Abstract 17399: Phenomapping: Hierarchical Cluster Analysis of Phenotypic Data for the Classification of Heart Failure and Preserved Ejection Fraction
Introduction: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. Improved phenotypic classification of HFpEF may lead to targeted therapies and improved clinical trial results. We hypothesized that hierarchical cluster analysis using gene expression software (creating a phenome-map by using phenotype data in place of gene expression data) would result in a novel HFpEF classification system.
Methods: We prospectively studied 397 HFpEF patients. Phenotypic data (74 unique continuous variables), including age, comorbidity burden, physical exam, ECG, lab tests (including BNP), PFTs, and echo parameters were collected on all patients. All phenotypic variables were standardized (i.e., mean±SD standardized to 0±1) to mimic gene expression data and then analyzed using Cluster and TreeView software. HFpEF patients were classified into groups based on the resulting dendrogram.
Results: The mean age was 65±13 years (63% female) and comorbidities were common. Patients met Framingham criteria for HF, LVEF >50%, and all had objective evidence of elevated LV filling pressures (elevated E/e’, BNP, PCWP, and/or LVEDP). A “phenomap” (phenome heat map, see Figure) of HFpEF patients was successfully created. Five unique, mutually exclusive groups of HFpEF patients were identified. These 5 categories of HFpEF patients had distinct etiology/pathophysiology profiles and outcomes (rate of HF hospitalization or death for groups 1-5 = 16%, 33%, 40%, 34%, and 48%, respectively; P<0.0001 [median follow-up time 14 months]). The lowest and highest risk group differed significantly across multiple phenotypes (Table).
Conclusions: This is the first study to use gene expression software for the phenotypic classification of a clinical syndrome. Given the heterogeneous nature of HFpEF, creation of a phenomap using hierarchical cluster analysis may be helpful in improved categorization of HFpEF and lead to development of novel targeted therapies. .
- © 2012 by American Heart Association, Inc.