title: Dynamic prediction of outcome for patients with severe aortic stenosis: application of joint models for longitudinal and time-to-event data.
abstract: BACKGROUND
  Physicians utilize different types of information to predict patient prognosis. For example: confronted with a new patient suffering from severe aortic stenosis (AS), the cardiologist considers not only the severity of the AS but also patient characteristics, medical history, and markers such as BNP. Intuitively, doctors adjust their prediction of prognosis over time, with the change in clinical status, aortic valve area and BNP at each outpatient clinic visit. With the help of novel statistical approaches to model outcomes, it is now possible to construct dynamic event prediction models, employing longitudinal data such as AVA and BNP, and mimicking the dynamic adjustment of prognosis as employed intuitively by cardiologists. We illustrate dynamic prediction of patient survival and freedom from intervention, using baseline patient characteristics and longitudinal BNP data that are becoming available over time, from a cohort of patients with severe aortic stenosis.
  
  
  METHODS
  A 3-step approach was employed: (1) construction of a mixed-effects model to describe temporal BNP progression, (2) jointly modeling the mixed-effects model with time-to-event data (death and freedom from intervention), and (3) using the joint model to build subject-specific prediction risk models. The dataset used for this purpose includes 191 patients with severe aortic stenosis who were followed over a 3-year time period.
  
  
  RESULTS
  In the mixed-effects model BNP was significantly influenced by time, baseline patient age, gender, LV fractional ejection fraction and creatinine. Additionally, the joint model showed that an increasing BNP trend over time was found to be a significant predictor of death.
  
  
  CONCLUSIONS
  By jointly modeling longitudinal data with time-to-event outcomes it is possible to construct individualized dynamic event prediction models that renew over time with accumulating evidence. It provides a potentially valuable evidence-based tool for everyday use in medical practice.
authors.affiliation: Department of Biostatistics, Erasmus MC, Rotterdam, The Netherlands. e.andrinopoulou@erasmusmc.nl.|Department of Cardiothoracic Surgery, Erasmus MC, Rotterdam, The Netherlands. e.andrinopoulou@erasmusmc.nl.
authors.forename: Eleni-Rosalina
authors.initials: ER
authors.lastname: Andrinopoulou
authors.affiliation: Department of Biostatistics, Erasmus MC, Rotterdam, The Netherlands. d.rizopoulos@erasmusmc.nl.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Rizopoulos
authors.affiliation: Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands. m.geleijnse@erasmusmc.nl.
authors.forename: Marcel L
authors.initials: ML
authors.lastname: Geleijnse
authors.affiliation: Department of Biostatistics, Erasmus MC, Rotterdam, The Netherlands. e.lesaffre@erasmusmc.nl.|KU Leuven, L-Biostat, Leuven, Belgium. e.lesaffre@erasmusmc.nl.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lesaffre
authors.affiliation: Department of Cardiothoracic Surgery, Erasmus MC, Rotterdam, The Netherlands. a.j.j.c.bogers@erasmusmc.nl.
authors.forename: Ad J J C
authors.initials: AJ
authors.lastname: Bogers
authors.affiliation: Department of Cardiothoracic Surgery, Erasmus MC, Rotterdam, The Netherlands. j.j.m.takkenberg@erasmusmc.nl.
authors.forename: Johanna J M
authors.initials: JJ
authors.lastname: Takkenberg
mesh_terms: D000367:Age Factors; D000368:Aged; D001024:Aortic Valve Stenosis / Q000097:blood / Q000401:mortality*; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D015233:Models, Statistical; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011379:Prognosis; D018570:Risk Assessment / Q000379:methods; D012737:Sex Factors; D013318:Stroke Volume; D013997:Time Factors
chemical_list: D015415:Biomarkers; D020097:Natriuretic Peptide, Brain; D003404:Creatinine