Ventricular Fractional Shortening Research Articles

Early detection and prediction of taxanes-induced cardiac dysfunction by assessment of myocardial deformation

Taxanes are extremely potent drugs, used in therapeutic regimes for breast cancer. However, the applicability is limited by the risk of cardiotoxicity. Guidelines define chemotherapy-induced cardiac dysfunction based on conventional parameters, such as left ventricular (LV) ejection fraction (EF) or fractional shortening (FS). Since normal EF or FS can mask LV impairment, our aim was to define other parameters, such as 4D LV deformation or biomarkers, able to diagnose early cardiac dysfunction, and to predict cardiotoxicity. Methods: 20 women with breast cancer (51±9 yrs), without cardiac disease, EF>50%, scheduled to be treated with taxanes, were assessed at baseline, after 1st cycle, and at the completion of treatment (cumulative dose of 417±154 g/m2). Conventional and 4D auto LV quantification echo were used to assess LV geometry, EF, FS, and systolic deformation: radial, longitudinal, circumferential strain (RS, LS, CS), and area strain (AS). STE was used to measure LV rotation: peak apical and basal rotation (RotA and RotB), LV twist (LVT), and twist and un-twist rate (TR and UTR). Cardiac troponin I and C-reactive protein were also measured. Results: After the 1st cycle of taxanes, there were reductions in longitudinal and radial deformation, and area strain, persistent after the completion of treatment, whereas LV dimensions, EF, FS, circumferential deformation, and rotation remained unchanged. On contrary, at the final of chemotherapy there was a significant decrease of EF (57±4% vs 63±3%, p=0.001), with no further changes of circumferential deformation and rotation or biomarkers level. A decrease of AS of 18% after the 1st cycle of taxanes was the best independent (r2=0.81, p=0.001) and accurate (100% sensitivity and 73% specificity, AUC 0.63) predictor of EF reduction at the completion of treatment. View this table: LV deformation and rotation Conclusion: Assessment of myocardial deformation by 4D echo detects early LV dysfunction and can predict further changes in EF, and therefore, can be used to monitor taxanes-induced cardiac dysfunction.

Hypertension, fluid overload and micro inflammation are associated with left ventricular hypertrophy in maintenance hemodialysis patients

This cross-sectional study aims to identify the potential risk factors of left ventricular hypertrophy (LVH) in hemodialysis (HD) patients. Echocardiography, anthropometric measurements and biochemical analyses were performed for 112 HD patients. In univariate analysis, body mass index, systolic blood pressure, diastolic blood pressure, glycosylated hemoglobin, glycated albumin, high sensitivity C-reactive protein (hs-CRP), cardiac troponin T (cTnT), amino-terminal pro-B-natriuretic peptide (NT-proBNP) and carotid artery intima-media thickness were positively correlated with left ventricular mass index (LVMI); pre-albumin, serum creatinine, left ventricular ejection fraction (LVEF) and fractional shortening were negatively correlated with LVMI. Linear regression analysis showed systolic blood pressure, NT-proBNP and LVEF were independently associated with LVMI. According to a binary logistic regression model, higher systolic blood pressure, NT-proBNP and hs-CRP levels showed independent correlation with LVH. Receiver operator characteristic curves analysis showed the associations between NT-proBNP and LVH more closely than hs-CRP and cTnT. The area under the curve for NT-proBNP, hs-CRP and cTnT was 0.762 (95% CI: 0.660–0.864, p < 0.001), 0.734 (95% CI: 0.624–0.844, p < 0.001) and 0.677 (95% CI: 0.563–0.790, p = 0.004), respectively. These data support the main conclusions: hypertension, fluid overload and micro inflammation are associated with LVH in maintenance HD patients. It demonstrates traditional and nontraditional risk factors all play important roles in the development of LVH.

Cardiac Expression of Human Type 2 Iodothyronine Deiodinase Increases Glucose Metabolism and Protects Against Doxorubicin-induced Cardiac Dysfunction in Male Mice

Altered glucose metabolism in the heart is an important characteristic of cardiovascular and metabolic disease. Because thyroid hormones have major effects on peripheral metabolism, we examined the metabolic effects of heart-selective increase in T3 using transgenic mice expressing human type 2 iodothyronine deiodinase (D2) under the control of the α-myosin heavy chain promoter (MHC-D2). Hyperinsulinemic-euglycemic clamps showed normal whole-body glucose disposal but increased hepatic insulin action in MHC-D2 mice as compared to wild-type (WT) littermates. Insulin-stimulated glucose uptake in heart was not altered, but basal myocardial glucose metabolism was increased by more than two-fold in MHC-D2 mice. Myocardial lipid levels were also elevated in MHC-D2 mice, suggesting an overall up-regulation of cardiac metabolism in these mice. The effects of doxorubicin (DOX) treatment on cardiac function and structure were examined using M-mode echocardiography. DOX treatment caused a significant reduction in ventricular fractional shortening and resulted in more than 50% death in WT mice. In contrast, MHC-D2 mice showed increased survival rate after DOX treatment, and this was associated with a six-fold increase in myocardial glucose metabolism and improved cardiac function. Myocardial activity and expression of AMPK, GLUT1, and Akt were also elevated in MHC-D2 and WT mice following DOX treatment. Thus, our findings indicate an important role of thyroid hormone in cardiac metabolism and further suggest a protective role of glucose utilization in DOX-mediated cardiac dysfunction.

Effect and safety analysis of carvedilol with metoprolol on children with dilated cardiomyopathy

Objective To compare the effect, safety and tolerance of carvedilol and metoprolol on children with dilated cardiomyopathy(DCM). Methods Children with DCM from Sep.2006 to Nov.2011 in Children's Hospital Affiliated to Chongqing Medical University were randomly divided into carvedilol group[(24 cases, 14 doys, 10 girls; (3.05±3.27) years old] and metoprolol group[(24 cases, 13 boys, 11 girls, (3.15±2.42) years old]. After controlling heart failure, the patients began to take oral carvedilol starting from 0.1 mg/(kg·d) or metoprolol starting from 0.5 mg/(kg·d). The 2 groups increased dose every 2 weeks.The largest dose was respectively 0.8 mg/(kg·d) or 2.0 mg/(kg·d), then maintaining the treatment for about 12 months.Cardiothoracic ratio, left ventricular end-diastolic volume(LVEDV), left ventricular end-systolic volume(LVESV), left ventricular ejection fraction(LVEF), left ventricular shortening fraction(LVFS), left ventricular mass(LVmass), drug safety and tolerance of 2 groups after treatment were evaluated. Results Cardiothoracic ratio, LVEDV, LVESV, LVmass significantly decreased but LVEF, LVFS significantly increased after treatment in comparison with before treatment in carvedilol group and metoprolol group(all P 0.05). The tolerated dose and safety of drug was slightly higher in carvedilol group compared with metoprolol group, but they did not have statistically significant difference(P>0.05). Conclusions Both carvedilol and metoprolol can reverse left ventricular remodeling and improve cardiac function of children with DCM.Carvedilol and metoprolol have higher safety and better tolerance.Safety and tolerance of carvedilol may be better, and thus has better application prospect. Key words: Carvedilol; Metoprolol; Dilated cardiomyopathy; Child

Subxiphoid echocardiographic evaluation of right heart function in patients with chronic obstructive pulmonary disease

PURPOSE: The purpose of this study is to evaluate by subxiphoid echocardiography the sensitivity and specificity of various echocardiographic parameters for early diagnosis and survival of patients with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS: Subxiphoid echocardiography was performed in 75 COPD patients to evaluate inferior vena cava dimension (IVCD), its collapsibility index (CI), end-diastolic right ventricular dimension (EDRVD), end-diastolic right ventricular thickness (EDRVT) (M-mode), right atrial area (RAA), right ventricular areas and right ventricular area shortening fraction. Results were compared to those of 30 healthy controls. Patients in sinus rhythm were divided in two according to there NYHA class (I+II and III+IV) an in three according to there acid-base blood gases status. RESULTS: All the indexes were equally and significantly changed in the patients with RVH/PH and those with COPD and atrial fibrillation (AF) when compared to controls. COPD patients with neither ECG criteria for RV hypertrophy (RVH), nor x-ray evidence of pulmonary hypertension (PH) presented with significantly greater EDRVA and RAA and normal IVC/CI. In both cases, according to cardiac and respiratory severity status subdivision, significant changes in any indexes with worsening of cardiac and respiratory failure were observed. Best sensitivity, specificity and predictive accuracy for early diagnosis were established for IVCD/CI and EDRVT. During the two-year study period, seven (9%) patients died in end stage respiratory and heart failure because of considerably reduced right heart performance. CONCLUSION: Subxiphoid echocardiography may be used for early detection of cor pulmonale, evaluation of right heart dysfunction and prognosis in COPD patients. Scripta Scientifica Medica 2013; 45(2): 55-60.

Determination and clinical significance of serum hypersensitivity C-reactive protein and hypersensitivity cardiac troponin in patients with coronary heart disease

Objective To research the determination of hypersensitivity C-reactive protein(Hs-CRP) and cardiac troponin T(Hs-cTnT) in patients with coronary heart disease,and to analyze the correlation with cardiac function.Methods The function of left ventricle and the serum levels of Hs-CRP and Hs-cTnT in 100 patients with coronary heart disease and 50 healthy subjects were detected.Results The function of left ventricle and the serum levels of Hs-CRP and Hs-cTnT were significantly different in patients with coronary heart disease and healthy subjects(P ＜0.01).The function of left ventricle and the serum levels of Hs-CRP and Hs-cTnT were significantly different in coronary heart disease patients with different New York Heart Association class(P ＜ 0.01).The serum levels of Hs-CRP and Hs-cTnT were positively correlated with class of New York Heart Association,left ventricular end diastolic diameter,and negatively correlated with left ventricular ejection fraction and fraction shortening (Absolute value of r:0.536 ～ 0.849,P ＜ 0.05).Conclusion The serum levels of Hs-CRP and Hs-cTnT significantly increase in patients with coronary heart disease,which is correlated to function of left ventricle,and it can be used as the indicators of cardiac function in patients with coronary heart disease. Key words: Coronary heart disease; Ventricular function,left; C-reactive protein; Troponin T

Fetal cardiac function in recipient twins undergoing fetoscopic laser ablation of placental anastomoses for Stage IV twin–twin transfusion syndrome

Cardiac dysfunction is common in the recipient fetus of twin-twin transfusion syndrome (TTTS). In this study, we aimed to document the severity of fetal cardiac dysfunction in Stage IV TTTS (fetal hydrops) and assess evolution of cardiac function longitudinally after fetoscopic laser surgery. We reviewed obstetric ultrasound examination data, pre- and postoperative echocardiograms and neonatal outcomes for 22 cases of Stage IV TTTS undergoing fetoscopic laser ablation of placental anastomoses between 1998 and 2011. Myocardial performance index, atrioventricular valve flow patterns, ventricular shortening fraction, ventricular hypertrophy, outflow tract obstruction and venous Doppler waveforms were assessed. Nineteen fetuses (86.4%) had ascites, eight (36.4%) had pleural effusions, nine (40.9%) had a pericardial effusion and 12 (54.5%) had subcutaneous edema at presentation. Preoperatively, cardiac function was grossly abnormal in all. Eight fetuses (36.4%) had functional pulmonary atresia and one (4.5%) had functional aortic atresia. Seventy-seven percent of recipient fetuses survived until birth. Postoperative echocardiographic follow-up (mean, 26 days) showed that indices of fetal cardiac function improved considerably, but never completely normalized. Six of the eight fetuses with functional pulmonary atresia (75.0%), as well as the fetus with functional aortic atresia, survived to birth. In all cases, the functional atresia resolved within 48 h of laser ablation therapy and none had structural valve anomalies at birth. All fetal effusions resolved after the laser. Fetoscopic laser ablation of placental anastomoses reverses cardiac dysfunction and valvulopathy, even in the most severe cases of TTTS. However, recovery takes longer than in early stage disease.

Cardiotoxicity in childhood cancer survivors: A problem with long-term consequences in need of early detection and prevention

I n this issue of Pediatric Blood & Cancer, Orgel et al. [1] report the prevalence of early post-treatment cardiac dysfunction in a multi-center, retrospective cohort of childhood acute myeloid leukemia (AML) survivors. After a median follow-up of 13 months from the end of treatment, patients demonstrated an 8.7% decline in left ventricular shortening fraction (LVSF) from baseline to the most recent post-treatment echocardiogram. Further, declines in LVSF greater than 10% were found in more than half of the cohort [1]. These declines were significantly associated with cumulative anthracycline dose, body-mass index percentile, and ethnicity. The authors conclude that children treated with an anthracycline-intensive regimen are at risk of late-onset cardiomyopathy, should be monitored with echocardiograms annually, and should be considered for cardioprotective strategies [1]. Cumulative anthracycline dose, age at diagnosis, gender, and length of follow-up, are all associated with late anthracyclineassociated cardiac dysfunction [2]. Although the anthracyclines used in this study were daunorubicin or mitoxantrone (mg/m), the authors used doxorubicin-equivalent doses to calculate anthracycline exposure, resulting in a mean cumulative anthracycline dose of 339 14mg/m. The findings of this study support that anthracycline-induced cardiotoxicity is dose-dependent, such that every 100mg/m increase in cumulative anthracycline dose was accompanied by a percent decrease of 7.4% (95% CI 11.1 to 3.7) in LVSF. Further, both this study and others [3] report declines in cardiac function even in children who received lower cumulative doses, suggesting that there is no risk-free dose of anthracycline. Shortening fraction is a measure of overall left ventricular (LV) systolic performance, which is influenced by heart rate, preload (initial stretching of the cardiomyocytes prior to contraction), afterload (the ventricular wall stress during ejection), and myocardial contractility. A decrease in LVSF at the end of anthracycline therapy is not uncommon in childhood cancer survivors, and is associated with decreased LVSF 11 years after diagnosis [3]. However, a more thorough evaluation of cardiac structure and function might include additional echocardiographic measures, such as LV mass and end-diastolic posterior wall thickness, which are also affected by anthracycline therapy. For example, LV mass and wall thickness are significantly reduced at 3, 6, and 8 years after diagnosis [4]. Altogether, these findings suggest there is a progressive and persistent deterioration of heart structure and function with time. While researchers and clinicians agree that there is a need for established guidelines to monitor cardiac function in these children, there is still a lack of evidence-based research determining the most effective mode and frequency of serial monitoring. Echocardiography, a minimally invasive method of measuring cardiac structure and function, is a useful and common modality used to monitor these children, but has limited sensitivity and specificity. The Children’s Oncology Group’s Long-Term Follow-Up Guidelines [5], referred to by Orgel et al., are based on recommendations from their core committee and is intended to standardize follow-up care in survivors of childhood cancers. They recommend echocardiograms or MUGA scans in varying frequencies depending on a child’s age at treatment, radiation exposure to the heart, and anthracycline dose. Further evidence-based research is required to validate these guidelines. Although they do not include gender, all of the other previously mentioned variables are generally the most common risk factors of cardiotoxicity. Given the varying frequency and severity of cardiotoxicity even among children receiving the same dose, researchers suspect there are still unknown risk factors that may influence cardiotoxicity, such as genetics, and as Orgel et al. [1] showed, body-mass index and ethnicity. Although echocardiographic measures help assess heart structure and function during therapy, it lacks the sensitivity and specificity to detect early cardiac injury and the ability to distinguish between short-term depressions in LV function and myocardial injury with late cardiac implications. Biochemical markers of cardiac injury and cardiomyopathy, such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), respectively, may also be useful in monitoring cardiotoxicity. Although not yet validated for clinical utility, elevations of these biomarkers during treatment are associated with abnormal echocardiographic findings 4 years after diagnosis [6]. As noted by Orgel et al., further efforts are needed to determine the validity and cost-effectiveness of using cardiac biomarkers and other screening models to predict cardiotoxicity [7]. The challenge lies in the ability to prospectively follow these children long enough to where sufficient vital status end points can be reached to reliably quantify the relationship between markers of cardiac injury and outcome.

Left ventricular function and right ventricular pacing for isolated congenital heart block.

BACKGROUND: Right ventricular pacing has been the treatment of choice in patients with congenital complete atrioventricular block (CAVB). However, the effect of chronic right ventricular pacing on left ventricular function in young patients is still controversial. AIM: The aim of the study was to assess the change in left ventricular systolic function in young patients (age ≤20 years) paced for isolated CAVB and to identify possible predictors of left ventricular systolic dysfunction. METHODS: We studied 55 young patients who underwent permanent right ventricular pacemaker implantation for CAVB in the absence of significant structural heart disease. We excluded patients affected by any condition known to affect left ventricular function. Echocardiographic data prior to and after pacemaker implantation were obtained. RESULTS: The mean age at the time of pacemaker implantation was 20 months, range 2.3-72 months. The mean duration of follow-up was 94.86 (range: 2-268 months). Chronic right ventricular pacing affected left ventricular shortening fraction (LVSF) significantly (pre = 37.8 ± 7.8 vs. post = 32.8 ± 5.5%, P = 0.0036). In 14 patients (25.4%), LVSF decreased by at least 7% (group A). The only parameter studied able to significantly discriminate the two groups was a better baseline LVSF in group A (baseline LVSF: 42.1 ± 5.2 vs. 32.2 ± 2.2%, P = 0.019; cut-off value >39%, P <0.0001; area under the curve = 0.887). CONCLUSION: Chronic right ventricular pacing in young patients without significant structural heart disease is responsible for a significant reduction in left ventricular systolic function, especially in patients with a good baseline LVSF. These patients need close follow-up not only for pacing parameters but also for left ventricular functional evaluation.

Left Ventricular Function in Nigerians With Type 2 Diabetes Mellitus With and Without Hypertension

Background . Diabetes mellitus is an established risk factor for cardiovascular events and has been found to be independently associated with abnormal left ventricular function. We therefore decided to embark on this study to assess the left ventricular function in our diabetic patients. Method . The study design was cross-sectional and conducted among patients attending out patient clinic of the Obafemi Awolowo University Teaching Hospitals complex (OAUTHC) Ile Ife, Osun State south western Nigeria. It comprised 75 consecutive patients with type 2 diabetes mellitus with or without hypertension and 50 apparently healthy age- and sex- comparable controls. Using a structured pre-evaluated questionnaire, the demographic and clinical data were obtained. All subjects had two-dimensional (2D) M-mode, and Doppler echocardiography using Sonoline G60s Ultrasound imaging system with 4.2 MHZ transducer equipped with simultaneous ECG tracing. Results . A total of 125 consecutive subjects were recruited comprising 75 patients with type 2 diabetes mellitus with or without hypertension and 50 apparently healthy age-and-sex comparable controls. There were no significant difference in left ventricular ejection fraction and fractional shortening between the patients and controls. The ratio of early trans-mitral flow to late atrial filling of the left ventricle (E/A ratio), isovolumic left ventricular relaxation time, and left ventricular deceleration time were predominantly prolonged among the study patients compared to the controls. Conclusion . This study showed that left ventricular systolic function was preserved among patients with type 2 diabetes mellitus. The abnormal diastolic function noted was predominantly that of impaired relaxation compared with controls. This is particularly more in hypertensive-diabetics than normotensive-diabetics. Keywords : Diabetes mellitus, Left ventricular function.

Abstract 3428: Effect of a non cardiotoxic Doxorubicin analog, 13-deoxy, 5-imino doxorubicin on decatenation of DNA by Topoisomerase II.

Abstract Anthracyclines such as doxorubicin are widely used to treat solid and hematological cancers. However, within the course of treatment they have the potential to cause life threatening chronic cardiotoxicity which limits their potential use. The cause of cardiotoxicity is not thoroughly understood, with previous research indicating the generation of reactive oxygen species and free iron accumulation as possible causes for cardiomyocyte death. Recent publications have shown the interaction between doxorubicin and Topoisomerase IIβ plays a key role in anthracycline induced cardiotoxicity. Topoisomerase enzymes are utilized during the coiling and uncoiling of DNA within the cell and are active targets of anthracyclines not only in tumoricidal action (Topoisomerase IIα) but also in the pathogenesis of cardiotoxicity (Topoisomerase IIβ). In this research we seek to further evaluate the interaction between doxorubicin, doxorubicin analogues and Topoisomerase IIβ. The analogues were selected due to previous chronic in vivo experiments in rabbits where classical manifestations of cardiotoxicity (including reduced left ventricular shortening fraction and pathological changes in cardiac tissue) were not observed. Furthermore, one analogue (13-deoxy, 5-imino doxorubicin) has shown promising clinical data suggesting a strong antineoplastic effect without the cardiotoxic effects. Doxorubicin and this analogue were placed in the presence of catenated DNA for 6 hours at 37°C prior to exposure to Topoisomerase IIα and β enzymes. The reaction was allowed to proceed for 30 minutes at 37°C and analyzed for decatenation of the DNA by the enzyme. This experiment was then repeated in cardiac H9c2 cells to assay possible differential inhibition at the cellular level. Citation Format: Nicole Frank, Richard Olson, Gerald M. Walsh, Todd Talley, Barry Cusack. Effect of a non cardiotoxic Doxorubicin analog, 13-deoxy, 5-imino doxorubicin on decatenation of DNA by Topoisomerase II. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3428. doi:10.1158/1538-7445.AM2013-3428

Effects of Early, Late, and Long-term Nonselective β-Blockade on Left Ventricular Remodeling, Function, and Survival in Chronic Organic Mitral Regurgitation

Mitral regurgitation (MR) produces sympathetic nervous system activation which is detrimental in other causes of heart failure. However, whether β-blockade is beneficial in MR has not been determined. Eighty-seven rats with significant organic MR were randomized to the β-blockade group (n=43) or the control group (n=44). Carvedilol was started in week 2 post MR induction and given for 23 to 35 weeks in the β-blockade group. Echocardiography was performed at baseline and at weeks 2, 6, 12, 24, 30, and 36 after MR induction. After 23 weeks of β-blockade, heart rates were significantly reduced by carvedilol (308 ± 25 versus 351 ± 31 beats per minute; P<0.001). Left ventricular end-diastolic (2.2 ± 0.7 versus 1.59 ± 0.6 mL; P<0.001), end-systolic volumes (0.72 ± 0.42 versus 0.40 ± 0.19 mL; P<0.001), and mass index (2.40 ± 0.55 versus 2.06 ± 0.62 g/kg; P<0.001) were significantly higher, and left ventricular fraction shortening (33 ± 7% versus 38 ± 7%; P<0.001) and ejection fraction (69 ± 11% versus 75 ± 7%; P<0.001) were significantly lower in the β-blockade group than in the control group. Systolic blood pressure was lower in the β-blockade group than in the control group (114 ± 10 versus 93 ± 12 mm Hg; P<0.005). Survival probability was significantly lower in the early β-blockade group than in the control group (88% versus 96%; P=0.03). Early and long-term nonselective β-blockade was associated with adverse left ventricular remodeling, systolic dysfunction, and a reduction in survival in the experimental rat model of organic MR.

Subclinical diastolic dysfunction in children with Wilson’s disease assessed by tissue Doppler echocardiography: a possible early predictor of cardiac involvement

Background The aim of this study was to evaluate the left ventricular systolic and diastolic functions and cardiac rhythm problems for the early detection of myocardial dysfunction in children with Wilson’s disease.Methods We compared patients who had Wilson’s disease (n = 22) with age- and sex-matched healthy control subjects (n = 21). The diagnosis of Wilson’s disease was based on clinical symptoms and laboratory tests (serum ceruloplasmin, urinary and hepatic copper concentrations). Standard echocardiographic examination, as well as pulsed-wave Doppler, tissue Doppler echocardiography examinations of all patients were performed. 24-hour ECG Holter monitoring was also performed in all subjects.Results All patients were asymptomatic on cardiological examination and had sinus rhythm on electrocardiography. Left ventricular ejection fraction, fractional shortening, wall thickness and left ventricular mass were similar in both groups. In comparison to healthy subjects, children with Wilson’s disease had signifi cantly lower mitral E velocity, mitral E/A ratio (P = 0.046, P= 0.021, respectively) and longer isovolumetric relaxation time values (P = 0.015) as estimated by pulsed wave Doppler echocardiography. Wilson patients had longer isovolumetric relaxation time (IVRT) values estimated by tissue Doppler echocardiography (P = 0.006) compared to the controls. On 24-hour ECG Holter monitoring, none of the Wilson patients showed life-threatening cardiac arrhythmia.Conclusion Our study showed results that might be consistent with subclinical diastolic dysfunction in cardiologically asymptomatic Wilson’s disease children which probably represents an early stage of cardiac involvement. Therefore it may be useful to monitor these signs in the follow-up of the patients.

Early cardiac outcomes following contemporary treatment for childhood acute myeloid leukemia: A north American perspective

Anthracycline agents are used for treatment of acute myeloid leukemia (AML) but may cause late-onset cardiomyopathy. Current frontline therapy for AML in North America, as reflected in the approach of the Children's Oncology Group (COG) and other pediatric consortia, is adapted from the anthracyline-intensive Medical Research Council (MRC) regimen. The purpose of this study was to describe early post-treatment cardiac function as a potential indicator of acute and long-term risk associated with this approach. A multi-center retrospective cohort analysis was conducted of AML survivors diagnosed from 2004 to 2009 and treated with MRC-based regimens. Change in left ventricular shortening fraction (LVSF) on echocardiogram was determined from baseline to latest post-treatment/pre-relapse value; associations with potential predictors were examined. This cohort of pediatric survivors (n = 52) was assessed at a median interval of 13 months from end of treatment. Mean cumulative anthracycline dose was 339 ± 14 mg/m(2) . Mean baseline and post-treatment LVSF were 39.3 ± 0.8% and 35.4 ± 0.9%, respectively; mean percent change for individuals was -8.4 ± 2.8% (P < 0.001). Cardiac-directed medications were initiated in four patients (7.7%). Decline in LVSF was significantly associated with cumulative anthracycline dose, increasing BMI and Hispanic ethnicity. Early, significant decline in LVSF was observed following treatment with these MRC-based regimens. Elevated BMI and Hispanic ethnicity were identified as new independent risk factors. Children and adolescents so treated are at substantial risk for late-onset cardiomyopathy, require monitoring with annual echocardiogram per current COG survivorship guidelines, and are good candidates for appropriate cardioprotection strategies.

Retinol dehydrogenase, RDH1l, is essential for the heart development and cardiac performance in zebrafish

Background Retinoic acid (RA) is a potent signaling molecule that plays pleiotropic roles in patterning, morphogenesis, and organogenesis during embryonic development. The synthesis from retinol (vitamin A) to retinoic acid requires two sequential oxidative steps. The first step involves the oxidation of retinol to retinal through the action of retinol dehydrogenases. Retinol dehydrogenases1l (RDH1l) is a novel zebrafish retinol dehydrogenase. Herein we investigated the role of zebrafish RDH1l in heart development and cardiac performance in detail. Methods RDH1l specific morpholino was used to reduce the function of RDH1l in zebrafish. The gene expressions were observed by using whole mount in situ hybridization. Heart rates were observed and recorded under the microscope from 24 to 72 hours post fertilization (hpf). The cardiac performance was analyzed by measuring ventricular shortening fraction (VSF). Results The knock-down of RDH1l led to abnormal neural crest cells migration and reduced numbers of neural crest cells in RDH1l morphant embryos. The reduced numbers of cardiac neural crest cells also can be seen in RDH1l morphant embryos. Furthermore, the morpholino-mediated knock-down of RDH1l resulted in the abnormal heart loop. The left-right determining genes expression pattern was altered in RDH1l morphant embryos. The impaired cardiac performance was observed in RDH1l morphant embryos. Taken together, these data demonstrate that RDH1l is essential for the heart development and cardiac performance in zebrafish. Conclusions RDH1l plays a important role in the neural crest cells development, and then ultimately affects the heart loop and cardiac performance. These results show for the first time that an enzyme involved in the retinol to retinaldehyde conversion participate in the heart development and cardiac performance in zebrafish.

All-Cause Mortality and Cardiovascular Outcomes With Prophylactic Steroid Therapy in Duchenne Muscular Dystrophy

This study sought to determine the impact of steroid therapy on cardiomyopathy and mortality in patients with Duchenne muscular dystrophy (DMD). DMD is a debilitating X-linked disease that afflicts as many as 1 in 3,500 boys. Although steroids slow musculoskeletal impairment, the effects on cardiac function and mortality remain unknown. We conducted a cohort study on patients with DMD treated with renin-angiotensin-aldosterone system antagonists with or without steroid therapy. Eighty-six patients, 9.1 ± 3.5 years of age, were followed for 11.3 ± 4.1 years. Seven of 63 patients (11%) receiving steroid therapy died compared with 10 of 23 (43%) not receiving steroid therapy (p = 0.0010). Overall survival rates at 5, 10, and 15 years of follow-up were 100%, 98.0%, and 78.6%, respectively, for patients receiving steroid therapy versus 100%, 72.1%, and 27.9%, respectively, for patients not receiving steroid therapy (log-rank p = 0.0005). In multivariate propensity-adjusted analyses, steroid use was associated with a 76% lower mortality rate (hazard ratio: 0.24; 95% confidence interval: 0.07 to 0.91; p = 0.0351). The mortality reduction was driven by fewer heart failure-related deaths (0% vs. 22%, p = 0.0010). In multivariate analyses, steroids were associated with a 62% lower rate of new-onset cardiomyopathy (hazard ratio: 0.38; 95% confidence interval: 0.16 to 0.90; p = 0.0270). Annual rates of decline in left ventricular ejection fraction (-0.43% vs. -1.09%, p = 0.0101) and shortening fraction (-0.32% vs. -0.65%, p = 0.0025) were less steep in steroid-treated patients. Consistently, the increase in left ventricular end-diastolic dimension was of lesser magnitude (+0.47 vs. +0.92 mm per year, p = 0.0105). In patients with DMD, steroid therapy is associated with a substantial reduction in all-cause mortality and new-onset and progressive cardiomyopathy.

Atrial natriuretic peptide exerts protective action against angiotensin II-induced cardiac remodeling by attenuating inflammation via endothelin-1/endothelin receptor A cascade

We aimed to investigate whether atrial natriuretic peptide (ANP) attenuates angiotensin II (Ang II)-induced myocardial remodeling and to clarify the possible molecular mechanisms involved. Thirty-five 8-week-old male Wistar-Kyoto rats were divided into control, Ang II, Ang II + ANP, and ANP groups. The Ang II and Ang II + ANP rats received 1 μg/kg/min Ang II for 14 days. The Ang II + ANP and ANP rats also received 0.1 μg/kg/min ANP intravenously. The Ang II and Ang II + ANP rats showed comparable blood pressure. Left ventricular fractional shortening and ejection fraction were lower in the Ang II rats than in controls; these indices were higher (P < 0.001) in the Ang II + ANP rats than in the Ang II rats. In the Ang II rats, the peak velocity of mitral early inflow and its ratio to atrial contraction-related peak flow velocity were lower, and the deceleration time of mitral early inflow was significantly prolonged; these changes were decreased by ANP. Percent fibrosis was higher (P < 0.001) and average myocyte diameters greater (P < 0.01) in the Ang II rats than in controls. ANP decreased both myocardial fibrosis (P < 0.01) and myocyte hypertrophy (P < 0.01). Macrophage infiltration, expression of mRNA levels of collagen types I and III, monocyte chemotactic protein-1, and a profibrotic/proinflammatory molecule, tenascin-C (TN-C) were increased in the Ang II rats; ANP significantly decreased these changes. In vitro, Ang II increased expression of TN-C and endothelin-1 (ET-1) in cardiac fibroblasts, which were reduced by ANP. ET-1 upregulated TN-C expression via endothelin type A receptor. These results suggest that ANP may protect the heart from Ang II-induced remodeling by attenuating inflammation, at least partly through endothelin 1/endothelin receptor A cascade.

460: Highly realistic simulator for teaching and training fetoscopic laser surgery in twin-to-twin transfusion syndrome

training fetoscopic laser surgery in twin-to-twin transfusion syndrome Suzanne Peeters, Lu-Ming Sun, Frans Klumper, Johanna Middeldorp, Rory Windrim, Enrico Lopriore, Dick Oepkes Leiden University Medical Center, Obstetrics, Leiden, Netherlands, Shanghai First Maternity and Infant Hospital, Obstetrics, Shanghai, China, Mt.Sinai Hospital, University of Toronto, Obstetrics, Toronto, ON, Canada, Leiden University Medical Center, Neonatology, Leiden, Netherlands OBJECTIVE: Fetoscopic laser surgery is the best treatment for TTTS. Success rate and safety depend on skills and experience of the fetal surgeons. Even large fetal treatment centers have limited numbers of cases, and animal models are lacking, therefore teaching and training this procedure is challenging. Aim of our project was to develop a simulator model with the highest possible level of realism. STUDY DESIGN: We injected fresh placentas from untreated monochorionic twins born between 16 and 26 weeks’ gestation with colored dye, realistic light red for veins and dark red for arteries. We inserted the injected placentas in a silicon high fidelity simulator originally developed to train ultrasound-guided obstetric procedures. Preparation, team setting and equipment were identical to real-life surgery. RESULTS: The training sessions included complete set-up and performance of the fetoscopic laser surgery, including identification of anastomoses, selective sequential laser coagulation and drawing of a ‘Solomon’ line. On video, the procedure was virtually identical to imaging in real patients. Using an internet-connection, telementoring of the simulator training sessions performed in centers on two other continents enabled off-site teaching. CONCLUSION: The training sessions included complete set-up and performance of the fetoscopic laser surgery, including identification of anastomoses, selective sequential laser coagulation and drawing of a ‘Solomon’ line. On video, the procedure was virtually identical to imaging in real patients. Using an internet-connection, telementoring of the simulator training sessions performed in centers on two other continents enabled off-site teaching, increasing training opportunities for start-up centers. 461 Fetal cardiac function in recipient fetuses of stage 4 twin-to-twin transfusion syndrome undergoing fetoscopic laser coagulation of placental anastomoses Tim Van Mieghem, Edgar Jaeggi, Rory Windrim, Lisa Hornberger, Greg Ryan Mount Sinai Hospital, Fetal Medicine Unit Obstetrics & Gynecology, Toronto, ON, Canada, Hospital for Sick Children, Fetal Cardiac Program Pediatric Cardiology, Toronto, ON, Canada, Stollery Children’s Hospital, Pediatric Cardiology, Edmonton, ON, Canada OBJECTIVE: Cardiac dysfunction is common in the recipient fetus of twin-to-twin transfusion syndrome (TTTS). Information on fetal cardiac dysfunction in stage 4 TTTS (fetal hydrops) is lacking. In this study, we document severity of fetal cardiac dysfunction in stage 4 TTTS and assess evolution of cardiac function longitudinally after fetoscopic laser. STUDY DESIGN: We retrospectively retrieved obstetric ultrasounds, preand postoperative echocardiograms and neonatal outcomes of 22 cases of stage 4 TTTS undergoing fetoscopic laser. The following echocardiographic parameters were assessed: myocardial performance index, atrio-ventricular valve flow patterns, ventricular shortening fraction, ventricular hypertrophy, outflow tract obstruction and venous Dopplers. RESULTS: Nineteen recipient fetuses (86%) had ascites, 8(36%) had pleural effusions, 9(41%) had a pericardial effusion and 12(55%) had subcutaneous edema at intial presentation. Preoperatively, fetal cardiac function was grossly abnormal in all cases. Eight fetuses (36%) had findings compatible with functional pulmonary atresia and 1 (4.5%) had functional aortic atresia. Postoperative survival of the recipient fetus was 77%. Echocardiographic follow-up at a mean of 26 days (range 1-82 days) postoperatively showed that indices of fetal cardiac function improved considerably, yet that cardiac function did not completely normalise. Six of eight fetuses with functional pulmonary atresia (75%), as well as the fetus with functional aortic atresia survived until birth. In all cases, the functional atresia resolved, often already within the first 48 hours after surgery and these fetuses did not have structural valve anomalies at birth. All fetal effusions resolved after the laser procedure. CONCLUSION: Fetoscopic laser coagulation of placental anastomoses reverses cardiac dysfunction and valvulopathy, even in the more severe cases of TTTS. Recovery however takes longer than in the early disease stages. Clinical characteristics and pregnancy outcomes

Simulation of Changes in Myocardial Tissue Properties During Left Ventricular Assistance With a Rotary Blood Pump

We considered a mathematical model to investigate changes in geometric and hemodynamic indices of left ventricular function in response to changes in myofiber contractility and myocardial tissue stiffness during rotary blood pump support. Left ventricular assistance with a rotary blood pump was simulated based on a previously published biventricular model of the assisted heart and circulation. The ventricles in this model were based on the one-fiber model that relates ventricular function to myofiber contractility and myocardial tissue stiffness. The simulations showed that indices of ventricular geometry, left ventricular shortening fraction, and ejection fraction had the same response to variations in myofiber contractility and myocardial tissue stiffness. Hemodynamic measures showed an inverse relation compared with geometric measures. Particularly, pulse pressure and arterial dP/dtmax increased when myofiber contractility increased, whereas increasing myocardial tissue stiffness decreased these measures. Similarly, the lowest pump speed at which the aortic valve remained closed increased when myofiber contractility increased and decreased when myocardial tissue stiffness increased. Therefore, simultaneous monitoring of hemodynamic parameters and ventricular geometry indirectly reflects the status of the myocardial tissue. The appropriateness of this strategy will be evaluated in the future, based on in vivo studies.

Role of fetal echocardiography in the evaluation of structure and function of fetal heart in diabetic pregnancies

Objective: To detect the structural and functional changes of fetal hearts in diabetic pregnancies by using Doppler echocardiography. Methods: This prospective study included 119 pregnant women divided into three groups. Group 1 included 47 pregnant patients with pre-existing diabetes mellitus (DM), group 2 included 40 patients with gestational diabetes and group 3 included 32 non-diabetic pregnant women. M-mode echocardiography was used to measure the thickness of the fetal ventricular walls and interventricular septum. The mitral and tricuspid early (E) and late (A) diastolic velocities and the ventricular shortening fraction were measured. Results: HbA1c % was significantly lower in gestational diabetes group compared with the pre-existing diabetes group. The interventricular septum was significantly thicker in the pre-existing diabetes group compared with other groups. Tricuspid and mitral E/A ratios were significantly lower in the pre-existing diabetes group compared with gestational diabetes and control groups. Moreover, there were no significant differences in the tricuspid and mitral E/A ratios between gestational diabetes group and the control group. The right and left ventricular shortening fractions were similar in the three groups. Conclusion: Fetuses of women with well-controlled gestational diabetes lack the diastolic dysfunction that is present in fetuses of women with pre-existing diabetes