Abstract 18193: The Effects of Heart Transplantation and LVAD Therapy on Intestinal Microbe-Generated Metabolite Trimethylamine-N-oxide (TMAO) in Heart Failure Patients

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Introduction: Intestinal microbe-dependent generation of trimethylamine-N-oxide (TMAO) is linked to increased mortality risk in heart failure (HF). Cardiorenal syndrome is prevalent in HF and TMAO levels are influenced by renal function. Increased permeability of the gut epithelium associated with intestinal congestion may also raise levels of gut-derived metabolites such as TMAO. Heart transplantation (HT) and left ventricular assist devices (LVADs) are treatments for advanced HF, improving congestion and renal function. The effect of these therapies on TMAO levels is unknown.

Hypothesis: TMAO levels are reduced after LVAD and HT implantation.

Methods: We enrolled 162 pts: 20 advanced HF pts (NYHA Class IV) enrolled prospectively prior to LVAD implantation and followed at 1 mo (n=14) and 3-6 mo (n=8) post LVAD. Concurrently, 67 HF pts (NYHA Class I-III), 27 pts post LVAD (>6mo), and 48 pts post HT (>6mo) were enrolled. Plasma TMAO was assessed via LCMS. Mixed-models regressed TMAO longitudinally before and after LVAD implantation and cross-sectionally in the remaining cohort.

Results: Pts were 60±14 yo, 76% male. Median [IQR] TMAO levels were 7.0[4-14] μM. Age/sex adjusted mean eGFR±SE values differed by disease phenotype: 68±4 (NYHA-Class I-III), 65±6 (Class IV), 101±8 (LVAD 1mo), 74±9 (LVAD 3-6mo), 56±5 (LVAD>6mo) and 60±4 ml/min/1.73 m2 (HT>6mo), p=0.005. CVP values by disease phenotype were: 7.3±08 (HF Class I-III), 9.9±1.2 (HF Class IV), 11.3±1.5 (LVAD 1mo) 6.5±2.4 (LVAD 3-6mo), 8.8±1.2 (LVAD >6mo) and 6.4±0.7 mmHg (HT >6mo), p=0.22. TMAO levels were lower 1 and 3 months after LVAD (p =0.01 and 0.02, respectively). Results were consistent after multivariable adjustment (Figure).

Conclusions: TMAO was reduced by >60% following LVAD implantation and remained reduced (although not statically significantly) after prolonged LVAD support and HT. Further study is necessary to determine the mechanisms responsible for these improvements.

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