Abstract Background Recent studies have demonstrated improved diagnostic accuracy for detecting coronary artery disease (CAD) when myocardial blood flow (MBF) is quantified in absolute terms, but ...there are no uniformly accepted cutoff values for hemodynamically significant CAD. Objectives The goal of this study was to determine cutoff values for absolute MBF and to evaluate the diagnostic accuracy of quantitative 15 OH2 O positron emission tomography (PET). Methods A total of 330 patients underwent both quantitative 15 OH2 O PET imaging and invasive coronary angiography in conjunction with fractional flow reserve measurements. A stenosis >90% and/or fractional flow reserve ≤0.80 was considered obstructive; a stenosis <30% and/or fractional flow reserve >0.80 was nonobstructive. Results Hemodynamically significant CAD was diagnosed in 116 (41%) of 281 patients who fulfilled study criteria for CAD. Resting perfusion was 1.00 ± 0.25 and 0.92 ± 0.23 ml/min/g in regions supplied by nonstenotic and significantly stenosed vessels, respectively (p < 0.001). During stress, perfusion increased to 3.26 ± 1.04 ml/min/g and 1.73 ± 0.67 ml/min/g, respectively (p < 0.001). The optimal cutoff values were 2.3 and 2.5 for hyperemic MBF and myocardial flow reserve, respectively. For MBF, these cutoff values showed a sensitivity, specificity, and accuracy for detecting significant CAD of 89%, 84%, and 86%, respectively, at a per-patient level and 87%, 85%, and 85% at a per-vessel level. The corresponding myocardial flow reserve values were 86%, 72%, and 78% (per patient) and 80%, 82%, and 81% (per vessel). Age and sex significantly affected diagnostic accuracy of quantitative PET. Conclusions Quantitative MBF measurements with the use of 15 OH2 O PET provided high diagnostic performance, but both sex and age should be taken into account.
Patients with coronary artery disease and/or type 2 diabetes mellitus (DM) generally exhibit more epicardial adipose tissue (EAT) than healthy controls. Recently, it has been proposed that EAT ...affects vascular function and structure by secreting proinflammatory and vasoactive substances, thereby potentially contributing to the development of cardiovascular disease. In the present study, the interrelation of EAT, coronary vasomotor function, and coronary artery calcium was investigated in patients with and without DM, who were evaluated for coronary artery disease. Myocardial blood flow (MBF) was assessed at rest and during adenosine-induced hyperemia using 15 O-water positron emission tomography combined with computed tomography to quantify coronary artery calcium and EAT in 199 patients (46 with DM). In this cohort (mean age 58 ± 10 years), the patients with DM had a greater body mass index, heart rate, and systolic blood pressure at rest (all p <0.05). Coronary artery calcium and the EAT volumes were comparable between those with and without DM. Both patient groups showed comparable MBF at rest and coronary vascular resistance. A lower hyperemic MBF and coronary flow reserve (CFR) and greater hyperemic coronary vascular resistance (all p <0.05) was observed in the patients with DM. A pooled analysis showed a positive association of EAT volume with hyperemic coronary vascular resistance but not with the MBF at rest, hyperemic MBF, or coronary vascular resistance at rest. In the group analysis, the EAT volume was inversely associated with hyperemic MBF (r = −0.16, p = 0.05) and CFR (r = −0.17, p = 0.04) and positively with hyperemic coronary vascular resistance (r = 0.26, p = 0.002) only in patients without DM. Multivariate regression analysis, adjusted for age, gender, and body mass index, showed an independent association between the EAT volume and hyperemic MBF (β = −0.16, p = 0.02), CFR (β = −0.16, p = 0.04), and hyperemic coronary vascular resistance (β = 0.25, p <0.001) in the non-DM group. In conclusion, these results suggest a role for EAT in myocardial microvascular dysfunction; however, once DM has developed, other factors might be more dominant in contributing to impaired myocardial microvascular dysfunction.
We studied the spatial relations among hyperemic myocardial blood flow (hMBF), contractile function, and morphologic tissue alterations in 19 patients with hypertrophic cardiomyopathy (HC). All ...patients were studied with oxygen-15 water positron emission tomography during rest and adenosine administration to assess myocardial perfusion. Cardiovascular magnetic resonance was performed to derive delayed contrast-enhanced images and to calculate contractile function (Ecc ) with tissue tagging. Eleven healthy subjects underwent similar positron emission tomographic and cardiovascular magnetic resonance scanning protocols and served as a control group. In the HC group, hMBF averaged 2.46 ± 0.91 ml/min/g and mean Ecc was −14.7 ± 3.4%, which were decreased compared to the control group (3.97 ± 1.48 ml/min/g and −17.7 ± 3.2%, respectively, p <0.001 for the 2 comparisons). Delayed contrast enhancement (DCE) was present only in patients with HC, averaging 6.2 ± 10.3% of left ventricular mass. In the HC group, Ecc and DCE in the septum (−13.7 ± 3.6% and 10.2 ± 13.6%) significantly differed from the lateral wall (−16.0 ± 2.8% and 2.4 ± 5.9%, p <0.001 for the 2 comparisons). In general, hMBF and Ecc were decreased in segments displaying DCE compared to nonenhanced segments (p <0.001 for the comparisons). In the HC group, univariate analysis revealed relations of hMBF to Ecc (r = −0.45, p <0.001) and DCE (r = −0.31, p <0.001). Multivariate analysis revealed that Ecc was independently related to hMBF (beta −0.37, p <0.001) and DCE (beta 0.28, p <0.001). In conclusion, in HC hMBF is impaired and related to contractile function independent from presence of DCE. When present, DCE reflected a progressed disease state as characterized by an increased perfusion deficit and contractile dysfunction.
Objectives The purpose of this study was to investigate the relationship between hepatic triglyceride content and both myocardial function and metabolism in type 2 diabetes mellitus (T2DM). ...Background Heart disease is the leading cause of mortality in T2DM. Central obesity and hepatic steatosis, both hallmark abnormalities in T2DM, have been related to increased risk of heart disease. Methods Sixty-one T2DM patients underwent myocardial perfusion and substrate metabolism measurements by positron emission tomography, using 15 Owater, 11 Cpalmitate, and 18 F-2-fluoro-2-deoxy- d -glucose. In addition, whole-body insulin sensitivity (M/I) was determined. Myocardial left ventricular function and high-energy phosphate metabolism were measured using magnetic resonance imaging and 31 P-magnetic resonance spectroscopy, respectively. Hepatic triglyceride content was measured by proton magnetic resonance spectroscopy. Patients were divided according to hepatic triglyceride content (T2DM-low ≤5.56% vs. T2DM-high >5.56%). Results In addition to decreased M/I (p = 0.002), T2DM-high patients had reduced myocardial perfusion (p = 0.001), glucose uptake (p = 0.005), and phosphocreatine/adenosine triphosphate (PCr/ATP) ratio (p = 0.003), compared with T2DM-low patients, whereas cardiac fatty acid metabolism and left ventricular function were not different. Hepatic triglyceride content correlated inversely with M/I (Pearson's r = −0.620, p < 0.001), myocardial glucose uptake (r = −0.413, p = 0.001), and PCr/ATP (r = −0.442, p = 0.027). Insulin sensitivity correlated positively with myocardial glucose uptake (r = 0.528, p < 0.001) and borderline with myocardial PCr/ATP (r = 0.367, p = 0.072), whereas a positive association was found between cardiac glucose uptake and PCr/ATP (r = 0.481, p = 0.015). Conclusions High liver triglyceride content in T2DM was associated with decreased myocardial perfusion, glucose uptake, and high-energy phosphate metabolism in conjunction with impaired M/I. The long-term clinical implications of hepatic steatosis with respect to cardiac metabolism and function in the course of T2DM require further study.
Abstract Background Diastolic dysfunction in hypertrophic cardiomyopathy (HCM) is accompanied by augmented left ventricular (LV) end-diastolic pressure, above all in the presence of LV outflow tract ...(LVOT) obstruction. Increased back-pressure may augment right ventricular (RV) afterload and induce an oxidative metabolic imbalance between the 2 ventricles. The aim was to study right-to-left ventricular oxidative metabolism in HCM and the effects of alcohol septal ablation (ASA). Methods and Results Twenty-one HCM patients were enrolled. Eleven healthy subjects served as a control group. Subjects underwent 2-dimensional echocardiography to assess LVOT gradient, left atrial size, and diastolic function. 11 CAcetate positron-emission tomography (PET) was performed to determine RV k2 and LV k2 , as a noninvasive index of oxidative metabolism. Seven HCM patients with LVOT obstruction, scheduled to undergo ASA, were also studied 6 months after the procedure. RV k2 was higher in HCM patients than i control subjects (0.081 ± 0.021 min−1 vs. 0.061 ± 0.017 min−1 ; P = .05), whereas LV k2 was similar between groups. Consequently, RV k2 /LV k2 was increased in the patients (0.85 ± 0.19 vs 0.59 ± 0.13; P = .004). In patients with obstructive HCM, ASA reduced RV k2 (0.085 ± 0.021 min−1 to 0.072 ± 0.022 min−1 ; P = .001). Inasmuch as LV k2 remained unaffected by the procedure, RV k2 /LV k2 was decreased after ASA (0.66 ± 0.18; P = .03). The absolute change in LVOT gradient was related to the absolute change in RV k2 ( r = 0.77; P = .044). Conclusions In HCM patients, RV oxygen consumption is increased in relation to the LV. ASA reduces RV oxygen consumption in HCM patients with LVOT obstruction, suggesting that increased LV loading conditions and diastolic dysfunction play a predominant role in augmenting RV workload in these patients.
Objectives This study was designed to evaluate myocardial substrate and high-energy phosphate (HEP) metabolism in asymptomatic men with well-controlled, uncomplicated type 2 diabetes with verified ...absence of cardiac ischemia, and age-matched control subjects, and to assess the association with myocardial function. Background Metabolic abnormalities, particularly an excessive exposure of the heart to circulating nonesterified fatty acids and myocardial insulin resistance are considered important contributors to diabetic cardiomyopathy in animal models of diabetes. The existence of myocardial metabolic derangements in uncomplicated human type 2 diabetes and their possible contribution to myocardial dysfunction still remain undetermined. Methods In 78 insulin-naive type 2 diabetes men (age 56.5 ± 5.6 years, body mass index 28.7 ± 3.5 kg/m2 , glycosylated hemoglobin A1c 7.1 ± 1.0%; expressed as mean ± SD) without cardiac ischemia and 24 normoglycemic control subjects (age 54.5 ± 7.1 years, body mass index 27.0 ± 2.5 kg/m2 , glycosylated hemoglobin A1c 5.3 ± 0.2%), we assessed myocardial left ventricular (LV) function by magnetic resonance imaging, and myocardial perfusion and substrate metabolism by positron emission tomography using H215 O, carbon11 C-palmitate, and 18-fluorodeoxyglucose 2-fluoro-2-deoxy-D-glucose. Cardiac HEP metabolism was assessed by phosphorous P 31 magnetic resonance spectroscopy. Results In patients, compared with control subjects, LV diastolic function (E/A ratio: 1.04 ± 0.25 vs. 1.26 ± 0.36, p = 0.003) and myocardial glucose uptake (260 ± 128 nmol/ml/min vs. 348 ± 154 nmol/ml/min, p = 0.015) were decreased, whereas myocardial nonesterified fatty acid uptake (88 ± 31 nmol/ml/min vs. 68 ± 18 nmol/ml/min, p = 0.021) and oxidation (85 ± 30 nmol/ml/min vs. 63 ± 19 nmol/ml/min, p = 0.007) were increased. There were no differences in myocardial HEP metabolism or perfusion. No association was found between LV diastolic function and cardiac substrate or HEP metabolism. Conclusions Patients versus control subjects showed impaired LV diastolic function and altered myocardial substrate metabolism, but unchanged HEP metabolism. We found no direct relation between cardiac diastolic function and parameters of myocardial metabolism.
Abstract Background The purpose of this study was to characterize ipsi- and contralateral cerebral hemodynamics before and after CEA. Methods Cerebral blood flow, CBV, and MVTT were measured in 10 ...patients before and after CEA using PET. Absolute and relative values of these parameters were calculated bilaterally for the entire arterial territories and hemispheres. Results For all territories in both hemispheres, the mean absolute postoperative CBF was significantly increased compared with preoperative CBF ( P < .05). Only in MCA was this increase higher in the ipsilateral than in the contralateral hemisphere ( P = .02). Cerebral blood volume was unaffected, whereas MVTT decreased in ipsilateral MCA ( P = .05). Conclusions The present findings suggest that, on the first day after CEA, absolute CBF is increased in all arterial territories on both ipsi- and contralateral sides, but that there are only minor changes in the relative distribution, whereas the CBV was unaffected.
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