Research Achievements - Original paper -
-
Effect of short-duration adaptive servo-ventilation therapy on cardiac function in patients with heart failure.
Takashi Koyama, Hiroyuki Watanabe, Gen Igarashi, Yoshikazu Tamura, Ken Ikeda, Shigenori Terada, Hiroshi Ito
Circulation journal : official journal of the Japanese Circulation Society 76 ( 11 ) 2606 - 13 2012.11 [Refereed]
Research paper (journal)
BACKGROUND: The aim of this study was to investigate whether short-duration adaptive servo-ventilation (ASV) therapy improves cardiac function in heart failure (HF) patients. METHODS AND RESULTS: Consecutive HF patients (n=86) were divided into 3 groups: group A, ASV for a mean of ≥4 h; group B, ASV for ≥1 to <4 h per day; and group C, no ASV or ASV <1 h. The frequency of ASV use did not significantly differ between groups A (79.3±19.2%) and B (70.9±17.4%). After 6 months, a significant increase in left ventricular ejection fraction (LVEF), significant decrease in plasma brain natriuretic peptide (BNP) and decrease in LV end-diastolic volume (LVEDV) were observed in groups A (LVEF, 5.0±8.1%; BNP, -24.9±33.7%; LVEDV, -6.2±10.1%) and B (LVEF, 3.5±5.5%; BNP, -16.5±24.6%; LVEDV, -5.1±8.2%) as compared with group C (LVEF, -1.5±6.0%, P=0.004, P=0.017; BNP, 2.8±10.2%, P=0.002, P=0.017; LVEDV, 0.8±9.1%, P=0.031, P=0.043). Significant correlation was seen between the total ASV time and changes of LVEF (r=0.369, P=0.002), BNP (r=-0.445, P<0.001), and LVEDV (r=-0.374, P=0.001). Admission rate was lower in groups A (4.1%) and B (7.1%) than in group C (25%, log-rank test; P=0.042, P=0.045). Multivariate analysis showed that the frequency of ASV use was a strong parameter for the improvement of LVEF (coefficient=0.284, standard error=0.035, P=0.019). CONCLUSIONS: Even a short-duration of ASV therapy may improve cardiac function in HF patients.
-
Right atrial giant myxoma occupying the right ventricular cavity.
Teruki Sato, Hiroyuki Watanabe, Megumi Okawa, Takako Iino, Kenji Iino, Kazuyuki Ishibashi, Hiroshi Yamamoto, Fumio Yamamoto, Hiroshi Ito
The Annals of thoracic surgery 94 ( 2 ) 643 - 6 2012.08 [Refereed]
Research paper (journal)
We report a case of a giant right atrial myxoma mimicking the right ventricular tumor. The 75-year-old patient underwent cardiac surgery, and the tumor was excised along with the stalk. Tricuspid valve annuloplasty was performed before closure of the right atriotomy. The tumor may have caused intraventricular stenosis, hepatic dysfunction, and progressive fatigue as a result of low cardiac output. This case is of special interest because the myxoma was very large compared with those ever reported, and a right atrial myxoma occupying the right ventricular cavity is rare.
-
A free-floating left atrial thrombus develops intermittent entrapment in the mid-ventricle during diastole.
Mikiko Fujiwara, Hiroyuki Watanabe, Yasunori Oguma, Genbu Yamaura, Kazuyuki Ishibashi, Hiroshi Yamamoto, Kiyoshi Nobori, Kenji Iino, Fumio Yamamoto, Hiroshi Ito
Heart and vessels 27 ( 4 ) 428 - 31 2012.07 [Refereed]
Research paper (journal)
Free-floating left atrial thrombi are rare. Here we report a case of a 75-year-old woman with atrial fibrillation who was admitted for treatment of acute myocardial infarction. A free-floating left atrial thrombus was found incidentally on echocardiography. Ten days after percutaneous coronary intervention, the patient had mild faintness with transient hypotension, and it was found that the left atrial thrombus had developed intermittent entrapment in the mid-ventricle during diastole, with abrupt rebound back to the left atrial cavity during systole. Urgent removal of the thrombus was performed successfully. Although the free-floating thrombus had appeared to be spherical, like a ball thrombus, on echocardiography, the excised thrombus was pedunculated. A cut section revealed a laminated thrombus with an onion-skin-like appearance.
-
Candesartan improves impaired endothelial function in the human coronary artery.
Kenji Iino, Hiroyuki Watanabe, Takako Iino, Mitsuaki Katsuta, Takashi Koyama, Toshimitsu Kosaka, Gen Terui, Hiroshi Ito
Coronary artery disease 23 ( 4 ) 278 - 83 2012.06 [Refereed]
Research paper (journal)
BACKGROUND: Endothelial dysfunction is closely related to cardiovascular events. Several studies have documented that angiotensin II type 1 receptor blockers (ARB) improve peripheral endothelial dysfunction. However, the effect of ARB on coronary endothelial function remains elusive. The purpose of this study was to ascertain the beneficial effects of ARB on human coronary artery endothelial function. METHODS AND RESULTS: Twenty-seven patients were randomly assigned to either the candesartan group (n=14) or the control group (n=13) and followed for 12 months. Coronary blood flow velocity was measured in the left anterior descending artery without stenosis using an intracoronary Doppler-tipped guide-wire. We evaluated coronary endothelial function as the coronary blood flow velocity reserve (CFR), which was defined as the percent change in the coronary blood flow velocity after an intracoronary acetylcholine infusion. At baseline, the CFR in both groups was below 300%, implying that these patients had endothelial dysfunction. After treatment with candesartan for 6 months, the CFR increased significantly from 199 ± 20 to 337 ± 27% (P<0.001), whereas the CFR did not change in the control group (194 ± 32 vs. 185 ± 41%, P=0.52). During 12 months of observation, the cardiovascular event-free survival rate of the patients with an increased CFR was significantly greater than the rate in patients with a decreased CFR (P=0.02). Moreover, the cardiovascular event-free survival rate was greater in the candesartan group than in the control group (P=0.04). CONCLUSION: Our results suggest that candesartan improves coronary endothelial dysfunction of human coronary arteries and may prevent cardiac events.
-
Impact of obesity on plasma B-type natriuretic peptide levels in Japanese community-based subjects.
Megumi Koizumi, Hiroyuki Watanabe, Yoshihiro Kaneko, Kenji Iino, Masaru Ishida, Toshimitsu Kosaka, Yutaka Motohashi, Hiroshi Ito
Heart and vessels 27 ( 3 ) 287 - 94 2012.05 [Refereed]
Research paper (journal)
The plasma B-type natriuretic peptide (BNP) concentration was recently shown to be inversely correlated with body mass index (BMI). However, very few attempts have been made to associate abdominal obesity and BNP in the Japanese general population. Here, we conducted a cross-sectional study, and examined 339 male and 429 female residents without heart disease in a rural Japanese community who received an annual health checkup in 2006. BNP was inversely associated with both BMI and abdominal circumference (AC) in the age-adjusted regression analysis (p < 0.05). Following adjustment for traditional risk factors, multiple regression analysis revealed that BNP was negatively correlated with AC (p < 0.05), but not BMI. Although metabolic syndrome was not associated with BNP levels, AC had an influence on low BNP levels in the multiple regression analysis using both AC and BMI concurrently (p < 0.05 for AC and p > 0.60 for BMI). These effects were more prominent in men than in women. Collectively, plasma BNP levels are inversely related with obesity, as measured by AC, in Japanese community-based subjects.
-
Adequate pulmonary stenosis allowed long-term survival in a patient with unoperated single ventricle.
Mai Terada, Hiroyuki Watanabe, Kenji Iino, Manabu Kakizaki, Masato Takahashi, Hiroshi Ito
Journal of the American College of Cardiology 59 ( 13 ) e25 2012.03 [Refereed]
Research paper (journal)
-
Two cases of calcified amorphous tumor mimicking mitral valve vegetation.
Mikiko Fujiwara, Hiroyuki Watanabe, Takako Iino, Yusuke Kobukai, Kazuyuki Ishibashi, Hiroshi Yamamoto, Kenji Iino, Fumio Yamamoto, Hiroshi Ito
Circulation 125 ( 10 ) e432-4 2012.03 [Refereed]
Research paper (journal)
-
Adaptive servo-ventilation improves renal function in patients with heart failure.
Takashi Koyama, Hiroyuki Watanabe, Shigenori Terada, Shin Makabe, Gen Igarashi, Kiyoshi Nobori, Hiroshi Ito
Respiratory medicine 105 ( 12 ) 1946 - 53 2011.12 [Refereed]
Research paper (journal)
BACKGROUND: Impaired cardiac function and sleep-disordered breathing (SDB) are associated with progression of chronic kidney disease (CKD) in heart failure (HF) patients. Adaptive servo-ventilation (ASV) therapy improves cardiac function in HF patients regardless of the SDB severity through hemodynamic support and prevention of repetitive hypoxic stress. This study was designed to test the hypothesis that ASV therapy improves renal function in HF patients with SDB. METHODS AND RESULTS: Of 59 consecutively enrolled HF patients, 43 with moderate-to-severe SDB underwent ASV therapy. HF patients were divided into the ASV-treated group (n = 27) and the non-ASV-treated group (n = 16). Estimated glomerular filtration rate (eGFR), echocardiographic parameters, and inflammatory biomarkers were measured before and 12 months after ASV initiation. Improvement in the eGFR was found in the ASV-treated group, but not in the non-ASV-treated group. There was a positive correlation between the increases in eGFR and left ventricular ejection fraction (r = 0.488, p = 0.001). The changes in high-sensitivity C-reactive protein were negatively correlated with change in the eGFR (r = -0.416, p = 0.006). CONCLUSIONS: ASV therapy could improve renal dysfunction in HF patients through hemodynamic support. Additionally, prevention of SDB with the use of ASV therapy could exert anti-inflammatory effects, which could contribute to the improvement of renal function in HF patients.
-
Endothelial progenitor cells are associated with response to chemotherapy in human non-small-cell lung cancer.
Ryo Morita, Kazuhiro Sato, Mariko Nakano, Hajime Miura, Hidesato Odaka, Kiyoshi Nobori, Toshimitsu Kosaka, Masaaki Sano, Hiroyuki Watanabe, Takanobu Shioya, Hiroshi Ito
Journal of cancer research and clinical oncology 137 ( 12 ) 1849 - 57 2011.12 [Refereed]
Research paper (journal)
PURPOSE: Bone marrow-derived endothelial progenitor cells (EPCs) play an important role in angiogenesis and tumor growth. However, the clinical relevance of EPCs in non-small-cell lung cancer (NSCLC) remains unclear. Recently, some reports suggested that EPCs correlate with clinical behavior of cancer patients. We assessed the hypothesis that EPCs correlate with efficient of therapy, prognosis, and clinicopathological factors, and EPCs may offer a possible biomarker for treatment outcome in NSCLC. METHODS: EPCs labeled with CD34, CD133, and vascular endothelial growth factor receptor-2 (VEGFR-2) antibodies were counted by flow cytometry in the peripheral blood of 31 NSCLC patients. We categorized two groups of NSCLC patients according to circulating EPC numbers. We examined age, pathological stage, histological type, Fluoro-D: -glucose Positron emission tomography (FDG-PET), response to therapy, progression-free survival, and tumor size of NSCLC patients and investigated whether these factors correlate with EPC counts. RESULTS: Circulating EPC numbers before antitumor therapy were increased in NSCLC patients compared with healthy controls (P < 0.05). In NSCLC patients, therapy was significantly effective in low circulating EPC group compared with that of high (P < 0.05). Furthermore, the low EPC group showed significantly longer progression-free survival times than that of high (P < 0.05). However, no significant associations with age, gender, histological type, pathological stage, or FDG-PET were detected. CONCLUSION: Peripheral blood levels of bone marrow-derived EPCs are significantly increased in patients with NSCLC and correlate with response to chemotherapy. EPCs may offer a possible biomarker for efficient of treatment and prognosis.
-
Low mean corpuscular hemoglobin level is a predictor of discontinuation of antiplatelet therapy in patients with acute coronary syndrome.
Masaru Ishida, Hiroyuki Watanabe, Kenji Iino, Megumi Okawa, Toshimitsu Kosaka, Hiroshi Ito
Internal medicine (Tokyo, Japan) 50 ( 24 ) 2933 - 9 2011.12 [Refereed]
Research paper (journal)
OBJECTIVE: Premature discontinuation of antiplatelet therapy (APT) increases the risk of thrombosis in patients who have undergone placement of a drug-eluting stent for acute coronary syndrome (ACS). The goal of the present study was to identify predictors of patients who would prematurely discontinue APT following stent implantation. METHODS: One-hundred and sixty-one ACS patients who underwent percutaneous coronary intervention in our institution between November 2004 and September 2008 were enrolled in this study. RESULTS: Over the 12-month follow-up period, 18 patients (11.2%) discontinued APT. Among baseline demographic and laboratory variables, multivariate analysis revealed that mean corpuscular hemoglobin (MCH) level was an independent risk factor for APT discontinuation (OR: 0.738, p=0.017). Kaplan-Meier survival analysis showed that the incidence of APT discontinuation was significantly higher in patients with low MCH (<30.0 pg) than in patients with high MCH (≥30.0 pg) (p=0.0006). CONCLUSION: Low baseline MCH level was a predictor of APT discontinuation in ACS patients. Thus, careful consideration should be made before employing a drug-eluting stent in patients with low MCH levels.
-
Expression of the transient receptor potential channel c3 correlates with a favorable prognosis in patients with adenocarcinoma of the lung.
Hajime Saito, Yoshihiro Minamiya, Hiroyuki Watanabe, Naoko Takahashi, Manabu Ito, Hiroshi Toda, Hayato Konno, Masafumi Mitsui, Satoru Motoyama, Jun-ichi Ogawa
Annals of surgical oncology 18 ( 12 ) 3377 - 83 2011.11 [Refereed]
Research paper (journal)
BACKGROUND: The cation channels of the transient receptor potential (TRP) superfamily are implicated in cancer formation; in particular, TRPC3 has been shown to contribute to the progression of human ovarian cancer. However, the relationship between TRP expression and the clinicopathological characteristics of lung cancer and patient prognosis is not well understood. Therefore, we investigated the relationship between TRP expression and the prognosis of patients with adenocarcinoma of the lung. METHODS: We used semiquantitative real-time reverse transcription polymerase chain reaction to assess the expression of TRP mRNA in tumor samples from 95 patients with adenocarcinoma of the lung. We then correlated the TRP mRNA levels with clinicopathological factors. We also used immunohistochemical staining to determine the localization of expressed TRP. RESULTS: The 5-year overall and disease-free survival rates among patients expressing higher levels of TRPC3 mRNA were significantly better than the corresponding rates among patients expressing lower levels (P=0.004, P=0.002, respectively, by log-rank test). Multivariate Cox proportional hazard analyses revealed that tumor size (hazard ratio, 2.46; 95% confidence interval [CI], 1.06 to 5.79; P=0.036), n2 (hazard ratio, 3.81; 95% CI, 1.29 to 11.77; P=0.015) and TRPC3 (hazard ratio, 2.71; 95% CI, 1.33 to 5.59; P=0.006) were independent factors affecting the 5-year overall survival rate. Immunohistochemistry showed that the cytoplasm of tumor cells were stained positively for TRPC3. CONCLUSIONS: Higher levels of TRPC3 expression in tumor cells are an independent predictor of a better prognosis in patients with adenocarcinoma of the lung.
-
The prevalence of apical wall motion abnormalities in patients with long-term right ventricular apical pacing.
Takako Sato-Iino, Hiroyuki Watanabe, Takashi Koyama, Kenji Iino, Toshimitsu Kosaka, Hiroshi Ito
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography 24 ( 5 ) 556 - 564 2011.05 [Refereed]
Research paper (journal)
BACKGROUND: Long-term right ventricular apical pacing (RVAP) can lead to adverse clinical outcomes. Although left ventricular (LV) dyssynchrony is the major causative factor, other potential mechanisms are not fully understood. We sought to clarify whether RVAP elicits apical wall motion abnormalities that contribute to LV contractile dysfunction. METHODS: We studied annual echocardiographic data over a 5-year period after pacemaker implantation (PMI) for 74 patients who underwent RVAP. The patients were divided into two groups according to the percentage of ventricular pacing: right ventricular (RV) pacing < 50% and RV pacing ≥ 50%. We assessed LV ejection fraction, LV end-diastolic volume, and left atrial dimension. To assess regional wall motion abnormalities, the wall motion score index was calculated. RESULTS: LV wall motion abnormality was observed in 64% of the subjects and was more pronounced in apical segments than in other segments. At 2 years after PMI, brain natriuretic peptide levels were significantly higher in the group with RV pacing ≥ 50% than in the group with RV pacing < 50%. The subjects with RV pacing ≥ 50% had higher LV end-diastolic dimension and lower ejection fraction at 3 years after PMI. CONCLUSION: Long-term RVAP elicits apical wall motion abnormalities that could in part contribute to LV contractile dysfunction.
-
Short-term prognosis of adaptive servo-ventilation therapy in patients with heart failure.
Takashi Koyama, Hiroyuki Watanabe, Gen Igarashi, Shigenori Terada, Shin Makabe, Hiroshi Ito
Circulation journal : official journal of the Japanese Circulation Society 75 ( 3 ) 710 - 2 2011.03 [Refereed]
Research paper (journal)
BACKGROUND: This study tested the hypothesis that adaptive servo-ventilation (ASV) therapy improves the prognosis of heart failure (HF) patients, regardless of the severity of sleep-disordered breathing (SDB). METHODS AND RESULTS: 88 consecutive patients were divided into 4 groups based on ASV therapy and SDB severity. The incidence of HF, brain natriuretic peptide (BNP) levels, and left ventricular ejection fraction (LVEF) were followed for 12 months. Fewer HF events, together with an increase in LVEF and a decrease in BNP, occurred in ASV-treated patients with both non-to-mild and moderate-to-severe SDB. CONCLUSIONS: ASV therapy improves the short-term prognosis in HF-patients, regardless SDB severity.
-
Abnormal coagulation and platelet profile in patients with obstructive sleep apnea syndrome.
Shigenori Terada, Takashi Koyama, Hiroyuki Watanabe, Shin Makabe, Gen Igarashi, Katsuhito Seki, Hiroshi Ito
International journal of cardiology 146 ( 3 ) 423 - 5 2011.02 [Refereed]
Research paper (journal)
-
TRPV1 and TRPA1 in pulmonary vagal afferents and their relations to airway sensitivity
Hiroyuki Watanabe, Takayoshi Ohba, Kazuhiro Satoh, Masaaki Sano, Takanobu Shioya and Hiroshi Ito
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 10 ( 1 ) 18 - 30 2011.02 [Refereed]
Research paper (journal)
In the last 15 years, studies of transient receptor potential (TRP) channels have significantly extended our knowledge about the molecular basis of sensory function in pulmonary vagal afferents. In particular, TRPV1 and TRPA1 channels are unique cellular sensors for a wide range of inflammatory mediators and noxious irritants. These channels act as the molecular integrator of multiple nociceptive stimuli and are involved in multiple cellular functions, ranging from transduction of sensory signals to the release of neuropeptides in pulmonary vagal afferents. Increased activity of TRPV1 channels is now recognized as a cause of airway hypersensitivity in inflammatory airway diseases. In this review, we summarize current knowledge about the activation mechanisms of TRPV1 and TRPA1, and discuss the possible functional implications of TRPV1 and TRPA1 in human physiology and pathophysiology, such as the cough reflex and hypersensitivity.
-
Cardiac Diagnosing by a Piezoelectric-transducer-based Heart Sound Monitor System
Shinichi Sato, Takashi Koyama, Kyoichi Ono, Gen Igarashi, Hiroyuki Watanabe, Hiroshi Ito, Mikio Muraoka
BIODEVICES 280 - 283 2011.01 [Refereed]
Research paper (journal)
-
Fluvastatin protects vascular smooth muscle cells against oxidative stress through the Nrf2-dependent antioxidant pathway.
Shin Makabe, Yoichiro Takahashi, Hiroyuki Watanabe, Manabu Murakami, Takayoshi Ohba, Hiroshi Ito
Atherosclerosis 213 ( 2 ) 377 - 84 2010.12 [Refereed]
Research paper (journal)
OBJECTIVE: HMG-CoA reductase inhibitors (statins) have pleiotropic actions, including the ability to reduce vascular oxidative stress. Transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important regulator of cellular oxidative stress. This study examined the role of Nrf2 in statin-mediated antioxidant effects in vascular smooth muscle cells. METHODS AND RESULTS: In cultured human coronary artery smooth muscle cells (hCASMCs), fluvastatin activated the nuclear translocation of Nrf2, as evaluated by Western blotting and immunocytochemical analyses. Nrf2-antioxidant response element (ARE) activity was measured with a luciferase assay after transfection of reporter plasmids containing AREs. Fluvastatin significantly increased the transcriptional activity of the ARE. Electromobility shift assays using an ARE probe detected a complex that was significantly increased in intensity by fluvastatin. Western blotting and luciferase assay revealed fluvastatin activated Nrf2 via the PI3K/Akt pathway. Statins upregulated the Nrf2-related antioxidant genes heme oxygenase-1, NAD(P)H quinone oxidoreductase-1, and glutamate-cysteine ligase modifier subunits. Inhibition of Nrf2 by siRNA reduced statin-induced upregulation of these antioxidant genes. Moreover, Nrf2 siRNA markedly reduced the cytoprotective effects of fluvastatin against H(2)O(2) administration in hCASMCs. CONCLUSIONS: Fluvastatin exerts cytoprotective effects against oxidative stress, inducing antioxidant genes through Nrf2/ARE in hCASMCs. These results suggest that the Nrf2/ARE pathway plays an important role in the regulation of statin-mediated antioxidant effects in vascular smooth muscle cells.