Association of resting left ventricular global longitudinal strain with myocardial perfusion abnormalities evaluated by 13 N-ammonia positron emission tomography in patients with stable angina pectoris and normal left ventricular ejection fraction.

AIMS: Little is known about whether resting left ventricular global longitudinal strain (GLS) impairment is associated with myocardial perfusion abnormalities evaluated using 13 N-ammonia positron emission tomography (13 N-NH3 -PET)-myocardial perfusion imaging (MPI). This study aimed to investigate the correlation between resting GLS and myocardial perfusion parameters in patients with a normal left ventricular ejection fraction (LVEF). We evaluated whether resting GLS can predict myocardial perfusion abnormalities in these patients. METHODS AND RESULTS: We selected 157 patients with suspected stable angina pectoris who underwent both ATP-stress NH3 -PET-MPI and 2-dimentional speckle tracing echocardiography. All subjects had a preserved LVEF and no known history of myocardial infarction. Patients were stratified into Group N (normal perfusion; summed stress score [SSS], 0-3; n = 101), Group M (mildly to moderately abnormal perfusion; SSS, 4-11; n = 41), or Group S (severely abnormal perfusion; SSS, 12+; n = 15). GLS was more impaired as myocardial perfusion abnormality severity increased (-17.9 ± 2.9% for Group N, -16.8 ± 3.1% for Group M, and -14.2 ± 3.5% for Group S; p < .001). GLS was weakly but significantly correlated with SSS (R = .32, p < .001), summed difference score (R = .32, p < .001), and myocardial blood flow during stress (R = -0.27, p < .001). Multivariate logistic regression analysis showed that male sex, diabetes mellitus, systolic blood pressure, and GLS were independent predictors of myocardial perfusion abnormality defined as Groups M and S. Additionally, the area under the curve for GLS for detecting myocardial perfusion abnormality was .65, and the optimal cutoff value for GLS was -16.5%, with sensitivity and specificity of 59% and 66%, respectively. CONCLUSION: In patients with suspected angina pectoris, resting GLS impairment despite a normal LVEF might aid the detection of hemodynamically significant coronary artery disease.

Prospective Analysis of Immunosuppressive Therapy in Cardiac Sarcoidosis With Fluorodeoxyglucose Myocardial Accumulation: The PRESTIGE Study.

BACKGROUND: Fluorodeoxyglucose positron emission tomography (18F-FDG-PET) can noninvasively assess active inflammatory myocardium in patients with cardiac sarcoidosis (CS). Prednisolone (PSL) is the initial drug of choice for active CS; however, its efficacy has not been prospectively evaluated. Moreover, there are no alternative systematic treatment strategies. OBJECTIVES: The goal of this study was to evaluate the efficacy of methotrexate (MTX) in patients refractory to PSL assessed by using cardiac metabolic activity (CMA) in 18F-FDG-PET. METHODS: A total of 59 patients with active CS were prospectively enrolled. CMA (standardized uptake value × accumulation area) was used as an indicator of active inflammation, and a 6-month regimen of PSL therapy was introduced, followed by a second FDG scan. Poor responders to PSL therapy (CMA reduction rate <70%) and patients with recurrent CS (CMA reduction rate ≥70% after initial PSL therapy but CMA recurred after an additional 6 months of therapy) were randomly assigned to the MTX or repeat PSL (re-PSL) therapy groups for another 6 months. RESULTS: Fifty-six patients completed the initial 6-month PSL therapy regimen. Median CMA reduced from 203.3 to 1.0 (P < 0.001), and 47 patients were allocated to the response group, 9 to the poor response group, and 2 to the recurrent group. Accordingly, 11 patients were randomly assigned to the MTX (n = 5) or re-PSL (n = 6) groups. After 6 months, neither group showed a significant reduction in CMA values. MTX was comparable to re-PSL in reducing CMA. CONCLUSIONS: The 6-month regimen of PSL was a potent therapeutic tool for active CS. When MTX was added to low-dose PSL in patients refractory to the initial PSL therapy, there was no significant difference compared with re-PSL. Further studies are needed to evaluate the therapeutic potential of MTX for active CS, including how MTX works when it is administered in higher doses or for longer periods.

Myocardial 123I-MIBG scintigraphy predicts an impairment in myocardial functional reserve during dobutamine stress in patients with idiopathic dilated cardiomyopathy.

PURPOSE: We investigated whether myocardial (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy predicts impairment of myocardial functional reserve in response to dobutamine stress in patients with idiopathic dilated cardiomyopathy (DCM). METHODS: Forty DCM patients (LVEF 39 ± 12 %) underwent myocardial (123)I-MIBG scintigraphy, echocardiography, and cardiac catheterization. Myocardial (123)I-MIBG uptake was quantified as the delayed heart to mediastinum (H/M) ratio and washout rate (WR). Local denervation was evaluated on polar map images. LV dP/dt (max) and T(1/2) were determined from left ventricular pressure curves at baseline and during dobutamine infusion (15 µg/kg /min). Patients were classified into two groups as follows: group A comprised 21 patients showing a delayed H/M ratio of <1.9 (median value); group B comprised 19 patients showing a delayed H/M ratio of ≥ 1.9. RESULTS: The percentage change in heart rate (%HR), LV dP/dt (max) (%LV dP/dt (max)), and T (1/2) (%T (1/2)) from baseline to dobutamine stress were significantly more reduced in group A than in group B (39.3 ± 20.2 %, 55.2 ± 24.1 %, p < 0.01; 102.3 ± 46.3 %, 152.0 ± 72.3 %, p < 0.05; 38.7 ± 15.3 %, 46.9 ± 15.4 %, p < 0.05, respectively). No significant differences between the two groups were observed in the echocardiographic parameters or baseline cardiac catheterization parameters. Significant correlations were found between delayed H/M ratio and %HR (r = 0.35, p < 0.05), %LV dP/dt (max) (r = 0.45, p < 0.05) and %T (1/2) (r = 0.34, p < 0.05). Significant inverse correlations were also found between WR and %HR (r = -0.37, p < 0.05), %LV dP/dt (max) (r = -0.60, p < 0.0001), and %T (1/2) (r = -0.34, p < 0.05). SPECT images revealed enhanced denervation from the inferoposterior to anterior wall in accordance with the advancement of global denervation. CONCLUSION: Reduced (123)I-MIBG uptake and increased washout were related to impairment in adrenergic myocardial functional reserve in idiopathic DCM.

Post-stress perfusion abnormalities detected on myocardial perfusion single-photon emission computed tomography predict long-term mortality after elective abdominal aortic aneurysm repair.

BACKGROUND: After abdominal aortic aneurysm (AAA) repair, relatively low survival during long-term follow-up remains an unresolved issue. Stress myocardial perfusion single-photon emission computed tomography (SPECT) well predicts future mortality overall, as well as providing diagnoses of coronary artery disease. The prognostic value of myocardial SPECT findings after AAA repair, however, remains unclear. METHODS AND RESULTS: This study followed 285 patients, all undergoing preoperative pharmacologic stress myocardial perfusion SPECT to determine summed stress score (SSS), then elective AAA repair by open AAA repair or endovascular aneurysm repair. The endpoint of the study was cardiac death. The median follow-up duration was 925 days (range, 541-1,095 days). Twenty-four (8%) died during follow-up. Kaplan-Meier analysis showed that patients with SSS≥9 had a significantly poorer prognosis than those with SSS<9 (76% vs. 93%, P=0.003). Multivariate Cox proportional hazards analysis indicated that SSS≥9, diabetes, and chronic kidney disease≥stage 3 could significantly and independently predict long-term cardiovascular mortality in patients after AAA repair (hazard ratio [HR], 4.2; 95% confidence interval [CI]: 1.8-9.7, P=0.001; HR, 3.0; 95% CI: 1.2-7.4, P=0.020; and HR, 4.1; 95% CI: 1.7-10.1, P=0.029, respectively). CONCLUSIONS: Preoperative pharmacologic stress myocardial perfusion SPECT is a useful method to predict long-term cardiovascular mortality for patients undergoing elective AAA repair.

Combined Prognostic Value of Preprocedural Protein-Energy Wasting and Inflammation Status for Amputation and/or Mortality after Lower-Extremity Revascularization in Hemodialysis Patients with Peripheral Arterial Disease.

Protein-energy wasting is associated with inflammation and advanced atherosclerosis in hemodialysis patients. We enrolled 800 patients who had undergone successful lower-extremity revascularization, and we investigated the association among the Geriatric Nutritional Risk Index (GNRI) as a surrogate marker of protein-energy wasting, C-reactive protein (CRP), and their joint roles in predicting amputation and mortality. They were divided into lower, middle, and upper tertiles (T1, T2, and T3) according to GNRI and CRP levels, respectively. Regarding the results, the amputation-free survival rates over 8 years were 47.0%, 56.9%, and 69.5% in T1, T2, and T3 of the GNRI and 65.8%, 58.7%, and 33.2% for T1, T2, and T3 of CRP, respectively (p < 0.0001 for both). A reduced GNRI [adjusted hazard ratio (aHR) 1.78, 95% confidence interval (CI) 1.24-2.59, p = 0.0016 for T1 vs. T3] and elevated CRP (aHR 1.86, 95% CI 1.30-2.70, p = 0.0007 for T3 vs. T1) independently predicted amputation and/or mortality. When the two variables were combined, the risk was 3.77-fold higher (95% CI 1.97-7.69, p < 0.0001) in patients who occupied both T1 of the GNRI and T3 of CRP than in those who occupied both T3 of the GNRI and T1 of CRP. In conclusion, patients with preprocedurally decreased GNRI and elevated CRP levels frequently experienced amputation and mortality, and a combination of these two variables could more accurately stratify the risk.

Diagnostic usefulness of the oedema-infarct ratio to differentiate acute from chronic myocardial damage using magnetic resonance imaging.

OBJECTIVES: To differentiate acute from chronic damage to the myocardium in patients with myocardial infarction (MI) using DE and T2w MR. METHODS: Short-axis T2w and DE MR images were acquired twice after the onset of MI in 36 patients who successfully underwent emergency coronary revascularisation. The areas of infarct and oedema were measured. The oedema-infarct ratio (O/I) of the left ventricular area was calculated by dividing the oedema by the infarct area. RESULTS: The oedema size on T2w MR was significantly larger than the infarct size on DE MR in the acute phase. Both the oedema size on T2w MR and the infarct size on DE MR in the acute phase were significantly larger than those in the chronic phase. The O/I was significantly greater in the acute phase compared with that in the chronic phase (P < 0.05). An analysis of relative cumulative frequency distributions revealed an O/I of 1.4 as a cut-off value for differentiating acute from chronic myocardial damage with the sensitivity, specificity, and accuracy of 85.1%, 82.7% and 83.9%, respectively. CONCLUSION: The oedema-infarct ratio may be a useful index in differentiating acute from chronic myocardial damage in patients with MI. KEY POINTS: MR can differentiate reversible from irreversible myocardial damage after myocardial infarction. MR is a useful modality to noninvasively differentiate the infarct stages. The O/I is an important index to decide therapeutic strategies.

Impact of Hemodialysis on Clinical Outcomes in Patients Undergoing Lower Extremity Bypass Surgery for Peripheral Artery Disease-10-year Follow-Up Study.

We investigated the clinical impact of hemodialysis on long-term outcomes of bypass surgery in patients with peripheral artery disease. We evaluated 660 consecutive patients who underwent successful bypass surgery (392 hemodialysis and 268 non-hemodialysis). The endpoint was amputation-free survival (AFS). To minimize differences in clinical characteristics between the 2 groups, propensity score matching was performed. The AFS rates for 10-year follow-up were 39.3% and 67.7% in hemodialysis and non-hemodialysis patients [hazard ratio (HR) 2.21, 95% confidence interval (CI) 1.65-3.01, P < .0001]. Cumulative incidence of amputation was higher in the hemodialysis group than in the non-hemodialysis group [(19.4 vs 8.4%, HR 2.15, 95% CI 1.29-3.74, P = .0027). In a matched cohort (n = 210 each), AFS was still lower in the hemodialysis patients (53.1 vs 66.3%, HR 1.94, 95% CI 1.36-2.82, P = .0003). However, there was no significant difference in amputation rate between the groups (10.5 vs 10.6%, HR .97, 95% CI 0.49-1.87, P = .93). In a sub-analysis of patients with critical limb ischemia, similar results were obtained. The 10-year AFS was consistently lower in the hemodialysis group than in the non-hemodialysis group. However, the amputation rate was comparable between the groups when matched for the differences in clinical characteristics.

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

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.

Relation of 99mTc-sestamibi washout with myocardial properties in patients with hypertrophic cardiomyopathy.

BACKGROUND: We sought to determine the relationship between (99m)Tc-sestamibi washout and myocardial properties in hypertrophic cardiomyopathy (HCM) patients. METHODS AND RESULTS: Twenty-four HCM patients underwent biventricular cardiac catheterization, with a micromanometer-tipped catheter, both at rest and during atrial pacing, echocardiography and myocardial (99m)Tc-sestamibi scintigraphy at rest. The (99m)Tc-sestamibi washout rate (WR) was calculated using initial and delayed planar images. The HCM patients were divided into two groups as follows: Group A consisted of 13 patients showing (99m)Tc-sestamibi WR < 22.5%; group B of 11 patients showing (99m)Tc-sestamibi WR ≥ 22.5%. Significant correlations were observed between (99m)Tc-sestamibi WR and percentage changes in pressure half-time (T (1/2)), as well as those in the maximum first derivative LV pressure (LV dP/dt (max)) (r = .43, P = .033; r = -.63, P = .001). The percentage changes in LV dP/dt (max) and those in T (1/2) were significantly more reduced in group B than in group A (P < .05). The biphasic force-frequency relation was more frequently observed in group B than in group A (82% vs. 18%). CONCLUSION: Increased (99m)Tc-sestamibi washout is associated with an impaired contractile reserve and prolonged relaxation, suggesting that myocardial (99m)Tc-sestamibi scintigraphy may be useful in noninvasively detecting the early impairment of myocardial function in HCM patients.

Volumetric analysis of coronary plaque characterization in patients with metabolic syndrome using 64-slice multi-detector computed tomography.

BACKGROUND: Metabolic syndrome (MetS) is associated with adverse cardiovascular events and mortality, where acute coronary syndrome significantly impacts on mortality and morbidity. In contrast, evidences have accumulated that the lipid-rich plaque might play a critical role in acute coronary syndrome. METHODS AND RESULTS: The study population consisted of 94 patients with suspected angina pectoris who underwent multi-detector computed tomography (MDCT). Of those, we identified 41 with MetS. In MDCT analysis, low-density plaque volume (LDPV) (42 ± 28 vs 24 ± 18 mm(3), P=0.0003), moderate-density plaque volume (105 ± 41 vs 82 ± 33 mm(3), P=0.003), total plaque volume (164 ± 70 vs 118 ± 59 mm(3), P=0.0008) and %LDPV (24.2 ± 10.0 vs 18.3 ± 7.1%, P=0.01) were significantly increased in the MetS group compared to the non-MetS group. Multivariate linear regression analysis after adjusting for confounding variables revealed that MetS was significantly correlated with an increase in %LDPV (ß=0.48, P=0.0001). Multivariate logistic regression analysis for lipid-rich plaque after adjusting for confounding variables indicated that MetS was significantly associated with lipid-rich plaque (odds ratio: 5.99, 95% confidence intervals: 1.94-18.6, P=0.002). CONCLUSIONS: Patients with MetS were strongly related to having a lipid-rich composition in their coronary plaque, as detected by MDCT.

Dobutamine-induced mechanical alternans is a marker of poor prognosis in idiopathic dilated cardiomyopathy.

1. To date, few prognostic indicators for ambulatory patients with idiopathic dilated cardiomyopathy (IDCM) have been identified. The purpose of the present study was to investigate the relationship between the occurrence of dobutamine-induced mechanical alternans (MA) and prognosis in ambulatory patients with IDCM. 2. Left ventricular pressure was measured during right atrial pacing and after intravenous infusion of dobutamine at incremental doses in 90 ambulatory patients with IDCM in sinus rhythm. Endomyocardial biopsy specimens were also obtained for quantitative analysis of gene expression. The patients were followed up for a mean of 2.5 years. 3. Patients were classified into three groups: (i) 60 patients who exhibited neither pacing- nor dobutamine-induced MA (Group N); (ii) 20 patients who manifested only pacing-induced MA (Group P); and (iii) 10 patients who developed both pacing- and dobutamine-induced MA (Group D). The sarcoplasmic/endoplasmic reticulum calcium ATPase 2a:phospholamban mRNA ratio was significantly higher in Group D patients than in patients in Groups N or P. Multivariate analysis revealed that dobutamine-induced MA (odds ratio 4.05; 95% confidence interval 1.35-12.2) was a significant independent predictor of cardiac events. Cardiac event-free survival in Group D was significantly lower than in Groups N or P, as determined by Kaplan-Meier analysis (P=0.002). 4. The occurrence of dobutamine-induced MA is a potentially useful clinical predictor of poor prognosis in ambulatory patients with IDCM in sinus rhythm.

Relation of functional and morphological changes in mitochondria to myocardial contractile and relaxation reserves in asymptomatic to mildly symptomatic patients with hypertrophic cardiomyopathy.

AIMS: To examine the relation between mitochondrial dysfunction and myocardial contractile and relaxation reserves in hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Thirty HCM patients (LVEF >or=60%) underwent biventricular cardiac catheterization analysis both at rest and during atrial pacing as well as myocardial (99m)Tc-sestamibi scintigraphy at rest to calculate washout rate. Endomyocardial biopsy specimens were obtained for quantitative mRNA analysis and electron microscopy. The HCM patients were divided into two groups-group A: normal force-frequency relation and a pressure half-time (T(1/2)) of <30 ms (n = 15); group B: abnormal force-frequency relation or T(1/2) of >or=30 ms (n = 15). The (99m)Tc-sestamibi washout rate was significantly correlated with T(1/2) for all patients (r = 0.74, P < 0.01) and was also significantly greater in group B (29.2 +/- 6.3%) than in group A (19.3 +/- 3.1%). The abundance of mRNAs for mitochondrial electron transport-related enzymes was significantly higher in group A than in group B. Mitochondria showed a greater variation in size and were more disorganized in group B than in group A. CONCLUSION: Mitochondria showed functional impairment and morphological disorganization in the left ventricle of HCM patients without baseline systolic dysfunction. These mitochondrial changes were associated with impaired myocardial contractile and relaxation reserves.

Molecular imaging of matrix metalloproteinase expression in atherosclerotic plaques of mice deficient in apolipoprotein e or low-density-lipoprotein receptor.

UNLABELLED: Matrix metalloproteinases (MMPs) are expressed in atherosclerotic plaques and play an important role in plaque instability. METHODS: Using (99m)Tc-labeled broad-spectrum MMP inhibitor (MPI), we performed noninvasive imaging of MMP expression with micro-SPECT/micro-CT in mice deficient in apolipoprotein E (ApoE(-/-), n = 14), mice deficient in low-density-lipoprotein receptor (LDLR(-/-), n = 14), and C57/BL6 mice as controls (n = 7). Seven ApoE(-/-) and 7 LDLR(-/-) received a high-cholesterol diet. After in vivo imaging, aortas were explanted, ex vivo images acquired, and the percent injected dose of MPI per gram (%ID/g) determined, followed by histologic characterization of atherosclerotic lesions. RESULTS: MPI uptake was noninvasively visualized in atherosclerotic lesions by micro-SPECT, with confirmation by micro-CT of anatomic location and aortic calcification. %ID/g in each part of the aorta was highest in ApoE(-/-) that were fed a high-cholesterol diet, followed by LDLR(-/-) that were fed a high-cholesterol diet, ApoE(-/-) that were fed normal chow, and LDLR(-/-) that were fed normal chow. The control mice had minimal MPI uptake. A significant correlation was noted between %ID/g and % area positive for macrophages (r = 0.81, P = 0.009), MMP-2 (r = 0.65, P = 0.013), and MMP-9 (r = 0.62, P = 0.008). CONCLUSION: This study demonstrates the usefulness of molecular imaging for noninvasive assessment of the extent of MMP expression in various transgenic mouse models of atherosclerosis receiving a normal or hyperlipidemic diet. It is conceivable that such a strategy may be translationally developed for identification of unstable atherosclerotic plaques.

Dual molecular imaging for targeting metalloproteinase activity and apoptosis in atherosclerosis: molecular imaging facilitates understanding of pathogenesis.

BACKGROUND: Macrophage apoptosis and MMP activity contribute to vulnerability of atherosclerotic plaques to rupture. By employing molecular imaging techniques, we investigated if apoptosis and MMP release are interlinked. METHODS: Atherosclerosis was produced in rabbits receiving high-cholesterol diet (HC), who underwent dual radionuclide imaging with (99m)Tc-labeled matrix metalloproteinase inhibitor (MPI) and (111)In-labeled annexin A5 (AA5) using micro-SPECT/CT. %ID/g MPI and AA5 uptake was measured, followed by histological characterization. Unmanipulated animals were used as disease controls. Correlation between MPI and AA5 uptake was undertaken and relationship confirmed in culture study of activated THP-1 monocytes. RESULTS: MPI and AA5 uptake was best visualized in HC diet animals (n = 6) and reduced significantly after fluvastatin treatment (n = 4) or diet withdrawal (n = 3). %ID/g MPI (.087 +/- .018%) and AA5 (.03 +/- .01%) uptake was higher in HC than control (n = 6) animals (.014 +/- .004%, P < .0001; .0007 +/- .0002%, P < .0001), and reduced substantially after diet or statin intervention. There was a significant correlation between MPI and AA5 uptake (r = .62, P < .0001), both correlated with pathologically verified MMP-9 activity, macrophage content, and TUNEL staining. In vitro studies demonstrated MMP-9 release in culture medium from apoptotic THP-1 monocytes. CONCLUSIONS: The present study suggests that apoptosis and MMP are interrelated in atherosclerotic lesions and the targeting of more than one molecular candidate is feasible by molecular imaging.

Identification of five phospho-beta-glycosidases from Lactobacillus gasseri ATCC33323T cultured in lactose medium.

Lactobacillus gasseri ATCC33323(T) has seven putative phospho-beta-glycosidase genes. Using column chromatography, we found that this strain cultured in lactose medium expresses five phospho-beta-glycosidases (LacG1, LacG2, Pbg1, Pbg2, and Pbg3), where these gene expressions can be suppressed by glucose. To our knowledge, this is the first report indicating that five glycosidases are induced from a single bacterial strain using a single carbon source, lactose.

Mineralocorticoid receptor antagonism ameliorates left ventricular diastolic dysfunction and myocardial fibrosis in mildly symptomatic patients with idiopathic dilated cardiomyopathy: a pilot study.

BACKGROUND: Mineralocorticoid receptor antagonism reduces mortality associated with heart failure by mechanisms that remain unclear. The effects of the mineralocorticoid receptor antagonist spironolactone on left ventricular (LV) function and chamber stiffness associated with myocardial fibrosis were investigated in mildly symptomatic patients with idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Twenty-five DCM patients with a New York Heart Association functional class of I or II were examined before and after treatment with spironolactone for 12 months. LV pressures and volumes were measured simultaneously, and LV endomyocardial biopsy specimens were obtained. Serum concentrations of the carboxyl-terminal propeptide (PIP) and carboxyl-terminal telopeptide (CITP) of collagen type I were measured. The patients were divided into 2 groups on the basis of the serum PIP/CITP ratio (< or =35, group A, n=12; >35, group B, n=13), an index of myocardial collagen accumulation. LV diastolic chamber stiffness, the collagen volume fraction, and abundance of collagen type I and III mRNAs in biopsy tissue were greater and the LV early diastolic strain rate (tissue Doppler echocardiography) was smaller in group B than in group A at baseline. These differences and the difference in PIP/CITP were greatly reduced after treatment of patients in group B with spironolactone, with treatment having no effect on these parameters in group A. The collagen volume fraction was significantly correlated with PIP/CITP, LV early diastolic strain rate, and LV diastolic chamber stiffness for all patients before and after treatment with spironolactone. CONCLUSIONS: Spironolactone ameliorated LV diastolic dysfunction and reduced chamber stiffness in association with regression of myocardial fibrosis in mildly symptomatic patients with DCM. These effects appeared limited, however, to patients with increased myocardial collagen accumulation.

Changes with age in left ventricular function and volumes at rest and postexercise in postmenopausal women.

OBJECTIVES: In postmenopausal women, it has been reported that the plasma estrogen levels diminish immediately after menopause, and that this phenomenon affects left ventricular (LV) function and volumes. However, the effects of age on LV function and volumes for a relatively short period in the postmenopausal women remain to be established. Electrocardiographically gated-myocardial single-photon emission computed tomography (SPECT) has recently provided accurate estimations of perfusion, cardiac systolic and diastolic functions. We investigated the age-related changes in LV function and volumes in postmenopausal women using electrocardiographically gated-myocardial scintigraphy. METHODS: Twenty-two consecutive healthy postmenopausal women (mean age of 63.8 +/- 9.4 years, from 42 to 77 years) without cardiac disease underwent stress/rest technetium-99m tetrofosmin gated-myocardial SPECT with 16 frames per cardiac cycle at baseline and follow-up (1.0 +/- 0.3 years later). LV ejection fraction (LVEF) and LV volumes were calculated by QGS software. Fourier series were retained for the analysis of the volume curve. From this volume curve, we derived the following diastolic indices: peak filling rate (PFR) and time to PFR (TPFR). RESULTS: End-systolic volume index (ESVI) significantly decreased at postexercise (p = 0.02) and tended to decrease at rest (p = 0.06) from the baseline to the follow-up study. LVEF significantly increased at both postexercise (p = 0.01) and rest (p = 0.03) from the baseline to the follow-up study. The TPFR at rest tended to be prolonged from the baseline to the follow-up study (p = 0.07). The absolute increase in LVEF at postexercise tended to decrease with age [4.8% (50s) vs. 3.4% (60s) vs. 1.2% (70s)]. CONCLUSIONS: An age-related change in cardiac performance is apparent at an approximately 1 year follow-up in postmenopausal women. In particular, the increase in LV systolic function tends to show the greatest value in the 50s subjects among the 3 generations.

Cardiac 123I-MIBG reflects left ventricular functional reserve in patients with nonobstructive hypertrophic cardiomyopathy.

UNLABELLED: Little is known about the relation between left ventricular (LV) functional reserve in response to exercise and cardiac sympathetic nervous function in patients with nonobstructive hypertrophic cardiomyopathy (HCM). We investigated whether an assessment of cardiac sympathetic nervous function by myocardial (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy might provide a sign of an abnormal LV functional reserve in response to exercise-induced beta-adrenergic stimulation in patients with HCM. METHODS: Thirty HCM patients underwent (123)I-MIBG scintigraphy and echocardiography at rest and subsequent biventricular cardiac catheterization at rest and during dynamic exercise. LV pressures were measured using a micromanometer-tipped catheter system. The early and delayed (123)I-MIBG images were quantified as a heart-to-mediastinum ratio (H/M). The plasma levels of brain natriuretic peptide (BNP) and norepinephrine (NE) were also measured. RESULTS: Patients were divided into 2 groups according to the delayed (123)I-MIBG H/M: group I consisted of 12 patients with a delayed H/M of < or =1.8 and group II had 18 patients with a delayed H/M of >1.8. Both the percentage increase from rest to exercise in LV isovolumic contraction (LV dP/dt(max)) and the percentage shortening of LV pressure half-time (T(1/2)) as an index of isovolumic relaxation were significantly less in group I than in group II (P < 0.05, respectively). A significant linear correlation was observed between the percentage increase in LV dP/dt(max) and (123)I-MIBG H/Ms (early H/M: r = 0.49, P < 0.01; delayed H/M: r = 0.54, P < 0.005, respectively). A significant linear correlation was also observed between the percentage shortening in T(1/2) and (123)I-MIBG H/Ms (early H/M: r = 0.58, P < 0.001; delayed H/M: r = 0.64, P < 0.0005, respectively). The plasma NE levels were significantly higher in group I than in group II (P < 0.01), whereas the plasma BNP levels were comparable in the 2 HCM groups. CONCLUSION: beta-Adrenergic enhancement of LV function during exercise may depend on the extent of cardiac sympathetic nervous innervation in HCM patients. Resting myocardial (123)I-MIBG scintigraphy can noninvasively evaluate LV functional reserve in response to exercise in patients with nonobstructive HCM.

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

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.