Serial electrocardiographic changes in myocardial infarction

Serial Electrocardiographic Changes in Myocardial Infarction

SUKETAMI TOMINAGA, MD* THOMAS STRASSER, MD? HENRY BLACKBURN, MD, FACC Baltimore, Minneapolis,

Maryland Minnesota

From the Laboratory of Physiobgical Hygiene, University of Minnesota, Minneapolis, Minn., the Institute of International Medicine, University of Maryland, Baltimore, Md. and the Institute of Social and Preventive Medicine and the Cardiological Center, University of Geneua, Geneva, Switzerland. This investigation was supported by grants from the National Hea,rt and Lung Institute to the Electrocardiographic Center, Coronary Drug Project, University of Minnesota (HE 11898), to the Coordinating Center, Coronary Drug Project, University of Maryland (HE 08888), to the Cardiovascular Clinical Research Center, University of Minnesota (HE 06314), and to Professor Ancel Keys (HE 04997-11). Manuscript received August 11, 1971, accepted October 15, 1971. * Present address: Institute of International Medicine, University of Maryland, Baltimore, Md. 21201. t Present address: Cardiovascular Disease Section, World Health Organization, Geneva. Switzerland. Address for reprints: Henry Blackburn, MID, Laboratory of Physiological Hygiene, Stadium Gate 27, University of Minnesota, Minneapolis, Minn. ‘Y5455,.

VOLUME 29, JUNE 1972

This study considers 2 principal questions: (1) the degree to which objective application of criteria from conventional simple electrocardiographic wave measurements can approach clinical diagnosis of myocardial infarction; and (2) the degree of independent diagnostic contribution made by serial electrocardiographic change. Systematic criteria for serial electrocardiographic change do not exist. Little is known about diagnostic information contained in serial data versus that in single records. A comparison is made of electrocardiographic values measured over time in putatively healthy male control subjects with those measured before, during and after documented myocardial infarction in men in long-term studies of general populations. There was little op portunity for bias in selection of the cases of infarction from these populations, and diagnosis was based on hospital documentation during the acute phase. A systematic computer search was made for electrocardiographic criteria giving maximal sensitivity for cases of clinical infarction while holding the false positive rate in normal subjects to less than 5 percent. Analysis gave the best discriminant criteria between normal subjects and patients with infarction on the basis of (1) measurements in single post-event records, (2) change between pre- and post-event records, (3) their combination. Serial electrocardiographic changes were also weighted according to the absolute wave amplitude. The most sensitive conventional criteria for diagnosis of old anterior infarction were based on absolute R wave amplitude plus loss of R amplitude in selected leads. Sensitivity was 70 to 80 percent for diagnosis of old anterior infarction using very simple criteria, 50 to 60 percent for old inferior infarction, and 30 to 50 percent for intermediate syndromes callled “coronary insufficiency.” Discriminant function analysis improved thediagnosis of old infarction and coronary insufficiency. However, in this comparison, among survivors of documented myocardial infarction, the objective application of criteria for serial electrocardiographic change between pre- and post-event records made only a modest independent contribution to diagnosis of old infarction beyond that obtained from measurements in the single electrocardiogram post-infarction. The contribution of serial change might better be studied over the longer run. Many biological measurements are more effective as predictors over time than as diagnostic discriminants at a given moment.

The physician often relies on changes between serial electrocardiograms in the diagnosis and management of apparent cardiovascular episodes. Among other things, he is concerned with the

767

TOMINAGA

ET At.

new appearance or evolution of S-T segment displacement, change in sense of the T wave, and the development of new or larger Q or QS waves, as well as arrhythmias and conduction defects. Such changes during acute episodes of coronary disease are often so distinct that the need for quantitative criteria does not arise. Moreover, residual electrocardiographic findings after infarction are often sufficiently obvious that precise objective comparison of serial tracings is not essential to diagnosis or good clinical management. On the other hand, several clinical situations call for a finer quantitative approach to criteria for serial electrocardiographic change. The most important of these is in the diagnosis of questionable or atypical clinical episodes. Another is in the evaluation of change observed between tracings taken in periodic examinations, especially when no documented clinical event has occurred in the interim. Another is in long-term therapeutic trials and population studies in which quantitative comparison of serial electrocardiograms provides the main objective evidence among living subjects of the frequency and course of cardiac involvement.l** Despite these several needs, no formalized body of criteria for significant serial change has been proposed or validated. Much recent work has attempted to transpose the more impressionistic and deductive elements of clinical electrocardiographic interpretation into measurable components. This has largely been occasioned by the requirements for precision and simple logic of special programs for automated computer analysis. This transposition has been and is still a tedious process. However, clinically useful by-products may obtain in the form of objective electrocardiographic criteria. These may lead in turn to a degree of reduced variability and, thus, to improved diagnosis and prediction from the electrocardiogram. In recent years much attention has been given to these computer programs for recognition, measurement, classification and diagnosis of wave amplitudes and durations. The diagnostic value of these programs has usually been tested in comparison groups of patients with clear-cut disease versus normal subjects. However, little attention has been given to the diagnostic value of changes between serial tracings. Probably no attention has been given to the possible improvement in diagnostic power to be obtained by combining criteria for serial electrocardiographic change with criteria commonly used for findings in a single tracing. This study considers 2 principal questions: (1) the degree to which the clinical diagnosis of myocardial infarction, made by cardiologists, can be achieved by straightforward manipulations of objective electrocardiographic measurements from records taken before, during and after acute coro768

nary episodes; and (2) the degree of independent or additive contribution of serial change to the diagnosis. In brief, the study involves detailed measurements of common wave amplitudes and durations made in conventional resting 12 lead electrocardiograms. These tracings were recorded serially in men followed up in long-term population studies who eventually had coronary disease. Records were available from routine scheduled examinations made before and after the acute coronary event. Electrocardiographic documentation of the acute phase was obtained in all cases and was available for measurement in most. Single and combined criteria for electrocardiographic amplitudes, and for serial changes between records, are tested for sensitivity in diagnosis of cases of infarction. In parallel, the specificity of the same criteria is determined to identify agematched control subjects, that is, men from the same longitudinal studies whose serial electrocardiograms were obtained within a similar observation period during which they remained “healthy.” A systematic search is made for the electrocardiographic amplitudes and intervals, and their serial changes, which best discriminate between men with clinically manifest infarction and their apparently healthy counterparts of the same age. The objective in this early approach to analysis of serial change is not to revalidate the electrocardiogram of myocardial infarction, or even the particular criteria used here. Such validation is traditionally based on totally independent evidence of infarction, such as that obtained by autopsy findings or radiographic techniques. The aim is rather to determine (1) the extent to which measured findings in single and serial electrocardiograms can detect and describe the survivors of cardiologist-diagnosed clinical coronary events, and (2) the degree to which such events are differentiated from changes in healthy men who display only “normal variability” between serial records. However, this report seeks a clinically practical approach to criteria for serial change and attempts to find, using a computer analysis, the best diagnostic discriminants from multiple and combined criteria. Finally, it attempts to elucidate the relative contribution of serial electrocardiographic change to the diagnosis of coronary events. Method Cases

The patients were 179 middle-aged men, aged 33 to 69 years (mean 53 years), who survived a first episode of infarction or an intermediate form of event here called “coronary insufficiency.” The diagnoses were based on a central review and assessment of all clinical data (including the electrocardiogram obtained during the acute phase) by the cardiologists in charge of several on-going studies of adult working men in the The American

Journal

of CARDIOLOGY

ELECTROCARDIOGRAM

United States: the Framingham Study? the Chicago Western Electric Study,’ the Los Angeles Civil Servant Study5 and the Minnesota CVD program.6 The diagnostic criteria used in these several centers are not uniform, but the cases are those considered by the investigators as the definitive coronary events in these studies. All diagnoses were validated by extensive documentation at the time of acute infarction and were made in systematic case study reviews. Definite diagnosis of infarction required a clinical episode along with distinct S-T segment and T wave findings with their expected evolution during the acute hospital phase, or distinct serum enzyme changes. Acute coronary insuficienc~ is the common term used in the United States for intermediate syndromes in which the clinical symptoms and signs are compatible with infarction but the electrocardiographic and enzyme changes are inadequate or atypical, and in which there is no Q wave evidence of myocardial necrosis. Each investigative group provided these electrocardiographic tracings : (1) The conventional 12 lead resting tracing from the scheduled examination prior to the year in which the subject’s first “coronary” event occurred (the “pre-event” electrocardiogram). (2) The single hospital tracing considered to be the most representative or diagnostic of those taken during the acute clinical episode (the “at-event” electrocardiogram). (3) The tracing from the scheduled study examination after the acute clinical episode (the “postevent” electrocardiogram) obtained 6 to 18 months after infarction. Controls The patients with coronary disease from the several studies were age-matched with, and serial electrocardiograms measured from, men of those studies who were found to be free of clinical cardiac manifestations or major illness both before and during the period between successive scheduled examinations. The “normal” serial electrocardiographic change here is therefore based on participants documented as “healthy” over the long term in these several populations. It represents changes due both to measurement and to biological variability between records made 2 years apart. This variability includes the very remote chance of occurrence of a clinically “silent” event among the normal control subjects. The clinical determination of “normality” was made independently of the electrocardiogram, except that subjects with gross arrhythmias or conduction defects were excluded, irrespective of apparent clinical health. It is reiterated that there is no bias in selection of “cases” here ; all cases in these prospective studies are included, but the diagnoses are only partly electrocardiographically dependent in that electrocardiographic findings during the acute phase of the coronary episode were involved in the investigator’s original diagnosis of infarction or coronary insufficiency. However, the cardiologist’s diagnosis of infarction is entirely independent of the findings in the post-event electrocardiogram itself. Measurements

The following detailed electrocardiographic measurements were made in each record before, at and after the event in the patients and in each of 2 succesVOLUME

29. JUNE

1972

IN MYOCAROIAL

INFARCTION

sive scheduled tracings, 2 years apart, in the normal subjects: (1) Q, R, S and T wave amplitudes when present in 12 conventional leads, (2) Q duration in leads showing Q waves, (3) QRS duration as the maximal duration found in any frontal plane lead, (4) P-R interval in lead II, and (5) QRS axis from leads I and III. Wave amplitudes and durations were measured in mounted conventional paper tracings (speed 25 mm/ set) in the next to last beat of each lead ; estimations were made to the nearest 0.i mm using 6 power magnification, with a standard error of measurement of about 0.25 mm (0.025 mv) for R wave amplitudes and 0.25 mm (0.01 second) for durations. The raw electrocardiographic data were punched on cards containing the subject identification numbers, age, classification of event (whether pre-, at, or post-event), the diagnostic code (including site and type of infarction), and the detailed wave measurements for individual leads. Computing the Diagnostic Power

A program was designed for computer reading of the punched cards for the identifying data and for the individual amplitudes and intervals, from each lead of each electrocardiogram, according to clinical grouping (anterior or inferior infarction or coronary insufficiency) . The total distribution of values for each measured item for each record was arrayed in linear classes by clinical grouping. These arrays formed the basis for subsequent computations of the sensitivity of given criteria for identifying the patients with disease, at given levels of specificity of the criteria for identifying normal subjects. Several computations of sensitivity and specificity were made. One was based on the absolute value of the electrocardiographic item in each serial record separately; this represents a conventional way of assessing diagnostic discrimination based on a given single record, without regard to serial comparisons. A second computation gave the diagnostic discrimination obtained by criteria for serial change alone. A third combined the results of serial change in a given item with criteria for the absolute value of the same item in the later record of the serial pairs. Another computation was made since 0 given amplitude change in a QRST complex having low amplitudes was considered likely to have more significance than the same degree of change in a complex with larger amplitudes. For this, a systematic though arbitrary weighting procedure was utilized. Next, a computer search was made for optimally discriminating single and multiple combined criteria (those giving maximal sensitivity with an “acceptable” rate of false positives), keeping in mind the desirability of a practical clinical system for objective evaluation of serial electrocardiographic change. Finally, a discriminant function computer program was run to find the maximally discriminating combinations of amplitude, serial changes and lead derivations for each phase and type of coronary event. Some of the straightforward computational steps used to determine criteria for optimal discrimination between the normal and coronary patient groups are illustrated below. Table I illustrates how diagnostic Absolute values: sensitivity and specificity were computed from the ab769

TOMINAGA

TABLE

ET

AL.

I

Determination of Diagnostic Sensitivity and Specificity from the Absolute R Wave Amplitude in Lead V1* Percentages Anterior Infarct R Amplitude (mm) < 0.5 1.0 1.5 2.0 2.5

Normal (no. = 50)

Pre-Event (no. = 78)

At-Event (no. = 46)

Post-Event (no. = 60)

28.3 28.3 28.3 32.6 37.0

21.2 28.8 36.4 37.9 40.9 43.9 45.5 47.0 50.0 50.0

0.0

0.0

0.0 0.0 0.0

0.0 0.0

0.0

0.0

0.0

3.0 3.5 4.0 4.5 5.0

0.0

37.0 39.1 39.1

0.0 0.0

0.0 0.0 0.0 2.6 2.6

5.5 6.0 6.5 7.0 7.5 8.0 a.5

2.0 2.0 2.0 2.0 4.0 4.0 4.0t

3.8 3.8 3.8 3.8 5.1 5.1 6.4

47.8 50.0 50.0 50.0 56:5 56: 5 63.01

53.0 53.0 53.0 53.0 57.6 57.6

9.0 9.5 10.0

6.0 a.0 a.0

6.4 9.0 9.0

63.0 67.4 67.4

59.1 60.6 60.6

10.5 11.0 11.5 12.0

12.0 12.0 12.0 12.0

17.9 17.9 23.1 23.1

73.9 73.9 73.9 73.9

66.7 66.7 71.2 71.0

50.0

100.0

100.0

100.0

100.0

0.0 0.0

* Cumulative percentages point. t False positive. $ Sensitivity.

of cases

47.8 47.8

found

below

59.1$

each

cut-off

solute electrocardiographic wave values. The first column shows successive limit points covering the range of amplitude measurements, in this example, the R wave amplitude in lead V4; column 2 shows the proportion of normal control subjects included within each successive increase of amplitude criterion. The next 3 columns illustrate the proportion of eases of anterior infarction identified by the same criteria, from tracings taken before, during and after the event. The usual computation involved a search for the highest sensitivity for case diagnosis which was consonant with a false positive rate less than 5 percent (which is equivalent to a specificity greater than 95 percent in detecting normal subjects). In the example of Table I, 3 different cut-off limits or criteria for R wave amplitude yieId the same specificity (96 percent specificity, 4 percent of normal subjects included), less than 7.5, 8.0 or 8.5 mm. However, the cut-off value of 8.5 mm for RV4 identifies the greatest proportion of oases of “acute” anterior infarction (63 percent of the

770

acute at-event record) for the same level of specificity, whereas it detects 59.1 percent of cases of “old anterior infarction” (in the post-event record). Increasing the diagnostic sensitivity is possible by extending the criterion cut-off point upward to 9.5 mm. This results in a false positive rate (8 percent) which arbitrarily throughout is considered unacceptable. If the population with infarction were identical in origin to the control group the proportion of cases identified by a given criterion in the pre-event records of the patients would be the same as that in the normal control subjects. The small differences found are readily understandable. The annual or scheduled electrocardiogram obtained in these patients in the examination made just before the year of infarction might be expected to show differences from the record taken at the same examination in those who later remained healthy. Serial change plus absolute amplitude: Table II illustrates how diagnostic sensitivity-specificity was determined by a combination of criteria for magnitude of the serial change in RVI (between the electrocardiogram taken before and that taken at the time of anterior infarction) plus criteria for the absolute value of RV4 amplitude applied in the second of the paired records, in this case, at the time of the coronary event. Figuratively, A is a vertically moving cut-off line which determines the proportion of the putatively healthy control men who showed a given serial amplitude change between scheduled examinations. Only 4 percent showed a loss of as much as 4 mm in RV4 amplitude between serial records. However, if one adds to this criterion another criterion, absolute RVI amplitude less than 9 mm, in the later record of the serial pair the combined criteria improve the specificity. The “best” line is at B, giving 98 percent specificity. In the lower part of the table the same cut-off point A for serial change (24 mm loss in RV4) results in detection of 71 percent of the cases of anterior infarction. Seventy-one percent of these men lost at least 4 mm RV, amplitude between the pre-event record and that of their acute infarction. When the cases are added which, in the at-event record, have an absolute RV, amplitude under 9 mm (B, found to be the optimal amplitude discriminant in Table I), the sensitivity for anterior infarction is increased from ‘71 to 79.4 percent, whereas the false positive rate for the same combination is only 2 percent. More complicated lines or combinations of criteria may occasionally achieve better discrimination. However, because of simplicity, this right angular line is considered more useful. Thus, a single simple observation of RV1 amplitude and its serial change between 2 records appears to provide an effective diagnostic discrimination between groups of patients with classic anterior infarction and selected normal subjects. Q/R ratios: To avoid Q/R ratios of infinity when R waves were absent (in QS patterns), R amplitudes of zero were arbitrarily assigned a value of 0.5 mm. To avoid Q/R ratios of zero in the absence of Q waves (that is, a Q wave less than 1.0 mm), no Q/R ratio was calculated. Amplitude weighting: The smaller the absolute change in amplitude, the greater was the weighting of

The

American

Journal

of

CARDIOLOGY

ELECTROCARDIOGRAM

IN MYOCARDIAL

INFARCTION

TABLE II Determination of Diagnostic Sensitivity-Specificity from Criteria for Serial Change Combined with Criteria for Absolute R Wave Amplitude in Lead V, A. Normal (no. = 50) Absolute Change in R Amplitude

False Positive

(R,osrR,d Percentage Distribution

(mm) <-10.0

__9*0to-9.9

(%)

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-_8.fJto

-8.9

-

_

-

-

_

-

-

-

_

-_7*0to

-7.9

-

-

-

-

-

-

-

-

-

-_6.0to

-6.9

_

_

_

_

-

_

_

_

_

-5.9 -4.9

-

-

_

-

-

-

-

-

-

2.0 2.0

-_3_0to__3.g -_2*0to__2*g -_1_0to -1.9

-

-

-

-

-

-

-

-

-

-0.1to-0.9

-

-

-

-

2.0

-

-

-

-

o.o-D.9

1.0-1.9

2.0-2.9

3.0-3.9

6.0-6.9

7.0-7.9

8.0-8.9

4.0 4.0 14.0 10.0 62.0 9.0+

__5*oto __4*0to

2 B

4 A

20.0

-

5.0-5.9

4.0-4.9

Absolute

R amplitude

(mm)

B. Anterior Infarction (no. = 48) Absolute Change in R Amplitude Sensitivity

(R.&w) Percentage Distribution

(mm)

<-10.0 -9.0 to -9.9 -8.0 to -8.9 -7.0 to -7.9 -6_Ot,, -6.9 -5.0 to -5.9

20.8 2.1

4.2 -

4.2 -

-

-

-

-

-

-

2.1 -

_ -

_ -

2.1 _ -

2.1

-

2.1 -

-

-

-

-

-

-

-

-3.0 to -3.9 -2.0 to -2.9 -_1*0to-1-g

2.1 -

-

-

-

-

-

-

-

-

-

I-

-0.1 to-o.9 20.0

2.1 -

0.0-0.9

1.0-1.9

2.0-2.9

3.0-3.9

4.0-4.9

5.0-5.9

-4.0

to -4.9

-

4.2 -

-

(%)

Absolute * Contribution Contribution Contributions

of serial change alone of absolute amplitude alone of both change and absolute

value

-

R amplitude

and curve employed were arbitrary, designed to provide similar relative change for large and small electrocarcliographic waves (available from authors). Multivariate Analysis

A discriminant analysis was performed utilizing functions of combined criteria and leads which appeared the most promising in the conventional analysis. Again, the goal was to find criteria giving maximal sensitivity in the identification of coronary cases, hold-

29, JUNE

1972

6.0-6.9

4.2 -

8.3 2.1 2.1 2.1 4.2 -

79.4* B

71.0 A

2.1 -

2.1 -

7.0-7.9

8.0-8.9

18.5 9.0+

(mm)

45.9%

the serial change (up to a factor of 3). The equation

VOLUME

at event

4.2 -

ing specificity constant as before, with a false positive rate always less than 5 percent. The University of Miami packaged program DISR was used.? The specific electrocardiographic variables entered into the discriminant analysis are given here: value feither at or nest-event) : T amplit&le in lead I Q/R ratio in lead aVF R amplitude in lead V1 Q amplitude in lead aVF Q amplitude in lead V4

Absolute

1. 2. 3. 4. 5.

771

TOMINAGA

ET AL.

Serial change (at or post-event value) : 6. T amplitude in lead I

7. 8. 9. 10.

Q/R ratio in R amplitude Q amplitude Q amplitude

value minus

pre-event

TABLE

Patients and Normal Subjects Complete Data are Available*

lead aVF in lead V4 in lead aVF in lead V;

for Whom

Clinical Diagnosis

These 5 absolute amplitudes and 5 serial amplitude changes were found to be the better discriminants in the conventional analyses just described. The number of patients and control subjects having complete data for all the listed criteria is shown in Table III.

Normal Anterior Inferior

Q wave amplitude (QA) : In Table IV the sensitivity of QA is determined for the detection of the various clinical case groups from a systematic screening of individual Q wave amplitudes, by

*The

Pre-Event and At-Event Comparison (no. of subjects)

Pre-Event and Post-Event Comparison (no. of subjects)

...

47

37 33 24

63 60 26

94

196

infarct infarct

Coronary Total

Results

TABLE

III

insufficiency

diagnostic

logic tree

absolute values plus American Documentation theauthors.

and the discriminant

functions

for

serial change are deposited with the Institute and are also available from

IV

Conventional

Analysis: Q Waves* A. Diagnostic

Discrimination

by Absolute Amplitude

of Q Waves

Percentages

ECG Lead

cut-off Values (2) (mm)

Anterior Infarct Normal Pre (no. = 50) (no. = 78)

(no.!

46)

Posterior Infarct

Coronary Insufficiency

Post (no. = 66)

Pre (no. = 72)

(no. A=’ 39)

Post (no. = 63)

Pre (no. = 29)

At (no. = 27)

Post (no. = 26)

I II

1.5 1.5

0.0 2.0

6.4 3.8

8.7 4.3

13.6 9.1

0.0 4.2

2.4 34.1

3.2 42.9

0.0 6.9

0.0 3.7

3.8 11.5

III aVL aVF Vl VZ VS Vr VS Ve

2.5 2.0 1.5 0.5 0.5 1.0 1.5 2.0 2.0

2.5 2.0 2.0 0.0 0.0 2.0 4.0 4.0 2.0

6.4 5.2 3.8 5.1 2.6 0.0 5.1 6.4 3.8

8.9 13.0 4.4 51.1 52.2 42.6 31.9 12.8 2.3

1.5 16.7 6.1 36.4 40.9 33.3 30.3 16.7 6.1

6.9 1.4 5.6 4.2 0.0 1.4 1.4 4.2 2.8

45.0 0.0 39.0 5.0 2.5 2.5 0.0 5.0 5.0

57.1 0.0 56.5 1.6 1.6 3.2 1.6 7.9 11.1

0.0 0.0 3.4 0.0 0.0 3.4 0.0 0.0 0.0

3.7 0.0 3.7 3.7 11.1 11.1 0.0 0.0 0.0

3.8 0.0 7.7 0.0 3.8 7.7 7.7 7.7 0.0

B. Diagnostic

Discrimination

by Magnitude

of Serial Change of Q Waves Percentages

ECG Lead

Serial Changef (Gain) 0)

(mm)

--

Anterior Infarct

Posterior Infarct .____-

Normal (no. = 50)

At-Pre (no. = 46)

Post-Pre (no. = 66)

At-Pre (no. = 39)

Post-Pre (no. = 63)

At-Pre (no. = 27)

Post-Pre (no. = 26)

I II III

1.0 1.0 1.0

0.0 0.0 2.0

4.2 4.2 14.7

9.1 3.0 4.5

0.0 29.3 56.2

0.0 39.5 63.6

0.0 0.0 7.4

0.0 3.8 7.6

aVL aVF VI Vf

1.0 1.0 0.1 0.1

0.0 2.0 0.0 4.0

15.7 8.4 50.0 54.2

15.1 1.5 36.4 40.9

0.0 36.6 7.3 4.8

0.0 50.8 1.6 1.6

0.0 3.7 3.7 7.4

0.0 3.7 0.0 0.0

V, V, V5 VS

0.1 1.0 1.0 1.0

2.0 0.0 0.0 2.0

50.0 31.4 12.6 12.5

37.9 28.8 13.5 6.0

4.8 4.9 4.8 7.3

3.2 0.0 4.8 11.1

7.4 0.0 0.0 010

3.8 3.8 11.5 3.4

*Values in this table are the percentage of cases which exceed the given cut-off lined values refer to text description of most sensitive criteria. t (x2 - XI).

772

Coronary Insufficiency

criteria.

In this and subsequent

The American

tables,

Journal

the under-

of CARDIOLOGY

ELECTROCARDIOGRAM

IN MYOCARDIAL

INFARCTION

QA (not tabulated) improves the discrimination only slightly (54 percent for recent anterior and 67 percent for old inferior infarction). Q wave duration was found to be far less efficient than Q wave amplitude and was not further analyzed. R wave amplitude (RA) : In Table V the absolute amplitude of R waves is found to be more sensitive than Q wave amplitude in identifying anterior infarcts, and less sensitive for inferior infarcts. The lower portion of Table V shows that serial loss of 6 mm or more in RV,, amplitude,

lead. Specificity is generally held constant at a level of less than 5 percent false positives. QA alone, from Q (or QS) waves in precordial leads in a single post-event record, detects slightly over 50 percent of recent and 40 percent of old anterior infarcts. Q (or QS) waves in leads III and aVF detect 5’7percent of old inferior infarcts. QA is understandably poor in discriminating between normal subjects and patients with coronary insufficiency because the absence of Q waves is a criterion for the clinical diagnosis. Serial change alone in Qa performs about as well as the absolute Q* alone. The appearance of precordial Q waves, for example, gives over 50 percent sensitivity for recent anterior infarction. An increase in 1.0 mm or more in Qm gives over 60 percent sensitivity for old inferior infarction. Weighting of serial change values for the actual

plus an absolute RA of less than 9 mm in the second of the 2 serial records, is the most efficient

discriminant for the group with anterior infarction versus the normal subjects. This simple criterion identifies 79.4 percent of the acute events and 68 percent of the old anterior infarcts at a

TABLE V Conventional

Analysis:

R Waves* A. Diagnostic

Discrimination

by Absolute Amplitude

Anterior Infarct

cut-off

of R Waves

Coronary Insufficiency

Posterior Infarct

Values (<) (mm)

Normal (no. = 50)

Pre (no. = 78)

At (no. = 46)

Post (no. = 66)

Pre (no. = 72)

I II III

2.5 3.0 0.5

2.0 4.0 12.0

9.0 5.1 11.5

23.9 25.5 a.7

15.2 18.2 4.5

5.6 8.3 15.3

10.0 32.5 40.0

7.9 19.0 28.6

0.0 10.3 10.3

7.4 18.5

11.1

11.5 15.4

aVL aVF

0.5 0.5 0.5 1.0 2.5 8.5 8.0 5.0

9.1 1.3 11.5 2.6 3.8 6.4 3.9 1.3

13.0 2.2 63.8 61.7 66.0 63.0 52.2 27.3

13.6 4.5 59.1 56.1 54.5 59.1 39.4 22.7

11.1 5.6 15.3 8.3 6.9 9.7 4.2 6.9

2.5 22.5 22.5 10.0 10.5 21.6 23.7 10.0

3.2 14.5 17.5 4.8 12.7 11.1 9.5 12.7

6.9 3.4 0.0 0.0 10.3 13.8 3.4 0.0

3.7 0.0 19.2 7.7 7.4 16.0 11.1 0.0

3.8 0.0 11.5 7.7 11.5 19.2 3.8 0.0

ECG Lead

VI VZ Va V4 VS V0

6.0 8.0 6.0 0.0 0.0 4.0 2.0 2.0

(no.!

39)

(noPf’63)

(no.‘:

29)

(no.!

27)

(no?26) 0.0

B. Diagnostic

2.0 2.0&R<6.0 3.0 2.0 3.0 l.O&R<2.0 3.0&R<7.0 7.0&R<3.0 6.0&R<9.0 5.0&R<8.0 3.0 *Values

2.0

39.7

27.3

14.5

4.8

7.4

23.0

0.0 0.0 2.0 2.0 2.0 2.0 4.0 2.0 2.0 2.0

33.3 12.6 31.3 16.8 50.0 45.9 69.1 79.4

25.6 4.5 18.1 10.5 37.8 48.4 63.3 68.0

31.7 8.0 4.8 20.6 6.4 6.4 14.5 14.4

11.1 7.4 7.4 22.2 11.1 3.7 18.5 22.2

71.0 47.9

49.8 30.1

38.9 12.1 9.7 34.1 9.7 4.8 19.6 34.7 39.0 26.9

11.1 19.4

14.8 14.1

0.0 3.8 11.5 3.8 3.8 7.6 7.6 19.0 7.6 11.5

in this table are the percentage of cases which exceed the given cut-offcriteria.

tcxz - Xl).

VOLUME

29, JUNE

1972

773

TOMINAGA

ET AL.

specificity level of 98 percent (use of this criterion gave 2 percent false positive results in normal subjects). Weighting of serial RA change by absolute amplitude of R waves (not tabulated) did not significantly improve the discrimination. Q/R amplitude ratio: In Table VI the Q/R ratio combines information available from both Q and R wave amplitudes. This ratio was found by others to be the single most effective electrocardiographic discriminant in the diagnosis of old infarction.a The sensitivity of Q/R ratio for anterior infarcts found in this comparison is less than that found for Q or R wave amplitude alone. However, Q/R is as sensitive or more sensitive than Q or R wave amplitude alone for the diagnosis of inferior infarction (Q/R in lead aVF is

68.3 percent sensitive ; QA in lead III is 57.1 percent sensitive). Improvement in diagnosis was obtained by weighting the values for Q/R according to the absolute amplitudes; the weighted ratio in lead II reached 78.8 percent sensitivity for old inferior innrction, at a 4 percent false positive rate (not tabulated) . R minus Q wave amplitude: Another manipulation made but not illustrated here utilized the combined information in Q and R wave amplitudes by subtraction of one from the other. RA-QA resulted in sensitivity for infarction on the order of, and not superior generally to, that obtained for Q and R amplitude alone. T wave amplitude: Because T waves are more

TABLE VI Conventional

Analysis: Q/R* A. Diagnostic Discrimination

by Absolute Value of Q/R Amplitude

Ratio

Percentages

cut-off Values (2)

ECG Lead

0.2 0.2 1.5 0.5 0.3 0.2 0.2 0.2 0.2 0.2 0.3

I II III aVL aVF V1 VZ V3 V4 VS Vg

Antejior Infarct Normal Pre (no. = 50) (no. = 78) 4.0 2.0 4.0 4.0 4.0 0.0 0.0 0.0 0.0 2.0 0.0

Posterior Infarct

Coronary Insufficiency

At (no. = 46)

Post (no. = 66)

Pre (no. = 72)

At (no. = 39)

Post (no. = 63)

Pre (no. = 29)

At (no. = 27)

Post (no. = 26)

22.9 18.7 8.5 18.7 12.8 11.5 11.5 10.0 28.2 29.2 10.6

27.3 12.1 1.5 18.2 7.6 10.6 12.8 16.0 25.9 22.2 7.6

2.8 4.2 5.6 5.6 4.2 1.4 0.0 0.0 0.0 1.4 1.4

4.9 43.9 36.1 0.0 46.3 2.6 2.5 2.5 2.5 7.3 9.8

4.8 65.1 32.2 0.0 62.9 0.0 0.0 1.6 0.0 4.8 9.5

3.4 3.4 0.0 6.9 0.0 0.0 3.4 3.4 0.0 0.0 0.0

14.8

11.5 11.5 3.8 0.0 3.8 0.0 3.8 3.8 3.8 3.8 0.0

5.1 2.6 5.1 3.8 2.6 1.3 0.0 0.0 0.0 0.0 1.3 B. Diagnostic

Discrimination

by Magnitude

3.7 0.0 3.7 0.0 0.0 7.7 3.8 3.7 3.7 3.7

of Serial Change of Q/R Ratio Percentages

Serial Change1 Gain & Absolute Ratio

ECG Lead

(>)

Coronary Insufficiency

Posterior Infarct

Normal (no. = 50)

At-Pre (no. = 46)

Post-Pre (no. = 66)

At-Pre (no. = 39)

Post-Pre (no. = 63)

At-Pre (no. = 27)

Post-Pre (no. = 26)

0.0 0.0

16.8 14.7 12.5 33.3

21.1 9.0 4.5 33.3

2.4 37.9 56.1 2.4

1.6 55.7 54.1 1.6

7.4 3.7 7.4 7.4

3.8 3.8 7.6 15.3

I II III aVL

0.1 0.1 0.4 0.1

aVF

0.1

4.0

12.6

9.0

46.4

68.3

3.7

7.6

Vl

0.1

0.0

50.0

36.4

7.3

1.6

3.7

0.0

0.0 0.0 0.0 0.0 0.0

42.1 43.7 41.6 25.0 8.4

37.9 34.9 34.9 19.6 7.5

4.8 4.9 4.8 7.3 9.7

1.6 1.6 0.0 0.0 9.6

7.4 3.7 3.7 3.7 3.7

3.8 3.7 3.7 3.7 0.0

0.1 & Q/R 0.1 & Q/R 0.1 0.1 0.1 & Q/R

VZ VI Vq VS VP, *Values t (xz -

774

Anterior Infarct

in this table

are the

2.0

4.0

2 0.2 > 0.2

2 0.2 percentage

of cases

which

exceed

the given

cut-off

criteria.

Xl).

The American

Journal

of CARDIOLOGY

ELECTROCARDIOGRAM

INFARCTION

amplitude gave generally good diagnostic results, particularly when weighted. Sensitivity of 79.3 percent was attained for recent anterior infarction, 72.7 percent sensitivity for old anterior infarction and 79.3 percent sensitivity for old inferior infarction, at the usual fixed levels of specificity. Optimally discriminating combined criteria: The simplest combinations of single and readily measured criteria were sought in a systematic computer search for best discriminants. Table VIII shows the best combinations of simple criteria based on absolute amplitudes in a given electrocardiogram-without regard to serial change. The highest sensitivity attained for the diagnosis of old anterior infarction was 81.8 percent in the particular criteria and lead combina-

sensitive clinically to ischemic changes than are QRS findings, the same types of comparisons were made in Table VII to determine sensitivity-specificity of T wave amplitude change alone. Generally T waves perform satisfactorily when comparing these well defined disease groups, one at a time, to the normal group. Weighted T wave change reached 66.6 percent sensitivity for cases of coronary insufficiency, where it was expected to be more effective than QRS changes. An effort R minus Q plus T wave amplitude: was also made (not illustrated) to utilize data from both depolarization and repolarization changes (which usually occur more or less simultaneously in infarction) by considering the absolute values and the changes of R, T and Q wave amplitudes. The computation of R minus Q plus T TABLE

IN MYOCARDIAL

VII

Conventional

Analysis: T Waves* A. Diagnostic

Discrimination

by Absolute Amplitude

of T Waves

Percentages Anterior Infarct

Posterior Infarct

cut-off Values (<) (mm)

(no. = 50)

Pre (no. = 78)

I

-1.0

0.0

3.8

55.6

38.5

2.8

II III aVL aVF

-1.0 -2.0 -2.0 -2.0

0.0 4.0 0.0 0.0

2.6 7.7 2.6 0.0

24.4 8.7 34.1 13.3

6.2 4.6 12.3 1.5

1.4 4.2 0.0 0.0

VI VZ

-2.0 -2.0

0.0 0.0

1.3 1.3

13.0 29.8

7.7 10.6

V, Vd VS

0.0 -1.0 -1.0

0.0 0.0 0.0

0.0 3.8 5.1

44.7 55.3 56.5

V6

-1.0

0.0

5.1

48.9

ECG Lead

Normal

(no. !

B. Diagnostic

46)

Post (no. = 66)

Discrimination

(no.E72)

(no.‘:b3)

(no.r29)

26.8

6.3

46.3 46.3 34.1 44.7

36.5 50.8 3.2 31.1

0.0 6.9

2.8 0.0

15.8 25.0

34.8 44.6 41.5

1.4 1.4 4.2

31.8

4.2

by Magnitude

(no. A=’ 39)

CoronaryInsufficiency

(no. A=’ 27)

(no.‘OSt26)

4.9 0.0

3.4 0.0 3.4 0.0 0.0

40.7 40.7 11.1 16.0 19.2 11.1 11.1

27.5 20.5 26.3

3.2 4.8 13.1

0.0 3.6 3.4

37.0 42.3 40.7

11.5 19.2 11.5 7.7 11.5 0.0 3.8 7.7 7.7 11.5

38.5

16.1

3.4

38.5

15.4

of Serial Change of T Waves Percentages

Serial Changet (Loss &Absolute Amplitude)

ECG Lead

(>)

(mm) 1.0

Anterior Infarct Normal (no. = 50)

At-Pre (no. = 46)

Post-Pre (no. = 66)

Posterior Infarct At-Pre (no. = 39)

Post-Pre (no. = 63)

Coronary Insufficiency At-Pre (no. = 27)

Post-Pre (no. = 26)

0.0

56.3

48.4

36.6

6.3

48.1

19.2

II

l.O&T<2.0

0.0

35.5

22.8

41.2

60.3

48.1

15.3

III aVL aVF

1.0 1.0 1.0 3.0 5.0 3.0 3.0 2.0 l.O&T<2.0

0.0 2.0 4.0 4.0 2.0 0.0 0.0 2.0 4.0

14.6 50.0 25.0 6.3 37.6 56.4 54.3 56.4 54.2

7.6 34.8 9.1 9.1 21.1 45.3 53.0 57.5 33.3

43.9 39.0 53.5 14.6 26.8 41.6 39.0 41.6 56.1

55.6 7.9 57.2 0.0 1.6 9.5 9.6 15.9 41.2

14.8 29.6 18.5 7.4 11.1 37.5 40.7 48.1 29.6

15.3 19.2 7.6 3.8 3.8 25.8 19.2 30.6 11.4

I

VI VZ V1 V4 V5 VS * Values

in this table

are the

percentage

of cases

which

exceed

the given

cut-off

criteria.

t (x2 + Xl).

VOLUME

29, JUNE

1972

775

TOMINAGA

ET AL.

TABLE VIII Conventional

Analysis: Diagnostic

Power for Combinations

of Optimally

Discriminating

Amplitude

Criteria

Percentages Anterior

Criteria

Q/R

Posterior

_

Infarct

Coronary

_

Insufficiency

Normal Pre Post At Post At Pre Pre At Pos (no. = 49)(no. = 77) (no. = 40) (no. = 66) (no. = 72) (no. = 33) (no. = 62) (no. = 29) (no. = 24) (no. = 26)

by Lead

R

Infarct

Q

R

aVL

(Z

(I)

(2)

(2)

0.2

2.0

1.0

5.0

6.0

16.9

75.0

78.8

23.6

27.3

17.7

17.2

25.0

23.1

0.2 0.5

1.0 2.0

2.0 2.0

3.0 3.0

4.0 4.0

7.8 13.0

75.0 72.5

74.2 81.8

11.1 22.2

12.1 27.3

6.5 17.7

6.9 17.2

12.5 25.0

7.7 23.1

0.5 0.5 0.5

1.0 1.0 0.0

5.0 2.0 2.0

3.0 3.0 3.0

4.0 2.0 0.0

6.5 3.9 0.0

72.5 70.0 60.0

77.3 71.2 56.1

11.1 9.7 2.8

18.2 12.1 0.0

8.1 6.5 1.6

17.2 6.9 3.4

16.7 12.5 8.3

11.5 7.7 3.8

Q

Q/R

Q/R

(l) 3.0

(L) 1.0

(i) 0.2

(2) 0.2

8.0

14.3

12.5

12.1

19.4

66.7

75.8

10.3

8.3

23.1

3.0 5.0

3.0 3.0

0.5 0.5

0.5 0.5

4.0 4.0

6.5 6.5

10.0 5.0

3.0 3.0

9.7 8.3

51.5 45.5

64.5 59.7

0.0 0.0

4.2 4.2

0.0 0.0

Q

aVF

aVF

it was possible to reach 75 percent sensitivity for infarction and 63.5 percent for any old infarction. At 98 percent specificity the sensitivity falls to 70.8 and 58.7 percent. Ninety-five percent confidence intervals were calculated for this set of data to indicate the general range required for significant differences between the sensitivity figures of this study. The 95 percent confidence intervals were computed as follows, assuming binomial distributions :

tions given (leads aVL, V, and V,). For old inferior infarction, in leads III and aVF, the best criteria gave 75.8 percent sensitivity. Serial change alone was found less effective diagnostically than the absolute wave amplitudes in post-event records (not tabulated). Moreover, optimal combinations of criteria for post-event amplitude plus serial change among several leads is simply too cumbersome as a practical approach to diagnosis, particularly in light of the small increase in yield obtained by their combination in this study. In Table IX an effort was made to reduce the criteria to their simplest, in a set of the stronger leads. Best criteria and combinations were sought from leads I, V4 and aVF. At 96 percent specificity TABLE

any recent

p +

1.96

P(1

-

P>

n

where n = number of cases, and p = proportion meeting abnormal criteria. Multivariate analysis results: Table X gives

IX

Conventional

Analysis: Diagnostic Power for Different

All Patients with Coronary

Levels of Discriminating

Amplitude

Criteria

in a Set of Leads(l,

aVF, Wfor

Heart Disease Versus Control Subjects Percentages

T

I

or

or

Q/R aVF

Insufficiency

(no. A=’ 72)

Post (no. = 126)

Pre (no. = 29)

At (no. = 24)

Post (no. = 26)

0.2 0.2

1.5 1.5

4.1 2.0

10.1 7.4

75.0 70.8

63.5 58.7

10.3 0.0

50.0 45.8

26.9 23.1

0.2 0.3 0.5

3.0 3.0 3.0

0.0 0.0 0.0

4.1 2.0 0.0

69.4 41.7 37.5

53.2 42.1 31.0

b.0 0.0 0.0

45.8 12.5 12.5

19.2 7.7 3.8

0.0 *o.o

5.0 2.0

0.0 -2.0 -2.0

1.0 2.0 1.0

limit

Patients with Coronary

Patients with infarction Pre (no. = 148)

(2)

Upper

Normal Subjects Pre (no. = 49)

(I)

interval

Q aVF (2) (mm)

(5)

* 95% confidence Lower limit

776

R Vq

or

for this

_~_.

row: 0.0

3.3

60.4

50.9

0.0

25.9

6.9

6.0

11.5

81.2

66.5

0.0

65.7

39.3

The American

Journal

of CARDIDLDDY

ELECTROCARDIOGRAM

IN MYOCARDIAL

INFARCTION

TABLE X Discriminant

Function Analysis: Maximal

Discrimination

by Site and Type of Manifestation Post-Event (Post- minus Pre-Event)

At-Event (At- minus Pre-Event) Anterior Infarct

Coronary Insufficiency

Posterior infarct

Anterior Infarct

Posterior Infarct

Coronary Insufficiency

YIO 4.3 85.7

Y_
YIO 4.3 61.6

Y
Y
YIO 4.3 61.6

A. Absolute Value Alone Criteria

YIO 2.1 60.7

Y
False positive (%) Sensitivity (%)

YIO 4.3 79.1

B. Absolute Value Plus Serial Change Criteria

YIO 2.1 75.8

YSO 4.3 91.9

False positive (%) Sensitivity (%)

YIO 2.1 79.1

the results of the first discriminant function analysis, which is between the normal group and each of the 3 patient groups, anterior infarction, inferior infarction and coronary insufficiency. Independent variables are the 5 amplitudes and 5 serial changes described under Method. Section A shows the greatest sensitivity attainable for amplitude criteria in the at-event and post-event records, at a false positive rate under 5 percent. Sensitivity for the acute stage event reached 86.5 percent for anterior and 60.7 percent for inferior infarction and 79.1 percent for coronary insufficiency. The corresponding sensitivity for post-event amplitudes was 85.7, 56.7 and 61.6 percent, respectively. However, maximal sensitivity was obtained in section B by the discriminant function, using absolute amplitudes plus serial change. Sensitivity based on the comparison of event with pre-event amplitudes was 91.7 percent

for anterior and 75.8 percent for inferior infarction and 79.1 percent for coronary insufficiency. Corresponding maximal sensitivity for the comparison of post- with pre-event records was 92.1, 65.0 and 61.6 percent, respectively. The combination of serial change plus absolute amplitudes resulted in greatest improvement in sensitivity for inferior infarction, which increased from 60.7 to 75.8 percent for at-event and from 56.7 to 65.0 percent for post-event records. There was some improvement for diagnosis of anterior infarction, from 86.5 to 91.9 percent for at-event and from 85.7 to 92.1 percent for post-event diagnosis. The combination with serial change brought about no improvement in coronary insufficiency diagnosis. Table XI shows the discriminant function analyses concerned with the proportion of correct diagnoses within each subgroup of normal subjects

TABLE Xl Discriminant

Function Analysis: Maximal

Discrimination

by Type of Manifestation,

Ignoring Site

Classification by Discriminant Analysis Classification by Clinical Diagnosis

At-Event no.

Normal

Cl

Post-Event Ml

Cl + Ml

no.

Normal

Cl

MI

Cl + Ml

47

93.6

4.3

2.1

6.4

A. Absolute Value Alone 93.6

4.3

2.1

6.4

24

20.8

66.7

12.5

79.2

26

38.3

42.3

19.4

61.7

70

20.0

27.2

52.8

80.0

123

28.4

26.0

45.6

71.6

47

93.6

4.3

2.1

6.4

47

(1) Normal (2) Coronary insufficiency (3) All infarction

B. Absolute Value plus Serial Change (1) Normal

47

95.8

2.1

2.1

4.2

24

20.8

66.7

12.5

79.2

26

38.3

50.0

11.7

61.7

70

21.4

25.8

52.8

78.6

123

24.3

27.7

48.0

75.7

(2) Coronary insufficiency (3) All infarction Cl = coronary

VOLUME

insufficiency;

29, JUNE

1972

Ml = myocardial

infarction.

777

TOMINAGA

ET AL.

(l), patients with coronary insufficiency (2), and those with infarction (3). Here, anterior and posterior infarction are not mutually exclusive. Column CI + MI gives the overall diagnostic power of discriminant function analysis, including sums of false positives, for all cases of infarction. Sensitivity of the method in separating normal from abnormal subjects was near 80 percent for the acute events and near 75 percent for the old coronary events. Serial change provided little additional discriminatory power above that obtained from post-event amplitudes alone. Diswssion One of the aims of this study is to determine the degree to which clinical diagnosis of myocardial infarction in living subjects can be achieved through simple manipulations of conventional electrocardiographic measurements. Conceivably this could add to the base of diagnostic criteria for exploration in automated computer programs. It could also provide a set of simple and unambiguous criteria that might aid the clinician in electrocardiographic evaluation. In fact, the objective electrocardiographic diagnosis of infarction from the wave measurements was reasonably successful. Seventy to 80 percent of old infarcts, among cases clinically diagnosed from acute phase documentation, were correctly identified from wave measurements and with simple criteria-at a false positive rate of less than 5 percent. However, the combinations found to be diagnostic, chiefly R wave amplitude, and Q/R ratio, are not here proposed as firmly validated new criteria of infarction ; there was no autopsy validation, and the number of cases was small. Advantages : These criteria were derived from serial records in healthy men and in patients with infarction as they occurred in general populations under long-term observation. The patients then survived long enough to have stable post-event electrocardiographic records made. It might be that criteria for old infarction derived from survivors of classic clinical events are more relevant to the real-life problem of such diagnosis in medical practice than are the electrocardiographic criteria now used, that is, those based on highly selected patient groups in referral hospitals, and then only among those selected for autopsy. As radiographic and other validating methods become more precise, there should develop a welcome improvement in electrocardiographic criteria, based on living patients. Limitations: Admittedly, the clinical diagnosis of infarction made by the investigators heading these long-term follow-up studies of initially healthy men are not totally independent of the electrocardiogram itself. However, they are entirely based on the acute-phase hospital docu-

778

mentation, so that the post-infarction records employed here played no direct part in the eventual clinical classification of patients with definite infarction. The comparisons made here before and after infarction may be considered, therefore, a contribution, if only a small one, to the evolution of electrocardiographic diagnostic criteria for infarction. False positives : The results given for specificity in these comparisons may be misleading, in that the percent of false positives in Tables IV to VIII (held under 5 percent for each subgroup comparison such as normal subjects versus patients with anterior infarction) can be partly additive for an overall normal versus infarct comparison. The true false positive rate is more likely to be closer to that of Table XI, in which 6.4 percent false positives occurred in the comparison of the normal group and the group with infarcts in both sites and coronary insufficiency cases (column CI + MI). The small numbers in the study is another limitation, especially in regard to the discriminant function analysis. However, the surmise is that a larger group of control subjects would probably result in a diminished proportion of false positives and therefore strengthen, not reduce, the differences found. In explanation of the small numbers, the manual measurements were made on paper tracings collected some years ago from these population studies. The objectives of the present study were limited to a first look for useful clues-with the plan to expand the effort, if indicated, using a much larger mass of data in magnetic tape-recorded material. The Diagnostic Contribution of Serial Electrocardiographic Change

The thesis leading to this study was that serial electrocardiographic change makes a substantial contribution to diagnosis of myocardial infarction. Thus, the essential question for discussion of the results is the fact that relatively little additional diagnostic value was obtained from information about serial electrocardiographic changes, beyond that obtained from findings in an individual tracing at or post-infarct. Can this modest result be generalized, or is it applicable only to this study, or is it due to an artefact of the material used and the analysis made here ? The possible influence on the results of the following is considered : ( 1) Inadequate numbers of cases ; (2) the selection of cases ; (3) misclassification due to serial electrocardiographic “improvement” after infarction ; (4) misclassification due to the criteria themselves; (5) misclassification due to technical or artefactual errors; (6) misclassification due to analytical errors; (7) the high correlation between

The American

Journal

of CARDIOLOGY

ELECTROCARDIOGRAM

IN MYOCARDIAL

INFARCTION

TABLE XII Crude Correlation Matrix for the 10 Electrocardiographic Indexes (no. = 170)* 1 1 Absolute

T amplitude

2 Absolute 3 Absolute

Q/R ratio in lead aVF R amplitude in lead Vc

4 Absolute aVF

Q amplitude

in lead

0.389

in lead I 7 Serial change

in Q/R

in lead aVF 8 Serial change

in R amplitude

in lead Vq 9 Serial change

in Q amplitude

in lead aVF 10 Serial change

in Q amplitude

* Absolute

0.327 0.215

-

29, JUNE

-0.152

9

10

-

-

-

-

-

-

-

_

-

-

-

1

7

0.543 -0.100

0.322 -0.339

1.000

-

-0.144

1.000

-

-

-

-

-

-

-

-

-

-

0.729

0.305

0.257

0.335

-0.227

1.000

-

-

-

-

0.320

0.996

0.247

0.518

-0.102

0.306

1.000

-

-

-

0.284

0.206

0.697

0.316

-0.446

0.359

0.203

1.000

-

-

0.405

0.580

0.280

0.923

-0.163

0.338

0.575

0.297

1.000

-

-0.111

-0.449

-0.177

-0.159 = Post-Event;

1972

-

8

6

5

-

~&I3

Serial

Change

-0.112

-0.373

= Post-Event

severity of electrocardiographic findings follc wing infarction and the amount of serial change. Numbers of cases: The question of the small numbers of cases in the study has already been mentioned. It is difficult to see how this would selectively affect the results for the relative diagnostic contribution of serial electrocardiographic change. Case selection : The method of selecting the acute-phase electrocardiogram could very well have reduced the diagnostic contribution of measured serial electrocardiographic change. It is emphasized that there was no selection of cases of infarction themselves; analysis was made of electrocardiograms from all cases called myocardial infarction during a given follow-up period in these longitudinal studies. However, the classification by the cardiologist was made on the basis of acutephase documents. Moreover, we selected from the acute phase record the one with the most typical acute pattern to represent the at-event electrocardiogram. This is bound to produce misclassifications in that the later stable post-infarction record is almost sure to be the same or better, not worse than the acute record. Moreover, cases of reinfarction were likely to be excluded from a given scheduled post-infarction examination in these studies. Misclassification : A detailed examination of the subjects misclassified by the discriminant function analysis is of interest to explain why that analysis did not approach 100 percent sensitivity within the group from which the function was derived. Four normal subjects were considered to have infarction on the basis of ranking procedure of the

VOLUME

4

ratio

V, values

1.000 0.249

3

in lead

5 Absolute Q amplitude in lead V4 6 Serial change in T amplitude

in lead

1.000

I

2

-0.172 minus

0.993

-0.227

1.000

Pre-Event.

discriminant function scores. In 1 normal subject there was a possible artefactual (instrumental) increase in R amplitude, giving a large change in Q/R ratio ; in 2 there was the loss of a very small initial R wave, and a resulting large change in Q/R ratio. In another healthy normal subject, sufficient combined minor serial electrocardiographic changes occurred to give him a high risk function score, with a loss of R and T amplitudes in V leads and in lead I. This problem is common to all discrimination studies made in cross section. Although clinically “normal” this subject might show, in a longer term follow-up period, subsequent excess risk of infarction, possibly related to these early serial electrocardiographic changes. Nevertheless, these 4 false positive misclassifications among the normal subjects reduced the power of discrimination. More significant, however, was the situation of missed cases of infarction, or false negatives. Of 12 missed cases of old inferior infarction, 11 misclassifications could be explained by “expected” improvement of the post-event record with reversion of acute phase changes toward normal. Of 9 missed cases of old anterior infarction, 8 could be so explained. Finally, 3 cases could be explained by failure to include findings in lateral leads V5 and V6 and aVL in the discriminant function program because individually they were not strong discriminants in the conventional analysis. Thus, misclassifications for expected reasons were a significant factor attenuating the power of the discriminant function analysis. More appropriate analysis of the sensitivity of this discriminant program would be the application of the coefficients found in part of the study group to mea-

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surements made in another part, or in a totally independent sample. The number of subjects available was insufficient to attempt this within the present study. Another more telling test of the sensitivity of these criteria and risk functions would be their application to the prediction of future cases within a given period in a general population. Correlation of absolute values versus serial change : One further explanation of the rather modest contribution of serial electrocardiographic change to diagnosis in this situation is contained in the correlations of Table XII between findings in the post-event record itself and the serial change between pre- and post-event records. In the case of T wave amplitude in lead I, the correlation with serial change is greater than 0.7, for R amplitude in V4 it is about 0.7 and for Q amplitude in aVF the correlation is about 0.6. A further factor may be that the discriminant function analysis gives equal weight to individual electrocardiographic findings, when, in fact, they are highly interdependent, such as S-T and T, Q and T wave changes, and the like. A diagnostically important but isolated serial change in a given electrocardiographic item may produce a low overall discriminant score. Finally, only 10 of many possible electrocardiographic variables were employed in the discriminant analysis. We have seen evidence that misclassification due to omitting lateral (aVL, V,) lead data results in attenuation of the diagnostic power of the method. A possible small independent effect of Q wave duration was also ignored. Moreover, the behavior of ratios in discriminant function analysis is problematical, particularly if the ratios are not normally distributed. Results of other studies: Generally, the results of the conventional electrocardiographic analysis made here agree substantially with other, more sophisticated analyses based on discrimination between single tracings recorded in normal subjects and after the event in abnormal survivor groups. For example, a major finding, that of optimal discrimination between patients with infarction and normal subjects from Q/R ratios in the Z lead,*~O is consistent with the finding here of excellent sensitivity for the Q/R ratio and R amplitude measured in lead V4. Yet clearly a more sophisticated approach to detailed electrocardiographic criteria is required, particularly to determine the probabilities of other abnormal conditions (hypertrophy, for example) .l”-12 Pipberger et al.l3 have emphasized this problem and have developed some classification programs to discriminate optimally between any arbitrary number of abnormal diagnostic groups simultaneously, rather than one disease group at a time versus normal subjects. Rautaharju14 has also pursued this question in population samples con780

taining multiple categories of diagnosis. His application of criteria that very adequately discriminated between patients with infarction and normal subjects resulted, when applied to populations containing representative (“real life”) frequencies of different disease categories, in unacceptably high levels of false positives. This larger problem in diagnosis considerably overwhelms, then, the particular question to which an answer has been sought here: What is the relative potential and independent contribution of serial electrocardiographic change to diagnosis of infarction? The rather small additional contribution of serial change to the diagnosis of myocardial infarction found in the present study leads back to the practical questions: In what clinical situations is information about serial change in the electrocardiogram essential? The obvious answers include: (1) evaluation of acute evolutive lesions, (2) evaluation of borderline clinical cases, and (3) accurate timing of coronary events. None of these questions was specifically considered here. It is concluded that detailed serial electrocardiographic change adds little to the objective diagnosis of old myocardial infarction among living survivors, beyond that obtained from measurement of the post-event record alone. Serial electrocardiographic change might better apply to the evaluation of less clear diagnostic situations than were employed here to test the discriminative power of quantitative electrocardiographic diagchange also nosis. Serial electrocardiographic might better be studied as an indicator of future risk of infarction or death over the long run.15 In the pre-event records of subjects who eventually had infarction, some findings were already present in the pre-infarction record which might have shown prognostic value if they had been serially analyzed. Many biological measurements are much more effective as predictors over time than as diagnostic discriminants at a given moment. This is especially so for the insidious atherosclerotic diseases. Finally, there is great interest in the question of predicting from the electrocardiogram among survivors of infarction the subsequent risk of reinfarction and death over a given period. This matter is considered in detail elsewhere.ls Acknowledgment The kind permission of the following investigators is acknowledged to reproduce and measure the electrocardiograms from documented coronary cases of their important on-going population studies: A. Keys and H. Taylor, Minneapolis, W. Kannel and T. R. Dawber,

Framingham, 0. Paul, Chicago, and J. Chapman and

A. Coulson, Los Angeles. The diligence and consistency of Alice Sweep, University of Minnesota student, in performing the meticulous wave measurements is gratefully acknowledged, as is the initial programming by R. Willis Parlin.

The Amcrlcan Journal of CARDIOLOGY

ELECTROCARDIOGRAM

IN MYOCARDIAL

INFARCTION

References 1. Rose, G, Blackburn H: Cardliovascular Survey Methods. WHO Monograph Series 56, Geneva, WHO Press, 1968 2. Coronary Drug Project Research Group: The Coronary Drug Project. Initial findings leading to modifications of its research ~protocol. JAMA 274:1303-1313, 1970 3. Dawber TR, Kannel WB, Lyell LP: An approach to longitudinal studies in a community: the Framingham study. Ann NY Acad Sci 107539-556, 1963 4. Paul O., Lepper MH, Phelan WH, et al: A longitudinal study of coronary heart disease. Circulation 12820-31, 1963 5. Chapman JM, Massey FJ: Results of the first ten years follow-up in the Los Angel,es Heart Study. J Chronic Dis 17:933-949,1964 6. Keys A, Taylor HL, Blackburn H, et al: Coronary heart disease among Minnesota business and professional men followed fifteen years. Circulation 28:381395, 1963 Clyde DJ, Cramer EM, Sherin RJ: Multivariate Statistical Programs, first edcition. University of Miami, Florida, Biometric Laboratory, 1966 Naval A, Cosma J, Pipberger HV: Reevaluation of the Q wave in the electrocardiographic diagnosis of ,myocardial infarction. Med Ann DC 33:349-353, 1967 Sotobata I, Richman H, Simonson E: Recognition of

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