis. Since ICI-induced myositis is often complicated by myocarditis, this case report highlights the importance of detecting concurrent myocarditis in patients with ICI-induced myositis through intensive cardiac assessments to improve clinical outcomes.

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Letter to Editor
Author's Reply
Announcement of Retraction
  • 2022 Volume 63 Issue 1 Pages 190
    Published: January 29, 2022
    Released on J-STAGE: January 29, 2022
    JOURNAL FREE ACCESS

    The editorial office of International Heart Journal would like to inform our readers that the experimental study titled "Emodin Attenuates Lipopolysaccharide-Induced Injury via Down-Regulation of miR-223 in H9c2 Cells" written by Yuping Yang, Zijun Jiang, Dong Zhuge and published in the March 2019 issue of International Heart Journal (Int Heart J 2019; 60: 436-443) has been retracted upon request from the authors.

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