Impact of Coronary Endothelial Dysfunction on Adverse Long-Term Outcome After Heart Transplantation

Kübrich, Marion; Petrakopoulou, Paraskevi; Kofler, Sieglinde; Nickel, Thomas; Kaczmarek, Ingo; Meiser, Bruno; Reichart, Bruno; Scheidt, Wolfgang von; Weis, Michael

doi:10.1097/tp.0b013e318170b4cd

Cited by 46 publications

(24 citation statements)

References 25 publications

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“…[13][14][15] Nevertheless, there is a considerable heterogeneity in the magnitude of vascular dysfunction in individuals with similar risk factor profile. 16,17 In this regard, vascular dysfunction may be seen as an important ''integrative factor'' of the inherent atherosclerotic risk in an individual, taking into account the cumulative risk of various coronary risk factors, unknown variables, and the genetic susceptibility of vascular endothelium toward coronary risk factors.…”

Section: Vascular Function and Myocardial Perfusionmentioning

confidence: 99%

Vascular dysfunction measured by fingertip thermal monitoring is associated with the extent of myocardial perfusion defect

Ahmadi

Usman

Shim

et al. 2009

Journal of Nuclear Cardiology

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Section: Vascular Function and Myocardial Perfusionmentioning

confidence: 99%

Vascular dysfunction measured by fingertip thermal monitoring is associated with the extent of myocardial perfusion defect

Ahmadi

Usman

Shim

et al. 2009

Journal of Nuclear Cardiology

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“…However, published data are not consistent between studies. Kübrich et al [62] , in a larger cohort, found no correlation between epicardial and microvascular disease and found that, whilst microvascular dysfunction demonstrated by CFR was a predictor of outcome (death or adverse cardiovascular event) in the univariate analysis, it did not predict outcome in the multivariate analysis.…”

Section: Echocardiographymentioning

confidence: 94%

Diagnosis and management of coronary allograft vasculopathy in children and adolescents

Dedieu

Greil

Wong

et al. 2014

WJT

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Coronary allograft vasculopathy remains one of the leading causes of death beyond the first year post transplant. As a result of denervation following transplantation, patients lack ischaemic symptoms and presentation is often late when the graft is already compromised. Current diagnostic tools are rather invasive, or in case of angiography, significantly lack sensitivity. Therefore a non-invasive tool that could allow early diagnosis would be invaluable.This paper review the disease form its different diagnosis techniques,including new and less invasive diagnostic tools to its pharmacological management and possible treatments. DEFINITION AND PHYSIOPATHOLOGYIn children, coronary allograft vasculopathy (CAV) remains the main limiting survival factor after heart transplantation and the major cause of mortality after the first year post transplant leading ultimately to graft loss [1,2] . One elegant etiological description of CAV is that of "immunologic mechanisms operating in a milieu of nonimmunologic risk factors" [3] . The process is believed to start off as a response to endothelial injury in the graft, originated by a complex interaction of multiple donor and recipient factors. The resulting endothelial dysfunction, leads to altered endothelial permeability and subsequent intimal hyperplasia as a consequence of the vascular remodeling originated by the inflammatory response. The immunologic events constitute the original trigger and noninflammatory events such as cytomegalovirus infection, ischemic time (reperfusion injury), increased donor age and classical cardiovascular risk factors (i.e., diabetes, dyslipidemias, smoking and hypertension), perpetuate the inflammatory response and increase the endothelial injury [4] . Typical lesions (Figures 1 and 2) consist of diffuse intimal proliferation leading to the development of luminal stenosis and small vessels occlusion which then limits blood supply to the graft causing chronic vascular injury and ultimately myocardial ischemia [5] . The lesions develop earlier and quicker than atherosclerotic lesions. REVIEW 276December 24, 2014|Volume 4|Issue 4|

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“…This effect could ultimately increase local cardiac inflammation and consequently facilitate the development of CAV. Although the function and effect of CNI-induced endothelial dysfunction in the pathogenesis of CAV is poorly understood, it has been demonstrated that both CsA and TAC induce vascular oxidative stress, increased endothelin-1 (ET-1) release, and contribute to the dysregulation of endothelial nitric oxide synthase (NOS) in the kidney [44,[62][63][64] . Indeed CNI-induced endothelial dysfunction includes the attenuation of the endothelium to release NO [65] , a physiologically relevant mechanism because decreased NO bioavailability is related to the production of reactive oxygen species (ROS) and thus oxidative stress [65] .…”

Section: Impact Of Immunosuppressive Regimens On Cavmentioning

confidence: 99%

Effects of Immunosuppressive agents on neutrophils inflammatory response in humans: An inflammatory perspective on coronary allograft vasculopathy

White

2016

Inflamm Cell Signal

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Cardiac transplantation (CTx) has improved survival in patients with advanced heart failure. Unfortunately, the conditional survival remains less than 15 years. The primary cause of mortality at 5 years following a CTx is the development of accelerated coronary atherosclerosis named coronary allograft vasculopathy (CAV). The neutrophils likely play an important role in this diffuse inflammatory process. Nevertheless, the contribution of the neutrophils on the pathogenesis of CAV is poorly understood. Regardless of their essential contribution for the prevention of graft rejection, immunosuppressive drugs (IDs) may have detrimental effects via some pro-inflammatory activities. This review presents the role of neutrophils on vascular inflammation and on the biologic effects of diverse immunosuppressive agents including mTOR inhibitors in the context of the pathophysiology of CAV. We investigated the impact of different IDs on the inflammatory responses of isolated human neutrophils harvested from healthy controls and herein, we reported on some novel characteristics of everolimus (EVE) on isolated neutrophils in comparison with other immunosuppressive agents. These biologic effects may contribute to their beneficial effects on the allograft vasculature and consequently on the prevention of CAV.

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Impact of Coronary Endothelial Dysfunction on Adverse Long-Term Outcome After Heart Transplantation

Abstract: This is the first study showing that epicardial endothelial dysfunction independently predicts outcome in HTx patients providing functional and prognostic information that complete angiographic risk factor assessment.

Cited by 46 publications

References 25 publications

Vascular dysfunction measured by fingertip thermal monitoring is associated with the extent of myocardial perfusion defect

Vascular dysfunction measured by fingertip thermal monitoring is associated with the extent of myocardial perfusion defect

Diagnosis and management of coronary allograft vasculopathy in children and adolescents

Effects of Immunosuppressive agents on neutrophils inflammatory response in humans: An inflammatory perspective on coronary allograft vasculopathy

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