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Prognosis of acute myocardial infarction complicated by primary ventricular fibrillation
Prognosis of Acute Myocardial Infarction Complicated by Primary Ventricular Fibrillation Solomon Behar, MD, Uri Goldbourt, PhD, Henrietta Reicher-Reiss, MD, Elieser Kaplinsky, MD, and the Principal Investigators of the SPRINT Study
In 5,839 consecutive patients with acute myocardial infarction (AMI), hospitalized between July 1981 and July 1983 in 14 coronary care units in Israel, the incidence of primary ventricular fibrillation (VF) was 2.1%. Patients with primary VF resembled counterparts without VF in terms of age, gender, frequency of previous AMI and past cigarette smoking habits. The hospital course of patients with primary VF revealed increased incidence of primary atrial fibrillation and atrioventricular block. lnueased serum levels of glutamic oxaloacetic transaminase and lactic dehydrogenase were noted among the patients with primary VF. In-hospital mortality rate was 18.8% in 122 patients with primary VF compared with 8.5% in 3,707 patients forming the reference group (p
From the Neufeld Cardiac ResearchInstitute, Sheba Medical Center, Tel-Hashomer, Israel. Data for patients with acute myocardial infarction in the Register were supportedby a researchgrant from Bayer AG (Wuppertal, Federal Republic of Germany) within the framework of the SPRINT Study. Manuscript received March 23, 1990; revised manuscript received June 26,1990, and acceptedJune 28. Address for reprints: Soloman Behar, MD, SPRINT Coordinating Center, Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Hashomer, 52621 Israel. 1208
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 66
entricular fibrillation (VF) remains a frequent and major, potentially lethal, complicationof acute myocardial infarction (AMI). Although there is general consensusthat secondaryVF is associatedwith markedly elevated in-hospital mortality and may represent poor prognosis for survivors of AMI, opinions vary as to the prognostic value of primary VF.l-3 We therefore undertook a study to determine the associationof primary VF with in-hospital mortality after AMI.
V
METHODS
From 1981 to 1983 we conducted a secondaryprevention study-the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT)-in 2,276 survivors of AM1 using nifedipine or placebo in 14 hospitals in Israel.4 During the study period, a logbook of all patients with AM1 was maintained (SPRINT Registry). The diagnosis of AM1 was confirmed by clinical electrocardiographic and enzymatic findings. Demographic and medical data were collected on special forms. Follow-up through mid-1988 was completedfor all hospital survivors of the Register. For the purpose of this study, primary VF was de fined as VF complicating a first or recurrent AM1 occurring within 48 hours of admissionin patients in Killip class I. According to this definition, no clinical or xray signs of congestive heart failure on admission to coronary care units were recorded and neither congestive heart failure, pulmonary edema,cardiogenic shock nor persistent hypotension (systolic blood pressure(90 mm Hg/48 hours) precededthe occurrenceof VF. Patients in an identical hemodynamic state (Killip class I) during their first 48 hours of hospitalization in the coronary care unit, without VF, were defined as the reference group. All patients with primary VF were connected to a monitoring system at bedside and to the central electrocardiographic monitor of the coronary care unit when the arrhythmia occurred. Immediate electrical cardioversion was provided and standard cardiopulmonary resuscitation maneuvers were begun without delay by the staff of the coronary care unit. The SPRINT Registry of AMI, including 5,839 patients, provides a good opportunity to evaluate the incidence, the in-hospital outcome and the long-term influence of primary VF on the prognosis of survivors of acute AMI. One hundred twenty-two of these patients fulfilled the criteria of primary VF and 3,730 patients formed the reference group. Statistical analysis: Age-adjusted prevalence of attributes correlating with primary VF has been calculated. Multivariate logistic analysis of hospital and mor-
TABLE I incidence of Primary Ventricular Fibrillation According to Gender, Age and Past History Case/Total Men Women 550 270 AMI location Anterior Inferior Non-Q-AM1 Previous MI f 0 AP + 0 Hypertension -IO Smoked cigarettes f 0
Ill Hospital Course With and Without Primary
p Value
99/4.315 23/ 1,524
(2.3) (1.5)
19/671 75/3,398 28/1,770
(2.8) (2.2) (1.6)
52/2.565 57/2,264 6/451
(2.0) (2.5)
NS co.05
Age group War) 5169
TABLE
(1.3) NS
23/1.432 96/4,297
(1.6) G-9)
48/2,867 69,‘2,790
(1.7)
71 73
1,969 1,369
(59) (60)
NS
(54) (37)
CO.05
-co.05
(2.5) co.05
(1.8) (2.2)
42/2,790 75/3,381
TABLE
NS
IV In-Hospital Mortality
(2.2) (2.0)
62/2,758 44/2,249
Primary VF (n = 122)
Reference (n = 3,707)
No.
W)
No.
W)
p Value
99
031)
2,828
(76)
NS NS
19 75 28
(16) (62) G-3
542 2,278 887
(15)
(61) (24) NS
52 57 6 23 48 42 62 60
(43) (47) (5) (19) (39) (34) (51)
1,434 1,621 322 700 1,728 1.464 1,897 61
Reference
Primary VF
TABLE II Characteristics of Patients with Primary Ventricular Fibrillation and of the Reference Group
Ape group (year) 250 51-69 270 AMI location Anterior Inferior Non-Q-AM1 Previous AMI AP Hypertension Smoked cigarettes Mean age (years)
Reference (n = 3,707)
NS
AMI = acute myocardial infarction; AP = angina pectoris; NS = not significant; + = positive: 0 = negative.
Men
VF (n = 122)
Men Women Age (years) 550 51-69 270 First AMI Recurrent Ml AP Hypertension Smoked cigarettes AMI location Anterior Inferior Non-Q-AM1
Case/Total
(%)
Case/Total
(%)
pValue
17/99 6/23
(17) (26)
184/2.828 131/879
(7) (15)
CO.01 NS
l/19 9/75 15/28 12/96 8/23 12/48 7/42 11/67
(5) (12) (54) (13) (35) (25) (17)
(1) (7) (17) (8) (9) (10) (9) (4)
NS
06)
7/542 158/2,278 1 SO/887 240/2,972 66/700 167/1,728 128/1,464 76/1.897
16/52 4/57
(31) (7) (17)
150/1,434 127/1.621 14/322
(11) (8) (4)
l/6
NS
Abbreviations as in Table I.
(39) w (9) (1% (47) W (51)
lar percent of previous AMIs but a lower incidence of angina pectoris compared with those of the reference NS group. The hospital course of patients with primary VF NS was more complicated than that in the reference group NS (Table III). Paroxysmal atria1 fibrillation and advanced AMI = acute myocardial infarction; AP = angina pectoris; NS = not significant; VF = atria1 ventricular block occurred about twice as often in ventricularfibrillation. patients whose primary VP complicated the infarction as in the reference group. High serum enzyme levels of tality after dischargeyielded estimates5of the covariate- glutamic oxaloacetic transaminase and lactic dehydroadjusted predictive power of primary VF in early (in- genasewere frequently found in patients with primary hospital) mortality. The SAS software was utilized, spe- VF. The most striking finding of this study was the macifically the FREQ6 and CATMOD’ procedures. jor effect of primary VF complicating AMI on the inhospital outcome (Table IV). Patients with primary VF ESULTS The incidence of primary VF in the SPRINT Reg- had a twofold mortality rate (18.8%) compared with ister population was 2.1% (122 of 5,839). The latter those in the reference group (8.5%). These statistics of rate did not vary markedly according to gender (men higher relative risk of hospital fatalities in patients with primary VF persistedin different subsetsof patients ac2.3%;women 1.5%), first (2.2%) versus recurrent AMI (1.6%), age, location of myocardial infarction and an- cording to gender, age, and clinical history. In a logistic regression,the estimated odds ratio for hospital mortaliamnestic features (Table I). The characteristics of patients with primary VP are ty equaled 2.86 when adjusted only for age, and 2.52 comparedwith those of the reference group in Table II. (95% confidence limits, 1.42 and 4.46) when adjusted Patients with primary VF had the samemean age, simi- for the combined effects of age, gender, location and -l-HE AMERICAN JOURNAL OF CARDIOLOGY
NOVEMBER 15, 1990
209
history of AMI, cerebrovascular accident and hypertension and the percent of patients with serum lactic dehydrogenase levels exceeding 4 times the upper normal limit. An appreciation of the usefulnessof the analysis, is obtained by the proportion of in-hospital deaths (54.8%) occurring in those with the highest 20% probability of mortality calculated by the logistic risk function. The excessof in-hospital mortality among patients with primary VF was due to electromechanical dissociation, cardiac rupture and standstill or intractable arrhythmia, but not due to pump failure. Thirteen patients died instantaneously from intractable arrhythmias, most occurring during recurrent chest pain with new electrocardiographic changes of ischemia, conduction disturbances, or both. Late hospital death after successful resuscitation occurred in 10 patients, 5 of whom had recurrent intractable arrhythmias. The Kaplan-Meyer survival curve,8 comparing mortality in patients with primary VF with that in reference patients is shown in Figure 1. Mortality rate over the first year after discharge was 3.0% for survivors of primary VF (3 of 99 patients) and 6.5% in the reference group (difference not significant). Mortality rate through 1988 (4.5 to 6.5-year follow-up) was 16.2 and 21.2% in the primary VF and reference groups, respectively. DISCUSSION The SPRINT Registry of patients with AMI, based on data of a large AM1 patient group collected from 14 of 21 coronary care units existing in Israel, establisheda reliable estimation of the incidence of primary VF. Most important, it has allowed the comparison of case fatality between patients with primary VF and counterparts receiving comparable medical care. Our results indicating a primary VF incidence of 2.1% in the coronary care unit are in accord with a number of previous studies9-l4 We found that primary VF, complicating AMI, strongly predicted in-hospital mortality. Patients
2 z
0.7 I
-
+1
- -- - - PRIMARY
0
REFERENCE
50
VF
1M
150
1 200
DAYS
FIGURE 1. Cumulative survival rate in patients with acute myocardial infarction complicated with primary ventricular ldation (VF) and in the reference graup patients. 1210
fi-
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 66
with Killip class I on admission to the coronary care unit had an in-hospital mortality rate of 18.8%if they presented with primary VF and only 8.5% if they did not. This highly significant statistical difference persisted for subsetsof patients according to age, gender, disease history and the location of the AM1 on previous infarctions sustained by the patient, and was borne out by multivariate analysis, yielding a covariate-adjusted odds ratio of 2.52. The 95% confidenceinterval provides a large range for the mortality risk during the acute phaseof AM1 associatedwith primary VF, between 1.5 and 4.5; however, it probably doubles the risk. Two recent pertinent studiesreachedconflicting conclusions. In the Multicenter Investigation of the Limitation of Infarct Size study,3 40 of 815 patients who presentedwith primary ventricular tachycardia/VF had an in-hospital mortality rate (8%) comparable to patients without primary VF (7%). In the much larger thrombolytic study-The Italian Group for the Study of Streptokinase in Myocardial Infarction (GISSI)*-the large group of 326 patients with primary VF who had a first AM1 showed twofold in-hospital mortality, as observed in comparison with the referencegroup (10.8 and 5.9%, respectively). The high rate of in-hospital mortality among patients with AM1 complicated by primary VF in GISSI and other clinical studies2J5J6was attributed to the correlation between the size of AMI, defined enzymatically or morphologically, and the incidence of VF. In our study, patients with primary VF, although in Killip class I, exhibited a higher rate of serious cardiac complications and a higher incidence of elevatedserum enzyme levels, supporting the view that AM1 complication by primary VF is more extensive. However, looking at large infarctions, as estimated by markedly elevated serum enzyme levels,we still observe (Table IV) an approximate twofold mortality associated with primary VF. Given that the occurrenceof primary VF and its outcome are not influenced by thrombolysis,17the extent of necrosisdoesnot appear to provide a satisfactory explanation of excessmortality in the group with primary VF. In the latter group, we also did not observean increaseof deaths due to pump failure. These results are dissimilar to the observationsof Volpi et al.* The major question relating to the mechanismof excessmortality found in patients with primary VF complicating AM1 remains unresolved. No clinical trial could definitely determine whether primary VF was a marker for patients at increasedrisk of death or, alternatively, VF increased the extent of the necrosisin the myocardium by a sudden decreasein coronary flow, thus acting as an independent prognostic factor, In our study most of the patients who died instantaneously or during recurrent arrhythmias had chest pain with concomitant ischemic electrocardiographic changes,suggesting that primary VF becomesintractable when occurring during an extension of the ischemic process. Finally, although the in-hospital prognosis of patients with primary VF in AM1 is clearly compromised, data from different studies indicate that these life-
threatening arrhythmias did not interfere with the late prognosis of the hospital survivors of AMI.2J1~18Our own data showed comparable mortality in patients resuscitatedfrom primary VF and in control subjectsin a prolonged follow-up period over an average 5.5 years. REFERENCES P. Pasternak RC, Braunwald E, Sobel BE. Acute myocardial infarction. In: Braunwald E, cd. Heart Disease: A Textbook of Cardiovascular Medicine. 3rd ed. vol. 2. Philadelphia: WB Saunders, 1984: 1222-l 3 13. 2. Volpi A, Maggioni A, Franzosi MG, Pampallona S, Mauri F, Jognoni G. Inhospital prognosis of patients with acute myocardial infarction complicated by primary ventricular fibrillation. N Engl J Med 1987;317:257-261. 3. Tofler GH, Stone PH. Muller JE, Rutherford JD, Willich SN, Gustafson NF, Poole WK, Sobel BE, Willerson JT, Robertson R, Passamani E, Braunwald E and the MILIS Study Group. Prognosis after cardiac arrest due to ventricular tachy cardia or ventricular fibrillation associated with acute myocardial infarction (The MILIS Study). Am J Cardiof 1987;60:755-760. 4. The Israeli SPRINT Study Group. Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT). A randomized intervention trial of nifedipine in patients with acute myocardial infarction. Eur Heart J 1988;9:354-364. 5. Bishop YMM, Feinberg SE, Holland PW. Discrete Multivariate Analysis: Theory and Practice. Cambridge, Massachusetts; The MIT Press, 1975. 6. The FREQ Procedure. SAS User’s Guide: Statistics. Version 5 Edition. Gary, NC: SAS Institute Inc, 1985:403-432. 7. The CATMOD Procedure. SAS User’s Guide: Statistics. Version 5 Edition. Gary, NC: SAS Institute Inc, 1985:171-253. 8. Kaplan EL, Meyer P. Nonparametric estimation from incomplete observations. J Am Sfat Assoc 1958;53:457-481. 9. Lawrie DM, Higgins MR. Gcdman MJ, Oliver MF, Julian DG, Donald KW. Ventricular fibrillation complicating acute myocardial infarction. Lancer 1968; 2:523-528. 10. Dhurandhar RW, MacMillan RL, Brown KWG. Primary ventricular fibrillation complicating acute myocardial infarction. Am J Cardiol 1971;27:347-351. 11. Lie KI, Wellens HJ, Durrer D. Characteristics and predictability of primary ventricular fibrillation. Eur J Cardiol 1974;1:379-384. 12. Carruth JE, Silverman ME. Ventricular fibrillation complicating acute myocardial infarction: reasons against the routine use of lidwaine. Am Heart J 1982;104:545-550. 13. Campbell RWF. Treatment and prophylaxis of ventricular arrhythmias in acute myocardial infarction. Am J Car&l 1983;52:(supp1)55C-59C. 14. Dub&C, Smeets JP, Denoulin JC, Pierard L, Foidart G, Henrard L, Julippe C, Preston L, Carlier J, Kulbertus HE. Incidence, clinical significance and prognosis of ventricular Ebriliation in the early phase of myccardial infarction. Eur Heart J 1986;7:945-951. 15. Conley MJ, McNeer JF, Lee KL, Wagner GS, Rosati RA. Cardiac arrest complicating acute myocardial infarction: predictability and prognosis. Am J Cardiol 1977;39:7-12. 16. Chapman BL. Relation of cardiac complications to SGOT level in acute myocardial infarction. Br Heart J 1972;34:890-896. 17. Dewhurst NG, Hannan WJ, Muir AL. Ventricular performance and prognosis after primary ventricular fibrillation complicating acute myocardial infarction. Eur Hem J 1984;5:275-281. 18. Geddes JS, Adgey AAI, Pantridge JF. Prognosis after recovery from VF complicating ischemic heart disease. Lancet 1967;2:273-275.
APPENDIX SPRINT study group: Henry N. Neufeld, MD (deceased);Jacob Agmon, MD; Solomon Behar, MD; Uri Goldbourt, PhD; Henrietta Reicher-Reiss, MD, Edward Abinader, MD; Jacob Barzilay, MD; Natalio Cristal, MD; Yaacov Friedman, MD; Nissim Kauli, MD; Yehezkiel Kishon, MD; Abraham Palant, MD; Benyamin Peled,MD, Leonardo Reisin, MD; Egon Riss, MD (deceased);Zwi Schlesinger, MD; Izhar Zahavi, MD; Monty Zion, MD. Executive board: Chairman Henry N . Neufeld, MD (deceased)(Sheba Medical Center, Tel Hashomer); Vice-Chairman: Jacob Agmon, MD (Beilinson Medical Center Petach Tikvah)-Members: Principal Investigators. Participating centers, principal investigators and physicians: Assaf Harofeh Hospital, Zerifin: Principal Inves-
tigator-Zwi Schlesinger, MD, physician-Moshe Algom, MD; Barzilai Medical Center, Ashkelon: Principal Investigator-Leonardo Reisin, MD; physician-Newton Yalom, MD; Be&son Medical Center, Petach Tikvah: Principal Investigator-Yaacov Friedman, MD; Carmel Hospital and Medical “Lin” Haifa: Principal Investigator-Abraham Palant, MD; physician-Ephraim Mayer, MD, Central Emek Hospital, Afula: Principal Investigator-Jacob Barzilay, MD; physician-Lev Bloch, MD; Hasharon Hospital, Petach Tikvah: Principal Investigator-Izhar Zahavi, MD; physician-Menathem Katz, MD, Hillel Yaffe Hospital, Hadera: Principal Investigator-Benyamin Peled, MD, MSc; physician-Zakki Abu-Moukh, MD; Kaplan Hospital, Rehovot: Principal Investigator-Nissim Kauli, MD; physician-Emanuel Liebman, MD; Rambam Medical Center, Haifa: Principal Investigator-Egon Riss, MD, MSc (deceased);physician-Jamil Hir, MD; Bnei Zion Center, Hazya: Principal Investigator-Edward Abinader, MD; acting Principal Investigator-Ehud Goldhammer, MD; physician-Salim Maalouf, MD; Shaare Zedek Medical Center, Jerusalem: Principal Investigator-Monty Zion, MD; physicians-David Rosenmann, MD, Jonathan Balkin, MD, Sheba Medical Cenfer, Tel Hashomer: PrincipaI Investigator-Henrietta Reicher-Reiss, MD; Soroka Medical Center, Beersheva: Principal Investigator-Natalio Cristal, MD; physician-Galina Getz, MD; Wolfson Medical Center, Holon: Principal Investigator-Yehezkiel Kishon, MD; physician-Ron Narinsky, MD; Coordinating Center, Sheba Medical Center, Tel Hashomer: Solomon Behar, MD (Director), Uri Goidbourt, PhD (Epidemiologist), Henrietta ReicherReiss, MD (Critical Events Supervisor), Lori Mandelzweig, MPH.
THE AMERICAN JOURNAL OF CARDIOLOGY
NOVEMBER 15, 1990
In 5,839 consecutive patients with acute myocardial infarction (AMI), hospitalized between July 1981 and July 1983 in 14 coronary care units in Israel, the incidence of primary ventricular fibrillation (VF) was 2.1%. Patients with primary VF resembled counterparts without VF in terms of age, gender, frequency of previous AMI and past cigarette smoking habits. The hospital course of patients with primary VF revealed increased incidence of primary atrial fibrillation and atrioventricular block. lnueased serum levels of glutamic oxaloacetic transaminase and lactic dehydrogenase were noted among the patients with primary VF. In-hospital mortality rate was 18.8% in 122 patients with primary VF compared with 8.5% in 3,707 patients forming the reference group (p
From the Neufeld Cardiac ResearchInstitute, Sheba Medical Center, Tel-Hashomer, Israel. Data for patients with acute myocardial infarction in the Register were supportedby a researchgrant from Bayer AG (Wuppertal, Federal Republic of Germany) within the framework of the SPRINT Study. Manuscript received March 23, 1990; revised manuscript received June 26,1990, and acceptedJune 28. Address for reprints: Soloman Behar, MD, SPRINT Coordinating Center, Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Hashomer, 52621 Israel. 1208
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 66
entricular fibrillation (VF) remains a frequent and major, potentially lethal, complicationof acute myocardial infarction (AMI). Although there is general consensusthat secondaryVF is associatedwith markedly elevated in-hospital mortality and may represent poor prognosis for survivors of AMI, opinions vary as to the prognostic value of primary VF.l-3 We therefore undertook a study to determine the associationof primary VF with in-hospital mortality after AMI.
V
METHODS
From 1981 to 1983 we conducted a secondaryprevention study-the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT)-in 2,276 survivors of AM1 using nifedipine or placebo in 14 hospitals in Israel.4 During the study period, a logbook of all patients with AM1 was maintained (SPRINT Registry). The diagnosis of AM1 was confirmed by clinical electrocardiographic and enzymatic findings. Demographic and medical data were collected on special forms. Follow-up through mid-1988 was completedfor all hospital survivors of the Register. For the purpose of this study, primary VF was de fined as VF complicating a first or recurrent AM1 occurring within 48 hours of admissionin patients in Killip class I. According to this definition, no clinical or xray signs of congestive heart failure on admission to coronary care units were recorded and neither congestive heart failure, pulmonary edema,cardiogenic shock nor persistent hypotension (systolic blood pressure(90 mm Hg/48 hours) precededthe occurrenceof VF. Patients in an identical hemodynamic state (Killip class I) during their first 48 hours of hospitalization in the coronary care unit, without VF, were defined as the reference group. All patients with primary VF were connected to a monitoring system at bedside and to the central electrocardiographic monitor of the coronary care unit when the arrhythmia occurred. Immediate electrical cardioversion was provided and standard cardiopulmonary resuscitation maneuvers were begun without delay by the staff of the coronary care unit. The SPRINT Registry of AMI, including 5,839 patients, provides a good opportunity to evaluate the incidence, the in-hospital outcome and the long-term influence of primary VF on the prognosis of survivors of acute AMI. One hundred twenty-two of these patients fulfilled the criteria of primary VF and 3,730 patients formed the reference group. Statistical analysis: Age-adjusted prevalence of attributes correlating with primary VF has been calculated. Multivariate logistic analysis of hospital and mor-
TABLE I incidence of Primary Ventricular Fibrillation According to Gender, Age and Past History Case/Total Men Women 550 270 AMI location Anterior Inferior Non-Q-AM1 Previous MI f 0 AP + 0 Hypertension -IO Smoked cigarettes f 0
Ill Hospital Course With and Without Primary
p Value
99/4.315 23/ 1,524
(2.3) (1.5)
19/671 75/3,398 28/1,770
(2.8) (2.2) (1.6)
52/2.565 57/2,264 6/451
(2.0) (2.5)
NS co.05
Age group War) 5169
TABLE
(1.3) NS
23/1.432 96/4,297
(1.6) G-9)
48/2,867 69,‘2,790
(1.7)
71 73
1,969 1,369
(59) (60)
NS
(54) (37)
CO.05
-co.05
(2.5) co.05
(1.8) (2.2)
42/2,790 75/3,381
TABLE
NS
IV In-Hospital Mortality
(2.2) (2.0)
62/2,758 44/2,249
Primary VF (n = 122)
Reference (n = 3,707)
No.
W)
No.
W)
p Value
99
031)
2,828
(76)
NS NS
19 75 28
(16) (62) G-3
542 2,278 887
(15)
(61) (24) NS
52 57 6 23 48 42 62 60
(43) (47) (5) (19) (39) (34) (51)
1,434 1,621 322 700 1,728 1.464 1,897 61
Reference
Primary VF
TABLE II Characteristics of Patients with Primary Ventricular Fibrillation and of the Reference Group
Ape group (year) 250 51-69 270 AMI location Anterior Inferior Non-Q-AM1 Previous AMI AP Hypertension Smoked cigarettes Mean age (years)
Reference (n = 3,707)
NS
AMI = acute myocardial infarction; AP = angina pectoris; NS = not significant; + = positive: 0 = negative.
Men
VF (n = 122)
Men Women Age (years) 550 51-69 270 First AMI Recurrent Ml AP Hypertension Smoked cigarettes AMI location Anterior Inferior Non-Q-AM1
Case/Total
(%)
Case/Total
(%)
pValue
17/99 6/23
(17) (26)
184/2.828 131/879
(7) (15)
CO.01 NS
l/19 9/75 15/28 12/96 8/23 12/48 7/42 11/67
(5) (12) (54) (13) (35) (25) (17)
(1) (7) (17) (8) (9) (10) (9) (4)
NS
06)
7/542 158/2,278 1 SO/887 240/2,972 66/700 167/1,728 128/1,464 76/1.897
16/52 4/57
(31) (7) (17)
150/1,434 127/1.621 14/322
(11) (8) (4)
l/6
NS
Abbreviations as in Table I.
(39) w (9) (1% (47) W (51)
lar percent of previous AMIs but a lower incidence of angina pectoris compared with those of the reference NS group. The hospital course of patients with primary VF NS was more complicated than that in the reference group NS (Table III). Paroxysmal atria1 fibrillation and advanced AMI = acute myocardial infarction; AP = angina pectoris; NS = not significant; VF = atria1 ventricular block occurred about twice as often in ventricularfibrillation. patients whose primary VP complicated the infarction as in the reference group. High serum enzyme levels of tality after dischargeyielded estimates5of the covariate- glutamic oxaloacetic transaminase and lactic dehydroadjusted predictive power of primary VF in early (in- genasewere frequently found in patients with primary hospital) mortality. The SAS software was utilized, spe- VF. The most striking finding of this study was the macifically the FREQ6 and CATMOD’ procedures. jor effect of primary VF complicating AMI on the inhospital outcome (Table IV). Patients with primary VF ESULTS The incidence of primary VF in the SPRINT Reg- had a twofold mortality rate (18.8%) compared with ister population was 2.1% (122 of 5,839). The latter those in the reference group (8.5%). These statistics of rate did not vary markedly according to gender (men higher relative risk of hospital fatalities in patients with primary VF persistedin different subsetsof patients ac2.3%;women 1.5%), first (2.2%) versus recurrent AMI (1.6%), age, location of myocardial infarction and an- cording to gender, age, and clinical history. In a logistic regression,the estimated odds ratio for hospital mortaliamnestic features (Table I). The characteristics of patients with primary VP are ty equaled 2.86 when adjusted only for age, and 2.52 comparedwith those of the reference group in Table II. (95% confidence limits, 1.42 and 4.46) when adjusted Patients with primary VF had the samemean age, simi- for the combined effects of age, gender, location and -l-HE AMERICAN JOURNAL OF CARDIOLOGY
NOVEMBER 15, 1990
209
history of AMI, cerebrovascular accident and hypertension and the percent of patients with serum lactic dehydrogenase levels exceeding 4 times the upper normal limit. An appreciation of the usefulnessof the analysis, is obtained by the proportion of in-hospital deaths (54.8%) occurring in those with the highest 20% probability of mortality calculated by the logistic risk function. The excessof in-hospital mortality among patients with primary VF was due to electromechanical dissociation, cardiac rupture and standstill or intractable arrhythmia, but not due to pump failure. Thirteen patients died instantaneously from intractable arrhythmias, most occurring during recurrent chest pain with new electrocardiographic changes of ischemia, conduction disturbances, or both. Late hospital death after successful resuscitation occurred in 10 patients, 5 of whom had recurrent intractable arrhythmias. The Kaplan-Meyer survival curve,8 comparing mortality in patients with primary VF with that in reference patients is shown in Figure 1. Mortality rate over the first year after discharge was 3.0% for survivors of primary VF (3 of 99 patients) and 6.5% in the reference group (difference not significant). Mortality rate through 1988 (4.5 to 6.5-year follow-up) was 16.2 and 21.2% in the primary VF and reference groups, respectively. DISCUSSION The SPRINT Registry of patients with AMI, based on data of a large AM1 patient group collected from 14 of 21 coronary care units existing in Israel, establisheda reliable estimation of the incidence of primary VF. Most important, it has allowed the comparison of case fatality between patients with primary VF and counterparts receiving comparable medical care. Our results indicating a primary VF incidence of 2.1% in the coronary care unit are in accord with a number of previous studies9-l4 We found that primary VF, complicating AMI, strongly predicted in-hospital mortality. Patients
2 z
0.7 I
-
+1
- -- - - PRIMARY
0
REFERENCE
50
VF
1M
150
1 200
DAYS
FIGURE 1. Cumulative survival rate in patients with acute myocardial infarction complicated with primary ventricular ldation (VF) and in the reference graup patients. 1210
fi-
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 66
with Killip class I on admission to the coronary care unit had an in-hospital mortality rate of 18.8%if they presented with primary VF and only 8.5% if they did not. This highly significant statistical difference persisted for subsetsof patients according to age, gender, disease history and the location of the AM1 on previous infarctions sustained by the patient, and was borne out by multivariate analysis, yielding a covariate-adjusted odds ratio of 2.52. The 95% confidenceinterval provides a large range for the mortality risk during the acute phaseof AM1 associatedwith primary VF, between 1.5 and 4.5; however, it probably doubles the risk. Two recent pertinent studiesreachedconflicting conclusions. In the Multicenter Investigation of the Limitation of Infarct Size study,3 40 of 815 patients who presentedwith primary ventricular tachycardia/VF had an in-hospital mortality rate (8%) comparable to patients without primary VF (7%). In the much larger thrombolytic study-The Italian Group for the Study of Streptokinase in Myocardial Infarction (GISSI)*-the large group of 326 patients with primary VF who had a first AM1 showed twofold in-hospital mortality, as observed in comparison with the referencegroup (10.8 and 5.9%, respectively). The high rate of in-hospital mortality among patients with AM1 complicated by primary VF in GISSI and other clinical studies2J5J6was attributed to the correlation between the size of AMI, defined enzymatically or morphologically, and the incidence of VF. In our study, patients with primary VF, although in Killip class I, exhibited a higher rate of serious cardiac complications and a higher incidence of elevatedserum enzyme levels, supporting the view that AM1 complication by primary VF is more extensive. However, looking at large infarctions, as estimated by markedly elevated serum enzyme levels,we still observe (Table IV) an approximate twofold mortality associated with primary VF. Given that the occurrenceof primary VF and its outcome are not influenced by thrombolysis,17the extent of necrosisdoesnot appear to provide a satisfactory explanation of excessmortality in the group with primary VF. In the latter group, we also did not observean increaseof deaths due to pump failure. These results are dissimilar to the observationsof Volpi et al.* The major question relating to the mechanismof excessmortality found in patients with primary VF complicating AM1 remains unresolved. No clinical trial could definitely determine whether primary VF was a marker for patients at increasedrisk of death or, alternatively, VF increased the extent of the necrosisin the myocardium by a sudden decreasein coronary flow, thus acting as an independent prognostic factor, In our study most of the patients who died instantaneously or during recurrent arrhythmias had chest pain with concomitant ischemic electrocardiographic changes,suggesting that primary VF becomesintractable when occurring during an extension of the ischemic process. Finally, although the in-hospital prognosis of patients with primary VF in AM1 is clearly compromised, data from different studies indicate that these life-
threatening arrhythmias did not interfere with the late prognosis of the hospital survivors of AMI.2J1~18Our own data showed comparable mortality in patients resuscitatedfrom primary VF and in control subjectsin a prolonged follow-up period over an average 5.5 years. REFERENCES P. Pasternak RC, Braunwald E, Sobel BE. Acute myocardial infarction. In: Braunwald E, cd. Heart Disease: A Textbook of Cardiovascular Medicine. 3rd ed. vol. 2. Philadelphia: WB Saunders, 1984: 1222-l 3 13. 2. Volpi A, Maggioni A, Franzosi MG, Pampallona S, Mauri F, Jognoni G. Inhospital prognosis of patients with acute myocardial infarction complicated by primary ventricular fibrillation. N Engl J Med 1987;317:257-261. 3. Tofler GH, Stone PH. Muller JE, Rutherford JD, Willich SN, Gustafson NF, Poole WK, Sobel BE, Willerson JT, Robertson R, Passamani E, Braunwald E and the MILIS Study Group. Prognosis after cardiac arrest due to ventricular tachy cardia or ventricular fibrillation associated with acute myocardial infarction (The MILIS Study). Am J Cardiof 1987;60:755-760. 4. The Israeli SPRINT Study Group. Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT). A randomized intervention trial of nifedipine in patients with acute myocardial infarction. Eur Heart J 1988;9:354-364. 5. Bishop YMM, Feinberg SE, Holland PW. Discrete Multivariate Analysis: Theory and Practice. Cambridge, Massachusetts; The MIT Press, 1975. 6. The FREQ Procedure. SAS User’s Guide: Statistics. Version 5 Edition. Gary, NC: SAS Institute Inc, 1985:403-432. 7. The CATMOD Procedure. SAS User’s Guide: Statistics. Version 5 Edition. Gary, NC: SAS Institute Inc, 1985:171-253. 8. Kaplan EL, Meyer P. Nonparametric estimation from incomplete observations. J Am Sfat Assoc 1958;53:457-481. 9. Lawrie DM, Higgins MR. Gcdman MJ, Oliver MF, Julian DG, Donald KW. Ventricular fibrillation complicating acute myocardial infarction. Lancer 1968; 2:523-528. 10. Dhurandhar RW, MacMillan RL, Brown KWG. Primary ventricular fibrillation complicating acute myocardial infarction. Am J Cardiol 1971;27:347-351. 11. Lie KI, Wellens HJ, Durrer D. Characteristics and predictability of primary ventricular fibrillation. Eur J Cardiol 1974;1:379-384. 12. Carruth JE, Silverman ME. Ventricular fibrillation complicating acute myocardial infarction: reasons against the routine use of lidwaine. Am Heart J 1982;104:545-550. 13. Campbell RWF. Treatment and prophylaxis of ventricular arrhythmias in acute myocardial infarction. Am J Car&l 1983;52:(supp1)55C-59C. 14. Dub&C, Smeets JP, Denoulin JC, Pierard L, Foidart G, Henrard L, Julippe C, Preston L, Carlier J, Kulbertus HE. Incidence, clinical significance and prognosis of ventricular Ebriliation in the early phase of myccardial infarction. Eur Heart J 1986;7:945-951. 15. Conley MJ, McNeer JF, Lee KL, Wagner GS, Rosati RA. Cardiac arrest complicating acute myocardial infarction: predictability and prognosis. Am J Cardiol 1977;39:7-12. 16. Chapman BL. Relation of cardiac complications to SGOT level in acute myocardial infarction. Br Heart J 1972;34:890-896. 17. Dewhurst NG, Hannan WJ, Muir AL. Ventricular performance and prognosis after primary ventricular fibrillation complicating acute myocardial infarction. Eur Hem J 1984;5:275-281. 18. Geddes JS, Adgey AAI, Pantridge JF. Prognosis after recovery from VF complicating ischemic heart disease. Lancet 1967;2:273-275.
APPENDIX SPRINT study group: Henry N. Neufeld, MD (deceased);Jacob Agmon, MD; Solomon Behar, MD; Uri Goldbourt, PhD; Henrietta Reicher-Reiss, MD, Edward Abinader, MD; Jacob Barzilay, MD; Natalio Cristal, MD; Yaacov Friedman, MD; Nissim Kauli, MD; Yehezkiel Kishon, MD; Abraham Palant, MD; Benyamin Peled,MD, Leonardo Reisin, MD; Egon Riss, MD (deceased);Zwi Schlesinger, MD; Izhar Zahavi, MD; Monty Zion, MD. Executive board: Chairman Henry N . Neufeld, MD (deceased)(Sheba Medical Center, Tel Hashomer); Vice-Chairman: Jacob Agmon, MD (Beilinson Medical Center Petach Tikvah)-Members: Principal Investigators. Participating centers, principal investigators and physicians: Assaf Harofeh Hospital, Zerifin: Principal Inves-
tigator-Zwi Schlesinger, MD, physician-Moshe Algom, MD; Barzilai Medical Center, Ashkelon: Principal Investigator-Leonardo Reisin, MD; physician-Newton Yalom, MD; Be&son Medical Center, Petach Tikvah: Principal Investigator-Yaacov Friedman, MD; Carmel Hospital and Medical “Lin” Haifa: Principal Investigator-Abraham Palant, MD; physician-Ephraim Mayer, MD, Central Emek Hospital, Afula: Principal Investigator-Jacob Barzilay, MD; physician-Lev Bloch, MD; Hasharon Hospital, Petach Tikvah: Principal Investigator-Izhar Zahavi, MD; physician-Menathem Katz, MD, Hillel Yaffe Hospital, Hadera: Principal Investigator-Benyamin Peled, MD, MSc; physician-Zakki Abu-Moukh, MD; Kaplan Hospital, Rehovot: Principal Investigator-Nissim Kauli, MD; physician-Emanuel Liebman, MD; Rambam Medical Center, Haifa: Principal Investigator-Egon Riss, MD, MSc (deceased);physician-Jamil Hir, MD; Bnei Zion Center, Hazya: Principal Investigator-Edward Abinader, MD; acting Principal Investigator-Ehud Goldhammer, MD; physician-Salim Maalouf, MD; Shaare Zedek Medical Center, Jerusalem: Principal Investigator-Monty Zion, MD; physicians-David Rosenmann, MD, Jonathan Balkin, MD, Sheba Medical Cenfer, Tel Hashomer: PrincipaI Investigator-Henrietta Reicher-Reiss, MD; Soroka Medical Center, Beersheva: Principal Investigator-Natalio Cristal, MD; physician-Galina Getz, MD; Wolfson Medical Center, Holon: Principal Investigator-Yehezkiel Kishon, MD; physician-Ron Narinsky, MD; Coordinating Center, Sheba Medical Center, Tel Hashomer: Solomon Behar, MD (Director), Uri Goidbourt, PhD (Epidemiologist), Henrietta ReicherReiss, MD (Critical Events Supervisor), Lori Mandelzweig, MPH.
THE AMERICAN JOURNAL OF CARDIOLOGY
NOVEMBER 15, 1990