Crescendo in depolarization and repolarization heterogeneity heralds development of ventricular tachycardia in hospitalized patients with decompensated heart failure

Abstract

Background: A critical need exists for reliable warning markers of in-hospital life-threatening arrhythmias. We used a new quantitative method to track interlead heterogeneity of depolarization and repolarization to detect premonitory changes before ventricular tachycardia (VT) in hospitalized patients with acute decompensated heart failure.

Methods and results: Ambulatory ECGs (leads V(1), V(5), and aVF) recorded before initiation of drug therapy from patients enrolled in the PRECEDENT (Prospective Randomized Evaluation of Cardiac Ectopy with Dobutamine or Nesiritide Therapy) trial were analyzed. R-wave heterogeneity (RWH) and T-wave heterogeneity (TWH) were assessed by second central moment analysis and T-wave alternans (TWA) by modified moving average analysis. Of 44 patients studied, 22 had experienced episodes of VT (≥4 beats at heart rates >100 beats/min) following ≥120 minutes of stable sinus rhythm, and 22 were age- and sex-matched patients without VT. TWA increased from 18.6±2.1 μV (baseline, mean±SEM) to 27.9±4.6 μV in lead V(5) at 15 to 30 minutes before VT (P<0.05) and remained elevated until the arrhythmia occurred. TWA results in leads V(1) and aVF were similar. RWH and TWH were elevated from 164.1±33.1 and 134.5±20.6 μV (baseline) to 299.8±54.5 and 239.2±37.0 μV at 30 to 45 minutes before VT (P<0.05), respectively, preceding the crescendo in TWA by 15 minutes. Matched patients without VT did not display elevated RWH (185.5±29.4 μV) or TWH (157.1±27.2 μV) during the 24-hour period.

Conclusions: This investigation is the first clinical demonstration of the potential utility of tracking depolarization and repolarization heterogeneity to detect crescendos in electrical instability that could forewarn of impending nonsustained VT. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00270400.

Conflict of interest statement

Conflict of Interest Disclosures: RLV and BDN are inventors of the Modified Moving Average method for T-wave alternans analysis, with patent assigned to Beth Israel Deaconess Medical Center and licensed to GE Healthcare, Inc., and Medtronic, Inc. The other authors have no conflicts of interest relevant to this investigation.

Figures

Figure 1

Depolarization and repolarization heterogeneity analysis. Flow chart for signal processing and computing of the second central moment calculation of R-wave heterogeneity (RWH) and T-wave heterogeneity (TWH). TOP: Electrocardiograms (ECGs) were simultaneously obtained from precordial leads V1, V5, and aVF of a representative PRECEDENT patient with decompensated heart failure who experienced ventricular tachycardia. ECGs were filtered to reduce high-frequency noise and to remove baseline wander. Ventricular and supraventricular premature beats as well as beats with a high noise level were removed. For each lead, the isoelectric level was made uniform. BOTTOM: The waveforms of successive beats were superimposed (Bn, Bn1, Bn2, etc.). Second central moment is a square function, because it is the computation of area around a central axis. The square root of the second central moment of simultaneous R waves [from beginning of Q wave to end of S wave, open box] and T waves [from J point to end of T wave (JT interval), black box] was computed from the superimposed waveforms to measure deviation across the entire waveform. The maximum square root of the second central moment was identified for each beat. An average RWH and TWH value was computed for each 15-s interval.

Figure 2

Increase in depolarization and repolarization heterogeneity prior to ventricular tachycardia. At 0–45 minutes prior to ventricular tachycardia (VT), R-wave heterogeneity (RWH) and T-wave heterogeneity (TWH) across leads V1, V5, and aVF were significantly increased above baseline in the 22 PRECEDENT patients with VT (dark grey bars) following a 2-hour quiescent period. Baseline was measured at 60–75 minutes before VT. PRECEDENT patients without VT (light grey bars) did not exhibit significant changes in RWH or TWH during a quiescent 120-minute observation period at a similar time of day (both N.S.).

Figure 3

Crescendo in depolarization and repolarization heterogeneity culminating in T-wave alternans prior to ventricular tachycardia. Example of development of ventricular tachycardia (VT) heralded by crescendo in R-wave and T-wave heterogeneity (RWH, open box; TWH, black box) (lower panel) and T-wave alternans (TWA) (upper panel) in lead V5 prior to the arrhythmia in a patient with decompensated heart failure.

Figure 4

Increase in T-wave alternans prior to ventricular tachycardia. At 0–30 minutes preceding ventricular tachycardia (VT), T-wave alternans (TWA) was increased significantly above baseline in leads V1, V5, and aVF in the 22 PRECEDENT patients with VT (dark grey bars) following a 2-hour quiescent period. Baseline was determined at 60–75 minutes prior to VT. PRECEDENT patients without VT (light grey bars) did not exhibit significant changes in TWA in these leads during a quiescent 120-minute observation period at a similar time of day.

Figure 5

Time course of heart rate prior to ventricular tachycardia. Heart rates across the 120-minute observation period did not change either in patients with ventricular tachycardia (VT) (dark grey bars) or in patients without VT (light grey bars).