Yves Etienne, MD, Marjaneh Fatemi, MD, Jean-Jacques Blanc, MD.,
From Cardiology department, Brest University Hospital, France.
Address for
correspondence: Pr J-J Blanc, Département de cardiologie,
CHU Cavale Blanche, Bd Tanguy Prigent, 29609 Brest Cedex , France.
E-mail: jean-jacques.blanc@chu-brest.fr
Abstract
Cardiac
resynchronisation therapy (CRT) using biventricular (BIV) pacing has
proved its effectiveness to correct myocardial asynchrony and improve
clinical status of patients with severe congestive heart failure (CHF)
and widened QRS. Despite a different effect on left ventricular
electrical dispersion, left univentricular (LV) pacing is able to
achieve the same mechanical synchronisation as BIV pacing in
experimental studies and in humans. This results in clinical benefits
of LV pacing at mid-term follow-up, with significant improvement in
functional class, quality of life and exercise tolerance at the same
extent as those observed with BIV stimulation in non randomised
studies. Furthermore these benefits are obtained at lesser costs and
with conventional dual-chamber devices. However, LV pacing has to be
compared to BIV pacing in randomised trials before being definitely
considered as a cost-effective alternative to BIV pacing.
Keywords: cardiac resynchronisation, left ventricular
pacing, heart failure
Introduction
Despite
advances in drug treatment, congestive heart failure (CHF) remains a
major health care problem associated with a poor quality of life and a
high mortality rate. During the past decade, cardiac resynchronisation
therapy (CRT) using biventricular (BIV) pacing emerged as a promising
technique improving quality of life, exercise tolerance and mortality
1-3, and is now an
admitted therapy in a selected population of patients with widened QRS
and severe CHF despite optimal pharmacological therapy
4,5. It has been well
documented that intraventricular conduction disturbances, namely left
bundle branch block, induce left ventricular (LV) activation
delay leading to discoordinated myocardial contraction and,
consecutively, to deleterious effects on myocardial systolic function,
diastolic filling time and mitral regurgitation
6.
Finally this dyssynchronised LV function exaggerates clinical symptoms
of CHF. The rationale for CRT is based upon the hypothesis that, by
correcting inter and intra-ventricular asynchrony, BIV pacing improves
LV function and favourably affects clinical condition and prognosis of
patients with severe CHF and prolonged QRS. However it has never been
demonstrated that electrical resynchronisation induced by BIV
pacing is a sine qua non condition to achieve better mechanical
coordination as, in experimental data, and despite electrical
dispersion, LV pacing does as well as BIV pacing on mechanical
synchronisation with similar hemodynamic benefit
7.
Many other
arguments support the concept that LV univentricular pacing by
reversing intraventricular dysynchrony is sufficient in humans to
improve LV function and clinical status at the same extent and at a
lower cost-effective ratio than BIV pacing and this is in accordance
with the fact that intraventricular asynchrony seems more relevant that
interventricular asynchrony to predict prognosis in patients with
dilated cardiomyopathy
8.
Hemodynamic effects of pacing
The first
clinical series with CRT were performed empirically using BIV pacing
9. However, since this period , several
studies in humans have reported similar hemodynamic benefit using
either LV or BIV pacing during acute studies, showing a decrease in
pulmonary pressures, an increase in cardiac outpout, systemic blood
pressure, and dP/dt when compared to baseline or to right ventricular
pacing in patients with severe CHF and intraventricular
conduction delays
10-12.
Some authors reported that LV stimulation had even a greater effect on
LV dP/dt than BIV
11,12.
This hemodynamic benefit was independent of atrio-ventricular
conduction as the same effects were observed in patients in sinus
rhythm or atrial fibrillation
13.
Furthermore, improvement in myocardial contractility induced by LV
pacing was obtained with the same extent of reduced energetic cost for
the myocardium than with BIV pacing
14.
Finally, a similar reduction in mitral regurgitation was observed by
echocardiography using the two pacing modes with a significant decrease
by 30 to 50 % in mitral jet area or mitral regurgitant orifice area in
non-randomised studies
15-17,
despite less striking effects upon LV reverse remodeling during LV
versus BIV pacing in some studies
15-17.
Clinical benefits
Whether or not
these hemodynamic benefits result in sustained improvement of clinical
status during permanent LV stimulation has not been extensively
investigated until now. However, some studies reported significant
improvement in both exercise tolerance and quality of life at
mid-term follow-up during chronic LV pacing
18,19 or failed to
demonstrate any superiority of BIV pacing over LV pacing on
clinical data
17,20.
Aurricchio et al compared 3 months of active LV pacing to 3 months of
inactive pacing in 86 patients with severe CHF and wide QRS duration.
They observed a significant increase in peak V0
2 (2.46
ml/mn/kg), in 6
minute walk distance (47 m) and a decrease in quality of life score
(8.1) during the active pacing period in the group of patients with the
longest QRS duration (above 150 ms)
18.
In another study comparing 2 active periods (4 weeks each) of uniLV and
BIV pacing to baseline in a cross-over design, the same authors
reported similar improvement in functional class, quality of life
score, and exercise tolerance in the 2 pacing modes
20. Our personal
studies lead to the same conclusions: by comparing to baseline, we
found after 12 months of LV pacing in 22 patients with severe CHF,
sinus rhythm and left bundle branch block a significant improvement in
NYHA functional class by 40%, exercise tolerance (6 minute walk
distance by 30 % and peak V0
2 by 26 %) and norepinephrine
level by 37%
19. Again and
in agreement with the previous studies, a similar improvement in
functional class and exercise performance was found in 2 groups of
patients (BIV: 12 pts – LV: 14 pts) after 6 months follow-up in a
non-randomised study, although, as expected, a significant decrease in
QRS duration (-19 ms) was showed only in the BIV pacing group
17.
LV pacing and ventricular
asynchrony
Are these
clinical effects correlated with improvement in myocardial synchrony?
This is an important issue on a physiopathological point of view and
for the selection of candidates for LV pacing. In an interesting
experimental study using a canine model of cardiac failure and left
bundle branch block, Leclercq et al examined mechanical and electrical
synchrony during right atrial, LV and BIV stimulation; as expected,
electrical dispersion decreased during BIV pacing whereas it increased
during LV pacing; however, despite this opposite action upon electrical
phenomena, the same improvement in mechanical coordination within the
LV, measured by tagged magnetic resonance imaging, was observed with LV
and BIV pacing, and this was correlated with improvement in
hemodynamics (25 % increase in dP/dt and aortic pulse pressure)
7. Similarly, in humans, LV dyssynchrony
measured either by echocardiographic phase analysis, echo-contrast, or
tissue Doppler imaging was improved significantly and almost at the
same extent during LV and BIV pacing
16,21,22. The decrease in
the septal to lateral contraction delay during LV pacing was
particularly correlated with an increase in LV ejection fraction or
dP/dt
21,22.
Cost effectiveness
By
comparison to BIV pacing, LV pacing offers several technical and
economical advantages : 1) if insertion of a third lead (the right
ventricular one) is not the most difficult part of the operative
procedure, it could prolong significantly its duration and the X-ray
exposure; 2) the presence of 3 leads instead of 2 induces
certainly more adverse events and increases the risk of venous
thrombosis or mechanical complications; 3) more importantly, uniLV
pacing needs only a less complex to program and less often subject to
dysfunction conventional dual-chamber pacemaker. Finally, BIV
pacing is more expensive than LV pacing as it implies implantation of a
supplementary right ventricular lead and of a specific and more costly
device: in Europe, the extra cost could be approximately evaluated at
30 % and this must be taken in account in the context of the growing
“epidemic” of heart failure consecutive to demographic ageing and
of the control of medical expenses in many countries.
So, at this
time, there are no arguments in favour of the hypothesis that, for
patients with severe CHF and enlarged QRS duration, BIV pacing would be
significantly more effective than LV pacing in terms of mechanical
coordination, hemodynamic and clinical benefits. However, our knowledge
about the effects of LV pacing still suffers some limitations: the
present studies are only observational and non-randomised. Furthermore,
it seems, as shown during acute hemodynamic studies, that in some
patients LV pacing would not be as effective as BIV pacing (but the
opposite is true also... ), and this could perhaps be the case in
patients with a dysfunctional right venricle but no study have focused
on this topic at this time. Finally and unlike BIV pacing
3,23, no study have
examined the effects of LV pacing on mortality and morbidity, and
whether or not LV pacing improves mortality in severe CHF remains to be
demonstrated. However, the ongoing trials comparing LV to BIV pacing
are not designed to show that one of these pacing modalities is better
than the other but just equivalent..... an argument to think that they
are really similar.
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