Effect of Continuous‐Flow Left Ventricular Assist Device Support on Coronary Artery Endothelial Function in Ischemic and Non‐Ischemic Cardiomyopathy

Abstract

The coronary vasculature encounters a reduction in pulsatility after implementing durable continuous‐flow left ventricular assist device (CF‐LVAD) circulatory support. Evidence exists that appropriate pulsatility is required to maintain endothelial cell homeostasis. We hypothesized that coronary artery endothelial function would be impaired after CF‐LVAD intervention. Coronary arteries from patients with end‐stage heart failure caused by ischemic (ICM, n=16) or non‐ischemic (NICM, n=22) cardiomyopathy were isolated from the LV apical core which was removed for the CF‐LVAD implantation. In 11 of these patients, paired coronary arteries were obtained from an adjacent region of myocardium after the CF‐LVAD intervention (n = 6 ICM, 5 NICM). Vascular function was assessed ex vivo using isometric tension procedures in these patients and in 7 non‐failing donor controls. Maximal endothelium‐dependent vasorelaxation to bradykinin (BK, 10−6 to 10−10 M) was blunted (p<0.05) in arteries from patients with ICM compared to NICM and donor controls, whereas responses to sodium nitroprusside (SNP, 10−4 to 10−9 M) were similar among the groups. Contrary to our hypothesis, vasorelaxation responses to BK and SNP were similar before and 219±37 days after CF‐LVAD support. Of these patients, an exploratory subgroup analysis revealed that BK‐induced coronary artery vasorelaxation was greater (p<0.05) after (87±6%) vs. before (54±14%) CF‐LVAD intervention in ICM patients, while SNP‐evoked responses were similar. Coronary artery endothelial function is not impaired by durable CF‐LVAD support, and in ICM patients appears to be improved. Investigating coronary endothelial function using in vivo approaches in a larger patient population is warranted.Support or Funding InformationJDS (AHA16GRNT31050004, NIH RO3AGO52848, NHLBI RO1 HL141540); LD, ND, TB (University of Utah Undergraduate Research Opportunities Program); JMC (University of Utah Graduate Research Fellowship); SGD (AHA Heart Failure Strategically Focused Research Network 16SFRN29020000, NHLBI RO1 HL135121, NHLBI RO1 HL132067).