Reduced T wave alternans in heart failure responders to cardiac resynchronization therapy: Evidence of electrical remodeling

BACKGROUND: T-wave alternans (TWA), a marker of electrical instability, can be modulated by cardiac resynchronization therapy (CRT). The relationship between TWA and heart failure response to CRT has not been clearly defined. METHODS AND RESULTS: In 40-patients (age 65±11 years, left ventricular ejection-fraction [LVEF] 23±7%), TWA was evaluated prospectively at median of 2 months (baseline) and 8 months (follow-up) post-CRT implant. TWA-magnitude (V(alt) >0μV, k≥3), its duration (d), and burden (V(alt) ·d) were quantified in moving 128-beat segments during incremental atrial (AAI, native-TWA) and atrio-biventricular (DDD-CRT) pacing. The immediate and long-term effect of CRT on TWA was examined. Clinical response to CRT was defined as an increase in LVEF of ≥5%. Native-TWA was clinically significant (V(alt) ≥1.9μV, k≥3) in 68% of subjects at baseline. Compared to native-TWA at baseline, DDD-CRT pacing at baseline and follow-up reduced the number of positive TWA segments, peak-magnitude, longest-duration and peak-burden of TWA (44±5 to 33±5 to 28±4%, p = 0.02 and 0.002; 5.9±0.8 to 4.1±0.7 to 3.8±0.7μV, p = 0.01 and 0.01; 97±9 to 76±8 to 67±8sec, p = 0.004 and <0.001; and 334±65 to 178±58 to 146±54μV.sec, p = 0.01 and 0.004). In addition, the number of positive segments and longest-duration of native-TWA diminished during follow-up (44±5 to 35±6%, p = 0.044; and 97±9 to 81±9sec, p = 0.02). Clinical response to CRT was observed in 71% of patients; the reduction in DDD-CRT paced TWA both at baseline and follow-up was present only in responders (interaction p-values <0.1). CONCLUSION: Long-term CRT reduces the prevalence and magnitude of TWA. This CRT induced beneficial electrical remodeling is a marker of clinical response after CRT.