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Europace (2004) 6, 400e406
The role of implantable cardioverter defibrillator
for primary vs secondary prevention of sudden
death in patients with idiopathic dilated
cardiomyopathy
Massimo Zecchina,), Andrea Di Lenardaa, Alessandro Proclemerb,
Giorgio Faganellob, Domenico Facchinb, Eugenio Petza,
Gianfranco Sinagraa
a
Struttura Complessa di Cardiologia, Az. Ospedaliera ‘‘Ospedali Riuniti’’, Trieste, Italy
Struttura Complessa di Cardiologia, Az. Ospedaliera ‘‘S. Maria degli Angeli’’, Udine, Italy
b
Submitted 14 October 2003, and accepted after revision 18 April 2004
KEYWORDS
dilated
cardiomyopathy;
sudden death;
implantable
defibrillator;
primary prevention of
ventricular
tachyarrhythmia;
secondary prevention
of ventricular
tachyarrhythmia
Abstract Aim To analyse the characteristics and outcome of patients with idiopathic dilated cardiomyopathy (DC) considered at high risk of sudden death (SD) and
treated with implantable cardioverter defibrillators (ICD) for primary prevention
(Group A) in comparison with patients treated with ICDs because of previous sustained ventricular tachyarrhythmias or syncope (Group B).
Methods Group A consisted of 27 patients with at least two of the following criteria: left ventricular end-diastolic diameter (LVEDD) R70 mm (74%), LV ejection fraction (LVEF) %30% (78%), non-sustained ventricular tachycardia (VT) (56%), long
history of disease (R48 months since diagnosis, 85%) and family history of SD
(11%). Group B consisted of 27 patients treated with ICDs because of sustained
VT/fibrillation (n ¼ 18) or syncope (n ¼ 9).
Results NYHA class, LVEF, LVEDD and amiodarone treatment were similar in the
two groups. Patients in group A were younger (46G15 vs 59G17 years,
P ¼ 0:0008), were more often treated with b-blockers (89% vs 62%; P ¼ 0:02) and
had a longer interval since diagnosis (86G60 vs 40G50 months; P ¼ 0:004). Twelve
month rates of appropriate intervention (AI) were 41% in Group A and 57% in group B
(P NS). In group A, after a mean follow-up of 21G14 months, patients showing the
combination of LVEF %30% and LVEDD R70 mm had the highest frequency of AI
(76% vs 10%, P ¼ 0:005). In group B, after a mean follow-up of 33G23 months, 78%
of patients with syncope had AI. Total and sudden deaths were 11% and 4% in group
A and 19% and 4% in group B (P NS).
) Corresponding author. S. C. di Cardiologia, Ospedale di Cattinara, 34100 Trieste, Italy. Tel.: D39-0403994828; fax: D390403994878.
E-mail address: [email protected] (M. Zecchin).
1099-5129/$30 ª 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.eupc.2004.04.009
Role of ICDs in primary and secondary prevention in DCM
401
Conclusions Patients with idiopathic DC treated with ICD for primary prevention
because they were considered at high risk of SD according to clinical criteria showed
a high rate of AI, similar to that of patients treated for secondary prevention. The
highest rate of AI was seen in patients with both severe dysfunction and dilatation
and in those with previous syncope.
ª 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights
reserved.
Introduction
Methods
Although mortality in idiopathic dilated cardiomyopthy (DC) has declined in the last two decades [1,2] sudden cardiac death accounts for
approximately 30% of all deaths in these patients.
While it is more frequent in the advanced stages
of the disease [3], it represents the first cause of
death for less severely affected patients [4]. However, because of the lack of reliable markers, risk
stratification in the individual patient is still an unresolved issue.
Amiodarone [5] and b-blocking agents [6e8]
may have a role in reducing sudden death incidence in patients with DCM, but data are not
conclusive.
In non-ischaemic cardiomyopathy, the role and
the benefit of an implantable cardioverter-defibrillator (ICD) for secondary prevention of sudden
death is well established [9e11], while it is still
uncertain which patients can benefit from ICD
treatment for primary prevention [12,13].
Some uncontrolled studies [14,15] suggested
that the rate of death due to heart failure was
higher during the first years after diagnosis while
patients who had long-term persistence of severe
left ventricular dysfunction and dilatation and
a history of non-sustained ventricular tachycardia
(VT) had the highest risk of sudden death.
Recently, Grimm and others [16] showed that in
patients with DC, left ventricular ejection fraction
!30% and non-sustained VT treated with ICD for
primary prevention had an incidence of appropriate interventions similar to that of patients treated
with ICD because of previous sustained VT, ventricular fibrillation (VF) or syncope. However, in that
study only 33% of patients in the primary prevention group were on optimal medical therapy including b-blockers.
The aim of our study was to evaluate the usefulness of primary prevention by ICD in patients with
DC considered at high risk of sudden death, in
spite of optimal medical treatment including
b-blockers and ACE inhibitors, in comparison
with patients treated with ICDs for secondary
prevention.
The study group consisted of 54 patients with DC
evaluated in two centres in north-east Italy (Trieste
and Udine) and treated with ICDs from September
1995 to December 31, 2002. In all patients the diagnosis of idiopathic DC was made according to the
WHO definition [17]. At enrolment 45 patients
(83%) underwent coronary angiography to exclude
significant coronary artery disease (stenosis O50%
in an epicardial vessel). In young patients (!35
years old) with no risk factors or in familial
cases, ischaemic heart disease was non-invasively
excluded. Twenty-three (43%) underwent an endomyocardial biopsy to rule out active myocarditis
and other specific myocardial diseases. In patients
with a long history of heart failure and a low clinical
probability of active myocarditis, endomyocardial
biopsy was not performed.
Patients with moderate to severe hypertension
(O170/100 mmHg), significant alcohol intake
(O100 g/day in the previous 6 months), severe valvulopathy, cor pulmonale, prognostically relevant
systemic diseases, arrhythmogenic right ventricular cardiomyopathy, ‘tachycardia induced’ cardiomyopathy, with suspected cardio-toxicity or
ischaemic cardiomyopathy diagnosed according to
the WHO definition [17] were excluded from the
analysis.
Most patients had been treated with ACE inhibitors; digoxin and diuretics were given as needed.
b-blockers (metoprolol or carvedilol) were given
to all patients without contraindications and
titrated to the highest tolerated dosage. Amiodarone (or rarely sotalol) was administered in the presence of unsustained but particularly frequent,
complex or symptomatic ventricular arrhythmias
or symptomatic supraventricular arrhythmias. No
patient was treated with class I antiarrhythmic
drugs.
Patient population was divided into two groups.
Group A ( primary prevention group) included 27
patients, without a history of sustained ventricular arrhythmias or syncope, treated with ICDs
because they were classified as high risk due
to the presence of at least two of the
402
following criteria: long history of disease defined
as an interval longer than 4 years since diagnosis
(n ¼ 23, 85.2%), left ventricular ejection fraction
%30% (n ¼ 21, 77.7%), end-diastolic diameter
R70 mm (n ¼ 20, 74.1%), non-sustained VT
(n ¼ 15, 55.5%), family history of DC and sudden
death (n ¼ 4, 14.8%).
Group B (secondary prevention group) included
27 patients treated with ICDs because of previous
cardiac arrest due to VF (11 patients) or sustained
VT (7 patients) or syncope presumed to be of
arrhythmic origin because of VT/VF inducibility at
electrophysiological evaluation (7 patients) or on
a clinical basis (2 patients).
All patients gave written informed consent to
ICD implantation.
Clinical, echocardiographic and Holter data of
the two groups were compared at the date of implantation. The clinical outcome, the incidence of
ICD shocks as well as antitachycardia pacing interventions were evaluated during follow-up in the
two groups.
The different types of ICD implanted were:
Ventak Mini II, AV II-IV, Prizm I-II, Vitality and
Renewal I (Guidant), Contour II (Ventitrex-S.
Jude), Belos (Biotronik), Defender II (Ela Medical), Jewel II and AT, Gem III, Insync and Marquis
(Medtronic). Ten single chamber, 13 dual chamber and 4 ICDs with biventricular pacing capabilities were used in group A and 14 single
chamber, 9 dual chamber and 2 ICDs with biventricular pacing capabilities were used in group B.
All devices had EGM storage capabilities. Antitachycardia pacing was generally programmed
for ventricular tachyarrhythmias in a range between 150e160 and 200e220 beats per minute
(bpm). All arrhythmias with a rate O 200e220
bpm were considered as VF and treated only
with shocks.
Statistical analysis
Differences among group means at baseline were
compared by one-way analysis of variance. Differences among proportions were compared using
the Chi-square test applying the Yates correction. The survivor functions from the time of
ICD implantation were analysed using the
KaplaneMeier method and compared by Mantel
Cox test.
For our statistical analysis, SPSS version 11.0
for Windows was used. Data were expressed as
averageGstandard deviation or as percentage.
Results were regarded as statistically significant
when P!0:05.
M. Zecchin et al.
Results
Baseline clinical data
Groups A and B had similar proportions of patients
in NYHA class IeII (74% vs 78%, P ¼ NS), mean left
ventricular ejection fraction (25G7% vs 28G8%;
P ¼ NS) and left ventricular end-diastolic diameter
(7.6G1.1 vs 7.1G1.1 cm; P ¼ NS). The number of
patients with spontaneous non-sustained VT and
sustained VT/VF inducibility was also similar in
the two groups (Table 1).
The two groups differed in terms of age at implantation (46G15 vs 59G17 years in group A and
B, respectively; P ¼ 0:008), b-blocker treatment
(89% vs 62%; P ¼ 0:02), interval since first symptom
(107G67 vs 53G41 months; P ¼ 0:0007) and since
diagnosis (86G60 vs 40G50 months; P ¼ 0:004)
(Table 1). In group A, 11 patients underwent electrophysiological evaluation: sustained monomorphic VT was inducible in 2 patients (18%) and VF
in 4 patients (36%). In group B, 16 patients underwent baseline electrophysiological evaluation: sustained monomorphic VT was inducible in 9 patients
(56%) and VF in 6 patients (38%). In the 9 patients
treated with ICD because of syncope, 7 underwent
electrophysiological evaluation: in all of them
sustained ventricular arrhythmias were inducible
(4 VT, 3 VF).
Outcome
The follow-up after ICD implantation was longer in
group B (33G23 months) than in group A patients
(21G14 months, P ¼ 0:01) (Table 2). Three patients (11%) in group A and 5 patients (19%) in group
B (P ¼ NS) died during follow-up. Sudden death
occurred in 1 patient (4%) in each group after an
arrhythmic storm only initially responsive to ICD
shocks; unfortunately, it was not possible to
acquire their post-mortem ICD-EGMs.
Two patients (7.4%) in group A and 4 patients
(14.8%) in group B (P ¼ NS) underwent heart
transplantation respectively after 19 and 39G12
months.
As shown in Table 3 and Fig. 1, the 12-month
cumulative risks of appropriate ICD intervention
were 41% in group A and 57% in group B (P ¼ NS).
During follow-up, 4 patients (15%) in group A only
had interventions for VT (!220 bpm), 4 (15%) only
interventions for VF, 3 (11%) for both. In group B, 6
patients (22%) only had interventions for VT, 1 (4%)
only for VF, 10 (37%) for both.
In group A, the 17 patients showing the combination of left ventricular ejection fraction %30% and
Role of ICDs in primary and secondary prevention in DCM
Table 1
403
Variables at ICD implantation
N
% of males
Age ( years)
NYHA class
History of syncope (% patients)
LBBB (% patients)
LVEF (%)
LVEDD (cm)
Non-sustained VT within 12 months (% patients)
VT/VF inducibility (% patients)
Patients treated with b-blockers (%)
Patients treated with amiodarone (%)
Patients treated with sotalol (%)
Patients treated with digoxin (%)
Primary symptom-implant interval (months)
Diagnosis-implant interval (months)
Group A ( primary)
Group B (secondary)
27
89
46G15
2.1G0.6
0
41
25G7
7.6G1.1
55
18/36
89
48
7
23
107G67
86G60
27
70
59G17
2.1G0.7
52
26
28G8
7.1G1.1
38
56/38
62
70
11
23
53G41
40G50
P
NS
0.008
NS
NS
NS
NS
NS
NS
0.02
NS
NS
NS
0.0007
0.004
LBBB, left bundle branch block; LVEF, left ventricular ejection fraction; LVEDD, left ventricular end-diastolic diameter; VT,
ventricular tachycardia; VF, ventricular fibrillation.
left ventricular end diastolic diameter R70 mm
had a 12-month incidence of appropriate interventions significantly higher than the other 10 patients without these characteristics (68% vs 0%;
P ¼ 0:01) (Fig. 2). The association of left ventricular ejection fraction %30% and history of non-sustained VT as well as left ventricular end-diastolic
ventricular diameter R70 mm and non-sustained
VT were not associated with a significantly higher
proportion of appropriate interventions during
follow-up.
In group B, 7 of 9 patients (78%) with syncope
had appropriate interventions (in 5 patients for
VF or VT with rate O220 bpm) during follow-up.
The incidence of inappropriate shocks was 22%
(6 patients) in group A and 19% (5 patients) in
group B (P ¼ NS). In group A, one patient received
inappropriate shocks due to sinus tachycardia
and the others due to atrial fibrillation (in three
patients with fast ventricular response detected
in the VF zone). In group B, one patient received
inappropriate shocks due to sinus tachycardia and
4 patients due to atrial fibrillation.
Table 2
Discussion
Our study showed that patients with idiopathic DC
treated with ICD for primary prevention because
they were considered to be at high risk of sudden
death on the basis of clinical criteria and patients
treated with ICD for secondary prevention had
a similar outcome and appropriate intervention
rate (41% and 57% respectively; P ¼ NS) during
the year following implantation. All patients were
on optimal medical treatment, included b-blockers
(metoprolol or carvedilol) at the highest dosage
tolerated; nearly 50% of patients in the primary
prevention group and 70% in the secondary prevention group were on amiodarone.
In patients with ischaemic heart disease, severe
or moderate to severe left ventricular dysfunction
[18], left ventricular dysfunction in conjunction
with spontaneous non-sustained and inducible sustained ventricular arrhythmias identifies patients
at higher risk of sudden death who can benefit from
an ICD [19,20].
Outcome in primary prevention and secondary prevention groups
No. of patients
Mean follow-up after implant (months)
Patients with follow-up O12 months (%)
Total deaths (%)
Heart failure deaths (%)
Sudden deaths (%)
Cardiac transplantations (%)
Group A ( primary)
Group B (secondary)
P
27
21G14
18 (66)
3 (11)
2 (8)
1 (4)
2 (7)
27
33G23
20 (74)
5 (19)
4 (15)
1 (4)
4 (15)
0.01
NS
NS
NS
NS
NS
404
M. Zecchin et al.
Table 3
ICD interventions during follow-up
Total ICD interventions during follow-up (% patients)
Total number of ICD interventions during follow-up
Total number of ICD shocks during follow-up
Appropriate ICD interventions after 12 months (% patients)
ICD implant, primary appropriate intervention interval (months)
Interventions for VT (150e220 bpm) during follow-up (% patients)
Interventions for VF (O220 bpm) during follow-up (% patients)
Inappropriate ICD shocks during follow-up (% patients)
Total inappropriate ICD shocks during follow-up
Appropriate Intervention rate (%)
80
Secondary Prevention
Primary Prevention
60
40
p = ns
20
Group B
(secondary)
P
63
220
28
41
15G14
56
26
22
9
48
974
58
57
15G18
26
41
19
12
NS
NS
NS
0.03
NS
NS
Grimm and others [15] identified the association
of non-sustained VT with left ventricular ejection
fraction !30% or with end-diastolic diameter
O70 mm as predictors of sudden death. The same
authors [16] showed that patients with a long history of disease, severe dysfunction and non-sustained
VT had the same rate of appropriate ICD interventions as patients with DC and previous cardiac
arrest or syncope of unknown origin during a
follow-up of 36 months.
The recently published DEFINITE study confirmed that patients with spontaneous ventricular
arrhythmias and left ventricular ejection fraction
%35% had a significant reduction of SD (80%) if
treated with an ICD [23]. Although not significant
( probably because of the low number of events),
total mortality reduction (34%) was similar to that
found in the MADIT II trial (31%) [18].
In contrast to these data, the AMIOVIRT [13]
showed that ICD implantation was not superior to
amiodarone in 103 patients with an ejection fraction lower than 35% and non-sustained VT. Possible
Appropriate interventions (%)
Most of these markers do not seem as useful in
patients with DC. The Cardiomyopathy Trial [12]
could not demonstrate that ICD reduced mortality
in patients with DC, symptomatic heart failure
and a left ventricular ejection fraction !30% as
the only risk factors. However, the trial was not
completed, as total mortality was much lower than
expected and only 104 patients of the planned 1348
were enroled; for this reason the study could not
reach any conclusion about the benefit of ICDs in
DC. In addition, only patients with a recent diagnosis (!9 months) were included; the outcome of
these patients is extremely unpredictable, as many
can significantly improve in the following years on
optimal medical treatment [21,22], also after exclusion of active myocarditis by endomyocardial biopsy. Moreover, in early onset DC the incidence of
sudden death can be relatively low compared with
the incidence of death due to pump failure [14].
Other authors have suggested that left ventricular dysfunction is not sufficient by itself to identify
patients with DC at higher risk of sudden death.
Group A
(primary)
LVEF ≤ 0.30 and LVEDD ≥ 70 mm (n=17)
LVEF > 0.30 or LVEDD < 70 mm (n=10)
80
60
p = 0.01
40
20
0
6
12
18
24
Follow-up (months)
0
0
6
12
18
24
follow-up (months)
Figure 1 Cumulative rate of appropriate interventions
during follow-up in the two groups.
Figure 2 Group A ( primary prevention): cumulative
rate of appropriate interventions during follow-up in
patients with left ventricular ejection fraction (LVEF)
%0.30 and left ventricular end-diastolic diameter
(LVEDD) R70 mm versus patients with LVEF R0.30 or
LVEDD %70 mm.
Role of ICDs in primary and secondary prevention in DCM
405
explanations could be the lower number of patients
enroled in the AMIOVIRT and also that ICD was
compared with amiodarone in this study.
However, it is likely that non-sustained VT has
little adjunctive role in predicting sudden death
in patients with DC, as suggested by several authors
[24,25] and recently by our group in a larger population [26]. In the present experience the rate of
ICD interventions was much higher in patients with
both severe left ventricular dysfunction and dilatation rather than in patients with non-sustained VT.
In addition, recent data from SCDHeFT seemed to
confirm that, in a larger population of patients with
heart failure and left ventricular ejection fraction
%35%, ICDs could significantly reduce total mortality by 23% [27] independently of spontaneous arrhythmias, and this was also evident in patients
with non-ischaemic cardiomyopathy.
In our study, another interesting point was the
high rate of interventions for VT (treated with antitachycardia pacing in most cases), also if no
patients had a history of sustained VT before
implantation. In addition, few cases had inducible
sustained ventricular arrhythmias at electrophysiological study but none of them had appropriate
interventions for VT during follow-up.
The secondary prevention group also included
patients with a history of syncope of unknown origin but presumably due to ventricular tachyarrhythmias [28,29]. It is well known that in this
group the risk of sudden death is considerable
[30] and the rate of appropriate ICD interventions
high [16,29], regardless of electrophysiological results [31]. Also in our study the rate of interventions, especially for fast VT, was very high in this
subgroup (78%).
patients with recent onset DC [12] or moderate to
severe left ventricular dysfunction and non sustained VT [13,23].
As in other studies [16], it has to be underlined
that ICD interventions are not synonymous with
aborted sudden death. However, 26% of patients
in group A were treated for VF or sustained VT with
rates higher than 220 bpm, a condition potentially
life-threatening especially in patients with severe
left ventricular impairment.
Study limitations
References
This was a two-centre, observational, non-randomized study analysing the efficacy of ICDs in patients
with DC. For secondary prevention we considered
only patients with class I indications for ICD implant
[11] and for primary prevention we identified
patients at higher risk on the basis of previous
published data [14,15].
The small size of the patient population was another limitation but at present no published studies
on much larger populations are available. Furthermore, in other published or presented trials on primary prevention of sudden death [12,13,23,27],
the patient population was selected on the basis
of few variables with a low positive predictive
value, such as left ventricular dysfunction and
heart failure [27], left ventricular dysfunction in
Clinical implications
This study is a preliminary observation on the potential benefit of ICDs for primary prevention in selected patients (i.e. long history of both severe left
ventricular dysfunction and dilatation despite optimal medical treatment) considered at high risk of
sudden death but otherwise with a good survival
expectancy without heart transplantation. In addition, the study confirmed that ICDs can be considered to be a treatment option in patients with
DC and syncope of unknown origin, because of
the high proportion of major arrhythmic events in
this population.
The CAT and AMIOVIRT failed to identify patients
who could benefit from ICD treatment, probably
because of the low number of patients enroled
and the low risk of the population selected, rather
than a real inefficacy of the treatment, confirmed
by other more recent trials [23,27]. Our report
underlines the need for careful patient selection;
along these lines, it is likely that also other new
parameters [32] will be useful.
[1] Fuster V, Gersh BJ, Giuliani ER, Tajik AJ, Brandeburg RO,
Frye RL. The natural history of idiopathic dilated cardiomyopathy. Am J Cardiol 1981;47:525e31.
[2] Di Lenarda A, Secoli G, Perkan A, et al. Changing mortality
in dilated cardiomyopathy. The Heart Muscle Disease Study
Group. Br Heart J 1994;72:S46e51.
[3] Saxon LA, Stevenson WG, Middlekauff HR, et al. Predicting
death from progressive heart failure secondary to ischemic
or idiopathic dilated cardiomyopathy. Am J Cardiol 1993;
72:62e5.
[4] Grandam A, Deedwania P, Cody R, et al. Predictors of total
mortality and sudden death in mild to moderate heart
failure. J Am Coll Cardiol 1989;14:564e70.
[5] Doval HC. Class III antiarrhythmic agents in cardiac failure:
lessons from clinical trials with a focus on the Grupo de
Estudio de la Sobrevida en la Insufficiencia Cardiaca en
Argentina (GESICA). Am J Cardiol 1999;84:109Re14R.
[6] MERIT HF Investigators. Effect of metoprolol CR/XL in
chronic heart failure: Metoprolol CR/XL Randomized
406
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
M. Zecchin et al.
Intervention Trial in Congestive Heart Failure (MERIT-HF).
Lancet 1999;353:2001e7.
Packer M, Fowler MB, Roecker EB, et al. Effect of carvedilol
on the morbidity of patients with severe chronic heart
failure: results of the carvedilol prospective randomized
cumulative survival (COPERNICUS) study. Circulation 2002;
106:2194e9.
CIBIS II Investigators. The Cardiac Insufficiency Bisoprolol
Study II (CIBIS II): a randomized trial. Lancet 1999;353:
9e13.
Ehlert FA, Cannom DS, Renfroe EG, et al. Comparison of
dilated cardiomyopathy and coronary artery disease in
patients with life-threatening ventricular arrhythmias:
differences in presentation and outcome in the AVID
registry. Am Heart J 2001;142:816e22.
Priori SG, Aliot E, Blomström-Lundqvist C, et al. Task Force
on Sudden Cardiac Death of the European Society of
Cardiology. Eur Heart J 2001;22:1374e450.
American College of Cardiology/American Heart Association Task Force. ACC/AHA/NASPE Guideline Update
for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices: 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;
106:2145e61.
Bansch D, Antz M, Boczor S, et al. Primary prevention of
sudden cardiac death in idiopathic dilated cardiomyopathy:
the Cardiomyopathy Trial (CAT). Circulation 2002;105:
1453e8.
Strickberger SA, Hummel JD, Bartlett TG, et al. Amiodarone
vs implantable cardioverter defibrillator: randomized trial
in patients with nonischemic dilated cardiomyopathy and
asymptomatic nonsustained ventricular tachycardiad
AMIOVIRT. J Am Coll Card 2003;41:1707e12.
Zecchin M, Lenarda A, Bonin M, et al. Incidence and
predictors of sudden cardiac death during long-term
follow-up in patients with dilated cardiomyopathy on
optimal medical therapy. Ital Heart J 2001;2:213e21.
Grimm W, Glaveris C, Hoffmann J, et al. Arrhythmia risk
stratification in idiopathic dilated cardiomyopathy based
on echocardiography, 12-lead electrocardiogram, signalaveraged electrocardiogram and 12-hour Holter electrocardiogram. Am Heart J 2000;140:43e51.
Grimm W, Hoffmann JJ, Muller HH, Maisch B. Implantable
defibrillator event rates in patients with idiopathic dilated
cardiomyopathy, nonsustained ventricular tachycardia on
Holter and a left ventricular ejection fraction below 30%.
J Am Coll Cardiol 2002;39:780e7.
WHO/ISFC Task Force. Report of the 1995 WHO/ISFC task
force on the definition and classification of cardiomyopathies. Circulation 1996;93:841e2.
Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction
and reduced ejection fraction. N Engl J Med 2002;346:
877e83.
Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with
an implanted defibrillator in patients with coronary disease
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
at high risk for ventricular arrhythmias. N Engl J Med 1996;
335:1933e40.
Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN,
Hafley G. The multicenter unsustained tachycardia trial
investigators: a randomized study of the prevention of
sudden death in patients with coronary heart disease.
N Engl J Med 1999;341:1882e90.
Di Lenarda A, Gregori D, Lardieri G, et al. Metoprolol in
dilated cardiomyopathy: is it possible to identify factors
predictive of improvement? J Card Fail 1996;2:87e102.
Di Lenarda A, Hlede S, Sabbadini G, et al. Improvement of
prognosis in idiopathic dilated cardiomyopathy: role of
early diagnosis and optimized medical treatment. Study
Group on Heart Muscles Diseases. G Ital Cardiol 1999;29:
1452e62.
Kadish A, Dyer A, Daubert JP, et al. For the defribillators
in non-ischemic cardiomyopathy treatment evaluation
(DEFINITE) investigators: prophylactic defribillator implantation in patients with nonischemic dilated cardiomyopathy. New Engl J Med 2004;350:2151e8.
von Olshausen K, Schafer A, Mehmel HC, Schwarz F, Senges
J, Kubler W. Ventricular arrhythmias in idiopathic dilated
cardiomyopathy. Br Heart J 1984;51:195e201.
Huang SK, Messer JV, Denes P. Significance of ventricular
tachycardia in idiopathic dilated cardiomyopathy: observations in 35 patients. Am J Cardiol 1983;51:507e12.
Zecchin M, Di Lenarda A, Brun F, et al. Is nonsustained ventricular tachycardia predictive for total and
sudden death in dilated cardiomyopathy? Eur Heart J 2003;
24(abstract suppl):695.
SCD-HeFT: ICD cuts all-cause mortality by 23% in NYHA class
2-3 HF. Presented at hotline session of the American
College of Cardiology Convention. New Orleans, LA, USA
March 2004.
Fazio G, Veltri EP, Tommaselli G, et al. Long term follow-up
of patients with nonischemic dilated cardiomyopathy and
ventricular tachycardias treated with implantable cardioverter defibrillators. Pacing Clin Electrophysiol 1991;14:
1905e10.
Knight B, Goyal R, Pelos F, et al. Outcome of patients with
nonischemic dilated cardiomyopathy and unexplained
syncope treated with an implantable defibrillator. J Am
Coll Cardiol 1999;33:1964e70.
Middlekauff HR, Stevenson WG, Stevenson LW, et al.
Syncope in advanced heart failure: high risk of sudden
death regardless of origin of syncope. J Am Coll Cardiol
1993;21:110e6.
Brilakis ES, Shen WK, Hammill SC, et al. Role of programmed ventricular stimulation and implantable cardioverter defibrillators in patients with idiopathic dilated
cardiomyopathy and syncope. Pacing Clin Electrophysiol
2001;24:1623e30.
Hohnloser SH, Klingenheben T, Bloomfield D, Dabbous O,
Cohen RJ: Usefulness of microvolt t-wave alternans for
prediction of ventricular tachyarrhythmic events in patients with dilated cardiomyopathy: results from a prospective observational study. J Am Coll Cardiol 2003;41:
2220e4.