Response to Letter Regarding Article, “Predictors of Response to Cardiac Resynchronization Therapy in The Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT)”
Authors: Ilan Goldenberg, Arthur J. Moss, W. Jackson Hall, Alon Barsheshet, Scott McNitt, Wojciech Zareba, Helmut Klein, Elyse Foster, Jeffrey J. Goldberger, Peter Santucci, David Wilber, Timothy Shinn, Scott Solomon, Jonathan S. Steinberg
Journal: Circulation (2012)

Trial With Cardiac Resynchronization Therapy (MADIT-CRT)"We agree with Varma et al that the findings of our current Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) substudy (regarding factors associated with response to cardiac resynchronization therapy with a defibrillator (CRT-D) 1 and the previous MADIT-CRT report by Singh et al (regarding the effect of left ventricular [LV] lead position on clinical outcomes in the same trial) 2 may appear contradictory.However, caution is necessary in comparing the results of the 2 studies for the following reasons.(1) In the present study, we identified 7 factors associated with significant reductions in left ventricular volumes (ie, echocardiographic response) in the study patients treated with CRT-D and used combined assessment of the identified factors to compare CRT-D with implantable cardioverter-defibrillator-only risk of heart failure or death (ie, clinical response).In contrast, in the study by Singh et al, clinical response in the CRT-D arm was assessed by the different LV lead positions.Our data show that the LV lead position did not correlate with echocardiographic response in MADIT-CRT and was therefore not included in the response score.(2) The study by Singh et al assessed clinical response according to the LV lead position only among the 799 CRT-D patients with clearly identifiable LV lead positions, whereas, in the present study, we compared clinical outcome between the 2 randomized treatment arms of the trial (nϭ1761 patients).Thus, it is possible that CRT-D patients in whom the LV lead position was implanted in the apical region had a higher risk in comparison with a nonapical lead position, but may still have a lower risk in comparison with implantable cardioverter-defibrillator-only patients.(3) The present study used an approach that combines 7 simple clinical and echocardiographic factors to identify the degree of clinical response to CRT-D in comparison with implantable cardioverter-defibrillator-only therapy.In contrast, the study by Singh et al used a different approach, which focused solely on the LV lead position as an independent predictor of clinical outcome following CRT-D implantation.Accordingly, the important differences in the design and results of the 2 MADIT-CRT substudies lead to 2 separate conclusions.First, CRT-D patients in whom the LV lead is implanted in an apical position are at increased risk for heart failure or death compared with those in whom the LV lead is implanted in nonapical regions.Second, the degree of clinical response to CRT-D in comparison with implantable cardioverterdefibrillator-only therapy is directly related to the number of factors associated with echocardiographically assessed volume reduction independently from the LV lead position.