I-37
CARDIAC RESYNCHRONISATION THERAPY IN
HEART FAILURE
ATRIO-BIVENTRIKULARNA ELEKTROSTIMULACIJA SRCA PRI SRČNEM POPUŠČANJU
Cecilia Fantoni, Angelo Auricchio
Division of Cardiology, University Hospital Magdeburg, Germany
Arrived 2005-04-27, accepted 2005-04-30; Zdrav Vestn 2005; 74: Supl. I: 37–40
Key words: chronic heart failure; cardiac resynchronisation
therapy; electro-mechanical dyssynchrony; defibrillator; left
bundle branch block; ventricular conduction disturbance;
cardiac resynchronisation therapy
Abstract – Cardiac resynchronisation therapy (CRT) is a new
therapeutic approach for a selected group of patients with
symptomatic heart failure (NYHA III-IV) despite optimal
medical therapy, due to dilated cardiomyopathy of any
etiology (LVEF≤ 35%, and LVEDD≥ 55 mm), who present with
electro-mechanical dyssynchrony (QRS≥ 120 msec). Safety and
effectiveness of CRT have been demonstrated by several
clinical trials, with patients achieving significant improve-
ment in both clinical symptoms as well as functional status
and exercise capacity. Furthermore, CRT has reduced
morbidity and mortality of heart failure patients. Whether or
not heart failure patients candidate to CRT should receive a
defibrillator (ICD) back-up remains debatable, although
growing evidence is pointing to extensive use of a defibrilla-
tor in such a population.
Ključne besede: kronično srčno popuščanje; atrio-biventri-
kularna elektrostimulacija srca; elektromehanična dissinhro-
nija; levokračni blok; kardioverter defibrilator
Izvleček – Atrio-biventrikularna elektrostimulacija srca
(CRT) je nov način zdravljenja nekaterih bolnikov z izraže-
nim srčnim popuščanjem (NYHA III-IV), ki se pojavi kljub ustre-
znemu zdravljenju z zdravili. Vzrok dilatacijske kardiomio-
patije ni pomemben (LVEF≤ 35%, in LVEDD≥ 55 mm), pač pa
je pomembna elektromehanična dissinhronija (QRS ≥ 120
ms). Varnost in učinkovitost CRT so pokazale številne klinič-
ne raziskave, kjer so ugotavljali izboljšanje kliničnih simpto-
mov, fizikalnih parametrov kot tudi telesne zmogljivosti. Ugo-
tovitve kažejo, da CRT zmanjšuje obolevnost in umrljivost pri
bolnikih s srčnim popuščanjem. Ni še povsem jasno, ali naj bi
bolniki, ki so kandidati za CRT, hkrati prejeli tudi kardiover-
ter defibrilator (ICD), narašča pa število dokazov, ki nedvo-
mno podpirajo široko uporabo ICD v tej populaciji bolnikov.
Introduction
Despite striking advances in medical therapy of heart failure
(HF) (1, 2), morbidity and mortality of HF patients remain high
(3). Heart transplantation and ventricular assist devices offer
an effective, but limited alternative therapy due to shortage
of organ availability and elevated costs. Cardiac resynchroni-
sation therapy (CRT) has emerged as an effective option in
selected HF patients with electro-mechanical dyssynchrony.
Its safety and clinical efficacy have been proved in several
prospective, randomised, controlled trials (4–7). Furthermore,
CRT has been proved able to reduce morbidity and mortality
of HF patients (8–10), especially when combined with a de-
fibrillator back-up (7).
Mechanical consequences of electrical
delays
»… Obviously the shorter the distance that must be transversed
in order to reach the Purkinje conducting system, the smaller
the fractionate contraction element derived from fiber to
fiber excitation and the greater the number of fractions excited
over the natural pathways, with the result that more vigorous
beats occur…« Wiggers. Am J Physiol 1925; 73: 346–78.
Wiggers first recognised the acute effects of a non-physiologi-
cal activation sequence on left ventricular function. The strict
relationship between conduction delays and abnormal
mechanical function has been later confirmed in many other
animal models (11) and in human beings (12).
HF patients often present with conduction delays located at
various levels of the conduction system, which may depress
cardiac performance. Spontaneous or pharmacologically
induced sinus node incompetence may contribute to further
reduce the already impaired functional capacity of HF
patients (13).
About 50% of HF patients show different degree of atrio-
ventricular block, being the most frequent one a prolonged
atrio-ventricular conduction time. Prolongation of atrio-
ventricular time delays ventricular contraction (and conse-
quently relaxation of the ventricle), so that early passive
filling overlaps the active one, with reduced atrial booster con-
tribution to ventricular filling. Finally, loss of atrio-ventricular
synchrony may determine a ventriculo-atrial tele-diastolic
gradient with early re-opening of the mitral valve leading to
significant so called »pre-systolic or diastolic« mitral regurgi-
tation (14). All together these phenomena lead to impaired
ventricular pre-load.
A significant prolongation of QRS complex of more than 120
ms may be found in approximately 30% of HF patients. The
negative prognostic value related to QRS widening, indepen-
dently of QRS morphology, has been shown in several studies
(15, 16). At our best understanding, prolongation of QRS du-
ration is the result of electrical asynchrony at the inter-ventri-
ZDRAV VESTN 2005; 74: I-37–40
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cular, intra-ventricular and intramural level (17). Prolongation
of QRS duration may result in mechanical ventricular dyssyn-
chrony which, at the present time, has only been identified at
the inter-ventricular and intra-ventricular level. Inter-ventricu-
lar delay is defined as the time difference between the onset of
pulmonary artery flow and the onset of aortic flow with respect
to the beginning of the QRS complex. A delay longer than 40
ms is usually considered indicative of significant inter-ventri-
cular dyssynchrony. Nevertheless, many studies have questio-
ned the real importance of such delay in impairing systolic func-
tion compared to intra-ventricular electrical delay (18).
Left bundle branch block is the most common intra-ventricu-
lar conduction disturbance occurring in patients with depres-
sed ventricular function. Recent electrophysiological findings
have demonstrated that left bundle branch block is a rather
complex and heterogeneous electrical disease (19–21). There
is increasing evidence that disarray of myocardial layers may
partly account for this heterogeneity (20). In patients with left
bundle branch block, the region of earliest ventricular activa-
tion (usually the inter-ventricular septum) contracts while the
remaining ventricular myocardium is still in a non-activated
phase. Thus, consistent part of contraction energy is wasted
as no effective intra-ventricular pressure can develop. At the
same time, the latest activated regions of the left ventricle
(usually the lateral and postero-lateral walls) are passively
stretched with increasing wall tension at this site and further
waste of energy. By the time that the latest depolarised
ventricular regions contract, the septum starts to relax and is
no more able to withstand the increasing pressure develop-
ment, and is pushed toward the right ventricle (paradoxical
septal motion). In this way, pressure is generated asynchroni-
cally by different regions of the left ventricle without effecti-
ve ejection and with higher waste of energy.
Furthermore, the delayed depolarisation of the lateral wall
causes a delayed and slow contraction of the postero-lateral
papillary muscle. This event, in the presence of a dilated cham-
ber and abnormal ventricular geometry, contributes to signifi-
cant worsening of mitral regurgitation. Finally, the heteroge-
neous electrical and mechanical ventricular activation may
further impair systolic ventricular function by delaying relax-
ation phase and reducing ventricular filling time.
Structural changes related to
electromechanical dyssynchrony
In different heart models (22–24), it has been demonstrated
that the abnormal loading and work distribution caused by
electro-mechanical dyssynchrony may induce regional
alterations of myocardial metabolism, gene expression and
protein synthesis (23). It may be postulated that these
changes could lead to rearrangement of both contractile and
non-contractile cells, fibrosis and apoptosis. Experimentally-
induced left bundle branch block causes eccentric hyper-
trophy (25) with an apico-basal and septo-lateral oriented
gradient and determines altered synthesis of stress kinases and
calcium-handling proteins in the high stress areas (23).
Furthermore, it has been demonstrated that mechanical
dyssynchrony causes a redistribution of regional flows (26)
with consequent chronic hypoperfusion of unloaded regions.
The meaning of such complex interactions between changes
in regional loading conditions, myocardial metabolism, gene
expression, protein synthesis and blood flow distribution
induced by an abnormal activation sequence is not fully
understood. All together it appears that mechanical dyssyn-
chrony arising from conduction disturbances favours mal-
adaptive structural remodeling process. Thus, it is conceiv-
able that dyysnchrony represents a newly appreciated
pathophysiological process which directly depresses ventri-
cular function and ultimately leads to further ventricular dila-
tation and progression of HF.
Cardiac resynchronisation therapy
CRT improves cardiac performance at reduced myocardial
metabolism cost through different mechanisms (27). Pre-
excitation of the left ventricular lateral wall with atrial-synchro-
nous left or biventricular pacing restores a normal atrio-
ventricular timing, resynchronises right and left ventricular
activation as well as septum and lateral wall contraction. In
addition to an improved coordination of the septal and
lateral wall contraction, reduction of mitral regurgitation and
improvement of ventricular filling (28, 29), recent data pos-
sibly suggest that CRT may improve cardiac efficiency by slo-
wing the heart rate (30). This may have a beneficial effect on
diastolic times and on myocardial oxygen demand.
Clinical and structural effects of CRT
Several prospective, randomised, controlled trials (4–6, 10, 31),
conducted in patients with functional NYHA class III-IV, due
to dilated cardiomyopathy of any etiology, presenting with
electro-mechanical dyssynchrony, have proven the safety and
clinical effectiveness of CRT. All these studies demonstrated a
significant improvement of quality of life, NYHA functional
class, exercise tolerance, and a significant reduction in the
hospitalisations for HF. Furthermore, there was a consistent
report of significant improvement of left ventricular ejection
fraction and partial reversal of maladaptive remodeling
process (28, 6). CRT also showed a favourable effect on sympa-
thetic-parasympathetic activity with a reduction of plasma
norepinephrine levels and increase of heart rate variability
(30). Finally, the recently concluded CARE-HF Study (Cardiac
Resynchronisation in Heart Failure) (10), demonstrated a
clear survival benefit in HF patients given by CRT in addition
to optimal medical therapy compared to optimal medical
therapy alone.
Based on these evidences, CRT is currently indicated (Class
IIa ACC/AHA/NASPE Guidelines, see Table 1) for patients with
symptomatic HF (NYHA III-IV) despite optimal medical the-
rapy, due to dilated cardiomyopathy of any etiology (LVEF≤
35%, and LVEDD≥ 55 mm), who present with ventricular elec-
trical dyssynchrony (QRS ≥ 130 msec) for the improvement
of symptoms, functional status and exercise capacity (32).
It has been reported that a small proportion of patients
treated with CRT remain symptomatic. These individuals are
usually considered as non-responder patients to CRT. All
randomised clinical CRT trials have used statistical techniques
to define the response of groups of patients to CRT. No stan-
dardised criteria are available to predict reliably the clinical
response of a given individual. The large clinical improvement
that is observed in some individuals after CRT has created the
perception that patients who do not exhibit such improve-
ment are not responding positively to CRT. However many
patients who do not show overt improvement may neverthe-
less benefit from a slowing of disease progression by living
longer and not undergoing hospitalisations. Although major
efforts have been made for identifying such patients, there
are still several unresolved issues in the definition of non-
responders and in how to best identify and then treat these
patients.
Effects on morbidity and mortality
The COMPANION trial (Comparison of Medical therapy, Pa-
cing, And Defibrillation in chronic heart failure) (7), has shown
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marked reduction in combined measures of morbidity and
mortality with both CRT alone and with CRT plus defibrillator
back-up (CRT-D) with a similar 1-year event-free survival
rate. Nevertheless, in contrast to CRT alone which demonstra-
ted a relative risk reduction in all-cause mortality of about
24% (p = 0.060), CRT-D provided a larger (36%) and signifi-
cant relative risk reduction in all-cause-mortality compared
to optimal drug therapy (p = 0.003). These results are con-
sistent with data of a recent meta-analysis showing that CRT
alone may be able to reduce all-cause mortality by about 21%
(8). Based on these data, the number of patients who needed
to be treated to save 1 life is about 25 for CRT alone and 14
when CRT combined to ICD is given. These numbers are
comparable with many pharmacological trials which enrolled
similarly sick HF patients.
The recently concluded CARE-HF trial (10) that randomised
813 advanced HF patients to optimal medical therapy alone or
in combination with a CRT device showed a 36% reduction in
the relative risk of all cause mortality with CRT compared with
medical therapy alone. Nevertheless, 32% and 35% of deaths
occurred among patients randomised to medical therapy and
to CRT respectively were sudden deaths that could have been
avoided by associating a defibrillator back-up.
Finally, results of the CARE-HF and COMPANION trials and
those from another important meta-analysis (9) were consi-
stent in showing a similar risk reduction for the combined
end-point – hospitalisations and death – in patients treated
with CRT. This finding may suggest a substantial reduction of
medical resources.
Implantation issues
The implantation technique is similar to a standard dual cham-
ber sequential pacemaker or implantable cardioverter-de-
fibrillator. The most challenging aspect for achieving resyn-
chronisation therapy is placing a permanent left ventricular
lead. A transvenous or thoracotomic approach can be used.
The transvenous approach requires the retrograde cannulation
of the coronary sinus, a selective angiography of the coro-
nary sinus and his tributaries which delineates the venous ana-
tomy and the final placement of a specifically designed
pacing lead into a coronary vein lying over the surface of the
left ventricle. Several reports have demonstrated the impor-
tance of targeting the latest activated wall which requires
implantation of a pacing lead into a lateral or postero-lateral
vein (1). The transvenous approach may be a difficult and
time-consuming technique. The major limitation is that
options for lead placement are governed largely by the
patient’s venous anatomy which shows considerable inter-
individual variability. In about 10% to 15% of cases, it is not
possible to achieve a satisfactory left ventricular pacing posi-
tion or left phrenic nerve stimulation may occur, so that a
thoracotomic approach becomes necessary.
Selection of patients
Duration of QRS complex has so far been used as the most
practical and readily available criteria to select patients can-
didate to CRT. Indeed, QRS duration is one of the simplest
ways to measure electrical abnormalities that may have a me-
chanical correlate. Baseline QRS duration has been shown to
be associated with degree of mechanical dyssynchrony and
with short-term clinical improvement obtained from CRT.
Nevertheless there are increasing data (34) suggesting that a
considerable proportion of HF patients presenting with
narrow QRS complex (< 120 ms) may present echocardio-
graphically-assessed mechanical dyssynchrony of similar mag-
nitude as patients with prolonged QRS duration (> 120 ms).
Recently introduced tissue Doppler imaging (TDI) techniques
permit precise evaluation of regional systolic and diastolic
synchrony by comparing the time to peak systolic contrac-
tion and early diastolic relaxation of multiple segments. TDI
appears to offer a comprehensive assessment of cardiac
mechanical synchrony. A number of parameters based on TDI
have been proposed to evaluate intra-ventricular dyssynchro-
ny but the validity of TDI and other echocardiographic para-
meters in selecting patients with both narrow and wide QRS
who can benefit from CRT need to be confirmed in prospec-
tive, randomised long-term studies.
Open questions
CRT is not currently indicated in patients with NYHA class II,
even though there are increasing data suggesting that appli-
cation of CRT in mildly symptomatic HF patients could pre-
vent or slow HF progression. Furthermore, the increasing
indications to ICD implantation, based on results of recent
big trials (MADIT, MADIT II, SCD-HeFT ) rise the problem of
considering implementation of the ICD-devices with a CRT
back-up in less symptomatic (NYHA II) pts.
Not enough data are so far available about CRT in patients
with atrial fibrillation, although preliminary results support
its efficacy in this clinical setting (35). Furthermore, there are
increasing evidences that the implantation of a CRT device
instead of a standard single- or dual-chamber pacemaker
may be appropriate for HF patients who undergo His-bundle
ablation.
The question of whether HF patients with a standard pace-
maker indication for bradycardia benefit from CRT is still
unanswered. Nevertheless, data of DAVID trial (36) encoura-
ges implantation of a CRT device in patients with impaired
ventricular systolic function candidate to chronic pacing.
Recent data suggest that also patients with narrow QRS
(< 120 ms), but with echocardiographic evidence of mecha-
nical dyssynchrony may benefit from CRT. Nevertheless, CRT
should not be extended to this group before results of
prospective randomised trials will be available.
The important issue raised by the COMPANION study (7) is
whether all HF patients candidate to CRT should be treated
with an additional ICD back-up. The recently concluded trial,
the Sudden Cardiac Death – Heart Failure Trial (SCD-HeFT)
(37), has provided further evidence that implantation of a
defibrillator in addition to best pharmacological therapy is
the most effective long-term (5 year) treatment compared to
conventional optimal therapy alone or with the adding of
amiodarone, to prolong life in HF patients. Therefore, despite
the fact that CRT-D devices have larger initial costs, and may
require more extensive follow-up than CRT alone, this
strategy may be more cost-effective particularly when mea-
sured in terms of quality-adjusted life-years gain.
Summary
Cardiac resynchronisation therapy is an effective, adjunctive
treatment to pharmacological therapy for a selected group
of HF patients who remain symptomatic despite optimal
medical therapy, and who present with electro-mechanical
dyssynchrony. Safety and effectiveness of CRT have been
demonstrated by many clinical trials, with patients achieving
significant improvement in symptoms, functional status and
exercise capacity. Furthermore, CRT promotes reverse re-
modeling and reduces morbidity and mortality of HF
patients. Thus, CRT should not be considered an alternative
to medical therapy but a synergistic therapy. Indeed, in those
patients in whom optimal dosage of ACE-Inhibitors or beta-
blockers can not be achieved because of hemodynamic in-
FANTONI C, AURICCHIO A. CARDIAC RESYNCHRONISATION THERAPY IN HEART FAILURE
I-40 ZDRAV VESTN 2005; 74: SUPPL I
tolerance or severe bradycardia, CRT may be considered in
order to support ventricular systolic function allowing to
optimise beta-blocking and ACE-inhibitor treatment. If CRT
should be delivered in NYHA class II, in HF patients with QRS
< 120 ms and in HF candidates to chronic pacing needs to be
confirmed by randomised controlled trials.
Table 1.  Current guidelines for cardiac resynchronisation
therapy.
AHA/ACC/NASPE Guidelines (32)
Pacing Recommendations (Class IIa Indication)
– Medically refractory heart failure
– Functional New York Heart Association Class III or IV
– Idiopathic dilated or ischemic cardiomyopathy
– QRS duration ≥ 130 ms
– Left ventricular ejection fraction ≤ 35%
– Left ventricular end diastolic diameter ≥ 55mm
References
1. Captopril Multicenter Research Group. A placebo-controlled trial of cap-
topril in refractory chronic congestive heart failure. J Am Coll Cardiol
1983; 2: 755–63
2. Merit-HF Study Group. Effect of metoprolol CR/XL in chronic heart failu-
re. Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart
Failure (MERIT-HF). Lancet 1999; 353: 2001–7.
3. Rodeheffer RJ, Naftel DC, Stevenson LW, et al. Secular trends in cardiac
transplant recipient and donor management in the United States, 1990 to
1994. Circulation 1996; 94: 2883–9.
4. Auricchio A, Stellbrink C, Sack S, et al. Long-term clinical effect of hemody-
namically optimised cardiac resynchronisation therapy in patients with
heart failure and ventricular conduction delay. J Am Coll Cardiol 2002; 39:
2026–33.
5. Cazeau S, Leclercq C, Lavergne T, et al. Effects of multisite biventricular
pacing in patients with heart failure and intraventricular conduction delay.
N Engl J Med 2001; 344: 873–80.
6. Abraham WT, Fisher WG, Smith AL, et al. Cardiac resynchronisation in
chronic heart failure. N Engl J Med 2002; 346: 1902–5.
7. Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronisation the-
rapy with or without an implantable defibrillator in advanced chronic
heart failure. N Engl J Med 2004; 350: 2140–50.
8. McAlister FA, Ezekowitz JA, Wiebe N, et al. Systematic review: cardiac
resynchronisation in patients with symptomatic heart failure. Ann Intern
Med 2004; 141: 381–90.
9. Bradley DJ, Bradley EA, Baughman KL, et al. Cardiac resynchronization
and death from progressive heart failure. A Meta-analysis of randomized
controlled trials. JAMA 2003; 289: 730–40.
10. Cleland JGF, Daubert JC, Erdmann E, et al. The effect of cardiac resynchro-
nization on morbidity and mortality in heart failure. N Engl J Med 2005;
352: 1539–49.
11. Liu L, Tockman B, Girouard S, et al. Left ventricular resynchronization
therapy in a canine model of left bundle branch block. Am J Physiol Heart
Circ Physiol 2002; 282: H2238–44.
12. Grines CL, Bashore TM, Boudoulas H, et al. Functional abnormalities in
isolated left bundle branch block. The effect of interventricular asyn-
chrony. Circulation 1989; 79: 845–53.
13. Kass DA. Ventricular resynchronization: Pathophysiology and identifica-
tion of responders. Rev Cardiovasc Med 2003; 4: S3–13.
14. Meisner JS, McQueen DM, Shida Y, et al. Effects of timing of atrial systole
on LV filling and mitral valve closure : computer and dog studies. Am J
Phisiol 1985; 249: H604–19.
15. Baldasseroni S, Opasich C, Gorini M, et al. Left bundle branch block is
associated with increased 1-year sudden and total mortality rate in 5517
outpatients with congestive heart failure: a report from the Italian Net-
work on Congestive Heart Failure Investigators. Am Heart J 2002; 143:
398–405.
16. Hesse B, Diaz LA, Snader CE, et al. Complete bundle branch block as an
independent predictor of all-cause mortality: report of 7,073 patients
referred for nuclear exercise testing. Am J Med 2001; 110: 253–59.
17. Auricchio A, Abraham WT. Cardiac resynchronisation therapy: Current
state of the art. Cost versus benefit. Circulation 2004; 109: 300–7.
18. Fauchier L, Marie O, Casset-Senon D, et al. Interventricular and intraven-
tricular dyssynchrony in idiopathic dilated cardiomyopathy. A prognostic
study with Fourier phase analysis of radionuclide angioscintigraphy. J Am
Coll Cardiol 2002; 40: 2022–30.
19. Rodriguez L-M, Timmermans C, Nabar A, et al. Variable patterns of septal
activation in patients with left bundle branch block and heart failure. J
Cardiovasc Electrophysiol 2003; 14: 135–41.
20. Auricchio A, Fantoni C, Regoli F, et al. Characterization of left ventricular
activation in patients with heart failure and left bundle branch block.
Circulation 2004; 109: 1133–9.
21. Fung JWH, Yu CM, Yip G, et al. Variable left ventricular activation pattern
in patients with heart failure and left bundle branch block. Heart 2004; 90:
17–9.
22. Prinzen FW, Hunter WC, Wyman BT, et al. Mapping of regional myocar-
dial strain and work during ventricular pacing: experimental study using
magnetic resonance imaging tagging. J Am Coll Cardiol 1999; 33: 1735–
42.
23. Spragg D, Leclercq C, Loghmani M, et al. Regional alterations in protein
expression in the dyssynchronus failing heart. Circulation 2003; 108: 929–
32.
24. Ukkonen H, Beanlands RS, Burwash IG, et al. Effect of cardiac resynchro-
nization on myocardial efficiency and regional oxidative metabolism. Cir-
culation. 2003; 107: 28–31
25. Van Oosterhout FM, Prinzen FW, Arts T, et al. Asynchronous electrical
activation induces asymmetrical hypertrophy of the left ventricular wall.
Circulation 1998; 98: 588–95.
26. Prinzen FW, Van Oosterhout FM, Arts T, et al. Mismatch of local myocardi-
al growth and blood flow during chronic ventricular pacing. Circulation
2000; 102: 196. 
27. Nelson G, Berger RD, Fetics BJ, et al. Left or biventricular pacing improves
cardiac function at diminished energy cost in patients with dilated cardio-
myopathy and left bundle branch block. Circulation 2000; 102: 3053–59.
28. Yu CM, Chau E, Sanderson JE, et al. Tissue Doppler echocardiographic
evidence of reverse remodeling and improved synchronicity by simulta-
neously delaying regional contraction after biventricular pacing therapy
in heart failure. Circulation 2002; 105: 438–45.
29. Abraham WT, Hayes DL. Cardiac resynchronization therapy for heart
failure. Circulation 2003; 108: 2596–603.
30. Adamson PB, Smith AL, Abraham WT, et al. Continuous autonomic asses-
sment in patients with symptomatic heart failure. Prognostic value of
heart rate variability measured by an implanted cardiac resynchronisation
device. Circulation 2004; 110: 2389–94.
31. Saxon LA, Boehmer JP, Hummel J, et al. Biventricular pacing in patients
with congestive heart failure : two prospective randomised trials. The
VIGOR CHF and VENTAK CHF Investigators. Am J Cardiol 1999; 83:
120D–3D.
32. Gregoratos G, Abrams J, Epstein AE, et al. ACC/AHA/NASPE 2002 guideli-
ne update for implantation of cardiac pacemakers and antiarrhythmia
devices: summary article: a report of the American College of Cardiology/
American Heart Association Task Force on Practice Guidelines (ACC/
AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines).
Circulation 2002; 106: 2145–61.
33. Butter C, Auricchio A, Stellbrink C, et al. Should stimulation site be tailored
in the individual heart failure patient. Am J Cardiol 2000; 86: K144–51.
34. Yu CM, Lin H, Zhang Q, et al. High prevalence of left ventricular systolic
and diastolic asynchrony in patients with congestive heart failure and
normal QRS duration. Heart 2003; 89: 54–60.
35. Leon AR, Greenberg JM, Kanuru N, et al. Cardiac resynchronisation in
patients with congestive heart failure and chronic atrial fibrillation: effects
to upgrading to biventricular pacing after chronic right ventricular pa-
cing. J Am Coll Cardiol 2002; 39: 1258–63.
36. Wilkoff BL, Cook JR, Epstein AE, et al. Dual-chamber pacing or ventricular
back-up pacing in patients with an implantable defibrillator: the dual
chamber and VVI implantable defibrillator (DAVID) trial. JAMA 2002;
288: 3115–23.
37. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable-defibril-
lator for congestive heart failure. N Engl J Med 2005; 352: 225–37.