Endocardial Volume Research Articles

Catheter based left atrial appendage closure in-hospital outcomes in Germany from 2016 to 2020

BackgroundNew and refined catheter based left atrial appendage (LAA) closure devices have been introduced in the past decade. The procedure can be performed using either an endocardial occlusion device or an epicardial loop stitch. We aimed to analyzed recent procedural safety.MethodsCatheter based LAA closures were identified in a complete nationwide German dataset via ICD and OPS codes from 2016 to 2020.ResultsFrom 2016 to 2020, 28,039 endocardial and 213 epicardial occlusions were performed. Numbers of endocardial procedures increased from 5259 in 2016 to 5917 in 2020 (p = 0.020) in 387 centers with shifting of patients’ characteristics towards older age (β = 0.29, p < 0.001), more heart failure (β = 1.01, p < 0.001) and renal disease (β = 0.67, p = 0.001) and without a significant trend for in-hospital safety except more bleeding (β = 0.12, p = 0.05). In-hospital major adverse cardiac and cerebrovascular events (MACCE) or pericardial puncture were independent on center procedure numbers.The loop stitch procedure was performed in 15 centers. Patients were younger (76.17 ± 8.16 vs. 73.16 ± 8.99, p < 0.001) and had a lower comorbidity index (2.29 ± 1.93 vs. 1.92 ± 1.64, p = 0.005). Adjusted risk difference for pericardial effusion (8.04%; 95% CI 3.01–13.08%; p = 0.002) and pericardial puncture (6.60%; 95% CI 3.85–9.35%; p < 0.001) was higher for the loop stitch procedure, while risk of bleeding (− 1.85%; 95% CI − 3.01 to − 0.69%; p = 0.002), intracerebral bleeding (− 0.37%; 95% CI − 0.59 to − 0.15%; p = 0.001) and shock (− 1.41%; 95% CI − 2.44 to − 0.39%; p = 0.007) was lower. No significant difference was observed for in-hospital MACCE.ConclusionsEndocardial occlusion was the major catheter based LAA closure procedure in Germany without improvements in in-hospital safety from 2016 to 2020. In-hospital MACCE was independent on endocardial LAAC center volumes. Conclusions on the comparison between the two procedure types must be made cautious as the LAA loop stitch occlusion was utilized limited in a minor number of centers.Graphical abstractCatheter based left atrial appendage closure in-hospital outcomes in Germany from 2016 to 2020

Mechano-energetic efficiency in patients with hypertrophic cardiomyopathy with and without sarcomeric mutations

Abstract Background Hypertrophic Cardiomyopathy (HCM) is mainly caused by sarcomeric mutations. In about 40% of cases the causal mutation is unknown. Myocardial mechano-energetic efficiency per unit of left ventricular (LV) mass (MEEi) is an echocardiographic parameter of LV pump performance. Sarcomeric mutations may affect energy efficiency. Purpose We investigated the effects of the presence of sarcomeric mutations on MEEi in patients with HCM. Methods We included 49 genetically screened HCM patients (50±10 years, 27% women) with LV ejection fraction &amp;gt;50%, LV maximal wall thickness &amp;gt;14 mm and no moderate to severe mitral regurgitation. MEEi was calculated as the ratio between stroke volume and heart rate, normalized by LV mass. Echo-LV mass was calculated as LV epicardial minus LV endocardial volumes in 4 and 2 chamber views multiplied by 1.05, a method validated with nuclear magnetic resonance. Results 27 HCM patients carried a sarcomeric mutation (HCM-Sarc; 55%). As shown in the table, patients with and without sarcomeric mutations (HCM-Sarc vs HCM-NoSarc) had similar LV ejection fraction, heart rate, LV mass and LV outflow tract gradient. HCM-Sarc showed early age at diagnosis, higher frequency of HCM family history and significantly reduced MEEi as compared with HCM-NoSarc. Presence of sarcomeric mutation could be predicted by younger age, lower MEEi and by family history of HCM (overall p&amp;lt;0.05). Conclusions In a population of HCM patients, the presence of a sarcomeric mutation is the only determinant of reduced the LV pump performance as estimated by MEEi. MEEi may be used as an imaging biomarker in sarcomeric mutation carriers. Funding Acknowledgement Type of funding sources: None.

Extracellular mechanical forces drive endocardial cell volume decrease during zebrafish cardiac valve morphogenesis

Organ morphogenesis involves dynamic changes of tissue properties while cells adapt to their mechanical environment through mechanosensitive pathways. How mechanical cues influence cell behaviors during morphogenesis remains unclear. Here, we studied the formation of the zebrafish atrioventricular canal (AVC) where cardiac valves develop. We show that the AVC forms within a zone of tissue convergence associated with the increased activation of the actomyosin meshwork and cell-orientation changes. We demonstrate that tissue convergence occurs with a reduction of cell volume triggered by mechanical forces and the mechanosensitive channel TRPP2/TRPV4. Finally, we show that the extracellular matrix component hyaluronic acid controls cell volume changes. Together, our data suggest that multiple force-sensitive signaling pathways converge to modulate cell volume. We conclude that cell volume reduction is a key cellular feature activated by mechanotransduction during cardiovascular morphogenesis. This work further identifies how mechanical forces and extracellular matrix influence tissue remodeling in developing organs.

Prenatal alcohol exposure causes structural and functional cardiac defects, which can be prevented with folate supplementation

Increased regurgitant blood flow has been linked to endocardial cushion defects and resultant congenital heart diseases (CHDs). Prenatal alcohol exposure (PAE) has been shown to alter early blood flow resulting in abnormal endocardial cushions and CHDs. Compounds, including folic acid (FA), mitigate PAE effects and prevent CHDs, but few studies have assessed their effects on blood flow. We modeled binge drinking in avian embryos at gastrulation. Embryos were exposed to ethanol alone, FA (3.2 μg/egg) alone, and the two simultaneously. We quantified in cardiac looping stages (equivalent to 4 weeks of human gestation) regurgitant blood flow with Doppler optical coherence tomography (OCT) and endocardial cushion volumes using OCT imaging. Incidences of abnormal body curvature and heart rates were also measured. Embryos exposed to ethanol showed significantly increased regurgitant blood flow compared to controls, while embryos given FA with ethanol had significantly reduced regurgitant blood flow but did not return to control levels. Ethanol exposure led to significantly smaller, abnormal endocardial cushions and the addition of FA improved their size, but they remained smaller than controls. Abnormal body curvatures after PAE were reduced in incidence but not fully prevented by FA. FA supplementation partially alleviated PAE induced abnormal cardiovascular function and morphology. Normal blood flow and endocardial cushions are both required to produce a healthy four-chambered heart. These findings support that FA supplementation should begin early in pregnancy to prevent heart as well as neural tube defects. Investigations into the efficacy of combinations of compounds to prevent PAE-induced defects is warranted.

Folic acid prevents functional and structural heart defects induced by prenatal ethanol exposure

Increased regurgitant blood flow has been linked to endocardial cushion defects and resultant congenital heart diseases (CHDs). Prenatal alcohol exposure (PAE) has been shown to alter early blood flow resulting in abnormal endocardial cushions and CHDs. Compounds, including folic acid (FA), mitigate PAE effects and prevent CHDs, but few studies have assessed their effects on blood flow. We modeled binge drinking in quail embryos at gastrulation. Embryos were exposed to ethanol alone, FA (3.2 μg/egg) alone, and the two simultaneously. We quantified in cardiac looping stages (equivalent to 4 weeks of human gestation) regurgitant blood flow with Doppler optical coherence tomography (OCT) and endocardial cushion volumes using OCT imaging. Incidences of abnormal body curvature and heart rates were also measured. Embryos exposed to ethanol showed significantly increased regurgitant blood flow compared to controls, while embryos given FA with ethanol had significantly reduced regurgitant blood flow but did not return to control levels. Ethanol exposure led to significantly smaller, abnormal endocardial cushions and the addition of FA improved their size, but they remained smaller than controls. Abnormal body curvatures after PAE were reduced in incidence but not fully prevented by FA. FA supplementation partially alleviated PAE induced abnormal cardiovascular function and morphology. Normal blood flow and endocardial cushions are both required to produce a healthy four-chambered heart. These findings support that FA supplementation should begin early in pregnancy to prevent heart as well as neural tube defects. Investigations into the efficacy of combinations of compounds to prevent PAE-induced defects is warranted.

Short term improvement of global left ventricular longitudinal strain by speckle tracking echocardiography after transcatheter aortic valve implantation in patients with severe aortic stenosis

Abstract Background Global longitudinal strain (GLS) has incremental value in assessing left ventricular (LV) function in patients with severe aortic stenosis (AS). Long-standing AS causes LV hypertrophy which predisposes to increased cardiac morbidity and mortality. The recent development of transcatheter aortic valve implantation (TAVI) device for treatment of severe symptomatic AS, offers an option for high risk patients. Objectives Our aim was to investigate the correlation between the time elapsed after performing a TAVI procedure and the LV GLS by Speckle tracking echocardiography (STE) and its correlation with progressive degree of regression in LV mass (LVM) by transthoracic echocardiography (TTE). Methods TTE was performed on 54 patients with severe AS who underwent TAVI procedure. TTE was performed at baseline (before the procedure) and then at 3 months and 6 months post TAVI. GLS was calculated for every patient from STE of the three apical views (apical 4, apical 2 and apical long axis views). The LV muscle volume was calculated by subtraction of LV pericardial volume from LV endocardial volume using biplane Simpson's formula. LVM was then calculated by multiplying LV mass volume by muscle density (1.05). Results The study included 54 patients with severe AS (average PG =79.5 mmHg and average mean gradient 40.5 mmHg), with a mean age of 79±10 years and 46 were male. All patients underwent TAVI and average mean gradient post TAVI was 7 mmHg. The mean ± SD of GLS were −15.3±2.0, −15.9±1.7 and −17.2±1.8 for STE obtained at baseline, 3- and 6-months post TAVI, respectively. There was significant difference in LV GLS when comparing baseline measurements with measurements obtained at both 3 months {mean difference ± SD (MD±SD) was 0.57±0.7 (p&amp;lt;0.001)} and at 6 months post TAVI was 1.8±0.8 (p&amp;lt;0.0001). There was significant difference when comparing LV GLS measurements at 3- and 6- months post TAVI MD±SD was 1.2±0.65 (p&amp;lt;0.001). The mean±SD of LVM was 118.5±31, 110.5±29.2 and 101.1±26.4 at baseline, 3- and 6-months post TAVI, respectively. There was significant difference between baseline and 3 months measurement of LVM, MD±SD is 7.6±6.0 (p&amp;lt;0.001). There was significant difference between baseline and 6 months measurement of LVM, MD±SD was 17.0±10.5 (p&amp;lt;0.0001). In addition, there was significant difference of LVM calculation at 3 and 6 months with MD±SD of 9.4±7.9 and (P&amp;lt;0.001). Conclusions In patient with severe AS that underwent TAVI, there is short term continues significant improvement of LV GLS by STE. This could be attributed to relieving the pressure overload and regression of LVM over time. Decreasing LV hypertrophy and increasing LV GLS on the short term indicate high efficacy of TAVI procedure and subsequently improving patient prognosis and quality of life. Funding Acknowledgement Type of funding source: None

Therapeutic Ultrasound Improves Myocardial Blood Flow and Reduces Infarct Size in a Canine Model of Coronary Microthromboembolism

Therapeutic ultrasound (TUS) has been used to lyse infarct-related coronary artery thrombus. There has been no study examining the effect of TUS specifically on myocardial microthromboemboli seen in acute myocardial infarction and acute coronary syndromes. The aim of this study was to test the hypothesis that TUS improves myocardial blood flow (MBF) and reduces infarct size (IS) in this situation by dissolving myocardial microthrombi. An open-chest canine model of myocardial microthromboembolism was created by disrupting a thrombus in the left anterior descending coronary artery, and 1.05- and 0.25-MHz TUS (n=7 each) delivered epicardially for 30min was compared with control (n=6). MBF and IS (as a percentage of left anterior descending coronary artery perfusion bed size) were measured 60min after treatment. In addition, immunohistochemistry was performed to assess microthrombi, and histopathology was performed to define inflammation. Transmural, epicardial, and endocardial myocardial blood volume and MBF (measured using myocardial contrast echocardiography) and percentage wall thickening were significantly higher 60min after receiving TUS compared with control. The ratio of IS to left anterior descending coronary artery perfusion bed size was significantly smaller (P=.03) in the 1.05-MHz TUS group (0.14±0.04) compared with the control (0.31±0.06, P=.04) and 0.25-MHz (0.36±0.08) groups. MBF versus percentage wall thickening exhibited a linear relation (r=0.65) in the control and 1.05-MHz TUS groups but not in the 0.25-MHz TUS group (r=0.29). The presence of myocardial microemboli in vessels >10μm in diameter was significantly reduced in the 1.05-MHz TUS group compared with the other two groups. The distribution and intensity of inflammation was higher in the 0.25-MHz TUS group compared with the other groups. TUS at 1.05MHz is effective in restoring myocardial blood volume and MBF, thus reducing IS by clearing the microcirculation of microthrombi. IS reduction is not seen at 0.25MHz, despite improvement in MBF, which may be related to the increased inflammation noted at this frequency. Because both acute myocardial infarction and acute coronary syndromes are associated with microthromboembolism, these results suggest that TUS could have a potential adjunctive role in the treatment of both conditions.

Left Ventricular Mass in Hypertrophic Cardiomyopathy Assessed by 2D-Echocardiography: Validation with Magnetic Resonance Imaging

We aim to validate echocardiographic left ventricular (LV) mass (echoLVM) in sixty-one patients with hypertrophic cardiomyopathy (HCM), using cardiac magnetic resonance measures (cmrLVM) as gold standard. cmrLVM was calculated using LV short-axis images, from base to apex, whereas echoLVM by LV epicardial minus LV endocardial volumes in 4 and 2 chamber views, using Simpson disk summation; trabeculae and papillary muscle were excluded in both cmrLVM and echoLVM. cmrLVM and echoLVM were not different by paired t test (145 ± 66 vs 147 ± 61; p = 0.240), and their correlation was good (r = 0.977; p < 0.0001). Intraclass correlation demonstrated reliability of echoLVM with cmrLVM (ρ = 0.987; Cls = 0.978-0.992; p < 0.0001). LV end-diastolic volume was higher by CMR than that by echo (137 ± 33 vs 85 ± 28mL, p < 0.0001), resulting in a lower mass/volume ratio (1.1 ± 0.4 vs 1.8 ± 0.8, p < 0.0001). EchoLVM may be determined in patients with HCM. However, mass/volume ratio is higher by echocardiography than that by CMR.

Validation of three-dimensional echocardiographic principal strain analysis for assessing left ventricular contractility: An animal study.

The three-dimensional (3D) principal strain represents the major direction and magnitude of the deformation by its definition and can be measured using 3D echocardiography. We aimed to validate 3D echocardiographic left ventricular (LV) global principal strains as an assessment of LV contractility by comparison with gold standard invasive measurements. In 14 beagles, the LV pressure-volume loop was recorded to invasively measure the end-systolic pressure-volume relationship (ESPVR) and dP/dt as reference indicators representing LV contractility. The echocardiographic image was obtained simultaneously, and endocardial motions and volume changes were extracted in the form of speckle-tracking point grids to calculate strains. High or low inotropic states were induced pharmacologically by using an intravenous infusion of dobutamine and esmolol, respectively. The direction of 3D endocardial global principal strain (GP1S) appeared to be circumferential. The dP/dt showed the highest Pearson's correlation coefficients with GP1S (r = -0.845, P < 0.001), whereas ESPVR showed the best correlation with global secondary strain (GP2S; r = -0.819, P < 0.001). In comparison with GP1S and GP2S, global circumferential (GCS) and longitudinal strains (GLS) tended to correlate less with invasive measurements, respectively. LV ejection fraction showed excellent correlations with GP1S or GCS, but the correlation with GLS was relatively weak. The correlations between invasive measurements and GP2S or GLS were strengthened when strains were corrected by the LV residual volume ratio, whereas those of GP1S or GCS were weakened after correction. The principal direction of the LV endocardial contraction presents circumferential behavior reflecting LV volume change. The 3D principal strains derived from 3D echocardiography are reliable indicators for LV contractility and seem better than conventional strains.

Image-based clustering and connected component labeling for rapid automated left and right ventricular endocardial volume extraction and segmentation in full cardiac cycle multi-frame MRI images of cardiac patients

A rapid method for left and right ventricular endocardial volume segmentation and clinical cardiac parameter calculation from MRI images of cardiac patients is presented. The clinical motivation is providing cardiologists a tool for assessing the cardiac function in a patient through the left ventricular endocardial volume's ejection fraction. A new method combining adapted fuzzy membership-based c-means pixel clustering and connected regions component labeling is used for automatic segmentation of the left and right ventricular endocardial volumes. This proposed pixel clustering with labeling approach avoids manual initialization or user intervention and does not require specifying the region of interest. This method fully automatically extracts the left and right ventricular endocardial volumes and avoids manual tracing on all MRI image frames in the complete cardiac cycle from systole to diastole. The average computational processing time per frame is 0.6s, making it much more efficient than deformable methods, which need several iterations for the evolution of the snake or contour. Accuracy of the automated method presented herein was validated against manual tracing-based extraction, performed with the guidance of cardiac experts, on several MRI frames. Dice coefficients between the proposed automatic versus manual traced ventricular endocardial volume segmentations were observed to be 0.9781 ± 0.0070 (for left ventricular endocardial volume) and 0.9819 ± 0.0058 (for right ventricular endocardial volume), and the Pearson correlation coefficients were observed to be 0.9655 ± 0.0206 (for left ventricular endocardial volume) and 0.9870 ± 0.0131 (for right ventricular endocardial volume). Graphical abstract The left ventricular endocardial volume segmentation methodology illustrated as a series of algorithms.

Improved cardiac remodeling after in vivo knockdown of type VI collagen following myocardial infarction

RationaleOur previous studies have shown that hearts of Col6−/− mice are protected from myocardial infarction (MI) injury, as these hearts exhibit reduced myocyte apoptosis, fibrosis and wall thinning leading to preserved long‐term cardiac function. The current project was designed to test whether knockdown of Col6 is feasible in the rat MI model and carries a similar cardioprotective effect during post‐MI remodeling.ObjectiveTo utilize a novel, non‐viral delivery method to deliver and determine whether siRNA‐mediated knockdown of Col6 is effective in the infarcted rat heart and affords cardioprotection in vivo in the weeks following MI injury.Methods and ResultsMI was induced via ligation of the left anterior descending artery (LAD) in adult Sprague‐Dawley rats and cardiac function was measured by transthoracic echocardiography. Calculated changes in endocardial volume, percent ejection fraction (%EF), and percent fractional shortening (%FAC) were performed at 1–6 weeks post‐MI. We witnessed a decrease in mean endocardial %EF of 44.7 ± 1.4 % in vehicle treated (control) rats, a parameter that was higher in siRNA treated hearts at 47.4 ± 1.8 %. A similar improvement was also seen in endocardial %FAC, which was 30.1 ± 1.4 % in vehicle treated rats versus 34.0 ± 1.3 % in siRNA treated rats. Knockdown of Col6 in vivo resulted in lower endocardial diastolic volume in siRNA treated rats (654.1 ± 81.3 μl in the vehicle group compared to 549.8 ± 8.4 μl for the siRNA treated group) and lower systolic volume in siRNA treated rats (362.7 ± 49.9 μl in the vehicle group compared to 291.6 ± 9.6 μl in the siRNA treated group).ConclusionssiRNA mediated Col6 knockdown using JET‐PEI as a novel delivery method was effective in vivo, reducing Col6 expression levels over 75% in the anterior wall of the LV. Echocardiography revealed that the siRNA injections preserved cardiac function and prevented left ventricular chamber dilation following MI, indicating that this approach may have a positive therapeutic benefit in the recovery from MI injury.Support or Funding InformationNIH R15HL132312This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair

This study sought to develop an automated segmentation approach based on histogram analysis of raw axial images acquired by light-sheet fluorescent imaging (LSFI) to establish rapid reconstruction of the 3-D zebrafish cardiac architecture in response to doxorubicin-induced injury and repair. Input images underwent a 4-step automated image segmentation process consisting of stationary noise removal, histogram equalization, adaptive thresholding, and image fusion followed by 3-D reconstruction. We applied this method to 3-month old zebrafish injected intraperitoneally with doxorubicin followed by LSFI at 3, 30, and 60 days post-injection. We observed an initial decrease in myocardial and endocardial cavity volumes at day 3, followed by ventricular remodeling at day 30, and recovery at day 60 (P < 0.05, n = 7–19). Doxorubicin-injected fish developed ventricular diastolic dysfunction and worsening global cardiac function evidenced by elevated E/A ratios and myocardial performance indexes quantified by pulsed-wave Doppler ultrasound at day 30, followed by normalization at day 60 (P < 0.05, n = 9–20). Treatment with the γ-secretase inhibitor, DAPT, to inhibit cleavage and release of Notch Intracellular Domain (NICD) blocked cardiac architectural regeneration and restoration of ventricular function at day 60 (P < 0.05, n = 6–14). Our approach provides a high-throughput model with translational implications for drug discovery and genetic modifiers of chemotherapy-induced cardiomyopathy.

Alignment of inducible vascular progenitor cells on a micro-bundle scaffold improves cardiac repair following myocardial infarction.

Ischemic heart disease is still the leading cause of death even with the advancement of pharmaceutical therapies and surgical procedures. Early vascularization in the ischemic heart is critical for a better outcome. Although stem cell therapy has great potential for cardiovascular regeneration, the ideal cell type and delivery method of cells have not been resolved. We tested a new approach of stem cell therapy by delivery of induced vascular progenitor cells (iVPCs) grown on polymer micro-bundle scaffolds in a rat model of myocardial infarction. iVPCs partially reprogrammed from vascular endothelial cells (ECs) had potent angiogenic potential and were able to simultaneously differentiate into vascular smooth muscle cells (SMCs) and ECs in 2D culture. Under hypoxic conditions, iVPCs also secreted angiogenic cytokines such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) as measured by enzyme-linked immunosorbent assay (ELISA). A longitudinal micro-scaffold made from poly(lactic-co-glycolic acid) was sufficient for the growth and delivery of iVPCs. Co-cultured ECs and SMCs aligned well on the micro-bundle scaffold similarly as in the vessels. 3D cell/polymer micro-bundles formed by iVPCs and micro-scaffolds were transplanted into the ischemic myocardium in a rat model of myocardial infarction (MI) with ligation of the left anterior descending artery. Our in vivo data showed that iVPCs on the micro-bundle scaffold had higher survival, and better retention and engraftment in the myocardium than free iVPCs. iVPCs on the micro-bundles promoted better cardiomyocyte survival than freeiVPCs. Moreover, iVPCs and iVPC/polymer micro-bundles treatment improved cardiac function (ejection fraction and fractional shortening, endocardial systolic volume) measured by echocardiography, increased vessel density, and decreased infarction size [endocardial and epicardial infarct (scar) length] better than untreated controls at 8weeks after MI. We conclude that iVPCs grown on a polymer micro-bundle scaffold are new promising approach for cell-based therapy designed for cardiovascular regeneration in ischemic heart disease.

Normal Values of Left Ventricular Mass Index Assessed by Transthoracic Three-Dimensional Echocardiography

Pathologic left ventricular (LV) hypertrophy is closely coupled with adverse cardiovascular events. However, normal values of LV mass determined by three-dimensional echocardiography (3DE) have not been established in a large number of healthy subjects over a wide age range. The aims of this study were to (1) validate the accuracy of 3DE for LV mass measurements against cardiac magnetic resonance (CMR), (2) establish the normal range of LV mass index in healthy subjects, and (3) investigate the effects of age, gender, and ethnic diversity on LV mass index. In protocol 1, both transthoracic 3DE and CMR were performed on the same day in 57 patients who underwent clinically indicated CMR examinations. In protocol 2, full-volume data sets were acquired with 3DE in 390 healthy subjects. The LV endocardial and epicardial borders were semiautomatically determined at end-diastole using three-dimensional echocardiographic software. LV mass was calculated as (LV epicardial volume--LV endocardial volume) × 1.05. Excellent correlation was observed between three-dimensional echocardiographic and CMR measurements of LV mass (r = 0.96). Bland-Altman analysis revealed bias of -4.8 g (-3.9% of the mean), with 95% limits of agreement of ± 27.7 g. Normal values of LV mass indexed to body surface area were found to be 70 ± 9 g/m(2) in men and 61 ± 8 g/m(2) in women. Significant age and gender dependence, but no racial dependence, was observed for LV mass index. Three-dimensional echocardiography is an accurate method for measuring LV mass. Age and gender dependence, but no ethnic dependence, of LV mass index was observed in Japanese and American populations. The reported normal reference values of 3DE-determined LV mass index according to age and gender could potentially be useful for diagnosing LV hypertrophy with excellent accuracy.

S-Nitrosoglutathione Reductase Deficiency Enhances the Proliferative Expansion of Adult Heart Progenitors and Myocytes Post Myocardial Infarction.

BackgroundMammalian heart regenerative activity is lost before adulthood but increases after cardiac injury. Cardiac repair mechanisms, which involve both endogenous cardiac stem cells (CSCs) and cardiomyocyte cell-cycle reentry, are inadequate to achieve full recovery after myocardial infarction (MI). Mice deficient in S-nitrosoglutathione reductase (GSNOR−⁄−), an enzyme regulating S-nitrosothiol turnover, have preserved cardiac function after MI. Here, we tested the hypothesis that GSNOR activity modulates cardiac cell proliferation in the post-MI adult heart.Methods and ResultsGSNOR−⁄− and C57Bl6/J (wild-type [WT]) mice were subjected to sham operation (n=3 GSNOR−⁄−; n=3 WT) or MI (n=41 GSNOR−⁄−; n=65 WT). Compared with WT,GSNOR−⁄− mice exhibited improved survival, cardiac performance, and architecture after MI, as demonstrated by higher ejection fraction (P<0.05), lower endocardial volumes (P<0.001), and diminished scar size (P<0.05). In addition, cardiomyocytes from post-MI GSNOR−⁄− hearts exhibited faster calcium decay and sarcomeric relaxation times (P<0.001). Immunophenotypic analysis illustrated that post-MI GSNOR−⁄− hearts demonstrated enhanced neovascularization (P<0.001), c-kit+ CSC abundance (P=0.013), and a ≈3-fold increase in proliferation of adult cardiomyocytes and c-kit+/CD45− CSCs (P<0.0001 and P=0.023, respectively) as measured by using 5-bromodeoxyuridine.ConclusionsLoss of GSNOR confers enhanced post-MI cardiac regenerative activity, characterized by enhanced turnover of cardiomyocytes and CSCs. Endogenous denitrosylases exert an inhibitory effect over cardiac repair mechanisms and therefore represents a potential novel therapeutic target.

95 Left Ventricular Mass Regression Occurs very early following Transcatheter Aortic Valve Implantation for Severe Aortic Stenosis

<h3>Background</h3> The effect of transcatheter aortic valve replacement (TAVR) on very early left ventricular remodelling has not previously been evaluated. Left ventricular mass (LVM) regression at 30 days (assessed using echocardiography) has been linked to a 50% reduction in re-hospitalisation in the first year following TAVR. We sought to establish using cardiac magnetic resonance (CMR) imaging, the reference standard imaging technique for LVM quantification, whether LVM regression occurs very early following-TAVR. <h3>Methods</h3> 27 patients with symptomatic severe aortic stenosis undergoing TAVR were prospectively enrolled between June 2013 and April 2014. Patients with contraindications to CMR were excluded and all patients provided informed written consent. All patients underwent an identical 1.5T CMR protocol (Intera, Philips) prior to and at a median of 5 days following TAVR (IQR 2 days). Multislice, multi-phase cine imaging was carried out using a standard steady-state free procession pulse sequence in the short axis to cover the entire left ventricle. Quantitative analysis was performed using dedicated computer software (CVI⁴², Circle Cardiovascular Imaging, Alberta, Canada). LVM was calculated by the formula (epicardial volume – endocardial volume) x myocardial density (1.05 g/cm³). <h3>Results</h3> Basic patient, echocardiographic and procedural characteristics can be seen in Table 1. At a median of 5 days following TAVR, mean LVM regressed by 12% from 129.5 +/- 32.5 g to 114.2+/-31 g and indexed LVM (LVMi) reduced from 69.4 ± 15.2 g/m² to 61.3 ± 15.1 g/m²(Figure 1). There was no significant change in indexed left ventricular diastolic volume (96.9 ± 24.5 to 96.8 ± 19.3 ml/m², p = 0.79), LV ejection fraction (54.0 ± 14.6 to 58.4 ± 27.4%, p = 0.49) or indexed left atrial volume (71.5 ± 22.6 to 67.7 ± 22.1 ml/m², p = 0.43). Mean LVM regression was similar between the Medtronic and Boston valve types (14.3 ± 10.4 gVs 16.5 ± 9.9 g, p = 0.58). There was no correlation between Valvulo-arterial impedance (ZVA) and LVM regression (r = 0.02, p = 0.93). There was no difference in mean LVMi regression according to gender (women 8.3 ± 2.8 g/m² Vs men 8.0 ± 5.7 g/m², p = 0.83). TAVR valve size did not appear to impact on early LVM regression. LVMi regression was similar between those with a normal baseline LVM and those with an elevated baseline LVM (defined as 83 g/m² in men and 67 g/m²) in women (7.8 ± 4.8 g Vs 9.0 ± 5.7 g, p = 0.60). 16 patients had evidence of late gadolinium enhancement (LGE) at baseline. There was a trend towards increased LVMi regression in those without LGE at baseline compared with those with LGE (10.1 ± 4.7 g/m²Vs 6.4 ± 4.7 g/m², p = 0.07). <h3>Conclusions</h3> LVM regression begins very early following TAVR and occurs before changes in cavity size or ejection fraction which is likely to be a result of an immediate reduction in wall stress. The type of valve implanted does not appear to influence early LVM regression. <h3>Funding</h3> This study was part funded by the BHF (PG/11/126/29321).

60 * Greater mechanical dyssynchrony is demonstrated by cardiac magnetic resonance cine imaging amongst heart failure patients awaiting cardiac resynchronisation therapy with strict left bundle branch block

Introduction: The era of cardiac resynchronisation therapy (CRT) has led to improved understanding of left ventricular activation and stricter criteria have been proposed for left bundle branch block (LBBB). These criteria have shown a greater prediction for LV mechanical dyssynchrony with 2D strain echocardiography and cardiac MRI tagging. We have further tested this hypothesis using cardiac cine MRI endocardial tracking technology and also investigated the impact of this measure of mechanical dyssynchrony on CRT response rate. Methods: We investigated a total of 47 patients awaiting CRT with traditional LBBB with a cardiac MRI pre implant. Offline analysis of the cine imaging was undertaken in order to determine the endocardial volume change systolic dyssynchrony index (SDI) of 16 segments. Pre-implant ECGs were analyzed for strict LBBB (QRS ≥ 140ms for men, ≥130ms for women and mid QRS notching/slurring in ≥2 contiguous leads). Reverse remodeling was assessed at 6 months with echocardiography. Response was defined as ≥15% improvement in LV end systolic volume. Results: These patients were aged 66.1±11.7 years, 83% were male, and 45% had an ischaemic etiology. On ECG analysis 83% had strict LBBB. In the strict LBBB group the SDI was 12.3±5.2% where as in the traditional LBBB group it was 6.7±2.5% (p=0.005). Presence of an ischaemic aetiology had no impact on SDI (p=0.216). Linear regression of SDI vs. amount of remodeling (change in LVESV) generates a regression coefficient of 2.02 (p=0.01) and a correlation coefficient of R=0.49 (p=0.01). ROC analysis determines the optimum SDI cut-off for response as 10% with an area under the curve of 0.797, a sensitivity of 81% and a specificity of 79%. Conclusion: In patients with LBBB selected for CRT under current guidance the presence of strict LBBB predicts increased mechanical dyssynchrony demonstrated as SDI with cine MRI. Presence of mechanical dyssynchrony defined as an SDI ≥10% is a good predictor of volumetric response to CRT in this cohort. ![Graphic][1] [1]: /embed/inline-graphic-1.gif

Abstract 18500: Determinants of Cardiac Loading During Long Duration Spaceflight

INTRODUCTION: Prolonged exposure to microgravity (bedrest) leads to a decrease in cardiac mass by ~1%/week due to reduced cardiac work. However, the magnitude of reduction with long duration spaceflight with modern countermeasures is unknown. One purpose of this study (Integrated CardioVascular) is to quantify cardiac work and mass in astronauts during 6 months on the International Space Station (ISS). METHODS: Data from 5 astronauts who completed a long duration stay on the ISS (~6 months) were analyzed. Cardiac mass (MRI) was measured pre- and post-flight. Continuous finger blood pressure waveforms (Volume-Clamp) for 24 hours were measured before and the end of flight (15 days before they returned to the earth). Cardiac mass was estimated by (epicardial volume - endocardial volume)*1.05 g/mL. Daily stroke work and cardiac work were calculated by the sum of each stroke volume (ΣSV, SV; stroke voluem) and stroke work (ΣSV*cmBPs, cmBPs; mean central blood pressure during systole) per day, respectively. The central blood pressure waveform was mathematically reconstructed from the finger blood pressure waveform. Beat-to-beat SV was estimated with BP waveform analysis (Modelflow). RESULTS: The %change in cardiac mass was variable (+1% on average) with divergent responses among astronauts (-4%~ +14%). All astronauts showed the reduction of cardiac work (-15±9%), while 4 of 5 showed the reduction of stroke work (-8±12%). A strong positive linear relationship was shown between % changes in cardiac work vs. mass (R 2 =0.471) as well as %changes in stroke work vs. cardiac mass (R 2 =0.905). CONCLUSIONS: Cardiac atrophy during long duration spaceflight is highly dependent on the relative changes in cardiac work and stroke work from preflight to the end of the mission. Current countermeasures may be protective in some, but not all astronauts.

Abstract 19009: Increased Endogenous C-kit + Cardiac Stem Cells Diminish Myocardial Infarction Damage in S-nitrosoglutathione Reductase Mice

Background. Cardiac tissue has endogenous cardiac stem cells (CSCs), which proliferate after myocardial infarction (MI) to support cardiac repair. As mice deficient in S-nitrosoglutathione reductase (GSNOR −/− ), an enzyme regulating S-nitrosothiol turnover, have preserved cardiac function after MI, we hypothesized that GSNOR −/− mice have higher levels of endogenous c-kit + CSCs post-MI. Methods. GSNOR −/− and WT (C57BL/6) mice were infarcted by permanent occlusion of the left anterior descending coronary artery. Cardiac performance was assessed by serial echocardiography. Histological sections were analyzed for infarct size and endogenous c-kit + /CD45 - CSCs were quantified by immunostaining. Results. There was no difference in ejection fraction (EF%) or endocardial volume (EDV, ESV) at baseline or 1 week post-MI, but at 8 weeks, EF% was improved (30.4±2.2 vs. 21.4±2.8, p&lt;0.05) and EDV and ESV were preserved in GSNOR −/− mice compared with WT (ESV 72.7±6.0 vs. 139.6±19.7 ul; p&lt;0.001, and EDV, 102.1±7.0 vs. 169.7±19.0 ul; p&lt;0.001, respectively). In addition, GSNOR −/− mice exhibited smaller scar size (34.6±2.8 vs. 62.2±7.9%, p&lt;0.05). The number of c-kit + /CD45 - CSCs was greater in post-MI GSNOR −/− hearts vs WT, independent of the zone analyzed (infarct+border zone: 6.3±0.8 vs. 2.3±0.9 cells/mm 3 , p&lt;0.05; remote zone: 0.4±0.1 vs. 0.1±0.05 cells/mm 3 , p&lt;0.05). Conclusion. Following MI, GSNOR −/− mice have preserved cardiac function, decreased remodeling and infarct size and increased c-kit + /CD45 - CSCs population in cardiac tissue during the remodeling phase. Thus, c-kit + CSCs contribute to cardioprotection in GSNOR −/− mice following MI, and suggest that enhanced S-nitrosylation based signaling contributes to CSC function following injury.

Détection des génomes de Cytomégalovirus et d’Herpès Simplex Virus dans les lavages broncho-alvéolaires au décours des pneumopathies : fréquence et interprétation

The aim of this study was to assess the effect of attenuation correction (AC) on left ventricular (LV) volumes and LV transient ischemic dilatation (TID) during dual-isotope single-photon emission computer tomographic (SPECT) myocardial perfusion imaging (MPI). Ninety-six patients (mean age 58 ± 11 years, 15% women, 38 patients completed exercise and 58 dipyridamole pharmacologic stress tests) assessed for known or suspected coronary artery disease underwent dual-isotope thallium-201 rest and technetium-99m sestamibi stress SPECT MPI with computed tomography–based AC. The TID ratio was calculated separately for non-AC and AC SPECT MPI studies as the ratio of the LV endocardial volume at stress divided by LV endocardial volume at rest. The mean and range of the gated LV ejection fraction during exercise and pharmacologic stress was 54 ± 12% (29% to 80%) and 58 ± 12% (27% to 80%), respectively. In the exercise stress group, the same mean LV endocardial volumes in non-AC and AC stress (76.4 ± 30 and 76.5 ± 28) and rest (66.3 ± 26 and 66.4 ± 24) studies were found (p = 0.90). There was no statistical difference between the mean exercise TID ratio in non-AC and AC studies (1.27 vs 1.31, respectively, p = 0.10). The same mean LV endocardial volumes in non-AC and AC in pharmacologic stress (79.9 ± 42 and 80 ± 41) and rest (71.4 ± 41 and 72.3 ± 37), respectively, were found (p = 0.50). There was no statistical difference between the mean dipyridamole TID ratio in non-AC and AC studies (1.20 vs 1.17, respectively, p = 0.10). In conclusion, LV volumes and TID indexes obtained on SPECT MPI with exercise or pharmacologic stress using dipyridamole are not affected by AC.