The importance of left ventricular function for long-term outcome after primary percutaneous coronary intervention

Abstract

In the present study we sought to determine the long-term prognostic value of left ventricular ejection fraction (LVEF), assessed by planar radionuclide ventriculography (PRV), after ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI).
In total 925 patients underwent PRV for LVEF assessment after PPCI for myocardial infarction before discharge from the hospital. PRV was performed with a standard dose of 500 Mbq of 99mTc-pertechnetate. Average follow-up time was 2.5 years.
Mean (+/- SD) age was 60 +/- 12 years. Mean (+/- SD) LVEF was 45.7 +/- 12.2 %. 1 year survival was 97.3 % and 3 year survival was 94.2 %. Killip class, multi vessel-disease, previous cardiovascular events, peak creatin kinase and its MB fraction, age and LVEF proved to be univariate predictors of mortality. When entered in a forward conditional Cox regression model age and LVEF were independent predictors of 1 and 3 year mortality.
LVEF assessed by PRV is a powerful independent predictor of long term mortality after PPCI for STEMI.

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BMC Cardiovascular Disorders
Open Access
Research article
The importance of left ventricular function for long-term outcome
after primary percutaneous coronary intervention
Pieter A van der Vleuten*
1
, Saman Rasoul
2
, Willem Huurnink
3
, Iwan CC van
der Horst
1
, Riemer HJA Slart
4
, Stoffer Reiffers, Rudi A Dierckx
4
, René A Tio
1
,
Jan Paul Ottervanger
2
, Menko-Jan De Boer
2
and Felix Zijlstra
1
Address:
1
Thoraxcentre, Department of Cardiology, University Medical Centre Groningen, The Netherlands,
2
Department of Cardiology, Isala
klinieken, Zwolle, The Netherlands,
3
Department of Nuclear Medicine, Isala klinieken, Zwolle, The Netherlands and
4
Department of Nuclear
Medicine and molecular imaging, University Medical Centre Groningen, The Netherlands
Email: Pieter A van der Vleuten* - p.a.van.der.vleuten@thorax.umcg.nl; Saman Rasoul - s.rasoul@isala.nl;
Willem Huurnink - w.huurnink@isalaklinieken.nl; Iwan CC van der Horst - i.c.van.der.horst@thorax.umcg.nl;
Riemer HJA Slart - r.h.j.a.slart@nucl.umcg.nl; Stoffer Reiffers - s.reiffers@isala.nl; Rudi A Dierckx - r.a.dierckx@nucl.umcg.nl;
René A Tio - r.a.tio@thorax.umcg.nl; Jan Paul Ottervanger - j.p.ottervanger@isala.nl; Menko-Jan De Boer - m.j.de.boer@isala.nl;
Felix Zijlstra - f.zijlstra@thorax.umcg.nl
* Corresponding author
Abstract
Background: In the present study we sought to determine the long-term prognostic value of left
ventricular ejection fraction (LVEF), assessed by planar radionuclide ventriculography (PRV), after
ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary
intervention (PPCI).
Methods: In total 925 patients underwent PRV for LVEF assessment after PPCI for myocardial
infarction before discharge from the hospital. PRV was performed with a standard dose of 500 Mbq
of
99m
Tc-pertechnetate. Average follow-up time was 2.5 years.
Results: Mean (± SD) age was 60 ± 12 years. Mean (± SD) LVEF was 45.7 ± 12.2 %. 1 year survival
was 97.3 % and 3 year survival was 94.2 %. Killip class, multi vessel-disease, previous cardiovascular
events, peak creatin kinase and its MB fraction, age and LVEF proved to be univariate predictors of
mortality. When entered in a forward conditional Cox regression model age and LVEF were
independent predictors of 1 and 3 year mortality.
Conclusion: LVEF assessed by PRV is a powerful independent predictor of long term mortality
after PPCI for STEMI.
Background
The management of patients with an acute ST-elevation
myocardial infarction (STEMI) has fundamentally
changed over the last twenty years. In the eighties throm-
bolytic agents were introduced and more recently primary
percutaneous coronary intervention (PPCI) has been
shown to be even more effective [1,2]. In patients surviv-
ing the first days after PPCI, risk stratification is of great
clinical relevance for the further (medical) management.
Among others, global left ventricular function has always
Published: 23 February 2008
BMC Cardiovascular Disorders 2008, 8:4 doi:10.1186/1471-2261-8-4
Received: 20 July 2007
Accepted: 23 February 2008
This article is available from: http://www.biomedcentral.com/1471-2261/8/4
© 2008 van der Vleuten et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0
),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

BMC Cardiovascular Disorders 2008, 8:4 http://www.biomedcentral.com/1471-2261/8/4
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been viewed as an important prognostic factor after acute
myocardial infarction. Earlier trials in large cohorts of
STEMI-patients, treated with either thrombolytic agents or
supportive care (no reperfusion-therapy), have confirmed
this prognostic value for a period of six months after myo-
cardial infarction [3-7].
Planar radionuclide ventriculography (PRV) is a well
established and widely used technique for the assessment
of left ventricular function. The technique is simple,
robust and easy to perform [8-10]. PRV assesses LVEF by
measurement of photon-activity of the bloodpool in the
left ventricle in both the end-diastolic and end-systolic
phase of the cardiac cycle. The aim of the present study
was to evaluate the long term prognostic value of LVEF,
assessed by routine PRV, in a large cohort of patients
treated with PPCI for STEMI.
Methods
As part of two consecutive multicentre randomized con-
trolled trials consecutive patients treated with PPCI for
STEMI in two large hospitals in the Netherlands were
entered in a registry [11,12]. The registry was opened in
April 1998 and was closed in December 2004. The inclu-
sion criteria differed in inclusion of all Killip classes in
GIPS 1 [11] versus only Killip 1 in GIPS 2 [12]. Baseline
characteristics such as medical history, cardiovascular risk
factors, heart rate and blood pressure, delay-times and
procedural parameters were recorded. For the present
study data from the registries of two large hospitals in The
Netherlands were used. Average follow-up time was 2.5
years. No patients were lost to follow-up. The present
study was conducted in accordance with the declaration
of Helsinki and was approved by the institutional review
boards of both cooperating hospitals.
PRV was performed in routine clinical practice before dis-
charge from the hospital, between day 1 and day 11 after
myocardial infarction. Four patients with atrial fibrilla-
tion were excluded. Measurements were performed using
the multiple-gated equilibrium method with in vivo label-
ling of red blood cells with 99mTc pertechnetate, after
pre-treatment with 1 mg. of stannous chloride. A γ-camera
(General Electric, Milwaukee, WI, U.S.A.) was used. The
camera head was positioned in the best septal LAO projec-
tion, typically with a caudal tilt of 5–10 degrees. R-wave
triggering was performed in a 20% beat acceptance win-
dow with 2/3 forward and 1/3 backward framing per car-
diac cycle, for 20 frames per R-R interval for a total of 6
minutes. LVEF was calculated using a Star View computer
(General Electric, Wisconsin, USA) using the fully auto-
matic PAGE program (version 2.3). The standard devia-
tion of the difference between repeat measurements
obtained by this technique is 1–2% [13].
Statistical analyses
Analyses were performed with the commercially available
package SPSS version 12.0.1 (SPSS inc, Chicago, IL, USA).
Continuous data of LVEF values were expressed as mean ±
standard deviation (SD). Mortality rates were calculated
according to the product-limit method. Further estima-
tion of risk was performed using Cox proportional haz-
ards models. Variables considered as potential predictors
for multivariable modelling were selected by univariate
analyses and were subsequently selected by stepwise for-
ward selection, with entry and retention in the model set
at a significance level of .05.
Results
PRV was not performed in 14 patients because they were
too hemodynamically unstable. Furthermore 10 patients
died before PRV could be performed. In total 925 patients
underwent routine PRV. Clinical and angiographic char-
acteristics are shown in Table 1. All patients underwent
PPCI of the infarct related artery, which was successful in
87.2% (defined as TIMI 3 flow in combination with a
myocardial blush grade ≥ 2). PRV was performed at a
median of 2 days after PPCI (range 1 day – 11 days). Mean
LVEF was 45.7 ± 12.2 % (interquartile-range: 37.0 % –
54.0 %).
Follow-up was obtained for all 925 patients. All-cause
mortality was 0.2 %, 0.9 %, 2.7 % and 5.8 % at 3 days, 30
days, 1 year and 3 years respectively. Three day mortality
in the entire registry was 2.3 %. Kaplan Meier curves for
all-cause mortality in the 925 patients who underwent
PRV before discharge are shown in Figure 1. The unad-
justed mortality rate increased exponentially with decreas-
ing LVEF (Figure 2).
By univariate Cox proportional hazards analysis several
baseline clinical characteristics and infarct related param-
eters were shown to be significant predictors of death. Sig-
nificant predictors of both 1 year and 3 year mortality
were age, history of MI, history of PCI, peak CK, peak CK-
MB-fraction and LVEF. Killip class, multivessel disease
and history of CABG were only significant univariate pre-
dictors of 3 year mortality. Details are shown in Table 2.
Sex, history of stroke, diabetes, hypertension, hyperlipi-
demia, smoking habit, positive family history, infarct-
duration, infarct location, TIMI flow after PPCI, myocar-
dial blush grade, use of G2b3a inhibitors, use of intra-aor-
tic balloon pump or mechanical ventilation were not
significant predictors of mortality. When a forward condi-
tional Cox proportional hazard model of only the factors
age and LVEF was implemented, none of the other varia-
bles provided incremental prognostic value (Table 3).

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Discussion
The present study shows that LVEF assessed shortly after
PPCI for STEMI, is a powerful predictor of long term sur-
vival. Earlier studies, most designed to establish the value
of various pharmacologic interventions after myocardial
infarction, have shown the prognostic value of global left
ventricular function, measured as LVEF, in terms of mor-
tality and re-admission rates for heart failure [14-17].
However, the follow-up duration and patient selection
differed from the present study.
The event-rate was relatively low for a post-infarction
cohort, with a 3 year mortality of only 5.8 %. The fact that
this study looks at data from patients who underwent PRV
on average 2 days after PPCI in the routine of daily clinical
practice, in most cases just before discharge or transfer to
another hospital, has systematically excluded patients
who were too hemodynamically unstable to undergo
PRV. For all analyses total mortality was used. It can be
hypothesized that the relationship between LVEF and
cause-specific mortality would be even stronger. The fact
that the traditional risk-factors for coronary artery disease
(sex, hypertension, diabetes, hyperlipidemia, smoking
and family history) were not significant predictors of mor-
tality may be explained by the fact that these risk-factors
for the most part contributed to the occurrence of the
index-MI itself and have only limited effect on the prog-
nosis after the index-MI. In addition, a number of these
risk-factors (hypertension, hyperlipidemia and smoking)
is usually treated more aggressively after the index-MI. The
fact that some infarct-treatment parameters, such as use of
mechanical ventilation and use of IABP, were not signifi-
cant predictors of mortality is most likely explained by the
relatively low numbers in this cohort with a relatively low
event-rate.
Noteworthy is the relatively small difference in prognosis
between the patient category with LVEF between 35 % and
Table 1: Baseline clinical and angiographic characteristics
Age, yrs (mean ± SD) 59.8 ± 12.0
Male sex 77.8
Body mass index, kg/m2 (mean ± SD) 26.7 ± 3.8
History of MI 9.9
History of PCI 5.1
History of CABG 2.8
History of stroke 2.8
Diabetes mellitus 9.7
Hypertension 28.5
Hyperlipidemia 22.1
Current smoker 50.7
Positive family history 42.3
Ischemia duration, min (mean ± SD)* 205 ± 212
Killip class 1 95.9
Killip class 2 2.4
Killip class 3 1.3
Killip class 4 0.4
Anterior MI 48.6
Multivessel disease 51.4
TIMI 3 flow after PCI 96.9
Successful reperfusion‡ 87.2
Intra-aortic balloon pump 5.0
Mechanical ventilation 0.5
Stent 57.6
Glycoprotein IIb/IIIa receptor blocker 21.2
Max CK, U/l (mean ± SD) 2450 ± 2159
Max CK-MB, U/l (mean ± SD) 248 ± 198
Data are displayed as percentage, unless otherwise indicated.
*Ischemia duration denotes time between onset of symptoms and
until PCI; ‡successful reperfusion denotes TIMI 3 flow and myocardial
blush grade 2 or 3;
CABG = coronary artery bypass grafting
CK = creatin kinase
CK-MB = creatin kinase myoglobin binding
MI = myocardial infarction
PCI = percutaneous coronary intervention
SD = standard deviation
TIMI = thrombolysis in myocardial infarction
Table 2: Predictors of 1 and 3 year mortality by univariate Cox
proportional hazard analysis.
1 year mortality
Characteristics Hazard ratio (95% CI) p
Age, per 10 years increase 2.00 (1.35 – 2.97) 0.001
Previous MI 2.91 (1.16 – 7.28) 0.023
Previous PCI 9.58 (4.13 – 22.21) < 0.001
Max CK, per 500 U/l increase 1.01 (1.00 – 1.02) 0.050
Max CK-MB, per 50 U/l increase 1.09 (1.01 – 1.18) 0.039
LVEF, per 5 % decrease 1.47 (1.25 – 1.73) < 0.001
3 year mortality
Characteristics Hazard ratio (95% CI) p
Age, per 10 years increase 1.63 (1.25 – 2.14) < 0.001
Previous MI 2.19 (1.06 – 4.52) 0.035
Previous PCI 5.16 (2.50 – 10.7) < 0.001
Previous CABG 3.27 (1.17 – 9.10) 0.024
Multi-vessel disease 1.50 (1.06 – 2.11) 0.021
Killip class, per class increase 1.73 (1.08 – 2.75) 0.022
Max CK, per 500 U/l increase 1.01 (1.00 – 1.02) 0.040
Max CK-MB, per 50 U/l increase 1.07 (1.01 – 1.14) 0.020
LVEF, per 5 % decrease 1.29 (1.15 – 1.46) < 0.001
CABG = coronary artery bypass grafting
CK = creatin kinase
CK-MB = creatin kinase myoglobin binding
LVEF = left ventricular ejection fraction
MI = myocardial infarction
PCI = percutaneous coronary intervention

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55 % and the patient category with LVEF above 55 %,
which is generally viewed as the lower limit of normal. In
contrast, there was a large difference in survival between
the patient category with LVEF between 35 % and 55 %
and the patient category with LVEF below 35, which is the
current cut-off point for implantable cardioverter defibril-
lator implementation (Figure 1).
The data in the present study suggest that markers of inf-
arct size, such as maximum creatin kinase myoglobin
binding level, Killip class and previous myocardial dam-
age from earlier events add up to a risk burden which is
related to global left ventricular function. LVEF can there-
fore be viewed as a representative of the final common
pathway of left ventricular damage when predicting long-
term prognosis after PPCI. The fact that this LVEF-assess-
ment can be performed just a few days after the index
myocardial infarction facilitates simple and fast risk strat-
ification after PPCI.
Besides PRV, LVEF can be measured by a number of tech-
niques, which all have their own specific advantages and
limitations. For instance echocardiography can be per-
formed easily and at low cost. However, the diagnostic
accuracy is limited [18]. Nuclear techniques such as posi-
tron emission tomography and single photon emission
Kaplan-Meier curve of 925 patients who underwent planar radionuclide ventriculography after primary percutaneous coronary intervention for ST-elevation myocardial infarctionFigure 1
Kaplan-Meier curve of 925 patients who underwent planar radionuclide ventriculography after primary percutaneous coronary
intervention for ST-elevation myocardial infarction. LVEF = Left Ventricular Ejection Fraction.

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computed tomography have better diagnostic accuracy,
but are more labour intensive and are not available in
every hospital. Recently, multi detector row computed
tomography has been propagated as very fast and accurate
technique for LVEF assessment [19]. However, besides
ionising radiation, this technique also requires the use of
intravenous nephrotoxic contrast agents. LVEF can even
be assessed directly after PPCI by contrast ventriculogra-
phy. Besides the obvious advantage of almost instant
LVEF-assessment, the main drawbacks from this approach
are the relatively high volume of nephrotoxic contrast, the
limited accuracy and the fact that LVEF can be severely
underestimated by myocardial stunning shortly after
STEMI. Magnetic resonance imaging is regarded by many
to be the gold standard for LVEF measurement [20].
Unfortunately, this technique is limited to patients with-
out intra-corporal devices such as pacemakers and is not
generally available for routine clinical patients.
Table 3: Predictors of 1 and 3 years mortality by forward conditional Cox proportional hazard analysis.
1 year mortality
Characteristics Hazard ratio 95% CI Wald χ
2
p
Age, per 10 years 2.01 1.33 – 3.03 11.1 0.001
LVEF, per 5 % decreasing 1.44 1.23 – 1.69 20.4 < 0.001
3 year mortality
Characteristics Hazard ratio 95% CI Wald χ
2
p
Age, per 10 years 1.64 1.25 – 2.15 12.6 < 0.001
LVEF, per 5 % decreasing 1.28 1.14 – 1.44 17.6 < 0.001
LVEF = left ventricular ejection fraction
Adjusted 3 year mortality rate for patients who underwent planar radionuclide ventriculography after primary percutaneous coronary intervention for ST-elevation myocardial infarction, grouped by left ventricular ejection fractionFigure 2
Adjusted 3 year mortality rate for patients who underwent planar radionuclide ventriculography after primary percutaneous
coronary intervention for ST-elevation myocardial infarction, grouped by left ventricular ejection fraction.
< 20 % 20 % - 39% 40 % - 59% > 60 %
Left Ventricular Ejection Fraction
0
0,05
0,1
0,15
0,2
0,25
0,3
Mean 3 year mortality

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Conclusion
In conclusion, LVEF assessed by PRV before discharge
from the hospital is a powerful independent predictor of
long term prognosis after PPCI for STEMI.
Abbreviations
CABG = Coronary artery bypass grafting, CK = Creatin
kinase, CK-MB = Creatin kinase myocardial band, LVEF =
Left ventricular ejection fraction, PCI = Percutaneous cor-
onary intervention, PPCI = Primary percutaneous coro-
nary intervention, PRV = Planar radionuclide
ventriculography, SD = Standard deviation, STEMI = ST-
elevation myocardial infarction, TIMI = Thrombolysis in
myocardial infarction (study group).
Competing interests
The author(s) declare that they have no competing inter-
ests.
Authors' contributions
PVV contributed in data-collection, data-analysis and
drafting the manuscript.
SR contributed in data-collection, data-analysis and draft-
ing the manuscript.
WH contributed in PRV acquisition in Zwolle and drafting
the manuscript.
ICH contributed in designing the study, data-analysis and
drafting the manuscript.
RHS contributed in PRV acquisition in Groningen and
drafting the manuscript.
SR contributed in designing the study, data-analysis and
drafting the manuscript.
RAD contributed in data-analysis and drafting the manu-
script.
RAT contributed in study-design, data-analysis and draft-
ing the manuscript.
JPO contributed in study-design and drafting the manu-
script.
MJB contributed in study-design and drafting the manu-
script.
FZ contributed in study-design, data-analysis and drafting
the manuscript.
All authors have read and approved the final version of
the manuscript.
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