Acta Med Scand 211: 157-162, 1982

Factors of Importance for QRS Complex Recovery after Acute Myocardial Infarction

Salim Yusuf,' Milagros Estrada-Yamamoto,2 Carlito P. re ye^,^ Johan Herlitz and Ake Hjalmarson

From Department of Medicine I , Sahlgren's Hospital, University of Goteborg, Goteborg, Sweden

ABSTRACT. The regression of the ECG signs of myocardial infarction has been studied in 101 pa- tients. A significant increase in R wave amplitude and decrease in Q wave depth on the standard ECG was observed over three months. In 21 % of the patients, Q waves disappeared completely. In inferior infarc- tion, these changes were more apparent in the lateral V leads than in the inferior limb leads. Patients with intraventricular conduction defects were excluded. Two factors associated with the Q and R wave changes have been identified. Lower heart rates ap- peared to facilitate the recovery of R waves, and smaller infarcts, as assessed by peak LDH, showed greater ECG recovery. This study raises the interest- ing possibility that modification of the heart rate may affect favourably the healing process after an acute myocardial infarction.

Key words: QRS changes, heart rate, infarct size, infarct localization, @blockade. Acta Med Scand 211: 157-162, 1982.

Received May 26, 1981.

Considerable interest has recently been focused on the evolution of electrocardiographic (ECG) changes during acute myocardial infarction (AMI), with the intention of intervention to prevent further development of Q waves and loss or R waves. Few studies have been performed to investigate ECG changes after hospital discharge. Although regres- sion of Q wave changes after an AM1 has been reported, little is known regarding the changes in R wave amplitude. The purpose of this paper was to describe the changes in Q and R waves during the first 3 months after an AMI. The possibility to mod- ify these changes with a &-selective blocker, me- toprolol, was investigated. Furthermore, we wanted to evaluate whether other factors, such as infarct localization, estimated infarct size and heart rate, could be of importance for Q and R wave recovery.

PATIENTS AND METHODS A total of 101 patients (95 men, 6 women), less than 70 years of age (mean 58.1+7.5), admitted to Sahlgren's Hospital, Goteborg, with definite ECG and enzyme evi- dence of AMI, were studied. All patients with intraven- tricular conduction defects, QRS duration of more than 110 msec, previous history of AM1 and those develop- ing reinfarction during a three-month follow-up were excluded. Sixty-seven patients had anterior (V,-V,) transmural infarct, 8 anterior subendocardial, 6 lateral (V5, V8, I, avL) and 20 inferior (11, 111, avF) infarct.

The patients were randomized into two groups at entry. In a double-blind manner, one group received placebo and the other 15 mg metoprolol i.v. followed by tablets of 50 mg every 6 hours for 48 hours and then 100 mg twice a day for 3 months.

Standard 12-lead ECGs were recorded once a day for 4 days and then every 2 or 3 days until discharge. The ECG showing the smallest R wave amplitude and largest Q wave as an expression of the final development of the infarct, was used as the baseline reading for the study. ECG was recorded again 3 months after discharge in the Postinfarc- tion Clinic. All ECGs were recorded on a 4- or 6-channel Mingograph (Elema-Schonander 34 or 69) at a paper speed of 50 mmlsec and standardization of 10 mm=l mV.

The amplitudes of the Q, R and S waves from each V lead, leads I , 11, 111, avL and avF were measured. The sum of all waves in the V leads of patients with anterior infarction was used, the sum of 11, Ill and avF of those with inferior infarction, and the sum of I, avL, and V5 and V6 of those with lateral infarction. The difference be- tween the first and the third months ECG tracing was

Abbreviations: ECG = electrocardiography (-phic), AM1 =acute myocardial infarction, LDH = lactate dehy- drogenase.

Present addresses: 'Cardiac Dept., The Radcliffe Infir- mary, University of Oxford, Oxford OX2 6HE, United Kingdom. Wept. of Medicine, University of Santo TO- mas Hospital, Espana Street, Sampaloc Manila, Philip- pines. 3Dept. of Medicine, Cardinal Santos Memorial Hospital, Manila, Philippines.

Correspondence to: J. Herlitz, MD, Dept. of Medicine I, Sahlgren's Hospital, S-413 45 Goteborg, Sweden.

Acrci Med Sccind 211

158 S . Yirsr!f'et (11.

R-amDl mm

..

- D 22

- 3 12 !

TRANSMURAL SUeENDOCARl ANTERIOR ANTERIOR

SD 9.8

.I r SD 10.L I mitia 3mont

,L LATERAL

.p<0.05 r.p<O.Ol ... p ~ 0 . 0 0 1

Fig. I . Changes in R wave amplitude in V leads in patients with anterior transmural, subendocardial anterior and lat- eral infarction over 3 months following AMI .

estimated for each wave. The reading o f the ECGs was blind. The medium value of 3 consecutive QRS complexes was registered. The PQ segment was used as baseline. Blood was drawn at I f -hour intervals for 48-108 hours (mean 81.9k26.7) for estimation of lactate dehydrogenase (LDH) I + I I levels, according to Brydon and Smith ( 3 ) . Peak values were used as an index of infarct size in each patient. A l l patients had been admitted early enough to obtain peak values.

Heart rate measurements were made from the same ECGs as analyses of QRS complexes during hospital stay and at three-month controls. The mediirm value o f these two measurements was applied when analysing the corre- lation between heart rate and QRS complex recovery.

. ~ t ( ~ / I . ~ l ~ c " i / tnethod.t Standard paired and unpaired r-tests were used. The vari- ance o f the data i s represented throughout by standard deviation.

RESULTS

Antcrior irati.vmircil in,firrc,tion ( n =67) The sum of K waves increased significantly from an initial mean value of 20.6rfl6.7 to 35.3k22.0 at 3 months (p<0.001, paired t-test) (Fig. I). The surn of Q waves decreased significantly from an initial mean of 30.6rf19.6 to 15.lt16.0 at 3 months

(p<0.001, paired t-test). In 14 (21 %) of the 67 pa- tients the Q waves disappeared by 3 months and were replaced by initial R waves. Thirty-four pa- tients were given metoprolol and 33 placebo.

Siib~ticloc~(irdirrI tinterior infiirction ( 1 1 = 8) The sum of R waves increased in the V leads from an initial mean value of 38.9k 12.5 to 60.Sk 17.0 at 3 months (p<0.005, paired r-test) (Fig. I ) . All pa- tients were given metoprolol. The mean heart rate was 56.9 beatslmin.

Ltiterul ittfiirction ( n =6) The sum of R waves increased from an initial mean of 22.0t10.4 to 34.3k9.8 at 3 months ( p t O . O 1 , paired t-test) (Fig. I) . Simultaneously, the sum of the Q waves decreased from an initial mean of 5.5k2. I to 3.7k I .8 (p t0 .05 , paired t-test). Five patients were given metoprolol and one placebo. The mean heart rate was 55 beats/min.

Ittfirior u~t i l l infiirction ( n =20) The sum of R waves in leads I I + I I I and avF did not alter significantly, changing from a mean of 14.0k8.5 initially to 13.6t6.3 at 3 months (Fig. 2). The sum of Q waves showed a small decrease from an initial value of 7.8k3.4 to 6.8k3.1 at 3 months (NS. paired t-test).

Some ECG changes of infarction were present in V , , VJ and V, in 12 patients. In contrast to the inferior leads, the sum of R waves in these V leads increased from an initial mean of 26.6t19.4 to 37.4k23.8 (pt0.1) (Fig. 2). The increase in the surn

amDI rnm

I" I I I 1 initial )months initial Jmonl

$ , Vs and V6 II ID and aVF 5

Fig. 2. Changes in R wave amplitude in lateral V leads and leads 11, 111 and a V F in patients w i th inferior wall infarc- tion over 3 months following AMI .

R-ampi mm

initial 3months initial 3 months PLACEBO METOPROLOL

Fig. 3. Changes in R wave amplitude in patients with anterior transmural infarction over 3 months following AMI. A comparison between placebo and metoprolol groups.

of R waves in the lateral leads (mean 1 I .3k7.1) was significantly greater than that in the inferior leads (2.03+2.46,p<0.001, paired t-test). Eleven patients were given placebo and 9 metoprolol.

The influence of'/3-bloc~Xtrde (trrinsrnural unterior infiirctioti) (ti =67) To assess the influence of P-blockade, we com- pared changes in the Q wave, the R wave and the R / Q ratio in the metoprolol (ri=34) and placebo (n=33) groups. The sum of R waves increased from initial mean values of 24.8k28.7 and 24.2k39.1 to 35.9t20.8 and 39.0k22.9 in the placebo and meto- prolol group, respectively (Fig. 3). The sum of Q waves decreased from a mean of 32.6k16.h t o 17.2k17.2 in the placebo group and from 26.6k21.6 to 1 1.5k13.1 in the metoprolol group.

Though the A R in the two groups did not reach statistical significance, a trend in favour of meto- prolol was observed. The A Q and R / Q ratio were not compared, as the starting point wa5 significantly different in the two groups.

The influence of heurt rtrte (n=67) All patients with anterior transmural infarction were allocated to 3 approximately equal groups ac- cording to the mean heart rate calculated from the baseline and 3-month ECG recordings which both took place after randomization. Group 1: heart rate 63 b e a t s h i n or less (n=22), group 11: heart rate 64-76 b e a t s h i n (;=23), group 111: heart rate >76 beatslmin (n=22) (Fig. 4).

The increase in the sum of R waves was signifi- cantly higher in group I (mean A R = 20.5k 11. I ) than in group I I (mean AR=+14.6+9.3, p<O.OS) and higher in group I 1 than 111 (mean AR=+9.3?8.8, p<0.025). The increase in group I was even more significant when compared to group 111 (p<O.O01). The number of patients receiving metoprolol de- creased progressively from group I (l7/22) through group I 1 (11/23) to group 111 (6/22).

'To find out if there was a similar trend of increas- ing R wave recovery with lower heart rate even in the absence of p-blockade, the placebo group was subdivided into 3 groups of 1 1 patients each (group I: heart rate ~ 7 2 beats/min, mean 64.7k6.6, group 11: heart rate 73-82 beats/min, mean 76.3k3.4, grotrp 111: heart rate >82 beats/min, mean 91.8k6.5). The AR in group I (23.2k12.4) was sig- nificantly greater than in group 11 (11.4k8.34, p < O . O I ) and the increase in group 11 was not sig- nificantly greater than in group 111 (7.2k7.8, p < O . l ) . The difference between groups I and I11 was highly significant (p<O.OOS) (Fig. 5) .

The patients treated with metoprolol were then subdivided into 3 groups. Group I: (heart rate 4 9 beats/min) mean heart rate 54.7k4.0, A R 17.9k8.3 ( n = 12). group 11: (heart rate 60-69 beatslmin) mean heart rate 64.1 k2.9, A R 15.8k9.9 ( n = 12), group 111: (heart rate 270 beats/min) mean heart rate 83.1 k I I .3, A R 11.0k9.9. There was no statistically significant difference between groups I and 11 or groups I 1 and 111, but a significant difference was found between groups I and 111 (p<O.OS).

r---- p<M01__- 7

+50

I. Grou I GrWPU Groupm HR& HR64-76 W 7 6 n.22 n.23 n.22

Fig. 4 . Changes in R wave amplitude in V leads plotted against heart rate in all patients with anterior transmural infarction over 3 months following AMI.

160 S. Yusuf rt tr l .

Group I Grwp II Group 111 Ms72 HR=73-62 HR>83 n=ll n=ll n=ll

Fig. 5 . Changes in R wave amplitude in V leads of un- treated patients with acute anterior transmural myocardial infarction plotted against heart rate.

QRS duration (n =40) The duration of the QRS complex, measured in 40 patients with anterior transmural infarction, was 83.6k14.4 msec in the initial recording and 86.4k 10.7 msec at 3 months (NS).

Peak LDH 1+1I in relation to heurt rute (n=66) The peak LDH I+II was compared in the 3 groups with low, middle and high heart rates. The LDH I+II peak was lower in the group with low heart rate when all patients were included. However, as this figure included a great number of patients given metoprolol, the LDH I f 1 1 peak in the 3 subgroups of placebo patients was compared. No significant difference was observed.

Peak LDH l+ll versus R wave recovery (n=65) Patients were divided into 2 groups according to infarct size as assessed by peak LDH I + I 1 values i.e., large infarcts (>21 units, n=32) and small in- farcts ( ~ 2 1 units, n=33). The increase in the mean of the sum of R waves was greater in patients with small infarcts (17.2k11.2) than in those with large (1 1.8+ 1 1 .O) (p<0.025) (Fig. 6).

DISCUSSION

In the present study a significant increase in R wave and a decrease in Q wave amplitudes occurred with- in 3 months after an AMI. The Q wave disappeared completely in 21 % of patients with anterior trans- mural infarction. This figure is consistent with the

observations of Pyorala and Kentala (17) who re- ported a decrease of 16% in the number of patients showing Minnesota-codable Q waves at 8 weeks after infarction. In contrast, studies comparing ECGs recorded 8-10 weeks and one year after AM1 showed little ECG improvement ( 1 1 , 14). This probably implies that a large proportion of these changes take place in the first 8-12 weeks after an AMI. In the same group of patients, a significant increase in the R wave amplitude could be noticed during the first 3 months after AMI.

There is a theory that p-blockade may have a protective effect on the ischemic myocardium (15). The investigation was made to find out whether the recovery of the QRS complex after an AM1 can be influenced by p-blockade. No clear difference in the increase in R wave amplitude during metoprolol and placebo treatment could be demonstrated.

The study was extended to find out whether heart rate, associated with p-blockade therapy, has some correlation with the recovery of R wave amplitude. Patients with lower heart rates showed greater re- covery of R wave amplitude. This was shown in the entire gorup of patients with anterior transmural infarction, also when subdivided and analysed separately for placebo and metoprolol adrninistra- tion. The exact mechanism causing the increase in R wave and decrease in Q wave amplitude is un- clear. Scar shrinkage has been postulated (7, 9) following which the edges of the healthy myocar- dium are brought under the recording electrode. This has not, however, been substantiated by actual experimental or direct observation. It is possible

:l------ Pc 0.025

Group I Group 11 LDHq21 LDH 221 n = 33 n.32

Fig. 6 . Changes in R wave amplitude in V leads of all anterior transmural infarction patients plotted against peak LDH I + I I .

Acrcr Med Sr,crnd 211

Recovery of ECG chunges rrfrer AM1 161

that at lower heart rates there is less mechanical stress to the infarct zone, which in turn may lead to better healing of the myocardium. Another mechanism by which a lower heart rate could bring about the changes observed may be decreased ischemia in the area around the infarct. Severe chronic ischemia is known to inhibit protein syn- thesis and leads to degeneration of the myocardium (10). In contrast, mild ischemia, as caused by a high work load, might be a stimulus for net protein synthesis and localized hypertrophy (8). Other mechanisms, not related to ischemia or scar shrink- age, are possibly responsible for the increase in R wave recovery in patients with low heart rate. Physical exercise is associated with higher heart rate and decrease in R wave amplitude. Progressive decrease in both systolic and diastolic heart vol- umes under the sympathetic drive of exercise may be responsible for this reduction in R wave amplitude (2). Administration of digitalis to animals resulted in an increase in R wave amplitude (13). Decreased heart rate and increased end-diastolic volume might explain this phenomenon (16). In the present study no significant change could be de- monstrated in heart rate between the observation period in hospital and the three-month control. In- traventricular conduction defects may also lead to an increase in R wave amplitude. However, this seems unlikely in the patients studied as the QRS width changed little and was not more than 100 msec in any of them.

It has been reported that patients with heart fail- ure after an AM1 showed little restitution of the QRS complex compared to patients without heart failure (14). This is in accordance with the theory that there is a connection between changes in QRS complex and the clinical status of the patient.

When trying to roughly estimate the infarct size, the peak value of the LDH I+11 was used. Pathoanatomic studies have shown a good correla- tion between the infarct size at autopsy and the peak value of this enzyme (6). Smaller infarcts, assessed by peak LDH I+II values, showed greater R wave recovery when compared to larger infarcts. This may imply that the healing process is better in small than in large infarcts. Hearts with smaller infarcts may have a better coronary artery circula- tion and/or a higher resistance to ischemic damage in the infarct border zone. Larger infarcts are more likely to cause heart failure with left ventricular dilatation and myocardial strain. Initially, we were

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surprised to observe no significant change in the R wave in leads 11, I11 and avF in inferior infarction, even when the V leads reflected a substantial im- provement in some patients. It seemed unlikely that the mechanism behind the increase in R wave amplitude should produce changes in the anterior wall different from those in the inferior wall in the same patient. It is, however, possible that this dif- ference may be an arterfact as the precordial leads are positioned closer to the heart than the limb leads (Poisson’s law) (4). Furthermore, the degree of re- covery of the inferior wall voltages may be insuffi- cient to cause a swing in the resultant vector to the inferior limb leads. This vector may lie closer to the horizontal axis and these changes may therefore be best reflected in the lateral V leads.

The significance and prognostic implications of R wave recovery and Q wave disappearance are un- clear, and a more extensive study will be required to elucidate these questions. It has been shown that the fewer the Minnesota-codable Q waves on the ECG 1-2 years after AMI, the lower the risk of sl;dden death (1, 5, 12). We do not know if this is related exclusively to an initial small infarct. Fur- thermore, it is not known whether the prognosis ac- tually improved in the 21 % of our patients in whom Q waves disappeared.

ACKNOWLEDGEMENTS This investigation was supported by a British Heart Foundation Travelling Scholarship, scholarships from the Swedish National Association against Heart and Chest Diseases, and grants from AB Hassle (Astra Pharmaceuti- cals), Sweden.

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13. Manoach, M . , Grosman, E., Varon, D. & Gitter, S.: Letter to the Editor: QRS amplitude changes during heart filling and digitalization. Am Heart J 83:292, 1972.

14. Mills, G. Y . , Simon, A. J. , Cisneros, F. & Katz, L. N.: Myocardial infarction. Observations on one hundred patients who survived up to six years. Arch Intern Med 84: 632, 1949.

15. Peter, T., Norris, R. M., Clarke, E . D. et al.: Reduc- tion of enzyme levels by propranolol after acute myocardial infarction. Circulation 57: 1091, 1978.

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