Background: Coronary allograft vasculopathy (CAV) is a leading cause of cardiac graft failure after 1 year post transplant. It is characterized by an inflammatory vascular process with underlying endothelial damage. Our group has recently discovered that gut microbiota-dependent formation of trimethylamine-N-oxide (TMAO) is mechanistically linked to cardiovascular disease (CVD) pathogenesis. Whether this process underlies the development of CAV is unknown.

Methods: We conducted a single center retrospective cohort study of 225 heart transplant recipients between 2009-2014 with serum samples collected as well as clinical and angiographic data available. Fasting TMAO was measured by liquid chromatography tandem mass spectrometry.

Results: In our cohort study, 75% of patients were males with mean age of 56.2±0.84 years, serum samples were collected at mean of 3.0±0.3 years post-transplant. 62 recipients (28%) had angiographic evidence of CAV. Compared to those without CAV, patients with CAV had similar rates of acute rejection (50% vs. 56%), CMV positive status (74% vs. 80%), dyslipidemia (50% vs. 39%) and hypertension (52% vs. 50%), but were more likely to be diabetic (53% vs. 37% p=0.035). Recipients with CAV had higher serum TMAO than those without CAV (median 7.2 [IQR: 4.5-15.2] ¯o;M vs 5.9 [IQR: 3.5-10.4] ¯o;M; p=0.001). Furthermore, a TMAO cutoff value of 6 ¯o;M or above was predictive of CAV development (OR: 1.9, 95% CI: 1.06, 3.54).

Conclusion: Elevated circulating TMAO level is associated with the presence of CAV in heart transplant recipients.

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