Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Advance online publication
Showing 1-25 articles out of 25 articles from Advance online publication
  • Hiroaki Kitaoka, Toru Kubo, Yoshinori L. Doi
    Type: REVIEW
    Article ID: CJ-20-0524
    Published: July 14, 2020
    [Advance publication] Released: July 14, 2020
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    Hypertrophic cardiomyopathy (HCM) is the most frequent hereditary cardiomyopathy, showing an autosomal-dominant f inheritance. A great deal of attention has been paid to genetics, left ventricular tract obstruction and the prediction and prevention of sudden cardiac death in HCM. Needless to say, these are very important, but we should recognize the heterogeneity in etiology, morphology, clinical course and management of this unique cardiomyopathy. Another important perspective is that HCM causes left ventricular remodeling over time and is a disease that requires lifelong management in the real world.

  • Shiro Adachi, Yoshihisa Nakano, Takahisa Kondo
    Type: EDITORIAL
    Article ID: CJ-20-0621
    Published: July 11, 2020
    [Advance publication] Released: July 11, 2020
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  • Masahide Harada
    Type: EDITORIAL
    Article ID: CJ-20-0640
    Published: July 11, 2020
    [Advance publication] Released: July 11, 2020
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  • Oto Inoue, Kosei Yamaguchi, Masayuki Takamura
    Type: EDITORIAL
    Article ID: CJ-20-0656
    Published: July 11, 2020
    [Advance publication] Released: July 11, 2020
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  • Yutaka Hosoi
    Type: EDITORIAL
    Article ID: CJ-20-0673
    Published: July 11, 2020
    [Advance publication] Released: July 11, 2020
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  • Kazuhiro Yamamoto, Miyuki Tsuchihashi-Makaya, Yoshiharu Kinugasa, Yuki ...
    Type: STATEMENT
    Article ID: CJ-20-0322
    Published: July 10, 2020
    [Advance publication] Released: July 10, 2020
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  • Ryuji Fukazawa, Junjiro Kobayashi, Mamoru Ayusawa, Hiromichi Hamada, M ...
    Type: JCS GUIDELINES
    Article ID: CJ-19-1094
    Published: July 08, 2020
    [Advance publication] Released: July 08, 2020
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  • Naoki Taniguchi, Yoko Miyasaka, Yoshinobu Suwa, Shoko Harada, Eri Naka ...
    Type: REVIEW
    Article ID: CJ-20-0258
    Published: July 08, 2020
    [Advance publication] Released: July 08, 2020
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    Atrial fibrillation (AF) is the most common sustained arrhythmia in adults and has unfavorable consequences such as stroke, heart failure (HF), and death. HF is the most common adverse event following AF and the leading cause of death. Therefore, identifying the association between AF and HF is important to establish risk stratification for HF in AF. Recent studies suggested that left atrial and ventricular fibrosis is an important link between AF and HF, and the prognostic impact may differ with respect to HF subtype, stratified with left ventricular ejection fraction (EF). Mortality risk in patients with concurrent AF and HF with reduced EF (HFrEF) appears slightly higher compared with those with concurrent AF and HF with preserved EF (HFpEF). On the other hand, the prognostic impact of HF in AF is similar between HFrEF and HFpEF. Further, left atrial size, as well as left atrial and left ventricular functional assessment, are reported to be useful for the prediction of HF in AF, incremental to the conventional risk factors. In this review, we focus on the epidemiological, pathophysiological, and prognostic associations between AF and HF, and review the clinical and echocardiographic predictors for HF in AF.

  • Yutaka Ogino, Tomoaki Ishigami, Yugo Minamimoto, Yuichiro Kimura, Eiic ...
    Type: ORIGINAL ARTICLE
    Subject Area: Peripheral Vascular Disease
    Article ID: CJ-20-0084
    Published: July 04, 2020
    [Advance publication] Released: July 04, 2020
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    Background:The efficacy and bleeding complications of direct oral anticoagulant (DOAC) therapy for cancer-associated venous thromboembolism (VTE) in routine clinical practice remain unclear. Moreover, data on long-term outcomes in patients with cancer-associated VTE who received DOAC therapy are limited.

    Methods and Results:This retrospective study enrolled 1,096 consecutive patients with acute VTE who received warfarin or DOAC therapy between April 2014 and May 2017. The mean follow-up period was 665±490 days. The number of cancer-associated VTE patients who received DOAC therapy was 334. Patients who could not be followed up and those prescribed off-label under-dose DOAC were excluded. Finally, 303 patients with cancer-associated VTE were evaluated. The number of cases of major bleeding and VTE recurrence was 54 (17.8%) and 26 (8.6%), respectively. In the multivariate analysis, the factors correlated with major bleeding were high cancer stage, high performance status, liver dysfunction, diabetes mellitus, and stomach cancer; those correlated with recurrent VTE were initial diagnosis of pulmonary embolism, uterine cancer, and previous cerebral infarction. Major bleeding was an independent risk factor of all-cause death. In the Kaplan-Meier analysis, those who received prolonged DOAC therapy had lower composite major bleeding and recurrent VTE risks than those who did not.

    Conclusions:In DOAC therapy for cancer-associated VTE, major bleeding prevention is important because it is an independent risk factor of death.

  • Kyohei Marume, Teruo Noguchi, Emi Tateishi, Yoshiaki Morita, Hiroyuki ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-19-1176
    Published: July 03, 2020
    [Advance publication] Released: July 03, 2020
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    Supplementary material

    Background:The clinical characteristics and prognostic outcomes of dilated cardiomyopathy (DCM) with a familial history (FHx) via pedigree analysis are unclear.

    Methods and Results:We conducted a prospective observational study of 514 consecutive Japanese patients with DCM. FHx was defined as the presence of DCM in ≥1 family member within 2-degrees relative based on pedigree analysis. The primary endpoint was a composite of major cardiac events (sudden cardiac death and pump failure death). The prevalence of FHx was 7.4% (n=38). During a median follow-up of 3.6 years, 77 (15%) patients experienced a major cardiac event. Multivariable Cox regression analysis identified FHx as independently associated with major cardiac events (hazard ratio [HR] 4.32; 95% confidence interval [CI], 2.04–9.19; P<0.001) compared with conventional risk factors such as age, QRS duration, and left ventricular volume. In the propensity score-matched cohort (n=38 each), the FHx group had a significantly higher incidence of major cardiac events (HR, 4.48; 95% CI, 1.25–16.13; P=0.022). In addition, the FHx group had a higher prevalence of a diffuse late gadolinium enhancement (LGE) pattern than the no-FHx group (32% vs. 17%, P=0.022).

    Conclusions:DCM patients with FHx had a worse prognosis, which was associated with a higher prevalence of a diffuse LGE pattern, than patients without FHx.

  • Hirohisa Kato
    Type: IN MEMORIAM
    Article ID: CJ-66-0180
    Published: July 02, 2020
    [Advance publication] Released: July 02, 2020
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  • Takashi Yamauchi, Hiroyuki Yamamoto, Hiroaki Miyata, Junjiro Kobayashi ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Surgery
    Article ID: CJ-20-0042
    Published: July 01, 2020
    [Advance publication] Released: July 01, 2020
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    Background:Perioperative risk during surgical aortic valve replacement (SAVR) is reportedly high in dialysis patients. We aimed to determine the postoperative mortality and morbidity and identify the perioperative risk factors of mortality during SAVR in dialysis-dependent patients.

    Methods and Results:From the Japan Adult Cardiovascular Surgery Database, we compared 2,875 dialysis-dependent patients with 18,839 non-dialysis patients who all underwent SAVR between January 2013 and December 2016. The operative mortality was 8.7% vs. 2.0% in the dialysis and non-dialysis groups, respectively. Multivariate stepwise logistic regression analysis for operative mortality revealed 8 independent risk factors including age (odds ratio [OR]=1.2), concomitant coronary artery bypass grafting (OR=1.5), peripheral arterial disease (OR=1.9), atrial fibrillation (OR=2.5), New York Heart Association class IV (OR=2.5), liver dysfunction (OR=5.8), reduced left ventricular function (OR=1.4), and history of previous cardiac surgery (OR=2.1). In addition, 8 postoperative predictors of operative mortality were identified including bleeding deep sternal infection (OR=3.4), prolonged ventilation (OR=5.4) and gastrointestinal complications (OR=10.3).

    Conclusions:Compared with non-dialysis patients, SAVR in dialysis patients was associated with high rates of mortality and morbidity. An appropriate surgical strategy and careful perioperative assessment and management for prevention of infection, and respiratory and gastrointestinal complications might contribute to improved clinical outcomes after SAVR in these patients.

  • Yuya Takahashi, Takanori Yamaguchi, Akira Fukui, Toyokazu Otsubo, Kei ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-20-0149
    Published: July 01, 2020
    [Advance publication] Released: July 01, 2020
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    Background:Renal dysfunction coexists with other known risk factors of left atrial (LA) structural remodeling, expressed as low-voltage zones (LVZs), and the recurrence of atrial fibrillation (AF) after ablation. This study aimed to determine whether renal dysfunction had an independent effect on the presence of LVZs and recurrence after AF ablation, using propensity score (PS) matching analysis.

    Methods and Results:448 consecutive patients who underwent their initial AF ablation were enrolled. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, with 126 (28%) patients having CKD. Using PS matching analysis, new subsets (CKD and non-CKD group, n=103 each) were obtained, matched for age, sex, AF type, and LA volume. The presence of LVZs defined as bipolar voltage <0.5 mV was higher in the CKD group than in the non-CKD group (31% vs. 17%, P=0.034). Multivariate analysis showed eGFR was an independent predictor of the presence of LVZs (odds ratio 1.31 per 10-mL/min/1.73 m2decrease, P=0.029). AF-free survival rate was significantly lower in the CKD patients during 20±9 months of follow-up (63% vs. 82%, P=0.019), and eGFR was shown to be an independent predictor of recurrence (hazard ratio 1.29 per 10-mL/min/1.73 m2decrease, P=0.006), but the presence of LVZs did not predict recurrence.

    Conclusions:Renal dysfunction independently predicted not only the recurrence of AF after ablation but also the presence of LVZs.

  • Yoshiyuki Orihara, Masanori Asakura, Nobuyuki Hida, Mikio Kawai, Toshi ...
    Type: ORIGINAL ARTICLE
    Subject Area: Pulmonary Circulation
    Article ID: CJ-19-1112
    Published: June 26, 2020
    [Advance publication] Released: June 26, 2020
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    Background:Qing-Dai (QD) treatment of patients with ulcerative colitis (UC) sometimes causes pulmonary arterial hypertension (PAH). However, the relationship of QD treatment to pulmonary arterial systolic pressure (PASP) in patients with UC has not been clarified.

    Methods and Results:The 27 patients with UC who were screened for PAH by transthoracic echocardiography (TTE) and underwent repeat TTE at 1 year were analyzed in this prospective observational study. Mean age was 44.0 years old, and median follow-up duration was 392. During the follow-up, 21 patients continued QD treatment (continuous group) and 6 patients discontinued the treatment (discontinuous group). In all patients, no significant difference in PASP levels between baseline and at follow-up was observed (21.4 vs. 21.3 mmHg, P=0.802). Furthermore, the mean PASP of patients in the continuous group did not differ from baseline to follow-up (21.4 mmHg to 22.6 mmHg, P=0.212); however, in the discontinuous group mean PASP was significantly decreased (21.5 mmHg to 16.8 mmHg, P=0.005). Moreover, changes in PASP from baseline to follow-up differed between the continuous and discontinuous groups (+1.1 mmHg vs. −4.7 mmHg, P=0.004). In addition, multivariable analyses revealed that only the duration of oral QD at baseline affected the increase of PASP.

    Conclusions:In patients with UC, QD treatment may have an undesirable association with an increase in PASP.

  • Kazutaka Aonuma, Hiro Yamasaki, Masato Nakamura, Takashi Matsumoto, Mo ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-20-0196
    Published: June 26, 2020
    [Advance publication] Released: June 26, 2020
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    Supplementary material

    Background:The SALUTE trial was a prospective, multicenter, single-arm trial to confirm the safety and efficacy of the WATCHMAN left atrial appendage closure (LAAC) device for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) in Japan.

    Methods and Results:A total of 54 subjects (including 12 roll-in subjects) with a WATCHMAN implant procedure were followed in 10 investigational centers. Follow-up visits were performed up to 2 years post-implant. The baseline CHA2DS2-VASc score was 3.6±1.6 and the baseline HAS-BLED score was 3.0±1.1. All 42 subjects in the intention to treat (ITT) cohort underwent successful implantation of the LAAC device without any serious complications, achieving the prespecified performance goal. The effective LAAC rate was maintained at 100% from 45 days to 12 months post-implant, achieving the prespecified performance goal. During follow-up, 1 subject died of heart failure, and 3 had ischemic strokes, but there were no cases of hemorrhagic stroke or systemic embolism. All events were adjudicated as unrelated to the WATCHMAN device/procedure by the independent Clinical Events Committee. All 3 ischemic strokes were classified as nondisabling based on no change in the modified Rankin scale score.

    Conclusions:Final results of the SALUTE trial demonstrated that the WATCHMAN LAAC device is an effective and safe alternative nonpharmacological therapy for stroke risk reduction in Japanese NVAF patients who are not optimal candidates for lifelong anticoagulation. (Trial Registration: clinicaltrials.gov Identifier NCT 03033134)

  • Te Li, Junlian Gu, Ou Yang, Jianmeng Wang, Yonggang Wang, Jian Kong
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-19-1060
    Published: June 25, 2020
    [Advance publication] Released: June 25, 2020
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    Supplementary material

    Background:Cardiac ischemia/reperfusion (I/R) injury will cause a large amount of cardiomyocyte loss and cascade reactions such as apoptosis, mitochondrial dysfunction, and excessive autophagy. Mesenchymal stem cells (MSCs) are promising therapeutic tools to replace damaged cardiomyocytes, but the underlying mechanism is still unknown.

    Methods and Results:Exosomes contain many microRNAs and protein, which are believed to have multiple biological functions. This study explored the role of bone marrow MSCs (BMMSCs)-derived exosomes under different oxidation levels in heart protection and miRNA-related mechanisms. Exosomes extracted from BMMSCs contained a high level of miR-29c, and its expression level changed after cells were treated under hypoxia/reoxygenation (H/R) conditions. In vivo I/R experiments also confirmed an expression change of miR-29c, and PTEN-Akt-mTOR is one of the predominant pathways that regulate autophagic change during this process.

    Conclusions:This study highlighted the role of miR-29c in regulating autophagy under cardiac I/R injury, which also extended existing mechanisms of a stem cell and its derivative to explore potential therapeutic interventions in ischemic heart diseases.

  • Hideaki Aihara, Michiaki Higashitani, Hideyuki Takimura, Kazuki Tobita ...
    Type: ORIGINAL ARTICLE
    Subject Area: Peripheral Vascular Disease
    Article ID: CJ-20-0218
    Published: June 24, 2020
    [Advance publication] Released: June 24, 2020
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    Supplementary material

    Background:The risk of restenosis after intervention is higher in femoropopliteal than in aortoiliac lesions. However, the appropriate endovascular therapy (EVT) for preventing restenosis after intervention for femoropopliteal lesions remains unknown. This study aimed to elucidate the relationship between lesion characteristics and patency after EVT using intravascular ultrasound (IVUS) measurement and to determine the predictors of restenosis on IVUS.

    Methods and Results:This prospective observational study was performed at 18 Japanese centers. We evaluated the lesion characteristics before and after EVT for femoropopliteal lesion using IVUS. Angiographic or duplex ultrasound follow-up was performed at 1 year after EVT. A total of 263 lesions underwent EVT between December 2016 and December 2017. In total, 20 lesions (8 cases of isolated common femoral artery lesion and 12 cases of restenosis lesion) were excluded, and 243 lesions were enrolled in this study. A total of 181 lesions were treated with stent placement, and 62 lesions were treated only with balloon angioplasty. In the case of stent use, a larger distal plaque burden was associated with restenosis, while a lower calcification angle was associated with higher patency in the case of balloon angioplasty alone.

    Conclusions:The factors related to patency differed depending on the treating modality. The findings suggest that IVUS is a useful tool for predicting patency because it can provide a more accurate evaluation after EVT for femoropopliteal lesions.

  • Yukiko Mizutani, Tetsuya Ishikawa, Shingo Watanabe, Sayuki Kobayashi, ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-20-0124
    Published: June 18, 2020
    [Advance publication] Released: June 18, 2020
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  • Subaru Tanabe, Yusuke Nakano, Hirohiko Ando, Hirofumi Ohashi, Kentaro ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-20-0276
    Published: June 18, 2020
    [Advance publication] Released: June 18, 2020
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    Supplementary material
  • Toru Shimaoka, Yan Wang, Masaki Morishima, Shinji Miyamoto, Katsushige ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-20-0310
    Published: June 18, 2020
    [Advance publication] Released: June 18, 2020
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    Supplementary material

    Background:Mechanisms for QT interval prolongation and cardiac arrhythmogenesis in hypomagnesemia are poorly understood. This study investigated the potential molecular mechanism for QT prolongation caused by magnesium (Mg) deficiency in rats by using the patch clamp technique and molecular biology.

    Methods and Results:Male Wistar rats were fed an Mg-free diet or a normal diet for up to 12 weeks. There was QT prolongation in the ECG of Mg-deficient rats, and cardiomyocytes from these rats showed prolongation of action potential duration. Electrophysiological studies showed that inward-rectifying K+current (IK1) and transient outward K+current (Ito) were decreased in Mg-deficient cardiomyocytes, and these findings were consistent with the downregulation of mRNA, as well as protein levels of Kir2.1 and Kv4.2. In Mg-deficient cardiomyocytes, transcription factors, GATA4 and NFAT, were upregulated, whereas CREB was downregulated. In contrast to Mg deficiency, cellular Mg2+overload in cultured cardiomyocytes resulted in the upregulation of Kir2.1 and Kv4.2, which was accompanied by the downregulation of GATA4 and NFATc4, and the upregulation of CREB. Activation of NFAT and inhibition of CREB reduced Kv4.2-Ito, whereas Kir2.1-IK1was reduced by CREB inhibition but not by NFTA activation.

    Conclusions:Intracellular Mg deficiency downregulates IK1and Itoin cardiomyocytes, and this is mediated by the transcription factors, NFAT and CREB. These results provide a novel mechanism for the long-term QT interval prolongation in hypomagnesemia.

  • Yasushi Yoshikawa, Yukikatsu Okada, Yutaka Okita, Hitoshi Yaku, Junjir ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Surgery
    Article ID: CJ-19-1113
    Published: June 16, 2020
    [Advance publication] Released: June 16, 2020
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    Background:This study retrospectively evaluated the long-term patient outcomes and durability of the Mosaic aortic porcine bioprosthesis in the Japan Mosaic valve long-term multicenter study.

    Methods and Results:We reviewed the records of 1,202 patients who underwent aortic valve replacement with the Mosaic bioprosthesis at 10 centers in Japan (1999–2014). Patient data were collected using Research Electronic Data Capture. Patient survival was determined by Kaplan-Meier methodology. Freedom from structural valve deterioration (SVD) and valve-related reoperation and death were determined by actuarial methods. The median (interquartile range [IQR]) age of the cohort was 76 (70–80) years. The median (IQR) follow-up period was 3.52 (1.71–5.35) years. The longest follow-up was 15.8 years. The 30-day mortality rate was 2.3%. The 12-year actuarial survival rate was 59.9±7.5%, and the freedom from valve-related death was 81.1±7.9%. The freedom from reoperation was 86.4±2.6% at 12 years. The freedom from SVD at 12 years was 93.5±2.9% for patients aged ≥65 years and 98.2±1.8% for those aged <65 years. The median (IQR) systolic pressure gradient was 17 (12–23) and 19 (12–25) mmHg at 1 and 10 years, respectively. The median (IQR) effective orifice area was 1.2 (1.1–1.5) and 1.1 (1–1.5) cm2at 1 and 10 years, respectively.

    Conclusions:The Mosaic porcine bioprosthesis showed satisfactory long-term outcomes over 12 years.

  • Shintaro Umemoto, Ichiro Sakamoto, Kohtaro Abe, Ayako Ishikita, Yuzo Y ...
    Type: ORIGINAL ARTICLE
    Subject Area: Pediatric Cardiology and Adult Congenital Heart Disease
    Article ID: CJ-20-0136
    Published: June 16, 2020
    [Advance publication] Released: June 16, 2020
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    Supplementary material

    Background:The latest guidelines recommend early intervention in adult atrial septal defect (ASD) patients with signs of right ventricular (RV) enlargement. However, the criteria of RV enlargement for optimal intervention remain unclear. We investigated the preoperative determinants for normalizing the RV volume after transcatheter closure of ASD in adults.

    Methods and Results:We retrospectively analyzed 52 ASD patients who underwent transcatheter closure. Cardiac magnetic resonance imaging (CMR) measured RV volume before and 1 year after the closure. The patients were divided into normalized (postoperative RV end-systolic volume index [RVESVI] <47 mL/m2and end-diastolic volume index [RVEDVI] <108 mL/m2) and non-normalized (postoperative RVESVI ≥47 mL/m2or RVEDVI ≥108 mL/m2) groups. Preoperative RVESVI was significantly smaller (72 mL/m2vs. 80 mL/m2) and RVEF was higher (56% vs. 51%) in the normalized group compared with the non-normalized group. Receiver-operating characteristic analysis for the normalization of postoperative RV volume showed that the preoperative threshold value of RVESVI was 75 mL/m2. In addition, multivariate analysis showed that preoperative RVESVI was an independent predictor for normalization of RV volume.

    Conclusions:Preoperative RVESVI is an independent predictor for normalization of RV volume at 1 year after transcatheter closure of ASD in adults. Early intervention before RVESVI reaches 75 mL/m2may confer optimal timing for normalizing RV volume.

  • Yangjing Xie, Qinghai You, Chaoran Wu, Shiyu Cao, Guangbo Qu, Xiaoxian ...
    Type: ORIGINAL ARTICLE
    Subject Area: Epidemiology
    Article ID: CJ-20-0348
    Published: June 13, 2020
    [Advance publication] Released: June 13, 2020
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    Background:To investigate the effect of cardiovascular disease (CVD) on the global pandemic, coronavirus disease 2019 (COVID-19), we analyzed the cases of laboratory-confirmed COVID-19 patients in Wuhan.

    Methods and Results:Data were extracted from the medical records. SARS-CoV-2 RNA was confirmed by RT-PCR. A total of 33 (53.2%) of 62 cases with CVD, who had higher prevalence of severe COVID-19 compared with non-CVD patients (P=0.027). The median age of all patients was 66.0 (53.3, 73.0) years old. Coronary artery disease (11.3%) and hypertension (38.7%) were the common coexisting CVDs in COVID-19 patients. High-sensitivity cardiac troponin I (hs-cTnI), creatinine, high-density lipoprotein-cholesterol, interleukin-6, C-reactive protein, prothrombin time, and D-dimer levels in the severe COVID-19 with CVD group were higher than in the non-severe COVID-19 with CVD group (P<0.05). For all patients, chest computed tomography (CT) showed ground-glass opacity (66.1%), local (21.0%), bilateral (77.4%), and interstitial abnormalities (4.8%). In COVID-19 patients with CVD, 27 (81.8%) were cured and discharged. 6 (18.2%) remained in hospital, including 2 (3.2%) patients requiring intubation and mechanical ventilation. The hs-cTnI levels in the remaining hospitalized patients were higher than in the discharged patients (P=0.047).

    Conclusions:CVDs play a vital role in the disease severity of COVID-19. COVID-19 could result in myocardial injury, which affects the prognosis of COVID-19.

  • Tassia Santos Rodrigues da Costa, Gustavo Santos Masson, Rosangela Apa ...
    Type: ORIGINAL ARTICLE
    Subject Area: Hypertension and Circulatory Control
    Article ID: CJ-19-1161
    Published: June 10, 2020
    [Advance publication] Released: June 10, 2020
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    Supplementary material

    Background:The effects of hypertension and exercise training (T) on the sequential interplay between renin-angiotensin system (RAS), autonomic control and heart remodeling during the development of hypertension in spontaneously hypertensive rats (SHR), was evaluated.

    Methods and Results:Time course changes of these parameters were recorded in 4-week-old SHR submitted to a T or sedentary (S) protocol. Wistar Kyoto rats served as controls. Hemodynamic recordings were obtained in conscious rats at experimental weeks 0, 1, 2, 4, and 8. The left ventricle (LV) was collected to evaluate RAS gene and protein expression, cardiomyocytes’ hypertrophy and collagen accumulation. Pre-hypertensive SHR exhibited augmented AT1R gene expression; at 5 weeks, they presented with elevated pressure, increased LV angiotensinogen and ACE mRNA expression, followed by sympathoexcitation (from the 8thweek onwards). Marked AT1R protein content, myocytes’s hypertrophy, collagen deposition and increased pressure variability were observed in 12-week-old sedentary SHR. In addition to attenuating all these effects, T activated Mas receptor expression augmented parasympathetic modulation of the heart, and delayed the onset and reduced the magnitude, but did not block the development of genetic hypertension.

    Conclusions:The close temporal relationship between changes in the LV ACE-Ang II-AT1R axis, autonomic control and cardiac remodeling at both the establishment of hypertension and during exercise training reveals the essential role played by the AT1R pathway in driving cardiac remodeling and autonomic modulation during the transition from the pre- to hypertensive phase.

  • – Sub-Analysis of the KYOTO HEART Study –
    Shinzo Kimura, Takahisa Sawada, Jun Shiraishi, Hiroyuki Yamada, Hiroak ...
    Article ID: CJ-12-0387
    Published: 2012
    [Advance publication] Released: September 12, 2012
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    This article was retracted. See the Notification.
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