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Randomized Controlled Trial
. 2016 Aug;35(8):1010-7.
doi: 10.1016/j.healun.2016.03.002. Epub 2016 Mar 17.

Index of microvascular resistance after early conversion from calcineurin inhibitor to everolimus in heart transplantation: A sub-study to a 1-year randomized trial

Ole Geir Solberg  1 , Knut Stavem  2 , Asgrimur Ragnarsson  3 , Dan Ioanes  4 , Satish Arora  3 , Knut Endresen  3 , Jūratė Šaltytė Benth  5 , Lars Gullestad  6 , Einar Gude  3 , Arne K Andreassen  3 , Lars Aaberge  3
Affiliations
Randomized Controlled Trial

Index of microvascular resistance after early conversion from calcineurin inhibitor to everolimus in heart transplantation: A sub-study to a 1-year randomized trial

Ole Geir Solberg et al. J Heart Lung Transplant. 2016 Aug.

Abstract

Background: Microvascular function in transplanted hearts can be evaluated by methods used in routine left heart catheterization follow-up after heart transplantation (HTx). This sub-study of a randomized study compared the effects of everolimus (EVR) and calcineurin inhibitor (CNI) treatment on microvascular function as expressed by the index of microvascular resistance (IMR) at 1 year after HTx. A secondary objective was to compare the change in IMR from 7-11 weeks to 1 year after HTx between randomized groups.

Methods: There were 70 HTx recipients included and randomly assigned to combination therapy (EVR and CNI with early CNI withdrawal) vs conventional CNI treatment. Coronary physiologic assessment was performed 7-11 weeks and 1 year after HTx. A linear mixed model was used to assess the group difference at 1 year and the difference in IMR change between 7-11 weeks and 1 year after HTx.

Results: At 1 year, there was no significant difference in IMR between the EVR group (17.5 mm Hg∙sec ± 8.9) (mean ± SD) and the CNI group (14.9 mm Hg∙sec ± 6.6, p = 0.17). The difference in IMR change between the 2 treatment arms was 1.6 mm Hg∙sec (95% confidence interval, -2.8 to 5.9; p = 0.49). Spearman's rank correlation coefficient at 1 year after HTx between IMR and maximal intimal thickness as assessed with intravascular ultrasound in the left anterior descending artery was -0.13 (p = 0.28).

Conclusions: In this prospective, open, randomized study comparing early CNI withdrawal with mammalian target of rapamycin inhibitors immunosuppression during the first year after HTx, early transition from CNI-based immunosuppression to EVR-based treatment did not result in differences in microvascular function as assessed by the IMR.

Keywords: coronary microcirculation; coronary physiology; everolimus; heart transplantation; index of microvascular resistance (IMR); mTOR inhibitors.

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