Patent Ductus Arteriosus in Adults-Long-Term Follow-Up: Nonsurgical Versus Surgical Treatment

280 JACC Vol. 8. No.2 August 1986:280-4

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 fore treatment had a worse prognosis (p = 0.09) than ductus arteriosus treated medically or surgically has not that of patients with normal heart size. Seven patients, been demonstrated. One hundred seventeen adult pa five in the nonsurgical and two in the surgical group, tients ranging in age from 18 to 81 years (mean 36) were presented with a pulmonary artery systolic pressure followed up for 1 to 37 years (mean 18). Forty-five pa greater than 100 mm Hg. Five of these patients are alive tients were treated nonsurgically and 72 had surgical and well at a mean follow-up time of 18 years. The two closure. The nonsurgical group experienced significantly nonsurvivors were in the nonsurgical group and died at more cyanosis (p =0.002) and had fewer diastolic mur 4 and 19 years of follow-up, respectively. Adult patients murs (p > 0.001) than did the surgical group. In the with patent ductus arteriosus should be treated sur nonsurgical group, patients with cardiomegaly before gically, especially if cardiomegaly is seen at initial pre treatment were more likely to die (p > 0.001) than were sentation. patients who did not have cardiomegaly. (J Am Coll Cardiol 1986;8:280-4) In the surgical group, patients with cardiomegaly be-

Patent ductus arteriosus is a rare entity in adults that may ment or medical therapy) and those who received surgical result in irreversible pulmonary hypertension, congestive therapy. heart failure and premature death. There are few studies Thirty-three patients received no therapy and 12 received relating surgical and nonsurgical treatment to long-term medical therapy alone. Sixty-eight patients (58%) under prognosis in adults with patent ductus arteriosus. In this went surgical closure of the patent ductus arteriosus. Four report we describe our experience with isolated patent ductus patients had combined medical and surgical therapy and arteriosus (with or without pulmonary hypertension) in the were considered as surgical patients. When all patients were adult. 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 Methods difference between the surgical and nonsurgical groups based Study patients. From 1951 to 1984, there were 117 on their admission functional class. patients seen at the Cleveland Clinic with a diagnosis of Clinical presentation. Symptoms at diagnosis were isolated patent ductus arteriosus, with or without pulmonary comparable in the two groups (Table 1). Thirty-seven (32%) hypertension. There were 95 women and 22 men in our of the total 117 patients presented with exercise intolerance. study group. We have achieved follow-up for 114 (97%) This was the most common symptom at presentation. Twenty of these 117 patients. The patients were classified into two nine percent of the patients complained of dyspnea. Cy groups: those who received nonsurgical therapy (no treat- anosis at initial presentation was more frequent in the non surgical group (p = 0.001). Nine patients in this group compared with no patients in the surgical group were cy From the Department of Cardiology, Cleveland Clinic Foundation, anotic on admission (p = 0.002). Thirty-seven patients Cleveland, Ohio. (32%) were asymptomatic at the time of initial presentation. Manuscript received August 13, 1985; revised manuscript received Ninety-seven percent of the patients (114 of 117) pre February 20, 1986, accepted March 19, 1986. Address for reprints: Douglas S. Moodie, MD, Cleveland Clinic Foun sented with a systolic murmur, generally of grade 2 to 4/6 dation, 9500 Euclid Avenue, Cleveland, Ohio 44106. in intensity. It was heard best at the left upper sternal border

Table 1. Symptoms at Presentation in 117 Patients pulmonary to systolic flow ratio (Qp/Qs) measuredin seven

Nonsurgically Surgically patients was 1.7. Treated Treated Nonsurgical follow-up. The length of follow-up of our 45 nonsurgical patientswas 1to 37 years (mean 15).Follow No. of patients 45 72 Asymptomatic 19 (42%) 18 (25%) up evaluation was obtained in 44 (98%) of the 45 patients. Symptomatic 26 (58%) 54 (75%) The age at follow-upranged from 28 to 92 years (mean 57). Exercise intolerance 11(24%) 26 (36%) Thirty-eight percent who were followed up (17 patients) of Dyspnea II (24%) 23 (32%) the 44 patients in the nonsurgical group had died at follow 9 (20%) o Cyanosis up (Table 2). Six patients died of congestive heart failure, Peripheral edema 5 (\ 1%) 4 (5%) Clubbing 3 (7%) o 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, in most patients. The intensity of the murmur was com one had congestive heart failure, one complained of angina parablein the surgicaland nonsurgicalgroups. A continuous pectoris, one required treatment for hypertension, one had murmur was heard in 61% of the 117patients. Four patients a cerebrovascular accidentand only one patientwas disabled presented with no heart murmur. Only 38% of the nonsur because of congestive heart failure. gical patients demonstrated a diastolic murmur, whereas At follow-up, 16(59%)of the 27 survivingnonsurgically 71% of the surgical patients had a diastolic murmur ranging treated patients were in functional class I, 8 (30%) were in in intensityfrom grade 2 to 5/6 (p > 0.001). The pulmonary class II and 3 (11 %) were in class III; no patient was in componentof the second heart sound was heard with equal class IV. Twenty-one (78%) of the 27 patients remained in intensity in the nonsurgical and surgical groups. The fre stable condition, whereas 5 (19%) were in improved con quency of a systolic thrill or third heart sound was not dition and 1 was in poorer condition. significantly different in the two groups. There was one intraoperative death, which involved a 29 The electrocardiogram revealed normal sinus rhythm in year old woman with severe pulmonary hypertension and 95% of patients. In the nonsurgical group 13 patients dem right ventricular dysfunction, who died during anesthesia onstrated right ventricular hypertrophy and 5 patients dem induction for correction of the patent ductus arteriosus and onstratedleft ventricularhypertrophy on electrocardiogram. was considered as a nonsurgical patient. In the surgical group, 10 patients had evidence of right Surgical group. There were 72 patients in the surgically ventricularhypertrophy and 13 patients had evidenceof left treated group consisting of 61 women and 11 men whose ventricular hypertrophy. mean age at presentation was 32 years (range 18 to 68). There was no difference between the surgical and non Cardiomegaly was seen in 34 (47%) of the patients. Twenty surgicalgroups based on the type or amount of medications patients demonstrated increased pulmonary vascularity on takenat their initialpresentation.Eighty-ninepatients(76%) the initial chest X-ray evaluation. were taking no medication. Infective endocarditis was seen Thirty-seven patients (51 %) were in functional class I at in 3 of the 117 patients preoperatively. the time they were first seen at the Cleveland Clinic, 32 A total of 16 patients (14%) demonstrated calcification (44%) were in class II and only 3 (4%) were in class III. of the ductus either on chest X-ray film or at surgery. In There were no patients in functional class IV at the time of the surgicalgroup, 11 patientshad ductus calcification; their age ranged from 28 to 70 years (mean 48.5). In the non surgical group, five patients had calcification; their mean Table 2. Cause of Death in 22 of 114 Patients at Follow-Up age was somewhat greater (61 years). Nonsurgically Surgically Nonsurgical group. There were 45 patients in the non Treated Treated surgical group (34 women and 11 men). The age at initial Cause of Death (n = 44) (n = 70) presentation ranged from 20 to 81 years (mean 43). Car Congestive heart failure (CHF) 4 I diomegaly was found in 45% of patients in this group at Myocardial infarction (MI) 2 2 the time of initial presentation. Sixteen patients (36%) dem CHF and MI I o onstrated increased pulmonary vascularity on the initial chest CHF. MI and renal failure I o X-ray film. Cerebrovascular accident I o Respiratory insufficiency I o The pulmonary artery pressure was measured at cardiac Sudden death 1 o catheterization in 17 of the 45 patients; the mean systolic Major hemorrhagic complication I o anddiastolicpressureswere66 and 37 mm Hg, respectively. Noncardiac 4 I A wide range of pulmonary artery pressure was seen. The Unknown I I mean cardiac index was 3.7 liters/min per m2 and the mean Total 17 (39%) 5 (7%) 282 FISHER ET AL. lACC Vol. 8. No.2 ADULT PATENT DUCTUS ARTERIOSUS: LONG-TERM FOLLOW·UP August 1986:280-4

initial presentation. Fifty-eight patients (81%) were taking follow-up, respectively. Finally, a 20 year old man with a no medication at initial presentation. pulmonary artery pressure of 128173 mm Hg was found to Cardiac catheterization was performed in 37 of the 72 be in functional class I at 19 years of follow-up. This patient patients. The mean pulmonary artery systolic pressure was also demonstrated a bidirectional shunt at the time of his 36 mm Hg (range IS to 118). The mean cardiac index was initial cardiac catheterization. 3.5 liters/min per m2 for the 20 patients for whom a cal One of the two patients who were operated on with a culation was obtained. The mean Qp/Qs ratio was 1.9: I in pulmonary artery systolic pressure greater than 100 mm Hg the 19 patients in whom it was measured. is in functional class I at 8 years of follow-up. At the time The size of the ductus varied widely. The largest ductal of surgery, he was found to have a very short but very wide diameter was 2.5 ern. One patient demonstrated aneurysmal patent ductus . The second patient, a 45 year old man with dilat ion. All patients underwent ductal division and ligature , a pulmonary artery pressure of 104/55 mm Hg, is currently except for two patients with a calcified ductus who required in functional class II with mild congestive heart failure. At cardiopulmonary bypass. the time of surgery he had a very wide ductus measuring Surgical follow-up. The follow-up period in 70 patients 2.5 em. In neither of these two patients were shunt flows (97%) ranged from I to 30 years (mean 19). The patients' available at initial study . Thus, five of our seven patients age at follow-up ranged from 25 to 77 years (mean 51). with a peak pulmonary artery systolic pressure greater than Two patients were lost to follow-up. Of the 70 patients 100 mm Hg are alive at a mean of 17 years of follow-up. followed up , 65 (93%) were alive at follow-up and 5 had Survival. Long-term follow-up was obtained in 114 of died (Table 2). Two patients died of myocardial infarction 117 patients with isolated patent ductus arteriosus. The 10 and one died of congestive heart failure unrelated to the year survival rate for all patients (surgical and nonsurgical) ductus arteriosus. The cause ofdeath was noncardiac in one was 90%; of those patients followed up for 25 years , the patient and unknown in one. In none of these five patient s overall survival was 78%. The group treated nonsurgically was death related to preoperative or postoperative pulmo consisted of 45 patients who received either no treatment nary hypertension. Fifty-two (80%) ofthe surviving surgical (33 patients) or medical therapy alone (12 patients). Patients patients were asymptomatic. Rare episodes of angina, short who were treated surgically had a significantly better sur ness of breath and easy fatigability were elicited. No patient vival rate than those patients treated nonsurgically (p = was disabled because of cardiovascular compromise at fol 0.003) (Fig. I). The pretreatment functional class was not lOW-Up. Eighty percent (52 of 65) were in functional class predictive of the degree of clinical impairment after treat I at follow -up and 60% of the patients had clinical improve ment for either the nonsurgical (p = 0.09) or the surgical ment after surgical treatment. In only one patient did the (p = 0.75) patients . Table 3 compares the clinical condition clinical course deteriorate from class I to class II at 13 years after treatment in the nonsurgical and surgical groups. Fig of follow-up (this patient had pulmonary hypertension). ure 2 illustrates the significant difference in long-term prog Crossover group. Three patients originally treated med nosis based on the presence of pretreatment cardiomegaly ically later underwent surgical closure of the patent ductus for the two groups. arteriosus and are considered in the nonsurgical group. Two Surgically treated patients had improved morbidity and of the three were in functional class I at presentation and mortality rates. At a mean follow-up of 19 years, 60% of at 10 and 12 years of follow-up, respectively. Surgical clo the surgically treated patients reported improvement com sure was performed electively at the patients' request. The pared with only 19% of the patients treated nonsurgically. third patient was in class I at presentation and required Because of the small number of patients who underwent surgical closure 3 years later for congestive heart failure . cardiac catheterization during this time, our hemodynamic This patient had an uneventful hospital course and is doing data were not helpful in predicting functional class after well I year later. treatment. 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 Discussion of initial presentation had long-term follow-up. In the five Patients with isolated patent ductus arteriosus who re nonsurgical patients a high pulmonary artery pressure may ceive medical therapy or no treatment have a decreased long have been the reason they were not treated surgically. Pul term life expectancy rate 0-3). Campbell (3) found that monary vascular resistance and pulmonary arteriolar resist 34% of patients died by age 40 , and 61% died by age 60. ance were not calculated in these five patients . One patient Other report s (4) have shown conflicting results. In our long died of right heart failure 4 years after diagnosis. A second term follow-up of 114 patients, mortality was 17% in the patient died of congestive heart failure after 16 years of nonsurgical group and only 7% in the surgical group. follow-up; before that time, she was in functional class II. Clinical presentation. Our data on clinical presentation Two patients are currently in class II at 19 and 26 years of are in agreement with those of several previous reports (5-9). lACC Vol. 8, No.2 FISHER ET AL. 283 August 1986:280--4 ADULT PATENT DUCTUS ARTERIOSUS: LONG-TERM FOLLOW-UP

(!) 1.0 (!) 1.0 ------z --._------,----, --...... ~ > '-- > > > 0:: 0.8 ~ ::::l 0.8 VI lfl z z p-O.09 o 2 ~ 0.6 I- 0.6 0:: 0:: 0 o lI.. lI.. 0 o 0:: f 0.4 lI.. 0.4 1&1 LU (n-4~) > -> --Nonsurgical Treatment I- E_ 0.2 - Cardiomegaly (n-34) Cl: 0.2 ---- Surgical Treatment (n-72) oJ oJ :::) ::::l 2 --- No Cardiomevaly (n-36) 2 :::) ::::l U 0.0 U 0.0 A 0 10 15 20 2~ 3530 0 5 10 15 20 25 30 3~ YEARS YEARS (!) 1.0 Figure 1. The statistically significant difference in survival be z > tween 45 patients (nonsurgical) who received either no treatment > or medicaltherapyand 72 patients who receivedsurgicaltreatment ~ 0.8 p >0.001 (p = 0.(03). lfl z o I- 0.6 0:: Most patients were women and often asymptomatic. Only o lI.. 61% of our patients presented with a continuous murmur. o ~ 0.4 The nonsurgical group experienced significantly more cy 1&1 --Cardlom.valy (n-20) anosis than did the surgical group (9 versus 0%) (p = > ~ 0.2 ---- No Cardiomegaly (n-24) 0.001). We believe that this represents increased pulmonary oJ :::) vascular resistance with right to left shunting in the non 2 :::) surgical group; however, because many of our patients were U 0.0 2~ diagnosed before measurement of pulmonary artery pressure B 0 10 15 20 30 35 was routinely performed, this could not be verified by our YEARS cardiac catheterization data. The nonsurgical group had a Figure 2. The cumulative survival for both the surgical (A) and lesser incidence of diastolic murmurs than did the surgical nonsurgical (B) treatment groups based on pretreatment cardio group (p > 0.001), possibly as a result of increased pul megaly. Those patients who present with an increased heart size appear to have a decreased life expectancy. monary artery systolic pressure. The complications of patent ductus arteriosus are well known (1-3,5,6,10-12). Eisenmenger's syndrome, conges tive heart failure, infective arteritis and calcification of the Surgical indications and results. The timing of surgical correction is controversial. Nadas and Fyler (13) recom ductus may occur. Kelly (5) reported that calcific deposits mended that an asymptomatic child with a patent ductus in the ductus arteriosus were common after age 30. In our arteriosus and normal heart size on chest X-ray film be adult series the incidence was 14%. Of the 11 patients who demonstrated calcification of the ductus at the time of sur treated medically. Black and Goldman (6) recommended gery, only 2 required cardiopulmonary bypass and all re that surgical ductus closure is indicated for asymptomatic children and young adults, symptomatic infants with in sponded to conventional surgical closure. There were no complications in our patients with calcified or aneurysmal tractable congestive heart failure and adults with pulmonary hypertension. In contrast, Marquis et al. (7) recommended patent ductus arteriosus. surgery in the older patient at diagnosis. They found that significant clinical deterioration with an increase in heart Table 3. Clinical Condition of 90 Patients at size could be prevented by surgery, and that left ventricular Last Follow-Up impairment was a major surgical risk even in patients with Nonsurgically Surgically a small patent ductus arteriosus. In the adult patient, surgical Treated Treated risk may be increased by pulmonary hypertension, aneurysm (n = 26) (n = 64) of the ductus with or without calcification and chronic en Stable 20 25 docarditis resulting in friable tissues (14). John et al. (15) Improved 5 38 followed up 131 patients with patent ductus arteriosus (mean Deteriorated I I age 22 years) for 1 to 11 years; 81% of the 62 patients who 284 FISHER ET AL. lACC VoL 8, No.2 ADULT PATENT DUCTUS ARTERIOSUS: LONG-TERM FOLLOW-UP August 1986:280-4

had hemodynamic evaluation had some elevation of pul ger's physiology) and enlargement of the cardiac silhouette monary artery pressure. Division and suture of the ductus are indications for early surgical intervention. We recom with aortic cross clamping under normothermic conditions mend surgical closure of the patent ductus at the time of was performed in 61 of their patients. They found excellent diagnosis in adults except when there is a right to left shunt. long-term survival in their surgically treated patients. Five early deaths occurred in those patients with severe pul monary hypertension (pressures of 70 to 150 mm Hg), but References there were no deaths in patients with pressures less than I. Abbott ME. Atlas of Congenital Cardiac Disease. New York: Amer 70 mm Hg. ican Heart Association, 1963:61. We have found that patients can tolerate a very high 2. Keys A, Shapiro M1. Patency of the ductus arteriosus in adults. Am pulmonary artery pressure for long periods without deteri Heart 1 1943;25:158-78. oration of their clinical status. Elevation of the pulmonary 3. CampbeII N. Natural history of persistent ductus arteriosus. Br Heart 11968;30:4-13. arteriolar resistance may indicate a subset of patients at high 4. OgawaK, ItoT, Ban M, Mizutani K, NagashimaM. Long-term results risk despite surgical treatment. Our study is in agreement of operated and non-operated patients with congenital heart diseases. with previous studies demonstrating calcification and aneu 1pn Circ 11981;45:238-42. rysmal dilation of the patent ductus arteriosus in the older 5. KeIIy DT. Patent ductus arteriosus in adults. Cardiovasc Clin population. Infective endarteritis is a rare complication and 1979;10:321-6. was observed in only three of our patients preoperatively. 6. Black LL, Goldman BS. Surgical treatment of the patent ductus ar teriosus in the adult. Ann Surg 1972;175:290-3. The endocarditis usually occurs on the pulmonary side of 7. Marquis RM, MiIIer HC, McCormack R1M, Matthews MB, Kitchin the ductus. One of our patients developed endocarditis of AH. Persistence of ductus arteriosus with left-to-right shunt in the the calcified mitral anulus 12 years after complete closure older patient. Br Heart 1 1982;48:469-84. of a patent ductus. 8. Trippestad A, Efskind L. Patent ductus arteriosus. Surgical treatment Conclusions. In a long term follow-up of 114 of 117 of 686 patients. Scand J Thorac Cardiovasc Surg 1972;6:38-42. adult patients evaluated between 1951 and 1984, we found 9. Lucht Y, Sondergaard T. Late results of operation for patent ductus arteriosus. Scand 1 Thorac Cardiovasc Surg 1971;5:223-6. that patients who present with cardiomegaly who are treated 10. Furuse A, Mituno A, Nohara F, Ito K, Saigusa M. Calcified patent nonsurgically have a much worse prognosis than do those ductus arteriosus. Jpn Heart J 1968;9:316-20. who are treated surgically. Twelve of 20 nonsurgical pa II. Fuster Y, Brandenburg RO, McGoon DC, Giuliana ER. Clinical ap tients with cardiomegaly died compared with 5 of 34 surgical proach and management of congenital heart disease in the adolescent patients. The higher frequency of patients with cyanosis in and adult. Cardiovasc Clin 1980;10:161-97. the nonsurgically treated group suggests that elevation of 12. Wright 1S, Newman DC. Ligation of the patent ductus. Technical considerations at different ages. 1 Thorac Cardiovasc Surg pulmonary arteriolar pressures at the time of initial presen 1978;75:695-8. tation may be a prognostic indicator of decreased long-term 13. Nadas AS, Fyler DC. Patent ductus arteriosus. In: Pediatric Cardiol survival. An increased left to right shunt, as suggested in ogy. 3rd ed. Philadelphia: WB Saunders, 1972:405-31. the surgical group by an increased frequency of diastolic 14. Bell-Thomson J, JeweII E, Ellis FH, Schwaber JR. Surgical technique murmurs, may also be an indication for surgical interven in the management of patent ductus arteriosus in the elderly patient. Ann Thorae Surg 1980;30:80-3. tion. The functional class at presentation was not predictive 15. John S, Muralidharan S, Mani GK, Krishnaswamy S, Sukumar IP. of long-term survival in our patient group. Elevation of The adult ductus. Review of surgical experience in 13I patients. 1 pulmonary arteriolar pressure (without apparent Eisenmen- Thorae Cardiovase Surg 1981;82:314-9.