Suppressive effects of conversion from mycophenolate mofetil to everolimus for the development of cardiac allograft vasculopathy in maintenance of heart transplant recipients

Watanabe, Takuya; Seguchi, Osamu; Nishimura, Kunihiro; Fujita, Tomoyuki; Murata, Yoshinori; Sato, Takuma; Sunami, Hiroshi; Nakajima, Seiko; Hisamatsu, Eriko; Sato, Toshio; Kuroda, Kensuke; Hieda, Michinari; Wada, Keita; Hata, Hiroyuki; Ishibashi‐Ueda, Hatsue; Miyamoto, Yoshihiro; Fukushima, Norihide; Kobayashi, Junjiro; Nakatani, Takeshi

doi:10.1016/j.ijcard.2015.10.082

Cited by 16 publications

(24 citation statements)

References 40 publications

(79 reference statements)

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“…17,19,30 Our present results show that DA was independently associated with worsening of morphological change on IVUS in the first post-HTx year regardless of EVL initiation during this year. Because our recipients seldom received EVL during the first post-HTx year (14.3% of all subjects and 20.8% in the DA group), this observation may be of limited significance.…”

Section: Discussionsupporting

confidence: 49%

“…30 Our previous study revealed that conversion to EVL from MMF in the maintenance of heart transplant recipients reduced worsening of morphological changes on IVUS compared with continuing MMF. 19 In our present study, the DA group tended to be converted to EVL from MMF during 3 years post-HTx compared with the DA-free group; nevertheless, the DA group experienced an ongoing reduction in luminal volume after 1 year post-HTx. On the other hand, the observational design of our study might prevent exact understanding of the correlation between EVL initiation and CAV progression after 1 year post-HTx.…”

Section: Discussioncontrasting

confidence: 44%

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Donor-Transmitted Atherosclerosis Associated With Worsening Cardiac Allograft Vasculopathy After Heart Transplantation

et al. 2017

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BackgroundThe influence of preexisting donor-transmitted atherosclerosis (DA) on cardiac allograft vasculopathy (CAV) development remains unclear.MethodsWe performed 3-dimensional intravascular ultrasound (3D-IVUS) analysis in 42 heart transplantation (HTx) recipients at 2.1 ± 0.9 months (baseline) and 12.2 ± 0.4 months post-HTx, as well as consecutive 3D-IVUS analyses up to 3 years post-HTx in 35 of the 42 recipients. Donor-transmitted atherosclerosis was defined as a maximal intimal thickness of 0.5 mm or greater at baseline. Changes in volumetric IVUS parameters were compared in recipients with (DA group) and without DA (DA-free group) at baseline, 1 year, and 3 years post-HTx.ResultsDonor-transmitted atherosclerosis was observed in 57.1% of 42 recipients. The DA group exhibited a significantly greater increase in plaque volume at 1 year post-HTx (P < 0.001), leading to increased percent plaque volume (plaque volume/vessel volume, [%]) (P < 0.001) and decreased luminal volume (P = 0.021). Donor-transmitted atherosclerosis was independently associated with a greater increase in percent plaque volume during the first post-HTx year (P = 0.011). From 1 to 3 years post-HTx, the DA group underwent continuous reduction in luminal volume (P = 0.022). These changes resulted in a higher incidence of angiographic CAV at 3 years post-HTx in the DA group (58.8% vs 5.6%, P = 0.002).ConclusionsThis volumetric IVUS study suggests that DA correlates with the worsening change in CAV several years post-HTx. Donor-transmitted atherosclerosis recipients may require more aggressive treatment to prevent subsequent CAV progression.

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Section: Discussionsupporting

confidence: 49%

Section: Discussioncontrasting

confidence: 44%

Donor-Transmitted Atherosclerosis Associated With Worsening Cardiac Allograft Vasculopathy After Heart Transplantation

et al. 2017

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“…Nine of these studies had a randomized controlled design, thus supporting strong evidence of the findings [73][74][75][76][77][78][79][80][81]. Most of studies (58%) investigated the effect of mTOR inhibitors (sirolimus or everolimus) in comparison with calcineurin inhibitors (CNIs, cyclosporin or tacrolimus) or to mycophenolate derivatives (MMF) [74,[76][77][78][79][80][82][83][84][85][86]. The other agents investigated for CAV prevention included induction therapies, tacrolimus versus cyclosporine, Ace inhibitors, aspirin, statins and granulocyte-colony-stimulating factor [73,75,81, [87][88][89][90][91][92][93].…”

Section: Prevention Of Cavmentioning

confidence: 99%

“…The low long-term tolerability of sirolimus may partially explain these findings, because more patients were discontinued sirolimus, than MMF, possibly contributing to the balancing of the outcomes. In addition, two studies, one of which randomized [78,83], found that late conversion to everolimus or sirolimus seems ineffective, possibly related to the difference in plaque composition at various stages of CAV development, while another small retrospective study supports opposite results with everolimus delaying late CAV progression [86]. Overall, these findings are in line with the reports discussed above about pathology and the CAV risk factors, supporting the model of two stages and morphologies CAV development: a first phase more related to immuno-inflammatory injury, characterized by concentric intimal hyperplasia, and a later phase in which the contribution of metabolic risk factors becomes more relevant, resulting in a different plaque and morphology composition, resembling that of native atherosclerosis.…”

Section: Immunosuppressive Treatmentsmentioning

confidence: 99%

Coronary artery disease in heart transplantation: new concepts for an old disease

et al. 2018

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Cardiac allograft vasculopathy (CAV) remains one of the main long-term complications after heart transplantation. We performed a systematic review focused on articles published in the previous 6 years to reappraise the novel evidences supporting risk factors, pathology, prevention, and treatment of CAV. We identified a search string for a literature search on PubMed. We excluded articles specifically focused on diagnosis/biomarkers/imaging only or complications of other diseases. We included 98 studies out of our search. Forty-eight articles describe risk factors for CAV, 13 pathology, 24 prevention, and 13 treatment for CAV. While confirming known concepts, we found supportive evidence that CAV pathophysiology may vary according to the time post-transplant and the prevalence of metabolic versus immune-mediated risk factors. Selective revascularization of focal lesions in patients with CAV may result in some clinical benefit, but CAV prevention, rather than treatment, by controlling risk factors and by using targeted immunosuppressive therapies is the most evidence-based approach to reduce disease progression.

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“…Autorzy sugerują, że korzystne efekty mogły stanowić wynik połączenia EVE z takrolimusem. Większość pacjentów we wcześniej opisanych badaniach przyjmowała EVE z cyklosporyną [28].…”

Section: Leczenieunclassified

Waskulopatia w przeszczepionym sercu — nowe trendy w diagnostyce i leczeniu

et al. 2017

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StreszczenieWaskulopatia naczyń wieńcowych (CAV) jest jednym z najpoważniejszych powikłań u pacjentów po transplantacji serca. Znajduje się ona wśród trzech najczęstszych przyczyn zgonów w tej grupie chorych w czasie powyżej 3 lat od przeszczepienia. Jest to przyspieszona forma miażdżycy o złożonej patogenezie, w której znaczącą rolę odgrywają zarówno mechanizmy immunologiczne, jak i zakażenia wirusowe. Klasyczne czynniki ryzyka rozwoju miażdżycy mają wpływ na postęp waskulopatii w późniejszym okresie po transplantacji. Ze względu na niespecyficzne objawy ważną rolę w rozpoznawaniu CAV odgrywa diagnostyka obrazowa. Oprócz angiografii, będącej "złotym standardem" diagnostycznym, na znaczeniu zyskują nowoczesne metody obrazowania. Wewnątrznaczyniowa ultrasonografia oraz jej połączenie z wirtualną histologią, a także optyczna tomografia koherencyjna pozwalają na dokładny pomiar wskaźnika MIT, który jest czynnikiem prognostycznym rozwoju CAV. Ponadto metody te umożliwiają ocenę budowy blaszek i odróżnianie zmian waskulopatycznych od klasycznej miażdżycy. Wciąż poszukuje się najkorzystniejszych połączeń leków immunosupresyjnych oraz antyproliferacyjnych, które stanowią podstawę w zapobieganiu i hamowaniu postępu waskulopatii. Zaobserwowano, że skuteczność tych samych farmaceutyków różni się w zależności od zastosowanego schematu leczenia. Oprócz leczenia farmakologicznego niektórzy pacjenci odnoszą korzyści z zabiegów angioplastyki lub pomostowania aortalno-wieńco-wego. Główne kierunki badań w zakresie CAV dotyczą metod wczesnego wykrywania zmian i skutecznego hamowania rozwoju tej groźnej patologii.

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Suppressive effects of conversion from mycophenolate mofetil to everolimus for the development of cardiac allograft vasculopathy in maintenance of heart transplant recipients

Abstract: Conversion to EVL from MMF in maintenance periods after HTx may decrease the rate of CAV progression based on IVUS indices.

Cited by 16 publications

References 40 publications

Donor-Transmitted Atherosclerosis Associated With Worsening Cardiac Allograft Vasculopathy After Heart Transplantation

Donor-Transmitted Atherosclerosis Associated With Worsening Cardiac Allograft Vasculopathy After Heart Transplantation

Coronary artery disease in heart transplantation: new concepts for an old disease

Waskulopatia w przeszczepionym sercu — nowe trendy w diagnostyce i leczeniu

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