Mycophenolate Mofetil Reduces Intimal Thickness by Intravascular Ultrasound After Heart Transplant: Reanalysis of the Multicenter Trial

Kobashigawa, Jon A.; Tobis, Jonathan M.; Mentzer, Robert M.; Valantine, Hannah A.; Bourge, Robert C.; Mehra, Mandeep R.; Smart, Frank W.; Miller, Leslie W.; Tanaka, Kõji; Li, Haiyan; Gjertson, David W.; Gordon, Robert D.

doi:10.1111/j.1600-6143.2006.01297.x

Cited by 89 publications

(48 citation statements)

References 19 publications

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“…106 Reanalysis revealed a significant decrease in the number of patients with first-year maximal intimal thickness Ն0.3 mm (a primary end point) in the MMF group. 107 Moreover, the first-year decrease in mean lumen area and the decrease in vessel area in the azathioprine group was significantly greater than in the MMF group. 107 These results were confirmed by Kaczmarek et al, 108 who detected (using multivariate Cox regression analysis) that MMF decreased the incidence of CAV significantly (Pϭ0.041).…”

Section: Mycophenolate Mofetilmentioning

confidence: 94%

Cardiac Allograft Vasculopathy

2008

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Abstract-Cardiac allograft vasculopathy (CAV) continues to limit the long-term success of cardiac transplantation.Recent insights have underscored the fact that innate and adaptive immune responses are involved in the pathogenesis of CAV. Vascular lesions are the result of cumulative endothelial injuries induced both by alloimmune responses and by nonspecific insults (including ischemia-reperfusion injury, viral infections, and metabolic disorders) in the context of impaired repair mechanisms. Intravascular ultrasound is the most sensitive method for detection of CAV, and progressive intimal thickening in the first posttransplant year identifies patients at high risk for future cardiovascular events. Encouraging results with regard to the detection of CAV by noninvasive methods should be an incentive to apply routine noninvasive imaging during mid-to long-term follow-up. Improved immunosuppressive drugs, including mycophenolate mofetil and proliferation signal inhibitors, as well as statins (in part via immunomodulation), have beneficial effects on CAV progression, although there is still a need to confirm the impact of vasodilators in improving outcome after heart transplantation. Coronary revascularization for CAV is only palliative, with no long-term survival benefit. Three main strategies for CAV prevention are currently under investigation: inhibition of growth factors and cytokines, cell therapy, and tolerance induction. However, because individual responses to an allograft change over time, assays to monitor the recipient's immune response and individualized methods for therapeutic immune modulation are clearly needed. (Circulation. 2008;117:2131-2141.)

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Section: Mycophenolate Mofetilmentioning

confidence: 94%

Cardiac Allograft Vasculopathy

2008

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“…In the re-analysis of the same study, it also showed less intimal thickening and wider lumen area [137] . Finally, Kaczmarek et al [138] , in 2006 demonstrated that MMF decreased CAV incidence.…”

Section: Mycophenolate Mofetilmentioning

confidence: 68%

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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“…Purine synthesis inhibitors: A long-term follow-up study of the first randomized MMF heart study (58,59) has confirmed that the benefits associated with this agent extend to three years following transplantation, with reduced graft loss due to rejection and a 36% reduction in overall mortality. A re-analysis of the intravascular ultrasound data from this trial also showed less progression of allograft coronary artery disease (ACAD) (60).…”

Section: Maintenance Therapymentioning

confidence: 77%