Body surface distribution of T wave alternans is modulated by heart rate and ventricular activation sequence in patients with cardiomyopathy

BACKGROUND: T wave alternans (TWA) is an electrocardiographic marker of heightened sudden death risk from ventricular tachyarrhythmias in patients with cardiomyopathy. TWA is evaluated from the 12-lead electrocardiogram, Frank lead, or Holter lead recordings, however these clinical lead configurations will not record TWA from adjacent regions of the body torso. OBJECTIVE: We tested the hypothesis that changing heart rate or ventricular activation may alter the body surface distribution of TWA such that the clinical ECG leads fail to detect TWA in some patients; thereby producing a false-negative test. METHODS: In 28 cardiomyopathy patients (left ventricular ejection fraction 28±6%), 114 unipolar electrograms were recorded across the body torso during incremental atrial pacing, followed by atrioventricular pacing at 100, 110 and 120bpm. TWA was measured from each unipolar electrogram using the spectral method. A clinically positive TWA test was defined as TWA magnitude (V(alt)) ≥1.9 uV with k ≥3 at ≤110bpm. RESULTS: Maximum V(alt) (TWA(max)) was greater from the body torso than clinical leads during atrial (p<0.005) and atrioventricular pacing (p<0.005). TWA(max) was most prevalent in the right lower chest with atrial pacing 100 bpm and shifted to the left lower chest at 120 bpm. TWA(max) was most prevalent in left lower chest with atrioventricular pacing at 100 bpm and shifted to the left upper chest at 120 bpm. Using the body torso as a gold standard, the false-negative rate for clinically positive TWA with clinical leads was 21% during atrial and 11% during atrioventricular pacing. Due to TWA signal migration outside the clinical leads, clinically positive TWA became false-negative when pacing mode was switched (atrial→atrioventricular pacing) in 21% of patients. CONCLUSIONS: The body surface distribution of TWA is modulated by heart rate and the sequence of ventricular activation in patients with cardiomyopathy, which can give rise to modest false-negative TWA signal detection using standard clinical leads.