JACI Yol, 19, 90. 5 Anhi1199I915-7

915

Editorial Comment

wor, (10) carefully defined cardiogenic shack with accepted criteria . It is therefore possible to compare their results with

Angioplasty Therapy of Cardiogenic Shock : Are Randomized Trials Necessary?*

those of other reported . sells Previous reports. To doe, 10 grooms (10-191 including that of Mv.»ai el al . (10) have evaluated treatment of cardiogenic shock with coronary angicplasty (lab€e 1) . Among the 327 patients studied, the cumulative survival rate

WILLIAM W. O'NEILL. MD. FACC

is 59%r r : 64% have had successft-1 repe fusion . suial,al is

Royal Oak, Michigan

In 1954. Griffith cc al. (1) reported an SOS% in-hospital

mortality rate for patients with cardiogenic shock after acute myocardial infarction . Thirty-five years later . despite dramatic advances in cardiac care . Goldberg et al . (2) found no improvement in this dismal prognosis . Cardiogenic shock has been refractory to such major advances as coronary care unit (CCU) management (3), intraaortic balloon counterpul . sation (41 and emergency coronary bypass surgery (5). Even after the revolution in care brought about by thrombolytic

therapy, cardiogenic shock still has a dismal prognosis . Treatment with intracoronary streptokinase (6) . intravenous streptokinase Mill and intravenous recombinant tissue-type plasminogen activator (91 has failed to improve outcome, The present study . Given the high mortality rate with conventional care, the 56% survival rate reported in this issue of the Journal by Moosvi and colleagues (10) is encouraging. These investigators found that the 32 patients with successful revaseularization had a greater likelihood of survival than did the 49 patients treated without revascutaritation . Furthermore . patients undergoing revascutarization within 24 h of the onset of shock had a 77% survival rate. These heartening results must he tempered by the major deficiencies in the trial design of the study . First, the observations are based on retrospective chain review. Second, the investigators 0W do not clearly define their criteria for the selection of some patients for aggressive therapy and others for conventional care . This lack suggests that case selection bias partly explains the favorable results

reported . For example, intraaonic balloon support was provided to 94%a of the revascularization group but to only 39%a of the conventional therapy group . These differences in management raise the possibility that aggressive care was offered to the patients who were the most fit and thus the most likely to survive . Despite these limitations. this study (10) provides clinicians with useful clues for managing patients with cardiogenic shock . Most important . the investi-

'Edimdals published to larmal of tae Amrdcnn Cotton cfCardiolgy reflect the views of the authors anddo nut necnsvity reprexnt the views or JACC or the American College of Cardiology . FoamtheDividonofCardietogy, William aeaumontnbspital . Royalo k . Mtehisan. Addttis far tecnntq : William W . O'Neill, MD, Division of Cardiology, 3601 West Thin... Mill, Road, Royal Oak, Michigan 4073. 01992 by the

American College of cardiology

clearly linked to repcrfusion status . The probability of survival is 73% in patients with successful ",perfusion but only 2210 in patients with unsuccessful reperfusion . Review of these reports suggests that subgroups of patients with shock .^.rc most likely to benefit from this aggressive therapy . Moosvi et al . (10) clearly demonstrate the role of early reperfusiou in improving survival probability . DrWood et at . (20) previously demonstrated a 60h survival rate for patients with cardiogenic shock treated with early bypass surgery . Early therapy appears crucial but ongoing necrusis lasting many hours (211 appears to occur after cardiogenic shock . For this reason, therapy up to 24 h after symptom onset may be efficacious . Further review of the published series (10-19) suggests that patients with severe three-vessel disease do not greatly benefit from coronary angioplasty . Lee et al. (12) found that 83% of patients who died after interventional therapy had severe multivessel disease . Finally, age appears to affect prognosis . We have yet to treat successfully a patient with severe cardiogenic shock who was >75 years old. In our institution we now believe that aggressive intervention is contraindicated in the extremely aged patient with cardiunesic shuck . Are randoesstrrafitriuls necessary? Given the accumulating evidence of the benefit of coronary angioplasty in patients with myocardial infarction and shock, fire randomized trials necessary in this group? Such fundamental advances as CCU care. internal mammary artery implantation and heart transplantalion have never been subjected to randomized clinical trials. One could argue that the consistently encouraging reports of angioplasty therapy-and the knowledge that patients in a control group would have a 90% chance of early death-make a randomized trial unethical . We (22) attempted to conduct a prospective randomized clinical trial of thrombolysis and angoplasty in shock (TACS) in 1985 . Over a 14-month period, 10 active interventions] centers could recruit only nine patients into this study, largely because of clinician reluctance to randomize patients to it nonaggressive strategy. Again, one must ask whether randomized trials are ethical or feasible in this condition . As a clinician and clinical researcher deeply interested in cardiogenic shock . I believe that randomized trials of therapy of this condition are mandatory . I am troubled that only reports of treatment with a positive outcome are being published. Furthermore, aggressive intervention with the attendant vascular manipulation, contrast medium load and risk of reperfusion arrhythmia- may actually harm margin . ally compensated patients . However, 1 also believe that 0715-10971525519



916

O'NEILL

JACC Val. 19. No. 5 April 1992:915-7

GOITORrAL COMMENT

Table L Impact of Coronary Angioplasty on Survival in Cardiogenic Shock in 10 Reported Studies overall Survival

Rc&mnec (Oral amhal O'Ncili II q Lcc(r21 Shard (131 Hansernm BrovrliSt Beadle adle 1161 Ellis lOt O'Keclcr191 Lee 1191 Mom (10) Total NR - not rcpnr4

n

(9a)

Reperfusian 1%,

Survival With Reperfuaivn IS)

SnrvPoal Wbhanr Reperfusiun In)

27 24 9 la 28 22 60

70 50 66 7n 43 50 68 59 55 NR 59

88 54 W an 61 68 NR NR 11 78 64

75 83 83 Iris 58 NR NR NR 64 6

11 25 0 18 NR NR NR 20 a

7s

27

40

69 39 327 1

much more information is required about case selection, adjunctive supportive therapy and the role of emergency bypass surgery before prospective randomized trials are conducted. This information can be gathered most quickly and eMlciently by a prospective multicenter registry . The National Heart, Lung, and Blood institute-sponsored batloon velvuloplasty registry and the industry-sponsored registry of supported angioplasty are superb models for such a registry. We need to determine the proportion of patients who are actually eligible for coronary angioplasty and the subgroups that are most likely to benefit . Once optimal aggressive treatment strategies are defined, randomized trials can be more intelligently designed . Conclusions. Given our present state of knowledge, we face a dilemma in the management of cardiugenic shock . Conventional care is futile ; aggressive care is promising but nut validated . For young patients presenting early and without other terminal comorbidities, I would act on the side of aggressive intervention . I would treat the extremely aged with comfort measures only . If aggressive intervention is selected, patients should be referred to centers experienced in interventional therapy of cardiugenic shock . Preferably those centers should have emergency surgery available and access to cardiac transplantation and cardiac support devices . Until randomized trials are performed, centers performing interventional therapy must carefully and comprehensively collate and publish their results . Such centers should be encouraged to enter into the multicenter registry of cardiogenic shock that is now being planned .

References 1 . Grifdlh GC, Wetiace WB. Cochran B, Nerlich WE, Fresher WO, The tremmem of shock associmed wish mywardiul infraction . Circuletton 1954 ;9:527-32, 2. (ioldbcrg NJ, Gore 1M . Alpert J5, et al. Ccadiogenic shack after acute

myocardial infarction : incidence and modality from a community-wide perspective, 19751. 1988, N East J bled 1991325 :1117-22. 3 . Killip T, Kimball Jr . Treatment of myocardial infarction in a coronary e unit : a two year experience 250 patients . Am J Cardiol 1967 :20:457-64 . with 4 . Scheldt 5, WilnerG, Mueller H, el al . Inrm-manic balloon couaterpulsatlon in cardiugenic shock . N End J Mad 1973 :28$ :979-84. 5 . Mundth E, Buckley MJ . Lindbach RC. Surgical intervention for the nmpscarinns of acah, mynrardial isehemir, Ann Surg 1973 ;178 :379. 6 . Kennedy J, Gensini G, Timmis G, Maynard C. Acute myocardial infarction treated with innacoranary streptokinase : a report of the Society for Cardiac Aneiography . Am J Cardiol 198505 :371-7 . 7 . GmppoltalianopeatoStudiodeltaSVeptochinasinell'InlurtoMiocurdica (GISSI) . Effectiveness of intravenous thrambolylic treatment in acute myocardialinfen tion . Lancet 1936:1 :397-402. R. Gmppe Italian per to Studio de11a Sopmvvivenaa trea'inrara ban . cardico (GISSI-21 . A factorial randomized trial of alleplase versus sueprakinase and heparin verses nn hapndn emnng 12,490 patients with acme myocardial infarction . Lancet 1990;3:16 :65-70 . 9. Garmhy PJ, Henolova M1 . Forman S, Rogers WJ . Has thrSmbulytic therapy improved survival from cardiugenic shack'! ihrmalsnlysis n myocardial inf rction (TIM[ II) results (abslr) . Circulation 1985Otlsuppl 11) :11-623. Id. Maneni AR, Khata F, Villanueva L, Ghearahtade M, nomhan L, ([pldaidin S . Early revsseularit,atinn improves snrvivalin eardiegenie shark complicating acute myocardial infacfion . J Am Call Cardiol 1992 ;19:92714. II . O'Neill W. Total E. George B. et al . Improvement in Ice vendculer function after lhrombalybc therapy and angioplaaty ; results of esTAMt Study 10batrl . Circulation t9h7t761sapp11V1 :IV-259. 12. Lee L, Bates E, Pitt B, Wslmn 3 . ".for N .O'Neill WW . Pereulaneoas tranalumlml coronary angioplaaty improves Survival in acute myocardial intention complicated by enrdtogenie shark . Circulation 19887g1134S5L 13. Shane 1, Rivers M, Greengart A, Hollander 0, Kaplan P, Gehnlcm E . Perautancous transtuminal coronary angioplasty In cardlegenic Rldck Iabstrl. J Am Coll Cordial 1986;7 :149A. 14 . Heuser R, Maddoux G, Owls ) . Kamo B, Had G, Shaded N, Coronary, angioplaaty in the lreatmeal of cardiresnic shock the therapy at chmec labmrl. J Am Call Cordial 190)27 :219A. 15 . Brown T. (Jordan D, Wheeler W, lannone L, Wickemeym W, Rough R . Percmaneous myocardial repedasion (PMR) reduces modality in agate myocardial infarction IMl) eorapikIned by cardinaenie shock tahalrl . Circulation 1985 ;721supp] IIn:111-209. 16. Bnalie B, Weintraub R, Stuckey T, et al . Outcomes of direct camnar angioplasty for acute myocardial infarction in candidates and nod . candidates for Ihrombolylic therapy . Am 3 Cardiol 1991;67:7-12.



JACC V01 . 19. No. S April 1992 :911-7

17 . Ellis 30, O'Neill WW . Bales ER, e1 al . Implications For pnlienr range

bum at, snrvivnl and Ie8 venlrindar .-al for recovery analyses in SIN) Pack healed will coronary angiuplasty for . .to myucendial infarclion . 3 Am Coll Cardial 1989:13:1251 l . I8 . O'Keefe JH. Rutherford ED . MaConahay DRR c1 al. Early and late results

of coronary angiuplasty without antecedent thrombolytic therapy fur neate myocardial Infarerion . Am J Cardiol 1989 :64 :1221-30.

19. Lee L. Erbei R. Brown TM . Laufer N . Meyer 1 . O'Neill WW . Mulli. ,enler registry of angioplnnry thenpy or cardiogenic % :luck : initial and long-term survival . 3 Am Call Cardial 1991 :17 .599-0d3 .

O'NEILL EDITORIAL COMMENT

917

:0. Dew'rod MA, Nmske RN, Hensley OR. e t al . tnirnnortrc bullauemrpulsatian with and without reperfusioa for myocardial infarction shock . Circulation 1980:61 :1105-12. 21 . Gualovilc AL . Sabei BE . Itch- P. Progressive namrc of myocardial

mjart in selrcled polemic with cardiuannic shock . Am J Cmdiol 197NN1 : 469-75. P_ . O'Neill WW. Advnmes in the therapy of cardiagenic shock . In: CaliT YR, ad . Acute Coronary Care in the lhrambolytia En . Chicago: Year Book Medical Puhlixhers tin prma) .