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.

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.

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.

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.

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.

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

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.

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.

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.

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

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.

Cerebral embolism due to atrial myopathy in a cardiac amyloidosis patient diagnosed by cardiac magnetic resonance imaging.

A 55-year-old woman was admitted with heart failure. On the third hospital day, she suddenly developed cerebral infarction. The resting 12-lead electrocardiography showed normal sinus rhythm, and atrial fibrillation or flutter were never detected on electrocardiographic monitoring throughout the whole hospital days. She had no other conventional risk factor for cerebral infarction. Transthoracic echocardiography showed left ventricular hypertrophy. Transesophageal echocardiogram revealed strong spontaneous echo contrast in the left atrium (LA), and the blood flow in the left atrial appendage was extremely decreased (22.3 cm/s). Late gadolinium enhancement in cardiac magnetic resonance (CMR) imaging showed global subendocardial hyperenhancement of the left ventricle and both atria. Endomyocardial biopsy specimen was positive for amyloid by Congo red staining. Marked amyloid infiltration to both atria might cause atrial dysfunction leading to thrombus formation in the LA. CMR is thought to be a useful noninvasive tool to detect atrial myopathy in cardiac amyloidosis patients. .

Molecular imaging of human ACE-1 expression in transgenic rats.

OBJECTIVES: The aim of this study was to develop a molecular imaging strategy that can monitor myocardial angiotensin-converting enzyme (ACE)-1 upregulation as a function of progressive heart failure. BACKGROUND: High-affinity technetium-99m-labeled lisinopril (Tc-Lis) has been shown to specifically localize in tissues that express ACE in vivo, such as the lungs. Whether Tc-Lis can also detect upregulation of ACE in the heart, by external in vivo imaging, has not been established. METHODS: Twenty-one ACE-1 over-expressing transgenic (Tg) and 18 wild-type control rats were imaged using in vivo micro single-positron emission computed tomography (SPECT)-computed tomography (CT) at 10, 30, 60, and 120 min after Tc-Lis injection. A subgroup of rats received nonradiolabeled (cold) lisinopril before the Tc-Lis injection to evaluate nonspecific binding. After imaging, the rat myocardium was explanted, ex vivo images were acquired, and percent injected dose per gram gamma-well was counted, followed by an assessment of enzyme-linked immunosorbent assay-verified ACE activity and messenger ribonucleic acid expression. RESULTS: On micro SPECT-CT, myocardial ACE-1 uptake was best visualized in Tg rats at 120 min after Tc-Lis injection. The quantitative uptake of Tc-Lis in the myocardium was 5-fold higher in mutant Tg than in control rats at each time point after tracer injection. The percent injected dose per gram uptake was 0.74 ± 0.13 in Tg myocardium at 30 min and was reduced substantially to 0.034 ± 0.003% when pre-treated with cold lisinopril (p = 0.029). Enzyme activity assay showed a >30-fold higher level of ACE-1 activity in the myocardium of Tg rats than in controls. The ACE-1 messenger ribonucleic acid was quantified, and lisinopril was found to have no effect on ACE-1 gene expression. CONCLUSIONS: The Tc-Lis binds specifically to ACE, and the activity can be localized in Tg rat hearts that over-express human ACE-1 with a signal intensity that is sufficiently high to allow external imaging. Such a molecular imaging strategy may help identify susceptibility to heart failure and may allow optimization of pharmacologic intervention.

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 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.

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

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.

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 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.

Effect of an antimicrobial agent on atherosclerotic plaques: assessment of metalloproteinase activity by molecular imaging.

OBJECTIVES: Technetium-99m-labeled matrix metalloproteinase inhibitor (MPI) was used for the noninvasive assessment of matrix metalloproteinase (MMP) activity in atherosclerotic plaques after minocycline (MC) intervention. BACKGROUND: MMP activity in atherosclerosis contributes to plaque instability. Some antimicrobial agents may attenuate MMP activity. METHODS: Atherosclerotic lesions were produced in 38 rabbits with a high cholesterol diet for 4 months; 5 groups of rabbits, in the fourth month, received fluvastatin (FS) (n = 6), low-dose MC (n = 7), high-dose MC (n = 7), a combination of low-dose MC and FS (n = 6), or no intervention (n = 12); 8 unmanipulated rabbits were used as disease controls. Micro-single-photon emission computed tomography imaging was performed in all animals after intravenous MPI administration, followed by pathologic characterization of the aorta. A cell culture study evaluated the effect of MC on MMP production by activated human monocytes. RESULTS: MPI uptake was visualized best in untreated atherosclerotic animals (percent injected dose per gram MPI uptake, 0.11 +/- 0.04%). MPI uptake was reduced in the FS (0.06 +/- 0.01%; p < 0.0001), high-dose MC (0.05 +/- 0.01%; p < 0.0001), and MC-FS (0.05 +/- 0.005%; p < 0.0001) groups. Low-dose MC did not resolve MPI uptake significantly (0.08 +/- 0.02; p = 0.167). There was no incremental benefit of the combination of MC and FS. MPI uptake showed a significant correlation with plaque MMP-2, and MMP-9 activity. MMP-9 release from tumor necrosis factor-alpha-activated macrophages was abrogated by incubation with MC. CONCLUSIONS: Molecular imaging of MMP activity in atherosclerotic plaque allows for the study of the efficacy of therapeutic interventions. MC administration resulted in substantial reduction in plaque MMP activity and histologically verified plaque stabilization. MC was found to be equally effective as FS.

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.