ORIGINAL ARTICLE

Electrocardiographic Screening for HypertrophicCardiomyopathy and Long QT Syndrome: The Driversof Cost-Effectiveness for the Prevention of Sudden Cardiac Death

Brett R. Anderson • Sean McElligott •

Daniel Polsky • Victoria L. Vetter

Received: 6 May 2013 / Accepted: 14 August 2013 / Published online: 5 September 2013

� Springer Science+Business Media New York 2013

Abstract It is universally recognized that the prevention of

sudden cardiac death (SCD) in youth is an important public

health initiative. The best approach remains uncertain. Many

European and Asian countries support the use of electro-

cardiograms (ECGs). In the United States, this is highly

controversial. Many debate its cost-effectiveness. We

designed a comprehensive economic model of two of the

most prevalent causes of SCD identifiable by ECG, hyper-

trophic cardiomyopathy (HCM) and long QT syndrome

(LQTS), to determine the drivers of uncertainty in the esti-

mate of cost-effectiveness. We compared the cost-effec-

tiveness of screening with history and physical examination

(H&P) plus ECG to the current United States standard, H&P

alone, for the detection and treatment of HCM and LQTS.

We used a Markov model on a theoretical cohort of healthy

12-year-olds over a 70-year time horizon from a societal

perspective, employing extensive univariable and probabi-

listic sensitivity analyses, to determine drivers of costs and

effectiveness. The incremental cost-effectiveness of adding

ECGs to H&Ps was $41,400/life-year saved. The model was

highly sensitive to the effect of identification and treatment

of previously undiagnosed individuals with HCM; however,

it was insensitive to many variables commonly assumed to

be significant, including the costs of ECGs, echocardio-

grams, and genetic testing, as well as the sensitivity and

specificity of ECGs. No LQTS-related parameters were

significant. This study suggests that the key to determining

the cost-effectiveness of ECG screening in the United States

lies in developing a better understanding of disease pro-

gression in the previously undiagnosed HCM population.

Keywords Cost-effectiveness � ECG screening �Sudden death � Hypertrophic cardiomyopathy � Long

QT syndrome

Introduction

It is estimated that[1,000 children and adolescents die each

year in the United States from sudden cardiac arrest [21, 28].

The prevention of these deaths is universally recognized as

an important public health goal, yet the best screening

method remains controversial [4, 29]. Many European and

Asian countries and organizations recommend screening

Electronic supplementary material The online version of thisarticle (doi:10.1007/s00246-013-0779-0) contains supplementarymaterial, which is available to authorized users.

B. R. Anderson

The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

B. R. Anderson (&)

Division of Pediatric Cardiology, NewYork-Presbyterian/

Morgan Stanley Children’s Hospital, 3959 Broadway,

CH-2N, New York, NY 10032-3784, USA

e-mail: bra2113@columbia.edu

B. R. Anderson

Columbia Presbyterian Medical Center, New York, NY, USA

S. McElligott

Department of Healthcare Management and Economics, The

Wharton School, University of Pennsylvania,

Philadelphia, PA, USA

D. Polsky

Division of General Internal Medicine, Perelman

School of Medicine, University of Pennsylvania,

Philadelphia, PA, USA

V. L. Vetter

Division of Pediatric Cardiology, The Children’s

Hospital of Philadelphia, Perelman School of Medicine,

University of Pennsylvania, Philadelphia, PA, USA

123

Pediatr Cardiol (2014) 35:323–331

DOI 10.1007/s00246-013-0779-0

electrocardiograms (ECGs) given (1) that many deaths occur

in asymptomatic children with undiagnosed conditions and

(2) that conditions, such as hypertrophic cardiomyopathy

(HCM) and long QT syndrome (LQTS), can be identified on

ECG even in asymptomatic children with negative family

histories [5, 18, 28]. Proponents of ECG screening further

emphasize the fact that inexpensive treatments, including

lifestyle modification, are commonly thought to decrease

mortality [6]. In the United States, in contrast, many have

raised concerns regarding the logistics, feasibility, and costs

of ECG screening and have suggested that low disease

prevalence, imperfect ECG sensitivity or specificity, and

costs of ECGs/follow-up diagnostics or treatments might

limit the cost-effectiveness of this strategy [15, 27, 37]. The

American Heart Association’s scientific statement on pre-

participation cardiovascular screening currently recom-

mends screening only for children involved in competitive

sports with history and physical examination (H&P), without

inclusion of ECG, because these children are presumed to be

at highest risk of sudden unexpected death [4, 27, 29].

Comprehensive economic analyses of ECG screening in

the United States are limited. Most either artificially decrease

estimates of costs by ignoring lifetime costs of treatment or

decrease estimates of life-years saved (LYS) by restricting

the number of years for which the models are run (for

example, to only years while playing sports). Other analyses

assume that all individuals will come to diagnosis before

adulthood, even without screening, or they overestimate

effectiveness and underestimate costs by focusing on limited

populations or by including the costs of H&P in calculations

of ECG costs [8, 10, 15, 20, 30, 33, 34, 38, 40, 41].

We sought to determine the key drivers of uncertainty in

an estimate of the comparative cost-effectiveness of

screening with ECG plus H&P, compared with H&P alone,

to identify potential barriers to the cost-effectiveness of

ECG screening.

Methods

Model Overview

We used a state transition Markov model to compare the

costs and benefits of two types of screening programs for a

hypothetical cohort of healthy children in the United States.

Unlike some previous studies, we included all children in the

model, not just athletes, because both ethical and practical

concerns have been raised regarding the implementation of

targeted ECG screening in the United States; given the dif-

ficulty in defining ‘‘athlete’’ and ‘‘activity level’’ in most

children, we did not want to overestimate the cost-effec-

tiveness of applying ECG screening to the general popula-

tion by limiting our study population. We focused on the

detection and treatment of two of the most common causes of

SCD that can be identified by ECG: HCM and LQTS [28].

We excluded conditions such as anomalous coronary arter-

ies, because they typically are not identifiable in asymp-

tomatic children in this age group either by H&P or ECG and

therefore do not impact incremental cost-effectiveness.

Wolff–Parkinson–White (WPW) syndrome was also exclu-

ded because it was assumed that the lower incidence of SCD

in this population and the high effectiveness of catheter

ablation would result in either a negligible or beneficial

effect on overall cost-effectiveness of an ECG screening

program and would be of limited utility in determining the

drivers of cost-effectiveness.

The two screening arms in our economic model were: (1)

H&P, screening with history and physical examination alone,

and (2) ECG/H&P, screening with ECG in addition to history

and physical examination. All children were assumed to enter

the model at 12 years of age (range 8–25 years). All children

entering the model were characterized as having HCM, hav-

ing LQTS, or having no underlying condition, based on esti-

mates of prevalence in the general United States population

(i.e., 1:500 for HCM [range 1:1,000–1:250]; 1:2,500 for

LQTS [range 1:5,000–1:1,250]). Wide ranges were used to

account for controversy in the literature regarding a variety of

factors for both diseases that influence estimates of prevalence

(e.g. definitions of athlete’s heart versus HCM and selection of

QTc cut-offs used in defining LQTS). Children were further

subdivided into true and false positives or true and

false negatives based on estimates of screening sensitivity and

specificity derived from the United States literature; wide

ranges were used to account for the variable sensitivity and

specificity of current ECG standards, recommended ‘‘mod-

ern’’ standards, and other future standards. True negatives

(i.e., healthy children) transitioned to death according to the

2007 United States Life Table [2]. False negatives initially

received no treatment, and diseases progressed according to

estimates of their natural histories (Fig. 1). Follow-up diag-

nostics, disease progressions, and treatments in true and

false positives were modeled separately and in detail for both

HCM and LQTS to represent the natural history of affected or

healthy children. Costs of follow-up evaluation and testing

were included in the model.

The model was run for 70 one-year cycles until each

theoretical subject either died or reached the age of

82 years. During each cycle, affected individuals transi-

tioned between health states based on estimates of proba-

bilities derived from the literature as shown in Figs. 2 and

3. The primary benefit was LYS. Screening, follow-up

diagnostic, and direct treatment costs were assigned to each

state and used to calculate total costs for each strategy. An

incremental cost-effectiveness ratio (ICER) was calculated

by dividing the difference in cumulative costs in the ECG/

H&P and H&P arms by the difference in LYS.

324 Pediatr Cardiol (2014) 35:323–331

123

Disease Progression and Treatment for HCM

True and false positives for HCM in both screening arms

were referred to cardiologists for ECGs, if not previously

obtained, and/or echocardiograms (ECHOs). After

accumulating costs of follow-up, false positives transi-

tioned to the true negative state. Initial health states for

individuals with HCM were ‘‘undiagnosed’’ (false nega-

tive), ‘‘diagnosed lower risk,’’ or ‘‘diagnosed higher risk.’’

Given that the exact criteria for risk stratification for

patients with HCM remain controversial, especially in

children, wide ranges were used around the probabilities of

being lower or higher risk. In defining point estimates,

preference was given to the probabilities cited in the 2003

ACC/ESC Expert Consensus Document on HCM and in

the ACCF/AHA Guideline for the Diagnosis and Treatment

of Hypertrophic Cardiomyopathy, which generally defined

lower risk patients as those individuals with no or mild

symptoms. The annual incidence of diagnosis and rates of

transitions between health states were also derived from the

literature [1, 9, 11, 22, 26].

All individuals with HCM were assumed to be risk-

stratified. Although the guidelines are not universally

adhered to in clinical practice, for the purposes of our

model, we assumed that management of all patients with

HCM followed the published guidelines, using established

criteria [1, 9, 11, 26]. All higher risk patients (defined

based on estimates of prevalence cited in these same

Fig. 1 Abbreviated decision tree, showing sample of model branching

Fig. 2 Bubble diagram for HCM. Circles represent disease-specific

health states. Straight arrows represent possible transitions. Curved

arrows represent possible continuation in the same health state. HCM

hypertrophic cardiomyophathy

Pediatr Cardiol (2014) 35:323–331 325

123

guidelines) were assumed to receive implantable cardio-

verter defibrillators (ICDs). Transition to the death state for

HCM could occur through all-cause mortality or HCM-

specific mortality. Early HCM studies estimated annual

mortality of 3–6 %/year, before the widespread use of

high-dose beta-blockers, calcium-channel blockers, or

ICDs, and often in centers with higher risk profiles [9, 11].

In community-based studies, more recent estimates of

mortality are 1 %/year for adults [26, 35, 36], 2 %/year for

children [23, 31], and B1 %/year for higher risk children

and adults after ICD placement without heart failure or

atrial fibrillation [24, 26]. In this model, we assumed that

community-based studies reflected outcomes for lower risk

patients. We assumed that the lowest mortality would occur

after age 55 years (0.5 %/year [range 0.25–1 %]) [16, 25,

35] and highest mortality between ages 16 and 55 years

(2 %/year [range 1–4 %]) [26, 35, 36]. Mortality before

puberty was assumed to be 1 %/year (range 0.5–2 %) [23,

31]. Because our model began at 12 years of age, we did

not include the observed higher mortality in children

\1 year of age [31]. Mortality in diagnosed higher risk

individuals depended on treatment strategies and comor-

bidities. Compared with those diagnosed as lower risk of

the same age, undiagnosed individuals with HCM were

assumed to have, on average, a relative risk of dying of

0.67 (range 0.33–1). The Supplemental Table reports all

transition probabilities and sources.

Disease Progression and Treatment for Long QT

Syndrome

True and false positives for LQTS in both screening arms

were referred to cardiologists for risk stratification, Holter

monitors, exercise stress tests, and ECGs if not previously

obtained. Because prolonged QTc on ECG is a major cri-

terion for LQTS diagnosis, it was assumed that false pos-

itives for LQTS, as diagnosed by ECG, would remain

presumptively diagnosed in the lower risk arm for life, thus

accumulating costs without receiving benefits. Similar to

HCM, the initial states for individuals with LQTS were

‘‘undiagnosed,’’ ‘‘diagnosed lower risk,’’ or ‘‘diagnosed

higher risk’’ [32]. As with HCM, the incidence of diagnosis

and rates of transitions between health states were derived

from literature estimates, with wide ranges to account for,

among other factors, differential cut-off values for QTc

used in the definition of LQTS in the literature. Follow-up

testing and treatments were assumed to correspond with

current United States standards [1, 12, 13, 17, 32].

Because most patients with LQTS in the United

States are given beta-blockers and/or mexiletine, for the

base case model, it was assumed that all identified true or

false positives for LQTS would incur costs of one of these

medications. Higher risk individuals could receive an ICD

or undergo left cervical sympathetic denervation, with or

without continued beta-blocker treatment. Given that

guidelines are less prescriptive for higher risk patients with

LQTS than for those with HCM, it was assumed that not all

patients would receive the same treatments; relative pro-

portions receiving each therapy were based on published

estimates in the literature.

Mortality estimates for LQTS in this model were

extrapolated from published reports; mortality was set at

0.1 %/year for lower risk individuals (0.05–0.2 %), at 1 %/

year for treated higher risk individuals (0.12–2.0 %), and

at 1.3 %/year (0.7–5.0 %) for undiagnosed/untreated indi-

viduals [12, 13, 17]. Figure 3 models health-state transi-

tions for individuals with LQTS. The Supplemental Table

reports all transition probabilities and sources.

Clinical Assumptions

As detailed previously, disease-transition probabilities

were collected from the literature or based on expert

opinion if no published estimates existed. The validity of

all inputs was tested in extensive univariable and proba-

bilistic sensitivity analyses over broad ranges, to account

for differences in published data, clinical practice vari-

ability, or differences that might arise when applying

screening to diverse United States populations with dif-

fering ethnic, racial, sex, or age compositions. In deter-

mining point estimates for all LQTS-related parameters,

Fig. 3 Bubble diagram for LQTS. Circles represent disease-specific

health states. Straight arrows represent possible transitions. Curved

arrows represent possible continuation in the same health state. ICD

implantable cardioverter defibrillator, LCSD left cervical sympathetic

denervation, LQTS long QT syndrome

326 Pediatr Cardiol (2014) 35:323–331

123

studies were used that generally defined LQTS as C460 ms

(Supplemental Table) [1, 12, 13, 17, 32].

Because individuals with undiagnosed HCM and LQTS

are unobserved, there are few to no data on disease pro-

gression before diagnosis. Some cost analyses have

focused only on athletes and/or used historic data from

Italy to calculate expected decreases in mortality with

screening and treatment [40]. Our model uses the follow-

ing, more conservative, assumptions:

1. Given that our model was applied to the general

United States population with screening at 12 years of

age, not just to competitive athletes, estimates of risk

reduction are lower than those reported in the Italian or

sports-related literatures.

2. Individuals with symptoms are more likely to be

diagnosed. Undiagnosed individuals are more likely

than diagnosed individuals to be lower risk.

3. For LQTS, ECGs identify more asymptomatic (and

lower risk) patients than H&P alone. Therefore, a

greater proportion of the patients identified as having

LQTS by ECG/H&P compared with H&P alone are

lower risk at diagnosis.

4. In patients with HCM, symptoms are relatively rare at

12 years of age. Therefore, we assume that the

overwhelming majority of HCM patients identified

by either screening method are lower risk (95 % [range

80–100 %]).

5. Lower risk individuals, for each disease, regardless of

diagnosis method, could progress to higher risk at the

same rate. Lower risk individuals, for each disease,

regardless of diagnosis method, respond similarly to

treatment.

6. Higher risk individuals, for each disease, regardless of

diagnosis method, also respond to treatment similarly.

Costs

The 2009 and 2010 Medicare Fee Schedules were used

to determine inpatient, outpatient technical, outpatient

procedural, physician, durable medical equipment, lab-

oratory, and diagnostic costs [3]; however, costs for

genetic testing, which have decreased due to rapid

recent changes in charges and availability, were esti-

mated from the recent reimbursement experience at The

Children’s Hospital of New York and The Children’s

Hospital of Philadelphia. Drug costs were estimated

using 2010 Costco prices [7]. The cost of initial H&P

was assumed to be equivalent in the two arms and

therefore was not included in the analysis. All costs and

LYS were discounted at 3 % (range 1–5 %). See Sup-

plemental Table.

Analysis

Analyses were performed from a societal perspective. The

incremental cost-effectiveness thresholds for ECG screening

were based on commonly accepted thresholds for willing-

ness to pay in the United States and set at B $50,000/LYS to

be highly cost-effective and B $100,000/LYS to be cost-

effective.

Uncertainty

To model the potential impact of uncertainty, we per-

formed both univariable and probabilistic (multivariable)

sensitivity analyses on all input variables. These analyses

allowed us to determine which inputs most influenced the

ICER and to test robustness of the model. We assumed a

beta distribution for all disease progression-, diagnostic-,

and treatment-related probabilities, with ranges based on

95 % confidence intervals from their estimates in the lit-

erature. Model inputs based on expert opinion were tested

over large but feasible ranges. Assumptions around age

were assumed to follow normal distributions. Uncertainty

around costs was modeled by setting tested ranges from 50

to 200 % of the base case estimates. Costs were assumed to

be gamma-distributed, with means set equal to the SD,

because of the long tails typically associated with health

care costs.

For univariable sensitivity analyses, the model was run

using low and high estimates for each variable, while

holding all other inputs at their base values. This allowed

us to estimate a range of ICERs for each variable and to

determine how much these ICERs deviated from the base

ICER estimate. Probabilistic sensitivity analyses were

performed using Monte Carlo simulation, whereby esti-

mated values for each variable were drawn from their

distributions and used to calculate ICER estimates. This

process was repeated 10,000 times to allow for model

uncertainty and to estimate confidence intervals.

All models around uncertainty were performed using

TreeAge Software (TreeAge, Williamstown, MA, USA)

with statistical analyses performed in STATA 11MP

(StataCorp LP, College Station, TX, USA) or EXCEL

(Microsoft, Richmond, WA, USA).

Results

The estimated ICER of ECG/H&P screening compared

with H&P alone for our base case model is $41,400/LYS at

an incremental cost of $140/child screened with an incre-

mental increase of 3.4 LYS/1,000 children screened

(Table 1). Compared with H&P alone, ECG/H&P averted

Pediatr Cardiol (2014) 35:323–331 327

123

360 deaths before age 21 and 760 deaths before age 40, at

an average lifetime cost of $0.8 M/death averted [39].

Cost-effectiveness analyses can be misleading if only the

base-case ICER is considered. The power of such analyses

lies in understanding sources of uncertainty. One-way sen-

sitivity analyses indicate that our model is largely insensitive

to variance in most input variables for both conditions,

including ECG false positive and negative rates, as well as

the costs of ECGs, echocardiograms, and other follow-up

testing. It is also insensitive to all LQTS disease and treat-

ment variables in this model, such as the prevalence of

LQTS (including the effects of variable QTc cut-offs used in

diagnosing LQTS), false positive and false negative rates

associated with screening, and rates of disease progression.

Conversely, it is highly sensitive to assumptions around the

effects of identifying and treating previously undiagnosed

youths with HCM (lower and higher risk) compared with

those diagnosed with lower risk HCM. Holding all other

variables constant and using the assumption that identifying

and treating previously undiagnosed HCM patients is simi-

lar to that in the currently diagnosed HCM population, the

estimated ICER for ECG/H&P screening versus H&P alone

is highly favorable at $16,500/LYS. However, using the

assumption that identification and treatment in this popula-

tion provides little benefit, the ICER becomes highly unfa-

vorable at $182,100/LYS. This one input accounts for

77.5 % of ICER variability. When all other inputs

parameters are allowed to vary across 95 % CIs, no other

variables caused ICER estimates to rise above the $100,000/

LYS threshold, such as the many variables commonly

assumed to be barriers to cost-effectiveness, including false

positive and negative rates for ECGs, the discount rate,

and the prevalence of HCM and LTQS in the general pop-

ulation. These variables each have B5.1 % effect on vari-

ability of the ICER (Fig. 4).

Probabilistic sensitivity analyses also demonstrate that

the incremental cost-effectiveness of ECG/H&P screening

compared with H&P alone is uncertain regarding just one

variable: the effect of identifying and treating previously

undiagnosed youths with HCM. As the result of the effect

of this one input on ICER variance, ECG/H&P remains

incrementally cost-effective 78 % of the time (Figs. 5, 6).

Discussion

We compared the United States cost-effectiveness of H&P/

ECG versus ECG alone by way of a theoretical economic

model of diagnosis, treatment, and disease progression for

HCM and LQTS, two of the most common causes of SCD

identifiable on ECG. We found an ICER of $41,400/LYS,

at an incremental cost of $140/child screened, with an

incremental increase of 3.4 LYS/1,000 children screened.

Although previous studies have offered similar point

Table 1 Estimated incremental cost-effectiveness of ECG/H&P screening compared with H&P alone

Screening Cost/child Incremental

costs/child

Effectiveness

(LYS/child)

Incremental effectiveness

(LYS/child)

ICER ($/LYS)

H&P $45.92 28.491

ECG/H&P $185.62 $139.70 28.494 0.0034 $41,400

ICER incremental cost-effectiveness ratio, LYS life-year saved

Fig. 4 Tornado graph, showing

results of univariable sensitivity

analyses for the 10 parameters

with the largest effects on cost

per LYS, comparing ECG/H&P

with H&P. Cumulative and

incremental percents of the total

variability in the incremental

cost-effectiveness ratio, as

explained by each parameter,

are denoted in the column on

the right. HCM hypertrophic

cardiomyopathy, H&P

screening arm with only history

and physical examination, ICER

incremental cost effectiveness

ratio, LYS life-year saved

328 Pediatr Cardiol (2014) 35:323–331

123

estimates for the incremental cost-effectiveness ratio, our

study focused on the variables that drive cost-effectiveness

or could act as barriers.

We performed extensive sensitivity analyses and deter-

mined that many factors previously assumed to be barriers to

cost-effectiveness do not appear to be actual obstacles. Many

have speculated that ECG screening in the United States

might or might not be cost-effective because of low preva-

lence of disease, high false positive rates associated with

screening (as the result of antiquated normal values), or costs

of ECGs, follow-up testing, or treatments. Sensitivity anal-

yses of the ICER to these inputs showed that only changes in

the prevalence of HCM, discount rate, and ECG false posi-

tive rate for HCM had just a mild (3.4, 4.4, and 5.1 %,

respectively) effect on the ICER. None moved the ICER

across the putative $100,000 threshold for cost-effective-

ness. The only variable that significantly impacted the cost-

effectiveness of ECG screening was related to the assumed

progression of disease in the undiagnosed HCM population.

An ICER point estimate is dependent on a number of

clinical assumptions, and these assumptions can make base

case estimates vary widely [8, 10, 15, 20, 33, 34, 38, 40,

41]. It is important, therefore, to focus on the results of the

sensitivity analyses rather than on point estimates alone.

Our model shows that a better understanding of disease

characteristics in the undiagnosed HCM population must

be determined to allow accurate assessment of the impact

of ECG screening in the United States.

Model Limitations

This model does not incorporate the psychosocial impact of

false positive screens or the false sense of security derived

from one-time negative screens by using quality-adjusted

life-years, because no verified data exist [14]. Although

improving ECG standards would lessen the effect, a sig-

nificant burden would fall on health care professionals to

counsel children and families, and the extent of that burden

is not captured here. Nevertheless, sensitivity analyses

suggest that even a modest effect on quality of life would

have a minimal effect on incremental cost-effectiveness.

Second, whereas maintenance costs are included in the

model, startup costs associated with the initiation of a

national screening program are not included. In theory,

one-time startup costs for a program that runs in perpetuity

represent only a fraction of the lifetime costs of such a

program. In the short-run, these costs, or other logistical

hurdles, might pose significant but not necessarily insur-

mountable barriers.

The greatest limitation of the model in this study, as is

true with any Markov simulation, is its basis on a theo-

retical cohort of patients and a number of assumptions. To

address this, we validated the sensitivity of our model to all

assumptions over wide ranges. This allowed us to account

for differences in published estimates of probabilities,

clinical practice variability, and differences that might arise

when applying screening to varied United States popula-

tions with variable ethnic, racial, sex, or age compositions.

We made assumptions to account for the predictable dif-

ferences between diagnosed and undiagnosed populations.

It is unknown whether disease progression in undiagnosed

individuals mirrors that in those currently diagnosed. It is

possible that ECG screening might identify a greater pro-

portion of exceptionally lower risk individuals, who might

never have presented but who would now be followed-up

for life, thus accumulating costs without accruing benefits.

In contrast, early implementation of low-cost (e.g. lifestyle

modification or beta-blockers and surveillance) or more

Fig. 5 Probabilistic sensitivity graph, showing the impact of uncer-

tainty in parameter inputs on the incremental costs and effectiveness

of ECG/H&P versus H&P screening as the result of 10,000 simulation

trials. Diagonal lines represent willingness to pay thresholds, and dots

to the right of these lines represent trials with lower ICERs

Fig. 6 Acceptability curve, showing the likelihood that ECG/H&P is

cost-effective, relative to H&P alone, for different willingness-to-pay

thresholds. P is the probability the ICER falls below the given

willingness-to-pay thresholds

Pediatr Cardiol (2014) 35:323–331 329

123

costly but highly effective (e.g. placement of ICDs) inter-

ventions in identified higher risk individuals might dra-

matically impact disease progression, thus improving

benefits and decreasing total costs.

In addition, this analysis only models two common

causes of SCD in youth. For other diseases, such as WPW

syndrome, it was assumed that the lower incidence of SCD

in this population and the high effectiveness of catheter

ablation would result in negligible or beneficial effect on

the ICER because the model would be dominated by the

effects of HCM and, to a lesser extent, LQTS. This is not to

say that the addition of WPW screening would not be cost-

effective. Rather, it is to say that the addition of WPW

screening would not significantly drive overall estimates of

the ICER.

Finally, our model does not capture the potential bene-

fits associated with the identification of family members

due to the genetic transmission of these conditions; this

approach was selected for modeling simplicity, but it

potentially underestimates LYS. Once a proband is iden-

tified, certainly it becomes more cost-effective to screen

family members because there is a higher probability of

identifying true positives. Therefore, screening family

members could decrease the ICER associated with a

screening program, thus making screening more cost-

effective; however, family screening is unlikely to alter the

drivers of cost-effectiveness.

Conclusion

In summary, ECG screening remains highly controversial

in the United States with limited data regarding potential

barriers to cost-effectiveness. We have shown that the

addition of ECG screening to history and physical exami-

nation could be cost-effective for the prevention of SCD in

youths in the United States and that many of the concerns

previously raised are not in fact valid barriers to cost-

effectiveness. We have shown that significant uncertainty

remains in the cost per potential LYS and that the key to

this uncertainty lies in developing a better understanding of

the disease profile and the impact of identification and

treatment in the currently undiagnosed HCM population.

Until this understanding is developed, one cannot defini-

tively conclude whether or not ECG screening in the

United States is cost-effective.

Therefore, we recommend that those considering ECG

screening make the objectives and scope of screening clear

to the participants and provide appropriate follow-up for

any presumed abnormal findings. Furthermore, it would be

beneficial for those conducting ECG screenings to pro-

spectively collect data on outcomes to allow for knowledge

improvement in this area so that future decisions on ECG

screening can be evidence-based. Similarly, those involved

in cardiac screening without ECGs also should collect

outcome data because a randomized clinical trial of H&P

plus ECG screening versus screening with H&P alone

appears to be prohibitive with regard to the numbers

required, time interval for follow-up, and overall costs, as

indicated by the National Institutes of Health Working

Group [19].

Conflict of interest None.

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