J. ELECTROCARDIOLOGY 10 (4), 1977 305-312

Prognostic Features of Ventricular Tachycardia Complicating Acute Myocardial Infarction BY SADAYAPPAK. DURAIRAJ, M.D., K. VENKATARAMAN, M.D., MARIA DE GUZMAN, M.D. AND L. JULIAN HAYWOOD, M.D.

experience reveals t h a t lidocaine is an extremely useful drug, e7-3~ doubts have been raised about its efficacy in the m a n a g e m e n t of ventricular arrhythmias during the early phase of AMI. 33-39 This clinical study, therefore, was u n d e r t a k e n to evaluate (1) the role of coupling intervals (CI), prematurity indices (PI) and the types of VT in the prognosis and therapeutic responses of VT; (2) the importance of underlying H R in the clinical course of VT; and (3) the efficacy of conventional doses of lidocaine in the t r e a t m e n t and prevention of VT.

SUMMARY Prognostic features of 115 patients with ventricular tachycardia complicating acute myocardial infarction were analyzed. Age, sex, infarct location and peak CPK levels were not significantly d i f f e r e n t w h e n c o m p a r i n g survivors (S) and non-survivors (NS). Highly significant clinical characteristics of NS compared to S were: heart rate, presence o f cardiogenic shock and a poor response to lidocaine therapy (P < 0.0001, 0.0003 and 0.001 respectively). Electrocardiographic features distinguishing S and NS were: coupling intervals (S = 522.9, NS = 389.9, P < 0.004), prematurity index (S = 1.36, NS = 1.04, P < 0.001), ventricular tachycardia rate (S = 132, NS = 174, P < 0.0013) and n u m b e r o f episodes of ventricular tachycardia (S = 4.04, NS = 6.75, P < 0.0058). These findings have importance for the evaluation of newer active

MATERIALS AND METHODS The records of 1000 consecutive patients admitted to the Coronary Care U n i t (CCU) of the Los Angeles County--University of Southern California Medical Center between May 1973 and December 1974 were reviewed. One hundred fifteen of 473 patients with AMI (24%) who had VT as a complication form the basis of this study; the study period was confined to the period of CCU stay. Admission to the 12-bed Coronary Care Unit was on a bed-availability basis. Monitoring: Patients were continuously monitored by c o n v e n t i o n a l e l e c t r o c a r d i o g r a p h i c monitoring instruments; rate meters with alarms were available for some patients, and an oscilloscope was beside each bed and at the central nurses' station. Memory loops were incorporated into the system for all patients with a 40-sec delay. Definitions: (A) Criteria for diagnosis of AMI: a clinical history of chest pain, the development of diagnostic Q waves and ST-T wave abnormalities and/or serial changes of CPK, SGOT and LDH enzymes. 1'2 (B) Ventricular tachycardia was defined as three or more successive beats of ventricular origin. 4°'ax (C) Coupling interval was measured in milliseconds from the onset of the Q wave of the previous sinus beat to the onset of the ~R' of the first beat of the VT. (D) Prematurity index was expressed as the ratio of the coupling interval of VT to the QT interval of the preceding sinus beat (QR/QT). (E) The clinical status of the patients was classified as per Killip as follows: Class 1, no failure; Class 2, mild to moderate failure; Class 3,

and prophylactic therapies. The incidence of ventricular tachycardia (VT) complicating acute myocardial infarction (AMI) varies from 10-52% in clinical reports, and, despite therapy, the associated mortality remains high. 1~ Although much has been written about the precursors of VT and ventricular fibrillation (VF), ~13 the prognostic features of VT complicating AMI itself have not been fully explored. Experimental studies indicate t h a t the relationship of heart rate (HR) to the genesis of ventricular arrhythmias remains controversial. 14"z6The role of H R in the clinical course of VT in m a n has not been well studied. Although coronary care

From the Los Angeles County - - University of Southern California Medical Center, Los Angeles, California. Supported by grant #MB00/46. Reprint requests to: L. Julian Haywood, M.D., Box 305, 1200 N. State St., Los Angeles, CA 90033. 305

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DURAIRAJ ET AL

pulmonary edema or severe failure; Class 4, cardiogenic shock with hypoperfusion. 2 (F) Response to conventional dose of lidocaine (50-100mg bolus followed by 2-4 mg of continuous infusion) was graded as follows: (1) rapid and complete suppression of VT, (2) incomplete suppression of VT with intermittent break through, (3) no effect on VT and (4) acceleration of VT or degeneration into ventricular fibrillation. The VTs were classified as per Schamroth's criteria 4°'41 as follows: Extrasystolic VT (EVT) - VTs with constant coupling intervals (rate usually greater than 100/min); parasystolic VT (PSVT) - varying coupling intervals with constant interectopic intervals; accelerated idioventricular rhythm - - same coupling and interectopic intervals, presence of fusion beats at the time of onset and offset, and slower rate (less than 100/min). VTs which could not be included in the above groups were designated as an unclassified group. The records were analyzed with reference to the following points: age, sex, location of MI: highest CPK recorded; Killip Class; presence or absence of PVCs; time of onset of VT with reference to the onset of MI; sinus rate at the time of onset of VT; type of VT; frequency of VT; longest duration of VT; shortest coupling interval; mode of therapy and response to therapy; development of ventricu-

lar fibrillation and outcome. Statistical analysis of these results was done using chi-square and Student's T test. P values less than 0.05 were considered significant.

RESULTS A m o n g t h e 479 p a t i e n t s w i t h AMI, 115 pat i e n t s h a d VT, a n incidence of 24.4%. T h e i r a g e s r a n g e d f r o m 2 4 - 9 4 y e a r s ( m e a n 58.2 years). Ninety-one w e r e m a l e s a n d 24 f e m a l e s . I n f a r c t location w a s a n t e r i o r in 70 p a t i e n t s , inferior in 37 a n d c o m b i n e d in 8. O f t h e 115 p a t i e n t s , 82 w e r e s u r v i v o r s (72,6%) a n d 33 w e r e n o n s u r v i v o r s (24.4%). T h e m o r t a l i t y r a t e for t h e t o t a l g r o u p w a s 13.5% (66 of 479 p a t i e n t s died). T h e d u r a t i o n of C C U s t a y for s u r v i v o r s w a s 5.2 a n d n o n s u r v i v o r s 6.5 d a y s (P v a l u e NS). Pertinent clinical data and the various c h a r a c t e r i s t i c s of t h e VTs a r e s u m m a r i z e d in T a b l e 1. It is s e e n t h a t t h e n o n s u r v i v o r s h a d s h o r t e r P I s a n d CIs, h i g h e r h e a r t r a t e s a n d f a s t e r V T r a t e s (Figs. 1-4). I n addition, pat i e n t s in Killip classes 3 a n d 4 h a d a h i g h e r mortality.

TABLE I Comparison of the Various Features of Patients with VT Between the Survivors and Nonsurvivors

NO.

FEATURES

1.

Age - mean

SURVIVORS

2.

Sex - male female

3.

Locationof MI Anterior Inferior

4. 5. 6. 7.

Comb. Time of onset - hrs. CPK level Heart rate - beats/min. Killip Class - 1

2 3 8.

9.

10. 11. 12. 13.

4 Response to therapy Responsive Nonresponsive Coupling interval - (msec) VT Rate - Beats/Min Prematurity index

Numberof VT episodes Durationof VT in seconds 100 seconds

NONSURVIVORS

PVALUE

NS/S

58.4O 66 16

60.03

0.9716 0.5723 0.5723

NS

49 28 6

22 0.3677 0.0726 0.8527 0.0001

NS NS NS S

K~

__.

,,:, 5 0 0

.~

"'

~

(,c >KF

I.rr < ,,, "r

Z _~ o. D

k-

~) 40

~"

20

R

I

Z

N-R

-'

~

m

~1.0

~

N-R

LU100 n-

.50

F>

0

R

--I-

R

N-R

R

N-R

-P:O.O001

R.

N-R

Fig. 5. Characteristics of responders and nonresponders to ]idocaine therapy. Nonresponders to ]idocaine had significant]}, higher mortality (|eft bar graph), higher heart rates, shorter coupling intervals, prematurity indices and faster VT rates. J. ELECTROCARDIOLOGY, VOL. 10, NO. 4, 1977

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DURAIRAJ ET AL

at slow heart rates the temporal disparity in r e c o v e r y t i m e s w a s i n c r e a s e d and t h e threshold to ventricular arrhythmias decreased. ~3,15'~6'1s It has been postulated that increased cholinergic activity increased ventricular ectopy and that by increasing the heart rate with atropine and isoproterenol this could be abolished. 22'~6 In contrast, recent clinical and experimental studies have emphasized that in acute ischemia, tachycardia is deleterious and may i n d u c e v e n t r i c u l a r a r r h y t h m i a s . 21'23'24 Epstein et al pointed out that cholinergic activity and bradycardia had a ~salutary effect" on ventricular irritability. 24'2~ Interestingly, Chadda et al observed in a canine infarction model that both slow and rapid heart rates i n c r e a s e d v e n t r i c u l a r i r r i t a b i l i t y and suggested an i n t e r m e d i a t e rate of 60-90 beats/min as the optimal anti-arrhythmic heart rate. 25 The present study confirms the association of malignant VT and rapid heart rates in man. It is of interest that there was no significant difference in heart rates in patients according to Killip's four clinical classes. However, nonsurvivors uniformly had higher heart rates and they responded poorly to lidocaine therapy. While 71% of patients with heart rates less than 100/min responded, only 43% of those with heart rates greater than 100/min responded well to therapy. In experimental AMI in dogs, procainamide and beta blockers have effectively suppressed VT when lidocaine has failed, especially when VT occurred with tachycardia. 3s In view of these observations and other experimental studies, the value of modification of heart rate with beta blockers in the lidocaine-resistant VTs deserves further study. Type of VT. Although there are scattered reports, the incidence and significance of the various types of VT in AMI have not been s y s t e m a t i c a l l y evaluated. In the present study, EVT was most commonly observed, and with two exceptions, all nonsurvivors had EVT (Table 2). We observed an incidence of PSVT of 3.5% while Salazar et al reported a 1.8% incidence among 630 patients with AMI. 44 The fact that all patients with PSVT survived supports the conclusion that PSVT is a relatively benign arrhythmia. The reported incidence of AIVR varies from 9-36% and generally it is considered that it requires no t r e a t m e n t . 45 Our s t u d y r e v e a l s the coexistence of AIVR and EVT, and similar observations have been reported by Massumi et al and deSoyza et al. 48'7 These results emphasize the need for close observation of patients with AMI and AIVR, and the potential need for therapy. In 11 of our patients, the VT could not be clearly classified into any of the known

groups. The prognostic importance of the various types of VT needs further evaluation. Efficacy of Lidocaine on VT. Various CCU studies have reported t h a t lidocaine suppressed ventricular ectopics in 80-95% of patientsY '31 Prophylactic use of lidocaine has been advocated in all patients with AMI. s,3°'32 On the contrary, Adgey et al reported that in 1/3 of their patients lidocaine was ineffective in abolishing ventricular ectopic beats. 33 Lidocaine has been considered hazardous in t h e p r e s e n c e of b r a d y - a r r h y t h m i a s and acidosis. 35 Recently, Geddes et al observed that lidocaine may facilitate re-entry, ss'37 Indeed, in five of Schamroth's 19 patients, ventricular irritability increased with lidocaine. 4°'41 E x p e r i m e n t a l and clinical studies also document that lidocaine in the usual t h e r a p e t u t i c doses is ineffective in abolishing early re-entry type arrhythmias with shorter prematurity indices. 34,35,3s Sixty-five percent of our patients developed VT while receiving usual therapeutic doses of lidocaine for PVCs. Failure of lidocaine to prevent serious ventricular tachyarrhythmias has been reported to occur in 30-40% of patients. 33'35,37 Furthermore, patients with VTs with short CIs and PIs, faster VT r a t e s and HRs r e s p o n d e d poorly to lidocaine therapy (Fig. 5). Unfortunately, lidocaine levels were not available in our patients. Accordingly, there are two explanations for the nonresponsiveness to lidocaine therapy. The first consideration is that these patients with VT and short CI and PI were true nonresponders despite adequate therapy. The second is t h a t t h e y did not receive adequate therapy. It has been suggested that suboptimal doses of lidocaine may actually worsen ventricular arrythmias. We feel the second explanation would not apply to all of our patients, since nonresponders usually received more boluses of lidocaine and higher infusion rates. Blood levels done in 12 subsequent patients who received comparable doses of lidocaine averaged 3.3 mgm/L.* These data suggest that the therapy of VT must be individualized and that VTs with short prematurity indices might indeed be better treated with drugs like procainamide and propranolol. These findings have importance for planning and evaluating active and p r o p h y l a c t i c t h e r a p y of v e n t r i c u l a r arrhythmias in acute myocardial infarction. *Unpublished data. REFERENCES 1. LOWN,B, VASSAUX,C, HOOD,W B, FAKHRO,A M, KAPLINSKY, E AND ROBERG, G: Unresolved problems in coronary care. Am J Cardiol 2"494, 1967 2. KIMBELL, J H AND KILLIP, T: Aggressive J. ELECTROCARDJOLOGY, VOL. 10, NO. 4, 1977

VT COMPLICATING AMI

3.

4.

5. 6.

7.

8.

9.

10.

11.

12.

13. 14.

15.

16.

17. 18. 19.

treatment of arrhythmias in acute myocardial infarction - procedures and results. Progr Cardiovasc Dis 10:483, 1968 WIGGERS, C J, WEGRIA, R AND PINERA, B: The effects of myocardial ischemia on fibrillation threshold - the mechanism of spontaneous ventricular fibrillation following coronary occlusion. Am J Physiol 131:309, 1940 SMIRK, F H AND PALMER, D G: A myocardial syndrome with particular reference to the occurrence of sudden death and premature systoles interrupting antecedent T waves. Am J Cardiol 6:620, 1960 WIGGERS, C J: Mechanism and nature of ventricular fibrillation. Am Heart J 20:399, 1940 WILLIAMS, D O, HOPE, R, EI-SHERIF, N, LAZZARA, R AND SCHERLAG, B J: Characteristics of malignant premature beat. Clin Res 22:14A, 1974 (abstract) DESOYZA, N, BISSETT, J.K, KANE, J J, MURPHY, M L AND DOHERTY,J E: Ectopic ventricular prematurity and its relationships to vent r i c u l a r t a c h y c a r d i a in acute m y o c a r d i a l infarction in man. Circulation 50:529, 1974 LIE, K I, HEIN, J J, WELLEN, S, DOWNAR,E AND DURRER, D: Observations on patients with primary ventricular fibrillation complicating acute m y o c a r d i a l infarction. C i r c u l a t i o n 52:755, 1975 WIT, A L AND BIGGER, J T: Possible elect r o p h y s i o l o g i c a l m e c h a n i s m s for l e t h a l a r r h y t h m i a s accompanying myocardial infarction. Circulation 52:Suppl III - 96, 1975 SCHERLAG, B J, HELFANT, R H, HAFT, J AND DAMATO, A N: Electrophysiology underlying ventricular arrhythmias due to coronary ligation. Am J Physiol 219: 1665, 1970 WALDO. A L AND KAISER, G A: Study of ventricular a r r h y t h m i a s associated with acute myocardial infarction in the canine heart. Circulation 47:1222, 1973 BOINEAU,J P AND Cox, J: Slow ventricular activation in acute myocardial infarction. A source of reentrant premature ventricular contraction. Circulation 48:702, 1973 HAN, J, GOEL, B G AND HANSON, C S: Reent r a n t beats induced in the ventricle during coronary occlusion. Am Heart J 80:778, 1970 ADGEY, A A J, GEDDES, J S, MULHOLLAND,H C, KEEGAN, D A J AND PANTRIDGE, J F: Incidence, significance and management of early bradyarrhythmia complicating acute myocardial infarction. Lancet 2:1097, 1968 HAN, J, MILLER, D, CHIZZONITTI,B AND MOE, G K: Temporal dispersion of recovery of excitability in atrium and ventricle as a function of heart rate. Am Heart J 71:481, 1966 HAN, J, DETRAGLIA,J, MELLET, D AND MOE, G K: Incidence of ectopic beats as a function of basic rate in the ventricle. Am Heart J 72:632, 1966 SOWTON, E, LEATHAM, A AND CARSON, P: The s u p p r e s s i o n of a r r h y t h m i a s by a r t i f i c i a l pacemaking. Lancet 2:1098, 1964 HAN, J: M e c h a n i s m s of v e n t r i c u l a r arrhythmias associated with myocardial infarction. Am J Cardiol 24:800, 1969 ALEXANDER,S AND PING, W: Fatal ventricular

J. ELECTROCARDIOLOGY, VOk. 10, NO. 4, 1977

20. 21. 22.

23.

24.

25.

26. 27.

28. 29.

30.

31. 32.

33. 34.

35. 36. 37.

311

fibrillation during carotid sinus stimulation. Am J Cardiol 18:289, 1966 ZIPES, D P: T h e c l i n i c a l s i g n i f i c a n c e of bradycardic rhythms in acute myocardial infarction. Am J Cardiol 24:814, 1969 NORRIS, R M, MERCER, C J AND YATES, S E: Sinus rate in acute myocardial infarction. Br Heart J 34:901,1972 KENT, K M, SMITH, E R, REDWOOD, D R AND EPSTEIN, S E: T h e d e l e t e r i o u s electrophysiological effects produced by increasing heart rate during experimental coronary occlusion. Clin Res 20:379, 1972 EPSTEIN, S E, REDWOOD, D R, KENT, K M AND SMITH, E R: The early phase of acute myocardial infarction. P h a r m a c o l o g i c aspects of therapy. Ann Int Med 78:918, 1973 KENT, K M, REDWOOD, D R, SMITH, E R AND EPSTEIN, S E: Electrical stability of acutely ischemic myocardium, influences of heart rate and vagal stimulation. Circulation 47:291, 1973 CHADDA, K, BANKA, V S AND HELFANT, R H: Rate dependent ventricular ectopia following coronary occlusion. The concept of an optimal anti-arrhythmic heart rate. Circulation 49:654, 1974 HAN, J: Atropine and acute myocardial infarction. Circulation 47:429, 1973 GIANELLY,R, VON DER GROEBER,J O, SPIVACK, A P AND HARRISON, D C: Effect of lidocaine on v e n t r i c u l a r a r r h y t h m i a s in p a t i e n t s with c o r o n a r y h e a r t d i s e a s e . N E n g l J Med 277:1215, 1967 CHOPRA, M P, PORTAL, R W AND ABER, C P: Lignocaine therapy after acute myocardial infarction. Br Med J 1:213, 1969 LIE, K, WELLENS, H J, VAN CAMPELLE, F J AND DURRER, D: Lidocaine in the prevention of primary ventricular fibrillation. N Engl J Med 291:1324,1974 VALENTINE, J L, FRET, M L, FORD, M AND SLOMAN, J G: Lidocaine in the prevention of sudden death in the pre-hospital phase of acute infarction. N Engl J Med 291:1327, 1974 LOWN, B AND VASSAUX, C: Lidocaine in acute myocardial infarction. Am H e a r t J 76:581, 1968 WYMAN, M G, AND HAMMERSMITH, L: Comprehensive treatment plan for the prevention of primary ventricular fibrillation in acute myocardial infarction. Am J Cardiol 33:661, 1974 ADGEY, A A J, GEDDES, J S, WEBB, S W, ALLEN, J D, JAMES, S AND ZAIDI, S A: Acute phase of myocardial infarction. Lancet 2:501, 1971 HOPE, R R, WILLIAMS,D O, EL-SHERIF, N, LAZZARA, R AND SCHERLAG,B J; The efficacy ofantiarrhythmic agents during acute myocardial ischemia and the role of heart rate. Circulation 50:507, 1974 NEVIN, M A: R e - e v a l u a t i n g t h e u s e of lidocaine. Geriatrics 28:48, 1973 GEDDES, J S, WEBB, S W AND ADGEY, A A J: Effect of lidocaine on "gating" mechanism. Am Heart J 88:260, 1974 GEDDES, J S, WEBB, S AND PANTRIDGE, J F: Limitations of lignocaine in control of early ventricular dysrhythmias complicating acute

312

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myocardial infarction. Br Heart J 34:964, 1972 38. OLIVE,W, GAMBLE,A B AND COHN,K: Effect of propranolol, procainamide and lidocaine on ventricular automaticity and re-entry in experimental myocardial infarction. Circulation 46:498, 1972 39. DUGHNSAN,S ANDCOHN,K: Detrimental effect of non-homogeneous distribution of lidocaine to the myocardium. Circulation 48:Suppl IV132, 1973 40. SCHAMROTH,L: Genesis and evolution of ectopic ventricular rhythms. Br Heart J 28:244, 1966 41. SCHAMROTH,L: The Disorders of Cardiac Rhythm. Blackwell Publications, Oxford, 1972 42. KHAN,M, HAMILTON,J T ANDMANNING,G W:

43. 44. 45. 46.

Early a r r h y t h m i a s following experimental coronary occlusion in conscious dogs and their modification by beta-adrenoreceptor blocking drugs. Am H e a r t J 86:347, 1973 ZIPES,D P, BESCH,H R AND WATANABE,A M: Role of slow current in cardiac electrophysiology. Circulation 51:761, 1975 SALAZAR,J AND MCKENDRICK, C S: Ventricular parasystole in acute myocardial infarction. Br Heart J 32:377, 1970 NORRIS, R M AND MERCER,C J: Significance of idioventricular rhythms in acute myocardial infarction. Prog Cardiovasc Dis 16:455, 1975 MASSUMI, R A AND ALI, N: A c c e l e r a t e d isorhythmic ventricular rhythms. Am J Cardiol 26:170, 1970

J. ELECTROCARDIOLOGY, VOL. 10, NO. 4, 1977