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Kimitake Imamura,
Akihiro Yoshida,
Asumi Takei,
Koji Fukuzawa,
Kunihiko Kiuchi,
Kaoru Takami,
Mitsuru Takami,
Mitsuaki Itoh,
Ryudo Fujiwara,
Atsushi Suzuki,
Tomoyuki Nakanishi,
Soichiro Yamashita,
Akinori Matsumoto, Ken-Ichi Hirata
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ABSTRACT: PURPOSE: Dabigatran is effective for both the prevention of stroke and bleeding in patients with atrial fibrillation (AF). However, the safety and efficacy of the use of dabigatran in the peri-procedural period for radiofrequency catheter ablation (RFCA) of AF is unknown. Therefore, the purpose of this study was to evaluate the safety and efficacy of dabigatran in the peri-procedural period for RFCA of AF and the duration of hospital stay. METHODS: Consecutive patients (n = 227) who underwent RFCA for AF were prospectively analyzed. Peri-procedural anticoagulant therapy with dabigatran (n = 101, D group) was compared with warfarin and heparin bridging (n = 126, W group). Dabigatran was discontinued 12-24 h before and restarted 3 h after the procedure. Warfarin was stopped 3 days before the procedure and unfractionated heparin was administered. RESULTS: Ischemic stroke occurred in one patient of the D group (0.8 %). There was no significant difference between the two groups in the incidence of major bleeding (three cases of cardiac tamponade in each group and one case of intracranial bleeding in the W group, p = 0.93) or minor bleeding (five cases in the D group vs. five in the W group, p = 0.54). The duration of hospital stay was significantly shorter in the D group than in the W group (7.2 vs. 10.3 days, p = 0.0001). CONCLUSIONS: Peri-procedural anticoagulation therapy with dabigatran for RFCA of AF was equally safe and effective compared with warfarin and heparin bridging. The use of dabigatran for RFCA of AF shortened the duration of hospital stay.
Journal of Interventional Cardiac Electrophysiology 04/2013; · 1.17 Impact Factor
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ABSTRACT: Background: Left ventricular (LV) dyssynchrony is not a stable phenomenon, but rather, changes dynamically. Given that the prognostic impact of dynamic dyssynchrony has not yet been elucidated, the objective was to investigate the clinical impact of dynamic dyssynchrony on patients with dilated cardiomyopathy (DCM). Methods and Results: Seventy DCM patients with ejection fraction 32±9% were retrospectively recruited, and 3-dimensional speckle-tracking area strain was used to measure both contractile reserve and changes in dyssynchrony during dobutamine stress. The standard deviation of time-to-peak area strain was adopted as the systolic dyssynchrony index. Event-free survival was then tracked over a 13-month period. A ≥7.55% increase in systolic dyssynchrony index during dobutamine stress (Δsystolic dyssynchrony index) was the best predictor of cardiovascular events with 77% sensitivity and 88% specificity. Multivariate Cox analysis indicated that not only the absence of contractile reserve (Δglobal area strain ≤21.1%: hazard ratio [HR], 15.29; P=0.01), but the presence of dynamic dyssynchrony (ΔLV dyssynchrony ≥7.55%: HR: 7.591; P=0.003) was an independent predictor of cardiovascular events. Importantly, absence of dynamic dyssynchrony and presence of contractile reserve were associated with the most favorable outcome (98%), whereas the reverse condition was associated with the worst outcome (20%, P<0.001). Conclusions: Dynamic dyssynchrony is a potential predictor of cardiovascular events in patients with DCM, while assessment of dynamic dyssynchrony in combination with contractile reserve may further improve prognostic risk stratification.
Circulation Journal 04/2013; · 3.77 Impact Factor
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ABSTRACT: OBJECTIVE: Intimal thickening is considered to result from the dedifferentiation of medial smooth muscle cells (SMCs) from a contractile to a synthetic phenotype, and their subsequent migration and proliferation. It is unknown whether nectin-like molecule (Necl)-5, which is overexpressed in cancer cells, is involved in intimal thickening.Approach and Results-Necl-5 was upregulated in mouse carotid artery after ligation. Compared with wild-type mice, intimal thickening after carotid artery ligation was milder in Necl-5 knockout mice. In vitro, the expression levels of SMC differentiation markers were higher, whereas the expression level of an SMC dedifferentiation marker was lower, in Necl-5 knockout mouse aortic SMCs (MASMCs) compared with wild-type MASMCs. The migration, proliferation, and extracellular signal-regulated kinase activity in response to serum were decreased in Necl-5 knockout MASMCs compared with wild-type MASMCs. In wild-type MASMCs, inhibition of extracellular signal-regulated kinase activity increased the expression levels of SMC differentiation markers and decreased their migration and proliferation in response to serum. CONCLUSIONS: The present findings indicate that Necl-5 plays a role in the formation of intimal thickening after carotid artery ligation by regulating dedifferentiation, migration, and proliferation of SMCs in an extracellular signal-regulated kinase-dependent manner. Our results suggest that Necl-5 may represent a potential therapeutic target to limit intimal thickening after vascular injury.
Arteriosclerosis Thrombosis and Vascular Biology 03/2013; · 6.37 Impact Factor
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Hideto Nakajima,
Tatsuro Ishida,
Seimi Satomi-Kobayashi,
Kenta Mori,
Tetsuya Hara,
Naoto Sasaki,
Tomoyuki Yasuda,
Ryuji Toh,
Hidekazu Tanaka,
Hiroya Kawai, Ken-Ichi Hirata
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ABSTRACT: Lipoprotein lipase has been considered as the only enzyme capable of generating lipid-derived fatty acids for cardiac energy. Endothelial lipase is another member of the triglyceride lipase family and hydrolyzes high-density lipoproteins. Although endothelial lipase is expressed in the heart, its function remains unclear. We assessed the role of endothelial lipase in the genesis of heart failure. Pressure overload-induced cardiac hypertrophy was generated in endothelial lipase-/- and wild-type mice by ascending aortic banding. Endothelial lipase expression in cardiac tissues was markedly elevated in the early phase of cardiac hypertrophy in wild-type mice, whereas lipoprotein lipase expression was significantly reduced. Endothelial lipase-/- mice showed more severe systolic dysfunction with left-ventricular dilatation compared with wild-type mice in response to pressure overload. The expression of mitochondrial fatty acid oxidation-related genes, such as carnitine palmitoyltransferase-1 and medium-chain acyl coenzyme A dehydrogenase, was significantly lower in the heart of endothelial lipase-/- mice than in wild-type mice. Also, endothelial lipase-/- mice had lower myocardial adenosine triphosphate levels than wild-type mice after aortic banding. In cultured cardiomyocytes, endothelial lipase was upregulated by inflammatory stimuli, whereas lipoprotein lipase was downregulated. Endothelial lipase-overexpression in cardiomyocytes resulted in an upregulation of fatty acid oxidation-related enzymes and intracellular adenosine triphosphate accumulation in the presence of high-density lipoprotein. Endothelial lipase may act as an alternative candidate to provide fatty acids to the heart and regulate cardiac function. This effect seemed relevant particularly in the diseased heart, where lipoprotein lipase action is downregulated.
Hypertension 03/2013; · 6.21 Impact Factor
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Hirotoshi Hariki,
Toshiro Shinke,
Hiromasa Otake,
Junya Shite,
Masayuki Nakagawa,
Takumi Inoue,
Tsuyoshi Osue,
Masamichi Iwasaki,
Yu Taniguchi,
Ryo Nishio,
Noritoshi Hiranuma,
Hiroto Kinutani,
Akihide Konishi, Ken-Ichi Hirata
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ABSTRACT: Background: Treatment of coronary bifurcation lesions using a single stenting strategy is preferable over that using a 2-stent technique. The benefit of final kissing inflation (FKI), however, has not been established. Methods and Results: Seventy-two patients (76 lesions) with true bifurcation lesions treated with a single drug-eluting stent with FKI (n=33 lesions) or without FKI (non-FKI, n=43 lesions) were enrolled in this study. Optical coherence tomography (OCT) was performed at 6-12 months after implantation. Based on the OCT findings, the percentage of jailing struts (number of jailing struts/total number of struts at the bifurcation lesion) was calculated. Percentage of uncovered struts and frequency of thrombus attachment were each evaluated at the proximal, bifurcation, and distal segments. Major adverse cardiac events (MACE) were also evaluated. The percentage of jailing struts was significantly lower in the FKI than in the non-FKI group (5.8±6.2% vs. 17.3±6.1%, P<0.01). Thrombus attachment was less frequent in the FKI group (24.2% vs. 46.5%, P=0.046), especially at side-branch orifices (3.0% vs. 27.9%, P<0.001). The percentage of uncovered struts was lower in the FKI than non-FKI group at the proximal, bifurcation, and distal segments. The incidence of MACE was not different in this small cohort. Conclusions: FKI might reduce the frequency of subclinical thrombus possibly by reducing the number of jailing struts.
Circulation Journal 02/2013; · 3.77 Impact Factor
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ABSTRACT: OBJECTIVE: Lecithin:cholesterol acyltransferase (LCAT) is thought to be important in reverse cholesterol transport. However, its association with coronary heart disease (CHD) and sudden death is controversial.Approach and Results-We prospectively studied 1927 individuals from the general population. Serum concentrations of apolipoprotein A-I, A-II, B, C-II, C-III, E, and LCAT activity measured as a serum cholesterol esterification rate were evaluated. We documented 61 events of CHD and sudden death during 10.9 years of follow-up. After adjustment for age and sex, LCAT activity was significantly associated with the risk of CHD and sudden death (hazard ratio, 3.02; 95% confidence interval, 1.49-6.12; P=0.002). In multivariate analysis adjusted for age, sex, current smoking status, history of diabetes mellitus, body mass index, systolic blood pressure, serum total cholesterol, and serum high-density lipoprotein cholesterol concentrations, the hazard ratio of LCAT activity for the risk of CHD and sudden death remained significant (hazard ratio, 3.07; 95% confidence interval, 1.35-7.01; P=0.008). However, when it was analyzed for men and women separately, this association remained significant only in women. CONCLUSIONS: Increased LCAT activity measured as a serum cholesterol esterification rate was a risk for CHD and sudden death in a Japanese general population.
Arteriosclerosis Thrombosis and Vascular Biology 02/2013; · 6.37 Impact Factor
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Kenta Mori,
Tatsuro Ishida,
Tomoyuki Yasuda,
Tomoko Monguchi,
Maki Sasaki,
Kensuke Kondo,
Minoru Hasokawa,
Hideto Nakajima,
Yoko Haraguchi,
Li Sun,
Masakazu Shinohara,
Ryuji Toh,
Kunihiro Nishimura, Ken-Ichi Hirata
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ABSTRACT: BACKGROUND: To identify new therapeutic targets for coronary artery disease (CAD), we investigated whether fasting serum concentration of apolipoprotein (apo) B48 could be a marker for CAD. METHODS: Patients with CAD were divided into those with new-onset CAD [i.e., those receiving percutaneous coronary intervention (PCI) for the first time] and those with chronic CAD (i.e., those receiving follow-up coronary angiography). Fasting serum biochemical analyses were performed on admission and 6months after the PCI. RESULTS: On admission, serum LDL-C concentrations in patients with chronic CAD (n=138), presumably receiving statin treatment, were lower than in patients with new-onset CAD (n=50, p<0.02) or without CAD (n=71, p<0.001). Nevertheless, apoB48 was higher in CAD patients than in those without CAD (p<0.001). After adjusting for classic cardiovascular risk factors, multivariate logistic regression analyses showed apoB48 to be an independent predictor of coronary risk in new-onset or chronic CAD, irrespective of the LDL-C levels. Moreover, apoB48 was markedly increased during the follow-up period in CAD patients having new lesion progression after the prior PCI. CONCLUSION: Fasting serum apoB48 concentration could be a marker of new onset as well as chronic CAD, and predict new lesion progression in secondary prevention.
Clinica chimica acta; international journal of clinical chemistry 02/2013; · 2.54 Impact Factor
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ABSTRACT: Endothelin-1 (ET-1) has been shown to be involved in human pulmonary fibrosis. However, recent clinical trials targeting the ET-1 pathway with ET-1 receptor antagonists failed to achieve beneficial outcomes. Another strategy opposing the actions of ET-1 is the inhibition of endothelin-converting enzyme-1 (ECE-1). We hypothesize that ECE-1 inhibition has beneficial effects on pulmonary fibrosis. Pulmonary fibrosis was induced by instilling bleomycin intratracheally into ECE-1 heterozygous knock-out mice (ECE-1+/-) and their wild type (ECE-1+/+). Lung inflammation and fibrosis were assessed on days 7, 14, and 28 after bleomycin instillation. The activity of ECE-1 and the levels of its related peptides, ET-1, bradykinin, atrial natriuretic peptide (ANP), and calcitonin gene-related peptide (CGRP) were determined. ECE-1+/- mice had less lung inflammation and limited fibrosis compared to the controls. ECE-1 activity was half-reduced in ECE-1+/- mice, which altered ET-1 and CGRP levels but not those of bradykinin and ANP. ET-1 levels were found to be lower in ECE-1+/- mice after the development of fibrosis, which is in contrast to the unaltered levels during inflammation. Reduced ECE-1 activity resulted in higher CGRP levels, which altered the pathological functionality of the lung, indicating the activation of CGRP pathway involving cAMP/EPAC1 and cAMP/PKA in ECE-1+/- mice. Bleomycin instillation on day 14 induced the accumulation of M2 macrophages expressing CGRP receptors in ECE-1+/- mice. Our results highlight that in vivo ECE-1-mediated degradation of CGRP promotes transition from lung inflammation to fibrosis. Further, our study identified M2 macrophages to be the target cells of CGRP action during this transition.
American Journal of Respiratory Cell and Molecular Biology 01/2013; · 5.13 Impact Factor
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Hiroyuki Kawamori,
Junya Shite,
Toshiro Shinke,
Hiromasa Otake,
Daisuke Matsumoto,
Masayuki Nakagawa,
Ryoji Nagoshi,
Amane Kozuki,
Hirotoshi Hariki,
Takumi Inoue,
Tsuyoshi Osue,
Yu Taniguchi,
Ryo Nishio,
Noritoshi Hiranuma, Ken-Ichi Hirata
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ABSTRACT: AIMS: We performed this study to clarify natural consequences of abnormal structures (stent malapposition, thrombus, tissue prolapse, and stent edge dissection) after percutaneous coronary intervention (PCI). METHODS AND RESULTS: Thirty-five patients treated with 40 drug-eluting stents underwent serial optical coherence tomography (OCT) imaging immediately after PCI and at the 8-month follow-up. Among a total of 73 929 struts in every frame, 431 struts (26 stents) showed malapposition immediately after PCI. Among these, 49 remained malapposed at the follow-up examination. The mean distance between the strut and vessel wall (S-V distance) of persistent malapposed struts on post-stenting OCT images was significantly longer than that of resolved malapposed struts (342 ± 99 vs. 210 ± 49 μm; P <0.01). Based on receiver-operating characteristic curve analysis, an S-V distance ≤260 µm on post-stenting OCT images was the corresponding cut-off point for resolved malapposed struts (sensitivity: 89.3%, specificity: 83.7%, area under the curve = 0.884). Additionally, 108 newly appearing malapposed struts were observed on follow-up OCT, probably due to thrombus dissolution or plaque regression. Thrombus was observed in 15 stents post-PCI. Serial OCT analysis revealed persistent thrombus in 1 stent, resolved thrombus in 14 stents, and late-acquired thrombus in 8 stents. Tissue prolapse observed in 38 stents had disappeared at the follow-up. All eight stent edge dissections were repaired at the follow-up. CONCLUSION: Most cases of stent malapposition with a short S-V distance, thrombus, tissue prolapse, or minor stent edge dissection improved during the follow-up. These OCT-detected minor abnormalities may not require additional treatment.
European heart journal cardiovascular Imaging. 01/2013;
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ABSTRACT: A 65-year-old man was referred to our hospital due to an acute onset of dyspnea and persistent fever. Echocardiography revealed an ejection fraction (EF) of 25% with diffuse severe left ventricular (LV) dysfunction. 18F-fluorodeoxy glucose-positron emission tomography imaging showed significantly increased uptake by the LV and right ventricular walls, indicating active inflammation. The histologic findings of the endomyocardial biopsy specimens indicated the presence of epithelioid cell granuloma. The final diagnosis was thus cardiac sarcoidosis with acute inflammation. Five-months after the initiation of steroid therapy, echocardiography showed an EF of 50%. This is a rare case in which acute inflammation led to acute heart failure mimicking acute myocarditis.
Internal Medicine 01/2013; 52(1):71-4. · 0.94 Impact Factor
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Tetsushi Yamamoto,
Hidekazu Tanaka,
Kensuke Matsumoto,
Tomoko Lee,
Hiroyuki Awano,
Mariko Yagi,
Takamitsu Imanishi,
Nobuhide Hayashi,
Yasuhiro Takeshima,
Hiroya Kawai,
Seiji Kawano, Ken-Ichi Hirata
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ABSTRACT: Myocardial damage in Duchenne muscular dystrophy (DMD) has lethal outcomes, making early detection of myocardial changes in patients with DMD vital, because early treatment can help prevent the development of myocardial fibrosis. The aim of the present study was, therefore, to test the hypothesis that transmural strain profile (TMSP) analysis can predict future left ventricular (LV) dysfunction in patients with DMD with preserved ejection fraction. We studied 82 consecutive patients with DMD without LV wall motion abnormality, with an ejection fraction of 60 ± 5% (all ≥55%) and age 11 ± 3 years. Echocardiography was performed at baseline and 1 year of follow-up. TMSP in the posterior wall was evaluated from the mid-LV short-axis view. A normal TMSP pattern (1 peak in the endocardium, group 1) was seen in 44 patients, and TMSP with a notch (2 peaks in the endocardium, group 2) in the remaining 38 (46%). Wall motion abnormality in the posterior wall was observed in 16 patients (42%) in group 2 at 1 year of follow-up but in none of the patients in group 1 (42% vs 0%; p <0.001). Importantly, multivariate analysis showed that only TMSP with a notch (odds ratios 1.524, p <0.001) was an independent determinant of the presence of LV posterior wall motion abnormality at 1 year of follow-up. In conclusion, subclinical LV dysfunction can be detected by evaluation of TMSP in patients with DMD who do not have wall motion abnormalities by conventional echocardiography. TMSP with a notch proved effective for evaluating subtle early changes in patients with DMD and might be useful for predicting LV dysfunction.
The American journal of cardiology 12/2012; · 3.58 Impact Factor
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Ryoji Nagoshi,
Toshiro Shinke,
Hiromasa Otake,
Junya Shite,
Daisuke Matsumoto,
Hiroyuki Kawamori,
Masayuki Nakagawa,
Amane Kozuki,
Hirotoshi Hariki,
Takumi Inoue, [......],
Naoki Miyoshi,
Tomofumi Takaya,
Shinichiro Yamada,
Yoshinori Yasaka,
Takatoshi Hayashi,
Mitsuhiro Yokoyama,
Hiroki Kato,
Makoto Kadotani,
Yoshio Ohnishi, Ken-Ichi Hirata
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ABSTRACT: Background: We hypothesized that the tissue components of in-stent restenosis (ISR) might differ between drug-eluting stents (DES) and bare-metal stents (BMS) and that these differences could be distinguished by qualitative and quantitative optical coherence tomography (OCT) analyses. Methods and Results: One-hundred and twenty-two initial ISR lesions (sirolimus-eluting stents: n=28; paclitaxel-eluting stents: n=51; BMS: n=43) were evaluated with OCT. Based on their OCT appearance, the lesions were classified as homogeneous, layered or heterogeneous. The optical properties of backscatter, attenuation and signal intensity of the neointimal tissue (NIT) were quantified. To evaluate the vascular response after balloon angioplasty (BA), the rate of reduction of the NIT area (NITA) was calculated (NITA before - after BA/NITA before BA at the minimum lumen cross-sectional area). Among the morphologic OCT patterns, the layered type was predominant with DES, whereas lesions were homogeneous with BMS (P<0.001). Backscatter and signal intensity were significantly higher with BMS (P<0.05 and P<0.001 respectively). The NITA reduction rate was significantly greater in the layered and heterogeneous groups than in the homogeneous group (P<0.01). Conclusions: The morphologic OCT patterns of the NIT in ISR differed significantly between DES and BMS, probably reflecting pathologic differences. Layered and heterogeneous tissues might respond better than homogeneous tissue to simple balloon dilatation, suggesting a possible direction for OCT-based ISR treatment strategies.
Circulation Journal 12/2012; · 3.77 Impact Factor
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ABSTRACT: Background: The development of right ventricular (RV) dysfunction in pulmonary hypertension (PH) patients is associated with adverse outcome, so that the assessment of RV function has become increasingly important in the management of such patients. The present objective was to test the hypothesis that RV free-wall longitudinal speckle-tracking strain (RV-free), an independent echocardiographic predictor of hemodynamic RV performance, can predict long-term outcome. Methods and Results: Forty-two PH patients were studied. RV-free was calculated by averaging the 3 regional peak systolic strains for the RV free wall. For comparison, tricuspid annular plane systolic excursion (TAPSE), RV fractional area change, RV index of myocardial performance, and tissue Doppler-derived tricuspid lateral annular systolic velocity were also studied. Long-term follow-up was performed for 4 years after adding PH-specific drugs. Receiver operating characteristic curve analysis identified RV-free ≤19.4% as the best predictor of cardiovascular events with 90% sensitivity, 69% specificity, and area under the curve of 0.819 (P=0.0001). Furthermore, the Kaplan-Meier curve indicated that patients with RV-free >19.4% experienced fewer cardiovascular events than those with RV-free ≤19.4% (log-rank P=0.0008). Importantly, the co-occurrence of RV-free ≤19.4% and TAPSE <16mm was associated with the highest frequency of cardiovascular events. Conclusions: RV-free may serve as a non-invasive predictor of cardiovascular events for PH patients. Combining RV-free with TAPSE may be more effective for predicting long-term cardiovascular events.
Circulation Journal 12/2012; · 3.77 Impact Factor
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ABSTRACT: Background: Effectiveness of functional mitral regurgitation (FMR) in heart failure patients is of growing importance for patient prognosis. The purpose of this study was to investigate whether regional myocardial contractile function as assessed by tissue Doppler strain rate imaging can predict reduction in FMR caused by dobutamine. Methods: Fifty-one patients with depressed left ventricular (LV) ejection fraction (32 ± 9%) secondary to dilated cardiomyopathy and FMR underwent evaluation of effective regurgitant orifice (ERO) of FMR, mitral valve deformation, global LV remodeling, and regional myocardial contractile function assessed by longitudinal peak systolic strain rate (Ssr) in 6 mid-LV segments from standard apical views. We also determined the average Ssr of segments attached to the papillary muscles, that is, the inferior, inferolateral, and anterolateral segments (PM segments Ssr). Low-dose (10 μg/kg per minute) dobutamine-induced reduction in ERO was compared with baseline variables. Results: Baseline valve tenting was associated with dobutamine-induced reduction in ERO (r = -0.30, P < 0.05). Receiver operating characteristic curve analysis showed that baseline valve tenting, LV sphericity index, inferior Ssr, inferolateral Ssr, and PM segments Ssr were predictors of dobutamine-induced ≥30% reduction in ERO. Importantly, only PM segments Ssr predicted dobutamine-induced ≥20% reduction in valve tenting with area under the curve of 0.67 (P < 0.05). Conclusions: Preserved myocardial contractile function in the segments attached to the PMs was associated with dobutamine-induced reduction in mitral valve tenting and FMR, suggesting that our findings are important for improvement in cardiac function and FMR with medical treatment.
Echocardiography 11/2012; · 1.24 Impact Factor
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Ryo Nishio,
Hidekazu Tanaka,
Yasunori Tsuboi,
Hiroto Kinutani,
Yu Taniguchi,
Mayumi Shigeru,
Ryuji Toh,
Yasushi Miura,
Yoshitada Sakai,
Noriaki Emoto,
Hiroya Kawai, Ken-Ichi Hirata
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ABSTRACT: : Although pulmonary arterial hypertension (PAH) and chronic heart failure (CHF) lead to exercise limitation, their pathophysiology is different. Our objective was to evaluate, using right heart catheterization and cardiopulmonary exercise testing, the difference in hemodynamic parameters and exercise capacity between PAH and CHF, which have the same subjective symptoms.
: We studied 20 PAH (mean pulmonary artery pressure: 36 ± 10 mmHg, all . 25 mmHg) and 20 CHF (ejection fraction: 35 ± 10%, all < 40%) patients who underwent both cardiopulmonary exercise testing and right heart catheterization. All patients were in New York Heart Association functional class II or III.
: Peak oxygen uptake (VO2) was lower for PAH patients than for CHF patients (11.7 ± 3.2 mL·kg·min vs 14.5 ± 4.6 mL·kg·min, P = .03), while the slope of ventilation to carbon dioxide production ratio (VE/VCO2) was higher for PAH patients than for CHF patients (41.0 ± 12.7 vs 28.0 ± 9.0, P = .001), despite the similarity in their New York Heart Association functional class. Peak VO2 and VE/VCO2 correlated with cardiac index for both groups. An important finding was that peak VO2 correlated with pulmonary vascular resistance for PAH patients (r = 20.46, P = .04) but not for CHF patients (r = 0.33, P = .15). Furthermore, peak VO2 correlated with pulmonary capillary wedge pressure for CHF patients (r = 20.47, P = .03) but not for PAH patients (r = 0.17, P = .47), while the VE/VCO2 slope correlated with pulmonary capillary wedge pressure (r = 0.67, P = .002) but not with pulmonary vascular resistance (r = 0.12, P = .63) for CHF patients.
: Peak VO2 and VE/VCO2 slope were worse for PAH patients than for CHF patients despite the similar subjective symptoms. This difference might be explained by an altered hemodynamic status.
Journal of cardiopulmonary rehabilitation and prevention 11/2012; 32(6):379-85. · 1.69 Impact Factor
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Tatsuro Ishida,
Kazuya Miyashita,
Mamoru Shimizu,
Noriaki Kinoshita,
Kenta Mori,
Li Sun,
Tomoyuki Yasuda,
Shigeyuki Imamura,
Katsuyuki Nakajima,
Kimber L Stanhope,
Peter J Havel, Ken-Ichi Hirata
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ABSTRACT: BACKGROUND:Endothelial lipase (EL) regulates the metabolism of HDL cholesterol (HDL-C). However, the role of EL in regulating plasma HDL-C concentrations and EL's potential involvement in atherosclerosis in humans has not been fully investigated due to the lack of reliable assays for EL mass. We developed an ELISA system for serum EL mass.METHODS:Human recombinant EL proteins, purified from cultured media of human EL-transfected CHO cells, were used as antigen and calibrator. Two specific monoclonal antibodies were generated in mice against recombinant EL protein for a sandwich ELISA. We measured EL mass in human serum using EL recombinant protein as a calibration standard.RESULTS:The EL antibodies did not cross-react with lipoprotein lipase and hepatic triglyceride lipase. The detection limit of the ELISA was 20 pg/mL, which is approximately 10 times lower than that of previous ELISA systems. Recovery of spiked EL in serum was 90%-105%. Assay linearity was intact with a >4-fold dilution of serum. Intra- and interassay CVs were <5%. The serum EL mass in 645 human subjects was [mean (SE)] 344.4 (7.7) pg/mL (range 55.2-1387.7 pg/mL). Interestingly, serum EL mass was increased in patients with diagnosed cardiovascular disease and inversely correlated with serum HDL-C concentrations. There was no difference in EL mass between pre- and post-heparin plasma samples.CONCLUSIONS:This ELISA should be useful for clarifying the impact of EL on HDL metabolism and EL's potential role in atherosclerosis.
Clinical Chemistry 10/2012; · 7.91 Impact Factor
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ABSTRACT: BACKGROUND: It has been suggested that the assessment of left ventricular contractile reserve during dobutamine infusion can improve prognostic evaluation for patients with idiopathic dilated cardiomyopathy (DCM). However, the assessment of contractile reserve is often subjective, while three-dimensional (3D) speckle-tracking can quantify three different components of strain simultaneously from all 16 left ventricular segments. The purpose of this study was to investigate the capability of multidirectional deformational indices assessed by 3D speckle-tracking strain to predict cardiac events in patients with DCM. Whether such assessment under dobutamine infusion can enhance this method's predictive capability was also evaluated by comparison with two-dimensional (2D) speckle-tracking. METHODS: Sixty-five patients with DCM with a mean ejection fraction of 34 ± 8% (all <45%) were prospectively recruited, and both 3D and 2D speckle-tracking echocardiography was used to measure global circumferential strain (GCS), radial strain, and longitudinal strain at baseline and during dobutamine infusion (20 μg/kg/min). Event-free survival was then tracked over 12 months. RESULTS: Among all indices of contractile reserve, increase in 3D GCS under dobutamine infusion ≤ 2.71% best predicted cardiovascular events, with 83% sensitivity, 80% specificity, and an area under the curve of 0.874 (P < .001). Furthermore, the area under the curve for increase in 3D GCS was significantly larger than that for both resting 3D GCS and increase in 2D GCS (P < .05 for both). On multivariate Cox analysis, increase in 3D GCS was the only independent predictor of cardiovascular events (hazard ratio, 0.635; P < .001). CONCLUSIONS: Assessment of contractile reserve using 3D GCS has the potential to predict cardiovascular events in patients with DCM and may thus have clinical implications for the management of such patients.
Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 10/2012; · 2.98 Impact Factor
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Junichi Imanishi,
Hidekazu Tanaka,
Kensuke Matsumoto,
Kazuhiro Tatsumi,
Tatsuya Miyoshi,
Mana Hiraishi,
Akihiro Kaneko,
Keiko Ryo,
Yuko Fukuda,
Akihiro Yoshida,
Mitsuhiro Yokoyama,
Hiroya Kawai, Ken-Ichi Hirata
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ABSTRACT: Although left ventricular (LV) mechanical dyssynchrony can predict the response to cardiac resynchronization therapy (CRT), the presence of baseline LV dyssynchrony might not be the only determinant of the response to CRT. The objectives of the present study were to test the hypothesis that a combined assessment of baseline LV dyssynchrony and its acute improvement can produce a more accurate prediction of the long-term outcomes after CRT. We studied 121 patients with heart failure undergoing CRT. LV dyssynchrony was determined by measuring the anteroseptal-to-posterior wall time delay using the speckle-tracking radial strain (≥130 ms was predefined as significant) and was assessed at baseline and 7 ± 3 days after CRT. Long-term unfavorable outcome events were tracked for 5 years. Acute improvement in LV dyssynchrony of ≥33% was predictive of the long-term outcome with an area under the curve of 0.67 (p = 0.0024). Using this cutoff value, the Kaplan-Meier curve showed that patients with acute improvement in LV dyssynchrony experienced fewer cardiovascular events than those without (log-rank p = 0.0002). The event-free survival of patients whose baseline LV dyssynchrony was ≥130 ms and whose acute improvement in LV dyssynchrony was ≥33% was greater than that of the patients with baseline LV dyssynchrony of ≥130 ms but with acute improvement in LV dyssynchrony of <33% (88% vs 65%, p = 0.012). In conclusion, the combined assessment of baseline LV dyssynchrony and its acute improvement after CRT produced a more accurate prediction of long-term outcomes after CRT.
The American journal of cardiology 09/2012; · 3.58 Impact Factor
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ABSTRACT: Aim: Endothelial lipase (EL) regulates plasma high-density lipoprotein-cholesterol (HDL-C) levels by promoting HDL catabolism. However, it remains unknown whether the inhibition of EL has beneficial effects on the genesis of vascular diseases. Here, we investigated the role of EL on vascular remodeling in mice.Methods: Vascular remodeling was developed by ligation of the left common carotid artery and neointimal lesions were histologically compared between EL-knockout (ELKO), EL-transgenic (ELTg), and wild-type (WT) mice. HDL was isolated from these mice, and effects of the HDL on cell growth and Erk activation were evaluated in vitro using cultured vascular smooth muscle cells.Results: Plasma HDL-C levels were 62% higher in ELKO and 13% lower in ELTg than in WT mice, after the carotid ligation. The size of neointimal lesion was significantly larger in ELTg and smaller in ELKO than in WT mice. Vascular expression of adhesion molecules was lower in ELKO and higher in ELTg compared with WT mice. Moreover, oxidative stress was attenuated in ELKO mice. HDL isolated from ELKO, ELTg, and WT mice inhibited expression of intercellular adhesion molecule-1, angiotensin II-induced activation of Erk, and growth of cultured vascular smooth muscle cells, whereas EL expression itself did not affect cell migration or growth.Conclusion: EL expression modulates vascular remodeling as well as plasma HDL-C levels. EL inactivation may increase HDL particles that can inhibit smooth muscle cell growth and migration.
Journal of atherosclerosis and thrombosis 09/2012; · 2.69 Impact Factor
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ABSTRACT: Atherosclerosis has been recognized as an inflammatory disease of the arterial wall, involving innate and adaptive immunity. Effector T cells are differentiated from naïve T cells stimulated by antigen-presenting cells such as macrophages and dendritic cells (DCs) and play critical roles in atherogenesis. Accumulating evidence revealed that several subsets of regulatory T cells (Tregs) inhibit atherosclerotic lesion formation via inhibiting the inflammatory response of effector T cells. In addition, the contribution of DCs to atherogenesis has been demonstrated. DCs have different functions for either stimulating or inhibiting T cell function depending on their origin and maturation stage. In particular, immature DCs, which have potential for inducing Tregs and inhibiting effector T cells, are sometimes called 'tolerogenic DCs' and suppress immune responses. Epidemiological studies have highlighted the increasing prevalence of vitamin D(3) deficiency and its association with increased risks of cardiovascular diseases. Some studies have raised interest in the immunomodulatory properties of vitamin D(3) beyond its well-established role in bone and calcium metabolism. The active form of vitamin D(3) (calcitriol) induces Tregs and tolerogenic DCs, which are both involved in maintaining immunologic tolerance to self and harmless antigens. Interestingly, recent evidence suggested that DCs in the intestinal immune system are involved in inducing Tregs; modulating the function of DCs and Tregs in the intestinal immune system might have beneficial effects on atherosclerosis. In this review, we focus on the function of DCs in vascular diseases and discuss vitamin D(3) therapy for the prevention of atherosclerosis.
Journal of atherosclerosis and thrombosis 08/2012; · 2.69 Impact Factor
