International Heart Journal
Online ISSN : 1349-3299
Print ISSN : 1349-2365
ISSN-L : 1349-2365
Volume 61 , Issue 1
Showing 1-30 articles out of 30 articles from the selected issue
Clinical Studies
  • Yang Gao, Changtai Xing, Wenjun Hao, Hongwei Zhao, Lili Wang, Bo Luan, ...
    2020 Volume 61 Issue 1 Pages 1-6
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: December 26, 2019
    JOURNALS FREE ACCESS

    Chronic heart failure (CHF) seriously affects the quality of patients' lives. Sacrubitril/valsartan is a combination angiotensin receptor-neprilysin inhibitor, a new therapeutic drugs to treat CHF.

    This study aims to observe the impact of sacrubitril/valsartan on clinical treatment and high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-brain natriuretic peptide (NT-ProBNP) serum levels, the improvement of the left atrial diameter (LAD) and left ventricular end diastolic dimension (LVEDD), and the left ventricular ejection fraction (LVEF) in patients with CHF.

    120 patients were randomly divided into a sacrubitil/valsartan group and a valsantan group, with 60 cases in each. Patients in the sacrubitil/valsartan group were administered sacrubitril/valsartan; while in the valsantan group, they were administered valsartan. The clinical effects, adverse reactions, and rehospitalization were observed eight weeks later, and hs-cTnT and NT-ProBNP serum levels and LAD, LVEDD, and LVEF were assayed.

    There were 53 cases of positive effect in the sacrubitil/valsartan group and 42 in the valsartan group (P < 0.05). Eight participants demonstrated adverse reactions in the sacrubitil/valsartan group, while 17 in the control group (P < 0.05). Hs-cTnT and NT-ProBNP serum levels, the measurements of LAD, LVEDD, and LVEF in the sacrubitil/valsartan group before the treatments were (24.47 ± 7.54) pg/mL, (10,356.94 ± 5,447.68) pg/mL, (49.41 ± 5.22) mm, (68.06 ± 6.20) mm and (31.12 ±6.65) %; in the valsartan group were (29.752 ± 10.03) pg/mL, (9,518.17 ± 5,905.17) pg/mL, (49.65 ± 4.91) mm, (67.06 ± 3.97) mm, and (30.41 ± 6.11) % (P > 0.05), while in the sacrubitil/valsartan group, the values decreased after the treatments to (17.92 ± 4.74) pg/mL, (3,881.59 ± 2,087.79) pg/mL, (42.18 ± 4.87) mm, (60.35 ± 7.12) mm and (45.35 ± 4.49) %; in the valsartan group to (25.81 ± 7.36) pg/mL, (6,278.35 ± 2,643.11) pg/mL, (46.53 ± 4.80) mm, (64.51 ± 4.34) mm, and (36.47 ± 5.21) % (P < 0.05). There were significant differences within the same group, before and after treatments (P < 0.05).

    Sacrubitril/valsartan treatment of patients with CHF improves their symptoms and is deserving of clinical application. This is also evident from significantly improved levels of serum hs-cTnT and NT-ProBNP and the left ventricular function.

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  • A Propensity Score-Matched Analysis
    Masaru Seguchi, Kenichi Sakakura, Kei Yamamoto, Yousuke Taniguchi, Hir ...
    2020 Volume 61 Issue 1 Pages 7-14
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    Acute myocardial infarction (AMI) in the very elderly is associated with high morbidity and mortality. Although there are earlier studies regarding AMI in octogenarians, clinical evidences of AMI in nonagenarians are sparse. The aim of the present study was to compare in-hospital outcomes of AMI between octogenarians and nonagenarians. We included consecutive 415 very elderly (≥ 80 years) with AMI and divided them into the nonagenarian group (n = 38) and the octogenarian group (n = 377). Clinical characteristics and in-hospital outcomes were compared between the two groups. Furthermore, we used propensity score matching to find the matched octogenarian group (n = 38). Percutaneous coronary interventions (PCI) to the culprit of AMI were similarly performed between the nonagenarian (86.8%) and octogenarian (87.0%) groups. The incidence of in-hospital death in the nonagenarian group (10.5%) was similar to that in the octogenarian group (12.5%) (P = 0.487). After using the propensity score matching, the incidence of in-hospital death was less in the nonagenarian group (10.5%) than in the matched octogenarian group (18.4%) without reaching statistical significance (P = 0.328). The length of hospitalization was significantly shorter in the nonagenarian group [7.0 (4.0-9.0)] than in the matched octogenarian group [10.0 (6.5-15.0)] (P = 0.01). In conclusion, the in-hospital mortality of nonagenarians with AMI was comparable to that of octogenarians with AMI. In-hospital outcomes in nonagenarians with AMI may be acceptable as long as acute medical management including PCI to the culprit of AMI is performed.

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  • A Community-Based Cohort Study
    Hidetaka Itoh, Hidehiro Kaneko, Hiroyuki Kiriyama, Tatsuya Kamon, Yosh ...
    2020 Volume 61 Issue 1 Pages 15-20
    Published: January 31, 2020
    Released: January 31, 2020
    JOURNALS FREE ACCESS

    Body weight gain in middle age is thought to be mainly attributable to body fat gain. However, the association between the change in body weight and change in fat weight is not fully understood. In this study, we aimed to clarify the association between the changes in body weight and fat weight in a middle-aged general population using a community-based cohort. We studied 3,193 subjects who underwent health check-ups. Fat weight was measured using a TANITA DC-270A body composition analyzer (Tanita Corporation, Tokyo). Good correlation was observed between the changes in body weight and fat weight (Pearson r = 0.88, P < 0.001). Among the study subjects, 408 (13%) were categorized in the weight loss group (weight loss ≥ 5%), 2,442 (76%) in the weight stable group, and 343 (11%) in the weight gain group (weight gain ≥ 5%). The percentage of change in fat weight in relation to the change in body weight was 65% on average in subjects with body weight loss, and 70% on average in those with body weight gain. Good correlation between changes in body weight and fat weight was observed regardless of age, gender, and baseline body mass index. A change in body weight was closely correlated with a change in fat weight among the middle-aged general population. Body weight change in the middle-age population appears to be mainly attributable to the change in fat weight.

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  • Tadashi Fujino, Hitomi Yuzawa, Toshio Kinoshita, Hideki Koike, Masaya ...
    2020 Volume 61 Issue 1 Pages 21-28
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    Catheter ablation is currently an established treatment for symptomatic paroxysmal atrial fibrillation (AF). We focused on elderly patients with a high prevalence of AF and attempted to identify the clinical factors associated with unsuccessful ablation outcomes.

    Among 735 consecutive patients who underwent AF ablation procedures, 108 (14.7%, 66 men) aged ≥ 75 years were included. Of them, 80 had paroxysmal AF, and the remaining 28 non-paroxysmal AF. All patients underwent pulmonary vein (PV) isolation and occasionally additional ablation. When AF recurred, redo ablation procedures were performed if the patient so desired.

    The mean number of ablation procedures was 1.1 ± 0.4 times per patient. During a mean follow-up of 38.7 ± 21.7 months, sinus rhythm was maintained in 100 patients (92.6%) without any antiarrhythmic drugs, but not in the remaining 8 (7.4%). Left atrial diameter (LAD, P < 0.001), left ventricular (LV) systolic diameter (P < 0.001), LV diastolic diameter (P = 0.001), non-PV AF foci (P = 0.036), and diabetes (P = 0.045) were associated with unsuccessful ablation procedures. Multivariate logistic regression analysis revealed a large LAD and non-PV AF foci were significant independent predictors of AF recurrences, with odds ratios of 0.76 (P = 0.019) and 0.04 (P = 0.023), respectively. In a total of 124 procedures, one major (0.8%) and 11 minor (8.9%) complications occurred.

    In elderly AF patients, catheter ablation of AF is effective and safe. Non-PV AF foci and a large LAD were independent clinical predictors of unsuccessful AF ablation outcomes.

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  • Cheng-Ching Wu, Chao-Sung Chang, Chia-Chang Hsu, Chao-Ping Wang, I-Tin ...
    2020 Volume 61 Issue 1 Pages 29-38
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    Low-circulating levels of adiponectin (ADPN) are associated with obesity, diabetes mellitus, and coronary artery disease. On the contrary, some studies have demonstrated a link between relatively high levels of plasma ADPN and heart failure, atrial fibrillation, and adverse outcome. However, little is known about the relationship between ADPN level and prolonged QT interval. The aim of this study was to investigate the association between plasma ADPN levels and prolonged QT interval in patients with stable angina.

    In this retrospective study, because the diverse disease severity and condition of the study population may have affected the results, we chose individuals with stable angina. Plasma ADPN concentrations were measured using enzyme-linked immunosorbent assays. A 12-lead ECG recording was obtained from each patient.

    We enrolled 479 stable-angina patients. Patients with an abnormal corrected QT (QTc) interval had higher median plasma ADPN levels than those with normal QTc intervals. Age- and sex-adjusted ADPN levels were positively associated with heart rate, QTc interval, left ventricular mass index, and creatinine but negatively associated with left ventricular ejection fraction, waist circumference, current smoking, total cholesterol, triglycerides, low-density lipoprotein cholesterol, albumin, and estimated glomerular filtration rate. A multiple logistic regression analysis revealed ADPN as an independent association factor for abnormal QTc interval. Increasing concentrations of sex-specific ADPN were independently and significantly associated with abnormal QTc interval, even after full adjustment of known biomarkers.

    Our results indicate that ADPN may play a role in the pathogenesis of abnormal QTc interval in patients with stable angina.

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  • Yuichiro Sagawa, Yasutoshi Nagata, Tetsuo Yamaguchi, Kentaro Mitsui, T ...
    2020 Volume 61 Issue 1 Pages 39-45
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and hypertrophic cardiomyopathy (HCM) implanted with implantable cardioverter-defibrillators (ICDs) may show a large decrease in R-wave amplitude during long-term follow-up. However, it is unclear whether this decrease is higher in these patients than in those without structural heart disease. This study investigated ICD-lead intracardiac parameters over a long duration in patients with ARVC and HCM and compared these parameters with those of a control group. We included 50 patients (mean age, 55.2 ± 17.2 years; 26% female) with ICD leads in the right ventricular apex, and compared 7 ARVC and 14 HCM patients with 29 control patients without structural heart disease. ICD-lead parameters, including R-wave amplitude, pacing threshold, and impedance during follow-up, were compared. The difference in these parameters between the time of implantation and year 5 were also compared. There were no significant differences in R-wave amplitude at implantation among the 3 groups. The change in R-wave amplitude between the time of implantation and year 5 was significantly greater in the ARVC group (−3.3 ± 5.4 mV, P = 0.012) in comparison to the control group (1.3 ± 2.8 mV); the HCM group showed no significant difference (−0.4 ± 2.3 mV, P = 0.06). Thus, in the ARVC group, R-wave amplitude at year 5 was significantly lower than that in the control group (5.7 ± 4.8 mV versus 12.5 ± 4.5 mV, P = 0.001). In ARVC patients with ICDs, ventricular sensing is likely to deteriorate during long-term follow-up; however, in HCM patients, sensing may not deteriorate.

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  • Tomonari Shimamoto, Kosuke Kiyohara, Tasuku Matsuyama, Tetsuhisa Kitam ...
    2020 Volume 61 Issue 1 Pages 46-53
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    We investigated the impact of bystander-initiated cardiopulmonary resuscitation (CPR), dispatcher assistance (DA), and location of arrest on survival and outcomes after out-of-hospital cardiac arrest (OHCA).

    From a nationwide population-based registry of OHCA patients in Japan, we enrolled adult patients with bystander-witnessed OHCA of medical origin between 2013 and 2015. The primary outcome measure was a neurologically favorable outcome, defined by cerebral performance category 1 or 2. Multivariable logistic regression analysis was used to assess the effects of bystander CPR and DA by location of arrest. A total of 104,621 cases were included (15,984 bystander CPR without DA [15.3%], 40,087 bystander CPR with DA [38.3%], and 48,550 no bystander CPR [46.4%]). In public locations, both the bystander-CPR-with-DA group (22.9% [1,068/4,665]; adjusted odds ratio (AOR), 1.62; 95% confidence interval (CI), 1.43-1.85) and the bystander-CPR-without-DA group (25.8% [918/3,557]; AOR, 1.43; 95% CI, 1.24-1.65) had neurologically favorable outcomes compared with the no-bystander-CPR group (9.9% [610/6,133]). In residential locations, the AORs were 1.44 (95% CI, 1.22-1.70) in the bystander-CPR-without-DA group and 1.60 (95% CI, 1.45-1.77) in the bystander-CPR-with-DA group. However, in nursing homes, bystander CPR was not associated with improved outcomes of OHCA, regardless of the implementation of DA.

    Bystander CPR with or without DA had better outcomes after OHCA in residential and public locations but not in nursing homes.

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  • Hitoshi Mori, Ritsushi Kato, Yoshifumi Ikeda, Kenta Tsutsui, Saki Hase ...
    2020 Volume 61 Issue 1 Pages 54-59
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    Right ventricular (RV) lead perforations are relatively rare but a potentially life-threatening complication of surgical implantations of cardiac implantable electronic devices (CIEDs). The result of percutaneous simple lead traction after lead perforations in the Japanese population has not been well clarified.

    We retrospectively studied 1359 patients (pacemakers [PMs], 973 patients; implantable cardioverter defibrillators [ICD], 386 patients) from April 2007 to December 2018 who underwent initial CIED implantation. Fifteen patients (1.1%) were diagnosed with RV lead perforations. The clinical data were evaluated in those patients, and the baseline characteristics and echocardiographic data were compared between the lead perforation group and the non-perforation group. The success and complication rates of the simple traction and repositioning of the RV lead were also assessed.

    The number of perforated RV leads was seven ICD leads (1.8%) and eight PM leads (0.82%). They were diagnosed on a median seven days (5.5-36.0) after the CIED implantation. Twelve patients were asymptomatic but were detected by an increased capture threshold. Three patients had pericarditis and stimulation of the diaphragm. Only one patient in the ICD lead group who took anticoagulants had a cardiac tamponade and needed an urgent pericardiocentesis (0.07%). No one required a thoracotomy or other devices related to complications after repositioning the RV lead. There was no significant difference in the baseline characteristics and echocardiographic parameters between the groups.

    RV lead perforations were relatively rare complications of CIED implantations. Percutaneous simple lead traction and repositioning the perforated lead was feasible and effective if the patients did not receive anticoagulants.

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  • Masao Takahashi, Gauthier Mouillet, Asmaa Khaled, Madjid Boukantar, Ro ...
    2020 Volume 61 Issue 1 Pages 60-66
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS
    Supplementary material

    Transcatheter aortic valve implantation (TAVI) using a transfemoral approach under local anesthesia with conscious sedation (LACS) is becoming an increasingly common TAVI strategy. However, patients who are awake during the TAVI procedure can experience stress, anxiety, and pain, even when LACS is used. Clinical hypnotherapy is an anxiolytic intervention that can be beneficial for patients undergoing invasive surgery. This study aimed to assess the perioperative outcomes of adjunctive hypnotherapy undergoing transfemoral TAVI with LACS.

    Consecutive patients (n = 143) with symptomatic severe aortic stenosis who underwent transfemoral TAVI with LACS only (n = 107) or with LACS and hypnotherapy (n = 36) between January 2015 and April 2016 were retrospectively included in the study. The clinical outcomes were compared between the two groups. The LACS with hypnotherapy group had a significantly shorter length of stay in the intensive care unit (ICU; LACS only versus LACS with hypnotherapy: 4.0 (4.0-5.5) days versus 3.0 (3.0-5.0) days, P < 0.01). Moreover, the use of anesthetics (propofol and remifentanil) and norepinephrine was significantly lower in the LACS with hypnotherapy group (e.g., for propofol, LACS only versus LACS with hypnotherapy: 96.4 ± 104.7 mg versus 15.0 ± 31.8 mg, P < 0.001). The multiple regression analysis showed that being male, hypnotherapy, and the composite complication score were independently associated with the length of stay in the ICU.

    The adjunctive hypnotherapy on LACS among transfemoral TAVI patients may facilitate perioperative management. However, a prospective randomized study is necessary to confirm the efficacy of hypnotherapy among TAVI patients.

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  • Gang Liu, Xun Hu, Ming Long, Zhi-Min Du, Yi Li, Cheng-Heng Hu
    2020 Volume 61 Issue 1 Pages 67-76
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    Pre-procedural serum albumin's impact on prognosis after transcatheter aortic valve replacement (TAVR) has been studied. Literature on the prognostic role of serum albumin in the survival of patients undergoing TAVR shows conflicting results. This meta-analysis was conducted to evaluate the impact of pre-procedural serum albumin on outcomes after TAVR. A comprehensive literature search of EMBASE, MEDLINE, and the Cochrane Library was undertaken through July 2019. The primary end points were 30-day and one-year all-cause mortality after TAVR. Risk ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random-effect model. Ten eligible studies with 8,236 patients were analyzed. Of the 8,236 patients undergoing TAVR, with a mean age of 83 years, 48.8% were men and were categorized into two groups according to low and normal serum albumin (cut-off value: 3.5 or 4 g/dL). Overall, low albumin was significantly associated with an approximately two-fold increase in 30-day all-cause mortality (HR, 2.09; 95% CI, 1.53-2.86) and a 61% increase risk for one-year mortality (HR, 1.61; 95% CI, 1.31-1.98) in patients after TAVR. Sensitivity analyses showed the results to be robust. The association of low albumin level with an increase in one-year mortality risk was not modified by study design, albumin cut-off value, Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM), and study quality. In conclusion, low albumin levels were associated with poor prognosis in patients after TAVR. Pre-procedural albumin can be used as a simple tool related to prognosis after TAVR.

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  • Takayoshi Tsutamoto, Hiroshi Sakai, Takashi Yamamoto, Yoshihisa Nakaga ...
    2020 Volume 61 Issue 1 Pages 77-82
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    This study aimed to evaluate whether the heart is the target organ of endogenous atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with heart failure (HF) with reduced ejection fraction (HFrEF).

    We measured the plasma levels of cyclic guanosine monophosphate (cGMP), which is a second messenger of ANP and BNP, in the aortic root (AO) and coronary sinus (CS) in 237 patients with HFrEF. Plasma levels of cGMP were significantly higher in the CS than those in the AO in 237 patients with HFrEF (10.0 ± 4.5 versus 10.5 ± 4.3 pmoL/mL, P < 0.0001) and were significantly higher in the CS than those in the AO (8.0 ± 3.6 versus 8.9 ± 3.8 pmoL/mL, P < 0.0001) in mild HF patients (New York Heart Association (NYHA) II, n = 114), but there was no difference in plasma cGMP between the AO and the CS (11.9 ± 4.4 versus 11.9 ± 4.3 pmoL/mL, NS) in severe HF patients (NYHA III-IV, n = 123). In mild HF patients, log (ANP + BNP) in the AO was an independent predictor of (CS-AO) cGMP among hemodynamics and nitrate therapy. There was a significant correlation between log [(CS-AO) ANP + (CS-AO) BNP] and (CS-AO) cGMP (r = 0.455, P < 0.0001) in mild HF patients.

    These findings indicate that cGMP is produced from the failing heart and that the heart is the target organ of endogenous ANP and BNP in patients with HFrEF. In severe HF patients, cGMP production may be attenuated because of the downregulation of biological receptors and/or increased cGMP degradation in the failing heart.

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  • Kazutaka Suzuki, Taichi Kato, Satoshi Koyama, Tsutomu Shinohara, Sachi ...
    2020 Volume 61 Issue 1 Pages 83-88
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    Percutaneous occlusion of atrial septal defect (ASD) has recently become a standard therapeutic strategy, but little is known about left atrial (LA) function thereafter. The present study aimed to determine LA function in 43 children with ASD and 13 controls based on LA strain measured by two-dimensional echocardiographic speckle tracking (2DE-ST). Among these children, 12 underwent surgery (ASD-S), 31 had device closure (ASD-D), and 13 were included as controls. LA strain was significantly decreased after ASD-D but was not significantly altered after ASD-S, indicating that percutaneous occlusion of an ASD might decrease LA function. Furthermore, the size of the ASD device negatively correlated with LA strain. These results imply that ASD occlusion devices negatively influence LA function and might be important when decided therapeutic strategies for ASD. LA strain measured by 2DE-ST should become a good indicator of LA function after ASD treatment in children.

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  • Asuka Minami Takano, Hiroshi Iwata, Katsutoshi Miyosawa, Atsushi Kimur ...
    2020 Volume 61 Issue 1 Pages 89-95
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS
    Supplementary material

    Thrombocytopenia is a frequent complication in patients requiring intra-aortic balloon pumping (IABP) counterpulsation. However, its prognostic impact has not been fully addressed. The objective of this study is to evaluate the impact of the change in the platelet number during IABP use on the prognosis after device removal.

    This is a retrospective observational study. Patients in the intensive cardiac care unit at three Juntendo University hospitals who underwent percutaneous implantation of IABP with or without veno-arterial extracorporeal membrane oxygenation (V-A ECMO), since 2012-2016, were enrolled in the study (n = 439). Patients who died during mechanical circulatory support (n = 47) were excluded. We evaluated the prognostic impact of the ratio of platelet reduction from the baseline (% PLT reduction) during IABP use on cardiovascular mortality after device removal.

    The median and the range of follow-up period were 298 days and 0-1,869 days, respectively. Unadjusted Kaplan-Meier analysis demonstrated that patients with a higher % PLT reduction had higher cardiovascular (CV) mortality. An adjusted Cox proportional hazard analysis demonstrated that a 10% higher % PLT reduction was associated with higher cardiovascular (CV) mortality (Hazard ratio: 1.3, 95% Confidence interval: 1.1-1.6, P < 0.001). Moreover, % PLT reduction and the maximum C-reactive protein (CRP) level during IABP use were positively correlated (r = 0.326, P < 0.001).

    The reduced number of platelets during IABP use was associated with an increased risk of CV mortality.

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  • Ippei Nakano, Shintaro Kinugawa, Hiroaki Hori, Arata Fukushima, Takash ...
    2020 Volume 61 Issue 1 Pages 96-102
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    Heart failure (HF) is associated with aberrant skeletal muscle impairments, which are closely linked to the severity of HF. A low level of brain-derived neurotrophic factor (BDNF), a myokine produced in the skeletal muscle, is known to be involved in reduced exercise capacity and poor prognosis in HF. However, little is known about the factors or conditions of skeletal muscle associated with BDNF levels. We investigated the association between serum BDNF levels and the skeletal muscle mass and function in HF patients (n = 60, 63 ± 13 years) and age-matched controls (n = 29, 61 ± 16 years). The serum BDNF level was significantly lower in the HF patients compared to the controls (24.9 ± 0.9 versus 28.6 ± 1.3, P = 0.021). In a univariate analysis, BDNF was significantly correlated with the peak oxygen uptake, estimated glomerular filtration rate, 10-m gait speed, and muscle strength, but not with the body mass index or lean mass in the HF group. A multiple linear regression analysis revealed that BDNF was independently associated with muscle strength (β-coefficient = 2.80, 95%CI: 1.89-11.8, P = 0.008). Serum BDNF levels were associated with exercise capacity and skeletal muscle function, but not with muscle mass. These novel findings may suggest that BDNF production is controlled by muscle function and activity and consequently regulates exercise capacity, highlighting the importance of adequate training regarding skeletal muscle in HF patients.

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  • Tatsuya Kamon, Hidehiro Kaneko, Hidetaka Itoh, Hiroyuki Kiriyama, Yosh ...
    2020 Volume 61 Issue 1 Pages 103-108
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS
    Supplementary material

    Waist circumference (WC) is measured for the assessment of abdominal obesity, whereas carotid intima-media thickness (IMT) is a marker of preclinical atherosclerosis. The relationship between WC and carotid IMT in the general population is not fully understood. In this study, we examined 1,182 subjects (658 men and 524 women, 62.3 ± 11.7 years on average) who underwent voluntary health check-ups and sought to determine the optimal cut-off value of WC for predicting carotid IMT thickness. Receiver operating characteristic curve analysis of WC was utilized to predict high carotid IMT (defined as carotid IMT ≥ 1.1 mm). We determined that the appropriate WC cut-off value was a WC ≥ 79 cm for men and women. There was a statistically significant difference in the prevalence of high carotid IMT between WC ≥ 79 cm and WC < 79 cm in both men and women. However, multivariable logistic regression analysis demonstrated that the WC category was independently associated with high carotid IMT in men, but not in women. Our study indicates that the optimal cut-off value of WC to identify preclinical atherosclerosis may be lower than the current Japanese diagnostic criteria for metabolic syndrome (MetS) in both men and women. Compared to women, the association between WC and preclinical atherosclerosis may be more pronounced in men.

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  • Yingzhi Chong, Qi Ren, Yuhong Li, Chaoran Li, Fumin Feng, Yong Zhou
    2020 Volume 61 Issue 1 Pages 109-114
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: December 26, 2019
    JOURNALS FREE ACCESS
    Supplementary material

    Lipoprotein-associated phospholipase A2 (Lp-PLA2) and high-sensitivity C-reactive protein (hs-CRP) have been reported to be associated with cardiovascular disease (CVD). However, whether the combination of these two markers can improve the prediction of CVD is unknown.

    A total of 1,921 participants without CVD, aged 40 years or older, were enrolled from 2010 to 2011. Plasma Lp-PLA2 and hs-CRP were measured at baseline. Participants were subsequently followed until December 2015. We identified a total of 148 cardiovascular events (myocardial infarction, stroke, and all-cause death). Cox proportional-hazard models were used to determine the association between two independent markers and cardiovascular outcomes. The C statistic, Net Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI) were used to determine the utility of the two markers in predicting cardiovascular risk.

    After adjustment for potential confounders, compared with the first quartile, hazard ratios (HRs) with 95% confidence interval (CI) for the third and fourth quartiles for Lp-PLA2 were 2.09 (1.17-3.73) and 2.62 (1.48-4.67), respectively, and HRs with 95%CI for the fourth quartile for hs-CRP was 1.78 (1.08-4.67). Compared with conventional risk factors, the combination of hs-CRP and Lp-PLA2 provided greater incremental information, and the C statistic increased by 0.013. The NRI and IDI were also statistically significant for cardiovascular events (P = 0.004 and P < 0.001, respectively).

    Hs-CRP and Lp-PLA2 have complementary effects in predicting cardiovascular outcomes in adults aged 40 years or older.

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Experimental Studies
  • Maozhi Huang, Jianping Zheng, Ziguo Chen, Chaoqun You, Qilei Huang
    2020 Volume 61 Issue 1 Pages 115-120
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    Coronary collateral circulation (CCC) plays a crucial role in myocardial blood supply, especially for ischemic myocardium. Previous study has shown that neuregulin-1 is a prominent angiogenic factor in diabetic cardiomyopathy, whereas the relationship between neuregulin-1 and CCC has not been investigated. Thus, we aimed to investigate relationship between circulating neuregulin-1 levels and CCC in stable coronary artery disease patients.

    Coronary artery disease patients with a stenosis of ≥ 90% as evidenced by coronary angiography were included in our study. According to the Rentrop-Cohen classification, coronary collateral degree was graded as 1 to 4. Patients with collateral degree grade 0 or 1 were enrolled in poor CCC group, whereas patients with grade 2 or 3 were enrolled in good CCC group.

    Plasma neuregulin-1 level was significantly increased in good collateral group and positively related to Rentrop grade (P < 0.01). Multivariate regression analysis and ROC (receiver operating characteristic curve) revealed that plasma neuregulin-1 could predict CCC status effectively.

    Increased plasma neuregulin-1 level was related to better CCC in patients with coronary artery disease. Neuregulin-1 was an independent and reliable predictor for good coronary collateral development and provided a potential therapeutic strategy to reduce myocardial ischemia injury.

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  • Kaoru Okishige, Takatoshi Shigeta, Rena A. Nakamura, Tatsuhiko Hirao, ...
    2020 Volume 61 Issue 1 Pages 121-127
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    Laserballoon-based pulmonary vein isolation has proven to be safe and effective. However, the influence of the laser energy titration on the lesion formation has never been fully investigated. The aim of this study was to determine the relationship between the delivered laser energy and lesion size, as well as the incidence of steam pop.

    The whole porcine heart was excised, and the left ventricular myocardium was separated into four specimens. Myocardial specimens were embedded in a warm mattress to keep the myocardial temperature around 37°C. The laserballoon was located so that the surface of the laserballoon was attached to the myocardium. The laser energy was irradiated against the surface of myocardium at 5.5, 8.5, 10.0, and 12.0 W for 3, 5, 10, and 20 seconds. The depth, surface area, and lesion volume were measured using a digital vernier caliper.

    At constant laser energy and time, the lesion size increased significantly with the increasing energy (P < 0.001) and application duration (P < 0.001). The steam pop was provoked when a 12.0 W laser energy was applied for longer than 16 seconds, and it occurred in 2 out of 8 lesions.

    The laserballoon demonstrated the ability to create a lesion formation in a dose- and time-dependent manner. Steam pop could be provoked with high-energy irradiation.

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  • Shin-Huei Liu, Chun-Ting Lai, Hau-Ruey Chen, Wei-Lun Lin, Shinya Yamad ...
    2020 Volume 61 Issue 1 Pages 128-137
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    Sleep and estrogen levels have an impact on neural regulation and are associated with cardiovascular (CV) events. We investigated the effects of estrogen on heart rate variability (HRV) and circadian cycle in spontaneously hypertensive rats (SHRs). Polysomnographic recording was performed in seven male and seven female SHRs during sleep. The electroencephalogram (EEG) and electromyogram (EMG) were evaluated to define active waking (AW), quiet sleep (QS), and paradoxical sleep (PS) stages. Cardiac activities were measured by RR interval of the electrocardiogram (ECG), mean arterial pressure (MAP), and power spectrum of HRV.

    In ECG, estrogen prolonged the RR interval in total sleep when compared with that at baseline in male SHRs (203.74 ± 6.61 versus 181.30 ± 8.06 ms, P < 0.001) and in female SHRs (169.21 ± 6.43 versus 160.76 ± 10.66 ms, P < 0.05). In HRV, the estrogen increased the high frequency (HF) in total sleep when compared with that at baseline in male SHRs (1.03 ± 0.28 versus 0.60 ± 0.43 ln (ms2), P < 0.001) and in female SHRs (0.71 ± 0.26 versus 0.42 ± 0.19 ln (ms2), P < 0.05).

    In male SHRs, estrogen increased the frequency of QS (26.50 ± 4.85 versus 20.79 ± 5.07, P < 0.01) and PS (25.64 ± 5.18 versus 20.14 ± 4.75, P < 0.05) stages when compared with baseline. In female SHRs, estrogen increased the percentage of delta waves in total sleep (79.87% ± 3.10% versus 76.71% ± 2.74%, P < 0.05) when compared with that at baseline.

    In HRV, estrogen leads to neuromodulation by increased parasympathetic tone in all SHRs, suggesting a lower risk to CV events. In sleep analyses, estrogen in male SHRs caused poor sleep quality. In contrast, estrogen in female SHRs demonstrated improved quality of sleep and decreased risk of hypertension.

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  • Zhong-Guang Sun, Guo Lu, Lin-Lin Zhao, Li-Zhen Zhang, Ai Li, Jing Jing ...
    2020 Volume 61 Issue 1 Pages 138-144
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: December 26, 2019
    JOURNALS FREE ACCESS

    Exercise preconditioning may protect against cardiac injury induced by lipopolysaccharide (LPS), but the mechanism is unresolved. The aim of this study is to explore whether the general control nonderepressible 2 (GCN2) kinase gene is associated with the protective effect of exercise preconditioning. Eight-week-old male C57BL/6J (n = 40) and GCN2 knockout (KO) (n = 40) mice were divided into four groups: control, LPS (L), exercise preconditioning (E), and exercise preconditioning LPS (EL). Mice in the exercise groups performed exercise for eight weeks. After exercise, all mice were given an equal volume of LPS or saline (10 μg/g). We measured the cardiac function using echocardiography and then collected heart tissue. Exercise preconditioning improved cardiac inflammation (interleukin-6, tumor necrosis factor α) and cardiac dysfunction (ejection fraction, fraction shortening) in C57 mice induced by LPS and also decreased the expression levels of GCN2, phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α), and activating transcription factor 4 (ATF4). Moreover, GCN2 KO decreased inflammation and cardiac dysfunction induced by LPS in sedentary mice. The inflammation and cardiac dysfunction in the GCN2 KO EL group were lower than in the C57 EL group, and the expression of GCN2, p-eIF2α, and ATF4 in the GCN2 KO EL group was lower than in the C57 EL group. Exercise preconditioning alleviated cardiac injury induced by LPS. GCN2 KO also improved cardiac injury. Exercise preconditioning promoted the effect of GCN2 KO in alleviating cardiac injury, and the GCN2 and eIF2α/ATF4 pathways play an important role in the process.

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  • Jingjing Chen, Shunen Xu, Wei Zhou, Lirong Wu, Long Wang, Wei Li
    2020 Volume 61 Issue 1 Pages 145-152
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    The aim of this study was to investigate the effect of exendin-4 (Ex-4) on ventricular arrhythmias and calcium sparks-mediated calcium leak in a myocardial infarction-heart failure model.

    We studied the influence of exendin-4 on ventricular arrhythmogenesis in a rat myocardial infarction-heart failure model. In vivo arrhythmia studies (electrocardiogram [ECG] telemetry studies), ex vivo arrhythmia studies calcium sparks tests, and analysis of total and phosphorylated ryanodine receptor (RyR) 2 and CaMK-II were carried out in sham group, myocardial infarction (MI) group, MI + Ex-4 and MI + Ex-4 + Exendin9-39 (Ex9-39) groups.

    ECG telemetry studies showed an antiarrhythmic effect of exendin-4 with reduction of spontaneous ventricular arrhythmias. Exendin-4 abbreviated the APD90, which was longer in the heart failure model, and increase the APD alternans thresholds. Exendin-4 also reduced the susceptibility to burst pacing-induced arrhythmia ex vivo. Subcellular sarcoplasmic reticulum (SR) calcium leak characteristics were tested in four groups of rat cardiomyocytes. Exendin-4 reduced calcium spark mass, spark frequency, and calcium leak, which may be due to reduced S2814-RyR2 and CaMK-II phosphorylation. Co-administration of exendin 9-39 with exendin-4 partly abolished the above-mentioned effect of exendin-4.

    These findings suggest that exendin-4 exerts an antiarrhythmic effect through decreasing SR calcium leak in spontaneous and burst pacing-induced ventricular arrhythmias, which may be due to reduced RyR2 phosphorylation and suppressed CaMK-II activity. Exendin-4 may act as a novel antiarrhythmic strategy in heart failure.

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  • Lu Li, Fangqin Wu, Yuan Xie, Wang Xu, Gang Xiong, Yuan Xu, Suli Huang, ...
    2020 Volume 61 Issue 1 Pages 153-159
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS
    Supplementary material

    A previous study and a gene-annotation enrichment analysis for potential targets of the microRNA miR-202-3p both suggest that this microRNA might be implicated in cardiovascular and metabolic diseases. In the present study, the role of miR-202-3p in the pathogenesis of coronary heart disease (CHD) was explored. We conduct a case-control study to detect the expression levels of miR-202-3p in peripheral blood cells and found that miR-202-3p expression was significantly higher in CHD cases than in controls (P < 0.001). miR-202-3p levels were negatively correlated with platelet distribution width (r = −0.348, P = 0.002) and mean platelet volume (r = −0.29, P = 0.01). Further functional analyses suggested that stimulation with oxidized low-density lipoprotein (ox-LDL) induced miR-202-3p expression, and that this microRNA suppressed the formation of ox-LDL-induced macrophage foam cells derived from THP-1 cells in a feedback manner. In addition, miR-202-3p overexpression modulated the expression of several key genes involved in foam cell formation, including that of ABCG4, NCEH1I, and SCARB2. In summary, miR-202-3p was associated with CHD, exerting a protective role against CHD by feedback suppression of ox-LDL-induced macrophage foam cell formation.

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  • Wenjing Feng, Yi Hu, Nina An, Zhe Feng, Jianya Liu, Jie Mou, Ting Hu, ...
    2020 Volume 61 Issue 1 Pages 160-168
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    Pulmonary arterial hypertension (PAH) is a serious and fatal cardiovascular disorder characterized by increased pulmonary vascular resistance and progressive pulmonary vascular remodeling. The underlying pathological mechanisms of PAH are multi-factorial and multi-cellular. Alginate oligosaccharide (AOS), which is produced by depolymerizing alginate, shows better pharmacological activities and beneficial effects. The present study was undertaken to investigate the effects and potential mechanisms of AOS-mediated alleviation of pulmonary hypertension. Pulmonary hypertension was induced in Sprague-Dawley rats by a single intraperitoneal injection of monocrotaline (MCT; 60 mg/kg). Five weeks after the injection of MCT, AOS (5, 10, and 20 mg·kg−1·d−1) was injected intraperitoneally for another three weeks. The results showed that AOS prevented the development of MCT-induced pulmonary hypertension and right ventricular hypertrophy in a dose-dependent manner. AOS treatment also prevented MCT-induced pulmonary vascular remodeling via inhibition of the TGF-β1/p-Smad2 signaling pathway. Furthermore, AOS treatment downregulated the expression of malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase, and pro-inflammatory cytokines, decreased macrophage infiltration, and upregulated the expression of anti-inflammatory cytokines. These findings indicate that AOS exerts anti-oxidative and anti-inflammatory effects in pulmonary arteries, which may contribute to the alleviation of pulmonary hypertension and pulmonary vascular remodeling.

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Case Reports
  • Shoji Haruta, Kiyohito Arai
    2020 Volume 61 Issue 1 Pages 169-173
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    We report the case of a 33-year-old woman with no history of coronary risk factors or chest pain who experienced intermittent chest pain at rest for several minutes from 2 PM. At 8 AM the next day, chest pain recurred and persisted for about 1 hour. She was transported to our hospital by ambulance, where electrocardiogram showed ST-elevation in the precordial leads, and blood tests showed elevation of cardiac markers. She was diagnosed with ST-elevation myocardial infarction. Because she was a young woman without any risk factors, coronary spastic angina was suspected. Coronary angiography without intracoronary nitrate administration revealed diffuse 75% stenosis in the proximal right coronary artery (RCA) and diffuse 90% stenosis in the left anterior descending artery (LAD). A coronary spasm provocation test elicited chest pain; coronary angiography showed 99% diffuse stenosis of LAD; and electrocardiogram showed precordial ST-segment elevation. Although intracoronary nitroglycerin injection attenuated the coronary spasm in the RCA and proximal LAD, 90% stenosis and coronary dissection were observed in the midportion of the LAD. When the imaging test that was carried out before the provocation test was reexamined, the dissection was recognized, and there was no clear dissection progress after the test. Intravascular ultrasound showed dissection of the LAD, as did angiography. We treated the patient using medical therapy instead of percutaneous coronary intervention.

    The patient did not suffer any anginal attack and improved sufficiently to be discharged. She remained free of attacks for about 10 years to the present time, and follow-up is continuing.

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  • Using an Ultra-High-Density 3-Dimensional Mapping System
    Hitoshi Mori, Naokata Sumitomo, Shota Muraji, Tomohiko Imamura, Noriyu ...
    2020 Volume 61 Issue 1 Pages 174-177
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    An 18-year-old male who had a past medical history of an intracardiac total cavopulmonary connection (TCPC) operation was referred to our hospital for radiofrequency catheter ablation (RFCA) of supraventricular tachycardia (SVT). Two types of SVTs were induced, and 3-dimensional (3D) maps were created using an ultra-high-density 3-dimensional mapping system (Rhythmia). The earliest atrial activation site (EAAS) of SVT1 was at the superior part of the conduit, and the EAAS of SVT2 was at the inferior part of the single atrium (SA). The SVTs were terminated by energy deliveries to the EAAS from the conduit in SVT1 and from inside the single atrium in SVT2. Detailed maps of the SVTs were important to understand the mechanisms of the SVTs. The Rhythmia system was useful for the detailed mapping of complex arrhythmias. The use of Rhythmia in patients after a TCPC is difficult, because puncturing the TCPC conduit and proceeding and manipulating the Orion catheter via a narrow puncture hole are difficult. We were the first to succeed in ablating two atrial tachycardias (ATs) originating from the inside and outside of the conduit after a TCPC operation by using an ultra-high-density 3-dimensional mapping system.

    Editor’s picks

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  • A Case Report and Literature Review
    Jiaming Li, Yinghua Cui, Xin Wang, Qinglei Wang, Hongjun Wang, Bo Yan
    2020 Volume 61 Issue 1 Pages 178-182
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: December 26, 2019
    JOURNALS FREE ACCESS

    Pompe disease (PD) is a rare and fatal neuromuscular disease, which is an autosomal recessive disorder. This is the first study to report a case of the compound heterozygous c.1822C>T and c.2297A>C mutations of the GAA gene in mainland Chinese patient, which led to the classic infantile-onset Pompe disease (IOPD) characterized by hypertrophic cardiomyopathy. This case highlights that the detection of GAA activity in peripheral blood by dried blood spot and GAA gene analysis can clarify the diagnosis of IOPD and provides the genetic counseling to those parents whose children have IOPD for giving birth in the future. Although PD is rare, and universal screening has not yet been established, we suggest that clinicians should consider the possibility of Pompe in the presence of hypertrophic cardiomyopathy.

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  • Chenyu Zhao, Jinyu Xu, Dan Cui, Kexiang Liu
    2020 Volume 61 Issue 1 Pages 183-185
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    Transcatheter closure of ostium secondum atrial septal defect has become an alternative method to surgical closure. However, the incidence of complications and long-term results of using large size (> 40 mm) Amplatzer septal occluders are unknown. This case reported a 59 years old woman, whom received transcatheter closure of atrial septal defect (36 mm) with a 40 mm Amplatzer septal occluder 10 years ago and was diagnosed with heart failure. Transthroacic echocardiography showed severe mitral valve regurgitation. Intra-operatively, we confirmed and removed the large device, but we found that the mitral annulus was badly damaged. Mitral valve replacement was performed. We believe large size devices need to be implanted cautiously, especially for the large defect with insufficient rims, and also routinely follow-up is necessary.

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  • A Case Report
    Yan-li Zhang, Xiao-cong Wang, Xiao-dong Li, Cong Hu, Li-ping Pei, Wei ...
    2020 Volume 61 Issue 1 Pages 186-190
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: December 26, 2019
    JOURNALS FREE ACCESS

    Rupture of aortic sinus aneurysms is a rare cardiac malformation that is commonly observed in the right coronary sinus but is rarely observed in the noncoronary sinus. Here, we report a case of aneurysm of the aortic sinus that ruptured into the left ventricular outflow tract and was diagnosed with left ventricular opacification. Left heart echocardiography can clearly demonstrate the structure of the heart and is one of the important diagnostic methods for diagnosing ruptured aortic sinus aneurysms. This observes the perfusion sequence of blood flow to clearly reveal the source, direction, and location of the ruptured aortic sinus aneurysm.

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  • Satoshi Akagi, Takashi Miki, Yasuhisa Sando, Nobuharu Fujii, Toshihiro ...
    2020 Volume 61 Issue 1 Pages 191-194
    Published: January 31, 2020
    Released: January 31, 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS

    Chronic-active Epstein-Barr virus infection (CAEBV) is a rare disease that can lead to pulmonary arterial hypertension (PAH). However, the treatment for CAEBV-associated PAH has not been established. We discuss a case of improved pulmonary hypertension after chemotherapy in a patient with CAEBV-associated PAH. A 44-year old man was admitted to our hospital because of an abnormal electrocardiogram and liver dysfunction detected by annual medical examination. Echocardiography showed a dilated right ventricle and an estimated right ventricular systolic pressure of 92 mmHg. Right heart catheterization revealed a mean pulmonary arterial pressure of 45 mmHg and pulmonary vascular resistance of 9.8 Wood units. Laboratory examination showed granular lymphocytes and 91% natural killer cells in lymphocyte subsets in peripheral blood. We diagnosed the patient as having CAEBV-associated PAH. After two cycles of chemotherapy without PAH-specific drugs, echocardiography showed improvement in the dilated right ventricle and an estimated right ventricular systolic pressure of 59 mmHg. Right heart catheterization revealed a mean pulmonary arterial pressure of 27 mmHg and pulmonary vascular resistance of 2.4 Wood units. Chemotherapy may improve pulmonary hypertension in patients with CAEBV-associated PAH.

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