EDITORIAL COMMENT
Resynchronization in Pediatrics
Who Needs It?*
Anne M. Dubin, MD, FACC*
Stanford University, Palo Alto, California
* Reprint requests and correspondence: Dr. Anne M. Dubin, 750 Welch Road, Suite 305, Palo Alto, California 94303 (Email: amdubin{at}stanford.edu).
Cardiac resynchronization therapy (CRT) has been shown to be a useful therapy in adult patients with left ventricular (LV) dysfunction and intraventricular conduction delay, improving exercise tolerance, heart failure symptoms, and survival (1–4).
At the same time, the evidence is mounting that conventional dual-chamber pacing might have detrimental effects (5–7). The Dual Chamber and VVI Implantable Defibrillator (DAVID), the Mode Selection Trial in Sinus-Node Function (MOST), and other trials have shown that right ventricular (RV) apical pacing has deleterious effects on LV function, most likely as a result of inducing LV dysynchrony (5,7,8). Right ventricular pacing has been shown to have adverse effects on LV cellular structure, ventricular geometry, and systolic and diastolic function, all leading to adverse hemodynamic response (5,8).
The efficacy of CRT in children and in older patients with congenital heart disease has not been fully established. Several studies of CRT in patients after surgery for congenital heart defects have shown improvement in hemodynamics in the acute post-operative period as well as more chronically (9–11). Janousek et al. (9) showed that CRT increased systolic blood pressure in post-operative pediatric patients with biventricular repairs and intraventricular conduction delay. Moreover, this group found that an increase in blood pressure positively correlated with initial QRS duration and extent of QRS shortening. Zimmerman et al. (11) examined the effect of resynchronization therapy on the post-operative pediatric patient after surgical repair. This group also found improvement in systolic blood pressure and cardiac index and a decrease in QRS duration. We have shown an improvement in cardiac output as well as in RV dP/dT in the acute setting of the catheterization laboratory with RV pacing in patients with right bundle branch block and congenital heart disease (10).
At first glance, the Pham et al. (12) results reported in this issue of the Journal seem at odds with these previously discussed studies. They found no change in systolic blood pressure either with conventional dual-chamber pacing or biventricular pacing when compared with baseline conditions. Why did these patients behave differently? It is likely that they are studying a different group of patients and that their data reflect this difference. The patients in this study, unlike the three aforementioned studies, did not have significant baseline intraventricular conduction delay (mean QRS duration of 95 ± 18 ms vs. a median QRS duration of 120 ms in the Janousek et al. [9] group and 166 ms in our study). The baseline QRS duration correlated well with the tissue Doppler index (TDI) results, which showed minimal dysynchrony in a baseline state. Thus, it is not surprising that biventricular pacing did not improve blood pressure in these patients—they were too well synchronized at baseline.
What does not follow from this logic, however, is the 35% increase in cardiac output with biventricular pacing from atrial pacing. Why should patients who are not dysynchronous at baseline (either by QRS duration or TDI results) have such an improvement in cardiac output with biventricular pacing? Why, with such an impressive change in cardiac output, was no change in systolic blood pressure seen? Obviously, this finding will need to be investigated further to determine whether this is a spurious result or whether another mechanism could explain these discordant results. We must consider the possibility that three-dimensional synchrony is not adequately captured by any of our current techniques and that an improvement in one plane might be accompanied by an unseen deterioration in another.
It is intriguing that these patients did not worsen with conventional pacing, despite TDI results, which suggest a significant loss of synchrony. These data support the hypothesis that the process leading to poor LV function with conventional pacing is not a direct mechanical outcome of dysynchrony but, most likely, has to do with chronic remodeling and ventricular geometry. Alternatively, it might be that otherwise healthy myocardium can compensate, in the short term, for significant degrees of dyssynchrony. Thus, although it is tempting to consider resynchronization as an alternative to conventional atrioventricular pacing in any patient requiring an "acute" pacing therapy, there might only be a subset of such patients who will improve with CRT.
Cardiac resynchronization therapy, although offering significant benefit to some patients, is clearly not for everybody. As is the case for many medical innovations, the details of patient selection are key to the successful deployment of this new treatment modality. Further work is necessary to delineate, in this complex and heterogenous group of patients, who will benefit and who will not.
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Footnotes
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* Editorials published in the Journal of American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. 
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References
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1. Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure N Engl J Med 2004;350:2140-2150.[Abstract/Free Full Text]2. Cazeau S, Ritter P, Lazarus A, et al. Multisite pacing for end-stage heart failureearly experience. Pacing Clin Electrophysiol 1996;19:1748-1757.[CrossRef][Medline] 3. Cazeau S, Leclercq C, Lavergne T, et al. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay N Engl J Med 2001;344:873-880.[Abstract/Free Full Text] 4. Young JB, Abraham WT, Smith AL, et al. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failurethe MIRACLE ICD trial. JAMA 2003;289:2685-2694.[Abstract/Free Full Text] 5. Nielsen JC, Kristensen L, Andersen HR, Mortensen PT, Pedersen OL, Pedersen AK. A randomized comparison of atrial and dual-chamber pacing in 177 consecutive patients with sick sinus syndromeechocardiographic and clinical outcome. J Am Coll Cardiol 2003;42:614-623.[Abstract/Free Full Text] 6. Sweeney MO, Hellkamp AS, Ellenbogen KA, et al. Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction Circulation 2003;107:2932-2937.[Abstract/Free Full Text] 7. Wilkoff BL, Cook JR, Epstein AE, et al. Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillatorthe Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 2002;288:3115-3123.[Abstract/Free Full Text] 8. O’Keefe Jr JH, Abuissa H, Jones PG, et al. Effect of chronic right ventricular apical pacing on left ventricular function Am J Cardiol 2005;95:771-773.[CrossRef][Web of Science][Medline] 9. Janousek J, Vojtovic P, Hucin B, et al. Resynchronization pacing is a useful adjunct to the management of acute heart failure after surgery for congenital heart defects Am J Cardiol 2001;88:145-152.[CrossRef][Web of Science][Medline] 10. Dubin AM, Feinstein JA, Reddy VM, Hanley FL, Van Hare GF, Rosenthal DN. Electrical resynchronizationa novel therapy for the failing right ventricle. Circulation 2003;107:2287-2289.[Abstract/Free Full Text] 11. Zimmerman FJ, Starr JP, Koenig PR, Smith P, Hijazi ZM, Bacha EA. Acute hemodynamic benefit of multisite ventricular pacing after congenital heart surgery Ann Thorac Surg 2003;75:1775-1780.[Abstract/Free Full Text] 12. Pham PP, Balaji S, Shen I, Ungerleider R, Li X, Sahn DJ. Impact of conventional versus biventricular pacing on hemodynamics and tissue Doppler imaging indexes of resynchronization postoperatively in children with congenital heart disease J Am Coll Cardiol 2005;46:2284-2289.[Abstract/Free Full Text]
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Impact of Conventional Versus Biventricular Pacing on Hemodynamics and Tissue Doppler Imaging Indexes of Resynchronization Postoperatively in Children With Congenital Heart Disease
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