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opinions and hypotheses
Biventricular Cardiac Pacing*
Promising New Therapy for Congestive Heart
Failure
S. Serge Barold, MD
(CHEST 2000; 118:1819 –1821)
Abbreviations: CHF ⫽ congestive heart failure; LV ⫽ left
ventricle; NYHA ⫽ New York Heart Association; RV ⫽ right
ventricle
ual-site or multisite ventricular pacing has reD cently
emerged as a possible new modality for
1
the treatment of patients with dilated cardiomyopathy and congestive heart failure (CHF) associated
with major intraventricular and interventricular conduction disorders. Multisite ventricular pacing or
resynchronization reduces the degree of electromechanical asynchrony by altering the pathways of
spontaneous depolarization. Modified activation is
translated into potentially beneficial long-term hemodynamic1,2 and antiarrhythmic effects.3,4
In 1994, Cazeau et al5 from France reported the
remarkable benefit of biventricular pacing in a patient with drug-refractory CHF, dilated cardiomyopathy, and left bundle-branch block (QRS ⫽ 200 ms).
The left ventricle (LV) and right ventricle (RV) were
paced simultaneously to achieve a more physiologic
depolarization sequence. Cazeau et al5 demonstrated
in a preoperative study that the benefit of biventricular pacing was in part due to improved atrioventricular synchrony and in part to ventricular resynchronization. Follow-up observations showed a sustained
improvement that depended on correct function of
the LV lead. Since this report, a substantial number
of short-term studies have shown that biventricular
pacing improves hemodynamics in CHF patients
with severe left ventricular systolic dysfunction and
major left-sided intraventricular conduction disorders.6 –10 A longer spontaneous QRS complex may be
predictive of a greater positive response to pacing.9,11
In some patients, single-site pacing from the LV
provides better hemodynamics than simultaneous
biventricular pacing.6,9
*From the Electrophysiology Institute, Broward General Hospital, Ft. Lauderdale, FL.
Correspondence to: S. Serge Barold, MD, 6237 NW 21st Court,
Boca Raton, FL 33496; e-mail: [email protected]
Intraventricular and interventricular conduction
delays cause an inefficient dyssynchronous pattern of
left ventricular activation with segments contracting
at different times. Consequently, there is a shorter
diastole and/or overlapping systole/diastole and aggravation of functional mitral regurgitation. The rationale
of biventricular pacing is to improve the sequence of
electrical activation (resynchronization) and create a
more coordinated and efficient left ventricular contraction.5,12–14 Resynchronization may also reduce functional mitral regurgitation.15 Patients with chronic atrial
fibrillation may also benefit.16 –18 In this instance, continual biventricular pacing often requires radiofrequency ablation of the AV junction to ensure control of
ventricular depolarization by the pacemaker.19 Only 20
to 30% of class III or class IV CHF patients have
conduction disorders (QRS ⬎ 140 ms) that make them
potential candidates for long-term biventricular pacing.19,20 More refined and sensitive markers of left
ventricular dyssynchrony than the simple ECG need to
be investigated to extend the benefit of biventricular
pacing to other CHF patients in the absence of an
obvious left-sided intraventricular conduction disorder
or even in the presence of right bundle-branch block.
Presentations on biventricular pacing for the treatment of CHF dominated the 21st annual meeting of
the North American Society of Pacing and Electrophysiology in Washington, DC, in May 2000, where the
preliminary results of the first randomized trial of this
therapy were reported.21 The Multisite Stimulation in
Cardiomyopathy Trial is a randomized crossover singleblind study of biventricular pacing in CHF patients
with stable sinus rhythm and a major intraventricular
conduction disorder. Biventricular pacing was activated
for 3 months and turned off for 3 months. The study,
involving 63 patients (left ventricular ejection fraction,
22 ⫾ 8%), revealed statistically significant improvements in the 6-min walking distance, New York Heart
Association (NYHA) class, and quality-of-life score, and
a reduction in hospitalizations.22 Observational longterm results of biventricular pacing in patients with
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dilated cardiomyopathy and CHF, either idiopathic or
due
to coronary artery disease, are also encouraging.1,2,12,19,23–27 A major ongoing prospective, nonrandomized, multicenter study of ventricular resynchronization2 is being conducted in patients with NYHA class
III/IV drug-refractory CHF, left ventricular dysfunction (left ventricular ejection fraction ⱕ 35%), left
ventricular end-diastolic diameter ⱖ 60 mm, and a
ventricular conduction delay QRS ⱖ 150 ms. A long
PR interval is not a prerequisite. The 12-month results
in survivors of an initial group of 103 patients suggest
that the benefits of ventricular resynchronization are
sustained through 12 months with a statistically significant reduction of the NYHA class, and improvement
in the 6-min hall walk distance and the quality-of-life
score. A French pilot study1 of biventricular pacing
initiated between March 1995 and December 1997
included 53 patients (68% in class IV NYHA) with
severe drug-refractory CHF (mean left ventricular
ejection fraction, 19.8% ⫾ 6.6; coronary artery disease
in 57%; mean QRS duration, 191 ⫾ 36 ms; and permanent atrial fibrillation in 42%). During a mean
follow-up period of 15.7 ⫾ 10.8 months, the mean
NYHA class decreased from 3.7 ⫾ 0.5 at the time of
implantation to 2.3 ⫾ 0.5 at 1 month (p ⬍ 0.001) and
remained stable (2.5 ⫾ 0.70) until the end of the
follow-up period.
The high and early mortality rate after biventricular pacing seems to reflect primarily the severity of
heart disease rather than the deleterious long-term
effect of pacing because this modality has been tried
largely in very sick CHF patients refractory to drug
therapy. Consequently, there may be a role for a
combined biventricular pacemaker and defibrillator
because sudden cardiac death accounts for 30 to
50% of the deaths in class IV patients.3,4,19,28 –31
Longer follow-up and other controlled studies will
be required to determine the role and safety of biventricular pacing in the treatment of CHF and its impact
on survival. Meaningful comparison of results will
require standardization of patient groups, drug therapy,
and the different noninvasive and invasive follow-up
procedures presently used by investigators. At this
time, long-term biventricular pacing is still considered
investigational in the United States.
So far, biventricular pacing has been accomplished
with somewhat modified conventional hardware.19,32
The critical left ventricular pacing site for optimal
hemodynamics varies from patient to patient.33–34 The
apex may not necessarily be the best site in the RV.
Significant shortening of the QRS complex by biventricular pacing may be a marker of a favorable longterm clinical response.25 The LV is often paced from
one of the tributaries of the coronary veins over the
epicardial surface of the LV.32,35 After a learning curve,
access can be achieved in up to 90% and is limited by
variability in venous anatomy.2,36 Left ventricular pacing can also be done with a limited thoracotomy, a
procedure generally considered undesirable in highrisk patients. A few patients have received two pacemakers synchronized to fire simultaneously in each
ventricle.37 The placement of permanent endocardial
LV leads by transseptal puncture is feasible, but it is
highly investigational because of the risk of catastrophic
embolic complications, even with anticoagulants.38 – 40
Multisite or left ventricular pacing is a promising
new therapeutic modality with great potential because of the very large and growing number of
patients with CHF. The ultimate success of the
ambitious efforts to resynchronize cardiac activity in
CHF will depend on defining its real benefit in a
variety of circumstances by rigorous scientific evaluation and the development of new technology or
further refinement of existing technology.41 For example, adjusted RV-LV stimulation delay—rather
than simultaneous activation—may enhance the hemodynamic response.42 Based on short-term data, it
is possible that in some patients, long-term singlesite left ventricular pacing may be hemodynamically
superior to biventricular pacing, probably because
right ventricular pacing may activate a substantial
portion of the LV, thereby interfering with the
resynchronization process provided by left ventricular pacing alone. This would have an enormous
impact on the methodology of pacing.
References
1 Leclercq C, Cazeau S, Alonso C, et al. Multisite biventricular
pacing in advanced heart failure: current status of the French
Pilot Study [abstract]. Pacing Clin Electrophysiol 1999; 22:
733
2 Gras D, Ritter P, Lazarus A, et al. Long-term outcome of
advanced heart failure patients with cardiac resynchronization
therapy [abstract]. Pacing Clin Electrophysiol 2000; 23:658
3 Daubert JC, Mabo P, Gras D, et al. Dual-site ventricular
pacing for prevention of ventricular tachycardia in patients
with intraventricular conduction block [abstract]. Eur J Cardiac Pacing Electrophysiol 1996; 6:134
4 Ramaswamy K, Zagrodsky JD, Page RL, et al. Biventricular
pacing decreases the inducibility of sustained monomorphic
ventricular tachycardia [abstract]. Pacing Clin Electrophysiol
2000; 23:748
5 Cazeau S, Ritter P, Bakdach S, et al. Four chamber pacing in
dilated cardiomyopathy. Pacing Clin Electrophysiol 1994;
17:1974 –1979
6 Blanc JJ, Etienne Y, Gilard M, et al. Evaluation of different
ventricular pacing sites in patients with severe heart failure:
results of an acute hemodynamic study. Circulation 1997;
96:3273–3277
7 Auricchio A, Stellbrink C, Block M, et al. Effect of pacing
chamber and atrioventricular delay on acute systolic function
of paced patients with congestive heart failure: the Pacing
Therapies for Congestive Heart Failure Study Group. The
Guidant Congestive Heart Failure Research Group. Circulation 1999; 99:2993–3001
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Editorials
8 Leclercq C, Cazeau S, Le Breton H, et al. Acute hemodynamic effects of biventricular pacing in patients with endstage heart failure. J Am Coll Cardiol 1998; 32:1825–1831
9 Kass DA, Chen HC, Curry C, et al. Improved left ventricular
mechanics from acute VDD pacing in patients with dilated
cardiomyopathy and ventricular conduction delay. Circulation
1999; 99:1567–1573
10 Saxon LA, Kerwin WF, Cahalan MK, et al. Acute effects of
intraoperative multisite ventricular pacing on left ventricular
function and activation/contraction sequence in patients with
depressed ventricular function. J Cardiovasc Electrophysiol
1998; 9:13–27
11 Kadhiresan V, Vogt J, Auricchio A, et al. Sensitivity and
specificity of QRS duration to predict acute benefit in heart
failure patients with cardiac resynchronization [abstract].
Pacing Clin Electrophysiol 2000; 23:555
12 Kerwin WF, Botnivick EH, O’Connell JW, et al. Ventricular
contraction abnormalities in dilated cardiomyopathy: effect of
biventricular pacing to correct interventricular dyssynchrony.
J Am Coll Cardiol 2000; 35:1221–1227
13 Varma C, Callaghan PO, New C, et al. Does acute multisite
pacing for heart failure improve ventricular coordination
[abstract]? Circulation 1999; 100(suppl I):I-514
14 Liu l, Tockman B, Belalcazar A, et al. Heart failure therapies
improve left ventricular electromechanical coordination in a
canine model of left bundle branch block [abstract]. Circulation 1999; 100(suppl I):I-122
15 Etienne Y, Valls-Bertault V, Mansourati J, et al. Permanent
left ventricular-based pacing improves mitral regurgitation in
patients with severe congestive heart failure [abstract]. Pacing
Clin Electrophysiol 2000; 23:596
16 Etienne Y, Mansourati J, Gilard M, et al. Evaluation of left
ventricular based pacing in patients with congestive heart failure
and atrial fibrillation. Am J Cardiol 1999; 83:1138 –1140
17 Leclercq C, Alonso C, Victor F, et al. Long-term results of
permanent biventricular pacing in patients with advanced
heart failure: comparison of patients with stable sinus rhythm
and chronic atrial fibrillation [abstract]. Pacing Clin Electrophysiol 2000; 23:635
18 Leclercq C, Victor F, Alonso C, et al. Comparative effects of
permanent biventricular pacing for refractory heart failure in
patients with stable sinus rhythm or chronic atrial fibrillation.
Am J Cardiol 2000; 85:1154 –1156
19 Daubert JC, Leclercq C, Alonso C, et al. Long-term experience with biventricular pacing in refractory heart failure. In:
Ovsyshcher IE, ed. Cardiac arrhythmias and device therapy:
results and perspectives for the new century, Armonk, NY:
Futura, 2000; 385–392
20 Saxon LA, Boehmer JP, Hummel J, et al. Biventricular pacing
in patients with congestive heart failure: two prospective
randomized trials. Am J Cardiol 1999; 83:120D–123D
21 Abstracts for the 21st annual meeting the North American
Society of Pacing and Electrophysiology, Washington DC.
Pacing Clin Electrophysiol 2000; 23:553– 801
22 Daubert C. Preliminary results of the MUSTIC trial of
biventricular pacing for congestive heart failure. Presented at:
21st annual meeting of the North American Society of Pacing
and Electrophysiology; May 2000; Washington, DC
23 Leclercq C, Alonso C, Mabo P, et al. Comparison of the
effects of cardiac resynchronization in patients with advanced
heart failure of either ischemic or non-ischemic origin [abstract]. Pacing Clin Electrophysiol 2000; 23:659
24 Bakker PF, Meijburg H, De Jonge N, et al. Beneficial effects
of biventricular pacing in congestive heart failure [abstract].
Pacing Clin Electrophysiol 1994; 17:820
25 Alonso C, Leclercq C, Victor F, et al. Electrocardiographic
predictive factors of long-term clinical improvement with
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
multisite biventricular pacing in advanced heart failure. Am J
Cardiol 1999; 84:1417–1421
Tang ASL, Green M, Gras D, et al. Cardiac resynchronization:
multicenter implant experience with atrio-biventricular pacing
[abstract]. Pacing Clin Electrophysiol 1999; 22:701
Sack S, Auricchio A, Kadhiresan V, et al. Long-term improvement with ventricular resynchronization therapy in heart
failure patients: does etiology of heart failure matter [abstract]? Pacing Clin Electrophysiol 2000; 23:555
Walker S, Levy T, Rex S, et al. Preliminary results with the
simultaneous use of implantable cardioverter defibrillators
and permanent biventricular pacemakers: implications for
device interaction and development. Pacing Clin Electrophysiol 2000; 23:365–372
Higgins S, Yong P, Scheck D, et al, for the Ventak CHF
Investigators. Biventricular pacing may diminish ICD shocks
[abstract]. Pacing Clin Electrophysiol 1999; 22:848
Stellbrink C, Auricchio A, Diem B, et al. Potential benefit of
biventricular pacing in patients with congestive heart failure
and ventricular tachyarrhythmia. Am J Cardiol 1999; 83:
143D–150D
Leclercq C, Alonso C, Pavin D, et al. Mortality in patients
treated with permanent biventricular pacing for advanced
heart failure: a 5 year single center experience [abstract].
Pacing Clin Electrophysiol 2000; 23:610
Daubert JC, Leclercq C, Pavin D, et al. Pacing therapy in
congestive heart failure: present status and new perspectives. In:
Barold SS, Mugica J, eds. Recent advances in cardiac pacing:
goals for the 21st century. Armonk, NY: Futura, 1998; 51– 80
Gras D, Mabo P, Bucknall C, et al. Does lead placement
affect outcome of cardiac resynchronization in heart failure
patients? Results from the InSync trial [abstract]. Pacing Clin
Electrophysiol 2000; 23:580
Auricchio A, Butter C, Stellbrink C, et al. Effect of left
ventricular stimulation site on the systolic function of heart
failure patients during ventricular resynchronization therapy
[abstract]. Pacing Clin Electrophysiol 2000; 23:589
Daubert JC, Ritter P, Le Breton H, et al. Permanent left
ventricular pacing with transvenous leads inserted into the
coronary veins. Pacing Clin Electrophysiol 1998; 21:239 –245
Ritter P, Gras D, Daubert C, on behalf of the MUSTIC
Group. Implant success rate of the transvenous left ventricular lead in the MUSTIC trial [abstract]. Pacing Clin Electrophysiol 2000; 23:580
Auricchio A, Stellbrink C, Sack S, et al. The Pacing Therapies
for Congestive Heart Failure (PATH-CHF) Study: rationale,
design, and endpoints of a prospective randomized multicenter study. Am J Cardiol 1999; 83:130D–135D
Jaı̈s P, Douard H, Shah D, et al. Endocardial biventricular
pacing. Pacing Clin Electrophysiol 1998; 21:2128 –2131
Leclercq F, Hager FX, Marcia JC, et al. Left ventricular lead
insertion using a modified transseptal catheterization technique: a totally endocardial approach for permanent biventricular pacing in end-stage heart failure. Pacing Clin Electrophysiol 1999; 22:1570 –1575
Leclercq F, Kassnasrallah S, Macia JC, et al. Transcranial
Doppler detection of microemboli during endocardial biventricular pacing in end-stage heart failure [abstract]. J Am Coll
Cardiol 2000; 35(suppl A):141A
Walker S, Levy TM, Coats AJ, et al. Biventricular pacing in
congestive cardiac failure: current experience and future
directions. The Imperial College Cardiac Electrophysiology
Group. Eur Heart J 2000; 21:884 – 889
Butter C, Auricchio A, Stellbrink C, et al. Non-simultaneous
biventricular stimulation: a new paradigm of ventricular
resynchronization therapy for heart failure patients [abstract].
Pacing Clin Electrophysiol 2000; 23:589
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