Response to Letter Regarding Article, “Left Ventricular Dyssynchrony Is Mandatory for Response to Cardiac Resynchronization Therapy”
We would like to thank Drs Naqvi and Motallebi for their interest in our recent study1 on unresolved issues in cardiac resynchronization therapy (CRT). Despite the promising results of CRT in major randomized trials, 30% to 40% of patients consistently fail to improve when the current guidelines are applied (New York Heart Association class III to IV, QRS duration >120 ms, and left ventricular (LV) ejection fraction <35%). Since this observation, numerous articles have addressed the issue of nonresponse after CRT. It has now become clear that the current selection criteria are relatively weak predictors of response after CRT.2 For example, a recent metaanalysis by Kashani et al (n=2063 patients) revealed that baseline QRS duration was not related to response in 33 out of 34 studies.2 This result was later explained by the fact that QRS is a poor marker of LV dyssynchrony, which is believed to be the key predictor of response after CRT.3 In contrast, >20 (primarily single-center) studies have now demonstrated that direct visualization of LV dyssynchrony using echocardiography is highly predictive for response. The recent Predictors of Response to CRT (PROSPECT) trial is the first study to assess the value of echocardiographic detection of LV dyssynchrony for prediction of response to CRT in a large multicenter setting.4 The preliminary data from this trial have recently been presented at the annual meeting of the European Society of Cardiology (2007), confirming that the majority of echocardiographic parameters indeed provide additional predictive value on top of the current guidelines, with an added value of ≈10% to predict clinical improvement and ≈10% to 20% to predict improvement in LV end-systolic volume. The predictive value of these parameters was however less strong than the results of previous single-center studies. The explanation for this difference is currently unclear but may be related to the relatively high inter–core laboratory variability.
Another issue raised by Drs Naqvi and Motallebi is the importance of LV scar tissue in relation to response to CRT. It has been recently demonstrated that patients with posterolateral scar tissue (usually in the area of the LV pacing lead) have no significant reduction in LV dyssynchrony after CRT, leading to unfavorable response and prognosis.5,6 Indeed, the presence of extensive scar tissue may (partially) explain the lack of resynchronization observed in a subset of patients in the current study. Unfortunately, data on scar tissue were not systematically collected in the present study. Finally, we agree that an immediate improvement in LV end-systolic volume after CRT is likely to be a result of acute LV resynchronization. Identification of patients with acute LV resynchronization therefore may provide a new parameter in the search for potential responders to CRT.
Bleeker GB, Mollema SA, Holman ER, Van de Veire N, Ypenburg C, Boersma E, van der Wall EE, Schalij MJ, Bax JJ. Left ventricular resynchronization is mandatory for response to cardiac resynchronization therapy: analysis in patients with echocardiographic evidence of left ventricular dyssynchrony at baseline. Circulation. 2007; 116: 1440–1448.
Bax JJ, Abraham T, Barold SS, Breithardt OA, Fung JW, Garrigue S, Gorcsan J III, Hayes DL, Kass DA, Knuuti J, Leclercq C, Linde C, Mark DB, Monaghan M, Nihoyannopoulos P, Schalij MJ, Stellbrink C, Yu CM. Cardiac resynchronization therapy. Part 1—Issues before implantation. J Am Coll Cardiol. 2005; 46: 2153–2167.
Ghio S, Chung WES, Leon AR, Tavazzi L, Sun JP, Nihoyannopoulos P, Merlino J, Abraham WT, Leclercq C. Results of the Predictors of Response to CRT (PROSPECT) trial. Paper presented at: European Society of Cardiology Congress 2007; September 4, 2007; Vienna, Austria.
Bleeker GB, Kaandorp TA, Lamb HJ, Boersma E, Steendijk P, de Roos A, van der Wall EE, Schalij MJ, Bax JJ. Effect of posterolateral scar tissue on clinical and echocardiographic improvement after cardiac resynchronization therapy. Circulation. 2006; 113: 969–976.