Phenotypic clustering of dilated cardiomyopathy patients highlights important pathophysiological differences

Figure 1. Summary of the aims and study design including data processing steps, survival analysis, and application.

Figure 2. Four mutually exclusive phenogroups as determined by hierarchical clustering of principal component using phenotypical information as input. The most distinct clinical characteristics are listed per phenogroup. Variables with an asterisk are key parameters to distinguish the phenogroups, as selected by supervised decision tree modelling (A). Characteristic plots of the four proposed phenogroups including their most representative clinical variables. The over- or underrepresentation of a variable within a cluster was analysed by v-test within the hierarchical clustering of principal component function, based on the hypergeometric distribution. A positive value indicates overrepresentation of this variable in the applicable phenogroup, a negative value indicates underrepresentation of the corresponding variable (B).

Figure 3. Analysis of RNA-sequencing data of endomyocardial biopsies from dilated cardiomyopathy patients. Principal component analysis (PCA) of RNA-sequencing data divided on phenogroup (PG). Principal component 1 shows strong division of PG4 and the others (A). Venn diagram of the number of significant differentially expressed genes in the comparison between two corresponding PG (FDR < 0.01 + fold change >1.5) (B). Significantly enriched Kyoto Encyclopaedia of Genes and Genomes pathways (P-value < 0.05) in the comparison between the PG (Table 4) (C).

Figure 4. Event-free survival stratified by phenogroup. Kaplan–Meier curves for the combined outcome of life-threatening arrhythmias, cardiovascular death, heart transplantation, or left ventricular assist device implantation stratified by phenogroup.

Figure 5. A simplified adaptation of the decision tree model shows the clinical parameters which are the core of the phenogroups. The black box indicates that the model cannot accurately place the patient in one of the four phenogroups (see Supplementary material online, Figure S5 for exact accuracy).

Figure 6. Event-free survival stratified by phenogroup as determined by the supervised decision tree model. Kaplan–Meier curves for the combined outcome of life-threatening arrhythmias, cardiovascular death, heart transplantation, or left ventricular assist device implantation stratified by phenogroup in the application cohort (Madrid and Trieste).