Tracking Method Improves Outcomes in CRT

The inability to predict individual responses has been the Achilles’ heel of heart failure RCTs, including CRT trials. It is remarkable, however, that for CRT, many more efforts have been devoted to identifying and predicting responders. Initial small single-center studies reported a favorable outlook for several echocardiographic measures of mechanical dyssynchrony in predicting responders. A subsequent large multicenter study, however, the PROSPECT (Predictors of Response to CRT) trial, failed to identify a useful measurement using conventional and tissue Doppler-based methods (Circulation 2008;117:2608-16).

This important study not only identified an important parameter for selecting responders but also provided indirect support for efforts aimed at identifying predictors of CRT response in individual patients. Khan et al. should be commended for the successful completion of this RCT, which is likely to not only stimulate further innovations in imaging modalities and technical approaches but also more clinical trials that incorporate the assessment of the role of surgical approaches in their design.

Jalal K. Ghali, M.D., is in the DMC Cardiovascular Institute in Detroit. These remarks were taken from his editorial accompanying Dr. Kahn’s report (J. Am. Coll. Cardiol. 2012 [doi:10.1016/j.jacc.2012.01.018]). He had no relevant disclosures.



Speckle-tracking echocardiography has been shown to significantly improve clinical outcomes when used in cardiac resynchronization therapy, according to results from a randomized, controlled trial.

The finding adds to the increasing body of evidence that individualized placement of the ventricular pacing lead in CRT – away from scar and on the most delayed segment of contraction – can result in better outcomes.

In research published online March 7 in the Journal of the American College of Cardiology, Dr. Fakhar Z. Khan of Papworth Hospital, Cambridge, U.K., and colleagues, showed that 70% of heart-failure patients treated with CRT guided by speckle-tracking saw improvement at 6 months, compared with 55% treated with unguided CRT (J. Am. Coll. Cardiol. 2012 [(doi:10.1016/j.jacc.2011.12.030]).

Cardiac resynchronization therapy is used to coordinate contractions in people with heart failure who have failed medical therapies. Speckle-tracking echocardiography is an imaging technique that tracks interference patterns and natural acoustic reflections to show tissue deformation and motion.

Because recent evidence has increasingly suggested that the optimal positioning of the left ventricular pacing lead in CRT is at the most delayed site of contraction and away from myocardial scar (J. Am. Coll. Cardiol. 2010;55:566-75; J. Am. Coll. Cardiol. 2010;56:774-81), speckle tracking has been used to help identify the ideal sites for each patient. Conventional CRT, by contrast, places the LV lead at a lateral or postlateral branch of the coronary sinus in all patients.

For their study comparing conventional unguided CRT with guided CRT, Dr. Khan and colleagues randomized 220 men and women scheduled to undergo CRT. In the study group (N = 110), patients were analyzed with two-dimensional speckle-tracking radial strain imaging to determine the ideal LV lead placing.

Controls (N = 110) underwent standard unguided CRT. Both patients and assessors were blinded to group assignment before and after surgery. The primary end point of the study was response at 6 months, defined as a 15% or greater reduction in left ventricular end-systolic volume, or LVESV.

Secondary end points included clinical response (defined as improvement in New York Heart Association functional class of at least 1 level), 2-year all-cause mortality, and heart failure–related hospitalization combined with all-cause mortality at 2 years. A total of seven patients in the intervention group and six in the control group died prior to the intervention or were lost to follow-up.

The results showed that the speckle-tracking group had significantly greater proportion of responders at 6 months than did the control group (70% vs. 55%). The tracking group also saw NYHA functional class improve in 83% of patients, compared with 65% in conventional CRT, also a significant difference. Though there were no significant differences in 2-year all-cause mortality, investigators saw significantly lower rates of the combined end point of all cause mortality and hospitalization.

"The conventional approach to resynchronization has been to direct the LV lead to the lateral and posterior wall based on the benefit shown in early hemodynamic studies and the observation that delayed segments predominate at these sites," Dr. Khan and colleagues wrote in their analysis.

"However, recent data support a more individualized approach to LV lead placement with significant interindividual and intraindividual variation in the optimal LV lead position."

Furthermore, the investigators wrote, "in this randomized study, subgroup analyses confirm previous reports that the greatest clinical response is seen in patients with a concordant LV lead, together with improved survival and a reduction in the combined end point of death and heart failure–related hospitalization."

Dr. Khan and colleagues argued that "an individualized approach to LV lead placement should be considered in all patients undergoing CRT for advanced heart failure."

The investigators noted that newer imaging techniques, such as three-dimensional speckle tracking, might be better than the one they used for their study. Inadequate image quality resulted in 11% of initially recruited patients being excluded before randomization, they said.

They also noted as a limitation of their study that it made no attempt to preselect patients on the basis of dyssynchrony parameters, nor did it consider the extent of total scar burden.

"The presence of both of these parameters would tend to reduce the overall benefit, although this would be distributed in both groups. CRT response may therefore be enhanced by integrating measures of dyssynchrony and total scar burden with a targeted approach to lead placement, and such an approach should be tested in future studies," Dr. Khan and colleagues wrote.

Dr. Khan’s study was funded by the Addenbrooke’s Charitable Trust, Papworth Hospital Research and Development Department, Cambridge Biomedical Research Center, the U.K. National Institute for Health Research. The authors had no relevant disclosures.

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