Therapeutic Decision Tree for Patients

with Sustained Ventricular

Tachyarrhythmias or Aborted Cardiac
Arrest: A Critical Review of the
Antiarrhythmics Versus Implantable
Defibrillator Trial and the Canadian
Implantable Defibrillator Study
Jeronimo Farre,

MD, PhD,

Jose A. Cabrera,
Jose M.Rubio,

MD, PhD,

Jose Romero,

MD,

and

MD

Antiarrhythmic drugs, mainly amiodarone and sotalol,

radiofrequency catheter ablation, and the implantable
cardioverter defibrillator (ICD) are the 3 therapeutic options in patients with sustained ventricular tachycardia
(VT) or ventricular fibrillation (VF). Idiopathic VT, incessant VT, frequently recurring, hemodynamically stable
VT, and VT based on bundle branch reentry, are candidates for radiofrequency catheter ablation. Patients with
high-risk ventricular tachyarrhythmias should receive
ICDs as initial therapy. Two studies, the Antiarrhythmics
Versus Implantable Defibrillator trial (AVID) and the Canadian Implantable Defibrillator Study (CIDS) have tried
to approach the problem of these high-risk ventricular
tachyarrhythmias. Although at 3 years, the ICD in AVID
demonstrated a significant relative risk reduction over
amiodarone of 31.5%, CIDS could not duplicate this
finding. At 3 years, the relative risk reduction con-

ferred by the ICD over amiodarone in CIDS was only

13.7%. A careful analysis of both studies suggests
that CIDS was insufficiently powered to demonstrate
statistically significant benefits similar to those shown
by AVID, and furthermore, seemed to include an undetermined number of low-risk VT patients. The problem in the CIDS trial in this regard was the recruitment
of patients in whom the inclusion criteria were met by
the arrhythmias induced during the electrophysiology
stimulation study, but which did not exist in real life.
In addition CIDS included 14% of patients with (1)
undocumented syncope and inducible monomorphic
sustained VT; or (2) long runs of spontaneous nonsustained VT. Under these circumstances, the therapeutic
implications of AVID remain unchallenged. 2000
by Excerpta Medica, Inc.
Am J Cardiol 2000;86(suppl):44K51K

ntil the 1980s, the therapeutic options available to

prevent arrhythmia recurrences and sudden elecU
tric death in patients with documented chronic recur-

PROGNOSIS OF PATIENTS WITH

DOCUMENTED VENTRICULAR
TACHYARRHYTHMIAS

rent sustained ventricular tachycardia (VT) or those

resuscitated from ventricular fibrillation (VF) were
limited to antiarrhythmic drugs or cardiac transplantation in very desperate cases. The implantable cardioverter defibrillator (ICD) and catheter ablation
techniques have widened the still limited therapeutic
options in this field. Surgical techniques developed in
the late 1970s have been almost abandoned due to an
unacceptably high mortality. The selection of the best
initial treatment in these patients is difficult. A number
of factors should be taken into consideration (Table
1).

Patients can be categorized into 2 major groups:

those resuscitated from cardiac arrest and those with
VT. Spontaneously occurring VT can be sustained and
nonsustained. Nonsustained VT is considered elsewhere in this symposium supplement.
Patients resuscitated from cardiac arrest: It is estimated that 80% of patients experiencing sudden
cardiac death have coronary artery disease and that the
great majority of the remaining patients have associated structural heart disease.1A minority of patients
surviving cardiac arrest due to VF or polymorphic VT
have no structural heart disease; the latter patients
have been considered elsewhere in this issue.
Patients that have been resuscitated from cardiac
arrest without identifiable precipitating factors are at
high risk of developing a second fatal episode. Studies
in the 1970s demonstrated that survivors from episodes of primary VF (VF not associated with acute
myocardial infarction or any other obvious identifiable
and correctable cause) had a 2-year mortality rate 3

From the Department of Cardiology, Fundacion Jimenez Daz, Madrid, Spain.

Address for reprints: Jeronimo Farre, Professor of Cardiology and
Chairman, Department of Cardiology, Fundacion Jimenez Daz, Av.
Reyes Catolicos2, 28040, Madrid, Spain.

44K

2000 by Excerpta Medica, Inc.

All rights reserved.

0002-9149/00/$ see front matter

PII S0002-9149(00)01228-5

times higher than that of patients resuscitated from VF

associated with acute myocardial infarction.2 Many of
these patients experience further episodes of VF.
Class I antiarrhythmic drugs have failed to reduce the
risk of sudden death in primary VF, even when guided
by repeated electrophysiologic stimulation studies or
periods of Holter monitoring. The initial Cardiac Arrest in Seattle: Conventional versus Amiodarone Drug
Evaluation (CASCADE) trial demonstrated that class
I antiarrhythmic drugs were less effective than amiodarone in reducing both total mortality and sudden
death in patients resuscitated from cardiac arrest. The
CASCADE protocol did not consider the use of an
ICD, and had to be modified after the investigators
realized that there was a 17% 1-year incidence of VF
or cardiac death in the first 146 patients of whom only
15% had received ICDs. Subsequently, 81% of the
recruited patients received ICDs apart from the antiarrhythmic drug treatment as initially planned in the
study.3 In the CASCADE trial, amiodarone provided a
98% 2-year survival free of syncopal shocks in patients having received ICDs. It seemed necessary to
investigate if this result was due to the ICD or solely
to amiodarone. This issue has been addressed by 3
randomized, prospective, trials: Antiarrhythmics Versus Implantable Defibrillator (AVID), Canadian Implantable Defibrillator Study (CIDS), and Cardiac Arrest Study Hamburg (CASH). Only AVID and CIDS
have come to a final publication 4,5 and these 2 studies
will be reviewed in detail in this article. The only
portion of the CASH study that has been published as
of this writing is the propafenone arm of the trial. An
interim analysis of the CASH results revealed a significantly higher total mortality and cardiac arrest
recurrence in patients randomized to propafenone
compared with those randomized to the ICD treatment
limb. For this reason, the propafenone arm was terminated and the study continued with the ICD, amiodarone, and metoprolol arms.6
Patients with spontaneous sustained VT: Patients
with idiopathic forms of sustained VT represent a
low-risk group as far as mortality is concerned. Idiopathic VT arising from the right ventricular outflow
tract and left VT of the so-called fascicular type are
the most frequent types of VT without demonstrable
structural heart disease. In childhood, idiopathic VT is
rare and a recent retrospective registry has shown no
mortality in a series of 98 patients followed-up for an
average of 47 months. Spontaneous resolution of this
arrhythmia is observed more frequently when the arrhythmia develops in the first year of life compared
with its occurrence beyond that age (89% resolution
rate vs 56%), or when its origin is right ventricular as
compared with left VT (76% vs 37%).7 The prognosis
of idiopathic VT is also benign in adults. VT truly
arising from the right ventricular outflow tract and
idiopathic fascicular left VT are best treated with
radiofrequency catheter ablation rather than with antiarrhythmic drugs.8 15
The prognosis of patients with structural heart disease developing spontaneous sustained VT depends
on several factors, the most important of which are:

(1) presentation as cardiac arrest; (2) New York Heart

Association (NYHA) class for dyspnea; (3) left ventricular ejection fraction; and (4) symptoms during the
episode, particularly syncope. In patients with a past
history of myocardial infarction, the presence of multiple myocardial infarctions and the time interval from
the last myocardial infarction to the presentation of
VT, also have prognostic implications.16 22 It is difficult to judge which of the aforementioned factors are
the most important to predict cardiac mortality and
above all, arrhythmic death. It is admitted that ventricular tachyarrhythmias presenting as cardiac arrest,
syncopal VT, or severely symptomatic VT in patients
with a depressed left ventricular ejection fraction,
probably represent the 3 categories at the highest risk
of sudden arrhythmic death. These serious ventricular tachyarrhythmias were the target of the AVID
study.23
Well-tolerated, sustained VT, or symptomatic,
nonsyncopal VT developing in patients with a preserved left ventricular ejection fraction (0.40) represent lower-risk scenarios.17,24 Sarter et al,24 in a
retrospective study of 124 patients who received electrophysiologically guided therapy for hemodynamically stable VT after remote myocardial infarction,
found a low sudden death rate during follow-up (2%,
3%, and 7%, at 1, 2, and 3 years, respectively). In
addition, a recent subanalysis of the AVID data has
suggested that patients with a relatively well-preserved left ventricular ejection fraction (0.35) may
not have better survival when treated with the ICD as
compared with amiodarone or sotalol.25 For these
reasons, in patients with structural heart disease and
hemodynamically stable VT, as well as in those in
whom the left ventricular ejection fraction is relatively
preserved, the ICD, amiodarone, sotalol, and radiofrequency catheter ablation are all reasonable therapeutic
options.

ROLE OF RADIOFREQUENCY
CATHETER ABLATION IN SUSTAINED
VENTRICULAR TACHYARRHYMIAS
DEVELOPING IN PATIENTS WITH
STRUCTURAL HEART DISEASE
Radiofrequency catheter ablation of VT in patients
with structural heart disease is a complex procedure.26 36 The major indications are listed in Table 2.
Most of the patients must have hemodynamically stable VT to allow mapping and repeated inductions of
the arrhythmia during the procedure. The use of antiarrhythmic drugs in patients with a left ventricular
ejection fraction 0.40 may render mappable a previously hemodynamically unstable VT. The indications, difficulties, methodology, and results of radiofrequency catheter ablation in patients after myocardial infarction who are developing sustained VT have
been reviewed elsewhere.31
An important problem in patients with structural
heart disease is the meaning of nonclinical VT that is
also induced during the procedure. Those that are
mappable should most likely be subjected to ablation.
The problem is ascertaining the meaning of nonmapA SYMPOSIUM: ELECTRICAL THERAPIES FOR THE HEART

45K

TABLE 1 Factors to Be Considered in Selection of Therapy for Patients with Documented

or Suspected Sustained Ventricular Tachycardia
1.
2.
3.
4.
5.
6.

Type of ventricular tachycardia, documented during the arrhythmic episode

Symptoms during the arrhythmic episode
Type and severity of underlying heart disease
Evidence based on controlled clinical trials conducted in similar patients
Suitability of the patient for the theoretically optimal therapy
Available resources

TABLE 2 Indications for Radiofrequency Catheter Ablation in Patients with Sustained

Ventricular Tachycardia
A. Idiopathic ventricular tachycardia
1. Idiopathic right ventricular outflow tract tachycardia
2. Fascicular idiopathic left ventricular tachycardia
B. Ventricular tachycardia in patients with structural heart disease
1. Incessant ventricular tachycardia
2. Hemodynamically stable ventricular tachycardia
3. Symptomatic ventricular tachycardia and left ventricular ejection fraction 0.35
4. Bundle branch reentry ventricular tachycardia

pable, hemodynamically unstable, rapid VT that is

frequently induced in these patients with programmed
electrical stimulation after the clinical VT has been
abolished. Most institutions opt for implanting an ICD
in these patients. This decision is usually based on an
intention to protect the patient against the potential
development of these previously not observed but
potentially lethal arrhythmias. The decision can be
justified if we take into consideration the observation
by Rothman et al32 that 53% of the patients in whom
apparent nonclinical VT is inducible after the successful ablation of the clinical VT develop recurrent arrhythmias including sudden death. Direct-current
shock ablation and intracoronary alcohol ablation
were used successfully in patients with incessant
VT.3739 Both methods have been replaced by radiofrequency catheter ablation techniques.40 42
Bundle branch reentry VT must be suspected in
various conditionsin general situations in which the
bundle branch system is diseased with or without
associated myocardial or valvular disease. Ventricular
dilation is a frequent additional factor that facilitates
bundle branch reentry. Radiofrequency ablation of the
right- and eventually of the left-bundle branch is effective in preventing further recurrences of bundle
branch reentry VT, provided that other types of VT
present in some patients are treated as well. This
implies the additional use of drugs and frequently of
an ICD in this patient population.43 49
Patients that have received ICDs may require the
use of catheter ablation techniques after the implant of
the device. This may be the result of a modification of
the arrhythmogenic substrate or a poor indication for
the ICD. The arrhythmogenic substrate can be modified either because of the natural evolution of the
underlying heart disease or, more frequently, due to
the concomitant administration of antiarrhythmic
drugs to treat supraventricular arrhythmias or to avoid
frequent shocks for syncopal VT or VF.50
46K THE AMERICAN JOURNAL OF CARDIOLOGY

ROLE OF THE ICD IN PATIENTS

WITH MALIGNANT SUSTAINED
VENTRICULAR TACHYARRHYTHMIAS
The publication of the AVID trial seemed to simplify the therapeutic approach to patients resuscitated
from cardiac arrest or with syncopal or severely symptomatic VT with a depressed left ventricular ejection
fraction.4 AVID found that the ICD significantly reduced mortality (39 20%, 27 21%, and 31
21% at 1, 2, and 3 years, respectively). A theoretically
similar study conducted in Canada,CIDS did not
duplicate these findings. Although a per-year mortality reduction of nearly 20% was found in patients
receiving the ICD, the differences did not reach statistical significance.5
The AVID trial: The AVID trial was a multicenter,
randomized study in patients with malignant ventricular tachyarrhythmias, designed to compare 2 treatment strategies: ICD and the 2 most effective antiarrhythmic agents (amiodarone and sotalol). At the end
of the study, 96.2% of the patients assigned to antiarrhythmic drug treatment had received amiodarone.
Thus, for practical purposes, the trial should be
viewed as a comparison between ICD and amiodarone. The AVID trial included patients (1) resuscitated
from VF; (2) with spontaneous syncopal sustained
VT; or (3) with sustained VT, a left ventricular ejection fraction 0.40 and severe symptoms (near-syncope, congestive heart failure, and/or angina). A registry was maintained of patients who qualified for the
study but did not undergo randomization as well as of
patients with VF or VT who were not eligible for
randomization. The recruitment of patients began on
June 1, 1993 and concluded on April 7, 1997. The
primary endpoint was overall mortality. Secondary
endpoints were cost and quality of life. Although the
goal was to enroll 1,200 patients, the trial was prematurely stopped when 1,016 patients had been randomized because the difference in the primary endpoint

VOL. 86 (9A)

NOVEMBER 2, 2000

TABLE 3 Comparison of Antiarrhythmics Versus Implantable

Defibrillator (AVID) and Canadian Implantable Defibrillator
Study (CIDS) Trials
AVID
Planned sample size (n)
Predicted 3-yr mortality (%)
Predicted 3-yr RRR by ICD (%)
Patients randomized (n)
Patients completing followup (%)
Age (yr)
Coronary artery disease (%)
Heart failure (%)
LVEF
Recruitment period (mo)
No ICD in ICD arm (%)
AMD dose at 3 yr (mg/day)
ICD patients receiving AMD
at 3 yr (%)
AMD patients receiving ICD
at 3 yr (%)
Mean follow-up (mo)
Deaths, n (%)
ICD mortality at 3 yr (%)
AMD mortality at 3 yr (%)
RRR at 3 yr (%)
VF or cardiac arrest (%)
Syncopal VT (%)
Other VT (%)
Undocumented syncope and
PES-VT (%)

1,200
30
30
1,016
99.7

CIDS
650
30
33
659
100

65
81
46
0.32 0.13
46
2
256
33.7

63.5
82
50
0.34 0.14
76
5.5
262
21.7

24.3

18.6

18.2
202 (20)
24.6
35.9
31.5
45
21
34
0

35.4
181 (27)
23.32
27.03
13.7
48
13
25
14

AMD amiodarone; ICD implantable cardioverter-defibrillator; PES-VT:

monomorphic VT induced with programmed electrical stimulation; RRR
relative risk reduction.

between both groups had crossed the statistical boundary for early termination of the study. The presumed
3-year mortality in the amiodarone group was 30%
and the anticipated relative mortality reduction provided by the ICD was estimated at 30% (Table 3).23
The CIDS trial: The CIDS trial was also a multicenter, randomized study in patients with malignant
ventricular tachyarrhythmias, designed to compare 2
initial treatment strategies: ICD and amiodarone. The
CIDS trial included patients with (1) documented VF;
(2) out-of-hospital cardiac arrest requiring defibrillation or cardioversion; (3) documented, sustained VT
causing syncope; (4) other documented, sustained VT
at a rate 150 beats per minute, causing presyncope
or angina, provided the patient had a left ventricular
ejection fraction 0.35; and (5) unmonitored syncope
with subsequent documentation of either spontaneous
VT lasting 10 seconds or sustained (30 seconds)
monomorphic VT induced by programmed ventricular
stimulation. It is important to note that patients were
considered to meet inclusion criteria 3 or 4 on the
basis of a ventricular tachyarrhythmia induced in the
electrophysiology laboratory if the following 2 conditions were fulfilled: (1) they had prior, spontaneous,
documented, sustained VT, and (2) the induced arrhythmia was monomorphic, sustained VT. Recruitment of patients began on October 1990 and ended by

January 1997. The mean duration of follow-up was

2.9 and 3.0 years for amiodarone and ICD patients,
respectively. The primary endpoint was overall mortality. The goal was to enroll 650 patients to detect a
relative mortality reduction of 33% by the ICD from a
presumed 3-year mortality rate of 30% in the amiodarone group (Table 3).
Major findings of the AVID and CIDS trials: The
AVID trial found a statistically significant reduction in
total mortality in the group of patients receiving the
ICD. The expected mortality at 3 years for the amiodarone group was 30% and the unadjusted observed
mortality at that interval was 35.9%. Because the ICD
group had a mortality of 24.6%, the relative risk
reduction was 31.5%. At 3 years, the CIDS trial did
not duplicate these results. The predicted mortality at
this interval was 30% for the amiodarone group and
the real mortality was 27.0%. Because at 3 years the
ICD group of the CIDS had a mortality of 23.3%, the
relative risk reduction was only 13.7%. The latter
figure probably better reflects the real outcome of the
CIDS trial than the per-year mortality rate. The peryear mortality rate (10.2% vs 8.3%, representing a
relative risk reduction by the ICD of 19.7%) is influenced by the long follow-up of 20% of the patients
who were exposed to risk for at least 4 years. In
addition, the study as planned had presumed a relative
risk reduction at 3 years of 33%. Thus, this is the
proper way of expressing the results.
Are the AVID and CIDS populations similar? Although the CIDS investigators state that both trials are
almost identical in terms of design and patient characteristics, this assumption must be questioned. Table
3 compares some of the characteristics of both studies.
Looking at that table it seems that the differences, if
any, are minimal. A few among such minor differences deserve further comment:
1. The mean left ventricular ejection fraction is
slightly higher in CIDS as compared with the AVID
(34 vs 32%, respectively). The mean left ventricular
ejection fraction in the AVID VT group was 0.29 and
the CIDS investigators do not provide this information. In the CIDS, some 12% of the patients had a left
ventricular ejection fraction 0.20. In the initial publication of the AVID study,5 this information is not
given. A subsequent article analyzing the ICD effectiveness in relation to the ventricular function indicates that 14% of the AVID patients had a left ventricular ejection fraction 0.20.25
2. A greater proportion of patients allocated to
receive ICDs did not get the device implanted in the
CIDS as compared with AVID (5.5% vs 2%). This
difference is particularly important if we take into
consideration that, of the 328 patients allocated to
receive ICDs, 7 (2.1%) died while waiting to get the
device. This penalty on the ICD arm of the CIDS trial
does not seem to have existed in the AVID study.51
3. Although the type of ventricular arrhythmias is
said to be similar in both trials, in our opinion this is
the area where the most important differences are
found or can be presumed to exist. This is discussed in
the following section of the article.
A SYMPOSIUM: ELECTRICAL THERAPIES FOR THE HEART

47K

FIGURE 1. Criteria numbers 3 and 4 for inclusion into the Canadian Implantable Defibrillator
Study (CIDS) trial could be met on the basis of the ventricular tachycardia (VT) induced during the stimulation study provided the latter was monomorphic and the patient had any kind
of spontaneously occurring sustained VT. This means that patients with asymptomatic sustained VT could qualify to be recruited if a syncopal, monomorphic, sustained VT was induced by programmed stimulation. They could also qualify if their left ventricular ejection
fraction was <0.35 and during the stimulation study the VT was symptomatic. In addition,
patients with symptomatic VT and a relatively preserved left ventricular ejection fraction
could qualify for the study if during the stimulation study a monomorphic, sustained, syncopal VT was induced. These types of patients were not enrolled in the Antiarrhythmics Versus
Implantable Defibrillator Trial (AVID) trial and clearly have a lower risk than the VT patients
included in the latter study.

Type of ventricular arrhythmias of patients in the

AVID and CIDS trials: The proportion of patients with

VF or resuscitated from a cardiac arrest with a procedure requiring cardioversion or defibrillation was similar in the AVID and CIDS trials (46% and 48%,
respectively). VT patients seem to be potentially very
different. As stated by the CIDS investigators, patients
having a documented sustained VT that is hemodynamically stable can meet the criteria for syncopal VT
if, independent of the value of the left ventricular
ejection fraction, a syncopal monomorphic sustained
VT was elicited during the electrophysiology study.
We do not know how many among the 13% of the
CIDS patients categorized as having syncopal VT met
this criterion on the basis of the arrhythmia induced by
programmed stimulation. Moreover, inclusion criteria
number 4, namely symptomatic VT in patients with a
left ventricular ejection fraction 0.35 can be met by
patients with this level of systolic dysfunction and
clinically occurring asymptomatic VT, if during the
electrophysiology study a nonclinical, symptomatic
VT is induced. The meaning of this is summarized in
Figure 1. Finally, in CIDS, but not in the AVID study,
14% of the recruited patients only had syncope of
unknown origin plus an inducible monomorphic VT
during the electrophysiology study.
It seems, therefore, that the CIDS trial has included
an undetermined number of patients with hemodynamically stable VT, irrespective of their left ventricular ejection fraction, as well as an also unknown
number of patients with either spontaneously occur48K THE AMERICAN JOURNAL OF CARDIOLOGY

ring VT (asymptomatic or symptomatic) and a preserved left ventricular function. These patients, as we
have already discussed, seem to be at low risk of
developing sudden arrhythmic death and, therefore,
little benefit from the ICD can be anticipated.
The AVID registry has shown that patients with
syncopal VT represent the group with the highest risk
of death. In addition, this registry has shown that
patients with unexplained syncope that are inducible
during the electrophysiology study represent a group
with a risk that seems lower than that of patients with
sustained VT/VF (Figure 2).52
Therefore, CIDS recruited more low-risk patients
(14% with syncope of unknown origin not enrolled in
the AVID) and fewer high-risk patients than AVID
(13% vs 21% syncopal VT). This 8% difference in the
high-risk syncopal VT group is an underestimation
because, in CIDS, an undetermined number of patients
categorized with syncopal VT did not have a spontaneously occurring syncopal VT.
Are other potential explanations for the AVID and
CIDS discrepancies? The CIDS investigators postulate

that the different concomitant use of -blocking

agents in their amiodarone patients may account for
their better than expected outcome due to the presumed and never totally demonstrated, positive interaction between both drugs. Thus, at 1 year, 17% of the
AVID amiodarone patients were on concomitant blockers as compared with 24% in CIDS. The AVID
investigators have shown using the registry data that
-blocker use improved survival only in patients with

VOL. 86 (9A)

NOVEMBER 2, 2000

FIGURE 2. This graph has been reconstructed from Figure 4 of Anderson et al,52 reporting
on the Antiarrhythmics Versus Implantable Defibrillator Trial (AVID) registry. As shown in the
AVID registry, patients with syncopal sustained VT represent a higher-risk group than patients with unexplained syncope who are inducible during a stimulation study. The Canadian
Implantable Defibrillator Study (CIDS) had fewer (>8%, because an undetermined number of
patients with syncopal VT were only so at the stimulation study but not during the spontaneously occurring arrhythmia) syncopal VT than AVID and a 14% low-risk group of patients
with unexplained syncope. The latter group was not randomized in the AVID trial. (Adapted
from Circulation.52)

VF or symptomatic VT who had not received either an

ICD or amiodarone. In patients receiving amiodarone,
there is a nonsignificant trend for improved survival
when -blockers are added, but a similar tendency
was found in ICD patients.53 Because the differences
in the concomitant use of -blockers between CIDS
and AVID are more marked in the ICD group (59% vs
40%, respectively) we refute the idea that -blocker
use accounts for the different outcome of both trials.
The crossover rate does not explain why CIDS has
not duplicated the AVID results (Table 3). Thus, at 3
years, 24.3% of the AVIDamiodarone patients and
18.6% of the CIDSamiodarone patients, received
ICDs. At this same interval, the ICD groups received
amiodarone in 33.7% of the AVID patients and in
21.7% of the CIDS patients.
The concomitant use of class I drugs or sotalol in
both studies is a concern. In CIDS, at 1 year, 8.4% of
the ICD patients also received a class I agent as
compared with 7.1% in AVID. More striking are the
differences with sotalol use. At 1 year, 21.5% of the
ICDCIDS patients received sotalol as compared with
1.8% of the ICDAVID patients. Whether these differences account for any practical consequence is
speculative.
Was CIDS sufficiently powered? The reader may ask,
why 2 studies, theoretically identical and departing
from almost the same assumptions, estimated sample
sizes totally differently for the very same outcome
(1,200 patients in AVID and 650 in CIDS). AVID
tested the null hypothesis that there was no difference
in overall mortality between therapy with an ICD and
amiodarone and considered a 2-sided level of 0.05

for comparisons of survival distributions. In other

words, AVID was powered to determine if either of
the 2 treatment strategies was superior to the other.
The CIDS analysis, however, was originally designed
as a 1-sided comparison exclusively to test the therapeutic superiority of the ICD over amiodarone. As
stated by the CIDS investigators in their recently
published study, they present 2-sided statistical results
in response to a demand from the reviewers and editor
of Circulation.5 In our opinion, the study was not
powered to demonstrate significant differences with
2-sided statistical tests. In this regard, a type II error
cannot be excluded.

CONCLUSIONS
Patients resuscitated from cardiac arrest, patients
with spontaneous syncopal sustained VT associated
with structural heart disease, and patients with clinically occurring severely symptomatic sustained VT
and a left ventricular ejection fraction 0.35, should
receive an ICD as initial therapy. In patients with
idiopathic VT, radiofrequency catheter ablation
should be tried as the first therapeutic option provided
this intervention is performed at an experienced center. Patients with hemodynamically stable VT and
patients with VT and preserved left ventricular function can be treated with drugs, preferably amiodarone,
or eventually sotalol, or even pure -blockers. In some
of these patients, radiofrequency catheter ablation can
be considered if an experienced team is available.
Incessant VT that cannot be controlled with drugs,
frequently recurring almost asymptomatic VT, and
VT due to bundle branch reentry, are clear candidates
A SYMPOSIUM: ELECTRICAL THERAPIES FOR THE HEART

49K

for radiofrequency catheter ablation. An ICD can also

be offered to a patient who has recurrences despite
optimal antiarrhythmic drug therapy and in whom the
antitachycardia pacing abilities of the device could be
used to terminate the arrhythmia and avoid the burden
of repeated hospital admissions. In patients with syncope of uncertain origin and inducible VT, the decisions must be individualized.
Despite the results of the CIDS trial, most of the
therapeutic implications of the AVID study remain
valid. The CIDS trial was not powered to show statistically significant differences with 2-sided tests, and
also included a significant proportion of VT patients
with a lower risk than the VT population of AVID.
The insufficient power and a low sudden death risk of
an undetermined number of VT patients most likely
accounts for the differences in outcome of the CIDs
and AVID trials.

1. Zipes DP, Wellens HJJ. Sudden cardiac death. Circulation 1998;98:2334

2351.
2. Cobb LA, Baum RS, Alvarez H III, Schaffer WA. Resuscitation from out-of-

hospital ventricular fibrillation: 4 years follow-up. Circulation 1975;52(suppl

III):III223III228.
3. Dolack GL. Clinical predictors of implantable cardioverter-defibrillator shocks
(results of the CASCADE trial). Am J Cardiol 1994;73:237241.
4. The Antiarrhythmics Versus Implantable Defibrillators (AVID) Investigators.
A comparison of antiarrhythmic-drug therapy with implantable defibrillators in
patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med
1997;337:1576 1583.
5. Connolly SJ, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS, Mitchell LB,
Green MS, Klein GJ, OBrien B. Canadian Implantable Defibrillator Study
(CIDS): a randomized trial of the implantable cardioverter defibrillator against
amiodarone. Circulation 2000;101:12971302.
6. Siebels J, Cappato R, Ruppel R, Schneider MAE, Kuck KH, and the CASH
investigators. Preliminary results of the Cardiac Arrest Study Hamburg (CASH).
Am J Cardiol 1993;72(suppl 16):109F113F.
7. Pfammatter JP, Paul T. Idiopathic ventricular tachycardia in infancy and
childhood: a multicenter study on clinical profile and outcome. Working Group
on Dysrhythmias and Electrophysiology of the Association for European Pediatric Cardiology. J Am Coll Cardiol 1999;33:206772.
8. Varma N, Josephson ME. Therapy of idiopathic ventricular tachycardia.
J Cardiovasc Electrophysiol 1997;8:104 116.
9. Wen MS, Taniguchi Y, Yeh SJ, Wang CC, Lin FC, Wu D. Determinants of
tachycardia recurrences after radio frequency ablation of idiopathic ventricular
tachycardia. Am J Cardiol 1998;81:500 503.
10. Smeets JL, Rodriguez LM, Timmermans C, Wellens HJJ. Radio frequency
catheter ablation of idiopathic ventricular tachycardias in children. PACE Pacing
Clin Electrophysiol 1997;20:2068 271.
11. Coggins DL, Lee RJ, Sweeney J, Chein WW, Van Hare G, Epstein L,
Gonzalez R, Griffin JC, Lesh MD, Scheinman MM. Radio frequency catheter
ablation as a cure for idiopathic tachycardia of both left and right ventricular
origin. J Am Coll Cardiol 1994;23:13331341.
12. Peinado R, Arenal A, Almendral J, Villacastin JP, Merino JL, MartinezAlday JD, Pastor A, Medina-Moreno O, Valero R, Delcan JL. Radio frequency
catheter ablation of ventricular tachycardia in patients without apparent structural
heart disease. Rev Esp Cardiol 1994;47:803 810.
13. Wen MS, Yeh SJ, Wang CC, Lin FC, Chen IC, Wu D. Radio frequency
ablation therapy in idiopathic left ventricular tachycardia with no obvious structural heart disease. Circulation 1994;89:1690 1696.
14. Klein LS, Shih HT, Hackett FK, Zipes DP, Miles WM. Radio frequency
catheter ablation of ventricular tachycardia in patients without structural heart
disease. Circulation 1992;85:1666 1674.
15. Nakagawa H, Beckman KJ, McClelland JH, Wang X, Arruda M, Santoro I,
Hazlitt HA, Abdalla I, Singh A, Gossinger H. Lazzara R. Radio frequency
catheter ablation of idiopathic left ventricular tachycardia guided by a Purkinje
potential. Circulation 1993;88:26072617.
16. DiCarlo LA, Morady F, Sauve MJ, Malone P, Davis JC, Evans-Bell T,
Winston SA, Scheinman MM. Cardiac arrest and sudden death in patients treated
with amiodarone for sustained ventricular tachycardia or ventricular fibrillation:
risk stratification based on clinical variables. Am J Cardiol 1985;55:372374.
17. Brugada P, Talajic M, Smeets J, Mulleneers R, Wellens HJJ. The value of the
clinical history to assess prognosis of patients with ventricular tachycardia or
ventricular fibrillation after myocardial infarction. Eur Heart J 1989;10:747752.
18. Herre JM, Sauve MJ, Malone P, Griffin JC, Helmy I, Langberg JJ, Goldberg
H, Scheinman MM. Long-term results of amiodarone therapy in patients with

50K THE AMERICAN JOURNAL OF CARDIOLOGY

recurrent sustained ventricular tachycardia or ventricular fibrillation. J Am Coll

Cardiol 1989;13:442 449.
19. Willems AR, Tijssen JG, van Capelle FJ, Kingma JH, Hauer RN, Vermeulen
FE, Brugada P, van Hoogenhuyze DC, Janse MJ. Determinants of prognosis in
symptomatic ventricular tachycardia or ventricular fibrillation late after myocardial infarction: the Dutch Ventricular Tachycardia Study Group of the Interuniversity Cardiology Institute of The Netherlands. J Am Coll Cardiol 1990;16:521
530.
20. Olson PJ, Woelfel A, Simpson RJ Jr, Foster JR. Stratification of sudden death
risk in patients receiving long-term amiodarone treatment for sustained ventricular tachycardia or ventricular fibrillation. Am J Cardiol 1993;71:823 826.
21. Sarter BH, Finkle JK, Gerszten RE, Buxton AE. What is the risk of sudden
cardiac death in patients presenting with hemodynamically stable sustained
ventricular tachycardia after myocardial infarction? J Am Coll Cardiol 1996;28:
122129.
22. Caruso AC, Marcus FI, Hahn EA, Hartz VL, Mason JW. Predictors of
arrhythmic death and cardiac arrest in the ESVEM trial: Electrophysiologic Study
Versus Electromagnetic Monitoring. Circulation 1997;96:1888 1892.
23. The AVID Investigators. Antiarrhythmics Versus Implantable Defibrillators
(AVID): rationale, design, and methods. Am J Cardiol 1995;75:470 475.
24. Sarter BH, Finkle JK, Gerszten RE, Buxton AE. What is the risk of sudden
cardiac death in patients presenting with hemodynamically stable sustained
ventricular tachycardia after myocardial infarction? J Am Coll Cardiol 1996;28:
122129.
25. Domanski MJ, Saksena S, Epstein AE, Hallstrom AP, Brodsky MA, Kim S,
Lancaster S, Schron E. Relative effectiveness of the implantable cardioverterdefibrillator and antiarrhythmic drugs in patients with varying degrees of left
ventricular dysfunction who have survived malignant ventricular arrhythmias.
AVID Investigators. Antiarrhythmics Versus Implantable Defibrillators. J Am
Coll Cardiol 1999;34:1090 1095.
26. Morady F, Harvey M, Kalbfleisch SJ, El-Atassi R, Calkins H, Langberg JJ.
Radio frequency catheter ablation of ventricular tachycardia in patients with
coronary artery disease. Circulation 1993;87:363372.
27. Gonska D-B, Cao K, Schaumann A, Dorszewski A, von zur Muhlen F,
Kreuzer H. Catheter ablation of ventricular tachycardia in 136 patients with
coronary artery disease: results and long-term follow-up. J Am Coll Cardiol
1994;24:1506 1514.
28. Kim YH, Sosa-Suarez G, Trouton TG, ONunain SS, Osswald S, McGovern
BA, Ruskin JN, Garan H. Treatment of ventricular tachycardia by transcatheter
radio frequency ablation in patients with ischemic heart disease. Circulation
1994;89:1094 1102.
29. Stevenson WG, Sager PT, Natterson PD, Saxon LA, Middlekauff HR, Wiener
I. Relation of pace mapping QRS configuration and conduction delay to ventricular tachycardia reentry circuits in human infarct scars. J Am Coll Cardiol
1995;26:481 488.
30. Wilber DJ, Kopp DE, Glascock DN, Kinder CA, Kall JG. Catheter ablation
of the mitral isthmus for ventricular tachycardia associated with inferior infarction. Circulation 1995;92:34813489.
31. Farre J, Rubio JM, Navarro F, Sanziani L, Rivas D, Romero J. Current role
and future perspectives for radio frequency catheter ablation of postmyocardial
infarction ventricular tachycardia. Am J Cardiol 1996;78:76 88.
32. Rothman SA, Hsia HH, Cossu SF, Chmielewski IL, Buxton AE, Miller JM.
Radio frequency catheter ablation of post infarction ventricular tachycardia:
long-term success and the significance of inducible nonclinical arrhythmias.
Circulation 1997;96:3499 3508.
33. Stevenson WG, Friedman PL, Sager PT, Saxon LA, Kocovic D, Harada T,
Wiener I, Khan H. Exploring post infarction reentrant ventricular tachycardia
with entrainment mapping. J Am Coll Cardiol 1997;29:1180 1189.
34. Stevenson WG, Friedman PL, Kocovic D, Sager PT, Saxon LA, Pavri B.
Radio frequency catheter ablation of ventricular tachycardia after myocardial
infarction. Circulation 1998;98:308 314.
35. Bogun F, Bahu M, Knight BP, Weiss R, Paladino W, Harvey M, Goyal R,
Daoud E, Man KC, Strickberger SA, Morady F. Comparison of effective and
ineffective target sites that demonstrate concealed entrainment in patients with
coronary artery disease undergoing radio frequency ablation of ventricular tachycardia. Circulation 199795:183190.
36. El-Shalakany A, Hadjis T, Papageorgiou P, Monahan K, Epstein L, Josephson ME. Entrainment/mapping criteria for the prediction of termination of ventricular tachycardia by single radio frequency lesion in patients with coronary
artery disease. Circulation 1999;99:22832289.
37. Breithardt G, Borggrefe M, Karbenn U, Schwarzmaier J, Rohner D. Successful catheter ablation of refractory incessant ventricular tachycardia in a case
with dilated cardiomyopathy. Eur Heart J 1986;7:817 819.
38. Haissaguerre M, Warin JF, Lemetayer P, Guillem JP, Blanchot P. Fulguration
of ventricular tachycardia using high cumulative energy: results in thirty-one
patients with a mean follow-up of twenty-seven months. PACE Pacing Clin
Electrophysiol 1989;12:245251.
39. Brugada P, de Swart H, Smeets JL, Wellens HJJ. Transcoronary chemical
ablation of ventricular tachycardia. Circulation 1989;79:475 482.
40. Jordaens L, Vertongen P, Provenier F. Radio frequency ablation of incessant
ventricular tachycardia to prevent multiple defibrillator shocks. Int J Cardiol
1992;37:117120.
41. Willems S, Borggrefe M, Shenasa M, Chen X, Hindricks G, Haverkamp W,
Wietholt D, Block M, Breithardt G. Radio frequency catheter ablation of ven-

VOL. 86 (9A)

NOVEMBER 2, 2000

tricular tachycardia following implantation of an automatic cardioverter defibrillator. PACE Pacing Clin Electrophysiol 1993;16:1684 1692.
42. Cao K, Gonska BD. Catheter ablation of incessant ventricular tachycardia:
acute and long-term results. Eur Heart J 1996;17:756 63.
43. Cohen TJ, Chien WW, Lurie KG, Young C, Goldberg HR, Wang YS,
Langberg JJ, Lesh MD, Lee MA, Griffin JC. Radio frequency catheter ablation
for treatment of bundle branch reentrant ventricular tachycardia: results and
long-term follow-up. J Am Coll Cardiol 1991;18:17671773.
44. Blanck Z, Dhala A, Deshpande S, Sra J, Jazayeri M, Akhtar M. Bundle
branch reentrant ventricular tachycardia: cumulative experience in 48 patients.
J Cardiovasc Electrophysiol 1993;4:253262.
45. Blanck Z, Jazayeri M, Dhala A, Deshpande S, Sra J, Akhtar M. Bundle
branch reentry: a mechanism of ventricular tachycardia in the absence of myocardial or valvular dysfunction. J Am Coll Cardiol 1993;22:1718 1722.
46. Blanck Z, Deshpande S, Jazayeri MR, Akhtar M. Catheter ablation of the left
bundle branch for the treatment of sustained bundle branch reentrant ventricular
tachycardia. J Cardiovasc Electrophysiol 1995;6:40 43.
47. Crijns HJ, Smeets JL, Rodriguez LM, Meijer A, Wellens HJJ. Cure of
interfascicular reentrant ventricular tachycardia by ablation of the anterior
fascicle of the left bundle branch. J Cardiovasc Electrophysiol 1995;6:486
492.
48. Mehdirad AA, Keim S, Rist K, Tchou P. Long-term clinical outcome of right

bundle branch radio frequency catheter ablation for treatment of bundle branch
reentrant ventricular tachycardia. PACE Pacing Clin Electrophysiol 1995;18:
21352143.
49. Merino JL, Carmona JR, Fernandez-Lozano I, Peinado R, Basterra N,
Sobrino JA. Mechanisms of sustained ventricular tachycardia in myotonic dystrophy: implications for catheter ablation. Circulation 1998;98:541546.
50. Strickberger SA, Man KC, Daoud EG, Goyal R, Brinkman K, Hasse C,
Bogun F, Knight BP, Weiss R, Bahu M, Morady F. A prospective evaluation of
catheter ablation of ventricular tachycardia as adjuvant therapy in patients with
coronary artery disease and an implantable cardioverter-defibrillator. Circulation
1997;96:15251531.
51. The AVID Investigators. Causes of death in the Antiarrhythmics Versus
Implantable Defibrillators (AVID) trial. J Am Coll Cardiol 1999;34:15521559.
52. Anderson JL, Hallstrom AP, Epstein AE, Pinski SL, Rosenberg Y, Nora MO,
Chilson D, Cannom DS, Moore R. Design and results of the Antiarrhythmics vs
Implantable Defibrillators (AVID) registry. Circulation 1999;99:16921699.
53. Exner DV, Reiffel JA, Epstein AE, Ledingham R, Reiter MJ, Yao Q, Duff HJ,
Follmann D, Schron E, Greene HL, et al. Beta-blocker use and survival in patients
with ventricular fibrillation or symptomatic ventricular tachycardia: the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial. J Am Coll Cardiol
1999;34:325333.

A SYMPOSIUM: ELECTRICAL THERAPIES FOR THE HEART

51K