Characterization of Diastolic Dysfunction in Twin-Twin Transfusion Syndrome: Association between Doppler Findings and Ventricular Hypertrophy

2011 ◽  
Vol 24 (8) ◽  
pp. 834-840 ◽  
Author(s):  
Allison Divanović ◽  
James Cnota ◽  
Richard Ittenbach ◽  
Xiao Tan ◽  
William Border ◽  
...  
Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Pamela D Winterberg ◽  
Rong Jiang ◽  
Bo Wang ◽  
Sonal Harbaran ◽  
Mary B Wagner

Introduction: The underlying mechanisms contributing to uremic cardiomyopathy during chronic kidney disease (CKD) are poorly understood, limiting treatment options. Hypothesis: We aimed to determine if altered calcium (Ca2+) handling in cardiomyocytes contributes to diastolic dysfunction in a mouse model of CKD. Methods: CKD was induced in male 129X1/SvJ mice through five-sixths nephrectomy in a two-stage surgery. Age-matched mice served as controls. Transthoracic echocardiography and speckle-tracking based strain analysis (Vevo2100, VisualSonics, Toronto, Canada) were performed at 8 weeks post-CKD (n=7-8) to assess heart structure and function. Cardiomyocytes isolated from mice with or without CKD (n=3 mice per group, 10-12 cells/mouse) were loaded with Fura 2-AM, paced by field stimulation (1 Hz), and imaged with a dual-excitation fluorescence photomultiplier system (IonOptix Inc, Milton, MA) to measure Ca2+ transients and sarcomere length. Sarcoplasmic reticulum Ca2+ content was determined following rapid application of caffeine.[[Unable to Display Character: &#8232;]] Results: CKD mice displayed left ventricular hypertrophy (LVAW;d 1.46 ± 0.134 vs 1.04 ± 0.129 mm; p<0.001) and decreased longitudinal strain (19 ± 4.1% vs 30 ± 2.3%; p<0.0001) compared to control mice. Resting sarcomere length was significantly shorter in cardiomyocytes isolated from CKD mice compared to normal mice (1.86 ± 0.054 vs 1.89 ± 0.047 nm; p = 0.016), but relaxation time was unchanged (0.21 ± 0.12 vs 0.21 ± 0.15 seconds, p=0.4). Unexpectedly, the baseline cytosolic Ca2+ content was lower in uremic myocytes (1.22 ± 0.353 vs 1.46 ± 0.252 AU, p=0.002). However, the Ca2+ transient amplitude (0.39 ± 0.177 vs 0.41 ± 0.167 AU, p=0.4) and sarcoplasmic reticulum Ca2+ content (1.15 ± 0.321 vs 1.24 ± 0.550 AU, p=0.4) were comparable between CKD and normal cardiomyocytes.[[Unable to Display Character: &#8232;]] Conclusions: Mice with CKD have signs of left ventricular hypertrophy and diastolic dysfunction on echocardiography. Cardiomyocytes isolated from mice with CKD have shorter diastolic sarcomere length implying impaired relaxation, yet paradoxically have decreased diastolic calcium. Thus Ca2+ accumulation during diastole does not appear to contribute to impaired relaxation in this model.


1995 ◽  
Vol 8 (3) ◽  
pp. 392
Author(s):  
Víctor G. Dávila-Román ◽  
Glenn E. Davison ◽  
Christopher S. Hall ◽  
James G. Miller ◽  
Samuel A. Wickline

2005 ◽  
Vol 64 (1) ◽  
Author(s):  
Maria Teresa Manes ◽  
Manlio Gagliardi ◽  
Gianfranco Misuraca ◽  
Stefania Rossi ◽  
Mario Chiatto

The aim of this study was to estimate the impact and prevalence of left ventricular geometric alterations and systolic and diastolic dysfunction in hemodialysis patients, as well as the relationship with cardiac troponin as a marker of myocardial damage. Methods: 31 patients (pts), 19 males and 12 females, age 58.1±16.4 (26 on hemodialysis, 5 on peritoneal dialysis) and 31 healthy normal controls were enrolled. Echocardiography measurements were carried out according to the American Society of Echocardiography recommendations. Left ventricular mass was calculated, according to the Devereux formula and indexed to height and weight 2.7. Doppler echocardiography was performed to study diastolic function by measurements of isovolumetric relaxation period (IVRT), E wave deceleretion time (DTE) and E/A ratio. Cardiac troponin was measured by a third generation electrochemiluminescence immunoassay. Statistical analysis was performed using the t-test for between-group comparisons and the Pearson and Spearman’s tests to investigate correlations; p values of &lt;0.05 were considered statistically significant. Results: Eccentric hypertrophy was the most frequent pattern (n=17; 55%), followed by normal cardiac geometry (n=7; 23%), and concentric hypertrophy (n=5; 16%). Only 6% of pts (n=2) showed concentric remodelling. Systolic dysfunction was present in terms of endocardial parameters in 3 pts (9%) (fractional shartening &lt;25%, EF&lt;50%), but in terms of midwall myocardial shortening in 51% (n=16). Diastolic dysfunction was present in 87% (n=27) with a pattern of impaired relaxation (in 5 without left ventricular hypertrophy). E/A was negatively correlated with age (r=-0.41, p=0.02); DTE was positively correlated with posterior wall thickness (r=0.36, p=0.05) and interventricular septum thickness (r=0.45, p=0.01); cardiac troponin was positively correlated with age (r=0.50, p=0.00), left ventricular mass (r=0.41, p=0.02), posterior wall thickness (r=0.41; p=0.02) and interventricular septum thickness (r=0.39, p=0.03) but not with diastolic dysfunction parameters. No significant difference was found in terms of duration of dialysis between patients with normal left ventricular geometry and those with left ventricular hypertrophy, but a significant difference in age was found (p=0.03). Pts with diastolic dysfunction had more frequent hypotensive episodes during dialysis (p &lt;0.01). Conclusion: Impaired geometry and cardiac function is frequently observed in pts undergoing hemodialysis. Diastolic dysfuction is associated to a geometric pattern of left ventricular hypetrophy, although it can be an isolated initial manifestation of myocardial damage. Depressed midwall myocardial shortening can discriminate left ventricular dysfunction better than traditional endocardial systolic indexes.


Author(s):  
Javier Larrasa-Alonso ◽  
María Villalba ◽  
Carlos Martí-Gómez ◽  
Paula Ortiz-Sánchez ◽  
Marina López-Olañeta ◽  
...  

Rationale: RNA-binding proteins (RBPs) play critical roles in human biology and disease. Aberrant RBP expression affects various steps in RNA processing, altering the function of the target RNAs. The RBP serine/arginine-rich splicing factor 4 (SRSF4) has been linked to neuropathies and cancer. However, its role in the heart is completely unknown. Objective: To investigate the role of SRSF4 in the heart. Methods and Results: Echocardiography of mice specifically lacking SRSF4 in the heart (SRSF4 KO) revealed left ventricular hypertrophy and increased cardiomyocyte area, which led to progressive diastolic dysfunction with age. SRSF4 KO mice showed altered electrophysiological activity under isoproterenol-induced cardiac stress, with a post-QRS depression and a longer QT interval, indicating an elevated risk of sudden cardiac death. RNA-Seq analysis revealed expression changes in several long non-coding RNAs (lncRNAs), including GAS5 (growth arrest specific 5), which we identified as a direct SRSF4 target in cardiomyocytes by individual-nucleotide-resolution cross-linking and immuno-precipitation (iCLIP). GAS5 is a repressor of the glucocorticoid receptor (GR) and was downregulated in SRSF4 KO hearts. This corresponded with elevated GR transcriptional activity in cardiomyocytes, leading to increases in hypertrophy markers and cell size. Furthermore, hypertrophy in SRSF4 KO cardiomyocytes was reduced by overexpressing GAS5. Conclusions: Loss of SRSF4 expression results in cardiac hypertrophy, diastolic dysfunction, and abnormal repolarization. The molecular mechanism underlying this effect involves GAS5 downregulation and consequent elevation of GR transcriptional activity. Our findings may help to develop new therapeutic tools for the treatment of cardiac hypertrophy and myocardial pathology in Cushing's syndrome patients.


2006 ◽  
Vol 12 (8) ◽  
pp. 601-607 ◽  
Author(s):  
Joachim H. Ix ◽  
Michael G. Shlipak ◽  
Glenn M. Chertow ◽  
Sadia Ali ◽  
Nelson B. Schiller ◽  
...  

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