Left ventricular assist device-induced reverse ventricular remodeling

Burkhoff, Daniel; Holmes, Jeffrey W.; Madigan, John D.; Barbone, Alessandro; Öz, Mehmet C.

doi:10.1053/pcad.2000.7190

Cited by 57 publications

(38 citation statements)

References 20 publications

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“…4,[8][9][10][11] Unloading of the heart by an LVAD leads to reversal of LV dilatation and to regression of LV myocyte hypertrophy. 1,3,12,31 The mechanisms of this reverse remodeling process are still largely unknown; therefore, the analysis of changes in the heart pre-and post-LVAD is important. The ECM, which consists of fibrillar collagens (type I and type III collagens) and a BM, forms a continuum between different cell types within the myocardium and provides a structural supporting network to maintain myocardial geometry.…”

Section: Discussionmentioning

confidence: 99%

Type IV collagen degradation in the myocardial basement membrane after unloading of the failing heart by a left ventricular assist device

Bruggink

Oosterhout

Jonge

et al. 2007

Laboratory Investigation

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After left ventricular assist device (LVAD) support in patients with end-stage cardiomyopathy, cardiomyocytes decrease in size. We hypothesized that during this process, known as reverse remodeling, the basement membrane (BM), which is closely connected to, and forms the interface between the cardiomyocytes and the extracellular matrix, will be severely affected. Therefore, the changes in the myocardial BM in patients with end-stage heart failure before and after LVAD support were studied. The role of MMP-2 in this process was also investigated. Transmission electron microscopy showed that the BM thickness decreased post-LVAD compared to pre-LVAD. Immunohistochemistry indicated a reduced immunoreactivity for type IV collagen in the BM after LVAD support. Quantitative PCR showed a similar mRNA expression for type IV collagen pre-and post-LVAD. MMP-2 mRNA almost doubled post-LVAD (Po0.01). In addition, active MMP-2 protein as identified by gelatin zymography and confirmed by Western blot analysis was detected after LVAD support and in controls, but not before LVAD support. Active MMP was localized in the BM of the cardiomyocyte, as detected by type IV collagen in situ zymography. Furthermore, in situ hybridization/immunohistochemical double staining showed that MMP-2 mRNA was expressed in cardiomyocytes, macrophages, T-cells and endothelial cells. Taken together, these findings show reduced type IV collagen content in the BM of cardiomyocytes after LVAD support. This reduction is at least in part the result of increased MMP-2 activity and not due to reduced synthesis of type IV collagen. Left ventricular assist devices (LVADs) are commonly used in patients with heart failure as a bridge to heart transplantation (HTx). In most cases, LVAD support extends the patient's lifespan and improves the quality of life. 1,2 In addition, pressure and volume unloading of the left ventricle (LV) by LVAD can reverse left ventricular dilatation and leads to regression of left ventricular hypertrophy and neurohormonal changes. [3][4][5][6] The understanding of this process, referred to as 'reverse remodeling,' 7 is important for a better insight into both myocardial events during LVAD support and the processes leading to heart failure. Additionally, several institutions described the possibility of LVAD explantation without the need for HTx (weaning). 4,[8][9][10][11] This requires a profound knowledge of the process of reverse remodeling.In previous studies with cardiac unloading, we demonstrated partial recovery of the contractile myofilaments in the cardiomyocytes 12 and decreased natriuretic peptide levels both in the plasma of the patients and in the heart. 5,6 Since reverse remodeling not only involves the cardiomyocytes but also the extracellular matrix (ECM), we have focused on the changes in ECM before and after LVAD support. The ECM, which consists of the fibrillar collagens, type I and III collagen, and comprises a basement membrane (BM) surrounding cardiomyocytes, forms a continuum between different cell types within t...

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Section: Discussionmentioning

confidence: 99%

Type IV collagen degradation in the myocardial basement membrane after unloading of the failing heart by a left ventricular assist device

Bruggink

Oosterhout

Jonge

et al. 2007

Laboratory Investigation

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“…15 They found that improvement of the LVEF is associated with a reduction in LV volume and restoration of a more elliptical chamber on the echocardiogram, which suggests that the remodeling process is reversible. Burkhoff et al reported that LV assist devices provide chronic pressure and volume unloading of the dilated left ventricle in patients with end-stage heart failure, 16 which is associated with reverse structural remodeling (normalization of the passive pressure -volume relationship), reverse molecular remodeling (increased expression of several genes involved in calcium metabolism that are down-regulated in heart failure), improved baseline contractility, and improved contractile response to increased heart rate and -agonist stimulation. In the chronic phase of the present patients, there was no significant difference in the medical therapy of the 2 groups.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Prognosis of Fulminant Myocarditis Rescued by Percutaneous Cardiopulmonary Support Device

Maejima

Yasu

Kubo

et al. 2004

Circ J

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“…[1][2][3] Recent reports demonstrate that LVAD support may be associated with adaptive remodeling of the ventricular myocardium, including reduced LV mass, wall thickness, and myocyte diameter; changes in LV pressure-volume relationships; and reversal of LV chamber dilation and molecular remodeling of proteins involved in Ca 2ϩ cycling. [3][4][5][6][7][8][9][10] In addition, LVAD support has been associated with salutary changes in cardiomyocyte function. Indeed, a small subgroup of patients can be successfully weaned from LVAD after recovery of ventricular function.…”

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confidence: 99%

Downregulation of Matrix Metalloproteinases and Reduction in Collagen Damage in the Failing Human Heart After Support With Left Ventricular Assist Devices

et al. 2001

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Background-Left ventricular assist device (LVAD) support of the failing heart induces salutary changes in myocardial structure and function. Matrix metalloproteinases (MMPs) are increased in the failing heart and are induced by stretch in cardiac cells in vitro. We hypothesized that mechanical unloading may affect LV plasticity by regulating MMPs and their substrates. Methods and Results-LV samples were collected from patients with dilated cardiomyopathy (DCM, nϭ14) or ischemic cardiomyopathy (ICM, nϭ16) at the time of implantation of the LVAD and again during cardiac transplantation. MMP-1, -3, and -9 were measured by ELISA, MMP-2 and -9 gelatinolytic activity by gelatin zymography, and tissue inhibitors of metalloproteinases (TIMPs) by Western blot. Total soluble and insoluble collagens were separated by pepsin solubilization, and the contents were determined by quantification of hydroxyproline. The undenatured soluble collagen was measured by Sircol collagen assay. The results showed that MMP-1 and -9 were decreased, whereas TIMP-1 and -3 were increased, but there was no change in MMP-2 and -3 and TIMP-2 and -4 after LVAD support. The undenatured collagen was increased, with the ratio of undenatured to total soluble collagens increased in ICM and that of insoluble to total soluble collagens increased in DCM after LVAD support. Conclusions-The reduced MMPs and increased TIMPs and ratios of undenatured to total soluble collagens and insolubleto total soluble collagens after LVAD support suggest that reduced MMP activity diminished damage to the matrix. These changes may contribute to the functional recovery and LV plasticity after LVAD support. Key Words: collagen Ⅲ metalloproteinases Ⅲ remodeling Ⅲ heart-assist device Ⅲ heart failure L eft ventricular assist devices (LVADs) provide mechanical support for the failing heart and serve as a bridge to cardiac transplantation, with the potential to be a destiny therapy for heart failure. [1][2][3] Recent reports demonstrate that LVAD support may be associated with adaptive remodeling of the ventricular myocardium, including reduced LV mass, wall thickness, and myocyte diameter; changes in LV pressure-volume relationships; and reversal of LV chamber dilation and molecular remodeling of proteins involved in Ca 2ϩ cycling. [3][4][5][6][7][8][9][10] In addition, LVAD support has been associated with salutary changes in cardiomyocyte function. Indeed, a small subgroup of patients can be successfully weaned from LVAD after recovery of ventricular function. 6,[11][12][13][14] Although it has been suggested that these beneficial changes are attributed to chronic unloading of the ventricular myocardium, the molecular mechanisms that play a role in LVAD-induced myocardial plasticity and LV remodeling remain undefined. See p 1089We hypothesized that the myocardial remodeling that occurs with LVAD unloading might be attributable to alterations in the components of the extracellular matrix, and specifically in the activity of matrix metalloproteinases (MMPs) and the physical pr...

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Left ventricular assist device-induced reverse ventricular remodeling

Cited by 57 publications

References 20 publications

Type IV collagen degradation in the myocardial basement membrane after unloading of the failing heart by a left ventricular assist device

Type IV collagen degradation in the myocardial basement membrane after unloading of the failing heart by a left ventricular assist device

Long-Term Prognosis of Fulminant Myocarditis Rescued by Percutaneous Cardiopulmonary Support Device

Downregulation of Matrix Metalloproteinases and Reduction in Collagen Damage in the Failing Human Heart After Support With Left Ventricular Assist Devices

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