title: Exploring Guidelines for Classification of Major Heart Failure Subtypes by Using Machine Learning.
abstract: BACKGROUND
  Heart failure (HF) manifests as at least two subtypes. The current paradigm distinguishes the two by using both the metric ejection fraction (EF) and a constraint for end-diastolic volume. About half of all HF patients exhibit preserved EF. In contrast, the classical type of HF shows a reduced EF. Common practice sets the cut-off point often at or near EF = 50%, thus defining a linear divider. However, a rationale for this safe choice is lacking, while the assumption regarding applicability of strict linearity has not been justified. Additionally, some studies opt for eliminating patients from consideration for HF if 40 < EF < 50% (gray zone). Thus, there is a need for documented classification guidelines, solving gray zone ambiguity and formulating crisp delineation of transitions between phenotypes.
  
  
  METHODS
  Machine learning (ML) models are applied to classify HF subtypes within the ventricular volume domain, rather than by the single use of EF. Various ML models, both unsupervised and supervised, are employed to establish a foundation for classification. Data regarding 48 HF patients are employed as training set for subsequent classification of Monte Carlo-generated surrogate HF patients (n = 403). Next, we map consequences when EF cut-off differs from 50% (as proposed for women) and analyze HF candidates not covered by current rules.
  
  
  RESULTS
  The training set yields best results for the Support Vector Machine method (test error 4.06%), covers the gray zone, and other clinically relevant HF candidates. End-systolic volume (ESV) emerges as a logical discriminator rather than EF as in the prevailing paradigm.
  
  
  CONCLUSIONS
  Selected ML models offer promise for classifying HF patients (including the gray zone), when driven by ventricular volume data. ML analysis indicates that ESV has a role in the development of guidelines to parse HF subtypes. The documented curvilinear relationship between EF and ESV suggests that the assumption concerning a linear EF divider may not be of general utility over the complete clinically relevant range.
authors.affiliation: Department of Computer Science, Universidad de A Coruña, Coruña, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Alonso-Betanzos
authors.affiliation: Department of Computer Science, Universidad de A Coruña, Coruña, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Bolón-Canedo
authors.affiliation: Cardiovascular Center Aalst, OLV Clinic, Aalst, Belgium.
authors.forename: Guy R
authors.initials: GR
authors.lastname: Heyndrickx
authors.affiliation: Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Peter Lm
authors.initials: PL
authors.lastname: Kerkhof
keywords: ejection fraction; heart failure phenotype; support vector machine; volume regulation graph