Circulation. 1997;96:1713-1716
(Circulation. 1997;96:1713-1716.)
© 1997 American Heart Association, Inc.
Predicting Arrhythmic Death
A Plea for Standardized Reporting Techniques and Data Based on Continuous Electrocardiographic Monitoring
Francis E. Marchlinski, MD
From the Electrophysiology Section, Allegheny University Hospitals,
Allegheny University of the Health Sciences, The Sidney Kimmel Foundation, and
The Philadelphia Heart Institute, Philadelphia, Pa.
Correspondence to Francis E. Marchlinski, MD, Electrophysiology Section, Allegheny University Hospitals, Broad and Vine, Mail Stop 471, Philadelphia, PA 19102-1192.
Key Words: Editorials arrhythmia mortality electrophysiology sudden death
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Introduction
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Large,
multicenter studies aimed at defining optimum treatment
strategies for
patients with documented ventricular arrhythmias
and
for patients at high risk of arrhythmia events have been
completed
and continue to be established.
1 2 3 4 After finding
the answer
to the proposed study questions, the participating
investigators
recognize that they have a wealth of data collected
prospectively.
Wisely, they struggle to analyze the data to
address important
clinical questions related to their study
population.
5 6 7 8 9 Frequently, they try to identify clinical
variables that
might predict an outcome event defined by the
study.
7 9
In this issue of Circulation, Caruso and
colleagues10 perform such an analysis in patients
who enrolled in the ESVEM trial. The authors demonstrate that left
ventricular ejection fraction was the only independent
predictor of arrhythmic death or cardiac arrest in the ESVEM patient
population. The authors' data add to a long list of publications that
have identified left ventricular ejection fraction as an
important predictor of arrhythmia events, arrhythmic death, or
cardiac arrest and overall mortality rate in patients who have a
history of documented arrhythmia episodes.11 12 13 14 15 16 17 18 19
The authors also suggest that their data may help to identify a patient
group with a very low risk for recurrent, life-threatening arrhythmic
events. They indicate that only 1 of 19 patients who presented
with a cardiac arrest and had a left ventricular ejection
fraction >40% developed a life-threatening arrhythmic event during
follow-up. They suggest that these data may be important in deciding
whether to advise the patient to have implantable defibrillator
therapy. A note of caution is advised. Subgroup analyses may
result in small patient numbers in the subgroups. Confidence limits on
this presumably small defined risk of developing a life-threatening
arrhythmia must be large. Furthermore, even a risk of 5% to
10% may be too great in patients with a left ventricular
ejection fraction >40% and an excellent long-term survival rate in
the absence of a recurrent life-threatening arrhythmic
event.20 Although the information on low-risk patient
groups provided by Caruso and colleagues serves as a good starting
point for additional investigation, it is inconclusive and should not
influence clinical decision making.
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Need for Standardized Reporting Techniques
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Caruso and colleagues also indicate in their report
10
that
clinical presentation does not predict an arrhythmic
death or
cardiac arrest. At first glance, these results appear to
contradict
previous reports.
21 22 23 24 25 These prior reports
suggested
that patients presenting with
hemodynamically stable ventricular
tachycardia
(VT) might be at low risk for fatal
arrhythmia events. However,
the difficulty in comparing study
results stems from a critical
problem that we face with many reports in
the cardiac arrhythmia
literature. There is no established
standard for classifying
patients on the basis of clinical
presentation of the arrhythmia.
Groups tend to be
lumped or split in what frequently seems to
be an arbitrary fashion.
There is a tendency to create some
categories based on ECG diagnosis,
some based on hemodynamic
tolerance of the arrhythmic
event (eg, cardiac arrest and syncope),
and some based on clinical
symptoms on presentation coupled
with the response to
programmed ventricular stimulation, eg,
syncope with
inducible VT. Patients seem to only fall into one
unique subgroup,
although it is well recognized that the same
patient can have multiple
different types of arrhythmic presentations
and arrhythmic
events. A classification schema that facilitates
comparison of study
results is needed. Our colleagues in heart
failure and cardiac
transplantation have gone to great effort
to establish a
cardiovascular functional class
system.
26 27 28 A report by Braunwald
29
simplified the classification of
unstable angina. We need a
classification system for ventricular
arrhythmia
presentation that permits uniform and reproducible
categorization.
The classification schema should couple
arrhythmia diagnosis
with associated
hemodynamic symptoms. This type of classification
will
facilitate comparison of the study results, aid in decision
making
regarding therapeutic interventions, and provide a reliable
reference
for selecting patients who are appropriate for entry
into research
protocols. Recognized modifiers that may influence
the ECG appearance
and/or hemodynamic tolerance of the arrhythmia
need
to be noted. These modifiers need not dilute the subgroup size
unless
a specific clinical question involving these modifiers is being
addressed.
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Classification Schema for Arrhythmia Presentation
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A suggested classification schema for arrhythmia
presentation
is provided in the
Table

. This classification moves from
right
to left in defining the seriousness of the
hemodynamic consequences
of the arrhythmia.
Patients would be classified on the basis
of the most serious
hemodynamic symptoms and most abnormal
ventricular
arrhythmia experienced. The strongest
argument for the described
classification schema comes from published
work that tried to
incorporate some assessment of
hemodynamic tolerance as part
of the classification
schema for ventricular arrhythmia clinical
presentation.
21 22 23 24 25 Brugada and
Andries
21 were among the initial investigators
to
emphasize the importance of distinguishing VT that produces
syncope
from VT that is well tolerated. In their report, they
indicated that
the sudden death risk was >20% in patients
with syncopal VT and <5%
in patients with VT that was tolerated
hemodynamically.
Sarter and colleagues
22 documented that patients
presenting
with VT without hemodynamic
embarrassment had a 7.3% risk of
sudden cardiac death during a mean
follow-up of 36 months. Additional
work by Saxon and
colleagues
23 demonstrated that the 4-year
survival rate in
patients with sustained ventricular arrhythmias
and
only symptoms of palpitations was much greater than in those
patients
with a cardiac arrest (64% versus 45%). A classification
schema based
on more than the ECG diagnosis is warranted.
Of note, patients who present with syncope who have inducible
arrhythmias are not included in the Table
. There are very few
data available to support including these patients in one of the
arrhythmia-presentation groups based on ECG
diagnosis or hemodynamic consequences of the arrhythmic
event. We30 reported previously that patients with syncope
and inducible VT appear to more closely mimic patients with a history
of cardiac arrest than those patients with uniform VT with respect to
first occurrence of and frequency of implantable defibrillator therapy.
Saxon and colleagues23 also noted that the 4-year survival
rate was identical for patients presenting with either syncope and
inducible ventricular arrhythmias or cardiac arrest
(45%) and much lower than for patients presenting with
hemodynamically tolerated VT (64%). If these study
results are corroborated, then perhaps it would be more appropriate to
include patients with syncope and inducible VT with those patients who
fall into categories 1A through 2B in the Table
. For the moment,
however, a separate analysis seems appropriate for the patient
with syncope and no documented arrhythmia but inducible
ventricular arrhythmias at
electrophysiological evaluation.
If an arrhythmia presentation occurs only in
association with antiarrhythmic drug therapy, it is worth noting.
Obviously, patients with clearly identifiable drug-induced
arrhythmia syndromes are excluded from the classification
process. Although the ability to induce VT and subsequent management
strategies do not appear to be significantly influenced by whether the
patient is receiving antiarrhythmic drug therapy at the time of
arrhythmic presentation, the presence of antiarrhythmic drug therapy
can influence the hemodynamic tolerance of the
arrhythmia and should be identified with an appropriate
subscript.31 32 An indication of the presence or absence
of structural heart disease is also appropriate. The long-term
prognosis of patients who present with sustained or nonsustained VT
in the absence of structural heart disease is uniformly
excellent.33 34 The prognosis of patients presenting
with a cardiac arrest without structural heart disease may be of more
concern.35 Rapid identification and thus the ability to
include or exclude such patients in any data analysis may be
important. A classification schema can incorporate important
information describing modifiers by using additional subscripts
(Table
).29
The suggested classification schema for arrhythmia
presentation should aid in (1) the communication about
patients with ventricular tachyarrhythmias,
(2) the design of study protocols to evaluate new or validate old
arrhythmia treatment strategies, and (3) the comparison of
study results. Of note, the classification schema will also facilitate
recognition by the healthcare provider of the importance of
"managing the patient" and not just the ECG when considering both
the short-term and long-term treatment strategies for
ventricular arrhythmias.
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Need for Data Based on Continuous ECG Monitoring
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Reports based on multicenter studies involving large patient
populations
that identify clinical predictors of outcome have been
helpful
in providing information that may be used to assist in
developing
a prognosis and in patient counseling and in some cases may
help
identify the usefulness of the most appropriate treatment
strategies.
1 2 11 Unfortunately, the studies do little to
enhance our understanding
of arrhythmogenesis. Causal relationships are
occasionally implied.
However, accurate reporting rarely promotes
statements that
go beyond simply describing the statistically
significant associations.
In addition, end points other than total
mortality are appropriately
subject to criticism
36 37 ;
implying that a sudden arrhythmic
death is synonymous with a
ventricular arrhythmia has been demonstrated
to be
inaccurate, especially in selected patient subgroups.
38
Classification of the type of death by committee in the absence
of ECG
documentation must be considered second best. Holter
and in-hospital
ECG recordings obtained serendipitously at the
time of a fatal
event have provided some insight into the mechanism
of fatal arrhythmic
episodes.
39 40 Intracardiac electrogram
recordings
from patients with implantable defibrillators have
furthered the data
collection in patients proven to be at high
risk for arrhythmic
events.
41 42 43 Unfortunately, snapshot
recordings of
events surrounding implantable defibrillator therapy
still do not
provide insight into the specificity of apparent
triggers for
arrhythmic events. Multiple surface ECG criteria
have also been
described as predictors of an increased risk
of fatal arrhythmic
events.
44 45 46 Yet their role as markers
of true triggering
events has not been determined. With the
development of simplified yet
sophisticated nonlead-dependent
body surface and even implantable ECG
recording capabilities
coupled with advances in computer
technology, we need to take
our understanding of arrhythmogenesis to
the next step.
47 We
need to consider, either as part of
the next multicenter study
designed to assess different treatment
strategies or as an independent
multicenter effort, a major investment
to provide all study
patients with the opportunity for continuous ECG
monitoring,
data collection, and analysis. The details and all
of the technical
considerations are beyond the scope of this editorial.
The technical
feasibility of such an effort is, however, without
question.
This effort will require both industry and government
support,
for it will be costly. However, the potential for
understanding
the mechanism of arrhythmogenesis as a result of such an
effort
provides a much greater opportunity for advancing therapy than
another
study that compares two effective treatment strategies to
define
a marginal treatment benefit.
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Acknowledgments
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The author thanks Erica Zado, PA, for her efforts in the
preparation
and review of this manuscript.
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Footnotes
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The opinions expressed in this editorial are not necessarily
those of the editors or of the American Heart Association.
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