- Email: [email protected]
Patent ductus arteriosus in adults-long-term follow-up: Nonsurgical versus surgical treatment
280
JACC Vol. 8. No.2 August 1986:280-4
Patent Ductus Arteriosus in Adults-Long-Term Follow-Up: Nonsurgical Versus Surgical Treatment RUSSELL G. FISHER, DO, DOUGLAS S. MOODIE, MD, FACC, RICHARD STERBA, MD, FACC, CARL C. GILL, MD, FACC Cleveland, Ohio
The long-term prognosis of adult patients with patent ductus arteriosus treated medically or surgically has not been demonstrated. One hundred seventeen adult patients ranging in age from 18 to 81 years (mean 36) were followed up for 1 to 37 years (mean 18). Forty-five patients were treated nonsurgically and 72 had surgical closure. The nonsurgical group experienced significantly more cyanosis (p 0.002) and had fewer diastolic murmurs (p > 0.001) than did the surgical group. In the nonsurgical group, patients with cardiomegaly before treatment were more likely to die (p > 0.001) than were patients who did not have cardiomegaly. In the surgical group, patients with cardiomegaly be-
=
Patent ductus arteriosus is a rare entity in adults that may result in irreversible pulmonary hypertension, congestive heart failure and premature death. There are few studies relating surgical and nonsurgical treatment to long-term prognosis in adults with patent ductus arteriosus. In this report we describe our experience with isolated patent ductus arteriosus (with or without pulmonary hypertension) in the adult.
Methods Study patients. From 1951 to 1984, there were 117 patients seen at the Cleveland Clinic with a diagnosis of isolated patent ductus arteriosus, with or without pulmonary hypertension. There were 95 women and 22 men in our study group. We have achieved follow-up for 114 (97%) of these 117 patients. The patients were classified into two groups: those who received nonsurgical therapy (no treat-
From the Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio. Manuscript received August 13, 1985; revised manuscript received February 20, 1986, accepted March 19, 1986. Address for reprints: Douglas S. Moodie, MD, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44106. © 1986 by the American College of Cardiology
fore treatment had a worse prognosis (p = 0.09) than that of patients with normal heart size. Seven patients, five in the nonsurgical and two in the surgical group, presented with a pulmonary artery systolic pressure greater than 100 mm Hg. Five of these patients are alive and well at a mean follow-up time of 18 years. The two nonsurvivors were in the nonsurgical group and died at 4 and 19 years of follow-up, respectively. Adult patients with patent ductus arteriosus should be treated surgically, especially if cardiomegaly is seen at initial presentation. (J Am Coll Cardiol 1986;8:280-4)
ment or medical therapy) and those who received surgical therapy. Thirty-three patients received no therapy and 12 received medical therapy alone. Sixty-eight patients (58%) underwent surgical closure of the patent ductus arteriosus. Four patients had combined medical and surgical therapy and were considered as surgical patients. When all patients were considered at initial diagnosis, 57 were in New York Heart Association functional class I, 51 in class II, 7 in class III and 2 in class IV. There was no statistically significant difference between the surgical and nonsurgical groups based on their admission functional class. Clinical presentation. Symptoms at diagnosis were comparable in the two groups (Table 1). Thirty-seven (32%) of the total 117 patients presented with exercise intolerance. This was the most common symptom at presentation. Twentynine percent of the patients complained of dyspnea. Cyanosis at initial presentation was more frequent in the nonsurgical group (p = 0.001). Nine patients in this group compared with no patients in the surgical group were cyanotic on admission (p = 0.002). Thirty-seven patients (32%) were asymptomatic at the time of initial presentation. Ninety-seven percent of the patients (114 of 117) presented with a systolic murmur, generally of grade 2 to 4/6 in intensity. It was heard best at the left upper sternal border 0735-1097/86/$3.50
lACC Vol. 8. No.2
Table 1. Symptoms at Presentation in 117 Patients
No. of patients Asymptomatic Symptomatic Exercise intolerance Dyspnea Cyanosis Peripheral edema Clubbing
281
FISHER ET AL. ADULT PATENT DUCTUS ARTERIOSUS: LONG-TERM FOLLOW-UP
August 1986:280-4
Nonsurgically Treated
Surgically Treated
45
72
19 (42%)
18 (25%) 54 (75%) 26 (36%)
26 (58%)
11(24%) II (24%)
9 (20%) 5 (\ 1%) 3 (7%)
23 (32%)
o 4 (5%)
o
in most patients. The intensity of the murmur was comparable in the surgicaland nonsurgicalgroups. A continuous murmur was heard in 61% of the 117patients. Four patients presented with no heart murmur. Only 38% of the nonsurgical patients demonstrated a diastolic murmur, whereas 71% of the surgical patients had a diastolic murmur ranging in intensityfrom grade 2 to 5/6 (p > 0.001). The pulmonary component of the second heart sound was heard with equal intensity in the nonsurgical and surgical groups. The frequency of a systolic thrill or third heart sound was not significantly different in the two groups. The electrocardiogram revealed normal sinus rhythm in 95% of patients. In the nonsurgical group 13 patients demonstrated right ventricular hypertrophy and 5 patients demonstrated left ventricularhypertrophy on electrocardiogram. In the surgical group, 10 patients had evidence of right ventricularhypertrophy and 13 patients had evidence of left ventricular hypertrophy. There was no difference between the surgical and nonsurgical groups based on the type or amount of medications taken at their initialpresentation. Eighty-ninepatients(76%) were taking no medication. Infective endocarditis was seen in 3 of the 117 patients preoperatively. A total of 16 patients (14%) demonstrated calcification of the ductus either on chest X-ray film or at surgery. In the surgical group, 11 patients had ductus calcification; their age ranged from 28 to 70 years (mean 48.5). In the nonsurgical group, five patients had calcification; their mean age was somewhat greater (61 years). Nonsurgical group. There were 45 patients in the nonsurgical group (34 women and 11 men). The age at initial presentation ranged from 20 to 81 years (mean 43). Cardiomegaly was found in 45% of patients in this group at the time of initial presentation. Sixteen patients (36%) demonstrated increased pulmonary vascularity on the initial chest X-ray film. The pulmonary artery pressure was measured at cardiac catheterization in 17 of the 45 patients; the mean systolic and diastolicpressureswere 66 and 37 mm Hg, respectively. A wide range of pulmonary artery pressure was seen. The mean cardiac index was 3.7 liters/min per m2 and the mean
pulmonary to systolic flow ratio (Qp/Qs) measured in seven patients was 1.7. Nonsurgical follow-up. The length of follow-up of our 45 nonsurgical patients was 1to 37 years (mean 15). Followup evaluation was obtained in 44 (98%) of the 45 patients. The age at follow-up ranged from 28 to 92 years (mean 57). Thirty-eight percent who were followed up (17 patients) of the 44 patients in the nonsurgical group had died at followup (Table 2). Six patients died of congestive heart failure, four of myocardial infarctionand four of noncardiacdisease. Fifteen patients (34%) were asymptomatic at the time of follow-up. They comprise 56% of the 27 patients who have survived. Eight patients complained of shortness of breath, one had congestive heart failure, one complained of angina pectoris, one required treatment for hypertension, one had a cerebrovascular accidentand only one patient was disabled because of congestive heart failure. At follow-up, 16 (59%) of the 27 surviving nonsurgically treated patients were in functional class I, 8 (30%) were in class II and 3 (11 %) were in class III; no patient was in class IV. Twenty-one (78%) of the 27 patients remained in stable condition, whereas 5 (19%) were in improved condition and 1 was in poorer condition. There was one intraoperative death, which involved a 29 year old woman with severe pulmonary hypertension and right ventricular dysfunction, who died during anesthesia induction for correction of the patent ductus arteriosus and was considered as a nonsurgical patient. Surgical group. There were 72 patients in the surgically treated group consisting of 61 women and 11 men whose mean age at presentation was 32 years (range 18 to 68). Cardiomegaly was seen in 34 (47%) of the patients. Twenty patients demonstrated increased pulmonary vascularity on the initial chest X-ray evaluation. Thirty-seven patients (51 %) were in functional class I at the time they were first seen at the Cleveland Clinic, 32 (44%) were in class II and only 3 (4%) were in class III. There were no patients in functional class IV at the time of
Table 2. Cause of Death in 22 of 114 Patients at Follow-Up Nonsurgically Treated
Surgically Treated
Cause of Death
(n = 44)
(n = 70)
Congestive heart failure (CHF) Myocardial infarction (MI) CHF and MI CHF. MI and renal failure Cerebrovascular accident Respiratory insufficiency Sudden death Major hemorrhagic complication Noncardiac Unknown Total
4
I
2
2
I I I I 1 I 4
o o
I
I
17 (39%)
5 (7%)
o
o o
o I
282
FISHER ET AL. ADULT PATENT DUCTUS ARTERIOSUS: LONG-TERM FOLLOW·UP
initial presentation . Fifty-eight patients (81 %) were taking no medication at initial presentation. Cardiac catheterization was performed in 37 of the 72 patients . The mean pulmonary artery systolic pressure was 36 mm Hg (range IS to 118). The mean cardiac index was 3.5 liters /min per m 2 for the 20 patients for whom a calculation was obtained . The mean Qp/Qs ratio was 1. 9: I in the 19 patients in whom it was measured . The size of the ductus varied widely . The largest ductal diameter was 2.5 ern . One patient demonstrated aneurysmal dilat ion . All patients underwent ductal division and ligature , except for two patients with a calcified ductus who required cardiopulmonary bypass. Surgical follow-up. The follow-up period in 70 patients (97%) ranged from I to 30 years (mean 19). The patients' age at follow-up ranged from 25 to 77 years (mean 51). Two patients were lost to follow-up . Of the 70 patients followed up , 65 (93%) were alive at follow-up and 5 had died (Table 2). Two patients died of myocardial infarction and one died of congestive heart failure unrelated to the ductus arteriosus. The cause of death was noncardiac in one patient and unknown in one. In none of these five patient s was death related to preoperative or postoperative pulmonary hypertension. Fifty-two (80%) of the surviving surgical patients were asymptomatic. Rare epi sodes of angina , shortness of breath and easy fatigability were elicited . No patient was disabled because of cardiovascular compromise at follOW-Up. Eighty percent (52 of 65) were in functional class I at follow -up and 60% of the patients had clinical improvement after surgical treatment. In only one patient did the clinical course deteriorate from clas s I to class II at 13 years of follow-up (this patient had pulmonary hypertension). Crossover group. Three patients originally treated medically later underwent surgical closure of the patent ductus arteriosus and are considered in the nonsurgical group. Two of the three were in functional class I at presentation and at 10 and 12 years of follow-up, respectively . Surgical closure was performed electively at the patients' request. The third patient was in class I at presentation and required surgical closure 3 years later for congestive heart failure . This patient had an uneventful hospital course and is doing well I year later. Pulmonary hypertension. Seven patients, five in the nonsurgical and two in the surgical group , with pulmonary artery peak systolic pressure above 100 mm Hg at the time of initial presentation had long-term follow-up . In the five nonsurgical patients a high pulmonary artery pressure may have been the reason they were not treated surgically. Pulmonary vascular resistance and pulmonary arteriolar resistance were not calculated in these five patients . One patient died of right heart failure 4 years after diagnosis. A second patient died of congestive heart failure after 16 years of follow-up; before that time, she was in functional class II. Two patients are currently in class II at 19 and 26 years of
lACC Vol. 8. No.2 August 1986:280-4
follow-up , respectively. Finally, a 20 year old man with a pulmonary artery pressure of 128173 mm Hg was found to be in functional class I at 19 years of follow-up . This patient also demonstrated a bidirectional shunt at the time of his initial cardiac catheterization . One of the two patients who were operated on with a pulmonary artery systolic pressure greater than 100 mm Hg is in functional class I at 8 year s of follow-up . At the time of surgery, he was found to have a very short but very wide patent ductus . The second patient, a 45 year old man with a pulmonary artery pressure of 104/55 mm Hg, is currently in functional class II with mild congestive heart failure. At the time of surgery he had a very wide ductus measuring 2.5 em. In neither of these two patients were shunt flows available at initial study . Thus, five of our seven patients with a peak pulmonary artery systolic pressure greater than 100 mm Hg are alive at a mean of 17 years of follow-up. Survival. Long-term follow-up was obtained in 114 of 117 patients with isolated patent ductus arteriosus. The 10 year survival rate for all patients (surgical and nonsurgical) was 90%; of those patients followed up for 25 years , the overall survival was 78%. The group treated nonsurgically consisted of 45 patients who received either no treatment (33 patients) or medical therapy alone (12 patients). Patients who were treated surgically had a significantly better survival rate than those patients treated nonsurgically (p = 0.003) (Fig. I). The pretreatment functional class was not predictive of the degree of clinical impairment after treat ment for either the nonsurgical (p = 0.09) or the surgical (p = 0 .75) patients . Table 3 compares the clinical condition after treatment in the nonsurgical and surgical groups . Figure 2 illustrates the significant difference in long-term prognosis based on the presence of pretreatment cardiomegaly for the two groups. Surgically treated patients had improved morbidity and mortality rates. At a mean follow-up of 19 years, 60% of the surgically treated patients reported improvement com pared with only 19% of the patients treated nonsurgically . Because of the small number of patients who underwent cardiac catheterization during this time, our hemodynamic data were not helpful in predicting functional class after treatment.
Discussion Patients with isolated patent ductus arteriosus who receive medical therapy or no treatment have a decreased longterm life expectancy rate 0-3). Campbell (3) found that 34% of patients died by age 40 , and 61% died by age 60 . Other report s (4) have shown conflicting results. In our longterm follow-up of 114 patients , mortality was 17% in the nonsurgical group and only 7% in the surgical group . Clinical presentation. Our data on clinical presentation are in agreement with those of several previous reports (5-9).
FISHER ET AL. ADULT PATENT DUCTUS ARTERIOSUS: LONG-TERM FOLLOW-UP
lACC Vol. 8, No.2 August 1986:280--4
(!)
z > > 0::
::::l
1.0
--._---------,----,
~
> >
~
0.8
o
~
0.6
0::
lI..
0
lI.. LU
f
0.4
>
E _
---- Surgical Treatment (n-72)
0.2
0.2
-
Cardiomegaly (n-34)
oJ :::)
--- No Cardiomevaly (n-36)
2
2
:::)
::::l U
0.4
1&1
- - Nonsurgical Treatment (n-4~)
->
ICl: oJ ::::l
0.6
o lI.. o
0
0::
p-O.09
z
z
I0::
0.8
lfl
VI
2
1.0 -----------------
(!)
-- .......'--
283
U
0.0 0
5
10
15
20
25
30
3~
A
0.0 0
10
Figure 1. The statistically significant difference in survival between 45 patients (nonsurgical) who received either no treatment or medicaltherapy and 72 patients who received surgicaltreatment (p = 0.(03).
Most patients were women and often asymptomatic. Only 61 % of our patients presented with a continuous murmur. The nonsurgical group experienced significantly more cyanosis than did the surgical group (9 versus 0%) (p = 0.001). We believe that this represents increased pulmonary vascular resistance with right to left shunting in the nonsurgical group; however, because many of our patients were diagnosed before measurement of pulmonary artery pressure was routinely performed, this could not be verified by our cardiac catheterization data. The nonsurgical group had a lesser incidence of diastolic murmurs than did the surgical group (p > 0.001), possibly as a result of increased pulmonary artery systolic pressure.
The complications of patent ductus arteriosus are well known (1-3,5,6,10-12). Eisenmenger's syndrome, congestive heart failure, infective arteritis and calcification of the ductus may occur. Kelly (5) reported that calcific deposits in the ductus arteriosus were common after age 30. In our adult series the incidence was 14%. Of the 11 patients who demonstrated calcification of the ductus at the time of surgery, only 2 required cardiopulmonary bypass and all responded to conventional surgical closure. There were no complications in our patients with calcified or aneurysmal patent ductus arteriosus. Table 3. Clinical Condition of 90 Patients at Last Follow-Up Surgically
Treated
Treated
(n = 26)
(n = 64)
20 5
25
I
2~
30
35
1.0
(!)
Stable Improved Deteriorated
20
YEARS
YEARS
Nonsurgically
15
38 I
z > >
~
0.8
p >0.001
lfl
z o I0::
0.6
~
0.4
o lI.. o 1&1
--Cardlom.valy (n-20)
> ~
0.2
oJ
---- No Cardiomegaly (n-24)
:::)
2 :::)
U
B
0.0
0
10
15
20
2~
30
35
YEARS Figure 2. The cumulative survival for both the surgical (A) and nonsurgical (B) treatment groups based on pretreatment cardiomegaly. Those patients who present with an increased heart size appear to have a decreased life expectancy.
Surgical indications and results. The timing of surgical correction is controversial. Nadas and Fyler (13) recommended that an asymptomatic child with a patent ductus arteriosus and normal heart size on chest X-ray film be treated medically. Black and Goldman (6) recommended that surgical ductus closure is indicated for asymptomatic children and young adults, symptomatic infants with intractable congestive heart failure and adults with pulmonary hypertension. In contrast, Marquis et al. (7) recommended surgery in the older patient at diagnosis. They found that significant clinical deterioration with an increase in heart size could be prevented by surgery, and that left ventricular impairment was a major surgical risk even in patients with a small patent ductus arteriosus. In the adult patient, surgical risk may be increased by pulmonary hypertension, aneurysm of the ductus with or without calcification and chronic endocarditis resulting in friable tissues (14). John et al. (15) followed up 131 patients with patent ductus arteriosus (mean age 22 years) for 1 to 11 years; 81 % of the 62 patients who
284
FISHER ET AL. ADULT PATENT DUCTUS ARTERIOSUS: LONG-TERM FOLLOW-UP
had hemodynamic evaluation had some elevation of pulmonary artery pressure. Division and suture of the ductus with aortic cross clamping under normothermic conditions was performed in 61 of their patients. They found excellent long-term survival in their surgically treated patients. Five early deaths occurred in those patients with severe pulmonary hypertension (pressures of 70 to 150 mm Hg), but there were no deaths in patients with pressures less than 70 mm Hg. We have found that patients can tolerate a very high pulmonary artery pressure for long periods without deterioration of their clinical status. Elevation of the pulmonary arteriolar resistance may indicate a subset of patients at high risk despite surgical treatment. Our study is in agreement with previous studies demonstrating calcification and aneurysmal dilation of the patent ductus arteriosus in the older population. Infective endarteritis is a rare complication and was observed in only three of our patients preoperatively. The endocarditis usually occurs on the pulmonary side of the ductus. One of our patients developed endocarditis of the calcified mitral anulus 12 years after complete closure of a patent ductus. Conclusions. In a long term follow-up of 114 of 117 adult patients evaluated between 1951 and 1984, we found that patients who present with cardiomegaly who are treated nonsurgically have a much worse prognosis than do those who are treated surgically. Twelve of 20 nonsurgical patients with cardiomegaly died compared with 5 of 34 surgical patients. The higher frequency of patients with cyanosis in the nonsurgically treated group suggests that elevation of pulmonary arteriolar pressures at the time of initial presentation may be a prognostic indicator of decreased long-term survival. An increased left to right shunt, as suggested in the surgical group by an increased frequency of diastolic murmurs, may also be an indication for surgical intervention. The functional class at presentation was not predictive of long-term survival in our patient group. Elevation of pulmonary arteriolar pressure (without apparent Eisenmen-
lACC VoL 8, No.2
August 1986:280-4
ger's physiology) and enlargement of the cardiac silhouette are indications for early surgical intervention. We recommend surgical closure of the patent ductus at the time of diagnosis in adults except when there is a right to left shunt.
References I. Abbott ME. Atlas of Congenital Cardiac Disease. New York: American Heart Association, 1963:61. 2. Keys A, Shapiro M1. Patency of the ductus arteriosus in adults. Am Heart 1 1943;25:158-78. 3. CampbeII N. Natural history of persistent ductus arteriosus. Br Heart 11968;30:4-13. 4. OgawaK, ItoT, Ban M, Mizutani K, NagashimaM. Long-term results of operated and non-operated patients with congenital heart diseases. 1pn Circ 11981;45:238-42. 5. KeIIy DT. Patent ductus arteriosus in adults. Cardiovasc Clin 1979;10:321-6. 6. Black LL, Goldman BS. Surgical treatment of the patent ductus arteriosus in the adult. Ann Surg 1972;175:290-3. 7. Marquis RM, MiIIer HC, McCormack R1M, Matthews MB, Kitchin AH. Persistence of ductus arteriosus with left-to-right shunt in the older patient. Br Heart 1 1982;48:469-84. 8. Trippestad A, Efskind L. Patent ductus arteriosus. Surgical treatment of 686 patients. Scand J Thorac Cardiovasc Surg 1972;6:38-42. 9. Lucht Y, Sondergaard T. Late results of operation for patent ductus arteriosus. Scand 1 Thorac Cardiovasc Surg 1971;5:223-6. 10. Furuse A, Mituno A, Nohara F, Ito K, Saigusa M. Calcified patent ductus arteriosus. Jpn Heart J 1968;9:316-20. II. Fuster Y, Brandenburg RO, McGoon DC, Giuliana ER. Clinical approach and management of congenital heart disease in the adolescent and adult. Cardiovasc Clin 1980;10:161-97. 12. Wright 1S, Newman DC. Ligation of the patent ductus. Technical considerations at different ages. 1 Thorac Cardiovasc Surg 1978;75:695-8. 13. Nadas AS, Fyler DC. Patent ductus arteriosus. In: Pediatric Cardiology. 3rd ed. Philadelphia: WB Saunders, 1972:405-31. 14. Bell-Thomson J, JeweII E, Ellis FH, Schwaber JR. Surgical technique in the management of patent ductus arteriosus in the elderly patient. Ann Thorae Surg 1980;30:80-3. 15. John S, Muralidharan S, Mani GK, Krishnaswamy S, Sukumar IP. The adult ductus. Review of surgical experience in 13I patients. 1 Thorae Cardiovase Surg 1981;82:314-9.
JACC Vol. 8. No.2 August 1986:280-4
Patent Ductus Arteriosus in Adults-Long-Term Follow-Up: Nonsurgical Versus Surgical Treatment RUSSELL G. FISHER, DO, DOUGLAS S. MOODIE, MD, FACC, RICHARD STERBA, MD, FACC, CARL C. GILL, MD, FACC Cleveland, Ohio
The long-term prognosis of adult patients with patent ductus arteriosus treated medically or surgically has not been demonstrated. One hundred seventeen adult patients ranging in age from 18 to 81 years (mean 36) were followed up for 1 to 37 years (mean 18). Forty-five patients were treated nonsurgically and 72 had surgical closure. The nonsurgical group experienced significantly more cyanosis (p 0.002) and had fewer diastolic murmurs (p > 0.001) than did the surgical group. In the nonsurgical group, patients with cardiomegaly before treatment were more likely to die (p > 0.001) than were patients who did not have cardiomegaly. In the surgical group, patients with cardiomegaly be-
=
Patent ductus arteriosus is a rare entity in adults that may result in irreversible pulmonary hypertension, congestive heart failure and premature death. There are few studies relating surgical and nonsurgical treatment to long-term prognosis in adults with patent ductus arteriosus. In this report we describe our experience with isolated patent ductus arteriosus (with or without pulmonary hypertension) in the adult.
Methods Study patients. From 1951 to 1984, there were 117 patients seen at the Cleveland Clinic with a diagnosis of isolated patent ductus arteriosus, with or without pulmonary hypertension. There were 95 women and 22 men in our study group. We have achieved follow-up for 114 (97%) of these 117 patients. The patients were classified into two groups: those who received nonsurgical therapy (no treat-
From the Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio. Manuscript received August 13, 1985; revised manuscript received February 20, 1986, accepted March 19, 1986. Address for reprints: Douglas S. Moodie, MD, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44106. © 1986 by the American College of Cardiology
fore treatment had a worse prognosis (p = 0.09) than that of patients with normal heart size. Seven patients, five in the nonsurgical and two in the surgical group, presented with a pulmonary artery systolic pressure greater than 100 mm Hg. Five of these patients are alive and well at a mean follow-up time of 18 years. The two nonsurvivors were in the nonsurgical group and died at 4 and 19 years of follow-up, respectively. Adult patients with patent ductus arteriosus should be treated surgically, especially if cardiomegaly is seen at initial presentation. (J Am Coll Cardiol 1986;8:280-4)
ment or medical therapy) and those who received surgical therapy. Thirty-three patients received no therapy and 12 received medical therapy alone. Sixty-eight patients (58%) underwent surgical closure of the patent ductus arteriosus. Four patients had combined medical and surgical therapy and were considered as surgical patients. When all patients were considered at initial diagnosis, 57 were in New York Heart Association functional class I, 51 in class II, 7 in class III and 2 in class IV. There was no statistically significant difference between the surgical and nonsurgical groups based on their admission functional class. Clinical presentation. Symptoms at diagnosis were comparable in the two groups (Table 1). Thirty-seven (32%) of the total 117 patients presented with exercise intolerance. This was the most common symptom at presentation. Twentynine percent of the patients complained of dyspnea. Cyanosis at initial presentation was more frequent in the nonsurgical group (p = 0.001). Nine patients in this group compared with no patients in the surgical group were cyanotic on admission (p = 0.002). Thirty-seven patients (32%) were asymptomatic at the time of initial presentation. Ninety-seven percent of the patients (114 of 117) presented with a systolic murmur, generally of grade 2 to 4/6 in intensity. It was heard best at the left upper sternal border 0735-1097/86/$3.50
lACC Vol. 8. No.2
Table 1. Symptoms at Presentation in 117 Patients
No. of patients Asymptomatic Symptomatic Exercise intolerance Dyspnea Cyanosis Peripheral edema Clubbing
281
FISHER ET AL. ADULT PATENT DUCTUS ARTERIOSUS: LONG-TERM FOLLOW-UP
August 1986:280-4
Nonsurgically Treated
Surgically Treated
45
72
19 (42%)
18 (25%) 54 (75%) 26 (36%)
26 (58%)
11(24%) II (24%)
9 (20%) 5 (\ 1%) 3 (7%)
23 (32%)
o 4 (5%)
o
in most patients. The intensity of the murmur was comparable in the surgicaland nonsurgicalgroups. A continuous murmur was heard in 61% of the 117patients. Four patients presented with no heart murmur. Only 38% of the nonsurgical patients demonstrated a diastolic murmur, whereas 71% of the surgical patients had a diastolic murmur ranging in intensityfrom grade 2 to 5/6 (p > 0.001). The pulmonary component of the second heart sound was heard with equal intensity in the nonsurgical and surgical groups. The frequency of a systolic thrill or third heart sound was not significantly different in the two groups. The electrocardiogram revealed normal sinus rhythm in 95% of patients. In the nonsurgical group 13 patients demonstrated right ventricular hypertrophy and 5 patients demonstrated left ventricularhypertrophy on electrocardiogram. In the surgical group, 10 patients had evidence of right ventricularhypertrophy and 13 patients had evidence of left ventricular hypertrophy. There was no difference between the surgical and nonsurgical groups based on the type or amount of medications taken at their initialpresentation. Eighty-ninepatients(76%) were taking no medication. Infective endocarditis was seen in 3 of the 117 patients preoperatively. A total of 16 patients (14%) demonstrated calcification of the ductus either on chest X-ray film or at surgery. In the surgical group, 11 patients had ductus calcification; their age ranged from 28 to 70 years (mean 48.5). In the nonsurgical group, five patients had calcification; their mean age was somewhat greater (61 years). Nonsurgical group. There were 45 patients in the nonsurgical group (34 women and 11 men). The age at initial presentation ranged from 20 to 81 years (mean 43). Cardiomegaly was found in 45% of patients in this group at the time of initial presentation. Sixteen patients (36%) demonstrated increased pulmonary vascularity on the initial chest X-ray film. The pulmonary artery pressure was measured at cardiac catheterization in 17 of the 45 patients; the mean systolic and diastolicpressureswere 66 and 37 mm Hg, respectively. A wide range of pulmonary artery pressure was seen. The mean cardiac index was 3.7 liters/min per m2 and the mean
pulmonary to systolic flow ratio (Qp/Qs) measured in seven patients was 1.7. Nonsurgical follow-up. The length of follow-up of our 45 nonsurgical patients was 1to 37 years (mean 15). Followup evaluation was obtained in 44 (98%) of the 45 patients. The age at follow-up ranged from 28 to 92 years (mean 57). Thirty-eight percent who were followed up (17 patients) of the 44 patients in the nonsurgical group had died at followup (Table 2). Six patients died of congestive heart failure, four of myocardial infarctionand four of noncardiacdisease. Fifteen patients (34%) were asymptomatic at the time of follow-up. They comprise 56% of the 27 patients who have survived. Eight patients complained of shortness of breath, one had congestive heart failure, one complained of angina pectoris, one required treatment for hypertension, one had a cerebrovascular accidentand only one patient was disabled because of congestive heart failure. At follow-up, 16 (59%) of the 27 surviving nonsurgically treated patients were in functional class I, 8 (30%) were in class II and 3 (11 %) were in class III; no patient was in class IV. Twenty-one (78%) of the 27 patients remained in stable condition, whereas 5 (19%) were in improved condition and 1 was in poorer condition. There was one intraoperative death, which involved a 29 year old woman with severe pulmonary hypertension and right ventricular dysfunction, who died during anesthesia induction for correction of the patent ductus arteriosus and was considered as a nonsurgical patient. Surgical group. There were 72 patients in the surgically treated group consisting of 61 women and 11 men whose mean age at presentation was 32 years (range 18 to 68). Cardiomegaly was seen in 34 (47%) of the patients. Twenty patients demonstrated increased pulmonary vascularity on the initial chest X-ray evaluation. Thirty-seven patients (51 %) were in functional class I at the time they were first seen at the Cleveland Clinic, 32 (44%) were in class II and only 3 (4%) were in class III. There were no patients in functional class IV at the time of
Table 2. Cause of Death in 22 of 114 Patients at Follow-Up Nonsurgically Treated
Surgically Treated
Cause of Death
(n = 44)
(n = 70)
Congestive heart failure (CHF) Myocardial infarction (MI) CHF and MI CHF. MI and renal failure Cerebrovascular accident Respiratory insufficiency Sudden death Major hemorrhagic complication Noncardiac Unknown Total
4
I
2
2
I I I I 1 I 4
o o
I
I
17 (39%)
5 (7%)
o
o o
o I
282
FISHER ET AL. ADULT PATENT DUCTUS ARTERIOSUS: LONG-TERM FOLLOW·UP
initial presentation . Fifty-eight patients (81 %) were taking no medication at initial presentation. Cardiac catheterization was performed in 37 of the 72 patients . The mean pulmonary artery systolic pressure was 36 mm Hg (range IS to 118). The mean cardiac index was 3.5 liters /min per m 2 for the 20 patients for whom a calculation was obtained . The mean Qp/Qs ratio was 1. 9: I in the 19 patients in whom it was measured . The size of the ductus varied widely . The largest ductal diameter was 2.5 ern . One patient demonstrated aneurysmal dilat ion . All patients underwent ductal division and ligature , except for two patients with a calcified ductus who required cardiopulmonary bypass. Surgical follow-up. The follow-up period in 70 patients (97%) ranged from I to 30 years (mean 19). The patients' age at follow-up ranged from 25 to 77 years (mean 51). Two patients were lost to follow-up . Of the 70 patients followed up , 65 (93%) were alive at follow-up and 5 had died (Table 2). Two patients died of myocardial infarction and one died of congestive heart failure unrelated to the ductus arteriosus. The cause of death was noncardiac in one patient and unknown in one. In none of these five patient s was death related to preoperative or postoperative pulmonary hypertension. Fifty-two (80%) of the surviving surgical patients were asymptomatic. Rare epi sodes of angina , shortness of breath and easy fatigability were elicited . No patient was disabled because of cardiovascular compromise at follOW-Up. Eighty percent (52 of 65) were in functional class I at follow -up and 60% of the patients had clinical improvement after surgical treatment. In only one patient did the clinical course deteriorate from clas s I to class II at 13 years of follow-up (this patient had pulmonary hypertension). Crossover group. Three patients originally treated medically later underwent surgical closure of the patent ductus arteriosus and are considered in the nonsurgical group. Two of the three were in functional class I at presentation and at 10 and 12 years of follow-up, respectively . Surgical closure was performed electively at the patients' request. The third patient was in class I at presentation and required surgical closure 3 years later for congestive heart failure . This patient had an uneventful hospital course and is doing well I year later. Pulmonary hypertension. Seven patients, five in the nonsurgical and two in the surgical group , with pulmonary artery peak systolic pressure above 100 mm Hg at the time of initial presentation had long-term follow-up . In the five nonsurgical patients a high pulmonary artery pressure may have been the reason they were not treated surgically. Pulmonary vascular resistance and pulmonary arteriolar resistance were not calculated in these five patients . One patient died of right heart failure 4 years after diagnosis. A second patient died of congestive heart failure after 16 years of follow-up; before that time, she was in functional class II. Two patients are currently in class II at 19 and 26 years of
lACC Vol. 8. No.2 August 1986:280-4
follow-up , respectively. Finally, a 20 year old man with a pulmonary artery pressure of 128173 mm Hg was found to be in functional class I at 19 years of follow-up . This patient also demonstrated a bidirectional shunt at the time of his initial cardiac catheterization . One of the two patients who were operated on with a pulmonary artery systolic pressure greater than 100 mm Hg is in functional class I at 8 year s of follow-up . At the time of surgery, he was found to have a very short but very wide patent ductus . The second patient, a 45 year old man with a pulmonary artery pressure of 104/55 mm Hg, is currently in functional class II with mild congestive heart failure. At the time of surgery he had a very wide ductus measuring 2.5 em. In neither of these two patients were shunt flows available at initial study . Thus, five of our seven patients with a peak pulmonary artery systolic pressure greater than 100 mm Hg are alive at a mean of 17 years of follow-up. Survival. Long-term follow-up was obtained in 114 of 117 patients with isolated patent ductus arteriosus. The 10 year survival rate for all patients (surgical and nonsurgical) was 90%; of those patients followed up for 25 years , the overall survival was 78%. The group treated nonsurgically consisted of 45 patients who received either no treatment (33 patients) or medical therapy alone (12 patients). Patients who were treated surgically had a significantly better survival rate than those patients treated nonsurgically (p = 0.003) (Fig. I). The pretreatment functional class was not predictive of the degree of clinical impairment after treat ment for either the nonsurgical (p = 0.09) or the surgical (p = 0 .75) patients . Table 3 compares the clinical condition after treatment in the nonsurgical and surgical groups . Figure 2 illustrates the significant difference in long-term prognosis based on the presence of pretreatment cardiomegaly for the two groups. Surgically treated patients had improved morbidity and mortality rates. At a mean follow-up of 19 years, 60% of the surgically treated patients reported improvement com pared with only 19% of the patients treated nonsurgically . Because of the small number of patients who underwent cardiac catheterization during this time, our hemodynamic data were not helpful in predicting functional class after treatment.
Discussion Patients with isolated patent ductus arteriosus who receive medical therapy or no treatment have a decreased longterm life expectancy rate 0-3). Campbell (3) found that 34% of patients died by age 40 , and 61% died by age 60 . Other report s (4) have shown conflicting results. In our longterm follow-up of 114 patients , mortality was 17% in the nonsurgical group and only 7% in the surgical group . Clinical presentation. Our data on clinical presentation are in agreement with those of several previous reports (5-9).
FISHER ET AL. ADULT PATENT DUCTUS ARTERIOSUS: LONG-TERM FOLLOW-UP
lACC Vol. 8, No.2 August 1986:280--4
(!)
z > > 0::
::::l
1.0
--._---------,----,
~
> >
~
0.8
o
~
0.6
0::
lI..
0
lI.. LU
f
0.4
>
E _
---- Surgical Treatment (n-72)
0.2
0.2
-
Cardiomegaly (n-34)
oJ :::)
--- No Cardiomevaly (n-36)
2
2
:::)
::::l U
0.4
1&1
- - Nonsurgical Treatment (n-4~)
->
ICl: oJ ::::l
0.6
o lI.. o
0
0::
p-O.09
z
z
I0::
0.8
lfl
VI
2
1.0 -----------------
(!)
-- .......'--
283
U
0.0 0
5
10
15
20
25
30
3~
A
0.0 0
10
Figure 1. The statistically significant difference in survival between 45 patients (nonsurgical) who received either no treatment or medicaltherapy and 72 patients who received surgicaltreatment (p = 0.(03).
Most patients were women and often asymptomatic. Only 61 % of our patients presented with a continuous murmur. The nonsurgical group experienced significantly more cyanosis than did the surgical group (9 versus 0%) (p = 0.001). We believe that this represents increased pulmonary vascular resistance with right to left shunting in the nonsurgical group; however, because many of our patients were diagnosed before measurement of pulmonary artery pressure was routinely performed, this could not be verified by our cardiac catheterization data. The nonsurgical group had a lesser incidence of diastolic murmurs than did the surgical group (p > 0.001), possibly as a result of increased pulmonary artery systolic pressure.
The complications of patent ductus arteriosus are well known (1-3,5,6,10-12). Eisenmenger's syndrome, congestive heart failure, infective arteritis and calcification of the ductus may occur. Kelly (5) reported that calcific deposits in the ductus arteriosus were common after age 30. In our adult series the incidence was 14%. Of the 11 patients who demonstrated calcification of the ductus at the time of surgery, only 2 required cardiopulmonary bypass and all responded to conventional surgical closure. There were no complications in our patients with calcified or aneurysmal patent ductus arteriosus. Table 3. Clinical Condition of 90 Patients at Last Follow-Up Surgically
Treated
Treated
(n = 26)
(n = 64)
20 5
25
I
2~
30
35
1.0
(!)
Stable Improved Deteriorated
20
YEARS
YEARS
Nonsurgically
15
38 I
z > >
~
0.8
p >0.001
lfl
z o I0::
0.6
~
0.4
o lI.. o 1&1
--Cardlom.valy (n-20)
> ~
0.2
oJ
---- No Cardiomegaly (n-24)
:::)
2 :::)
U
B
0.0
0
10
15
20
2~
30
35
YEARS Figure 2. The cumulative survival for both the surgical (A) and nonsurgical (B) treatment groups based on pretreatment cardiomegaly. Those patients who present with an increased heart size appear to have a decreased life expectancy.
Surgical indications and results. The timing of surgical correction is controversial. Nadas and Fyler (13) recommended that an asymptomatic child with a patent ductus arteriosus and normal heart size on chest X-ray film be treated medically. Black and Goldman (6) recommended that surgical ductus closure is indicated for asymptomatic children and young adults, symptomatic infants with intractable congestive heart failure and adults with pulmonary hypertension. In contrast, Marquis et al. (7) recommended surgery in the older patient at diagnosis. They found that significant clinical deterioration with an increase in heart size could be prevented by surgery, and that left ventricular impairment was a major surgical risk even in patients with a small patent ductus arteriosus. In the adult patient, surgical risk may be increased by pulmonary hypertension, aneurysm of the ductus with or without calcification and chronic endocarditis resulting in friable tissues (14). John et al. (15) followed up 131 patients with patent ductus arteriosus (mean age 22 years) for 1 to 11 years; 81 % of the 62 patients who
284
FISHER ET AL. ADULT PATENT DUCTUS ARTERIOSUS: LONG-TERM FOLLOW-UP
had hemodynamic evaluation had some elevation of pulmonary artery pressure. Division and suture of the ductus with aortic cross clamping under normothermic conditions was performed in 61 of their patients. They found excellent long-term survival in their surgically treated patients. Five early deaths occurred in those patients with severe pulmonary hypertension (pressures of 70 to 150 mm Hg), but there were no deaths in patients with pressures less than 70 mm Hg. We have found that patients can tolerate a very high pulmonary artery pressure for long periods without deterioration of their clinical status. Elevation of the pulmonary arteriolar resistance may indicate a subset of patients at high risk despite surgical treatment. Our study is in agreement with previous studies demonstrating calcification and aneurysmal dilation of the patent ductus arteriosus in the older population. Infective endarteritis is a rare complication and was observed in only three of our patients preoperatively. The endocarditis usually occurs on the pulmonary side of the ductus. One of our patients developed endocarditis of the calcified mitral anulus 12 years after complete closure of a patent ductus. Conclusions. In a long term follow-up of 114 of 117 adult patients evaluated between 1951 and 1984, we found that patients who present with cardiomegaly who are treated nonsurgically have a much worse prognosis than do those who are treated surgically. Twelve of 20 nonsurgical patients with cardiomegaly died compared with 5 of 34 surgical patients. The higher frequency of patients with cyanosis in the nonsurgically treated group suggests that elevation of pulmonary arteriolar pressures at the time of initial presentation may be a prognostic indicator of decreased long-term survival. An increased left to right shunt, as suggested in the surgical group by an increased frequency of diastolic murmurs, may also be an indication for surgical intervention. The functional class at presentation was not predictive of long-term survival in our patient group. Elevation of pulmonary arteriolar pressure (without apparent Eisenmen-
lACC VoL 8, No.2
August 1986:280-4
ger's physiology) and enlargement of the cardiac silhouette are indications for early surgical intervention. We recommend surgical closure of the patent ductus at the time of diagnosis in adults except when there is a right to left shunt.
References I. Abbott ME. Atlas of Congenital Cardiac Disease. New York: American Heart Association, 1963:61. 2. Keys A, Shapiro M1. Patency of the ductus arteriosus in adults. Am Heart 1 1943;25:158-78. 3. CampbeII N. Natural history of persistent ductus arteriosus. Br Heart 11968;30:4-13. 4. OgawaK, ItoT, Ban M, Mizutani K, NagashimaM. Long-term results of operated and non-operated patients with congenital heart diseases. 1pn Circ 11981;45:238-42. 5. KeIIy DT. Patent ductus arteriosus in adults. Cardiovasc Clin 1979;10:321-6. 6. Black LL, Goldman BS. Surgical treatment of the patent ductus arteriosus in the adult. Ann Surg 1972;175:290-3. 7. Marquis RM, MiIIer HC, McCormack R1M, Matthews MB, Kitchin AH. Persistence of ductus arteriosus with left-to-right shunt in the older patient. Br Heart 1 1982;48:469-84. 8. Trippestad A, Efskind L. Patent ductus arteriosus. Surgical treatment of 686 patients. Scand J Thorac Cardiovasc Surg 1972;6:38-42. 9. Lucht Y, Sondergaard T. Late results of operation for patent ductus arteriosus. Scand 1 Thorac Cardiovasc Surg 1971;5:223-6. 10. Furuse A, Mituno A, Nohara F, Ito K, Saigusa M. Calcified patent ductus arteriosus. Jpn Heart J 1968;9:316-20. II. Fuster Y, Brandenburg RO, McGoon DC, Giuliana ER. Clinical approach and management of congenital heart disease in the adolescent and adult. Cardiovasc Clin 1980;10:161-97. 12. Wright 1S, Newman DC. Ligation of the patent ductus. Technical considerations at different ages. 1 Thorac Cardiovasc Surg 1978;75:695-8. 13. Nadas AS, Fyler DC. Patent ductus arteriosus. In: Pediatric Cardiology. 3rd ed. Philadelphia: WB Saunders, 1972:405-31. 14. Bell-Thomson J, JeweII E, Ellis FH, Schwaber JR. Surgical technique in the management of patent ductus arteriosus in the elderly patient. Ann Thorae Surg 1980;30:80-3. 15. John S, Muralidharan S, Mani GK, Krishnaswamy S, Sukumar IP. The adult ductus. Review of surgical experience in 13I patients. 1 Thorae Cardiovase Surg 1981;82:314-9.