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

J Am Heart Assoc. 2016 Feb 12;5(2):e002160. doi: 10.1161/JAHA.115.002160.

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.

Methods and 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.

Clinical trial registration: URL: http://www.isrctn.com/. Unique identifier: ISRCTN70429960.

Keywords: blood pressure; heart failure; heart rate–blood pressure variation.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Benzazepines / adverse effects
  • Benzazepines / therapeutic use*
  • Blood Pressure / drug effects*
  • Cardiovascular Agents / adverse effects
  • Cardiovascular Agents / therapeutic use*
  • Double-Blind Method
  • Female
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Heart Failure / physiopathology
  • Heart Rate / drug effects*
  • Hospitalization
  • Humans
  • Ivabradine
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Office Visits*
  • Predictive Value of Tests
  • Risk Assessment
  • Risk Factors
  • Systole
  • Time Factors
  • Treatment Outcome

Substances

  • Benzazepines
  • Cardiovascular Agents
  • Ivabradine

Associated data

  • ISRCTN/ISRCTN70429960