Methods and Results—Twenty-one beagles and small mongrel dogs without coronary stenosis (controls), or with moderate to severe acute coronary artery stenosis underwent MRI and PET imaging at rest and during dipyridamole vasodilation or dobutamine stress to induce a wide range of changes in cardiac perfusion and oxygenation. MRI first-pass perfusion imaging was performed to quantify myocardial blood flow (MBF) and volume (MBV). The MRI blood-oxygen-level-dependent (BOLD) technique was used to determine the myocardial oxygen extraction fraction (OEF) during pharmacologic hyperemia. Myocardial oxygen consumption (MVO2) was determined by Fick’s law. In the same dogs, ¹⁵O-water and ¹¹C-acetate were used to measure MBF and MVO₂, respectively by PET. Regional assessments were performed for both MR and PET. MRI data correlated nicely with PET values for MBF (R² = 0.79, P < 0.001), MVO₂ (R² = 0.74, P < 0.001), and OEF (R² = 0.66, P < 0.01).

Conclusions—Cardiac MRI methods may provide an alternative to radionuclide imaging in settings of myocardial ischemia. Our newly developed quantitative MRI oxygenation imaging technique may be a valuable non-invasive tool to directly evaluate myocardial energetics and efficiency.

Methods and Results—Echocardiograms of 105 patients (3 apical views) were blindly analyzed by 12 experienced readers. Visual segmental scores (VSS) and peak systolic longitudinal strain were assigned to each of 18 segments per-patient. Ranges of peak systolic longitudinal strain that best fit VSS (by ROC analysis) were used to generate automatic segmental scores (ASS). Comparisons of ASS and VSS were performed on 1952 analyzable segments. There was agreement of WM scores between both methods in 89.6% of normal, 39.5% of hypokinetic and 69.4% of akinetic segments. Correlation between methods was r=0.63, (p<0.0001). Inter- and intra-observer reliability using ICC (inter-class correlation) for scoring segmental WM into three scores by ASS was 0.82 and 0.83 and by VSS 0.70 and 0.69, respectively. Compared to VSS (majority rule), ASS had a sensitivity, specificity and accuracy of 87%, 85% and 86%, respectively. ASS and VSS had similar success rates for correct identification of WM abnormalities in territories supplied by culprit arteries. VSS had greater specificity and positive predictive values whereas ASS had higher sensitivity and negative predictive values for identifying the culprit artery.

Conclusions—Automatic quantification of WM on echocardiograms by this tool performs as well as visual analysis by experienced echocardiographers, with a greater reliability and similar agreement to angiographic findings.

Method and Results—252 patients with carcinoid syndrome underwent a range of investigations including two-dimensional (2D) transthoracic echocardiography (TTE), three-dimensional (3D) TTE and transoespheageal echocardiography (TEE) and cardiac magnetic resonance imaging (CMR). 52 patients had evidence of carcinoid heart disease. Involvement of the tricuspid, pulmonary, mitral and aortic valves were found in 47(90%), 36(69%), 15(29%) and 14(27%) respectively. Myocardial metastases were found in 2 (3.8%) of patients. Several patterns of disease were identified depending on the extent and severity to which each leaflet and its associated sub-vavlular apparatus was affected. 13 out of 15 (87%) patients with left sided carcinoid involvement had a patent foramen ovale. Three patients with severe degree of shunting had severe valvular regurgitation. Patients with mild/moderate degree of shunting had mild or moderate valvular regurgitation. 3D TTE/TEE provided detailed anatomical information particularly for the TV and PV. CMR allowed complimentary assessment of VHD and delineation of myocardial metastases. Gallium-68 octreotate positron emission tomography (PET) identified neuroendocrine metastases.

Conclusion—Carcinoid heart disease is a heterogeneous disease with a wide spectrum of echocardiographic findings. A multi-modality approach is needed in patients with this complex pathology.

Methods and Results—2D circular (x r²), 3D circular and 3D planimetered annular and LVOT areas by TEE were compared to "gold standard" MSCT planimetered areas before TAVI. Mean MSCT planimetered annular area was 4.65±0.82cm² before TAVI. Annular areas were underestimated by 2D-TEE circular (3.89±0.74cm², p<0.001), 3D-TEE circular (4.06±0.79cm², p<0.001), and 3D-TEE planimetered annular areas (4.22±0.77cm², p<0.001). Mean MSCT planimetered LVOT area was 4.61±1.20cm² before TAVI. LVOT areas were underestimated by 2D-TEE circular (3.41±0.89cm², p<0.001), 3D-TEE circular (3.89±0.94cm², p<0.001), and 3D-TEE planimetered LVOT areas (4.31±1.15cm², p<0.001). 3D-TEE planimetered annular and LVOT areas had the best agreement with respective MSCT planimetered areas. After TAVI, MSCT planimetered (4.65±0.82 vs. 4.20±0.46cm², p<0.001) and 3D-TEE planimetered (4.22±0.77 vs. 3.62±0.43cm², p<0.001) annular areas decreased, whereas MSCT planimetered (4.61±1.20 vs. 4.84±1.17cm², p=0.002) and 3D-TEE planimetered (4.31±1.15 vs. 4.55±1.21cm², p<0.001) LVOT areas increased. Aortic annulus and LVOT became less elliptical after TAVI.

Conclusions—Before TAVI, 2D and 3D-TEE aortic annular/LVOT circular geometric assumption underestimated the respective MSCT planimetered areas. After TAVI, 3D-TEE and MSCT planimetered annular areas decreased as it assumes the internal dimensions of the prosthetic valve. However, planimetered LVOT areas increased due to a more circular geometry and "splinting" by the prosthetic valve.

Methods and Results—159 HF patients referred for CRT underwent an extensive echocardiographic evaluation at baseline and at 6-month follow-up. LV dyssynchrony was derived from speckle-tracking analysis. Calibrated IB was obtained from the parasternal long-axis view. The mean value of calibrated IB of the antero-septal and posterior wall was used to estimate myocardial ultrasound reflectivity. CRT-response was defined as reduction ≥15% of LV end-systolic volume. At baseline LV dyssynchrony was significantly larger in responders as compared to non-responders (188±96ms vs. 115±68ms, p<0.001) and CRT-responders showed less myocardial ultrasound reflectivity as compared to non-responders (-20.8±3.0dB vs. -17.0±3.0dB, p<0.001). At multivariable logistic regression analysis independent predictors for CRT-response were LV dyssynchrony, renal function and myocardial ultrasound reflectivity. Importantly, myocardial ultrasound reflectivity provided an incremental value to CRT-response (Chi-square change=40, p<0.001). Considering ischemic HF patients, the only independent predictor of CRT-response was myocardial ultrasound reflectivity whereas in non-ischemic HF patients independent predictors of LV reverse remodeling were myocardial ultrasound reflectivity, LV dyssynchrony and renal function.

Conclusions—Assessment of myocardial ultrasound reflectivity is important in the prediction of CRT-response in ischemic and non-ischemic patients.

Methods and Results—Seventy children, age 6-19 years, with obesity and atherosclerosis promoting risk factors such as dyslipidemia, hypertension, insulin resistance and tobacco smoke exposure; or with familial dyslipidemia, underwent carotid artery ultrasound. Advanced "vascular age" (VA) was defined as having maximum CIMT that was ≥ 25^th percentile for a race and sex matched 45 year-old. Mean age was 13.0±3.3 years. Forty (57%) of 70 children had body mass index (BMI) ≥ 95^th percentile for age and sex. Maximum CIMT for obese children was 0.53±0.05 mm; for familial dyslipidemic children 0.52±0.04 mm. Advanced VA was seen in 30 (75%) of obese children and 22 (73%) of familial dyslipidemic children. Thirty (75%) of obese children had > 3 mutable atherosclerosis-promoting risk factors; these children had a non significantly higher maximum CIMT compared to obese children with ≤ 3 risk factors (0.54±0.06 mm vs. 0.52±0.03 mm, p=0.07). Obese children with high fasting triglyceride levels were more likely to have an advanced VA.

Conclusions—VA is advanced and comparable in obese children with atherosclerosis promoting risk factors and in children with familial dyslipidemia. Advanced VA is prevalent in obese children with high fasting triglyceride levels.

Methods and Results—The time-course of acute inflammatory cell infiltration was quantified by FACS analysis of enzymatically digested hearts of FVB mice (n=12) following LAD ligation. Mac-1+Gr-1^high neutrophil infiltration peaked at day 4. BMCs were harvested from transgenic FVB mice expressing firefly luciferase (Fluc) and green fluorescent protein (GFP). Afterwards, 2.5x10⁶ BMCs were injected into the left ventricle of wild-type FVB mice either immediately (Acute BMC) or 7 days (Sub-acute BMC) after MI, or after a sham procedure (n=8 per group). In vivo bioluminescence imaging (BLI) showed an early signal increase in both BMC groups at day 7, followed by a non-significant trend towards improved BMC survival in the Sub-acute BMC group that persisted until the BLI signal reached background levels after 42 days. Compared to controls (MI + saline injection), echocardiography showed a significant preservation of fractional shortening at 4 weeks (Acute BMC vs saline; P<0.01) and 6 weeks (both BMC groups vs saline; P<0.05), but no significant differences between the two BMC groups. FACS analysis of BMC injected hearts at day 7 revealed that GFP+ BMCs expressed hematopoietic (CD45, Mac-1, Gr-1), minimal progenitor (Sca-1, c-kit), and no endothelial (CD133, Flk-1) or cardiac (Trop-T) cell markers.

Conclusion—Timing of BMC delivery has minimal effects on intramyocardial retention and preservation of cardiac function. In general, there is poor long-term engraftment and BMCs tend to adopt inflammatory cell phenotypes.

Methods and Results—Twenty-two patients (age 62±8 yrs, 16 men) with CAD (at least 1 stenosis ≥50% on quantitative coronary angiography-QCA) and 10 normal volunteers (age 58±6 yrs, 6 men) underwent 3T BOLD CMR and PET. For BOLD CMR 4-6 mid-ventricular short-axis images were acquired at rest and during adenosine stress (140 µg/kg/min). Using PET with oxygen-15 labeled water, MBF was measured at baseline and during adenosine in the same slices. BOLD images were divided into 6 segments and mean signal intensities (SI) calculated. Taking ≥50% stenosis on QCA as the gold standard, cut-off values for stress MBF (< 2.45ml/min/g – AUC 0.83) and BOLD SI change (< 3.74% - AUC 0.78) were determined to define ischemic segments. BOLD CMR and PET agreed on the presence or absence of ischemia in 18 of the 22 patients (82%), and in all normals. On a per segment analysis, 40% of myocardial segments with stress MBF below the cut-off of 2.45ml/min/g did not show deoxygenation, whereas 88% of segments with normal perfusion also had normal oxygenation measurements.

Conclusions—Regional myocardial perfusion and oxygenation may be dissociated, indicating that in patients with CAD reduced perfusion does not always lead to deoxygenation.

Methods and Results—In a prospective observational study 305 T2DM patients (diabetes duration: 4.5±5.3 years) referred consecutively to a diabetes clinic for the first time were screened for LV systolic and diastolic function by echocardiography. Vascular function was estimated using noninvasive estimation of pulse pressure, carotid arterial compliance, total arterial compliance, and valvulo-arterial impedance. The prevalences of LV diastolic dysfunction and left atrial volume index (LAVI) >32 ml/m² were 40% and 32%, respectively. The prevalence of myocardial ischemia on myocardial perfusion scintigraphy (MPS) was more frequent in patients with grade 2 diastolic dysfunction and LAVI >32 ml/m² compared with those having normal or grade 1 diastolic dysfunction (p=0.002) or LAVI ≤32 ml/m² (p<0.001), respectively. Predictors of grade 2 diastolic dysfunction and LA dilatation were summed stress score (SSS) on MPS, total arterial compliance, and valvulo-arterial impedance, whereas pulse pressure and carotid arterial compliance were not, after adjusting for age, male gender, and diabetes duration. On multivariable modeling, SSS (p<0.001) and valvulo arterial impedance (p=0.027) remained predictors of grade 2 diastolic dysfunction, and only SSS (p<0.001) was a predictor of LA dilatation.

Conclusion—Abnormal LV filling is closely associated with abnormal myocardial perfusion on MPS, whereas the association of LV filling with vascular function is less prominent.

Methods and Results—We included 114 healthy children and adolescents, uniformly distributed spanning an age range of 4 to 20 years, as required by the Lambda-Mu-Sigma (LMS)-method to achieve a percentile distribution, thus avoiding arbitrary age categories. Subjects underwent axial volumetry (1.5-Tesla scanner) using standardized 2D steady-state free-precession and flow protocols. Percentiles were computed for age 8-20 years (99 subjects) as breathholds were more consistent in this group. When indexed for body surface area (BSA) or height, the centile curves of ventricular volumetric parameters showed allometric increase until adolescence, when a plateau was reached, with values comparable to published adult reference data. In contrast, ventricular mass centiles increased without plateau. There was a significant gender difference with centiles reflecting larger values in boys than in girls (p<0.05) when ventricular volumes were indexed to BSA or height, but not when indexed to weight (exception: mass). There was excellent agreement of axial and short-axis volumetry, and of volumetric and flow-derived stroke volumes.

Conclusions—Percentiles for ventricular volumes and mass in healthy children have been established to serve as reference values in pediatric heart disease. Significant gender differences were noted when indexing volumes to BSA or height. Unisex centiles related to weight may be considered for chamber volumes albeit not for mass.

Methods and Results—A total of 147 patients (mean age 61±11 years) admitted for acute myocardial infarction were included. All patients underwent 2D echocardiography within 48 hours of admission. Significant relations were observed between baseline AFI global LV strain and peak level of troponin T (r = 0.64), peak level of creatine phosphokinase (r = 0.62), wall motion score index (WMSI; r = 0.52) and viability index assessed with single photon emission computed tomography (SPECT; r = 0.79). At 1-year follow-up, LV ejection fraction (LVEF) was reassessed. Patients with absolute improvement in LVEF ≥5% at 1-year follow-up (n = 70; 48%) had a higher (more negative) baseline AFI global LV strain (p<0.0001). Baseline AFI global LV strain was a predictor for change in LVEF at 1-year follow-up. A cutoff value for baseline AFI global LV strain of -13.7% yielded a sensitivity of 86% and a specificity of 74% to predict LV functional recovery at 1-year follow-up.

Conclusions—AFI global LV strain early after acute myocardial infarction reflects myocardial viability and predicts recovery of LV function at 1-year follow-up.