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Circ Heart Fail. Author manuscript; available in PMC 2021 April 17.
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Published in final edited form as:

Circ Heart Fail. 2020 April ; 13(4): e006101. doi:10.1161/CIRCHEARTFAILURE.119.006101.

Epidemiology and Outcomes of Acute Decompensated Heart

Failure in Children
Javier J. Lasa, MD1,2, Michael Gaies, MD, MPH, MSc3, Lauren Bush, MPH4, Wenying Zhang,
MS4, Mousumi Banerjee, PhD5, Jeffrey A. Alten, MD6, Ryan J. Butts, MD7, Antonio G.
Cabrera2, Paul A. Checchia, MD1, Justin Elhoff, MD1, Angela Lorts, MD6, Joseph W.
Rossano, MD8, Kurt Schumacher, MD3, Lara S. Shekerdemian, MD1, Jack F. Price, MD2,
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Pediatric Cardiac Critical Care Consortium (PC4)

(1)Division
of Critical Care Medicine, Texas Children’s Hospital, Baylor College of Medicine,
Houston, TX
(2)Division of Cardiology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX
(3)Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI
(4)PC4 Data Coordinating Center, Michigan Congenital Heart Outcomes Research and Discovery
Unit, University of Michigan, Ann Arbor, MI
(5)Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor,
Michigan
(6)Department of Pediatrics, Heart Institute, Cincinnati Children’s Hospital Medical Center,
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Cincinnati, OH
(7)UTSouthwestern Department of Pediatrics, Division of Cardiology, UT Southwestern Medical
Center, Dallas, Texas
(8)Division
of Cardiology, Children’s Hospital of Philadelphia, University of Pennsylvania School of
Medicine, Philadelphia, PA

Abstract
Background: Acute decompensated heart failure (ADHF) is a highly morbid condition among
adults. Little is known about outcomes in children with ADHF. We analyzed the Pediatric Cardiac
Critical Care Consortium (PC4) registry to determine the epidemiology, contemporary treatments,
and predictors of mortality in critically ill children with ADHF.
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Methods: CICU patients ≤ 18 years of age meeting PC4 criteria for ADHF were included. ADHF
was defined as systolic or diastolic dysfunction requiring continuous vasoactive or diuretic
infusion, respiratory support, or mechanical circulatory support. Demographics, diagnosis,
therapies, complications, and mortality are described for the cohort. Predictors of CICU mortality
were identified using logistic regression.

Corresponding Author: Javier J. Lasa, MD, FAAP, Assistant Professor, Department of Pediatrics, Divisions of Critical Care Medicine
and Cardiology, Texas Children’s Hospital/Baylor College of Medicine, West Tower, B06041, 6621 Fannin Street, Houston, TX
77030, Office: 832-826-0610, Fax: 832-825-7422, [email protected].
Disclosures: none
 Lasa et al. Page 2

Results: Among 26,294 consecutive admissions (23 centers), 1,494 (6%) met criteria for
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analysis. Median age was 0.93 years (IQR 0.1–9.3 years). CHD patients comprised 57% of the
cohort. Common therapies included: vasoactive infusions (88%), central venous catheters (86%),
mechanical ventilation (59%), and high flow nasal cannula (46%). Common complications were
arrhythmias (19%), cardiac arrest (10%), sepsis (7%), and acute renal failure requiring dialysis
(3%). Median length of CICU stay was 7.9 days (IQR 3–18 days) and the CICU readmission rate
was 22%. Overall CICU mortality was 15% although higher for patients with CHD vs non-CHD
(19% vs 11%, p<0.001). Independent risk factors associated with CICU mortality included age <
30 days, CHD, vasoactive infusions, ventricular tachycardia, mechanical ventilation, sepsis,
pulmonary hypertension, ECMO, and cardiac arrest.

Conclusions: ADHF in children is characterized by co-morbidities, high mortality rates, and

frequent readmission, especially among patients with CHD. Opportunities exist to determine best
practices around appropriate use of mechanical support, cardiac arrest prevention, and optimal
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heart transplantation candidacy to improve outcomes for these patients.

Introduction
Acute decompensated heart failure (ADHF) is a final common pathway for children with
congenital and/or acquired heart disease, usually resulting in admission to a cardiovascular
intensive care unit (CICU) for specialized care with high risk for cardiac arrest and death. 1,2
Multiple reports in adults have described the clinical characteristics and outcomes of ADHF,
but our understanding of ADHF in children remains limited due to the heterogeneous nature
of pediatric cardiovascular illnesses.2–11 Children may present with failed palliation of
congenital/ structural heart disease (CHD), acquired cardiomyopathies, or acute
exacerbations of chronic heart failure from abnormal circulations (e.g., Fontan circulation
for functional single ventricle). 12–14 Previous studies in children suggest that the frequency
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of hospitalization for ADHF may be increasing and that inpatient outcomes for ADHF are
poor. 2,15,16 Those data have been confounded, however, by reliance on reviews of
administrative databases or by a focus on one particular etiology of heart failure (e.g.,
cardiomyopathy) to the exclusion of others.

Consequently, a gap exists in our understanding of the demographics, treatment strategies,

complications and outcomes for children with a broad array of etiologies for ADHF. More
specifically, providers seek a basic understanding of risk factors for mortality while
searching for best practices amongst a range of centers and practice variability. Describing
the epidemiology of ADHF in children and identifying risk factors for death will add to our
current knowledge of this complex cohort while motivating quality improvement strategies
to achieve better clinical outcomes.
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In this context, we conducted an analysis of pediatric CICU admissions to define the

epidemiology of critical ADHF and to determine risk factors for mortality in a multicenter
North American clinical registry dedicated to this patient population (Pediatric Cardiac
Critical Care Consortium; PC4). We hypothesized that morbidity and mortality rates are high
in children with ADHF admitted to the CICU and that patients with pre-existing CHD are at
greatest risk of poor outcomes.

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Methods
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Study Design and Cohort

The Pediatric Cardiac Critical Care Consortium (PC4) is a quality improvement
collaborative that collects data on all patients with primary cardiac disease admitted to the
CICU service of participating hospitals17. PC4 maintains a clinical registry to support
research and quality improvement initiatives. At the time of this analysis, 23 centers were
submitting cases to the PC4 Registry.

Each participating center has a trained data manager who has completed a certification
exam. The data managers collect and enter data in accordance with the standardized PC4
Data Definitions Manual. The PC4 registry shares common terminology and definitions with
applicable data points from the International Pediatric and Congenital Cardiac Code
(IPCCC), Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database, and
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American College of Cardiology Improving Pediatric and Adult Congenital Treatment

(IMPACT) Registry, as previously described17. Participating centers are audited on a regular
schedule and audit results suggest complete, accurate and timely submission of data across
centers, with the most recent published results demonstrating a major discrepancy rate of
0.6% across 29,476 fields18. Because of the sensitive nature of the data collected for this
study, requests to access the dataset from qualified researchers trained in human subject
confidentiality protocols may be sent to the PC4 Data Coordinating Center at
[email protected].

The University of Michigan Institutional Review Board provides oversight for the PC4 Data
Coordinating Center; this study was reviewed and approved with waiver of informed
consent.
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Definitions and Patient Selection

Patients ≤18 years of age admitted to CICUs at participating PC4 centers between August
2014 and April 2017 were included in this analysis if acute decompensated heart failure
(AHDF) was identified at the time of admission to the CICU, either as the primary diagnosis
or a concurrent comorbidity. The PC4 definition of ADHF, established by a consensus panel
of physicians and nurses within the collaborative, was utilized for this analysis: the presence
of documented systolic and/or diastolic ventricular dysfunction and receipt of at least one of
the following critical care therapies: (a) continuous infusion of a vasoactive and/or diuretic
agent, (b) respiratory support including mechanical ventilation as well as non-invasive high
flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), or bilevel positive
airway pressure (BiPAP), or (c) any form of mechanical circulatory support during the CICU
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admission. Participating PC4 institution data collection teams were made up of clinical data
abstractors as well as clinical champions (CICU physicians) who collaborated to ensure
accurate interpretation of electronic medical records, including non-invasive imaging
reports. Additional PC4 definitions of clinical conditions and complications utilized in this
analysis can be found in Supplemental Table 1.

Cardiac diagnoses and operative procedures are defined according to the International
Pediatric and Congenital Cardiac Code. 19 The ADHF population was stratified by presence

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of underlying CHD versus lack of CHD (i.e. structurally normal heart) and/or those having
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undergone prior heart transplantation, regardless of history of CHD prior to transplantation.

ADHF patients with structurally normal hearts were grouped together with those having
undergone prior heart transplantation. Patients undergoing any cardiothoracic surgical
procedure during the ADHF CICU encounter, including extracorporeal membrane
oxygenation (ECMO), ventricular assist device (VAD) placement and/or heart
transplantation, were also included. Therefore, patients with CHD were included if they met
criteria for ADHF at the time of admission, whether or not they subsequently had
cardiothoracic surgery in the same admission. CICU admissions were excluded from
analysis if the patient presented with hospice care/do-not-resuscitate orders.

Twenty-three centers participating in the PC4 registry at the time of analysis had submitted
qualifying cases. Both hospital-level and CICU admission-level descriptive analyses were
performed with all inferential analyses utilizing the CICU admission as the episode of
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analysis.

Outcomes
Patient demographics (age, gender), presence of extracardiac abnormalities or chromosomal
abnormalities/syndromes, weight at CICU admission, CICU resource utilization (mechanical
ventilation, pharmacotherapies, arterial/venous access), CICU complications including
cardiac arrest and use of extracorporeal membrane oxygenation (ECMO) rescue during
active CPR (E-CPR) were chosen a priori as potential factors associated with mortality in
the ADHF population. Mortality in the CICU environment is described for the cohort as well
as amongst the CHD and non-CHD groups of ADHF patients.

Statistical Analysis
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Data are presented as frequency (percentage) for categorical variables and median with
interquartile range for continuous variables. To identify patient and clinical characteristics
associated with CICU mortality, univariate comparisons were performed using the Wilcoxon
rank sum test for continuous variables, and chi-square or Fisher exact test as appropriate for
categorical data.

Depictions of variability in mortality across PC4 centers are not annualized as centers
contributed data to the registry at different time points during the study era. Raw (observed)
mortality rates are presented as percentages. Several variables identified a priori as possible
predictors of mortality were subsequently excluded from the final model.

To better understand predictors of mortality, we performed a stratified univariate analysis

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dividing the cohort into patients who underwent a cardiothoracic surgical procedure during
their ADHF admission (N=310) versus those who did not (N=1184). Only non-surgical
ADHF admissions were subsequently included in our multivariate analysis of mortality for
two reasons: 1) Key differences in variables collected between surgical and non-surgical
patients made combining them in one model potentially misleading, 2) The small sample
size of the surgical cohort limited additional multivariable analysis in this subgroup. Factors
associated with CICU mortality among non-surgical patients in unadjusted analysis (p < 0.1)
were included in a multivariable logistic regression model to determine independent

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associations (p < 0.05) with mortality. We also tested models including laboratory values
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such as B-type natriuretic protein and creatinine, but there was a high percentage of missing
values as these studies were not obtained on all patients at the time of admission. We
evaluated missingness and found no difference in the distribution of missing data between
patients who died and those survived. Addition of laboratory values (actual and predicted)
did not improve model performance and resulted in larger standard errors for the
coefficients, so we excluded laboratory variables from our final multivariable analysis. These
results are not presented further.

Adjusted odds ratios and 95% confidence intervals (CI) for each predictor are reported. We
ran the model accounting for clustering at the hospital-level using a hospital random-effect
term. We also evaluated the model adding a random-effect term at the patient-level to
account for multiple CICU admissions by the same patient.
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We could not perform stratified multivariable analyses in the two disease subgroups (CHD
and non-CHD + status-post transplant) due to sample size constraints. Therefore, to explore
the impact of disease heterogeneity on predictors of mortality we performed a second
multivariable analysis and tested interactions with CHD. Key independent variables
associated with mortality in the initial model (age, and exposure to mechanical ventilation,
vasoactive infusions, and ECMO) were included with diagnosis as interaction terms to test
whether they differentially impacted the effect of diagnosis on mortality. All analyses were
performed using SAS Version 9.4 (SAS Institute, Cary, NC) or STATA Version 14
(StataCorp LLC, TX), with statistical significance at a p value of less than 0.05.

Results
Patient Characteristics
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Between August 1, 2014 and April 4, 2017, a total of 26,294 CICU admissions were
submitted to the PC4 collaborative by 23 participant centers. Of these CICU admissions,
1,494 unique ADHF admissions (1,371 hospitalizations) were identified. (Figure 1) Table 1
displays demographic, clinical, and laboratory characteristics at the time of CICU admission
for the entire cohort as well as CHD and non-CHD subgroups. Patients with underlying
CHD comprised 57% (N=852) of admissions. The median age at presentation for ADHF
was 0.93 years (Interquartile range [IQR] 0.1 – 9.3 years), and patients with CHD were
significantly younger than patients without CHD. Patients with ADHF and CHD had
significantly lower weight at CICU admission and were more likely to have extra-cardiac
congenital anomalies, chromosomal abnormalities and/or known syndromes when compared
to non-CHD patients. Only 4% of patients (58/1494) had undergone a previous
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cardiothoracic surgical procedure during the same hospitalization and among patients with
prior heart transplantation presenting in ADHF, 80% (32/40) were identified as having
rejection at the time of admission.

Critical Care Resource Utilization and Complications

Therapies, procedures, and complications in the CICU are displayed in Table 2. Nearly 60%
of ADHF admissions included invasive mechanical ventilation, for a median duration of 5.2

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days (IQR: 2–13 days). Patients with CHD were more likely to receive mechanical
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ventilation and had higher rates of reintubation within 48 hours of planned extubation when
compared to their non-CHD counterparts. Supplemental Table 2 displays the spectrum of
vasoactive/inotropic medications used in the care of ADHF patients. Milrinone was the most
commonly administered vasoactive agent (80% of admissions). Non-CHD patients were
treated with milrinone more frequently than their CHD counterparts while CHD patients
were exposed to more calcium and vasopressin infusions than non-CHD patients. The
frequency of vasoactive medication prescription varied considerably between individual
centers. Milrinone had the highest rate of utilization during ADHF admissions among sites,
ranging from 60% to 100% of ADHF admissions across the consortium. (Supplemental
Table 3)

The median length of CICU stay for all ADHF admissions was 7.9 days (IQR: 3.0–18.1
days, Table 3). Length of CICU stay was significantly longer for CHD patients than non-
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CHD patients (8.4 days [IQR 3.2–18.9] vs 6.8 days [IQR 3.0–17.5]; p=0.027) . No
difference in ICU readmission rates was appreciated between the two groups (179/852
[23%] CHD vs 122/642 [21%] non-CHD; p=0.43), although 22% of ADHF admissions were
classified as an unplanned readmission to the CICU within 48 hours of previous discharge
(N=301). Readmission to the hospital within 30 days (all-cause hospital readmission) was
noted in 11% (N=147) of ADHF patients with a higher readmission rate seen in the CHD
cohort.

Complication rates are also displayed in Table 2. The most common complication was
arrhythmia treated with pharmacologic therapy and/or cardioversion/defibrillation. Of all
complications, only central line-associated blood stream infection was significantly greater
amongst CHD patients in comparison to the non-CHD cohort. Stroke was observed in 69
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(5%) ADHF CICU encounters. Of these encounters, 35 (50%) were in patients undergoing
mechanical circulatory support via VAD and/or ECMO (VAD only 9/35 [26%], ECMO only
22/35 [63%], VAD and ECMO 4/35 [11%]).

The most severe morbidity, cardiac arrest, occurred in 10% of ADHF admissions (N=152).
No differences were noted between CHD and non-CHD subgroups for cardiac arrest
incidence nor for cardiac arrest duration. E-CPR was utilized in over a third of cardiac
arrests (35%, N=53/152).

Disparate utilization rates were noted between ECMO and VAD. While ECMO was utilized
in 12% of the overall cohort (N=173), only 4% (N=65) underwent VAD implantation during
the CICU admission. Of the 65 ADHF admissions in which a VAD was implanted, 24
(36.9%) also underwent heart transplantation during the same hospitalization. Non-CHD
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patients were more likely to be both listed for heart transplantation (83/642 [13%] vs 76/852
[9%]; p=0.013) and undergo heart transplantation during the same hospitalization. ECMO
support and VAD implantation were also more commonly used by non-CHD patients than
their CHD counterparts (ECMO 89/642 [14%] vs 84/852 [10%]; p=0.017 and VAD 51/642
[8%] vs 14/852 [2%]; p<0.001).

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Mortality and Associated Risk Factors

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The CICU mortality rate for the overall ADHF cohort was 15% (N=231). Variation in
mortality across the participating PC4 centers is displayed in Figure 2. Mortality in the
CICU ranges from 0% (single center with n=6 total admissions entered into PC4 at the time
of data abstraction) to as high as 25% of CICU admissions per center. In contrast to CICU-
level outcomes, hospitalization-level morbidity and mortality are described in Supplemental
Table 4. Hospital mortality reached 19% for the overall ADHF cohort and similar to CICU
mortality rates, was much higher for CHD patients.

We evaluated the association of patient characteristics, coexisting high-risk diagnoses,

therapies received, and complications with CICU mortality solely in patients who did not
undergo cardiothoracic surgical procedures during their CICU admission (n=1184; Table 4).
Presence of CHD, extra-cardiac anomalies, neonatal age at presentation, pre-existing high-
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risk diagnoses (CPR as reason for admission; any cardiomyopathy including dilated,
hypertrophic, and restrictive; pulmonary hypertension), peak vasoactive inotrope score
within 2 hours of admission, mechanical ventilation, ECMO, and key complications were
some of the important univariate risk factors for CICU mortality.

Although a smaller cohort, patients who underwent cardiothoracic surgical procedures

(N=310) during ADHF admissions were analyzed for univariate associations with mortality
with results presented as Supplementary Table 5. Heart transplants were performed for a
total of 66 admissions. Overall mortality was 10% and of those that died, 2 (6%) had
undergone transplantation during CICU admission. Cardiac arrest occurred in 11% of
encounters with ECPR utilized in 43% of arrests.

Several factors persisted as independent risk factors for CICU mortality for the larger cohort
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of non-surgical patients after multivariable logistic regression (Table 5). Independent risk
factors associated with CICU mortality included age < 30 days, presence of CHD, any use of
vasoactive infusion, ventricular tachycardia, mechanical ventilation, sepsis, pulmonary
hypertension, use of ECMO, and cardiac arrest. When classified by CPR duration categories,
admissions experiencing cardiac arrest of > 20 minutes duration were found to have higher
odds of CICU mortality than cardiac arrest of < 20 minutes and all other variables included
in the multivariate model.

In our exploratory model to test interactions between CHD, age, vasoactive infusions,
mechanical ventilation, and ECMO, only the interaction between age and CHD was
statistically significant (p=0.002). Although all age groups interacted with CHD to increase
the risk of mortality compared to non-CHD, the strongest effect was the interaction between
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CHD and neonates; neonates with CHD and ADHF had a 16-fold greater odds of mortality
than the reference group (children >1 year, no CHD; adjusted OR 16.2 [95% CI 7.2 – 36.4],
p<0.001; Supplemental Table 6).

Discussion
This large, multi-center study represents the first analysis of ADHF in a prospective
observational cohort of critically ill children. Our study showed that ADHF occurred in 6%

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of all CICU admissions and that nearly 1 in 5 ADHF-related hospitalizations resulted in

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death. Congenital heart disease was present in over half of those hospitalized with ADHF
and was associated with greater resource utilization, higher complication rates, longer length
of stay, increased likelihood of readmission, and poorer survival when compared to children
without CHD. Important additional risk factors associated with death include age <1 year,
need for mechanical ventilation, vasoactive infusion exposure, ECMO, cardiac arrest,
ventricular tachycardia, co-existing pulmonary hypertension and hepatic failure.

One of the important observations from this analysis is the negative impact of CHD on
outcomes in children with ADHF. This highly co-morbid patient population (younger age at
presentation, frequent extra-cardiac anomalies and genetic syndromes) not only suffered
greater morbidity and mortality compared to their counterparts without CHD, but they were
also less likely to receive potentially life-saving therapies such as ECMO, VAD, and cardiac
transplantation. This may be due in part to their younger age and smaller size at the time of
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hospitalization, but also due to the heterogenous anatomical and pathophysiological features
of CHD, which may complicate or preclude mechanical circulatory support in this group.
Possibly recognizing a disparity, the Organ Procurement and Transplantation Network
recently revised its listing criteria for children awaiting cardiac transplantation, giving
waitlist priority to children with CHD. Advances in technology may soon bring new
treatment options for this population, especially if further miniaturization of mechanical
circulatory support devices proves feasible. 20–23 In the interim, this study provides further
evidence for risk stratification and anticipatory management of CHD patients with ADHF.

Another important observation from this study is the difference between adult and pediatric
hospitalizations for ADHF. Our data showed that children with ADHF are more acutely ill
than has been described in adults, with greater use of vasoactive infusions and mechanical
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ventilation, longer lengths of stay, and higher mortality rates. 9,11,15,24,25 Although the
definitive clinical features of HF are present in both adults and children (i.e., ventricular
dysfunction, fluid retention, neurohormonal activation), the manifestations of ADHF and
presentation appear to be different. Although adults with ADHF may present in cardiogenic
shock, they are more likely to present with features of congestion and fluid overload,
requiring treatment with diuretics, rather than with features of a low cardiac output state or
respiratory failure necessitating the addition of vasoactive medications or mechanical
ventilation. 26 Children in the PC4 cohort were at high risk of respiratory failure requiring
mechanical ventilation and utilized vasoactive medications at high rates.

Indeed, inotropic medications are utilized in 14–53% of adults hospitalized in an ICU for
ADHF 6,9,26, while the children in our study were treated with inotropes much more
frequently (up to 88%). In fact, at least one of the PC4 sites administered milrinone in 100%
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of patients with ADHF. Such routine use of inotropes was not completely unexpected.
Although the definition of ADHF includes the potential treatment with vasoactive agents,
prior studies in children hospitalized with advanced heart failure have reported similarly
high rates of inotrope use. 2,3,27 Notwithstanding the acuity of illness, such extensive use of
inotropes is curious given the known adverse effects and mortality risks associated with their
use in adults. This common management may represent a dearth of evidence-based
treatment options in pediatric ADHF.

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The higher mortality rate in children with ADHF reinforces the differences with adults.
8,25,28
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In our study, hospital-wide and CICU-specific mortality rates were 19% and 15%,
respectively, compared to reports of 4–9% all-cause 30-day mortality in adults with acute
HF syndromes admitted to higher acuity units.5,6,10,15,24,26,29 Separate studies in children
with advanced HF have reported lower mortality rates but always in cohorts that
encompassed ICU and non-ICU locations and excluded patients with CHD. 2,12,15,16 Few
adults who are hospitalized for ADHF have CHD as its etiology and, unlike children, about
half of adults with ADHF have preserved ventricular systolic function, which is less likely to
require an ICU admission. Hence, these patients have low mortality rates and shorter ICU
and hospital stays. 24

Wide variability in CICU mortality across the collaborative was also noted, ranging from 0%
to 25% across centers, although not risk-adjusted for patient complexity or referral center for
transplant-center status. Several factors may contribute to this mortality including case-mix
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variability and institutional volume. We speculate that institutional volume may contribute to
variability in mortality, particularly for centers that perform cardiac transplantation. Cardiac
arrest occurred in a minority of ADHF patients admitted to the CICU (10%), but the event
was strongly associated with death, regardless of whether or not the patients had CHD. This
incidence of cardiac arrest in CICU patients with ADHF is higher than reported for all CICU
patients in the PC4 registry.30 Previously identified risk factors for cardiac arrest in the
pediatric population such as underlying cardiovascular disease and younger age were highly
prevalent in our cohort of ADHF patients. 31,32

Readmission to the CICU during hospitalization was common in this cohort (22%). Several
patient factors may necessitate a readmission for ADHF and include arrhythmias, worsening
symptoms, and need for initiation or escalation of vasoactive therapies. Critical care bed
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space capacity remains a finite hospital resource that requires active management, especially
in the current era of increased pediatric ADHF admissions. Organizational factors including
average daily census and nurse-bed ratio limitations may play a role in encouraging
premature transfer from critical care to acute care wards. In addition, quality of care
provided in the CICU may also impact their need for readmission during the same
hospitalization. Premature discontinuation of vasoactive therapies and failure to initiate
standard-of-care oral heart failure medications may determine a patient’s need for continued
higher level of care. Such a high rate of CICU readmissions, or “bounce backs”, represents
an opportunity for further investigation of clinical predictors that may determine candidacy
for transfer to lower acuity settings from the CICU environment. Of note in our study, the
overall 30-day hospital readmission rate for our cohort (11%) was lower than previously
published reports in children (13 – 34%)2, and may be an under-representation since patients
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may have been readmitted to other non-PC4 centers after discharge from a PC4 center.

This study has several important limitations. Although PC4 diagnostic criteria for ADHF are
consistent with adult studies, a consensus definition of ADHF in children does not exist.
Secondly, certain quantitative surrogate markers of heart failure (e.g., ejection fraction, left
ventricular end-diastolic dimension) were not collected due to the myriad of ventricular
anatomies in the cohort, but qualitative assessments were required in conjunction with
receipt of certain therapies (vasoactives, diuretic infusions, mechanical ventilation,

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mechanical circulatory support). Lastly, we are also aware of the potential impact of
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unmeasured confounders not captured by this data set.

In summary, although children with ADHF comprise a minority of admissions to pediatric

CICU’s, these patients carry high burdens of morbidity and mortality during their CICU
admissions, especially in patients with underlying CHD. Complex critical care resources are
frequently employed in this population yet significant variability in therapeutic utilization
exists across sites. Mechanical circulatory support appears to be utilized less frequently in
the CHD population and, lastly, readmission rates to the ICU are exceedingly high. We hope
the results of this study will provide a foundation for the development of risk adjustment
models that explore true variation in CICU resource utilization and mortality across pediatric
CICUs while also identifying high-performing centers with respect to management of the
ADHF population. Ultimately, we expect these results will inform the heart failure,
transplant, and critical care communities while also fueling targeted research and quality
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improvement initiatives that reduce CICU related morbidity and mortality in the ADHF
population, especially among those patients with underlying CHD.

Supplementary Material
Refer to Web version on PubMed Central for supplementary material.

Acknowledgements
The investigative team acknowledges the data collection teams and clinical champions from each of the PC4
hospitals for their efforts in obtaining the high-quality data used in this analysis.

Funding Sources
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This study was supported in part by funding from the University of Michigan Congenital Heart Center, Champs for
Mott, and the Michigan Institute for Clinical & Health Research (NIH/NCATS UL1TR002240). Dr. Gaies is
supported in part by funding from the National Institutes of Health/National Heart, Lung, and Blood Institute
(K08HL116639).

Non-standard Abbreviations and Acronyms:

ADHF acute decompensated heart failure

BiPAP bilevel positive airway pressure

CHD congenital heart disease

CI confidence interval

CICU cardiac intensive care unit

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CPAP continuous positive airway pressure

ECMO extracorporeal membrane oxygenation

HFNC high flow nasal cannula

IMPACT American College of Cardiology Improving Pediatric and Adult

Congenital Treatment Registry

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IPCCC International Pediatric and Congenital Cardiac Code

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IQR interquartile range

PC4 Pediatric Cardiac Critical Care Consortium

STS Society of Thoracic Surgeons Congenital Heart Surgery Database

VAD ventricular assist device

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What is new?
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• In this report from Pediatric Cardiac Critical Care Consortium (PC4) registry,
acute decompensated heart failure (ADHF) accounted for 6% of all admission
to a pediatric cardiac intensive care unit.

• Compared to adults, ADHF in children is characterized by higher acuity,

including higher rates of ICU mortality (16%), ICU readmission (22%),
mechanical ventilation (59%) and CPR (10%).

• Congenital heart disease is diagnosed in more than half of children

hospitalized with ADHF and is strongly associated with mortality.

• Vasoactive therapies, such as milrinone and epinephrine infusions, are

commonly prescribed, though their administration varies widely across
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centers in the PC4.

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What are the clinical implications?

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• Data from the PC4 registry provide a contemporary characterization of ADHF

along with significant evidence of variability in both management and
outcomes for pediatric patients admitted to ICU with ADHF.

• This analysis identifies opportunities for improved treatment strategies of

ADHF across participating centers by shedding light on risk factors for
morbidity, readmissions, and mortality.
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Figure 1.
Patient selection flow-sheet
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Figure 2.
Variation in CICU mortality across participating PC4 centers
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Table 1.

Clinical characteristics of patients admitted to CICUs with acute decompensated heart failure
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All ADHF Encounters CHD Non-CHD

p-value
n (%) n (%) n (%)
CICU Encounters 1494 (100) 852 (57) 642 (43)

Age, years (median, IQR) 0.93 (0.1 – 9.3) 0.37 (0.1 – 2.7) 5.02 (0.4 – 13.8) <0.001

Neonate (<30 days) 311 (21) 219 (26) 92 (14) <0.001

Infant (30 days – <1 year) 443 (30) 323 (38) 120 (19)

Child (1 year - <18 years) 740 (49) 310 (36) 430 (67)

Weight at CICU admission, kg 8 (3.9–26) 5.3 (3.5–11.7) 17.7 (6–51.5) <0.001

Male gender 814 (55) 476 (56) 338 (53) 0.22

Race <0.001

Caucasian 900 (60) 547 (64) 353 (55)

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Black 337 (23) 163 (19) 174 (27)

Asian 49 (3) 31 (4) 18 (3)

Native American 6 (<1) 3 (<1) 3 (<1)

Native Pacific Islander 2 (<1) 1 (<1) 1 (<1)

Other/Multiracial 148 (10) 84 (10) 64 (10)

Unknown 52 (3) 23 (3) 29 (5)

Pre-existing High-Risk Diagnoses ( n=1184) 376 (32) 191 (33) 185 (31) 0.51

Arrhythmia 41 (3) 11 (2) 30 (5) <0.001

CPR reason for admit 50 (4) 28 (5) 22 (4) 0.34

Pulmonary hypertension 68 (6) 44 (8) 24 (4) 0.009

Heart transplant rejection 32 (3) 0 (0) 32 (5) <0.001

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Cardiomyopathy 461 (39) 66(11) 395(66) 0.003

Myocarditis 100 (8) 6(1) 94(16) <0.001

Extra-cardiac Anomalies 210 (14) 159 (19) 51 (8) <0.001

Chromosomal Abnormality 122 (8) 115 (14) 7 (1) <0.001

Syndrome(s) 240 (16) 209 (24) 31 (5) <0.001

Tracheostomy Present 16 (1) 13 (2) 3 (<1) 0.05

Primary Insurance Type 0.08

Public 853 (57) 497 (58) 356 (55)

Private 555 (37) 307 (36) 248 (39)

Non-U.S. Insurance 8 (1) 1 (<1) 7 (1)

None/Self 27 (2) 15 (2) 12 (2)

Unknown 51 (3) 32 (4) 19 (3)

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Source of CICU Admission 0.99

Home 39 (3) 22 (3) 17 (3)

Current Hospital 919 (62) 525 (62) 394 (61)

Outside Hospital 536 (36) 305 (36) 231 (36)

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Key: ADHF, acute decompensated heart failure; CICU, cardiac intensive care unit; CHD, congenital heart disease; CPR, cardiopulmonary
resuscitation
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Table 2.

Therapies, procedures, and complications during CICU admissions for acute decompensated heart failure.
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All ADHF Encounters CHD Non-CHD

n=1494 n=852 n=642 p-value
(%) (%) (%)
CICU Encounters 1494 (100) 852 (57) 642 (43)

Respiratory Support

Mechanical Ventilation 876 (59) 553 (65) 323 (50) <0.001

Total Mechanical Ventilation duration, median days (IQR) 5.2 (2–13) 5.3 (2–13) 5.2 (2–13) 0.68

Reintubation (within 48 hours after planned extubation) 80 (9) 60 (11) 20 (6) 0.021

Positive airway pressure (CPAP/BiPAP) 381 (26) 244 (29) 137 (21) 0.001

High-flow Nasal Cannula 682 (46) 454 (53) 228 (35) <0.001

Inhaled Nitric Oxide Use 286 (19) 176 (21) 110 (17) 0.09

Critical Care Resources

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Central venous line during CICU encounter 1284 (86) 719 (84) 565 (88) 0.047

Arterial line 841 (56) 508 (60) 333 (52) 0.003

Foley catheter 700 (47) 424 (50) 276 (43) 0.009

VIS (peak within 2 hours of admission) 5 (5–10) 5 (5–10) 5 (3.8–10) 0.24

Complications

Arrhythmia 291 (19) 153 (18) 138 (22) 0.09

Stroke 69 (5) 39 (5) 30 (5) 0.93

Intracranial Hemorrhage 44 (3) 24 (3) 20 (3) 0.74

Seizure 50 (3) 31 (4) 19 (3) 0.47

Continuous Renal Replacement Therapy for Acute Renal Failure 50 (3) 27 (3) 23 (4) 0.66

Pneumonia 52 (3) 31 (4) 21 (3) 0.70

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Central Line-associated Bloodstream Infection 43 (3) 32 (4) 11 (2) 0.019

Sepsis 98 (7) 59 (7) 39 (6) 0.51

Urinary Tract Infection 51 (3) 32 (4) 19 (3) 0.40

Hepatic Failure 52 (3) 33 (4) 19 (3) 0.34

Ventricular Tachycardia 120 (8) 42 (5) 78 (12) <0.001

Cardiac Arrest During CICU Encounter 152 (10) 97 (11) 55 (9) 0.08

E-CPR (% of Cardiac Arrest) 53 (35) 29 (30) 24 (44) 0.09

Cardiac arrest time, minutes (IQR) 20 (4–44) 20 (4–40) 21 (6–52) 0.36

Mechanical Circulatory Support

ECMO 173 (12) 84 (10) 89 (14) 0.017

ECMO Length of Support, day 5.6 (3.1–10.1) 5.3 (3.1–9.8) 5.6 (3.1–10.1) 0.89
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VAD placement 65 (4) 14 (2) 51 (8) <0.001

Listed for Heart Transplantation 159 (11) 76 (9) 83 (13) 0.013

Any Cardiothoracic Surgery During the CICU Encounter 310 (21) 267 (31) 43 (7) <0.001

Heart transplantation 66 (22) 38(14) 28 (65) <0.001

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Key: CICU, cardiac intensive care unit; CPAP, continuous positive airway pressure; BiPAP, bilevel positive airway pressure; PICC, peripherally
inserted central catheter; ARDS, acute respiratory distress syndrome; E-CPR, extracorporeal cardiopulmonary resuscitation; ECMO, extracorporeal
membrane oxygenation; VIS, Vasoactive-Inotropic Score (Gaies M., Jeffries H.E., Niebler R.A., et al. Vasoactive-Inotropic Score (VIS) is
Associated with Outcome After Infant Cardiac Surgery: An Analysis from the Pediatric Cardiac Critical Care Consortium (PC4) and Virtual PICU
System Registries. Pediatric Critical Care Medicine. 2014 July; 15(6):529–537); VAD, ventricular assist device
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Table 3.

Mortality and disposition outcomes

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All ADHF
CHD Non-CHD OR/
Encounters
n=852 n=642 OR/IRR* 95% CI p-value
n=1494
(%) (%) IRR*
(%)
Length of CICU stay, days median †
7.9 (3.0–18.1) 8.4 (3.2–18.9) 6.8 (3.0 –17.5) 1.26 1.12 – 1.42 <0.001
(IQR)

CICU Mortality 231 (15) 159 (19) 72 (11) 1.82 1.35 – 2.45 <0.001

Withdrawal of life-sustaining
167 (72) 111 (70) 56 (78) 0.66 0.34 – 1.27 0.21
therapy

Length of ICU stay, days (IQR; †

9.4 (3.4–25.2) 9.1 (2.9–26.7) 10.4 (4.3–21.6) 1.12 0.79 – 1.58 0.53
non-survivors)

VAD or ECMO 222 (15) 95 (11) 127 (20) 0.51 0.38 – 0.68 <0.001

CICU Mortality 95 (43) 56 (59) 39 (31) 3.24 1.86 – 5.65 <0.001

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Brain Death 7 (<1) 1 (<1) 6 (1) 0.12 0.01 – 1.04 0.05

Readmission to CICU During

301 (22) 179 (23) 122 (21) 1.11 0.86 – 1.44 0.43
Hospitalization

All-cause Readmission within 30

147 (11) 96 (12) 51 (9) 1.45 1.01 – 2.07 0.043
Days of Hospital Discharge

Key: IRR, incidence rate ratio; CI, confidence interval; OR, odds ratio
*
Unadjusted
†
Incidence rate ratio
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Table 4.

Associations with CICU mortality in acute decompensated heart failure admissions who did not undergo
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cardiothoracic surgical procedures.

CICU Encounter Mortality

All ADHF Encounters
Yes No p-value
(n=1184)
(n=200) (n=984)
Congenital Heart Disease

Yes 585 (49) 130 (65) 455 (46) <0.001

No 599 (51) 70 (35) 529 (54)

Male Gender 657 (55) 123 (62) 534 (54) 0.06

Extra-cardiac Anomalies 164 (14) 39 (20) 125 (13) 0.01

Chromosomal Abnormality and/or Syndrome(s) 189 (16) 38 (19) 151 (15) 0.19

Neonate (< 30 days) 193 (16) 63 (32) 130 (13) <0.001

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Infant (30 days to <1 year) 326 (28) 51 (26) 275 (28)

Child (1 year to <18 years) 665 (56) 86 (43) 579 (59)

Race

Caucasian, non-Hispanic 516 (44) 87 (44) 429 (44) 0.95

Hispanic, any race 247 (21) 39 (20) 208 (21)

Black, non-Hispanic 271 (23) 48 (24) 223 (23)

All other races, non-Hispanic 150 (13) 26 (13) 124 (13)

Pre-existing High-Risk Diagnoses

Arrhythmia 41 (4) 9 (5) 32 (3) 0.38

CPR reason for admit 50 (4) 25 (13) 25 (3) <0.001

Pulmonary hypertension 68 (6) 22 (11) 46 (5) <0.001

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Heart transplant rejection 31 (3) 6 (3) 25 (3) 0.71

Cardiomyopathy 461 (39) 60 (30) 401 (41) 0.005

Myocarditis 100 (8) 9 (5) 91 (9) 0.03

Any Vasoactive/Inotrope Infusion 1009 (85) 193 (97) 816 (83) <0.001
Vasoactive/Inotrope Infusion Within 2 hrs. of CICU Admission 747 (63) 131 (65.50) 616 (63) 0.44

VIS (Peak, within 2 hrs. of CICU Admission) 5 (5–10) 7.5 (5–12) 5 (5–8) <0.001

VIS Categories

> 7.5 225 (19) 63 (32) 162 (16) <0.001

< 7.5, > 2.5 496 (42) 62 (31) 434 (44)

< 2.5 463 (39) 75 (38) 388 (39)

Mechanical ventilation 573 (48) 188 (94) 385 (39) <0.001

Mechanical ventilation, duration (hours, median, IQR; n=573) 113 (40–260) 134 (40–393) 105 (41–224) 0.05
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VAD placement 42 (4) 6 (3) 36 (4) 0.65

ECMO 20 (10) 68 (34) 52 (5) <0.001

Complications

Sepsis 77 (7) 31 (16) 46 (5) <0.001

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CICU Encounter Mortality

All ADHF Encounters
Yes No p-value
(n=1184)
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(n=200) (n=984)
Hepatic failure 36 (3) 29 (15) 7 (1) <0.001

CRRT for acute renal failure 37 (3) 21 (11) 16 (2) <0.001

Stroke 50 (4) 20 (10) 30 (3) <0.001

Ventricular tachycardia 94 (8) 41 (21) 53 (5) <0.001

Cardiac arrest during ICU encounter 117 (10) 81 (41) 36 (4) <0.001

E-CPR (% of Cardiac Arrest) 38 (32) 26 (32) 12 (33) 0.89

Cardiac arrest time (minutes, median, IQR) 21 (4–48) 30 (13–49) 5 (1–24) <0.001

Key: CICU, cardiac intensive care unit; CPR, cardiopulmonary resuscitation; CRRT, continuous renal replacement therapy; E-CPR, extracorporeal
cardiopulmonary resuscitation; ECMO, extracorporeal membrane oxygenation; VIS, Vasoactive-Inotropic Score (Gaies M., Jeffries H.E., Niebler
R.A., et al. Vasoactive-Inotropic Score (VIS) is Associated with Outcome After Infant Cardiac Surgery: An Analysis from the Pediatric Cardiac
Critical Care Consortium (PC4) and Virtual PICU System Registries. Pediatric Critical Care Medicine. 2014;15:529–537); VAD, ventricular assist
device
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Table 5:

Multivariate logistic regression model of risk factors associated with CICU mortality in acute decompensated
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heart failure admissions

Risk Factor Odds Ratio Z-score 95% Confidence Interval p-value

Cardiac arrest during ICU admission

< 20 minute duration 4.36 4.81 2.4 – 7.9 <0.001

> 20 minute duration 20.30 5.16 6.5 – 63.4 <0.001

Hepatic failure 13.05 4.78 4.6 – 37.4 <0.001

Mechanical ventilation 7.41 4.77 3.3 – 16.9 <0.001

Neonate, <30 days (ref. group: >1 year - <18 year) 3.65 4.03 2.0 – 6.9 <0.001

CHD (reference group: non-CHD/transplant) 3.47 4.58 2.0 – 5.9 <0.001

ECMO 2.96 4.07 1.8 – 5.0 <0.001

Use of any vasoactive therapy 2.93 3.20 1.5 – 5.7 0.001

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Ventricular tachycardia 2.60 2.18 1.1 – 6.1 0.029

Pulmonary hypertension 2.08 2.39 1.1 – 3.8 0.017

Sepsis 1.63 2.04 1.0 – 2.6 0.042

Myocarditis 0.22 −2.27 0.1 – 0.8 0.023

Key: CICU, cardiac intensive care unit; CHD, congenital heart disease, ECMO, extracorporeal membrane oxygenation
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