Study patients
The mean age of the selected four PDA-ES patients were 28.5 years (ranging from 19 to 34 years) with WHO FCⅡ-Ⅲ. The baseline information of demographic characteristics, echocardiographic and hemodynamic parameters were shown in Table 1.
Table 1.Baseline demographic characteristics and echocardiography parameters of all patients
Patient
No.
|
Sex
|
Age
(years)
|
WHO FC
|
6MWD
(m)
|
LVEF
(%)
|
RV sizes
(mm)
|
PASP
(mmHg)
|
PDA sizes
(mm)
|
1
|
M
|
29
|
Ⅲ
|
440
|
53
|
69*42
|
115
|
10
|
2
|
F
|
19
|
Ⅱ
|
400
|
67
|
57*29
|
120
|
9
|
3
|
F
|
32
|
Ⅱ-Ⅲ
|
170
|
72
|
68*40
|
144
|
9
|
4
|
F
|
34
|
Ⅲ
|
450
|
67
|
75*35
|
104
|
11
|
Abbreviation: PDA, patent ductus arteriosus; WHO FC, WHO functional class; 6MWD, six-minute walking distances ;PASP, pulmonary artery systolic pressure; LVEF, left ventricular ejection fraction; RV, right ventricle.
The mean PVR was 22.19 Wood U (ranging from 14.70 to 36.91 Wood U). The mean PASP and aortic systolic pressure were 126 mmHg (ranging from 105 to 145 mmHg) and 129 mmHg (ranging from 113 to 144 mmHg), respectively.Baseline hemodynamic parameters measured by RHC and the change of Qp/Qs after 100% oxygen inhalation were shown in Table 2.
Table 2.Baseline hemodynamics parameters measured by the right heart catheterization
Patient
No.
|
RAP
(mm Hg)
|
PAP
(mm Hg)
|
TPR
(Wood U)
|
PVR
(Wood U)
|
Qp/Qs
|
|
|
|
|
|
Baseline
|
O2 test
|
1
|
13/6/9
|
105/73/81
|
18.95
|
16.14
|
1.73
|
2.92
|
2
|
5/0/2
|
105/65/85
|
15.82
|
14.70
|
2.13
|
2.46
|
3
|
9/2/5
|
143/63/95
|
40.31
|
36.91
|
1.00
|
1.72
|
4
|
11/3/7
|
134/72/98
|
23.13
|
21.01
|
1.10
|
2.60
|
Abbreviation: RAP, right atrium pressure; sPAP, systolic pulmonary artery pressure; TPR,total pulmonary resistance; PVR, pulmonary vascular resistance. Qp/Qs, pulmonary-systemic blood flow ratio
Diagnostic treatment and repair strategy
After initiation of PAH-targeted drug therapy for 6 months, the first attempt of TCC failed because PASP measured by RHC did not decrease or the reduction was less than 20%. After targeted drug therapy was adjusted and extended to 12 months,all the criterias were met and the PDA occluder was released following trial occlusion. There was no residual shunt for all after TCC. All patients were discharged 1-2 days after TCC with PAH-targeted drugs. Initial and adjusted PAH-targeted drugs were shown in Table 3. Changes of SPAP, AOP and SaO2 before and after trial occlusion were shown in Table 4.
Table 3. Initial and adjusted PAH-targeted drugs regimen before TCC
Paitent (No.)
|
intial
|
adjusted
|
1
|
vardenafil 5mg bid
|
vardenafil 5mg bid
bosentan 125mg bid
|
2
|
tadanafil 20mg qd
|
tadalafil 20mg qd
bosentan 125mg bid
|
3
|
bosentan 125mg bid
tadanafil 20mg qd
|
bosentan 125mg bid
tadanafil 20mg qd
|
4
|
ambrisentan 5mg qd
tadalafil 20mg qd
|
ambrisentan 5mg qd
tadalafil 20mg qd
|
Table 4. Comparisons between pre-occlusion and post-occlusion parameters
Patient No.
|
PASP(mmHg)
|
|
AOP(mmHg)
|
|
SaO2 (%)
|
|
Before occlusion
|
After occlusion
|
|
Before occlusion
|
After occlusion
|
|
Before occlusion
|
After occlusion
|
1
2
3
4
|
105
116
138
145
|
66
68
74
72
|
113
122
137
144
|
124
127
150
153
|
96
97
92.3
97.2
|
98
100
100
100
|
Abbreviation: PASP, pulmonary artery systolic pressure; AOP, aorta pressure; SaO2,systemic arterial oxygen saturation.
Follow-up
At one-year follow-up, Cases 1 and 2 discontinued targeted-drug therapy because PASP decreased to near normal. Case 2 was treated with ambrisentan again as PASP rose to 72 mmHg at 60-month follow-up. PASP of Case 3 decreased to 98mmHg at 12-month follow-up but rose to 140mmHg at 36-month after she stopped targeted drug therapy without doctor consultant, she was prescribed with bosentan and sildenafil again. PASP of Case 4 decreased to 70mmHg at the first year, but rose again to 87mmHg at the 24-month and 131mmHg at the 36-month. She used macitentan instead of ambrisentan at the 29-month.
All the four patients showed improved 6MWD, WHO FC and SaO2 without enlarged RV size during a mean follow-up of 52.0 months (range 32-72).Relevant PASP, RV size, WHO FC and PAH-targeted drugs regimen during follow-ups were shown in Tables 5 and 6.
Table 5.PASP changes during follow-up
Patient (No.)
|
PASP (mmHg)
|
|
|
12m
|
24m
|
36m
|
48m
|
60m
|
72m
|
1
|
31
|
28
|
27
|
/
|
/
|
/
|
2
|
58
|
57
|
55
|
53
|
72
|
62
|
3
|
98
|
140
|
140
|
/
|
/
|
/
|
4
|
70
|
87
|
131
|
/
|
/
|
/
|
Abbreviation: PASP, pulmonary artery systolic pressure measured by echocardiography.
Table 6.RV size ,WHO FC ,6MWD and PAH-targeted drugs at the last follow-up
Paitent (No.)
|
RV size (mm)
|
WHO FC
|
6MWD
|
drugs
|
1
|
50*25
|
Ⅰ
|
550
|
/
|
2
|
55*28
|
Ⅰ
|
500
|
ambrisentan
|
3
|
68*46
|
Ⅱ
|
440
|
bosentan,sildenafil
|
4
|
69*40
|
Ⅱ
|
490
|
macitentan,tadalafil
|
Abbreviations: RV, right ventricle; WHO FC,WHO functional class; 6MWD,six-minute walking distances.