title: Effect of Visit-to-Visit Variation of Heart Rate and Systolic Blood Pressure on Outcomes in Chronic Systolic Heart Failure: Results From the Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial (SHIFT) Trial.
abstract: BACKGROUND
  Elevated resting heart rate (HR) and low systolic blood pressure (SBP) are related to poor outcomes in heart failure (HF). The association between visit-to-visit variation in SBP and HR and risk in HF is unknown.
  
  
  RESULTS
  In Systolic Heart Failure Treatment with the If inhibitor ivabradine Trial (SHIFT) patients, we evaluated relationships between mean HR, mean SBP, and visit-to-visit variations (coefficient of variation [CV]=SD/mean×100%) in SBP and HR (SBP-CV and HR-CV, respectively) and primary composite endpoint (cardiovascular mortality or HF hospitalization), its components, all-cause mortality, and all-cause hospitalization. High HR and low SBP were closely associated with risk for primary endpoint, all-cause mortality, and HF hospitalization. The highest number of primary endpoint events occurred in the highest HR tertile (38.8% vs 16.4% lowest tertile; P<0.001). For HR-CV, patients at highest risk were those in the lowest tertile. Patients in the lowest thirds of mean SBP and SBP-CV had the highest risk. The combination of high HR and low HR-CV had an additive deleterious effect on risk, as did that of low SBP and low SBP-CV. Ivabradine reduced mean HR and increased HR-CV, and increased SBP and SBP-CV slightly.
  
  
  CONCLUSIONS
  Beyond high HR and low SBP, low HR-CV and low SBP-CV are predictors of cardiovascular outcomes with additive effects on risk in HF, but with an unknown effect size. Beyond HR reduction, ivabradine increases HR-CV. Low visit-to-visit variation of HR and SBP might signal risk of cardiovascular outcomes in systolic HF.
  
  
  BACKGROUND
  URL: http://www.isrctn.com/. Unique identifier: ISRCTN70429960.
authors.affiliation: Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany michael.boehm@uks.eu.
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.affiliation: Robertson Center for Biostatistics, University of Glasgow, United Kingdom.
authors.forename: Michele
authors.initials: M
authors.lastname: Robertson
authors.affiliation: Division of Cardiovascular Medicine and the Howard Gilman Institute for Heart Valve Disease and the Schiavone Institute for Cardiovascular Translational Research, State University of New York Downstate Medical Center, New York, NY.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Borer
authors.affiliation: Robertson Center for Biostatistics, University of Glasgow, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.affiliation: Institute of Cardiometabolism and Nutrition (ICAN), Pierre et Marie Curie Paris VI University, La Pitié-Salpétrière Hospital, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Komajda
authors.affiliation: Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Mahfoud
authors.affiliation: Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ewen
authors.affiliation: Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.affiliation: Maria Cecilia Hospital, GVM Care and Research, Ettore Sansavini Health Science Foundation, Cotignola, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Tavazzi
mesh_terms: D000368:Aged; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D006760:Hospitalization; D006801:Humans; D000077550:Ivabradine; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009819:Office Visits; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D013599:Systole; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001552:Benzazepines; D002317:Cardiovascular Agents; D000077550:Ivabradine
keywords: blood pressure; heart failure; heart rate–blood pressure variation