CLINICAL RESEARCH STUDY

Prevalence of Asymptomatic Left Ventricular Systolic

Dysfunction in At-risk Medical Inpatients
L. David Martin, MD,a Simon Mathews, MD,b Roy C. Ziegelstein, MD,b Carol Martire, RDCS,c Eric E. Howell, MD,d
David B. Hellmann, MD,c Glenn A. Hirsch, MD, MHSb
a
Division of Chemical Dependence, bDivision of Cardiology, cDivision of Hospitalist Medicine, and dDivision of Rheumatology,
Department of Medicine, Johns Hopkins Bayview Medical Center, The Johns Hopkins University School of Medicine, Baltimore, Md.

ABSTRACT

BACKGROUND: Asymptomatic left ventricular systolic dysfunction is an important risk factor for heart
failure and death. Given the availability of patients, trained personnel, and equipment, the hospital is an
ideal setting to identify and initiate treatment for left ventricular systolic dysfunction. The purpose of this
study was to determine the prevalence of asymptomatic left ventricular systolic dysfunction in patients 45
years of age or older with at least one clinical heart failure risk factor admitted to a general medical service.
METHODS: Bedside, hand-carried echocardiography provided quantitative assessment of left ventricular systolic
function in 217 medical inpatients 45 years of age or older who had at least one heart failure risk factor. Patients
with known or suspected heart failure or with an assessment of left ventricular function in the past 5 years were
excluded. We measured the prevalence of asymptomatic left ventricular systolic dysfunction, defined by left
ventricular ejection fraction of 50% or lower, and its association with heart failure risk factors.
RESULTS: Of 207 patients with interpretable images, 11 (5.3%) had a left ventricular ejection fraction of
50% or lower. Patients with left ventricular systolic dysfunction had more heart failure risk factors than
those without left ventricular systolic dysfunction (3.09 ⫾ 0.8 vs 2.5 ⫾ 1.0, P ⫽ .04). The total number of
heart failure risk factors trended towards an association with a greater prevalence of asymptomatic left
ventricular systolic dysfunction, but this did not reach significance (odds ratio 1.74; 95% confidence
interval, 0.97-3.12, P ⫽ .06).
CONCLUSIONS: Asymptomatic left ventricular systolic dysfunction is present in about 1 of every 20 general
medical inpatients with at least one risk factor for heart failure. Because treatment of asymptomatic left
ventricular systolic dysfunction may reduce morbidity, further studies examining the costs and benefits of using
hand-carried ultrasound to identify this important condition in general medical inpatients are warranted.
© 2013 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2013) 126, 68-73

KEYWORDS: Echocardiography; Epidemiology; Hand-carried ultrasound; Heart failure; Portable ultrasound; Systolic
function

Heart failure is a common, costly, disabling, and life-threat-
ening condition. American Heart Association and American
College of Cardiology guidelines recognize that certain con-
ditions including increasing age, diabetes mellitus, coronary
Funding: None.
Conflict of Interest: None.
Authorship: All authors had access to the data and contributed to the
preparation of the manuscript.
Requests for reprints should be addressed to Glenn A. Hirsch, MD,
MHS, Division of Cardiology, Department of Medicine, Johns Hopkins
Bayview Medical Center, The Johns Hopkins University School of Med-
icine, 4940 Eastern Ave., Suite 2400, 301 Bldg., Baltimore, MD 21224.
E-mail address: ghirsch@jhmi.edu
artery disease, smoking, hypertension, and excessive alco-
hol intake are prevalent in patients diagnosed with heart
failure.1 Patients with these conditions are classified as
having “pre-heart failure” or Stage A heart failure.2 Stage B
heart failure patients have objective signs of structural heart
disease but are asymptomatic. Reducing the frequency of
incident heart failure requires better identification and man-
agement of clinical and echocardiographic risk factors, in-
cluding asymptomatic left ventricular systolic dysfunction.
Not surprisingly, population-based studies have shown a
high prevalence of asymptomatic cardiac abnormalities in
patients at risk for heart failure.3,4 Data on the prevalence of
asymptomatic left ventricular systolic dysfunction in the

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http://dx.doi.org/10.1016/j.amjmed.2012.06.020
Martin et al Prevalence of Asymptomatic Systolic Dysfunction 69

general population are lacking, but estimates have ranged initiating treatment for left ventricular systolic dysfunction,
from 1%-4%, depending on the population studied and on given the availability of patients, trained personnel, and
how left ventricular systolic dysfunction was defined and equipment. The following study was performed to determine
measured.4-7 The prevalence of asymptomatic left ventric- the prevalence of asymptomatic left ventricular systolic dys-
ular systolic dysfunction in selected high-risk populations function in patients 45 years of age and older with at least one
may be as high as 15%.8-10 heart failure risk factor admitted to a
Asymptomatic left ventricular general medical service.
systolic dysfunction has prognostic
CLINICAL SIGNIFICANCE
importance, even when the left ven-
METHODS
tricular ejection fraction is only ● Heart failure is common in patients with
mildly reduced. In the Framing- heart failure risk factors. Asymptomatic Study Population
ham cohort, individuals with mild left ventricular systolic dysfunction has The study took place on the inpa-
asymptomatic left ventricular sys- tient general medical service at
prognostic significance, and treatment
tolic dysfunction had rates of con- Johns Hopkins Bayview Medical
gestive heart failure and death that
can improve outcomes.
Center, an academic medical cen-
were 2- to 4-fold higher than those ● Left ventricular systolic dysfunction is ter in Baltimore, Maryland. Adult
of individuals with normal left more accurately detected with ultra- patients admitted to the medical
ventricular systolic function.6 The sonography than the history and phys- service between January 2010 and
Echocardiographic Heart of Eng- ical examination. Hand-carried ultra- January 2011 were eligible to par-
land Screening Study showed that sound now provides noncardiovascular ticipate if they were 45 years of
the 5-year survival rate of those age or older, had at least one clin-
specialists access to this technology.
with asymptomatic mild left ven- ical heart failure risk factor, and
tricular systolic dysfunction was ● The prevalence of asymptomatic and provided informed, written con-
69%, compared with 93% in the unsuspected left ventricular systolic sent. Heart failure risk factors in-
general population.11 The mortal- dysfunction is not uncommon on gen- cluded age ⬎60 years, male sex,
ity rate of patients even with “bor- eral medicine inpatient wards in those hypertension, diabetes mellitus,
derline” left ventricular systolic at risk of heart failure. coronary artery disease, current
dysfunction (left ventricular ejec- smoking, and excessive alcohol
tion fraction 40%-50%) was 1.3- use.1 The age cutoff of 45 years or
fold higher than the mortality rate older for enrollment was based on
of those whose ejection fraction was over 50%.11 These prior studies.3,4 The Johns Hopkins School of Medicine
observations are important because treating asymptomatic Institutional Review Board approved the study protocol.
left ventricular systolic dysfunction with angiotensin-con- Study patients were selected as follows: A research echo-
verting enzyme (ACE) inhibitors has been shown to reduce cardiography sonographer (CM) or study investigator (LDM)
12-14
morbidity and mortality. determined whether patients admitted to the medical service
Due in part to its poor prognosis and the likelihood that
were eligible on the basis of the inclusion criteria above.
treatment will improve outcomes, identifying asymptomatic
Screening included review of admission histories and physical
left ventricular systolic dysfunction may have a potentially
examinations and review of the electronic medical record that
important impact on public health. The poor diagnostic
included care at both Johns Hopkins Bayview Medical Center
accuracy of the history and physical examination to detect
and The Johns Hopkins Hospital since 1980. Specifically, the
left ventricular systolic dysfunction, including suboptimal
electronic medical record was examined to review clinical
specificity of the electrocardiogram and biomarkers such as
notes and all prior estimates of left ventricular function includ-
brain natriuretic peptide, suggest a need for more accurate
15-18 ing echocardiograms, ventriculograms, and nuclear imaging
tests to screen for this condition. Echocardiography is
one such test, but barriers to widespread echocardiographic studies. After receiving permission from the patients’ attending
screening include the high cost and limited availability of physicians, eligible patients were approached for study enroll-
gold-standard devices. Until recently, echocardiographic ment and asked about any history of heart failure or “poor heart
screening also was limited by the large size of the full- squeeze.” Equivocal responses led to further questioning about
featured conventional machines. Hand-carried echocardiog- possible heart failure symptoms. Patients with an established
raphy offers a technically adequate method that can be heart failure diagnosis or current suspicion for heart failure
easily brought to the patient and appears to be cost-effective were excluded from the study, as were patients who were
for screening in patients at elevated risk for left ventricular known to have had an assessment of left ventricular function
systolic dysfunction.19,20 Even so, the relatively low prev- within the past 5 years.
alence of asymptomatic left ventricular systolic dysfunction
in the population suggests that the optimal approach would Assessment of Left Ventricular Function
be to screen individuals at greatest risk.5,17 The hospital The research echocardiography sonographer performed lim-
setting may be particularly well suited for identifying and ited, bedside echocardiograms on eligible inpatients using a
70
hand-carried device (SonoSite MicroMaxx; SonoSite Inc.,
Bothell, Wash). Left ventricular ejection fraction was esti-
mated by standard echocardiographic views including the
parasternal long- and short-axis views and apical 2-, 4-, and
3-chamber views. At least one board-certified, experienced
cardiologist (RCZ or GAH) reviewed all echocardiograms.
The interpreting cardiologist was masked to any clinical
information about the patient.
Statistical Analysis
Power calculations based on an anticipated 5% prevalence of
asymptomatic left ventricular systolic dysfunction showed that
detecting a prevalence of at least 5% ⫾ 3% using an alpha of
0.05 required the enrollment of 203 subjects with completed
studies. To account for up to 10% of uninterpretable studies,
223 subjects were targeted for enrollment.
The prevalence of asymptomatic left ventricular sys-
tolic dysfunction was defined as the total number of cases
of left ventricular systolic function ⱕ50%, divided by the
enrolled inpatient population with adequate echocardio-
graphic image quality for interpretation during the study
period. Comparison of continuous variables was assessed
using nonparametric Wilcoxon rank-sum tests. The pres-
ence of asymptomatic left ventricular systolic dysfunction
and the association with clinical heart failure risk factors was
assessed using univariate, multivariate, and backwards step-
wise multivariate logistic regressions with a P-value ⬍.02
required for inclusion in the final model. Excessive alcohol use
was defined by a history of alcohol abuse or dependence in the
medical record. STATA statistical software (StataCorp, 2009,
Stata Statistical Software: Release 11. College Station, Tex)
was used to perform the analyses. A P-value ⬍.05 was con-
sidered statistically significant.
RESULTS
Study Populations
Of the 229 patients approached for the study, 6 were ex-
cluded based on additional history concerning for heart
failure. Among 223 consented patients, 5 were discharged
and 1 declined before performance of scanning. A total of
207 of the remaining 217 patients (95.4%) had interpretable
cardiac images. The characteristics of these 207 patients are
summarized in Table 1. The most common heart failure risk
factors were hypertension (67.2% of study patients), age
⬎60 years (48.3%), and male sex (47.8%). The average
number of heart failure risk factors was 2.6 ⫾ 1.0. On av-
erage, the limited hand-carried echocardiograms took
7.7 ⫾ 2.2 minutes to perform.
Prevalence of Left Ventricular Systolic
Dysfunction
A total of 11 of 207 patients were found to have asymp-
tomatic left ventricular systolic dysfunction, consistent with
an overall prevalence of 5.3%. The left ventricular ejection
fraction values and the heart failure risk factors present in
The American Journal of Medicine, Vol 126, No 1, January 2013
Table 1 Heart Failure Risk Factors Present in Study
Participants
n ⫽ 207
Age, years, mean ⫾ SD (range) 63.7 ⫾ 13.4 (45-94)
Age ⬎60 years, n (%) 100 (48.3)
Male sex, n (%) 99 (47.8)
Hypertension, n (%) 139 (67.2)
Diabetes mellitus, n (%) 49 (23.7)
Current smoker, n (%) 62 (30.0)
Coronary artery disease, n (%) 29 (14.0)
Excessive alcohol use, n (%) 51 (24.6)
Number of heart failure risk 2.6 ⫾ 1.0 (1-5)
factors*, mean ⫾ SD (range)
*Heart failure risk factors include age ⬎60 years, history of hyper-
tension, diabetes mellitus, current smoking, coronary artery disease,
excessive alcohol use, and male sex.1
those with left ventricular systolic dysfunction are displayed
in Table 2. Patients with left ventricular systolic dysfunc-
tion had more clinical heart failure risk factors than those
with preserved left ventricular systolic function (3.09 ⫾ 0.8
vs 2.5 ⫾ 1.0, respectively; P ⫽ .04). Both coronary artery
disease and male sex were associated with an increased
odds of having left ventricular systolic dysfunction in the
univariate analyses (coronary artery disease: odds ratio
[OR] 3.91; 95% confidence interval [CI], 1.07-14.3; P ⫽ .04
and male sex: OR 5.3; 95% CI, 1.11-25.1; P ⫽ .04). After
multivariate adjustment, only male sex was still signifi-
cantly associated with an increased odds of left ventricular
systolic dysfunction (OR 2.96; 95% CI, 1.1-8.00; P ⫽ .03).
The total number of heart failure risk factors trended to-
wards an association with a greater prevalence of asymp-
tomatic left ventricular systolic dysfunction, but this did not
reach statistical significance (OR 1.74; 95% CI, 0.97-3.12;
P ⫽ .06).
Of those found to have asymptomatic left ventricular
systolic dysfunction, 6 of 11 patients (55%) were not taking
ACE inhibitors at hospital admission. By discharge, ACE
inhibitors had been added or increased in 3 of 11 study
patients (27%) found to have asymptomatic left ventricular
systolic dysfunction. ACE inhibitors were contraindicated
in 3 of 11 study patients.
DISCUSSION
Our study shows that the prevalence of asymptomatic left
ventricular systolic dysfunction among medical inpatients
with at least one heart failure risk factor at our institution is
⬃5%. Patients with left ventricular systolic dysfunction had
more heart failure risk factors than those without left ven-
tricular systolic dysfunction, and the total number of heart
failure risk factors trended towards an association of a
greater prevalence of asymptomatic left ventricular systolic
dysfunction. Of the 11 patients with asymptomatic left ven-
tricular systolic dysfunction, none had fewer than 2 heart
failure risk factors, suggesting that selectively screening
Martin et al Prevalence of Asymptomatic Systolic Dysfunction
Table 2 Left Ventricular Systolic Function and Number of Heart Failure Risk Factors in Those with Left Ventricular Systolic
Dysfunction
Left Ventricular
Patient Ejection Fraction (%)
1 20
2 45
3 50
4 40
5 40
6 40-45
7 40-45
8 40-45
9 45
10 45-50
11 50
Heart failure risk factors are the same as in Table 1.
patients with 2 or more risk factors could be considered if
further studies confirm this finding. It is important to note
that we did not assess left ventricular systolic function in
patients with no heart failure risk factors.
Screening involves the identification of asymptomatic
disease in order to prevent morbidity or mortality related to
that condition. A screening test should have a high sensi-
tivity and specificity; it should be easy to perform, safe,
quick, and inexpensive. Ideally, the test should be able to be
performed when the patient is already seeing a physician for
other reasons. The hospital setting may be ideal for left
ventricular systolic dysfunction screening, given the avail-
ability of patients, trained personnel, and equipment. How-
ever, for routine screening to be endorsed, evidence from
well-conducted randomized-controlled trials must show that
the benefits from screening (and treatment) outweigh poten-
tial harms (resource/opportunity costs, misdiagnosis or
overdiagnosis and inappropriate labeling, adverse effects
and costs of inappropriate or unnecessary treatment).21,22
Although asymptomatic left ventricular systolic dysfunction
is a potentially treatable risk factor for congestive heart
failure and cardiac death, an acceptable screening strategy
has not been identified. The current study adds to what is
known in several ways. First, the study for the first time
documents a significant prevalence of unsuspected left ven-
tricular systolic dysfunction among at-risk medical inpa-
tients with no clinical symptoms of heart failure. The overall
prevalence of asymptomatic left ventricular systolic dys-
function in a Framingham community-based cohort of men
and women over age 40 years was 3% (6% for men, 0.8%
for women), but the prevalence of asymptomatic left ven-
tricular systolic dysfunction among general medical inpa-
tients has not been well described.6 The results of one prior,
smaller study of nonspecialists performing hand-carried ul-
trasound on unselected general medical inpatients are diffi-
cult to compare with our current study due to a large number
of false-positive examinations in the sub-group compared
with gold-standard echocardiography (positive predictive
71
Number of Heart
Risk Factors Failure Risk Factors
Age, diabetes, smoking, hypertension 4
Age, coronary artery disease, hypertension, male 4
Diabetes, hypertension, male 3
Age, coronary artery disease, male 3
Age, coronary artery disease, hypertension, male 4
Smoking, hypertension, male 3
Diabetes, hypertension, male 3
Age, smoking, coronary artery disease, male 4
Male, excessive alcohol use 2
Male, excessive alcohol use 2
Age, smoking 2
value for detecting left ventricular systolic dysfunction,
44%).23 In the present study, patients with known or sus-
pected left ventricular systolic dysfunction were excluded,
and the number needed to screen to detect one patient with
occult left ventricular systolic dysfunction in this population
of inpatients over age 45 years with at least one heart failure
risk factor was ⬃20. This population may provide a good
target for studies of the risks and benefits of routine screen-
ing. Second, the current study corroborates the findings of
other studies on the feasibility of bedside assessment of left
ventricular function using hand-carried echocardiogra-
phy.19,24-27 Hand-carried ultrasound may reduce cost com-
pared with conventional echocardiography, particularly if it
can be used as a point-of-care test by clinicians to assess left
ventricular systolic function. This, in turn, is predicated on
the development and implementation of focused training
programs and certification of competency.
A screening study that re-classifies patients from Stage A
to Stage B heart failure should have a significant impact on
prognosis and treatment. Indeed, the American Heart Asso-
ciation Councils on Epidemiology and Prevention have rec-
ommended appropriate studies to identify and treat asymp-
tomatic individuals with left ventricular systolic dysfunction
and to prevent the onset of heart failure symptoms.1 The
frequency of screening at-risk individuals remains undeter-
mined and will be a primary determinant of cost-effective-
ness. The benefits of detecting asymptomatic left ventricular
systolic dysfunction derive chiefly from the potential for
currently untreated individuals to begin ACE inhibitors.2
The prevalence of ACE inhibitor use among patients with
asymptomatic left ventricular systolic dysfunction for other
reasons (eg, hypertension) could diminish the potential ben-
efit from screening. In the present study, 55% of those with
asymptomatic left ventricular systolic dysfunction were not
taking ACE inhibitors at hospital admission, but by dis-
charge, ACE inhibitors had been added or increased in 27%.
Our study has several limitations. Levels of natriuretic
peptides and electrocardiograms were not reviewed, al-
72
though both may help identify patients likely to have
asymptomatic left ventricular systolic dysfunction.17,18
However, attempts to incorporate biomarkers and the 12-
lead electrocardiogram with clinical risk factors have not
proven sufficiently specific to be optimally useful as a
screening strategy.15-18 There also may be other risk factors
that correlate with the presence of asymptomatic left ven-
tricular systolic dysfunction that we did not examine in this
study, such as obesity, peripheral arterial disease, stroke,
low socioeconomic status, physical inactivity, obstructive
sleep apnea, chronic kidney disease, significant cardiac val-
vular disease, and human immunodeficiency virus infection,
among others.1,28-30 In addition, we did not measure the
prevalence of asymptomatic left ventricular systolic dys-
function among inpatients with no heart failure risk factors,
and we did not collect data on whether study patients’ new
diagnoses of asymptomatic left ventricular systolic dysfunc-
tion changed their clinical evaluation, extended their hospi-
tal length of stay, or affected their satisfaction with hospital
care. Finally, echocardiograms in this study were performed
by a trained sonographer, a finite resource that could not
absorb additional, uncompensated workload in most inpa-
tient settings which is why training noncardiology special-
ists, such as primary care physicians or hospitalist provid-
ers, is desirable. Optimally, bedside ultrasound screening by
hospitalist providers could be performed as part of the
routine admission evaluation in patients with heart failure
risk factors. However, the level of training required for
hospitalists to achieve competency in cardiac hand-carried
ultrasound has not been determined.27 Although the sonog-
rapher-performed study echocardiograms averaged nearly 8
minutes to complete, they included 6 probe positions and 9
measurement subsets; however, the literature suggests that
echocardiography limited to a single parasternal long-axis
view accurately detects left ventricular ejection fraction
ⱕ40%.31
CONCLUSION
This study shows that the prevalence of asymptomatic left
ventricular systolic dysfunction among at-risk general med-
ical inpatients at an academic medical center was ⬃5% and
was associated with the number of clinical heart failure risk
factors present. Thus, the number needed to screen to detect
1 patient with occult left ventricular systolic dysfunction
was ⬃20. Further investigation into training nonspecialists
to accurately perform limited hand-carried ultrasound and
the cost-effectiveness and clinical outcomes of widespread
screening of at-risk populations is warranted.
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