Sustained reversal of electrical remodeling during and after left ventricular assist device (LVAD) support

2004 ◽  
Vol 23 (2) ◽  
pp. S52-S53
Author(s):  
J Hardy ◽  
C Terracciano ◽  
P Tansley ◽  
E Birks ◽  
C Bowles ◽  
...  
Keyword(s):  
Left Ventricular Assist Device ◽  
Ventricular Assist Device ◽  
Left Ventricular ◽  
Electrical Remodeling ◽  
Assist Device ◽  
Ventricular Assist ◽  
Left Ventricular Assist ◽  
Lvad Support

Abstract 13291: Left Ventricular Assist Device Support is Associated with Sustained Cardiac CamKII Activation and Increased MEF2

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Estibaliz Castillero ◽  
Ruiping Ji ◽  
Xiaokan Zhang ◽  
Vivian Choi ◽  
Ayesha Mannan ◽  
...  
Keyword(s):  
Left Ventricular Assist Device ◽  
Ventricular Assist Device ◽  
Cardiac Tissue ◽  
Left Ventricular ◽  
Assist Device ◽  
Ventricular Assist ◽  
Left Ventricular Assist ◽  
Before And After ◽  
Dependent Protein ◽  
Lvad Support

Background: Ca2+/calmodulin-dependent protein kinase (CaMK)II has been implicated in impaired myocardial Ca2+ signaling and may play an important role in the development of heart failure (HF). The objective of this study was to characterize CAMKII signaling in patients with HF before and after prolonged left ventricular assist device (LVAD) support. Methods: LV apex tissue pairs were collected in patients with dilated cardiomyopathy (n=10) at LVAD implantation and explantation. Normal cardiac tissue was used as control (n=4). Total protein, as well as cytoplasmic and nuclear fractions, were analyzed by Western Blot analysis. Results: The duration of LVAD support ranged from 48 to 595 days (mean = 271±54) with no patient exhibiting myocardial recovery. Total CamKIIδ levels in failing hearts were significantly higher than normal hearts and increased after LVAD, mainly due to an increase in cytoplasmic CaMKIIδC, which regulates Ca2+ handling (Table 1). Nuclear CaMKIIδB, which regulates Ca2+ gene transcription, did not change. Calmodulin remained increased in the nuclear and cytoplasmic fractions after LVAD. CaMKII autonomous, non-CaM-dependent activity, reflected by phosphorylation in Thr207, was increased pre- and post LVAD in cytoplasmic CaMKIIδC. The CaMKII-dependent myocyte enhancer factor 2 (MEF2) was increased pre- and significantly further post LVAD in the nucleus while decreased in the cytoplasm, suggesting translocation into the nucleus after LVAD support. Class IIa HDACs 4 and 5 interact with MEF2, resulting in repression of MEF2-dependent genes. Phosphorylated levels of HDAC4 and HDAC5 were increased pre- and post LVAD, which would result in activated MEF2. Conclusions: This study shows for the first time an increase of the hypertrophic factor MEF2 associated with persistent activation of CamKIIδC after prolonged LVAD support, which may have implications for cardiac remodeling during mechanical support.

Minimal-Access Left Ventricular Assist Device Explantation

2012 ◽  
Vol 7 (4) ◽  
pp. 300-302 ◽  
Author(s):  
Anson Cheung ◽  
Jia-Lin Soon
Keyword(s):  
Left Ventricular Assist Device ◽  
Ventricular Assist Device ◽  
Left Ventricular ◽  
Minimal Access ◽  
Assist Device ◽  
Heartmate Ii ◽  
Ventricular Assist ◽  
Off Pump ◽  
Left Ventricular Assist ◽  
Lvad Support

Patients on left ventricular assist device (LVAD) support can be successfully bridged to recovery. A novel explantation technique is reviewed. Six HeartMate II patients were successfully explanted off-pump through a combination of a left anterior minithoracotomy and a subxiphoid incision. A retrospective review of the institutional LVAD database was performed. The median LVAD support duration was 191 days (range, 69–307 days). There was no procedural or 30-day mortality associated with the LVAD explantation, and all patients are in New York Heart Association I to II at a median follow-up of 688 days (range, 127–1033 days). This procedure was associated with minimal blood transfusion and short intensive care unit stay (median, 1 day; range, 1–5 days) and hospitalization (median, 4.5 days; range, 3–19 days). One postexplant embolic cerebral infarct occurred. The HeartMate II LVAD can be safely explanted through a less conventional minimal-access approach.

Alterations of gene expression in failing myocardium following left ventricular assist device support

2003 ◽  
Vol 14 (3) ◽  
pp. 251-260 ◽  
Author(s):  
YingJie Chen ◽  
Soon Park ◽  
Yunfang Li ◽  
Emil Missov ◽  
Mingxiao Hou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Left Ventricular Assist Device ◽  
Ventricular Assist Device ◽  
Left Ventricular ◽  
Assist Device ◽  
Ventricular Assist ◽  
Left Ventricular Assist ◽  
Gene Transcripts ◽  
Lvad Support

Chronic unloading of the failing heart with a left ventricular assist device (LVAD) can decrease cardiac mass and myocyte size and has the potential to improve contractile function. To study the effect of chronic ventricular unloading on myocardial gene expression, a microarray (U133A, Affymetrix) profiling gene expression was compared before and after LVAD support in seven patients with idiopathic dilated cardiomyopathy and end-stage heart failure. On average, 1,374 ± 155 genes were reported as “increased” and 1,629 ± 45 as “decreased” after LVAD support. A total of 130 gene transcripts achieved the strict criteria for upregulation and 49 gene transcripts for downregulation after LVAD support. Upregulated genes included a large proportion of transcription factors, genes related to cell growth/apoptosis/DNA repair, cell structure proteins, metabolism, and cell signaling/communication. LVAD support resulted in downregulation of genes for a group of cytokines. To validate the array data, 10 altered genes were confirmed by real-time RT-PCR. Further study showed that the phosphoinositide-3-kinase-forkhead protein pathway and proteins related to nitric oxide synthesis, including eNOS and dimethylarginine dimethylaminohydrolase isoform 1 (DDAH1, an enzyme regulating endogenous nitric oxide synthase activity), were significantly increased during the cardiac remodeling process. Increased eNOS and DDAH1 expression after LVAD support may contribute to improved endothelial function of the failing hearts.

Abstract 15556: Effects of Left Ventricular Assist Device Support on microRNA Levels

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Teresa Wang ◽  
Emily O’Brien ◽  
Marc Samsky ◽  
Joseph Rogers ◽  
Adrian Hernandez ◽  
...  
Keyword(s):  
Left Ventricular Assist Device ◽  
Ventricular Assist Device ◽  
Multiple Testing ◽  
Left Ventricular ◽  
Assist Device ◽  
Ventricular Assist ◽  
Therapeutic Modalities ◽  
Left Ventricular Assist ◽  
End Stage ◽  
Lvad Support

Objectives: To examine changes in a broad panel of circulating microRNAs (miRs) following left ventricular assist device (LVAD) support in advanced heart failure (HF). Background: LVAD therapy unloads the failing heart and may result in partial reversal of the end stage HF phenotype; however, molecular changes with support have not been well defined. MicroRNAs are small nucleotide RNAs involved in the pathogenesis of HF and have been postulated to have a potential role as circulating biomarkers or as therapeutic modalities. Human studies of the role of miRs in end stage HF have been limited. Methods: 23 distinct miRs, previously shown to play a role in the pathogenesis of HF, were measured in frozen plasma collected from 40 individuals prior to continuous flow LVAD implantation, and at a median of 96.5 (interquartile range, IQR: 72.25-149.75) days after implantation. Quantitative real-time PCR was performed for miR amplification. Ultimately, 19 miRs (miR-15b, -16, -21, -24, -27a, -29a, -92a, -103, -126, -133a, -146a, -146b, -155, -159a, -195, -221, -222, -320, -423) were expressed in >80% of patient samples. Wilcoxon Rank Sum Tests were used to compare median relative quantification values pre- and post-LVAD placement. Results: The median age of patients was 67 years, and 60% were INTERMACS 1-2 prior to LVAD implantation. Following LVAD implantation, seven miRs (miR-21, -92a, -103, -159a, -195, -320, -423) were downregulated while 12 miRs (miR-15b, -16, -24, -27a, -29a, -126, -133a, -146a, -146b, -155, -221, -222) were up-regulated. After correction for multiple testing, only miR-155 was associated with significant up-modulation in plasma expression levels with LVAD support. Conclusions: While most plasma levels of miRs associated with cardiovascular pathophysiology remained unchanged with LVAD support, miR-155, which has been shown to play a role in cardiac hypertrophy, was up-regulated. The biological relevance of miR-155 in this setting requires further study.

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