Measures Of Systolic Function Research Articles

Strain Imaging and Ventricular Arrhythmia.

Ventricular arrhythmia is one of the main causes of sudden cardiac death. Hence, identifying patients at risk of ventricular arrhythmias and sudden cardiac death is important but can be challenging. The indication for an implantable cardioverter defibrillator as a primary preventive strategy relies on the left ventricular ejection fraction as a measure of systolic function. However, ejection fraction is flawed by technical constraints and is an indirect measure of systolic function. There has, therefore, been an incentive to identify other markers to optimize the risk prediction of malignant arrhythmias to select proper candidates who could benefit from an implantable cardioverter defibrillator. Speckle-tracking echocardiography allows for a detailed assessment of cardiac mechanics, and strain imaging has repeatedly been shown to be a sensitive technique to identify systolic dysfunction unrecognized by ejection fraction. Several strain measures, including global longitudinal strain, regional strain, and mechanical dispersion, have consequently been proposed as potential markers of ventricular arrhythmias. In this review, we will provide an overview of the potential use of different strain measures in the context of ventricular arrhythmias.

Echocardiographic values for normal conditioned and unconditioned North American whippets.

Echocardiographic reference intervals have not been reported for North American whippets, or for whippets that have undergone pet-level athletic training. To develop normal echocardiographic reference intervals for North American whippets and investigate differences in echocardiographic parameters based on athletic conditioning in pet whippets engaged in competitive sports. One-hundred healthy North American whippets. Dogs were examined at national shows between 2005 and 2009. Echocardiographic reference intervals were constructed and the effect of athletic conditioning on parameters of structure and function was assessed. Two dimensional, M-mode, Doppler and tissue Doppler reference ranges for healthy North American whippets are presented. Measures of left ventricular (LV) chamber diameter were larger in conditioned whippets (N=25) and remained significantly larger than in unconditioned whippets (N=16) when normalized for weight using allometric equations. Calculated LV mass was higher in conditioned dogs than in unconditioned dogs, and this difference persisted when LV mass was normalized by weight. Mitral E velocity was higher in conditioned dogs than in unconditioned dogs, whereas E/A and measures related to systolic function were not different. Pet whippets in peak athletic condition have larger hearts than do less conditioned whippets, but measures of systolic function are similar. Whippet pet athletes may show eccentric LV hypertrophy at peak condition. Normal values for cardiac size and function in North American whippets might be considered abnormal if population-specific whippet reference intervals are not used in analysis.

Abstract P196: Metabolomic Associations With Cardiac Function and Incident Heart Failure in Multi-Ethnic Populations

Introduction: Measures of cardiac structure and function provide important diagnostic and prognostic information for heart failure (HF). Few studies have assessed the associations of circulating metabolites with cardiac structure and function. Hypothesis: We hypothesize that circulating metabolites that reflect aging process are associated with cardiac structure and function measures and incident HF. Methods: Participants from the Atherosclerosis Risk in Communities (ARIC) study visit 5 and the Hispanic Community Health Study / Study of Latinos (HCHS/SOL) study visit 1 who had serum metabolite measures but not prevalent HF were included. Linear regressions were used to examine the associations of metabolites with ten cardiac structure and function variables adjusting for clinical risk factors in each race and study strata, followed by random-effect meta-analyses. The Cox regression was applied to examine the relationship between those identified metabolites and incident HF post visit 5 in ARIC. Results: Among 589 analyzed metabolites, 179 were associated with cardiac structure or function measures in 706 Blacks, 3,358 Whites, and 1,380 Hispanics (FDR < 0.05). Forty-one metabolites were related to two or more measures, where 22 were associated with incident HF (308 HF cases, p<0.05, Figure). Metabolites were more associated with cardiac size or diastolic function compared to systolic function measures, i.e., C-glycosyltryptophan, an amino acid that is strongly correlated with age, was positively associated with left ventricular mass index (LVMI) and left atrial volume index(LVAI), as well as an increased risk of HF (HR=1.48); and dodecadienoate (12:2), a dicarboxylate that may have anti-aging property, was negatively associated with LVMI and LVAI, as well as a decreased risk of HF (HR=0.84). Conclusions: We identified multiple metabolites associated with cardiac structure and function measures in multi-ethnic populations, highlighting metabolic pathways in aging and their impact on HF.

Association of Left Ventricular Systolic Function with Diagonal Branch Flow in Patients with First Anterior ST-Elevation Myocardial Infarction Treated with Primary Angioplasty

Background: There are few studies about the impact of diagonal branch blood flow on echocardiographic findings in patients with first acute anterior myocardial infarction undergoing primary angioplasty. Objectives: We aimed to compare left ventricular systolic function measures in patients with first acute anterior ST-segment elevation myocardial infarction (STEMI) treated with primary angioplasty based on diagonal branch blood flow after the procedure. Methods: This study was a single-center study that enrolled patients with their first acute anterior STEMI treated with primary angioplasty in our center between October 2020 and March 2021. Patients were divided into two groups: The patients with final thrombolysis in myocardial infarction (TIMI) flow III in diagonal (sufficient diagonal flow) and patients with final TIMI flow less than III in diagonal (insufficient diagonal flow) after the procedure. The left ventricular Wall-Motion Score Index (WMSI) and left ventricular ejection fraction (LVEF) were compared between the two groups. Results: A total of 107 patients with first anterior STEMI treated with primary PCI were enrolled in the present study, of which 13 patients (12.1%) had insufficient diagonal flow after primary coronary angioplasty. The LVEF was lower in patients with insufficient diagonal flow (32.92 ± 7.29% vs. 39 ± 8.68%, P = 0.018). Also, this group had higher LV WMSI (1.68 ± 0.28 vs. 1.49 ± 0.26, P = 0.029). Conclusions: The present study showed that in patients with first acute anterior STEMI undergoing primary angioplasty, insufficient diagonal branch flow after the procedure was associated with worse left ventricular systolic function and higher LV WMSI.

Changes in cardiac function in Navy divers during four days of successive dives in very cold diving conditions.

There is limited knowledge of cumulative effect of repetitive cold-water diving on cardiac function. Single cold dives cause some known cardiological risks, such as malign arrhythmia, due to a concurrent activation of the sympathetic and parasympathetic autonomic nervous system. A previous study from warmer water dives has shown that successive dives cause a decrease in vagal tone and a less responsive cardiovascular system. The aim of this study was to evaluate changes in cardiac function with 2D echocardiography during 4 days of diving in near-freezing water. Left ventricle systolic function measures did not show any uniform changes. E/A ratio seemed to decrease successively with the number of dives. The diastolic tissue velocity of relaxing basal septum (e') showed a decreasing trend as well. Diastolic blood pressure seemed to increase from predive (mean: 83 RR mmHg) to postdive values (mean: 87 RR mmHg) (p=NS). Heart rate decreased significantly from predive (mean: 71 bpm, range: 56-103) to postdive values (mean: 60 bpm, range: 37-88) (p < 0.03). The study was conducted in very cold condition and with limited number of divers. Results of this preliminary study suggested a decreasing trend in left ventricular diastolic function in successive cold dives. Cumulative changes in cardiac function may cause health risks that need to be considered during cold water diving operations.

Too Little of a Good Thing: Strong Associations Between Cardiac Size and Fitness Among Women

BackgroundCardiorespiratory fitness (CRF) is associated with functional impairment and cardiac events, particularly heart failure (HF). However, the factors predisposing women to low CRF and HF remain unclear. ObjectivesThis study sought to evaluate the association between CRF and measures of ventricular size and function and to examine the potential mechanism linking these factors. MethodsA total of 185 healthy women aged >30 years (51 ± 9 years) underwent assessment of CRF (peak volume of oxygen uptake [Vo2peak]) and biventricular volumes at rest and during exercise by using cardiac magnetic resonance (CMR). The relationships among Vo2peak, cardiac volumes, and echocardiographic measures of systolic and diastolic function were assessed using linear regression. The effect of cardiac size on cardiac reserve (change in cardiac function during exercise) was assessed by comparing quartiles of resting left ventricular end-diastolic volume (LVEDV). ResultsVo2peak was strongly associated with resting measures of LVEDV and right ventricular end-diastolic volume (R2 = 0.58-0.63; P < 0.0001), but weakly associated with measures of resting left ventricular (LV) systolic and diastolic function (R2 = 0.01-0.06; P < 0.05). Increasing LVEDV quartiles were positively associated with cardiac reserve, with the smallest quartile showing the smallest reduction in LV end-systolic volume (quartile [Q]1: −4 mL vs Q4: −12 mL), smallest augmentation in LV stroke volume (Q1: +11 mL vs Q4: +20 mL) and cardiac output (Q1: +6.6 L/min vs Q4: +10.3 L/min) during exercise (interaction P < 0.001 for all). ConclusionsA small ventricle is strongly associated with low CRF because of the combined effect of a smaller resting stroke volume and an attenuated capacity to increase with exercise. The prognostic implications of low CRF in midlife highlight the need for further longitudinal studies to determine whether women with small ventricles are predisposed to functional impairment, exertional intolerance, and HF later in life.

S-29-5: EARLY CHANGES IN LEFT ATRIAL STRAIN AND GLOBAL VENTRICULAR FUNCTION IN HYPERTENSIVE PATIENTS WITH HEART FAILURE WITH PRESERVED EF

Background: Hypertension is one of leading causes in heart failure with preserved ejection fraction (HFpEF).Left atrial (LA) maximal volume and index (LAVI) had a prognostic value in patients with heart failure and incidence of atrial fibrilation (AF). Recently, LA mechanical function and LA strain have been introduced as alternative methods to assess LA performance more accuratly. Aim: To evaluate the relation between early changes in LA function and strain (PALS) and correlate the association with global left ventricular (LV) function and longitudinal strain (GLS) in patients with HFpEF.and arterial hypertension. Methods: We evaluated 152 subjects in sinus rhythm: 22 normals (31y ± 5), and 70 pts with HFpEF (65y ± 12), 60 pts HFrEF (64 y ± 10). Echocardiography was performed in all patients and follow up after 12 monts and analyzed offline in order to extract the global and segmental strain values of the LV and LA and LA volume and LAVI. Results: The two groups of patients were comparable for most of clinical variables. LV volumes, ejection fraction, stroke volume, and mitral valve effective regurgitant orifice were similar between the two groups. The LA diameter and maximal volume were higher in HFrEF group. The GLS is significantly reduced in HFrEF group. LV GLS is the main parameter for myocardial dysfunction, which changed significantly in the HFrEF (p &lt; 0,001) at 12mFU. Reduced PALS in HFrEF was associated with impairment of all measures of LV systolic and diastolic function and events of atrial fibrilation / 33 % in HFrEF and 12 % in HFpEF/ and the correlation between global longitudinal strain and PALS was highly significant (p &lt; 0.001; r = 0.71). At 12mFU, PALS was significantly associated with lower global longitudinal strain in group with HFrEF (p &lt; 0.001, r = 0.61), LAVI &gt; 28 ml/m2 (p &lt; 0.01,r = 0.57) and slightly decreased in HFpEF /p &lt; 0.5, r = 0.34/. ROC analysis shows the cut of value of 29 % for PALS which correlated with AF events. Conclusions: PALS and GLS are significantly reduced in HFpEF patients and decreased in HFpEF. PALS provides additional,prognostic value beyond LA volume and LAVI. Severe LV myocardial dysfunction and reduced GLS and decreased PALS, even still normal LAVI is a prognostic index for AF.

Cardiac strain is lower among women with HIV in relation to monocyte activation.

Women with HIV (WWH) face heightened risks of heart failure; however, insights on immune/inflammatory pathways potentially contributing to left ventricular (LV) systolic dysfunction among WWH remain limited. Massachusetts General Hospital, Boston, Massachusetts. Global longitudinal strain (GLS) is a sensitive measure of LV systolic function, with lower cardiac strain predicting incident heart failure and adverse heart failure outcomes. We analyzed relationships between GLS (cardiovascular magnetic resonance imaging) and monocyte activation (flow cytometry) among 20 WWH and 14 women without HIV. WWH had lower GLS compared to women without HIV (WWH vs. women without HIV: 19.4±3.0 vs. 23.1±1.9%, P<0.0001). Among the whole group, HIV status was an independent predictor of lower GLS. Among WWH (but not among women without HIV), lower GLS related to a higher density of expression of HLA-DR on the surface of CD14+CD16+ monocytes (ρ = -0.45, P = 0.0475). Further, among WWH, inflammatory monocyte activation predicted lower GLS, even after controlling for CD4+ T-cell count and HIV viral load. Additional studies among WWH are needed to examine the role of inflammatory monocyte activation in the pathogenesis of lower GLS and to determine whether targeting this immune pathway may mitigate risks of heart failure and/or adverse heart failure outcomes. Clinical trials.gov registration: NCT02874703.

Cardiac function’s in patients with chronic kidney disease

Background: To assess the cardiac functions in patients with chronic kidney disease (CKD).Methods: 150 patients with CKD were randomly selected. 12 lead ECG were performed to detect CVD. All Patients were diagnosed with CKD. The left ventricular ejection fraction (LVEF) and fractional shortening (FS) were taken as measures of LV systolic function. Diastolic function was determined by measuring early to late peak velocities (E/A) ratio by spectral Doppler LV inflow velocity. Results: Male: female 95 and 55, hypertension 67% was leading cause of CKD. Diastolic dysfunction as denoted by E/A ratio of less than 0.75 or more than 1.8 was present in 64% of patients. Regional wall motion abnormality (RWMA) was present in 14%. LVH was present in 74%. Systolic dysfunction as measured by reduced fractional shortening (&lt;25%) and decreased LVEF (&lt;52%) was present in 8% and 12% respectively. PE was noted in 15% of patients. Valvular calcification in 8% of CKD patients. Mean LV internal diameter in diastole was 41±6 mm. Mean Interventricular septum diameters in systole was11.9±1.21 mm. Mean LA diameter was 29±4 mm. Statistically significant difference was noted in LVH and E/A ratio in hypertensive group as compared to normotensive group.Conclusions: LV diastolic dysfunction also happens in patients who having the early stage of CKD. Hypertensive patients along with CKD had found higher widespread presence of diastolic and systolic dysfunction as compared to normotensive.

The role of 3D speckle tracking echocardiography in the diagnosis of obstructive sleep apnea and its severity

There is a consistent relationship between obstructive sleep apnea (OSA) and cardiovascular diseases. It is already recognized that OSA may influence the geometry and function of the right ventricle (RV). This has encouraged the development of echocardiographic evaluation for screening of OSA and its severity. Three-dimensional speckle tracking echocardiography (3D STE) is in assumption better, compared with 2D STE, because it overcomes the standard 2D echo limitations. Thus, the purpose of our study is to evaluate whether 3D STE measurements, could predict the positive diagnosis and severity of OSA. We enrolled 69 patients with OSA and 37 healthy volunteers who underwent a cardiorespiratory sleep study. 2DE was performed in all patients. RVEF and 3D RVGLS were measured by 3DSTE. NT pro BNP plasma level was also assessed in all participants. 3D RV GLS (− 13.5% vs. − 22.3%, p < 0.001) and 3D RVEF (31.9% vs. 50%, p < 0.001) were reduced in patients with OSA, compared with normal individuals. 3D Strain parameters showed better correlation to standard 2D variables, than 3D RVEF. Except for NT pro BNP (p = 0.059), all parameters served to distinguish between severe and mild-moderate cases of OSA. 3D STE may be a reliable and accurate method for predicting OSA. Consequently, 3D RV GLS is a good tool of assessing the RV global function in OSA, because it correlates well with other established measurements of RV systolic function. Furthermore, 3D RV GLS was a precise parameter in identifying severe cases of OSA, while NT pro BNP showed no association.

1103 A SINGLE CENTER EXPERIENCE ON RIGHT VENTRICULAR VS. BIVENTRICULAR FAILURE ASSESSMENT GUIDED BY CMRI AND 3-D ECHOCARDIOGRAPHY

Abstract Background Currently, echocardiography represents the first-line diagnostic test for risk stratification in myocardial dysfunctions, cardiomyopathies (CM) and valvular heart diseases. Three-dimensional (3D) echo imaging improves the accuracy of cardiac chamber volumes evaluation in complex cardiac anatomies and eliminates the need for geometric modelling as well as the errors caused by foreshortened views. On the other side, cardiac magnetic resonance imaging (CMRi) has limited availability and relative high costs, whereas it provides the most accurate and reproducible measurement of atrial, biventricular global and regional systolic function, and can detect myocardial oedema, fibrosis, infiltration, and perfusion defects. Moreover, fibrosis detection by late gadolinium enhancement (LGE) contributes to ventricular tachyarrhythmias (VT) risk stratification. Our experience considers the diagnostic and prognostic role of an integrated approach guided by CMRi and 3-D echocardiography in two different subtypes of arrhythmogenic cardiomyopathy (ACM). Methods In December 2018, a sixty-six-year-old man, without familiar history of sudden cardiac death (SCD) or cardiomyopathies was admitted to emergency department for dyspnoea and chest pain. First ECG showed a VT with right bundle branch block morphology, rapidly cardioverted. In July 2019, a fifty-six-year-old woman, without family history of SCD or ACM, with previous sustained VT episode with right ventricular (RV) outflow tract pattern was admitted to our centre for further examinations. In both cases routine exams were carried out, and, in the suspicious of ACM, genetic tests, 3-D echo and CMRi were performed. Results in the first case, 3-D echo showed hypo-akinesia of left ventricular posterior-lateral wall, reduced ejection fraction (EF) 40%; enlargement of right chambers (RV end-diastolic volume, EDV, 194 ml; RV end-systolic volume, ESV, 152 ml) with reduced indices of systolic function (TAPSE 13 mm; FAC 25%; RV S’ 7 cm/s). CMRi showed global hypokinesia and free lateral wall bulging with RV EDV 235 ml; RV ESV 147 ml; RV EF 26% and reduced left ventricular EF 36%. In the second case, 3-D echo documented RV EDV 175 ml; RV ESV 64 ml with preserved systolic function (TAPSE 20 mm; FAC 47%; global longitudinal strain, GLS, -19%) and bulging of medio-distal free wall, normal EF 57%; GLS -22.7%. At CMRi there was evidence of slight RV dilatation (RV EDV 193 ml; RV ESV 88 ml) and hypokinetic, mildly-reduced global systolic function (EF 49%), images of LGE due to possible diffuse myocardial fibrosis of the free wall with morpho-functional anomalies of the RV. Both cases had negative genetic tests. ACM diagnosis was made according to Padua criteria, and programmed ventricular stimulation (sustained VT induction with hemodynamic instability) mandated cardioverter/defibrillator implantation in both cases. Conclusions In our experience, an integrated approach guided by CMRi and 3-D echocardiography in subtypes of ACM plays a pivotal role for assessing diagnosis by refining disease characterization through additional parameters. The non-invasive high-risk stratification was confirmed by electrophysiologic studies. Further studies for prognostic correlation between CMRi/advanced echocardiography and arrhythmic phenotype are mandatory.

TRANSTHORACIC SHOCKS LEAD TO REGIONAL BI-VENTRICULAR DIASTOLIC DYSFUNCTION IN TERRITORIES WITH ACUTE MYOCARDIAL INJURY

<h3>Introduction</h3> Electric defibrillations and cardioversion are standard interventions to terminate arrhythmia. Recent evidence hints to acute post shock myocardial injury. However, that injury may follow unique pathways in every individual. Common functional measures such as ejection fraction are limited in that they represent only global ventricular function. Cardiovascular magnetic resonance feature tracking (CMR-FT) is a technique that can quantify myocardial contraction and relaxation on a regional level. The purpose of this analysis was to investigate the impact of acute myocardial injury after serial transthoracic shocks on regional systolic and diastolic myocardial deformation in a healthy animal model. <h3>Methods</h3> Ten healthy anaesthetized swine were scanned in a 3 Tesla MRI with a standard short axis cine and a clinical T1 mapping sequence in three short axis slices to detect myocardial edema. Five transthoracic shocks with 200 Joules each were applied within five minutes. Five hours post-shock the same images were re-acquired. Six control animals underwent the same protocol without shocks. Changes in regional peak strain as a measure of systolic function, and early diastolic strain rate as a measure of diastolic function were evaluated using CMR-FT analysis in circumferential orientation for both the left (LV) and right ventricle (RV). T1 maps of the LV were analyzed and reported per myocardial AHA segment as a measure of myocardial edema. For the RV, a region of interest (ROI) was contoured in each of the 3 short-axis slices. The regional changes in strain in comparison to the development of myocardial injury (ΔT1 mapping) over the course of 5h were statistically assessed using a mixed effects model accounting for the electrical intervention and multiple measurements per individual. <h3>Results</h3> Global circumferential peak strain worsened in both ventricles (LV: -15.6±3.3% to -13.0±3.6%, p<0.01; RV: -16.1±2.3% to -12.8±4.8%, p=0.03). Additionally, LV early diastolic strain rate slowed from baseline to the 5h timepoint (1.19±0.35 to 0.95±0.37/s, p = 0.02) in shocked animals. Whereas no change was observed for any global strain parameters in the control group. There was no linear association with regional LV peak strain with T1 changes (p=0.97). However, an increase in T1 was colocalized to a reduction in early diastolic strain rate (p = 0.03), where early diastolic strain rate slowed by -0.25/s every 100ms increase in T1. On the other hand, both RV systolic and diastolic function worsened in the presence of increased regional RV T1 with a change in peak strain of 2.7% and a deceleration of diastolic strain rate (–0.42/s) per 100ms increase in RV T1 (p<0.05). <h3>Conclusions</h3> Serial transthoracic shock in a healthy swine model attenuate biventricular systolic function, but it is the development of regional diastolic dysfunction that is associated with the onset of colocalized myocardial edema. Future studies are warranted to assess these effects of electrical interventions in clinical settings.

COMPARISON OF GLOBAL LONGITUDINAL STRAIN WITH LEFT VENTRICULAR EJECTION FRACTION AS A PREDICTOR FOR IABP INSERTION IN PATIENTS UNDERGOING OFF-PUMP CORONARY ARTERY BYPASS GRAFTING: A PILOT STUDY

<h3>Objective</h3> Prophylactic use of intra-aortic balloon pump (IABP) mainly depends on left ventricular (LV) systolic function. Global longitudinal strain (GLS) is the most studied parameter for LV strain. It has proved to be more sensitive than LV ejection fraction (EF) as a measure of LV systolic function and is a strong predictor of outcome. The primary aim was to determine whether GLS can be used as a reliable marker and its cut-off value for IABP insertion in patients undergoing elective off-pump coronary artery bypass grafting (OPCABG). The secondary aim was to correlate echocardiographic parameters with intensive care unit (ICU) parameters to predict early post-operative outcome. <h3>Design</h3> A prospective observational clinical study. <h3>Setting</h3> Single university hospital. <h3>Participants</h3> 100 adult patients scheduled for elective OPCABG. <h3>Intervention</h3> None <h3>Measurements and Main Results</h3> 2D speckle tracking echocardiography (STE) estimated GLS was computed and LV EF measured by 3D echocardiography. The study predicted that IABP insertion correlates better with GLS (post-revascularization > pre-revascularization) than with 3D LV EF. Receiver operating characteristics (ROC) curve analysis revealed highest area under the curve (AUC, 0.972) with cut-off value of > -9.8% for GLS with maximum combined sensitivity and specificity compared to 3D LV EF (AUC, 0.938) with cut-off value of ≤44%. ICU parameters show better correlation with E/e'> GLS > WMSI than 3D LV EF. <h3>Conclusion</h3> GLS is a better predictor of IABP insertion compared to 3D LV EF in patients undergoing OPCABG.

Detection of early cardiac disease manifestation in propionic acidemia - Results of a monocentric cross-sectional study.

In propionic acidemia (PA) myocardial involvement is common and includes development of cardiomyopathy, life-threatening acute heart failure, and acquired long-QT syndrome. We sought to investigate which echocardiographic parameters of left ventricular systolic and diastolic function indicate early cardiac disease manifestation in PA. This is a prospective observational study (cross-sectional design) in a Tertiary Medical Care Center. Individuals with confirmed PA were enrolled and the following cardiac investigations were performed in all study individuals: echocardiographic measurements of systolic and diastolic left ventricular (LV) function (LV fractional shortening (LV-FS), LV ejection fraction by biplane modified Simpson's (LV-EF), mitral annular plane systolic excursion (MAPSE), LV global longitudinal strain (LV-GLS) by speckle tracking echocardiography (STE), pulsed Doppler analyses of mitral valve (MV) inflow velocities (MV E/A) and MV deceleration time (DT-E), tissue doppler imaging (TDI) of the mitral annulus (MV E/e'), and LV myocardial performance index (LV-MPI). LV and left atrial (LA) diameters were assessed. 12‑lead electrocardiograms (ECG) were recorded and corrected QT intervals (QTc) calculated. Clinical phenotype and laboratory parameters at the time of cardiac investigation were assessed. Besides descriptive analyses we analyzed frequency, onset, and combinations of echocardiographic and ECG data as well as their correlations with clinical and biochemical findings. The effects of 'age at visit' and LV functional parameters on QTc were analyzed with multiple regression. A total of 18 patients with confirmed PA were enrolled. Median age at PA onset was 6 days (range 1-357 days). Median age at visit for cardiac evaluation was 13.1 years (range 0.6-28.1 years). LV-GLS was abnormal in 72.2%, LV-EF in 61.1%, MAPSE in 50%, MV E/e' in 44.4%, LV-MPI in 33.3%, LV-FS in 33.3%, and MV E/A in 27.8%. In cases with normal or near normal LV-FS, LV-GLS was pathological in 5/10, LV-EF in 4/10, and MAPSE in 3/10. The probability of developing LV dysfunction - systolic and diastolic - increases with age. LV-MPI is a reliable parameter to indicate systolic LV-dysfunction in combination with a dilated LV, i. e. dilated cardiomyopathy (DCM) in PA. Multiple regression reveals a significant positive association between LV diameters and QTc. Abnormal LV-GLS significantly correlates with reduced muscle strength, muscle tone and/or abnormal gross motor function. Our data suggests a high prevalence of cardiac disease manifestation in PA, considerably higher than in previous studies, where only LV-FS was used to assess LV function. Usage of advanced echocardiographic techniques, such as LV-GLS assessment, may allow for early detection of subtle LV dysfunction in PA, and may lead to timely cardiac treatment but also consideration of liver transplantation to prevent development of manifest cardiac complications.

Echo-Doppler measures of right ventricular systolic function are affected by reduced left ventricular systolic function.

Objective right ventricular (RV) systolic function assessment is attained using a series of well-described and validated echo-Doppler measurements. However, how left ventricular (LV) systolic function influences these RV functional measurements has not been previously studied. Consequently, we conducted a retrospective proof-of-concept analysis to answer this important question. A total of 100 echocardiographic studies were included and patients were divided into two groups according to their LV ejection fraction (LVEF). The following RV variables were acquired including, tricuspid annular systolic plane excursion (TAPSE), velocity of the systolic motion (TA TDI s'), RV outflow tract velocity time integral (VTI), pulmonary vascular resistance (PVR), and the TAPSE to pulmonary artery systolic pressure (PASP) ratio. Not only TAPSE, TA DI s', RVOT VTI, PVR, and TAPSE/PASP were all significantly different between patients with normal versus abnormal LVEF; but most importantly, RVOT VTI (p<.0001) was the best discriminatory variable in assessing normal versus abnormal LVEF followed by TAPSE (p=.0001). Using receiver operating characteristic curve analysis, an RVOT VTI value>11 identified patients with a normal LVEF with a sensitivity of 90% and specificity of 76%. Based on our results, reduced LVEF affects the RV, likely mediated by mechanisms of interventricular dependence. Therefore, RV analysis cannot be performed in isolation as it not only reflects intrinsic RV systolic function but also, is dependent on LV systolic function. In cases of reduced LVEF, additional measures of RV assessment should be used to provide better objective assessments.

Abstract 11782: Senolytic Therapy Improves Diastolic Cardiac Function in Aged Mice

Introduction: Cellular senescence, an irreversible arrest of the cell cycle, is a recognized hallmark of aging that contributes to age-related multi-organ dysfunction and diseases. Evidence suggests that cardiomyocyte senescence plays a critical role in the development of age-related cardiac dysfunction. We tested the hypothesis that targeting senescent cells via intermittent administration of the senolytic drugs dasatinib and quercetin (D&amp;Q) will improve cardiac dysfunction in old mice. Methods: 21-month-old C57Bl/6 mice were treated with D&amp;Q or vehicle via oral gavage on a bi-monthly basis for three months. Systolic and diastolic cardiac function were assessed using echocardiography. Expression of inflammatory and matrix metalloproteinase genes was assessed using quantitative polymerase chain reactions. Cardiac tissue morphology was assessed by histological analysis. Results: D&amp;Q treatment improved ejection fraction (EF) in old mice (60.3% vs. 64.5%, con vs. D&amp;Q, p = 0.0207, n=18). Global longitudinal strain was improved by D&amp;Q treatment (-13.99% vs. -17.03%, con vs. D&amp;Q, p=.0005, n=18). Measures of diastolic function were improved after D&amp;Q treatment (n=18 for all): E/E’ (27.60 vs. 20.08, con vs. D&amp;Q, p&lt;.0001), isovolumetric relaxation time (IVRT, 22.74ms vs. 14.99ms, con vs. D&amp;Q, p&lt;.0001), and reverse longitudinal strain rate (rLSR, 4.64 1/s vs. 13.41 1/s, con vs. D&amp;Q, p&lt;.0001). Expression of inflammatory and matrix metalloproteinase genes ( cd3e, foxp3, tnf- α, mcp-1, mmp9 ) was lower in hearts from D&amp;Q treated compared to control mice (p≤0.05). Extracellular matrix collagen expression was lower in cardiac tissue from D&amp;Q treated compared to control (p&lt;0.01). Conclusions: For the first time we report a significant improvement in diastolic function in aged mice when treated long term with the senolytic therapy dasatinib and quercetin. Measurements of systolic function also improved, but not to the same degree as observed for diastolic function. Overall, senolytic therapy with D&amp;Q represents an attractive option to explore for the treatment of diastolic heart failure in humans.

Abstract 12798: Plasma Ferritin, Incident Heart Failure Phenotypes, And Cardiac Dysfunction in Late Life: The Atherosclerosis Risk in Communities Study

Introduction: Iron deficiency affects 10% of adults aged 70 years or older and is associated with worse symptom burden and a higher risk of hospitalization in adults with heart failure (HF) with reduced ejection fraction (HFrEF) in mid-life. However, the relationships between iron deficiency and incident HF, HFrEF and HF with preserved EF (HFpEF) in late life remain incompletely understood. Hypothesis: Iron deficiency, as measured by lower plasma ferritin levels, is associated with an increased risk of incident HF, HFrEF, and HFpEF in older adults. Methods: We included 3,567 participants (mean age 75 years, 56% women and 14% Black) from the ongoing, ARIC study who had plasma ferritin measured by an aptamer assay (SomaLogic) and were free from prevalent HF and anemia (Hb &lt;13 for men and &lt;12 for women). The associations of log 2 -transformed plasma ferritin with adjudicated incident overall HF, HFrEF (LVEF &lt; 50%) and HFpEF were estimated using Cox proportional hazards models. The associations of plasma ferritin with echocardiographic measures of cardiac size and function at Visit 5 were estimated with linear regression models. All models were adjusted for age, sex, race, smoking, body mass index, coronary heart disease, diabetes, hypertension, atrial fibrillation and eGFR. Results: Over a median 7 years of follow-up, 312 incident HF events occurred (140 HFrEF, 137 HFpEF, 51 unknown EF). Lower ferritin level was associated with a higher risk of overall HF and HFpEF, but not HFrEF ( Figure ). Lower ferritin levels associated with a higher E/e' ratio (standardized beta [95% CI]: 0.06 [0.03-0.08]; P&lt;0.01). Plasma ferritin levels did not associate with LV mass index or measures of LV systolic function (ejection fraction, global longitudinal strain; all P &gt; 0.05). Conclusion: Lower plasma ferritin levels associate with higher LV filling pressure and greater risk of incident HF, and in particular HFpEF, in late life. Iron deficiency may contribute to the pathophysiology of HF in late life.

Indicators of haemodynamic instability and left ventricular function in a porcine model of esmolol induced negative inotropy

To investigate if the Hypotension Prediction Index was an early indicator of haemodynamic instability in a negative inotropy porcine model, and to assess the correlation of commonly measured indicators of left ventricular systolic function. Eight anaesthetised pigs were volume resuscitated and then underwent an incremental infusion of esmolol hydrochloride (0-3000 mg/hr), following which it was then reduced in a stepwise manner. Full haemodynamic measurements were taken at each stage and measurements of left ventricular systolic function including left ventricular stroke work index, ejection fraction and peripheral dP/dT were obtained. At an infusion rate of 500 mg/hr of esmolol there were no significant changes in any measured variables. At 1000 mg/hr MAP was on average 11 mmHg lower (95% CI 1 to 11 mmHg, p = 0.027) with a mean of 78 mmHg, HPI increased by 33 units (95% CI 4 to 62, p = 0.026) with a mean value of 63. No other parameters showed significant change from baseline values. Subsequent increases in esmolol showed changes in all parameters except SVV, SVR and PA mean. Correlation between dP/dt and LVSWI was 0.85 (95% CI 0.77 to 0.90, p < 0.001), between LVEF and dP/dt 0.39 (95% CI 0.18 to 0.57, p < 0.001), and between LSWI and LVEF 0.41 (95% CI 0.20 to 0.59, p < 0.001). In this model haemodynamic instability induced by negative inotropy was detected by the HPI algorithm prior to any clinically significant change in commonly measured variables. In addition, the peripheral measure of left ventricular contractility dP/dt correlates well with more established measurements of LV systolic function.

Different Associations of Systolic Blood Pressure and Body Mass Index With Cardiac Structure and Function in Young Children.

Both elevated systolic blood pressure (SBP) and excess weight can lead to early cardiovascular organ damage in children. In this study, we investigated whether there is a difference in the associations of SBP and body mass index (BMI) with cardiovascular structure and function in 4-year-old children. In 1474 children (52.3% males) from the Shanghai Birth Cohort, physical examination and echocardiography were performed. Standardized linear regression models were used to evaluate the associations of BMI Z score and SBP Z score with cardiovascular parameters and to compare the strengths of these associations. The incidence of SBP elevation significantly increased in overweight children. SBP was positively related to heart rate, left ventricular (LV) ejection fraction and fraction shortening (β=1.824 [95% CI, 1.014-2.634], 0.579 [0.294-0.864], and 0.480 [0.257-0.704], respectively). BMI Z score was positively associated with LV mass index (β=1.225 [0.863-1.587]) and the risk of LV hypertrophy (odds ratio=1.428 [1.157-1.761]) but negatively related to measures of systolic function, including LV ejection fraction, LV fraction short, and global longitudinal strain (β=-0.417 [-0.735 to -0.099], -0.302 [-0.551 to -0.053], and -0.392 [-0.621 to -0.163], respectively). No noteworthy additive or multiplicative interactions between BMI and SBP were detected. Elevations in both BMI and SBP were related to cardiac structure and function in children as young as 4 years old. Elevated SBP was associated with increased heart rate and LV ejection at the early stage of BP elevation. BMI showed a closer relationship with left heart diameters and geometry than SBP.

Impact of Sacubitril/Valsartan Compared With Ramipril on Cardiac Structure and Function After Acute Myocardial Infarction: The PARADISE-MI Echocardiographic Substudy.

Angiotensin-converting enzyme inhibitors attenuate left ventricular (LV) enlargement after acute myocardial infarction (AMI). Preclinical data suggest similar benefits with combined angiotensin receptor neprilysin inhibition, but human data are conflicting. The PARADISE-MI Echo Study (Prospective ARNI Versus ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After Myocardial Infarction) tested the effect of sacubitril/valsartan compared with ramipril on LV function and adverse remodeling after high risk-AMI. In a prespecified substudy, 544 PARADISE-MI participants were enrolled in the Echo Study to undergo protocol echocardiography at randomization and after 8 months. Patients were randomized within 0.5 to 7 days of presentation with their index AMI to receive a target dose of sacubitril/valsartan 200 mg or ramipril 5 mg twice daily. Echocardiographic measures were performed at a core laboratory by investigators blinded to treatment assignment. The effect of treatment on change in echo measures was assessed with ANCOVA with adjustment for baseline value and enrollment region. The primary end points were change in LV ejection fraction (LVEF) and left atrial volume (LAV), and prespecified secondary end points included changes in LV end-diastolic and end-systolic volumes. Mean age was 64±12 years; 26% were women; mean LVEF was 42±12%; and LAV was 49±17 mL. Of 544 enrolled patients, 457 (84%) had a follow-up echo at 8 months (228 taking sacubitril/valsartan, 229 taking ramipril). There was no significant difference in change in LVEF (P=0.79) or LAV (P =0.62) by treatment group. Patients randomized to sacubitril/valsartan demonstrated less increase in LV end-diastolic volume (P=0.025) and greater decline in LV mass index (P=0.037), increase in tissue Doppler e'lat (P=0.005), decrease in E/e'lat (P=0.045), and decrease in tricuspid regurgitation peak velocity (P=0.024) than patients randomized to ramipril. These differences remained significant after adjustment for differences in baseline characteristics. Baseline LVEF, LV end-diastolic volume, LV end-systolic volume, LV mass index, LAV, and Doppler-based diastolic indices were associated with risk of cardiovascular death or incident heart failure. Treatment with sacubitril/valsartan compared with ramipril after AMI did not result in changes in LVEF or LAV at 8 months. Patients randomized to sacubitril/valsartan had less LV enlargement and greater improvement in filling pressure. Measures of LV size, systolic function, and diastolic properties were predictive of cardiovascular death and incident heart failure after AMI in this contemporary, well-treated cohort. URL: https://www. gov; Unique identifier: NCT02924727.