Association of Killip class on admission and left

ventricular dilatation after myocardial infarction:

A closer look into an old clinical classification
Aleksandar N. Nes
kovic, MD, Petar Otas
evic, MD, Milovan Bojic, MD, PhD, and Aleksandar D. Popovic, MD, PhD
Belgrade, Yugoslavia

Background Early identification of patients in whom left ventricular dilatation is likely to occur may have important
therapeutic implications. Thus the purpose of this study was to evaluate the relation between Killip class on admission and
subsequent left ventricular dilatation after acute myocardial infarction.

Methods and Results We serially evaluated 129 consecutive patients by two-dimensional and Doppler echocardiography on days 1, 2, 3, and 7, at 3 and 6 weeks, and at 3, 6, and 12 months after infarction. Killip class on admission
>1 was found in 29 of 129 (22.5%) patients, and they had significantly higher end-systolic and end-diastolic volume indexes
and wall motion score index from day 1 onward compared with patients with Killip class 1, whereas ejection fraction was
lower during the follow-up period in these patients. Patients with Killip class >1 showed the progressive increase of end-diastolic (68.2 2.99 to 88.0 7.55 ml/m2, p = 0.001) and end-systolic volume indexes (43.9 2.67 to 56.3 6.18 ml/m2,
p = 0.004) during the follow-up period, whereas ejection fraction and wall motion score index remained unchanged. In
patients with Killip class 1, end-systolic volume index did not change (30.8 1.06 to 33.8 2.15 ml/m2, p = 0.064), ejection fraction increased (49.3% 0.99% to 51.8% 1.17%, p = 0.027), and wall motion score index decreased (1.50
0.03 to 1.35 0.04, p < 0.001). End-systolic volume index was the major independent correlate of Killip class, followed by
history of diabetes and peak creatine kinase level. No association was found between Doppler indexes of diastolic filling
and Killip class on admission.

Conclusions Killip class >1 on admission is associated with both acute and long-term left ventricular dilatation. On the
other hand, Killip class 1 is associated with favorable left ventricular functional indices, and it appears that left ventricular
function in these patients may improve over time. Initial end-systolic volume index but not ejection fraction is the major correlate of Killip class. (Am Heart J 1999;137:361-7.)

It has been shown that complex alterations in left

ventricular geometry can occur after acute myocardial
infarction.1 These changes can profoundly affect left
ventricular systolic and diastolic function and thereby
patient outcome. It has been demonstrated that left
ventricular dilatation may ensue in the earliest phase
of myocardial infarction.1-4 Early identification of
patients in whom left ventricular dilatation is likely to
occur may have important therapeutic implications.
Several sophisticated approaches5,6 have been proFrom the Cardiovascular Research Center, Dedinje Cardiovascular Institute and Belgrade University Medical School.
Presented in part at the XIXth Congress of the European Society of Cardiology,
August 24-28, 1997, Stockholm, Sweden.
Submitted October 23, 1997; accepted January 20, 1998.
Reprint requests: Aleksandar D. Popovic, MD, PhD, Cardiovascular Research Center,
Dedinje Cardiovascular Institute, Milana Tepica 1, 11040 Belgrade, Yugoslavia.
Copyright 1999 by Mosby, Inc.
0002-8703/99/$8.00 + 0 4/1/89744

posed to identify these patients, but many of them are

expensive, time consuming, and/or demand highly
trained personnel.
The aim of this study was to evaluate the association of Killip class on admission and the likelihood of
left ventricular dilatation in the first year after myocardial infarction.

Methods
Patients
The study group consisted of 129 consecutive patients
with first acute myocardial infarction who met the following
criteria: (1) age 70 years, (2) chest pain lasting >30 minutes, (3) ST-segment elevation 2 mm in 2 electrocardiographic leads, (4) transient elevation of creatine kinase
and/or MB isoenzyme, and (5) echocardiogram performed
within 24 hours from the onset of pain. Killip class on
admission was determined as the following: class 1 patients
were free of rales and a third heart sound; class 2 patients

American Heart Journal

February 1999

362 Neskovic et al

Table I. Clinical and angiographic characteristics

Killip class 1
Age (years)
Sex (F/M)
Diabetes mellitus
Hypertension
Cigarette smoking
Anterior infarct
Q-wave infarction
Peak CK level (IU/L)
Thrombolysis
Multivessel CAD
TIMI <3
Diuretics
ACE inhibitors
Digoxin
1-Year mortality

54.5 0.88
24/76
13/99 (13.1%)
37/99 (37.4%)
62/99 (62.6%)
34/100 (34%)
87/100 (87%)
964 61.34
32/100 (32%)
51/89 (57.3%)
39/89 (43.8%)
30/97 (30.9%)
6/97 (6.2%)
6/97 (6.2%)
3/100 (3%)

Killip class >1

58.1 1.54
12/17
11/28 (39.3%)
11/28 (39.3%)
7/28 (25%)
19/29 (65.5%)
28/29 (96.5%)
1607 250.64
18/29 (62.1%)
9/19 (68.4%)
13/19 (68.4%)
20/27 (74.1%)
9/27 (29.6%)
8/27 (29.6%)
9/29 (31%)

p Value
0.045
NS
0.002
NS
0.001
0.002
NS
0.001
0.003
NS
NS
0.0001
0.0001
0.0001
0.001

Values are given as mean standard error. NS, nonsignificant.

Table II. Independent correlates of Killip class on admission

p Value
Initial end-systolic volume index
Diabetes mellitus
Peak creatine kinase level
Age
Smoking
Initial wall-motion score index
Thrombolysis
Sex
Initial ejection fraction
Extent of coronary artery disease
Initial end-diastolic volume index
Patency of the infarct-related artery
Infarct location

0.0004
0.0044
0.0048
0.059
0.131
0.186
0.291
0.361
0.417
0.454
0.516
0.619
0.620

MHz transducer, and studies were stored on videotape for

further analysis.
Left ventricular end-diastolic volume, end-systolic volume,
and ejection fraction were determined from apical two- and
four-chamber views with Simpsons biplane formula. Tracing of
endocardial borders in end-diastole and end-systole was performed in the technically best cardiac cycle. The volumes were
normalized to body surface area and expressed as indexes.
Transmitral flow recordings were obtained after quiet
expiration at the tips of the mitral leaflets. Modal velocity
was traced in three consecutive beats and averaged. Studies
with atrial fibrillation, severe mitral regurgitation, and heart
rate >100 beats/min were excluded. The following Doppler
indexes were measured: (1) early filling deceleration time,
(2) peak early and (3) atrial filling velocities, and (4) the
ratio of peak early and atrial filling velocities.
Wall motion score index was calculated by dividing the
left ventricle into 16 segments according to the recommendations of the American Society of Echocardiography.8

had rales up to 50% of each lung field regardless of the

presence of the third heart sound; class 3 patients had rales
in more than half of each lung field; and class 4 patients
were in cardiogenic shock.7 Killip class was assessed by a
single physician.
In 79 patients, intravenous streptokinase was administered in a dose of 1,500,000 U over 30 to 60 minutes. The
remaining 50 patients did not receive thrombolytic therapy
at the discretion of their attending cardiologist because they
were admitted late after the onset of pain or they had contraindication for thrombolysis.

Coronary angiography was performed in 108 patients

before hospital discharge as a part of the study protocol.
Seventy percent area stenosis of the major coronary vessel
was considered significant. Patency of the infarct-related
artery was assessed with Thrombolysis In Myocardial Infarction (TIMI) criteria.9 Successful reperfusion was defined as
TIMI grade 3.

Echocardiograms

Statistical analysis

Complete two-dimensional and Doppler echocardiographic

examinations were performed on days 1, 2, 3, and 7, at 3
and 6 weeks, and 3, 6, and 12 months after acute myocardial
infarction, as a part of the study protocol. We used the Acuson 128 imaging system (Mountain View, Calif.) with a 2.5

All data are expressed as mean standard error. The chisquare test and t test were used for comparisons between the
subgroups for categorical and continuous variables, respectively. A p value < 0.05 was considered significant. A multiple
logistic regression model (that included age, sex, history of

Coronary angiography

American Heart Journal

Volume 137, Number 2

Neskovic et al 363

Figure 1

A, Association of end-diastolic volume and Killip class 1 year after myocardial infarction. EDVi, End-diastolic volume index.*p < 0.01 between groups; p < 0.001 between groups. B, Association of end-systolic volume and Killip class 1 year after myocardial infarction. ESVi, End-systolic volume index.*p < 0.01 between groups; p <
0.001 between groups. Values are given as mean standard error.

smoking and diabetes, infarct location, peak creatine kinase

level, thrombolysis, initial end-diastolic volume index, endsystolic volume index, ejection fraction, and wall motion
score index, extent of coronary artery disease, and patency
of the infarct-related artery) was used for identification of
independent correlates of Killip class on admission.

Results
Killip class 1 was found in 100 of 129 (77.5%)
patients; Killip class >1 was found in 29 of 129 (22.5%)

patients (26 patients with class 2 and 3 patients with

class 3) on admission. Baseline clinical and angiographic characteristics of patients enrolled are shown
in Table I. Patients with Killip class 1 and Killip class
>1 were similar regarding sex, history of hypertension,
incidence of Q-wave infarction, extent of coronary
artery disease, and patency of the infarct-related
artery. However, in patients with Killip class >1 there
was a higher incidence of diabetes and anterior infarction and a lower incidence of cigarette smoking; in

American Heart Journal

February 1999

364 Neskovic et al

Figure 2

Association of wall motion score index and Killip class 1 year after myocardial infarction. WMSi, Wall motion
score index. p < 0.001 between groups. Values are given as mean standard error.

Table III. Doppler indexes of left ventricular filling

Doppler indexes

Killip class 1

Early filling deceleration time (msec)

Peak E-wave velocity (m/sec)
Peak A-wave velocity (m/sec)
E/A ratio

184 6.93
0.52 0.01
0.58 0.02
1.01 0.07

Killip class >1

p Value

164 11.25
0.46 0.06
0.58 0.04
0.82 0.11

0.15
0.42
0.99
0.16

Values are given as mean standard error.

addition, they were older, had higher peak creatine

kinase level, and had higher 1-year mortality rates.
Thrombolysis, diuretics, digoxin, and angiotensin-converting enzyme (ACE) inhibitors were more frequently
used in patients with Killip class >1. Likewise, the use
of ACE inhibitors and diuretics was more common in
these patients during the follow-up period. However,
the rate of myocardial revascularization was similar in
both groups.
Multiple logistic regression identified end-systolic
volume index as the major independent correlate of
Killip class, followed by history of diabetes and peak
creatine kinase level (Table II).
Patients with Killip class >1 had significantly higher
left ventricular end-diastolic and end-systolic volume
indexes (Fig. 1, A and B), and left ventricular wall
motion score index (Fig. 2) from day 1 onward compared with patients with Killip class 1. Conversely,

ejection fraction was significantly lower during the

follow-up period in patients with Killip class >1 (Fig.
3). Patients with Killip class >1 showed progressive
increase of end-diastolic (68.2 2.99 to 88.0 7.55
ml/m2, p = 0.001) and end-systolic volume indexes
(43.9 2.67 to 56.3 6.18 ml/m2, p = 0.004) during
the follow-up period; ejection fraction (37.0%
1.94% to 38.1% 2.50%, p = 0.66) and wall motion
score index (1.79 0.08 to 1.77 0.12, p = 0.84)
remained unchanged. However, in patients with Killip class 1, despite an increase in end-diastolic volume index (59.7 1.15 to 67.2 2.52 ml/m2, p <
0.001), end-systolic volume index did not change
(30.8 1.06 to 33.8 2.15 ml/m2, p = 0.064); in addition, ejection fraction increased (49.3% 0.99% to
51.8% 1.17%, p = 0.027) and wall motion score
index decreased (1.50 0.03 to 1.35 0.04, p <
0.001) at 1 year.

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Volume 137, Number 2

Neskovic et al 365

Figure 3

Association of ejection fraction and Killip class 1 year after myocardial infarction. EF, Ejection fraction. p <
0.001 between groups. Values are given as mean standard error.

No association was found between Killip class and

measured Doppler indexes of left ventricular filling
(Table III).

Discussion
Our findings demonstrate that Killip class on admission may predict subsequent left ventricular dilatation
and changes in left ventricular systolic function in 1
year after myocardial infarction. The evidence of heart
failure on admission identifies patients who will
increase both end-diastolic and end-systolic volume in
the following period. White et al.10 have demonstrated
that end-systolic volume is the major determinant of
survival in patients after myocardial infarction. Similarly, our patients with Killip class >1 had higher endsystolic volume from day 1 onward, which was translated into a higher 1-year mortality rate. On the other
hand, our data revealed that patients in Killip class 1
on admission would not increase their end-systolic
volume and were likely to improve ejection fraction
and regional wall motion over 1 year after infarction. It
is well known that clinical evidence of heart failure
after acute myocardial infarction is usually present
when the region of abnormal contraction exceeds 20%
to 25% of the total left ventricular perimeter determined by angiography,11 and both animal12 and clinical studies13 have demonstrated that left ventricular

dilatation is related to the extent of myocardial necrosis in a linear fashion. In addition to infarct size,14-16
anterior infarct location17 and patency of the infarctrelated artery18 have been identified as major predictors of left ventricular dilatation after myocardial
infarction. We found that patients with Killip class >1
had larger infarcts, more extensive regional wall
motion abnormalities, and more frequently had anterior infarction. Furthermore, initial end-systolic volume
and peak creatine kinase level were identified as the
independent correlates of Killip class.
Although we have previously shown that early filling
deceleration time correlates with infarct size,19 no
association was found between Killip class and this as
well as with the other indexes of left ventricular diastolic function. It has been reported that the ratio of
peak early and atrial filling velocities was not helpful
in identifying patients with pump failure after myocardial infarction.20
Left ventricular enlargement after myocardial infarction is associated with decreased survival from congestive heart failure,21 and the risk of death is directly
related to left ventricular size.22 According to our
study, it appears that by using simple clinical Killip
classification, patients in whom left ventricular dilatation is likely to occur can be identified on admission.
This is extremely important because attempts to pre-

366 Neskovic et al

vent or minimize this process can be initiated immediately. Because infarct size is the major determinant of
left ventricular dilatation, an energetic attempt toward
its reduction should be made by using thrombolysis,23-25
or direct26 or rescue angioplasty.27 Favorable effects
on left ventricular volumes, probably through modification of distending or deforming forces, have been
demonstrated for ACE inhibitors28 and intravenous
nitroglycerin.29 Considering possible hazards of the
administration of ACE inhibitors during first hours of
infarction,10 identification of patients prone to left ventricular dilatation by using Killip classification on
admission may allow early administration of these
agents only in selected patients who are likely to benefit the most and to avoid or postpone their use in
others. Also, there is a wealth of evidence demonstrating that the administration of an ACE inhibitor within a
few days after acute myocardial infarction markedly
reduces mortality rates in patients with impaired left
ventricular function.31

Limitations
The major limitation of the study is the small number of patients in Killip class 3 and the fact that none
of them was in Killip class 4. However, when only Killip class 1 and 2 patients were included in the analysis,
the results were the same. Also, because electrocardiographic inclusion criterion required at least 2 mm of
ST-segment elevation, it is possible that several
patients with small infarcts were not included in the
study. Because they would probably be Killip class 1
patients, we believe that their potential exclusion did
not affect the results of the study.
In conclusion, our data demonstrate that Killip class
on admission can be used to identify patients in whom
left ventricular dilatation is likely to occur after myocardial infarction. Early identification of these patients
with the use of simple clinical classification may have
important therapeutic implications. Killip class >1 is
associated with both acute and long-term dilatation. On
the other hand, Killip class 1 is associated with favorable left ventricular functional indices, and it appears
that left ventricular function in these patients may
improve over time. Initial end-systolic volume but not
ejection fraction is the major correlate of Killip class.

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