Download Atrial Septal Defect in Patients Ages 60 Years or Older

CIRCULATION
402
23. Oyer PE, Stinson EB, Griepp RB, Shumway NE: Valve
replacement with the Starr-Edwards and Hancock prostheses:
comparative analysis of late morbidity and mortality. Ann Surg
186: 301, 1977
24. Cohn LH, Sanders JH, Collins JJ: Actuarial comparison of
VOL 64, No 2, AUGUST 1981
Hancock porcine and prosthetic disc valves for isolated mitral
valve replacement. Circulation 54 (suppl III): III-60, 1976
25. Cohn LH, Koster JK, Mee RBB, Collins JJ: Long-term followup of the Hancock bioprosthesis heart valve: a 6-year review.
Circulation 60 (suppl I): 1-87, 1979
Atrial Septal Defect in Patients Ages 60 Years
or Older: Operative Results and Long-term
Postoperative Follow-up
MARTIN G. ST. JOHN SUTTON, MB., ABDUL J. TAJIK, M.D.,
AND DWIGHT C. MCGOON, M.D.
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SUMMARY Between 1955 and 1977, 66 patients ages 60 years or older underwent operative closure of
secundum atrial septal defect. Of these, 56 (85%) were catheterized preoperatively. The 56 patients were
divided into three groups to assess the effects of pulmonary hypertension on operative mortality, symptoms and
longevity. The 17 group 1 patients had peak systolic pulmonary artery pressures (PAPs) of less than 40 mm
Hg; the 21 group 2 patients had PAPs of 40-60 mm Hg; and the 18 group 3 patients had PAPs of more than
60 mm Hg. Among the three groups, there was no significant difference in Qp/Qs, right or left atrial pressures,
right or left ventricular end-diastolic pressures and Qs, although pulmonary vascular resistance was
significantly higher (p < 0.01) in group 3 than in group 1. Four patients died, yielding an operative mortality of
6%. All four patients had undergone additional operative procedures. Operative mortality was unrelated to preoperative symptom class, PAP or pulmonary vascular resistance. Forty-seven patients were followed up for
2-20 years (mean 6.6 years), and of these, 41 (87%) improved by at least one functional class. Symptomatic
benefit occurred in all groups, regardless of preoperative PAP, pulmonary vascular resistance or functional
class. Actuarial survival curves showed that longevity at 5 and 10 years postoperatively was significantly increased (p < 0.01) for patients with atrial septal defect treated surgically compared with that predicted for
age-matched patients treated medically.
ATRIAL SEPTAL DEFECT is one of the most common forms of congenital heart disease in adults.' The
few long-term survival studies of patients with atrial
septal defect treated medically have indicated that the
average age at death is 39-49 years.2-- Although survival into the eighth and ninth decades has been
documented,"-8 there is a yearly attrition rate of
5-10% in patients more than 40 years old who are
treated medically.9' 10 Surgical closure of atrial septal
defects in children and young adults with large left-toright shunts can be recommended with confidence
because surgical mortality is low,'1 the frequent
debilitating symptoms that develop in the third to fifth
decades of life may be obviated,'1- and life expectanFrom the Division of Cardiovascular Diseases and Internal
Medicine, and the Section of Thoracic, Cardiovascular and General
Surgery, Mayo Clinic and Mayo Foundation, Rochester,
Minnesota.
Presented in part at the 28th Annual Scientific Sessions of the
American College of Cardiology, Miami, Florida, March 1979.
Dr. St. John Sutton's present address: Division of Cardiology,
University of Pennsylvania, 3400 Spruce Street, Philadelphia,
Pennsylvania.
Address for correspondence: A. J. Tajik, M.D., Mayo Clinic, 200
First Street SW, Rochester, Minnesota 55905.
Received December 19, 1979; revision accepted November 26,
1980.
Circulation 64, No. 2, 1981.
cy may return to normal. In contrast, the efficacy of
surgical as opposed to medical treatment in elderly
patients (60 years of age or older) is still debated.
Surgical experience is limited and mortality figures
vary and are increased by the higher incidence of pulmonary hypertension and heart failure"'19 and by the
necessity of associated atrioventricular valve and
coronary artery operations. In addition, the likelihood of long-term symptomatic improvement and the
effect on life expectancy after surgery in this age group
are unknown.
We reviewed a large series of patients with atrial
septal defect who were 60 years of age or older. We investigated the effects of preoperative symptam class,
preoperative hemodynamics, associated disease, and
atrial fibrillation on surgical mortality, postoperative
symptom class and longevity.
Materials and Methods
Between January 1955 and December 1977, 72
patients who were 60 years of age or older had the
diagnosis of atrial septal defect established at the
Mayo Clinic. The oldest patient was 83 years old. Of
the 72 patients, 37 (51%) had the condition diagnosed
between 1971 and 1977. The diagnosis of atrial septal
defect was established by cardiac catheterization in 62
patients (82%) and by operation in 66 patients (92%).
ASD IN THE ELDERLY/St. John Sutton et al.
Of the 72 patients, 64 had secundum atrial septal
defect and eight had sinus venosus defect associated
with partial anomalous pulmonary venous connections. Two patients were considered unsuitable surgical candidates, one because of metastatic carcinoma
and the other because of severe pulmonary hypertension, with a pulmonary vascular resistance greater
than 20 U*m2. Surgical closure was recommended for
70 patients, but three refused operation and one had
an operation at another institution. The 66 other
patients (47 females and 19 males, a ratio of 2.5:1),
mean age 64.5 years, underwent surgical repair of
atrial septal defect at the Mayo Clinic and are the subject of this report.
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Clinical Features
The correct clinical diagnosis of atrial septal defect
before referral for cardiac catheterization or operation
was made in 30 of the 66 patients (45%). Primary
diagnosis of mitral valve disease with prominent
mitral regurgitation presumed on a rheumatic basis
was made in 23 patients. Primary diagnosis was
considered to be a dilated form of cardiomyopathy in
eight patients (12%) and aortic valve disease in three
(5%) (only present in one patient). Of the 66 patients,
25 (38%) had atrioventricular valve regurgitation,
14 with mitral regurgitation and 11 with tricuspid
regurgitation.
The preoperative functional classification of the 66
patients who underwent operation for closure of atrial
septal defect was assessed using the New York Heart
Association (NYHA) classification. Four patients
were in functional class I, 18 were in class II, 20 were
in class III and 24 were in class IV.
The preoperative roentgenograms of the chest
showed that only two patients had normal heart size
and that 64 had increased heart size (cardiothoracic
ratio . 0.5). Electrocardiograms showed that 30
patients (45%) were in sinus rhythm, 34 (52%) had
atrial fibrillation, one (1.5%) had atrial flutter and one
(1.5%) had complete atrioventricular block. Thirtyfive percent had right-axis deviation, 56% had complete right bundle branch block and 6% had left ventricular hypertrophy.
403
but six (10.7%). In two of these six patients, the
arteriolar resistance was moderately elevated, to 8.1
and 8.5 U*m2, and in the other four patients the
arteriolar resistance was markedly elevated to levels
greater than 10 U.m2 (10.6, 11.0, 13.2, and 14.3
U.m2). Although mean values for peak systolic PAP
were significantly different between groups 1, 2 and 3,
there was no statistically significant difference in left
atrial pressure, right atrial pressure, Qp/Qs (fig. 1),
percent oxygen saturation of systemic arterial blood,
right ventricular end-diastolic pressure, left ventricular end-diastolic pressure or systemic index. Pulmonary arteriolar resistance, however, was significantly greater (p < 0.01) in group 3 than in group
1. With increased peak systolic PAP, there was deterioration in functional class: in group 1, 38% of the
patients; in group 2, 69%; and in group 3, 76% were in
classes III and IV. In addition, there was an increased
incidence of atrial fibrillation with increased PAP,
shown by the presence of atrial fibrillation in 20% of
patients in group 1 and in 67% in each of groups 2
and 3.
The remaining 10 patients (15%) were referred for
operation without catheterization; the clinical
diagnosis was atrial septal defect in four, mitral valve
disease in five and pericardial disease in one; in the
latter six patients, the diagnosis of atrial septal defect
6. Or.
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Results
Hemodynamics
Fifty-six of the 66 patients (85%) underwent preoperative cardiac catheterization.
To investigate the relationship between pulmonary
artery pressure (PAP) and functional class and the
effects of PAP on surgical mortality and postoperative functional class and survival, patients were arbitrarily divided into three groups. Group 1 consisted of
17 patients with a peak systolic PAP of less than 40
mm Hg; group 2, 21 patients with a PAP of 40-60 mm
Hg; and group 3, 18 patients with a PAP of greater
than 60 mm Hg (table 1). In 18 (32%) of the 56
patients, PAP was greater than 60 mm Hg, but pulmonary arteriolar resistance was below 7 U_m2 in all
[
U
aL
3
2
Group 1
I
0
VZ
I
a
0o
10
I
0
Peak systolic
pulmonary artery pressure
(mm Hg)
FIGURE 1. Relationship ofpulmonary arterysystolic pressure to ratio of the pulmonary-to-systemic flow (Qp/Qs) in
54 patients.
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VOL 64, No 2, AUGUST 1981
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TABLE 1. Hemodynamic Data in 56 Catheterized Patients Ages 60 Years or Older with Atrial Septal
Defect
Group 1
Group 2
Group 3
(n 21)
(n =17)
(n =18)
RAP (mm Hg)
6.5 ± 2.3
8.0 ± 2.9
8.6 ± 3.6
(4 12)
(3 -16)
(4 12)
7.8 ± 2.5
8.3 ± 2.3
RVEDP (mm Hg)
8.1 ± 3.3
(5 -13)
(5 15)
(4 -13)
32.7 ± 4.5
47.0 ± 5.4
72.1 ± 11.8
Systolic PAP (mm Hg)
(40 - 59)
(60 - 94)
(24 39)
17.0 ± 4.6
23.9 ± 5.0
12.6 ± 3.4
Diastolic PAP (mm Hg)
(6 - 18)
(10 - 25)
(13 48)
Mean PAP (mm Hg)
19.1 ± 3.4
21.4 ± 3.6
43.1 ± 5.6
(22 35)
(13 24)
(32 63)
8.9 ± 2.9
10.4 ± 3.5
11.3 ± 3.6
PAW or LAP (mm Hg)
(6 15)
(4 15)
(6 15)
2.51 ± 0.63
2.58 ±0.62
2.50 ±0.96
Qp/Qs
(1.7 4.2)
(1.5 - 3.2)
(1.6 3.7)
±
±
2.84
0.80
3.00
± 0.72
2.61
0.63
Qs (1/min/M2)
(1.9 3.7)
(1.9 3.6)
(1.8 - 4.0)
93.7 ± 3.5
92.8 ± 3.3
94.7 ± 2.6
02 arterial saturation (%)
(92 98)
(93 - 98)
(87 - 97)
±
±
± 28
156
30
156
146
28
SAP
Systolic
(mm Hg)
(110 - 210)
(110 210)
(103 205)
81 ± 17
Diastolic SAP (mm Hg)
80 ± 13
79 ± 12
(61 97)
(59 110)
(60 - 114)
LVEDP (mm Hg)
11.2 ± 4.4
11.4 ± 2.7
13.3 ± 3.7
(5 -19)
(6 -20)
(8 -19)
(n 9)
(n 6)
(n 6)
4.10 ± 1.76
2.78 ± 0.92
6.80 ± 5.17
(1.6 - 8.5)
(1.2 5.2)
(2.8 - 14.3)
Values are mean ± SD; ranges are in parentheses.
Abbreviations: RAP = right atrial pressure; RVEDP = right ventricular end-diastolic pressure; PAP =
pulmonary artery pressure; PAW = pulmonary artery wedge pressure; LAP = left atrial pressure; Qp =
pulmonary blood flow; Qs = systemic blood flow; SAP = systemic arterial pressure; LVEDP = left
ventricular end-diastolic pressure; Rpa = pulmonary arteriolar resistance.
Rpa (U. im2)
was made at operation. These 10 patients make up
group 4.
Systemic hypertension, defined as a resting blood
pressure above 150/90 mm Hg, was noted in 25 (38%)
of the 66 patients, which was significantly greater
(p < 0.01) than in an age-matched normal population.
Operation
The atrial septal defect was closed by direct suture
in 47 of the 66 patients (71%), while in 19 (29%),
closure was accomplished using a Dacron patch graft.
In eight (12%), patch graft was necessitated by the
presence of a sinus venosus defect associated with partial anomalous pulmonary venous connections. In 18
patients (27%), additional surgical procedures were
performed: 13 had atrioventricular valve surgery, two
aortocoronary bypass grafts, one aortic valve replacement, one partial pericardiectomy and one implantation of a permanent electronic pacing system for
chronic complete atrioventricular block preoperatively. The incidence of tricuspid regurgitation necessitating operative correction was not different
between the three groups, indicating that severe
tricuspid regurgitation varied independently of PAP.
Hospital mortality, defined as death within 30 days
of surgical closure of atrial septal defect, was 6% (four
of 66 patients). The four patients who died had all undergone additional surgical procedures: one aortocoronary bypass graft, two tricuspid valve annuloplasties, and one tricuspid valve replacement. Although
the number of deaths was small, there was no statistically significant difference in the mortality rate of
patients in functional classes III and IV compared
with those in symptom classes I and II, nor was there
any difference in mortality rate between patients with
mild pulmonary hypertension (group 1) and those with
significant pulmonary hypertension (groups 2 and 3).
In addition, among the six patients with pulmonary
arteriolar resistance (Rpa) greater than 8 U*m2, only
ASD IN THE ELDERLY/St. John Sutton et al.
405
1009
one died during operation (Rpa 14.3 Uem2), and this
resulted primarily from perioperative myocardial infarction after coronary bypass grafting.
Follow-Up
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Follow-up information was obtained on all operative survivors. For analysis of long-term results, we
elected to include patients who had a minimal followup of 2 years (47 patients). This excluded the patients
who underwent permanent ventricular pacing or aortic
valve replacement and the survivor with coronary
bypass grafts (who were followed up for 9-18 months
only). The duration of follow-up was 2-20 years
(mean 6.6 years). There were 14 late deaths during
follow-up, and these occurred 2.5-17 years (mean 7
years) after operation. Of these 14 deaths, two were in
group 1, four in group 2, six in group 3 and two in
group 4, a mean of 3, 7, 8 and 6 years, respectively.
There was no significant difference in the age at which
deaths occurred in the four groups: 67 years in group
1, 73 years in group 2, 70 years in group 3 and 71 years
in group 4. Eight patients died of cerebrovascular accidents, six of whom had documented long-standing
systemic hypertension. In four of the deaths that involved cerebrovascular accidents, autopsy revealed no
intracardiac thrombosis in association with the
closure site of the atrial septal defect; the atrial septal
defects were completely closed, and in each case,
death had resulted from intracerebral hemorrhage and
not thromboembolism. None of the four patients was
taking oral anticoagulants.
Three patients died from congestive heart failure.
Two were in functional class IV before operation and
remained the same after operation, and one patient
deteriorated 5 years after atrial septal defect closure.
Three other patients died, one after a mitral valve
replacement 4½/2 years later, one of staphylococcal
pneumonia and one at home in whom no autopsy was
done. Five of the six patients with pulmonary
arteriolar resistance greater than 8 U*m2 (range
8.5-14.3 U.m2) were followed up for more than 2
years (mean 5.8 years). One patient died at operation.
There was only one late death, which occurred 8 years
postoperatively.
Survival
To assess the yearly attrition rate and the effects of
operation on longevity, actuarial survival curves were
constructed for patients who survived the operation
and were compared with survival curves of an agematched normal population (fig. 2). A survival curve
was also constructed using a yearly attrition rate of
7.5%, a figure derived by Campbell9 from the collected
long-term follow-up studies of patients who were more
than 60 years of age and who were treated medically.
These data demonstrated that patients treated surgically lived significantly (p < 0.01) longer than
patients treated medically, and this statistical
difference first became apparent 4-5 years after operation (fig. 2). Postoperative survival rates in the surgically treated patients at 5 and 10 years were not
Years after operation
100O
q.)
*..
8
10
12 14 16 18 20
Years after operation
FIGURE 2. Survival of patients with atrial septal defect
treated surgically compared to survival of age-matched normal population (expected curve) and to survival of patients
with atrial septal defect treated medically (unoperated
curve). (top) Observed curve represents patients who survived operation. (bottom) Observed curve represents all
patients, including operative deaths.
significantly different from those of an age-matched
normal population; but at 15 years, the sample size of
postoperative patients was too small for meaningful
statistical comparison with normal subjects or
patients treated medically.
Postoperative Symptoms
Comparison of the preoperative and postoperative
symptom classes (fig. 3) in patients followed up for
more than 2 years showed that 41 of 47 (87%) were improved by at least one functional class and six were unchanged; of these six patients, two were in class I
preoperatively. No patient deteriorated, although one
patient developed congestive heart failure 5 years after
atrial septal defect closure. Two patients remained in
functional class IV postoperatively, and both subsequently died of congestive heart failure 2½/2 years later.
CIRCULATION
406
Group
Synnptom
C 'loss
Pre op
1
~ ~
lI
Post-op
0
im
X3
(25)
No Catheterization
Pre-op
2
7
(58)
(20)
2
(17)
0
2
2
2
(17)
2
(VT)
Totol
Group 4
Group 3
7
7
mE
Group 2
VOL 64, No 2, AUGUST 1981
(20)
3
3
Post-op
2
(4) 12
15
(32)
4
14
24
(80)
(30)
(5)
0
(60)
.3t
0
(8)
FIGURE 3. New York Heart Association functional classification of patients with atrial septal defect.
Forty-seven patients werefollowed upfor 2 years or more after operation. Numbers within parentheses are
percentages.
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Eight patients, who all died suddenly from cerebrovascular accident, had maintained their postoperative
symptomatic improvement before death.
Improvement in symptoms varied independently of
preoperative PAP, right and left atrial pressures, right
and left ventricular end-diastolic pressures, Qp/Qs,
pulmonary vascular resistance, and preoperative functional class. Postoperatively, functional classes I and
II contained 75% of the patients in group 1, 85% in
group 2, and 83% in group 3, whereas preoperatively,
these classes contained 58% of the patients in group 1,
31% in group 2, and 24% in group 3 (fig. 3). These data
indicated that patients in all three groups had symptomatic improvement and that improvement was not
confined to group 1 but occurred as frequently in
patients with significant pulmonary hypertension
(group 3). Furthermore, all five postoperative survivors (preoperative arteriolar resistance more than 8
U m2) experienced good-to-excellent relief of symptoms (three class II and two class I). One patient, after
initial improvement, had symptomatic deterioration 5
years later and died 8 years postoperatively.
Discussion
The controversy regarding the efficacy of the surgical (compared with medical) treatment of patients
with secundum atrial septal defect who are 60 years of
age or older has remained unresolved because of the
small and varied surgical experiences, the scarcity of
data regarding the natural history of patients treated
medically, and the lack of detailed, long-term followup studies in a large number of patients who have undergone operation. Formerly, pulmonary hypertension, large left-to-right shunts, high right atrial
pressure, atrial fibrillation, congestive heart failure,
and other cardiac or pulmonary diseases were
regarded as contraindications to surgical intervention
because of the high mortality and morbidity rates and
the small likelihood of either symptomatic benefit or
prolongation of life.17' 18 Thus, these strict criteria discouraged surgical repair of atrial septal defect in many
symptomatic elderly patients.
Although occasionally, a patient with atrial septal
defect may remain asymptomatic into the eighth
and ninth decades,20 21 in our study, as in other
studies,9'-", 16 18 most patients had disabling symptoms
long before that age, with two-thirds in functional
classes III and IV. The few studies on the natural history of patients with atrial septal defect treated medically indicated that symptoms became progressively
more severe with age,2' 4 and this was believed to
result from left ventricular dysfunction,22-25 recurrent
pulmonary emboli, or repeated pulmonary infection.26
However, left ventricular dysfunction in patients with
atrial septal defect in our experience27 was only rarely
encountered. The severity of preoperative symptoms
in patients 60 years of age or older tended to vary
directly with peak systolic PAP, but was independent
of right and left atrial pressures, right and left ventricular end-diastolic pressures, Qp/Qs, and the presence
of atrial fibrillation. The correlation between functional class and peak systolic PAP was illustrated by
the large proportion of patients (58%) in group 1 who
were in functional classes I and II compared with the
significantly (p < 0.01) smaller percentage (24%) of
patients in symptom classes I and II in group 3. However, this relationship between functional class and
pulmonary pressure was complicated, because 42% of
the patients in group 1 were in functional classes III
and IV and the severity of their symptoms could not
be explained on the basis of the presence of mitral or
tricuspid regurgitation. Similarly, one-fourth of the
patients in group 3 were in functional class II, indicating that PAP per se did not necessarily dictate
the presence of functional limitation.
The chest roentgenogram was of limited value in
predicting the severity of the hemodynamic abnormality in any given patient because all but two patients
had cardiomegaly, and these two patients had pulmonary artery pressures of less than 40 mm Hg. Electrocardiograms showed a higher incidence of atrial fibrillation with pulmonary hypertension and not, as
previously reported,'8 with the magnitude of Qp/Qs,
which was not significantly different in patients with
sinus rhythm and atrial fibrillation. Electrocardio-
ASD IN THE ELDERLY/St. John Sutton et al.
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graphic evidence of left ventricular hypertrophy indicated the presence of additional abnormalities systemic hypertension, mitral regurgitation and, in
one patient, severe aortic stenosis.
Atrioventricular valve regurgitation occurred in 25
(38%) of the 66 patients, 14 of whom had mitral
regurgitation and 11 triscuspid regurgitation. In eight
of the patients, mitral regurgitation was caused by
mitral valve prolapse, an association demonstrated
both angiocardiographically28' 29 and echocardiographically30 to be more prevalent in patients with atrial
septal defect than in the normal popuiation. Mitral
regurgitation, however, was only severe enough to
warrant operative repair or replacement in four of
the 14 patients. Tricuspid regurgitation was no more
frequent in patients with significant pulmonary hypertension (group 3) than in patients with mildly elevated
PAP (group 1). Although the incidence of tricuspid
regurgitation was less than that of mitral regurgitation, it was repaired more often at operation.
The correct preoperative or precatheterization
diagnosis of atrial septal defect was made by the
referring physician in relatively few cases, probably
because atrial septal defect is usually not suspected
clinically in the elderly. Diagnostic difficulties arise
because of the unobtrusive auscultatory signs of atrial
septal defect and the confusion with rheumatic mitral
valve disease.21' 81, 32 This confusion occurs because the
coexistence of atrial fibrillation, systolic murmurs of
tricuspid and mitral regurgitation and diastolic murmurs resulting from increased flow across the
tricuspid valve simulates the auscultatory findings of
mixed mitral valve disease. The larger number of
patients 60 years of age or older with atrial septal
defect diagnosed during the more recent years (37
patients, 1971-1977), compared with the earlier
decades (35 patients, 1955-1970), does not reflect an
increased incidence of atrial septal defect, but rather,
greater clinical awareness and the introduction of
echocardiography into routine cardiologic practice,
which has facilitated the noninvasive recognition of
right ventricular volume overload.
Pulmonary pressures in patients ages 60 years or
older varied widely, but despite the high incidence of
pulmonary hypertension, most of the patients still had
large left-to-right shunts.18 The size of the left-to-right
shunt varied independently of PAP and atrial fibrillation. Prolonged exposure of the pulmonary vascular
bed to increased pulmonary blood flow does not invariably result in pulmonary vascular disease, and this
was demonstrated by the small proportion10-2' (10.2%)
of these patients with pulmonary arteriolar resistance
greater than 8 U.m2. This low incidence of pulmonary vascular disease in elderly patients with atrial
septal defect may be a spurious finding overall,
because patients with atrial septal defect and
associated severe pulmonary vascular disease may not
survive into the seventh decade. Pulmonary vascular
obstructive disease may develop in patients with atrial
septal defect in any decade of life, and one cannot
predict if this will occur."' 16
The overall operative mortality for atrial septal
407
defect repair compared favorably with that in other
studies of older patients (older than 40 years).'6' 18 In
this study, no patients died who had closure of atrial
septal defect alone. Operative mortality was unaffected by the presence of pulmonary hypertension
(group 3), congestive heart failure (functional class
IV), the magnitude of the left-to-right shunt, or atrial
fibrillation. All the above factors have been regarded
as adversely affecting the surgical outcome of atrial
septal defect closure as a result of studies of patients
operated on by the atrial-well technique.'7 The only
factor influencing mortality in this study was
associated operative procedures, which were necessary
in 27% of patients. Thus, surgical repair of atrial septal defect in the elderly can be performed at an acceptable risk and therefore is recommended even in
patients with significant pulmonary hypertension (pulmonary arteriolar resistance greater than 8 U.m2), as
demonstrated by the five patients who survived more
than 2 years and in whom resistance varied from
8.1-13.2 U*m2.
Two of the major aims of this study were to determine the long-term effects of operation on symptoms
and longevity. Of the 47 postoperative survivors
followed up for a minimum of 2 years, 41 (87%) were
symptomatically improved by at least one functional
class and six (13%) were unchanged, although one
patient who was initially improved deteriorated again
5 years after atrial septal defect closure. Postoperative symptomatic improvement was not confined
to patients in group 1; it occurred as frequently in
group 3. Most patients experience a large decrease in
PAP after closure of atrial septal defect."' 18, 33-35
However, elderly patients, unlike younger patients,
have little or no decrease in pulmonary vascular
resistance.'6 Thus, the postoperative symptomatic
benefit probably results from restoration of the Qp/Qs
to unity, and hence a decrease in PAP and right ventricular work, rather than being due to any change in
pulmonary vascular resistance. The operation also
may improve lung compliance, which had been
reduced by the hypertensive, hyperkinetic pulmonary
circulation.36
Eight of the 14 late deaths were due to cerebrovascular accidents and involved patients in whom the
postoperative symptomatic improvement had been
maintained. Thromboembolism causing cerebrovascular accidents is a recognized complication after
closure of atrial septal defect and is unrelated to the
type of closure;37 that is, patch graft or direct suture.
Thromboembolism is reportedly more frequent in
patients with atrial fibrillation and severe pulmonary
hypertension.37 Although six of the eight patients with
cerebrovascular accidents had atrial fibrillation and
three had pulmonary hypertension, these six also had
long-standing systemic hypertension. Of four patients
who died after cerebrovascular accident and on whom
an autopsy was performed, three had systemic hypertension and death resulted from intracerebral hemorrhage, not from thromboembolism. No patient had intracardiac thrombosis, and the atrial septal defects
were completely closed. In patients with atrial septal
CIRCULATION
408
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defect in this age group, cerebrovascular accidents
may have resulted from hemorrhage secondary to
systemic hypertension rather than from thromboembolism, as previously reported.37
Actuarial survival curves were constructed for
patients followed up for more than 2 years to assess
the merits of operative closure of atrial septal defect.
These data demonstrated that longevity was
significantly (p <0.01) increased in patients who were
60 years of age or older who underwent operation,
compared with that predicted from survival statistics
for patients of the same age with atrial septal defect
who were treated medically.9 In addition, the postoperative 5- and 10-year survival rates of patients with
atrial septal defect were the same as those for the normal population.
Our data, which represent the first long-term
follow-up study of a large number of patients 60 years
of age or older who underwent operative closure of
atrial septal defect, indicate that (1) atrial septal
defect in the elderly is not rare and must be considered
in a patient with congestive heart failure and associated atrioventricular valve regurgitation; (2) most
patients (67%) have disabling symptoms (functional
classes III and IV); (3) the severity of symptoms
increases with increase in PAP and right ventricular
work; (4) most patients are symptomatically improved
on a long-term basis by operation; (5) surgical closure
can be performed, with a low risk of mortality; (6)
operative mortality is not increased by the presence of
congestive heart failure or pulmonary hypertension;
(7) operation significantly increases longevity and
restores the patients' subsequent survival to normal;
and (8) operative closure of atrial septal defect can be
recommended for all patients 60 years old or older, except for those with the most severe pulmonary
vascular obstructive disease and those with associated
debilitating medical illnesses that result in shortened
survival.
Acknowledgment
We are grateful to Peter C. O'Brien, Ph.D., for his help with the
statistical analysis.
Addendum
Between January 1978 and December 1980, 18 additional patients
ages 60 years or older had operative closure of atrial septal defect
(secundum type in 17 patients, sinus venosus in one patient). The
mean age was 69 years (range 60-82 years). Atrial septal defect was
closed with direct suture in 12 patients (67%) and with patch grafting in six (33%). Associated procedures were performed in eight of
the 18 patients (coronary artery bypass grafting in three, mitral
valve replacement for severe mitral regurgitation in two, mitral an-
nuloplasty in one and tricuspid valve annuloplasty for severe tricuspid regurgitation in three). Severe pulmonary hypertension
(peak pulmonary artery pressure 80 mm Hg, pulmonary arteriolar
resistance 11 U.m2) was noted in only one of 14 patients (7%) in
whom preoperative cardiac catheterization was performed. This
patient had an uneventful postoperative course and is symptomatically improved. There was one death (operative mortality 6%).
The patient was an 82-year-old woman who underwent associated
aortocoronary bypass graft surgery and tricuspid valve annuloplasty. She was dismissed on the twelfth postoperative day but had a
cerebrovascular accident on the twentieth postoperative day and
VOL 64, No 2, AUGUST 1981
died 8
days later. Autopsy revealed evidence of recent cerebral and
myocardial infarctions. The atrial septal repair was intact and no in-
tracardiac thrombus was seen.
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The Serum Digoxin Test and Digoxin Toxicity:
A Bayesian Approach to Decision Making
STEPHEN A. ERAKER, M.D., M.P.H.,
AND
LEWIS SASSE, M.D.
SUMMARY The clinician may often be uncertain about the presence of digoxin toxicity. This uncertainty is
particularly important when the clinician must make initial thrapeutic decisions about continuing or discontinuing digoxin. We describe a method that helps to clarify the role of the serum digoxin test in decreasing the
uncertainty surrounding the diagnosis and treatment of toxicity. The relation between the test and toxicity was
first determined in our patient population. An approach to the interpretation of the test based on the likelihood
ratio was then developed by combining our data with selected data from the literature. The relation between
the pretest risk of toxicity (the estimated risk of toxicity in the population under investigation before the test
result is known) and the predictive value of the test was established. This relation was also used to analyze the
importance of the degree of elevation of the test. The appropriate threshold probability for institution of treatment of toxicity was then determined by an interview technique. The test was able to make the patient's
probability of toxicity cross the threshold probability for treatment of toxicity for an intermediate range of
pretest risk. Our analysis suggests that the serum digoxin test may have a critical effect on therapeutic
decisions and can be best considered as contributing to the spectrum of risk.
THE DILEMMA of the diagnosis and treatment of
digoxin toxicity is faced by many clinicians. No
diagnostic test can definitely confirm the presence of
toxicity. Given this uncertainty, discontinuing digoxin
is beneficial when toxicity is present but may be harmful if toxicity is absent; failing to discontinue digoxin
may be disastrous when toxicity is present.
The value of the serum digoxin test in resolving this
dilemma has been questioned.' The magnitude of the
problem is indicated by studies that report a
prevalence of toxicity on admission to the hospital of
From the Division of Clinical Pharmacology, Department of
Medicine, Stanford University Medical Center, Stanford, and the
Department of Internal Medicine, Kaiser-Permanente Medical
Center, Los Angeles, California.
Supported in part by a grant from the Southern California Permanente Medical Group and NIH Clinical Pharmacology training
grant GM07065.
Address for correspondence: Stephen A. Eraker, M.D., M.P.H.,
Department of Medicine, Veterans Administration Medical Center,
2215 Fuller Road, Ann Arbor, Michigan 48105.
Received November 14, 1979; revision accepted November 26,
1980.
Circulation 64, No. 2, 1981.
up to 20%, with significant morbidity and mortality.2 6
This study was designed to clarify the role of the test
in decreasing the uncertainty surrounding the
diagnosis and treatment of toxicity.7
The premise of this analysis is that the value of a
laboratory result is determined by its ability to influence the diagnostic or therapeutic decision making
process. The serum digoxin test can sometimes
critically influence this process. The test result is best
viewed as part of a spectrum of risk for toxicity.
Methods
The charts of all patients who had a serum digoxin
test ordered at Kaiser Foundation Hospital, Los
Angeles, California, from April 1 to April 21, 1977
were requested for review. All patients had received
Lanoxin (Burroughs-Wellcome). During the 3-week
study period, 1 10 tests on 66 patients were evaluated.
Electrocardiographic Data
All ECGs or rhythm strips obtained subsequent to
the day before the initial test were interpreted by one
of the investigators. The ECGs were divided into the
Atrial septal defect in patients ages 60 years or older: operative results and long-term
postoperative follow-up.
M G John Sutton, A J Tajik and D C McGoon
Downloaded from http://circ.ahajournals.org/ by guest on April 28, 2017
Circulation. 1981;64:402-409
doi: 10.1161/01.CIR.64.2.402
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1981 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
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