CORRESPONDENCE: LETTER TO THE EDITOR
Deciphering Gene Expression Profiling in Cardiac Resynchronization Therapy
Takeshi Aiba, MD, PhD,
Andreas Barth, MD, PhD and
Gordon F. Tomaselli, MD*
* Department of Cardiology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 844, Baltimore, Maryland 21205 (Email: gtomasel{at}jhmi.edu).
We read with interest the article by Vanderheyden et al. (1). We applaud the authors for an ambitious study and the first report of gene expression in human cardiac resynchronization therapy. The limitations of the work were elucidated by both the authors and the editorial commentator (2). However, we have questions about several aspects of the article concerning both the functional as well as the gene expression measurements that make interpretation of the work problematic.
First, the magnitude of the effect of cardiac resynchronization therapy in all patients (Table 3 in Vanderheyden et al. [1]) and responders (Table 4 in Vanderheyden et al. [1]) is quite striking. More disturbing, however, is that the magnitude of the beneficial response, on average, was greater in the overall group than in the subset of responders. This result was true for ejection fraction (EF), left ventricular (LV) end-diastolic volume, several measures of dyssynchrony, and phospholamban.
Some, but not all, of these differences may be accounted for by baseline differences between responders and nonresponders, which raises other issues regarding the findings. However, it is difficult to imagine how the overall increase in EF exceeds that in the responder group despite the similarity in baseline EF in both responders and nonresponders. The same is true of the decrement in LV end-diastolic volume.
Finally, the definition of responders raises some questions. There are clear differences in estimates of improvement in LV ejection fraction and changes in chamber size in the 2 groups, but there is also evidence for mechanical synchronization of LV, interventricular, and atrioventricular contraction in both groups. Thus, the mechanism of clinical improvement likely involves more than simple mechanical resynchronization, and the gene expression signature is likely a manifestation of more than resynchronization alone.
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1. Vanderheyden M, Mullens W, Delrue L, et al. Myocardial gene expression in heart failure patients treated with cardiac resynchronization therapy: responders versus nonresponders J Am Coll Cardiol 2008;51:129-136.[Abstract/Free Full Text]2. Cappola TP. Molecular remodeling in human heart failure J Am Coll Cardiol 2008;51:137-138.[Free Full Text]
Related Article
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- Marc Vanderheyden, Wilfried Mullens, and Jozef Bartunek
J. Am. Coll. Cardiol. 2008 52: 1177-1178.
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