Journal of Neonatal-Perinatal Medicine 6 (2013) 267–272 267

DOI 10.3233/NPM-1370213
IOS Press

Case Report

Cardiogenic shock as the initial presentation

of neonatal systemic hypertension
N. Xiaoa,∗ , A. Tandonb , S. Goldsteina and A. Lortsb
a Division of Pediatric Nephrology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
b The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

Received 09 January 2013

Revised 23 April 2013
Accepted 16 July 2013

Abstract. Neonatal systemic hypertension is an underappreciated etiology of cardiac failure. We present a series of three neonates
who presented in cardiogenic shock secondary to severe hypertension, recognized after initial resuscitation efforts. Although
the underlying etiology of the hypertension varied, all three patients had improved hemodynamics after their blood pressure was
controlled. These cases suggest that neonates presenting in cardiogenic shock with hypertension, and without structural heart
disease, may benefit from a thorough renal evaluation and institution of anti-hypertensive therapy.

Keywords: Infant, neonate, cardiogenic shock, hypertension

1. Introduction 2. Patient presentation

Cardiogenic shock in infancy is usually the result of 2.1. Case 1

congenital, structural heart disease (specifically left-
sided obstructive lesions), a familial myocardial abnor-
mality, myocarditis, or a metabolic syndrome. Severe
systemic hypertension is a rare but important cause of
cardiac failure [1–3]. When an infant presents in car-
diogenic shock with an echocardiogram negative for
structural heart disease, secondary hypertension must
be ruled out after initial stabilization. A thorough diag-
nostic workup and timely management of systemic
hypertension are essential to minimize the effects of
increased afterload on the dysfunctional myocardium.
We describe the clinical course, diagnostic workup
and long term follow-up of three neonatal cases where
hypertension led to cardiogenic shock.
∗ Corresponding
author: Dr. Nianzhou Xiao, Pediatric Nephrol-
ogy and Hypertension, Cincinnati Children’s Hospital Medical
Center, 3333 Burnet Avenue – S215, Cincinnati, 45229 OH, USA.
Tel.: +1 513 636 8647; E-mail: Nianzhou.Xiao@cchmc.org.
A term female newborn with an uneventful deliv-
ery was transferred to the nursery on day of life 1
(DOL 1) for poor feeding; by DOL 3 she appeared pale,
mottled, developed prolonged capillary refill, tachycar-
dia, tachypnea, and fatigued quickly with feeds. Her
systolic blood pressures (SBP) were 110–120 mmHg,
measured with oscillometric blood pressure cuff.
Normal SBP range for term infant at DOL 3 is
65–89 mmHg [4]. She had cultures drawn and antibi-
otics were started. On DOL 5 she was acidotic
and transferred to our neonatal intensive care unit
(NICU). This patient had not had an umbilical line.
On admission, she was gray and mottled, had diffi-
cult to palpate pulses, and had poor activity. She had
increased respiratory effort, with a respiratory rate of
50 breaths per minute, heart rate of 180 beats per
minute, blood pressure of 114/85, and oxygen satu-
ration 100% on room air. There were no murmurs or

1934-5798/13/$27.50 © 2013 – IOS Press and the authors. All rights reserved
268 N. Xiao et al. / Cardiogenic shock as the initial presentation of neonatal systemic hypertension
140 Renin=388
Aldosterone=320
120 BNP=8737
Blood pressure (mmHg)
100
80
60
40
Nitroprusside
20
0
5 6
Fig. 1. Sequence of blood pressure, antihypertensive therapy, and important lab results for case 1. BNP, brain natriuretic peptide. DOL, day of
life. SBP, systolic blood pressure. DBP, diastolic blood pressure.
gallops. An echocardiogram demonstrated normal car-
diac anatomy and an unobstructed aortic arch but poor
biventricular systolic function (left ventricular shorten-
ing fraction of 11%), which prompted a transfer to our
cardiac intensive care unit (CICU). The brain natri-
uretic peptide (BNP) level, a marker of myocardial
dysfunction, was >8737 pg/mL (normal <100 pg/mL);
and her serum lactate was elevated to 5.4 mmol/L (nor-
mal <1.5 mmol/l). All other laboratory values were
within normal limits; specifically, a blood urea nitro-
gen level (BUN) of 8 mg/dL and serum creatinine
level of 0.7 mg/dL (likely reflecting maternal creatinine
levels).
Once intubated and stabilized, she had signifi-
cant hypertension (Fig. 1) despite increasing doses
of a nitroprusside infusion from 0.5 mcg/kg/min to
2 mcg/kg/min. Intravenous enalaprilat (highest dose:
20 mcg/kg per dose every six hours) was added to the
antihypertensive regimen on DOL 6. Both a peripheral
plasma renin activity measurement and aldosterone
level (not available until later) collected on DOL 6 were
elevated at 388 ng/mL/hr (normal: 2.0–35.0 ng/mL/hr)
and 320 ng/dL (normal: 5.0–132.0 ng/dL), respec-
tively. Renal ultrasound showed a right kidney
measuring 4.1 cm and a left kidney measuring 4.8 cm.
There was no right renal arterial waveform so a right
renal arterial thrombosis was suspected. The infant and
mother had an extensive thrombophilia work up, which
revealed a normal thrombotic profile for age, negative
Renin=62.8 BNP=406
Enalaprilat
Enalapril
Enoxaparin
7 8 9 10 11 12 13 14 15 16 17 18 19 20
DOL
SBP median DBP median
anti-phospholipid antibody profile and normal genetic
polymorphism, which includes factor V Leiden 1691,
prothrombin 20210, MTHFR 677, MTHFR 1298, and
PAI-1 (5G/4G). Therapeutic enoxaparin was initiated
on DOL 8. A CT angiogram done on DOL 9 confirmed
a right renal artery embolism/thrombosis, and a small
right kidney infarct. After three days of enoxaparin
treatment, her blood pressure improved. The renin
activity level decreased to 62.8 ng/mL/hr and BNP
level checked on DOL 15 decreased to 406 pg/mL. A
renal ultrasound on DOL 18 showed increased blood
flow within the right kidney. The infant’s BP persis-
tently improved and she was discharged home on oral
enalapril and subcutaneous enoxaparin on DOL 20.
She has been followed for 6 months. An echocardio-
gram at 3 months of age revealed normal bilateral
ventricular function (Table 1).
2.2. Case 2
A term female presented on DOL 34 after two days
of newly developed poor feeding and increased respi-
ratory distress at home. In the emergency department,
she was in cardiogenic shock with poor respiratory
effort and poor perfusion. Heart rate was 158 beats
per minute, respiratory rate was 34 breaths per minute
and BP was 73/59 mmHg (normal range for age is
75–95/37–55 mmHg) [4], higher than expected given
clinical status. Four extremity blood pressures were
 N. Xiao et al. / Cardiogenic shock as the initial presentation of neonatal systemic hypertension 269

Table 1

Initial BP improved Discharge or after

Case 1
BUN (5–17 mg/dL) 8 12 19
Creatinine (age dependent) 0.7 0.4 0.5
Renin (newborn: 2.0–35.0 ng/mL/hr; 388 62.8 NA
1–12 months: 2.4–37.0 ng/mL/hr)
Aldosterone (5.0–132.0 ng/dL) 320 NA NA
Lactate (0.7–2.1 mmol/l) 5.4 1 1.4
BNP (<100 pg/ml) 8737 406 NA
SF (35–45%) 11 35 41
MR (−) + + +
Hepatomegaly (−) +++ ++ –
Case 2
BUN (5–17 mg/dL) 12 10 12
Creatinine (age dependent) 0.3 0.3 0.2
Renin (newborn: 2.0–35.0 ng/mL/hr; NA NA NA
1–12 months: 2.4–37.0 ng/mL/hr)
Aldosterone (5.0–132.0 ng/dL) NA NA NA
Lactate (0.7–2.1 mmol/l) 11.4 0.9 1.4
BNP (<100 pg/ml) NA 7923 NA
SF (35–45%) NA 36 38
MR (−) +++ ++ ++
Hepatomegaly (−) ++ + –
Case 3
BUN (5–17 mg/dL) 13 3 9
Creatinine (age dependent) 0.6 0.3 0.3
Renin (newborn: 2.0–35.0 ng/mL/hr; NA 39.2 NA
1–12 months: 2.4–37.0 ng/mL/hr)
Aldosterone (5.0–132.0 ng/dL) NA 58.2 NA
Lactate (0.7–2.1 mmol/l) 14.9 1.3 1.1
BNP (<100 pg/ml) 13567 2919 59
SF (35–45%) 33 39 41
MR (−) +++ ++ +
Hepatomegaly (−) +++ ++ –

concordant. Oxygen saturations were in the low 80%
range. The cardiac examination found a new III/VI
systolic regurgitant murmur heard best over the apex.
She was intubated emergently, given a fluid bolus,
and admitted to the CICU. A bedside echocardiogram
showed moderate to severe mitral regurgitation with
left atrial and left ventricular dilation, an unobstructed
aortic arch, mildly depressed biventricular systolic
function, and normal coronaries. Her BP trended up
to 95/58 mmHg as she was stabilized (Fig. 2). Renal
ultrasound with Doppler was unremarkable. Kidney
function testing showed normal BUN of 12 mg/dL
and a creatinine of 0.3 mg/dL. Enalapril was initi-
ated to further reduce afterload and to achieve optimal
blood pressure control. To augment her blood pres-
sure control she received a nitroprusside infusion for
24 hours from DOL 35 to DOL 36, and two doses of
amlodipine. She was successfully extubated three days
after admission. A repeat echocardiogram on DOL 39
showed a decrease in mitral regurgitation with normal
right and left ventricular systolic function. She was
discharged home on enalapril after 7 days of hospital-
ization (DOL 40).
During follow up, her BP has remained high but is
controlled with titration of enalapril. Her most recent
echocardiogram, one year after the event, showed a
significant decrease in the left ventricular size and left
atrial size with normal systolic function. The etiology
of her hypertension remains unknown.
2.3. Case 3
A term female presented to the emergency depart-
ment (ED) on DOL 9 with poor perfusion and a
decrease in activity level. The pregnancy, delivery and
immediate post-partum period were all uncomplicated.
In the ED, she was unresponsive, with mottled skin,
poor pulses and poor respiratory effort. The respira-
270 N. Xiao et al. / Cardiogenic shock as the initial presentation of neonatal systemic hypertension

120
BNP=7923

100
Blood pressure (mmHg)

80

60

40

Nitroprusside
20 Enalapril
Amlodipine

0
34 35 36 37 38 39 40 DOL
SBP median DBP median

Fig. 2. Sequence of blood pressure, antihypertensive therapy, and important lab results for case 2. BNP, brain natriuretic peptide. DOL, day of
life. SBP, systolic blood pressure. DBP, diastolic blood pressure.

160
Renin=39.2
BNP=13597 BNP=59
Aldosterone=58.2
140
BNP=2919
Blood pressure (mmHg)

120

100

80

60

40
Nitroprusside
20 Captopril Enalapril
Nicardipine
Amlodipine
0
9 11 13 15 17 19 21 23 25
DOL
SBP median DBP median

Fig. 3. Sequence of blood pressure, antihypertensive therapy, and important lab results for case 3. BNP, brain natriuretic peptide. DOL, day of
life. SBP, systolic blood pressure. DBP, diastolic blood pressure.

tory rate was 26 breaths per minute, heart rate was 196
beats per minute and blood pressure was 64/56 mmHg
(normal range for age is 68–88/41–59 mmHg) [4].
Physical exam revealed grade II-III/VI systolic regur-
gitant murmur and severe hepatomegaly. She was
intubated emergently, given a 10 mL/kg normal saline
bolus, and started on a prostaglandin infusion. She
quickly responded with better perfusion. One hour
later, however, her blood pressure elevated to 116/94
(Fig. 3). Her BNP was elevated at 13567 pg/mL. Initial
echocardiogram showed severe mitral regurgitation
with a dilated left atrium, low normal biventricular
systolic function, widely patent aortic arch and bilat-
eral pleural effusions. The prostaglandin infusion was
discontinued. To control her hypertension, an intravas-
cular nitroprusside infusion (between 0.5 mcg/kg/min
to 2 mcg/kg/min) was started and subsequently cap-
topril was prescribed. Renal Doppler ultrasound
 N. Xiao et al. / Cardiogenic shock as the initial presentation of neonatal systemic hypertension
showed patent main renal arteries and main renal
veins bilaterally. Blood pressures stayed above 100/60
until a nicardipine drip (between 0.4 mcg/kg/min
to 0.5 mcg/kg/min) was started on DOL 13. She
was converted to an oral anti-hypertensive regimen
including amlodipine and enalapril, and both the nitro-
prusside and nicardipine infusions were weaned off by
DOL 20 with blood pressures of 80’s/40’s. On DOL
25, BNP normalized to 59 pg/mL. Repeat echocardio-
gram showed her improved mitral regurgitation and
systolic function had normalized. The pleural effusions
and hepatomegaly had resolved. The patient was dis-
charged home on enalapril with well controlled blood
pressures.
Her serum creatinine level was 0.3–0.4 and remained
stable 6 months later. A renal ultrasound at 1 year of age
remained normal, and a repeat echocardiogram about 1
year after the event showed continued improvement of
her mitral regurgitation. The child remains on enalapril
to ensure blood pressure control.
3. Discussion
The incidence of hypertension has been reported to
range from 0.2–0.3% of all neonates [5], and is most
common in preterm infants in NICUs with multiple
co-morbidities. Our three patients were all presumed
to be healthy term infants until they presented in car-
diogenic shock at DOL 4, 35, and 9, respectively. In
each case, hypertension became evident quickly after
the start of resuscitation. The initial blood pressure
was measured with oscillometric blood pressure cuff,
and later via both constant peripheral arterial line and
intermittent oscillometric method. BP measurements
from the two methods matched well. Echocardiograms
were done to rule out significant structural heart dis-
ease, specifically left-sided obstructive cardiac lesions,
and to further define the cardiac phenotype. At pre-
sentation, all three patients had evidence of cardiac
dysfunction with variable left ventricular dimensions
and mitral valve annulus dilation leading to valvular
regurgitation. The variation in chamber enlargement is
due to alterations in preload, which correlates with the
length of time that the newborn had been in low car-
diac output. Unlike the patients in the Patterson et al
study our patients did not have dilated aortic roots when
compared to normal controls [1]. In our cases there
was no evidence of structural heart disease resulting in
a workup for the etiology of cardiac collapse, includ-
271
ing a thorough evaluation for the causes of systemic
hypertension in neonates.
Neonates that present poorly perfused due to a
cardiac problem are usually hypotensive and require
vasoconstrictors to establish adequate blood pressure.
These three infants, however, had normal blood pres-
sure or were hypertensive when they were in shock and
after their initial resuscitation they all became hyper-
tensive. Interestingly, their hypertension (more obvi-
ous in cases 2 and 3) was not responsive to vasodilators.
Instead, they required angiotensin-converting enzyme
(ACE) inhibition for hypertension management, and
with better blood pressure control the severity of
their mitral regurgitation and/or systolic dysfunction
improved. In case 1, enoxaparin was added about 28
hours after the initiation of enalaprilat so it is hard to
argue blood pressure improvement was mainly due to
adding enalaprilat. However, patient’s BP continued
to decrease and remained well controlled by enalapril
when nitroprusside was discontinued on DOL 11.
These cases illustrate that systemic hypertension can
cause cardiogenic shock, and that a complete evalu-
ation and the timely institution of anti-hypertensives
should be considered in the neonatal patient with
hypertension and systolic dysfunction or mitral regur-
gitation. Elevated blood pressures in the neonate
should not be dismissed without further evaluation.
The initial renal evaluation should include palpation of
femoral pulses, serum electrolytes, serum creatinine,
plasma renin activity measurement, serum aldosterone
level, urinalysis and a Doppler renal ultrasound in addi-
tion to an echocardiogram and cardiac biomarkers such
as BNP.
The laboratory tests recommended can be are diffi-
cult to interpret in newborns. Koch and Singer reported
that plasma BNP decreases during the first 2 week
of life by almost 5 folds [6]. Because individual val-
ues vary greatly, BNP values less than 100 pg/ml are
usually taken as normal. In our presented cases, ini-
tial BNP values were significantly elevated by both
standards. Renin activity varies with age and patient’s
position. For infants, the reference values were avail-
able for supine position only [7]: the normal range
for 1–7 days is 2.0–35.0 ng/mL/hr; for 1–12 months
is 2.4–37.0 ng/mL/hr. The initial renin activity for case
1 was significantly elevated (388 ng/mL/hr) which is
consistent with the underlining causes of hyperten-
sion: renal arterial thrombosis. If renin activity is
noticed to be significantly elevated during hyperten-
sion workup, etiologies limiting kidney blood supply
272 N. Xiao et al. / Cardiogenic shock as the initial presentation of neonatal systemic hypertension
(such as arterial stenosis and thrombosis) should be
strongly suspected.
Renal ultrasound may help to narrow the differential
diagnosis and guide hypertension management before
other results are available. Hypertension due to high
renin levels usually responds to ACE inhibitors, but
this class of drugs is contraindicated in cases of bilat-
eral renal arterial stenosis. In all three cases, renal
ultrasound ruled out bilateral renal arterial obstruc-
tion, thus ACE inhibitors could be cautiously used
to achieve optimal BP control. In case 1, renal ultra-
sound with Doppler identified the right renal arterial
thrombosis and anti-coagulation was added to treat the
underlying cause and prevent further kidney damage.
We suggest that systemic hypertension associated car-
diogenic shock can be reversed with adequate blood
pressure control.
Financial disclosure statement
The authors have no financial relationships or con-
flicts of interest relevant to this article.
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