The aim of this study was to evaluate which regional myocardial parameters derived from speckle tracking echocardiography could demonstrate myocardial ischemic memory in a brief ischemia-reperfusion dog model.
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.
The purpose of this study was to evaluate the ability of a novel cardiac magnetic resonance (CMR) real-time phase contrast (RT-PC) flow measurement technique to reveal the discordant respirophasic changes in mitral and tricuspid valve in flow indicative of the abnormal hemodynamics seen in constrictive pericarditis (CP).
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.
The purpose of this study was to determine whether right ventricular (RV) volumes are more accurately and reproducibly measured by cardiac magnetic resonance (CMR) in an axial orientation or in a short-axis orientation in patients with congenital heart disease (CHD).
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.
A prospective, multicenter 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging study was performed to estimate the correlations among arterial FDG uptake and atherosclerotic plaque biomarkers in patients with peripheral artery disease.
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.
This study aims to provide insight into cellular kinetics using molecular imaging after different transplantation methods of bone marrow–derived mononuclear cells (MNCs) in a mouse model of peripheral artery disease (PAD).
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.
The aim of this study was to image expression of receptor for advanced glycation end products (RAGE) in a mouse model of myocardial reperfusion injury.
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.
This study sought to examine the capability of optical frequency domain imaging (OFDI) to characterize various morphological and histological responses to stents implanted in human coronary arteries.
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.
To develop a new noninvasive approach to quantify left ventricular (LV) pressures using subharmonic emissions from microbubbles, an ultrasound scanner was used in pulse inversion grayscale mode; unprocessed radiofrequency data were obtained with pulsed wave Doppler from the aorta and/or LV during Sonazoid infusion. Subharmonic data (in dB) were extracted and processed. Calibration factor (mm Hg/dB) from the aortic pressure was used to estimate LV pressures. Errors ranged from 0.19 to 2.50 mm Hg when estimating pressures using the aortic calibration factor, and were higher (0.64 to 8.98 mm Hg) using a mean aortic calibration factor. Subharmonic emissions from ultrasound contrast agents have the potential to noninvasively monitor LV pressures.
]]>Cardiac resynchronization therapy (CRT) is a novel therapy for patients with refractory heart failure (HF). Large clinical trials evaluating CRT have demonstrated significant improvements in cardiac survival, decreases in recurrent HF hospitalization, and improvements in indexes of quality of life. Although numerous mechanisms are involved in CRT's therapeutic effects, correction of both interventricular and intraventricular mechanical dyssynchrony has been postulated as the key mechanism. To date, most large randomized controlled trials evaluating CRT have identified dyssynchronous patients on the basis of prolongation of the QRS complex from the baseline electrocardiogram. Concerns have been raised regarding the use of this measure for patient selection, stemming from a significant 30% to 40% nonresponse rate to CRT. Because of the cost and invasive nature of CRT, optimal patient selection for this therapy has become a priority for HF specialists and electrophysiologists. Cardiac imaging modalities have attempted to fulfill this need to improve patient selection by identifying mechanical dyssynchrony. Although early echocardiographic studies reported promising results, more recent larger scale studies have curtailed this enthusiasm, with a lack of established selection criteria for CRT in the current practice guidelines. This review summarizes the evidence to date and the potential role of imaging modalities in the selection and care of patients with HF referred for CRT.
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