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Indian Pediatr 2011;48:
773-778 |
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Echocardiographic Parameters of Patent Ductus
Arteriosus in Preterm Infants |
A Khositseth, P Nuntnarumit and P Chongkongkiat
From the Department of Pediatrics, Faculty of Medicine,
Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Correspondence to: Anant Khositseth, Department of
Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol
University, 270 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand.
Email: [email protected]
Received: June 18, 2010;
Initial review: August 2, 2010;
Accepted: September 14, 2010.
Published online:
2011 March 15.
PII: S0974755910INPE00035-1
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Objective: To analyze cardiovascular parameters by
echocardiography in preterm infants with patent ductus arteriosus (PDA).
Setting: Tertiary-care pediatric university
hospital.
Design: Cross-sectional, hospital-based study.
Participants: 58 preterm infants, gestational age
less than 33 weeks.
Measurements: A complete 2-dimension, M-mode, color
doppler echocardiography was performed in each preterm infant at
approximately 48 hours of life.
Results: Each preterm was categorized into
hemodynamically significant PDA (hsPDA) (n=17, 29.3%), non-hemodynamically
significant PDA (non-hsPDA) (n = 12, 20.7%), and no PDA (non-PDA) (n=29,
50%). Gestational age (29.4 ± 1.2 wk) and birth weight (1237 ± 358 g) of
infants in hsPDA were significantly lower than those in non-PDA group
(30.8 ±1.3 wk, 1543 ± 361 g, P = 0.001), as compared to those in
the non-hsPDA group (29.5 ± 2.3 wk, 1296 ± 462 g). Cardiovascular
parameters including left atrium/aorta ratio, left atrium volume index,
left ventricular dimensions and volumes, stroke volume, and cardiac output
in hs-PDA were significantly greater than those in non-hsPDA and non-PDA.
LV systolic and diastolic functions were not significantly different in
each group. LV global function in hsPDA (0.34 ± 0.13) was significantly
lower than that in non-PDA (0.45 ± 0.13, P = 0.01).
Conclusions: In preterm infants with hsPDA, there
was a volume load of the left heart causing increased stroke volume and
cardiac output. The hsPDA could be detected by echocardiography even in
the first 48 hours. The left atrial volume index may be a better indicator
of the volume load of the heart.
Key words: Diastolic function, Echocardiography,
Left ventricular dimension, Patent ductus arteriosus, Preterm, Systolic
function.
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Patent ductus arteriosus (PDA) in preterm infants is common with an
incidence of 34% by echocardiography on day 3 of life [1]. It is more
common in preterm infants with birth weight (BW) <1000 g (58.8%) than in
those with BW >1000 g (25%) and more common in those with gestational age
(GA) <30 weeks (wk) (52.2%) than in those with GA >30 wk (23.7%) [1].
Although PDA can be found in normal healthy term and preterm infants up to
72 h [2], some preterm infants, especially with respiratory distress may
have PDA beyond that period [3]. PDA is associated with morbidities,
especially in preterm infants, resulting in pulmonary hemorrhage,
pulmonary congestion, pulmonary edema, and congestive heart failure [4].
Bronchopulmonary dysplasia, intraventricular hemorrhage, and necrotizing
enterocolitis are also increased in preterm infants with PDA [5,6]. PDA
can cause volume overload of the left atrium (LA) and left ventricle (LV).
Our study was conducted to analyze the echocardiographic findings in
preterm infants at early age with hemodynamically significant PDA (hsPDA)
compared to those with non-hemodynamically significant PDA (non-hsPDA) and
those without PDA.
Methods
A cross-sectional study was conducted at the neonatal
intensive care unit (NICU) and sick newborn nursery in the setting of a
tertiary-care pediatric university hospital. All preterm infants, GA <33
wk were eligible. We excluded infants with congenital heart defects (CHDs)
other than PDA, major congenital anomalies, Apgar score <3 at 5 minute,
clinical sepsis or septicemia, necrotizing enterocolitis, renal failure,
persistent pulmonary hypertension, and those receiving indomethacin or
ibuprofen. Echocardiography was performed in each patient at approximately
2 days of age. This study was approved by the Institutional Review Board,
and written consent for participation was obtained from the parents or
guardians.
Two-dimensional, color doppler, and M-mode
echocardiography using a Sonos Helwett-Peckard 4500 echocardiography
machine with curvilinear 8 MHz transducer was performed to assess the
narrowest diameter of the PDA at its pulmonary end and to rule out other
CHDs by a single pediatric cardiologist blinded to the clinical
information.
An M-mode in the parasternal short axis view at the
level of the base of the heart and papillary muscles was performed to
measure the left atrium (LA) and the aortic root (Ao) ratio (LA/Ao) and
left ventricle (LV) dimensions including left ventricular end-diastolic
dimension (LVEDD), left ventricular end-systolic dimension (LVESD) [7].
The left ventricular end-diastolic dimension index (LVEDDI) and left
ventricular end-systolic dimension (LVESDI) were equal to LVEDD and LVESD
divided by body surface area (BSA), respectively. The left ventricular
end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were
calculated by Teichholzs method [8]. Left ventricular end-diastolic
volume index (LVEDVI, ml/m 2) was equal to LVEDV divided by BSA.
The left ventricular ejection fraction (LVEF) and the
left ventricular fractional shortening (LVFS) were calculated using the
previously described formula [7]. The normal values for LVEF and LVFS are
³55% and
³25%, respectively
[7]. Predicted LVEDD was calculated according to the formula of Henry [9].
The ratio of LVEDD to predicted LVEDD expressed in percentage (%LVEDD) was
calculated using the following formula: %LVEDD = [(measured LVEDD)/(predicted
LVEDD)]*100. The normal value for %LVEDD is <112% [10].
Cardiac output (CO) was calculated from stroke volume (SV)
multiplied by heart rate and SV was equal to LVEDV minus with LVESV. SV
and CO were represented as mL/kg and mL/min/kg, respectively. A
measurement of left atrial volume (LAV) was obtained from the prolate
ellipse method using apical 4-chamber and parasternal long-axis views at
ventricular end systole (maximum LA size). All 3 dimensions (D1, D2, and
D3) were measured and to calculate LAV by using formula: [D1 Χ D2 Χ D3] Χ
[0.523] [11]. Left atrium volume index (LAVI) was equal to LAV divided by
BSA.
Left ventricular diastolic function was assessed by
pulse-wave Doppler at the tip of the mitral valve inflow to measure E, A,
E/A ratio, and deceleration time (DT). Left ventricular myocardial
performance index (LV MPI) or Tei index has been devised to incorporate
both systolic and diastolic time intervals in expressing global
ventricular performance [12].
A hsPDA was diagnosed by findings of
³2 of these 3
echocardiographic findings: PDA narrowest diameter >1.4 mm, the percentage
of the ratio of the time velocity interval (TVI) of the diastolic
retrograde flow to the TVI of the systolic anetero-grade flow along the
descending aorta ≥30%,
and LA/Ao ≥1.5 [4],
whereas non-hsPDA was the presence of PDA, but not meet the above
criteria. The non-PDA group had no PDA.
Clinical diagnosis of hsPDA was defined as an infant
with at least two of the following findings namely heart murmur,
persistent tachycardia (heart rate >160/ min.), active precordium,
bounding pulse or pulse pressure >25 mmHg, hepatomegaly, pulmonary
hemorrhage or increasing ventilatory support, and cardiomegaly or
pulmonary congestion.
Students t test was used for continuous
variables or Mann-Whitney U test if data were not normal distribution.
Pearson correlation was used to demonstrate correlation. P value
<0.05 was considered to be statistically significant.
Results
Of 58 preterm infants (31 males), those whose GA were
30.1 ± 1.7 wk and BW 1402 ± 403 g; 17 (29%) had hsPDA whereas 12 (21%) had
non-hsPDA, and 29 (50%) had no PDA (non-PDA). Overall, GA, BW, and BSA in
PDA group were significantly less than those in non-PDA group (30.8±1.3
wk, 1543 ± 361 g, 0.13 m 2; P<0.001, P<0.007, P=0.006).
GA, BW, and BSA in hsPDA group were not significantly different from those
in non-hsPDA group and those in non-hsPDA were also not significantly
different from those in non-PDA group, however, those in hsPDA group were
significantly lower than those is non-PDA group (Table I).
Mean heart rate in all patients was 149±10/min and not significantly
different in each group. Only 4 patients were clinically diagnosed as
having hsPDA. Echocardio-graphy was performed in hsPDA, non-hsPDA, and
non-PDA groups at mean age of 44.2 ± 10.7, 41.7 ± 10.9, 45.4 ± 9.1 h,
respectively (P>0.05). As expected, mean PDA diameter in hsPDA (2.4
± 0.8 mm) was significantly larger than in non-hsPDA (1.1 ± 0.3 mm), P<0.0001.
Cardiovascular parameters assessed by echocardiography were summarized in
Table II. Overall, LA/AO ratio, LAVI, LVESDI, LVEDDI, %LVEDD,
LVEDVI, LVESVI, SV, and CO in hsPDA group were significantly greater than
those in non-hsPDA and non-PDA groups whereas those parameters in non-hsPDA
and non-PDA were not significantly different. LV systolic function and
diastolic function were not significant different in all three groups. LV
global function in hsPDA group (0.34 ± 0.13) was significantly lower than
that in non-PDA group (0.45 ± 0.13). However, LV MPI in hsPDA and non-hsPDA
(0.39 ± 0.12) were not significantly different and LV MPI in non-hsPDA and
non-PDA were also not significantly different.
TABLE I Patient Characteristics of The Study Population
Patient characteristics |
PDA |
No PDA(n = 29) |
P value |
|
hsPDA(n = 17) |
non-hsPDA(n = 12) |
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|
Gestational age (wk) |
29.4 ± 1.2 |
29.5 ± 2.3 |
30.8 ± 1.3 |
0.001 |
Birthweight (g) |
1.237 ± 358 |
1.296 ± 462 |
1.543 ± 361 |
0.008 |
Age at echo (h) |
44.2 ± 10.7 |
41.7 ± 10.9 |
45.4 ± 9.1 |
NS |
PDA size (mm) |
2.4 ± 0.8 |
1.1 ± 0.3 |
0 |
<0.001* |
Body surface araq (m2) |
0.11 |
0.12 |
0.13 |
0.007 |
Heart rate (/min) |
151 ± 11 |
148 ± 13 |
147 ± 9 |
NS |
NS: No significant difference between the three groups;
Significance of difference between hsPDA group and non-hsPDA group,
non-hsPDA group and no PDA group*, and hsPDA and no PDA group; echo
echocardiography; hsPDA: hemodynamically significant patent ductus
arteriosus; M: male; non-hsPDA: non hemodynamically significant
patent ductus arteriosus; PDA: patent ductus arteriosus |
LVEDVI was represented as volume load of the left
ventricle. LA/AO ratio was correlated fairly with LVEDVI (r = 0.361, P<0.01);
however, LAVI was correlated more with LVEDVI (r = 0.633, P<0.001).
Table II Echocardiographic Parameters of the Study Population
Cardiovascular Parameters |
PDA |
No PDA(n = 29) |
P value |
|
hsPDA(n = 17) |
non-hsPDA(n = 12) |
|
|
LA/AO
|
1.5 ± 0.3 |
*1.2 ± 0.2 |
1.2 ± 0.2* |
0.001, 0.02 |
LAVI (mL/m2) |
9.1 ± 4.2 |
*6.1 ± 2.0 |
5.4 ± 2.0* |
0.003, 0.03 |
LVOT (mm) |
5.3 ± 0.7 |
5.2 ± 0.6 |
5.3 ± 0.5 |
NS |
LVESDI
(mm/m2) |
9.2 ± 1.6 |
*7.6 ± 2.1 |
7.4 ± 1.3* |
0.0001, 0.03 |
LVEDDI
(mm/m2) |
13.2 ± 2.0 |
*11.7 ± 1.6 |
11.0 ± 1.3* |
0.001, 0.03 |
%LVEDD
(%) |
109.2 ±14.5 |
*97.5 ± 13.7 |
97.1 ± 11.1* |
0.003, 0.04 |
LVEDVI (mL/m2) |
52.6 ± 18.6 |
*40.2 ± 14.0 |
40.4 ± 12.1* |
0.009, 0.04 |
LVESVI (mL/m2) |
19.9 ± 7.0 |
*13.9 ± 7.2 |
14.0 ± 5.8* |
0.004, 0.04 |
SV (mL/kg) |
3.1 ± 1.1 |
*2.4 ± 0.6 |
2.2 ± 0.5* |
0.005, 0.04 |
SVI (mL/m2) |
33.1 ± 12.8 |
26.3 ± 8.1 |
26.3 ± 7.2 |
NS |
CO (mL/kg) |
462 ± 154 |
*352 ± 101 |
323 ± 78* |
0.002, 0.04 |
CI (mL/min/m2) |
#4.9 ± 1.8 |
*3.9 ± 1.2 |
#3.9 ± 1.0* |
0.04, NS |
LV EF (%) |
62 ± 5 |
68 ± 12 |
66 ± 8 |
NS |
LV FS (%) |
31 ± 4 |
36 ± 13 |
34 ± 6 |
NS |
E/A ratio |
0.9 ± 0.2 |
1.0 ± 0.4 |
0.9 ± 0.2 |
NS |
DT (ms) |
81 ± 43 |
97 ± 42 |
103 ± 25 |
NS |
LV MPI |
0.34 ± 0.13 |
*0.39 ± 0.12 |
0.45 ± 0.13* |
0.01 |
AO, aorta; CI, cardiac index; CO, cardiac output; DT, deceleration time; LA, left atrium; LAVI, left atrial volume index;
LVEDDI, left ventricular end-diastolic dimension index; LVEDVI, left ventricular end-diastolic volume index;
LV EF, left ventricular ejection fraction; LV FS, left ventricular fractional shortening;
LV MPI, left ventricular myocardial performance index; LVOT, left ventricular outflow tract;
LVESDI, left ventricular end-systolic dimension index; LVESVI, left ventricular end-systolic volume index;
SV, stroke volume; SVI, stroke volume index; %LVEDD, the percentage of the ratio of left ventricular end-diastolic
dimension to predicted left ventricular end-diastolic dimension. Significance of difference between hsPDA group
and non-hsPDA group, non-hsPDA group and no PDA group*, and hsPDA and no PDA group;
hsPDA: hemodynamically significant patent ductus arteriosus; M: male; non-hsPDA: non hemodynamically significant
patent ductus arteriosus: PDA, patent ductus arteriosus.
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Discussion
In this study, the incidence of PDA in preterm infants
<33wk gestation on the second day of life was 50%. However, only 29% had
hsPDA while 21% had non-hsPDA. Mean GA and BW in hsPDA group were
significantly lower than in non-PDA group whereas those in non-hsPDA group
were not significantly different from the other two groups. These findings
demonstrated that hsPDA was found to be more common in those with lower GA
and BW. Clinical diagnosis of hsPDA in the early age of neonates was not
sensitive and specific.
Systolic and diastolic LV dimensions, the LA dimension,
and the LA volume in hsPDA were significantly increased. These findings
confirmed that in hsPDA, when compared to non-hsPDA and non-PDA, there was
volume load to the left side of the heart as a result of left to right
shunt from the descending aorta across the PDA into the pulmonary artery,
which then returned to LA and LV. The SV and CO were also significantly
increased in hsPDA when compared to those in non-hsPDA or non-PDA. There
was significant higher SV and CO in hsPDA group when compared to non-hsPDA
and non-PDA groups which were consistent with the previous reports
[13,14]. Walther, et al. [14] reported 25 preterm infants with BW
<1250 g and found that 11 preterm infants who had CO between 190 and 310
mL/min/kg which was within the normal range never developed symptomatic
PDA when compared to 14 preterm infants developing symptomatic PDA had an
increase in left ventricular output from their baseline more than 60 mL/min/kg
at least 24 h before symptoms developed. Lindner, et al. [13]
reported that neonates with symptomatic PDA had high SV (2.69, 1.98-4.10
mL/kg) and CO (419, 305-562 mL/min/kg), which later decreased to 1.63
(1.22-1.98) mL/kg and 246 (191-292) mL/min/kg after PDA ligation. One of
the echocardiographic parameters which was found to be sensitive for
detecting sign of volume load to the left ventricle was LAVI. In this
study, LAVI in hsPDA group was significantly higher when compared to LAVI
in non-hsPDA and non-PDA groups. Moreover, LAVI was more correlated to
LVEDVI (r =0.633) than LA/AO ratio (r = 0.363). Previous
reports suggesting LA/AO ratio as a sensitive and specific parameter in
detecting PDA may be limited since the aorta was probably enlarged due to
the high SV and CO, leading to no change in LA/AO [1]. We suggest that
LAVI should be considered when performing the echocardiography to detect
hsPDA which had hemodynamic signi-ficance. In early neonatal life (within
2 days), hsPDA could be diagnosed by echocardiography even without
clinical symptoms. Heart rate in each group was not significantly
difference. Afilune, et al. [1] also found that on the third day of
life, only 52% of preterm neonates with PDA had clinical symptoms.
Systolic function and diastolic function of the left
ventricle were not significantly different in each group even in hsPDA
which had left ventricular volume overload and higher SV and CO.
Interestingly, LV MPI in hsPDA group was significantly lower than LV MPI
in non-PDA group. Murase, et al. [15] reported that LV MPI at 48 h
was not significantly different in preterm neonates with PDA and without
PDA (0.35 ± 0.16 vs 0.36 ± 0.16). However, in that report they did
not categorize hs-PDA and non-hsPDA. LV MPI represents the ratio of the
sum of isovolumic relaxation time (IVRT) and isovolumic contraction time (IVCT)
to the left ventricular ejection time (ET). Systolic dysfunction results
in a prolongation of the IVCT and a shortening of ET [12]. Both systolic
and diastolic dysfunction cause abnormality in myocardial relaxation
resulting inprolongation of the IVRT. Murase, et al. [15] reported
the effect of PDA on LV MPI in very low birth weight infants and found
that there was no significant relationship between LV MPI and
echocardiographically detectable PDA. The LV MPI of infants with PDA and
without PDA at any age since birth (12, 24, 36, 48, 72, and 96 h) were not
significant different. LV MPI at 48 h, the same period of time as that of
our study, was 0.35 ± 0.22 and 0.36 ± 0.16. However, in this study, we
found that LV MPI in hsPDA group was significantly lower than in non-PDA
group. Although there was no statistically significant time-course
difference in LV MPI of neonates at any GA, however, at postnatal age from
48 to 96 h, the LV MPI tended to be higher in preterm who had higher GA
and BW [15]. This may explain why in this study, the LV MPI in non-PDA was
higher than LV MPI in hsPDA group, since GA and BW in non-PDA group were
significantly higher than those in hsPDA group.
We conclude that in preterm infants with hsPDA, there
was a volume load of the left heart causing increased stroke volume and
cardiac output. Echocardiography was more sensitive in detecting hsPDA as
early as within 48 hours of age. The left atrial volume index was found to
be the better indicator of the volume load of the heart than the left
atrium to the aorta ratio.
Contributors: All authors contributed to study
design, data acquisition, literature review and drafting the manuscript.
Funding: Faculty of Medicine Ramathibodi Hospital,
Mahidol University.
Competing interests: None stated.
What is Already Known?
Left atrium to aorta ratio is increased in hemodynamically
significant patent ductus in preterm infants.
What This Study Adds?
Left atrial volume index
is more sensitive than left atrium to aorta ratio in determining
volume load of the left heart.
Cardiac functions including
systolic and diastolic function are normal even volume load of the
left heart.
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