Pediatric Cardiology

https://doi.org/10.1007/s00246-021-02611-3

ORIGINAL ARTICLE

Epidemiology of Pediatric Heart Failure in the USA–a 15‑Year

Multi‑Institutional Study
Raysa Morales‑Demori1   · Elena Montañes2 · Gwen Erkonen1 · Michael Chance3 · Marc Anders1 · Susan Denfield4

Received: 26 January 2021 / Accepted: 7 April 2021

© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021

Abstract
The epidemiology of pediatric heart failure (HF) has been characterized for congenital heart disease (CHD) and cardiomyo‑
pathies (CM), but the impact of CM associated with CHD has not been studied. This study aims to describe the characteris‑
tics and outcomes of inpatient pediatric HF patients with CHD, CM, and CHD with CM (CHD + CM) across the USA. We
included all HF patients with CM diagnoses with and without CHD using ICD 9/10 codes ≤ 19 years old from January 2004
to September 2019 using the Pediatric Health Information System database. We identified 67,349 unique patients ≤ 19 years
old with HF, of which 87% had CHD, 7% had CHD + CM, and 6% had CM. Pediatric HF admissions increased significantly
from 2004 to 2018 with an associated increase in extracorporeal circulatory support (ECLS) use. Heart transplantation (HTX)
increased only in the CHD and CHD + CM groups. CHD patients required less ECLS with and without HTX; however, they
had significantly higher inpatient mortality after those procedures than the other groups (p < 0.001). CM patients were older
(median 115 months) and had the lowest inpatient mortality after HTX with and without ECLS (p < 0.05). CHD + CM showed
the highest overall inpatient mortality (15%), and cumulative hospital billed charges (median US$ 541,374), all p < 0.001.
Pediatric HF admissions have increased from 2004 to 2018. ECLS use and HTX have expanded in this population, with an
associated decrease in inpatient mortality in the CHD and CM groups. CHD + CM patients are a growing population with
the highest inpatient mortality.

Keywords  Epidemiology · Heart failure · Pediatrics · Cardiomyopathy · Congenital Heart Disease · Outcomes

Introduction etiologies such as primary or secondary cardiomyopathies,

Pediatric heart failure (HF) differs substantially from adult
HF. Most pediatric HF is due to structural congenital
heart defects with volume and/or pressure overload. Other
Marc Anders and Susan Denfield share senior authorship.
* Raysa Morales‑Demori
demori@bcm.edu
1
Department of Pediatrics, Division of Critical Care, Baylor
College of Medicine, Texas Children’s Hospital, 6651 Main
St. MC E1420, Houston, TX, USA
2
Department of Pediatrics, Division of Cardiology, Hospital
12 de Octubre, Madrid, Spain
3
Quality Outcomes & Analytics Specialist, Texas Children’s
Hospital, Houston, TX, USA
4
Department of Pediatrics, Division of Cardiology, Baylor
College of Medicine, Texas Children’s Hospital, Houston,
TX, USA
infections, or neurohumoral factors can lead to acquired
heart disease and secondary cardiac failure [1]. Initial
approaches for a unified pediatric HF definition were char‑
acterized by symptoms rather than underlying etiologies or
pathophysiological changes [2]. A more refined description
developed by The International Society for Heart and Lung
Transplantation defined pediatric HF as the “clinical and
pathophysiologic syndrome that results from ventricular sys‑
tolic or diastolic dysfunction, volume or pressure overload,
alone or in combination”[3].
The epidemiology of adult HF has been extensively
researched; however, the incidence, prevalence, and resource
utilization of pediatric HF are not as well characterized.
Worldwide, primary pediatric HF’s reported incidence var‑
ies widely between 0.87 and 7.4 per 100,000 children [4].
Rossano et al. [5] described an increase in pediatric HF in
the USA from 15.2 per 100,000 children in 2003 to 17.9 per
10,000 children in 2006. Nandi et al. [6] showed an increase
in pediatric HF hospitalizations from 2000 to 2009 from

13
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6478 to 9560 with a corresponding increase in median hos‑
pital billed charges from US$35,079 to US$72,087. Using
the Pediatric Health Information System database (PHIS),
Burstein et  al. [7] reported in 2019, that advanced HF
occurred in 0.6% of pediatric patients with congenital heart
disease (CHD). The mortality reached 26%, with median
hospital costs of US$252,000, primarily due to the hospital
length of stay [7].
Pediatric studies that report comprehensive age-depend‑
ent epidemiology and resource utilization of HF in the USA
are few in number [4, 5, 7–9]. No studies have assessed the
impact of the combined diagnoses of CHD and CM. This
study aims to describe the prevalence of pediatric HF in
patients with cardiomyopathies, or a combination of CHD
with CM, from January 2004 to September of 2019 using the
PHIS database. We report patients’ characteristics, resource
utilization (intensive care admission, extracorporeal mem‑
brane oxygenation, ventricular assist device, heart transplan‑
tation), their association with inpatient mortality, hospital
length of stay, and hospital billed charges. This represents
the largest comprehensive multi-institutional review of inpa‑
tient hospital outcomes for pediatric HF to date.
Material and Methods
Data Source
We performed a multicenter retrospective cohort study uti‑
lizing the PHIS database. PHIS is an administrative database
that contains deidentified inpatient, emergency department,
ambulatory surgery, and observation encounter-level data
from 50 non-for-profit, tertiary care pediatric hospitals in
the USA, which are affiliated with the Children’s Hospi‑
tal Association (Lenexa, KS). Data quality and reliability
are assured through a joint effort between the Children’s
Hospital Association and participating hospitals. Portions
of the data submission and data quality processes for the
PHIS database are managed by Truven Health Analytics
(Ann Arbor, MI). For the purposes of external benchmark‑
ing, participating hospitals provide discharge/encounter data
including demographics, diagnoses, and procedures. Nearly
all these hospitals also submit resource utilization data
(including pharmaceuticals, imaging, and laboratory) to the
PHIS database. Data are subjected to a number of reliability
and validity checks before being included in the database
[10]. Details of PHIS have been previously described, and it
has been used to study hospital mortality as well as resource
utilization particularly for less common or more specialized
diagnoses and procedures [10, 11]. This database utilizes
International Classification of Diseases, ninth edition (ICD9
code) and since 2014 tenth edition (ICD10 code) for diag‑
nosis and procedures. The Institutional Review Board of
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Pediatric Cardiology
Baylor College of Medicine deemed this study exempt from
review under 45 CFR 46.102(f).
Study Population
All hospitalizations for pediatric patients ≤ 19-year-old with
the diagnosis of HF (ICD9 codes: 398.91 402.xx, 404.xx,
428.xx, 429.4, 997.1 and ICD10 codes: I09.81, I11.0, I13.x,
I50.xxx, I97.xxx, P29.0) from January 2004 to September
2019 were included. The most frequent CHD and CM diag‑
noses observed in the three different groups (CHD, CM,
CHD + CM) are shown in Appendix Table 3. CHD and CM
distribution in the CHD + CM group throughout the study
years are described in Appendix Table 4. On 2014, there
was a coding transition from ICD 9 to ICD10 that reflects
the distribution difference, especially in the CM condition.
Age groups were divided into newborns (≤ 28 days), infants
(29–365 days), children (366 days–< 10 years) and adoles‑
cents (10–19 years). Other characteristics included sex, race/
ethnic group, history of prematurity (ICD9: 765.2 × and
ICD10: P07.2 × and P07.3x), and insurance. Insurance was
labeled as public aid if their primary payor was Medicare,
Medicaid, TRICARE, CHIP or Charity; or commercial
insurance if it was commercial PPO, HMO or self-pay.
Patients with CHD were identified by ICD9 (424.x, 745.
xx-747.xx) and ICD10 (I34.x-I37, I42.4, Q20.x-Q26.x). Car‑
diomyopathies (hypertrophic obstructive, dilated, nutritional
and metabolic, toxic, primary, secondary, or other) were
included utilizing ICD9 (425.xx) and ICD10 (I42.x). Demo‑
graphic information was described for patients with CHD,
CM or a combination of both (CHD + CM). The following
variables were accounted for as absolute numbers and per‑
centages per individual during the study period: frequency
of hospital admissions, intensive care unit (ICU) admissions,
surgical procedures, surgical or infectious complications,
and use of mechanical invasive ventilation. Extracorporeal
membrane oxygenation (ECMO) procedures (ICD9: 39.65,
ICD10 procedure codes: 5A15223, 5A1522F, 5A1522G,
5A1522H), ventricular assist device (VAD) implanta‑
tions (ICD9 code 37.5x, 37.6x; ICD10 procedure codes:
02HAxRZ, 02HAxRJ, 02HAxRS, 02RK0JZ, 5A02210,
5A02115, 5A02116, 5A02216, 5A02215, 5A02216,
5A0221D) and heart transplantation (ICD 9 code 33.6,
37.51; ICD 10 procedure code: 02YA0Zx) were reviewed.
ECMO, heart transplantation (HTX) and VAD procedure
frequency and outcomes were analyzed separately (HTX,
ECMO and VAD) and in combination (ECMO + VAD,
VAD + HTX, ECMO + HTX and ECMO + VAD + HTX).
For patients admitted multiple times to the same institution,
only demographic information (age, race/ethnicity) from
their first hospitalization was included. The following vari‑
ables are reported as cumulative: Hospital and ICU length of
Pediatric Cardiology
stay (LOS) in days and hospital billed charges in US Dollars
(US$).
Outcome variables for all groups (CHD, CM and
CHD + CM) were defined as rate of hospital inpatient mor‑
tality, need of multiple admissions, cumulative hospital
LOS, ICU LOS and hospital billed charges. Trends in admis‑
sions, inpatient mortality, VAD, ECMO, HTX and median
hospital billed charges were described from January of 2004
to December 2018. Patients admitted in 2019 were excluded
from trends analysis.
Statistical Analyses
Data were not normally distributed. Categorical and dichoto‑
mous variables were expressed as exact numbers with per‑
centages, whereas continuous variables were expressed as
median with 25–75th interquartile ranges (IQR). Chi-square
analysis was used to look for associations between categori‑
cal variables, Wilcoxon-Mann–Whitney and Spearman rank
tests were used to compare continuous variables. Statistical
significance on univariate testing was defined as p < 0.05
with inclusion cutoff for logistic regression analysis set as a
probability value of p ≤ 0.05. A multivariable logistic regres‑
sion model using backward elimination was developed for
all variables with p ≤ 0.10 in univariate analysis. For all sig‑
nificant outcomes, we report odds ratios (OR) as unit odds
ratios with 95% confidence intervals. Statistical analyses
were carried out using SPSS Statistics version 25 (IBM,
Inc., Armonk, NY).
Results
Over the study period 91,480 hospital encounters of 67,349
unique patients were identified. The majority of admissions
(77,807) were in pediatric HF patients with CHD (85%), rep‑
resenting 58,386 (87%) unique patients; while the CM group
comprised 7960 (9%) encounters with 4,080 (6%) unique
patients and 5713 (6%) hospital admissions in CHD + CM,
with 4883 (7%) unique patients identified, respectively.
Characteristics of Pediatric HF Patients
with Congenital Heart Disease
Fifty three percent of the patients were male, with median
age of 3 months [IQR 0–11]. Thirty two percent (18,711)
of patients were newborns and 43% (25,293) were infants
on their first admission. Thirty eight percent (22,056) were
White race and 21% (11,983) were Hispanics. The most
frequent diagnoses were atrial septal defects (31,088), ven‑
tricular septal defects (23,367), and patent ductus arteriosus
(21,583) (Appendix Table 3). Forty six percent (26,673) had
public aid insurance. Ninety one percent (53,353) required
ICU admission, 79% (46,220) required invasive ventilation,
44% (25,631) had an infection, 79% (46,198) underwent a
surgical procedure out of which 71% (33,091) had a surgi‑
cal complication. Twenty one percent (12,031) of patients
had multiple admissions. Cumulative hospital LOS was
15 days [6–39], cumulative ICU LOS of 5 days [2–15], and
cumulative hospital billed charges were US$ 241,878 [IQR
115,517–614,382] (Table 1).
Inpatient mortality was 10% (5611). By univariate and
multivariate analysis, factors associated with increased
inpatient mortality were newborn age on first admis‑
sion [OR 3.2 (3.0–3.4)], public aid insurance [OR 1.1
(1.1–1.2)], history of prematurity [OR 2.8 (2.6–3.0)],
ICU admission [OR 2.3 (2.0–2.7)], surgical complication
[OR 1.3 (1.2–1.4)], infection [OR 2.8 (2.7–3.0)], ECMO
procedure [OR 14.3 (13.3–15.3), VAD procedure [OR
9.0 (5.9–13.9)],  ECMO + VAD [OR 12.7 (9.5–16.8)],
ECMO + HTX [OR 5.0 (4.0–6.2)], ECMO + VAD + HTX
[OR 4.0 (2.5–6.4)], all p < 0.05. Factors associated with
decreased inpatient mortality were White race [OR 0.83
(0.79–0.88)], commercial insurance [OR 0.80 (0.75–0.85)],
history of multiple hospital admissions [OR 0.82
(0.76–0.88)], surgical procedure [OR 0.69 (0.65–0.73)], and
HTX [OR 0.52 (0.40–0.69)], all p < 0.001.
From 2004 through 2018, pediatric HF admissions in
patients with CHD have doubled from 4222 (2004) to 8076
(2018) representing 87% of all pediatric HF admissions.
During the study period, mortality decreased from 5.8%
(2004) to 4.8% (2018), associated with an increase in VAD
procedures from 0.2% (2004) to 0.6% (2018), an increase
in ECMO procedures from 3.3% (2004) to 4.6% (2018)
and an increase in HTX procedures from 1.2% (2004) to
2.0% (2018). Median hospital billed charges per encounter
increased from US$ 86,742 (2004) to US$ 244,526 (2018).
All trends were statistically significant p < 0.001 (Fig. 1).
Characteristics of Pediatric HF Patients
with Cardiomyopathies
Fifty five percent of patients were male, with median age
on their first admission of 115 months [IQR 17–185]. Most
were adolescents (49%; 2003) or children (30%; 1227) on
their first admission. Thirty four percent (1373) were White
race, and 19% (783) Hispanics. Public aid (44%; 1804) was
the principal payor. The most frequent diseases were other
primary cardiomyopathies (2332), dilated cardiomyopa‑
thy (734), unspecified cardiomyopathy (280), secondary
cardiomyopathy, unspecified (265) (Appendix Table  3).
Twenty-eight percent (1157) of the patients had multiple
hospitalizations; 86% (3515) required ICU admissions, 59%
(2389) required invasive ventilation, and 60% (2431) had
an infection. Forty seven percent (1927) underwent a sur‑
gical procedure, out of which 58% (1120) had a surgical
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 Pediatric Cardiology

Table 1  Description of patients with CHD, CM, and CHD + CM

CHD N = 58,386 CM N = 4080 CHD + CM N = 4883

Male, N (%)* 31,106 (53%) 2235 (55%) 2490 (51%)

Age in months of first admission, median [IQR 25–75]* 3 [0–11] 115 [17–182] 16 [2–133]
Age distribution
 Newborn, N (%)* 18,711 (32%) 179 (4%) 750 (15%)
 Infants, N (%)* 25,293 (43%) 670 (16%) 1469 (30%)
 Children, N (%)* 9726 (17%) 1227 (30%) 1284 (26%)
 Teenager, N (%)* 4646 (8%) 2003 (49%) 1377 (28%)
Race/ethnicity
 White, N (%)* 22,056 (38%) 1373 (34%) 1802 (37%)
 Hispanics, N (%) 11,983 (21%) 783 (19%) 968 (20%)
 African American, N (%)* 6096 (10%) 585 (14%) 745 (15%)
Insurance
 Public aid, N (%)* 26,673 (46%) 1804 (44%) 2607 (53%)
 Commercial, N (%)* 20,107 (34%) 1455 (36%) 1750 (36%)
 Prematurity, N (%)* 5445 (9%) 63 (2%) 255 (5%)
 Inpatient mortality, N (%)* 5611 (10%) 556 (14%) 733 (15%)
 Number of patients who had multiple admissions, N (%)* 12,031 (21%) 1157 (28%) 2167 (44%)
 Cumulative hospital LOS, median [IQR 25–75]* 15 [6–39] 21 [8–48] 35 [15–78]
 ICU admissions, N (%)* 53,353 (91%) 3515 (86%) 4582 (94%)
 Cumulative ICU LOS in days, median [IQR 25–75]* 5 [2–15] 9[2–22] 15 [5–38]
 Invasive ventilation, N (%)* 46,220 (79%) 2389 (59%) 3654 (74%)
 Surgical procedure, N (%)* 46,198 (79%) 1927 (47%) 3106 (64%)
 Surgical complication, N (%)* 33,091 (71%) 1120 (58%) 2773 (89%)
 Infection, N (%)* 25,631 (44%) 2431 (60%) 3257 (67%)
 Cumulative billed charges in US$, median [IQR 25–75]* 241,878 [115,517–614,382] 285,053 541,374 [199,411–1,402,980]
[97,836–
790,295]

*p < 0.05 between groups

Fig. 1  Pediatric HF with Pediatric HF with CHD trend from 2004-2018

CHD trend in mortality, VAD,
ECMO, and heart transplanta‑ 20%
tion procedures from 2004 to
2018 18%
16%
14%
12%
10%
8%
6%
4%
2%
0%
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
% mortality % VAD % heart transplant % ECMO

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Pediatric Cardiology
complication. Cumulative median hospital length of stay
was 21 days [IQR 8–48], cumulative median ICU LOS was
9 days [IQR 2–22] and cumulative median billed hospital
charges were US$285,053 [IQR 97,836–790,295] (Table 1).
Inpatient mortality was 14% (556). By univariate and
multivariate analysis, variables associated with increased
inpatient mortality included history of prematurity [OR 2.8
(1.6–4.8)], invasive ventilation [OR 5.2 (4.0–6.6)], infection
[OR 2.1 (1.7–2.5)], ECMO procedures [OR 5.3 (4.1–7.0)]
and ECMO + VAD [OR 2.9 (1.9–4.5)], all p ≤ 0.005. Fac‑
tors associated with decreased inpatient mortality were
HTX [OR 0.06 (0.03–0.15)] and VAD + HTX [OR 0.46
(0.28–0.74)], both p < 0.05.
From 2004 to 2018, the number of cardiomyopathy
admissions increased from 316 (2004) to 710 (2018), rep‑
resenting an increase in admissions from 7% (2004) to
8% (2018) of all HF patient hospitalizations. VAD proce‑
dures increased from 3% (2004) to 7% (2018); ECMO use
increased from 4%(2004) to 5% (2018),HTX decreased from
14% (2004) to 13% (2018) and inpatient mortality decreased
from 11% (2004) to 6% (2018) (Fig.  2).Median billed
charges per encounter increased from US$ 72,329 (2004)
to US$ 176,369 in 2018. All these trends were statistically
significant (p < 0.05), except for ECMO p = 0.31 (Fig. 2).
Characteristics of Pediatric HF Patients
with Congenital Heart Disease
and Cardiomyopathies
Of those with the combined diagnosis of CHD + CM, 51%
were male, with median age of 16 months old [IQR 2–133].
Most were infants (30%; 1469), and adolescents (28%;
1377). Thirty seven percent (1802) were White race, and
Fig. 2  Pediatric HF with Cardi‑ Pediatric HF with CM trend from 2004-2018
omyopathy trend in admissions,
mortality, VAD, ECMO, and 20%
heart transplantation procedures
18%
from 2004 to 2018
16%
14%
12%
10%
8%
6%
4%
2%
0%
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
% mortality
% VAD procedures
% ECMO
20% (968) Hispanics. Public aid was the principal payor
(53%, 2607). The most frequent CHD in this group were
mitral valve disorders (2573), atrial septal defect (1676)
ventricular septal defect (626) and patent ductus arteriosus
(587). The most frequent CM in this group were other hyper‑
trophic cardiomyopathy (2783), cardiomyopathy, unspeci‑
fied (1086), cardiomyopathy in other diseases classified
elsewhere (417) and other cardiomyopathies (250) (Appen‑
dix Table 3). Forty four percent (2167) required multiple
hospital admissions. Ninety four percent (4582) required
ICU admission, 74% (3654) needed mechanical ventilation,
67% (3257) had an infection, 64% (3106) underwent a sur‑
gical procedure, out of which 89% (2773) had a surgical
complication. Median cumulative hospital and ICU LOS in
days was 35 [IQR 15–78] and 15 [IQR 5–38] respectively.
Median cumulative billed charges were US$ 541,374 [IQR
199,411–1,402,980].
Inpatient mortality was 15% (733). By univariate and mul‑
tivariable analysis, variables associated with increased inpa‑
tient mortality were newborn age [OR 1.8 (1.5–2.2)], history
of prematurity [OR 1.9 (1.4–2.5)], use of invasive ventilation
[OR 4.5 (3.4–5.9)], infection [OR 2.1 (1.8–2.6)], VAD [OR
4.3 (2.9–6.4)], ECMO [OR 3.9 (3.1–4.9)], ECMO + VAD
[OR 3.7 (2.7–5.0)], ECMO + HTX [OR 1.4 (1.0–2.0), all
p < 0.05. Variables associated with decreased inpatient mor‑
tality were VAD + HTX [OR 0.57 (0.40–0.81)] and HTX
[OR 0.22 (0.15–0.32)], both p < 0.05.
From 2004 to 2018, there has been an increase in
admissions from 4.0% to 6.2% (p < 0.001). Appendix
Table 4 shows the distribution of CHD and CM through‑
out the study years, with mitral valve disorders and atrial
septal defects being the most frequent CHD during the
study period. Regarding cardiomyopathies, other primary
% CM admissions of all HF
% heart transplantation
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 Pediatric Cardiology

cardiomyopathies were the most frequent from 2004 to 2015,
and dilated cardiomyopathy in 2016–2019. Over this time
frame, in inpatient mortality was 6.7% in 2004, peaked in
2006 at 15.1%, and since then, has downtrended to 9.0% by
2018 (p = 0.095). VAD procedures have increased from 3.4%
(2004) to 11.2% (2018), p < 0.001. HTX was performed in
11.7% in 2004, increased to 17% in 2008, and has remained
unchanged since then (p = 0.738). ECMO use increased from
6.7% (2004) to 11.2% by 2018, p = 0.002 and median billed
hospital charges per admission increased from US$118,944
in 2004 to US$364,948 in 2018, p = 0.001.
Comparison of Pediatric HF Patients with CHD, CM
and CHD with CM (CHD + CM)
When comparing pediatric HF patients with CHD, CM,
and CHD + CM, patients with CHD comprised the major‑
ity of pediatric HF (87%). CHD patients were admitted at a
younger age (median 3 months), had lower inpatient mortal‑
ity (10%), required more use of invasive ventilation (79%),
and underwent more surgical procedures (79%). However,
these patients had the least cumulative hospital (median
15 days), ICU LOS (median 5 days), and cumulative hos‑
pital billed charges (median in US$ 241,878), all p < 0.001.
(Table 1) CHD patients were less likely to undergo HTX
and had less ECLS use, but had the highest inpatient mortal‑
ity after those procedures compared to CM and CHD + CM
groups, all p < 0.001. (Table 2).
Patients with CM were older on their first hospitali‑
zation (median 115 months), had fewer ICU admissions
(86%), multiple hospital admissions (59%), use of invasive
ventilation (59%), or surgical procedures (47%). (Table 1)
These patients had the lowest inpatient mortality after
HTX, VAD, ECMO + VAD, VAD + HTX, ECMO + HTX,
and ECMO + VAD + HTX procedures, compared to CHD
and CHD + CM groups, all p < 0.05. (Table2).
Patients with CHD + CM had the overall highest inpa‑
tient mortality (15%) and required more hospital (44%)
and ICU admissions (94%). They had a longer cumulative
hospital (median 35 days) and ICU LOS (median 15 days),
higher incidence of surgical complications (89%), more
infections (67%), and the highest cumulative billed charges
in US$ (median US$ 541,374). CHD + CM patients were
more likely to undergo HTX and use of extracorporeal
circulatory support with and without HTX, all p < 0.001.
(Table 2).
All groups had an increase in hospital billed charges
per admission from 2004 to 2018; however, CHD + CM
patients had the highest median billed charges per hospital
admission (US$118,944 in 2004 to US$364,948 in 2018),
p < 0.001. When comparing outcome trends per hospi‑
talization year from 2004 to 2018, inpatient mortality has
decreased in patients with CHD (5.8% in 2004 to 4.6% in
2018) and CM (from 10% in 2004 to 7% in 2018), but not
in patients with CHD + CM (6.8% in 2004 to 9% in 2018).
There has been an increase in extracorporeal circulatory
support in all three groups. VAD procedures significantly
increased in the CHD + CM group (1.9% in 2004 to 10.5%
in 2018). ECMO use increased, but primarily in patients
with CHD + CM (6.7% in 2004 and 11.2% in 2018). HTX
increased in patients with CHD (1.2% in 2004 to 2% in
2018), overall increased in CHD + CM (11.7%in 2004 to
17% in 2018) but has remained unchanged since 2008; and
downtrended in patients with CM (14% in 2004 to 13% in
2018). (Figs. 1, 2 and 3).

Table 2  Outcomes of heart CHD N = 58,386 CM N = 4080 CHD + CM N = 4883

transplantation, VAD and
ECMO procedures in patients HTX, N (%)* 978 (2%) 465 (11%) 743 (15%)
with CHD, CM and CHD + CM
HTX mortality N (%)* 52 (5%) 5 (1%) 32 (4%)
VAD, N (%)* 84 (0.1%) 65 (2%) 100 (2%)
VAD mortality, N (%)* 41 (49%) 18 (28%) 42 (42%)
ECMO, N (%)* 3674 (6%) 242 (6%) 347 (7%)
ECMO mortality, N (%)* 1877 (51%) 101 (42%) 130 (38%)
ECMO + VAD, N (%)* 195 (0.3%) 101 (3%) 175 (4%)
ECMO + VAD mortality, N (%)* 111 (57%) 31 (31%) 66 (38%)
VAD + HTX, N (%)* 146 (0.3%) 259 (6%) 371 (8%)
VAD + HTX mortality, N (%)* 30 (21%) 18 (7%) 35 (9%)
ECMO + HTX, N (%)* 359 (0.6%) 134 (3%) 248 (5%)
ECMO + HTX mortality, N (%)* 123 (34%) 26 (19%) 49 (20%)
ECMO + VAD + HTX, N (%)* 84 (0.1%) 68 (2%) 116 (2%)
ECMO + VAD + HTX mortality, N (%)* 25 (30%) 12 (18%) 24 (21%)

*p < 0.05 between groups

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Pediatric Cardiology
Fig. 3  Pediatric HF with Car‑ Pediatric HF with CHD+CM trend from 2004-2018
diomyopathy and Congenital
Heart Disease trend in admis‑ 20%
sions, mortality, VAD, ECMO 18%
and heart transplantation proce‑ 16%
dures from 2004 to 2018 14%
12%
10%
8%
6%
4%
2%
0%
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
% mortality
% VAD
% ECMO
Discussion
While adult HF epidemiology has been well researched and
characterized, there are fewer studies on pediatric HF inci‑
dence and prevalence [5–7, 9]. This is the largest study to
date that describes the epidemiology, patient characteris‑
tics, and pediatric HF admissions outcomes in the US. It
also documents an under-recognized group of pediatric HF
patients with the combined diagnoses of CHD + CM, the
group with the highest mortality and need for cardiac trans‑
plantation that is in growing need of further concentrated
investigation.
This is the first study reporting HF patients’ outcomes
with the combined diagnoses of CHD with CM. Of 91,480
heart failure admissions, 6% (5713) were specifically coded
as CHD + CM, not simply CHD with heart failure, suggest‑
ing a growing recognition of this combined phenotype, also
manifested by the increased number of admissions with
this condition throughout the years (Graph 3 and Appendix
Table 4). The CHD + CM group highlights pediatric HF’s
heterogeneous nature that arises from a wide spectrum of
underlying etiologies with very different prognoses, man‑
agement, and outcomes. CM in patients with CHD could be
primary or secondary [10, 11]. There has been an increased
awareness of CHD and its association with genetic condi‑
tions, causing an increase in genetic screening (pre/postna‑
tally), and finding abnormalities associated to cardiomyo‑
pathies and other comorbidities. [12, 13] There are known
associations between CHD and congenital CM; some may
be explained by genetic disorders, such as the association
between Ebstein anomaly and left ventricular noncompac‑
tion secondary to MHY7 gene mutation [14], RASopathies
and 1p36 deletion [12]. Abnormal molecular in utero path‑
ways that delineate cardiac and myocardial structure may
explain CHD and primary CM’s association [11]. Complex
% CHD+CM admissions of all HF
% heart transplant
CHD with single or biventricular ventricular physiology
are additionally at risk of developing CM due to abnormal
hemodynamics, arrhythmia, ischemia and/or valvular dis‑
ease [10, 11]. Chronic unrepaired significant valvular dis‑
ease causes ventricular volume overload and may progress to
irreversible cardiac remodeling [10]. The CHD + CM group
represented 7% of all unique pediatric HF patients and is
the group with the highest inpatient mortality (15%). These
patients had increased use of ECLS support and HTX with‑
out a significant change in inpatient mortality throughout
the study period, most likely secondary to their complexity.
CHD, in isolation, remains the most common cause of
HF in children, consistent with prior national [5–7, 15] and
international [16] reports. Seventy percent of our patients
were younger than one year on their first hospitalization,
emphasizing that most pediatric HF admissions happen dur‑
ing infancy [7, 8]. However, CHD becomes a less frequent
cause of HF in older children. Overall, inpatient mortality
in the CHD group was demonstrated to be lower compared
to CM patients with or without CHD. These findings may be
explained by the fact that pediatric HF in patients with CHD
usually improves or resolves once a corrective surgery or
interventional procedure is performed [7, 9]. Newborn age
on the first admission in patients with CHD with and without
CM and prematurity was associated with increased inpatient
mortality. Genetic syndromes, single ventricle physiology,
or other comorbidities not analyzed in this study may have
also contributed to increased inpatient mortality in those
patients [17]. Additionally, size limitation may have affected
VAD candidacy [8].
Our study did not quantify or differentiate outcomes by
the complexity of CHD lesions. Factors such as associated
extracardiac comorbidities, the lack of a definite treatment
and/or a deleterious natural history of some of the underlying
etiologies (such as neuromuscular disorders, mitochondrial
disease, malignancy) may contribute to the higher inpatient
13

mortality identified in patients with CM [8, 9], especially in
those with CHD. CM patients were more likely to undergo
ECLS procedures and HTX when compared to patients with
CHD. The anatomy and physiology in CM patients are gen‑
erally more amenable to ECLS support, with the endpoint
being heart transplant.
We identified a gradual increase in the use of mechanical
circulatory support (ECMO/VAD) and heart transplantation
procedures (Figs. 1, 2 and 3). Our study demonstrated the
increased use of extracorporeal circulatory support in the HF
population. Consistent with older studies [18, 19], the use of
ECMO in isolation, or in combination with VAD or HTX,
continues to be associated with higher inpatient mortality.
Additional end organ injuries that trigger the use of extra‑
corporeal support were not reviewed in our study but may
explain the increased mortality in this group. In contrast,
inpatient mortality was lower in patients who underwent
VAD and HTX, in comparison to VAD only, consistent with
prior reports [18, 19]. An increase in VAD use in the pedi‑
atric HF population in the current era has been previously
reported [20, 21]. It correlated with a decrease in inpatient
mortality due to earlier implantation consideration and opti‑
mization of postoperative management [21]. As opposed to
a previous report [19] inpatient mortality was lower in HTX
recipients who did not require VAD or ECMO. Nonetheless,
CHD still has the highest inpatient mortality for HTX with
or without extracorporeal circulatory support when compar‑
ing all three groups.
Our study demonstrated that the pediatric HF population
is continuing to increase [5, 9, 22], and these patients face
significant morbidity, often requiring multiple hospitaliza‑
tions, ICU admissions, and complex therapies. In particular,
the use of mechanical support as a bridge to heart transplan‑
tation or destination therapy has gradually increased in our
pediatric HF population [5], leading to rising hospitaliza‑
tion costs for these patients [21]. Pediatric HF prevalence
is likely to continue to increase [22], especially as pediatric
patients with complex CHD survive to adulthood. As hos‑
pitals become more skilled with medical management and
mechanical circulatory support as a bridge to heart trans‑
plantation or destination therapy, these patients’ inpatient
mortality may continue to decrease. However, the cumu‑
lative hospital billed charges per patient will most likely
continue to increase [22, 23].
Limitations
This study is limited by its retrospective nature. The use of
an administrative database has its own limitations, as there
may be diagnoses not reported by institutions or other
confounding factors associated with patient mortality not
13
Pediatric Cardiology
represented by ICD 9 or 10 codes. There is a lack of ability
to determine comorbidities’ timing in relation to patients’
clinical status and indications for certain procedures.
Patients are de-identified, and each one was assigned a
unique number per institution. If patients sought medical
care in more than one PHIS institution, they might have
been double-counted within the same database or counted
as a different disease if separate ICD9/10 codes were used.
There was a transition from ICD9 to ICD 10 during the
study period, which may affect the distribution of patients’
diagnoses codes. Mortality may have been underestimated
if patients died in the outpatient setting or in another insti‑
tution not included in the PHIS network. Certain congeni‑
tal heart diseases may require multiple ICD9/10 codes and
are not mutually exclusive, resulting in multiple ICD code
entries per patient. Additionally, there may be ICD9/10
coding variability within institutions that may cause that
a patient with a similar disease is coded differently for
CHD and/or CM.
Conclusion
Pediatric HF admissions have increased from 2004 to
2018 in patients with CHD, CM, and CHD + CM, as have
hospital billed charges. However, inpatient mortality has
decreased for those with CHD and CM, possibly due to
increasing management expertise, including increas‑
ing VAD support and utilization of HTX in CHD and
CHD + CM patients. Strategies to avoid ECMO should be
a priority, given its association with increased inpatient
mortality. Finally, patients with CHD + CM are an under-
recognized group with the highest mortality and need for
transplant who require increased recognition and study.
Appendix
See Tables
 Pediatric Cardiology

Table 3  Most frequent CHD and CM in the CHD, CM and CHD + CM groups by unique patient
CHD N = 58,386 CM N = 4,080 CHD + CM N = 4,883
N (%) N (%) N (%) N (%)

Ostium secundum type atrial 31,088 (53%) Other primary cardiomyopathies 2332 (57%) Mitral valve disorder/ Nonrheu‑ 2573 (53%) Other hypertrophic cardiomyo‑ 2783 (57%)
septal defect/ Atrial septal matic mitral (valve) insuf‑ pathy
defect ficiency/ Congenital mitral
insufficiency
Ventricular septal defect 23,367 (40%) Dilated cardiomyopathy 734 (18%) Ostium secundum type atrial 1676 (34%) Cardiomyopathy, unspecified 1086 (22%)
septal defect/ Atrial septal
defect
Patent ductus arteriosus 21,583 (37%) Cardiomyopathy, unspecified 280 (7%) Ventricular septal defect 626 (13%) Cardiomyopathy in other dis‑ 417 (9%)
eases classified elsewhere
Other specified congenital 7611 (13%) Secondary cardiomyopathy, 265 (6%) Patent ductus arteriosus 587 (12%) Other cardiomyopathies 250 (5%)
anomalies of heart unspecified
Hypoplastic left heart syndrome 6133 (11%) Cardiomyopathy in other dis‑ 232 (6%) Tricuspid valve disorders, speci‑ 555 (11%) Other restrictive cardiomyo‑ 219 (5%)
eases classified elsewhere fied as nonrheumatic/ Non‑ pathy
rheumatic tricuspid (valve)
insufficiency
Tetralogy of Fallot 5616 (10%) Other hypertrophic cardiomyo‑ 127 (3%) Congenital insufficiency of 531 (11%) Obstructive hypertrophic cardio‑ 218 (5%)
pathy aortic valve/ Aortic valve myopathy
disorders
Other endocardial cushion 5412 (9%) Cardiomyopathy due to drug and 105 (3%) Other specified congenital 472 (10%) Cardiomyopathy due to drug 143 (3%)
defect external agent anomalies of heart and external agent
Coarctation of aorta (preductal) 4803 (8%) Other restrictive cardiomyopathy 91 (2%) Hypoplastic left heart syndrome 237 (5%) Endomyocardial fibrosis 134 (3%)
(postductal)
Double outlet right ventricle 4554 (8%) Hypertrophic obstructive cardio‑ 57 (1%) Coarctation of aorta(preductal) 236 (5%) Other primary cardiomyopathies 117 (2%)
myopathy (postductal)

13
 Pediatric Cardiology

Table 4  Distribution of CHD and CM in the CHD + CM group in 2004–2007, 2008–2011, 2012–2015 and 2016–2019 by hospital admissions

2004– 2008– 2012– 2016–

2007 N = 833 2011 N = 1231 2015 N = 1668 2019 N = 1931

Cardiomyopathies
 Other primary cardiomyopathies 742 1062 1199 –
 Secondary cardiomyopathy, unspecified 36 64 83 –
 Hypertrophic obstructive cardiomyopathy/other hypertrophic cardiomyopathy 31 40 153 258
 Cardiomyopathy in other diseases classified elsewhere 24 49 60 –
 Nutritional and metabolic cardiomyopathy 4 16 16 –
 Dilated cardiomyopathy – – 102 1085
 Cardiomyopathy, unspecified – – 40 332
 Other cardiomyopathies – – 24 180
 Other restrictive cardiomyopathy – – 5 116
Congenital Heart Diseases
 Mitral valve disorder/nonrheumatic or congenital mitral (valve) insufficiency 307 490 307 929
 Ostium secundum type atrial septal defect/atrial septal defect 170 325 170 602
 Ventricular septal defect 99 124 189 203
 Other specified congenital anomalies or malformations of heart 85 143 151 91
 Tricuspid valve disorders specified nonrheumatic 52 101 110 236
 Patent ductus arteriosus 52 89 159 171

Cardiomyopathies ICD codes: Other primary cardiomyopathies (ICD9 425.4), Secondary cardiomyopathy, unspecified (ICD9 425.9), Hyper‑
trophic obstructive cardiomyopathy/Other hypertrophic cardiomyopathy (ICD9 425.1, 425.11 and 425.18 ICD10 I42.2), Cardiomyopathy in
other diseases classified elsewhere (ICD9 425.8), Nutritional and metabolic cardiomyopathy (ICD9 425.7), Dilated cardiomyopathy (ICD10
I42.0), Cardiomyopathy, unspecified (ICD10 I42.9), Other cardiomyopathies (ICD 10 I42.8) and Other restrictive cardiomyopathy (ICD10 I42.5)
Congenital Heart Disease ICD codes: Mitral valve disorders (ICD9 424.0), nonrheumatic or congenital mitral (valve) insufficiency (ICD10
I34.0), Ostium secundum type atrial septal defect (ICD9 745.5), Atrial septal defect (ICD10 Q21.1), Ventricular septal defect (ICD 9 745.4
and ICD10 Q21.0), Other specified congenital anomalies or malformations of heart (ICD9 746.89 and ICD10 Q24.8), Tricuspid valve disorders
specified nonrheumatic (ICD9 424.2), Patent ductus arteriosus (ICD9 747.0 and ICD10 Q25.0)

Author Contributions  All authors contributed to the study conception
and design. Material preparation, data collection, and analysis were
performed by RMD and MA. The first draft of the manuscript was writ‑
ten by RMD and MA, and all authors commented on previous versions
of the manuscript. All authors read and approved the final manuscript.
Funding None.
Declarations  mortality of heart failure-related hospitalizations in children
Conflict of interest None.
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