Introduction
Patients with continuous flow destination therapy (DT) left ventricular assist devices
(LVAD) are a heterogenous population that may have distinct phenotypic clusters.
Hypothesis
We hypothesize there will be distinct phenotypic clustering of individuals with DT
LVADs by their clinical characteristics at implantation that are associated with different
long-term risk profiles.
Methods
We analyzed 8245 patients with a continuous flow DT LVADs in INTERMACS and selected
25 baseline clinical characteristics including demographic, echocardiographic, hemodynamic,
and laboratory data. Variables with >10% missingness were excluded except for left
ventricular dimensions which were imputated. Unsupervised K-means clustering derived
phenogroups and the optimal number of clusters was assessed by minimization of the
Bayesian Information Criterion. The final dataset included 5999 patients with 18 selected
variables for 4 distinct phenogroups. Survival analyses for events considered competing
risk for cumulative incidence of transplant or the composite endpoint of death or
heart transplant when appropriate.
Results
Of the 4 phenogroups, phenogroup 1 (n=1163, 19%) was older (median age 71 years),
primarily white (81%), and most frail (9%). Phenogroup 4 (n=517, 9%) was younger (41
years), heavier (108 kg), and more diverse (white race 46%) with the least frailty
(3%), largest left ventricles (LVEDD 7.5 cm), and highest rate of non-adherence (8%)
amongst the clusters. Phenogroups 2 (n=648, 11%) and 3 (n=3671, 61%) were of intermediate
age (69 & 61 years), weight (87 & 90 kg), and ventricular size (LVEDD 6.5 & 6.9 cm).
The cumulative incidence of death, heart transplant, bleeding, LVAD malfunction and
LVAD thrombosis differed among phenogroups (Figure A-D). The highest cumulative incidence
of death and the lowest rate of heart transplant was seen in phenogroup 1 (P<0.001).
For adverse outcomes, the cumulative incidence of bleeding was lowest in phenogroup
4 (P<0.001) while the cumulative incidence of LVAD malfunction and device thrombosis
were lowest in phenogroup 1 (P<0.001 for both). Finally, the cumulative incidence
of stroke (P=0.08), infection (P=0.08), and renal dysfunction (P=0.91) were not statistically
different between phenogroups.
Conclusions
Our exploratory unsupervised machine learning analysis highlighted 4 phenogroups that
differed in fatal and non-fatal adverse events. These observations underscore the
influence of phenotypic heterogeneity on post-LVAD implantation outcomes.
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Copyright
© 2020 Published by Elsevier Inc.
