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In-Hospital Arrhythmia Development and Outcomes in Pediatric Patients With Acute Myocarditis
In-Hospital Arrhythmia Development and Outcomes in Pediatric Patients With Acute Myocarditis
Arrhythmias
were
associated
with
low
voltages
on
the
electrocardiogram (14 of 34, 41% vs 6 of 47,13%; odds ratio [OR] 4.78, 95%
confidence interval [CI] 1.60 to 14.31) and worse outcome (mechanical
support, orthotopic heart transplant, or death; OR 7.59, 95% CI 2.61 to
22.07) but were not statistically significantly associated with a fulminant
course, ST changes, initial myocardial function, lactate, creatinine level, Creactive protein and/or erythrocyte sedimentation rate, or troponin I level,
after adjusting for multiple comparisons. Subacute arrhythmias were
associated with preceding ST changes (10 of 15, 67% vs 15 of 59, 25%, OR
5.87, 95% CI 1.73 to 19.93). All patients surviving to discharge had
arrhythmia resolution or control before discharge (10 on antiarrhythmic),
with 1 exception (patient with complete heart block requiring a pacemaker).
At 1-year follow-up, there were 3 recurrences of ventricular arrhythmias, but
no arrhythmia-related mortality. In conclusion, arrhythmias are common in
pediatric patients with myocarditis, occurring in nearly 1/2 of all hospitalized
children and are associated with a worse outcome. Early identification of
subacute
arrhythmias
using
electrocardiographic
changes
may
help
arrhythmia treatment. 2014 Elsevier Inc. All rights reserved. (Am J Cardiol
2014;113:535-540)
these findings, we defined additional patients if (4) left ventricular enddiastolic volume z score was <3 and recovery of systolic function occurred
within 1 year of diagnosis. Exclusion criteria included a history of congenital
heart disease, cardiomyopathy, or arrhythmias.
the need for any of the following: mechanical support, orthotopic heart
transplant (OHT), or death.
All electrocardiograms (ECGs) obtained during the hospital course were
evaluated by 2 pediatric electrophysiologists. Timing of development and
resolution
of
electrocardiographic
changes
including
ST
elevation
or
depression, low voltages, and left bundle branch block (LBBB) was recorded
and compared with arrhythmia onset. Low voltage was defined as <0.5 mV
in all limb leads or <1.0 mV in all precordial leads. Abnormal ST segments
were defined as >0.2 mV ST elevation or depression in at least 2 leads. ST
segments were not evaluated if the patient had CHB or an intraventricular
conduction delay.
Statistical analysis was performed using SAS, version 9.3 (SAS Institute
Inc., Cary, North Carolina). Continuous variables are presented as medians
with ranges. Categorical variables are presented as counts with percentages.
Univariate binary logistic regression models were built to predict associations
between arrhythmias, worse outcomes, and subacute arrhythmias. Variables
for the primary analysis were chosen before data collection. Because of the
small numbers of patients and to account for multiple comparisons in the
planned primary analysis of arrhythmia predictors, the Bonferroni correction
was applied and statistically significant data were defined as a p value of
<0.0056. Subsequent to the primary analysis, a secondary analysis of
electrocardiographic findings and associations with worse outcomes and
subacute arrhythmias was performed. Because these variables were not
chosen a priori, this analysis was termed exploratory, and a standard p value
of <0.05 was used.
Results
A total of 85 patients (59% men) presented at a median age of10 years
(range, 1 day to 18 years). Demographic data and presenting symptoms are
listed in Table 1. Arrhythmias occurred in 38 (45%) of 85 patients, acutely in
16, subacutely in 12, and both acute and subacute in 9. In 1 patient, the
timing of arrhythmia onset was unknown. Among the 85 patients, a
fulminant course was seen in 41 (50%). A majority (80%) received
intravenous immunoglobulin, and 21% received steroids in addition to
intravenous
immunoglobulin.
Sixteen patients
did
occur
either
at
presentation
(acute)
or
during
their
of
all
ventricular
arrhythmias,
including
those
for
which
predictors
for
the
development
of
subacute
who did not develop new arrhythmias, patients with subacute arrhythmias
were more likely to demonstrate ST elevation or depression before subacute
arrhythmia onset (10 of 15, 67% vs 15 of 59, 25%; OR 5.9, 95% CI 1.7 to
19.9) but not low voltages (Table 3).
During hospitalization, 32 (84%) of 38 patients received antiarrhythmic
medication(s) for a median period of 11 days (range, 1 to 144).
Antiarrhythmic therapy was initiated for SVT in 13%, high-grade ventricular
ectopy in 3%, and VT or VF in 88%. At discharge, 10 patients remained on
antiarrhythmic therapy (1 for SVT, 1 for high-grade ventricular ectopy, and 8
for VT). Median follow-up for patients with clinically significant arrhythmias
was 2 years (range, 11 days to 13 years). During the follow-up period,
antiarrhythmic medication was discontinued in 4 patients; however, in 2
patients discharged home without medications, antiarrhythmic therapy was
restarted because of nonsustained VT noted on outpatient monitoring at 2
and 3 months after discharge. At the last follow-up, 5 of the 10 patients were
still on antiarrhythmic medications for ventricular arrhythmias (4 VT and 1
high-grade ventricular ectopy). Among these 5 patients who remain on
antiarrhythmic therapy, follow-up ranged from 1 to 30 months.
Cardiopulmonary resuscitation (CPR) was required at presentation for 15
patients.
Four
patients
required
CPR
for
arrhythmias
during
their
places the patient at 3 times the risk for clinically significant arrhythmias, an
elevated lactate level increases the risk eightfold, elevated creatinine level
4.5-fold, and ST changes 2.9-fold. These findings may merit clinical
consideration. Interestingly, the initial degree of myocardial function is not
associated with arrhythmia development. Therefore, mild dysfunction does
not equate to less arrhythmia risk, and clinicians should have a heightened
awareness regardless of the degree of myocardial dysfunction.
Because of multiple comparisons and potentially related predictor values
(i.e., poor myocardial function and elevated lactate or creatinine levels), the
Bonferroni
correction
was
applied
to
prevent
false
positives.
This
edema
may
be
an
explanation
for
both
arrhythmia
vs
ventricle
vs
conduction
system
and
subendocardium
vs
epicardium), may explain why some patients have only VT or heart block,
whereas others have both. Progression or extension of myocardial edema
may explain why some patients are susceptible to the development of new
arrhythmias after admission. Such myocardial edema could potentially
which
patients
may
develop
arrhythmias
after
initial
In our exploratory analysis, our data also suggest a similar finding among
pediatric patients, with an LBBB pattern resulting in an eightfold increase in
risk for a clinically worse outcome.
This is a retrospective study limited to available clinical information.
Identifying patients with a definitive diagnosis of myocarditis is a challenge.
Only 1/2 (52%) of all patients received endomyocardial biopsy, and of those,
just >2/3 (68%) had a pathologically confirmed diagnosis. Acute myocarditis
was a clinical diagnosis in most cases. Although we attempted to exclude
patients with primary dilated cardiomyopathy, we cannot eliminate potential
inclusion of this group of patients. By attempting to exclude the patients with
dilated cardiomyopathy, we also likely excluded some patients with chronic
myocarditis. Electrocardiographic interpretation was limited to available
ECGs, and the number of ECGs per patient varied, which may have affected
our data. Potentially, patients who were clinically ill may have undergone
more electrocardiographies. Lastly, follow-up of arrhythmias varied. Some
patients received outpatient Holter or event monitors, whereas others did
not. We therefore cannot exclude the possibility of uncaptured or occult
arrhythmias that occur on an outpatient basis. Although the findings in this
study are very interesting, many predictors were analyzed. Despite the high
ORs suggesting a clinical effect, data that were not statistically significant
should be interpreted with caution because of a greater probability of false
positives. The findings in this study warrant further investigation and
replication.
Table 1. Demographics, clinical presentation, and initial laboratory values
Variable
Arrhythmia
No Arrhythmia
Men
(%)
85 20/38 (53)
Median age
Gastrointestinal
Upper
(%)
30/47 (64)
yrs)
85 17/38 (45)
85 12/38 (32)
27/47 (57)
26/47 (55)
85 16/38 (42)
19/47 (40)
respiratory
Dyspnea
Palpitations
85 3/38 (8)
Laboratory values at presentation
Elevated
protein
reactive
C- 46 15/18 (83)
3/47 (6)
23/28 (82)
Elevated
81 9/36 (25)
4/45 (9)
creatinine
Elevated
74 28/34 (82)
26/40 (65)
aspartate
Elevated brain
22 9/12 (75)
natriuretic peptide
ID pathogen found 64 16/32 (50)
Initial echocardiogram
Mechanical
85 17/38 (45)
6/10 (60)
14/32 (44)
6/47 (13)
support
Median length of
85 19 (5 244)
hospital stay (days)
8 (171)
Arrhythmia (%)
No Arrhythmia (%)
OR
95% CI
79
81
15/32 (47)
14/34 (41)
11/47 (23)
6/47 (13)
0.0319
0.0051*
2.9
4.8
1.1-7.6
1.6-14.3
Elevated creatinine 81
Elevated CRP/ESR
53
Troponin I
49
Myocardial function
9/36 (25)
17/21 (81)
4.4 (0.1-50.0)
4/45 (9)
27/32 (84)
2.0 (0.1-46.4)
0.0102
0.7458
0.7219
0.5783
4.5
0.8
1.0
1.4-14.3
0.2-3.4
0.96-1.1
Mild vs severe
Worse outcome
20/38 (53)
6/47 (13)
1.5
7.6
0.6-4.2
2.6-22.1
Arrhythmia
Any ST change
Any low voltage
85
0.0002*
Worse outcome is defined as the need for mechanical support, orthotopic heart transplant,
or death. CRP = C-reactive protein; ESR = erythrocyte sedimentation rate.
* p <0.0056 considered statistically significant.
OR
95% CI
2/58 (3)
0.0197
7.8
1.4-43.6
No Subacute Arrhythmia
OR
95% CI
Worse outcome
LBBB
81
5/23 (22)
n
Subacute arrhythmia
Subacute Arrhythmia
Preceding
voltages
Worse
low
80
3/19 (16)
13/61 (21)
0.6008
0.7
0.2-2.7
outcome is defined as the need for mechanical support, orthotopic heart transplant,
or death.