Publications by authors named "Hidehito Funahashi"

7 Publications

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Epicardial fat volume correlates with severity of coronary artery disease in nonobese patients.

J Cardiovasc Med (Hagerstown) 2014 May;15(5):384-90

aDepartment of Cardiology, Nagoya University Graduate School of Medicine, Nagoya bDepartment of Cardiology, Handa City Hospital, Handa cDepartment of Cardiology, Tsushima City Hospital, Tsushima, Japan.

Objective: It has been reported that epicardial adipose tissue could locally modulate the coronary artery functions through secretion of proinflammatory and anti-inflammatory cytokines. Epicardial fat tissue is further implicated in the pathogenesis of coronary artery disease (CAD) because of its proximity to the adventitia of the major epicardial coronary arteries. We investigated the relationship between epicardial fat volume (EFV) and severity of CAD in nonobese patients using 64-slice multidetector computed tomography (MDCT).

Methods: One hundred and forty nonobese patients (BMI <25 kg/m2) were enrolled. EFV and visceral fat area were measured by MDCT. Patients were classified according to the plaque components (noncalcified, mixed and calcified) and severity of CAD. Inflammatory biomarkers were also measured, and compared with each CT parameter.

Results: EFV was significantly correlated with the extent or severity of CAD. Patients with noncalcified or mixed plaque had a greater EFV than those with calcified plaque. Log-transferred high sensitivity C-reactive protein (CRP) was significantly correlated with EFV (r = 0.24, P = 0.04). Adiponectin level was significantly inversely correlated with visceral fat area (r = 0.38, P = 0.0001).

Conclusion: Increased EFV is associated with more severe CAD and noncalcified or mixed coronary plaques in nonobese patients.
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http://dx.doi.org/10.2459/JCM.0b013e32836094daDOI Listing
May 2014

Increased (99m)Tc-sestamibi washout reflects impaired myocardial contractile and relaxation reserve during dobutamine stress due to mitochondrial dysfunction in dilated cardiomyopathy patients.

J Am Coll Cardiol 2013 May 13;61(19):2007-17. Epub 2013 Mar 13.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Objectives: This study investigated whether the technitium-99m sestamibi (MIBI) washout rate (WR) would predict mitochondrial damage and myocardial dysfunction in patients with dilated cardiomyopathy (DCM).

Background: Myocardial mitochondrial damage reduces adenosine triphosphate production, resulting in myocardial dysfunction. Increased myocardial (99m)Tc-MIBI washout is reportedly caused by mitochondrial dysfunction.

Methods: Twenty DCM patients (New York Heart Association functional class I-III) underwent myocardial (99m)Tc-MIBI scintigraphy and cardiac catheterization. Myocardial MIBI uptake was quantified as an early and delayed heart-to-mediastinum ratio, and WR was calculated. Maximum first derivative of left ventricular (LV) pressure (LV dP/dtmax) (an index of myocardial contractility) and LV pressure half-time (T1/2) (an index of myocardial relaxation) were calculated by the left ventricular pressure curve at baseline and during dobutamine infusion (15 μg/kg/min at maximum). Endomyocardial biopsy specimens were obtained for quantitative mRNA analysis and electron microscopy. The patients were divided into two groups as follows: 1) group A of 10 patients showing a WR ≤ 24.3% (median value) and 2) group B of 10 patients showing a WR >24.3%.

Results: WR was significantly correlated with the percentage changes in LV dP/dtmax (%LV dP/dtmax) (r: -0.59; p = 0.01) and T1/2 (r: -0.57; p = 0.03) from baseline to peak dobutamine stress. The %LV dP/dtmax was significantly greater in group B than in group A. The abundance of mRNAs for mitochondrial electron transport-related enzymes was more significantly reduced in group B than in group A. Electron microscopy revealed significant correlations between WR and the severity of mitochondrial damage (r: 0.88; p = 0.048) and glycogen accumulation (r: 0.90; p = 0.044).

Conclusions: Increased (99m)Tc-MIBI washout may predict mitochondrial dysfunction and the impairment of myocardial contractile and relaxation reserves during dobutamine stress in DCM patients.
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http://dx.doi.org/10.1016/j.jacc.2013.01.074DOI Listing
May 2013

Impact of mild to moderate renal dysfunction on left ventricular relaxation function and prognosis in ambulatory patients with nonischemic dilated cardiomyopathy.

Int Heart J 2011 ;52(6):366-71

Department of Cardiology, Nagoya University Graduate School of Medicine, Aichi, Japan.

The relationship between mild-to-moderate renal dysfunction and cardiac diastolic dysfunction and cardiac events in patients with nonischemic dilated cardiomyopathy (NDCM) has not been fully elucidated. The aim of this study was to investigate the relationship between renal and cardiac function, as well as clinical outcome in patients with NDCM.We measured plasma BNP and eGFR, and performed cardiac catheterization in 135 patients with NDCM. LV dP/dt(max)and T(1/2) were determined as indexes of LV contractility and isovolumic relaxation, respectively. During a mean follow-up of 4.8 years, we monitored all patients for the occurrence of cardiac events, which were defined as cardiac death (from worsening HF or sudden death) and unscheduled admission for decompensated HF. Patients were classified into 3 groups on the basis of eGFR (mL min(-1) 1.73 m(-2)): eGFR ≥ 90 (n = 23, group A), 60 ≤ eGFR < 90 (n = 70, group B), and 30 ≤ eGFR < 60 (n = 42, group C). Whereas LV dP/dt(max) did not significantly differ among the 3 groups, T(1/2) was significantly longer in groups B and C than in group A (P < 0.01). Event-free survival in group C was significantly lower than that in groups A and B (P = 0.014, log-rank test). These results suggest that even mild renal dysfunction is associated with LV isovolumic relaxation impairment. In addition, moderate impairment of renal function is independently associated with cardiac events in patients with NDCM.
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http://dx.doi.org/10.1536/ihj.52.366DOI Listing
February 2012

Association between cardiopulmonary exercise and dobutamine stress testing in ambulatory patients with idiopathic dilated cardiomyopathy: a comparison with peak VO₂ and VE/VCO₂ slope.

Int J Cardiol 2013 Jan;162(3):234-9

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: Both peak VO(2) and VE/VCO(2) slope are considered to be useful predictors of cardiovascular events. The left ventricular (LV) response to dobutamine stress testing (DST) also provides useful prognostic information. However, the relationship between these variables has not been fully investigated. Therefore, the aim of this study is to investigate the association between myocardial contractile reserve measured by DST and cardiopulmonary exercise testing (CPX) variables in patients with idiopathic dilated cardiomyopathy (IDCM).

Methods: Thirty-eight patients were subjected to CPX as well as cardiac catheterization for measurement of LV pressure. The maximum first derivative of LV pressure (LV dP/dt(max)) was measured at baseline and during dobutamine infusion at incremental doses of 5, 10, and 15 μg kg(-1)min(-1). LV dP/dt(max) at baseline and the percentage increase in LV dP/dt(max) (ΔLV dP/dt(max)) induced by DST served as indices of LV contractility and myocardial contractile reserve, respectively.

Results: Peak VO(2), and VE/VCO(2) slope were 18.6 mL kg(-1)min(-1) and 32.3, respectively. Peak VO(2) was not correlated with LV dP/dt(max) at baseline. However, peak VO(2) was significantly correlated with ΔLV dP/dt(max), and the correlation became more pronounced as the dose of dobutamine was increased. There was no correlation between VE/VCO(2) slope and ΔLV dP/dt(max). Multivariate regression analysis revealed that ΔLV dP/dt(max) was independently correlated with peak VO(2) (p=0.011).

Conclusions: Peak VO(2), but not VE/VCO(2) slope, may reflect myocardial contractile reserve in ambulatory patients with IDCM. This study population is small, and therefore large confirmatory studies are needed.
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http://dx.doi.org/10.1016/j.ijcard.2011.05.065DOI Listing
January 2013

Association of diabetes mellitus with myocardial collagen accumulation and relaxation impairment in patients with dilated cardiomyopathy.

Diabetes Res Clin Pract 2011 Jun 16;92(3):348-55. Epub 2011 Mar 16.

Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya 466-8550, Japan.

Aims: To assess the effects of diabetes mellitus (DM) on myocardial collagen accumulation, myocardial relaxation, and prognosis in patients with dilated cardiomyopathy (DCM).

Methods: A total of 102 consecutive DCM patients with a New York Heart Association functional class of I or II were enrolled. Patients were allocated to two groups on the basis of the presence (DCM+DM group, n = 30) or absence (DCM-DM group, n = 72) of DM. Cardiac catheterization performed and left ventricular pressure were measured in all patients. The pressure half-time (T(1/2)) was determined as an index of myocardial relaxation function. Endomyocardial specimens were subjected to histological analysis.

Results: The T(1/2) was significantly longer (P < 0.001) and the collagen volume fraction was significantly greater (P = 0.018) in the DCM + DM group than in the DCM-DM group. Multivariate analysis showed that DM was significantly associated with increased incidence of cardiac events (hazard ratio, 3.7; 95% confidence interval, 1.05 to 13.16; P = 0.03).

Conclusions: The prognosis of DCM patients with DM was worse than that of those without DM. Impairment of myocardial relaxation, increased myocardial fibrosis, and mitochondrial degeneration associated with DM may underlie this difference.
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http://dx.doi.org/10.1016/j.diabres.2011.02.023DOI Listing
June 2011

Altered microRNA expression associated with reduced catecholamine sensitivity in patients with chronic heart failure.

J Cardiol 2011 May 2;57(3):338-44. Epub 2011 Mar 2.

Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Japan.

Aims: MicroRNAs (miRNAs) are small non-coding RNAs discovered as potential new gene regulators. Their roles in the development of chronic heart failure (CHF), however, are largely unknown. Reduced catecholamine sensitivity is an early step of CHF. We examined whether altered expression of miRNAs was related to reduced catecholamine sensitivity in patients with CHF.

Methods And Results: Maximum first derivative of left ventricular pressure (LV dP/dt(max)) at baseline and during infusion of dobutamine (10 μg kg(-1)min(-1)) were determined in 14 asymptomatic or mildly symptomatic (New York Heart Association class I or II) patients with idiopathic dilated cardiomyopathy (DCM). We performed microarray analysis for a total of 485 miRNAs using endomyocardial biopsy specimens from these 14 patients. Patients were classified into 2 groups based on a percent increase in LV dP/dt(max) by dobutamine infusion (ΔLV dP/dt(max)). These are Group I (n=7) with ΔLV dP/dt(max)>90%, and Group II (n=7) with ΔLV dP/dt(max)<90%. Out of 485 miRNAs, 32 were differentially expressed in the myocardium with reduced catecholamine sensitivity. Among those, four miRNAs were decreased and one miRNA was increased in the Group II compared to the Group I (p<0.01). LVEF measured by left ventriculography at baseline did not differ between the 2 groups. Also there were no differences in plasma norepinephrine levels between the 2 groups.

Conclusions: Altered expression of several miRNAs was related to the reduced catecholamine sensitivity in mildly symptomatic patients with DCM. These findings shed light on the potential of miRNAs to provide possible etiologic insights as well as therapeutic targets for CHF.
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http://dx.doi.org/10.1016/j.jjcc.2011.01.009DOI Listing
May 2011

Accuracy of 64-slice multidetector computed tomography for classification and quantitation of coronary plaque: comparison with integrated backscatter intravascular ultrasound.

Int J Cardiol 2011 May 2;149(1):95-101. Epub 2010 May 2.

Department of Cardiology, Chubu Rosai Hospital, and Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: Noninvasive assessment of coronary plaque is important for coronary risk stratification. Whereas integrated backscatter intravascular ultrasound (IB-IVUS) has proven effective for analysis of the tissue components of coronary plaque, plaque assessment by 64-slice multidetector computed tomography (MDCT) has not been established. We therefore evaluated the accuracy of MDCT compared with IB-IVUS for identification of coronary plaque components and determination of plaque volume.

Methods: Thirty-one sites in 17 coronary vessels (7 left anterior descending, 5 left circumflex, and 5 right coronary arteries) with substantial stenosis were visualized by both 64-slice MDCT and IB-IVUS. Coronary plaque was evaluated by MDCT and the findings were compared with those of IB-IVUS at the same sites and for the same vessel lengths. Plaque was classified as low-attenuated, fibrous, or calcified, and the volume of each plaque component and total plaque volume were calculated.

Results: Total plaque volume per vessel determined by MDCT was significantly correlated with that determined by IB-IVUS (r=0.704, P<0.05, n=17). However, the volumes of individual plaque components determined by the two approaches were not correlated. The predominant plaque morphology as determined by the two approaches was consistent in 12 of the 17 vessels (70.6%), whereas calcified and low-attenuated plaques were overestimated by MDCT in the remaining vessels.

Conclusions: MDCT is a promising approach for noninvasive detection of different types of coronary plaque and may therefore contribute to coronary risk stratification. The ability of MDCT to determine the volume of individual plaque components, however, is limited.
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http://dx.doi.org/10.1016/j.ijcard.2010.04.002DOI Listing
May 2011
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