Correspondence
Biventricular Pacing
N Engl J Med 2010; 362:956-959March 11, 2010
- Article
To the Editor:
Yu et al. (Nov. 26 issue)1 found that among patients with bradycardia, the left ventricular ejection fraction at 12 months was 7 percentage points lower in the patients who were randomly assigned to right ventricular pacing than in those who were assigned to biventricular pacing. They conclude that “adverse cardiac remodeling can be prevented by biventricular pacing.”
However, this trial may fail to differentiate between adverse remodeling and the immediate mechanical dyssynchrony induced by right ventricular pacing.2-4 Given that results of follow-up echocardiography were reported only at 12 months and that these echocardiographic studies were performed when the pacing therapies were still active, it is possible that the reduced left ventricular ejection fraction was caused by pacing dyssynchrony alone.
An analysis of echocardiographic findings from the 1-, 3-, 6-, and 9-month follow-up visits might provide additive information beyond the baseline and 12-month data. For example, an expanded graph that shows the interaction between left ventricular ejection fraction and time might show an immediate separation of the curves with pacing dyssynchrony, but a slower separation with remodeling.
Alternatively, it may be worthwhile to perform a crossover analysis in the right-ventricular-pacing group to determine whether the reduced left ventricular ejection fraction normalizes when the system is changed to biventricular pacing — which would suggest that remodeling is a less important factor than pacing dyssynchrony.
John W. McEvoy, M.B.
Johns Hopkins Hospital, Baltimore, MD
jmcevoy1@jhmi.edu No potential conflict of interest relevant to this letter was reported.
4 References1
Yu C-M ,Chan JY-S ,Zhang Q , et al. Biventricular pacing in patients with bradycardia and normal ejection fraction. N Engl J Med 2009;361:2123-2134
Full Text | Web of Science | Medline2
Liu WH ,Chen MC ,Chen YL , et al. Right ventricular apical pacing acutely impairs left ventricular function and induces mechanical dyssynchrony in patients with sick sinus syndrome: a real-time three-dimensional echocardiographic study. J Am Soc Echocardiogr 2008;21:224-229
CrossRef | Web of Science | Medline3
Fang F, Chan JY, Yip GW, et al. Prevalence and determinants of left ventricular systolic dyssynchrony in patients with normal ejection fraction received right ventricular apical pacing: a real-time three-dimensional echocardiographic study. Eur J Echocardiogr 2009 November 20 (Epub ahead of print).
4
Yu CM ,Lin H ,Fung WH ,Zhang Q ,Kong SL ,Sanderson JE . Comparison of acute changes in left ventricular volume, systolic and diastolic functions, and intraventricular synchronicity after biventricular and right ventricular pacing for heart failure. Am Heart J 2003;145:E18-E18
CrossRef | Web of Science | Medline
To the Editor:
In the article by Yu et al., right ventricular apical pacing was programmed to a dual-chamber rate-adaptive mode with dominant (97%) right ventricular apical pacing. It is well known that right ventricular apical pacing alters the normal sequence of ventricular activation, resulting in an increase in the composite end point of death or heart failure.1,2 The percentage of right ventricular pacing can be reduced remarkably by dual-chamber pacing with a long atrioventricular delay or single-chamber atrial pacing in sinus-node dysfunction,3 and by single-chamber ventricular pacing with a lower backup rate in an implantable cardioverter–defibrillator.2 Right ventricular outflow tract pacing may prevent the deleterious effects of right ventricular apical pacing in patients with atrioventricular block.4 Moreover, patients with preserved left ventricular function are less vulnerable to right ventricular apical pacing than are those with reduced left ventricular function.1,2 Biventricular pacing is more technically demanding and expensive than is right ventricular apical pacing. Therefore, the use of biventricular pacing should be limited to patients with pacemaker-induced heart failure that cannot be prevented by conventional technologies.
Haruo Tomoda, M.D., Ph.D.
Tokyo Heart Institute, Tokyo, Japan
tokyoheart@abelia.ocn. ne. jp No potential conflict of interest relevant to this letter was reported.
4 References1
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
CrossRef | Web of Science | Medline2
Wilkoff BL ,Cook JR ,Epstein AE , et al. Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 2002;288:3115-3123
CrossRef | Web of Science | Medline3
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 syndrome: echocardiographic and clinical outcome. J Am Coll Cardiol 2003;42:614-623
CrossRef | Web of Science | Medline4
Tse HF ,Yu C ,Wong KK , et al. Functional abnormalities in patients with permanent right ventricular pacing: the effect of sites of electrical stimulation. J Am Coll Cardiol 2002;40:1451-1458
CrossRef | Web of Science | Medline
To the Editor:
In single-site pacing, early contraction at the stimulation site when remote regions are still relaxed generates low pressure that is ineffective for ejection. Late activation of remote regions also results in inefficient ejection since the early-activated region now undergoes paradoxical stretch.1 This heterogeneous contractile pattern, which is termed dyssynchrony, reduces stroke volume, which (for a given end-diastolic volume) inevitably increases end-systolic volume and reduces the ejection fraction. The drop in ejection fraction is thus a predictable consequence of right ventricular pacing. Indeed, the absence of a drop in ejection fraction is incompatible with the concept of dyssynchrony, and the results reported by Yu et al. may simply be explained by a reduction in dyssynchrony with biventricular pacing rather than by a reduction in remodeling. I would suggest that the salient finding of this study is not the difference in mean ejection fraction between the two groups, but the 9% of the patients in the right-ventricular-pacing group and the 1% of the patients in the biventricular-pacing group who had a precipitous drop in ejection fraction. These outliers deserve further characterization, since the ratio of benefit to cost and risk of alternative pacing strategies may be greatest in this subpopulation.
Hoong Sern Lim, M.D.
University Hospital Birmingham, Birmingham, United Kingdom
hsern@doctors.net. uk No potential conflict of interest relevant to this letter was reported.
1 References1
LeClercq C ,Kass DA . Retiming the failing heart: principles and current status of cardiac resynchronization. J Am Coll Cardiol 2002;39:194-201
CrossRef | Web of Science | Medline
Author/Editor Response
We agree with McEvoy that a serial echocardiographic assessment may help to clarify the issue of the prevention of adverse cardiac remodeling with the use of biventricular pacing, and two substudies are ongoing: in one, the echocardiographic changes at 3, 6, and 9 months will be evaluated to shed additional light on the baseline and 12-month findings that we reported in our article; in the other, patients originally assigned to the right-ventricular-pacing group will be switched to a biventricular pacing mode, and serial clinical and echocardiographic assessments will be performed.
We agree with Tomoda's comment that there are alternative ways to minimize the adverse effect of right ventricular pacing on left ventricular systolic function. When our study was planned, reliable pacing algorithms to minimize ventricular pacing were not available, and programming a markedly prolonged atrioventricular delay may not be effective in preventing right ventricular pacing and may possibly lead to adverse events.1 Moreover, the potential benefit offered by right ventricular outflow tract pacing is far from conclusive, since there is no randomized trial that provides convincing evidence that such pacing has an advantage over right ventricular apical pacing. However, we do not agree that biventricular pacing should be adopted only when heart failure has occurred. In a recent observational study, cardiovascular mortality was increased by a factor of 11 among those in whom heart failure developed after conventional right ventricular apical pacing,2 suggesting that prevention may be the preferred approach unless very frequent follow-up clinical assessment is performed.
Lim has raised an interesting issue about the relation between the presence of left ventricular dyssynchrony and echocardiographic assessment of left ventricular ejection fraction and volumes. We do not agree that the findings of the 12-month comparison between the two groups were simply the result of a reduction in dyssynchrony with biventricular pacing. In the recent Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction trial (REVERSE; ClinicalTrials.gov number, NCT00271154),3 changes in left ventricular ejection fraction and volumes were observed when cardiac resynchronization therapy was turned on and off right after implantation, but such on–off effects in left ventricular volume measurements were not observed after 1 year of pacing therapy. Furthermore, left ventricular reverse remodeling was accompanied by a decrease in left ventricular mass.4 Of course, we cannot directly apply these results to the patients in our study, who did not have heart failure, but these findings may suggest that left ventricular end-systolic volume as measured by three-dimensional echocardiography systems, which was also a primary end point in our study, is a reliable measurement that reflects the remodeling effect with pacing on or off. The two substudies mentioned above may help to clarify these uncertainties.
Cheuk-Man Yu, M.D., F.R.C.P.
Joseph Y.S. Chan, F.H.K.A.M.
Jeffrey W.-H. Fung, M.D., F.R.C.P.
Chinese University of Hong Kong, Hong Kong, China
cmyu@cuhk.edu. hk Since publication of their article, the authors report no further potential conflict of interest.
4 References1
Nielsen JC ,Pedersen AK ,Mortensen PT ,Andersen HR . Programming a fixed long atrioventricular delay is not effective in preventing ventricular pacing in patients with sick sinus syndrome. Europace 1999;1:113-120
CrossRef | Web of Science | Medline2
Zhang XH ,Chen H ,Siu CW , et al. New-onset heart failure after permanent right ventricular apical pacing in patients with acquired high-grade atrioventricular block and normal left ventricular function. J Cardiovasc Electrophysiol 2008;19:136-141
CrossRef | Web of Science | Medline3
St John Sutton M ,Ghio S ,Plappert T , et al. Cardiac resynchronization induces major structural and functional reverse remodeling in patients with New York Heart Association class I/II heart failure. Circulation 2009;120:1858-1865
CrossRef | Web of Science | Medline4
Zhang Q ,Fung JW ,Auricchio A , et al. Differential change in left ventricular mass and regional wall thickness after cardiac resynchronization therapy for heart failure. Eur Heart J 2006;27:1423-1430
CrossRef | Web of Science | Medline
