Hypoxia and Myocardial Remodeling in Human Cardiac Allografts: A Time-course Study

Gramley, Felix; Lorenzen, Johann; Kettering, Klaus; Himmrich, Ewald; Plumhans, Cedric; Koellensperger, Eva; Münzel, Thomas

doi:10.1016/j.healun.2009.05.038

Cited by 39 publications

(41 citation statements)

References 40 publications

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“…This is interesting; until today, histological studies found no link between rejection burden and the development of interstitial myocardial fibrosis . On the other hand, patients with severe or repeated rejection episodes may have received higher doses of immunosuppressive treatment in periods after heart transplantation, which is associated with myocardial fibrosis . In addition, a high rejection burden is associated with a significantly reduced longitudinal myocardial deformation , microvascular CAV , and macrovascular CAV , all of which potentially could influence LV filling.…”

Section: Discussionmentioning

confidence: 99%

Clinical features, exercise hemodynamics, and determinants of left ventricular elevated filling pressure in heart-transplanted patients

et al. 2015

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SummaryThis study aimed to assess clinical, functional, and hemodynamic characteristics of heart-transplanted (HTX) patients during exercise. We performed comprehensive echocardiographic graft function assessment during invasive hemodynamic semi-supine exercise test in 57 HTX patients. According to hemodynamics findings, patients were divided into Group A: normal left ventricular (LV) filling pressure (FP): pulmonary capillary wedge pressure (PCWP) <15 mmHg at rest and <25 mmHg at peak exercise, and Group B: elevated LV-FP: PCWP ≥15 mmHg at rest or ≥25 mmHg at peak exercise. Thirty-one patients (54%) had normal LV-FP and 26 patients (46%) had elevated LV-FP. The latter had higher cumulative rejection burden (P < 0.01) and were more symptomatic (NYHA class >1) (P < 0.05), and cardiac allograft vasculopathy (CAV) was more prevalent (P < 0.05). With exercise, the changes in both left-and right-sided filling pressures were significantly increased, whereas LV longitudinal myocardial deformation was lower (P < 0.05) in patients with elevated LV-FP than in patients with normal LV-FP. No between-group difference was observed for cardiac index or LV ejection fraction (LVEF) during exercise. In conclusion, elevated LV-FP can be demonstrated in approximately 50% of HTX patients. Patients with elevated LV-FP have impaired myocardial deformation capacity, higher prevalence of CAV, and higher rejection burden, and were more symptomatic. Exercise test with the assessment of longitudinal myocardial deformation should be considered in routine surveillance of HTX patients as a marker of restrictive filling (ClinicalTrials.gov Identifier: NCT02077764).

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Section: Discussionmentioning

confidence: 99%

Clinical features, exercise hemodynamics, and determinants of left ventricular elevated filling pressure in heart-transplanted patients

et al. 2015

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“…Various theories have been advanced for how fibrosis begins, including altered tension/stress in the myocardium, activation of TGF-β signaling, or inappropriate activation of fibroblast to myofibroblast conversion [28]. Hypoxia has also been proposed to be pro-fibrotic in the heart via induction of hypoxia-inducible factor (HIF)-1α, which may explain the increased fibrosis in cardiac allograft remodeling, because graft perfusion may be suboptimal [29]. This parallels the situation in dermal wound healing, where hypoxia-induced HIF-1α upregulation results in increased ECM production [30].…”

Section: Myocardial Infarction Repair and Fibrosismentioning

confidence: 99%

Common threads in cardiac fibrosis, infarct scar formation, and wound healing

Czubryt

2012

Fibrogenesis Tissue Repair

102

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Wound healing, cardiac fibrosis, and infarct scar development, while possessing distinct features, share a number of key functional similarities, including extracellular matrix synthesis and remodeling by fibroblasts and myofibroblasts. Understanding the underlying mechanisms that are common to these processes may suggest novel therapeutic approaches for pathologic situations such as fibrosis, or defective wound healing such as hypertrophic scarring or keloid formation. This manuscript will briefly review the major steps of wound healing, and will contrast this process with how cardiac infarct scar formation or interstitial fibrosis occurs. The feasibility of targeting common pro-fibrotic growth factor signaling pathways will be discussed. Finally, the potential exploitation of novel regulators of wound healing and fibrosis (ski and scleraxis), will be examined.

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“…After cardiac transplant, the allograft is exposed to multiple factors that promote the development of myocardial remodeling and fibrosis . Whereas, in the early phase, reperfusion damage and rejection episodes alter the myocardial structure, cardiac allograft vasculopathy that results in ischemia further contributes to tissue remodeling of the allograft in the late phase . Histological studies have shown that the degree of interstitial fibrosis in cardiac transplant patients increases during the years after transplant .…”

Section: Discussionmentioning

confidence: 99%

“…Histological studies have shown that the degree of interstitial fibrosis in cardiac transplant patients increases during the years after transplant . Gramley et al showed that, within a 10‐year follow‐up, the mean percentage of LV fibrosis increases from 12 up to 29% . The authors proposed that, in addition to former rejection episodes, hypoxia and small vessel disease, mainly based on allograft vasculopathy, may play an essential role in this process.…”

Section: Discussionmentioning

confidence: 99%

Assessment of sympathetic reinnervation after cardiac transplantation using hybrid cardiac PET/MRI: A pilot study

Beitzke

Wielandner

Wollenweber

et al. 2019

Magnetic Resonance Imaging

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Background Sympathetic reinnervation after heart transplantation (HTX) is a known phenomenon, which has an impact on patient heart rate variability and exercise capacity. The impact of reinnervation on myocardial structure has not been evaluated yet. Propose To evaluate the feasibility of simultaneous imaging of cardiac reinnervation and cardiac structure using a hybrid PET/MRI system. Study type Prospective / pilot study. Subjects Ten patients, 4–21 years after cardiac transplantation. Field Strength/Sequence 3 T hybrid PET/MRI system. Cine SSFP, T1 mapping (modified Look–Locker inversion recovery sequence) pre/postcontrast as well as dynamic [11C]meta‐hydroxyephedrine ([11C]mHED) PET. Assessment All MRI and PET parameters were evaluated by experienced readers using dedicated postprocessing software packages for cardiac MRI and PET. For all parameters a 16‐segment model for the left ventricle was applied. Statistical Tests Mann–Whitney U‐test; Spearman correlations. Results Thirty‐six of 160 myocardial segments showed evidence of reinnervation by PET. On a segment‐based analysis, mean native T1 relaxation times were nonsignificantly altered in segments with evidence of reinnervation (1305 ± 151 msec vs. 1270 ± 112 msec; P = 0.1), whereas mean extracellular volume (ECV) was significantly higher in segments with evidence of reinnervation (35.8 ± 11% vs. 30.9 ± 7%; P = 0.019). There were no significant differences in wall motion (WM) and wall thickening (WT) between segments with or without reinnervation (mean WM: 7.6 ± 4 mm vs. group B: 9.3 ± 7 mm [P = 0.13]; WT: 79 ± 63% vs. 94 ± 74% [P = 0.27]) under resting conditions. Data Conclusion The assessment of cardiac reinnervation using a hybrid PET/MRI system is feasible. Segments with evidence of reinnervation by PET showed nonsignificantly higher T1 relaxation times and a significantly higher ECV, suggesting a higher percentage of diffuse fibrosis in these segments, without impairment of rest WM and WT. Level of Evidence: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:1326–1335.

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Hypoxia and Myocardial Remodeling in Human Cardiac Allografts: A Time-course Study

Cited by 39 publications

References 40 publications

Clinical features, exercise hemodynamics, and determinants of left ventricular elevated filling pressure in heart-transplanted patients

Clinical features, exercise hemodynamics, and determinants of left ventricular elevated filling pressure in heart-transplanted patients

Common threads in cardiac fibrosis, infarct scar formation, and wound healing

Assessment of sympathetic reinnervation after cardiac transplantation using hybrid cardiac PET/MRI: A pilot study

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