Reverse Remodeling of the Myocardial Extracellular Matrix After Prolonged Left Ventricular Assist Device Support Follows a Biphasic Pattern

Bruggink, Annette H.; Oosterhout, Matthijs F.M. van; Jonge, Nicolaas de; Ivangh, Bas; Kuik, J. van; Voorbij, Ron H.A.M.; Cleutjens, Jack P.M.; Gmelig-Meyling, F.H.J.; Weger, Roel A. de

doi:10.1016/j.healun.2006.05.011

Cited by 104 publications

(83 citation statements)

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“…[35][36][37] In a previous study of our group, 15 we have shown that reverse remodeling of type I and III collagen in the ECM follows a biphasic pattern. Initially, an increase of type I and III collagen turnover takes place, which is paralleled by an increase of the ECM volume.…”

Section: Basement Membrane Degradation After Lvad Ah Bruggink Et Almentioning

confidence: 76%

“…It is known that MMP-2 is able to degrade type IV collagen and is upregulated during heart failure. 14,24,25 Because we have shown changes in cardiomyocyte size and ECM volume after unloading of the LV by LVAD support 12,15 and given the close connection between type IV collagen and the cardiomyocyte, we hypothesized that the BM surrounding the cardiomyocyte must be reshaped when the cardiomyocytes become smaller by unloading of the heart by an LVAD. If so, MMP-2 (collagenase IV) can play a major role in this process of remodeling.…”

mentioning

confidence: 97%

“…13,14 We have shown that reverse remodeling of type I and III collagen in the ECM follows a biphasic pattern. 15 Initially, an increase of type I and III collagen turnover took …”

mentioning

confidence: 99%

“…13,14 We have shown that reverse remodeling of type I and III collagen in the ECM follows a biphasic pattern. 15 Initially, an increase of type I and III collagen turnover took place, which was paralleled by a volume increase of the ECM. Subsequently, this turnover reduced and the ECM volume decreased, together with a restoration of the collagen network.…”

mentioning

confidence: 99%

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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: Basement Membrane Degradation After Lvad Ah Bruggink Et Almentioning

confidence: 76%

mentioning

confidence: 97%

“…13,14 We have shown that reverse remodeling of type I and III collagen in the ECM follows a biphasic pattern. 15 Initially, an increase of type I and III collagen turnover took …”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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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“…Heart transplantation (HTx) has proven to be an effective long-term treatment for these patients. However, due to the shortage of donor organs some patients with severe end-stage heart failure need to be supported with a left ventricular assist device (LVAD) as bridge to HTx [2][3][4]. Proinflammatory cytokines are up-regulated in patients with heart failure and have been implicated in the pathophysiology of this disease [5,6].…”

Section: Introductionmentioning

confidence: 99%

TNFα in patients with end-stage heart failure on medical therapy or supported by a left ventricular assist device

Bruggink

Oosterhout

Jonge

et al. 2008

Transplant Immunology

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Background: In the heart elevated levels of TNFα can cause lethal heart failure, like Dilated Cardiomyopathy (DCM). The level of TNFα production is in part determined by promoter gene polymorphisms. We investigated whether the TNFα promoter gene polymorphism is in this way involved in the outcome of end-stage heart failure and predicts whether patients require left ventricular assist device (LVAD) support or can be kept on medical therapy (MT)while awaiting heart transplantation (HTx). As most patients in this study received a heart transplant, the role of the TNFα polymorphisms in transplant rejection was studied as well. Methods and results:In twenty nine patients with DCM, 35 patients with Ischemic Heart Disease (IHD; both on MT), 26 patients on LVAD support and 61 cardiac transplant donors TNFα plasma level was detected by EASIA. In both patients groups high levels of TNFα plasma levels was observed however, in patients supported by LVAD this increase was much higher compared to patients on MT. Furthermore, this increase seems to be associated with the TNF 1 allele ('G' at position −308) instead of the TNF2 allele (A at position −308). The promoter polymorphisms at positions −238, −244 and −308 were observed by polymerase chain reaction and sequencing. Polymorphism at positions −238, −244 and −308 did not show any relevant differences between the groups. However, at position −308, a trend of a higher incidence of the TNF2 allele (an "A" at position −308) in DCM patients compared to donors was shown. The distribution of the TNF1 and TNF2 alleles was not different in patients on medical therapy compared to the patients supported by a LVAD. No association was found between patients' TNFα promoter gene polymorphism and rejection. However, patients that received a donor heart with the TNF2 allele developed more rejection episodes, compared to patients that received a donor heart with the TNF1 allele. Conclusion: TNFα levels are high in patients with end-stage heart failure on MT, but even higher in patients on LVAD support. These high TNFα plasma levels however, are not correlated with the TNF2 allele but seems to be associated with the TNF1 allele. Furthermore, in HTx the donor TNFα gene seem to play a more important role in severity of acute rejection than that of the patient.

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Outcomes of patients after successful left ventricular assist device explantation: a EUROMACS study

Antonides

Schoenrath

et al. 2020

ESC Heart Failure

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Aims Sufficient myocardial recovery with the subsequent explantation of a left ventricular assist device (LVAD) occurs in approximately 1-2% of the cases. However, follow-up data about this condition are scarcely available in the literature. This study aimed to report the long-term outcomes and clinical management following LVAD explantation. Methods and results An analysis of the European Registry for Patients with Mechanical Circulatory Support was performed to identify all adult patients with myocardial recovery and successful explantation. Pre-implant characteristics were retrieved and compared with the non-recovery patients. The follow-up data after explantation were collected via a questionnaire. A Kaplan-Meier analysis for freedom of the composite endpoint of death, heart transplantation, LVAD reimplantion, or heart failure (HF) relapse was conducted. A total of 45 (1.4%) cases with myocardial recovery resulting in successful LVAD explantation were identified. Compared with those who did not experience myocardial recovery, the explanted patients were younger (44 vs. 56 years, P < 0.001), had a shorter duration of cardiac disease (P < 0.001), and were less likely to have ischaemic cardiomyopathy (9% vs. 41.8%, P < 0.001). Follow-up after explantation could be acquired in 28 (62%) cases. The median age at LVAD implantation was 43 years (inter-quartile range: 29-52), and 23 (82%) were male. Baseline left ventricular ejection fraction was 18% (inter-quartile range: 10-20%), and 60.7% of the patients had Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 or 2. Aetiologies of HF were dilated cardiomyopathy in 36%, myocarditis in 32%, and ischaemic in 14% of the patients, and 18% had miscellaneous aetiologies. The devices implanted were HeartMate II in 14 (50%), HVAD in 11 (39%), HeartMate 3 in 2 (7%), and 1 unknown with a median duration of support of 410 days (range: 59-1286). The median follow-up after explantation was 26 months (range 0.3-73 months), and 82% of the patients were in New York Heart Association Class I or II. Beta-blockers were prescribed to 85%, angiotensin-converting enzyme inhibitors to 71%, and loop diuretics to 50% of the patients, respectively. Freedom from the composite endpoint was 100% after 30 days and 88% after 2 years. Conclusions The survival after LVAD explantation is excellent without the need for heart transplantation or LVAD reimplantation. Only a minority of the patients suffer from a relapse of significant HF.

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Reverse Remodeling of the Myocardial Extracellular Matrix After Prolonged Left Ventricular Assist Device Support Follows a Biphasic Pattern

Cited by 104 publications

References 39 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

TNFα in patients with end-stage heart failure on medical therapy or supported by a left ventricular assist device

Outcomes of patients after successful left ventricular assist device explantation: a EUROMACS study

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