Incidence and Size of Patent Foramen Ovale During the

First 10 Decades of Life: An Autopsy Study of 965 Normal

Hearts

PHILIP T. HAGEN, M . D . , Resident in Internal Medicine*; DAVID G. SCHOLZ, M . D . , Mayo Medical Schoolt;
WILLIAM D. EDWARDS, M . D . , Department of Pathology

The incidence and size of the patent foramen ovale were studied in 965 autopsy specimens of human hearts,
which were from subjects who were evenly distributed by sex and age. Neither incidence nor size of the defect
was significantly different between male and female subjects. The overall incidence was 27.3%, but it pro-
gressively declined with increasing age from 34.3% during the first three decades of life to 25.4% during the 4th
through 8th decades and to 20.2% during the 9th and 10th decades. Among the 263 specimens that exhibited
patency in our study, the foramen ovale ranged from 1 to 19 mm in maximal potential diameter (mean, 4.9 mm).
In 98% of these cases, the foramen ovale was 1 to 10 mm in diameter. The size tended to increase with increasing
age, from a mean of 3.4 mm in the first decade to 5.8 mm in the 10th decade of life.

The presence of an interatrial channel in the fetal heart
has been known since the time of Galen. 1 This channel,
the foramen ovale, is bordered by the I imbus of the fossa
ovalis (septum secundum) and is guarded by the valve of
the fossa ovalis (septum primum). The latter serves as a
flap-valve to ensure unidirectional blood flow through its
fenestration (ostium secundum) from the right atrium to
the left atrium (Fig. 1).
Functional closure of the foramen ovale occurs post-
natally as pressure in the left atrium exceeds that in the
right atrium. As a result, the valve of the fossa ovalis is
pressed against the I imbus and forms a competent seal.
During the first year of life, fibrous adhesions, which
develop between the I imbus and the valve, effect a
permanent anatomic seal in most infants and thereby
produce an imperforate atrial septum. 2
In a substantial number of persons, however, the for-
amen ovale does not anatomically seal and therefore
maintains a potential interatrial channel through which
blood may shunt whenever right atrial pressure exceeds
left atrial pressure.3 This condition has been designated
"probe patency of the foramen ovale" by Patten2 and
" v a l v u l a r c o m p e t e n t patent f o r a m e n o v a l e " by
Schroeckenstein and associates.4
*Mayo Graduate School of Medicine, Rochester, Minnesota.
tPresent address: Iowa City, Iowa.
Address reprint requests to Dr. W. D. Edwards.
Our purpose was to study age-related changes in the
incidence and size of the patent foramen ovale. Because
it was unclear whether congenital or acquired heart
diseases might affect the natural history of the patent
foramen ovale, we chose to study only normal hearts.
MATERIAL AND METHODS
Specimens of normal human hearts were procured from
the tissue registry at our institution. For the study, hearts
were considered normal if there was no clinical history or
autopsy evidence of cardiovascular disease; accord-
ingly, hearts were excluded if there was a history of
hypertension or cardiomyopathy or if there was autopsy
evidence of critical coronary atherosclerosis or function-
ally important valvular or congenital heart disease.
We obtained the most recently available autopsy spec-
imens of normal hearts from 50 male and 50 female
subjects for each of the first nine decades of life. For the
10th decade, normal hearts were available from only 42
women and 23 men. Because the foramen ovale is patent
at birth and anatomically closes in most persons during
the first year of life, we excluded from the study those
specimens from infants younger than 1 year old. Al-
though the selection of the 965 hearts for the study was
nonrandom, it was certainly nonbiased.
For each heart in which the foramen ovale was patent,
the maximal size of the potential orifice was measured in

Mayo Clin Proc 59:17-20, 1984 17

18 PATENT FORAMEN OVALE Mayo Clin Proc, January 1984, Vol 59

Fig. 1. Patent foramen ovale, shown in autopsy specimen from 85-year-old man. A, Right atrial (RA) view shows a probe in foramen ovale,
between limbus and valve (10 of fossa ovalis. B, Left atrial (LA) view shows same probe as in A exiting through ostium secundum, the prominent
fenestration in the valve. Normally, when left atrial pressure exceeds right atrial pressure, the valve of the fossa ovalis is pressed against the limbus
and thereby closes the foramen ovale. IVC = inferior vena cava; MV = mitral valve; SVC = superior vena cava; TV = tricuspid valve.

millimeters with use of calibrated probes. Periodic cross-
checks of the measurements revealed no interobserver
variation.
RESULTS
The incidence of patent foramen ovale was 27.3% (263
of 965) for all age groups combined and 26.8% (127 of
473) for males and 27.6% (136 of 492) for females. No
statistically significant difference was found in the inci-
dence between males and females when the data were
analyzed by decades. The incidence progressively de-
clined with increasing age, however (Fig. 2). The for-
amen ovale was patent in approximately a third of per-
sons 1 to 29 years of age, in about a fourth of those from
30 to 79 years of age, and in roughly a fifth of subjects
older than 80 years. The incidence in the first group
differed significantly from that in the second group (P =
0.0069) and that in the third group (P = 0.0012).
When the foramen ovale was patent, its maximal
potential diameter ranged from 1 to 19 mm (mean, 4.9
mm) (Fig. 3). Among these 263 cases, the foramen ovale
was 2 to 6 mm in 72%, 2 to 8 mm in 86%, and 1 to 10 mm
in 98%. No statistically significant difference in size was
observed between specimens from males and females.
The size, however, tended to increase with increasing
age, from a mean of 3.4 mm in the first decade to 5.8 mm
in the 10th decade (Fig. 4). These measurements were
made in formalin-fixed specimens and may be slightly
less than those made in fresh specimens, because of mild
shrinkage of fixed fibroelastic elements.
DISCUSSION
Among those features of the fetal circulation which may
persist beyond the neonatal period, patency of the for-
amen ovale is the most common. Through this potential
passageway, the right side of the heart may communicate
directly with the left side of the heart, and thereby the
pulmonary circulation may be bypassed.
Accordingly, any condition that results in higher right
atrial pressure than left atrial pressure may produce a

51
36
34 50 -
33
42
30 40 -
25 26 26 26
24 32
P e r c e n t of 22 No. of 3

1
1
patent 20 19 patent 30
' 3 p.

foramen foramen 21
ovale ovale 20 -

i
16
10 "12
10 {*]
,2
7

0
1-9
'Z
10-19 20-29 30-39 40-49 50-59 60-69 70-79 80-89 90-99

12 3 4 5 6 7 8 9 10 1112 13 14 15 16 17 18 1920
Age groups (years) s ze of p a t e n t f o r a m e n ovale (mm)

Fig. 2. Incidence of patent foramen ovale for age groups by decades. Fig. 3. Size distribution of patent foramen ovale in 263 cases.
Overall, foramen ovale was patent in 263 of 965 specimens.
Mayo Clin Proc, January 1984, Vol 59 PATENT FORAMEN OVALE 19

25

m (3.4) (4.4) (4.3) (3.9) (5.3) (5.7) (6.1) (5.3) (65) (5.8)
20

15 "
Diameter
of PFO (mm)
10 -


9



f
-zssr
*
3$

w


mi nu JltA
*

1-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 80-89 90-99

Age groups (years)

Fig. 4. Size distribution of patent foramen ovale (PFO) shown for age groups by decades in 263 cases, m = mean diameter.

right-to-left shunt with systemic arterial desaturation and
possible paradoxic embolization. J b Such conditions in-
clude crying in the neonate, 7 the Valsalva maneuver, 8
use of positive end-expiratory pressure,5 pulmonary em-
bolization, 4 , 9 pulmonary hypertension, 4 chronic ob-
structive pulmonary disease,' 0 pulmonary valvular ste-
n o s i s , 5 " congestive heart failure, 5 1 2 the aftermath of
m y o c a r d i a l i n f a r c t i o n ' 3 1 4 or c a r d i o p u l m o n a r y
b y p a s s , 5 ' 5 ' 6 platypnea orthodeoxia generally in as-
sociation with pneumonectomy,' 7 ' 9 and neurosurgical
procedures complicated by air embolization. 2 0
In contrast, patency of the foramen ovale may be
beneficial and provide a portal of access from the sys-
temic venous circulation to the left side of the heart
during cardiac catheterization, not only in infants but
also in older persons. 2 ' 2 2 Although intentional perfora-
tions of the atrial septum may allow similar access to the
left side of the heart in persons with anatomically sealed
foramina, progressive age-related fibroelastic thickening
of the valve of the fossa ovalis 23 may hinder this trans-
septal approach in some older subjects.
Accordingly, studies concerning the incidence and
size of the patent foramen ovale have clinical impor-
tance. In specimens from subjects beyond 1 year of age,
we observed patency in 27.3% of 965 normal hearts, and
other investigators' 24 " 29 have reported a similar inci-
dence (Table 1). The variation among results may be due
in part to small cohort size in some studies. Moreover,
Schroeckenstein and associates4 have suggested that
lower values may be anticipated when autopsy reports
rather than actual specimens are reviewed.
Among persons younger than 30 years old, we ob-
served a patent foramen ovale in 34.3%; however, pa-
tency had declined to 25.4% in the 4th through 8th
decades and was only 20.2% in the 9th and 10th dec-
ades. Late anatomic closure of the foramen ovale appar-

Table 1.Incidence of Patent Foramen Ovale (PFO) in Various Studies

No. of Incidence Age (yr) of
Year Authors hearts of PFO (%) patients

1897 Parsons and Keith 2 4 399 26 All ages

1900 Fawcett and Blachford 2 '' 306 31.7 >10
1918 Scammon and Norris 2 '' 1,809* 29 >1
1931 Patten' 4,083* 24.6 Mostly adults
1934 Seib 27 500 17 >20
1948 Wright et a l 2 " 492 22.9 Mostly adults
1972 Schroeckenstein et al 4 144 35.4 >20
1979 Sweeney and Rosenquist 2 64 31 >10
1984 Hagen et al 965 27.3 >1
'Combined review of literature.
20 PATENT FORAMEN OVALE
ently occurs in some persons. Patten1 also reported an
age-related decrease in incidence, from 34.5% to 27.2%
to 22.4% for the age groups 5 to 20 years, 21 to 40 years,
and more than 40 years, respectively. Scammon and
Norris 26 found an incidence of 33% for ages 6 to 20 years
and 28% for those older than 20 years.
Other investigators have not emphasized these age-
related changes. In most instances, however, abnormal
rather than normal hearts have been studied. Perhaps the
altered hemodynamics that accompany common forms
of chronic heart disease may favor patency and thereby
hinder late anatomic closure of the foramen ovale. If so,
then one would predict an incidence of patency similar to
that in normal young age groups. In fact, the values
reported in some studies of abnormal hearts (35.4%,
31.7%, and 31 % ) 4 , 2 5 ' 2 9 are similar to our values for
normal hearts from persons 1 to 29 years of age (34.3%).
Although early investigators observed a patent for-
amen ovale somewhat more frequently in women than in
men, 2 4 , 2 5 neither our data nor those of Schroeckenstein
and associates4 showed any statistically significant dif-
ference in incidence between sexes. Furthermore, Seib 27
reported no difference in incidence of patent foramen
ovale between whites and blacks.
Among those reports (including the current study) in
which the diameter of the foramen ovale was measured,
the average size was 5 to 6 mm, 2 4 , 2 5 ' 2 7 " 2 9 and the vast
majority were 1 to 10 mm in diameter. 2 4 , 2 8 , 2 9 None-
theless, we observed a tendency toward increasing size
with increasing age, from a mean of 3.4 mm in the first
decade to 5.8 mm in the 10th decade. Although stretch-
ing of the valve of the fossa oval is (and ostium secundum)
may account for this age-related enlargement, other fac-
tors may also play a role. Perhaps those foramina that
anatomically seal late in life are the smallest passageways
and this factor may thereby account for both the de-
creasing incidence and the increasing size with age.
ACKNOWLEDGMENT
We acknowledge Duane M. Ilstrup, Section of Medical
Research Statistics, for the statistical analyses in this
study.
REFERENCES
1. Patten B M : The closure of the foramen ovale. Am J Anat
48:19-44, 1931
2. Patten BM: Developmental defects at the foramen ovale. Am J
Pathol 14:135-161, 1938
3. Gross P: The patency of the so-called "anatomically open but
functionally closed" foramen ovale. Am Heart ] 10:101-109,
1934
4. Schroeckenstein RF, Wasenda G), Edwards JE: Valvular com-
petent patent foramen ovale in adults. M i n n M e d 55:11-13, 1972
5. Moorthy SS, Losasso A M : Patency of the foramen ovale in the
critically ill patient. Anesthesiology 41:405-407, 1974
Mayo Clin Proc, January 1984, Vol 59
6. Gazzaniga AB, Dalen JE: Paradoxical embolism: its patho-
physiology and clinical recognition. Ann Surg 171:137-142,
1970
7. Prec KJ, Cassels DE: Oximeter studies in newborn infants during
crying. Pediatrics 9:756-762, 1952
8. Kronik G, Msslacher H: Positive contrast echocardiography in
patients with patent foramen ovale and normal right heart hemo-
dynamics. Am J Cardiol 49:1806-1809, 1982
9. Kovacs GS, Hill JD, Aberg T, Blesovsky A, Gerbode F: Patho-
genesis of arterial hypoxemia in pulmonary embolism. Arch Surg
93:813-823, 1966
10. Daly JJ: Venoarterial shunting in obstructive pulmonary disease.
N Engl J Med 278:952-953, 1968
11. Selzer A, Carnes W H : The role of pulmonary stenosis in the
production of chronic cyanosis. Am Heart J 45:382-395, 1953
12. Pieroni DR, Valdes-Cruz L M : Atrial right-to-left shunt in infants
with respiratory and cardiac distress but without congenital heart
disease: demonstration by contrast echocardiography. Pediatr
Cardiol 2:1-5, 1982
13. Morris AL, Donen N: Hypoxiaand intracardiac right-to-left shunt:
complicating inferior myocardial infarction with right ventricular
extension. Arch Intern Med 138:1405-1406, 1978
14. Manno BV, Bemis CE, Carver J, Minz GS: Right ventricular
infarction complicated by right to left shunt. J Am Coll Cardiol
1:554-557, 1983
15. Morthy SS, Losasso A M , Gibbs PS: Acquired right-to-left intra-
cardiac shunts and severe hypoxemia. Crit Care Med 6:28-31,
1978
16. Byrick RJ, Kolton M , Hart JT, Forbath PG: Hypoxemia following
cardiopulmonary bypass. Anesthesiology 53:172-174, 1980
17. Schnabel TG Jr, Ratto O, Kirby CK, Johnson J, Comroe JH Jr:
Postural cyanosis and angina p e c t o r i s f o l l o w i n g p n e u -
monectomy: relief by closure of an interatrial septal defect. J
Thorac Surg 32:246-250, 1956
18. Begin R: Platypnea after p n e u m o n e c t o m y . N Engl J Med
293:342-343, 1975
19. Dlabal PW, Stutts BS, Jenkins D W , Harkleroad LE, Stanford WT:
Cyanosis following right pneumonectomy: importance of patent
foramen ovale. Chest 81:370-372, 1982
20. Gronert GA, Messick JM Jr, Cucchiara RF, Michenfelder JD:
Paradoxical air embolism from a patent foramen ovale. An-
esthesiology 50:548-549, 1979
21. Aldridge HE: Transseptal left heart catheterization without needle
puncture of the interatrial septum. Am J Cardiol 13:239-242,
1964
22. Bloomfield DA, Sinclair-Smith BC: The limbic ledge: a landmark
for transseptal left heart catheterization. Circulation 31:103-107,
1965
23. Hutchins G M , Moore G W , Jones JF, Miller ST: Postnatal endo-
cardial fibroelastosis of the valve of the foramen ovale. Am J
Cardiol 47:90-94, 1981
24. Parsons FG, Keith A: Seventh report of the Committee of Col-
lective Investigation of the Anatomical Society of Great Britain
and Ireland, for the year 1896-97. J Anat Physiol 32:164-186,
1897
25. Fawcett E, Blachford JV: The frequency of an opening between
the right and left auricles at the seat of the foetal foramen ovale. J
Anat Physiol 35:67-70, 1900
26. Scammon RE, Norris EH: O n the time of the post-natal oblit-
eration of the fetal blood-passages (foramen ovale, ductus ar-
teriosus, ductus venosus). Anat Rec 15:165-180, 1918
27. Seib GA: Incidence of the patent foramen ovale cordis in adult
American whites and American negroes. AmJ Anat 55:511-525,
1934
28. Wright RR, Anson BJ, Cleveland HC: The vestigial valves and the
interatrial f o r a m e n of the a d u l t h u m a n heart. Anat Rec
100:331-335, 1948
29. Sweeney LJ, Rosenquist GC: The normal anatomy of the atrial
septum in the human heart. Am Heart J 98:194-199, 1979