THE IMPACT OF IMPLANTABLE CARDIOVERTER- DEFIBRILLATORS ON MORTALITY AMONG PATIENTS ON THE WAITING LIST FOR HEART TRANSPLANTATION

Transcription

1 THE IMPACT OF IMPLANTABLE CARDIOVERTER- DEFIBRILLATORS ON MORTALITY AMONG PATIENTS ON THE WAITING LIST FOR HEART TRANSPLANTATION Implantable cardoverter-defbrllators were nvestgated for ther mpact on mortalty n 228 consecutve heart transplant canddates on the watng lst for transplantaton (207 patents wthout and 21 wth mplantable cardoverter-defbrllator therapy). The mortalty rate n 207 patents wthout mplantable cardoverter-defbrllator therapy was 23.2% and n 21 patents wth mplantable cardoverter-defbrllator therapy was 4.7%. In a Cox proportonal hazards model for all 228 study patents (mortalty whle on the watng lst: 21.5%; transplantaton rate: 54.8%), the absence of an mplantable cardoverter-defbrllator was only a margnally sgnfcant predctor of mortalty (p = 0.079). However, the absence of an mplantable cardoverter-defbrllator was a powerful predctor of mortalty for a subgroup of 134 patents wth hgh-grade ventrcular arrhythmas on Holter electrocardography (mortalty whle on the watng lst: 26.1%; transplantaton rate: 54.5%; p = 0.022) and for a subgroup of 58 survvors of sudden cardac death (mortalty whle on the watng lst: 22.4%; transplantaton rate: 56.9%; p = 0.018). Implantable cardoverter-defbrllator therapy can be strongly recommended n transplant canddates wth a hstory of sudden cardac death. Recommendatons for an expanded, prophylactc use of mplantable cardoverter-defbrllator therapy n heart transplant canddates cannot be gven. (J THORAC CARDIOVASC SURG 1995; 110:532-9) Mchael Grmm, MD, a Georg Weselthaler, MD, a Raymond Avanessan, MD, a Georg Grmm, MD, b Herwg Schmdnger, MD, Wolfgang Schrener, PhD, a Andrea Podczeck, MD, a Ernst Wolner, MD, a and Gnther Laufer, MD, Venna, Austra p atents wth severe heart falure who are regstered for heart transplantaton face a hgh rsk of death from sudden cardac death whle on the watng lst, manly because of ventrcular tachyarrhythmas. 1-3 A recent multcenter tral showed that more than 40% of all deaths n patents on the watng lst are sudden n nature. 1 Implantable cardoverter-defbrllators (ICDs) were shown to reduce cardac mortalty n patents wth mpared left ventrcular functon by preventon From the Department of Cardothoracc Surgery a and the Second Department of Internal Medcne, c Unversty of Venna; the Second Department of Internal Medcne, b Landeskrankenhaus Klagenfurt; and the Thrd Department of Internal Medcne, a Wlhelmnensptal, Venna, Austra. Receved for publcaton June 23, Accepted for publcaton Dec. 20, Address for reprnts: Mchael Grmm, MD, Department of Cardothoracc Surgery, Unversty of Venna, Wfhrnger Gfrtel 18-20; A-1090 Venna, Austra. Copyrght 1995 by Mosby-Year Book, Inc /95 $ /1/63014 of sudden cardac death. 4 In patents wth an ejecton fracton less than 30%, ICD therapy resulted n a 5-year actuaral freedom from sudden cardac death of 89.9%. 5 Avalablty of transvenous systems wth bphasc shock delvery s a major advantage for the safety of ths technque, 6 and low surgcal mortalty at mplantaton and effcacy of ICD therapy n a seres of transplant canddates were recently shown.7, 8 These encouragng data and the dffculty n dentfyng those partcular transplant canddates who are at rsk for sudden cardac death whle on the watng lst 9 have stmulated the dscusson about an expanded use of ICD therapy as a prophylactc brdge to heart transplantaton. However, general prophylactc ICD therapy wth an approxmately $40,000 devce n all patents regstered for transplantaton would cause an enormous burden on health care resources? The am of ths study was to nvestgate by a Cox proportonal hazards model the mpact of ICD therapy on the mortalty n patents regstered for heart transplantaton. Furthermore, the ra- 532

2 The Journal of Thoracc and Volume 110, Number 2 Grmm et al 533 Table I. Baselne characterstcs Subgroup of patents wth hgh-grade ventrcular arrhythmas on Subgroup of survvors of All study patents Holter ECG sudden cardac death Patents wth ICD (n = 228) (n = 134) (n = 58) therapy (n = 21) ICD therapy (%) 21 (9.2) 21 (15.7) 21 (36.2) 21 (100) Age (yr) Sex (male:female) 198:30 117:17 50:8 18:3 Cause of heart falure (Idop:Isch,%) 138:90 80:34 31:27 12:9 NYHA class 3.2 +_ _ _ _+ 0.5 Absence of snus rhythm (%) 78 (34.2) 52 (38.8) 20 (34.5) 9 (40) LVEF (%) 16.1 _ _ _+ 4.2 Cardac ndex (L/mn/m 2) * 2.2 _ _+ 0.4 CVP (mm Hg) _ _ _+ 5.7 PVR (Wood unts) " " 2.5 _ _ 0.8 Antarrhythmc drug at lstng (%) 25 (11)* 21 (15.8) 14 (24.6) 6 (30) Ventrcular arrhythma on Holter ECG (%) 134 (58,8)* 134 (100) 55 (94.8) 21 (I00) Values are expressed as mean value plus or mnus the standard devaton or as a proporton. Idop, Idopathc heart falure; Isch, schemc heart falure; NY/-/A, New York Heart Assocaton; LVEF, left ventrcular ejecton fracton; CVP, central venous pressure; PVR, pulmonary vascular resstance. *p < 0.05 between patents wth and wthout ICD therapy among all study patents and wthn both subgroups (for exact values see Results secton). Table II. Follow-up of patents on the watng lst Subgroup of patents wth hgh-grade ventrcular Subgroup of survvors All study patents arrhythmas on Holter ECG of sudden cardac Patents wth ICD (n = 228) (n = 134) death (n = 58) therapy (n = 21) Follow-up tme (mo)* 11 ( ) 11 (0.5-20) 11 (0.5-20) 11 (1-20) Watng tme to transplantaton (mo)t 4 ( ) 4 (0.5-20) 4 (0.5-20) 4 (1-20) Calculaton of follow-up tmes and watng tmes to transplantaton derved from Kaplan-Meer analyss. Values are expressed as medan and range. Startng pont: regstraton on the watng lst. *End pont: stll watng at the end pont of study.?end pont: transplantaton. pact of ICD therapy was calculated for the subgroup of patents wth hgh-grade ventrcular arrhythmas seen on Holter electrocardography (ECG) and :for the subgroup of patents who had already had an event of sudden cardac death before regstraton. Patents and methods Baselne characterstcs and follow-up. We revewed the hstory of 228 consecutve heart transplant canddates regstered :by the transplant center of the Unversty of Venna, Austra, to the Eurotransplant watng lst between March 1, 1992 (startng pont of the study: on ths date the frst patent wth an ICD was regstered), and October 31, 1993 (end pont of the study). The ndcaton for transplantaton n all patents was end-stage heart dsease, wth unacceptable prognoss for survval and unacceptable dsablty even after careful consderaton of all other medcal and surgcal therapy. lo All baselne character- stcs of study patents were recorded wthn 4 weeks before regstraton and are presented n Table I. Twenty-one out of the 228 patents were regstered wth ICD therapy, whch was gven for an event of ventrcular tachyarrhythma before regstraton that necesstated external electrc defbrllaton (medan mplantaton tme of the ICDs before regstraton: 6 months, range from 0.25 to 84 months). Whle on the watng lst all patents were montored clncally wth comparable ntensty. ICD functon was montored wth respect to adequate dscharges; ICD dscharges were counted durng follow-up whle the patent was on the watng lst. At the tme of regstraton for transplantaton patents were treated wth angotensnconvertng enzyme nhbtors (94.7%), dgtals (93.8%), duretcs (95.2%), antarrhythmc drugs (11%; amodarone n = 23 and sotalol n = 22), and permanent antcoagulaton therapy (77.5%). Intravenous catecholamnes were admnstered n 11.5% and prostaglandns n 4% of the patents. Follow-up tmes on the watng lst and watng tmes to transplantaton are presented n Table II.

3 5 3 4 Grmm et al. The Journal of Thoracc and August 1995 Subgroups Subgroup wth hgh-grade ventrcular arrhythmas on Holter ECG. In 134 patents (21 wth and 113 wthout ICD therapy) hgh-grade ventrcular arrhythmas (couplets/trplets and/or ventrcular arrhythmas ---4 consecutve complexes at a rate >-120/ran) were present on Holter ECG, whch was done wthn 4 weeks before regstraton?' 11 Subgroup of survvors of sudden cardac death. Before regstraton for transplantaton 58 patents (21 wth and 37 wthout ICD therapy) had had an event of sudden cardac death and were successfully resusctated. Sudden cardac death was classfed by one or a combnaton of the followng: the lack of worsenng of the clncal settng wthn 1 hour before cardac arrest, the need for external electrc defbrllaton for resusctaton, or ECG documentaton of lfe-threatenng ventrcular arrhythmas. 4 Documented rhythm durng cardac arrest was ventrcular fbrllaton n 36 patents (62%), ventrcular tachycarda n 20 patents (34%), and unknown n 2 patents (4%). In the majorty of the 37 patents wthout ICD therapy, ICD therapy was avoded for nonmedcal reasons (costs, n = 16; referrng centers refused use of ICDs, n = 8; ICD refused by the patent, n = 5) and n the mnorty of patents for medcal reasons (worsenng of the clncal settng after resusctaton, n = 2; ntenton to avod thoracotomy n the elderly, n = 2; ntenton to awat transplantaton n the hosptal, n = 4). Patents wth ventrcular tachyarrhythmas durng an epsode of pump falure or after a new Q wave myocardal nfarcton were not ncluded n ths subgroup. Death on the watng lst: evaluaton of crcumstances. For evaluaton of crcumstances of death that occurred whle the patent was on the watng lst, personal or telephone contact was made wth the physcans of the patents or ther famly members. Sudden cardac death whle on the watng lst was defned as death occurrng as a result of recurrent cardac arrest or wthn 1 hour of the development of symptoms n a patent prevously n stable condton or an unobserved death n a patent known to be n stable condton durng the precedng 24 hours. Pump falure death whle a patent was on the watng lst was defned as death as a result of one or more of the followng: progressve heart falure, recurrent myocardal nfarcton, or precedng symptoms of more than 1 hour. 4 Unknown death whle a patent was on the watng lst was defned as an event for whch there was no knowledge about crcumstances. Statstcal analyss. Comparsons between patents wth and wthout ICD therapy were made by unpared t test and X 2 analyss; level of sgnfcance was set at p -< In the Cox proportonal hazards model, patents who dd not de whle on the watng lst were censored at the tme of transplantaton or at the last follow-up whle on the watng lst at the end pont of the study. Covarables used for calculaton of ndependent predctors of mortalty were the absence of ICD therapy and baselne characterstcs (Table I). All varables that reached statstcal sgnfcance n unvarate analyss entered stepwse multvarate analyss. The estmaton of relatve rsk and 95% confdence lmts was calculated for each sgnfcant pre- dctor from the proportonal hazard model. Cox proportonal model analyss was done wth BMDP statstcal software, 1990 verson (BMDP Statstcal Software, Inc., Los Angeles, Calf.). Actuaral freedom from mortalty whle on the watng lst was calculated by Kaplan-Meer analyss wth the use of SAS statstcal software (SAS Insttute Inc., CarT, N.C.). Results Baselne characterstcs and follow-up. Detaled baselne characterstcs of all study patents, of subgroups, and of patents wth ICDs are presented n Table I. All 228 study patents. Mean pulmonary vascular resstance was lower n the 21 patents wth ICDs (1.8 Wood unts) as compared wth that n the 207 patents wthout ICDs (2.8 Wood unts). Hgh-grade ventrcular arrhythmas on Holter ECG occurred more frequently n the 21 patents wth ICDs (100%) as compared wth the frequency n the 207 patents wthout ICDs (54.6%). Antarrhythmc drug therapy was gven to 6 of 21 patents wth ICDs (30%), but only to 19 of 207 patents wthout ICDs (9.2%). Subgroup of l 34 patents wth hgh-grade ventrcular arrhythmas on Holter ECG. Mean cardac ndex (2.3 L/ran per square meter) and mean pulmonary vascular resstance (1.8 Wood unts) were better n the 21 patents wth ICDs as compared wth respectve values n the 113 patents wthout ICDs (mean cardac ndex, 2.1 L/ran per square meter; mean pulmonary vascular resstance, 2.7 Wood unts). Subgroup of 58 survvors of sudden cardac death. There was no dfference n baselne characterstcs between the 21 patents wth and the 37 patents wthout ICDs. In all 228 study patents and n the subgroups, follow-up tmes and watng tmes to transplantaton were comparable n patents wth and wthout ICDs (Table II). Outcome. Outcomes of all 228 study patents, of subgroups, and of patents wth ICD therapy are presented n Table III. The total mortalty rate n all 228 study patents was 21.5%. Notably, wthn the whole study populaton and n the subgroup of patents wth hgh-grade ventrcular arrhythmas on Holter ECG sudden cardac death occurred more frequently than death from pump falure. In the subgroup of survvors of sudden cardac death, the most common event of death was pump falure. The mortalty rate n 207

4 The Journal of Thoracc and Volume 110, Number 2 Grmm et al l... m C) ' ~g I...!... 3 : I I I Months Fg. 1. Actuaral freedom from mortalty n patents on watng lst. Lne 1, 21 patents wth ICD therapy; lne 2, subgroup of survvors of sudden cardac death (n = 58, ncludng 21 patents wth ICD therapy); lne 3, all study patents (n = 228, ncludng 21 patents wth ICD therapy); lne 4, subgroup of patents wth hgh-grade ventrcular arrhythmas on Holter ECG (n = 134, ncludng 21 patents wth ICD therapy). Table III. {Outcome Death whle on the watng lst (%) 49 (21.5) Sudden cardac death (%) 28 (12.3) Pump falure death (%) 20 (8.8) Unknown cause of death (%) 1 (0.4) Stll on the watng lst (%) 54 (23.7) Receved transplantaton (%) 125 (54.8) Subgroup of patents wth hgh-grade ventrcular Subgroup of survvors All study patents arrhythmas on Holter ECG of sudden cardac Patents wth ICD (n = 228) (n = 134) death (n = 58) therapy (n = 21) 35 (26.1) 13 (22.4) 1 (4.7) 19 (14.2) 6 (10.3) (11.2) 7 (12.1) 1 (4.7) 1 (0.7) (19.4) 12 (20.7) 6 (28.5) 73 (54.5) 33 (56.9) 14 (66.7) patents wthout ICDs was 23.2% and the rate was 4.7% n 21 patents wth ICDs. The actuaral freedom from mortalty whle on the watng lst n all 228 study patents, subgroups, and patents wth ICD therapy s shown n Fg. 1. ICD dscharges durng follow-up whle the patent was on the watng lst occurred n 17 (80.9%) of the 21 patents wth ICDs. The medan number of ICD dscharges that occurred n those patents was 18.5 (range 1: to 370). Cox proportonal hazards model. The sgnfcant predctors of mortalty whle patents were on the watng lst, relatve rsk, and 95% confdence lmts are presented n Table IV. All presented varables were statstcally sgnfcant n unvarate analyss. All study patents (n = 228). Stepwse multvarate survval analyss revealed that mortalty was most powerfully predcted by central venous pressure (p < ), cardac ndex (p = 0.002), and the absence of snus rhythm (p = 0.035). The absence of

5 536 Grmm et al The Journal of Thoracc and August 1995 Table IV. Multvarate predctors of mortalty n patents on the watng lst (Cox proportonal hazards model) All study patents (n = 228) CVP < Cardac ndex Absence of snus rhythm Absence of ICD therapy Ventrcular arrhythmas on Holter ECG Cause of heart falure Subgroup of patents wth hgh-grade ventrcular arrhythmas on Holter ECG (n = 134) Cardac ndex CVP Absence of ICD therapy Absence of snus rhythm Subgroup of survvors of sudden cardac death (n = 58) Age Absence of ICD therapy p Value Relatve rsk 95% confdence lmts Covarables used were baselne characterstcs and the absence of ICD therapy (see Table I); all sgnfcant varables from unvarate analyss entered stepwse multvarate analyss. CVP, Central venous pressure. ICD therapy (p = 0.079), the presence hgh-grade ventrcular arrhythmas on Holter ECG (p = 0.079), and the cause of heart falure (p = 0.080) were margnally sgnfcant ndependent predctors of mortalty. Subgroup of patents wth hgh-grade ventrcular arrhythmas on Holter ECG (n = 134). Death whle patents were on the watng lst was strongly predcted by cardac ndex (p = 0.001), central venous pressure (p = 0.014), and the absence of ICD therapy (p = 0.022), whereas the absence of snus rhythm was only margnally predctve (p = 0.073). Subgroup of survvors of sudden cardac death (n = 58). Age (p = 0.005) and the absence of ICD therapy Co = 0.018) were sgnfcant ndependent predctors of mortalty. Antarrhythmc therapy had no mpact on mortalty n patents on the watng lst for all 228 patents and subgroups. Dscusson In the cohort of 228 unselected, consecutve heart transplant canddates, ICD therapy had no mpact on mortalty whle the patents were on the watng lst. However, n 134 patents wth hgh-grade ventrcular arrhythmas on Holter ECG and, partcularly, n 58 patents wth a hstory of sudden cardac death ICD therapy had a sgnfcant mpact on mortalty. Wthn the study perod 28 (12.3%) of 228 consecutve patents ded of sudden cardac death whle on the watng lst. In the 21 patents wth ICDs there was no sngle event of sudden cardac death. Ths suggests that the conventonal ndcaton for ICD therapy, that s, survvng an event of sudden cardac death, seems neffectve to protect the entre populaton of heart transplant canddates. 6' s Despte the safety and effcacy of ICDs n transplant canddates, 6-8 a more expanded, and therefore prophylactc, use of ICD therapy wll reman a matter of dscusson. The dffcultes n dentfyng transplant canddates at rsk for sudden cardac death prospectvely and the enormous cost (approxmately $40,000 per devce) of ICD devces force the crtcal desgn of ICD prophylaxs n transplant canddates. In the subgroup of 134 patents wth hgh-grade ventrcular arrhythmas on Holter ECG (ncludng 21 patents wth ICDs) ICD therapy had a sgnfcant mpact on mortalty. We observed a 14.2% rate of sudden cardac deaths and an overall mortalty rate of 26.1%. The presence of hgh-grade ventrcular arrhythmas on Holter ECG n advanced heart falure s an accepted predctor of cardac mortalty.12, 13 A sgnfcant assocaton of couplets/trplets or nonsustaned ventrcular tachycarda wth ncreased rsk of sudden cardac death n patents wth heart falure was recently shown; 14' 15 however, ths stll remans a matter of dscusson) 6 Hgh-grade ventrcular arrhythmas may ncrease mortalty by trggerng lfe-threatenng arrhythmas that ether result n sudden cardac death or n poorly tolerated hemodynamc compromse and deteroraton because of pump falure) 7 ICDs detect and mmedately termnate ventrcular arrhythmas and, therefore, may not only prevent sudden cardac death but also death from arrhythma-nduced pump falure) 7

6 The Journal of Thoracc and Volume 110, Nurnber 2 Grmm et al. 537 Effcacy of ICD therapy n the termnaton of potental lfe-threatenng arrhythmas s reflected n the hgh ncdence of (medan 18.5) adequate ICD dscharges n 17 of our 21 patents wth ICDs durng our short follow-up perod. Our fndngs ndcate that patents wth hgh-grade ventrcular arrhythmas on Holter ECG comprse a subpopulaton at certan rsk of sudden cardac death whle on the watng lst. Because heart transplant canddates wth nducble ventrcular arrhythma on electrophysologc stmulaton have a sgnfcantly hgher prevalence of lethal arrhythmc events, 18 expanded electrophysologc stmulaton could possbly be helpful n dentfyng patents who mght receve potental beneft from prophylactc ICD brdge to transplantaton. However, ths has to be nvestgated by means of a prospectve randomzed study. Although not prevously reported, t was not surprsng to us that ICD therapy dramatcally decreased mortalty n survvors of sudden cardac death on the transplant watng lst. In ths subgroup of 58 survvors of sudden cardac death (ncludng 21 patents wth ICDs) we observed a 10.3% rate of sudden cardac deaths and an overall mortalty rate of 22.4%. Although n ths subpopulaton the rsk of early recurrence of lethal arrhythma s sgnfcant, 19 n our seres pump falure death (12.1%) occurred more frequently than sudden cardac death (10.3%). In severty of heart falure the 21 patents wth ICDs were comparable to the 37 patents wthout ICDs at the tme of regstraton (Table I). However, mortalty was strldngly lower n the ICD-treated patents wth respect to sudden cardac death and pump falure death. It can be doubted that all ICD dscharges n 80.9% of our patents wth ICDs (medan 18.5, up to 2170) treated ventrcular tachycardas that were spontaneous n nature. Much more, follow-up on the watng lst revealed a marked correlaton of ICD actvty wth worsenng of ventrcular functon, as reported prevously, s' 20 Therefore we speculate that the low number of pump falure deaths n our patents wth ICDs does not mark patents wth ICDs as "less sck," but we beleve that mmedate and consequent termnatons of frequently occurrng ventrcular arrhythmas, whch otherwse would have trggered hemodynamc deteroraton, markedly supported preventon from pump falure death. ICD therapy was not gven to 37 of the 58 survvors of sudden death, manly because of nonmedcal reasons such as cost or refusal of ICD therapy by referrng medcal centers. The approaches of awatng transplantaton under close Holter montorng out of the hosptal and of awatng transplantaton n the hosptal turned out not to be effectve alternatves to ICD therapy. For ths purpose, we beleve that transplant canddates wth a hstory of sudden cardac death should receve ICD therapy whenever possble, even when watng tme to transplantaton s expected to be short. The major am of ICD therapy whle a patent s on the watng lst for heart transplantaton s shortterm survval untl transplantaton. Under the assumptons of further lmted avalablty of donor organs and a decreased mortalty wth prophylactc ICD therapy, watng tmes to transplantaton and tme-dependent rsk of deteroraton caused by pump falure wll ncrease for the patents. An overrepresentaton of ICD therapy n transplant canddates wll result n a great pool of patents wth crtcal end-stage dsease wth severe pump falure, 5 whch would fnally negatvely affect the outcome of the entre transplant program by ncreased peroperatve mortalty after transplantaton. 21 Further studes wll be necessary to evaluate whch percentage of patents lsted wth ICD therapy optmzes overall survval for patents on the watng lst, wthout sgnfcant dsadvantages for patents lsted wthout ICDs. Therefore too enthusastc use of prophylactc ICD therapy should be avoded. To optmze the cost-beneft rato of short-term ICD brdge to transplantaton, technology wll have to focus on cheaper, smpler, or reusable devces. It seems lkely that emprc use of amodarone and sotalol n patents who are heart transplant canddates would be cheaper than ICD therapy and more sutable for expanded prophylaxs of lethal arrhythmas. 22 Studes on emprc use of amodarone n advanced heart falure report effectve suppresson of ventrcular arrhythmas; unfortunately ths benefcal effect dd not necessarly correlate wth ncreased survval. 23' 24 As we calculated n multvarant analyss, therapeutc, that s, nonemprc, use of antarrhythmc therapy wth sotalol and amodarone had no mpact on mortalty. It s hoped that ongong work wthn the Congestve Heart Falure Survval Study of Antarrhythmc Therapy wll help to determne beneft from prophylactc antarrhythmc therapy. 25 The study s lmted by ts retrospectve desgn and the fact that ICD therapy was not randomly assgned. Another major bas was that the low number of patents wth ICD therapy resulted n dscrepancy of sample szes wthn the groups. The latter and dfferences n baselne characterstcs of patents

7 538 Grmm et al. The Journal of Thoracc and August 1995 wth and wthout ICDs were corrected for nfluencng factors by the Cox model used. Another potental source of undetected bas s the hgh number of referrng centers, whch results n a varety of approaches toward preventon and treatment of lfethreatenng ventrcular arrhythmas. Another lmtaton of ths study s the nablty to exactly dscrmnate between tachyarrhythma and electromechancal dssocaton as the rhythm at the tme of sudden cardac arrest. 26 Fnally, t has to be stated that ths study only focused on a few months of events n patents on the heart transplant watng lst. Therefore the conclusons drawn n ths study should not be extrapolated to long-term outcome of patents wth heart falure. We conclude that ICD therapy should be gven, whenever possble, to heart transplant canddates wth a hstory of sudden cardac death before regstraton. For all other transplant canddates no recommendatons for prophylactc ICD brdge to transplant can be made. However, further studes should clarfy whether vgorous electrophysologc stmulaton n patents wth hgh-grade ventrcular arrhythmas on Holter ECG s helpful n dentfyng transplant canddates at rsk for sudden cardac death on the watng lst. REFERENCES 1. DEFIBRILAT Study Group. Actuaral rsk of sudden death whle awatng cardac transplantaton n patents wth atherosclerotc heart dsease. Am J Cardol 1991;68: McManus RP, O'I-Iar DP, Betznger JM, et al. Patents who de awatng heart transplantaton. J Heart Lung Transplant 1993;12: van den Broek SAJ, van Velhusen D J, de Graeff PA, et al. Mode of death n patents wth congestve heart falure: comparson between possble canddates for heart transplantaton and patents wth less advanced dsease. J Heart Lung Transplant 1993;12: Powell AC, Fuchs T, Fnkelsten DM, et al. Influence of mplantable cardoverter-defbrllators on the longterm prognoss of survvors of out-of-hosptal cardac arrest. Crculaton 1993;88: Km SG, Maloney JD, Pnsk SL, et al. Influence of left ventrcular functon on survval and mode of death after mplantable defbrllator therapy (Cleveland Clnc Foundaton and Montefore Medcal Center experence). Am J Cardol 1993;72: The Cardomyopathy Tral Investgators. Cardomyopathy tral. PACE Pacng Cln Electrophysol 1993; 16: Jeevanandam V, Belefeld MR, Auter JS, et al. The mplantable defbrllator: an electronc brdge to cardac transplantaton. Crculaton 1992;86(Suppl):II Bolng SF, Deeb GM, Morady F, et al. Automatc nternal cardoverter defbrllator: a brdge to heart transplantaton. J Heart Lung Transplant 1991;10: Barr CS, Naas A, Freeman M, Lang CC, Struthers AD. QT dsperson and sudden unexpected death n chronc heart falure. Lancet 1994;343: Mudge GH, Goldsten S, Addonzo LJ, et al. Task force 3: recpent gudelnes/prortzaton. J Am Col Cardol 1993;22: Koegh AM, Baron DW, Hcke JB. Prognostc gudes n patents wth dopathc or schemc dlated cardomyopathy assessed for cardac transplantaton. Am J Cardol 1990;65: De Mara R, Gavazz A, Carol A, Ometto R, Bagn A, Camern F. Ventrcular arrhythmas n dlated cardomyopathy as an ndependent prognostc hallmark. Am J Cardol 1992;69: Fletcher RD, Cntron GB, Johnson G, Orndorff J, Carson P, Cohn JN. Enalaprl decreases prevalence of ventrcular tachycarda n patents wth chronc congestve heart falure: the V-HeFT II VA Cooperatve Studes Group. Crculaton 1993;87(Suppl):VI Mtra RL, Buxton AE. The clncal sgnfcance of nonsustaned ventrcular tachycarda. J Cardovasc Electrophysol 1993;4: Podrch PJ, Fogel R, Fuchs TT. Ventrcular arrhythma n congestve heart falure. Am J Cardol 1992; 69:82G-95G. 16. Dunn FG, Prngle SD. Sudden cardac arrest, ventrcular arrhythmas and left ventrcular hypertrophy. J Hypertens 1993;11: Brugada P, Andres E. The ratonale for prophylactc mplantaton of a defbrllator n "hgh-rsk" patents. PACE Pacng Cln Electrophysol 1993;16: Lndsay BD, Osborn JL, Schechtman KB, Kenzara JL, Ambos HD, Can ME. Prospectve detecton of vulnerablty to sustaned ventrcular tachycarda n patents awatng heart transplantaton. Am J Cardol 1992;69: Swerdlow CD, Wnkle RA, Mason JW. Determnants of survval n patents wth ventrcular tachyarrhythmas. N Engl J Med 1983;308: Sweeney MO, Ruskn JM. Mortalty benefts and the mplantable cardoverter-defbrllator. Crculaton 1994;89: Stevenson LW, Warner SL, Hamlton MA, et al. Modelng dstrbuton of donor hearts to maxmze early canddate survval. Crculaton 1992;86(Suppl): Nora M, Zpes DP. Emprc use of amodarone and sotalol. Am J Cardol 1993;72:62F-9F. 23. Ncklas JM, McKenna WJ, Stewart RA, et al. Prospectve, double-blnd, placebo-controlled tral of low-

8 The Journal of Thoracc and Volume 110, Number 2 Grmm et al 539 dose amodarone n patents wth severe heart falure and asymptomatc frequent ventrcular ectopy. Am Heart J 1991;122: Hamer A, Arkles B, Johns J. Benefcal effects of low dose amodarone n patents wth congestve cardac falure: a placebo-controlled tral. J Am Coll Cardol 1989;14: Sngh S, Benett B. Ventrcular arrhythma assocated wth congestve heart falure: the role of amodarone. J Cln Pharmacol 1991;31: Luu M, Stevenson WG, Stevenson LW, Baron K, Walden J. Dverse mechansms of unexpected cardac arrest n advanced heart falure. Crculaton 1989;80: