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(Circulation. 1997;96:1713-1716.)
© 1997 American Heart Association, Inc.
Articles |
Predicting Arrhythmic Death
A Plea for Standardized Reporting Techniques and Data Based on Continuous Electrocardiographic Monitoring
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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 Top Introduction Need for Standardized Reporting...Classification Schema for...Need for Data Based...References |
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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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TopIntroductionNeed for Standardized Reporting...Classification Schema for...Need for Data Based...References |
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Caruso and colleagues also indicate in their report10 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 Braunwald29 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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TopIntroductionNeed for Standardized Reporting...Classification Schema for...Need for Data Based...References |
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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
Andries21 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 colleagues22 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
colleagues23 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.
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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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TopIntroductionNeed for Standardized Reporting...Classification Schema for...Need for Data Based...References |
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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 criticism36 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 non–lead-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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References |
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TopIntroductionNeed for Standardized Reporting...Classification Schema for...Need for Data Based...References |
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1. Mason JW, for the ESVEM Investigators. A comparison of electrophysiologic testing with Holter monitoring to predict antiarrhythmic-drug efficacy for ventricular tachyarrhythmias. N Engl J Med. 1993;329:445-451.
2. Echt DS, Liebson PR, Mitchell B, Peters RW, Obias-Mann D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL, Huther ML, Richardson DW, and the CAST Investigators. Mortality and morbidity in patients receiving encainide, flecainide or placebo: the Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991;324:781-788.[Abstract]
3. The CASCADE Investigators. Randomized antiarrhythmic drug therapy in survivors of cardiac arrest. Am J Cardiol. 1993;72:280-287.[Medline] [Order article via Infotrieve]
4. The AVID Investigators. Antiarrhythmics Versus Implantable Defibrillators (AVID): rationale, design, and methods. Am J Cardiol. 1995;75:470-475.[Medline] [Order article via Infotrieve]
5.
The ESVEM Investigators. Determinants of predicted
efficacy of antiarrhythmic drugs in the Electrophysiologic Study Versus
Electrocardiographic Monitoring trial. Circulation. 1993;87:323-329.
6.
Reiter M, Mann D, Reiffel J, Hahn E, Hartz V, for the
ESVEM Investigators. Significance and incidence of concordance of drug
efficacy predictions by Holter monitoring and
electrophysiological study in the ESVEM
trial. Circulation. 1995;91:1988-1995.
7. Hallstrom A, Platt CM, Greene HL, Huther M, Gottlieb S, DeMaria A, Young JB, for the CAST Investigators. Relationship between heart failure, ejection fraction, arrhythmia suppression and mortality: analysis of the Cardiac Arrhythmia Suppression Trial. J Am Coll Cardiol. 1995;25:1250-1257.[Abstract]
8. Hallstrom AP, Anderson JL, Carlson M, Davies R, Greene HL, Kammerling JM, Romhilt DW, Duff HJ, Huther M, for the CAST Investigators. Time to arrhythmic, ischemic, and heart failure events: exploratory analyses to elucidate mechanisms of adverse drug effects in the Cardiac Arrhythmia Suppression Trial. Am Heart J. 1995;130:71-79.[Medline] [Order article via Infotrieve]
9.
Anderson JL, Platia EV, Hallstrom A, Henthorn R, for
the CAST Investigators. Interaction of baseline characteristics with
the hazard of encainide, flecainide and moricizine therapy in patients
with myocardial infarction: a possible explanation for the increased
mortality in the Cardiac Arrhythmia Suppression Trial (CAST).
Circulation. 1994;90:2843-2852.
10.
Caruso AC, Marcus FI, Hahn EA, Hartz VL, Mason JW, and
the ESVEM Investigators. Predictors of arrhythmic death and cardiac
arrest in the ESVEM trial. Circulation. 1997;96:1888-1892.
11.
Kim SG, Fischer JD, Choue CW, Gross J, Ferrick KJ,
Brodman R, Furman S. The influence of left
ventricular function on the outcome of patients treated
with implantable defibrillators. Circulation. 1992;85:1304-1310.
12. Kim SG, Maloney JD, Pinski SL, Choue CW, Ferrick KJ, Roth JA, Gross J, Brodman R, Furman S, Fischer JD. Influence of left ventricular function on survival and mode of death after implantable defibrillator therapy (Cleveland Clinic Foundation and Montefiore Medical Center Experience). Am J Cardiol. 1993;72:1263-1267.[Medline] [Order article via Infotrieve]
13.
Grimm W, Flores BT, Marchlinski FE. Shock
occurrence and survival in 241 patients with implantable cardioverter
defibrillator therapy. Circulation. 1993;87:1880-1888.
14. Steurer G, Brugada J, DeBacquer D, Gursoy S, Frey B, Tsakonas K, Celiker A, Andries E, Brugada P. Value of clinical variables for risk stratification in patients with sustained ventricular tachycardia and history of myocardial infarction. Am J Cardiol. 1993;72:349-351.[Medline] [Order article via Infotrieve]
15. 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;55:372-374.[Medline] [Order article via Infotrieve]
16. Olson PJ, Woefel A, Simpson RJ Jr, Foster JR. Stratification of sudden death in patients receiving long-term amiodarone treatment for sustained ventricular tachycardia or ventricular fibrillation. Am J Cardiol. 1984;53:1558-1563.[Medline] [Order article via Infotrieve]
17. Herre JM, Sauve MJ, Malone P, Griffin JC, Helmy I, Langberg JJ, Goldberg H, Scheinman JJ. Long-term results of amiodarone therapy in patients with recurrent sustained ventricular tachycardia or ventricular fibrillation. J Am Coll Cardiol. 1989;13:442-449.[Abstract]
18. Swerdlow CD, Winkle RA, Mason JW. Determinants of survival in patients with ventricular tachyarrhythmias. N Engl J Med. 1983;308:1436-1442.[Abstract]
19. Wilber DJ, Garan H, Finkelstein D, Kelly E, Newell J, McGovern B, Ruskin JN. Out-of-hospital cardiac arrest: use of electrophysiologic testing in the prediction of long-term outcome. N Engl J Med. 1988;318:19-24.[Abstract]
20. Lessmeier TJ, Lehman MH, Steinman RT, Fromm BS, Akhtar M, Calkins H, DiMarco JP, Epstein AE, Estes NAM, Fogoros FE, Wilber D. Implantable cardioverter-defibrillator therapy in 300 patients with coronary artery disease presenting exclusively with ventricular fibrillation. Am Heart J. 1994;128:211-218.[Medline] [Order article via Infotrieve]
21. Brugada P, Andries E. The patient with ventricular arrhythmias can be offered optimal treatment on the basis of simple clinical variables. PACE Pacing Clin Electrophysiol. 1991;14:1201-1204.[Medline] [Order article via Infotrieve]
22. 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;28:122-129.[Abstract]
23. Saxon LA Uretz MS, Denes P. Significance of the clinical presentation in ventricular tachycardia/fibrillation. Am Heart J. 1989;118:695-701.[Medline] [Order article via Infotrieve]
24. Adhar GC, Larson LW, Bardy GH, Greene HL. Sustained ventricular arrhythmias: differences between survivors of cardiac arrest and patients with recurrent sustained ventricular tachycardia. J Am Coll Cardiol. 1988;12:159-165.[Abstract]
25. Brugada P, Talajic M, Smeets J. Risk stratification of patients with ventricular tachycardia or ventricular fibrillation: the value of clinical history. Eur Heart J. 1989:10:747-752.
26.
Goldman L, Hashimoto B, Cook EF, Loscalzo A.
Comparative reproducibility and validity of systems for assessing
cardiovascular functional class: advantages of a new
specific activity scale. Circulation. 1981;64:1227-1234.
27. The Criteria Committee of the New York Heart Association, Inc. Diseases of the Heart and Blood Vessels: Nomenclature and Criteria for Diagnosis. 6th ed. Boston, Mass: Little, Brown & Co; 1964.
28. Selzer A, Cohn K. Functional classification of cardiac disease: a critique. Am J Cardiol. 1972;30:306-308.[Medline] [Order article via Infotrieve]
29.
Braunwald E. Unstable angina: a
classification. Circulation. 1989;80:410-414.
30. Menz V, Schwartzman D, Nallamothu N, Grimm W, Hoffman J, Callans DJ, Gottlieb CG, Marchlinski FE. Does the initial presentation of patients with implantable defibrillators influence the outcome? PACE Pacing Clin Electrophysiol. 1997;20:173-176.[Medline] [Order article via Infotrieve]
31. Buxton AE, Rosenthal ME, Marchlinski FE, Miller JM, Flores B, Josephson ME. Usefulness of the electrophysiologic laboratory for evaluation of proarrhythmic drug response in coronary artery disease. Am J Cardiol. 1991;67:835-842.[Medline] [Order article via Infotrieve]
32. Kadish AH, Buxton AE, Waxman HL, Flores B, Josephson ME, Marchlinski FE. Usefulness of electrophysiologic study to determine the clinical significance of arrhythmia recurrences during amiodarone therapy. J Am Coll Cardiol. 1987;10:90-96.[Abstract]
33. Buxton AE, Marchlinski FE, Doherty JU, Cassidy DM, Vassallo JA, Flores BT, Josephson ME. Repetitive, monomorphic ventricular tachycardia: clinical and electrophysiologic characteristics in patients with and patients without organic heart disease. Am J Cardiol. 1984;54:997-1002.[Medline] [Order article via Infotrieve]
34.
Ohe T, Shimomura K, Aihara N. Idiopathic
sustained left ventricular tachycardia:
clinical and electrophysiologic characteristics.
Circulation. 1988;77:560-568.
35. Meissner MD, Lehman MH, Steinman RT, Mosteller RD, Ahktar M, Calkins H, Cannom DS, Epstein AE, Fogoros RN, Liem LB, Marchlinski FE, Myerburg RJ, Veltri EP. Ventricular fibrillation in patients without structural heart disease: a multicenter experience with implantable cardioverter-defibrillator therapy. J Am Coll Cardiol. 1993;21:1406-1412.[Abstract]
36.
Zipes DP. Implantable
cardioverter-defibrillator: lifesaver or a device looking for a
disease? Circulation. 1994;89:2934-2936.
37. Epstein AE, Carlson MD, Fogoros RN, Higgins SL, Venditti FJ. Classification of death in arrhythmia trials. J Am Coll Cardiol. 1996;27:433-442.[Abstract]
38.
Luu M, Stevenson WG, Stevenson LW, Baron K, Walden
J. Diverse mechanisms of unexpected cardiac arrest in advanced
heart failure. Circulation. 1989;80:1675-1680.
39. Bayes de Luna A, Coumel P, Leclercq JF. Ambulatory sudden cardiac death: mechanisms of production of fatal arrhythmia on the basis of data from 157 cases. Am Heart J. 1989;117:151-159.[Medline] [Order article via Infotrieve]
40. Kempf FC, Josephson ME. Cardiac arrest recorded on ambulatory electrograms. Am J Cardiol. 1984;53:1577-1582.[Medline] [Order article via Infotrieve]
41. Grimm W, Flores BT, Marchlinski FE. Symptoms and electrocardiographically documented rhythm preceding spontaneous shocks in patients with implantable cardioverter defibrillators. J Am Coll Cardiol. 1993;71:408-414.
42.
Nunain SO, Roelke M, Trouton T, Osswald S, Kim YH,
Sosa-Suarez G, Brooks DR, McGovern B, Guy M, Torchiana DF, Vlahakes GJ,
Garan H, Ruskin JN. Limitations and late complications of
third-generation automatic cardioverter-defibrillators.
Circulation. 1995;91:2204-2213.
43. Marchlinski FE, Gottlieb CD, Schwartzman D, Gonzalez-Zuelgarey J, Callans DJ. Electrical events associated with ventricular tachycardia initiation and their prevention. In: Zipes DP, Jalife J, eds. Cardiac Electrophysiology From Cell to Bedside. 2nd ed. Philadelphia, Pa: WB Saunders & Co; 1995:863-877.
44. Valkama JO, Huikuri HV, Koistinen MJ, Yli-Mayry S, Airaksinen KE, Myerburg RJ. Relation between heart rate variability and spontaneous and induced ventricular arrhythmias and patients with coronary artery disease. J Am Coll Cardiol. 1995;25:437-443.[Abstract]
45.
Rosenbaum DS, Jackson LE, Smith JM, Garan H, Ruskin JN,
Cohen RJ. Electrical alternans and vulnerability to
ventricular arrhythmias. N Engl
J Med. 1994;330:235-241.
46. Bogun F, Chan KK, Harvey M, Goyal R, Castellani M, Niebauer M, Daoud E, Man KC, Strickberger SA, Morady F. QT dispersion in nonsustained ventricular tachycardia and coronary artery disease. Am J Cardiol. 1996;77:256-259.[Medline] [Order article via Infotrieve]
47. Leitch J, Klein G, Yee R, Lee B, Kallok M, Combs W, Erickson M, Bennett T. Feasibility of an implantable arrhythmia monitor. PACE Pacing Clin Electrophysiol. 1992;15:2232-2235.[Medline] [Order article via Infotrieve]
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