title: Prognostic capacity of a clinically indicated exercise test for cardiovascular mortality is enhanced by combined analysis of exercise capacity, heart rate recovery and T-wave alternans.
abstract: BACKGROUND
  Exercise capacity, heart rate recovery and T-wave alternans are independent predictors of cardiovascular mortality. We tested whether these parameters contain supplementary prognostic information.
  
  
  METHODS
  A total of 3609 consecutive patients (2157 men) referred for a routine, clinically indicated bicycle exercise test were enrolled in the Finnish Cardiovascular Study (FINCAVAS). Exercise capacity was measured in metabolic equivalents, heart rate recovery as the decrease in heart rate from maximum to one minute post-exercise, and T-wave alternans by time-domain Modified Moving Average method.
  
  
  RESULTS
  During 57-month median follow-up (interquartile range 35-78 months), 96 patients died of cardiovascular causes (primary endpoint) and 233 from any cause. All three parameters were independent predictors of cardiovascular mortality when analysed as continuous variables. Adding metabolic equivalents (p < 0.001), heart rate recovery (p = 0.002) or T-wave alternans (p = 0.01) to the linear model improved its predictive power for cardiovascular mortality. The combination of low exercise capacity (<6 metabolic equivalents), reduced heart rate recovery (≤12 beats/min) and elevated T-wave alternans (≥60 μV) yielded the highest hazard ratio for cardiovascular mortality of 16.5 (95% confidence interval 4.0-67.7, p < 0.001). Harrell's C index was 0.719 (confidence interval 0.665-0.772) for cardiovascular mortality with previously defined cutpoints (<8 units for metabolic equivalents, ≤18 beats/min for heart rate recovery and ≥60 μV for T-wave alternans).
  
  
  CONCLUSIONS
  The prognostic capacity of the clinical exercise test is enhanced by combined analysis of exercise capacity, heart rate recovery and T-wave alternans.
authors.affiliation: Department of Internal Medicine, Helsinki University Central Hospital, Finland Department of Clinical Physiology, Tampere University Hospital, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Minkkinen
authors.affiliation: Department of Internal Medicine, University of Helsinki and South Karelia Central Hospital, Lappeenranta, Finland.
authors.forename: Tuomo
authors.initials: T
authors.lastname: Nieminen
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Verrier
authors.affiliation: Department of Clinical Physiology, Tampere University Hospital, Finland School of Medicine, University of Tampere, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Leino
authors.affiliation: School of Medicine, University of Tampere, Finland Department of Clinical Chemistry, Tampere University Hospital, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.affiliation: Department of Biomedical Engineering, Tampere University of Technology and BioMeditech, Tampere, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Viik
authors.affiliation: Tampere University of Applied Sciences, Finland.
authors.forename: Rami
authors.initials: R
authors.lastname: Lehtinen
authors.affiliation: Department of Cardiology, Tampere University Hospital, Finland.
authors.forename: Kjell
authors.initials: K
authors.lastname: Nikus
authors.affiliation: Department of Clinical Physiology, Tampere University Hospital, Finland School of Medicine, University of Tampere, Finland.
authors.forename: Tiit
authors.initials: T
authors.lastname: Kööbi
authors.affiliation: Science Centre, Pirkanmaa Hospital District, Finland.
authors.forename: Väinö
authors.initials: V
authors.lastname: Turjanmaa
authors.affiliation: Department of Clinical Physiology, Tampere University Hospital, Finland School of Medicine, University of Tampere, Finland mika.kahonen@uta.fi.
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
mesh_terms: D000200:Action Potentials; D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000401:mortality* / Q000503:physiopathology; D002423:Cause of Death; D016009:Chi-Square Distribution; D004562:Electrocardiography; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D005387:Finland; D006329:Heart Conduction System / Q000503:physiopathology*; D006339:Heart Rate; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D020127:Recovery of Function; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
keywords: Cardiovascular mortality; T-wave alternans; exercise capacity; heart rate recovery