Predictive value of beat-to-beat QT variability index across the continuum of left ventricular dysfunction: competing risks of noncardiac or cardiovascular death and sudden or nonsudden cardiac death

Abstract

Background: The goal of the present study was to determine the predictive value of beat-to-beat QT variability in heart failure patients across the continuum of left ventricular dysfunction.

Methods and results: Beat-to-beat QT variability index (QTVI), log-transformed heart rate variance, normalized QT variance, and coherence between heart rate variability and QT variability have been measured at rest during sinus rhythm in 533 participants of the Muerte Subita en Insuficiencia Cardiaca heart failure study (mean age, 63.1±11.7; men, 70.6%; left ventricular ejection fraction >35% in 254 [48%]) and in 181 healthy participants from the Intercity Digital Electrocardiogram Alliance database. During a median of 3.7 years of follow-up, 116 patients died, 52 from sudden cardiac death (SCD). In multivariate competing risk analyses, the highest QTVI quartile was associated with cardiovascular death (subhazard ratio, 1.67 [95% CI, 1.14-2.47]; P=0.009) and, in particular, with non-SCD (subhazard ratio, 2.91 [1.69-5.01]; P<0.001). Elevated QTVI separated 97.5% of healthy individuals from subjects at risk for cardiovascular (subhazard ratio, 1.57 [1.04-2.35]; P=0.031) and non-SCD in multivariate competing risk model (subhazard ratio, 2.58 [1.13-3.78]; P=0.001). No interaction between QTVI and left ventricular ejection fraction was found. QTVI predicted neither noncardiac death (P=0.546) nor SCD (P=0.945). Decreased heart rate variability rather than increased QT variability was the reason for increased QTVI in the present study.

Conclusions: Increased QTVI because of depressed heart rate variability predicts cardiovascular mortality and non-SCD but neither SCD nor extracardiac mortality in heart failure across the continuum of left ventricular dysfunction. Abnormally augmented QTVI separates 97.5% of healthy individuals from heart failure patients at risk.

Figure 1

Histograms showing QTVI distribution. Histograms showing the distribution of the QTVI in healthy IDEAL subjects (empty bars) and heart failure participants of MUSIC study patients (full bars).

Figure 2

Survival in heart failure. Nelson-Aalen cumulative hazard estimates for the cardiovascular death (A), non-cardiac death (B), sudden cardiac death (C) and non-sudden cardiac death (D) in 4 categories of patients: those with the highest QTVI quartile and LVEF ≤35%, patients with the highest QTVI quartile and LVEF>35%, those with the lower 3 QTVI quartiles and LVEF ≤35%, patients with the lower 3 QTVI quartiles and LVEF >35%.

Figure 3

Cumulative incidence functions for the cardiovascular death (A), non-cardiac death (B), sudden cardiac death (C) and non-sudden cardiac death (D) in 4 categories of patients.

Figure 4

Kaplan-Meier curves for the probabilities of all-cause death (A), cardiovascular death (B), and sudden cardiac death (C) in patients with available QT variability results (Included), and those who were excluded from QT variability analysis as non-analyzable. Increased QT variability index (QTVI) predicts cardiovascular mortality and specifically non-sudden cardiac death, but not sudden cardiac death and not non-cardiac death in heart failure across a continuum of left ventricular dysfunction. Abnormally elevated QTVI separates 97.5% of healthy individuals from subjects at risk. Further investigation of QTVI as a potential screening tool in the general population is warranted.