Full text of DOI:10.1007/PL00007266

Heart Vessels (2000) 15:144–146
© Springer-Verlag 2000
CASE REPORT
Michi Wakaumi · Tsuyoshi Shiga · Katsuhiro Nozaki
Katsuhito Fujiu · Kazuhiro Shimaya · Naoko Ishizuka
Naoki Matsuda · Hiroshi Kasanuki
Plasma brain natriuretic peptide as a parameter to assess efficacy of
continuous intravenous infusion of prostacyclin (epoprostenol) to treat
severe primary pulmonary hypertension: a case report
Received: July 3, 2000 / Accepted: October 14, 2000
Abstract Continuous intravenous infusion of prostacyclin furosemide, 20mg daily; spironolactone, 25mg daily;
(epoprostenol) as a treatment for primary pulmonary digoxin, 0.125mg daily; aspirin, 81mg daily; ticlopidine,
hypertension (PPH) definitely improves the patient’s qual- 100mg twice daily; and a continuous infusion of heparin,
ity of life, but few accurate parameters have been found to 10000 units daily. Right heart catheterization revealed a
evaluate the efficacy of the treatment. We observed a pa- right atrial pressure of 22mmHg, right ventricular systolic
tient with severe PPH whose plasma brain natriuretic pep- pressure of 135mmHg, right ventricular end-diastolic pres-
tide (BNP) level changed significantly as her condition and sure of 31mmHg, and pulmonary arterial mean pressure of
symptoms changed. Plasma BNP may be considered as one 92mmHg. However, cardiac output was not measured be-
of the parameters for assessing the efficacy of prostacyclin cause it was difficult to perform and retain catheterization of
treatment.
the pulmonary artery. The right ventricular systolic pressure
estimated by Doppler echocardiography1 was also high,
at 125mmHg. The plasma brain natriuretic peptide (BNP)
level was 1069pg/ml (normal: less than 20pg/ml). Continu-
ous intravenous infusion of epoprostenol was commenced.
As systemic arterial pressure might decline suddenly
with this treatment, her initial dose was set at 4ng/kg per
min. Any sudden increase in the dosage might cause severe
symptoms, such as headache and vomiting, so we increased
her dosage by only 0.3 to 0.5ng/kg per min, every 2–4 weeks.
The hemodynamics before and during continuous intrave-
nous infusion of epoprostenol are shown in Table 1.
One month after starting the epoprostenol regimen, she
was able to walk within her hospital room and her plasma
BNP level had declined to 885pg/ml. At 2 months she was
able to walk 100m without rest on a level surface, and her
plasma BNP level had declined further to 397pg/ml (Fig. 1).
However, her pulmonary artery mean pressure measured
during right heart catheterization and her right ventricular
systolic pressure estimated by Doppler echocardiography
were still high, at 74mmHg and 102mmHg, respectively. At
3 months she was able to walk 200m without rest on a level
surface and her plasma BNP level had further declined to
191.7pg/ml. However, shortly thereafter, during an excur-
sion outside the hospital, her feeling of malaise returned
and her plasma BNP level returned to 275pg/ml. Two
weeks after this incident, she developed a fever and a
cough, and a return of edema in her legs and shortness
of breath. Her plasma BNP level had risen to 398pg/ml
(Fig. 1). Six months after commencing the epoprostenol
regimen, she was capable of walking 300m without rest on
a level surface, was graded in NYHA functional class III,
Key words Pulmonary hypertension · Prostacyclin · Brain
natriuretic peptide
Case report
The patient was an 18-year-old woman being treated for
primary pulmonary hypertension (PPH). At the age of 14
years she began to complain of frequent fatigue and experi-
enced difficulty climbing one flight of stairs. At age 17 she
started having increasingly severe episodes of shortness
of breath, and her face and limbs became edematous.
Echocardiography showed enlargement of the right atrium
and ventricle, and right heart catheterization revealed an
elevated pulmonary artery mean pressure of 72mmHg.
Upon arrival at our hospital she was graded New York
Heart Association (NYHA) functional class III. She was
given a calcium channel blocker, nitrate, and a PDE III
inhibitor, but no improvement was seen in her symptoms.
During her hospitalization inflammation of the upper respi-
ratory tract caused her symptoms to worsen, and her status
became NYHA functional class IV. She was administered
M. Wakaumi · T. Shiga ( ) · K. Nozaki · K. Fujiu · K. Shimaya · N.
Ishizuka · N. Matsuda · H. Kasanuki
Department of Cardiology, The Heart Institute of Japan, Tokyo
Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo
162-8666, Japan
Tel. ϩ81-3-3353-8111; Fax ϩ81-3-3356-0441
e-mail: mshiga@hij.twmu.ac.jp

145
Table 1. Hemodynamics at the baseline and during continuous intravenous infusion of
epoprostenol
Baseline During epoprostenol treatment
At 2 months At 4 months At 6 months
Heart rate (beats/min)
90
112/80
22
86
112/78
12
73
116/72
5
70
110/72
3
Systemic arterial pressure (mmHg)
Right atrial mean pressure (mmHg)
Right ventricular systolic pressure
(mmHg)
135
115
120
99
Right ventricular end-diastolic
pressure (mmHg)
Pulmonary arterial mean pressure
(mmHg)
Cardiac output (l/min)
Pulmonary vascular resistance (units)
Systemic vascular resistance (units)
31
92
18
74
11
70
6
61
a
a
–
2.95
18.3
26.1
–
–
–
3.88
14.2
21.1
–
–
a Not performed
Fig. 1. Changes in plasma levels
of atrial natriuretic peptide
(ANP) and brain natriuretic
peptide (BNP) during continu-
ous intravenous infusion of
epoprostenol. Plasma ANP level
(small solid circles), plasma BNP
level (large solid circles), and
estimated right ventricular
systolic pressure (RVSP) using
Doppler echocardiography (open
circles)
and her plasma BNP had declined to 100pg/ml (Fig. 1). epoprostenol, also known as prostacyclin, has been used
Pulmonary artery mean pressure measured during right with success to treat this condition.2 The drug’s anti-
heart catheterization was 61mmHg and right ventricular thrombotic effect on platelets and its effect as a powerful
systolic pressure estimated by Doppler echocardiography systemic as well as pulmonary arterial vasodilator have
was 81mmHg.
been described.3 Intravenous infusion of epoprostenol for
As shown in Fig. 1, the plasma atrial natriuretic the treatment of PPH clearly improves the quality of life of
peptide (ANP) level had decreased during continuous in- the patient, but its effect on pulmonary artery pressure is
travenous infusion of epoprostenol but the change in slight, and few parameters have been found which reflect its
plasma ANP was small compared with that of plasma BNP. efficacy.
The plasma noradrenaline level had also decreased from
PPH diminishes right heart function by increasing right
0.22ng/ml (at baseline) to 0.17ng/ml (6 months after com- ventricular afterload.4 It has also been reported that dimin-
mencing the epoprostenol regimen) but did not always ished right ventricular function due to pulmonary hyper-
reflect her condition.
tension is associated with a lowering of plasma BNP.5 The
following mechanism is thought to cause elevation of the
plasma BNP level associated with pulmonary hypertension.
(1) During pulmonary hypertension resistance increases
within blood vessels in the lungs, resulting in an elevation of
right ventricular afterload and diminished right heart func-
Discussion
PPH is a progressive disease which may lead to death. tion which, in turn, results in elevation of plasma BNP. In
In recent years, long-term intravenous infusion of this case, we found elevated right ventricular end-diastolic

146
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pressure and decreased cardiac output which had been
improved during the continuous intravenous infusion of
epoprostenol. This finding supports the possibility of right
ventricular dysfunction due to pulmonary hypertension. (2)
It has been reported that patients with pulmonary hyperten-
sion have high levels of plasma endothelin-16 and that a high
level of endothelin-1 messenger RNA exists in the endothe-
lial cells of pulmonary arteries of such patients.7 Since
endothelin-1 has been described as a causative element in
the production of plasma BNP,8 the increase of endothelin-
1 due to pulmonary hypertension may be a causative factor
in the elevation of plasma BNP level.
Plasma ANP and noradrenaline levels had declined dur-
ing continuous intravenous infusion of epoprostenol, but
changes in these hormones were small compared with that
of plasma BNP. The plasma BNP level may reflect the
patient’s condition because plasma BNP is produced in the
cardiac ventricular tissue via constitutive pathways9 and its
level immediately responds to ventricular overload result-
ing in the production of BNP messenger RNA.10 It has also
been reported that during cardiac insufficiency, changes in
the plasma BNP level reflect the patient’s symptoms more
closely than do levels of other hormones.11,12 Since plasma
ANP levels are influenced by several factors including
blood pressure, postural change, and sodium intake, plasma
BNP may be more suitable than plasma ANP for evaluation
of the pathophysiology of pulmonary hypertension.5 In this
case, we also found that the plasma BNP level decreased as
the patient’s condition improved and rose as it temporarily
worsened.
Hemodynamic data and exercise tests are commonly
used to assess epoprostenol intravenous treatment for
PPH.13 However, it is too risky to perform these tests
many times in NYHA functional class IV patients. Even
echocardiography, which requires the patient to remain in a
stationary position, may be a burden for these patients.
In patients with severe PPH, measuring the plasma BNP
level would be easier to perform and less invasive. Plasma
BNP may be considered as one of the parameters for assess-
ing the efficacy of prostacyclin treatment.
References
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tricular systolic pressure by Doppler ultrasound in patients with
tricuspid regurgitation. Circulation 70:657–662