Mechanical Dyssynchrony by Tissue Doppler Cross-Correlation is Associated with Risk for Complex Ventricular Arrhythmias after Cardiac Resynchronization Therapy


Tissue Doppler cross-correlation analysis has been shown to be associated with long-term survival after cardiac resynchronization defibrillator therapy (CRT-D). Its association with ventricular arrhythmia (VA) is unknown.


From two centers 151 CRT-D patients (New York Heart Association functional classes II–IV, ejection fraction ≤ 35%, and QRS duration ≥ 120 msec) were prospectively included. Tissue Doppler cross-correlation analysis of myocardial acceleration curves from the basal segments in the apical views both at baseline and 6 months after CRT-D implantation was performed. Patients were divided into four subgroups on the basis of dyssynchrony at baseline and follow-up after CRT-D. Outcome events were predefined as appropriate antitachycardia pacing, shock, or death over 2 years.


Mechanical dyssynchrony was present in 97 patients (64%) at baseline. At follow-up, 42 of these 97 patients (43%) had persistent dyssynchrony. Furthermore, among 54 patients with no dyssynchrony at baseline, 15 (28%) had onset of new dyssynchrony after CRT-D. In comparison with the group with reduced dyssynchrony, patients with persistent dyssynchrony after CRT-D were associated with a substantially increased risk for VA (hazard ratio [HR], 4.4; 95% CI, 1.2–16.3; P = .03) and VA or death (HR, 4.0; 95% CI, 1.7–9.6; P = .002) after adjusting for other covariates. Similarly, patients with new dyssynchrony had increased risk for VA (HR, 10.6; 95% CI, 2.8–40.4; P = .001) and VA or death (HR, 5.0; 95% CI, 1.8–13.5; P = .002).


Persistent and new mechanical dyssynchrony after CRT-D was associated with subsequent complex VA. Dyssynchrony after CRT-D is a marker of poor prognosis.

Ventricular arrhythmias (VAs) are of increased prevalence in patients with symptomatic heart failure (HF) with depressed left ventricular (LV) ejection fractions and are a significant cause of sudden cardiac death. Cardiac resynchronization defibrillator therapy (CRT-D) has been shown to reduce morbidity and mortality, but reported effects on VAs are conflicting. Different single-center and multicenter trials have suggested CRT-D as antiarrhythmic, proarrhythmic, or not associated with the occurrence of VAs.

A few studies have shown that mechanical heterogeneity of LV segmental contraction is associated with VA in patients with HF of various etiologies. CRT-D reduces LV mechanical dyssynchrony, which in theory would reduce the occurrence of VA. However, a subset of patients have been reported to deteriorate after CRT-D, which may increase the risk for VA and death. These patients are important to recognize and may even benefit from discontinuation of CRT-D.

LV dyssynchrony by cross-correlation analysis (CCA) of tissue Doppler myocardial systolic acceleration has been associated with favorable reverse remodeling and long-term survival after CRT-D. The association of dyssynchrony by CCA with risk for VA is unknown. Accordingly, the aim of this study was to investigate the association between changes in LV dyssynchrony with VAs after CRT-D implantation.


Study Population

We included a series of patients with HF who underwent CRT-D implantation for routine clinical indications and underwent Doppler tissue imaging echocardiography before and a median of 6 months after CRT-D implantation. This cohort comprised patients with symptomatic HF in New York Heart Association functional classes II to IV, with LV ejection fractions ≤ 35% and QRS durations ≥ 120 msec, who were receiving optimal medical therapy and had undergone successful CRT-D device implantation. Patients with atrial fibrillation and right ventricular pacing were excluded. Overall, 151 patients were included from two different centers (131 patients from the University of Pittsburgh Medical Center from 2002 to 2011 and 20 patients from Aalborg University Hospital from 2011 to 2013). A total of 235 patients were initially enrolled from the two centers. Of these, 18 patients (8%) died or underwent heart transplantation or LV assist device implantation before 6-month follow-up echocardiography, and 63 (27%) were excluded because of a lack of follow-up echocardiography. Three (1%) were excluded as a result of loss to follow-up. The respective institutional review boards approved the study protocol, and patients gave informed consent before the study. The study design was prospective, with CCA applied to the selected study cohort from a consecutive patient series meeting the inclusion criteria with prespecified end points. A single observer performed the CCA analysis on the total study population blinded to the outcomes. Ischemic cardiomyopathy was defined as a previously documented history of myocardial infarction, prior revascularization, or presence of significant coronary artery disease (≥70% stenosis in at least one major coronary artery). All patients underwent CRT-D device implantation with a right atrial lead, right ventricular apical lead, and LV lead through the coronary sinus implanted in the posterolateral or lateral LV free wall.


All echocardiographic studies (GE Vivid 7 and E9; GE Vingmed Ultrasound AS, Horten, Norway) were performed to obtain color tissue Doppler cine loops of three cardiac cycles in each of the three standard apical views. Image sector width and depth were adjusted to optimize frame rates at 112 ± 10 frames/sec. Offline analysis was performed using EchoPAC PC version BT11 (GE Vingmed Ultrasound AS). LV volumes and LV ejection fraction were assessed using the biplane Simpson rule. The inter- and intraobserver variability of end-systolic volume from our echocardiography laboratory has been reported previously.

CCA of Myocardial Systolic Acceleration

The CCA method has previously been discussed in detail. Briefly, regions of interest measuring 7 × 15 mm were placed on the basal segments of the opposing walls in each of the standard apical views, and the resulting velocity text files were saved. These text files were then imported into a customized Excel spreadsheet (Microsoft Corporation, Redmond, WA), which has a prewritten algorithm to perform CCA analysis. This customized Excel spreadsheet with a macro written for CCA was provided as supplemental material to previously published work. The Excel spreadsheet first converts the velocity data into myocardial acceleration curves by time differentiation. A three-point filter for noise was used to filter the resulting acceleration curves. CCA of the acceleration traces was performed according to the following equation:

<SPAN role=presentation tabIndex=0 id=MathJax-Element-1-Frame class=MathJax style="POSITION: relative" data-mathml='Xccd=∑i[(xi−x¯)(yi−d−y¯)]∑i(xi−x¯)2∑i(yi−d−y¯)2,’>Xccd=i[(xix¯)(yidy¯)]i(xix¯)2i(yidy¯)2,Xccd=∑i[(xi−x¯)(yi−d−y¯)]∑i(xi−x¯)2∑i(yi−d−y¯)2,
Xcc d = ∑ i [ ( x i − x ¯ ) ( y i − d − y ¯ ) ] ∑ i ( x i − x ¯ ) 2 ∑ i ( y i − d − y ¯ ) 2 ,

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Apr 21, 2018 | Posted by in CARDIOLOGY | Comments Off on Mechanical Dyssynchrony by Tissue Doppler Cross-Correlation is Associated with Risk for Complex Ventricular Arrhythmias after Cardiac Resynchronization Therapy

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