Myocardial ischemic memory imaging, denoting the visualization of abnormalities provoked by ischemia and sustained even after restoration of perfusion, can convey important clinical information. We previously reported that post-systolic shortening (PSS) remains in the risk area after recovery from brief ischemia. However, it is still unclear whether abnormalities in other regional deformation parameters persist after relief from brief ischemia.

Echocardiographic data were chronologically acquired from 11 dogs during 2 min of coronary occlusion followed by reperfusion. Regional systolic and diastolic deformation parameters, including parameters related to PSS, were measured from radial and circumferential strain and from strain rate analyzed in the risk and normal areas. Strain imaging diastolic index (SI-DI), which had been proposed as a parameter for assessing ischemic memory, was also calculated.

Peak systolic strain, end-systolic strain, and peak systolic strain rate decreased in the risk area during occlusion but recovered to the baseline level immediately after reperfusion. Strain rate during early diastole decreased during occlusion; however, the decrease did not persist after reperfusion. Post-systolic strain index (PSI) and time-to-peak strain index, which are parameters of PSS, increased during occlusion. These increases persisted until 10 to 20 min after reperfusion (circumferential PSI: 0.02 ± 0.04 [baseline] vs. 0.08 ± 0.04 [20 min], p < 0.05). SI-DI did not show a significant change during occlusion because of a large variation.

Although abnormalities of PSS-related parameters alone persisted after recovery from 2-min occlusion, abnormalities of other deformation parameters, such as strain rate during early diastole, did not. These data suggest that assessment of PSS by speckle tracking echocardiography is useful for detecting myocardial ischemic memory.

Definitive diagnosis of CP requires identification of constrictive hemodynamics with or without pericardial thickening. CMR to date has primarily provided morphological assessment of the pericardium.

Sixteen patients (age 57 ± 13 years) undergoing CMR to assess known or suspected CP and 10 controls underwent RT-PC that acquired simultaneous mitral valve and tricuspid valve inflow velocities over 10 s of unrestricted breathing. The diagnosis of CP was confirmed via clinical history, diagnostic imaging, cardiac catheterization, intraoperative findings, and histopathology.

Ten patients had CP, all with increased pericardial thickness (6.2 ± 1.0 mm). RT-PC imaging demonstrated discordant respirophasic changes in atrioventricular valve inflow velocities in all CP patients, with mean ± SD mitral valve and tricuspid valve inflow velocity variation of 46 ± 20% and 60 ± 15%, respectively, compared with 16 ± 8% and 24 ± 11% in patients without CP (p < 0.004 vs. patients with CP for both) and 17 ± 5% and 31 ± 13% in controls (p < 0.001 vs. patients with CP for both). There was no difference in atrioventricular valve inflow velocity variation between patients without CP compared with controls (p > 0.3 for both). Respiratory variation exceeding 25% across the mitral valve yielded a sensitivity of 100%, a specificity of 100%, and an area under the receiver-operating characteristic curve of 1.0 to detect CP physiology. Using a cutoff of 45%, variation of transtricuspid valve velocity had a sensitivity of 90%, a specificity of 88%, and an area under the receiver-operating characteristic curve of 0.98.

Accentuated and discordant respirophasic changes in mitral valve and tricuspid valve inflow velocities characteristic of CP can be identified noninvasively with RT-PC CMR. When incorporated into existing CMR protocols for imaging pericardial morphology, RT-PC CMR provides important hemodynamic evidence with which to make a definite diagnosis of CP.

There is little agreement on the most suitable imaging plane for RV volumetric analysis in the setting of abnormal RV physiology.

Measurements of RV volumes from datasets acquired in axial and short-axis orientations were made in 50 patients with CHD. RV stroke volumes (SV) calculated using these 2 methods were compared with forward flow measured in the pulmonary trunk by phase contrast (PC) imaging. Repeated volume measurements were made to assess intraobserver and interobserver reliability. Bland-Altman plots and Lin's concordance correlation coefficient (CCC) were used for all analyses of agreement.

Analysis of all subjects revealed a statistically significant difference in interobserver reliability of RV end-systolic volume (ESV) measurements that favored the axial method (p = 0.047). The magnitude of measurement differences between observers in this case was small (–2.8 ml/m²; 95% confidence interval: –5.6 to 0.0). There was no difference between the 2 contouring methods in terms of intraobserver reliability in measurements of RV end-diastolic volume (EDV), ESV, ejection fraction, or SV (p > 0.05 in all cases). In subjects with RV EDV ≥150 ml/m², RV SV measured using axial contours yielded better agreement with forward flow measured in the pulmonary trunk (CCC = 0.63) than did measurements made using short-axis contours (CCC = 0.56; p = 0.007).

Trends favoring the axial orientation in terms of reproducibility were not clinically significant. In subjects with RV EDV ≥150 ml/m², the axial orientation yields RV volume measurements that agree more closely with flow measured in the pulmonary trunk than does the short-axis orientation.

Inflammation within atherosclerotic plaques is associated with instability of the plaque and future cardiovascular events. Previous studies have shown that ¹⁸F-FDG-PET/CT is able to quantify inflammation within carotid artery atherosclerotic plaques, but no studies to date have investigated this correlation in peripheral arteries with immunohistochemical confirmation.

Thirty patients across 5 study sites underwent ¹⁸F-FDG-PET/CT imaging before SilverHawk atherectomy (FoxHollow Technologies, Redwood City, California) for symptomatic common or superficial femoral arterial disease. Vascular FDG uptake (expressed as target-to-background ratio) was measured in the carotid arteries and aorta and femoral arteries, including the region of atherectomy. Immunohistochemistry was performed on the excised atherosclerotic plaque extracts, and cluster of differentiation 68 (CD68) level as a measure of macrophage content was determined. Correlations between target-to-background ratio of excised lesions, as well as entire arterial regions, and CD68 levels were determined. Imaging was performed during the 2 weeks before surgery in all cases.

Twenty-one patients had adequate-quality ¹⁸F-FDG-PET/CT peripheral artery images, and 34 plaque specimens were obtained. No significant correlation between lesion target-to-background ratio and CD68 level was observed.

There were no significant correlations between CD68 level (as a measure of macrophage content) and FDG uptake in the peripheral arteries in this multicenter study. Differences in lesion extraction technique, lesion size, the degree of inflammation, and imaging coregistration techniques may have been responsible for the failure to observe the strong correlations with vascular FDG uptake observed in previous studies of the carotid artery and in several animal models of atherosclerosis.

MNC therapy is a promising treatment for PAD. Although clinical translation has already been established, there is a lack of knowledge about cell behavior after transplantation and about the mechanism whereby MNC therapy might ameliorate complaints of PAD.

MNCs were isolated from F6 transgenic mice (FVB background) that express firefly luciferase (Fluc) and green fluorescence protein (GFP). Male FVB and C57Bl6 mice (n = 50) underwent femoral artery ligation and were randomized into 4 groups receiving the following: 1) single intramuscular (IM) injection of 2 x 10⁶ MNCs; 2) 4 weekly IM injections of 5 x 10⁵ MNCs; 3) 2 x 10⁶ MNCs intravenously; and 4) phosphate-buffered saline as control. Cells were characterized by flow cytometry and in vitro bioluminescence imaging (BLI). Cell survival, proliferation, and migration were monitored by in vivo BLI, which was validated by ex vivo BLI, post-mortem immunohistochemistry, and flow cytometry. Paw perfusion and neovascularization was measured with laser Doppler perfusion imaging (LDPI) and histology, respectively.

In vivo BLI revealed near-complete donor cell death 4 weeks after IM transplantation. After intravenous transplantation, BLI revealed that cells migrated to the injured area in the limb, as well as to the liver, spleen, and bone marrow. Ex vivo BLI showed presence of MNCs in the scar tissue and adductor muscle. However, no significant effects on neovascularization were observed, as monitored by LDPI and histology.

This is one of the first studies to assess kinetics of transplanted MNCs in PAD using in vivo molecular imaging. MNC survival is short-lived, MNCs do not preferentially home to injured areas, and MNCs do not significantly stimulate perfusion in this particular model.

RAGE and its ligands are implicated in the pathogenesis of ischemia/reperfusion injury and infarction. We hypothesized that RAGE-directed quantitative imaging of myocardial uptake of technetium-99m (^99mTc)-anti-RAGE F(ab')₂ in a mouse model of myocardial ischemic injury can detect RAGE expression and show quantitative differences between early (18 to 20 h) and later times (48 h) after reperfusion.

Twenty-five wild-type (WT) mice underwent left anterior descending coronary artery occlusion for 30 min. Mice were injected with 19.98 ± 1.78 MBq of ^99mTc anti-RAGE F(ab')₂ at 2 time points after reperfusion (at 18 to 20 h [n = 8] and at 48 h [n = 12]) and 5 h later with 6.14 ± 2.0 MBq of thallium-201 (²⁰¹Tl). Five WT mice were injected with nonspecific F(ab')₂ and ²⁰¹Tl 18 to 20 h after reperfusion. Six WT mice underwent sham operation without coronary intervention. After injection with ²⁰¹Tl, all mice immediately underwent dual isotope single-photon emission computed tomography/computed tomography. At completion of imaging, hearts were counted and sectioned.

The uptake of ^99mTc-anti-RAGE F(ab')₂ in the ischemic zone from the scans as mean percentage injected dose was significantly greater at 18 to 20 h (5.7 ± 2.1 x 10^–3%) as compared with at 48 h (1.4 ± 1.1 x 10^–3%; p < 0.001) after reperfusion. Disease and antibody controls showed no focal uptake in the infarct. Gamma well counting of the myocardium supported the quantitative scan data.

By immunohistochemical staining there was greater caspase-3 and RAGE staining at 18 to 20 h versus at 48 h (p = 0.04 and p = 0.01, respectively). On dual immunofluorescence, RAGE colocalized mainly with injured cardiomyocytes undergoing apoptosis.

RAGE expression in myocardial ischemic injury can be imaged in vivo using a novel ^99mTc-anti-RAGE F(ab')₂. RAGE plays a role in several cardiovascular diseases and is a potential target for clinical imaging.

A precise assessment of vascular responses to stents may help stratify the risk of future adverse events in patients who have been treated with coronary stents.

Fourteen human stented coronary segments with implant duration ≥1 month from 10 hearts acquired at autopsy were interrogated ex vivo by OFDI and intravascular ultrasound (IVUS). Comparison with histology was assessed in 134 pairs of images where the endpoints were to investigate: 1) accuracy of morphological measurements; 2) detection of uncovered struts; and 3) characterization of neointima.

Although both OFDI and IVUS provided a good correlation of neointimal area with histology, the correlation of minimum neointimal thickness was inferior in IVUS (R² = 0.39) as compared with OFDI (R² = 0.67). Similarly, IVUS showed a weak correlation of the ratio of uncovered to total stent struts per section (RUTSS) (R² = 0.24), whereas OFDI maintained superiority (R² = 0.66). In a more detailed analysis by OFDI, identification of individual uncovered struts demonstrated a sensitivity of 77.9% and specificity of 96.4%. Other important morphological features such as fibrin accumulation, excessive inflammation (hypersensitivity), and in-stent atherosclerosis were characterized by OFDI; however, the similarly dark appearance of these tissues did not allow for direct visual discrimination. The quantitative analysis of OFDI signal reflections from various in-stent tissues demonstrated distinct features of organized thrombus and accumulation of foamy macrophages.

The results of the present study reinforce the potential of OFDI to detect vascular responses that may be important for the understanding of long-term stent performance, and indicate the capability of this technology to serve as a diagnostic indicator of clinical success.

HIV cardiomyopathy is an important cause of heart failure and death. ICR is associated with better survival and improvement of LVEF in patients with ischemic and nonischemic cardiomyopathies. However, the prognostic value of ICR in patients with HIV cardiomyopathy is unknown.

Patients with HIV cardiomyopathy and a LVEF <45% who were referred for DSE were enrolled. ICR was evaluated by the delta wall motion score index (WMSI), calculated as the difference between rest and peak WMSI. Patients were followed for cardiac death and change in LVEF on follow-up.

Sixty patients (75% men; age, 54 ± 9 years) with HIV cardiomyopathy (mean LVEF, 28 ± 11%) formed the study group. After 2.4 ± 2.1 years, 11 cardiac deaths occurred (event rate of 7.6%/year). A receiver-operating characteristic curve identified a WMSI of 0.38 as an optimal cut point for the presence of ICR, with a specificity of 88% and a sensitivity of 73% for the prediction of cardiac death. On univariable analysis, the absence of ICR (hazard ratio: 6.6; 95% confidence interval: 1.93 to 22.62; p = 0.003) and New York Heart Association functional class IV (hazard ratio: 7.2; 95% confidence interval: 2.20 to 23.65; p = 0.001) were the only predictors of cardiac death. After 2.1 ± 1.8 years, 41 patients had a follow-up echocardiogram. LVEF improvement from baseline occurred in 23 patients (56%), more so in patients with ICR than without ICR. A WMSI of 0.59 predicted improvement in the LVEF with a specificity of 78% and a sensitivity of 74%.

The presence of ICR during DSE can risk-stratify and predict subsequent improvement in LVEF in patients with HIV cardiomyopathy.

Myocardial fibrosis may be an important contributor to myocardial impairment in MS, and aldosterone antagonism may reduce fibrosis.

Eighty patients (age 59 ± 11 years) with MS, already being treated with angiotensin II inhibition, were randomized to spironolactone 25 mg/day or placebo for 6 months. Each patient underwent baseline and follow-up conventional echocardiography and color tissue Doppler imaging. Raw data files were used to measure calibrated integrated backscatter and to calculate radial and longitudinal strain. Blood was obtained at baseline and follow-up to measure fibrosis markers (procollagen type III amino-terminal propeptide and procollagen type I carboxy-terminal propeptide [PICP]).

The spironolactone group showed significant improvement of LV function, myocardial reflectivity, and LV hypertrophy, with a parallel decrease in levels of PICP and procollagen type III amino-terminal propeptide. No analogous changes were seen in the placebo group. Baseline strain (β = 0.47, p < 0.0001), spironolactone therapy (β = –0.38, p < 0.0001), and change in PICP level (β = –0.19, p < 0.03) were independently associated with LV systolic function improvement (increase in strain). Correlates of LV diastolic function improvement (increase in early diastolic mitral annular velocity) were baseline early diastolic mitral annular velocity (β = 0.47, p < 0.0001), spironolactone therapy (β = –0.21, p < 0.03), change in PICP level (β = –0.23, p < 0.02), and age (β = 0.22, p < 0.04). Favorable effects of spironolactone on cardiac function were not demonstrated in patients with less fibrosis (the lower baseline PICP tertile) or preserved function (the upper baseline strain tertile).

Addition of spironolactone to standard angiotensin II inhibition improved myocardial abnormalities and decreased fibrotic markers in MS. The magnitude of benefit on cardiac performance is determined mainly by baseline LV dysfunction and collagen turnover as well its response to intervention.

Measurements of regional myocardial perfusion at rest and during vasodilatation are used to determine perfusion reserve, which indicates the presence and distribution of myocardial ischemia. ASL CMR is a perfusion imaging technique that does not require any contrast agents, and is therefore safe for use in patients with end-stage renal disease, and capable of repeated or continuous measurement.

Myocardial ASL scans at rest and during adenosine infusion were incorporated into a routine CMR adenosine induced vasodilator stress protocol and was performed in 29 patients. Patients who were suspected of having ischemic heart disease based on first-pass imaging also underwent x-ray angiography. Myocardial ASL was performed using double-gated flow-sensitive alternating inversion recovery tagging and balanced steady-state free precession imaging at 3-T.

Sixteen patients were found to be normal and 13 patients were found to have visible perfusion defect based on first-pass CMR using intravenous gadolinium chelate. In the normal subjects, there was a statistically significant difference between MBF measured by ASL during adenosine infusion (3.67 ± 1.36 ml/g/min), compared to at rest (0.97 ± 0.64 ml/g/min), with p < 0.0001. There was also a statistically significant difference in perfusion reserve (MBF_stress/MBF_rest) between normal myocardial segments (3.18 ± 1.54) and the most ischemic segments in the patients with coronary artery disease identified by x-ray angiography (1.44 ± 0.97), with p = 0.0011.

This study indicates that myocardial ASL is capable of detecting clinically relevant increases in MBF with vasodilatation and has the potential to identify myocardial ischemia.

Current cardiac magnetic resonance methods require 2 separate scans for assessment of myocardial edema and cardiac function.

Mini-pigs (n = 13) with experimentally induced reperfused myocardial infarction and patients with reperfused ST-segment elevation myocardial infarction (n = 26) underwent cardiac magnetic resonance scans on days 2 to 4 post-reperfusion. Cine bSSFP, T2-weighted short TI inversion recovery (T2-STIR), and late gadolinium enhancement were performed at 1.5-T. Cine bSSFP and T2-STIR images were acquired with a body coil to mitigate surface coil bias. Signal, contrast, and the area of edema were compared. Additional patients (n = 10) were analyzed for the effect of microvascular obstruction on bSSFP. A receiver-operator characteristic analysis was performed to assess the accuracy of edema detection.

An area of hyperintense bSSFP signal consistent with edema was observed in the infarction zone (contrast-to-noise ratio: 37 ± 13) in all animals and correlated well with the area of late gadolinium enhancement (R = 0.83, p < 0.01). In all patients, T2-STIR and bSSFP images showed regional hyperintensity in the infarction zone. Normalized contrast-to-noise ratios were not different between T2-STIR and bSSFP. On a slice basis, the volumes of hyperintensity on T2-STIR and bSSFP images correlated well (R = 0.86, p < 0.001), and their means were not different. When compared with T2-STIR, bSSFP was positive for edema in 25 of 26 patients (96% sensitivity) and was negative in all controls (100% specificity). All patients with microvascular obstruction showed a significant reduction of signal in the subendocardial infarction zone compared with infarcted epicardial tissue without microvascular obstruction (p < 0.05).

Myocardial edema from ST-segment elevation myocardial infarction can be detected using cine bSSFP imaging with image contrast similar to T2-STIR. This new imaging approach allows evaluation of cardiac function and edema simultaneously, thereby reducing patient scan time and increasing efficiency. Further work is necessary to optimize edema contrast in bSSFP images.

Hemorrhage can contribute to reperfusion injury in myocardial infarction and may have significant implications for patient management. There is currently no validated imaging method to assess reperfusion hemorrhage in vivo. T2*-CMR appears suitable because it can create image contrast on the basis of magnetic field effects of hemoglobin degradation products.

In 14 mongrel dogs, myocardial infarction was experimentally induced. On day 3 post-reperfusion, an in vivo CMR study was performed including a T2*-weighted gradient-echo imaging sequence for hemorrhage, standard sequences for LV function, and post-contrast sequences for microvascular obstruction and myocardial necrosis. Ex vivo, thioflavin S imaging and triphenyl-tetrazoliumchloride (TTC) staining were performed to assess microvascular obstruction, hemorrhage, and myocardial necrosis. Images were analyzed by blinded observers, and comparative statistics were performed.

Hemorrhage occurred only in the dogs with the largest infarctions and the greatest extent of microvascular obstruction, and it was associated with more compromised LV functional parameters. Of 40 hemorrhagic segments on TTC staining, 37 (92.5%) were positive for hemorrhage on T2*-CMR (kappa = 0.96, p < 0.01 for in vivo/ex vivo segmental agreement). The amount of hemorrhage in 13 affected tissue slices as determined by T2*-CMR in vivo correlated strongly with ex vivo results (20.3 ± 2.3% vs. 17.9 ± 1.6% per slice; Pearson r = 0.91; r² = 0.83, p < 0.01 for both). Hemorrhage size was not different between in vivo T2*-CMR and ex vivo TTC (mean difference 2.39 ± 1.43%; p = 0.19).

T2*-CMR accurately quantified myocardial reperfusion hemorrhage in vivo. Hemorrhage was associated with more severe infarct-related injury.

Cell transplantation is being widely investigated as a potential therapy in heart failure. Noninvasive imaging techniques are frequently used to investigate therapeutic effects of cell therapies in the preclinical and clinical settings. Previous studies have shown that cardiac MDCT can accurately quantify myocardial scar tissue and determine left ventricular (LV) volumes and ejection fraction (LVEF).

Twenty-two minipigs were randomized to intramyocardial injection of phosphate-buffered saline (placebo, n = 9) or 200 million mesenchymal stem cells (MSC, n = 13) 12 weeks after myocardial infarction (MI). Cardiac magnetic resonance and MDCT acquisitions were performed before randomization (12 weeks after MI induction) and at the study endpoint 24 weeks after MI induction. None of the animals received medication to control the intrinsic heart rate during first-pass acquisitions for assessment of LV volumes and LVEF. Delayed-enhancement MDCT imaging was performed 10 min after contrast delivery. Two blinded observers analyzed MDCT acquisitions.

MDCT demonstrated that MSC therapy resulted in a reduction of infarct size from 14.3 ± 1.2% to 10.3 ± 1.5% of LV mass (p = 0.005), whereas infarct size increased in nontreated animals (from 13.8 ± 1.3% to 16.5 ± 1.5%; p = 0.02) (placebo vs. MSC; p = 0.003). Both observers had excellent agreement for infarct size (r = 0.96; p < 0.001). LVEF increased from 32.6 ± 2.2% to 36.9 ± 2.7% in MSC-treated animals (p = 0.03) and decreased in placebo animals (from 33.3 ± 1.4% to 29.1 ± 1.5%; p = 0.01; at week 24: placebo vs. MSC; p = 0.02). Infarct size, end-diastolic LV volume, and LVEF assessed by MDCT compared favorably with those assessed by cardiac magnetic resonance acquisitions (r = 0.70, r = 0.82, and r = 0.902, respectively; p < 0.001).

This study demonstrated that cardiac MDCT can be used to evaluate infarct size, LV volumes, and LVEF after intramyocardial-delivered MSC therapy. These findings support the use of cardiac MDCT in preclinical and clinical studies for novel myocardial therapies.

The animal's age and start time and duration of a high-fat diet have effects on plaque composition in atherosclerotic mice.

The aortas of atherosclerotic low-density lipoprotein receptor deficient mice expressing only apolipoprotein B100 (LDLR^–/–ApoB^100/100) and atherosclerotic and diabetic mice overexpressing insulin-like growth factor II (IGF-II/LDLR^–/–ApoB^100/100) were investigated at 4, 6, and 12 months of age and older after varying durations of high-fat diet. C57BL/6N mice on normal chow served as controls. Plaque size (intima-to-media ratio), macrophage density (Mac-3 staining), and plaque uptake of ¹⁸F-FDG were studied by means of in vivo positron emission tomography/computed tomography by ex vivo autoradiography and by histological and immunohistochemical methods.

From the ages of 4 to 6 months and 12 months and older, the plaque size increased and the macrophage density decreased. Compared with the controls, the in vivo imaging showed increased aortic ¹⁸F-FDG uptake at 4 and 6 months, but not at 12 months and older. Autoradiography showed focal ¹⁸F-FDG uptake in plaques at all time points (average plaque-to-normal vessel wall ratio: 2.4 ± 0.4, p < 0.001) with the highest uptake in plaques with high macrophage density. There were no differences in the plaque size, macrophage density, or uptake of ¹⁸F-FDG between LDLR^–/–ApoB^100/100 and IGF-II/LDLR^–/–ApoB^100/100 mice at any time point.

The 6-month-old LDLR ^–/– ApoB^100/100 and IGF-II/LDLR ^–/– ApoB^100/100 mice demonstrated highly inflamed, large, and extensive atherosclerotic plaques after 4 months of a high-fat diet, presenting a suitable model for studying the imaging of atherosclerotic plaque inflammation with ¹⁸F-FDG. The presence of type 2 diabetes did not confound evaluation of plaque inflammation with ¹⁸F-FDG.

Diagnosing PAV stenosis, especially in mechanical valves, may be challenging and has significant clinical implications.

Doppler echocardiography was quantitated in 88 patients with PAV (44 mechanical and 44 bioprosthetic; age 63 ± 16 years; valve size range 18 to 25 mm) of whom 22 patients had documented PAV stenosis, 22 had PPM, and 44 served as controls. Quantitative Doppler parameters included ejection dynamics (AT, ET, and AT/ET) and conventional PAV parameters.

Patients with PAV stenosis had significantly lower effective orifice area (EOA) values and higher gradients compared with controls and PPM. Flow ejection parameters (AT and AT/ET) were significantly longer in the stenotic valves compared with PPM and controls (respective values for AT: 120 ± 24 ms, 89 ± 16 ms, and 71 ± 15 ms; for AT/ET: 0.4, 0.32, and 0.3, p ≤ 0.001). Patients with PPM had gradients and ejection dynamics that were intermediate between normal and stenotic valves. Receiver-operator characteristic (ROC) curve analysis showed that AT and AT/ET discriminated PAV stenosis from PPM and controls (area under ROC curve = 0.92 and 0.88, respectively). Combining AT with the conventional Doppler velocity index gave the highest area under the curve of 0.98 but was not statistically different from that of AT alone (p = 0.12). A cutoff of AT = 100 ms had a sensitivity and specificity of 86% for identifying PAV stenosis; for an AT/ET = 0.37, the sensitivity and specificity were 96% and 82%, respectively. Analysis by valve type (mechanical and biological) revealed similar results; however, biological valves had slightly higher areas under the curve for all systolic time intervals.

Ejection dynamics through PAV, particularly AT and AT/ET, are reliable angle-independent parameters that can help evaluate valve function and identify PAV stenosis.

The frequency, manifestations, and severity of acute adverse reactions associated with gadolinium-based contrast agents in the specific setting of cardiovascular magnetic resonance have not been systematically evaluated yet.

This is a multicenter and multinational registry with consecutive enrollment of patients in 45 European centers. During the current observation, 17,767 doses of gadolinium-based contrast agent were administered to 17,767 patients. The mean dose was 25.6 ml (range 5 to 80 ml), which is equivalent to 0.128 mmol/kg (range 0.012 to 0.3 mmol/kg).

Thirty acute adverse reactions due to contrast administration occurred (0.17%). All reactions were classified as mild according to the American College of Radiology definition. The most frequent complaints following contrast administration were rashes and hives (9 of 30), followed by nausea (7 of 30), and anxiety (6 of 30). The event rate ranged from 0.06% (linear nonionic agent gadodiamide) to 0.47% (linear ionic agent gadobenate dimeglumine). Interestingly, we also found different event rates between the three main indications for CMR imaging, ranging from 0.1% (risk stratification in suspected coronary artery disease) to 0.42% (viability in known coronary artery disease).

The incidence of acute adverse reactions after administration of gadolinium-based contrast in the "off-label" setting of CMR in our population was not different from the incidence in the U.S. Food and Drug Administration–approved general radiology setting. Thus, the off-label use of gadolinium-based contrast in CMR should be regarded as safe concerning the frequency, manifestation, and severity of acute events.

Constrictive pericarditis patients studied by CMR will occasionally demonstrate pericardial DHE following gadolinium contrast administration.

We identified 25 CP patients who underwent pericardiectomy following CMR-gadolinium study. We also assessed 10 control subjects with no evidence of pericardial disease referred for cardiac viability imaging. A novel 14-segment pericardial model was used to determine pericardial DHE score and thickness score. Histopathology of pericardial specimens was reviewed and evaluated semiquantitatively on a 4-point scale for the extent of calcification, fibrosis, inflammation, and neovascularization.

DHE was present in 12 (48%) CP patients (DHE+ group), and absent in 13 CP patients (DHE– group) and all control patients. The DHE+ group had greater fibroblastic proliferation and neovascularization, as well as more prominent chronic inflammation and granulation tissue. Fibroblastic proliferation and chronic inflammation correlated with DHE presence quantitated by DHE score (Spearman r = 0.578, p < 0.002, and r = 0.590, p < 0.002, respectively), but not with pericardial thickness. Segmental analysis demonstrated no significant difference in the percentage of patients with different pericardial segmental thickness; however, overall, in each segment, the DHE+ group tended to have greater pericardial thickness.

The presence of pericardial DHE on CMR is common in patients with CP, and its presence is associated with histological features of organizing pericarditis, which may be a target for future focused pharmacological interventions. Patients with CP without pericardial DHE had more pericardial fibrosis and calcification, as well as lesser degrees of pericardial thickening.

The atherosclerotic disease process is characterized by infiltration and retention of oxidized lipids in the artery wall, triggering a disproportionate inflammatory response. Efforts have been made to use noninvasive imaging to quantify this inflammatory response in the vessel wall. Recently, carotid FDG-PET has been shown to reflect the metabolic rate of glucose, a process known to be enhanced in inflamed tissue.

Carotid inflammation was quantified in 82 CAD patients (age 62 ± 10 years) as the maximum target-to-background ratio (_wholevesselTBR_max). Furthermore, we assessed the maximal standardized uptake value values (_wholevesselSUV_max), the single hottest segment (SHS), and the percent active segments (PAS) of the FDG uptake in the artery wall, measured by FDG-PET.

Whole-vessel TBR_max >1.8 was present in 67%, >2.0 in 39%, >2.2 in 23%, and >2.4 in 12% of the population. Multiple linear regression analysis with backward elimination revealed that body mass index (BMI) ≥30 kg/m² (p < 0.0001), age >65 years (p = 0.01), smoking (p = 0.02), and hypertension (p = 0.01) were associated with _wholevesselTBR_max. The number of components of the metabolic syndrome was also associated with _wholevesselTBR_max (p = 0.02). In similar analyses, _wholevesselSUV_max was associated with BMI ≥30 kg/m² (p < 0.0001), age >65 years (p = 0.004), male gender (p = 0.02), and hypertension (p = 0.04); SHS with BMI ≥30 kg/m² (p < 0.0001), age >65 years (p = 0.02), smoking (p = 0.04), and hypertension (p = 0.05); PAS with BMI ≥30 kg/m² (p = 0.001), smoking (p = 0.03), and hypertension (p = 0.01).

Carotid inflammation as revealed by FDG-PET is highly prevalent in the CAD population and is associated with obesity, age over 65 years, history of hypertension, smoking, and male gender. Artery wall FDG uptake increased when components of the metabolic syndrome clustered.

Previous studies have used different methods for the measurement of the valve EOA following TAVI. Factors influencing the EOA of transcatheter valves are unknown.

A total of 122 patients underwent TAVI with the use of the Edwards-SAPIEN valve (Edwards Lifesciences, Irvine, California). The EOA was measured by transthoracic echocardiography at hospital discharge, 6 months and 1 year after TAVI with the use of 2 methods as described in previous studies. In Method #1 (EOA₁), LVOT diameter (LVOTd) entered in the continuity equation was measured at the base of prosthesis cusps whereas, in Method #2 (EOA₂), LVOTd was measured immediately proximal to the prosthesis stent.

The average EOA₂ (1.57 ± 0.41 cm²) was larger (p < 0.01) than the EOA₁ (1.21 ± 0.38 cm²). Accordingly, incidence of severe PPM (indexed EOA ≤0.65 cm²/m²) was 3-fold lower with the use of EOA₂ than with EOA₁ (9% vs. 33%; p < 0.001). Mean transprosthetic gradient correlated better (p = 0.03) with indexed EOA₂ (r = –0.70, p < 0.0001) than with indexed EOA₁ (r = –0.58, p < 0.0001). Intraobserver and interobserver variability were lower for EOA₂ compared to EOA₁ (intra: 5% vs. 7%, p = 0.06; inter: 6% vs. 14%; p < 0.001). Aortic annulus size was the sole independent determinant (p = 0.01) of prosthetic valve EOA₂. The average EOA varied from 1.37 ± 0.23 cm² for aortic annulus size <19 mm up to 1.90 ± 0.17 cm² for size >23 mm.

When estimating the EOA of Edwards-SAPIEN valves by Doppler-echocardiography, it is recommended to use the LVOT diameter and velocity measured immediately proximal to the stent. The main determinant of the EOA of transcatheter valves is the patient's annulus size and these valves provide excellent hemodynamics even in patients with a small aortic annulus.

Cardiac resynchronization therapy is effective in heart failure patients with LV dysfunction and wide QRS complex. However, many patients still fail to respond. We hypothesized that presence of extensive LV dilation might prevent response to CRT, despite LV mechanical dyssynchrony.

We studied 78 heart failure patients (68 ± 9 years of age, 77% men) with both electrical (QRS width >120 ms) and mechanical intraventricular dyssynchrony (by tissue Doppler imaging and/or left lateral wall post-systolic contraction). Echocardiographic evaluation was performed at baseline and 6 to 8 months after CRT. As an indication of LV remodeling, end-diastolic volume index and end-systolic volume index (ESVI) and sphericity index were measured. Long-term (40 ± 23 months) clinical follow-up (events: cardiac death and hospital admission for heart failure) was also obtained.

At follow-up after CRT, in the overall population, ejection fraction increased from 26 ± 6% to 35 ± 11% (p < 0.0001), whereas end-diastolic volume index (from 144 ± 43 ml/m² to 119 ± 55 ml/m²), ESVI (from 108 ± 37 ml/m² to 82 ± 49 ml/m², p < 0.0001 for both), and sphericity index (from 0.60 ± 0.22 to 0.53 ± 0.15, p = 0.0036) all significantly decreased. By multiple linear regression analysis, after controlling for confounding factors, change in LV ejection fraction at follow-up resulted independently and negatively associated with baseline ESVI (p = 0.001), with much lower improvement after implant in the highest tertile of baseline ESVI. During follow-up, 31 patients (39.7%) had a cardiac event. By Cox regression model, baseline ESVI was the most powerful predictor of events, with event-rate/year increasing with increasing tertiles of ESVI (6.3%, 10.1%, and 23.8%, respectively, p < 0.05).

In this nonrandomized, open-label clinical study, despite intraventricular electrical and mechanical dyssynchrony, extensive LV remodeling at baseline negatively impacted CRT results in terms of LV function improvement and incidence of cardiac events at follow-up.

Left atrial maximal volume (LAmax) is known to predict mortality in patients with acute myocardial infarction. In a previous pilot study, however, we found that LA function in terms of fractional change and left atrial ejection fraction (LAEF) assessed by multidetector computed tomography (MDCT) is more closely related to clinical heart failure than LAmax.

We prospectively included 384 patients presenting with non–ST-segment elevation myocardial infarction (NSTEMI) who underwent retrospectively gated, 64-slice MDCT coronary angiography and subsequent measurements of LA size and function. All patients were treated according to the current guidelines based on invasive coronary angiography. Patients were followed for a minimum of 2 years. The study endpoint was all-cause mortality.

The median follow-up time was 36 months (range 10 to 1,551 days). During follow-up, 35 (9%) patients died. Overall, 1- and 2-year survival in the study cohort was 97% and 94%. LA size and mechanical function was obtained in all patients: mean LAmax was 55 ± 11 ml/m², LA minimal volume 31 ± 11 ml/m², fractional change 45 ± 9%, and LAEF 32 ± 9%. Using a Cox proportional hazards model with adjustments for age, number of diseased coronary vessels, left ventricular ejection fraction (LVEF), and Killip class, both fractional change (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.45 to 0.94) and LAEF (HR: 0.63; 95% CI: 0.44 to 0.91) remained independent predictors of mortality. In contrast to this, LAmax was not significantly associated with an increased risk of mortality in this population.

In a low-risk group of patients with NSTEMI, reduced LA function is an independent predictor of mortality and provides prognostic value incremental to that of LAmax.

ROA is an accepted parameter of MR severity. However, there are little data on the shape of the ROA in various forms of MR.

Direct assessment of ROA was performed with a 1.5-T CMR scanner using a breath-hold fast imaging with steady-state free precession. The regurgitant orifice shape and the anatomy of the mitral valve apparatus including mitral annulus, mitral leaflet angles, and mitral valve tenting area were assessed.

We studied 74 patients. MR severity was mild in 39%, moderate in 27%, and moderate-to-severe or severe in 34%. Mitral valve pathology was degenerative in 26%, prolapse in 22%, flail in 33%, and functional in 19%. For all patients, ROA correlated significantly with regurgitant fraction (r = 0.80, p < 0.001). The ROA shape index as expressed by the ratio of the larger length to the smaller length was a median of 2.04 (interquartile range [IQR]: 1.49 to 3.08) over all patients. CMR revealed significant asymmetry of the ROA geometry in functional MR 3.91 (IQR: 2.79 to 4.84) compared with prolapse 2.14 (IQR: 1.80 to 3.04), flail 2.20 (IQR: 1.69 to 2.91), and degenerative MR 1.24 (IQR: 1.09 to 1.57), all p < 0.01. The assessment of mitral valve geometry demonstrated that patients with functional MR had significantly increased leaflet angles, mitral valve tenting area, and mitral annulus area (all p < 0.05). Of note, the orifice shape index correlated with increasing leaflet angles in patients with functional MR (r = 0.68, p = 0.005).

Direct assessment of ROA by CMR revealed significant asymmetry of ROA in various forms of MR, particularly in patients with functional MR. The slitlike appearance in functional MR correlates with a distended mitral apparatus.

Inflammation is an essential component of vulnerable or high-risk atheromas. Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, possesses potent anti-inflammatory properties. We aimed to quantify noninvasively the anti-inflammatory effects of pioglitazone on atheroma using ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI).

Atherosclerotic plaques were induced in the aorta of 15 New Zealand white rabbits by a combination of a hyperlipidemic diet and 2 balloon endothelial denudations. Nine rabbits continued the same diet, whereas 6 rabbits received pioglitazone (10 mg/kg orally) in addition to the diet. Twelve animals underwent ¹⁸F-FDG-PET/CT, and 15 animals underwent DCE-MRI at baseline, 1 month, and 3 months after treatment initiation. Concomitantly, serum metabolic parameters were monitored. After imaging was completed, aortic histologic analysis and correlation analysis were performed.

The ¹⁸F-FDG-PET/CT imaging detected an increase in average standardized uptake value in the control group (p < 0.01), indicating progressive inflammation, whereas stable standardized uptake values were observed in the treatment group, indicating no progression. The DCE-MRI analysis detected a significant decrease in the area under the curve for the pioglitazone group (p < 0.01). Immunohistologic examination of the aortas demonstrated a significant decrease in macrophage and oxidized phospholipid immunoreactivity in the pioglitazone group (p = 0.04 and p = 0.01, respectively) with respect to control animals, underlining the imaging results. Serum metabolic parameters showed no difference between groups. Strong positive correlations between standardized uptake value and macrophage density and between area under the curve and neovessels were detected (r ² = 0.86 and p < 0.0001, and r ² = 0.66 and p = 0.004, respectively).

Both ¹⁸F-FDG-PET/CT and DCE-MRI demonstrate noninvasively the anti-inflammatory effects of pioglitazone on atheroma. Both imaging methods seem suited to monitor inflammation in atherosclerosis.

Atherosclerosis is intrinsically an inflammatory disease. Although hyperglycemia is associated with an increased risk of atherosclerotic cardiovascular disease, there are no clinical data to show the preference of any specific oral hypoglycemic agents to prevent atherosclerotic plaque inflammation.

A total of 56 impaired glucose tolerant or diabetic patients with carotid atherosclerosis underwent a complete history, determinations of blood chemistries, anthropometric variables, and FDG-PET. They were randomly assigned to receive either pioglitazone (15 to 30 mg) or glimepiride (0.5 to 4.0 mg) for 4 months with titration to optimal dosage. Effects of the drugs on atherosclerotic plaque inflammation were evaluated by FDG-PET at study completion. Plaque inflammation was measured by blood-normalized standardized uptake value, known as a target-to-background ratio.

The study was completed in 31 pioglitazone-treated patients and 21 glimepiride-treated patients. Although both treatments reduced fasting plasma glucose and hemoglobin A1c values comparably, pioglitazone, but not glimepiride, decreased atherosclerotic plaque inflammation. Compared with glimepiride, pioglitazone significantly increased high-density lipoprotein cholesterol level. High-sensitivity C-reactive protein was decreased by pioglitazone, whereas it was increased by glimepiride. Multiple stepwise regression analysis revealed that the increase in high-density lipoprotein cholesterol level was independently associated with the attenuation of plaque inflammation.

Our present study suggests that pioglitazone could attenuate atherosclerotic plaque inflammation in patients with impaired glucose tolerance or in diabetic patients independent of glucose lowering effect. Pioglitazone may be a promising strategy for the treatment of atherosclerotic plaque inflammation in impaired glucose tolerance or diabetic patients. (Detection of Plaque Inflammation and Visualization of Anti-Inflammatory Effects of Pioglitazone on Plaque Inflammation in Subjects With Impaired Glucose Tolerance and Type 2 Diabetes Mellitus by FDG-PET/CT; NCT00722631)