- Email: [email protected]
Congenital Patent Ductus Arteriosus: An Evaluation of its Surgical Treatment
CONGENITAL PATENT DUCTUS ARTERIOSUS: A'N EVALUATION OF ITS SURGICAL TREATMENT
GEORGE E.
BURCH,
M.D., F.A.C.P.*
SINCE the early description of the ductus arteriosus by Galen,! there has been, until several years ago, relatively iittle change in the management of patients with a persistence of the ductus. Treatment was entirely medical, emphasis being placed on restriction of activity and the subsequent management of congestive heart failure and bacterial endarteritis as major complications. A great advance in the treatment of this condition occurred in 1938 when Graybiel, Strieder and Boyer2 reported the first attempt to ligate a patent ductus arteriosus despite the fact that the patient died. This attempt at least gave impetus to further trials at ligation. As early as 1907 Munr0 3 developed an operative approach for ligation of a patent ductus and presented clinical evidence to prove the rational basis for such an operation, but his suggestion was ignored for thirty-one years. Success was finally achieved in 1939, when Gross and Hubbard4 reported the first ligation of a patent ductus arteriosus followed by recovery. Because of the striking benefit obtained by Gross and Hubbard and .the impressive results following operation in the' hands of others, there has developed a wave of enthusiastic interest in the surgical treatment of patent ductus arterio~us. This can be readily understood, since the development of a safe operative procedure to correct a persistent ductus arteriosus has made it possible to convert an irreversible type of heart disease into a reversible or curable one. These rapid developments have prompted an analysis of the surgical results to date in order to evaluate better the indications and contraindications for operation. 4
PHYSIOLOGICAL CONSIDERATIONS
Eppinger, Burwell and Gross 5 , 6 and Eppinger and Burwell7 studied the circulation of the blood through the patent ductus arteriosus in man at operation and also in qogs. In these latter investigations a fistulous connection was made between the ~.ta and the pnlmonaJ:y ~XeJ:Y. Th~.J?.looA._~~~.<>'??.~J;Y~_~._.!~.~~?~_.:f~?m the. a~E~a to. th~._£.lll IJl9~~-.-EJ~, as would be expected on tlie oasis of the pressures in the two circulatory systems. Rarely was there any flow of blood in the From the Section on Internal iVledicine, Ochsner Clinic and the Department of Medicine, Tulane University School of Medicine, New Orleans. «c Associate Professor of Internal Medicine, Tulane University School of Medicine; Visiting Physician, Charity Hospital in New Orleans and Touro Infirmary:; CO'psultant in Cardiovascular Diseases, Ochsner Clinic. ~
388
CONGENITAL PATENT DUCTUS ARTERIOSUS
389
reverse direction, that is, from the pulmonary artery to the aorta. }J1j§. gplains_lh~J:~p_s~nce of cY~1J.o~is. In their patients, from 4 to 19 liters of blood per minute was found to enter directly from the aorta into the pulmonary artery. This represented from 45 to 75 per cent of all the blood leaving the left ventricle. The blood entering the pulmonary artery returns to the left ventricle via the lungs without reaching the peripheral circulation. In order to compensate for the loss of blood in the periphery, the volume output from the left ventricle must increase. This occurs without much change in that of the right ventricle, The result is a considerable increase in the work of the left ventricle, lili vent.!.icut~_~!!larK~~.~_nt, strain and eventual failure. There is some increase in the work of the rIght -veritricle~'~is-"it'-'mustcirculate the added amount of blood entering the pulmonary artery from the aorta. Eppinger and his associates5 found the left ventricle pumping four times the volume of blood expelled,by the right ventricle. These effects on ventricular work explain the normal axis deviation or mild left axis deviation and the rare right axis deviation in the electrocardiogram. The patent ductus arteriosus is associated with many of the hemodynamic and other cardiophysiologic manifestations so well known in aortic regurgitation and arteriovenous aneurysm. The roentgenologic signs observed by teleoroentgenography, fluoroscopy or roentgenokymography, easily explained on the basis of the disturbed physiologic condition already discussed, are as follows: 6 ,7 ( 1) greatly increased excursions of the left ventricle, (2) increased pulsations of the pulmonary artery, (3) overfilling or engorgement of the pulmonary conus and pulmonary vessels, (4)- increased pulsations of the bronchovascular structure, particularly prominent near the hilar regions, and (5) enlargement of the left ventricle. The changes in hemodynamics also explain the typical "machinelike" murmur and the other mUJ;murs so commonly heard in this anomaly. The former murmur is characteristic when properly located in the region of the Eulmonary valve of the chest. Further details of changes in the dynamics of the circulation can be found in the papers of Eppinger and his associates. It is well to point out at this time that when the ductus is successfully ligated, the circulation Jjr..aID.-ati-
ci1lli:-".re.tllrn~.IQ_JIQrnJ~J..~i!hjQ...~._~Qn:. . Ji.me, ~~~~.!:-._QJ_§ec..Q!l~ls_ ..to
hours. 5 It···is beyond the scope of this paper to discuss the anatomy, embryology, method of closure and other physiologic phenomena associated with patent ductus arteriosus. The papers of Franklin,l Boyd,S Barclay et al.,9 Noback and Rehman,10 Kennedy,ll Kennedy and Clark12 and Jager and W ollenman, 13 in .addition to the standard textbooks, may be consulted by those interested in these phases of the subject.
390
GEORGE E. BURCH RESULTS OF LIGATION OR EXCISION
Since the failure of Graybiel, Strieder and Boyer2 in 1938 to ligate a patent ductus arteriosus with superimposed infection, there have been in the literature many reports on the surgical treatment of this anomaly. Gross and Hubbard4 in 1939 reported the first successful ligation. Since then these authors and others have reported many surgical results at such a rapid rate that it is difficult to determine the chronologie order of publication, especially since several authors have written several reports on the same patients within a few months' interval. In spite of these facts an attempt has been made to list in chronological order of publication from most of the available reports the results of ligation of the patent ductus arteriosus (Tabulation) .. By this means at least an impression of the published results can be obtained. It nlust be remembered that there have been many unrecorded cases, especially fatal ones, which are less apt to be reported. Therefore, such statistics will indicate only the trend of the results of surgical treatment. ANALYSIS OF LITERATURE
In 1938 Graybiel, Strieder and Boyer2 attempted to ligate a patent ductus arteriosus complicated by subacute bacterial endarteritis (Streptococcus viridans) but the patient died. Gross and I:-Iubbard 4, in 1939 reported a successful ligation in a 7%-year-old girl who showed signs of impairment in growth and cardiac enlargement. Gross14. reported his results in 4 patients one month later and at the same time described a surgical approach for the operation; three of the cases were new and the results were likewise successful. Jones and his associates15 reported during the next month their immediate results in 7 cases. All of these patients were apparently cured or greatly benefited. One, however, died thirty days later of an infection due to the hemolytic Staphylococcus aureus. These authors included an addendum to this same report in which they cited 6 more successful operations making a total of 13 cases with only 1 death. Several months later they16 reported their results in 11 cases in more detail. It is a bit confusing from these articles to know which were the patients previously reported. The success of the operation is modified somewhat in the later report, since in 6 of the 11 patients a systolic murmur remained. Of course, a sufficient length of time must elapse before the results in such patients can be properly evaluated. Such overlapping of cases and. variations in descriptions make an evaluation of the results in the literature difficult. Stephens,17 in the discussion of the paper of Jones and his co-workers,16 reported a death from infection on t~e tb.ird postoperative day. Gross, Emerson and Green 18 reported a c'ase of successful ligation of the ductus but the patient is probably one previoQ~ly reported by Gross. 14 Gross19 summarized his
CONG£:NtTAL PATENT DUCTUS ARTERtOSUS
391
results in 4 cases in which the ductus was ligated without a single death. Touroff and Tuchman20 reported a successful ligation in a 51-yearold woman with a patent ductus and superimposed endarteritis (Streptococcus viridans). This same patient had made a spontaneous recovery from endarteritis under medical treatment twelve and a half years before. Gross,21 summarizing his experience with ligation in 10 patients, reported 1 death from infection postoperatively, no improvement in 1 case and remarkable improvement in the remaining 8. Kerr 22 in the discussion of Gross's paper 21 cited 2 cases, a young girl who died from infection and a child who showed no improvement following ligation. In the latter case "Kerr suggested the possibility of multiple cardiac lesions as the reason "that complete cure was not effected by the operation. Touroff and Vesell23 reported a cure in a 29-year-old woman who had a patent ductus arteriosus with a superimposed subacute Streptococcus viridans endarteritis. These same writers24 later reviewed their results with ligation in 4 patients with subacute Streptococcus viridans endarteritis superimposed upon a patent ductus arteriosus. One patient, apparently the one mentioned above,23 was cured, 2 died of hemorrhage and the other continued to show bacteremia, as the duct was too short for excision and was only ligated. Gross25 summarized his results again in 13 patients subjected to ligation of the ductus. One died of infection, 1 was not benefited and 11 were definitely improved or cured. Gale and his co-workers 26 reported a successful ligation in a 19-yearold girl. Miangolarra and Hu1l27 described a successful ligation in a 20-year-old woman and a death from hemorrhage in a 12-year-old boy. Castellano and co-workers28 reported a case of a patent ductus arteriosus in which ligation resulted in cure. Gebauer and Nicho129 ligated the ductus in three patients; the 39-year-old woman died of hemorrhage but the 11- and 14-year-old children recovered and were clinically improved. Bourne and his associates30 ligated the ductus in a 23-year-old man with subacute bacterial endarteritis (Streptococcus viridans and Haemophilus influenzae) in whom the cultures remained positive, although the patient was well sixteen months later. Ligation was also performed in a 19-year-old girl with subacute bacterial endarteritis (Streptococcus viridans), and she was well eleven months later. SulfonamideS were used in treating both 'of these patients. Bourne31 again "reported the same 19-year-old patient elsewhere. Shapiro and Keys32 studied 23 of their patients with patent ductus and reviewed patients operated on by observers. A more detailed analysis is presented by these authors in a later paper (vide infra). Came's and Gonzalez Sabathie33 presented the case of a 10-year-old boy who made an excellent recovery following ligation of a patent ductus.
SUMMARY OF MOST OF CASE REPORTS IN LITERATURE ON LIGATION OF PATENT DUCTUS ARTERIOSUS TABULATED IN CHRONOLOGICAL ORDER OF PUBLICATION·
Vol
'0 N
Results J.,.
Patients
Date Published
Author
Cure Age
GraybieI, Strieder & Boyer Gross & Hubbard4 •••.•.••
2 •••••••••• /
May 1938
, •.••••••• J
Feb. 1939
Grossl4
,
1 Mar. 1939
7~.
I~I
Stephens17 ••••••••••••••••••••••••• I April 1939
Grossl9 •••••••••••••••••••
Aug. 1939
1
Sept. 1939
, •• , •••••
Bullock, Jones & Dolley16 Touroff& Tuchman20 ."
, •••••• 1
Gr0ss21 . • • • . • . . • • • . . . . . . . . . • . . • . ' Kerr-
,
TourGff & Vesel121 • ~
, Dec. 1939
,
---June 1940
• • • • . • • • . '"
---Oct. 1940 ---Oct. 1940 ----
.•
··· ..
Oct. 1940
••••••••••••••••
----
Touroff & Vesell24 •••••••••••••••••.• GrossU Gale et
•.•••.•••...••.•....•..•.•••
Oct. 1940
April 1941
Miangolarra & Hul127 ••••••••••••••• I April 1941 CastellanQ et al. 2B •••••••••••••••••• .'1 April 1941
Hem. I In£.
Remarks Others S.V.
__ -
4
26
-- 11
--
7, 7
17,11
F.
H. Staph. aureus
M.
4M. 7 F. _11_l~O
~ n
4
4
Cd
1 died of Staph. aureus
F.
----10 ... 8 - --- F. 2 . ... ----- - --........ ..... 1 29 - - F.- - -1------
I
-I:
4 F.
19 F. -I 12
20
t,'%j
~
1 M.
51
24-63
~ ~ C)
~I-I-I-
- - - -4-31
Pt. died of H. Staph. aureus
_1_13_t~
f Dec. 1940
a1. 26 .••••••• , ••• , •••••..•••• 1
Deaths
Not Cured
Imp.
Sex I Cases
Jones, Dolley & Bullockl5 , • • • . . . . . • . . 1 April 1939 Gross, Emerson & Green1• ••••
J
• M.
F.
'
__4_
1
13
11
......
1 died of Staph. aureus 1 died of Staph. aureus
S.V.
1
S.V. in all
1
1 died of Staph. aureus
---'---
- - - - - --- --_.---
I_ - _2 1 _ _1_ _-
S.V.
=
Gebauer & NiehoI29 ••••••••••.••...• 1 June 1941
11, 14,39
Bourne et al.lo ....•....•........... I Oct. 1941
23 19
--I
BourneS! Carnes & G. Sabathie33
I
Oct. 1941
1
Dec. 1941
--I
J
--
16,5,18 21,4,12 35
Johnson et al.34 ••••••••••••••••••••• 1 Feb. 1942 Winn et
'1- Feb.
aU5
TourofI et a1. 3().
--!
Nixon38 • • . • • • • . • • • . • . • . . • • • . • • . • . . i July 1942 TQurofI39 •••••
"
•.•••••••• "
•••••..
1
Oct. 1942
Dayton & Lindskog40
I Dec. 1942
Humphreysu
1
Dec. 1942
Dolley & Jones42 ••••••••••••••••.... 1
1942
Touroff44 •••••••••••••••••••••..... I Feb. 1943 Harrington45
I July
Shapiro & Keys4s
1
Shapiro & Keys46
1
19'43
Aug. 1943 Aug. 1943
__3_1_ _
1_ _ _ 1_ _ _ 1_ _'_
F.
1 had S.V. 1 had H. infiuenzae
F.
S.V.
--M. ~-
5 F. 2 M.
45
1942
Vedoyaet al.IT .••••.•••••••••••.... I May 1942
-
---
S.V. in 1
F.
- -F.- 1 - 29
Mar. 1942
. • • • • • • • • • • • . • • • • . ..
19 10
~1 M.
S.B.E.
1 - -
s.v.
-I
11, 4 29, 11
4 F.
Cause unknown
4
I
-I-i----
29,51 18, 9
25
3 F.
'
1 M.·
-
4·
S.V.inall
4
S.V.
F.
-_._-1.-
16 113 HI - - j-.... - -11813 --
1 died of S.B.E. P. o. aneurysm
Staph. aureus S.B.E. in all
9-6_3 ~._121_ 6·
107 . 33
* No attempt has been made to collect all cas~s which have been reported. Explanation of abbreviations: S.V. = Streptococcus viridans S.B.E. = Subacute bacterial endarteritis H. Staph. aureus = Hemolytic Staphylococcus aureus Imp. = Improved Hem. = Hemorrhage Inf. = Infection
6
'1-:""1_
8~1_""
I 20
6
o
Z
G') t:'j
Z
~ t-I
I'C
F.
15
(j
S.B.E.in 1 Wron~ ves-I. All unc?mplicated
sel lIgated . S.B.E. m 2 p.o. in 2 cases S.B.E. in all
~Z
~
~
~
(J)
> ~ ~ tJ:j ~
o c:: )ססoo4
(J)
CI)
\j..)
\0
v.J
394
GEORG~
E. BURCH
Johnson and his associates 34 reported 7 patients in whom the ductus \vas ligated. One died of hemorrhage, one had subacute bacterial endarteritis (Streptococcus viridans) and died seven months after operation and in ··5 the ligations were successful. Winn, Hughes and Sanders35 ligated a ductus in a patient with subacute bacterial endarteritis (Streptococcus viridans) and supplemented this with sulfapyridine and heparin. One year later the patient was in excellent health. Touroff, Vesell and Chasnoff36 reported their second patient with patent ductus arteriosus with subacute bacterial endarteritis (Streptococcus virida~s) who was cured by ligation. Vedoya and his associates37 described their results with ligation in 4 patients. One patient died at operation, 1 was benefited and in two the results were e~cellent. Nixon38 reported a successful ligation in a 15 -year-old girl. Touroff89 reported 4 additional ligations in patients with a patent ductus with superimposed Streptococcus viridans endarteritis. This brought Touroff's personal series of patent ductus associated with endarteritis to 8. Since this report appeared, Touroff had had 2 additional patients suffering from patent ductus arteriosus complicated by infection who were cured by operation. Dayton and Lindskog40 reported a cure by ligation of another patent ductus arteriosus complicated by Streptococcus viridans endarteritis. Humphreys 41 reported 16 ligations; all results were excellent except tor a stormy convalescence in two instances. However, one year later 1 patient died of an aneurysm that developed postoperatively in the ductus and another died of bacterial endarteritis two months following operation. Dolley and Jones 42 summarized their results again. In their series of 18 cases ranging in age from 4 to 31 years, ligation was accomplished without a single immediate operative death. One patient died several days later of a staphylococcic infection in the region of the ductus. In 4 other patients a murmur developed and in one of these a continuous murmur recurred. Keys and Shapiro 43 made another analysis of collected cases. These cases will be taken up in greater detail when their third and apparently most recent analysis is discussed. Touroff44 in his next report added 3 more cases of ligation of patent ductus arteriosus complicated by endarteritis, making a total of 11 cases, which formed the basis for his most recent report. Two patients died of hemorrhage; 6 recovered without the aid of chemotherapy; 3 continued to have positive blood cultures and 1 of these died eight months later. Harrington45 reported a successful ligation in a patient with a superimposed subacute bacterial endarteritis (Streptococcus viridans); he has operated on 5 other patients with good results. Shapiro and Keys46 described the results of 140 ligations by 25 surgical-teams, a great number of which were collected by personal correspondence with -surgeons. The remainder were collected from the literature. Of these, 107 were uncomplicated and 33 were associated with a
CONGENITAL PATENT DUCTUS ARTERIOSUS
395
superimposed bacterial endarteritis. Seven of the patients were from the author's series. Of the 107 uncomplicated cases, 81 were successful except for a distant short systolic murmur that remained in a few instances over the pulmonic area. In 14 the continuous murmur remained. In 6 death resulted from rupture of the duct; in 2 bacterial endarteritis developed after operation; in 1 case mediastinitis with death resulted; in 1 there was no duct to ligate (a direct anastomosis between the aorta and pulmonary artery was found so nothing was done); in 3 a vessel other than the duct was ligated (the aorta in one instance) and 2 of these died; and in 2 the diagnosis was mistaken. There was a total of 9 deaths in the 107 cases (the 2 with endarteritis after operation were not included), a mortality rate. of 8.5 per cent. Of the 33 patients operated upon in the presence of superimposed bacterial endarteritis, 20 seemed to have been completely cured clinically. Five patients died at operation of rupture of the duct and in 8 fever persisted in spite of operation. This gives an apparently favorable prognosis of more than 50 per cent in a disease with a previous mortality of almost 100 per cent. In the preceqing table the reports which have been discussed are sUITlmarized in tabular form. CLINICAL PICTURE
The clinical picture of patent ductus arteriosus may vary considerably in specific cases but in general the syndrome is fairly characteristic. 19 , 21,47 The m.~~t__~Q!e~entative feature is a loud harsh murnmr best heard over the region oT the pulmonary valve. It is usually continuous with systolic exacerbations. The l~~ snappy, second pu1lllonic heart soun4.1!~ard with.the 111~rmur producesa "machine-liKe" effec~. The _~ystolic I)1U~II1~r._i.s£re~GeJ1dQand --the-diast.ok_QJ!~_i~_.ge cresce!]:Qp. There usually is a definite systolic_-Ihrill and often a continuous one with systolic exacerbations. The murmurs and thrills may be best elicited with the subject l~ni!!KiQI.w.ar.d and the lungs emptied ~_._gI'!~!!nllm. The murmurs and thrills are produced by the blood flowing fronl the aorta into the pulmonary artery. These manifestations vary· in degree with the size and anatomic nature of the ductus. 'fhe patients will usually give a history of the presence of a murmur from birth or since their first physical exanlination. These patients usually present no cyanosis, since aerated blood is entering the pulmonary circuit from the aorta. As the patient becomes older, the increased burden on the heart begins to manifest itself by ,cardiac enlargemetzt. After a time cqngestive heart failure develops and the manifestations of left and. right ventricular decompensation will gradually appear and become progressively worse. If bacterial infection of the ductus develops, then there will be a picture of bacterial endQcarditiJ with the embolic phenomena present mainly in the lungs. The S,treptococcus viridans is the most common offendina- organisJ.I1. There
396.
GEORGE E. BURCH
may be a wide pu~se .pressur~ with an elevated systolic~ess!!!.e and even a slightly lowered diastolic pressure. This may result in peripheral vascular signs similar to those of aortic regurgitation. These patients often sh
In the presence of patent ductus arteriosus the life expectancy in untreated cases has been variously stated but in general the findings are essentially the same. Of 92 patients studied by Abbott,4 one-fourth died of bacterial endarteritis and an additional one-half died of slow or rapid heart failure. The average age at death in this group of 92 cases was 24 years. Gross and his associates18 estimated that a child with a patent ductus has one chance in four to live a normal length of life, one chance in four to die of bacterial endarteritis and almost two chances in four that he will die of heart failure. Bullock and his coworkers 16 found in 80 cases reviewed by them that 11 (14 per cent) died as a result of the congenital lesion by -the age of 14; by 30 one-half were dead; by 40, 71 per cent were dead and 2 lived to the age of 66 years. Eighteen patients (23 per cent). died of congestive heart failure; 5 (6 per cent) of rupture of the ductus; 42 (53 per cent) of bacterial endarteritis; and 4 (5 per cent) of an associated condition. Thus, 69 (86 per cent) died as a result of the lesion. In 5 the cause of death was not given and in 6 (7 per cent) death was attributed to unrelated cause~. Shepiro and Keys4.6 found from a review of the literature that 80 per"cent of such patients eventually died of the cardiac lesion. Pa-
CONGENITAL PATENT DUcrUS ARTERIOSUS
397
tients alive at 17 years of age average 35 years at death, 40 per cent dying of subacute bacterial endarteritis and most of the remainder of congestive heart failure. Wilson and Lubschez48 found no deaths from congestive heart failure and bacterial endarteritis in 38 patients with uncomplicated patent ductus. There was one unexplained sudden death. Twenty-four were between 10 and 20 years, 12 between 20 and 30 years and 2 over 30 years of age. The incidence of persistent ductus arteriosus varies with the series reported. Bullock and his associates16 found 133 instances of congenital heart disease in 21,000 autopsies at Los Angeles County Hospital. Thirty-six of these were cases of patent ductus, 21 of which had other associated defects. Twenty died before the age of 9 months; 10 with uncomplicated patent ductus \vere less than 2 months old. Every patient died as a result of this lesion. Wilson and Lubschez48 estimated that 1 to 2 per cent of cases of organic heart disease in the adult and 5 to 12 per cent in children are the result of congenital malformations. An analysis of 54,842 reported autopsies revealed that congenital defects constituted 1.3 per cent of all cases, the reported incidences varying from 0.6 to 5.4 per cent. Of 152 patients with congenital cardiac malformations on whom autopsies were performed at the New York Nursery and Child's Hospital, 10.5 ,per cent were cases of patent ductus arteriosus. Of the 54,842 autopsies, 63 (0.11 per cent) of these patients had a patent ductus. Of the total congenital anomalies, 10.3 per cent were patent ductus arteriosus. Keys and Shapir0 43 estimated that about 20,000 persons in the United States have a patent ductus arteriosus. About two thirds of them are females. CAUSES OF FAILURE FOLLOWING LIGATION
Gross 25 attributes poor results of operation to (1) failure to find the ductus, (2) a ductus too short to ligate, (3) ligation of a wrong vessel, (4) hemorrhage from the ductus, (5) incomplete obliteration of the ductus, (6) associated cardiovascular abnormalities, (7) wound sepsis, (8) postoperative pneumonia as well as pulmonary embolism preoperatively. The nature of these causes of failure is obvious. Most of them~ are technical considerations whereas some will enter into the surgical problem as they do in any major surgical procedtlre in the thorax. Hemorrhage is particularly apt to occur in patients \vith superimposed bacterial endarteritis. The infection renders the ductus friable, which results in rupture or cutting through of the ligature. With improvement in the operative procedure there will undoubtedly be fewer failures. INDICATIONS FOR OPERATION
The indications for operation are not too definite at present but certain generally accepted concepts may be enumerated.
398
GEORGE E. BURCH
1. The surgical risk is still not good enough in average hands to recommend operation to all patients with patent ductus arterios.us. With further 'improvement of the operative technic such a recommendation may be made, especially in view of the mo~bidity and short duration of life associated with this defect. 2. Because of the high mortality rate in those patients with superimposed endarteritis who are not subjected to ligation and the greater than 50 per cent cure (vide supra) following ligation, the operation should be recommended when endarteritis is present. 23 The prerequi- . sites for successful operation are (a) that the vegetations be confined to the ductus and (b) that the ductus be of sufficient length to permit excision. (These can be determined, at present, only at the time of operation. ) 3. The operation should be performed in the presence of definite cardiac decompensation, especially if it is progressing. 21 (This would include patients who are showing signs of progressive failure, a large heart and serious disturbances. in cardiac mechanism.) 4. Ligation of the ductus is indicated in patients showing definite retardation of physical and mental development. COMMENT
It can be seen from the foregoing that the problem of patent ductus arteriosus is still unsettled. The mean mortality_ rate determined from the results of operations performed by many surgeons is about 8.5 per cent in cases of uninfected ducti. This does not represent the results that may be expected when a surgeon has had experience with only an occasional case or with many cases. Furthermore, as shown by Shapiro and Keys,46 over 20 per cent of the patients operated on in 107 uncomplicated cases either died or were not benefited materially as far as the murmur \vas concerned. There is no doubt that the life expectancy in persistent ductus arteriosus is considerably reduced. It is apparent too that most patients with an uncomplicated ductus are spectacularly benefited by ligation. It is also true, ho,vever, that these patients have only been followed four years after operation and only time will determine exactly what influence the operation has on the- duration of life. Furthermore, in the presence of superimposed bacterial endarteritis the mortality rate for untreated cases is approximately 100 per cent, but ligation has reduced this to less than 50 per cent (vide supra) after a follow-up of about one year~ Therefore, ligation should not only be recommended but urged if the patient has an associated endarteritis. The same is true in patients who have progressive cardiac damage and decompensation or patients with definite impairment of mental and physical development. One would nevertheless hesitate to recommend or assume the responsibilities for operation in a patient who has a patent ductus without any evi-
CONGENITAL PATENT DUCTUS ARTERIOSUS
399
dence of embarrassment of health. Dolley and Jones 42 found the operation easier to perform in children 4, 5, and 6 years old. If this proves to be true, then the age of the patient will influence considerably the time at which operation should be recommended. It is conceivable that in the future the operation will usually be recommended as soon as a patent ductus is discovered. No such recommendation can be made at this time with the operative mortality averaging 8.5 per cent and even being greater 'in average hands. Until the surgeons have developed a procedure that is relatively safe and the ~esults can be predicted 'preoperatively with a greater degree of certainty, the operation should be reserved for those special indications already listed. SUMMARY
Most of the available case reports in the literature on ligation of patent ductus arteriosus have been reviewed. The average surgical mortality was found to be 8.5 per cent in uninfected ducti. The rate varies considerably, however, depending on the surgeon and his experience (Tabulation). The operation has, been recommended for all patients with the anomaly if there is a superimposed bacterial endarteritis; more than 50 per cent of such patients have been cured by ligation of the ductus. It is also strongly advised for patients with progressive cardiac failure and for patients with definite impairment of physical and mental growth. Poor results following ligation may be attributed to: (1) failure to find the ductus, (2) ligation of the wrong vessel, (3) wound sepsis, (4) hemorrhage, (5) a ductus too short for ligation, (6) postoperative • pneumonia, (7) associated cardiovascular abnormalities and (8) incomplete obliteration of the ductus. t
BIBLIOGRAPHY
1. Franklin, K.
J.:
Ductus Venosus (Arantii) and Ductus Arteriosus (Botalli). Bull. Hist. Med., 9:580-584 (1\,lav) 1941. 2. Graybiel, A., Strieder, J. W. and Boyer, N. H.: An Attempt ·to Obliterate the Patent Ductus Arteriosus in a Patient \vith Subacute Bacterial Endarteritis. Am. Heart J., 15:621-624 (May) 1938. 3. l\1unro, J. C.: Ligation of the Ductus Arteriosus. Ann. Surg., 46:335, 1907. 4. Gross, R. E. and Hubbard, J. P.: Surgical Ligation of a Patent Ductus Arteriosus; Repoit of First Successful Case. J.A.M.A., 112:729-731 (Feb. 25) 1939.
5. Eppinger, E. C., Burwell, C. S. and Gross, R. E.: The Effects of the Patent Ductus Arteriosus on the Circulation. J. Clin. Investigation, 20:127-143
(March) 1941.
6. Burwell, C. S., Eppinger, E. C. and Gross, R. E.: The Signs of Patent Ductus
Arteriosus Considered in Relation to Measurements of the Circulation. Tr. A. Am. Physicians, 55:71-79 (May) 1940. 7. Eppinger, E. C. and Burwell, C. S.: The Mechanical Effects of Patent Ductus Arteriosus on the Heart and their Relation to the X-ray Signs. J .A.M.A., 115:1262-1266 (Oct. 12) 1940.
400
GEORGE E. BURCH
8. Boyd, J. D.: The Nerve Supply of the Mammalian Ductus Arteriosus. J. Anat. 75:457-468 (July) 1941. 9. Barclay, A. E., Barcroft, J., Barron, D. H., Franklin, K. J. and Prichard, M. 1\1. L.: Pulmonary Circulation Times Before and After Functional Closure of the Ductus Arteriosus. J. Physio!., 101:375-377 (Nov.) 1942. 10. Noback, G'. J. and Rehman, I.: The Ductus Arteriosus in the Human Fetus and Newborn Infant. Anat. Rec., 81 :505-527 (Dec.) 1941. 11. Kennedy, J. A.: A New Concept of the Cause of Patency of the Ductus Arteriosus. Am. J. M. Sc., 204:570-573 (Oct.) 1942. 12. Kennedy, J. A. and Clark, S. L.: Observations on the Physiological Reactions of the Ductus Arteriosus. Am. J. Physiol., 136:140-147 (March) 1942. 13. Jager, B. V. and WoUenman, o. J., Jr.: An Anatomical Study of the . Closure of the Ductus Arteriosus. Am. J. Path., 18:595-613 (July) 1942. 14. Gross, R. E.: A Surgical Approach for Ligation of a Patent Ductus Arteriosus. New England J. Med., 220:510-514 (Mar.' 23) 1939. IS. Jones, J. C., Dolley, F. S. and Bullock, L. T.: The Diagnosis and Surgical Therapy of Patent Ductus Arteriosus. J. Thoracic Surg., 9:413-430 (April) 1939.
16. Bullock, L. T., Jones, J. C. and Dolley, F. S.: The Diagnosis and the Effects of Ligation of the Patent Ductus Arteriosus., A Repon of Eleven Cases. J. Pediat., 15:786-801 (Dec.) 1939. ' 17. Stephens, H. B.: Discussion on Jones, J. C., Dolley, F. S. and Bullock, L. T.: The Diagnosis and Surgical Therapy of Patent Ductus Arteriosus. J. Thoracic Surg., 9:413 (April) 1939. 18. Gross, R. E., Emerson, P. and Green, Hyman: Surgical Exploration and Closure of a Patent Ductus, Arteriosus. Report of Second Successful Case. Surgery, 6:201-205 (Aug.> 1939. 19. Gross, R. E.: Surgical Managenlent of the Patent Ductus Aneriosus; With Summary of Four Surgically Treated Cases. Ann. Surg., 110:321-356 (Sept.) 1939. 20. Touroff, A. S. W. and Tuchman, L. R.: Subacute Streptococcus Viridans Endarteritis Superimposed on Patent Ductus Arteriosus; Spontaneous Re- • covery. Recurrence After Twelve and One-half Years. Recovery Following Operative Treatment. Am. Heart J., 23:857-862 (June) 1940. 21. Gross, R. E.: Experiences with Surgical Treatment in Ten Cases of Patent Ductus Arteriosus. J.A.M.A., 115:1257-1262 (Oct. 12) 1940. 22. Kerr, \V. J.: Discussion of Gross, R. E.: Experiences \vith Surgical Treatment in Ten Cases of Patent Ductus Arteriosus. J.A.M.A., 115:1257-1262 (Oct. 12) 1940. Eppinger, E. C. and Bunvell, C. S.: The Mechanical Effects of Patent Ductus Arteriosus on the Heart and Their Relation to the X-ray Signs. J.A.M.A., 115:1262-1266 (Oct.) 1940 and Touroff, A. S. \V. and Vescll, H.: Subacute Streptococcus Viridans Endarteritis Com.. plicating Patent Ductus Arteriosus: Recovery Following Surgical Treatment. J.A.M.A., 115:1270-1272 (Oct. 12) 1940. 23. Touroff, A. S. \\-'. and Vesell, H.: Subacute Streptococcus Viridans Endarteritis Complicating Patent Ductus Arteriosus; Recovery Follo\ving Surgical Treatment. J.A.M.A., 115:1270-1272 (Oct. 12) 1940. 24. Touroff, A. S. W. and Vesell, H.: Experiences in the Surgical Treatment of Subacute Streptococcus Viridans Endarteritis Complicating Patent Ductus Arteriosus. J. Thoracic Surg., 10:59-83 (Oct.) 1940. 25. Gross, R. E.: Surgical Closure of the Patent Ductus Arteriosus. ]. Pediat., 17:716-733 (Dec.) 1940. 26. Gale, ]. W., Pohle, F. ]. and Romaine, H.: Successful Ligation of Patent ...{,
CONGENITAL PATENT DUCTUS ARTERIOSUS
401
Ductus Arteriosus; Report of Case. Wisconsin M. J., 40:296-298 (April) 1941. 27. Miangolarra, C. J. and Hull, E.: Successful Ligation of a Patent Ductus Arteriosus. Surgery, 9:597-602 (April) 1941. 28. Castellano, T., ~laldonado Allende I. y Finochietto, E.: "Ductus Arteriosus." Ligadura del conducto arterial persistente. A prop6sito de un caso, operado con exIto. Presna med. argent., 28:825-828 (April 16) 1941. 29. Gebauer, P. W. and Nichol, A. D.: Ligation of the Patent Ductus Aneriosus. Ohio State M. J., 37:538-543 (June) 1941. 30. Bourne, G., Keele, K. D. and ~rubbs, o. S.: Ligation and Chemotherapy for Infection of Patent Ductus Arteriosus. Lancet, 2:444-446 (Oct. 18) 1941. 31. Bourne, Geoffrey: Changes in Renal Function and Persistence of the l\tfurmur after Ligature of a Patent Ductus Arteriosus. Brit. Heart J., 3:228232 (Oct.) 1941. 32. Shapiro, }\'1. J. and Keys, A.: Clinical and Physiologic Analysis of T\ventythree Patients with Persistent Patent Ductus Arteriosus. (\Vith the assistance of Antonio Violante, M.D.) Internat. Clin., 4:148-164 (Dec.) 1941. 33. Carnes, O. y Gonzalez Sabathie, L.: Persistencia del conducto arterioso; Operaci6n; curaci6n. An. de cir., 7:256-266 (Dec.) 1941. 34. Johnson, J., Jeffers, W. A. and Margolies, A. L.: The Technique of the Ligation of the Patent-Ductus Arteriosus. J. Thoracic Surg.,11:346-356 (Feb.) 1942. 35. Winn, W. A., Hughes, C. L. and Sanders, J. M.: Subacute Bacterial Endarteritis Complicating Patent Ductus Arteriosus; Case Report \vith Recov~ry Follo\ving Sulfapyridine-Heparin Therapy. Ann. Int. Med., 18:242-250 (Feb.) 1942. 36. Touroff, A. S. W., Vesell, I-I. and Chasnoff, J.: Operative Cure of Subacute Streptococcus Viridans Endaneritis Superimposed on Patent Ductus Arteriosus. J.A.MA., 118:890-892 (March 14) 1942. 37. Vedoya, R., Gonzalez Videla, J. and Albanese, A. R.: Persistencia Del Conducto Artcrioso. Intervenci6n Quirurgica en cuatro casos. Rev. Arg. de Cardio!., 9:94-110 (May-June) 1942. 38. Nixon, J. \V.: Ligation of a Patent Ductus Arteriosus: Report of a Successful Case. Surgery, 12:31-40 (July) 1942. ' 39. Touroff, A. S. W.: Further Experiences in the Surgical Treatment of Sub. acute Streptococcus Viridans Endarteritis Superimposed on Patent Ductus Arteriosus. J. Thoracic Surg., 12:1-17 (Oct.) 1942. 40. Dayton, A. B. and Lindskog, G. E.: Patent Ductus Aneriosus Complicated by Subacute Bacterial Endarteritis: Report of a Case Successfully Treated by Chemotherapy and Surgery. Yale J. BioI. & Med., ]5:259-262 (Dec.) 1942. 41. Humphreys, G. H.: Ligation of the Patent Ductus Arteriosus. A Report of the Results in Seven Cases. Surgery, 12:841-860 (Dec.) 1942. 42. Dolley, F. S. and Jones, J. C.: The Surgical Treatment of Persistently Patent Ductus Arteriosus. Brunn Med. Surg. Trib-qtes, pp. 123-131, 1942. 43. Keys, A. and Shapiro, M. J.: Patency of the Ductus Arteriosus in Adults. Am. Heart J., 25:158-186 (Feb.) 1943. 44. Touroff, A. S. W.: The Results of Surgical Treatment of Patency of the Ductus Arteriosus ~omplicated by Subacute Bacterial Endarteritis. Am. Heart J., 25:187-210 (Feb.) 1943. 45. Harrington, S. W.: Patent Ductus Arteriosus with Bacterial Endarteritis: Transpleural Ligation through Posterolateral Approach: Report of a Case. Proe. Staff Meet., Mayo Clin., 18:217-222 (July 14) 1943.
402
GEORGE E. BURCH
46. Shapiro, M. J. and Keys, A.: The Prognosis of Untreated Patent Ductus Arteriosus and the Results of Surgical Intervention. A Clinical Series of 50 Cases and an Analysis of 139 Operations. Am. J. Med. Sc., 206:174-183 (Aug.) 1943.
47. Hubbard, J. P.: The Diagnosis and Evaluation of Compensated and Uncompensated Patency of the Ductus Arteriosus. J. Pediat., 22:50-59 (Jan.) 1943. 48. Wilson, May G. and Lubschez, Rose: Prognosis for Children \vith Congenital Anomalies of the Heart and Central Vessels; Life Expectancy in Patent Ductus Arteriosus. J. Pediat., 21 :23-30 (July) 1942. 49. Kennedy, J. A. and Clark, S. L.: Observations on the Ductus Arteriosus of the Guinea Pig in Relation to its Method of Closure. Anat. Rec., 79: 349-363 (March) 1941.
GEORGE E.
BURCH,
M.D., F.A.C.P.*
SINCE the early description of the ductus arteriosus by Galen,! there has been, until several years ago, relatively iittle change in the management of patients with a persistence of the ductus. Treatment was entirely medical, emphasis being placed on restriction of activity and the subsequent management of congestive heart failure and bacterial endarteritis as major complications. A great advance in the treatment of this condition occurred in 1938 when Graybiel, Strieder and Boyer2 reported the first attempt to ligate a patent ductus arteriosus despite the fact that the patient died. This attempt at least gave impetus to further trials at ligation. As early as 1907 Munr0 3 developed an operative approach for ligation of a patent ductus and presented clinical evidence to prove the rational basis for such an operation, but his suggestion was ignored for thirty-one years. Success was finally achieved in 1939, when Gross and Hubbard4 reported the first ligation of a patent ductus arteriosus followed by recovery. Because of the striking benefit obtained by Gross and Hubbard and .the impressive results following operation in the' hands of others, there has developed a wave of enthusiastic interest in the surgical treatment of patent ductus arterio~us. This can be readily understood, since the development of a safe operative procedure to correct a persistent ductus arteriosus has made it possible to convert an irreversible type of heart disease into a reversible or curable one. These rapid developments have prompted an analysis of the surgical results to date in order to evaluate better the indications and contraindications for operation. 4
PHYSIOLOGICAL CONSIDERATIONS
Eppinger, Burwell and Gross 5 , 6 and Eppinger and Burwell7 studied the circulation of the blood through the patent ductus arteriosus in man at operation and also in qogs. In these latter investigations a fistulous connection was made between the ~.ta and the pnlmonaJ:y ~XeJ:Y. Th~.J?.looA._~~~.<>'??.~J;Y~_~._.!~.~~?~_.:f~?m the. a~E~a to. th~._£.lll IJl9~~-.-EJ~, as would be expected on tlie oasis of the pressures in the two circulatory systems. Rarely was there any flow of blood in the From the Section on Internal iVledicine, Ochsner Clinic and the Department of Medicine, Tulane University School of Medicine, New Orleans. «c Associate Professor of Internal Medicine, Tulane University School of Medicine; Visiting Physician, Charity Hospital in New Orleans and Touro Infirmary:; CO'psultant in Cardiovascular Diseases, Ochsner Clinic. ~
388
CONGENITAL PATENT DUCTUS ARTERIOSUS
389
reverse direction, that is, from the pulmonary artery to the aorta. }J1j§. gplains_lh~J:~p_s~nce of cY~1J.o~is. In their patients, from 4 to 19 liters of blood per minute was found to enter directly from the aorta into the pulmonary artery. This represented from 45 to 75 per cent of all the blood leaving the left ventricle. The blood entering the pulmonary artery returns to the left ventricle via the lungs without reaching the peripheral circulation. In order to compensate for the loss of blood in the periphery, the volume output from the left ventricle must increase. This occurs without much change in that of the right ventricle, The result is a considerable increase in the work of the left ventricle, lili vent.!.icut~_~!!larK~~.~_nt, strain and eventual failure. There is some increase in the work of the rIght -veritricle~'~is-"it'-'mustcirculate the added amount of blood entering the pulmonary artery from the aorta. Eppinger and his associates5 found the left ventricle pumping four times the volume of blood expelled,by the right ventricle. These effects on ventricular work explain the normal axis deviation or mild left axis deviation and the rare right axis deviation in the electrocardiogram. The patent ductus arteriosus is associated with many of the hemodynamic and other cardiophysiologic manifestations so well known in aortic regurgitation and arteriovenous aneurysm. The roentgenologic signs observed by teleoroentgenography, fluoroscopy or roentgenokymography, easily explained on the basis of the disturbed physiologic condition already discussed, are as follows: 6 ,7 ( 1) greatly increased excursions of the left ventricle, (2) increased pulsations of the pulmonary artery, (3) overfilling or engorgement of the pulmonary conus and pulmonary vessels, (4)- increased pulsations of the bronchovascular structure, particularly prominent near the hilar regions, and (5) enlargement of the left ventricle. The changes in hemodynamics also explain the typical "machinelike" murmur and the other mUJ;murs so commonly heard in this anomaly. The former murmur is characteristic when properly located in the region of the Eulmonary valve of the chest. Further details of changes in the dynamics of the circulation can be found in the papers of Eppinger and his associates. It is well to point out at this time that when the ductus is successfully ligated, the circulation Jjr..aID.-ati-
ci1lli:-".re.tllrn~.IQ_JIQrnJ~J..~i!hjQ...~._~Qn:. . Ji.me, ~~~~.!:-._QJ_§ec..Q!l~ls_ ..to
hours. 5 It···is beyond the scope of this paper to discuss the anatomy, embryology, method of closure and other physiologic phenomena associated with patent ductus arteriosus. The papers of Franklin,l Boyd,S Barclay et al.,9 Noback and Rehman,10 Kennedy,ll Kennedy and Clark12 and Jager and W ollenman, 13 in .addition to the standard textbooks, may be consulted by those interested in these phases of the subject.
390
GEORGE E. BURCH RESULTS OF LIGATION OR EXCISION
Since the failure of Graybiel, Strieder and Boyer2 in 1938 to ligate a patent ductus arteriosus with superimposed infection, there have been in the literature many reports on the surgical treatment of this anomaly. Gross and Hubbard4 in 1939 reported the first successful ligation. Since then these authors and others have reported many surgical results at such a rapid rate that it is difficult to determine the chronologie order of publication, especially since several authors have written several reports on the same patients within a few months' interval. In spite of these facts an attempt has been made to list in chronological order of publication from most of the available reports the results of ligation of the patent ductus arteriosus (Tabulation) .. By this means at least an impression of the published results can be obtained. It nlust be remembered that there have been many unrecorded cases, especially fatal ones, which are less apt to be reported. Therefore, such statistics will indicate only the trend of the results of surgical treatment. ANALYSIS OF LITERATURE
In 1938 Graybiel, Strieder and Boyer2 attempted to ligate a patent ductus arteriosus complicated by subacute bacterial endarteritis (Streptococcus viridans) but the patient died. Gross and I:-Iubbard 4, in 1939 reported a successful ligation in a 7%-year-old girl who showed signs of impairment in growth and cardiac enlargement. Gross14. reported his results in 4 patients one month later and at the same time described a surgical approach for the operation; three of the cases were new and the results were likewise successful. Jones and his associates15 reported during the next month their immediate results in 7 cases. All of these patients were apparently cured or greatly benefited. One, however, died thirty days later of an infection due to the hemolytic Staphylococcus aureus. These authors included an addendum to this same report in which they cited 6 more successful operations making a total of 13 cases with only 1 death. Several months later they16 reported their results in 11 cases in more detail. It is a bit confusing from these articles to know which were the patients previously reported. The success of the operation is modified somewhat in the later report, since in 6 of the 11 patients a systolic murmur remained. Of course, a sufficient length of time must elapse before the results in such patients can be properly evaluated. Such overlapping of cases and. variations in descriptions make an evaluation of the results in the literature difficult. Stephens,17 in the discussion of the paper of Jones and his co-workers,16 reported a death from infection on t~e tb.ird postoperative day. Gross, Emerson and Green 18 reported a c'ase of successful ligation of the ductus but the patient is probably one previoQ~ly reported by Gross. 14 Gross19 summarized his
CONG£:NtTAL PATENT DUCTUS ARTERtOSUS
391
results in 4 cases in which the ductus was ligated without a single death. Touroff and Tuchman20 reported a successful ligation in a 51-yearold woman with a patent ductus and superimposed endarteritis (Streptococcus viridans). This same patient had made a spontaneous recovery from endarteritis under medical treatment twelve and a half years before. Gross,21 summarizing his experience with ligation in 10 patients, reported 1 death from infection postoperatively, no improvement in 1 case and remarkable improvement in the remaining 8. Kerr 22 in the discussion of Gross's paper 21 cited 2 cases, a young girl who died from infection and a child who showed no improvement following ligation. In the latter case "Kerr suggested the possibility of multiple cardiac lesions as the reason "that complete cure was not effected by the operation. Touroff and Vesell23 reported a cure in a 29-year-old woman who had a patent ductus arteriosus with a superimposed subacute Streptococcus viridans endarteritis. These same writers24 later reviewed their results with ligation in 4 patients with subacute Streptococcus viridans endarteritis superimposed upon a patent ductus arteriosus. One patient, apparently the one mentioned above,23 was cured, 2 died of hemorrhage and the other continued to show bacteremia, as the duct was too short for excision and was only ligated. Gross25 summarized his results again in 13 patients subjected to ligation of the ductus. One died of infection, 1 was not benefited and 11 were definitely improved or cured. Gale and his co-workers 26 reported a successful ligation in a 19-yearold girl. Miangolarra and Hu1l27 described a successful ligation in a 20-year-old woman and a death from hemorrhage in a 12-year-old boy. Castellano and co-workers28 reported a case of a patent ductus arteriosus in which ligation resulted in cure. Gebauer and Nicho129 ligated the ductus in three patients; the 39-year-old woman died of hemorrhage but the 11- and 14-year-old children recovered and were clinically improved. Bourne and his associates30 ligated the ductus in a 23-year-old man with subacute bacterial endarteritis (Streptococcus viridans and Haemophilus influenzae) in whom the cultures remained positive, although the patient was well sixteen months later. Ligation was also performed in a 19-year-old girl with subacute bacterial endarteritis (Streptococcus viridans), and she was well eleven months later. SulfonamideS were used in treating both 'of these patients. Bourne31 again "reported the same 19-year-old patient elsewhere. Shapiro and Keys32 studied 23 of their patients with patent ductus and reviewed patients operated on by observers. A more detailed analysis is presented by these authors in a later paper (vide infra). Came's and Gonzalez Sabathie33 presented the case of a 10-year-old boy who made an excellent recovery following ligation of a patent ductus.
SUMMARY OF MOST OF CASE REPORTS IN LITERATURE ON LIGATION OF PATENT DUCTUS ARTERIOSUS TABULATED IN CHRONOLOGICAL ORDER OF PUBLICATION·
Vol
'0 N
Results J.,.
Patients
Date Published
Author
Cure Age
GraybieI, Strieder & Boyer Gross & Hubbard4 •••.•.••
2 •••••••••• /
May 1938
, •.••••••• J
Feb. 1939
Grossl4
,
1 Mar. 1939
7~.
I~I
Stephens17 ••••••••••••••••••••••••• I April 1939
Grossl9 •••••••••••••••••••
Aug. 1939
1
Sept. 1939
, •• , •••••
Bullock, Jones & Dolley16 Touroff& Tuchman20 ."
, •••••• 1
Gr0ss21 . • • • . • . . • • • . . . . . . . . . • . . • . ' Kerr-
,
TourGff & Vesel121 • ~
, Dec. 1939
,
---June 1940
• • • • . • • • . '"
---Oct. 1940 ---Oct. 1940 ----
.•
··· ..
Oct. 1940
••••••••••••••••
----
Touroff & Vesell24 •••••••••••••••••.• GrossU Gale et
•.•••.•••...••.•....•..•.•••
Oct. 1940
April 1941
Miangolarra & Hul127 ••••••••••••••• I April 1941 CastellanQ et al. 2B •••••••••••••••••• .'1 April 1941
Hem. I In£.
Remarks Others S.V.
__ -
4
26
-- 11
--
7, 7
17,11
F.
H. Staph. aureus
M.
4M. 7 F. _11_l~O
~ n
4
4
Cd
1 died of Staph. aureus
F.
----10 ... 8 - --- F. 2 . ... ----- - --........ ..... 1 29 - - F.- - -1------
I
-I:
4 F.
19 F. -I 12
20
t,'%j
~
1 M.
51
24-63
~ ~ C)
~I-I-I-
- - - -4-31
Pt. died of H. Staph. aureus
_1_13_t~
f Dec. 1940
a1. 26 .••••••• , ••• , •••••..•••• 1
Deaths
Not Cured
Imp.
Sex I Cases
Jones, Dolley & Bullockl5 , • • • . . . . . • . . 1 April 1939 Gross, Emerson & Green1• ••••
J
• M.
F.
'
__4_
1
13
11
......
1 died of Staph. aureus 1 died of Staph. aureus
S.V.
1
S.V. in all
1
1 died of Staph. aureus
---'---
- - - - - --- --_.---
I_ - _2 1 _ _1_ _-
S.V.
=
Gebauer & NiehoI29 ••••••••••.••...• 1 June 1941
11, 14,39
Bourne et al.lo ....•....•........... I Oct. 1941
23 19
--I
BourneS! Carnes & G. Sabathie33
I
Oct. 1941
1
Dec. 1941
--I
J
--
16,5,18 21,4,12 35
Johnson et al.34 ••••••••••••••••••••• 1 Feb. 1942 Winn et
'1- Feb.
aU5
TourofI et a1. 3().
--!
Nixon38 • • . • • • • . • • • . • . • . . • • • . • • . • . . i July 1942 TQurofI39 •••••
"
•.•••••••• "
•••••..
1
Oct. 1942
Dayton & Lindskog40
I Dec. 1942
Humphreysu
1
Dec. 1942
Dolley & Jones42 ••••••••••••••••.... 1
1942
Touroff44 •••••••••••••••••••••..... I Feb. 1943 Harrington45
I July
Shapiro & Keys4s
1
Shapiro & Keys46
1
19'43
Aug. 1943 Aug. 1943
__3_1_ _
1_ _ _ 1_ _ _ 1_ _'_
F.
1 had S.V. 1 had H. infiuenzae
F.
S.V.
--M. ~-
5 F. 2 M.
45
1942
Vedoyaet al.IT .••••.•••••••••••.... I May 1942
-
---
S.V. in 1
F.
- -F.- 1 - 29
Mar. 1942
. • • • • • • • • • • • . • • • • . ..
19 10
~1 M.
S.B.E.
1 - -
s.v.
-I
11, 4 29, 11
4 F.
Cause unknown
4
I
-I-i----
29,51 18, 9
25
3 F.
'
1 M.·
-
4·
S.V.inall
4
S.V.
F.
-_._-1.-
16 113 HI - - j-.... - -11813 --
1 died of S.B.E. P. o. aneurysm
Staph. aureus S.B.E. in all
9-6_3 ~._121_ 6·
107 . 33
* No attempt has been made to collect all cas~s which have been reported. Explanation of abbreviations: S.V. = Streptococcus viridans S.B.E. = Subacute bacterial endarteritis H. Staph. aureus = Hemolytic Staphylococcus aureus Imp. = Improved Hem. = Hemorrhage Inf. = Infection
6
'1-:""1_
8~1_""
I 20
6
o
Z
G') t:'j
Z
~ t-I
I'C
F.
15
(j
S.B.E.in 1 Wron~ ves-I. All unc?mplicated
sel lIgated . S.B.E. m 2 p.o. in 2 cases S.B.E. in all
~Z
~
~
~
(J)
> ~ ~ tJ:j ~
o c:: )ססoo4
(J)
CI)
\j..)
\0
v.J
394
GEORG~
E. BURCH
Johnson and his associates 34 reported 7 patients in whom the ductus \vas ligated. One died of hemorrhage, one had subacute bacterial endarteritis (Streptococcus viridans) and died seven months after operation and in ··5 the ligations were successful. Winn, Hughes and Sanders35 ligated a ductus in a patient with subacute bacterial endarteritis (Streptococcus viridans) and supplemented this with sulfapyridine and heparin. One year later the patient was in excellent health. Touroff, Vesell and Chasnoff36 reported their second patient with patent ductus arteriosus with subacute bacterial endarteritis (Streptococcus virida~s) who was cured by ligation. Vedoya and his associates37 described their results with ligation in 4 patients. One patient died at operation, 1 was benefited and in two the results were e~cellent. Nixon38 reported a successful ligation in a 15 -year-old girl. Touroff89 reported 4 additional ligations in patients with a patent ductus with superimposed Streptococcus viridans endarteritis. This brought Touroff's personal series of patent ductus associated with endarteritis to 8. Since this report appeared, Touroff had had 2 additional patients suffering from patent ductus arteriosus complicated by infection who were cured by operation. Dayton and Lindskog40 reported a cure by ligation of another patent ductus arteriosus complicated by Streptococcus viridans endarteritis. Humphreys 41 reported 16 ligations; all results were excellent except tor a stormy convalescence in two instances. However, one year later 1 patient died of an aneurysm that developed postoperatively in the ductus and another died of bacterial endarteritis two months following operation. Dolley and Jones 42 summarized their results again. In their series of 18 cases ranging in age from 4 to 31 years, ligation was accomplished without a single immediate operative death. One patient died several days later of a staphylococcic infection in the region of the ductus. In 4 other patients a murmur developed and in one of these a continuous murmur recurred. Keys and Shapiro 43 made another analysis of collected cases. These cases will be taken up in greater detail when their third and apparently most recent analysis is discussed. Touroff44 in his next report added 3 more cases of ligation of patent ductus arteriosus complicated by endarteritis, making a total of 11 cases, which formed the basis for his most recent report. Two patients died of hemorrhage; 6 recovered without the aid of chemotherapy; 3 continued to have positive blood cultures and 1 of these died eight months later. Harrington45 reported a successful ligation in a patient with a superimposed subacute bacterial endarteritis (Streptococcus viridans); he has operated on 5 other patients with good results. Shapiro and Keys46 described the results of 140 ligations by 25 surgical-teams, a great number of which were collected by personal correspondence with -surgeons. The remainder were collected from the literature. Of these, 107 were uncomplicated and 33 were associated with a
CONGENITAL PATENT DUCTUS ARTERIOSUS
395
superimposed bacterial endarteritis. Seven of the patients were from the author's series. Of the 107 uncomplicated cases, 81 were successful except for a distant short systolic murmur that remained in a few instances over the pulmonic area. In 14 the continuous murmur remained. In 6 death resulted from rupture of the duct; in 2 bacterial endarteritis developed after operation; in 1 case mediastinitis with death resulted; in 1 there was no duct to ligate (a direct anastomosis between the aorta and pulmonary artery was found so nothing was done); in 3 a vessel other than the duct was ligated (the aorta in one instance) and 2 of these died; and in 2 the diagnosis was mistaken. There was a total of 9 deaths in the 107 cases (the 2 with endarteritis after operation were not included), a mortality rate. of 8.5 per cent. Of the 33 patients operated upon in the presence of superimposed bacterial endarteritis, 20 seemed to have been completely cured clinically. Five patients died at operation of rupture of the duct and in 8 fever persisted in spite of operation. This gives an apparently favorable prognosis of more than 50 per cent in a disease with a previous mortality of almost 100 per cent. In the preceqing table the reports which have been discussed are sUITlmarized in tabular form. CLINICAL PICTURE
The clinical picture of patent ductus arteriosus may vary considerably in specific cases but in general the syndrome is fairly characteristic. 19 , 21,47 The m.~~t__~Q!e~entative feature is a loud harsh murnmr best heard over the region oT the pulmonary valve. It is usually continuous with systolic exacerbations. The l~~ snappy, second pu1lllonic heart soun4.1!~ard with.the 111~rmur producesa "machine-liKe" effec~. The _~ystolic I)1U~II1~r._i.s£re~GeJ1dQand --the-diast.ok_QJ!~_i~_.ge cresce!]:Qp. There usually is a definite systolic_-Ihrill and often a continuous one with systolic exacerbations. The murmurs and thrills may be best elicited with the subject l~ni!!KiQI.w.ar.d and the lungs emptied ~_._gI'!~!!nllm. The murmurs and thrills are produced by the blood flowing fronl the aorta into the pulmonary artery. These manifestations vary· in degree with the size and anatomic nature of the ductus. 'fhe patients will usually give a history of the presence of a murmur from birth or since their first physical exanlination. These patients usually present no cyanosis, since aerated blood is entering the pulmonary circuit from the aorta. As the patient becomes older, the increased burden on the heart begins to manifest itself by ,cardiac enlargemetzt. After a time cqngestive heart failure develops and the manifestations of left and. right ventricular decompensation will gradually appear and become progressively worse. If bacterial infection of the ductus develops, then there will be a picture of bacterial endQcarditiJ with the embolic phenomena present mainly in the lungs. The S,treptococcus viridans is the most common offendina- organisJ.I1. There
396.
GEORGE E. BURCH
may be a wide pu~se .pressur~ with an elevated systolic~ess!!!.e and even a slightly lowered diastolic pressure. This may result in peripheral vascular signs similar to those of aortic regurgitation. These patients often sh
In the presence of patent ductus arteriosus the life expectancy in untreated cases has been variously stated but in general the findings are essentially the same. Of 92 patients studied by Abbott,4 one-fourth died of bacterial endarteritis and an additional one-half died of slow or rapid heart failure. The average age at death in this group of 92 cases was 24 years. Gross and his associates18 estimated that a child with a patent ductus has one chance in four to live a normal length of life, one chance in four to die of bacterial endarteritis and almost two chances in four that he will die of heart failure. Bullock and his coworkers 16 found in 80 cases reviewed by them that 11 (14 per cent) died as a result of the congenital lesion by -the age of 14; by 30 one-half were dead; by 40, 71 per cent were dead and 2 lived to the age of 66 years. Eighteen patients (23 per cent). died of congestive heart failure; 5 (6 per cent) of rupture of the ductus; 42 (53 per cent) of bacterial endarteritis; and 4 (5 per cent) of an associated condition. Thus, 69 (86 per cent) died as a result of the lesion. In 5 the cause of death was not given and in 6 (7 per cent) death was attributed to unrelated cause~. Shepiro and Keys4.6 found from a review of the literature that 80 per"cent of such patients eventually died of the cardiac lesion. Pa-
CONGENITAL PATENT DUcrUS ARTERIOSUS
397
tients alive at 17 years of age average 35 years at death, 40 per cent dying of subacute bacterial endarteritis and most of the remainder of congestive heart failure. Wilson and Lubschez48 found no deaths from congestive heart failure and bacterial endarteritis in 38 patients with uncomplicated patent ductus. There was one unexplained sudden death. Twenty-four were between 10 and 20 years, 12 between 20 and 30 years and 2 over 30 years of age. The incidence of persistent ductus arteriosus varies with the series reported. Bullock and his associates16 found 133 instances of congenital heart disease in 21,000 autopsies at Los Angeles County Hospital. Thirty-six of these were cases of patent ductus, 21 of which had other associated defects. Twenty died before the age of 9 months; 10 with uncomplicated patent ductus \vere less than 2 months old. Every patient died as a result of this lesion. Wilson and Lubschez48 estimated that 1 to 2 per cent of cases of organic heart disease in the adult and 5 to 12 per cent in children are the result of congenital malformations. An analysis of 54,842 reported autopsies revealed that congenital defects constituted 1.3 per cent of all cases, the reported incidences varying from 0.6 to 5.4 per cent. Of 152 patients with congenital cardiac malformations on whom autopsies were performed at the New York Nursery and Child's Hospital, 10.5 ,per cent were cases of patent ductus arteriosus. Of the 54,842 autopsies, 63 (0.11 per cent) of these patients had a patent ductus. Of the total congenital anomalies, 10.3 per cent were patent ductus arteriosus. Keys and Shapir0 43 estimated that about 20,000 persons in the United States have a patent ductus arteriosus. About two thirds of them are females. CAUSES OF FAILURE FOLLOWING LIGATION
Gross 25 attributes poor results of operation to (1) failure to find the ductus, (2) a ductus too short to ligate, (3) ligation of a wrong vessel, (4) hemorrhage from the ductus, (5) incomplete obliteration of the ductus, (6) associated cardiovascular abnormalities, (7) wound sepsis, (8) postoperative pneumonia as well as pulmonary embolism preoperatively. The nature of these causes of failure is obvious. Most of them~ are technical considerations whereas some will enter into the surgical problem as they do in any major surgical procedtlre in the thorax. Hemorrhage is particularly apt to occur in patients \vith superimposed bacterial endarteritis. The infection renders the ductus friable, which results in rupture or cutting through of the ligature. With improvement in the operative procedure there will undoubtedly be fewer failures. INDICATIONS FOR OPERATION
The indications for operation are not too definite at present but certain generally accepted concepts may be enumerated.
398
GEORGE E. BURCH
1. The surgical risk is still not good enough in average hands to recommend operation to all patients with patent ductus arterios.us. With further 'improvement of the operative technic such a recommendation may be made, especially in view of the mo~bidity and short duration of life associated with this defect. 2. Because of the high mortality rate in those patients with superimposed endarteritis who are not subjected to ligation and the greater than 50 per cent cure (vide supra) following ligation, the operation should be recommended when endarteritis is present. 23 The prerequi- . sites for successful operation are (a) that the vegetations be confined to the ductus and (b) that the ductus be of sufficient length to permit excision. (These can be determined, at present, only at the time of operation. ) 3. The operation should be performed in the presence of definite cardiac decompensation, especially if it is progressing. 21 (This would include patients who are showing signs of progressive failure, a large heart and serious disturbances. in cardiac mechanism.) 4. Ligation of the ductus is indicated in patients showing definite retardation of physical and mental development. COMMENT
It can be seen from the foregoing that the problem of patent ductus arteriosus is still unsettled. The mean mortality_ rate determined from the results of operations performed by many surgeons is about 8.5 per cent in cases of uninfected ducti. This does not represent the results that may be expected when a surgeon has had experience with only an occasional case or with many cases. Furthermore, as shown by Shapiro and Keys,46 over 20 per cent of the patients operated on in 107 uncomplicated cases either died or were not benefited materially as far as the murmur \vas concerned. There is no doubt that the life expectancy in persistent ductus arteriosus is considerably reduced. It is apparent too that most patients with an uncomplicated ductus are spectacularly benefited by ligation. It is also true, ho,vever, that these patients have only been followed four years after operation and only time will determine exactly what influence the operation has on the- duration of life. Furthermore, in the presence of superimposed bacterial endarteritis the mortality rate for untreated cases is approximately 100 per cent, but ligation has reduced this to less than 50 per cent (vide supra) after a follow-up of about one year~ Therefore, ligation should not only be recommended but urged if the patient has an associated endarteritis. The same is true in patients who have progressive cardiac damage and decompensation or patients with definite impairment of mental and physical development. One would nevertheless hesitate to recommend or assume the responsibilities for operation in a patient who has a patent ductus without any evi-
CONGENITAL PATENT DUCTUS ARTERIOSUS
399
dence of embarrassment of health. Dolley and Jones 42 found the operation easier to perform in children 4, 5, and 6 years old. If this proves to be true, then the age of the patient will influence considerably the time at which operation should be recommended. It is conceivable that in the future the operation will usually be recommended as soon as a patent ductus is discovered. No such recommendation can be made at this time with the operative mortality averaging 8.5 per cent and even being greater 'in average hands. Until the surgeons have developed a procedure that is relatively safe and the ~esults can be predicted 'preoperatively with a greater degree of certainty, the operation should be reserved for those special indications already listed. SUMMARY
Most of the available case reports in the literature on ligation of patent ductus arteriosus have been reviewed. The average surgical mortality was found to be 8.5 per cent in uninfected ducti. The rate varies considerably, however, depending on the surgeon and his experience (Tabulation). The operation has, been recommended for all patients with the anomaly if there is a superimposed bacterial endarteritis; more than 50 per cent of such patients have been cured by ligation of the ductus. It is also strongly advised for patients with progressive cardiac failure and for patients with definite impairment of physical and mental growth. Poor results following ligation may be attributed to: (1) failure to find the ductus, (2) ligation of the wrong vessel, (3) wound sepsis, (4) hemorrhage, (5) a ductus too short for ligation, (6) postoperative • pneumonia, (7) associated cardiovascular abnormalities and (8) incomplete obliteration of the ductus. t
BIBLIOGRAPHY
1. Franklin, K.
J.:
Ductus Venosus (Arantii) and Ductus Arteriosus (Botalli). Bull. Hist. Med., 9:580-584 (1\,lav) 1941. 2. Graybiel, A., Strieder, J. W. and Boyer, N. H.: An Attempt ·to Obliterate the Patent Ductus Arteriosus in a Patient \vith Subacute Bacterial Endarteritis. Am. Heart J., 15:621-624 (May) 1938. 3. l\1unro, J. C.: Ligation of the Ductus Arteriosus. Ann. Surg., 46:335, 1907. 4. Gross, R. E. and Hubbard, J. P.: Surgical Ligation of a Patent Ductus Arteriosus; Repoit of First Successful Case. J.A.M.A., 112:729-731 (Feb. 25) 1939.
5. Eppinger, E. C., Burwell, C. S. and Gross, R. E.: The Effects of the Patent Ductus Arteriosus on the Circulation. J. Clin. Investigation, 20:127-143
(March) 1941.
6. Burwell, C. S., Eppinger, E. C. and Gross, R. E.: The Signs of Patent Ductus
Arteriosus Considered in Relation to Measurements of the Circulation. Tr. A. Am. Physicians, 55:71-79 (May) 1940. 7. Eppinger, E. C. and Burwell, C. S.: The Mechanical Effects of Patent Ductus Arteriosus on the Heart and their Relation to the X-ray Signs. J .A.M.A., 115:1262-1266 (Oct. 12) 1940.
400
GEORGE E. BURCH
8. Boyd, J. D.: The Nerve Supply of the Mammalian Ductus Arteriosus. J. Anat. 75:457-468 (July) 1941. 9. Barclay, A. E., Barcroft, J., Barron, D. H., Franklin, K. J. and Prichard, M. 1\1. L.: Pulmonary Circulation Times Before and After Functional Closure of the Ductus Arteriosus. J. Physio!., 101:375-377 (Nov.) 1942. 10. Noback, G'. J. and Rehman, I.: The Ductus Arteriosus in the Human Fetus and Newborn Infant. Anat. Rec., 81 :505-527 (Dec.) 1941. 11. Kennedy, J. A.: A New Concept of the Cause of Patency of the Ductus Arteriosus. Am. J. M. Sc., 204:570-573 (Oct.) 1942. 12. Kennedy, J. A. and Clark, S. L.: Observations on the Physiological Reactions of the Ductus Arteriosus. Am. J. Physiol., 136:140-147 (March) 1942. 13. Jager, B. V. and WoUenman, o. J., Jr.: An Anatomical Study of the . Closure of the Ductus Arteriosus. Am. J. Path., 18:595-613 (July) 1942. 14. Gross, R. E.: A Surgical Approach for Ligation of a Patent Ductus Arteriosus. New England J. Med., 220:510-514 (Mar.' 23) 1939. IS. Jones, J. C., Dolley, F. S. and Bullock, L. T.: The Diagnosis and Surgical Therapy of Patent Ductus Arteriosus. J. Thoracic Surg., 9:413-430 (April) 1939.
16. Bullock, L. T., Jones, J. C. and Dolley, F. S.: The Diagnosis and the Effects of Ligation of the Patent Ductus Arteriosus., A Repon of Eleven Cases. J. Pediat., 15:786-801 (Dec.) 1939. ' 17. Stephens, H. B.: Discussion on Jones, J. C., Dolley, F. S. and Bullock, L. T.: The Diagnosis and Surgical Therapy of Patent Ductus Arteriosus. J. Thoracic Surg., 9:413 (April) 1939. 18. Gross, R. E., Emerson, P. and Green, Hyman: Surgical Exploration and Closure of a Patent Ductus, Arteriosus. Report of Second Successful Case. Surgery, 6:201-205 (Aug.> 1939. 19. Gross, R. E.: Surgical Managenlent of the Patent Ductus Aneriosus; With Summary of Four Surgically Treated Cases. Ann. Surg., 110:321-356 (Sept.) 1939. 20. Touroff, A. S. W. and Tuchman, L. R.: Subacute Streptococcus Viridans Endarteritis Superimposed on Patent Ductus Arteriosus; Spontaneous Re- • covery. Recurrence After Twelve and One-half Years. Recovery Following Operative Treatment. Am. Heart J., 23:857-862 (June) 1940. 21. Gross, R. E.: Experiences with Surgical Treatment in Ten Cases of Patent Ductus Arteriosus. J.A.M.A., 115:1257-1262 (Oct. 12) 1940. 22. Kerr, \V. J.: Discussion of Gross, R. E.: Experiences \vith Surgical Treatment in Ten Cases of Patent Ductus Arteriosus. J.A.M.A., 115:1257-1262 (Oct. 12) 1940. Eppinger, E. C. and Bunvell, C. S.: The Mechanical Effects of Patent Ductus Arteriosus on the Heart and Their Relation to the X-ray Signs. J.A.M.A., 115:1262-1266 (Oct.) 1940 and Touroff, A. S. \V. and Vescll, H.: Subacute Streptococcus Viridans Endarteritis Com.. plicating Patent Ductus Arteriosus: Recovery Following Surgical Treatment. J.A.M.A., 115:1270-1272 (Oct. 12) 1940. 23. Touroff, A. S. \\-'. and Vesell, H.: Subacute Streptococcus Viridans Endarteritis Complicating Patent Ductus Arteriosus; Recovery Follo\ving Surgical Treatment. J.A.M.A., 115:1270-1272 (Oct. 12) 1940. 24. Touroff, A. S. W. and Vesell, H.: Experiences in the Surgical Treatment of Subacute Streptococcus Viridans Endarteritis Complicating Patent Ductus Arteriosus. J. Thoracic Surg., 10:59-83 (Oct.) 1940. 25. Gross, R. E.: Surgical Closure of the Patent Ductus Arteriosus. ]. Pediat., 17:716-733 (Dec.) 1940. 26. Gale, ]. W., Pohle, F. ]. and Romaine, H.: Successful Ligation of Patent ...{,
CONGENITAL PATENT DUCTUS ARTERIOSUS
401
Ductus Arteriosus; Report of Case. Wisconsin M. J., 40:296-298 (April) 1941. 27. Miangolarra, C. J. and Hull, E.: Successful Ligation of a Patent Ductus Arteriosus. Surgery, 9:597-602 (April) 1941. 28. Castellano, T., ~laldonado Allende I. y Finochietto, E.: "Ductus Arteriosus." Ligadura del conducto arterial persistente. A prop6sito de un caso, operado con exIto. Presna med. argent., 28:825-828 (April 16) 1941. 29. Gebauer, P. W. and Nichol, A. D.: Ligation of the Patent Ductus Aneriosus. Ohio State M. J., 37:538-543 (June) 1941. 30. Bourne, G., Keele, K. D. and ~rubbs, o. S.: Ligation and Chemotherapy for Infection of Patent Ductus Arteriosus. Lancet, 2:444-446 (Oct. 18) 1941. 31. Bourne, Geoffrey: Changes in Renal Function and Persistence of the l\tfurmur after Ligature of a Patent Ductus Arteriosus. Brit. Heart J., 3:228232 (Oct.) 1941. 32. Shapiro, }\'1. J. and Keys, A.: Clinical and Physiologic Analysis of T\ventythree Patients with Persistent Patent Ductus Arteriosus. (\Vith the assistance of Antonio Violante, M.D.) Internat. Clin., 4:148-164 (Dec.) 1941. 33. Carnes, O. y Gonzalez Sabathie, L.: Persistencia del conducto arterioso; Operaci6n; curaci6n. An. de cir., 7:256-266 (Dec.) 1941. 34. Johnson, J., Jeffers, W. A. and Margolies, A. L.: The Technique of the Ligation of the Patent-Ductus Arteriosus. J. Thoracic Surg.,11:346-356 (Feb.) 1942. 35. Winn, W. A., Hughes, C. L. and Sanders, J. M.: Subacute Bacterial Endarteritis Complicating Patent Ductus Arteriosus; Case Report \vith Recov~ry Follo\ving Sulfapyridine-Heparin Therapy. Ann. Int. Med., 18:242-250 (Feb.) 1942. 36. Touroff, A. S. W., Vesell, I-I. and Chasnoff, J.: Operative Cure of Subacute Streptococcus Viridans Endaneritis Superimposed on Patent Ductus Arteriosus. J.A.MA., 118:890-892 (March 14) 1942. 37. Vedoya, R., Gonzalez Videla, J. and Albanese, A. R.: Persistencia Del Conducto Artcrioso. Intervenci6n Quirurgica en cuatro casos. Rev. Arg. de Cardio!., 9:94-110 (May-June) 1942. 38. Nixon, J. \V.: Ligation of a Patent Ductus Arteriosus: Report of a Successful Case. Surgery, 12:31-40 (July) 1942. ' 39. Touroff, A. S. W.: Further Experiences in the Surgical Treatment of Sub. acute Streptococcus Viridans Endarteritis Superimposed on Patent Ductus Arteriosus. J. Thoracic Surg., 12:1-17 (Oct.) 1942. 40. Dayton, A. B. and Lindskog, G. E.: Patent Ductus Aneriosus Complicated by Subacute Bacterial Endarteritis: Report of a Case Successfully Treated by Chemotherapy and Surgery. Yale J. BioI. & Med., ]5:259-262 (Dec.) 1942. 41. Humphreys, G. H.: Ligation of the Patent Ductus Arteriosus. A Report of the Results in Seven Cases. Surgery, 12:841-860 (Dec.) 1942. 42. Dolley, F. S. and Jones, J. C.: The Surgical Treatment of Persistently Patent Ductus Arteriosus. Brunn Med. Surg. Trib-qtes, pp. 123-131, 1942. 43. Keys, A. and Shapiro, M. J.: Patency of the Ductus Arteriosus in Adults. Am. Heart J., 25:158-186 (Feb.) 1943. 44. Touroff, A. S. W.: The Results of Surgical Treatment of Patency of the Ductus Arteriosus ~omplicated by Subacute Bacterial Endarteritis. Am. Heart J., 25:187-210 (Feb.) 1943. 45. Harrington, S. W.: Patent Ductus Arteriosus with Bacterial Endarteritis: Transpleural Ligation through Posterolateral Approach: Report of a Case. Proe. Staff Meet., Mayo Clin., 18:217-222 (July 14) 1943.
402
GEORGE E. BURCH
46. Shapiro, M. J. and Keys, A.: The Prognosis of Untreated Patent Ductus Arteriosus and the Results of Surgical Intervention. A Clinical Series of 50 Cases and an Analysis of 139 Operations. Am. J. Med. Sc., 206:174-183 (Aug.) 1943.
47. Hubbard, J. P.: The Diagnosis and Evaluation of Compensated and Uncompensated Patency of the Ductus Arteriosus. J. Pediat., 22:50-59 (Jan.) 1943. 48. Wilson, May G. and Lubschez, Rose: Prognosis for Children \vith Congenital Anomalies of the Heart and Central Vessels; Life Expectancy in Patent Ductus Arteriosus. J. Pediat., 21 :23-30 (July) 1942. 49. Kennedy, J. A. and Clark, S. L.: Observations on the Ductus Arteriosus of the Guinea Pig in Relation to its Method of Closure. Anat. Rec., 79: 349-363 (March) 1941.