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Combined noninvasive assessment of the patent ductus arteriosus in the preterm infant before and after indomethacin treatment
Combined Noninvasive Assessment of the Patent Ductus Arteriosus in the Preterm Infant Before and After Indomethacin Treatment JEFFREY F. SMALLHORN, FRACP, FRCP (C), ROBERT GOW, MD, PETER M. OLLEY, FRCP (C), ROBERT M. FREEDOM, FRCP (C), PAUL R. SWYER, FRCP (C), MAX PERUVIAN, FRCP (C), and RICHARD D. ROWE, FRCP (C), FRCP (Ed)
Fifteen preterm infants who weighed 0.7 to 2.0 kg and had clinical evidence of a patent ductus arteriosus (PDA) were studied by combined 2-dimensional and Doppler echocardiography before and after the administration of indomethacin. In 10 patients the PDA was widely patent at the time of the study and in 5 the lumen was narrow. In this latter group, the PDA was narrow at the pulmonary artery end in 2 patients, in the middle in 2 patients and at the aortic end and the middle in 1 patient. After the administration of intravenous indomethacin, the PDA closed completely in 12 patients and constricted in 3. The patterns of closure could be documented in those in whom serial studies were performed. In 3 patients, closure occurred after a single dose of in-
domethacin, in 3 after 2 doses and in the rest after a full course of 3 doses. Doppler interrogation at the aortic and pulmonary artery end of the PDA demonstrated the shunting patterns and provided a reliable assessment of patency after the ductal lumen was outside the range of lateral resolution following constriction. In no case did the PDA reopen after the course of indomethacin. This combined approach is a reliable method of assessing a PDA before and after a course of indomethacin. It should provide the means to answer many of the questions regarding the effect of various manipulations on the PDA in the preterm infant.
Patent ductus arteriosus (PDA) is a common finding in small preterm infants. No reliable noninvasive technique is available that allows the clinician to accurately assess the size and monitor the progress of a PDA before and after pharmacologic manipulation with indomethacin. M-mode echocardiography (echo) has many limitations and provides only indirect evidence of a left-to-right s h u n t J Similarly, although Doppler echo is sensitive in detecting the presence of a left-to-right shunt, it provides only indirect evidence of a shunt, which itself depends on pulmonary and systemic resistance.2,3 With 2-dimensional echo, a PDA can be directly visualized along its entire length in the full-term infant and older child. 4 With the advent of even higher frequency transducers, it would seem logical that this approach could be applied to the small preterm infant. This study aims to evaluate the combined role of direct visualization by high-frequency, 2-dimensional echo,
with left-to-right shunt detection by pulsed Doppler echo, and to determine whether this approach could be used to monitor the progress of a PDA after pharmacologic manipulation with indomethacin.
(Am J Cardiol 1984;54:1300-1304)
Methods During a period of 4 months, 15 preterm infants with clinical evidence of a PDA were admitted to the study. They weighed 0.7 to 2.0 kg (mean 1.27) and gestational age ranged from 26 to 33 weeks (mean 29).s The age at the initial study ranged from 3 to 19 days (mean 7.5) (Table I). An ATL MK 600 ultrasound machine with a 7.5-MHz short-focus transducer was used for the real-time assessment, while the pulsed Doppler interrogation was carried out at a frequency of 5 MHz. The infants were studied using a suprasternal approach, often with the transducer in the left or right supraclavicular region. Initially, the aortic arch was visualized in its long axis and then with counterclockwise and leftward angulation; the ductal region was sought. The PDA was visualized along its entire length in each case, using minimal gain settings in order to image the lumen (Fig. 1). The minimal diameter of the PDA was noted and compared with the descending aortic dimension at the level of the diaphragm. The Doppler interrogation was performed during simultaneous visualization, with the sample volume placed at the pulmonary artery and aortic end of the PDA. The flow patterns at each of these positions was then documented. Indomethacin was administered intravenously in a standard 3-dose regimen. This combined procedure was performed in
From the Departments of Paediatrics, Division of Cardiology, and Neonatology, The Hospital for Sick Children, Toronto, Ontario, Canada. Manuscript received April 5, 1984; revised manuscript received July 30, 1984, accepted July 31, 1984. Address for reprints: Jeffrey F. Smallhorn, FRACP, Division of Cardiology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. 1300
December 1, 1984 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 54
TABLE I Case
1301
Clinical Data
Birth Weight (kg)
Gestational Age (wk)
Age at Study (days)
Narrowing Before Indomethacln
Status After Indomethacin C
1
1.3
32
4
--
2
1.6
31
4
--
C
3 4
0.8 0.9
28 26
5 4
---
C C
5
2.0
33
10
--
C
6
1.3
28
4
--
P
7
1.9
32
4
--
P
8 9
0.9 1.0
26 29
3 9
---
C C
10
0.9
28
14
--
P
11
1.08
28
19
+
C
12 13 14 15
1.7 1.8 0.7 1.2
31 33 24 31
17 4 7 5
-I-I-I-I-
C C P C
C -- closed; P = patent.
each patient before and within 24 hours after the last dose of indomethacin. Serial studies at least 4 hours after the last dose of indomethacin were possible in some of the patients (Table II). Closure was defined as no visible lumen plus an absent left-to-right shunt detection by Doppler. Constriction was defined as a change in luminal diameter, but with persistent left-to-right shunting by Doppler. For practical reasons, a study was not possible in every case after each dose.
Results The PDA was imaged in every patient, irrespective of the age or weight at the initial study.
FIGURE 1. Top left, a suprasternal cut obtained with leftward anteclockwise rotation of the transducer. The widely patent ductus arteriosus is indicated by the arrow between the left pulmonary artery (Ipa) and the descending aorta (ao). Top right, specimen from a different patient cut to simulate the echocardiographic appearance. The aortic end of the ductus is indicated by the arrow. Bottom, closure (C) at the pulmonary artery end after a single dose of indomethacin. MPA = main pulmonary artery.
In 10 patients (66%), the PDA was initially assessed as being widely patent along its entire length (Table II). In 5 (34%), there appeared to be folds or cushions (Table II). In these latter patients the PDA appeared to be narrow at the pulmonary artery end in 2 (Fig. 2), in the middle in 2 (Fig. 3) and in the middle plus aortic end in 1 patient. In general, the older the patient at the time of the initial examination, the more likely they were to have evidence of intimal cushions or folds (Table I). In those with a wide PDA, the lumen at its narrowest point was two-thirds or equal to the size of the de-
1302
NONINVASIVE ASSESSMENT OF PATENT DUCTUS IN PRETERM INFANT
T A B L E II
Duclal A p p e a r a n c e
Case
Before Indomethacin
First Dose
Second Dose
Third Dose
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
W W W W W W W W W W Narrow middle -t- Ao end Narrow middle Narrow PA end Narrow middle Narrow PA end
NA NA NA Narrow middle NA NA Narrow middle NA Closed PA lumen Narrow middle lumen seen Unchanged Closed middle NA NA Closed whole length
Narrow middle Closed at PA end NA NA Narrow PA end No change Narrow whole length Narrow PA end NA Narrow lumen not seen NA NA Closed whole length Narrow middle NA
Closed whole length NA Closed PA end -I- middle Closed whole length Closed whole length Narrow middle Closed whole length Closed whole length NA Unchanged Closed Ao end NA NA Unchanged NA
Ao = aorta; NA = not assessed; PA = pulmonary artery; W = widely patent.
scending aorta at the diaphragm. In those with an irregular lumen, the size could not be determined. In the group with a wide PDA (cases 1 to 10) (Table II), closure after a single dose of indomethacin occurred
FIGURE 2. A suprasternal cut showing a patent ductus arteriosus that is narrowed at the pulmonary artery end. The small arrows indicate the aorta (ao) and pulmonary artery and some of the patent ductus arteriosus. The ductus is visualized along its entire length. A = anterior; I -- Inferior; P = posterior; S = superior; other abbreviations as in Figure 1.
in I (Fig. 1). In i patient, closure occurred after 2 doses and in another after 3 doses. In 2, ductal constriction occurred with persistent left-to-right shunting. In the group with a narrowed PDA (cases 11 to 15) (Table II), closure after I dose occurred in 2 patients and after 2 doses in 2. In I patient the ductal lumen remained unchanged despite indomethacin administration. In 1 patient (no. 6), no change was observed after 2 doses; however, some buckling was noted in the middle after a third dose (Fig. 4). After a fourth dose, the PDA responded further by narrowing in the middle plus pulmonary artery end (Fig. 4). The patterns of closure or constriction varied throughout the group Table II. Most PDAs appeared to close or constrict along the whole length (Fig. 4); in 1 PDA the closure occurred in the middle (Fig. 3), in 2 PDAs at the pulmonary artery end (Fig. 1) and 1 PDA at the aortic end. After a course of indomethacin the lumen appeared obliterated in all patients but 1 (patient 14). In this patient a second course was administered, after which the PDA closed completely. In no patient with complete closure did the PDA later reopen. Among those in whom constriction occurred, 2 patients improved clinically. In both, the clinical signs of a PDA disappeared despite its detection by Doppler. In I patient, the clinical signs disappeared; however, the child required prolonged ventilation. Repeat examination revealed no change in the ductal appearance, with Doppler interrogation identifying persistent left-to-right shunting. Doppler interrogation alone did not permit differentiation between vessels of differing sizes. A left-toright shunt was detected at the pulmonary artery end (Fig. 5), with evidence of runoff when sampling at the aortic end in each patient. Detection of the presence of left-to-right shunting by Doppler was very sensitive, even when the lumen was no longer visible by 2-dimensional echo (Fig. 6). Discussion
FIGURE 3. A suprasternal cut showing a patent ductus arteriosus that is narrowed in the middle. The aortic and pulmonary artery ends (small arrows) are widely patent. Abbreviations as in Figures 1 and 2.
The incidence of PDA in infants.who weigh less than 1,750 g is approximately 30%. This incidence varies according to weight; in those who weigh less than 1,000 g, the incidence is 42%, whereas in those who weigh 1,500 to 1,750 g the incidence is only 7%.5 The recent National Collaborative Study reported the complexity of using
December 1, 1984 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 54
noninvasive criteria to make the diagnosis of a hemodynamically significant PDA. s M - m o d e echo to assess the leftatrial/aorticratio was unsatisfactory, with 49% having an abnormal value before ductal ligation and 26% after surgical intervention. Using the suprasternal 2-dimensional echocardiographic approach, a P D A can be visualized along its entire length.4 With the use of higher frequency transducers, the P D A can be visualized in the small preterm infant as well. Similarly, the 2-dimensional echocardiographic suprasternal approach can be used to follow the progress of a P D A after pharmacologic manipulation with indomethacin. Although this study was designed only to assess the feasibilityof this technique, it m a y provide the answers to questions regarding the "winking" P D A and the effect of various interventions which are claimed to maintain ductal patency. 6,v The irregularitiesin the lumen of the P D A are folds or intimal cushions and represent the macroscopic features of a closing PDA. 8 Data from autopsy specimens suggest that most close initiallyat the pulmonary artery end with eventual obliteration along their entire length. This is postulated to be due to the lower pulmonary artery pressure offering a smaller distending force to oppose constriction.9 In the group of patients assessed, although obliteration along the entire length usually commencing at the pulmonary artery end was more frequent, it was by no means universal. The lateral resolution of the 7.5-MHz transducer is approximately 1.3 raM, indicating that even a small
FIGURE 4. Top left, a suprastemal cut showing a widely patent ductus arteriosus before indomethacin therapy. Top right, buckling in the center of the ductus after the administration of indomethacin. The aortic and pulmonary artery ends (small arrows) are widely patent. Bottom, after 4 doses of indomethacin. The ductus is now narrowed along its entire length with a prominent fold in the center. Abbreviations as in Figures 1 and 2.
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P D A can be visualized. If the lumen size fallsoutside this range, then an accurate assessment of patency is impossible by this technique alone. Doppler ultrasound, by assessing the frequency shift at any particular site, is very sensitive in detecting a left-to-right shunt at ductal level.2,3 So far, shunting has been assessed by sampling in the main pulmonary artery in the high precordial short-axis cut. Confusion m a y occur with diastolic turbulence from other lesions, such as pulmonary regurgitation, unless the sample volume is placed in the mouth and along the length of the PDA. Likewise, even in the presence of a PDA, a left-to-right shunt detected by sampling in the main pulmonary artery alone provides no information regarding size,the degree of shunting detected being dependent on the relative pulmonary and systemic resistances.2 Problems m a y occur with a direct assessment of size in the presence of intimal cushions or folds, when the lumen cannot be visualized. Although the pulmonaryto-systemic flow ratio m a y be assessed using Doppler echo, I° the question of what size shunt is significant in this age group is debatable. The technique we have described is possible even in the very small preterm infant, with the suprasternal approach avoiding the problems of lung hyperinflation due to assisted ventilation. Provided the examinations are gentle and warm aquasonic jelly is used, few problems occur. The occasional bradycardia that results from handling the baby may be seen, which can be anticipated if the infant is monitored with an electrocar-
1304
NONiNVASIVEASSESSMENT OF PATENT DUCTUS IN PRETERM INFANT
FIGURE 5. Top, a suprasternal cut in a patient with a large patent ductus arteriosus. The sample volume (arrow) had been placed at the pulmonary artery end of the ductus arteriosus. Bottom, a Doppler tracing showing left-to-right shunting through the patent ductus arteriosus. Abbreviations as in Figure 1.
diogram and PO2 electrode. Thus, this combined approach can be used to make an accurate diagnosis and monitor the progress of a PDA in the small preterm infant.With further application, many of the unanswered questions regarding the natural history of the PDA in this age group may be resolved. References 1. Allen HD, GoldbergSJ, Valdso-CruzLM, Sahn DJ. Use of echocardiography in newborns with patent ductus arteriosus: a review. Pediatr Cardiol 1982;3:65-70. 2. Stevenson JG, Kawaborl I, Guntharoth WG. Noninvasive detection of pulmonary hypertension patent ductus arteriosus by pulsed Doppler echocardiography. Circulation 1979;60:355-359. 3. Danlels O, Hopman JCW, Sloallnga GBA, Busch HJ, Peer PGM. Doppler flow characteristics in the main pulmonaryartery and the LA/Ao ratio before and after ductal closure in healthy newborns. Pediatr Cardio11982;3:99104. 4. Smallhom JF, Huhta JC, Anderson RH, Macartney FJ. Suprasternal cross-sectionalechocardiographyin assessmentof patentductus arteriosus. Br Heart J 1982;48:321-330. 6. El,son RC, Packham GJ, Lang P, Talnar NS, Larar TJ, LIn L, Dooley KJ, Nadas AS. Evaluation of the preterm infant for patent ductus arteriosus. Pediatrics 1983;71:364-372. 6. Green T, Thoml0~ TR, JohnsonDE, Lock JE. Furosemidepromotespatent
FIGURE 6. Top, a suprasternal cut showing a patent ductus arteriosus (DA), which appears to be closed by direct visualization. Middle, the Doppler sample volume was placed in the pulmonary artery end of the ductus arteriosus. Bottom, forward flow down the main pulmonary artery (MPA) during systole with evidence of some abbreviated diastolic flow representing some persistent left-to-right shunting through the patent ductus arteriosus. DIAS = diastole; LPA = left pulmonary artery; SYS = systole.
ductus arteriosus in premature infants with the respiratory-distress syndrome. N Engl J Med 1983;308:743-748. 7. Bell EF, Warburton D, Stonestreet BS, Oh W. Effect of fluid administration on the developmentof symptomaticpatent ductus arterlosusand congestive heart failure In premature infants. N Engl J Med 1983;302:598-604. 8. Gltlanberger-DeGroet A. Persistent ductus arteriosus: most probably a primary congenital malformation. Br Heart J 1977;36:610-618. 9. Olley PM, Ceceanl F. The ductus arteriosus: persistence and patency. In: Godman MJ, Marquis RM, eds. Pediatric Cardiology. Heart Disease in the Newborn. London: Churchill Livingston, 1979:15-24. 10. Barron JV, Sahn DJ, Valdes-Cruz LM, OIIvlera C, Goldberg SJ, Grenadier E, Allen HD. Clinical utility of two-dimensional Doppler echocardiographic techniques for estimatingpulmonaryto systemic blood flow ratios in children with left to right shunting atrial septal defect, ventricular septal defect or patent ductus arteriosus. JACC 1984;3:169-178.
Fifteen preterm infants who weighed 0.7 to 2.0 kg and had clinical evidence of a patent ductus arteriosus (PDA) were studied by combined 2-dimensional and Doppler echocardiography before and after the administration of indomethacin. In 10 patients the PDA was widely patent at the time of the study and in 5 the lumen was narrow. In this latter group, the PDA was narrow at the pulmonary artery end in 2 patients, in the middle in 2 patients and at the aortic end and the middle in 1 patient. After the administration of intravenous indomethacin, the PDA closed completely in 12 patients and constricted in 3. The patterns of closure could be documented in those in whom serial studies were performed. In 3 patients, closure occurred after a single dose of in-
domethacin, in 3 after 2 doses and in the rest after a full course of 3 doses. Doppler interrogation at the aortic and pulmonary artery end of the PDA demonstrated the shunting patterns and provided a reliable assessment of patency after the ductal lumen was outside the range of lateral resolution following constriction. In no case did the PDA reopen after the course of indomethacin. This combined approach is a reliable method of assessing a PDA before and after a course of indomethacin. It should provide the means to answer many of the questions regarding the effect of various manipulations on the PDA in the preterm infant.
Patent ductus arteriosus (PDA) is a common finding in small preterm infants. No reliable noninvasive technique is available that allows the clinician to accurately assess the size and monitor the progress of a PDA before and after pharmacologic manipulation with indomethacin. M-mode echocardiography (echo) has many limitations and provides only indirect evidence of a left-to-right s h u n t J Similarly, although Doppler echo is sensitive in detecting the presence of a left-to-right shunt, it provides only indirect evidence of a shunt, which itself depends on pulmonary and systemic resistance.2,3 With 2-dimensional echo, a PDA can be directly visualized along its entire length in the full-term infant and older child. 4 With the advent of even higher frequency transducers, it would seem logical that this approach could be applied to the small preterm infant. This study aims to evaluate the combined role of direct visualization by high-frequency, 2-dimensional echo,
with left-to-right shunt detection by pulsed Doppler echo, and to determine whether this approach could be used to monitor the progress of a PDA after pharmacologic manipulation with indomethacin.
(Am J Cardiol 1984;54:1300-1304)
Methods During a period of 4 months, 15 preterm infants with clinical evidence of a PDA were admitted to the study. They weighed 0.7 to 2.0 kg (mean 1.27) and gestational age ranged from 26 to 33 weeks (mean 29).s The age at the initial study ranged from 3 to 19 days (mean 7.5) (Table I). An ATL MK 600 ultrasound machine with a 7.5-MHz short-focus transducer was used for the real-time assessment, while the pulsed Doppler interrogation was carried out at a frequency of 5 MHz. The infants were studied using a suprasternal approach, often with the transducer in the left or right supraclavicular region. Initially, the aortic arch was visualized in its long axis and then with counterclockwise and leftward angulation; the ductal region was sought. The PDA was visualized along its entire length in each case, using minimal gain settings in order to image the lumen (Fig. 1). The minimal diameter of the PDA was noted and compared with the descending aortic dimension at the level of the diaphragm. The Doppler interrogation was performed during simultaneous visualization, with the sample volume placed at the pulmonary artery and aortic end of the PDA. The flow patterns at each of these positions was then documented. Indomethacin was administered intravenously in a standard 3-dose regimen. This combined procedure was performed in
From the Departments of Paediatrics, Division of Cardiology, and Neonatology, The Hospital for Sick Children, Toronto, Ontario, Canada. Manuscript received April 5, 1984; revised manuscript received July 30, 1984, accepted July 31, 1984. Address for reprints: Jeffrey F. Smallhorn, FRACP, Division of Cardiology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. 1300
December 1, 1984 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 54
TABLE I Case
1301
Clinical Data
Birth Weight (kg)
Gestational Age (wk)
Age at Study (days)
Narrowing Before Indomethacln
Status After Indomethacin C
1
1.3
32
4
--
2
1.6
31
4
--
C
3 4
0.8 0.9
28 26
5 4
---
C C
5
2.0
33
10
--
C
6
1.3
28
4
--
P
7
1.9
32
4
--
P
8 9
0.9 1.0
26 29
3 9
---
C C
10
0.9
28
14
--
P
11
1.08
28
19
+
C
12 13 14 15
1.7 1.8 0.7 1.2
31 33 24 31
17 4 7 5
-I-I-I-I-
C C P C
C -- closed; P = patent.
each patient before and within 24 hours after the last dose of indomethacin. Serial studies at least 4 hours after the last dose of indomethacin were possible in some of the patients (Table II). Closure was defined as no visible lumen plus an absent left-to-right shunt detection by Doppler. Constriction was defined as a change in luminal diameter, but with persistent left-to-right shunting by Doppler. For practical reasons, a study was not possible in every case after each dose.
Results The PDA was imaged in every patient, irrespective of the age or weight at the initial study.
FIGURE 1. Top left, a suprasternal cut obtained with leftward anteclockwise rotation of the transducer. The widely patent ductus arteriosus is indicated by the arrow between the left pulmonary artery (Ipa) and the descending aorta (ao). Top right, specimen from a different patient cut to simulate the echocardiographic appearance. The aortic end of the ductus is indicated by the arrow. Bottom, closure (C) at the pulmonary artery end after a single dose of indomethacin. MPA = main pulmonary artery.
In 10 patients (66%), the PDA was initially assessed as being widely patent along its entire length (Table II). In 5 (34%), there appeared to be folds or cushions (Table II). In these latter patients the PDA appeared to be narrow at the pulmonary artery end in 2 (Fig. 2), in the middle in 2 (Fig. 3) and in the middle plus aortic end in 1 patient. In general, the older the patient at the time of the initial examination, the more likely they were to have evidence of intimal cushions or folds (Table I). In those with a wide PDA, the lumen at its narrowest point was two-thirds or equal to the size of the de-
1302
NONINVASIVE ASSESSMENT OF PATENT DUCTUS IN PRETERM INFANT
T A B L E II
Duclal A p p e a r a n c e
Case
Before Indomethacin
First Dose
Second Dose
Third Dose
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
W W W W W W W W W W Narrow middle -t- Ao end Narrow middle Narrow PA end Narrow middle Narrow PA end
NA NA NA Narrow middle NA NA Narrow middle NA Closed PA lumen Narrow middle lumen seen Unchanged Closed middle NA NA Closed whole length
Narrow middle Closed at PA end NA NA Narrow PA end No change Narrow whole length Narrow PA end NA Narrow lumen not seen NA NA Closed whole length Narrow middle NA
Closed whole length NA Closed PA end -I- middle Closed whole length Closed whole length Narrow middle Closed whole length Closed whole length NA Unchanged Closed Ao end NA NA Unchanged NA
Ao = aorta; NA = not assessed; PA = pulmonary artery; W = widely patent.
scending aorta at the diaphragm. In those with an irregular lumen, the size could not be determined. In the group with a wide PDA (cases 1 to 10) (Table II), closure after a single dose of indomethacin occurred
FIGURE 2. A suprasternal cut showing a patent ductus arteriosus that is narrowed at the pulmonary artery end. The small arrows indicate the aorta (ao) and pulmonary artery and some of the patent ductus arteriosus. The ductus is visualized along its entire length. A = anterior; I -- Inferior; P = posterior; S = superior; other abbreviations as in Figure 1.
in I (Fig. 1). In i patient, closure occurred after 2 doses and in another after 3 doses. In 2, ductal constriction occurred with persistent left-to-right shunting. In the group with a narrowed PDA (cases 11 to 15) (Table II), closure after I dose occurred in 2 patients and after 2 doses in 2. In I patient the ductal lumen remained unchanged despite indomethacin administration. In 1 patient (no. 6), no change was observed after 2 doses; however, some buckling was noted in the middle after a third dose (Fig. 4). After a fourth dose, the PDA responded further by narrowing in the middle plus pulmonary artery end (Fig. 4). The patterns of closure or constriction varied throughout the group Table II. Most PDAs appeared to close or constrict along the whole length (Fig. 4); in 1 PDA the closure occurred in the middle (Fig. 3), in 2 PDAs at the pulmonary artery end (Fig. 1) and 1 PDA at the aortic end. After a course of indomethacin the lumen appeared obliterated in all patients but 1 (patient 14). In this patient a second course was administered, after which the PDA closed completely. In no patient with complete closure did the PDA later reopen. Among those in whom constriction occurred, 2 patients improved clinically. In both, the clinical signs of a PDA disappeared despite its detection by Doppler. In I patient, the clinical signs disappeared; however, the child required prolonged ventilation. Repeat examination revealed no change in the ductal appearance, with Doppler interrogation identifying persistent left-to-right shunting. Doppler interrogation alone did not permit differentiation between vessels of differing sizes. A left-toright shunt was detected at the pulmonary artery end (Fig. 5), with evidence of runoff when sampling at the aortic end in each patient. Detection of the presence of left-to-right shunting by Doppler was very sensitive, even when the lumen was no longer visible by 2-dimensional echo (Fig. 6). Discussion
FIGURE 3. A suprasternal cut showing a patent ductus arteriosus that is narrowed in the middle. The aortic and pulmonary artery ends (small arrows) are widely patent. Abbreviations as in Figures 1 and 2.
The incidence of PDA in infants.who weigh less than 1,750 g is approximately 30%. This incidence varies according to weight; in those who weigh less than 1,000 g, the incidence is 42%, whereas in those who weigh 1,500 to 1,750 g the incidence is only 7%.5 The recent National Collaborative Study reported the complexity of using
December 1, 1984 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 54
noninvasive criteria to make the diagnosis of a hemodynamically significant PDA. s M - m o d e echo to assess the leftatrial/aorticratio was unsatisfactory, with 49% having an abnormal value before ductal ligation and 26% after surgical intervention. Using the suprasternal 2-dimensional echocardiographic approach, a P D A can be visualized along its entire length.4 With the use of higher frequency transducers, the P D A can be visualized in the small preterm infant as well. Similarly, the 2-dimensional echocardiographic suprasternal approach can be used to follow the progress of a P D A after pharmacologic manipulation with indomethacin. Although this study was designed only to assess the feasibilityof this technique, it m a y provide the answers to questions regarding the "winking" P D A and the effect of various interventions which are claimed to maintain ductal patency. 6,v The irregularitiesin the lumen of the P D A are folds or intimal cushions and represent the macroscopic features of a closing PDA. 8 Data from autopsy specimens suggest that most close initiallyat the pulmonary artery end with eventual obliteration along their entire length. This is postulated to be due to the lower pulmonary artery pressure offering a smaller distending force to oppose constriction.9 In the group of patients assessed, although obliteration along the entire length usually commencing at the pulmonary artery end was more frequent, it was by no means universal. The lateral resolution of the 7.5-MHz transducer is approximately 1.3 raM, indicating that even a small
FIGURE 4. Top left, a suprastemal cut showing a widely patent ductus arteriosus before indomethacin therapy. Top right, buckling in the center of the ductus after the administration of indomethacin. The aortic and pulmonary artery ends (small arrows) are widely patent. Bottom, after 4 doses of indomethacin. The ductus is now narrowed along its entire length with a prominent fold in the center. Abbreviations as in Figures 1 and 2.
1303
P D A can be visualized. If the lumen size fallsoutside this range, then an accurate assessment of patency is impossible by this technique alone. Doppler ultrasound, by assessing the frequency shift at any particular site, is very sensitive in detecting a left-to-right shunt at ductal level.2,3 So far, shunting has been assessed by sampling in the main pulmonary artery in the high precordial short-axis cut. Confusion m a y occur with diastolic turbulence from other lesions, such as pulmonary regurgitation, unless the sample volume is placed in the mouth and along the length of the PDA. Likewise, even in the presence of a PDA, a left-to-right shunt detected by sampling in the main pulmonary artery alone provides no information regarding size,the degree of shunting detected being dependent on the relative pulmonary and systemic resistances.2 Problems m a y occur with a direct assessment of size in the presence of intimal cushions or folds, when the lumen cannot be visualized. Although the pulmonaryto-systemic flow ratio m a y be assessed using Doppler echo, I° the question of what size shunt is significant in this age group is debatable. The technique we have described is possible even in the very small preterm infant, with the suprasternal approach avoiding the problems of lung hyperinflation due to assisted ventilation. Provided the examinations are gentle and warm aquasonic jelly is used, few problems occur. The occasional bradycardia that results from handling the baby may be seen, which can be anticipated if the infant is monitored with an electrocar-
1304
NONiNVASIVEASSESSMENT OF PATENT DUCTUS IN PRETERM INFANT
FIGURE 5. Top, a suprasternal cut in a patient with a large patent ductus arteriosus. The sample volume (arrow) had been placed at the pulmonary artery end of the ductus arteriosus. Bottom, a Doppler tracing showing left-to-right shunting through the patent ductus arteriosus. Abbreviations as in Figure 1.
diogram and PO2 electrode. Thus, this combined approach can be used to make an accurate diagnosis and monitor the progress of a PDA in the small preterm infant.With further application, many of the unanswered questions regarding the natural history of the PDA in this age group may be resolved. References 1. Allen HD, GoldbergSJ, Valdso-CruzLM, Sahn DJ. Use of echocardiography in newborns with patent ductus arteriosus: a review. Pediatr Cardiol 1982;3:65-70. 2. Stevenson JG, Kawaborl I, Guntharoth WG. Noninvasive detection of pulmonary hypertension patent ductus arteriosus by pulsed Doppler echocardiography. Circulation 1979;60:355-359. 3. Danlels O, Hopman JCW, Sloallnga GBA, Busch HJ, Peer PGM. Doppler flow characteristics in the main pulmonaryartery and the LA/Ao ratio before and after ductal closure in healthy newborns. Pediatr Cardio11982;3:99104. 4. Smallhom JF, Huhta JC, Anderson RH, Macartney FJ. Suprasternal cross-sectionalechocardiographyin assessmentof patentductus arteriosus. Br Heart J 1982;48:321-330. 6. El,son RC, Packham GJ, Lang P, Talnar NS, Larar TJ, LIn L, Dooley KJ, Nadas AS. Evaluation of the preterm infant for patent ductus arteriosus. Pediatrics 1983;71:364-372. 6. Green T, Thoml0~ TR, JohnsonDE, Lock JE. Furosemidepromotespatent
FIGURE 6. Top, a suprasternal cut showing a patent ductus arteriosus (DA), which appears to be closed by direct visualization. Middle, the Doppler sample volume was placed in the pulmonary artery end of the ductus arteriosus. Bottom, forward flow down the main pulmonary artery (MPA) during systole with evidence of some abbreviated diastolic flow representing some persistent left-to-right shunting through the patent ductus arteriosus. DIAS = diastole; LPA = left pulmonary artery; SYS = systole.
ductus arteriosus in premature infants with the respiratory-distress syndrome. N Engl J Med 1983;308:743-748. 7. Bell EF, Warburton D, Stonestreet BS, Oh W. Effect of fluid administration on the developmentof symptomaticpatent ductus arterlosusand congestive heart failure In premature infants. N Engl J Med 1983;302:598-604. 8. Gltlanberger-DeGroet A. Persistent ductus arteriosus: most probably a primary congenital malformation. Br Heart J 1977;36:610-618. 9. Olley PM, Ceceanl F. The ductus arteriosus: persistence and patency. In: Godman MJ, Marquis RM, eds. Pediatric Cardiology. Heart Disease in the Newborn. London: Churchill Livingston, 1979:15-24. 10. Barron JV, Sahn DJ, Valdes-Cruz LM, OIIvlera C, Goldberg SJ, Grenadier E, Allen HD. Clinical utility of two-dimensional Doppler echocardiographic techniques for estimatingpulmonaryto systemic blood flow ratios in children with left to right shunting atrial septal defect, ventricular septal defect or patent ductus arteriosus. JACC 1984;3:169-178.