A left ventricular phantom for 3D echocardiographic twist measurements

Under embargo until: 2020-09-18Traditional two-dimensional (2D) ultrasound speckle tracking echocardiography (STE) studies have shown a wide range of twist values, also for normal hearts, which is due to the limitations of short-axis 2D ultrasound. The same limitations do not apply to three-dimensional (3D) ultrasound, and several studies have shown 3D ultrasound to be superior to 2D ultrasound, which is unreliable for measuring twist. The aim of this study was to develop a left ventricular twisting phantom and to evaluate the accuracy of 3D STE twist measurements using different acquisition methods and volume rates (VR). This phantom was not intended to simulate a heart, but to function as a medium for ultrasound deformation measurement. The phantom was made of polyvinyl alcohol (PVA) and casted using 3D printed molds. Twist was obtained by making the phantom consist of two PVA layers with different elastic properties in a spiral pattern. This gave increased apical rotation with increased stroke volume in a mock circulation. To test the accuracy of 3D STE twist, both single-beat, as well as two, four and six multi-beat acquisitions, were recorded and compared against twist from implanted sonomicrometry crystals. A custom-made software was developed to calculate twist from sonomicrometry. The phantom gave sonomicrometer twist values from 2.0° to 13.8° depending on the stroke volume. STE software tracked the phantom wall well at several combinations of temporal and spatial resolution. Agreement between the two twist methods was best for multi-beat acquisitions in the range of 14.4–30.4 volumes per second (VPS), while poorer for single-beat and higher multi-beat VRs. Smallest offset was obtained at six-beat multi-beat at 17.1 VPS and 30.4 VPS. The phantom proved to be a useful tool for simulating cardiac twist and gave different twist at different stroke volumes. Best agreement with the sonomicrometer reference method was obtained at good spatial resolution (high beam density) and a relatively low VR. 3D STE twist values showed better agreement with sonomicrometry for most multi-beat recordings compared with single-beat recordings.publishedVersio

Speckle tracking derived strain in neonates: planes, layers and drift

The aims of this study was to assess the effect of using a four chamber versus a three plane model on speckle tracking derived global longitudinal strain, the effects of drift compensation, the effect of assessing strain in different layers and finally the interplay between these aspects for the assessment of strain in neonates. Speckle tracking derived longitudinal strain was obtained from 22 healthy neonates. ANOVA, Bland–Altman analyses, coefficients of variation and assessment of intraclass correlation coefficients were conducted to assess the effect of the abovementioned aspects as well as assess both inter-observer and intra-observer variability. Neither the use of the three plane model versus the four chamber model nor the use of drift compensation had a substantial effect on global longitudinal strain (less than 1%, depending on which layer was being assessed). A gradient was seen with increasing strain from the epicardial to endocardial layers, similar to what is seen in older subjects. Finally, drift compensation introduced more discrepancy in segmental strain values compared to global longitudinal strain. Global longitudinal strain in healthy neonates remains reasonably consistent regardless of whether the three plane or four chamber model is used and whether drift compensation is applied. Its value increases when one moves from the endocardial to the epicardial layer. Finally, drift compensation introduces more discrepancy for regional measures of longitudinal strain compared to global longitudinal strain.publishedVersio

Effect of Temporal and Spatial Smoothing on Speckle–Tracking‑Derived Strain in Neonates

Clinical application of strain in neonates requires an understanding of which image acquisition and processing parameters affect strain values. Previous studies have examined frame rate, transmitting frequency, and vendor heterogeneity. However, there is a lack of human studies on how user-regulated spatial and temporal smoothing affect strain values in 36 neonates. This study examined nine different combinations of spatial and temporal smoothing on peak systolic left ventricular longitudinal strain in 36 healthy neonates. Strain values were acquired from four-chamber echocardiographic images in the software-defined epicardial, midwall, and endocardial layers in the six standard segments and average four-chamber stain. Strain values were compared using repeated measure ANOVAs. Overall, spatial smoothing had a larger impact than temporal smoothing, and segmental strain values were more sensitive to smoothing settings than average four-chamber strain. Apicoseptal strain decreased by approximately 4% with increasing spatial smoothing, corresponding to a 13–19% proportional change (depending on wall layer). Therefore, we recommend clinicians be mindful of smoothing settings when assessing segmental strain values.publishedVersio

Myocardial energy metabolism and ultrastructure with polarizing and depolarizing cardioplegia in a porcine model

OBJECTIVES: This study investigated whether the novel St. Thomas’ Hospital polarizing cardioplegic solution (STH-POL) with esmolol/adenosine/magnesium offers improved myocardial protection by reducing demands for high-energy phosphates during cardiac arrest compared to the depolarizing St. Thomas’ Hospital cardioplegic solution No 2 (STH-2). METHODS: Twenty anaesthetised pigs on tepid cardiopulmonary bypass were randomized to cardiac arrest for 60 min with antegrade freshly mixed, repeated, cold, oxygenated STH-POL or STH-2 blood cardioplegia every 20 min. Haemodynamic variables were continuously recorded. Left ventricular biopsies, snap-frozen in liquid nitrogen or fixed in glutaraldehyde, were obtained at Baseline, 58 min after cross-clamp and 20 and 180 min after weaning from bypass. Adenine nucleotides were evaluated by high-performance liquid chromatography, myocardial ultrastructure with morphometry. RESULTS: With STH-POL myocardial creatine phosphate was increased compared to STH-2 at 58 min of cross-clamp [59.9 ± 6.4 (SEM) vs 44.5 ± 7.4 nmol/mg protein; P < 0.025], and at 20 min after reperfusion (61.0 ± 6.7 vs 49.0 ± 5.5 nmol/mg protein; P < 0.05), ATP levels were increased at 20 min of reperfusion with STH-POL (35.4 ± 1.1 vs 32.4 ± 1.2 nmol/mg protein; P < 0.05). Mitochondrial surface-to-volume ratio was decreased with polarizing compared to depolarizing cardioplegia 20 min after reperfusion (6.74 ± 0.14 vs 7.46 ± 0.13 µm2/µm3; P = 0.047). None of these differences were present at 180 min of reperfusion. From 150 min of reperfusion and onwards, cardiac index was increased with STH-POL; 4.8 ± 0.2 compared to 4.0 ± 0.2 l/min/m2 (P = 0.011) for STH-2 at 180 min. CONCLUSIONS: Polarizing STH-POL cardioplegia improved energy status compared to standard STH-2 depolarizing blood cardioplegia during cardioplegic arrest and early after reperfusion.publishedVersio

Left ventricular dysfunction after two hours of polarizing or depolarizing cardioplegic arrest in a porcine model

Introduction: This experimental study compares myocardial function after prolonged arrest by St. Thomas’ Hospital polarizing cardioplegic solution (esmolol, adenosine, Mg2+) with depolarizing (hyperkalaemic) St. Thomas’ Hospital No 2, both administered as cold oxygenated blood cardioplegia. Methods: Twenty anaesthetized pigs on tepid (34°C) cardiopulmonary bypass (CPB) were randomised to cardioplegic arrest for 120 min with antegrade, repeated, cold, oxygenated, polarizing (STH-POL) or depolarizing (STH-2) blood cardioplegia every 20 min. Cardiac function was evaluated at Baseline and 60, 150 and 240 min after weaning from CPB, using a pressure-conductance catheter and epicardial echocardiography. Regional tissue blood flow, cleaved caspase-3 activity and levels of malondialdehyde were evaluated in myocardial tissue samples. Results: Preload recruitable stroke work (PRSW) was increased after polarizing compared to depolarizing cardioplegia 150 min after declamping (73.0±3.2 vs. 64.3±2.4 mmHg, p=0.047). Myocardial tissue blood flow rate was high in both groups compared to the Baseline levels and decreased significantly in the STH-POL group only, from 60 min to 150 min after declamping (p<0.005). Blood flow was significantly reduced in the STH-POL compared to the STH-2 group 240 min after declamping (p<0.05). Left ventricular mechanical efficiency, the ratio between total pressure-volume area and blood flow rate, gradually decreased after STH-2 cardioplegia and was significantly reduced compared to STH-POL cardioplegia after 150 and 240 min (p<0.05 for both). Conclusion: Myocardial protection for two hours of polarizing cardioplegic arrest with STH-POL in oxygenated blood is non-inferior compared to STH-2 blood cardioplegia. STH-POL cardioplegia alleviates the mismatch between myocardial function and perfusion after weaning from CPB.publishedVersio

One-year impact of bariatric surgery on left ventricular mechanics: results from the prospective FatWest study

Aims Patients with severe obesity are predisposed to left ventricular (LV) hypertrophy, increased myocardial oxygen demand, and impaired myocardial mechanics. Bariatric surgery leads to rapid weight loss and improves cardiovascular risk profile. The present prospective study assesses whether LV wall mechanics improve 1 year after bariatric surgery. Methods and results Ninety-four severely obese patients [43 ± 10 years, 71% women, body mass index (BMI) 41.8 ± 4.9 kg/m2, 57% with hypertension] underwent echocardiography before, 6 months and 1 year after gastric bypass surgery in the FatWest (Bariatric Surgery on the West Coast of Norway) study. We assessed LV mechanics by midwall shortening (MWS) and global longitudinal strain (GLS), LV power/mass as 0.222 × cardiac output × mean blood pressure (BP)/LV mass, and myocardial oxygen demand as the LV mass-wall stress-heart rate product. Surgery induced a significant reduction in BMI, heart rate, and BP (P < 0.001). Prevalence of LV hypertrophy fell from 35% to 19% 1 year after surgery (P < 0.001). The absolute value of GLS improved by—4.6% (i.e. 29% increase in GLS) while LV ejection fraction, MWS, and LV power/mass remained unchanged. In multivariate regression analyses, 1 year improvement in GLS was predicted by lower preoperative GLS, larger mean BP, and BMI reduction (all P < 0.05). Low 1-year MWS was associated with female sex, preoperative hypertension, and higher 1-year LV relative wall thickness and myocardial oxygen demand (all P < 0.001). Conclusion In severely obese patients, LV longitudinal function is largely recovered one year after bariatric surgery due to reduced afterload. LV midwall mechanics does not improve, particularly in women and patients with persistent LV geometric abnormalities.publishedVersio

Human NCU-G1 can function as a transcription factor and as a nuclear receptor co-activator

<p>Abstract</p> <p>Background</p> <p>Novel, uncharacterised proteins represent a challenge in biochemistry and molecular biology. In this report we present an initial functional characterization of human kidney predominant protein, NCU-G1.</p> <p>Results</p> <p>NCU-G1 was found to be a highly conserved nuclear protein rich in proline with a molecular weight of approximately 44 kDa. It is localized on chromosome 1 and consists of 6 exons. Analysis of the amino acid sequence revealed no known transcription activation domains or DNA binding regions, however, four nuclear receptor boxes (LXXLL), and four SH3-interaction motives in addition to numerous potential phosphorylation sites were found. Two nuclear export signals were identified, but no nuclear localization signal. In man, NCU-G1 was found to be widely expressed at the mRNA level with especially high levels detected in prostate, liver and kidney. Electrophoretic mobility shift analysis showed specific binding of NCU-G1 to an oligonucleotide representing the footprint 1 element of the human cellular retinol-binding protein 1 gene promoter. NCU-G1 was found to activate transcription from this promoter and required presence of the footprint 1 element. In transiently transfected Drosophila Schneider S2 cells, we demonstrated that NCU-G1 functions as a co-activator for ligand-activated PPAR-alpha, resulting in an increased expression of a CAT reporter gene under control of the peroxisome proliferator-activated receptor-alpha responsive acyl-CoA oxidase promoter.</p> <p>Conclusion</p> <p>We propose that NCU-G1 is a dual-function protein capable of functioning as a transcription factor as well as a nuclear receptor co-activator.</p

Impact of aortic valve stenosis on myocardial deformation in different left ventricular levels: A three-dimensional speckle tracking echocardiography study

Background: Global systolic left ventricular (LV) myocardial function progressively declines as degenerative aortic valve stenosis (AS) progresses. Whether this results in uniformly distributed deformation changes from base to apex has not been investigated. Methods: Eighty-five AS patients underwent three-dimensional (3D) echocardiography in this cross-sectional study. Patients were grouped by peak jet velocity into mild (n = 32), moderate (n = 31), and severe (n = 22) AS. 3D speckle tracking derived strain, rotation, twist, and torsion were obtained to assess global LV function and myocardial function at the apical, mid, and basal levels. Results: Global longitudinal strain (GLS) was lower in patients with severe AS (-16.1 ± 2.4% in mild, -15.5 ± 2.5% in moderate, and -13.5 ± 3.0% in severe AS [all p < .01]). Peak basal and mid longitudinal strain (LS), basal rotation and twist from apical to basal level followed the same pattern, while peak apical LS was higher in moderate AS compared to severe AS (all p < .05). In multivariate analyses, lower GLS was particularly associated with male sex, higher body mass index and peak aortic jet velocity, lower basal LS with higher filling pressure (E/e’) and LV mass, lower mid LS with higher RWT and presence of AS symptoms, and lower apical LS with male sex and higher systolic blood pressure, respectively (all p < .05). Conclusion: Using 3D speckle tracking echocardiography reveals regional and global changes in LV mechanics in AS related to the severity of AS, LV remodeling and presence of cardiovascular risk factors.publishedVersio

The influence of region of interest width in fetal 2D-speckle tracking echocardiography late in pregnancy

Speckle tracking echocardiography is a promising method for assessment of myocardial function in fetal and neonatal hearts, but further studies are necessary to validate and optimize the settings for use in fetal cardiology. Previous studies have shown that the definition of the region of interest (ROI) affects strain values in adults. The aim of this study was to investigate how different widths of ROI influences measurements of four-chamber longitudinal systolic strain in fetuses late in pregnancy. Thirty-one singleton, healthy fetuses born to healthy mothers underwent an echocardiographic examination during gestational week 37. Speckle tracking was performed with two different settings for ROI width; the narrowest and second most narrow, provided both widths were assessed as suitable for the myocardial wall thickness of the fetus. We found an inverse correlation between the ROI width and the strain values. Four-chamber longitudinal strain changed from − 20.7 ± 3.6% to − 18.0 ± 4.4% (p < 0.001) with increasing ROI width. Further, strain decreased from the endocardium to the epicardium with multilayer measurements. Different widths of ROI influenced the strain measurements significantly in the fetal heart, comparable to what has been reported in adults. A standardization of the ROI setting could improve the interpretation, and reduce variability in fetal strain measurements.publishedVersio