Excitation and Contraction of the Failing Human Heart In Situ and Effects of Cardiac Resynchronization Therapy: Application of Electrocardiographic Imaging and Speckle Tracking Echo-Cardiography

Abstract

Despite the success of cardiac resynchronization therapy (CRT) for treating heart failure (HF), the rate of nonresponders remains 30%. Improvements to CRT require understanding of reverse remodeling and the relationship between electrical and mechanical measures of synchrony. The objective was to utilize electrocardiographic imaging (ECGI, a method for noninvasive cardiac electrophysiology mapping) and speckle tracking echocardiography (STE) to study the physiology of HF and reverse remodeling induced by CRT. We imaged 30 patients (63% male, mean age 63.7 years) longitudinally using ECGI and STE. We quantified CRT-induced remodeling of electromechanical parameters and evaluated a novel index, the electromechanical delay (EMD, the delay from activation to peak contraction). We also measured dyssynchrony using ECGI and STE and compared their effectiveness for predicting response to CRT. EMD values were elevated in HF patients compared to controls. However, the EMD values were dependent on the activation sequence (CRT-paced vs. un-paced), indicating that the EMD is not intrinsic to the local tissue, but is influenced by factors such as opposing wall contractions. After 6 months of CRT, patients had increased contraction in native rhythm compared to baseline pre-CRT (baseline: −8.55%, 6 months: −10.14%, p = 0.008). They also had prolonged repolarization at the location of the LV pacing lead. The pre-CRT delay between mean lateral LV and RV electrical activation time was the best predictor of beneficial reduction in LV end systolic volume by CRT (Spearman’s Rho: −0.722, p < 0.001); it outperformed mechanical indices and 12-lead ECG criteria. HF patients have abnormal EMD. The EMD depends upon the activation sequence and is not predictive of response to CRT. ECGI-measured LV activation delay is an effective index for CRT patient selection. CRT causes persistent improvements in contractile function.