Echocardiographic Measures Of Cardiac Function Research Articles

Effect of remote ischaemic conditioning on left ventricular function in ST-segment elevation myocardial infarction patients: The CONDI-2 echocardiographic sub-study.

Remote ischaemic conditioning (RIC) applied to the arm by inflation and deflation of a pneumatic cuff has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PPCI). However, the effect of RIC on left ventricular ejection fraction (LVEF) following infarct healing remains unknown. To investigate whether RIC applied in the ambulance before PPCI can improve left ventricular (LV) function in STEMI patients 3 months following infarction. Echocardiography was performed in a total of 694 patients from the CONDI-2 study a median of 112 days (IQR 63) after the initial admission. LVEF and LV end-diastolic and end-systolic volumes were calculated using the modified Simpsons biplane method of disks. LV global longitudinal strain (GLS) was estimated using 2-dimensional cine-loops with a frame rate > 55 frames/second, measured in the three standard apical views. There was no difference in the measured echocardiographic parameters in the RIC group as compared to the control group, including LV EF, LV GLS, tricuspid annular plane systolic excursion or left ventricular volumes. In the control group, 32% had an ejection fraction < 50% compared to 37% in the RIC group (p = 0.129). In this largest to date randomized imaging study of RIC, RIC as an adjunct to PPCI was not associated with a change in echocardiographic measures of cardiac function compared to standard PPCI alone.

Echocardiographic predictors of symptomatic cardiotoxicity among patients undergoing chemotherapy: A systematic review and meta-analysis.

Chemotherapeutic agents have been associated with cardiotoxicity; thus, they require close monitoring. Several echocardiographic variables have been investigated as early predictors of symptomatic cardiotoxicity in patients undergoing chemotherapy. To identify if global longitudinal strain (GLS) is a better predictor of symptomatic cardiotoxicity compared to left ventricular ejection fraction (LVEF) in patients receiving chemotherapy. MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials were searched from inception through December 2020. Adults who developed symptomatic cardiotoxicity (New York Heart Association [NYHA] Class III-IV heart failure, cardiac arrest, or cardiac death) after undergoing chemotherapy with pre- and postchemotherapy echocardiographic measures of cardiac function were included. The primary focus was on the prediction of symptomatic cardiotoxicity. Estimates were reported as random effects hazard ratios (HR) with 95% confidence intervals (CI). Four studies met inclusion criteria. The most common malignancy identified in the included studies was breast cancer, and the most common chemotherapeutic agent utilized was anthracyclines. Most studies utilized the Simpson biplane method to measure echocardiographic parameters. Pooled results demonstrated no significant association between LVEF and the prediction of symptomatic cardiotoxicity (HR 1.48; 95% CI, 0.96-2.27; P = 0.07). However, 2 studies that analyzed GLS found it to be a strong predictor of symptomatic cardiotoxicity (HR 1.46; 95% CI, 1.34-1.58; P < .001). There was no significant association between symptomatic cardiotoxicity and baseline left ventricular end diastolic volume, end systolic volume, or end diastolic volume index. GLS may predict symptomatic cardiotoxicity and be used to monitor patients on chemotherapy for symptomatic cardiac dysfunction. While the pooled results for baseline LVEF identified that it is not a predictor of symptomatic cardiotoxicity, this differs from the findings of the only randomized trial included in this meta-analysis. The data for baseline GLS as a predictor of symptomatic cardiotoxicity is encouraging, but definite evidence that GLS may be superior to LVEF is lacking. Prospective randomized, blinded trials are required to identify if 1 echocardiographic parameter may be superior to the other.

Investigating the Relationship Between Cardiac Function and Insulin Sensitivity in Horses: A Pilot Study.

Metabolic syndrome in humans is commonly associated with cardiovascular dysfunction, including atrial fibrillation and left ventricular diastolic dysfunction. Although many differences exist between human and equine metabolic syndrome, both of these conditions share some degree of insulin resistance. The aims of this pilot study were to investigate the relationship between insulin sensitivity and cardiac function. Seven horses (five mares, two geldings, aged 17.2 ± 4.2 years, weight 524 ± 73 kg) underwent insulin-modified frequently sampled intravenous glucose tolerance testing to determine insulin sensitivity (mean 2.21 ± 0.03 × 10−4 L/min/mU). Standard echocardiograms were performed on each horse, including two-dimensional, M-mode, and pulse-wave tissue Doppler imaging. Pearson and Spearman correlation analyses were used to determine the association of insulin sensitivity with echocardiographic measures of cardiac function in 5 horses. Insulin sensitivity was found to be significantly correlated with peak myocardial velocity during late diastole (r = 0.89, P = 0.0419), ratio between peak myocardial velocity in early and late diastole (r = −0.92, P = 0.0263), isovolumetric relaxation time (r = −0.97, P = 0.0072), and isovolumetric contraction time (ρ = −0.90, P = 0.0374). These preliminary data suggest that decreased insulin sensitivity is correlated with alterations in both systolic and diastolic function, as measured with tissue Doppler imaging (TDI). Due to the small sample size of this study, the relationship between insulin sensitivity and myocardial function in horses requires further investigation.

Abstract 13286: Ryanodine Receptor Inhibition Prevents Sudden Cardiac Death by Preserving Cardiac Repolarization Reserve in Stressed Arrhythmogenic Hearts

Introduction: Current therapies for preventing sudden cardiac death (SCD) are limited. Prior studies have shown that cardiac stress-induced ryanodine receptor (RyR2) hyperactivity increases sarcoplasmic calcium leak, leading to ventricular tachyarrythmias (VT) and SCD. We hypothesized that inhibition of RyR2 with dantrolene sodium (DS) reduces Ca 2+ leak and mitigates VT and SCD risk in pressure-overloaded arrhythmogenic hearts. Methods: We used an established guinea pig model that uniquely recapitulates key features of human SCD, including a high incidence of spontaneous VT in freely ambulating animals, randomized to placebo vs. DS treatment. We performed in vivo (e.g., VT/SCD incidence, ECG heart rate and QT variability, echocardiographic measures of cardiac function) and ex vivo (e.g., pressure-volume, electrophysiology) studies. We performed intention to treat analysis for 4-week VT-free survival. Results: About half the animals receiving placebo had SCD by 4 weeks. By contrast, dantrolene treatment reduced SCD incidence by 50%. Compared to placebo, dantrolene treatment preserved chronotropic competency during transient β-adrenergic challenge, and improved heart rate variability (SDNN: 11±1.1 vs 17±2.8 ms, p&lt;0.05), reduced QT variability (0.52±0.13 vs 0.19±0.08 (log, ms, p&lt;0.05), and improved cardiac function (fractional shortening: 26±1.9 vs 45±4.5 %, p&lt;0.05). In perfused excised hearts, dantrolene treatment mitigated VT (induced by isoproterenol or burst pacing). Conclusion: Inhibition of RyR2 hyperactivity by dantrolene treatment prevents VT and SCD by increasing cardiac repolarization reserve. Dantrolene also improved overall cardiac electromechanical function in stressed arrhythmogenic hearts. Targeted inhibition of RyR2 hyperactivity may be an effective therapeutic strategy for preventing VT and SCD.

The Relationship Between Oxygen Uptake and the Rate of Myocardial Deformation During Exercise

ABSTRACT Background: The relationship between resting echocardiographic measures of cardiac function and exercise capacity is weak. The details of ventricular augmentation may provide insight into determinants of cardiac efficiency for optimal exercise performance. The aims of this study were to establish how much of the variability in exercise performance could be explained by myocardial recruitment and which parameters describing cardiac function were most closely related to exercise performance. Methods: Untrained volunteers were recruited before training for the London Marathon. All performed a cardiopulmonary exercise test combined with stress echocardiography. Systolic and diastolic longitudinal velocities (S′ and E′), left ventricular ejection fraction (LVEF), stroke volume (SV), and strain (GLS) were obtained throughout exercise. Results: A variety of parameters including S′, E′, GLS, and SV showed a correlation with V̇o2 throughout exercise (ρ = 0.83, P &amp;lt; 0.0001). At the prespecified sample point (respiratory exchange ratio &amp;gt; 1.0) only SV and S′ were predictive of V̇o2peak. LVEF and E′ as well as both global longitudinal and circumferential strain showed no correlation with V̇o2peak. The systolic efficiency slope (SES) that we developed by determining the individual regression lines for V̇o2 and S′ showed a relationship between with V̇o2 peak for both septal S′, r = 0.57, P &amp;lt; 0.001, and lateral S′, r = 0.53, P &amp;lt; 0.001. Conclusion: A detailed description of myocardial function is described, linear for S′ and E′ and a plateau for EF and GLS. S′ during exercise is a better predictor of exercise performance than LVEF, SV, or GLS. The SES slope predicted V̇o2peak, suggesting the process driving systolic velocity and its augmentation is a key determinant of exercise ability.

Eccentric Left Ventricular Hypertrophy and Left and Right Cardiac Function in Chronic Heart Failure with or without Coexisting COPD: Impact on Exercise Performance.

AimOur aim was to assess: 1) the impact of the eccentric left ventricular hypertrophy (ELVH) on exercise performance in patients diagnosed with chronic heart failure (CHF) alone and in patients with co-existing CHF and chronic obstructive pulmonary disease (COPD) and 2) the relationship between left and right cardiac function measurements obtained by doppler echocardiography, clinical characteristics and primary measures of cardiorespiratory fitness.MethodsThe current study included 46 patients (CHF:23 and CHF+COPD:23) that performed advanced pulmonary function tests, echocardiography and symptom-limited, incremental cardiopulmonary exercise testing (CPET) on a cycle ergometer.ResultsPatients with CHF+COPD demonstrated a lower work rate, peak oxygen uptake (VO2), oxygen pulse, rate pressure product (RPP), circulatory power (CP) and ventilatory power (VP) compared to those only diagnosed with CHF. In addition, significant correlations were observed between VP and relative wall thickness (r: 0.45 p: 0.03),VE/VCO2 intercept and Mitral E/e’ ratio (r: 0.70 p: 0.003) in the CHF group. Significant correlations were found between indexed left ventricle mass and RPP (r: −0.47; p: 0.02) and relative VO2 and right ventricle diameter (r: −0.62; p: 0.001) in the CHF+COPD group.ConclusionCompared to a diagnosis of CHF alone, a combined diagnosis of CHF+COPD induced further impairments in cardiorespiratory fitness. Moreover, echocardiographic measures of cardiac function are related to cardiopulmonary exercise performance and therefore appear to be an important therapeutic target when attempting to improve exercise performance and functional capacity.

Abstract 14293: Echocardiographic Predictors of Symptomatic Cardiotoxicity Among Patients Undergoing Chemotherapy: Systematic Review and Meta-analysis

Introduction: Chemotherapeutic agents have been associated with cardiotoxicity and thus require close monitoring. Several echocardiographic variables have been investigated as early predictors of symptomatic cardiotoxicity (SC) in patients undergoing chemotherapy. Hypothesis: We hypothesized that global longitudinal strain (GLS) is a better predictor of SC compared to left ventricular ejection fraction (LVEF) in patients receiving chemotherapy. Methods: MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials were searched from through March 2019. Adults who developed SC (symptomatic congestive heart failure, decline in LVEF &lt;50%, cardiac death) after undergoing chemotherapy with pre- and post-chemotherapy echocardiographic measures of cardiac function were included. Primary focus was on the prediction of SC. Estimates were reported as random effects hazard ratios (HR) with 95% confidence intervals (CI). Results: Eight studies met inclusion criteria. Six studies analyzed LVEF and demonstrated a significant association between LVEF and the prediction of SC (HR 1.27; 95% CI, 1.02-1.57; P=0.03) (Figure 1) . Two studies that analyzed GLS found it to be a strong predictor of SC in patients undergoing chemotherapy (HR 1.46; 95% CI, 1.34-1.58; P=&lt;.001) (Figure 2) . Conclusions: Both LVEF and GLS can predict SC, and therefore can be utilized for monitoring patients on chemotherapy for cardiac dysfunction. The data for GLS is more homogenous but definite evidence that GLS may be superior to LVEF is lacking. More randomized blinded trials are required to identify if one echocardiographic parameter may be superior to the other.

Factors Associated With Cognitive Impairment in Heart Failure With Preserved Ejection Fraction.

Cognitive impairment is prevalent in heart failure and is associated with higher mortality rates. The mechanism behind cognitive impairment in heart failure with preserved ejection fraction (HFpEF) has not been established. The aim of this study was to evaluate associations between abnormal cardiac hemodynamics and cognitive impairment in individuals with HFpEF. A secondary analysis of Atherosclerosis Risk in Communities (Atherosclerosis Risk in Communities) study data was performed. Participants free of stroke or dementia who completed in-person assessments at visit 5 were included. Neurocognitive test scores among participants with HFpEF, heart failure with reduced ejection fraction (HFrEF), and no heart failure were compared. Sociodemographics, comorbid illnesses, medications, and echocardiographic measures of cardiac function that demonstrated significant (P < .10) bivariate associations with neurocognitive test scores were included in multivariate models to identify predictors of neurocognitive test scores among those with HFpEF. Multiple imputation by chained equations was used to account for missing values. Scores on tests of attention, language, executive function, and global cognitive function were worse among individuals with HFpEF than those with no heart failure. Neurocognitive test scores were not significantly different among participants with HFpEF and HFrEF. Worse diastolic function was weakly associated with worse performance in memory, attention, and language. Higher cardiac index was associated with worse performance on 1 test of attention. Cognitive impairment is prevalent in HFpEF and affects several cognitive domains. The current study supports the importance of cognitive screening in patients with heart failure. An association between abnormal cardiac hemodynamics and cognitive impairment was observed, but other factors are likely involved.

Effects of single-dose protons or oxygen ions on function and structure of the cardiovascular system in male Long Evans rats

PurposeStudies are required to determine whether exposures to radiation encountered during manned missions in deep space may have adverse effects on the cardiovascular system. Most of the prior studies on effects of simulated space radiation on the heart and vasculature have been performed in mouse models. To provide data from a second animal species, two studies were performed to assess effects of high-energy charged particle radiation on the heart and abdominal aorta in a rat model. Materials and methodsIn study A, male Long Evans rats were exposed to whole-body protons (250 MeV, 0.5 Gy) or oxygen ions (16O, 600 MeV/n, 0.5 Gy), and ultrasonography was used to measure in vivo cardiac function and blood flow parameters at 3, 5, 9 and 12 months after radiation, followed by tissue collection at 12 months. In study B, male Long Evans rats were exposed to 16O (1 GeV/n, 0.01-0.25 Gy), and hearts collected at 6 to 7 and 12 months for histology and western-blots. ResultsBoth protons (250 MeV) and 16O (600 MeV/n) caused a decrease in left ventricular posterior wall thickness at 3-5 months, but did not change echocardiographic measures of cardiac function. In Pulsed-wave Doppler assessment of the abdominal aorta, an increase was seen in mean velocity, peak velocity, and velocity time integral at 12 months after 16O (600 MeV/n), suggesting a change in vascular function. There were no significant changes in histopathology or histological quantification of total collagens in heart or aorta. On the other hand, an increase was seen in a 75 kDa peptide of collagen type III in the left ventricle of rats exposed to protons (250 MeV) and 16O (600 MeV/n and 1 GeV/n), suggesting that radiation caused remodeling of existing collagens in the heart. 16O (600 MeV/n and 1 GeV/n) caused increases in left ventricular protein levels of immune cell markers CD2, CD4, CD8, and CD68. ConclusionA single low dose of whole body protons or 16O in male Long Evans rats did not change cardiac function or induce gross pathological changes in the heart or aorta, but induced mild changes in vascular function and remodeling of existing collagens in the heart. Altogether, studies in prior mouse models and the current work in rats indicate minor changes in cardiac function and structure after a low dose of single-ion radiation.

Abstract P276: Discordance Between Changes in NT-proBNP and Cardiac Function Following Bariatric Surgery

Background: The N-Terminal of pro-B-type natriuretic peptide (NT-proBNP) is a potent biomarker for heart failure (HF), reflecting left ventricular dilation and stress. The association among obesity, HF, and NT-proBNP is complex, with paradoxically lower levels of NT-proBNP in obese individuals, despite their elevated HF risk. Furthermore, a few studies have reported decreased HF risk, but also increases in NT-proBNP, after weight loss via bariatric surgery. However, studies have not simultaneously evaluated changes in NT-proBNP and cardiac function after bariatric surgery. Hypothesis: There will be discordance between improvements in cardiac filling pressures (as reflected by E/e’) and increases in NT-proBNP with weight loss following bariatric surgery. Methods: We conducted a single-center analysis of participants in the BARI-Heart Study who underwent bariatric surgery and attended study visits 3-6 months and 2 weeks before surgery, and 6 and 12 months after surgery. We examined pre- and post-surgery changes in NT-proBNP and in echocardiographic measures of cardiac function. We also assessed the correlation between NT-pro-BNP and E/e’, at 2 weeks pre- and 6 months post-surgery. Results: Among 71 BARI-Heart participants (mean age 45 years, 74% female, 87% white, mean BMI 47.0 kg/m 2 ), there were no significant pre-surgery changes in BMI, NT-proBNP, or E/e’. By 6-12 months, there were marked reductions in BMI and significant increases in NT-proBNP, but decreases in E/e’ ( Figure ). Changes from surgery to the 6 month visit in NT-proBNP and E/e’ were associated (r=0.295; p=0.02). There was a tendency towards stronger correlations between NT-proBNP and E/e’ post- (r= 0.436; p&lt;0.001) versus pre-surgery (r = 0.209; p=0.09). Conclusions: Weight loss is associated with increases in NT-proBNP despite reduced LV filling pressures, suggesting a non-cardiac etiology underlying increases in NT-proBNP after weight loss. The interpretation of NT-proBNP for cardiac dysfunction may change with decreasing adiposity.

TNF-alpha inhibition for the treatment of cardiac sarcoidosis

BackgroundTumor necrosis factor alpha (TNF-α) inhibitors are increasingly being used for treating refractory cardiac sarcoidosis. There is a theoretical risk, however, that these therapies can worsen heart failure, and reports on efficacy and safety are lacking. MethodsWe conducted a retrospective review of all cardiac sarcoidosis patients seen at Stanford University from 2009 to 2018. Data were collected on patient demographics, diagnostic testing, and treatment outcomes. ResultsWe identified 77 cardiac sarcoidosis patients, of which 20 (26%) received TNF-α inhibitor treatment. The majority were treated for progressive heart failure or tachyarrhythmia, along with worsening imaging findings. All TNF-α inhibitor treated patients demonstrated meaningful benefit, as assessed by changes in advanced imaging, echocardiographic measures of cardiac function, and prednisone use. ConclusionsA large cohort (n = 77) of cardiac sarcoidosis patients has been treated at Stanford University. Roughly one-fourth of these patients (n = 20) received TNF-α inhibitors. Of these patients, none had worsening heart failure and all saw clinical benefit. These results help support the use of TNF-α inhibitors for the treatment of cardiac sarcoidosis based on real-world evidence and highlight the need for future prospective studies.

Cognitive Impairment is Associated with Abnormal Cardiac Hemodynamics in Heart Failure with Preserved Ejection Fraction

Introduction Cognitive impairment (CI) is prevalent in heart failure and is associated with higher mortality rates. The mechanism behind CI in heart failure with preserved ejection fraction (HFpEF) has not been established. The purpose of this study was to evaluate associations between abnormal cardiac hemodynamics and CI in individuals with HFpEF. Hypothesis Diastolic dysfunction, systolic dysfunction, and impaired ventricular vascular coupling will be associated with CI in HFpEF. Methods This was a secondary analysis of data from the Atherosclerosis Risk in Communities Study. Individuals who completed in-person neurocognitive assessments at visit 5 were included. Individuals with stroke or dementia were excluded. Participants were classified as having HFpEF, heart failure with reduced ejection fraction (HFrEF), or no heart failure. Independent variables included echocardiographic measures of cardiac function and factors hypothesized to influence CI in HFpEF based on an extensive literature review. Dependent variables included scores on neurocognitive tests. Descriptive statistics were used to describe sample characteristics and identify significant differences among those with HFpEF, HFrEF, and no heart failure. Bivariate analysis identified predictors for multivariate models and evaluated collinearity. Multiple imputation by chained equations was conducted to account for missing values. Multiple linear regression identified independent predictors of CI. Results Scores on tests of attention, language, executive function, and global cognitive function were worse among individuals with HFpEF than those with no heart failure. The effect of HFpEF on CI was small to moderate. Worse diastolic function was weakly associated with worse performance in memory, attention, and language. Higher cardiac index was associated with worse performance on one test of attention. No association between ventricular-vascular coupling and CI was identified. Older age, history of hypertension, and high numbers of depressive symptoms also were associated with CI. Conclusions Cognitive impairment is prevalent in HFpEF and affects several cognitive domains. The current study supports the need to screen individuals with HFpEF for CI. As CI is associated with worse outcomes, early identification and appropriate intervention has the potential to mitigate the effect of CI on outcomes, including mortality rates. The current study demonstrated an association between abnormal cardiac hemodynamics and CI. Although abnormal hemodynamics may contribute to CI in HFpEF, other factors may be involved. Future research should explore other mechanisms that contribute to CI in HFpEF.

Equivalence of G1/GPER Monotherapy Compared with Dual Administration of G1 and Lisinopril in Preventing Diastolic Dysfunction due to Estrogen Loss in SHR

IntroductionThe increased prevalence of heart failure with preserved ejection fraction (HFpEF) in women after menopause is linked to estrogen deficiency‐induced increases in systolic hypertension and chamber stiffness, with corresponding reductions in myocardial relaxation. New evidence reveals that the anti‐remodeling and lusitropic benefits of estrogen in preventing diastolic dysfunction, the precursor of HFpEF, may be due, in part, to a GPER‐mediated suppression of cardiac ACE activity. The aim of this study was to investigate the effects of monotherapy with the GPER specific agonist G1 against ACE inhibition on preserving diastolic function after estrogen loss and compare it to combination therapy, G1 plus lisinopril, in a hypertensive rodent model.MethodsTwenty SHR females underwent bilateral ovariectomy (OVX) while 5 SHRs received sham surgery at 11–12 weeks of age; 8 weeks post‐surgery, rats were randomized (n=5/group) to receive either a subcutaneous blank (vehicle) or G‐1 pellet (100 mg/kg) plus drinking water with or without lisinopril (Lis)(10 mg//kg, PO). Body weight and tail cuff blood pressures were recorded weekly and water consumption was measured daily. Following 2 months of treatment, rats were lightly anesthetized (Isoflurane) for echocardiographic measures of cardiac function and structure. LV tissue RAS activity was evaluated by HPLC. Data were analyzed by ANOVA. P&lt;0.05 was considered significant.ResultsLisinopril and combination therapy with Lis + G1 reversed OVX‐related increases in blood pressure (Fig. 1) and reduced LV weight/tibia length. Monotherapy with G1 had no overt impact on either parameter. Even so, profound and significant increases in myocardial relaxation (e’) were observed with G1 monotherapy and combination G1 + Lis therapy when compared to vehicle and Lis‐treatments alone (Fig. 2). Compared to vehicle, relative wall thicknesses (RWT) were also significantly reduced by monotherapy with G1 (36% reduction, P &lt; 0.0001), and this occurred to an extent that was modestly greater than that resulting from lisinopril monotherapy (20% reduction, P &lt;0.05). Lisinopril did not add to G1's benefit on RWT. Moreover, G1 had the greatest suppressive effect on cardiac ACE activity when compared to combination therapy and ACE inhibition alone (Fig. 3).ConclusionsMonotherapy with G1 was as effective at preventing OVX‐induced impairments in myocardial relaxation and increases in wall thickness as combination therapy with G1+ Lisinopril, and was better than ACE inhibition alone in the OVX‐SHR. The study reveals a novel action of G1 in suppressing cardiac ACE activity by a blood pressure‐independent mechanism and ACE‐mediated angiotensin II formation.Support or Funding InformationAG033727 (LG); P01‐HL051952 (LG, CMF)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effects of Vitamin D on Blood Pressure, Arterial Stiffness, and Cardiac Function in Older People After 1Year: BEST-D (Biochemical Efficacy and Safety Trial of Vitamin D).

BackgroundThe relevance of vitamin D for prevention of cardiovascular disease is uncertain. The BEST‐D (Biochemical Efficacy and Safety Trial of vitamin D) trial previously reported effects of vitamin D on plasma markers of vitamin D status, and the present report describes the effects on blood pressure, heart rate, arterial stiffness, and cardiac function.Methods and ResultsThis was a randomized, double‐blind, placebo‐controlled trial of 305 older people living in United Kingdom, who were allocated vitamin D 4000 IU (100 μg), vitamin D 2000 IU (50 μg), or placebo daily. Primary outcomes were plasma concentrations of 25‐hydroxy‐vitamin D and secondary outcomes were blood pressure, heart rate, and arterial stiffness in all participants at 6 and 12 months, plasma N‐terminal prohormone of brain natriuretic peptide levels in all participants at 12 months, and echocardiographic measures of cardiac function in a randomly selected subset (n=177) at 12 months. Mean (SE) plasma 25‐hydroxy‐vitamin D concentrations were 50 (SE 2) nmol/L at baseline and increased to 137 (2.4), 102 (2.4), and 53 (2.4) nmol/L after 12 months in those allocated 4000 IU/d, 2000 IU/d of vitamin D, or placebo, respectively. Allocation to vitamin D had no significant effect on mean levels of blood pressure, heart rate, or arterial stiffness at either 6 or 12 months, nor on any echocardiographic measures of cardiac function, or plasma N‐terminal prohormone of brain natriuretic peptide concentration at 12 months.ConclusionsThe absence of any significant effect of vitamin D on blood pressure, arterial stiffness, or cardiac function suggests that any beneficial effects of vitamin D on cardiovascular disease are unlikely to be mediated through these mechanisms.Clinical Trial Registration URL: https://www.clinicaltrialsregister.eu/ctr-search/search. Unique identifier: EudraCT number: 2011–005763‐24a

Institution of Veno-arterial Extracorporeal Membrane Oxygenation Does Not Lead to Increased Wall Stress in Patients with Impaired Myocardial Function.

The effect of veno-arterial extracorporeal membrane oxygenation (VA ECMO) on wall stress in patients with cardiomyopathy, myocarditis, or other cardiac conditions is unknown. We set out to determine the circumferential and meridional wall stress (WS) in patients with systemic left ventricles before and during VA ECMO. We established a cohort of patients with impaired myocardial function who underwent VA ECMO therapy from January 2000 to November 2013. Demographic and clinical data were collected and inotropic score calculated. Measurements were taken on echocardiograms prior to the initiation of VA ECMO and while on full-flow VA ECMO, in order to derive wall stress (circumferential and meridional), VCFc, ejection fraction, and fractional shortening. A post hoc sub-analysis was conducted, separating those with pulmonary hypertension (PH) and those with impaired systemic output. Thirty-three patients met inclusion criteria. The patients' median age was 0.06years (range 0-18.7). Eleven (33%) patients constituted the organ failure group (Gr2), while the remaining 22 (66%) patients survived to discharge (Gr1). WS and all other echocardiographic measures were not different when comparing patients before and during VA ECMO. Ejection and shortening fraction, WS, and VCFc were not statistically different comparing the survival and organ failure groups. The patients' position on the VCFc-WS curve did not change after the initiation of VA ECMO. Those with PH had decreased WS as well as increased EF after ECMO initiation, while those with impaired systemic output showed no difference in those parameters with initiation of ECMO. The external workload on the myocardium as indicated by WS is unchanged by the institution of VA ECMO support. Furthermore, echocardiographic measures of cardiac function do not reflect the changes in ventricular performance inherent to VA ECMO support. These findings are informative for the interpretation of echocardiograms in the setting of VA ECMO. ECMO may improve ventricular mechanics in those with PH as the primary diagnosis.

Moderated Posters: Congenital heart diseaseP374Classic-pattern dyssynchrony in adult patients with a Fontan circulationP375Outcome of pregnancy in patients with coarctation of aortaP376Diffuse myocardial fibrosis is not associated with decreased contractility: a magnetic resonance T1 mapping and feature tracking studyP377Cardiovascular abnormalities in patients with osteogenesis imperfecta: case-control studyP378Serial assessment of left ventricular systolic function by speckle tracking in patients with coarctation of

Moderated Posters: Congenital heart diseaseP374Classic-pattern dyssynchrony in adult patients with a Fontan circulationP375Outcome of pregnancy in patients with coarctation of aortaP376Diffuse myocardial fibrosis is not associated with decreased contractility: a magnetic resonance T1 mapping and feature tracking studyP377Cardiovascular abnormalities in patients with osteogenesis imperfecta: case-control studyP378Serial assessment of left ventricular systolic function by speckle tracking in patients with coarctation of

Feasibility and Reproducibility of Echocardiographic Measures in Children with Muscular Dystrophies.

Cardiac disease is a major cause of death in patients with muscular dystrophies. The use of feasible and reproducible echocardiographic measures of cardiac function is critical to advance the field of therapeutics for dystrophic cardiomyopathy. Participants aged 8 to 18 years with genetically confirmed Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, or limb-girdle muscular dystrophy were enrolled at five centers, and standardized echocardiographic examinations were performed. Measures of systolic and diastolic function and speckle-tracking echocardiography-derived cardiac strain were reviewed independently by two central readers. Furthermore, echocardiographic measures from participants with DMD were compared with those from retrospective age-matched control subjects from a single site to assess measures of myocardial function. Forty-eight participants (mean age, 13.3 ± 2.7 years) were enrolled. Shortening fraction had a greater interobserver correlation (intraclass correlation coefficient [ICC] = 0.63) compared with ejection fraction (ICC = 0.49). One reader could measure ejection fraction in only 53% of participants. Myocardial performance index measured by pulse-wave Doppler and Doppler tissue imaging showed similar ICCs (0.55 and 0.54). Speckle-tracking echocardiography showed a high ICC (0.96). Focusing on participants with DMD (n = 33), significantly increased mitral A-wave velocities, lower E/A ratios, and lower Doppler tissue imaging mitral lateral E' velocities were observed compared with age-matched control subjects. Speckle-tracking echocardiography demonstrated subclinical myocardial dysfunction with decreased average circumferential and longitudinal strain in three distinct subgroups: participants with DMD with normal shortening fractions, participants with DMD aged < 13 years, and participants with DMD with myocardial performance index scores < 0.40 compared with control subjects. In a muscular dystrophy cohort, assessment of cardiac function is feasible and reproducible using shortening fraction, diastolic measures, and myocardial performance index. Cardiac strain measures identified early myocardial disease in patients with DMD.

Evaluation of traditional and novel measures of cardiac function to detect anthracycline-induced cardiotoxicity in survivors of childhood cancer

Cardiovascular disease is the leading noncancer cause of death among survivors of childhood cancer. Ejection fraction (EF) and fractional shortening (FS) are common echocardiographic measures of cardiac function, but newer imaging modalities may provide additional information about preclinical disease. This study aimed to evaluate these modalities in detection of anthracycline-induced cardiac toxicity. We compared mean radial displacement, EF, and FS among 17 adult survivors of childhood cancer exposed to ≥ 300 mg/m(2) of anthracyclines to 17 age- and sex-matched healthy controls. Survivors with a history of cardiac-directed radiation, diabetes, or heart disease were excluded. Survivors (35% male), mostly with history of treatment for a solid tumor, had a median age at diagnosis of 15 years (1-20) and 27 years (18-50) at evaluation. Median anthracycline exposure was 440 (range 300-645) mg/m(2). FS (35.5 vs. 39.6%, p < 0.01) and radial displacement (5.6 vs. 6.7 mm, p = 0.02) were significantly lower in survivors compared to controls, respectively. Although the mean EF was lower in survivors versus controls (55.4 vs. 59.7%), it was not statistically significant (p = 0.057). All echocardiographic measures were inversely associated with anthracycline dose, though radial displacement was no longer significantly correlated with anthracycline dose after controlling for survival time (p = 0.07), while EF remained correlated (p = 0.003). Radial displacement, EF, and FS are lower in childhood cancer survivors compared to controls. In this study, radial displacement added no new information beyond the traditional measures, but clinical utility remains undetermined and requires further longitudinal study.

Cardiovascular Regulation During Body Unweighting by Lower Body Positive Pressure

We hypothesized that human cardiovascular responses to standing in reduced gravity environments, as on the Moon or Mars, could be modeled using a lower body positive pressure (LBPP) chamber. Heart rate, blood pressure, body segment fluid shifts, ECG, indexes of sympathetic, parasympathetic balance, and baroreflex control of the heart and periphery plus echocardiographic measures of cardiac function were recorded from seven men and seven women supine and standing at 100% (Earth), 40% (-Mars), and 20% (-Moon) bodyweights (BW). The fluid shifted from the chest was greater when standing at 100% BW than at 20% and 40% BW, while fluid pooled in the abdomen was similar at all BWs. Compared to moving from supine to standing at 100% BW, moving to 20% and 40% BW resulted in smaller decreases in stroke volume and pulse pressure, smaller increases in heart rate and smaller decreases in parasympathetic control of heart rate, baroreflex slope, numbers of blood pressure ramps, and much reduced indexes of sympathetic drive to the heart and periphery. However, peripheral vascular resistance, systolic pressure, and baroreflex effectiveness were elevated during 20% and 40% BW, compared to supine and standing at 100% BW. Standing at reduced bodyweight suppressed indexes of sympathetic control of heart rate and peripheral vasomotion. Regulatory responses indicated a combination of arterial and cardiopulmonary baroreflex control: mean heart rate, vasomotion, and baroreflex sensitivity appeared to be more under cardiopulmonary control while baroreflex effectiveness appeared to be driven more by the arterial baroreflex.

Improvement in collagen metabolism after 12 weeks’ cardiac resynchronization therapy in patients with ischaemic cardiomyopathy

To investigate the effects of cardiac resynchronization therapy (CRT) on collagen metabolism biomarkers and their relationship to cardiac function, in patients with ischaemic cardiomyopathy (ICM). Serum levels of matrix metalloproteinase (MMP)-9, tissue inhibitor of MMP-9 (TIMP-1), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal telopeptide of type I collagen (ICTP) were quantified before and after 12 weeks' treatment, in patients with ICM receiving CRT and standard medical therapy (CRT group) or standard medical therapy alone (non-CRT group), and in controls. Cardiac function was measured echocardiographically. MMP-9, TIMP-1, ICTP and the MMP-9/TIMP-1 ratio were significantly higher, and the PICP/ICTP ratio significantly lower, in patients with ICM (n = 27) compared with controls (n = 20). After 12 weeks' treatment, MMP-9, TIMP-1, ICTP and the MMP-9/TIMP-1 ratio were significantly higher, and the PICP/ICTP ratio significantly lower, in the non-CRT group (n = 15) compared with the CRT group (n = 12). The PICP/ICTP ratio correlated positively with TIMP-1 and negatively with MMP-9. The early/atrial ratio and left ventricular ejection fraction correlated positively and negatively, respectively, with the MMP-9/TIMP-1 ratio. Echocardiographic measurements of cardiac function were significantly worse in patients with ICM compared with controls and improved significantly after treatment in the CRT group. In ICM, collagen degradation biomarkers were elevated and correlated positively with cardiac function. CRT partially reversed the deterioration in collagen metabolism and enhanced cardiac function.