Prognostic factors affecting the all-cause death and sudden cardiac death rates of post myocardial infarction patients with low left ventricular ejection fraction.
ABSTRACT Post myocardial infarction (post-MI) patients with low left ventricular ejection fraction (LVEF) have been candidates for an implantable cardioverter-defibrillator (ICD) since the Multicenter Automatic Defibrillator Implantation Trail II (MADIT II). However, due to the high costs of ICDs, widespread usage has not been accepted. Therefore, further risk stratification for post-MI patients with low LVEF may aid in the selection of patients that will benefit most from ICD treatment.
Four hundred and seventeen post-MI patients with low LVEF (< or = 35%) were enrolled in the study. All the patients received standard examination and proper treatment and were followed up to observe the all-cause death rate and sudden cardiac death (SCD) rate. Then COX proportional-hazards regression model was used to investigate the clinical factors which affect the all-cause death rate and SCD rate.
Of 55 patients who died during (32 +/- 24) months of follow-up, 37 (67%) died suddenly. After adjusting for baseline clinical characteristics, multivariate COX proportional-hazards regression model identified the following variables associated with death from all causes: New York Heart Association (NYHA) heart failure class > or = III (Hazard ratio: 2.361), LVEF < or = 20% (Hazard ratio: 2.514), sustained ventricular tachycardia (Hazard ratio: 6.453), and age > or = 70 years (Hazard ratio: 3.116). The presence of sustained ventricular tachycardia (Hazard ratio: 6.491) and age > or = 70 years (Hazard ratio: 2.694) were specifically associated with SCD.
In the post-MI patients with low LVEF, factors as LVEF < or = 20%, age > or = 70 years, presence of ventricular tachycardia, and NYHA heart failure class > or = III predict an adverse outcome. The presence of sustained ventricular tachycardia and age > or = 70 years was associated with occurrence of SCD in these patients.
Chin Med J 2009;122(7):802-806
Prognostic factors affecting the all-cause death and sudden
cardiac death rates of post myocardial infarction patients
with low left ventricular ejection fraction
DAI Shi-mo, ZHANG Shu, CHEN Ke-ping, HUA Wei, WANG Fang-zheng and CHEN Xin
Keywords: myocardial infarction; death, sudden, cardiac; heart failure
Background Post myocardial infarction (post-MI) patients with low left ventricular ejection fraction (LVEF) have been
candidates for an implantable cardioverter-defibrillator (ICD) since the Multicenter Automatic Defibrillator Implantation
Trail II (MADIT II). However, due to the high costs of ICDs, widespread usage has not been accepted. Therefore, further
risk stratification for post-MI patients with low LVEF may aid in the selection of patients that will benefit most from ICD
Methods Four hundred and seventeen post-MI patients with low LVEF (≤35%) were enrolled in the study. All the
patients received standard examination and proper treatment and were followed up to observe the all-cause death rate
and sudden cardiac death (SCD) rate. Then COX proportional-hazards regression model was used to investigate the
clinical factors which affect the all-cause death rate and SCD rate.
Results Of 55 patients who died during (32±24) months of follow-up, 37 (67%) died suddenly. After adjusting for
baseline clinical characteristics, multivariate COX proportional-hazards regression model identified the following
variables associated with death from all causes: New York Heart Association (NYHA) heart failure class ≥III (Hazard ratio:
2.361), LVEF ≤20% (Hazard ratio: 2.514), sustained ventricular tachycardia (Hazard ratio: 6.453), and age ≥70 years
(Hazard ratio: 3.116). The presence of sustained ventricular tachycardia (Hazard ratio: 6.491) and age ≥70 years (Hazard
ratio: 2.694) were specifically associated with SCD.
Conclusions In the post-MI patients with low LVEF, factors as LVEF ≤20%, age ≥70 years, presence of ventricular
tachycardia, and NYHA heart failure class ≥III predict an adverse outcome. The presence of sustained ventricular
tachycardia and age ≥70 years was associated with occurrence of SCD in these patients.
Chin Med J 2009;122(7):802-806
everal previous randomized trials have shown that
cardioverter-defibrillator (ICD) will result in a mortality
benefit for post myocardial infarction (post-MI) patients
with reduced left ventricular (LV) systolic function.1-3
Much clinical evidence has proven that prophylactic
implantation of an ICD can reduce the incidence of
sudden cardiac death (SCD), however the relatively low
accuracy of left ventricular ejection fraction (LVEF) as a
predictor of SCD results in unnecessary implantation of
ICD in a large proportion of patients. Due to the relatively
high costs of this therapy,4-7 widespread usage of the ICD
has not been accepted by most patients, particularly in
those countries with less access to public medical care.
There is an obvious need for other risk predictors of SCD,
in addition to the measurement of LVEF, to better predict
which patients will benefit most from ICD implantation.
Also, post-MI patients are at a high risk of unfavorable
prognosis, thus further risk stratification for these patients
is helpful to formulate a proper patient evaluation and
treatment plan in clinical practice. Furthermore, no study
has investigated the factors affecting the prognosis in
Chinese post-MI patients with low LVEF. For these
reasons, we enrolled post-MI patients with low LVEF
(LVEF ≤35%) in the current study, and collected their
of an implantable
clinical characteristics in detail. Statistical methods were
used to analyze the relationship between their clinical
characteristics and death or ICD implantation in order to
find some predictors for SCD to guide ICD therapy.
The trial began on March 27, 1990, and ended on
December 31, 2004. The patients enrolled were identified
from a consecutively recruited population at Fu Wai
Hospital. The inclusion criteria were that they had a MI
one month or more before entry, as documented by the
finding of an abnormal Q wave on electrocardiography,
elevated cardiac enzyme levels shown by laboratory
testing during hospitalization for suspected MI, a fixed
Center for Arrhythmia Diagnosis and Treatment, Fu Wai Hospital
and Cardiovascular Institute, Chinese Academy of Medical
Sciences & Peking Union Medical College, Beijing 100037, China
(Dai SM, Zhang S, Chen KP, Hua W, Wang FZ and Chen X)
Correspondence to: Dr. ZHANG Shu, Center for Arrhythmia
Diagnosis and Treatment, Fu Wai Hospital and Cardiovascular
Institute, Chinese Academy of Medical Sciences & Peking Union
Medical College, Beijing 100037, China (Tel: 86-10-68334688.
Fax: 86-10-68334688. Email: firstname.lastname@example.org)
Chinese Medical Journal 2009;122(7):802-806
defect on thallium scanning, or localized akinesis on
ventriculography with evidence of obstructive coronary
disease on angiography, and an LVEF of 35% or less
within three months before entry, as assessed by
Patients were excluded if they had the following
conditions: MI within a month as evidenced by
measurement of cardiac enzyme levels; advanced
cerebrovascular disease; childbearing age women without
taking medically prescribed contraceptive measures;
autoimmune or inflammatory disease, hematologic
disease, chronic renal failure or hepatic or malignant
disease; or any conditions other than cardiac disease that
was associated with a high likelihood of death during the
The patients enrolled underwent a standard physical
examination including blood tests, chest X-ray,
electrocardiography, and echocardiography. LV dimensions
and valvular abnormalities
echocardiography. Coronary angiography was performed
to assess the degree of stenosis of the coronary arteries.
Based on the coronary angiography, revascularization
intervention (PCI) and/or coronary artery bypass grafting
(CABG) was performed as needed, and the patients were
prescribed the appropriate use of beta-blockers,
angiotensin-converting-enzyme inhibitors, and/or lipid-
lowering drugs. Patients with sustained ventricular
tachycardia were treated with amiodarone, while those
patients with atrial fibrillation received amiodarone or
class I antiarrhythmic agents.
Follow-up and end points
Follow-up was performed by outpatient visits, telephone,
and chart review. The patients were followed up every
three months after enrollment thereafter until the trial was
stopped. At each follow-up visit an appropriate clinical
evaluation was carried out, medication use was recorded.
The patients underwent a final evaluation within one
month after the completion of the study.
These were completed in 417/452 patients (92.2%) with
35 patients lost to follow up (7.8%) because we can not
make a contact with them. And we excluded the lost
patients from our study. The average follow-up duration
was (32±24) months (range 1–72 months). The primary
end point was all-cause death. Each death was
categorized to be due to a SCD, a non-sudden cardiac
death, or a non-cardiac cause. We defined SCD for
patients who died suddenly and unexpectedly within 1
hour of cardiac symptoms in the absence of progressive
cardiac deterioration. This category included several
patients whose time course of death was prolonged by
unsuccessful resuscitative measures, as well as patients
who died within 1 hour of the onset of cardiac symptoms
in the setting of stable heart failure.8 We confirmed the
information of patients′ death by the death certificates in
were assessed by
our hospital or information feedback from family
members of the patients. The patients who underwent
ICD implantation, were hospitalized for any cardiac
reason, and suffered acute MI were reported.
Epidata 3.0 was used to store the data from patients and
analyses were made with SPSS statistical software
version 13.0 for Windows. Cumulative probabilities of
survival were estimated with the Kaplan-Meier method.9
Continuous variables were presented as mean ± standard
deviation (SD). Dichotomous variables were presented as
numbers and percentages. The clinical variables of the
deaths were compared with the survivors using the
2-sample t-test for independent samples when dealing
with approximately normally distributed variables. A P
value <0.05 was considered statistically significant.
Categorical variables were compared using the chi-square
test and Fisher′s exact test. Univariate and multivariate
COX proportional-hazards regression models were used to
determine the relationship between clinical characteristics
at baseline, all-cause deaths, and the incidence of SCD.10
Main variables tested in the initial model were as follows:
age, hypertension, diabetes mellitus, hypercholestero-
lemia, tobacco use, history of atrial fibrillation, and
presence of sustained ventricular tachycardia, history of
coronary angioplasty, history of coronary bypass surgery,
LVEF, New York Heart Association (NYHA) heart failure
class, ECG abnormalities, and medications at last contact.
The final model was built by a stepwise procedure with a
significance level of 0.05 as a criterion for entry into the
Clinical characteristics of patients
Baseline characteristics of 417 patients were as follows:
age (61±11) years, gender (male 84%), NYHA heart
failure class ≥III (49%), syncope (9.8%), hypertension
(53%), diabetes (29%), cigarette smoker (69%),
hyperlipidemia (37%), history of wine drinking (33%),
coronary bypass surgery (31%), coronary angioplasty
(18%), atrial fibrillation (7.6%), sustained ventricular
tachycardia (10%), QRS interval >0.12 second (11%),
bundle-branch block (5%), left bundle-branch block
(1.9%), and LVEF (29.09±6.49)%.
Outcome of follow-up
A follow-up until March 2006 revealed that 55 patients
died. Thirty-seven deaths (67%) were due to SCD, 15 to
non-SCD deaths, and the other 3 to pulmonary embolism,
respiratory failure and sepsis respectively. One hundred
and twenty (28%) patients were hospitalized for cardiac
cause, 3 patients underwent heart transplantation, and 11
patients suffered from subsequent acute MI. Clinical
characteristics were compared between the survivors and
the non-survivors (Table 1). More survivors were male
and they were younger than the non-survivors. The
defect (3.1%), right
Chin Med J 2009;122(7):802-806
Table 1. Clinical characteristics of survivors and non-survivors
Age ≥70 years (n (%))
Male sex (n (%))
NYHA heart failure class (n (%))
Hypertension (n (%))
Syncope (n (%))
Diabetes (n (%))
History of cigarette smoker (n (%))
Hyperlipemia (n (%))
Wine drinking (n (%))
Coronary bypass surgery (n (%))
Coronary angioplasty (n (%))
Atrial fibrillation (n (%))
Sustained ventricular tachycardia (n (%))
QRS interval >0.12 second (n (%))
LVEF ≤20% (n (%))
Medication at last contact (n (%))
ACEIs & ARBs
Class I antiarrhythmic agents
ACEI: angiotensin converting enzyme inhibitors; ARB: angiotensin receptor
blockers; NS: not significant.
survivors had a higher rate of coronary bypass surgery
and coronary angioplasty than the non-survivors. The
non-survivors had a higher NYHA heart failure class, a
lower LVEF, and a longer history of sustained ventricular
tachycardia and syncope than the survivors. There were
no differences in the prevalence of hypertension, diabetes,
atrial fibrillation, or hyperlipidaemia between the two
groups. Regarding the use of medications, the survivors
received more diuretics, beta-blockers, calcium-channel
blockers, and less amiodarone than the non-survivors.
Results of Cox analysis
According to the outcome of the follow-up, we analyzed
the relationship between
characteristics and all-cause deaths. Univariate Cox
analysis showed that patients with NYHA heart failure
class ≥III (Class III: Patients with marked limitation of
activity; they are comfortable only at rest. Class IV:
Patients who should be at complete rest, confined to bed
or chair; any physical activity brings about discomfort
and symptoms occur at rest), LVEF ≤20%, and age ≥70
years, history of sustained ventricular tachycardia
(Ventricular arrhythmia lasts for at least 30 seconds and
generally requires termination by anti-arrhythmia drugs,
cardioversion) correlated with all-cause deaths. All
variables are the initial variables when the patients were
enrolled in the study. Multivariate COX analysis adjusting
for these four factors showed a consistently increased risk
associated with NYHA class ≥III (B=0.859, Hazard ratio
(HR): 2.361, P ≤0.001), LVEF ≤20% (B=0.922, HR: 2.514,
the patients′ clinical
techniques or electrical
P=0.011), sustained ventricular tachycardia (B=1.865, HR:
6.453, P <0.001), and age ≥70 years (B=1.104, HR: 3.116,
P <0.001) (Table 2). Kaplan-Meier estimates of the effect
of the four factors on cumulative probability of all-cause
death are presented in Figures 1–4. There is an early and
progressive separation of the probability of death between
the two arms of the trial in all figures, so the effect of
factors on the death rate is significant.
Table 2. Variables affecting the rate of all-cause death in our study
Variables B SE
NYHA class ≥III 0.859 0.284
LVEF ≤20% 0.9220.362
Age ≥70 years 1.104 0.276
B: regression coefficient; CI: confidence interval; SE: standard error.
We then analyzed the relationship between the patients′
clinical characteristics and SCD. In multivariate Cox
analysis we found that the presence of sustained
ventricular tachycardia (B=1.87, HR: 6.491, P <0.001),
and age ≥70 years (B=0.991, HR: 2.694, P=0.003) is
correlated with SCD.
95% CI for HR
Figure 1. Kaplan-Meier estimates of the cumulative probability
of all-cause death of post-MI patients with LVEF ≤35% for
presence of sustained ventricular tachycardia vs non-sustained
The present study is to specifically target Chinese
post-MI patients with low LVEF in order to analyze the
factors correlating with all-cause deaths and SCD. Two
main findings are presented. First, NYHA heart failure
class ≥III, presence of sustained ventricular tachycardia,
age ≥70 years, and LVEF ≤20% are factors which predict
an adverse outcome. Second, the presence of sustained
ventricular tachycardia and age ≥70 years predicts
patients at a higher risk of SCD. Earlier studies have
proven that left ventricular dysfunction (low LVEF)
predisposes post-MI patients to SCD.11 The Multicenter
Automatic Defibrillator Implantation Trail II (MADIT II)
trial demonstrated that implantation of an ICD can reduce
the mortality of post-MI patients with low LVEF,3 due to
the ICD preventing SCD. In this study, the incidence of
SCD makes up 67% of the total deaths, demonstrating
Chinese Medical Journal 2009;122(7):802-806
Figure 2. Kaplan-Meier estimates of the cumulative probability
of all-cause death of post-MI patients with LVEF ≤35% for
NYHA heart failure class ≥III vs NYHA heart failure class <III.
Figure 3. Kaplan-Meier estimates of the cumulative probability
of all-cause death of post-MI patients with LVEF ≤35% for
LVEF ≤20% vs LVEF >20%.
Figure 4. Kaplan-Meier estimates of the cumulative probability
of all-cause death of post-MI patients with LVEF ≤35% for age
≥70 years vs age <70 years.
that SCD is the main cause of death in post-MI patients
with low LVEF. As the previous studies have shown, ICD
implantation therapy may improve the prognosis of these
Spontaneous sustained ventricular
association with structural heart disease is a class I
indication for ICD therapy.12 This study demonstrated
that sustained ventricular tachycardia is an independent
predictor for both SCD and all-cause death, and its HR is
higher than other risk predictors. Therefore, post-MI
patients with sustained ventricular tachycardia are at a
very high risk of SCD and all-cause death. Thus,
according to our results ICD therapy might greatly benefit
post-MI patients with sustained ventricular tachycardia.
Some studies have found that history and degree of
congestive heart failure (CHF) are more closely
associated with non-SCD than with SCD.11,13 The results
of our study demonstrat that NYHA heart failure class
≥III is an independent predictor of all-cause death and
unassociated with SCD. We should use effective methods
including medication and resynchronization treatment to
control CHF degree of post-MI patients with low LVEF.
Although the degree of CHF is not associated with SCD,
we still can not rule out the probability that an ICD could
reduce mortality in these patients.
ICD trials recruiting cardiac arrest survivors from the
entire spectrum of left ventricular systolic function have
unanimously reported that the majority of benefits
observed was within the subgroup with systolic
dysfunction of the left ventricle.14 In the MADIT trial,
stratification of the study population into ejection fraction
<25% and those above indicate a higher benefit in the
subgroup with lowest LVEF.15 A possible interaction was
not tested and the number of events was probably too few
to yield significant differences. In MADIT II, the
interaction was neither clinically nor statistically
significant.3 In this study we dichotomized the LVEF at
20% and ≤20%, 25% and ≤25%, 30% and ≤30%, and
only found that LVEF ≤20% was an independent
predictor of all-cause death. This result indicates that
post-MI patients with LVEF ≤30% or with LVEF ≤25%
have a similar death rate to post-MI patients with LVEF
≤35%, and only LVEF ≤20% can predict an adverse
prognosis. Similar to MADIT II, lower LVEF does not
predict the patients at a highest risk of SCD.
Advanced age has proven to be a predictor of adverse
outcome in ischemic heart disease patients because it
relates more frequently to low LVEF, hypertension,
atrioventricular block, left bundle branch block, and less
frequent CABG surgery.16 Patients with advanced age
often have an unfavorable prognosis. The patients at age
≥70 years were not only at a high risk of all-cause death,
but also at a high risk of SCD. Therefore for post-MI
patients with advanced age and low LVEF, ICD
implantation can decrease the incidence of SCD.
Previous studies have shown that PCI CABG,
beta-blockers, statins and other medicine can prevent
SCD in post-MI patients.17,18 We found no treatment
reduced the incidence of SCD and all-cause death,
although in COX analysis, PCI and CABG did not affect
the occurrence of all-cause death and SCD because the
survivors had a higher incidence of receiving CABG and
coronary angioplasty than the non-survivors. We can not
rule out the protective effect of these two treatments due
to the small sample size. The results of the current study
are important for ICD therapy, showing that post-MI
Chin Med J 2009;122(7):802-806
patients with low LVEF are at a higher risk of SCD and
thus may benefit from ICD therapy. Of course, in addition
to patients with advanced age or sustained ventricular
tachycardia, other patients may also benefit from ICD
therapy if the economic factors are eliminated.
Furthermore, because of the effect of cardiac resyn-
chronization therapy in
demonstrated by some
chronization therapy defibrillator might be used to
prevent patients from SCD.
Thirty-five patients were lost to follow up (7.8%) and
their outcomes may affect the results of the study despite
their small number. The study was performed in a single
center setting and although the patients came from many
areas of China, the study population may not represent
the entire Chinese population. However, it is in itself an
advantage, as all patients were evaluated according to an
identical protocol reflecting daily clinical practice. The
classification of SCD is inaccurate and it is only a marker
of arrhythmic death. Further, not all deaths classified as
sudden or arrhythmic can be prevented by ICD
implantation. In addition, the observational nature of the
study design is an obvious limitation of the present study,
because we can not exclude the patients without sustained
ventricular tachycardia and with age <70 years who may
also benefit from ICD implantation.
In conclusion, the data of the present study demonstrated
that in post-MI patients with LVEF <35%, age ≥70 years,
LVEF ≤20%, NYHA heart failure class ≥III, and presence
of sustained ventricular tachycardia can be predictors of
all-cause death. The presence of sustained ventricular
tachycardia and age ≥70 years was associated with
occurrence of SCD.
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(Received December 24, 2008)
Edited by QIAN Shou-chu and LIU Huan
the American College of