Left Ventricular Area Research Articles

Association of left ventricular global area strain derived from resting 3D speckle-tracking echocardiography and exercise capacity in individuals undergoing treadmill exercise test.

Background: Left ventricular (LV) global area strain (GAS) is a novel index derived from resting 3D speckle-tracking echocardiography (STE), and its clinical significance has rarely been studied. We examined the association of LV GAS and exercise capacity in a health check-up population.Methods: We recruited 94 symptom-free participants (52.2 ± 11.7 years, 62.8% male) without substantial structural heart disease or coronary heart diseases who were undergoing a routine health examination. All participants underwent resting echocardiography and symptom-limited treadmill exercise test according to the Bruce protocol. Four strain parameters were obtained from the analysis, namely 3D GAS (GAS3d), global longitudinal strain, global circumferential strain, and global radial strain.Results: After multivariate analysis for factors of exercise time, we observed a significant association in LV GAS3d (P < 0.001). We divided participants into preserved and impaired exercise capacity groups according to the cutoff value of 8 metabolic equivalent of tasks. LV GAS3d (OR 1.24, 95% CI 1.10-1.39, P < 0.001) was an independent predictor of impaired exercise capacity and the optimal cut-off value was -19.96% at a sensitivity of 77.8% and at a specificity of 92.1%. LV GAS3d could improve the discriminatory power of exercise capacity in individuals with early mitral filling velocity to average mitral annulus velocity ratio (E/e') ≥ 8.Conclusions: LV GAS3d was significantly associated with exercise time and exhibited incremental predictive value on E/e' for exercise capacity in participants undergoing treadmill exercise test.

Automatic morphological classification of mitral valve diseases in echocardiographic images based on explainable deep learning methods.

Carpentier's functional classification is a guide to explain the types of mitral valve regurgitation based on morphological features. There are four types of pathological morphologies, regardless of the presence or absence of mitral regurgitation: Type I, normal; Type II, mitral valve prolapse; Type IIIa, mitral valve stenosis; and Type IIIb, restricted mitral leaflet motion. The aim of this study was to automatically classify mitral valves using echocardiographic images. In our procedure, after the classification of apical 4-chamber (A4C) and parasternal long-axis (PLA) views, we extracted the systolic/diastolic phase of the cardiac cycle by calculating the left ventricular area. Six typical pre-trained models were fine-tuned with a 4-class model for the PLA and a 3-class model for the A4C views. As an additional contribution, to provide explainability, we applied the Gradient-weighted Class Activation Mapping (Grad-CAM) algorithm to visualize areas of echocardiographic images where the different models generated a prediction. This approach conferred a proper understanding of where various networks "look" into echocardiographic images to predict the four types of pathological mitral valve morphologies. Considering the accuracy metric and Grad-CAM maps and by applying the Inception-ResNet-v2 architecture to classify Type II in the PLA view and ResNeXt50 architecture to classify the other three classes in the A4C view, we achieved an 80% rate of model accuracy in the test data set. We suggest an explainable, fully automated, and rule-based procedure to classify the four types of mitral valve morphologies based on Carpentier's functional classification using deep learning on transthoracic echocardiographic images. Our study results infer the feasibility of the use of deep learning models to prepare quick and precise assessments of mitral valve morphologies in echocardiograms. According to our knowledge, our study is the first one that provides a public data set regarding the Carpentier classification of MV pathologies.

Abstract 12327: Intravenous Waveform Analysis Correlates With Volume Status in Resuscitation in In-Vivo Rat Model

Introduction: Current volume status markers under-perform. Dynamic markers demonstrate improved outcomes in goal directed fluid therapy but maintain validity in a narrow range of clinical parameters. In addition, they assess volume responsiveness over total volume status. Repeated echo assessments may be infeasible. Hypothesis: Intravenous waveform analysis-derived F1 more closely models volume status than current markers in a rat resuscitation model. Methods: Seven Sprague Dawley rats were anesthetized and mechanically ventilated. Pressure transductions occurred via cannulation of the right femoral vein, left femoral artery and right internal jugular vein. Hemorrhage and resuscitation occurred via the left femoral vein. Heparinized rats were bled to 80% of the estimated blood volume (EBV) then resuscitated with their own whole blood in increments of 2% of the EBV until euvolemia was reached. Cardiac output (CO) and left ventricular end diastolic area (LVEDA) were calculated with echocardiography. Fast Fourier transform was performed on venous waveforms to obtain the heart rate linked F1 amplitude. Pearson’s correlation coefficients were compared using Fisher’s Z transformation. Mixed effects modeling goodness-of-fit was assessed with Akaike information criterion (AIC). Significance was set at p=.05. Results: F1 had the strongest correlation with volume status, r= .70, followed by CO, r=.55, LVEDA, r=.55, mean arterial pressure (MAP), r=.50, central venous pressure r= -.02, and pulse pressure variation (PPV), r=.01. When compared, F1 rho was significantly greater than that of all variables except CO and LVEDA, p=.09 and p=.07, respectively. In mixed effects regression, F1 displayed the most significant AIC, -274, followed by CO at -239. Conclusions: The novel marker F1 is strongly correlated with volume status during whole blood resuscitation. F1 may be superior to current markers for directing volume resuscitation therapy.

Abstract 10935: Identification of Small-Molecule ERBB4 Agonists to Treat Heart Failure

Introduction: Heart failure is a complex syndrome with a poor prognosis. The neuregulin-1 (NRG1)/ERBB4 axis has been shown to be cardioprotective and is a possible target for heart failure therapy. Clinical trials with NRG1 are ongoing, but require intravenous administration. Our aim is to develop a small-molecule ERBB4 agonist with cardioprotective properties. Methods: A high-throughput diversity screening (HTS) of 10,240 compounds was performed on a cellular ERBB4/ERBB4 dimerization assay. Ligand binding of hit compounds was tested in co-administration studies with NRG1 (0.1 μM) and competition binding assays with fluorescently labeled NRG1 (0.03 μM). Selectivity, post-receptor phosphorylation, and cell toxicity of hit compounds were determined using Luminex® RTK phosphoprotein, U2OS ERBB2/ERBB3 dimerization and adenylate kinase assays. Biological effects were studied in vitro in different doses (4-32 μM) on TGF-β-induced collagen synthesis by human dermal and atrial fibroblasts, and on angiotensin II (AngII, 1000 ng/kg/min)-induced left ventricular (LV) remodeling in mice with 2 selected hit compounds (83 μg/kg/h), administrated through osmotic pumps (N=4-5/group). After 28 days, left ventricular myocardial fibrosis and cardiomyocyte cross sectional area (CSA) were analyzed. Results: The HTS resulted in 8 similar pyrimidine derivatives inducing ERBB4/ERBB4 but not ERBB2/ERBB3 dimerization (Emax 9 to 33% relative to NRG1, and EC50 6x10 -6 M to 2x10 -7 M). Two compounds were excluded due to in vitro toxicity. The other 6 compounds were non-toxic and induced ERBB4, but not ERBB1, ERBB2 or ERBB3 phosphorylation in EFO-21 cells. Competition assays showed allosteric binding, and co-administration studies with NRG1 revealed that compounds potentiated NRG1-induced ERBB4 receptor dimerization up to 2.5 fold. Selected compounds showed significant dose-dependent antifibrotic effects in cultured human atrial and dermal fibroblasts and significantly attenuated AngII-induced LV myocardial fibrosis by 76%±26%, whereas cardiomyocyte CSA was not affected. Conclusions: We identified novel pyrimidine derivative small-molecule ERBB4 agonists with antifibrotic properties, both in vitro and in a mouse model of AngII-induced LV fibrosis.

Abstract 11633: Three-Dimensional Speckle-Tracking Echocardiographic Assessment of Ventricular Dyssynchrony and Arrhythmic Risk in Mitral Valve Prolapse

Introduction: Dyssynchrony indices based on two-dimensional speckle tracking echocardiography have demonstrated added value in identifying patients with mitral valve prolapse (MVP) with a higher prevalence of arrhythmic complications and the potential for sudden cardiac death, but measurements are restricted to a single plane, and complex left ventricular (LV) dyssynchrony patterns may be overlooked. Hypothesis: The purpose of this study was to investigate whether three-dimensional speckle-tracking echocardiography helps in detecting MVP at higher arrhythmic risk. Methods: We studied 21 arrhythmic MVP patients (group 1) with a history of complex ventricular ectopy on holter and/or event monitor (n=17) or defibrillator implant (n=2), 21 MVPs with no arrhythmic complications (group 2) and 21 healthy controls (group 3). 3D LV longitudinal strain (3DE-LVLS) and area strain (3DE-LVAS) were determined (17 segments). 3D LV dyssynchrony index (3DE-LVDI) was obtained as the standard deviation of the times to peak area strain in 17 segments, normalized to RR interval. Results: MVP patients had significantly higher LV dyssynchrony index compared to controls (9.4±3.9% vs 4.3±2.5%, p=0.002) although they had similar LV ejection fraction (64% vs 61%, p=0.51). Group 1 and group 2 had similar LV ejection fraction and clinical data (p&gt;0.05). Bileaflet prolapse was more frequent in group 1 pts (52% vs 24%, p=0.03). Moderate mitral regurgitation was present in 9/21 group 1 pts and 3/21 group 2 pts (p=0.04). Group 1 pts had greater LV dyssynchrony index when compared with group 2 (10.7±4.1% vs 5.1±2.9%, p=0.0001). By ROC (receiver operating characteristics) curves, 3DE-LVDI and 3DE-LVAS cutoff values of 10.2% and -23.8%, respectively, had 89% and 85% sensitivity and 79% and 76% specificity in identifying the presence of significant arrhythmias with areas under the curve 0.87 and 0.84. Conclusions: Impairment of LV deformation parameters determined by three-dimensional speckle tracking echocardiography may help detect increased arrhythmic risk in patients with MVP.

Visualization of Dynamic Expression of Myocardial Sigma-1 Receptor After Myocardial Ischemia and Reperfusion Using Radioiodine-Labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) Imaging.

This study chronologically evaluated the expression of the intensity and distribution of the sigma-1 receptor (σ1R) demonstrated by radiolabeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) in a rat model of myocardial ischemia and reperfusion. The left coronary artery was occluded for 30 min, followed by reperfusion. Dual-tracer autoradiography with 125I-OI5V and 99 mTc-MIBI was performed to assess the spatiotemporal changes in 125I-OI5V uptake (n=5-6). Significant and peaked 125I-OI5V uptake in the ischemic area was observed at 3 days after reperfusion, and the 125I-OI5V uptake ratio of ischemic area to normally perfused left ventricular area decreased gradually from 3 to 28 days (mean value±SD; 0.90±0.12 at 1 day, 1.89±0.19 at 3 days, 1.52±0.17 at 7 days, 1.34±0.13 at 14 days, and 1.16±0.14 at 28 days, respectively). Triple-tracer autoradiography with 125I-OI5V, 99 mTc-MIBI, and 201TlCl was performed to evaluate 125I-OI5V uptake in the ischemic area in relation to the residual perfusion at 7 days (n=4). The 125I-OI5V uptake ratio of the non-salvaged area was higher compared to that of the salvaged area in the ischemic area. 123I-OI5V and 99 mTc-MIBI SPECT/CT was performed 3 days after reperfusion (n=3), and the in vivo images showed clear uptake of 123I-OI5V in the perfusion defect area. The present study confirmed the spatiotemporal expression pattern of σ1R expression. Non-invasive σ1R imaging with 123I or 125I-OI5V was feasible to monitor the expression of σ1R after myocardial ischemia and reperfusion.

Valvular changes after aortic valve neo-cuspidization in children: A case series.

Aortic valve neo-cuspidization (AVNeo), a procedure wherein the aortic valve is reconstructed utilizing an autologous pericardium, has recently been more commonly performed in children. However, the postoperative morphological changes in the aortic valve of pediatric patients remain unknown. The current study aimed to describe the intraoperative and postoperative findings of aortic regurgitation (AR) and stenosis (AS) after AVNeo in children. This case series describes the morphological changes in AR and AS, and their severity, between the perioperative period and 3 months postoperative period after AVNeo in children (<18 years) who underwent AVNeo between April 2016 and March 2020. Data were collected at two measurement points: (i) intraoperative transesophageal echocardiography after weaning from cardiopulmonary bypass (io-TEE); (ii) postoperative transthoracic echocardiography 3 months after the procedure (po-TTE). Seven patients were included in this case series. The number of postoperative AR sites and the ratio of AR jet area to the left ventricular outflow tract area showed a tendency to decrease between io-TEE and po-TTE. All AR sites were integrated during the postoperative period. One patient identified developed intraoperative AS, which maintained its severity after AVNeo. Most cases exhibited spontaneous improvement in AR, while one developed postoperative AS. Further prospective investigation is, therefore, needed to explore surgical outcomes following AVNeo among children.

An innovative ovine model of severe cardiopulmonary failure supported by veno-arterial extracorporeal membrane oxygenation

Refractory cardiogenic shock (CS) often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain end-organ perfusion. Current animal models result in heterogenous cardiac injury and frequent episodes of refractory ventricular fibrillation. Thus, we aimed to develop an innovative, clinically relevant, and titratable model of severe cardiopulmonary failure. Six sheep (60 ± 6 kg) were anaesthetized and mechanically ventilated. VA-ECMO was commenced and CS was induced through intramyocardial injections of ethanol. Then, hypoxemic/hypercapnic pulmonary failure was achieved, through substantial decrease in ventilatory support. Echocardiography was used to compute left ventricular fractional area change (LVFAC) and cardiac Troponin I (cTnI) was quantified. After 5 h, the animals were euthanised and the heart was retrieved for histological evaluations. Ethanol (58 ± 23 mL) successfully induced CS in all animals. cTnI levels increased near 5000-fold. CS was confirmed by a drop in systolic blood pressure to 67 ± 14 mmHg, while lactate increased to 4.7 ± 0.9 mmol/L and LVFAC decreased to 16 ± 7%. Myocardial samples corroborated extensive cellular necrosis and inflammatory infiltrates. In conclusion, we present an innovative ovine model of severe cardiopulmonary failure in animals on VA-ECMO. This model could be essential to further characterize CS and develop future treatments.

Exercise-induced changes of ventricular function in male and female amateur marathon runners as assessed by three-dimensional echocardiography

Abstract Introduction The long-term endurance training is associated with an increased risk of both right (RV) and left ventricular (LV) dysfunction. However, males and females exhibit different cardiac adaptation to exercise. The aim of our study was to evaluate three-dimensional (3D) echocardiographic parameters of ventricular function before and after the marathon in male and female amateur athletes, and compare them between sexes. Methods The study included 40 male (39±8 years) and 27 female (40±7 years) amateur athletes. Echocardiography was performed 2–3 weeks before (Stage 1) and immediately after (Stage 2) the marathon run. RV and LV area and function were assessed using standard and 3D echocardiography. Results After the marathon, there was a significant increase in the RV size (indexed RV end-diastolic volume, 51.1±12.0 vs. 59.0±9.1 ml/m2, p=0.003 in males; 48.8±11.0 vs. 60.0±11.1 ml/m2, p&amp;lt;0.001 in females), with a decrease in the LV dimensions (indexed LV end-diastolic volume, 57.1±11.9 vs. 53.0±9.4 ml/m2, p=0.026 in males; 66.2±7.9 vs. 60.1±9.5 ml/m2, p=0.001 in females). RV systolic contractility, as assessed by ejection fraction (EF) and fractional area change (FAC), significantly decreased at Stage 2 in both studied groups, while post-race decrease in LVEF was observed only in males (p&amp;lt;0.05 for the interaction sex and stage). Conclusions In both male and female amateur athletes, marathon running resulted in RV dilatation and reduction in function, with concomitant decrease in LV dimensions. However, 3D analysis revealed that strenuous exercise alters LV systolic function to a greater degree in men relative to women. Funding Acknowledgement Type of funding sources: None.

Assessment of intracardiac flow dynamics for the evaluation of patients with aortic stenosis

Abstract Background Assessment of intracardiac flows and turbulence has acquired rising significance in the past few years, due to the development and introduction of technologies for non-invasive cardiovascular imaging. Recent studies have shown that alterations in intracardiac fluid dynamics can be helpful to identify abnormalities in cardiac function. Purpose This study investigates the additional information provided by the quantitative assessment of intracardiac flow dynamics for the evaluation of patients with aortic stenosis (AS), by using an advanced echocardiography vortex-based approach. Methods Sixty-one patients with severe AS (33 females) and 38 healthy sex- and BSA-matched controls (CTRL) (15 females) were prospectively included and underwent echocardiographic assessment of intracardiac flow dynamics. Echocardiographic measurements were performed on apical three chamber views. The HyperDoppler software adapted to the echo-scanner without contrast injection was used to assess intracardiac vortex properties. The following parameters were obtained: vortex area (VA) (the ratio between the total vortex area and the left ventricular (LV) area); vortex length (VL) (the longitudinal length of the vortex relative to the total LV length; vortex depth (VD) (the distance of the vortex center from the LV base relative to the total LV long axis). Inter-rater variability was measured using intraclass correlation coefficients (ICCs) between two independent operators. Results Patients with severe AS (mean gradient: 47,5±13,9 mmHg; aortic valve area: 0.7±0.2 cm2; ejection fraction: 53±7%) had increased LV wall thickness (p&amp;lt;0.001) and mass index (p&amp;lt;0.001) compared with controls. Greater indexed left atrial volume (p&amp;lt;0.001), E/e' (p&amp;lt;0.001) and trans-tricuspid gradient (p&amp;lt;0.001) were also observed in the AS group. The assessment of VA, VL and VD was feasible in the whole population. Their calculation was reliable, as ICCs were very good for VA (0.878, p=0.033), VL (0.960, p=0.004) and VD (0,905, p=0.021). Mean VA was significantly larger in patients with severe aortic stenosis compared with CTRL (p=0.033). VL and VD (p=0.026 and p&amp;gt;0.001, respectively) were significantly higher in AS patients compared with CTRL. Among those who underwent TAVR, we observed a significant difference in the delta values of VA and VL pre-postTAVR in patients with and without significant paravalvular leak (p&amp;lt;0.05). Conclusions The newly defined VA, VL and VD, quantitative indices of vortical flow, were significantly increased in the LV cavity of patients with severe AS compared to normal subjects. These indices, whose measurement was feasible and reliable, might provide complementary information to standard echocardiography, useful for the further diagnostic and prognostic characterization of the heterogeneous population of patients with severe AS. Funding Acknowledgement Type of funding sources: None.

Assessment of intracardiac flow dynamics for the evaluation of patients with different ventricular geometry

Abstract Background Over the last decades growing evidence have demonstrated the promising role of intracardiac flow dynamic analysis in evaluating cardiac performance. Diastolic forces contribute to the formation of vortices, complex structures capable of kinetic energy storage and responsible of a smoother transition of blood from left ventricular (LV) inlet to outlet. Change in shape and location of these structures has been related with cardiovascular disease and prognosis. Purpose To investigate quantitative changes in vortices parameters in patients with different ventricular geometry. Methods We enrolled 72 consecutive patients (age 66±11 years, 49 male, 68%) with LV concentric hypertrophy (CH, n=15), eccentric hypertrophy (EH, n=13), concentric remodeling (CR, n=15) and normal LV geometry (CTRL, n=29). Each patient underwent a complete echocardiographic examination and a non-invasive intracardiac fluid dynamic analysis by Color Vector Flow Mapping. A 3-chamber apical view with a frame rate between 22 and 25 Hz has been acquired and subsequently analyzed offline by a semi-automatic software obtaining the following parameters: vortex area (VA) (the ratio between the total vortex area and the left ventricular (LV) area); vortex length (VL) (the longitudinal length of the vortex relative to the total LV length; vortex depth (VD) (the distance of the vortex center from the LV base relative to the total LV long axis). Bland Altman Plot has been used to assess intra and inter-observer variability. Results Mean VD was higher in CR, CH and EH compared to CTRL (p=0.013, p=0.001 and p=0.022, respectively). Moreover, CH showed higher VL (p=0.006) and larger VA (p=0.012) compared to CTRL. A similar trend was noticed in EH patients, despite did not reach statistical significance (p=0.21 and p=0.07 for VA and VL respectively). No significative differences in vortices parameters have been observed between CH and EH. Conclusion(s) This is the first study providing quantitative echocardiographic parameters of vortex location and morphology in different LV geometries. Higher values of VD were found in CR, CH and EG. Quantitative intra dynamic fluid assessment was feasible and reliable in the whole population and could provide additional information to the standard echocardiographic examination. Funding Acknowledgement Type of funding sources: None.

Impact of Annular Oversizing on Paravalvular Regurgitation and ValveHemodynamics: New Insights From PARTNER 3.

This study sought to investigate the impact of computed tomography (CT)-based area and perimeter oversizing on the incidence of paravalvular regurgitation (PVR) and valve hemodynamics in patients treated with the SAPIEN 3 transcatheter heart valve (THV). The incremental value of considering annular perimeter or left ventricular outflow tract measurements and the impact of THV oversizing on valve hemodynamics are not well defined. The PARTNER 3 (Placement of Aortic Transcatheter Valves 3) trial included 495 low-surgical-risk patients with severe aortic stenosis who underwent THV implantation. THV sizing was based on annular area assessed by CT. Area- and perimeter-based oversizing was determined using systolic annular CT dimensions and nominal dimensions of the implanted THV. PVR, effective orifice area, and mean gradient were assessed on 30-day transthoracic echocardiography. Of 485 patients with available CT and echocardiography data, mean oversizing was 7.9 ± 8.7% for the annulus area and 2.1 ± 4.1% for the perimeter. A very low incidence of≥moderate PVR (0.6%) was observed, including patients with minimal annular oversizing. Incidence of≥mild PVR and need for procedural post-dilatation were inversely related to the degree of oversizing. For patients with annular dimensions suitable for 2 THV sizes, the larger THV with both area and perimeter oversizing was associated with the lowest incidence of≥mild PVR (12.0% vs 43.4%; P<0.0001). Left ventricular outflow tract area oversizing was not associated with PVR. THV prosthesis size, rather than degree of oversizing, had greatest impact on effective orifice area and mean gradient. In low-surgical-risk patients, a low incidence of≥moderate PVR was observed, including patients with minimal THV oversizing. The degree of prosthesis oversizing had the greatest impact on reducing mild PVR and incidence of post-dilatation, without impacting valve hemodynamics. In selected patients with annular dimensions in between 2 valve sizes, the larger THV device oversized to both the annular area and perimeter reduced PVR and optimized THV hemodynamics.

Accuracy of electroanatomical mapping-guided cardiac radiotherapy for ventricular tachycardia: pitfalls and solutions.

To analyse and optimize the interobserver agreement for gross target volume (GTV) delineation on cardiac computed tomography (CCT) based on electroanatomical mapping (EAM) data acquired to guide radiotherapy for ventricular tachycardia (VT). Electroanatomical mapping data were exported and merged with the segmented CCT using manual registration by two observers. A GTV was created by both observers for predefined left ventricular (LV) areas based on preselected endocardial EAM points indicating a two-dimensional (2D) surface area of interest. The influence of (interobserver) registration accuracy and availability of EAM data on the final GTV and 2D surface location within each LV area was evaluated. The median distance between the CCT and EAM after registration was 2.7 mm, 95th percentile 6.2 mm for observer #1 and 3.0 mm, 95th percentile 7.6 mm for observer #2 (P = 0.9). Created GTVs were significantly different (8 vs. 19 mL) with lowest GTV overlap (35%) for lateral wall target areas. Similarly, the highest shift between 2D surfaces was observed for the septal LV (6.4 mm). The optimal surface registration accuracy (2.6 mm) and interobserver agreement (Δ interobserver EAM surface registration 1.3 mm) was achieved if at least three cardiac chambers were mapped, including high-quality endocardial LV EAM. Detailed EAM of at least three chambers allows for accurate co-registration of EAM data with CCT and high interobserver agreement to guide radiotherapy of VT. However, the substrate location should be taken in consideration when creating a treatment volume margin.

Echocardiographic assessment of dilated cardiomyopathy in dogs

Dilated cardiomyopathy (DCM) is a frequent cause of cardiac disability, congestive heart failure (CHF), and arrhythmic death in dogs. The etiology of DCM is usually idiopathic/genetic, but some causes of a DCM phenotype are reversible. The disease is classified into preclinical (occult) and clinical (overt) stages; the latter stems from heart failure with reduced ejection fraction. DCM is further characterized by clinical, electrocardiographic, circulating biomarker, and imaging abnormalities. The diagnosis of clinical DCM with CHF is straightforward; however, identification of the preclinical stage can be challenging. Echocardiography is central to the diagnosis of both stages and characterized by left ventricular (LV) systolic dysfunction with progressive chamber dilation and variable enlargements of the left atrium and right-sided chambers. Left ventricular dilation is defined by increased LV end-diastolic volumes, areas, and internal dimensions normalized to body size or indexed to the aorta. Systolic dysfunction is characterized by decreased LV ejection fraction, increased end-systolic volume, and reduced shortening across minor and longitudinal LV axes. Dyssynchrony can confound the interpretation of linear indices of systolic function. A comprehensive echocardiogram in DCM includes two-dimensional and M-mode studies, spectral and tissue Doppler imaging, and potentially three-dimensional echocardiography and myocardial strain imaging. Echocardiographic findings should be interpreted within the context of identifiable risks and comorbidities, physical diagnosis, complementary diagnostic testing, and limitations of current reference intervals. Ambiguous examinations should be repeated. Specific echocardiographic criteria for the diagnosis of DCM are proposed to encourage discussion and additional outcome and breed-specific echocardiographic studies of canine DCM.

Impact of Arrhythmia on Myocardial Perfusion: A Computational Model-Based Study

(1) Background: Arrhythmia, which is an umbrella term for various types of abnormal rhythms of heartbeat, has a high prevalence in both the general population and patients with coronary artery disease. So far, it remains unclear how different types of arrhythmia would affect myocardial perfusion and the risk/severity of myocardial ischemia. (2) Methods: A computational model of the coronary circulation coupled to the global cardiovascular system was employed to quantify the impacts of arrhythmia and its combination with coronary artery disease on myocardial perfusion. Furthermore, a myocardial supply–demand balance index (MSDBx) was proposed to quantitatively evaluate the severity of myocardial ischemia under various arrhythmic conditions. (3) Results: Tachycardia and severe irregularity of heart rates (HRs) depressed myocardial perfusion and increased the risk of subendocardial ischemia (evaluated by MSDBx), whereas lowering HR improved myocardial perfusion. The presence of a moderate to severe coronary artery stenosis considerably augmented the sensitivity of MSDBx to arrhythmia. Further data analyses revealed that arrhythmia induced myocardial ischemia mainly via reducing the amount of coronary artery blood flow in each individual cardiac cycle rather than increasing the metabolic demand of the myocardium (measured by the left ventricular pressure-volume area). (4) Conclusions: Both tachycardia and irregular heartbeat tend to increase the risk of myocardial ischemia, especially in the subendocardium, and the effects can be further enhanced by concomitant existence of coronary artery disease. In contrast, properly lowering HR using drugs like β-blockers may improve myocardial perfusion, thereby preventing or relieving myocardial ischemia in patients with coronary artery disease.

Abstract P143: Assessment Of Biventricular And Aortic Function In Arterial Systemic Hypertension By Speckle Tracking Echocardiography

Background: The purpose of the present study was to assess whether systemic arterial hypertension is associated with abnormal right ventricular (RV) structure and function as assessed by three-dimensional speckle tracking echocardiography and how those changes are related to left ventricular (LV) strain, left ventricular hypertrophy (LVH) and aortic (Ao) function. Methods: We examined 115 hypertensive (mean age, 65±16 years; 52% male) and 115 healthy adults (mean age, 68±13 years; 54% male). Patients were divided into two groups: patients with LVH (Group I, LVMI&gt;115g/m 2 men, LVMI&gt;95g/m 2 women) and patients without LVH (group II). LV longitudinal (LS), circumferential, radial and area (GAS) strains were calculated by three-dimensional speckle tracking echocardiography (3DSTE). RV free-wall longitudinal strain (LS) was determined by 3DSTE. Aortic (Ao) distensibility and stiffness index (SI) were calculated using accepted formulae. The corrected aortic strain (Ao-S) by two-dimensional speckle tracking echocardiography was calculated as the global aortic strain /pulse pressure. Data analysis was performed offline (GE EchoPAC). Results: Overall, Ao-SI was increased (r=0.74, p=0.003) and Ao-S was decreased (r=0.79, p=0.002) in hypertensive patients compared with controls. Ao-SI had a negative correlation with Ao-S (r=-0.76, p&lt;0.001). Ao-S correlated with LV and RV longitudinal strain (r=0.62,p=0.02, and r=0.58,p&lt;0.05, respectively) and LV and RV area strain (r=0.66,p=&lt;0.01, and r=0.53,p&lt;0.05, respectively). RV-LS and LV-GAS were lower in Group 1 patients compared to Group 2 (r=0.81, p&lt;0.001), and lower in Group 2 patients compared to controls (r=0.59, p=0.02). There was a positive correlation between LV and RV LS (r=0.52, p&lt;0.05). RV-LS was independently associated with Ao-S (β=0.37, p=0.01), LV-GAS (β=0.32, p=0.027) and LV-LS (β=0.26, p=0.034) in the whole hypertensive population. Conclusions: In systemic hypertension there is a complex interaction between LV strain, RV strain and Ao strain. Reduced RV strain can occur even in the absence of LV hypertrophy.

Cardiac Performance in the First Year of Age Among Preterm Infants Fed Maternal Breast Milk

There is a beneficial association between human breast milk exposure in the neonatal period and cardiac mechanics in adults who were born preterm. It is unknown whether this benefit is apparent in infants in the first year of age. To test the hypothesis that higher consumption of mother's own milk in preterm infants is associated with enhanced cardiac performance during the first year of age. This cross-sectional study of cardiac and nutritional data at an academic medical center included 80 individuals born preterm and 100 individuals in the control group born full-term. All births were between 2011 and 2013. Two-dimensional echocardiograms were performed at 32 weeks' and 36 weeks' postmenstrual age and at 1 year's corrected age in individuals born preterm and at 1 month and 1 year of age in individuals born full-term. Statistical analysis was performed from January to May 2021. Consumption of mother's own milk. Main study outcomes included echocardiography measures of right and left ventricle longitudinal strain (function), left ventricle mass index and right ventricular areas (morphology), and pulmonary vascular resistance (pulmonary hemodynamics) at age 1 year. Of 180 infants included in the study, 97 (54%) were Black infants and 89 (49%) were female infants. Among the 80 infants born in the preterm cohort, 43 (54%) were female infants and 43 (54%) were Black infants. The median gestational age at birth of the preterm infants was 27.0 weeks (interquartile range, 26.0-28.0 weeks) and the median birth weight was 960 g (interquartile range, 800-1138). For each week of exposure to mother's own milk, preterm infants had greater magnitudes of right ventricular strain (eg, right longitudinal strain: β, 0.021; 95% CI, 0.002-0.041; P < .001) and left ventricular strain (eg, left longitudinal strain: β, 0.065; 95% CI, 0.049-0.080; P = .01), larger right ventricle areas (eg, systolic area: β, 0.026; 95% CI, 0.011-0.042; P = .009), larger left ventricle mass index (β, 0.045; 95% CI, 0.024-0.073; P = .003), and decreased pulmonary vascular resistance (eg, pulmonary artery acceleration time: β, 0.041; 95% CI, 0.018-0.063; P < .001) at 1 year's corrected age, even after accounting for gestational age and common neonatal morbidities. Cardiac values approached those seen in controls born full-term with increased mother's own milk exposure. There were no differences in any of the cardiac indices at 32 weeks' postmenstrual age, but with each week of exposure, right ventricle function (eg, right longitudinal strain: β, 0.016; 95% CI, 0.002-0.031; P < .001) was greater and pulmonary pressured (eg, pulmonary artery acceleration time: β, 0.0032; 95% CI, 0.0013-0.0062; P < .001). This study found that preterm infants with higher consumption of mother's own milk had enhanced cardiac performance at age 1 year, suggesting that mother's own milk consumption may play a dynamic modulator role on cardiac mechanics in preterm-born infants and help in normalization of the preterm cardiac phenotype.

A neonatal leporine model of age-dependent natural heart regeneration after myocardial infarction

ObjectivesNeonatal rodents and piglets naturally regenerate the injured heart after myocardial infarction. We hypothesized that neonatal rabbits also exhibit natural heart regeneration after myocardial infarction. MethodsNew Zealand white rabbit kits underwent sham surgery or left coronary ligation on postnatal day 1 (n = 94), postnatal day 4 (n = 11), or postnatal day 7 (n = 52). Hearts were explanted 1 day postsurgery to confirm ischemic injury, at 1 week postsurgery to assess cardiomyocyte proliferation, and at 3 weeks postsurgery to assess left ventricular ejection fraction and scar size. Data are presented as mean ± standard deviation. ResultsSize of ischemic injury as a percentage of left ventricular area was similar after myocardial infarction on postnatal day 1 versus on postnatal day 7 (42.3% ± 5.4% vs 42.3% ± 4.7%, P = .9984). Echocardiography confirmed severely reduced ejection fraction at 1 day after postnatal day 1 myocardial infarction (33.7% ± 5.3% vs 65.2% ± 5.5% for postnatal day 1 sham, P = .0001), but no difference at 3 weeks after postnatal day 1 myocardial infarction (56.0% ± 4.0% vs 58.0% ± 3.3% for postnatal day 1 sham, P = .2198). Ejection fraction failed to recover after postnatal day 4 myocardial infarction (49.2% ± 1.8% vs 58.5% ± 5.8% for postnatal day 4 sham, P = .0109) and postnatal day 7 myocardial infarction (39.0% ± 7.8% vs 60.2% ± 5.0% for postnatal day 7 sham, P < .0001). At 3 weeks after infarction, fibrotic scar represented 5.3% ± 1.9%, 14.3% ± 4.9%, and 25.4% ± 13.3% of the left ventricle area in the postnatal day 1, postnatal day 4, and postnatal day 7 groups, respectively. An increased proportion of peri-infarct cardiomyocytes expressed Ki67 (15.9% ± 1.8% vs 10.2% ± 0.8%, P = .0039) and aurora B kinase (4.0% ± 0.9% vs 1.5% ± 0.6%, P = .0088) after postnatal day 1 myocardial infarction compared with sham, but no increase was observed after postnatal day 7 myocardial infarction. ConclusionsA neonatal leporine myocardial infarction model reveals that newborn rabbits are capable of age-dependent natural heart regeneration.

Selective FPR2 Agonism Promotes a Proresolution Macrophage Phenotype and Improves Cardiac Structure-Function Post Myocardial Infarction

Dysregulated inflammation following myocardial infarction (MI) leads to maladaptive healing and remodeling. The study characterized and evaluated a selective formyl peptide receptor 2 (FPR2) agonist BMS-986235 in cellular assays and in rodents undergoing MI. BMS-986235 activated G proteins and promoted β-arrestin recruitment, enhanced phagocytosis and neutrophil apoptosis, regulated chemotaxis, and stimulated interleukin-10 and monocyte chemoattractant protein-1 gene expression. Treatment with BMS-986235 improved mouse survival, reduced left ventricular area, reduced scar area, and preserved wall thickness. Treatment increased macrophage arginase-1 messenger RNA and CD206 receptor levels indicating a proresolution phenotype. In rats following MI, BMS-986235 preserved viable myocardium, attenuated left ventricular remodeling, and increased ejection fraction relative to control animals. Therefore, FPR2 agonism improves post-MI healing, limits remodeling and preserves function, and may offer an innovative therapeutic option to improve outcomes.

The impact of fluid status and decremental PEEP strategy on cardiac function and lung and kidney damage in mild-moderate experimental acute respiratory distress syndrome

BackgroundWe evaluated the effects of abrupt versus gradual PEEP decrease, combined with standard versus high-volume fluid administration, on cardiac function, as well as lung and kidney damage in an established model of mild-moderate acute respiratory distress syndrome (ARDS).MethodsWistar rats received endotoxin intratracheally. After 24 h, they were treated with Ringer’s lactate at standard (10 mL/kg/h) or high (30 mL/kg/h) dose. For 30 min, all animals were mechanically ventilated with tidal volume = 6 mL/kg and PEEP = 9 cmH2O (to keep alveoli open), then randomized to undergo abrupt or gradual (0.2 cmH2O/min for 30 min) PEEP decrease from 9 to 3 cmH2O. Animals were then further ventilated for 10 min at PEEP = 3 cmH2O, euthanized, and their lungs and kidneys removed for molecular biology analysis.ResultsAt the end of the experiment, left and right ventricular end-diastolic areas were greater in animals treated with high compared to standard fluid administration, regardless of PEEP decrease rate. However, pulmonary arterial pressure, indicated by the pulmonary acceleration time (PAT)/pulmonary ejection time (PET) ratio, was higher in abrupt compared to gradual PEEP decrease, independent of fluid status. Animals treated with high fluids and abrupt PEEP decrease exhibited greater diffuse alveolar damage and higher expression of interleukin-6 (a pro-inflammatory marker) and vascular endothelial growth factor (a marker of endothelial cell damage) compared to the other groups. The combination of standard fluid administration and gradual PEEP decrease increased zonula occludens-1 expression, suggesting epithelial cell preservation. Expression of club cell-16 protein, an alveolar epithelial cell damage marker, was higher in abrupt compared to gradual PEEP decrease groups, regardless of fluid status. Acute kidney injury score and gene expression of kidney injury molecule-1 were higher in the high versus standard fluid administration groups, regardless of PEEP decrease rate.ConclusionIn the ARDS model used herein, decreasing PEEP abruptly increased pulmonary arterial hypertension, independent of fluid status. The combination of abrupt PEEP decrease and high fluid administration led to greater lung and kidney damage. This information adds to the growing body of evidence that supports gradual transitioning of ventilatory patterns and warrants directing additional investigative effort into vascular and deflation issues that impact lung protection.