ATRIAL SEPTOSTOMY FOR PULMONARY HYPERTENSION
Julio Sandoval MD 1
Abraham Rothman MD 2
Tomas Pulido MD 1
Cardiopulmonary Department, Ignacio Chavez National Institute of Cardiology, Mexico
City, Mexico;
2
and the Division of Pediatric Cardiology, University of California, San Diego, California
1
Address reprint requests to Julio Sandoval, MD, Departamento de Cardiopulmonar, Instituto Nacional de
Cardiologia, Ignacio Chavez, Juan Badiano No. 1, Colonia Seccion XVI, Tlalpan 14080, Mexico D.F.
Mexico. e-mail: sandoval@compuserve.com.mx
BACKGROUND AND RATIONALE
Treatment of primary pulmonary hypertension (PPH) is based on knowledge of the
pathophysiology of this condition and the accepted forms of intervention that attempt to
alleviate pulmonary microvascular obstruction through the use of anticoagulants, oral
vasodilators, long-term infusion of prostacyclin, and lung transplantation.[3] [11] [15] [17] [22] It
seems clear now, however, that a beneficial long-term response to oral vasodilators in PPH
is restricted to only 25% or less of the population.[17] [22] For the larger group of patients with
severe disease, interventions such as the long-term infusion of prostacyclin and lung
transplantation have been shown to be beneficial,[3] [15] [22] but their worldwide application is
limited by technical difficulties and cost. Accordingly, the search for alternative therapies is
warranted.
The rationale for the use of atrial septostomy (AS) in PPH is supported by two
observations. First, survival in PPH is influenced largely by the functional status of the
right ventricle; right ventricular failure and recurrent syncope are associated with a poor
short-term prognosis.[6] Second, several experimental and clinical observations suggest that
an interatrial defect might be of benefit in the setting of severe pulmonary hypertension.
Early animal studies by Austen et al[1] showed that an interatrial communication allowed
decompression of a hypertensive right ventricle and augmentation of systemic blood flow,
particularly during exercise. In addition, clinical studies show that patients with PPH who
have a patent foramen ovale live longer than those without intracardiac shunting.[9] [21]
Likewise, patients with Eisenmenger's syndrome seem to live longer and have heart failure
less frequently than patients with PPH.[12] [29] Together, these studies suggest that
deterioration in symptoms, right heart failure, and death in PPH are associated with
obstruction to systemic flow and dilatation and failure of the right ventricle. The presence
of an atrial septal defect in this setting would allow right-to-left shunting to increase
systemic output, which, in spite of the drop in systemic arterial oxygen saturation, would
produce an increase in systemic oxygen transport. Furthermore, the shunt at the atrial level
would allow decompression of the right atrium and right ventricle, alleviating signs and
symptoms of right heart failure.
Blade balloon atrial septostomy (BBAS) as a palliative therapy for refractory PPH first was
reported by Rich and Lam in 1983.[18] Subsequent studies, particularly those of Nihill et al[14]
and Kerstein et al,[13] have shown that BBAS can be performed successfully in patients with
advanced PPH and can bring about significant clinical and hemodynamic improvement. In
addition to symptomatic improvement, there seems to be a trend toward improved survival
in patients with severe PPH who have undergone successful blade atrial septostomy
(BBAS). Similar results have been obtained with the use of graded balloon dilation atrial
septostomy (BDAS), a variant of BBAS.[10] [19]
WORLDWIDE EXPERIENCE WITH ATRIAL SEPTOSTOMY IN THE
TREATMENT OF PRIMARY PULMONARY HYPERTENSION
The precise role of AS in the treatment of PPH remains uncertain because most of the
knowledge regarding its use comes from small series or case reports. To have a better sense
of the beneficial effects and risks of AS, the authors have reviewed the literature regarding
the results of this intervention in the setting of pulmonary hypertension. Important issues
derived from this review were discussed and debated at the World Symposium--Primary
Pulmonary Hypertension 1998 in Evian, France. Most issues regarding the role of AS in the
setting of PPH presented in this article represent the consensus of the participants of the AS
subcommittee in that meeting.[23] Recent information about the long-term effects of this
procedure also are provided.
Population of Patients
The series analyzed in this review includes a total of 64 patients with severe pulmonary
hypertension.[5] [8] [10] [13] [14] [16] [18] [19] [24] [25] [26] [27] [28] In most (78%) of them, a diagnosis of PPH, not
associated with any other condition, was established. The patients had a mean age of 25 ±
13 years (range = 0.33 to 51 years) and 80% were women. Most patients who underwent
AS had severe PPH not responsive to conventional treatment (which included oral
vasodilators, if clinically indicated, but excluded chronic intravenous prostacyclin), with
severe exercise-related dyspnea (83%), syncope or near syncope (51%), and evidence of
right heart failure (60%). In some of the patients, the procedure was performed on an
emergency basis; in others it was performed electively for severe pulmonary hypertension
and functional limitation.
The baseline hemodynamic profile of these patients demonstrates the severity of their
pulmonary hypertension. The mean pulmonary artery (PA) pressure (mPAP) was 66 ± 19
mm Hg, the mean cardiac index (CI) was 2.07 ± 0.54 L/minute/m2 , and the calculated
pulmonary vascular resistance (PVR) index was 30 ± 14 u/m2 . Right ventricular
dysfunction in most of these patients was also evident in an elevated mean right atrial
pressure (mRAP) of 13 ± 8 mm Hg.
Procedure
Two types of AS were used. A combined procedure of BBAS[13] [14] was performed in 35
(55%) of the 64 patients, and BDAS[10] [19] [24] ( Fig. 1 ) was performed in the remainder. All
procedures followed a similar protocol--that is, standard right and left heart catheterization
performed under conscious sedation, with oxygen supplementation and hemodynamic
monitoring in the cardiac catheterization laboratory. The difference between the two
procedures is that, in contrast to BBAS, in BDAS, the Park blade septostomy catheter is not
used and the interatrial orifice is created by puncture with a Brockenbrough needle and use
of progressively larger balloon catheters in a step-by-step fashion.
Figure 1. Balloon dilation atrial septostomy procedure. Puncture of interatrial septum is performed with
a Brockenbrough needle followed by progressive dilation of the orifice with a balloon catheter. Note the
waist in of the balloon at the level of the septum (arrow). Transesophageal echo-Doppler shows the
right-to-left shunt (red jet) that has been created (right panel). Al = Left atrium; AD = right atrium.
Regardless of the technique employed, several issues regarding patient selection and
preparation for the procedure, monitoring of variables during the procedure, and
management of patients after the intervention have been described in the series under
analysis. These issues are summarized at the end of this article in the section on
recommendations to minimize the risk for complications.
Immediate Outcome
There were 10 procedure-related deaths, as defined by death occurring immediately or
within 1 month after the procedure. In most of the reports, these patients were considered
terminally ill. The baseline (preprocedure) hemodynamic profile of this group is shown in
Table 1 . These patients were in severe right ventricular failure, as evident by a high right
atrial pressure and a low cardiac index. In most patients who died immediately after the
procedure, severe and refractory arterial hypoxemia was the leading cause of death.
TABLE 1 -- UNIVARIATE ANALYSIS RELATING PROCEDURAL DEATH WITH
SELECTED BASELINE VARIABLES IN PATIENTS WITH PRIMARY PULMONARY
HYPERTENSION WHO UNDERWENT ATRIAL SEPTOSTOMY
Variable
Alive (n)
Dead (n)
P Value
Age, years
23.6 ± 13 (48)
27.0 ± 13.5 (10)
0.49
7 (12)
5 (12)
11.3 ± 6.2 (48)
22 ± 9.6 (10)
Gender, male
mRAP mm Hg
0.038
0.0032 *
TABLE 1 -- UNIVARIATE ANALYSIS RELATING PROCEDURAL DEATH WITH
SELECTED BASELINE VARIABLES IN PATIENTS WITH PRIMARY PULMONARY
HYPERTENSION WHO UNDERWENT ATRIAL SEPTOSTOMY
Variable
Alive (n)
Dead (n)
4 (48)
8 (10)
65 ± 16.7 (48)
76 ± 27 (10)
0.27
10 (48)
4 (10)
0.23
2.19 ± 0.49 (47)
1.60 ± 0.69 (10)
0.005 *
3 (47)
5 (10)
28 ± 9.7 (47)
42 ± 22.5 (10)
PVRI > 55 u/m2
1 (47)
6 (10)
<0.0001
PVRI > 55 + RAP
>20
0 (47)
4 (10)
0.0005
93.6 ± 4.6 (48)
94.4 ± 4.5 (10)
0.53
3 (48)
0 (10)
1.00
64 ± 17 (47)
38 ± 16 (10)
0.0001 *
1-year survival <0.4
3 (47)
6 (10)
0.0003
Septostomy type
(BB)
23 (48)
6 (10)
0.48
mRAP >20 mm Hg
mPAP mm Hg
mPAP >80 mm Hg
CI L/minute/m2
CI < 1.5 L/minute/m2
PVRI u/m2
SaO2
SaO2 < 85%
Predicted 1-year
survival (%)
P Value
<0.0001
0.002
0.31
BB = Blade balloon, CI = cardiac index, mPAP = mean pulmonary artery pressure, mRAP
= mean right atrial pressure, PVRI = pulmonary vascular resistance index, SaO2 = arterial
oxygen saturation.
chi-square's test (two-tail Fisher's exact test)
*Mann-Whitney's Test U
Univariate analysis of periprocedural death with selected variables was performed in an
attempt to identify the baseline hemodynamic characteristics associated with a poor
immediate outcome. A baseline mRAP greater than 20 mm Hg, a PVR index greater than
55 u/m2 , and a predicted 1-year survival expectancy (using the equation of a multicenter
National Institutes of Health [NIH] study[5] ) lower than 40% all were associated
significantly with periprocedural death (P < 0.0001) (see Table 1 ).
The clinical status of patients after septostomy in whom clinical outcome was available was
reported as improved in 47 of 50 patients (94%) and unchanged in three. Exercise
endurance, as assessed by the 6-minute walk, was improved in most of the patients after
septostomy in one study.[24]
Immediate Hemodynamic Effects
As shown in Table 2 , except for the decrease in systemic arterial oxygen saturation (SaO2 ),
most of the changes in hemodynamic variables after septostomy, although statistically
significant (P < 0.001), were only of moderate magnitude. The mRAP decreased by 3 mm
Hg, equivalent to the concomitant increase in mean left atrial pressure. Cardiac index
increased about 0.7 L/minute/m2 , which resulted in an increase in systemic oxygen
transport despite a drop in SaO2 . There were no significant changes in mPAP or mean
systemic artery pressure after the procedure.
TABLE 2 -- IMMEDIATE HEMODYNAMIC EFFECTS OF ATRIAL SEPTOSTOMY
IN PATIENTS WITH PRIMARY PULMONARY HYPERTENSION
Variable (n)
Baseline
After
mRAP, mm Hg (56)
13 ± 7.8
10 ± 5.6
<0.001
mLAP, mm Hg (43)
5.2 ± 2.6
8.2 ± 3.1
<0.001
CI, L/minute/m2 (54)
2.13 ± 0.51
2.80 ± 0.62
<0.001
SaO2 (60)
93.4 ± 4.7
82 ± 10.5
<0.001
66.5 ± 19
*
PValue
mPAP, mm Hg (56)
65 ± 17
0.26
PVRI, u/m2 (51)
28 ± 11.5
25 ± 11.5
<0.005
mSAP, mm Hg (53)
81 ± 16
82 ± 15
0.51
SOT mL/minute/m2
(45)
407 ± 117
461 ± 123
<0.001
mLAP = Mean left atrial pressure, SOT = systemic oxygen transport. Rest of abbreviations
as in Table 1 .
*Paired t test.
Mechanism of Action
of Atrial Septostomy
A separate analysis was performed for patients in whom a complete set of hemodynamic
variables before and after the procedure was obtained ( Table 3 ). The variables that
changed and their level of significance were similar to those obtained for the group as a
whole. This analysis, however, allowed the authors to perform several correlations among
the different variables to better understand the mechanism of action of AS in the setting of
severe pulmonary hypertension. The magnitude of decrease in mRAP and interatrial
gradient, for instance, were not the same for all patients. It seems that patients with higher
baseline mRAP and interatrial gradient had a more significant change in these variables
after septostomy ( Fig. 2 ). The increase in CI after septostomy was higher in patients who
had a greater decrease in interatrial gradient, and the drop in SaO2 was larger in patients
with a higher increase in CI after the procedure ( Fig. 3 ).
TABLE 3 -- IMMEDIATE EFFECTS OF ATRIAL SEPTOSTOMY IN PATIENTS
WITH PRIMARY PULMONARY HYPERTENSION WITH COMPLETE
HEMODYNAMIC DATA
Variable (n= 39)
Baseline
After
mRAP, mm Hg
12 ± 7
9±5
<0.001
mLAP, mm Hg
5.4 ± 2.7
7.8 ± 2.5
<0.001
7±7
1 ± 4.5
<0.001
CI, L/minute/m2
2.17 ± 0.53
2.79 ± 0.60
<0.001
SaO2
93.4 ± 4.3
83 ± 10.3
<0.001
mPAP, mm Hg
63 ± 18
68 ± 20
0.09
PVRI, U/m2
27 ± 10
25 ± 12
0.053
mSAP, mm Hg
86 ± 14
85 ± 14
0.76
406 ± 115
465 ± 118
<0.001
Interatrial gradient,
mm Hg
SOT mL/minute/m2
*
PValue
Abbreviations as in Tables 1 and 2 .
*Paired t test.
Figure 2. Correlation between the change in mean right atrial pressure (mRAP) and the change in
interatrial gradient after septostomy, with the baseline values of these parameters. Patients with a higher
baseline mRAP and interatrial gradient showed a higher change after the procedure.
Figure 3. Correlation between the change in interatrial gradient and the change in cardiac index after
septostomy. Patients with a greater change in interatrial gradient had a higher increase in cardiac index.
Moreover, when these patients were analyzed separately according to baseline mRAP as
less than 10 mm Hg, between 10 and 20 mm Hg, or more than 20 mm Hg, a different
hemodynamic response to the procedure became evident ( Table 4 ). There was almost no
change in the hemodynamic variables after septostomy in patients with a baseline mRAP
less than 10 mm Hg, whereas a large hemodynamic change occurred in patients with a
baseline mRAP greater than 20 mm Hg. Patients with a baseline mRAP between 10 and 20
mm Hg had an intermediate, although significant, change after the procedure.
TABLE 4 -- HEMODYNAMIC EFFECTS AFTER ATRIAL SEPTOSTOMY
ACCORDING TO THE BASELINE RIGHT ATRIAL PRESSURE
Group (n)
Change %RAP
Change % CI
Change% SaO2 Change% SOT
RAP < 10 mm
Hg (15)
-5.5 ± 47
13 ± 14
-4.4 ± 4.3
8 ± 13
RAP 10-20 mm
Hg (18)
-31 ± 22
39 ± 27
-14 ± 7
19 ± 22
RAP > 20 mm
Hg (6)
-32 ± 20
69 ± 49
-17 ± 15
34 ± 22
Abbreviations as in Tables 1 and 2 .
It seems then, that the beneficial hemodynamic effects after septostomy (i.e., an increase in
cardiac index and systemic oxygen transport) are more pronounced in patients with a more
compromised baseline hemodynamic profile, as previously reported.[16] It is important to
stress, however, that it is in this group, with a baseline mRAP greater than 20 mm Hg, in
which procedure-related deaths occurred.
Although the hemodynamic changes after septostomy seem only moderate (particularly in
the group with baseline mRAP less than 10 mm Hg), it has to be stressed that these
measurements represent only the resting state. The net beneficial hemodynamic effect of
septostomy is likely to be different at exercise, as shown in dogs with right ventricular
hypertension[1] ( Fig. 4 ). To the authors' knowledge, the hemodynamic effects of AS during
exercise in humans have yet to be determined. Follow-up transesophageal echocardiograms
performed in some of the patients at rest and during mild supine exercise, however, support
the concept that the decompression and shunting effects of AS become more pronounced
during exercise[24] (Fig. 5 (Figure Not Available) ).
Figure 4. Comparison of the hemodynamic response at rest (R), during mild exercise (ME), and severe
exercise (SE) of dogs with chronic right ventricular hypertension with and without (control = 5)
(circles), an atrial septal defect (ASD = 5) (squares). As opposed to controls, dogs with an ASD were
able to increase left ventricular (LV) output without a significant increment in right ventricular end-diastolic
pressure (RVEDP). (Data from Austen WG: Experimental studies of the surgical treatment of primary
pulmonary hypertension. J Thorac Cardiovas Surg 48:448, 1964; with permission.)
Figure 5. (Figure Not Available) Follow-up transesophageal echocardiogram from a patient who underwent
atrial septostomy. A, Echocardiogram at rest showing enlargement of the right ventricle and right atrium. An
atrial septal defect is defined clearly (arrow). B, Doppler demonstration of the functioning septal defect is
established by the existence of a mild right-to-left shunt at rest. Simultaneous measurement of SaO2 by pulse
oximetry at rest is 84%. C, Augmentation of right-to-left shunt at mild supine exercise can be demonstrated
clearly. The SaO2 decreased to 68%. (From Sandoval J: Graded balloon atrial septostomy in severe primary
pulmonary hypertension. A therapeutic alternative for patients nonresponsive to vasodilator treatment. J Am
Coll Cardiol 32:297, 1998; with permission.)
From these data and observations, several physiologic mechanisms seem to be involved in
the hemodynamic and beneficial clinical effects after AS. In the setting of severe PPH and
right ventricular dysfunction (i.e., those with a marked increase in baseline mRAP), a
decompression effect of the right heart chambers occurs. Relief of right ventricular wall
stress results in improved right ventricular function. For those with less severe right
ventricular dysfunction at baseline and only mild to moderate hemodynamic changes after
septostomy, the benefit of the procedure may be more likely to occur during exercise by
preventing further right ventricular dilation and dysfunction and by allowing right-to-left
shunting to increase cardiac output. Finally, an increase in systemic oxygen transport and
delivery also may produce beneficial effects on peripheral oxygen use, particularly during
exercise,[4] and be responsible for the observed improvement in functional class and exercise
tolerance of the patients, in spite of only mild to moderate changes in catheterization
hemodynamics.
Long-term Hemodynamic Effects
The only work regarding the long-term hemodynamic effects of AS in PPH is from the
Columbia University group.[13] They found an improvement in right ventricular function
over time after septostomy, with a further decrease in mRAP and a further increase in CI
and systemic oxygen transport in 8 of 15 patients who had repeat hemodynamic evaluation
7 to 27 months after septostomy (Fig. 6 (Figure Not Available) ). These positive results
mirror the long-term improvement in right ventricular function (i.e., decompression effect)
shown by follow-up echocardiography after septostomy in some of these patients ( Fig. 7 ).
[7]
Figure 6. (Figure Not Available) Immediate, short-, and long-term hemodynamic effects of atrial septostomy
in 15 patients with primary pulmonary hypertension. Mean right atrial pressure was lower, and cardiac index
and systemic oxygen transport were higher at long-term follow-up than immediately after the procedure.
(Adapted from Kerstein D: Blade balloon atrial septostomy in patients with severe primary pulmonary
hypertension. Circulation 91:2028, 1995; with permission.)
Figure 7. Echocardiographic findings before and after atrial septostomy. Decrease in transverse
diameters in right atrium (RA), right ventricle (RV), and pulmonary artery (PA) and in right ventricular
area, along with an increase in the right ventricular percent change in area are consistent with a
decompression effect after the procedure. (Data from Espinola-Zavaleta N: Echocardiographic evaluation of
patients with primary pulmonary hypertension before and after atrial septostomy. Echocardiography 16:625,
1999; with permission.)
Long-term Outcome and Survival After Septostomy
Not all patients have clinical improvement after the procedure. In a recent article, Rothman
et al[20] showed that long-term clinical outcome after septostomy seems to depend on the
immediate hemodynamic response to the procedure. Compared with patients with no
clinical improvement after the procedure, those with significant clinical benefit had a
higher increase in CI and systemic oxygen transport (52 ± 17% and 37 ± 13%, respectively,
versus 15 ± 16% and 4 ± 13%, respectively; P < 0.005).
Among the 54 patients who survived the procedure in the worldwide experience, there were
eight late deaths and, in at least five of them, the cause of death was progression of disease.
The remaining patients were alive at the time of their report and four of them survived to
receive lung transplantation. Figure 8 shows the Kaplan-Meier survival estimates in the 54
patients who survived AS. The median survival of the group was 19.5 months (range 2-96
months). In this figure, a predicted survival curve constructed with mean values of the
survival estimates predicted by the equation of the NIH study (for patients on conventional
therapy alone, excluding chronic intravenous infusion of prostacyclin) also is plotted for
comparison. Although no formal statistics are applied, there seems to be an improvement in
the survival of patients with severe PPH after septostomy.
Figure 8. Kaplan-Meier survival curve in 54 patients from the worldwide collective experience who
had a successful atrial septostomy (squares) as compared with their estimated survival derived from the
equation of the National Institutes of Health (NIH) study[6] (circles).
The duration of this initial beneficial effect on survival seems to be limited by late deaths,
primarily as a result of progression of the pulmonary vascular disease. As an example, in
Figure 9 , the authors updated the survival estimates of a series of patients reported
previously.[24] After 3 years of follow-up, the survival of patients diminished considerably.
Progression of pulmonary vascular disease in some of the patients occurred, with
reappearance of dyspnea and progressive cyanosis (increase in right-to-left shunt). This
occurrence was associated with a reduction in pulmonary perfusion on lung scans ( Fig. 10
).
Figure 9. Updated survival estimates of 15 patients with primary pulmonary hypertension (PPH) from a
study previously reported.[23] Survival curves for patients without vasodilator treatment (circles) and
predicted estimates (triangles) are plotted for comparison. AS = atrial septostomy group (squares).
Figure 10. Lung perfusion scan from a patient with primary pulmonary hypertension before and 2 years
after septostomy. A decrease in pulmonary perfusion can be appreciated.
SUMMARY
Atrial septostomy represents an additional, promising strategy in the treatment of severe
PPH. Experience with this procedure still is limited; however, based on analyses of the
worldwide experience, several general conclusions and recommendations can be made.[23]
1. Atrial septostomy can be performed successfully in selected patients with advanced
pulmonary vascular disease.
2. Patients with primary pulmonary hypertension who have undergone successful AS
have shown:
a significant clinical improvement
beneficial and long-lasting hemodynamic effects at rest
a trend toward improved survival
3. The procedure-related mortality of the collective experience is high (16%). Several
recommendations can be made to minimize the risk:
Atrial septostomy should be attempted only in institutions with an established track
record in the treatment of advanced pulmonary hypertension, where septostomy is
performed with low morbidity.
Atrial septostomy should not be performed in patients in whom death is impending or
who have severe right ventricular failure and are on maximal cardiorespiratory support. An
mRAP greater than 20 mm Hg, PVR index greater than 55 u/m2 , and a predicted 1-year
survival less than 40% are significant predictors of procedure-related death.
Before cardiac catheterization, patients should have an acceptable baseline systemic
oxygen saturation (> 90% in room air) and optimized cardiac function (adequate right heart
filling pressure, additional inotropic support if necessary).
During cardiac catheterization, the following are mandatory:
-- Supplemental oxygen
-- Mild sedation to prevent anxiety
-- Careful monitoring of variables (left atrial pressure, SaO2 , and mRAP)
-- Step by step procedure
After AS, it is important to optimize oxygen delivery. Transfusion of packed red blood
cells or erythropoietin (before and following the procedure, if needed) may be necessary to
increase oxygen content.
1. Because the disease process in PPH is unaffected by the procedure (late deaths), the
long-term effects of an AS must be considered to be palliative.
2. Despite its risk, AS may represent a viable alternative for selected patients with
severe PPH. Indications for the procedure may include:
Recurrent syncope or right ventricular failure, despite maximal medical therapy,
including oral calcium-channel blockers or continuous intravenous prostacyclin (Fig. 11
(Figure Not Available) )[2]
Figure 11. (Figure Not Available) The role of atrial septostomy in the current management of primary
pulmonary hypertension. The procedure should be considered after short-term (perhaps 6 months) failure of
maximal medical therapy. RVF = right ventricular failure; RHC = right heart catheterization; TX = treatment;
PGI2 = prostacyclin. (Adapted from Barst RJ: Role of atrial septostomy in the treatment of pulmonary
vascular disease. Thorax 55:95, 2000; with permission.)
As a bridge to transplantation
When no other option exists
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