Download Screening for left ventricular systolic dysfunction among patients

Screening for left ventricular systolic dysfunction
among patients with risk factors for heart failure
David W. Baker, MD, MPH,a Robert C. Bahler, MD,b Robert S. Finkelhor, MD,b and Michael S. Lauer, MDc
Chicago, Ill, and Cleveland, Ohio
Background
The prevalence of left ventricular systolic dysfunction (LVSD) among individuals at risk for heart failure
(HF) and the feasibility of screening have not been clearly defined. This study determined the prevalence of LVSD with the
use of a limited screening echocardiogram among patients with risk factors for HF but no prior HF.
Methods
General medicine patients ⱖ60 years of age with hypertension, diabetes, coronary artery disease, or previous myocardial infarction (MI) but no history of HF or reduced left ventricular ejection fraction (LVEF) were eligible. Medical history and symptoms of breathlessness were determined by interview and chart review; consenting patients underwent electrocardiography and echocardiography. The outcome was LVEF ⱕ45%, based on visual estimation from the
echocardiogram.
Results
Of the 482 patients who completed the study, only 1 patient could not have the LVEF visually estimated. A
total of 7.9% of patients had LVEF ⱕ45%. The prevalence was 15.4% among those with a prior MI and 6.7% among
those without prior MI. In multivariate analysis, prior MI (adjusted odds ratio, 2.75; 95% CI, 1.14 to 6.64) and probable
or definite left ventricular hypertrophy by electrocardiography (adjusted odds ratio, 3.57; 95% CI, 1.22 to 10.48) were
the strongest predictors of LVEF ⱕ45%.
Conclusions Screening for LVSD among high-risk patients is feasible and has substantial yield, even among patients without prior MI. In light of the low cost of screening and the available therapies to prevent progression of LVSD to
overt HF, controlled clinical trials of screening high-risk subgroups appear to be justified. (Am Heart J 2003;146:
736 – 40.)
See related Editorial on page 570.
The prognosis of patients with congestive heart failure remains poor despite recent therapeutic advances,
emphasizing the need for prevention. Early detection
of patients with left ventricular systolic dysfunction
(LVSD) may be a promising strategy.1–3 Many people
appear to have asymptomatic LVSD,1,4,5 and these individuals have an increased risk of heart failure.6
Most patients with heart failure have identifiable risk
factors.7–12 We therefore conducted screening echocardiography in more than 500 general medical patients
From the aDepartment of Medicine and the Division of General Internal Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Ill, bDepartment of Medicine and Division of Cardiology, MetroHealth Medical Center, Cleveland, Ohio, and
the cDepartment of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland,
Ohio.
This project was supported by grant 9740079N from the American Heart Association.
Submitted August 1, 2002; accepted March 11, 2003.
Reprint requests: David W. Baker, MD, Northwestern University Medical School, Suite
200, 676 N St Clair St, Chicago, IL 60611.
E-mail: [email protected]
© 2003, Mosby, Inc. All rights reserved.
0002-8703/2003/$30.00 ⫹ 0
doi:10.1016/S0002-8703(03)00396-X
with risk factors for heart failure (coronary artery disease, hypertension, or diabetes) but no previous diagnosis of heart failure to determine the prevalence of
LVSD among high-risk patients and the feasibility of
screening with a brief, limited echocardiogram.
Methods
Study population
This study was approved by the MetroHealth Medical Center Institutional Review Board. Patients were recruited from
the General Medicine and Geriatric clinics at MetroHealth
between March 1998 and June 2000. Eligibility criteria included age ⱖ60 years; a history of hypertension, diabetes, or
coronary artery disease (CAD, including prior myocardial infarction (MI), angina, or revascularization procedure); and no
history of heart failure or documented reduced left ventricular ejection fraction (LVEF). Exclusion criteria were inability
to speak English, MI in the last year, and echocardiography
within the last year. If a patient was eligible on the basis of
an initial interview, the study was explained and consent was
obtained for an electrocardiogram and limited echocardiogram.
American Heart Journal
Volume 146, Number 4
Data collection
The initial questionnaire assessed past history of heart failure, diabetes, hypertension, angina, MI, coronary artery bypass grafting (CABG), angioplasty, stroke, and other medical
conditions. Participants were questioned about orthopnea,
paroxysmal nocturnal dyspnea (PND), dyspnea on exertion
with routine activities, and changes in exercise tolerance
over the previous year. Echocardiography was performed by
a technician using a Sonos 2500 imaging system with tissue
harmonics, with the patient supine and/or in left lateral supine position. M-mode recordings of the left ventricle were
performed under 2-D guidance, and parasternal long-axis,
parasternal short-axis, and apical 4- and 2-chamber views
were recorded.
Visual estimation of the LVEF was used as our primary
measurement. Echocardiograms were interpreted by a primary reviewer without knowledge of patients’ clinical data. A
second reviewer estimated LVEF for the first 50 echocardiograms; the correlation between the 2 readings was 0.87. If
the LVEF was ⱕ0.45, the patient was notified and their physician was informed of the results, along with suggestions for
changes in medical treatment to prevent further myocardial
damage.
The electrocardiograms were reviewed in a blinded fashion
to determine conduction and axis abnormalities and evidence
of left ventricular hypertrophy. Presence and location of old
MI were determined through the use of Minnesota Code criteria.13 Left ventricular hypertrophy (LVH) was determined
by the modified Romhilt-Estes criteria, with classification as
no LVH (⬍3 points), possible LVH (3 points), and probable
or definite LVH (ⱖ4 points).14 We classified the electrocardiogram as normal if there was sinus rhythm (with no more
than 1 premature atrial or ventricular contraction), a rate of
between 50 and 99 beats per minute, no conduction abnormalities, a QRS axis between 0 and 90 degrees, and no evidence of LVH or MI.
Charts were reviewed in a blinded fashion to determine
vital signs from the last 3 visits, medical diagnoses, antihypertensive and other cardiac medications, serum creatinine, and
hemoglobin A1c. Adequacy of blood pressure control was
determined on the basis of the average systolic and average
diastolic blood pressures from the last 3 visits, with categorization into Joint National Commission stages 1 through 4.15
Statistical analyses
Analyses were conducted with the use of Stata, version 7
(Stata Corporation, College Station, Tex). Our main dependent variable was LVEF ⱕ0.45 (yes/no). Medical conditions
(eg, hypertension) were considered present if they were either reported by either the patient or recorded in the chart.
Bivariate associations between independent variables (all categoric) and LVSD were assessed by means of Fisher exact
test. Multivariate analyses were conducted with logistic regression. A probability value of .05 was used to determine
statistical significance.
Results
Of the 1809 patients screened for the study, 78
(4.3%) refused to be interviewed and 760 (42.0%)
Baker et al 737
were ineligible because they lacked risk factors for
heart failure or they had a previous history of heart
failure. Of the 971 eligible patients, 510 participated
(51.6%). The average time (⫾SD) to complete the
screening echocardiogram was 6.5 (⫾3.0) minutes. Of
the 510 participants, 28 (5.5%) were excluded because
prior heart failure or low LVEF was documented in
their chart. Only one patient was excluded because
the echocardiogram was of insufficient quality to allow
visual estimation of LVEF, leaving 481 patients for analysis (Table I).
The distribution of LVEF is shown in Figure 1; 7.9%
had LVEF ⱕ0.45. The clinical characteristics most
strongly associated with low LVEF were male sex, history of previous MI, prior revascularization (CABG or
PTCA), angina, stroke, and LVH on electrocardiogram
(Table I). Duration of hypertension, number of medications, and average systolic blood pressure in clinic
were not significantly associated with low LVEF. Diabetes was only weakly associated with LVEF ⱕ0.45,
even among patients with retinopathy, neuropathy, or
nephropathy. There was a graded risk between the
presence and severity of LVH and the prevalence of
LVEF ⱕ0.45 (Table I). Having a normal electrocardiogram did not rule out LVSD. Of the 221 patients
judged to have no significant electrocardiographic abnormalities, the LVEF was ⱕ0.45 for 15 (7.2%) patients.
A total of 9.8% of participants reported PND, 11.9%
reported orthopnea, and 26.0% reported dyspnea on
exertion. However, these symptoms of breathlessness
were not significantly associated with having an LVEF
of ⱕ0.45 (Table I). Among participants with no symptoms of breathlessness and no history of prior MI, the
prevalence of LVEF of ⱕ0.45 was 6.9%.
We created 4 mutually exclusive categories, based
on patients’ Framingham risk factors for heart failure:
hypertension only; diabetes but no overt CAD; CAD
without prior MI; and prior MI. The prevalence of
LVEF ⬍0.45 increased across these categories (Figure
2), ranging from 5.4% for patients with hypertension
alone up to 15.4% for those with a prior MI.
In multivariate analysis with only clinical conditions
included, the adjusted odds ratio (AOR) of having
LVEF ⱕ0.45 was 2.88 (95% CI, 1.20 to 6.92) for a
prior MI compared with patients with hypertension
alone (Table II,model 1). The risk was similar for CAD
without prior MI (ie, angina, CABG, or PTCA), although this was not significant (AOR, 2.71; 95% CI,
0.98 to 7.51; P ⫽ .055). Prior stroke, diabetes without
overt CAD, and stroke were not associated with an
increased risk of having LVEF ⱕ0.45. When electrocardiographic findings were added to the multivariate
analysis (Table II, model 2), evidence of probable or
definite LVH was strongly associated with having LVEF
ⱕ0.45 (AOR, 3.52; 95% CI, 1.19 to 10.36). The addi-
American Heart Journal
October 2003
738 Baker et al
Table I. Prevalence of left ventricular systolic dysfunction (LVEF
ⱕ0.45) according to selected patient characteristics
Variable Category
All patients
Demographics
Age (y)
60–64
65–69
70–74
ⱖ75
Sex
Male
Female
Race/ethnicity
White
Black
Hispanic
Other
Symptoms
Paroxysmal nocturnal dyspnea
Yes
No
Orthopnea
Yes
No
Dyspnea on Exertion
Yes
No
Medical conditions
Previous MI*
No
Yes, ⱕ5 y ago
Yes, ⬎5 y ago
Yes, unknown
Prior CABG/PTCA*
No
Yes
Angina†
No
Yes
Diabetes*
No
Yes, no TOD
Yes, with TOD
Hypertension*
No
Yes
Duration of hypertension (y)
ⱕ5
6–10
⬎10
Unknown
Number of antihypertensive
medications
0
1
2
ⱖ3
Average systolic BP‡
ⱕ140
141–160
161–180
⬎180
No. (%)
LVEF
<0.45 (%)
481 (100.0)
7.9
154 (32.0)
118 (24.5)
105 (21.8)
105 (21.6)
7.8
5.9
10.5
7.7
.67
130 (27.0)
351 (73.0)
13.9
5.7
.007
312 (64.9)
147 (30.6)
18 (3.7)
4 (0.8)
8.3
6.8
11.1
0.0
.78
47 (9.8)
434 (90.2)
4.3
8.3
.57
57 (11.9)
424 (88.1)
5.3
8.3
.60
125 (26.0)
356 (74.0)
6.4
8.4
.57
416 (86.5)
14 (2.9)
30 (6.2)
21 (4.4)
6.7
7.1
13.3
23.8
.03
429 (89.2)
52 (10.8)
6.3
21.2
.001
414 (86.1)
67 (13.9)
6.8
14.9
.03
330 (68.6)
84 (17.5)
67 (13.9)
7.3
9.5
9.0
.71
29 (6.0)
452 (94.0)
13.8
7.5
.27
163 (36.1)
95 (21.0)
159 (35.2)
35 (7.7)
8.6
5.3
6.9
11.4
.59
35 (7.7)
191 (42.3)
166 (36.7)
60 (13.3)
2.9
8.9
7.2
6.7
.84
142 (31.4)
221 (48.9)
74 (16.4)
15 (3.3)
7.0
8.1
5.4
13.3
.61
Table I. continued
Variable Category
No. (%)
LVEF
<0.45 (%)
P
P
Stroke
No
Yes
ECG findings
LVH¶
No
Possible
Probable-definite
Abnormal ECG
No
Yes
408 (84.8)
73 (15.2)
6.9
13.7
.06
416 (86.5)
41 (8.5)
24 (5.0)
6.7
12.2
20.8
.02
221 (46.0)
260 (54.0)
7.2
8.5
.74
BP, Blood pressure; MI, myocardial infarction; LVEF, left ventricular ejection fraction; CABG, coronary artery bypass grafting; PTCA, percutancous transluminal
coronary angiography; TOD, target organ damage; ECG, electrocardiogram;
LVH, left ventricular hypertrophy.
*Based upon either patient history or documentation of the diagnosis in the chart.
†Based upon documentation of the diagnosis in the chart.
‡As recorded at the last 3 clinic visits.
¶Based on Romhilt-Estes criteria, where ⬍3 points is no LVH, 3 points is possible
LVH, and ⱖ4 points is probable or definite LVH.
Figure 1
Visual estimates of LVEF were recorded in 5-percentage-point
increments.
tion of electrocardiographic findings to the multivariate model had little effect on the adjusted odds ratios
for the clinical conditions (Table II, difference between model 2 and model 1). Men were also at increased risk (adjusted odds ratio, 2.22; 95% CI, 1.11 to
4.47) of having LVEF ⱕ0.45.
Among the 38 patients with low LVEF, 34.2% were
receiving an ACE inhibitor and 8.4% were prescribed a
␤-blocker (Table III). The mean systolic blood pressure
(⫾SD) for this group was 145.7 mm Hg (⫾21.0) and
the mean diastolic blood pressure (⫾SD) was 77.9 mm
Hg (⫾12.9). Only 32.7% had an average blood pressure of ⬍140/90; 80.8% had an average blood pressure
American Heart Journal
Volume 146, Number 4
Baker et al 739
Table II. Adjusted odds ratios (95% CI) for having a left ventricular ejection fraction of ⱕ0.45* based on medical conditions only (model
1), and medical conditions plus ECG evidence of LVH (model 2)
Variable
Heart failure risk factors
Hypertension only
Diabetes, no coronary artery disease
Coronary artery disease, no MI
Prior MI
Prior stroke
Left ventricular hypertrophy‡
None
Possible
Probable - definite
Model 1
P
Model 2
P
REF
1.32 (0.54, 3.25)
2.71 (0.98, 7.51)
2.88 (1.20, 6.92)
1.86 (0.84, 4.10)
–
.55
.06
.02
.12
REF
1.22 (0.49, 3.02)
2.49 (0.89, 6.98)
2.74 (1.13, 6.63)
1.99 (0.90, 4.40)
–
.68
.08
.02
.09
REF
–
1.90 (0.67, 5.33)
3.52 (1.19, 10.36)
.22
.02
*Based on visual estimation of ejection fraction from echocardiogram. The c statistic (area under the receiver-operator curve) was 0.77 for model 1 and 0.80 for model 2.
‡Based on electrocardiogram using Romhilt-Estes criteria.
Table III. Use of evidence-based therapies to prevent heart
failure among patients with LVEF ⱕ0.45 and ⬎0.45.
ACE inhibitor prescribed (%)
␤-Blocker prescribed (%)
Blood pressure control (%)*
⬍140 mm Hg systolic, ⬍90
mm Hg diastolic
140–159 mm Hg systolic OR
90–99 mm Hg diastolic
160–179 mm Hg systolic OR
100–109 mm Hg diastolic
ⱖ180 mm Hg systolic OR
ⱖ110 mm Hg diastolic
LVEF
<0.45
(n ⴝ 38)
LVEF
>0.45
(n ⴝ 443)†
34.2
18.4
42.6
22.0
32.7
34.2
48.1
50.0
16.3
10.5
2.9
5.3
Figure 2
P
.31
.61
.71
*Based upon the average blood pressure recorded at the last 3 clinic visits. If separate blood pressure readings were taken by the nurse and the doctor, the doctor’s recorded value was used. If the blood pressure was recorded in both arms,
the higher of the two readings was used.
†Information on prescribed medications was not available for two patients, reducing the total number available for analysis to 441.
of ⬍160/100 (Table III). None of the patients with low
LVEF had optimal treatment to prevent development
of heart failure (ie, ␤-blocker, ACE inhibitor, and mean
systolic blood pressure ⬍140 mm Hg).
Discussion
Screening patients at high risk for development of
heart failure with a limited echocardiogram is feasible
and identifies a significant number of patients with
LVSD. Patients with a past history of MI and those
with definite or probable LVH by electrocardiography
are particularly at risk. Patients with CAD who had not
had a previous MI and those with a history of stroke
were also had a higher risk of LVSD, but these trends
did not reach statistical significance. Our ability to de-
Based on visual estimation of LVEF from echocardiogram. The difference in prevalence of LVEF ⬍0.45 across all groups was significant at P ⫽ .025.
termine associations between other clinical characteristics and LVSD (ie, stroke, diabetes) was limited by the
relatively small number of patients with LVSD.
Three minimal criteria have been proposed to judge
whether screening for a disease might be worthwhile.16 First, how great is the burden of the disease?
The prevalence of LVSD in this study ranged from
5.4% for patients with hypertension alone up to 15.4%
for patients with a previous MI (Figure 2). This is
greater than the proportion of women found to have
breast cancer with biannual screening mammography
and clinical breast examination over a 10-year period
(3.7%)17 and the proportion of people found to have
colorectal cancer with annual or biannual screening
with fecal occult blood testing over a 13-year period
(2.3%).18
Second, is the course of the disease favorably altered
by early detection and treatment? Patients with LVSD
or ventricular dilation have a substantial risk of development heart failure or sudden death.6,19,20 Treatment
American Heart Journal
October 2003
740 Baker et al
of LVSD with an ACE inhibitor reduced the risk of
heart failure by 37% in the SOLVD trial19 and the risk
of death by 19% among patients with LVSD after a recent acute MI.20 The ability of ␤-blockers to improve
LVEF and decrease the risk of death and progressive
disease among patients with overt heart failure offers
hope that ␤-blockers may further decrease the risk of
progression from LVSD to heart failure.21 In contrast,
screening for colorectal cancer reduced mortality rates
from colorectal cancer by 33% but did not reduce
overall mortality rates.18
Third, is there a simple, reliable, inexpensive test
available to detect the condition? Echocardiography is
simple and acceptable to patients, and screening for
depressed LVEF would be relatively inexpensive. Visual estimation of the LVEF was possible for almost all
patients in our study, and the interobserver reliability
was good. Visual estimation of LVEF has been shown
to predict future cardiac events,22 which supports the
validity of using this to guide care. Serum brain natriuretic peptide (BNP) is another possible screening test,
but the accuracy of BNP and other natriuretic peptides
for detecting asymptomatic LVSD remains unclear.2,23
Thus, the three necessary criteria to justify screening
high-risk individuals for LVSD appear to be met. Studies are now needed to determine whether screening
alters treatment, improves clinical outcomes, and is
cost-effective.
We would like to thank Miriam Palmer, Annitta
Morehead, Dr James Thomas, and the cardiac sonographers at MetroHealth Medical Center.
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