A Novel Interventional Approach to LV Pseudoaneurysm Compressing on LAD by Utilizing LAA Closure Device.

We describe the novel transcatheter approach, with off-label application of LAA closure device, coiling, and concurrent left anterior descending stenting in the setting of left ventricular (LV) pseudoaneurysm. This case underlines collaboration among interventional cardiology, cardiothoracic, and neurosurgery teams in a challenging, nonsurgical candidate with high risk of LV pseudoaneurysm rupture, and death. (Level of Difficulty: Advanced.).

Imaging and quantification of myocardial perfusion using real-time three-dimensional echocardiography.

OBJECTIVES: We tested the feasibility of real-time three-dimensional echocardiographic (RT3DE) perfusion imaging and developed and validated an algorithm for volumetric analysis of myocardial contrast inflow. The study included three protocols wherein perfusion was measured: 1) in an ex-vivo model of controlled global coronary flow, 2) in an in-vivo model during regional perfusion variations, and 3) in humans during pharmacologically induced hyperemia. BACKGROUND: The RT3DE technology offers an opportunity for myocardial perfusion imaging without multi-slice reconstruction and repeated contrast maneuvers. METHODS: Electrocardiographically triggered harmonic RT3DE datasets were acquired (Philips 7500) while infusion of Definity was initiated and reached a steady state. Protocol 1 was performed in nine isolated rabbit hearts and included three coronary flow levels. In protocol 2, changes in regional perfusion caused by partial left anterior descending artery occlusion were measured in five pigs. In protocol 3, adenosine-induced changes in perfusion were measured in eight normal volunteers. Myocardial video-intensity (MVI) was measured over time in three-dimensional (3D) slices to calculate peak contrast inflow rate (PCIR). In pigs, PCIR was measured on a regional basis and validated against microspheres. RESULTS: The RT3DE imaging allowed selection of slices for perfusion analysis in rabbit hearts, pigs, and humans. Administration of contrast resulted in clearly visible and quantifiable changes in MVI. In rabbits, The PCIR progressively decreased with coronary flow (p < 0.0001). In pigs, coronary occlusion caused a 59 +/- 26% decrease in PCIR exclusively in the left anterior descending artery territory (p < 0.05) in agreement with microspheres. In humans, adenosine increased PCIR to 198 +/- 57% of baseline (p < 0.05). CONCLUSIONS: Contrast-enhanced RT3DE imaging provides the basis for volumetric imaging and quantification of myocardial perfusion.

Color encoding of endocardial motion improves the interpretation of contrast-enhanced echocardiographic stress tests by less-experienced readers.

BACKGROUND: We hypothesized that color encoding of endocardial motion could aid less-experienced readers in detection of wall-motion abnormalities at rest and stress in patients with poor acoustic windows. METHODS: Color-encoded images (color kinesis) were obtained at rest and peak dobutamine stress in 4 standard views during intravenous infusion of contrast agent in 117 patients with poorly visualized endocardium. In 101 of 117 patients (86%), in whom contrast enhancement allowed endocardial tracking, images were reviewed by two expert readers without color overlays. Each reader graded regional wall motion as normal, abnormal, or uninterpretable, and their consensus grades served as a gold standard. The same images were then reviewed and graded with and without color overlays by 3 cardiology fellows. The accuracy of the interpretation was calculated against the gold standard separately for the 3 vascular territories (left anterior descending, left circumflex, and right coronary arteries) and averaged for the 3 fellows. RESULTS: With the addition of color encoding: (1) the number of uninterpretable segments decreased by 55% at rest and 61% at peak stress; and (2) all 3 fellows reached higher levels of accuracy in all 3 vascular territories both at rest (6%-82% average) and at stress (73%-80%). CONCLUSION: The addition of color encoding of wall motion to contrast-enhanced images obtained in patients with poor acoustic windows during stress tests improves the interpretation of regional left ventricular function by less-experienced readers.

Quantitative diagnosis of stress-induced myocardial ischemia using analysis of contrast echocardiographic parametric perfusion images.

AIMS: Parametric imaging of myocardial perfusion provides useful visual information for the diagnosis of coronary artery disease (CAD). We developed a technique for automated detection of perfusion defects based on quantitative analysis of parametric perfusion images and validated it against coronary angiography. METHODS AND RESULTS: Contrast-enhanced, apical 2-, 3- and 4-chamber images were obtained at rest and with dipyridamole in 34 patients with suspected CAD. Images were analyzed to generate parametric perfusion images of the standard contrast-replenishment model parameters A, beta and A.beta. Each parametric image was divided into six segments, and mean parameter value (MPV) was calculated for each segment. Segmental MPV ratio between stress and rest was defined as a flow reserve index (FRI). Receiver operating characteristics (ROC) analysis was used in a Study group (N=17) to optimize FRI threshold and the minimal number of abnormal segments per vascular territory (LAD and non-LAD), required for automated detection of stress-induced perfusion defects. The optimized detection algorithm was then tested prospectively in the remaining 17 patients (Test group). LAD and non-LAD stenosis >70% was found in 19 and 17 patients, respectively. In the Study group, FRI threshold was: LAD=0.95 and non-LAD=0.68, minimal number of abnormal segments was four and two, correspondingly. Sensitivity, specificity and accuracy in the Test group were: 75%, 67% and 71% in the LAD, and 75%, 75% and 75% in the non-LAD territories. CONCLUSION: Automated quantitative analysis of contrast echocardiographic parametric perfusion images is feasible and may aid in the objective detection of CAD.

Rapid online quantification of left ventricular volume from real-time three-dimensional echocardiographic data.

AIMS: Determination of left ventricular (LV) volumes and ejection fraction (EF) from two-dimensional echocardiographic (2DE) images is subjective, time-consuming, and relatively inaccurate because of foreshortened views and the use of geometric assumptions. Our aims were (1) to validate a new method for rapid, online measurement of LV volumes from real-time three-dimensional echocardiographic (RT3DE) data using cardiac magnetic resonance (CMR) as the reference and (2) to compare its accuracy and reproducibility with standard 2DE measurements. METHODS AND RESULTS: CMR, 2DE, and RT3DE datasets were obtained in 50 patients. End-systolic and end-diastolic volumes (ESV and EDV) were calculated from the 2DE images using biplane method of disks. ES and ED RT3DE datasets were analysed using prototype software designed to automatically detect the endocardial surface using a deformable shell model and calculate ESV and EDV from voxel counts. 2DE and RT3DE-derived volumes were compared with CMR (linear regression, Bland-Altman analysis). In most patients, analysis of RT3DE data required <2 min per patient. RT3DE measurements correlated highly with CMR (r: 0.96, 0.97, and 0.93 for EDV, ESV, and EF, respectively) with small biases (-14 mL, -6.5 mL, -1%) and narrow limits of agreement (SD: 17 mL, 16 mL, 6.4%). 2DE measurements correlated less well with CMR (r: 0.89, 0.92, 0.86) with greater biases (-23 mL, -15 mL, 1%) and wider limits of agreement (SD: 29 mL, 24 mL, 9.5%). RT3DE resulted in lower intra-observer (EDV: 7.9 vs. 23%; ESV: 7.6 vs. 26%) and inter-observer variability (EDV: 11 vs. 26%; ESV: 13 vs. 31%). CONCLUSION: Semi-automated detection of the LV endocardial surface from RT3DE data is suitable for clinical use because it allows rapid, accurate, and reproducible measurements of LV volumes, superior to conventional 2DE methods.

Sex differences in in vitro pro-inflammatory cytokine production from peripheral blood of multiple sclerosis patients.

We compared the patterns of the pro-inflammatory cytokines, interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha), and the anti-inflammatory cytokines, interleukin-10 (IL-10) and tumor growth factor-beta (TGF-beta) from peripheral blood of male and female patients with relapsing-remitting (RR) and secondary progressive (SP) forms of multiple sclerosis (MS). The relationships between pro-inflammatory cytokines and disability (expanded disability status scale, EDSS) were also examined. Peripheral blood anti-coagulated with heparin was obtained from 47 MS patients (30 women and 17 men) and activated with phorbol-12-myristate 13 acetate (PMA) and ionomycin in the presence of brefeldin A and stained for flow cytometry with fluorescently labeled antibodies against intracellular IFN-gamma, TNF-alpha, IL-2, IL-4 and IL-10. The T cells were delineated with peridinin chlorophyll protein (Per-CP) labeled anti-CD3 antibody. The stained samples were analyzed on a flow cytometer to assess the intracellular pro-inflammatory cytokine patterns. The levels of interleukin-10 (IL-10) and tumor growth factor-beta (TGF-beta) were measured in plasma using enzyme-linked immunoassay. The percentage of TNF-alpha-producing CD3 positive cells was significantly higher (P=0.045) in men (mean+/-S.D., 39+/-13%) than in women (mean+/-S.D., 29+/-13%) RR-MS patients. The percentage of CD3 positive cells producing IFN-gamma was significantly correlated with EDSS in females but not in males (Spearman rank correlation r(S)=0.49, P=0.018). The secretion of the pro-inflammatory cytokines, IFN-gamma and TNF-alpha, is influenced by gender in MS patients and may contribute to the sexual dimorphism of MS.

Interferon beta-1a for early multiple sclerosis: CHAMPS trial subgroup analyses.

The objective of this work was to assess the effect of interferon beta-1a (Avonex) on the rate of development of clinically definite multiple sclerosis and brain magnetic resonance imaging changes in subgroups based on type of presenting event, baseline brain magnetic resonance imaging parameters, and demographic factors in the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) trial. After the onset of a first demyelinating event, 383 patients with brain magnetic resonance imaging evidence of subclinical demyelination were treated with corticosteroids and randomly assigned to receive weekly intramuscular injections of 30 microg interferon beta-1a or placebo. The treatment effect within subgroups was assessed in proportional hazards models both for the development of clinically definite multiple sclerosis and for a combined outcome of development of clinically definite multiple sclerosis or >1 new or enlarging T2 lesions on brain magnetic resonance imaging. A beneficial effect of treatment was noted in all subgroups evaluated. Adjusted rate ratios for the development of clinically definite multiple sclerosis in the optic neuritis, brainstem-cerebellar, and spinal cord syndrome subgroups were 0.58 (p = 0.05), 0.40 (p = 0.03), and 0.30 (p = 0.01) and for the development of the combined clinically definite multiple sclerosis/magnetic resonance imaging outcome were 0.50 (p < 0.001), 0.41 (p = 0.001), and 0.40 (p = 0.004), respectively. A treatment benefit on both outcome measures also was seen in subgroups based on baseline brain magnetic resonance imaging parameters, gender, and age. Interferon beta-1a is beneficial when initiated at the first clinical demyelinating event in patients with brain magnetic resonance imaging evidence of subclinical demyelination. The beneficial effect is present for optic neuritis, brainstem-cerebellar syndromes, and spinal cord syndromes.