Noriko Oyama-Manabe

Validation Study on the Accuracy of Echocardiographic Measurements of Right Ventricular Systolic Function in Pulmonary Hypertension

BACKGROUND The accuracy of echocardiographic parameters of right ventricular (RV) function has not been sufficiently validated in patients with pulmonary hypertension (PH). The aim of this study was to evaluate whether echocardiographic measurements reliably reflect RV systolic function in PH using cardiac magnetic resonance imaging (CMRI)-derived RV ejection fraction (RVEF) as a gold standard. METHODS A total of 37 consecutive patients with PH, 20 with pulmonary arterial hypertension, 12 with chronic thromboembolic PH, and five others, were prospectively studied. All patients underwent echocardiography, CMRI, and right-heart catheterization within a 1-week interval. Associations between five echocardiography-derived parameters of RV systolic function and CMRI-derived RVEF were evaluated. RESULTS All five echocardiography-derived parameters were significantly correlated with CMRI-derived RVEF (percentage RV fractional shortening: r = 0.48, P = .0011; percentage RV area change: r = 0.40, P = .0083; tricuspid annular plane systolic excursion [TAPSE]: r = 0.86, P < .0001; RV myocardial performance index: r = -0.59, P < .0001; and systolic lateral tricuspid annular motion velocity: r = 0.63, P < .0001). Compared with the other indices, TAPSE exhibited the highest correlation coefficient. Of the five echocardiographic measurements, only TAPSE significantly predicted CMRI-derived RVEF in multiple regression analysis (P < .0001). Intraobserver and interobserver reproducibility was favorable for all five indices and was particularly high for TAPSE and systolic lateral tricuspid annular motion velocity. CONCLUSIONS Echocardiographic measurements are promising noninvasive indices of RV systolic function in patients with PH. In particular, TAPSE is superior to other indices in accuracy.

Systemic Oxidative Stress Is Associated With Lower Aerobic Capacity and Impaired Skeletal Muscle Energy Metabolism in Patients With Metabolic Syndrome

OBJECTIVE Systemic oxidative stress is associated with insulin resistance and obesity. We tested the hypothesis that systemic oxidative stress is linked to lower aerobic capacity and skeletal muscle dysfunction in metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS The incremental exercise testing with cycle ergometer was performed in 14 male patients with MetS and 13 age-, sex-, and activity-matched healthy subjects. Systemic lipid peroxidation was assessed by serum thiobarbituric acid reactive substances (TBARS), and systemic antioxidant defense capacity was assessed by serum total thiols and enzymatic activity of superoxide dismutase (SOD). To assess skeletal muscle energy metabolism, we measured high-energy phosphates in the calf muscle during plantar flexion exercise and intramyocellular lipid (IMCL) in the resting leg muscle, using 31P- and 1proton-magnetic resonance spectroscopy, respectively. RESULTS Serum TBARS were elevated (12.4 ± 7.1 vs. 3.7 ± 1.1 μmol/L; P < 0.01), and serum total thiols and SOD activity were decreased (290.8 ± 51.2 vs. 398.7 ± 105.2 μmol/L, P < 0.01; and 22.2 ± 8.4 vs. 31.5 ± 8.5 units/L, P < 0.05, respectively) in patients with MetS compared with healthy subjects. Peak VO2 and anaerobic threshold normalized to body weight were significantly lower in MetS patients by 25 and 31%, respectively, and inversely correlated with serum TBARS (r = −0.49 and r = −0.50, respectively). Moreover, muscle phosphocreatine loss during exercise was 1.4-fold greater in patients with MetS (P < 0.05), and IMCL content was 2.9-fold higher in patients with MetS (P < 0.01), indicating impaired skeletal muscle energy metabolism, and these indices positively correlated with serum TBARS (r = 0.45 and r = 0.63, respectively). CONCLUSIONS Systemic oxidative stress was associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in patients with MetS.

Quantification of myocardial blood flow using dynamic 320-row multi-detector CT as compared with 15O-H2O PET

AbstractObjectivesThis study introduces a method to calculate myocardium blood flow (MBF) and coronary flow reserve (CFR) using the relatively low-dose dynamic 320-row multi-detector computed tomography (MDCT), validates the method against 15O-H2O positron-emission tomography (PET) and assesses the CFRs of coronary artery disease (CAD) patients.MethodsThirty-two subjects underwent both dynamic CT perfusion (CTP) and PET perfusion imaging at rest and during pharmacological stress. In 12 normal subjects (pilot group), the calculation method for MBF and CFR was established. In the other 13 normal subjects (validation group), MBF and CFR obtained by dynamic CTP and PET were compared. Finally, the CFRs obtained by dynamic CTP and PET were compared between the validation group and CAD patients (n = 7).ResultsCorrelation between MBF of MDCT and PET was strong (r = 0.95, P < 0.0001). CFR showed good correlation between dynamic CTP and PET (r = 0.67, P = 0.0126). CFRCT in the CAD group (2.3 ± 0.8) was significantly lower than that in the validation group (5.2 ± 1.8) (P = 0.0011).ConclusionsWe established a method for measuring MBF and CFR with the relatively low-dose dynamic MDCT. Lower CFR was well demonstrated in CAD patients by dynamic CTP.Key Points• MBF and CFR can be calculated using dynamic CTP with 320-row MDCT. • MBF and CFR showed good correlation between dynamic CTP and PET. • Lower CFR was well demonstrated in CAD patients by dynamic CTP.

Right atrial volume and phasic function in pulmonary hypertension.

BACKGROUND Few studies have focused on right atrial (RA) structure and function in pulmonary hypertension (PH). We sought to evaluate RA volume and phasic function using cardiac magnetic resonance (CMR), and to examine their clinical relevance in PH. METHODS We prospectively studied 50 PH patients and 21 control subjects. RA volume and indices of phasic function (reservoir volume, ejection fraction [EF], and conduit volume) were evaluated by CMR. RESULTS Maximum RA volume index was significantly higher in PH patients (56 [44-70] ml/m(2)) than in controls (40 [30-48] ml/m(2)) (p<0.001). Reservoir volume index was significantly lower in PH than in controls (p<0.001), but conduit volume index was higher in PH than in controls (p=0.008). RA EF was similar when comparing the two groups (p=0.925). Interestingly, RA EF was increased in PH patients with WHO functional class III patients as compared with controls (p<0.001) but was reduced in advanced PH patients with WHO functional class IV (p<0.01). Maximum RA volume and RA EF significantly correlated with pulmonary hemodynamic indices, atrial and brain natriuretic hormone levels, and CMR-derived right ventricular indices. By contrast, RA reservoir volume correlated with cardiac index and 6-minute walk distance. CONCLUSIONS PH is associated with increased size, decreased reservoir function, and increased conduit function of the right atrium. RA systolic function indicated by RA EF increases in patients with mild to moderate PH but decreases in patients with advanced PH. Varying associations between RA indices and conventional PH indices suggest their unique role in the management of PH.

Associations among the plasma amino acid profile, obesity, and glucose metabolism in Japanese adults with normal glucose tolerance

BackgroundAmino acids (AAs) are emerging as a new class of effective molecules in the etiology of obesity and diabetes mellitus. However, most investigations have focused on subjects with obesity and/or impaired glucose regulation; the possible involvement of AAs in the initial phase of glucose dysregulation remains poorly understood. Furthermore, little attention has been given to possible associations between the pattern/degree of fat deposition and the plasma AA profile. Our objective was therefore to determine the relationships between plasma AA concentrations and the type/degree of obesity and glucose regulation in Japanese adults with normal glucose tolerance.MethodsEighty-three subjects with normal glucose tolerance were classified as obese or nonobese and as visceral obesity or nonvisceral obesity. Correlations between the plasma levels of 23 AAs and somatometric measurements, visceral fat area (VFA), subcutaneous fat area (SFA), and 75-g oral glucose tolerance test results were analyzed.ResultsObesity or visceral obesity was associated with higher levels of branched-chain AAs (isoleucine, leucine, and valine), lysine, tryptophan, cystine, and glutamate but lower levels of asparagine, citrulline, glutamine, glycine, and serine (p < 0.04). Age- and gender-adjusted analyses indicated that VFA was positively correlated with tryptophan and glutamate levels, whereas VFA and SFA were negatively correlated with citrulline, glutamine, and glycine levels (p < 0.05). The fasting and 2-h plasma glucose levels or the homeostasis model assessment of insulin resistance were positively correlated with valine, glutamate, and tyrosine levels but negatively correlated with citrulline, glutamine, and glycine levels. The homeostasis model assessment for the β-cell function index was positively correlated with leucine, tryptophan, valine, and glutamate levels but negatively correlated with citrulline, glutamine, glycine, and serine levels (p < 0.05).ConclusionsThe present study identified specific associations between 10 AAs and the type/degree of obesity, and indices of glucose/insulin regulation, in Japanese adults with preserved glucose metabolism. With the growing concern about the increasing prevalence of obesity and diabetes, the possible roles of these AAs as early markers and/or precursors warrant further investigation.

Paradoxical interventricular septal motion as a major determinant of late gadolinium enhancement in ventricular insertion points in pulmonary hypertension.

Background This study investigated the major clinical determinants of late gadolinium enhancement (LGE) at ventricular insertion points (VIPs) commonly seen in patients with pulmonary hypertension (PH). Methods Forty-six consecutive PH patients (mean pulmonary artery pressure ≥25 mmHg at rest) and 21 matched controls were examined. Right ventricular (RV) morphology, function and LGE mass volume at VIPs were assessed by cardiac magnetic resonance (CMR). Radial motion of the left ventricular (LV) wall and interventricular septum (IVS) was assessed by speckle-tracking echocardiography. Paradoxical IVS motion index was then calculated. Univariate and multivariate regression analysis were conducted to characterize the relationship between LGE volume at VIPs and PH-related clinical indices, including the paradoxical IVS motion index. Results Mean pulmonary arterial pressure (MPAP) of PH patients was 38±9 mmHg. LGE at VIPs was observed in 42 of 46 PH patients, and the LGE volume was 2.02 mL (0.47–2.99 mL). Significant correlations with LGE volume at VIPs were observed for MPAP (r = 0.50) and CMR-derived parameters [RV mass index (r = 0.53), RV end-diastolic volume index (r = 0.53), RV ejection fraction (r = −0.56), and paradoxical IVS motion index (r = 0.77)]. In multiple regression analysis, paradoxical IVS motion index alone significantly predicted LGE volume at VIPs (p<0.001). Conclusions LGE at VIPs seen in patients with PH appears to reflect altered IVS motion rather than elevated RV pressure or remodeling. Long-term studies would be of benefit to characterize the clinical relevance of LGE at VIPs.

Lower aerobic capacity was associated with abnormal intramuscular energetics in patients with metabolic syndrome

Lower aerobic capacity is a strong and independent predictor of cardiovascular morbidity and mortality in patients with metabolic syndrome (MetS). However, the mechanisms are not fully elucidated. We tested the hypothesis that skeletal muscle dysfunction could contribute to the lower aerobic capacity in MetS patients. The incremental exercise tests with cycle ergometer were performed in 12 male patients with MetS with no habitual exercise and 11 age-, sex- and activity-matched control subjects to assess the aerobic capacity. We performed 31phosphorus-magnetic resonance spectroscopy (MRS) to assess the high-energy phosphate metabolism in skeletal muscle during aerobic exercise. Proton-MRS was also performed to measure intramyocellular lipid (IMCL) content. Peak oxygen uptake (peak VO2; 34.1±6.2 vs. 41.4±8.4 ml kg−1 min−1, P<0.05) and anaerobic threshold (AT; 18.0±2.4 vs. 23.1±3.7 ml kg−1 min−1, P<0.01) adjusted by lean body mass were lower in MetS patients than control subjects. Phosphocreatine (PCr) loss during exercise was 1.5-fold greater in MetS, suggesting reduced intramuscular oxidative capacity. PCr loss was inversely correlated with peak VO2 (r=−0.64) and AT (r=−0.60), respectively. IMCL content was threefold higher in MetS and was inversely correlated with peak VO2 (r=−0.47) and AT (r=−0.52), respectively. Moreover, there was a positive correlation between IMCL content and PCr loss (r=0.64). These results suggested that lean-body aerobic capacity in MetS patients was lower compared with activity-matched healthy subjects, which might be due to the reduced intramuscular fatty acid oxidative metabolism.

Diagnostic Accuracy of Lymph Node Metastasis Depends on Metabolic Activity of the Primary Lesion in Thoracic Squamous Esophageal Cancer

The metabolic activity of the primary tumor is an important variable in 18F-FDG PET interpretation for presurgical staging, because this activity is likely to affect the possibility of detection of malignant involvement in lymph nodes (LNs). The purpose of this study was to reevaluate the diagnostic accuracy of 18F-FDG PET/CT for the presurgical staging of esophageal squamous cell carcinoma (SCC) in correlation with the 18F-FDG avidity of the primary lesions. Methods: One hundred fifty-six patients (mean age ± SD, 61.4 ± 8.0 y) underwent 18F-FDG PET/CT before surgical esophagectomy and LN dissection. LN metastasis was identified using the fusion of PET and CT images with increased 18F-FDG uptake greater than the background activity of the adjacent structures. The results of the patients’ 18F-FDG PET/CT examinations for LN involvement were compared with the histopathologic results to investigate the diagnostic accuracy of 18F-FDG PET/CT for tumor staging. In addition, we examined the correlation between the diagnostic accuracy of 18F-FDG PET/CT for LN involvement and the 18F-FDG avidity of the primary lesions, to investigate the effect of tumor aggressiveness on the diagnosis of LN metastasis. Results: The diagnostic accuracy of 18F-FDG PET/CT for LN metastasis showed a low sensitivity, ranging from 29.3% to 53.3%, whereas the specificity was higher than 89.8% in regional thoracic nodes and in remote areas of the cervical and abdominal regions. The 18F-FDG uptake of the primary lesions positively correlated with that of the metastatic LNs in the thoracic field (R = 0.52, P < 0.05). As a result, our receiver-operating-characteristic analyses demonstrated an area under the curve value of 0.73, with the optimal cutoff value at a maximum standardized uptake value of 3.3 in patients with mid to high 18F-FDG avidity in the primary lesions (maximum standardized uptake value ≥ 5). Conclusion: This study showed that the avidity of the primary esophageal SCCs affected the detectability of lymph nodal metastases. If primary lesions of esophageal SCC present with a low 18F-FDG uptake, PET/CT may have a limited role for initial staging because of low sensitivity to detect lymph node metastases.

Quantification of myocardial blood flow with dynamic perfusion 3.0 Tesla MRI: Validation with 15o‐water PET

To develop and validate a method for quantifying myocardial blood flow (MBF) using dynamic perfusion magnetic resonance imaging (MBFMRI) at 3.0 Tesla (T) and compare the findings with those of 15O‐water positron emission tomography (MBFPET).

Right atrial volume and reservoir function are novel independent predictors of clinical worsening in patients with pulmonary hypertension

BACKGROUND Symptoms and signs and indices of right heart function are predictors of clinical outcomes in patients with pulmonary hypertension (PH). However, the significance of right atrial (RA) indices has not been sufficiently investigated. We investigated whether RA parameters predict outcomes in patients with pre-capillary PH. METHODS Study subjects were 68 patients with pre-capillary PH. RA size and function (systolic, reservoir, and conduit functions) were evaluated by cardiac magnetic resonance imaging. RESULTS During the mean follow-up period of 24 months, 16 of 68 patients experienced clinical worsening (CW), defined as hospitalization because of right heart failure, lung transplantation, or PH-related death. Kaplan-Meier and log-rank test showed that World Health Organization functional class, pericardial effusion, increased brain natriuretic peptide concentration, reduced right ventricular ejection fraction (RVEF), increased minimum RA volume index, and decreased RA reservoir volume were associated with CW-free survival. The combination of RVEF and RA reservoir function was a better predictor of CW-free survival. In univariate Cox hazard proportional analysis, CW was associated with the RA reservoir volume index (hazard ratio [HR] = 0.80). In multivariate analysis, CW was associated with World Health Organization functional class (HR = 4.3), RA minimum volume index (HR = 1.07), and RA reservoir volume index (HR = 0.73). CONCLUSIONS RA volume and reservoir function and their combined use with RVEF are novel predictors of CW in patients with pre-capillary PH.