Left Ventricular Peak Research Articles

Exercise Training Normalizes Timing of Left Ventricular Untwist Rate, but Not Peak Untwist Rate, in Individuals with Type 2 Diabetes and Diastolic Dysfunction: A Pilot Study

There is limited information regarding the role of left ventricular (LV) twist and the effect of exercise in type 2 diabetes (T2D). The aim of this study was to compare LV twist parameters in patients with T2D versus healthy control subjects and the effects of high-intensity interval exercise (HIIE) and moderate-intensity exercise (MIE) on LV twist in patients with T2D with diastolic dysfunction. This study, which included both prospective and retrospective components, included 47 patients with T2D and diastolic dysfunction and 37 healthy individuals. Patients with T2D were randomized to HIIE (4×4min at 90%-95% of maximal heart rate, three times a week, 120min/wk; n=24) or MIE (210min/wk; n=23) for 12weeks and examined with echocardiography (LV twist by speckle-tracking method) at baseline and posttest. The control subjects received no intervention and were matched according to age, gender, and body mass index to those completing the intervention. In total, 37 subjects completed 12weeks of MIE (n=17) or HIIE (n=20). LV peak untwist rate (UTR) was similar in patients with T2D and control subjects (P˃.05). At baseline, LV peak UTR, relative to total diastolic period, occurred 5.8 percentage points later in patients with T2D compared with control subjects (P=.004). Time to peak UTR was shortened by 6.5 percentage points (P=.002) and 7.7 percentage points (P<.001) after MIE and HIIE, respectively. Time to peak UTR was similar to that in control subjects after exercise interventions. In patients with T2D and diastolic dysfunction, LV peak UTR was similar, but time to peak LV UTR was delayed compared with control subjects. Twelve weeks of endurance exercise normalized the timing of UTR.

Impact of Septal Reduction on Left Atrial Size and Diastole in Hypertrophic Cardiomyopathy.

Both myectomy and alcohol septal ablation (ASA) can substantially reduce left ventricular (LV) outflow obstruction, relieve symptoms, and improve outcomes in hypertrophic cardiomyopathy (HCM). It is unclear whether septal reduction decreases left atrial (LA) size and improves diastolic function. The aim of this study was to analyze the consequences of septal reduction on LA size and diastolic function in a cohort of patients with HCM. Forty patients (mean age: 50 ± 14, male sex 64%) with HCM who underwent septal reduction (myectomy or alcohol septal ablation) were studied. Retrospective analyses of echocardiograms preprocedure, postprocedure, and at 1 year of follow-up were performed. Thirty-one patients had septal myectomy and 9 ASA. The degree of reduction in rest peak LV outflow tract gradient was significant (57 ± 32 vs. 23 ± 20 mmHg at 1 year, P < 0.001). Maximal interventricular septal thickness decreased from 22 ± 6 mm preprocedure to 19 ± 4 mm postprocedure (P < 0.001); moderate-to-severe mitral regurgitation (MR) was initially present in 34% of the sample and only 2% after the procedure. Average LA volume index (LAVI) decreased from 63 ± 20 to 55 ± 20 mL/m(2) at the 1-year follow-up (P < 0.001). We did not observe a significant improvement in diastolic function at Doppler (E/A 1.2 ± 0.4 vs. 1.1 ± 0.5, P = 0.07; E' 7.6 ± 3.6 vs. 6.9 ± 3.0, P = 0.4) pre- and postprocedure, respectively). At 1 year, only 5% of the patients were severely symptomatic (NYHA III). On multivariate analysis, a significant change in the LVOT gradient during stress (Δ gradient ≥30 mmHg) was the only variable independently associated with LAVI reverse remodeling >10 mL/m(2) [OR = 6.4 (CI 95% 1.12-36.44), P = 0.04]. Septal reduction is effective in the relief of LV obstruction and symptoms in patients with HCM. The hemodynamic changes result in a significant LA reverse remodeling, but not in an improvement of diastolic function in these patients.

Effect of short-term insulin pump therapy on left ventricular systolic function in type 2 diabetes mellitus patients evaluated by three-dimensional speckle tracking imaging

Objective To assess the improvements of left ventricular systolic function by three-dimensional speckle tracking imaging (3D-STI) in type 2 diabetes mellitus (T2DM) patients after short-term insulin pump intensive therapy. Methods Thirty-five T2DM patients complicated with microangiopathy and thirty-two healthy volunteers were studied, underwent the dynamic image of the four-chamber view, three-dimensional images of left ventricle were obtained for all the individuals. The left ventricular global longitudinal strain (LVGLS), left ventricular global circumferential strain (LVGCS), left ventricular ejection fraction (LVEF), peak basal and apical rotation (LV-ProtB, LV-ProtA), peak LV twist (LV-tw ) were calculated using TomTec software.After insulin pump intensive therapy for two weeks, all the indexes were reexamined in T2DM patients. Results Compared with control group, the LVGLS, LVGCS, LV-tw and LV-ProtA were significantly decreased in diabetes mellitus group before and after treatment (P<0.01 or P<0.05). Compared with diabetes mellitus patients before treatment, the LVGLS, LVGCS had significant higher level after treatment(P<0.05). The LVGLS, LVGCS, LV-tw and LV-ProtA were significantly correlated with LVEF in type 2 diabetes mellitus patients and normal controls. Conclusions Insulin pump intensive treatment could improve left ventricular systolic function in type 2 diabetes patients complicated with microangiopathy. 3D-STI can be sensitive to accurately assess the therapeutic effect and has the important clinical value. Key words: Echocardiography; Type 2 diabetes mellitus; Insulin pump intensive therepy; Three dimensional speckle tracking imaging

Effect of free-breathing on left ventricular rotational mechanics in healthy subjects and patients with duchenne muscular dystrophy.

Cardiovascular magnetic resonance imaging exams can be performed during free-breathing. This may be especially important for boys with Duchenne muscular dystrophy (DMD) given their frequently limited breath-hold abilities. The impact of the respiratory compensation method on quantitative measurements of left ventricular (LV) rotational mechanics is incompletely understood. The purpose of this study was to evaluate differences in LV rotational mechanics acquired during breath-holding (BH), free-breathing with averaging (AVG), and free-breathing with respiratory bellows gating (BEL). LV short-axis tagged images from healthy subjects (N = 16) and DMD patients (N = 5) were acquired with BH, AVG, and BEL. LV twist and circumferential-longitudinal shear (CL-shear) angle were measured using the Fourier Analysis of STimulated echoes (FAST) method. Peak LV twist estimates using BEL were significantly lower compared with BH in both healthy subjects (10.2 ± 3.6 ° versus 12.9 ± 2.3 °, P = 0.003) and patients with DMD (8.6 ± 3.6 ° versus 10.5 ± 3.6 °, P = 0.004). AVG results were in between BEL and BH. No significant differences in CL-shear were detected between BEL and BH. Breath-holding directly affects estimates of peak LV twist, but not CL-shear. Using a free-breathing strategy for the evaluation of cardiac function is important for intrasubject longitudinal studies, intersubject comparisons, and multicenter trials for patients with DMD. Magn Reson Med 77:864-869, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Cardiac structure and function in adolescent Sherpa; effect of habitual altitude and developmental stage

The purpose of this study was to examine ventricular structure and function in Sherpa adolescents to determine whether age-specific differences in oxygen saturation (SpO2 ) and pulmonary artery systolic pressure (PASP) influence cardiac adaptation to chronic hypoxia early in life. Two-dimensional, Doppler, and speckle-tracking echocardiography were performed on adolescent (9-16 yr) highland Sherpa (HLS; 3,840 m; n = 26) and compared with age-matched lowland Sherpa (LLS; 1,400 m; n = 10) and lowland Caucasian controls (LLC; sea level; n = 30). The HLS were subdivided into pre- and postadolescence; SpO2 was also recorded. Only HLS exhibited a smaller relative left ventricular (LV) end-diastolic volume; however, both HLS and LLS demonstrated a lower peak LV untwisting velocity compared with LLC (92 ± 26 and 100 ± 45 vs. 130 ± 43°/s, P < 0.05). Although SpO2 was similar between groups, PASP was higher in post- vs. preadolescent HLS (30 ± 5 vs. 25 ± 5 mmHg, P < 0.05), which negatively correlated with right ventricular strain rate (r = 0.50, P < 0.01). Much like their adult counterparts, HLS and LLS adolescents exhibit slower LV diastolic relaxation, despite residing at different altitudes. These findings suggest fundamental differences exist in the diastolic function of Sherpa that are present at an early age and may be retained after migration to lower altitudes. The higher PASP in postadolescent Sherpa is in contrast to previous reports of lowland children at high altitude and, unlike that in lowlanders, was not explained by differences in SpO2 ; thus different regulatory mechanisms seem to exist between these two distinct populations.

Cardiac remodeling and dysfunction in childhood obesity: a cardiovascular magnetic resonance study.

BackgroundObesity affects nearly one in five children and is associated with increased risk of premature death. Obesity-related heart disease contributes to premature death. We aimed to use cardiovascular magnetic resonance (CMR) to comprehensively characterize the changes in cardiac geometry and function in obese children.Methods and resultsForty-one obese/overweight (age 12 ± 3 years, 56 % female) and 29 healthy weight children (age 14 ± 3 years, 41 % female) underwent CMR, including both standard cine imaging and displacement encoded imaging, for a complete assessment of left ventricular (LV) structure and function. After adjusting for age, LV mass index was 23 % greater (27 ± 4 g/m2.7 vs 22 ± 3 g/m2.7, p <0.001) and the LV myocardium was 10 % thicker (5.6 ± 0.8 mm vs 5.1 ± 0.8 mm, p <0.001) in the obese/overweight children. This evidence of cardiac remodeling was present in obese children as young as age 8. Twenty four percent of obese/overweight children had concentric hypertrophy, 59 % had normal geometry and 17 % had either eccentric hypertrophy or concentric remodeling. LV mass index, thickness, ejection fraction and peak longitudinal and circumferential strains all correlated with epicardial adipose tissue after adjusting for height and gender (all p <0.05). Peak longitudinal and circumferential strains showed a significant relationship with the type of LV remodeling, and were most impaired in children with concentric hypertrophy (p <0.001 and p = 0.003, respectively).ConclusionsObese children show evidence of significant cardiac remodeling and dysfunction, which begins as young as age 8. Obese children with concentric hypertrophy and impaired strain may represent a particularly high risk subgroup that demands further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12968-016-0247-0) contains supplementary material, which is available to authorized users.

Impact of Severe Obesity and Weight Loss on Systolic Left Ventricular Function and Morphology: Assessment by 2-Dimensional Speckle-Tracking Echocardiography.

Obesity is associated with an increased risk of heart failure. Little is known about the impact of dietary changes on the cardiac sequelae in obese patients. Twenty-one obese subjects underwent a 12-week low calorie fasting phase of a formula diet. Transthoracic two-dimensional speckle-tracking echocardiography was performed to obtain systolic left ventricular strain before and after weight loss. Body mass index decreased significantly from 38.6 ± 6.2 to 31.5 ± 5.3 kg/m2, and the total percentage fat loss was 19%. Weight reduction was associated with a reduction in blood pressure and heart rate. Left ventricular longitudinal global peak systolic strain was in the lower normal range (−18.7 ± 3.2%) before weight loss and was unchanged (−18.8 ± 2.4%) after 12 weeks on diet with substantial weight loss. Also, no significant change in global radial strain after weight loss was noted (41.1 ± 22.0 versus 43.9 ± 23.3, p = 0.09). Left atrial and ventricular dimensions were in normal range before fasting and remained unchanged after weight loss. In our study obesity was associated with normal systolic left ventricular function. A 12-week low calorie diet with successful weight loss can reduce blood pressure and heart rate. Systolic left ventricular function and morphology were not affected by rapid weight reduction.

Mechanical effects of left ventricular midwall fibrosis in non-ischemic cardiomyopathy.

BackgroundLeft ventricular (LV) mid-wall fibrosis (MWF), which occurs in about a quarter of patients with non-ischemic cardiomyopathy (NICM), is associated with high risk of pump failure. The mid LV wall is the site of circumferential myocardial fibers. We sought to determine the effect of MWF on LV myocardial mechanics.MethodsPatients with NICM (n = 116; age: 62.8 ± 13.2 years; 67 % male) underwent late gadolinium enhancement cardiovascular magnetic resonance (CMR) and were categorized according to the presence (+) or absence (−) of MWF. Feature tracking (FT) CMR was used to assess myocardial deformation.ResultsDespite a similar LVEF (24.3 vs 27.5 %, p = 0.20), patients with MWF (32 [24 %]) had lower global circumferential strain (Ɛcc: −6.6 % vs −9.4 %, P = 0.004), but similar longitudinal (Ɛll: −7.6 % vs. −9.4 %, p = 0.053) and radial (Ɛrr: 14.6 % vs. 17.8 % p = 0.18) strain. Compared with − MWF, + MWF was associated with reduced LV systolic, circumferential strain rate (−0.38 ± 0.1 vs −0.56 ± 0.3 s−1, p = 0.005) and peak LV twist (4.65 vs. 6.31°, p = 0.004), as well as rigid LV body rotation (64 % vs 28 %, P <0.001). In addition, +MWF was associated with reduced LV diastolic strain rates (DSRcc: 0.34 vs. 0.46 s−1; DSRll: 0.38 vs. 0.50s−1; DSRrr: −0.55 vs. −0.75 s−1; all p <0.05).ConclusionsMWF is associated with reduced LV global circumferential strain, strain rate and torsion. In addition, MWF is associated with rigid LV body rotation and reduced diastolic strain rates. These systolic and diastolic disturbances may be related to the increased risk of pump failure observed in patients with NICM and MWF.

Characterisation of cardiomyopathy by cardiac and aortic magnetic resonance in patients new to hemodialysis.

ObjectivesCardiomyopathy is a key factor in accelerated cardiovascular mortality in haemodialysis (HD) patients. We aimed to phenotype cardiac and vascular dysfunction by tagged cardiovascular magnetic resonance (CMR) imaging in patients recently commencing HD.MethodsFifty-four HD patients and 29 age and sex-matched controls without kidney disease were studied. Left ventricular (LV) mass, volumes, ejection fraction (EF), concentric remodelling, peak-systolic circumferential strain (PSS), peak diastolic strain rate (PDSR), LV dyssynchrony, aortic distensibility and aortic pulse wave velocity were determined.ResultsGlobal systolic function was reduced (EF 51 ± 10%, HD versus 59 ± 5%, controls, p < 0.001; PSS 15.9 ± 3.7% versus 19.5 ± 3.3%, p < 0.001). Diastolic function was decreased (PDSR 1.07 ± 0.33s-1 versus 1.31 ± 0.38s-1, p = 0.003). LV mass index was increased (63[54,79]g/m2 versus 46[42,53]g/m2, p < 0.001). Anteroseptal reductions in PSS were apparent. These abnormalities remained prevalent in the subset of HD patients with preserved EF >50% (n = 35) and the subset of HD patients without diabetes (n = 40). LV dyssynchrony was inversely correlated to diastolic function, EF and aortic distensibility. Diastolic function was inversely correlated to LV dyssynchrony, concentric remodelling, age and aortic pulse wave velocity.ConclusionPatients new to HD have multiple cardiac and aortic abnormalities as characterised by tagged CMR. Cardio-protective interventions are required from initiation of therapy.Key Points• First characterisation of cardiomyopathy by tagged CMR in haemodialysis patients.• Diastolic function was correlated to LV dyssynchrony, concentric remodelling and aortic PWV.• Reductions in strain localised to the septal and anterior wall.• Bioimpedance measures were unrelated to LV strain, suggesting volume-independent pathogenetic mechanisms.• Multiple abnormalities persisted in the HD patient subset with preserved EF or without diabetes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00330-015-4096-2) contains supplementary material, which is available to authorized users.

Volume depletion provided by blood donation alters twist mechanics of the heart: Preload dependency of left ventricular torsion

Objectives: The crucial role of twisting motion on both left ventricular (LV) contraction and relaxation has been clearly identified. However, the reports studying the association between LV torsion and loading conditions have revealed conflicting outcomes. Previously normal saline infusion was shown to increase LV rotation. Our aim was to test this phenomenon after volume depletion in healthy volunteer blood donors. Design: A total of 26 healthy male volunteers were included in the study. LV end-diastolic and end-systolic diameter, LV ejection fraction, LV diastolic parameters, LV apical and basal rotation and peak systolic LV torsion were measured by speckle-tracking echocardiography before and after 450 mL blood donation. Results: Blood donation led to a significant decrease in end-diastolic LV internal diameter (48.7 ± 0.4 versus 46.4 ± 0.4 mm; p < 0.001) and cardiac output (6.2 ± 1.0 versus 5.1 ± 0.7 L/min; p < 0.001). There was a significant decrease in the magnitude of peak systolic apical rotation (4.4 ± 1.9° versus 2.9 ± 1.5°; p < 0.001) but no change in basal rotation (2.6 ± 1.4° versus 2.7 ± 1.6°; p = 0.81). Peak systolic LV Torsion decreased after blood donation (6.9 ± 1.9° versus 5.7 ± 2.1°; p = 0.028). Conclusions: LV apical rotation and peak systolic LV torsion seem to be preload dependent. Preload reduction provided by 450-mL blood donation decreased LV torsion in healthy male volunteers. Volume dynamics should be taken into account in the evaluation of LV torsion.

Abstract 19981: Relationship of Cardiorespiratory Fitness and Adiposity With Left Ventricular Peak Systolic Strain in Middle-age Adults: The Dallas Heart Study

Introduction: Low cardiorespiratory fitness (CRF) and obesity are associated with an increased risk for heart failure (HF). However, the mechanisms through which CRF and adiposity might increase HF risk are not fully understood. Because impaired left ventricular (LV) peak systolic strain is an early subclinical marker of HF, we evaluated the association of CRF and adiposity with LV peak systolic strain. Methods: We studied Dallas Heart Study-II participants without cardiovascular disease who had CRF estimated as the peak oxygen uptake from a submaximal treadmill test using the Givoni’s equation and Hellerstein’s formula and total body fat measured by dual x-ray absorptiometry. The participants also had ECG-gated tissue-tagged cardiac MRI imaging using 3-T MRI. Peak mid-wall systolic circumferential strain (Ecc) was determined by harmonic phase imaging. Associations of CRF and measures of overall adiposity [percent body fat (%BF)] and visceral adiposity [waist circumference (WC)] with Ecc were determined using multivariable adjusted linear regression analysis. Results: A total of 1,493 participants (57% women, 42% African Americans) were included in the analysis. After adjustment for baseline risk factors, higher LV mass (β = 0.17; P&lt; .0001), lower ejection fraction (β = -0.32; P = &lt; .0001), higher hs-cTnT levels (β = 0.06; P= 0.04), and lower CRF (β = -0.16; P&lt; .0001) were each associated with higher Ecc (indicating worse systolic function). Higher WC was also significantly associated with higher Ecc (β = 0.07; P= .0006) while %BF was not associated with Ecc (P= 0.08). The relationship between CRF and Ecc did not change after additional adjustment for %BF and other significant confounders (Table). Conclusion: Lower CRF, but not total body fat, is associated with reduced peak systolic strain independent of LV mass and ejection fraction.These findings highlight the independent contributions of low fitness in mid-life towards heart failure risk at a later age.

Abstract 15439: Obese Children With Concentric Hypertrophy and Impaired Cardiac Strain: A Potentially High-risk Subgroup Identified With Cardiac Magnetic Resonance

Objectives: Obesity affects nearly one in five children and is associated with increased risk of premature death. Heart disease may contribute to this premature death. We aimed to use cardiac magnetic resonance (CMR) to comprehensively assess the prevalence and severity of heart disease in obese children, with the hypothesis that obese children have cardiac remodeling and impaired cardiac function compared to healthy weight children. Methods and Results: Twenty obese (age 12 ± 3 years, 60% female) and 20 healthy weight children (age 13 ± 3 years, 50% female) underwent CMR, including both standard cine imaging and displacement encoded imaging, for a complete assessment of left ventricular (LV) structure and function. After adjusting for age, obese children had a 27% increase in LV mass (p &lt;0.001, Figure 1A) and a 12% increase in LV thickness (obese = 5.5 ± 0.7 mm, healthy = 5.0 ± 0.7 mm, p = 0.01). This evidence of cardiac remodeling was present in obese children as young as age 8. Forty percent of obese children had concentric hypertrophy, 40% had normal geometry and 20% had either eccentric hypertrophy or concentric remodeling. LV ejection fraction and peak strains were not different between the healthy weight and obese groups. However, peak longitudinal strain showed a significant relationship with the type of LV remodeling, and was most impaired in obese children with concentric hypertrophy (Figure 1B). Conclusions: Obese children show evidence of significant heart disease, which begins as young as age 8. The presence of concentric hypertrophy in 40% of obese children along with the association with impaired cardiac strain in these children may represent a high-risk subgroup. Given the associations between pediatric obesity and early mortality, these early signs of heart disease in obese children demand further investigation.

Temporal Trends of Cardiac Chambers Function with Trastuzumab in Human Epidermal Growth Factor Receptor II-Positive Breast Cancer Patients.

Trastuzumab has substantially improved overall survival and reduced the risk of disease recurrence in patients with human epidermal growth factor receptor type II (HER-II)-positive breast cancer. However, this benefit may be at the increased risk of cardiotoxicity. We aimed to explore the early subclinical left and right ventricular as well as atrial dysfunction, in trastuzumab-treated patients with HER-II-positive breast cancer, using velocity vector imaging. Echocardiography images were acquired in 50 patients with HER-II-positive breast cancer undergoing trastuzumab therapy. All patients had baseline and 3-6 months and 12-15 months of follow-up echocardiograms after initiation of trastuzumab therapy. Subendocardial borders of all the cardiac chambers were traced from the apical views to obtain volumetric and deformation indices. Mean age was 60 ± 13 years. Left ventricular (LV) ejection fraction as well as conventional indices of right ventricular (RV) function did not change with trastuzumab. The RV peak systolic global longitudinal strain (GLε) significantly decreased (-24.53 ± 6.03 vs. -21.28 ± 5.11 vs. -21.84 ± 5.15, baseline vs. first and second follow-ups, P = 0.01). LV peak systolic GLε was reduced by 1.19 at early follow-up (P < 0.05). Left atrial reservoir and booster pump functions as well as right atrial reservoir function were reduced through follow-up as well. The RV exhibited greater change in strain after trastuzumab treatment when compared to the LV. Atria function was reduced by trastuzumab as well. The repercussion of these findings and their potential implication will warrant further study.

A porcine model of hypertensive cardiomyopathy: implications for heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFPEF) evolves with the accumulation of risk factors. Relevant animal models to identify potential therapeutic targets and to test novel therapies for HFPEF are missing. We induced hypertension and hyperlipidemia in landrace pigs (n = 8) by deoxycorticosteroneacetate (DOCA, 100 mg/kg, 90-day-release subcutaneous depot) and a Western diet (WD) containing high amounts of salt, fat, cholesterol, and sugar for 12 wk. Compared with weight-matched controls (n = 8), DOCA/WD-treated pigs showed left ventricular (LV) concentric hypertrophy and left atrial dilatation in the absence of significant changes in LV ejection fraction or symptoms of heart failure at rest. The LV end-diastolic pressure-volume relationship was markedly shifted leftward. During simultaneous right atrial pacing and dobutamine infusion, cardiac output reserve and LV peak inflow velocities were lower in DOCA/WD-treated pigs at higher LV end-diastolic pressures. In LV biopsies, we observed myocyte hypertrophy, a shift toward the stiffer titin isoform N2B, and reduced total titin phosphorylation. LV superoxide production was increased, in part attributable to nitric oxide synthase (NOS) uncoupling, whereas AKT and NOS isoform expression and phosphorylation were unchanged. In conclusion, we developed a large-animal model in which loss of LV capacitance was associated with a titin isoform shift and dysfunctional NOS, in the presence of preserved LV ejection fraction. Our findings identify potential targets for the treatment of HFPEF in a relevant large-animal model.

OP21.07: Fetal and neonatal diastolic cardiac strain rate: normal reference ranges and reproducibility in a prospective, longitudinal cohort of pregnancies

Background: Normative fetal diastolic strain rate values have not been comprehensively reported. The aims of this study were to report normative data for diastolic strain rate parameters across gestation and upon delivery, determine the effect of advancing gestational age on these measures, and compare interobserver variability at multiple gestational age time points. Methods: Sixty gravid women were enrolled before 20 weeks’ gestation. The following measures were obtained by two blinded observers at five time points across gestation and at 4 to 8 weeks’ postnatal age: global left ventricular circumferential strain rate peak E and A waves, global left and right ventricular longitudinal strain rate peak E and A waves, and mitral and tricuspid valve E/A ratios. Reproducibility was assessed using intraclass correlation and Bland-Altman analysis. Least square means analysis was used to evaluate for changes across gestational age. Results: Left ventricular longitudinal and circumferential diastolic strain rate values decreased across gestation, while right ventricular longitudinal values remained stable. With delivery, left ventricular values remained fairly stable, while right ventricular values increased. Intraclass correlations for diastolic strain rate values were 0.68 to 0.94 at $24 weeks’ gestation and 0.25 to 0.82 for values at 20 to 21 weeks’ gestation. Intraclass correlations ranged from 0.49 to 0.90 for mitral valve and tricuspid valve E/A ratios across gestation. Conclusions: Fetal measures of diastolic strain rate have acceptable reproducibility after 24 weeks’ gestation. The described changes across gestation likely reflect intrinsic myocardial adaptation to loading conditions. These reference ranges can be used to assess effects of various disease states on fetal myocardial deformation. (J Am Soc Echocardiogr 2016;29:663-9.)

Mitral Annular Kinetics, Left Atrial, and Left Ventricular Diastolic Function Post Mitral Valve Repair in Degenerative Mitral Regurgitation.

The relationship of mitral annular (MA) kinetics to left ventricular (LV) and left atrial (LA) function before and after mitral valve (MV) repair has not been well studied. Here we sought to provide comprehensive analysis that relates to MA motions, and LA and LV diastolic function post MV repair. Three-dimensional analyses of mitral annular motion, LA function, and LV volumetric and diastolic strain rates were performed on 35 degenerative mitral regurgitation (MR) patients at baseline and 1-year post MV repair, and 51 normal controls, utilizing cardiac magnetic resonance imaging with tissue tagging. All had normal LV ejection fraction (EF) at baseline. LV and LA EFs decreased 1-year post-surgery vs. controls. LV early diastolic myocardial strain rates decreased post-surgery along with decreases in normalized early diastolic filling rate, E/A ratio, and early diastolic MA relaxation rates. Post-surgical LA late active kick remained higher in MR patients vs. control. LV and LA EFs were significantly associated with peak MA centroid to apex shortening. Furthermore, during LV systolic phase, peak LV ejection and LA filling rates were significantly correlated with peak MA centroid to apex shortening rate, respectively. While during LV diastolic phase, both peak early diastolic MA centroid to apex relaxation rate and LA ejection rate were positively significantly associated with LV peak early diastolic filling rate. MA motion is significantly associated with LA and LV function. Mitral annular motion, left atrial function, and LV diastolic strain rates are still impaired 1 year post MV repair. Long-term effects of these impairments should be prospectively evaluated.

Abstract 64: Conditional Knockout of Activin Like Kinase-1 (ALK-1) Leads to Heart Failure Without Maladaptive Remodeling

Activin like kinase 1 (ALK1) mediates signaling via the TGFb family of ligands. ALK1 activity promotes endothelial proliferation and migration. Reduced ALK1 activity is associated with arteriovenous malformations. No studies have examined the effect of global ALK1 deletion on indices of cardiac remodeling. We hypothesized that reduced levels of ALK1 promote maladaptive cardiac remodeling. Methods: We employed an ALK1 conditional knockout mice (cKO) harboring the ROSA26-CreER knock-in allele whereby a single dose of intraperitoneal tamoxifen triggered ubiquitous Cre recombinase mediated excision of floxed ALK1 alleles. Tamoxifen treated wild-type (WT-Tam; n=5) and vehicle treated ALK1-cKO mice (cKO-Veh; n=5) served as controls for tamoxifen treated ALK1-cKO mice (cKO-Tam; n=15). Results: ALK1 cKO-Tam mice demonstrated reduced 14-day survival compared to cKO-Veh controls (33% vs 100%, respectively, p&lt;0.01). Seven days after treatment, ALK1 cKO mice began to exhibit reduced left ventricular (LV) fractional shortening, progressive LV dilation, and gastrointestinal bleeding. After 14 days total body mass was reduced, but LV and lung mass increased in cKO-Tam not cKO-Veh mice. Peak LV systolic pressure, contractility, and arterial elastance were reduced, but LV end-diastolic pressure and stroke volume increased in cKO-Tam, not cKO-Veh mice. LV ALK1 mRNA and protein levels were reduced in cKO-Tam, not cKO-Veh mice. LV levels of other TGFb-family ligands and receptors (ALK5, TBRII, BMPRII, Endoglin, BMP7, BMP9, and TGFB1) were unchanged between groups. Cardiomyocyte area and LV levels of BNP were increased in cKO-Tam mice, but LV levels of b-MHC, SerCA, and calcineurin were unchanged. No increase in cardiac fibrosis Type I collagen, CTGF, or PAI-1 levels were observed between groups. No differences were observed for any variable studied between cKO-Veh and WT-Tam mice. Conclusion: Global deletion of ALK1 is associated with the development of high output heart failure without maladaptive remodeling. Future studies exploring the functional role of ALK1 in cardiac remodeling are required.

An examination of the cardiac actions of PD117,302, a κ-opioid receptor agonist

These studies examined the opioid and non-opioid in vivo and in vitro actions of PD117,302 (((±)-trans-N-methyl-N-[2-(l-pyrrolidinyl)-cyclohexyl]benzo[b]thiophene-4-acetamide), a kappa (κ)-opioid receptor agonist. PD117,302 selectively labeled the κ-opioid receptor in guinea pig cerebellar membranes and in mice the ED50 for analgesia was 2.3µmol/kg. A non opioid cardiovascular assessment of PD117,302 showed that it dose-dependently increased left-ventricular peak systolic pressure in rat isolated perfused hearts but reduced heart rate and blood pressure in anaesthetized rats. Over the concentration range 0.3–30µM in vitro, and dose-range 0.25–4µmol/kg in vivo, PD117,302 dose-dependently prolonged the P-R interval, QRS width and Q-T interval of the rat heart ECG. Naloxone (either 1µM or 8µmol/kg) did not antagonize the observed ECG effects of PD117,302. Cardiac electrical stimulation studies in anesthetized rats showed that threshold currents for capture and fibrillation were increased and effective refractory period (ERP) prolonged. In rats subject to coronary artery occlusion PD117,302 reduced arrhythmia incidence. Intracellular cardiac action potential studies qualified the ECG changes produced by PD117,302 such that there was a dose-dependent reduction in the maximum rate of depolarization of phase 0 (dV/dtmax) and prolongation of the action potential duration (APD). In isolated cardiac myocytes PD117,302 dose-dependently (1–100µM) reduced peak Na+ current and produced a hyperpolarizing shift in the inactivation curve. Transient outward and sustained outward K+ currents were blocked by PD117,302. Thus, the ECG changes and antiarrhythmic effects observed in vivo result from direct blockade of multiple cardiac ion channels.

TU-F-CAMPUS-I-03: Quantitative Cardiac MRI Reveals Functional Abnormalities in Intrauterine Growth Restricted (IUGR) Baboons

Purpose: Developmental programming occurs in utero, when epigenetic adaptations Result in offspring phenotypes that lead to health consequences persisting throughout life. Programming of cardiac health, due to prenatal malnutrition, has been reported in rodents but not in primate species. Our aim was to determine IUGR is associated with impaired cardiac function in later life in a baboon model. Methods: Intrauterine growth restricted (IUGR, mothers were subjected to a 30% calories reduction) baboons were scanned with cine cardiac MRI measuring ejection fraction, left ventricular (LV) volumes, LV peak filling rate (LVPFR) and the LV 3D sphericity index (3DSI). Baboons were anesthetized and the respirator was turned off during scans. Three groups of baboons were studied: adult control (CTR): N=21 (11M, 10 F), age = 5.9±1.3 yr., IUGR: N=9(4M, 5F), age = 4.6±0.5 yr., and normal elderly adults (ELD): N=11(5M, 6 F), age = 15.3±2.4 yr. Images were analyzed using CMR42 software. LV end-diastolic volume (EDV) and end-systolic volumes (ESV) were referenced to body-surface areas (BSA). Linear regression, correlation and ANOVA with Bonferroni correction were performed between for each of the three groups (p<.05 deemed significant). Results: Systolic LV function in all three groups was normal. There were significant differences between the three groups for 3DSI and LVPFR by ANOVA. (p<.01) Linear regression and correlation were performed between 3DSI and LVFR data for each of the three groups. CTR: r=0.01(p=NS); IUGR: r=0.881 (p<.02); ELD: r=0.724 (p<.05). Conclusions: All subjects had normal systolic function but diastolic dysfunction was associated with IUGR and aging. Results are consistent with reports of increased fibrosis and changes in the distribution of titin isoforms in IUGR fetal baboon heart tissues. The data suggest that developmental programming, due to IUGR, accelerates processes leading to diastolic heart dysfunction, which is common with aging. GDC:NIH/K25-KDK089012A. AJK:NIH/R25-EB016631 PN: EU/BRAINAGE-IMPACT OF PRENATAL STRESS ON BRAIN AGE(FP7-HEALTH-2011).

Left ventricular shape and mass impact torsional dynamics in asymptomatic patients with chronic aortic regurgitation and normal left ventricular ejection fraction.

Chronic aortic regurgitation (AR) is associated with a unique pattern of left ventricular (LV) volume and pressure overload, leading to LV remodelling. LV torsional motion, a key component of LV performance, can be altered in this setting. We aimed to assess the impact of LV remodelling on LV torsional dynamics parameters using speckle-tracking echocardiography (STE) in asymptomatic AR patients. We prospectively enrolled 60 patients with chronic AR and LVEF > 50% and 55 healthy controls. LV rotation, twisting and untwisting were assessed using STE. Patients with AR had higher LV diameters, volumes and mass, a more spherical LV shape than controls, but similar LVEF. In AR patients we found reduced peak LV apical rotation and decreased (2.1 ± 0.8 vs 2.9 ± 0.9°/cm, p < 0.001) and delayed (time to peak LV twist: 0.94 ± 0.12 vs 0.99 ± 0.09, p = 0.004) peak LV torsion. Also, peak LV untwisting velocity was decreased (-123.5 ± 41.5 vs -152.3 ± 55.0°/s, p = 0.002) due to lower peak LV apical diastolic rotation rate. LV shape influenced LV torsional dynamics, a more spherical LV displaying reduced peak LV apical rotation and diastolic rotation rate and decreased LV twist. A more hypertrophied LV had a lower peak LV torsion, peak LV apical diastolic rotation rate and peak LV untwisting velocity. LV apical rotation and torsion are decreased and LV twist is delayed in patients with chronic AR and normal LVEF, detecting early subclinical LV dysfunction before LVEF declines. Also, LV untwisting is reduced in these patients. LV remodelling impairs LV torsional dynamics parameters in this setting.