Left Ventricular Pump Research Articles

Modification of ventriculo-arterial coupling by spironolactone in nonischemic dilated cardiomyopathy.

AimsWe sought to clarify the role of ventriculo–arterial (V–A) coupling in the treatment of nonischemic dilated cardiomyopathy (NIDCM) by adding a mineralocorticoid receptor antagonist (MRA) to conventional anti‐failure therapy.Methods and resultsWe employed cardiac magnetic resonance imaging to quantify left ventricular (LV) contractility and V–A coupling in normal subjects at rest (n = 11) and in patients with NIDCM (n = 12) before and after long term anti‐failure therapy, in which MRA was added to conventional anti‐failure therapy. After ≥6 months' treatment in NIDCM patients, LV volumes and mass decreased, and the LV ejection fraction increased from a median of 24% (17, 27) (interquartile range IQR) to 47 (42, 52) (P < 0.002), with a marked reduction in arterial elastance (Ea) from 2.89 mmHg/mL (2.34, 4.0) to 1.50 (1.29, 1.95) (P < 0.002), similar to Ea of normal subjects, 1.53 (1.34, 1.67) (P > 0.05). The V–A coupling ratio, Ea/end‐systolic elastance (single‐beat method), decreased by −1.08 (−1.96, −0.55), (P = 0.003), as did Ea/end‐systolic pressure/end‐systolic pressure ratio, −0.54 (0.35, 0.87), (P = 0.002). The preload recruitable stroke work (PRSW) increased as did PRSW indexed for Ea (both P = 0.002), which reflected ‘total circulatory performance’.ConclusionsIn NIDCM, adding MRA to conventional anti‐failure therapy markedly improved LV ejection fraction and reduced peripheral vascular resistance, due to both improved LV contractility and especially to enhanced V–A coupling, as Ea decreased to normal. Total circulatory performance was a sensitive indicator of both LV pump performance and the arterial loading conditions.

Changes in left ventricular size, geometry, pump function and left heart pressures during healthy aging.

There are cross-sectional and longitudinal imaging studies using echocardiography and cardiac magnetic resonance in healthy adult subjects which have demonstrated associations of left ventricular (LV) structure and pump function with age. There are also cross-sectional data regarding the relationships of age with invasively measured left heart chamber pressures. Increasing age is associated with decreases in LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), end-diastolic length (LVEDL), stroke volume (SV) and cardiac output (CO), and increases in relative wall thickness (RWT), LV mass/LVEDV ratio (LVMVR) and ejection fraction (LVEF). Older age is not accompanied by a change in mean left atrial (LA) pressure, but there is both direct and indirect evidence which suggests that LV end-diastolic pressure (LVEDP) increases with age. LVEDV remains lower in older than younger subjects during fluid infusion and the resulting increases in LA pressure. The combination of an increase in LVEF with reductions of both SV and CO demonstrates an age-related increase in divergence between LVEF and LV pump function. A lower LVEDV in older compared to younger subjects can be characterized as an aging-related decrease in LV capacity, with the higher LVEDP in older subjects also indicating a reduction of preload reserve.

Improved Efficiency of Intraventricular Blood Flow Transit Under Cardiac Stress: A 4D Flow Dobutamine CMR Study.

Introduction: The effects of heart rate, inotropy, and lusitropy on multidimensional flow patterns and energetics within the human heart remain undefined. Recently, reduced volume and end-diastolic kinetic energy (KE) of the portion of left ventricular (LV) inflow passing directly to outflow, Direct flow (DF), have been shown to reflect inefficient LV pumping and to be a marker of LV dysfunction in heart failure patients. In this study, we hypothesized that increasing heart rate, inotropy, and lusitropy would result in an increased efficiency of intraventricular blood flow transit. Therefore, we sought to investigate LV 4D blood flow patterns and energetics with dobutamine infusion.Methods: 4D flow and morphological cardiovascular magnetic resonance (CMR) data were acquired in twelve healthy subjects: at rest and with dobutamine infusion to achieve a target heart rate ~60% higher than the resting heart rate. A previously validated method was used for flow analysis: pathlines were emitted from the end-diastolic (ED) LV blood volume and traced forward and backward in time to separate four functional LV flow components. For each flow component, KE/mL blood volume at ED was calculated.Results: With dobutamine infusion there was an increase in heart rate (64%, p < 0.001), systolic blood pressure (p = 0.02) and stroke volume (p = 0.01). Of the 4D flow parameters, the most efficient flow component (DF), increased its proportion of EDV (p < 0.001). The EDV proportion of Residual volume, the blood residing in the ventricle over at least two cardiac cycles, decreased (p < 0.001). The KE/mL at ED for all flow components increased (p < 0.001). DF had the largest absolute and relative increase while Residual volume had the smallest absolute and relative increase.Conclusions: This study demonstrates that it is feasible to compare 4D flow patterns within the normal human heart at rest and with stress. At higher heart rate, inotropy and lusitropy, elicited by dobutamine infusion, the efficiency of intraventricular blood flow transit improves, as quantified by an increased relative volume and pre-systolic KE of the most efficient DF component of the LV volume. The change in these markers may allow a novel assessment of LV function and LV dysfunction over a range of stress.

Abstract 14879: Heart Failure With Preserved Ejection Fraction Patients Do Not Augment Longitudinal Pumping During Exercise

Introduction: Left ventricular (LV) pumping from longitudinal motion is highly efficient and a major contributor to stroke volume (SV). Patients with heart failure with preserved ejection fraction (HFpEF) have diminished longitudinal ventricular motion but the effect on LV pumping is unknown. This study aimed to determine the contribution of longitudinal pumping in HFpEF compared to healthy age-matched controls at rest and submaximal exercise when exercise induced SV reserve is maximal. Methods: Cardiopulmonary exercise testing with concurrent 3D echocardiography was performed in 30 subjects (HFpEF n = 20, age 69±5 years, Senior Control (CON): n = 10, age 70±4 years) at rest and during exercise at a targeted heart rate of 100 bpm (HFpEF 66±18% VO 2 Max, CON: 49±13% VO 2 Max, p = 0.014). LV volumes and mitral annular excursion (MAE), a novel metric of systolic function, were measured using multi-beat 3D acquisition at rest and during sub-maximal exercise. MAE volume (MAEV) was measured by multiplying MAE by short axis area at the base of the ventricle. Relative longitudinal pumping was calculated as the quotient of MAEV and SV (%). Results: Mitral annular excursion (MAE) at rest was lower in HFpEF (Figure) and increased significantly less during sub-maximal exercise compared to controls (CON Δ3.3mm vs HFpEF Δ1.1mm, group p = 0.002, group x exercise p = 0.011). MAEV was similar in HFpEF compared to controls at reest but did not augment in HFpEF compared to controls (CON Δ7.1 ml vs HFpEF Δ1.9 ml, group x exercise p = 0.002). Relative longitudinal pumping increased significantly with exercise in CON but remained unchanged in HFpEF (CON Δ7.9% vs HFpEF Δ-0.7%, group x exercise p = 0.043). Conclusions: Longitudinal pumping does not increase in HFpEF patients despite exercising at a higher relative metabolic demand than their healthy peers. This lack of longitudinal pumping reserve may contribute to and help identify cardiac limitations during exercise commonly seen in HFpEF patients.

Left atrial function assessed by speckle tracking echocardiography in anthracycline-induced cardiotoxicity: a case report.

BackgroundThe onset prevention and early diagnosis in cardiotoxicity due to cancer chemotherapy are important, and it is important to detect cardiac dysfunction at an early stage and start treatment to enhance the therapeutic effect.Case summaryA 31-year-old female with breast cancer received chemotherapy with epirubicin (400 mg/m2) and cyclophosphamide followed by docetaxel. Two months after the initiation of her chemotherapy, the left ventricular (LV) ejection fraction (LVEF) determined by echocardiography fell to 41.2%, and she was diagnosed with cancer therapy-related cardiac dysfunction (CTRCD). Three months after the initiation of cancer treatment, the peak velocity of late diastolic transmitral Doppler flow (A wave) became undetectable. Peak longitudinal strain (LS) and peak LS rate, which reflect left atrium (LA) reservoir function, gradually declined like the LVEF and LV-global LS (GLS). Seven months after the initiation of cancer treatment, she was diagnosed with acute decompensated heart failure. The changes in peak LS and peak LS at the onset were greater than those in LVEF and LV-GLS.DiscussionThis is a case report suggesting that LA reservoir function might be a more sensitive indicator than LVEF or LV-GLS in detecting CTRCD and that LA booster function might be the earliest. Left atrium reservoir function might be a more sensitive than conventional LV pump function and optimal indicator in CTRCD.

Global risk factors of contrast-induced acute kidney injury: systematic review and meta-analysis

Abstract Background Administration of iodinated contrast is common but may be associated with contrast-induced acute kidney injury (CI-AKI), particularly in at-risk patients. There is no recent systematic review of potentially modifiable risk factors. Methods We searched MEDLINE, Embase and the Cochrane Database of Systematic Reviews (to 30 th June 2019) for observational studies assessing risk factors associated with CI-AKI. Twelve potentially modifiable risk factors were finally included in this thematic review and meta-analysis. Random or fixed meta-analysis was performed to derive the adjusted odds ratio (aOR), and the population attributable risk (PAR) was calculated for each risk factor globally and by region. Findings We included 157 studies (2,297,863 participants). The global incidence of CI-AKI was 5.4%. The potentially modifiable risk factors included high contrast volume (PAR 33%), eight cardiovascular risk factors (diuretic use, multivessel coronary artery disease, acute coronary syndrome, hypertension, hypotension, heart failure, reduced left ventricular ejection fraction and intra-aortic balloon pump use) (combined PAR 76.2%) and three noncardiovascular risk factors (renal dysfunction, diabetes mellitus and anaemia) (combined PAR 47.4%) with geographical differences. Bubble chart of the 12 risk factors Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National Science Foundation of China

Dapagliflozin Influences Ventricular Hemodynamics and Exercise-Induced Pulmonary Hypertension in Type 2 Diabetes Patients - A Randomized Controlled Trial.

This prospective randomized multicenter open-label trial evaluated whether sodium-glucose cotransporter-2 inhibitor (SGLT2-i) improves left ventricular (LV) pump function and suppresses elevation of LV filling pressure (LVFP) and right ventricular systolic pressure (RVSP) during exercise in type 2 diabetes mellitus (T2DM) patients. Based on HbA1c and LV ejection fraction, 78 patients with poorly controlled T2DM were randomly assigned to D-group (dapagliflozin 5 mg/day add-on) or C-group (conventional therapy add-on). Physical examination, home and office blood pressure examination, blood tests, and echocardiography at rest and during ergometer exercise were performed at baseline and at 1.5 and 6 months after treatment. The primary endpoint was defined as the change in RVSP (mmHg) between baseline and 6-month follow up. The secondary endpoints were changes in LVFP (ratio), stroke volume index (SVi; mL/m2), and cardiac index (CI; L/min/m2). Both RVSP and LVFP during exercise significantly decreased from baseline to 6 months after starting treatment in the D-group (P<0.001). No changes to either parameter was observed in the C-group. The SVi and CI did not improve in either group. Both home and office blood pressure significantly decreased in the D-group. Decreases in HbA1c were somewhat greater in the C-group. Dapagliflozin significantly improved RVSP and LVFP during exercise in patients with T2DM and cardiovascular risk, which may contribute to favorable effects on heart failure.

A Stepwise Approach to Left Ventricular Assist Device Pump Thrombosis

Pump thrombosis (PT) is a detrimental complication of left ventricular assist device (LVAD) therapy. There is no consensus on optimal PT treatment. The aim of this study was to present a treatment strategy for patients with PT. The hospital records of patients who underwent isolated LVAD implantation between May 2013 and October 2018 were retrospectively evaluated. Pump thrombosis was suspected in the setting of impaired flow/power parameters and haemolysis. Protocols for the management of suspected PT varied by patient presentation. Parameters that increased the PT risk were investigated by dividing the patients into two groups according to the presence of PT. Preoperative and operative data were analysed. Pump thrombosis was observed in 20 of 81 patients. All patients with PT presented elevated lactate dehydrogenase levels and higher power and/or low-/high-flow alarm at admission. All patients were treated initially with intravenous unfractionated heparin infusion; three patients did not require further treatment, one patient died due to sudden cardiac arrest, and three patients underwent urgent surgery for LVAD exchange. Thirteen (13) patients received tissue plasminogen activator infusion; eight were discharged without any signs of thrombosis, and three were bridged to transplant. One (1) major bleeding event leading to death was observed. Freedom from second PT was found in 91% cases at 6 months and in 68.2% at 1 year. We found that a larger left ventricle and the type of pump determined the risk of PT. Low-dose thrombolytic therapy should be considered as a feasible treatment option for patients with PT.

Left ventricular ejection fraction using manual and semi-automated biplane method of discs in very preterm infants.

Biplane left ventricular ejection fraction (LVEF) is a valuable echocardiographic parameter for assessment of LV systolic pump efficiency in adults and children, but not often reported in preterm infants. The primary aim of this study was to longitudinally measure biplane LVEF in very preterm infants during the neonatal intensive care period. Secondary aim was to compare manual and semi-automatic determination of LVEF for agreement and variability. Stable preterm infants less than 30weeks gestation were scanned on day 3, day 28, and at 36weeks postmenstrual age. The LV endocardium was traced manually and semi-automatically using integrated speckle tracking software in apical 4-chamber and apical 3-chamber images to obtain end-diastolic volume and end-systolic volume, and calculate LVEF. Agreement between methods and variability within and between observers was determined using an interclass correlation coefficient (ICC) and Bland-Altman analysis. Sixty-six preterm infants with a mean birth weight of 1100 (239)g were analyzed. The average manual biplane LVEF was 58 (3)%, 59 (3)%, and 55 (4)% at the three respective time points. Manual LVEF showed good agreement with semi-automatic LVEF (ICC 0.76) with a small bias of -1.5 (3.0)%. Interobserver variability of LVEF improved with semi-automatic tracing of the LV endocardial border (ICC manual 0.68 vs semi-automatic 0.80). Left ventricular systolic pump efficiency in preterm infants remains stable during the neonatal intensive care period. Semi-automatic biplane LVEF has less interobserver variability and can be used interchangeably with manual biplane LVEF.

P989Determinants of beat-to-beat left ventricular function during atrial fibrillation: a combined clinical-computational study

Abstract Funding Acknowledgements Netherlands Organisation for Scientific Research (NWO-ZonMw, VIDI grant 016.176.340) Background The rapid irregular atrial electrical activity during atrial fibrillation (AF) is associated with an irregular and variable left ventricular (LV) systolic pump function. The mechanisms determining LV function during AF remain incompletely understood. Purpose To assess the reliability of global longitudinal strain (GLS) as a measure of LV function during AF, and to elucidate how beat-to-beat changes in LV preload and afterload affect LV function during AF. Methods Beat-to-beat speckle-tracking echocardiography was performed in patients with persistent AF. A hundred consecutive beats in each patient were imaged during AF and we evaluated the relation between GLS in the image plane (4-chamber view) and (pre-)preceding cycle length (CL) in these patients. We used the CircAdapt cardiovascular system model to simulate cardiac mechanics and hemodynamics during AF for each individual patient 1) by imposing the exact irregular sequence of CL as measured in the patient and 2) by making the atrial myocardium non-contractile. These simulations enabled beat-to-beat quantification of preload (end-diastolic volume, EDV), afterload (systolic aortic pressure) and GLS during AF. Results Clinical data and simulations both showed a negative non-linear relation between preceding CL and GLS (Panel A). Non-linearity was more pronounced at low preceding CLs (&amp;lt;750ms), while GLS at preceding CLs &amp;gt;750ms showed less dependence on CL. Simulating ventricular failure by a reduction in ventricular contractility led to a lower overall GLS and a loss of non-linear response at low CL (Panel A, right, diamonds). Increased GLS at high preceding CL (purple box) was explained by a higher preceding EDV (higher preload) (p &amp;lt; 0.002, Panel B), reflecting the Frank-Starling mechanism of contractile myocardium. At a given preceding CL, variability in GLS was explained by the afterload of the preceding beat, with a lower preceding afterload (systolic aortic pressure) leading to higher GLS (Panel C, yellow box, p &amp;lt; 0.002), but not by changes in preceding preload (Panel C, p non-significant). Preload of the pre-preceding beat also correlated with changes in GLS (Panel C, p &amp;lt; 0.005). Conclusions During AF, GLS depends non-linearly on the preceding CL, with GLS measures performed at longer preceding CLs (&amp;gt;750ms in our cohort) showing a low beat-to-beat variability. Beat-to-beat hemodynamic changes in preceding afterload could explain differences in LV function at same preceding CL. Our combined clinical-computational study highlights the variability in GLS measurement during AF and provides new insight into the potential hemodynamic mechanisms determining LV function in AF patients. Abstract Figure.

Plasma Homocysteine and Cardiovascular Organ Damage in a Population with a High Prevalence of Risk Factors.

It is unclear whether plasma homocysteine (Hcy) has a direct noxious impact on the cardiovascular (CV) system or whether its association with cardiovascular events (CVEs) is mediated by established risk factors. To explore the role of Hcy in CV impairment, the study evaluated cross-sectional relationships between plasma Hcy and indices of CV organ damage together with the associations of these indices with the history of CVEs. In 269 patients with a high prevalence of diabetes, dyslipidemia, and hypertension, the carotid intima-media thickness, ankle-brachial index (ABI), reactive hyperemic index, carotid-femoral pulse wave velocity (cfPWV), left ventricular (LV) mass, and cardiac index were measured. 132 patients had carotid plaque, 31 ABI < 0.90, 126 endothelial dysfunction, 66 increased cfPWV, 125 LV hypertrophy (LVH), 153 decreased cardiac index, and 115 a history of CVEs. Plasma Hcy levels were related to LV mass and ABI, after adjustment for covariates and creatinine. Significantly higher Hcy levels were found in patients with LVH (8.5 [4.4] vs 7.6 [2.8] μmol/L; adjusted P = .001) and ABI < 0.9 (10.4 [3.8] vs 7.9 [3.4] μmol/L; adjusted P = .001) than in those with LV mass and ABI within limits. Hcy levels were comparable between patients with and without carotid plaques, increased arterial stiffness, impaired endothelial, and LV pump function. Within markers of CV organ damage, only LVH was associated with a history of CVEs. This study demonstrated an independent association between Hcy and LV mass as well as between LVH and a history of CVEs and suggests that LVH may represent 1 of the pathophysiologic links between Hcy and CV risk.

Predicting left ventricular contractile function via Gaussian process emulation in aortic-banded rats.

Cardiac contraction is the result of integrated cellular, tissue and organ function. Biophysical in silico cardiac models offer a systematic approach for studying these multi-scale interactions. The computational cost of such models is high, due to their multi-parametric and nonlinear nature. This has so far made it difficult to perform model fitting and prevented global sensitivity analysis (GSA) studies. We propose a machine learning approach based on Gaussian process emulation of model simulations using probabilistic surrogate models, which enables model parameter inference via a Bayesian history matching (HM) technique and GSA on whole-organ mechanics. This framework is applied to model healthy and aortic-banded hypertensive rats, a commonly used animal model of heart failure disease. The obtained probabilistic surrogate models accurately predicted the left ventricular pump function (R2 = 0.92 for ejection fraction). The HM technique allowed us to fit both the control and diseased virtual bi-ventricular rat heart models to magnetic resonance imaging and literature data, with model outputs from the constrained parameter space falling within 2 SD of the respective experimental values. The GSA identified Troponin C and cross-bridge kinetics as key parameters in determining both systolic and diastolic ventricular function.This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’.

Focusing Heart Failure Research on Myocardial Fibrosis to Prioritize Translation

Heart failure (HF) has traditionally been defined by symptoms of fluid accumulation and poor perfusion, but it is now recognized that specific HF classifications hold prognostic and therapeutic relevance. Specifically, HF with reduced ejection fraction is characterized by reduced left ventricular systolic pump function and dilation and HF with preserved ejection fraction is characterized primarily by abnormal left ventricular filling (diastolic failure) with relatively preserved left ventricular systolic function. These forms of HF are distributed equally among patients with HF and likely require distinctly different strategies to mitigate the morbidity, mortality, and medical resource utilization of this disease. In particular, HF is a significant medical issue within the US Department of Veterans Affairs (VA) hospital system and constitutes a major translational research priority for the VA. Because a common underpinning of both HF with reduced ejection fraction and HF with preserved ejection fraction seems to be changes in the structure and function of the myocardial extracellular matrix, a conference was convened sponsored by the VA, entitled, “Targeting Myocardial Fibrosis in Heart Failure” to explore the extracellular matrix as a potential therapeutic target and to propose specific research directions. The conference was conceptually framed around the hypothesis that although HF with reduced ejection fraction and HF with preserved ejection fraction clearly have distinct mechanisms, they may share modifiable pathways and biological mediators in common. Inflammation and extracellular matrix were identified as major converging themes. A summary of our discussion on unmet challenges and possible solutions to move the field forward, as well as recommendations for future research opportunities, are provided.

Are increased left ventricular strains compensatory effects in lipedema? Detailed analysis from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study.

Lipedema is a chronic, common but underdiagnosed disease masquerading obesity, with female predominance, characterized by disproportional abnormal adipose tissue distribution of the lower and also upper extremities. The present study was designed to determine whether lipedema is associated with three-dimensional (3D) speckle-tracking echocardiography (3DSTE)-derived left ventricular (LV) deformation abnormalities, and to assess the effects of 1-hour use of medical compression stockings (MCS). The present study comprised 19 female patients with lipedema (mean age: 42.2 ± 12.4 years), compared to 28 age-matched healthy female controls (mean age: 42.0 ± 9.8 years). Lipedema patients showed larger left atrial and LV dimensions and greater LV ejection fraction than controls, without significant difference in other echocardiography variables. Lipedema patients had greater 3DSTE-derived global and mean segmental LV circumferential and area strains than controls. Following 1-hour use of wearing MCS, neither global and nor mean segmental LV strains showed significant impairment or improvement. Increased LV strains could be compensatory effects maintaining LV pumping function in lipedema. Short-term wearing of MCS has no global effect on LV strains.

Admission blood glucose and echocardiography to predict major adverse cardiac events in acute coronary syndrome: a review

A life-threatening presentation of coronary artery disease is acute coronary syndrome (ACS). The major adverse cardiac events (MACE) after acute coronary syndrome include life threatening arrhythmias, cardiac failure, cardiogenic shock, recurrent ischemia and sudden death. Patients with severe and moderate LV dysfunction are more likely to have triple vessel disease. Regional wall motion abnormality assessed by regional wall motion index using 2D-echocardiography correlates with infarct size which in turn predicts the occurrence of major adverse cardiac events (MACE) in patients with acute coronary syndrome. The cause for cardiogenic shock is left ventricular pump failure due to extensive damage to the myocardium and infarct related mechanical complications. In patients admitted with acute coronary syndrome, 5% develop ventricular tachycardia or ventricular fibrillation especially after 48 hours after hospital admission. Hyperglycemia causes stronger sympathetic activation in patients with severe illness and hence increased glucose levels. Insulin resistance not only causes hyperglycemia but can also lead to reduced energy production in the heart and lower tolerance to hypoperfusion and acts as an indicator of systemic and organ specific metabolic dysregulation and also stress hyperglycemia is implicated in the activation of pathological processes that causes cellular and tissue injury like increasing free radical formation and oxidative stress, inducing prothrombotic stress and worsening endothelial function. Hence higher levels of admission time blood glucose, hypoglycaemia during hospital stay, persistent hyperglycemia are considered as poor prognostic markers in patients with acute coronary syndrome.

Transplantation of Endothelial Progenitor Cells in Obese Diabetic Rats Following Myocardial Infarction: Role of Thymosin Beta-4.

Endothelial progenitor cells (EPCs) are bone-marrow derived cells that are critical in the maintenance of endothelial wall integrity and protection of ischemic myocardium through the formation of new blood vessels (vasculogenesis) or proliferation of pre-existing vasculature (angiogenesis). Diabetes mellitus (DM) and the metabolic syndrome are commonly associated with ischemic heart disease through its pathological effects on the endothelium and consequent endothelial dysfunction. Thymosin-β4 (Tβ4) which expressed in the embryonic heart is critical in epicardial and coronary artery formation. In this study, we explored the effects of Tβ4 treatment on diabetic EPCs in vitro and intramyocardial injection of Tβ4-treated and non-Tβ4 treated EPCs following acute myocardial infarction (MI) of diabetic rats in vivo. It was found that 10 ng/mL Tβ4 increased migration, tubule formation, and angiogenic factor secretion of diabetic EPCs in vitro. In vivo, although implantation of Tβ4 treated diabetic EPCs significantly increased capillary density and attracted more c-Kit positive progenitor cells into the infarcted hearts as compared with implantation of non-Tβ4 treated diabetic EPCs, the significantly improved left ventricular ejection fraction was only found in the rats which received non-Tβ4 treated EPCs. The data suggests that a low dose Tβ4 increases diabetic EPC migration, tubule formation, and angiogenic factor secretion. However, it did not improve the effects of EPCs on left ventricular pump function in diabetic rats with MI.

Global Longitudinal Strain, Ejection Fraction, Ventriculo‐Arterial Coupling and Their Interrelationships in Heart Failure Patients with Different Phenotypes

Ejection fraction (EF) is a popular metric to evaluate left ventricular (LV) systolic function. The EF is a ratio, based on paired volume measurements, similar as the more recently introduced ventriculo‐arterial coupling (VAC) index, being the ratio of two elastances. Their dimensionless nature requires consideration of the associated companion (i.e., the hypotenuse calculated from the constituent pair and denoted as EFC and VACC, respectively). This insight becomes clear when considering the LV volume domain representation.Global longitudinal strain (GLS) has been advanced as a preferred alternative for EF. Reportedly, the connection between EF and GLS is weak, thus confirming that these ratio‐based metrics focus on partial and likely dissimilar aspects of LV pump function. To overcome these limitations the present study addresses the relationships between GLS and EF or VAC (assuming vanishing intercept), as well as the newly introduced complementary metrics EFC and VACC.In 25 heart failure (HF) patients (43 – 83 years, 9 women) end‐systolic volume (ESV), end‐diastolic volume (EDV), diastolic interventricular septal thickness (IVST), and posterior wall thickness (PWT) were determined by echocardiography. Data are analyzed following informed consent. IVST and PWT were used to derive LV mass (LVM). GLS was obtained via speckle tracking echocardiography. When appropriate, these data were indexed (i) to body surface area (BSA).Significant sex‐specific differences were found for BSA (P&lt;0.0001), LVM (P=0.04) and stroke volume (P=0.02), but the latter not when normalized to BSA. The volume regulation graph (VRG) which relates ESV to EDV yields R=0.92, implying an inverse nonlinear relationship, either logarithmic or of the more robust type EF = 1+c1ESV / (c2+ESV), where c1 and c2 are population‐based constants. These data indicate that a sex‐specific cut‐off at ESVi=30 mL/m2 for men and at ESVi=20 mL/m2 for women separates the two major HF phenotypes, also demonstrating that the current practice of phenotyping via the ratio based metric EF is undesired and not required. LVM correlates (P&lt;0.001) with EDV (R=0.76) and with EFC (R=0.76). GLS moderately correlates with EF (R=−0.63, P&lt;0.001), VAC (R=−0.65, P&lt;0.001), EFC (R=0.49, P=0.025), and with VACC (R=0.43, P=0.03).The interpretation of EF, VAC and GLS in terms of physiology is debatable, as each refers to a ratio without physical dimension(s). In contrast, EFC and VACC carry a clear physical unit (namely mL), comparable to the primary variables ESV and EDV. The fact that GLS only moderately correlates with major clinically used metrics such as EF and VAC, suggests that there is a future place for the GLS companion, which deserves evaluation of its physiology‐based impact.Support or Funding InformationnoneEjection fraction (EF) versus end‐systolic volume index (ESVi) for two heart failure (HF) phenotypes, distinguished on the basis of a criterion applied to ESVi, which differs for women (red line) and men (blue line).Figure 1

Increased Platelet Glycoprotein IIb/IIIa Activation Precedes Continuous-Flow Left Ventricular Assist Device Pump Thrombosis Events

Continuous-flow left ventricular assist devices (CFLVAD) in management of end-stage heart failure continues to expand. Adverse events however remain high. Better understanding of platelet activation in the context of CFLVAD therapy may help reduce bleeding and pump thrombosis (PT) risks to patients. Whole blood was collected 15 days post CFLVAD implant. Blood samples were stimulated, stained with anti- CD61, gpIIb/IIIa complex (PAC-1), CD62P, fixed, and analyzed by flow cytometry. Unstimulated blood +/- RDGS were prepared as controls. Platelets were gated as CD61+ and CD62P and PAC-1 signal determined activation. Adverse events (PT/bleeding) were determined through INTERMACS. Median age was 62 years, 21% female, 17 implanted with centrifugal and 2axial flow pumps. Groups consisted of those without an adverse event (No event, n=11), PT (w or w/o bleed, n=3), and Bleeding event only (n=5). Healthy volunteers (n=5) were recruited to serve as controls. CFLVAD implantation alone did not increase PAC-1 platelet activation in patients 15 days post implant. In addition, CFLVAD implantation did not prevent platelets from becoming activated following stimulation. In patients with PT, PAC-1 was higher in unstimulated blood (9.9%) when compared to No event (2.22% p=0.023) and healthy controls (0.66% p=0.028). This elevation of PAC-1 was detected before the clinical manifestation of pump thrombosis (8, 139, 274 days). In addition, following stimulation, PAC-1 was increased significantly in PT patients (89.6%) compared to both No event (54.8% p<0.001) and Bleeding event (60.2% p=0.011) groups. Platelet gpIIb/IIIa activation from PT patients was evident prior to thrombus development. PT patients even had the largest response to stimulation. This increase in platelet activation could serve as a predictor of device-related thrombosis events and may have important implications in targeted therapy to reduce PT in CFLVAD patients.

A New Approach to Evaluating the Pumping Function of the Heart by the Myocardial Work.

The function of left ventricular (LV) contractility consists of two aspects, the force of myocardial contraction, which provides a sufficient pressure gradient to open the heart valves, and deformation, which determines the actual cardiac output [1, 2]. The relationship between the characteristics of LV deformation and LV volume parameters remains poorly understood. The LV work may reflect the dependence between the volume and deformation characteristics of the left ventricle. Myocardial work indexes can more accurately describe the systolic LV function when the LV ejection fraction (EF) and global longitudinal strain (GLS) are not informative enough [3, 4]. A new approach was proposed for evaluating the LV pumping function, and a parameter was developed to characterize the efficiency of myocardial work for the cardiac cycle period from the aortic valve opening (AVO) to its closure (AVC), that is, the phase of blood ejection from the left ventricle.

546 Machine-learning based exploration of echocardiographic patterns and clinical parameters to understand their relation to death or transplant in pediatric dilated cardiomyopathy

Abstract Background Pediatric dilated cardiomyopathy (DCM) affects left ventricular (LV) function and carries a high risk of death or heart transplantation. However, the relation of LV regional function and inefficiency to clinical outcomes is underexplored. Purpose The aim of this study was to understand the relationship of regional LV mechanics, global LV function and clinical characteristics to the outcomes of death or heart transplant in children with DCM; through the integration of a vast amount of information enabled by unsupervised machine learning techniques. Methods DCM was defined by a LV end-diastolic dimension z-score &amp;gt; 2 and LV ejection fraction (EF) &amp;lt;55%. Longitudinal strain curves were sampled at 6 LV lateral wall and septal locations from the 4ch apical view. In addition, we analyzed other echo parameters including the aortic outflow pattern as a measure of LV pump function, QRS duration, LV EF, indexed end-diastolic LV dimension, global longitudinal strain and patient characteristics including age, weight, body surface area and medications (diuretics, ACE inhibitor, beta-blockers, mineralocorticoid receptor antagonist, digoxin, inotropes, antiarrhythmics). We used an unsupervised machine learning algorithm (multiple kernel learning) to reduce the dimensionality of these data, and position patients based on similarities. We subsequently used k-means clustering to recover homogeneous groups of patients. We then interpreted the data patterns associated to each of the groups for the occurrence of death or transplant through non-linear regression analysis (multi-scale kernel regression). Results 50 children with DCM (age 0 to 18 years) were analyzed. Clustering on the two first dimensions of the low-dimensional space resulted in three clusters (Figure A), with significantly different proportions of the composite outcome of death or heart transplant (Cl1 = 79%, Cl2 = 50%, Cl3 = 20%; p = 0.01). The group with the highest proportion of death or transplant (cluster 1) comprised the oldest and most frequently medicated subjects, with impaired LVEF and GLS, and with the widest QRS duration (p &amp;lt; 0.01) (Figure B). The group with the second highest proportion of death or transplant (cluster 2) comprised patients with the lowest LVEF (p &amp;lt; 0.01) and GLS (p &amp;lt; 0.001), reduced and delayed peak aortic outflow velocity and severely impaired basal and apical LV strain (Figure C). In contrast, the group with highest transplant-free survival (cluster 3) had the highest LVEF and GLS values, the most synchronous LV contraction as assessed by strain and QRS duration and the highest amplitude and earliest peaking aortic flow. Conclusion Our results serve as a proof-of-concept that machine-learning based approaches can be useful to explore and understand which regional and global echo parameters in combination with clinical parameters are associated with a higher risk of death or transplant in pediatric DCM. Abstract 546 Figure