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If It Is Not Broken, Don’t Fix It: Avoidance of Right VentricularPacing in Cardiac Resynchronization Therapy

DAVID H. BIRNIE, M.B., CH.B., M.D. and ANTHONY S.L. TANG, M.D.

From the University of Ottawa Heart Institute, Ottawa, Ontario, Canada

Editorial Comment

Cardiac resynchronization therapy (CRT) has been shownto reduce morbidity and mortality and lead to reverse re-modeling in heart failure (HF) patients with dyssynchrony.1,2

Recently revised guidelines promote CRT to a class I recom-mendation for patients with Class III or ambulatory Class IVHF and prolonged QRS duration.3 Over a relatively short pe-riod, there have been remarkable advances in CRT researchand technology, but much work remains. The key remainingresearch questions include how to maximize response to CRT;how to select patients for CRT; whether CRT can be helpfulin patients with narrow QRS and in patients with less severeHF; and the role of CRT in patients with atrial fibrillation.

The paper by Lee et al.4 provides data potentially relatedto the first of these issues. They performed acute invasivestudies on 17 patients with HF and a wide QRS (>120 ms)or narrow QRS with echo documented mechanical dyssyn-chrony. They measured right ventricular (RV) and left ven-tricular (LV) hemodynamics during intrinsic sinus rhythmand during temporary VDD pacing in three different modes.The first mode they termed “LV prepacing“ with the timingof LV pacing, determined by measuring the interval betweenright atrial to right ventricular activation (A-RVs). LV stimu-lation was assessed, starting at 60 ms before A-RVs and thenat each of 50/40/30/20/10 ms before A-RVs. The aim of thismode was to produce fusion between a wavefront producedby intrinsic conduction down the intact right bundle with asecond wavefront stimulated by LV pacing. Indeed, the term“fusion pacing” perhaps better describes this mode. The sec-ond pacing mode they assessed was “LV postpacing.” LVstimulation was examined at AV intervals 10/20/30/40/50/60ms longer than the A-RVs interval. Finally, they also assessedconventional biventricular pacing with simultaneous RV andLV stimulation. They tested four different AV intervals dur-ing conventional biventricular pacing and used LV hemody-namics to optimize the AV interval, but did not optimize VVintervals. It is important to note that the RV electrode wasplaced at the RV apex during all pacing modes.

The paper had three main findings. First, they found thatoptimized LV prepacing and optimized biventricular pac-ing produced similar and significant improvement in LVdP/dtmax. Furthermore, there were trends for LV prepacing toproduce greater LV hemodynamic benefit than biventricularpacing as assessed by pressure volume loops. The second im-portant finding was that optimized biventricular pacing led to

J Cardiovasc Electrophysiol, Vol. 18, pp. 505-506, May 2007.

Address for correspondence: Dr. D. Birnie, University of Ottawa Heart Insti-tute, 40 Ruskin Road, Ottawa, ON, Canada K1Y 4W7. Fax: (613) 761-4407;E-mail: dbirnie@ottawaheart.ca

doi: 10.1111/j.1540-8167.2007.00799.x

a deterioration in RV hemodynamics compared with intrinsicsinus rhythm. In contrast, optimized LV prepacing preservedRV function. For example, biventricular pacing produced a3.1 ± 7.4% fall in RVdP/dtmax compared with LV prepacing,which resulted in a 2.1±6.3% increase. Furthermore, the datafrom RV pressure volume loops suggested a greater differ-ence between the modes. With biventricular pacing, there wasa 24.2 ± 21.2% decrease in RV stroke volume, compared withLV prepacing, where there was only a 3.9 ± 10.7% decrease.The third important observation was that LV postpacing pro-duced only a modest improvement in the LV hemodynamics,about 50% of that achieved by both biventricular pacing andLV prepacing.

Van Gelder5 performed a similar study in 34 patients theday after CRT implantation. Although similar to the paper ofLee et al., there are some important differences. They used adifferent algorithm to produce fusion pacing and they did notassess RV function. They found that fusion pacing produceda higher LV dP/dtmax of 983 ± 213 versus 957 ± 174 forsimultaneous biventricular pacing and 919 ± 164 for true LVonly pacing (without evidence of fusion).

The difference in results may be related to any or all ofa greater degree of dyssynchrony in the Van Gelder paper(QRS duration of 174 ± 25 ms) compared with the Lee co-hort (QRS duration 138 ± 25 ms); the different algorithmsemployed to obtain fusion; and a type II error in the Lee paper.Regardless, the combined data from the two papers suggestthat fusion pacing seems at least as good as biventricularpacing in terms of LV hemodynamics (with the caveat that ithas not been compared with sequential biventricular pacing).Furthermore, fusion pacing preserved RV function, whereasbiventricular pacing with RV apical pacing led to deteriora-tion in RV function. Whether alternate site RV pacing wouldhave the same negative impact is unclear. Preliminary datasuggest that RV septal pacing may produce lesser RV dyssyn-chrony and better RV hemodynamics (Personal communica-tion, D Gras and S. Cazeau). RV dysfunction has been shownto be an independent predictor of poor outcome in advancedHF patients.6,7 There are few data on the effects of biventric-ular pacing on RV function. Bleeker and colleagues8 recentlyshowed evidence of RV reverse remodeling with reduction inRV size and tricuspid regurgitation. They postulated that themechanism was LV resynchronization leading to secondaryreductions in pulmonary artery pressure and subsequentlyRV size. The importance of the observation that fusion pac-ing preserves RV function requires further investigation. Inaddition, high RV pressure is an independent predictor ofpoor outcome after conventional biventricular pacing.9

The relative merits of LV pacing and biventricular pac-ing have been assessed in a number of other acute experi-ments10,11 and also chronic studies.12,13 In some studies, LVpacing has shown marginal advantages and in others, the find-ings have been essentially neutral. It seems likely that much

506 Journal of Cardiovascular Electrophysiology Vol. 18, No. 5, May 2007

of the benefit of LV pacing in these studies relates to fusion.However, additional mechanisms including a reduction in di-astolic ventricular interaction have been suggested14 and fur-thermore, in at least one study, patients with complete heartblock benefited from LV pacing.15 In many ways, fusion pac-ing can be regarded as optimized LV pacing in patents withintact right bundle conduction.

In conclusion, Lee et al.4 provide intriguing data that LVprepacing “fusion pacing” may have some hemodynamic ad-vantages over conventional biventricular pacing, in particularwith regard to RV function. In addition, fusion pacing has anumber of additional theoretical advantages over biventricu-lar pacing, including a reduction in battery drain, a potentialfor dynamic AV interval modulation, and perhaps easier de-vice optimization (only one interval to be adjusted). Thisearly data should stimulate additional work to test the theoryin chronically implanted patients with end points includingobjective functional capacity, LV function, and a full assess-ment of RV function. Their data are also consistent with whatwe have learned about the deleterious effects of RV apicalpacing in patients with conventional pacemakers.16 If addi-tional work confirms and extends Lee et al.’s findings, thenavoidance of RV apical pacing in patients with CRT may bebest if there is intact right bundle conduction. Hence, in theend the paradigm “if it is not broken, don’t fix it” may becorrect.

References

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2. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappen-berger L, Tavazzi L: The effect of cardiac resynchronization on morbid-ity and mortality in heart failure. N Engl J Med 2005;352:1539-1549.

3. Hunt SA: ACC/AHA 2005 guideline update for the diagnosis and man-agement of chronic heart failure in the adult: A report of the AmericanCollege of Cardiology/American Heart Association Task Force on Prac-tice Guidelines (Writing Committee to Update the 2001 Guidelines forthe Evaluation and Management of Heart Failure). J Am Coll Cardiol2005;46:e1-82.

4. Lee KL, Burnes JE, Mullen TJ, Hettrick DA, Tse HF, Lau CP: Avoid-ance of right ventricular pacing in cardiac resynchronization therapyimproves right ventricular hemodynamics in heart failure patients. JCardiovasc Electrophysiol 2007;18:497-504.

5. van Gelder BM, Bracke FA, Meijer A, Pijls NH: The hemodynamiceffect of intrinsic conduction during left ventricular pacing as comparedto biventricular pacing. J Am Coll Cardiol 2005;46:2305-2310.

6. Ghio S, Gavazzi A, Campana C, Inserra C, Klersy C, Sebastiani R,Arbustini E, Recusani F, Tavazzi L: Independent and additive prognos-tic value of right ventricular systolic function and pulmonary arterypressure in patients with chronic heart failure. J Am Coll Cardiol2001;37:183-188.

7. Gorcsan J III, Murali S, Counihan PJ, Mandarino WA, Kormos RL:Right ventricular performance and contractile reserve in patients withsevere heart failure. Assessment by pressure-area relations and associ-ation with outcome. Circulation 1996;94:3190-3197.

8. Bleeker GB, Schalij MJ, Nihoyannopoulos P, Steendijk P, Molhoek SG,van Erven L, Bootsma M, Holman ER, van der Wall EE, Bax JJ: Leftventricular dyssynchrony predicts right ventricular remodeling after car-diac resynchronization therapy. J Am Coll Cardiol 2005;46:2264-2269.

9. Tedrow UB, Kramer DB, Stevenson LW, Stevenson WG, BaughmanKL, Epstein LM, Lewis EF: Relation of right ventricular peak systolicpressure to major adverse events in patients undergoing cardiac resyn-chronization therapy. Am J Cardiol 2006;97:1737-1740.

10. Blanc JJ, Etienne Y, Gilard M, Mansourati J, Munier S, Boschat J,Benditt DG, Lurie KG: Evaluation of different ventricular pacing sitesin patients with severe heart failure: results of an acute hemodynamicstudy. Circulation 1997;96:3273-3277.

11. Kass DA, Chen CH, Curry C, Talbot M, Berger R, Fetics B, Nevo E:Improved left ventricular mechanics from acute VDD pacing in pa-tients with dilated cardiomyopathy and ventricular conduction delay.Circulation 1999;99:1567-1573.

12. Blanc JJ, Bertault-Valls V, Fatemi M, Gilard M, Pennec PY, EtienneY: Midterm benefits of left univentricular pacing in patients with con-gestive heart failure. Circulation 2004;109:1741-1744.

13. Gasparini M, Bocchiardo M, Lunati M, Ravazzi PA, Santini M, ZardiniM, Signorelli S, Passardi M, Klersy C: Comparison of 1-year effectsof left ventricular and biventricular pacing in patients with heart failurewho have ventricular arrhythmias and left bundle-branch block: The Bivs Left Ventricular Pacing: An International Pilot Evaluation on HeartFailure Patients with Ventricular Arrhythmias (BELIEVE) multicenterprospective randomized pilot study. Am Heart J 2006;152:155-157.

14. Bleasdale RA, Turner MS, Mumford CE, Steendijk P, Paul V, Ty-berg JV, Morris-Thurgood JA, Frenneaux MP: Left ventricular pac-ing minimizes diastolic ventricular interaction, allowing improvedpreload-dependent systolic performance. Circulation 2004;110:2395-2400.

15. Hay I, Melenovsky V, Fetics BJ, Judge DP, Kramer A, Spinelli J,Reister C, Kass DA, Berger RD: Short-term effects of right-left heartsequential cardiac resynchronization in patients with heart failure,chronic atrial fibrillation, and atrioventricular nodal block. Circulation2004;110:3404-3410.

16. Sweeney MO, Hellkamp AS, Ellenbogen KA, Greenspon AJ, Freed-man RA, Lee KL, Lamas GA: Adverse effect of ventricular pacing onheart failure and atrial fibrillation among patients with normal baselineQRS duration in a clinical trial of pacemaker therapy for sinus nodedysfunction. Circulation 2003;107:2932-2937.