Delineating Pathways to Death by Multisystem Organ Failure in Patients with a Left Ventricular Assist Device (LVAD)

Purpose Multisystem organ failure (MOF) is the second leading cause of death in patients undergoing LVAD therapy. In actuality, MOF is a composite of adverse events (AEs) rather than a singular diagnosis. The objective of this study is to identify the key AEs preceding mortality attributed to MOF. Methods We analyzed 3,765 AE's in 554 patients (2006-to-2015) with a continuous flow LVAD whose death was reported due to MOF in the INTERMACS database. For each patient (pt), all AEs that preceded the endpoint death were identified and chronologically ordered into sequences. Hierarchical clustering, a machine learning algorithm for clustering, was used to create a descriptive model of the proportions of each adverse event sequence antecedent to MOF (Figure 1). Results Two major groups of adverse event sequences were identified: Group 1 (118 pts, 1,461 AEs) and Group 2 (436 pts, 2,304 AEs). Group 1 (Grp1) was temporally distinguished from Group 2 (Grp2) by having a longer median time to death (10 months vs 2 months) and a greater median number of AEs per pt (11/ pt vs 5/pt). In both groups, the most common AEs preceding death were renal and respiratory failure (86% Grp1 and 75% Grp2). Unlike Grp2, Grp1 had more prolonged sequences of recurrent bleeding (66% of pts) originating mainly from the GI tract (51%). Grp 1 also had recurrent infections in 65% of pts that were categorized as bacterial pneumonia in 32%. Furthermore, the predominant sequence in Grp1 that led to MOF was bleeding-to-infection-to-death in 83% of the pt's AE sequences, whereas MOF most commonly (62%) followed renal failure or respiratory failure, in Grp2. Conclusion This study used a state of the art machine learning approach to identify two predominant types and sequences of AEs that incite MOF associated mortality. One group died of bleeding and repeated infections with a longer survival while the second group died very early following renal and respiratory complications.