Left ventricular remodelling and haemodynamic effects of multisite biventricular pacing in patients with left ventricular systolic dysfunction and activation disturbances in sinus rhythm: sub-study of the MUSTIC (Multisite Stimulationin Cardiomyopathies) trial
A. Duncana,*,
D. Waita,
D. Gibsona and
J.-C. Daubertb
a The Echocardiography Department, The Royal Brompton Hospital, Sydney Street,London SW3 6NP, UK
b Centre Cardio-Pneumologique, CHU, Rennes, France
Received May 31, 2002;
revised July 9, 2002;
accepted July 10, 2002
* Corresponding author. Tel.: +44-207-351-8209; fax: +44-207-351-8604
E-mail address: a.duncan{at}ic.ac.uk
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Abstract
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Aims To use echocardiography to determine early and late haemodynamic effects of atrio-biventricular (A-BiV) pacing on left ventricular (LV) function and their interrelations with exercise tolerance.
Methods Thirty-four patients with ejection fraction <35% (18 idiopathic dilated cardiomyopathy (DCM) and 16 ischaemic cardiomyopathy, in sinus rhythm and with intra-ventricular conduction delay (IVCD)) were implanted with transvenous A-BiV pacemakers. Echocardiographic measurements were compared before implantation, after 3 months A-BiV pacing, and 3 months inactive pacing (ventricular inhibited pacing at 40beatsmin1as part of a crossover design, and at 9- and 12-month longitudinal follow-up.
Results Total isovolumic time (IVT) halved after 3 months A-BiV pacing (from 20.1±4.4 to 10.7±4.9smin1,
) and did not change thereafter. LV cavity size fell after 3 months (end-diastolic dimension (EDD) 7.3±0.8 to 6.8±0.8cm,
, and end-systolic dimension (ESD) 6.2±0.8 to 5.9±0.8cm,
), with a further fall in EDD and ESD (by 8.4±7.8 and 8.8±7.8mm, respectively, both
) after 12 months. Although not a primary end-point of the study, the 12-month reduction in LVEDD and LVESD was greater in idiopathic DCM (by 8.9 and 9.8mm,
, respectively) compared with ischaemic cardiomyopathy. The 6-min walk rose by 15% (
) and peak VO2by 10%
after 3 months, with no further increase by 12 months, and no difference between idiopathic DCM and ischaemic cardiomyopathy. The increase in peak VO2at 12 months correlated with the fall in ESD (
,
).
Conclusions A-BiV pacing shortens total IVT, reduces LV cavity size, and increases exercise tolerance in patients with DCM and IVCD. Ischaemic cardiomyopathy does not affect the exercise response, although it does reduce the extent of reverse remodelling.
Key Words: Atrio-biventricular Pacing Dilated cardiomyopathy Intra-ventricular conduction delay Total isovolumic time Ventricular asynchrony
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1. Introduction
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Intra-ventricular conduction delay (IVCD) is common in patients with severe heart failure13 and causes left ventricular (LV) asynchrony. Septal minor and long axis contraction are delayed,4,5 time to maximum rate of rise of ventricular pressure is prolonged, and the duration of mitral regurgitation6 and isovolumic periods are increased, so that diastolic filling time at rest is reduced.7,8 These effects become more marked during dobutamine stress.9 Biventricular pacing has been proposed as a means of altering the electrical activation sequence in patients with heart failure and IVCD, with the aim of restoring synchronous LV contraction.
Short-term studies using atrio-biventricular (A-BiV) pacing in patients with severe congestive heart failure and IVCD report haemodynamic improvement by altering the ventricular activation sequence,1017 and recent results from the MUSTIC trial18 suggest A-BiV pacing significantly improves exercise tolerance and quality of life in such patients. However, the mechanisms by which A-BiV pacing improves mechanical LV function and exercise tolerance in the medium term are complex and not well understood. We therefore used echocardiography to correlate the haemodynamic effects of A-BiV pacing with changes in cavity size and exercise tolerance up to 12 months after the onset of pacing in a sub-study of patients participating in the MUSTIC study.
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2. Material and methods
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2.1. Study design
The MUSTIC trial18 is a single-blind, randomized, controlled, crossover study, with patients recruited from 15 European centres. Inclusion began in March 1998 and lasted 12 months. Pacemaker implantation was performed after a 1-month observation period to verify clinical stability. Once satisfactory A-BiV performance had been confirmed, the pacing system was programmed inactive (ventricular inhibited pacing at 40beatsmin1basic rate). Baseline observations were made at this stage. Two weeks after implantation, patients were randomized to receive either active A-BiV pacing for 3 months followed by a 3-month period during which the pacemaker was inactive, or a 3-month run-in period with the pacemaker inactive followed by a 3 months active A-BiV pacing. Treatment order was decided according to a randomized block design, stratified per investigation centre. In order to determine the effects of 3 months active A-BiV pacing, patients in active mode during the first arm of the crossover were combined with patients in active mode during the second arm of the crossover. The single-blind crossover phase (active vs inactive) was followed by a longitudinal period during which the pacing system was programmed according to the patient's preferred study period during the crossover phase. Patients were restudied 3 and 6 months after completion of the crossover phase (i.e. at 9 and 12 months following randomization). The Ethics Committee in participating centres approved the study protocol, and all patients gave their written informed consent before inclusion.
2.2. Patient selection and pacemaker implantation
Sixty-seven patients were recruited into the study. Entry criteria included an ejection fraction less than 35%, an end-diastolic diameter greater than 60mm, and QRS duration greater than 150ms. All were in sinus rhythm and had been stable in NYHA Class III under optimized treatment for at least 1 month before inclusion. Exclusion criteria and pacemaker implantation technique have been reported previously.18,19
2.3. Echocardiographic evaluation
Transthoracic echocardiography was performed at baseline and at 3, 6, 9, and 12 months thereafter. Using the left parasternal long axis view, a cross-sectional 2D-guided M-mode of the LV minor axis was obtained with the cursor at the tips of the mitral valve leaflets, and a 2D image of the LV outflow tract diameter was also recorded. Using pulsed-Doppler, transmitral and transaortic flow velocities were obtained from the apical four- and five-chamber views, respectively, with the sample volume at the tips of the valve leaflets. Mitral regurgitation was recorded using colour flow in both the apical four- and two-chamber views.20 Recordings were obtained at a sweep speed of 50100mms1with an ECG superimposed, stored on videotape, and analysed at the core centre (Royal Brompton Hospital, UK). Two independent observers performed final videotape analysis off-line, after manual recalibration on an Agilent Sonos 5500 ultrasound scanner.
2.4. Measurements
2.4.1. Echocardiogram
LV end-diastolic and end-systolic dimensions (EDD and ESD) were measured from M-mode recordings using leading edge methodology according to ASE criteria.21 LV ejection time and aortic velocity time integral (VTI) were determined from the aortic pulsed Doppler trace. Ejection time was measured as the interval between the onset of forward aortic flow to the onset of the aortic closure artefact. Early (E) and late (A) mitral flow velocities were determined from the mitral Doppler trace with respect to baseline. LV filling time was measured from the onset of the transmitral E wave to the end of the A wave (Fig. 1). Total isovolumic time (IVT; the total period, expressed in seconds per minute, when the heart is neither ejecting or filling) is characteristically prolonged at rest in patients with IVCD.7 Total IVT, in seconds per minute, was thus calculated as 60(total ejection time+total filling time), (where total ejection and filling times were derived as the product of the corresponding time interval and heart rate, also expressed in seconds per minute). In addition, the Z ratio was calculated as the percentage of the cardiac cycle spent either ejecting or filling ((ejection time+filling time)/RR interval).8 Mitral regurgitation within the left atrium was measured in the apical four- and two-chamber colour displays, and the average jet area was expressed in cm2.

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Fig. 1 Superimposed aortic and mitral Doppler recordings from a patient with IVCD. Ejection time (ET) was measured as the interval between the onset and end of forward aortic flow and filling time (FT) from the onset of the transmitral E wave to the end of the A wave. The two components of total IVT are shaded. In IVCD, IVT may occupy up to one-third of the total cardiac cycle. ECG=electrocardiogram; PCG=phonocardiogram.
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2.4.2. ECG and exercise tolerance (other core centres)
At baseline, 3, 6, 9, and 12 months, echo results were correlated with previously determined values of QRS duration from a 12-lead surface ECG, 6-min walked distance, and NYHA classification. Values were also available for cardio-pulmonary exercise testing at baseline, 3, 6, and 12 months. These results, for the whole group of patients, have been reported in full elsewhere.18
2.5. Statistical analysis
Power calculations for the MUSTIC study have been previously reported,18 and these included an estimated 20% increase in filling time with active pacing. Based on previous reports which suggested a 40% (80ms) increase in filling time with right ventricular (DDD) pacing in patients with dilated cardiomyopathy (DCM) and left bundle branch block,8 and a standard deviation of the difference in filling time of 60ms measured on two separate occasions under the same circumstances, the number of patients required to have 80% power to detect a statistically significant difference in filling time at the 5% level would be 26. In the event, we studied a 34 patient sample.
Results are expressed as mean±standard deviation. Analyses were based on the intention-to-treat principle. However, serial echocardiographic results were assessed only in patients who had echocardiography at baseline and both crossover and follow-up phases. A paired Student's t-test was used to compare between baseline and subsequent pacing stages, and the P-value significance threshold was taken as
. Correlation was performed by linear regression analysis. An analysis of variance (ANOVA), which considered all the patients as a single group, was used to identify the individual contributions of ischaemic cardiomyopathy and idiopathic DCM to changes in haemodynamic parameters after A-BiV pacing.
2.6. Reversibility, carry-over effects, and reproducibility
The reversibility of pacing and the possibility of a carry-over effect were investigated in the patients initially assigned to active pacing. The former was assessed by comparing 3 months active followed by 3 months inactive pacing, and the latter by comparing 6-month values with baseline. Long-term reproducibility was determined by comparison of baseline values with those at 3 months in patients initially assigned to inactive pacing. Reproducibility was assessed using the root mean square (RMS) difference between duplicate values, and the corresponding value of the coefficient of variation (the ratio of RMS difference/mean value).
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3. Results
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3.1. Study population
Sixty-seven patients were originally recruited to the study. Details of patient dropout are described in Fig. 2. Three patients died during the crossover period (two suddenly in active mode, and one myocardial infarction in inactive mode). Three had decompensating heart failure (one in the initial crossover phase led to premature switch to active pacing, another in the second crossover phase during active pacing due to rapidly progressing aortic stenosis, and a third in inactive mode due to persistent atrial fibrillation). Three patients died between end crossover and 12-month follow-up, all in active BiV pacing. Two died between 6 and 9 months (one of septicaemia, one sudden cardiac death), and the third died between 9 and 12 months (stroke). A fourth patient was withdrawn (implantable defibrillator inserted).

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Fig. 2 Mortality and dropout rates. In total, seven patients died, 15 dropped out, and echo data for each pacing stage was incomplete in 11. The remaining 34 patients were studied.
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At 12 months follow-up, complete echocardiographic data was available for 34 of the original 67 patients, and the results of these (mean age 63±10 years, 26 males) are reported. All had IVCD and were in NYHA class III at inclusion; 33 were receiving an ACE inhibitor or angiotensin II receptor blocker, 31 a diuretic, 14 digoxin, 13 a beta-blocker, nine amiodarone, and six spironolactone. Eighteen patients had idiopathic (DCM) and 16 had ischaemic cardiomyopathy (12 with significant (>70%) stenosis at coronary angiography (six had three-vessel disease, four had two-vessel disease, and two had single-vessel disease) and four with documented previous myocardial infarction). At the end of the crossover period, 33 of the 34 patients preferred A-BiV pacing to inactive pacing. One patient preferred inactive pacing, but was reprogrammed in the active mode at 9 months due to severe heart failure decompensation. All patients were therefore programmed biventricular at 12-month follow-up.
3.2. Baseline
At baseline (Table 1), total ejection and filling times were short, one-third of the cardiac cycle was isovolumic and Z ratio was low. Ejection and filling times were not different in ischaemic cardiomyopathy (ejection time 16.1±1.5smin1, filling time 24.3±4.7smin1) compared with idiopathic DCM (ejection time 17.4±3.1smin1and filling time 22.4±4.6smin1). All patients had LV cavity dilatation (Table 2) and there was no difference in cavity size between patients with ischaemic cardiomyopathy (EDD 7.1±0.8cm, ESD 6.0±0.9cm) and idiopathic DCM (EDD 7.5±0.8cm, ESD 6.4±0.8cm). Mitral regurgitation was 8.1±4.2cm2, and there was no difference in the regurgitant jet area between ischaemic cardiomyopathy and idiopathic DCM.
3.3. Effect of atrio-bioventricular pacing
3.3.1. Three months A-BiV pacing
QRS duration shortened (by mean of 20ms
) in all but five patients with A-BiV pacing, although intrinsic QRS duration had not changed at 3 months (Table 1). Total ejection and filling times increased (by 2.6±2.5 and 7.2±5.5smin1, respectively, both
), so that total IVT fell in all patients (by 9.4±4.8smin1,
, Fig. 3 (top)) and Z ratio increased (by 16±8%,
). LV cavity size fell (EDD by 4.5±5.2mm,
, ESD by 3.2±7.1mm,
) (Fig. 4, Table 2), as did the area of the mitral regurgitant jet (by 1.9±4.1cm2,
). Aortic VTI, stroke volume, and cardiac output did not change. Mitral E wave decreased
but mitral A wave and E:A ratio did not change. Exercise tolerance increased significantly (6-min walk rose by 53±95m,
and peak VO2by 1.5±3.1mlkgmin1,
, Table 2), while NYHA fell by 25%
.

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Fig. 3 (Top) Changes in total IVT in individual patients. Total IVT fell in all patients at 3 months and did not change thereafter, though it reverted to baseline values when the pacemaker was switched from active to inactive. (Bottom) Relation between total IVT and RR interval. Total IVT fell early after initiation of pacing (3 months), with no additional change at 12 months. There was no significant correlation between total IVT and RR interval at any stage.
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Fig. 4 Changes in LV dimensions in individual patients. LVEDD, upper panel) and ESD (lower panel) fell with A-BiV pacing. This effect, though apparent after 3 months active pacing, was more marked at 9 and 12 months.
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3.3.2. Twelve months after randomization
There were no significant differences between any values at 9 and 12 months, so 12-month values are quoted. QRS duration remained shorter than baseline
at 12 months (i.e. after a total of 9 months active A-BiV pacing), while intrinsic QRS duration was unchanged (Table 1). Total ejection and filling times were longer (mean increase of 2.4±3.4smin1,
and 6.3±6.2smin1,
, respectively) (Table 1) although there was no difference in either time compared with 3 months active A-BiV pacing. In all but three patients, total IVT was shorter at 12 months than at baseline (mean difference 9.3±6.1smin1
), a fall that was independent of heart rate (Fig. 3 (bottom)). LV cavity size was significantly reduced by 12 months compared with baseline. EDD fell by 8.4±7.8mm (14%) and ESD fell by 8.8± 7.8mm (18%) (both
, Fig. 4, Table 2). This included a further fall in LV dimensions compared with 3 months active A-BiV pacing (mean additional fall of 5.6±7.2mm at end-diastole,
, and of 8.1±7.7mm at end-systole,
). Mitral regurgitant jet area fell (by 2.2±4.0cm2
), but aortic VTI, stroke volume, cardiac output, and E:A ratio were no different at 1 year compared to baseline. The 6-min walk and peak VO2significantly increased compared to baseline (by 64±72m,
and 2.5±3.5mlkg1min1,
, respectively, Table 2), and NYHA class fell (by 25%,
). However, there was no additional increase in exercise tolerance between 3 and 12 months active A-BiV pacing. The increase in peak VO2from baseline to 12 months correlated with the overall fall in ESD in individual patients (
,
, Fig. 5), but not with the change in total IVT, either at 3 months or at 12 months.

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Fig. 5 Relation between the increase in peak VO2at 12 months (i.e. after 9 months A-BiV) pacing and the fall in end-systolic dimension, demonstrating correlation between the two. Changes in peak VO2did not correlate with those in total IVT.
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3.3.3. Influence of aetiology
Though LV cavity size fell both in patients with idiopathic DCM and ischaemic cardiomyopathy by 12 months (Table 3), the reduction was significantly greater in idiopathic DCM (by 8.9mm at end-diastole,
, and by 9.8mm at end-systole,
, Table 4). Exercise tolerance increased in the group as a whole at 12 months, though the increment in 6-min walk or peak VO2was no different between patients with ischaemic cardiomyopathy and idiopathic DCM (Table 3). However, NYHA class fell further in idiopathic DCM (by 0.7 class,
after 3 months A-BiV pacing and by 0.4 class by 12 months,
). Aortic VTI and stroke volume increased by a greater amount in idiopathic DCM compared with ischaemic cardiomyopathy (by 4.4cm
and 11.0ml
after 3 months A-BiV pacing, and by 7.4cm
and 19.0ml
ml at 12 months). Total ejection and filling times and filling pattern were not influenced by whether or not coronary artery disease was present.
3.3.4. Reversibility and carry-over effects of A-BiV pacing
Reversibility of pacing: 14 patients were initially assigned 3 months active followed by 3 months inactive pacing. Switching to inactive pacing effectively reversed the effects of A-BiV pacing. It shortened total ejection and filling times (from 19.3±2.4 to 16.6±2.3smin1,
and from 30.6±6.7 to 26.6±4.7smin1,
, respectively), so that total IVT increased (from 11.2±4.1 to 16.8±4.4smin1,
). It had no effect on LV cavity size, mitral regurgitation, stroke volume, or exercise tolerance. Carry-over effects: total filling time was longer and total IVT was shorter at the end of 3 months inactive pacing when it followed 3 months active pacing compared with baseline (both
), suggesting a possible carry-over effect of A-BiV pacing. No other carry-over effects were found.
3.3.5. Reproducibility
Measurement reproducibility was assessed in 20 patients. Total ejection and total filling times were highly reproducible (ranges for intra- and interobserver coefficients of variability were 12% and 23%, respectively). The reproducibility for LV cavity dimension was less striking (intra- and interobserver coefficients of variability were 1011% and 1214%, respectively).
Long-term reproducibility was determined by comparing 19 patients in inactive mode for the first 3 months of the crossover period with baseline values. RMS difference for ejection and filling times were 46 and 134ms and 7mm for both EDD and ESD.
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4. Discussion
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The aim of pacing in patients with DCM is to mitigate the asynchrony caused by associated abnormal activation, which increases the total duration of mechanical systole. In patients with left bundle branch block, whether or not accompanied by cavity dilatation, the two isovolumic periods are abnormally prolonged at the expense of ejection and filling times.7,8 Total IVT, however, is not prolonged due to cavity dilatation alone,8 and can thus be used to dissociate the effects of reduced ejection fraction from those of abnormal activation. In the present study, all patients had a reduced ejection fraction and initial QRS duration of more than 150ms. The presence of resting asynchrony was demonstrated by abnormal timing. Total ejection and filling times were shorter, total IVT longer, and Z ratio lower (all
) than previously described values in patients with cavity dilatation without IVCD.8 Approximately half the patients studied had idiopathic cardiomyopathy, and the remainder had ischaemic cardiomyopathy. However, at baseline, both groups were identical in terms of all variables measured.
The most consistent effect of A-BiV pacing was to shorten total IVT, independently of heart rate. Before active A-BiV pacing, total IVT occupied one-third of the cardiac cycle, but following active pacing it halved, reverting to values seen in patients with DCM and no IVCD in all but three patients. This effect, which occurs within 12beats of the onset of pacing4 was present in full in all patients after 3 months of A-BiV pacing and did not change thereafter. However, it reverted once the pacemaker was switched back to inactive. Furthermore, it occurred equally in patients with ischaemic cardiomyopathy and idiopathic DCM. In addition, the measurement of total ejection and filling times proved to be highly reproducible, demonstrating the robust ability of total IVT to quantify myocardial performance, irrespective of heart rate. Although mean QRS duration decreased with active pacing, underlying QRS duration remained quite unaltered throughout the study, with no evidence of progression to more advanced conduction disturbances. A-BiV pacing was also accompanied by a reduction in LV cavity size (reverse remodelling) and a fall in the magnitude of mitral regurgitation, findings that are consistent with previous studies.22,23 Although the fall in LV cavity size could be detected by 3 months, its greatest effects were delayed, and manifest only at the end of 12 months. This reduction in LV dimensions was large and substantially greater than that found with pharmacological intervention alone24,25 and yet it occurred in patients already receiving conventional drug therapy. Furthermore, reverse remodelling was significantly more extensive in patients with idiopathic DCM than those with ischaemic cardiomyopathy. Additional echocardiographic changes were small. Resting stroke volume was higher at 12 months in patients with idiopathic cardiomyopathy, and although there were small changes in transmitral flow pattern, values remained in the normal range throughout and thus appeared of little significance as measures of changes in either relaxation or filling pressure.
4.1. Mechanisms
The striking fall in total IVT probably reflected the altered pattern of ventricular activation with A-BiV pacing. This was not simply due to shortening of the QRS duration alone,26 since QRS duration increased in five patients and there was no correlation between changes in QRS duration and those in total IVT. Instead, it probably reflected some more complex alteration in the actual sequence of intra-ventricular conduction. The prompt reduction in total IVT, which became manifest at 3 months and was unchanged thereafter, differed strikingly from the time course of the fall in cavity size, which was apparent at 3 months but was more marked at 9 and 12 months. Furthermore, total IVT fell regardless of whether the cardiomyopathy was ischaemic in origin or not, whereas significant reverse remodelling occurred much more extensively in patients with idiopathic DCM. Reversing the mechanical effects of asynchrony by pacing thus appeared to have a permissive role on reverse remodelling, rather than being its direct cause. Once total IVT has normalized, remodelling starts to occur, particularly in those patients with idiopathic DCM. In common with previous studies, exercise tolerance increased with A-BiV pacing, whether assessed by 6-min walk, peak VO2, or NYHA class. This improvement occurred consistently, and its extent in individual patients at 12 months correlated weakly with the fall in ESD. However, it seems unlikely that increased exercise tolerance was simply a function of reverse remodelling, since it occurred in both ischaemic cardiomyopathy and idiopathic DCM, and was effectively complete by 3 months. It thus appears more directly related to altered ventricular activation.
4.2. Limitations
On ethical grounds, the trial design did not include a normal group or patients with DCM and normal activation, so that appropriate values for comparison were derived from previous studies. In common with previous studies, there was a significant dropout, so that follow-up data to 12 months were available in only half the total patient population randomized. Although this was a single-blind study, it was possible to deduce from the echocardiogram, at least in some patients, whether or not biventricular stimulation was switched on. The distinction between pacing response in ischaemic cardiomyopathy and idiopathic DCM was not a primary end-point of this study, so angiography did not form part of the protocol. Nevertheless, highly significant differences were found between patients with confirmed coronary artery disease at angiography and those with no history of angina or previous myocardial infarction. The position of the LV lead was variable and likely to have been influenced in individual patients by coronary vein anatomy. Echo and exercise data were not acquired simultaneously, reducing the likelihood of demonstrating high correlations between changes in individual patients. Values for exercise tolerance were those of the patients included in the sub-study and are therefore not necessarily identical with those previously reported.18 Extending the trial beyond 12 months would probably not have yielded any further reverse remodelling, as there was no difference in LV cavity size between 9 and 12 months. The relatively low incidence of beta-blocker usage reflects the times at which the patients were randomized. Perhaps the most significant limitation is that echocardiographic studies were performed at rest, so that they may well have missed important factors limiting exercise tolerance under control conditions whose modification by pacing might have given valuable information about underlying mechanisms.
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5. Conclusions
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Correcting asynchrony appears to be a crucial step in the response to A-BiV pacing of patients with DCM and left bundle branch block; therefore it is essential to confirm that such asynchrony is present in any patient in whom this mode of treatment is being considered. By contrast, the presence of ischaemic cardiomyopathy does not appear to affect the response in terms of exercise tolerance, although it does reduce the extent of reverse remodelling. Whether the increase in ejection fraction is associated with any improvement in prognosis is not clear, and would require a considerably larger trial than the present one to demonstrate it. Even so, the clinical implications of the increased exercise tolerance alone, as reflected in NYHA class, is clearly worthwhile. Although this study validates the therapeutic value of A-BiV pacing in patients with DCM and major IVCD, the exact nature of the electrical and mechanical interrelations require further exploration in order to increase the benefits already obtainable from this important new approach to therapy in patients with severe heart failure.
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Appendix A
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In addition to the authors, the following persons participated in the Study: Study board: J.-C. Daubert (Chair), C. Linde (Co-Chair), C. Bailleul, S. Cazeau, L. Kappenberger, R. Sutton; Safety and Adverse Events Committee: C. Alonso, H.J. Dargie, P. Lechat; Independent Statistics Centre: J.S. Hulot, P. Lechat; Technical Advisers: D. Gras, P. Ritter, S. Walker; Core Analysis Centre: C. Alonso, Rennes, France (Electrocardiography and Holter monitoring), D. Gibson, London (Echocardiography), C. Linde, Stockholm (quality of life), W. McKenna, London (cardiopulmonary exercise testing); Study Team: C. Bailleul (study manager), K. Coombs, C. Fournier, M. Limousin (Ela Recherche), L. Mollo, S. Myrum (Medtronic), J.-M. Torralba, M.-C. Vandrell; InvestigatorsFrance: E. Aliot, S. Cazeau, J. Clémenty, J.-C. Daubert, C. De Chillou, J.-C. Deharo, P. Djiane, S. Garrigue, D. Gras, L. Guize, M. Jarwe, S. Kacet, D. Klug, T. Lavergne, A. Lazarus, C. Leclercq, A. Lemouroux, P. Mabo, J. Mugica, A. Otmani, J.-L. Rey, P. Ritter, N. Sadoul, N. Savon; Germany: T. Lawo, B. Lemke, S. von Dryander; Italy: G. Ansalone, R. Ricci, M. Santini; Sweden: F. Braunschweig, F. Gadler, C. Linde; Switzerland: X. Jeanrenaud, L. Kappenberger, X. Lyon; United Kingdom: M. Fitzgerald, M.D. Gammage, G.A. Haywood, W.J. McKenna, T. Levi, A.J. Marshall, H. Marshall, F. Osman, V. Paul, E. Rowland, R. Sutton, C. Varma, S. Walker.
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Acknowledgments
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We sincerely thank ELA Recherche and Medtronic Inc. for their technical assistance and financial support. We also thank the European Society of Cardiology, owner of the MUSTIC study data, the Centre Hospitalier Universitaire de Rennes, promoter of the study in France, and the Swedish Heart and Lung Association and the Swedish Medical Research Council for supporting the study (grant no. B96-11626-01).
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Footnotes
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All investigators and institutions are listed in Appendix A.
This study was supported by ELA Recherche, Medtronic and the Swedish Heart and Lung Association and by a grant from the Swedish Research Council (B96-11626-01). Dr Duncan was supported by the Special Cardiac Fund of the Royal Brompton Hospital, and Professor Daubert was a paid consultant for Medtronic.
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Related articles in EHJ:
- Multi-chamber pacing: a perfect solution for cardiac mechanical dyssynchrony?
- John G.F. Cleland, Justin Ghosh, Nasrin K. Khan, Stefano Ghio, Luigi Tavazzi, and Gerry Kaye
EHJ 2003 24: 384-390.
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