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Gut microbial imbalance may contribute to endotoxemia, inflammation, and oxidative stress in heart failure (HF). Changes occurring in the intestinal microbiota and inflammatory/oxidative milieu during HF progression and following left ventricular assist device (LVAD) or heart transplantation (HT) are unknown. We aimed to investigate variation in gut microbiota and circulating biomarkers of endotoxemia, inflammation, and oxidative stress in patients with HF (New York Heart Association, Class I-IV), LVAD, and HT.We enrolled 452 patients. Biomarkers of endotoxemia (lipopolysaccharide and soluble [sCD14]), inflammation (C-reactive protein, interleukin-6, tumor necrosis factor-α, and endothelin-1 adiponectin), and oxidative stress (isoprostane) were measured in 644 blood samples. A total of 304 stool samples were analyzed using 16S rRNA sequencing.Gut microbial community measures of alpha diversity were progressively lower across worsening HF class and were similarly reduced in patients with LVAD and HT (p0.05). Inflammation and oxidative stress were elevated in patients with Class IV HF vs all other groups (all p0.05). Lipopolysaccharide was elevated in patients with Class IV HF (vs Class I-III) as well as in patients with LVAD and HT (p0.05). sCD14 was elevated in patients with Class IV HF and LVAD (vs Class I-III, p0.05) but not in patients with HT.Reduced gut microbial diversity and increased endotoxemia, inflammation, and oxidative stress are present in patients with Class IV HF. Inflammation and oxidative stress are lower among patients with LVAD and HT relative to patients with Class IV HF, whereas reduced gut diversity and endotoxemia persist in LVAD and HT.

Introduction: The HeartMate (HM3) left ventricular assist device (LVAD) uniquely features an artificial pulse (AP) (designed to reduce blood stasis and simulate physiologic pulsatility) that alters arterial blood pressure (BP) tracings ( Fig. 1A ). Pulsatility Index (PI) corresponds to the magnitude of flow pulse through the LVAD and is used as a surrogate measure of arterial pulse pressure (PP). The effect of the AP on: i) relative contribution of systolic BP (SBP) and diastolic BP (DBP) to mean arterial pressure (MAP) calculation; and ii) association between PP and PI is presently unknown. Thus, we aimed to compare: i) MAP calculations; and ii) relation of PI with PP in HM3 vs HM II (LVAD with no AP) pts with arterial line (A-line) monitoring. Methods: A-line BP and LVAD PI data were prospectively collected in 48 HM3 and 29 HMII pts. MAP was calculated with the formula conventionally used in non LVAD pts (MAP = 2/3 DBP + 1/3 SBP) and compared to A-line MAP. Among HM3 pts, a multiple linear regression model was fit with A-line SBP and DBP as predictor variables, and A-line MAP as the dependent variable to derive the HM3 MAP Formula . The relation between arterial PP and PI in HM3 and HMII pts was assessed using Pearson’s correlation. Results: MAP calculated using the conventional formula accurately estimated A-line MAP in HMII pts, but overestimated A-line MAP in HM3 pts. The HM3 MAP Formula more closely approximated A-line MAP. Mean observed difference (MOD) and mean absolute difference (MAD) between calculated MAPs and A-line MAPs are reported in Fig. 1B . While median PP was similar in HM3 and HMII pts (16 vs 20 mmHg, p=0.11), median PI was significantly higher in HMII pts (3.45 vs 5.6, pr 0.47, p=0.01). However, no significant correlation was found between PI and PP in HM3 pts ( r 0.24, p=0.1; Fig. 1C ). Conclusions: In HM3 pts, the AP significantly alters the relative contribution of SBP and DBP to MAP. Unlike in HM2 pts, PI does not relate to arterial PP in HM3 pts.

Introduction: Cardiac allograft vasculopathy (CAV) is a leading cause of death after heart transplant (HT). Inflammation is a known cardiovascular risk factor, with gut derived endotoxemia potentially instigating this process, leading to endothelial damage. Our prior work showed that elevation of biomarkers of inflammation (endothelin-1 (ET-1)) and endotoxemia (lipopolysaccharide (LPS)) persists after HT. We investigated the association of LPS and ET-1 with subsequent development of CAV. Methods: Pts who met the following criteria were included: i) blood sampling ≥6 mo post-HT; ii) no evidence of CAV at the time of sampling. Pts were followed up to 2.3y after sampling. Cox-PH was used to regress freedom from CAV on LPS and ET-1 (≤ vs >median), time from HT to sampling (≤ vs >1y), interaction among variables. Results: 33 HT pts enrolled, mean age 57±11y; 70% male; median time post-HT 1.96(0.5-3.7)y. 17(52%) pts developed CAV at 0.7(0.6-1)y following blood collection. Baseline characteristics of pts who developed CAV vs not were similar, except for longer median time post-HT in pts who developed CAV: 2.4(0.7-5.3) vs 1.05(0.5-2.7)y, p=0.1. Median LPS and ET-1 for the entire cohort were 0.34(0.28-0.45) EU/ml and 1.83(1.26-2.72) pg/ml. Pts with >median LPS or ET-1 values trended towards higher risk of developing CAV: HR 1.79(0.66, 4.85), p=0.3 ( Fig.1A ); HR 2.05(0.71, 5.92), p=0.2 ( Fig.1B ). No association was observed between time post-HT and CAV: HR=0.87 comparing ≤ vs. >1y, p=0.8. Pts with both >median LPS and ET-1 levels (n=7) were at significantly higher risk of CAV: HR 2.96(1.06, 8.27), p=0.039, compared to others ( Fig.1C ). When examining pts sampled within the first year of HT (N=14), pts with >median LPS (N=5) were at particularly increased risk of CAV: HR 9.71(0.97, 96.9), p=0.05, while pts with >median ET-1 were not. Conclusions: Elevated LPS and ET-1 synergistically associate with increased CAV risk post-HT. Further studies are warranted to validate these findings.

Purpose Left ventricular assist device (LVAD) is an established treatment for advanced heart failure (aHF) with notable improvement in patient survival, yet complications remain. AHF is associated with gut microbial community dysbiosis (i.e. reduced diversity of microbial communities). Changes in gut diversity following LVAD might offer a precision medicine oriented approach to predicting the clinical trajectory of patients. In this analysis we explored longitudinal trends in gut microbial diversity before/after LVAD. Methods We prospectively enrolled 66 AHF patients (59.4±13.4 yrs old; 88% M; 56% White). A total of n=99 stool samples (n=34 pre-LVAD, n=36 LVAD 1 mo, n=29 LVAD 3-6 mo) were collected. 16S rRNA sequencing was performed on all samples. Alpha diversity metrics (number and evenness of bacterial taxa within samples) were estimated using Shannon index and the # of observed taxa. Repeated measures models were used to regress alpha diversity on time post-LVAD, adjusted for age, gender and race/ethnicity. Beta diversity (microbial difference between samples) was estimated by Bray-Curtis dissimilarity. DESeq regression analyses explored differences in individual taxa over time and the false discovery rate (FDR) adjusted for multiple comparisons Results Alpha diversity (# observed) increased by 3-6 mo following LVAD implantation (p=0.004, Figure 1). Trends were consistent for Shannon index (Figure 1). No differences in beta diversity were observed following LVAD (p=0.23). There were 32 taxa that differed between pre- vs. post-LVAD 3-6 mo with FDR Conclusion After an initial trend for decrease in gut microbial diversity at 1 mo, these metrics increased by 3-6 mo post-LVAD, which could be reflective of improved clinical status. Future studies are necessary to determine the relevance of these findings to clinical outcomes among LVAD patients and to explore the biological relevance of the taxa underlying these changes.

We report a case of renal artery stenosis most probably secondary to chronic pancreatitis. The patient had a traumatic pancreatic fistula. This was followed by numerous attacks of pancreatitis in the following years. At a relatively young age, he developed hypertension. Examinations revealed a right renal artery stenosis which was successfully treated by a percutaneous angioplasty. This rare complication should be kept in mind as a possible complication of pancreatitis.

e21028 Background: The aim of this study was to assess the clinical response (complete clinical response and partial clinical response) (CR) and pathological complete response (no residual invasive...