Methods and Results— We included 7348 consecutive patients (mean age, 64±13 years; 51% men) referred for SPECT-MPI between March 2002 and October 2006. Renal function was estimated using the estimated glomerular filtration rate formula. Patients were followed up for the incidence of all-cause mortality. Patients with decreased glomerular filtration rate were more often older, with higher prevalence of conventional risk factors (P<0.001). After a median follow-up of 2.6 years (25th to 75th percentiles, 1.5 to 3.7), 693 (9.4%) patients died. The risk of death increased with worsening kidney function. At each stage of impaired renal function, patients with abnormal SPECT-MPI had increased hazard of adverse events (P<0.0001). Using Cox proportional hazards analysis, the magnitude of total perfusion deficit and ischemia on MPI were associated with worse outcome after adjusting for confounding variables including glomerular filtration rate and ejection fraction.

Conclusions— SPECT-MPI adds modest incremental prognostic information to identify patients at higher relative risk of death across a wide spectrum of renal function.

Methods and Results— Two hundred four eligible subjects from 252 consecutive subjects undergoing late postgadolinium myocardial enhancement (LGE) cardiac magnetic resonance and Doppler echocardiography were investigated. Subjects with normal diastolic function exhibited no or minimal fibrosis (median LGE score, 0; interquartile range, 0 to 0). In contrast, the majority of patients with cardiomyopathy (regardless of underlying cause) had abnormal diastolic function indices and substantial fibrosis (median LGE score, 3; interquartile range, 0 to 6.25). Prevalence of LGE positivity by diastolic filling pattern was 13% in normal, 48% in impaired relaxation, 78% in pseudonormal, and 87% in restrictive filling (P<0.0001). Similarly, LGE score was significantly higher in patients with deceleration time <150 ms (P<0.012), and it progressively increased with increasing left ventricular filling pressure estimated by tissue Doppler imaging–derived E/E' (P<0.0001). After multivariate analysis, LGE remained significantly correlated with degree of diastolic dysfunction (P=0.0001).

Conclusions— Severity of myocardial fibrosis by LGE significantly correlates with the degree of diastolic dysfunction in a broad range of cardiac conditions. Noninvasive assessment of myocardial fibrosis may provide valuable insights into the pathophysiology of left ventricular diastolic function and therapeutic response.

Methods and Results— We examined the effect of CRT on 34 patients with functional MR before and after CRT (209±81 days). MR regurgitant volume, closing forces on MV (derived from Doppler transmitral pressure gradients), including dP/dt and a factor (closing pressure ratio) expressing how long the peak closing gradient is maintained over systole (closing pressure ratio=velocity time integral/MR peak velocityxmitral regurgitation time), and dyssynchrony by tissue Doppler were measured. End-diastolic volume, end-systolic volume, mitral valve annular area (MAA) and contraction (percent change in MAA from end-diastole to midsystole), leaflet closing area (leaflet area during valve closure), and tenting volume (volume under leaflets to annular plane) were measured by 3D echocardiography. After CRT, end-diastolic volume (253±111 versus 221±110 mL, P<0.001) and end-systolic volume (206±97 versus 167±91 mL, P<0.001) decreased and ejection fraction (19±6 versus 27±9%, P<0.001) increased. MR regurgitant volume decreased from 35±17 to 23±14 mL (P<0.001), MAA from 11.6±3.5 to 10.5±3.1 cm² (P<0.001), leaflet closing area from 15.4±5 to 13.7±3.8 cm² (P<0.001), and tenting volume from 5.7±2.6 to 4.6±2.2 mL (P<0.001). Peak velocity (and therefore transmitral closing pressure) was more sustained throughout systole, as reflected by the increase in the closing pressure ratio (0.77±0.1 versus 0.84±0.1 before CRT versus after CRT, P=0.01); dP/dt also improved after CRT. There was no change in dyssynchrony or MAA contraction.

Conclusions— Reduction in MR after CRT is associated with favorable changes in MV geometry and closing forces on the MV. It does so by favorably affecting the force balance acting on the MV in 2 ways: reducing tethering through reversal of LV remodeling and increasing the systolic duration of peak transmitral closing pressures.

Methods and Results— In each of 10 anesthetized sheep, sonomicrometry crystals were implanted on the endocardium and epicardium at the LV basal, mid, and apical anterior and lateral walls. LV 3D-STI data sets were obtained from the apical approach at a frame rate of approximately 30 frames/s. Segmental longitudinal (LS), radial (RS), and circumferential strain (CS) measurements by 3D-STI were compared with those by sonomicrometry at baseline and during pharmacological stress tests (dobutamine and propranolol infusion) and acute myocardial ischemia induced by coronary artery occlusion. Data were available from 136 LS, 108 CS, and 175 RS measurements. Good correlations were observed between strain measurements by 3D-STI and those by sonomicrometry (LS: r=0.89, P<0.001; RS: r=0.84, P<0.001; CS: r=0.90, P<0.001). In each segmental study, significant correlations of the 3 strain components were observed (LS: r=0.65 to 0.68, P<0.001; RS: r=0.59 to 0.70, P<0.001; CS: r=0.71 to 0.78, P<0.001).

Conclusions— The newly developed 3D-STI technique can estimate LV regional circumferential, longitudinal, and radial strain components with reasonable correlation to sonomicrometry data. This methodology could be applied clinically to assess alteration of myocardial function by accurately measuring strain in basal, mid, and apical LV segments, even during pharmacological and ischemic interventions. Therefore, 3D-STI appears to be a reliable tool to assess LV regional wall function.

Methods and Results— Mice with transient coronary ligation were injected intravenously at the onset of reperfusion with AnxCLIO-Cy5.5 (n=7) or the control probe Inact_CLIO-Cy5.5 (n=6). T2*-weighted MR images (9.4 T) were acquired within 4 to 6 hours of reperfusion. The contrast-to-noise ratio between injured and uninjured myocardium was measured. The mice were then injected with Gd-DTPA-NBD, and delayed-enhancement imaging was performed within 10 to 30 minutes. Uptake of AnxCLIO-Cy5.5 was most prominent in the midmyocardium and was significantly greater than that of Inact_CLIO-Cy5.5 (contrast-to-noise ratio, 8.82±1.5 versus 3.78±1.1; P<0.05). Only 21±3% of the myocardium with accumulation of AnxCLIO-Cy5.5 showed delayed-enhancement of Gd-DTPA-NBD. Wall thickening was significantly reduced in segments with delayed enhancement and/or transmural accumulation of AnxCLIO-Cy5.5 (P<0.001). Fluorescence microscopy of AnxCLIO-Cy5.5 and immunohistochemistry of Gd-DTPA-NBD confirmed the presence of large numbers of apoptotic but potentially viable cardiomyocytes (AnxCLIO-Cy5.5 positive, Gd-DTPA-NBD negative) in the midmyocardium.

Conclusions— A novel technique to image cardiomyocyte apoptosis and necrosis in vivo within 4 to 6 hours of injury is presented and reveals large areas of apoptotic but viable myocardium in the midmyocardium. Strategies to salvage the numerous apoptotic but potentially viable cardiomyocytes in the midmyocardium in acute ischemia should be investigated.

Methods and Results— Female mice with overexpression of Gaq were studied. Two weeks postpartum, these mice develop a cardiomyopathy characterized by low levels of CM apoptosis and minimal myocardial necrosis or inflammation. The mice were injected with the annexin-labeled nanoparticle (AnxCLIO-Cy5.5) or a control probe (CLIO-Cy5.5) and imaged in vivo at 9.4 T. Uptake of AnxCLIO-Cy5.5 occurred in isolated clusters, frequently in the subendocardium. Myocardial T2* was significantly lower (7.6±1.5 versus 16.8±2.7 ms, P<0.05) in the mice injected with AnxCLIO-Cy5.5 versus CLIO-Cy5.5, consistent with the uptake of AnxCLIO-Cy5.5 by apoptotic CMs. A strong correlation (r²=0.86, P<0.05) was seen between in vivo T2* (AnxCLIO-Cy5.5 uptake) and myocardial caspase-3 activity.

Conclusions— The ability of molecular MRI to image sparsely expressed targets in the myocardium is demonstrated in this study. Moreover, a novel platform for high-resolution and specific imaging of CM apoptosis in heart failure is established. In addition to providing novel insights into the pathogenesis of CM apoptosis, the developed platform could facilitate the development of novel antiapoptotic therapies in heart failure.

Methods and Results— A total of 101 patients with normal LV systolic function underwent CMR and echocardiography (echo) within 7 days. LV-METRIC generated LV filling profiles via automated segmentation of contiguous short-axis images (204±39 images, 2:04±0:53 minutes). Diastolic function by CMR was assessed via early:atrial filling ratios, peak diastolic filling rate, time to peak filling rate, and a novel index—diastolic volume recovery (DVR), calculated as percent diastole required for recovery of 80% stroke volume. Using an echo standard, patients with versus without diastolic dysfunction had lower early:atrial filling ratios, longer time to peak filling rate, lower stroke volume–adjusted peak diastolic filling rate, and greater DVR (all P<0.05). Prevalence of abnormal CMR filling indices increased in relation to clinical symptoms classified by New York Heart Association functional class (P=0.04) or dyspnea (P=0.006). Among all parameters tested, DVR yielded optimal performance versus echo (area under the curve: 0.87±0.04, P<0.001). Using a 90% specificity cutoff, DVR yielded 74% sensitivity for diastolic dysfunction. In multivariate analysis, DVR (odds ratio, 1.82; 95% CI, 1.13 to 2.57; P=0.02) was independently associated with echo-evidenced diastolic dysfunction after controlling for age, hypertension, and LV mass (²=73.4, P<0.001).

Conclusions— Automated CMR segmentation can provide LV filling profiles that may offer insight into diastolic dysfunction. Patients with diastolic dysfunction have prolonged diastolic filling intervals, which are associated with echo-evidenced diastolic dysfunction independent of clinical and imaging variables.

Methods and Results— Positron emission tomography (PET) imaging was used to quantitatively assess myocardial glucose uptake (MGU) in 6 adult subjects with the PRKAG2 cardiac syndrome and 6 healthy, matched control subjects using the glucose analogue ¹⁸F-Fluoro-2-deoxyglucose (FDG). Studies were performed under a euglycemic hyperinsulinemic clamp to ensure stable blood glucose levels. Rubidium-82 perfusion scans were performed to ensure that myocardial differences in myocardial glucose uptake were not the result of significant myocardial scar. In adult patients with phenotypic expression of disease, the median myocardial glucose uptake of the left ventricle was 0.18 µmol/min/g (interquartile range, 0.14, 0.24), compared with 0.40 µmol/min/g (interquartile range, 0.30 to 0.45) in the control group (P=0.01). The median blood glucose during FDG-PET imaging was 4.72 mmol/L (interquartile range, 4.32 to 4.97) in the PRKAG2 group and 4.38 mmol/L (interquartile range, 3.90, 4.79) in the control group (P=NS). The significant decrease observed in myocardial glucose uptake in affected patients occurred in the absence of significant myocardial scar.

Conclusions— The PRKAG2 cardiac syndrome is associated with a reduction of glucose uptake in adult patients affected with this genetic condition. In this pilot study, ¹⁸F-FDG-PET imaging is a useful tool to assess alterations in myocardial glucose transport in this inherited metabolic disease and provide insight into the biochemical pathophysiology of the diseased state.

Methods and Results— This study consisted of a dose-escalating, single-blinded phase and a placebo-controlled, double-blinded phase conducted in healthy, young adults with documented mild, intermittent, asthma. In the single-blinded phase, 3 sequential cohorts of 8 subjects received intravenous binodenoson (0.5, 1.0, and 1.5 µg/kg). In the double-blinded phase, commenced after medical review of results from the single-blinded phase, subjects were randomly assigned 2:1 to either binodenoson 1.5 µg/kg (n=41) or placebo (n=22). The primary end point was clinically significant bronchoconstriction, defined as a decrease in forced expiratory volume in 1 second of ≥20% from the preinjection measure. Secondary safety end points were changes from preinjection measure in forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow during the middle 50% of the forced vital capacity; vital signs; pulse oximetry; and adverse events. Binodenoson caused no clinically significant bronchoconstriction or alterations in pulmonary function parameters and transiently increased heart rate and systolic blood pressure. The most common treatment-emergent adverse events were tachycardia, dizziness, and flushing.

Conclusions— Binodenoson was safe, well tolerated, and caused no clinically significant bronchoconstriction or pulmonary responses in a small population of healthy subjects with mild, intermittent asthma.

Methods and Results— Of 546 consecutive individuals undergoing echocardiography for assessment of resting left ventricular function, 91 died over a period of 5.2±1.5 years. In addition to Simpson biplane EF, WMSI was determined by 2 experienced readers and GLS was calculated from 3 standard apical views using 2D speckle tracking. The incremental value of EF, WMSI, and GLS to significant clinical variables was assessed in nested Cox models. Clinical factors associated with outcome (model ²=20.2) were age (hazard ratio [HR], 1.46; P<0.01), diabetes (HR, 1.88; P=0.01), and hypertension (HR, 1.59; P<0.05). Although addition of EF (HR, 1.23; P=0.03) or WMSI (HR, 1.28; P<0.01) added to the predictive power of clinical variables, the addition of GLS (HR, 1.45; P<0.001) caused the greatest increment in model power (²=34.9, P<0.001). GLS also provided incremental value in subgroups with EF >35% and those with and without wall motion abnormalities. A GLS ≥–12% was found to be equivalent to an EF ≤35% for the prediction of prognosis. Intraobserver and interobserver variations for EF and GLS were similar.

Conclusions— GLS is a superior predictor of outcome to either EF or WMSI and may become the optimal method for assessment of global left ventricular systolic function.

Methods and Results— Left ventricular muscarinic receptor density was measured in vivo by positron emission tomography using the specific antagonist [¹¹C]methylquinuclidinyl benzilate ([¹¹C]MQNB) in 11 patients 43±20 days after myocardial infarction and 9 healthy volunteers. The extent of myocardial damage was quantified by delayed contrast-enhanced MRI. Three short-axis slices from each subject were analyzed in matched positron emission tomography and MRI images. A 2-injection positron emission tomography protocol was used; [¹¹C]MQNB time-activity curves were obtained in 6 regions per slice and fitted to a 3-compartment ligand-receptor model. Four classes of myocardial regions were considered: normal (in volunteers); remote, supplied by healthy or <70% diameter reduction arteries and without MRI signs of damage; potentially damaged, supplied by infarct-related or >70% diameter reduction arteries and without signs of damage; and damaged, with damage. The muscarinic receptor density in remote (67±30 pmol/mL tissue; n=86) and potentially damaged (71±30 pmol/mL tissue; n=42) regions of patients was higher than in normal regions of volunteers (32±17 pmol/mL tissue; n=156; P<0.001). The muscarinic receptor density in damaged regions (42±21 pmol/mL tissue; n=58) was reduced compared with remote and potentially damaged regions (P<0.001) but was not significantly different from normal regions in volunteers (P=0.093).

Conclusions— Vagal control in patients with chronic myocardial infarction involves muscarinic receptor upregulation in remote nondamaged left ventricular regions. Our results suggest that the receptor density remains within normal values in myocardial regions containing damaged tissue.

Methods and Results— The study used 18 male ZDF rats (fa/fa) with 6 rats in each group: an untreated group; a group treated with metformin (16.6 mg/kg/d), and a group treated with rosiglitazone (4 mg/kg). Each rat was scanned at age 14 weeks (baseline) and subsequently at 19 weeks with small-animal positron emission tomography to estimate myocardial glucose utilization (MGU) and myocardial utilization (MFAU), oxidation (MFAO), and esterification (MFAE). Treatment lasted for 5 weeks after baseline imaging. At week 19, rats were euthanized and hearts were extracted for expression analysis of select genes encoding for GLUT transporters and fatty acid transport and oxidation genes. In addition, echocardiography measurements were obtained at weeks 13 and 18 to characterize cardiac function. Metformin had no significant effect on either MGU or MFAU and MFAO. In contrast, rosiglitazone tended to enhance MGU and significantly reduced MFAU and MFAO. Rosiglitazone-induced increase in glucose uptake correlated significantly with increased expression of GLUT4, whereas diminished MFAO correlated significantly with decreased expression of FATP-1 and MCAD. Finally, changes in fractional shortening as a measure of cardiac function were unchanged throughout the study.

Conclusions— Treatment with rosiglitazone enhanced glucose utilization and diminished MFAO, thus reversing the metabolic phenotype of the diabetic heart.

Methods and Results— Standard 2D Doppler echocardiography, tissue Doppler imaging, and 2D speckle strain imaging were performed in 52 hypertensive subjects with normal ejection fraction and 52 control subjects of similar age. Peak systolic (S'), and diastolic (E') annular velocities were obtained by tissue Doppler imaging, whereas longitudinal myocardial systolic velocity (V_l) and circumferential, longitudinal, and radial strains (_c, _l, _r) were obtained by speckle tracking. Midwall shortening and peak basal longitudinal strain (_l) were used as indices of regional function. Hypertensive subjects had lower velocities—tissue Doppler imaging E' and S', and V_l—and evidence of reduced regional function. Surprisingly, however, global values did not differentiate hypertensive subjects from control subjects. Among hypertensive patients, significant inverse associations were found between left ventricular mass and global longitudinal and circumferential (both P<0.05).

Conclusions— Hypertensive heart disease with normal ejection fraction is associated with reduced myocardial velocities and reduced regional function but normal global . Our data suggest that velocity abnormalities occur early in hypertension and may be an appropriate target for preventive strategies because they occur before abnormalities in global .

Methods and Results— Sixteen rabbits with aortic plaque and 6 normal control rabbits underwent gadofluorine-M-enhanced MRI. Eight rabbits had advanced atherosclerotic lesions, whereas the remaining 8 had early lesions. Magnetic resonance atherosclerotic plaque enhancement was meticulously compared with plaque inflammation and neovessel density as assessed by histopathology. Advanced plaques and early atheroma were enhanced after gadofluorine-M injection. Control animals displayed no enhancement. After accounting for the within-animal correlation of observations, mean contrast-to-noise ratio was significantly higher in advanced plaques than compared with early atheroma (4.29±0.21 versus 3.00±0.32; P=0.004). Macrophage density was higher in advanced plaques in comparison to early atheroma (geometric mean=0.50 [95% CI, 0.19 to 1.03] versus 0.25 [0.07 to 0.42]; P=0.05). Furthermore, higher neovessel density was observed in advanced plaques (1.83 [95% CI, 1.51 to 2.21] versus 1.29 [0.99 to 1.69]; P=0.05). The plaque accumulation of gadofluorine-M correlated with increased neovessel density as shown by linear regression analysis (r=0.67; P<0.001). Confocal and fluorescence microscopy revealed colocalization of gadofluorine-M with plaque areas containing a high density of neovessels.

Conclusion— Gadofluorine-M-enhanced MRI is effective for in vivo detection of atherosclerotic plaque inflammation and neovascularization in an animal model of atherosclerosis. These findings suggest that gadofluorine-M enhancement reflects the presence of high-risk plaque features believed to be associated with plaque rupture. Gadofluorine-M plaque enhancement may therefore provide functional assessment of atherosclerotic plaque in vivo.

Methods and Results— CMR planimetry of the orifice area was performed in 65 patients (43/22 stented/stentless prostheses; mean time since implantation, 3.1±2.8 years; mean orifice area [TTE], 1.70±0.43 cm²; 62 normally functioning prostheses, 2 severe stenoses, and 1 severe regurgitation) in an imaging plane perpendicular to the transprosthetic flow using steady-state free-precession cine imaging under breath-hold conditions on a 1.5-T MR system. CMR results were compared with TTE (continuity equation, n=65) and TEE (planimetry, n=31). CMR planimetry was readily feasible in 80.0%; feasible with limitation in 15.4% because of stent, flow, and sternal wire artifacts; and impossible in 4.6% because of flow artifacts. Correlations of the orifice areas by CMR with TTE (r=0.82) and CMR with TEE (r=0.92) were significant. The average difference between the methods was –0.02±0.24 cm² (TTE) and 0.05±0.15 cm² (TEE). Agreement was present for stented and stentless devices and independent of orifice size. Intraobserver and interobserver variabilities of CMR planimetry were 6.7±5.4% and 11.5±7.8%.

Conclusions— The assessment of aortic bioprostheses with normal orifice areas by CMR is technically feasible and provides orifice areas with a close correlation to echocardiography and low observer dependency.

Methods and Results— We measured Ao, SVC, IVC, right (RPA) and left (LPA) PA, and left (LPV) and right (RPV) PV flows in 17 patients with SCPC during routine cardiac MRI studies using through-plane phase-contrast velocity mapping. Two independent measures of SPCF were obtained: model 1, Ao–(SVC+IVC); and model 2, (LPV–LPA)+(RPV–RPA). Values were normalized to body surface area, Ao, and PV, and comparisons were made using linear regression and Bland-Altman analysis. SPCF ranged from 0.2 to 1.4 L/min for model 1 and 0.2 to 1.6 L/min for model 2, for an average indexed SPCF of 0.5 to 2.8 L/min/m²: 11% to 53% (mean, 37%) of Ao and 19% to 77% (mean, 54%) of PV. The mean difference between model 1 and model 2 was 0.01 L/min (P=0.40; 2-SD range, –0.45 to 0.47 L/min).

Conclusions— We present a noninvasive method for SPCF quantification in patients with SCPC. It should provide an important clinical tool in treating these patients. Furthermore, we show that SPCF is a significant hemodynamic burden in many patients with bidirectional Glenn shunt physiology. Future investigations will allow objective study of the impact of collateral flow on outcome.

Methods and Results— We evaluated left atrial size in 230 healthy participants (mean age, 76±5 years) free of prevalent cardiac disease, rhythm abnormality, hypertension, and diabetes selected from the Cardiovascular Health Study, a prospective community-based study of risk factors for cardiovascular disease in 5888 elderly participants. In addition to the standard long-axis measurement, we obtained left atrial superoinferior and lateral diameters and used these dimensions to estimate left atrial volume. These measurements were used to generate reference ranges for determining left atrial enlargement in older men and women, based on the 95% percentiles of the left atrial dimensions in healthy participants, both unadjusted, and after adjustment for age, height, and weight. In healthy elderly subjects, indices of left atrial size do not correlate with age or height but with weight and other measures of body build.

Conclusions— These data provide normative reference values for left atrial size in healthy older women and men. The results should be useful for refining diagnostic criteria for left atrial dilation in the older population and may be relevant for cardiovascular risk stratification.

Methods and Results— Myocardial perfusion SPECT (MPS) was visually assessed using a standard semiquantitative approach, yielding summed scores that were used for preliminary interpretation using 5 levels of certainty. The interpreter was permitted to then shift the level of certainty in the final interpretation by 1 degree, based on nonperfusion MPS variables and available clinical information. To examine the prognostic value of expressing levels of clinical certainty, we evaluated 20 740 unique consecutive patients who underwent rest Tl-201/stress Tc-99m sestamibi MPS (34.3% vasodilator stress), of whom 845 (4.4%) were lost to follow-up and 1695 were excluded from prognostic analysis due to an early revascularization (<60 days after MPS). The remaining 18 200 patients (59.1% men; age, 65±13 years) were followed up for cardiac death for a mean of 2.7±1.7 years. During the follow-up, a total of 591 cardiac death events occurred. By univariable analysis, there were substantial differences in the distribution of follow-up cardiac death by the category of clinical MPS certainty. The clinical certainty was found to be an independent multivariable predictor of cardiac death in the study population and better identified patients at increased risk of cardiac death than the approaches based solely on the standard categories of summed perfusion scores or based solely on categories of segmental perfusion scores.

Conclusions— The use of multicategory reporting of MPS results incorporating nonperfusion MPS results and clinical information enhances risk stratification compared with both a dichotomous normal/abnormal approach or approaches based solely on segmental categories of perfusion scores. Whether this enhanced risk stratification based on the clinical certainty of the MPS interpretation leads to a more effective therapeutic regimen, tailored to the individual patient’s need, requires further prospective evaluation.

Methods and Results— A porcine model of left anterior descending coronary artery occlusion/reperfusion was studied. Seven animals underwent PET-CT within 3 days of infarction, and a control group of 3 animals was scanned at >4 weeks. Perfusion and glucose uptake were assessed by [¹³N]-ammonia/[¹⁸F]-deoxyglucose (FDG), and 64-slice CT delayed contrast enhancement was measured. In the acute infarct model, CT revealed a no-reflow phenomenon suggesting microvascular obstruction in 80% of all infarct segments. PET showed increased FDG uptake in 68% of the CT-defined infarct segments. Ex vivo staining and histology showed active inflammation in the acute infarct area as an explanation for increased glucose uptake. In chronic infarction, CT showed no microvascular obstruction and agreed well with matched perfusion/metabolism defects on PET.

Conclusions— Perfusion/metabolism PET and delayed enhancement CT can be combined within a single hybrid PET-CT session. Increased regional FDG uptake in the acute infarct area is frequently observed. In contrast to the chronic infarct setting, this indicates tissue inflammation that is commonly associated with microvascular obstruction as identified by no reflow on CT. The consequences of these pathophysiological findings for subsequent ventricular remodeling should be explored in further studies.

Methods and Results— To evaluate the clinical utility of 64-slice CT in the preoperative assessment in patients with VHD, we prospectively studied 452 consecutive patients undergoing routine cardiac catheterization for eligibility. Two hundred thirty-seven patients underwent both MSCT and XA. Segment-based, vessel-based, and patient-based agreement between CTA and XA was estimated assuming that "nonevaluable" segments were positive for significant coronary stenosis. In a patient-based analysis, sensitivity, specificity, positive predictive value, and negative predictive values of CTA were 95%, 89%, 66%, and 99%, respectively; in vessel-based analysis, 90%, 92%, 48%, and 99%, respectively; and in segment-based analysis, 89%, 97%, 38%, and 100%, respectively. No significant differences were found between patients with or without atrial fibrillation. A CAC value of 390 was the best cutoff for the identification of patients with positive or inconclusive CTA (which would not be exempted from XA in the clinical setting).

Conclusions— In the preoperative assessment of patients with predominant VHD, the diagnostic accuracy of 64-slice CTA for ruling out the presence of significant coronary artery disease is very good even when including patients with irregular heart rhythm. Using this approach, CAC quantification before CTA can be successfully used to identify patients who should be referred directly to XA, sparing unnecessary exposure to radiation.

Methods and Results— A high-resolution contrast-enhanced MRI examination of the carotid artery was performed in 1769 participants. Measures of carotid wall volume and maximum thickness; lipid core presence, volume and maximum area; and fibrous cap thickness were performed centrally. The sample was, on average, 70 years of age, 57% female, 81% white, and 19% black. Greater age, total and low-density lipoprotein cholesterol, male sex, white race, diabetes, hypertension, and smoking as measured at baseline were all significant predictors of increased wall volume and maximum wall thickness 18 years later. An analysis of lipid core was restricted to the 1180 participants with maximum wall thickness ≥1.5 mm. Lipid core was observed in 569 individuals (weighted percentage, 42%). Baseline age and total and low-density lipoprotein cholesterol were predictors of presence of lipid core 18 years later; however, these relationships were attenuated after adjustment for wall thickness. Concurrently measured low-density lipoprotein cholesterol was associated with greater lipid core volume, independent of wall thickness. Concurrently measured glucose and body mass index were inversely associated fibrous cap thickness.

Conclusions— Traditional atherosclerosis risk factors are related to increased wall volume and wall thickness 2 decades later, but they do not discriminate characteristics of plaque composition (core and cap) independent of wall size.

Methods and Results— Twenty-three triathletes underwent conventional and speckle tracking imaging echocardiography at rest before and immediately after an ultralong distance triathlon. Measurements included LV longitudinal, circumferential and radial strains, LV rotations, and LV torsion. After the race, LV systolic dysfunction was characterized by a decrease in LV longitudinal, radial, and circumferential strains, especially for apical radial strains (44.6±15.1% versus 31.1±13.8%, P<0.001). Peak torsion was slightly decreased (8.3±5.1° versus 6.4±3.9°, respectively, P=0.09) and significantly delayed (91±18% versus 128±31% of systolic duration, P<0.001) beside end-ejection. Peak untwisting was also depressed and delayed beside isovolumic relaxation.

Conclusions— This study documented major alterations in cardiac strains and torsion after an ultralong distance triathlon. LV systolic strains were depressed but not delayed, whereas twisting was decreased and delayed. This altered pattern hampered the rapid untwisting during isovolumic relaxation phase, reducing LV diastolic suction and early filling.

Methods and results— Hypercholesterolemic LDLR^–/–ApoB^100/100 mice on a Western diet and normally fed adult C57BL/6 control mice were injected with ¹⁸F-galacto-RGD and ³H-deoxyglucose followed by imaging with a small animal PET/CT scanner. The aorta was dissected 2 hours after tracer injection for biodistribution studies, autoradiography, and histology. Biodistribution of ¹⁸F-galacto-RGD was higher in the atherosclerotic than in the normal aorta. Autoradiography demonstrated focal ¹⁸F-galacto-RGD uptake in the atherosclerotic plaques when compared with the adjacent normal vessel wall or adventitia. Plaque-to-normal vessel wall ratios were comparable to those of deoxyglucose. Although angiogenesis was not detected, ¹⁸F-galacto-RGD uptake was associated with macrophage density and deoxyglucose accumulation in the plaques. Binding to atherosclerotic lesions was efficiently blocked in competition experiments. In vivo imaging visualized ¹⁸F-galacto-RGD uptake colocalizing with calcified lesions of the aortic arch as seen in CT angiography.

Conclusions— ¹⁸F-Galacto-RGD demonstrates specific uptake in atherosclerotic lesions of mouse aorta. In this model, its uptake was associated with macrophage density. ¹⁸F-Galacto-RGD is a potential tracer for noninvasive imaging of inflammation in atherosclerotic lesions.

Methods and Results— Forty patients with a history of abnormal single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) underwent adenosine stress 64-row (n=24) or 256-row (n=16) detector CTP and CTA. A subset of 27 patients had invasive angiography available for quantitative coronary angiography. CTA and quantitative coronary angiography were evaluated for stenoses ≥50%, and SPECT-MPI was evaluated for fixed and reversible perfusion deficits using a 17-segment model. CTP images were analyzed for the transmural differences in perfusion using the transmural perfusion ratio (subendocardial attenuation density/subepicardial attenuation density). The sensitivity, specificity, positive predictive value, and negative predictive value for the combination of CTA and CTP to detect obstructive atherosclerosis causing perfusion abnormalities using the combination of quantitative coronary angiography and SPECT as the gold standard was 86%, 92%, 92%, and 85% in the per-patient analysis and 79%, 91%, 75%, and 92% in the per vessel/territory analysis, respectively.

Conclusions— The combination of CTA and CTP can detect atherosclerosis causing perfusion abnormalities when compared with the combination of quantitative coronary angiography and SPECT.

Methods and Results— Ninety-one patients (age, 65±11 years) with previous myocardial infarction scheduled for ICD implantation underwent cine MRI to evaluate left ventricular function and volumes and contrast-enhanced MRI for characterization of scar tissue (infarct gray zone as measure of infarct tissue heterogeneity, infarct core, and total infarct size). Appropriate ICD therapy was documented in 18 patients (20%) during a median follow-up of 8.5 months (interquartile range, 2.1 to 20.3). Multivariable Cox proportional hazards analysis revealed that infarct gray zone was the strongest predictor of the occurrence of spontaneous ventricular arrhythmia with subsequent ICD therapy (hazard ratio, 1.49/10 g; CI, 1.01 to 2.20; ²=4.0; P=0.04).

Conclusions— Infarct tissue heterogeneity on contrast-enhanced MRI is the strongest predictor of spontaneous ventricular arrhythmia with subsequent ICD therapy (as surrogate of sudden cardiac death) among other clinical and MRI variables, that is, total infarct size and left ventricular function and volumes, in patients with previous myocardial infarction.

Methods and Results— We used cardiac MRI to examine age-related differences in LV structure and function in 5004 participants without overt cardiovascular disease when enrolled in the Multi-Ethnic Study of Atherosclerosis; 1099 participants received additional strain analyses by MRI tagging. We also assessed the relation of age-associated remodeling with cardiovascular outcomes using Cox proportional hazard models adjusting for cardiovascular risk factors. Although LV mass decreased with age (–0.3 g per year), the mass-to-volume ratio markedly increased (+5 mg/mL per year, P<0.0001), driven by a substantial reduction in end-diastolic volume (–0.8 mL per year, P<0.0001). Age was also associated with a significant fall in stroke volume (–0.4 mL per year, P<0.0001), along with strain patterns reflecting systolic (P<0.0001) as well as diastolic (P<0.01) myocardial dysfunction—despite a modestly enhanced ejection fraction (+0.1% per year, P<0.0001). Increased mass-to-volume ratio conferred a significant risk for total cardiovascular events; this trend was strongest among younger (<65 years; hazard ratio, 3.69 [CI, 1.34 to 10.10]) versus older (≥65 years; hazard ratio, 1.68 [CI 0.77 to 3.68]) individuals with the highest compared to lowest mass-to-volume ratio quintile (P_interaction=0.013).

Conclusions— Age is associated with a phenotype of LV remodeling marked by increased mass-to-volume ratio and accompanied by systolic as well as diastolic myocardial dysfunction that is not reflected by preserved ejection fraction. This pattern of ventricular remodeling confers significant cardiovascular risk, particularly when present earlier in life.

Methods and Results— Invasive coronary angiography (ICA) and MDCT coronary angiography were performed on 132 consecutive patients (82 men; age 63±11 years) affected by DCM (ejection fraction, 34±10%) of unknown etiology. In 2 patients (1.5%), MDCT was not feasible because of atrial fibrillation. Of the remaining 130 patients, 88 exhibited normal and 42 exhibited diseased coronary arteries in both MDCT and ICA. All patients with coronary artery disease except for 1 were correctly classified by MDCT as 1-vessel (11 cases), 2-vessel (13 cases), and 3-vessel (18 cases) disease. In the segment-based analyses, the overall feasibility for MDCT was 98.5% (1902 of 1930 segments). Segment-based and patient-based analyses for the detection of luminal stenosis of >50% and >70% were performed. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MDCT for the detection of >50% stenosis were 98.1%, 99.9%, 98.7%, 99.8%, and 99.7%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MDCT for the detection of >70% stenosis were 99.5%, 98.6%, 94.1%, 99.9%, and 99.4%, respectively.

Conclusions— Excellent feasibility and diagnostic accuracy, combined with low invasiveness, make 64-slice MDCT an ideal imaging modality for the anatomic evaluation of coronary circulation in patients with DCM of unknown etiology.

Methods and Results— DSI tractography was performed at 4.7 T in excised rat hearts 3 weeks after left coronary artery ligation (n=4) and in 4 age-matched controls. Fiber architecture in the control hearts varied smoothly from endocardium to epicardium, producing a symmetrical array of crossing helical structures in which orthogonal myofibers were separated by fibers with intermediate helix angles. Fiber architecture in the infarcted hearts was severely perturbed. The infarct boundary in all cases was highly irregular and punctuated repeatedly by residual myofibers extending from within the infarct to the border zones. In all infarcts, longitudinal myofibers extending toward the basal-anterior wall and transversely oriented myofibers extending toward the septum lay in direct contact with each other, forming nodes of orthogonal myofiber intersection or contact.

Conclusions— DSI tractography resolves 3D myofiber architecture and reveals a complex network of orthogonal myofibers within infarcted myocardium. Meshlike networks of orthogonal myofibers in infarcted myocardium may resist mechanical remodeling but also probably increase the risk for lethal reentrant arrhythmias. DSI tractography thus provides a new and important readout of tissue injury after myocardial infarction.

Methods and Results— The stress echocardiography criteria were applied to 298 consecutive patients who underwent stress echocardiography. Patients were rated as appropriate, uncertain, inappropriate, or not classifiable. Results were compared with those of a previous analysis in the same patients using the single-photon computed tomography myocardial perfusion imaging (SPECT MPI) criteria. The level of agreement between 2 cardiac nurse abstractors for categorizing appropriateness by the stress echocardiography criteria was good (=0.72). Overall, 54% of patients were classified as appropriate, 8% as uncertain, and 19% as inappropriate; 19% were not classifiable. By the SPECT MPI criteria, 64% of patients were classified as appropriate, 9% as uncertain, and 18% as inappropriate; 9% were not classifiable (P<0.001 compared with stress echocardiography criteria). By the stress echocardiography criteria, 6 clinical situations or indications accounted for more than 90% of the inappropriate tests; most of these involved asymptomatic patients.

Conclusions— Applying stress echocardiography appropriateness criteria to a patient population is feasible, although 1 in 5 of our patients was not classifiable. Overall, the stress echocardiography criteria classified patients differently compared with the SPECT MPI criteria. Future refinements of the appropriateness criteria for stress imaging should address gaps in the criteria and disparities between the stress echocardiography and SPECT MPI criteria.

Methods and Results— APC blood flow was quantifiable in 24 of 36 retrospectively analyzed MRI studies. Sixteen studies were performed after the bidirectional cavopulmonary connections (group A) and 8 after the Fontan operation (group B). APC blood flow was calculated by subtracting the blood flow volume through the pulmonary arteries from that through the pulmonary veins. The ratio of pulmonary to systemic blood flow (Qp/Qs) was 0.93±0.26 in group A and 1.27±0.16 in group B. APC flow was 1.42 (0.58 to 3.83) L/min/m² and 0.82 (0.50 to 1.81) L/min/m² in groups A and B, respectively. The mean inaccuracies corresponded to 7.9±14.5% and 7.1±13.6% of ascending aortic flow in groups A and B, respectively. Qp/Qs was negatively correlated with a younger age at the time of the bidirectional cavopulmonary connections operation (r=0.62, P=0.01) and positively correlated with the age at the time of the Fontan completion (r=0.81, P=0.01). Patients with a previous right-sided modified Blalock-Taussig shunt had more collateral flow to the right lung than those without.

Conclusions— APC blood flow can be noninvasively measured in bidirectional cavopulmonary connections and Fontan patients, using MRI in the majority of patients and results in a significant left-to-right shunt.

Methods and Results— Five control and 7 atherosclerotic rabbits were sequentially imaged after administration of Gd-DTPA (0.2 mmol/kg) and GdF (0.1 mmol/kg) using a T₁-weighted pulse sequence on a 3-T MRI scanner. Diseased aortic wall could be distinguished from normal wall based on wall-to-muscle contrast-to-noise values after GdF administration. RAM-11 (macrophages) and CD-31 (endothelial cells) immunostaining of MR-matched histological sections revealed that GdF accumulation was related to the degree of inflammation at the surface of plaques and the extent of core neovascularization. Importantly, an MR measure of GdF accumulation at both 1 and 24 hours after injection but not Gd-DTPA at peak enhancement was shown to correlate with a quantitative histological morphology index related to these 2 plaque features.

Conclusions— GdF-enhanced MRI of atherosclerotic plaques allows noninvasive quantitative information about plaque composition to be acquired at multiple time points after injection (within 1 and up to 24 hours after injection). This dramatically widens the imaging window for assessing plaque stability that is currently attainable with clinically approved MR agents, therefore opening the possibility of whole-body (including coronary) detection of unstable plaques in the future and potentially improved mitigation of cataclysmic cardiovascular events.

Methods and Results— B-mode ultrasound and 3.0-T MRI scans of the left and right common carotid arteries were repeated 3 times in 15 healthy younger volunteers (age, 26±2.6 years), 15 healthy older volunteers (age, 57±3.2 years), and 15 subjects with cardiovascular disease and carotid atherosclerosis (age, 63±9.8 years). MWT was 0.711 (SD, 0.229) mm and mean CCIMT was 0.800 (SD, 0.206) mm. MWT and CCIMT were highly correlated (r=0.89, P<0.001). The intraclass correlation coefficients for interscan and interobserver and intraobserver agreements of MRI MWT measurements were larger than 0.95 with small confidence intervals, indicating excellent reproducibility. Power calculations indicate that 89 subjects are required to detect a 4% difference in MRI MWT compared with 469 subjects to detect similar differences with ultrasound IMT in follow-up studies.

Conclusions— The study data for carotid MRI and ultrasound IMT showed strong agreement, indicating that both modalities measure the thickness of the intima and media. The advantage of MRI over ultrasound is that the measurement variability is smaller, enabling smaller sample sizes and potentially shorter study duration in cardiovascular prevention trials.