title: Resting heart rate and risk of adverse cardiovascular outcomes in asymptomatic aortic stenosis: the SEAS study.
abstract: BACKGROUND
  An elevated resting heart rate (RHR) may be an early sign of cardiac failure, but its prognostic value during watchful waiting in asymptomatic aortic stenosis (AS) is largely unknown.
  
  
  METHODS
  RHR was determined by annual ECGs in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study of asymptomatic mild-to-moderate AS patients. Primary endpoint in this substudy was major cardiovascular events (MCEs) and secondary outcomes its individual components. Multivariable Cox-models using serially-measured RHR were used to examine the prognostic impact of RHR per se.
  
  
  RESULTS
  1563 patients were followed for a mean of 4.3years (6751 patient-years of follow-up), 553 (35%) MCEs occurred, 10% (n=151) died, including 75 cardiovascular deaths. In multivariable analysis, baseline RHR was independently associated with MCEs (HR 1.1 per 10min(-1) faster, 95% CI: 1.0-1.3) and cardiovascular mortality (HR 1.3 per 10min(-1) faster, 95% CI: 1.0-1.7, both p≤0.03). Updating RHR with annual in-study reexaminations, time-varying RHR was highly associated with excess MCEs (HR 1.1 per 10min(-1) faster, 95% CI: 1.1-1.3) and cardiovascular mortality (HR 1.4 per 10min(-1) faster, 95% CI: 1.2-1.7, both p≤0.006). The association of RHR with MCEs and cardiovascular mortality was not dependent on atrial fibrillation status (both p≥0.06 for interaction).
  
  
  CONCLUSIONS
  RHR is independently associated with MCEs and cardiovascular death in asymptomatic AS (Clinicaltrials.gov; unique identifier NCT00092677).
authors.affiliation: Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, Denmark. Electronic address: greve_anders@outlook.com.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Greve
authors.affiliation: Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Casper N
authors.initials: CN
authors.lastname: Bang
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Ronan M G
authors.initials: RM
authors.lastname: Berg
authors.affiliation: Medicinsk Afdeling, OUH Svendborg Sygehus, Denmark.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Egstrup
authors.affiliation: Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Rossebø
authors.affiliation: Department of Medicine, Institution of Public Health and Clinical Medicine, Umeå University, Skelleftå, Sweden.
authors.forename: Kurt
authors.initials: K
authors.lastname: Boman
authors.affiliation: Department of Cardiology and Angiology, University Heart Center Rostock, Rostock School of Medicine, Rostock, Germany.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Nienaber
authors.affiliation: Manchester Academic Health Sciences Centre, Manchester, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Ray
authors.affiliation: Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Gohlke-Baerwolf
authors.affiliation: Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: Olav W
authors.initials: OW
authors.lastname: Nielsen
authors.affiliation: Weill Cornell Medical College, New York, NY, United States.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Okin
authors.affiliation: Weill Cornell Medical College, New York, NY, United States.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Devereux
authors.affiliation: Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.affiliation: Weill Cornell Medical College, New York, NY, United States; Glostrup University Hospital, Copenhagen, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Wachtell
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001024:Aortic Valve Stenosis / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D001281:Atrial Fibrillation / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology*; D001384:Azetidines / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D005500:Follow-Up Studies; D014943:Global Health; D006333:Heart Failure / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012146:Rest / Q000502:physiology*; D019821:Simvastatin / Q000627:therapeutic use*; D015996:Survival Rate / Q000639:trends; D013997:Time Factors
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D019821:Simvastatin; D000069438:Ezetimibe
keywords: Aortic valve stenosis; Resting heart rate; Risk stratification