© 2014, Wiley Periodicals, Inc. DOI: 10.1111/echo.12457
Echocardiography for Patent Ductus Arteriosus Including Closure in Adults Reema Chugh, M.D., F.A.C.C.,* and Morris M. Salem, M.D., F.A.C.C., F.S.C.A.I.† *Cardiology Division, CMOB 308, Kaiser Permanente Medical Center, Panorama City, California; and †Pediatric Cardiology, Kaiser Permanente—Los Angeles Medical Center, Los Angeles, California
Patent ductus arteriosus (PDA) represents at least 5–10% of all congenital heart defects (CHDs) making it a very important commonly diagnosed lesion. Although spontaneous closure of the PDA occurs within 24 to 48 hours after birth in the majority, those children who do not have natural or surgical closure may have a persistent PDA into adulthood. The diagnosis is most often conﬁrmed by echocardiography that also guides catheter-based interventions and surgeries. Echocardiography continues to be the most important tool in long-term follow-up of residua and sequelae. (Echocardiography 2014;00:1–15) Key words: congenital heart defects, transthoracic echocardiography, transesophageal echocardiography, transcatheter closure, congenital heart disease, cardiovascular diseases Patent ductus arteriosus (PDA) is a vascular structure connecting the inferior curvature of the proximal descending aorta to the roof of the main pulmonary artery near the origin of the left pulmonary artery. Under normal circumstances via a complex biphasic process, contraction of medial smooth muscle in the vessel wall causes spontaneous closure of the PDA within 24 to 48 hours after birth. The closure process continues when smooth muscle ﬁbers are replaced with connective tissue resulting in formation of a ligamentum arteriosum within 2 to 3 weeks. Failure of this process to occur leads to a persistent PDA.1 Historical Perspective: The simple entity called PDA has an interesting story in the history of medicine. Its understanding has taken a staircase approach over many centuries starting with the initial description by Galen in the early ﬁrst century AD. He famously wrote the following: “Nature is neither lazy nor devoid of foresight. Having given the matter thought, she knows in advance that the lung of the fetus does not require the same arrangements of a perfected lung endowed with motion. She has therefore anastomosed the pulmonary artery with the aorta.”2 Leonardo Botallo from Address for correspondence and reprint requests: Reema Chugh, M.D., F.A.C.C., Cardiologist/Specialist in Adult Congenital Heart Disease and Heart Disease in Pregnancy, Cardiology Division, CMOB 308, Kaiser Permanente Medical Center, Panorama City, CA. Fax: 818-375-2907; E-mail: [email protected]
Piedmont, Italy was controversially associated with the rediscovery of the arterial duct and therefore it is sometimes referred to as ductus Botallo.3 In 1628, William Harvey introduced the concept of fetal circulation and understanding of the dynamic concept of the cardiovascular system. Harvey determined that the two ventricles work in-parallel in the fetus as opposed to working in-series in the adult. He thereby explained the nature of fetal blood ﬂow in the PDA. In 1888, Dr. John Munro conducted a series of dissections on cadavers of newborn infants in Boston demonstrating the technical feasibility of a surgical approach to the PDA. Having never operated on a live patient, in 1907 he nevertheless made a bold proposal for a surgery that would eliminate the PDA via a “sternal splitting operation.” There are no reports documenting that his proposal was taken seriously.4 In 1937, John Strieder of Boston had technical difﬁculties achieving complete closure of PDA in a woman who succumbed a few days after the surgery.5 Dr. Robert E. Gross successfully ligated a PDA in a 7-year-old child, thus heralding the true birth of cardiac surgery in 1938.5 Around the same period, Dr. E. K. Frey also performed several PDA ligations in Germany.4 Surgeons were emboldened by the success of this surgery. Within a period of 6 years, the repair of coarctation of aorta was performed followed by the Blalock–Taussig–Thomas shunt in 1944.6 A new era in catheter-based interventions was heralded by the closure of the PDA in 1967, with the efforts of Portsmann et al. who successfully 1
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used a conical Ivalon plug in over 100 patients.7,8 This pioneering effort was followed by the Rashkind and Cuaso umbrella-type device in 1979 and they developed more modiﬁcations of this device over the years.9 Many more global developments of the PDA closure devices were unfortunately plagued by complicated delivery systems, procedural complications, and unsatisfactory total occlusion rates. In 1992, Cambier et al. reported the use of Gianturco coils for transcatheter closure of PDA which led to widespread transcatheter coil occlusion for closure of the small to moderate patent ductus.10 Since then, newer devices and techniques have been developed to treat more moderate and large PDAs that were previously not amenable to catheter-based interventions. Since 2003, the Amplatzer duct occluder devices have been approved in the United States by the Food and Drug Administration thus allowing closure of large PDAs that are well over 5 mm in diameter.11 The development of minimally invasive surgical techniques has paralleled the development of transcatheter techniques. Laborde et al. achieved PDA closure by video-assisted thoracoscopic surgery in 1991.12,13 Epidemiology and Genetics: Because the PDA is a fetal structure, its occurrence is more frequent in children and there is a low incidence in adults, either because of spontaneous or surgical/catheter-based closure. The incidence of isolated PDA is between 1 per 2000 and 1 per 5000 births.14 Premature infants have an increased incidence of 20% if born after 32 weeks’ of gestation, and up to 60% if born before 28 weeks’ of gestation. A greater incidence is reported in children born at high altitudes and this is believed to be due to failure of low oxygen tension to constrict the ductus.15,16 PDA occurs nearly twice as often in females than in males with no racial predilection. However, the incidence has been reported equally between the sexes when there is a speciﬁc exposure to a teratogen, such as in congenital rubella. In contrast to premature infants, in whom PDA is generally due to developmental immaturity, in term infants it is usually associated with signiﬁcant structural abnormalities. More often, it is associated with genetic syndromes, including those with deﬁned chromosomal aberrations (such as trisomy 21, 4p–syndrome), single-gene mutations (such as Carpenter’s syndrome, Holt– Oram syndrome), and X-linked mutations (such as incontinentia pigmenti). Although most cases of PDA appear sporadic, many may have a multifactorial inheritance, with a genetic predisposi-
tion which in the presence of an environmental trigger makes it occur at a vulnerable time. In some patients, PDA may have resulted from an autosomal recessive inheritance with incomplete penetrance.17 In a family that has one offspring with a PDA, there is an approximately 3% chance of its occurrence in another offspring. Origin of the PDA: The ductus arteriosus arises from the left sixth primitive aortic arch and connects the proximal left pulmonary artery to the descending aorta, just distal to the left subclavian artery.1 The architecture of the PDA differs from that of the aorta and pulmonary artery. In its walls, the medial and subintimal layers have well-developed muscle sheets that are continuous with the elastica of the aorta. In theory, this architecture predisposes the PDA tissue to contract and obliterate the lumen under appropriate signals and conditions such as the increase in oxygen tension postdelivery. Another theory states that there is an obligatory postnatal increase in aortic pressure and simultaneous fall in pulmonary pressure favors closure of the PDA through mechanical traction/ torsion on the ductus.5 Normally, ductal closure is a biphasic process that begins with a slow anatomical phase that is initiated in the last trimester of pregnancy. During this time, there is proliferation of the intimal layer via augmentation of the laminated collagen and elastic tissue producing ridges and folds. This is followed by the postnatal phase where smooth muscle reactivity and contraction create anatomical obliteration of the cavity followed by eventual “scarring” and ligamentum formation. A ﬂaw in any component of this organized process results in the patency of the ductus arteriosus. Classiﬁcation: A universally accepted system for anatomical classiﬁcation of the PDA, called the Krichenko classiﬁcation, is based on its angiographic appearance.18,19 The ﬁve Krichenko PDA subtypes as shown in Figure 1 are: (1) Type A (conical) with subtypes 1, 2, and 3; (2) Type B (window) with subtypes 1, 2, and 3; (3) Type C (tubular); (4) Type D (complex); and (5) Type E (elongated); with a relative incidence of approximately 85% for Type A, 10% for both Types D and E combined, and 5% for both Types B and C combined. Clinical Presentation: History: Patients with a moderate-to-large PDA may present with dyspnea (due to progressive left heart enlargement and impaired function resulting in
Echocardiography in Patent Ductus Arteriosus
Figure 1. Types of patent ductus arteriosus (PDA) adapted from Krinchenko’s classiﬁcation.
heart failure) and palpitations (due to left atrial enlargement predisposing to atrial arrhythmias). Exercise tolerance is limited in individuals with Eisenmenger physiology. Physical Examination: Depending on the size of the PDA and associated defects, the physical examination can vary. In case of a trivial “silent” PDA, the diagnosis is only made by an echocardiogram. Adults with a very large, nonrestrictive PDA can have suprasystemic pressures and develop Eisenmenger physiology with a right-to-left shunt and lose the “continuous machinery murmur.” Instead, they may oftentimes have “differential” cyanosis on physical examination, with deeper cyanosis of the lower extremities associated with clubbing. This is more prominent in the toes and is of a milder degree in the left hand. The cyanosis and clubbing are conspicuously absent in the right hand making “differential cyanosis” the most speciﬁc physical sign of a large PDA with reversal of the shunt. Finger pulse oximetry may be used to unveil asymmetric hypoxemia when cyanosis and clubbing not clinically apparent. Other ﬁndings include a right ventricular lift, a mid-systolic murmur, a palpable/loud second heart sound that is closely split (or reversed split), followed by an end-diastolic murmur of hypertensive pulmonary regurgitation.1 A small PDA presents with a long ejection and continuous “machinery” murmur which envelopes the second heart sound, is heard best in the ﬁrst left intercostal space and radiates to the
back. In case of a moderate PDA, besides the classic “machinery” murmur, there may be bounding peripheral pulses due to a hyperdynamic circulation. Chronic severe aortic regurgitation should be considered in the differential diagnosis. Associated Defects, Variations, and Differential Diagnosis: PDA usually presents as an isolated defect in adults but it may occur in conjunction with a ventricular septal defect, coarctation of aorta, aortic or mitral valve defects, complex congenital heart defects (CHDs) including congenitally corrected transposition of the great arteries and tetralogy of Fallot. PDA has important physiological and clinical similarities to an aortic-pulmonary (AP) window/ AP septal defect although the two are not embryologically related.1 The differential diagnosis of a small PDA includes (1) coronary artery ﬁstula, (2) aortic stenosis with regurgitation, or a (3) ventricular septal defect with aortic regurgitation. Based on echocardiography, the presence of turbulent ﬂow noted in the pulmonary artery with the use of color Doppler echocardiography can be seen in other defects such as ruptured aortic aneurysm into the pulmonary artery, aortopulmonary septal defect, coronary artery ﬁstula draining into the pulmonary trunk, pulmonary stenosis, and constriction of the main pulmonary artery. These conditions can be ruled out while considering a diagnosis of PDA by delineating the origin of the jet from the ductus.20 3
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third decade, 2–2.5% in the fourth decade and increases at the rate of 4% each year thereafter, with a 33% mortality by the age of 40 years and 60% by 60 years of life.14 In early life, heart failure is the most common cause of mortality while in later years there may be other contributing causes including infective endarteritis. Operated: Following repair or device closure of an isolated PDA early childhood, the long-term prognosis is usually favorable with no restriction of normal life activities. Some patients may have small residual or recanalized PDAs that needs follow-up. Those with moderate to large PDAs that are operated later or have associated CHDs encounter more residua and sequelae.
Figure 2. Lateral radiograph with an arrow showing a calciﬁed patent ductus arteriosus in an elderly woman.
PDA may present as bilateral, left-sided, or right-sided PDA in association with a right aortic arch or as a part of the vascular ring.1 Electrocardiogram: There is no characteristic electrocardiographic abnormality that is diagnostic of a PDA. Signs of left ventricular overload may manifest as left ventricular hypertrophy, left atrial enlargement (prolonged biﬁd P-waves in leads II, III, aVF, V5, and V6), and a prolonged PR interval. Atrial ﬁbrillation or ﬂutter may occur in long-standing native PDA. In individuals with Eisenmenger’s physiology, right atrial enlargement (peaked P-waves in II, III, aVF, V1, and V2), biventricular hypertrophy with predominantly right ventricular hypertrophy (right-axis deviation and tall R-wave in V5-6) may be seen. Chest Radiography: Older individuals may have calciﬁcation that is especially apparent on a lateral radiograph as shown in Figure 2. Moderate to large restrictive PDAs present with varying degree of vascular prominence and cardiac chamber enlargement. On the other hand, in Eisenmenger physiology, there is paucity of pulmonary vascularity. In addition, dilatation/calciﬁcation of pulmonary artery and right ventricular hypertrophy may be more evident. Long-Term Complications, Residua and Sequelae: The overall mortality in adults with an unoperated PDA (without correction for the size of the PDA) is estimated to be about 1–1.5% in the 4
Unoperated: Congestive heart failure: Children and adults with moderate to large PDAs develop symptoms of congestive heart failure due to increased blood ﬂow to the lungs resulting in left heart volume overload. Patients with small to moderate PDAs often remain asymptomatic during infancy and childhood. While some may remain asymptomatic in adulthood, others will develop congestive heart failure due to signiﬁcant, chronic left heart volume overload in their 20s. Echocardiography plays an important role in assessment and follow-up of left heart size and ventricular function. Atrial arrhythmias: Enlargement of the left atrium due to volume overload predisposes to atrial ﬁbrillation and ﬂutter. Endarteritis: Before the era of routine antibiotic use and surgical ligation of PDAs, the incidence of infective endarteritis was reported to be at least 1% per year. In the current era, it is much lower and reasons for this decline are multifactorial. These include the improved availability of health/dental care, more widespread use of antibiotics, use for infective endocarditis prophylaxis and early closure of PDA over the past few decades. In developing countries where health resources and access to health care are limited, infective endarteritis associated with ductus arteriosus remains a signiﬁcant health issue. It occurs more often in the second and third decades of life. In these cases, vegetations usually occur on the pulmonary artery end of the ductus with the infected emboli traveling to the lungs rather than to the systemic circulation. Two-dimensional transthoracic (2DTTE) as well transesophageal echocardiograms (2DTEE) are useful in assessment of PDA complicated by endarteritis of the pulmonary artery.
Echocardiography in Patent Ductus Arteriosus
M-Mode acquired from the parasternal short axis may show a diminished pulmonic valve “a-” wave. There may be anomalous echoes with erratic movement distal to the pulmonary valve suspicious of vegetations. Although the pulmonary valve may appear normal in the parasternal short-axis view, there may be abnormal “shaggy” echodensities with coarse diastolic ﬂuttering attached to the lateral wall of the pulmonary artery, where the jet of the ﬂow from the ductus arteriosus strikes and makes it a vulnerable site for endarteritis.21 Pulmonary vascular disease: Large PDAs that offer minimal resistance to ﬂow are considered nonrestrictive and the degree of shunting will depend on the pulmonary vascular resistance. Eventually, there is onset of pulmonary vascular disease and reversal of the shunt (as the right heart pressures rise above the left heart/systemic pressures) leading to Eisenmenger’s physiology. Although Eisenmenger’s physiology is less often associated with a PDA than with a large atrial or ventricular septal defect, it is more likely to be fatal when associated with a PDA. Unfortunately, closure of the PDA at this stage is contraindicated.22 Aneurysm of ductus arteriosus: Although rare, an aneurysm may form either spontaneously or postoperatively, from local or generalized dilatation of the ductal tissue. It usually occurs in the setting of closed pulmonary end of the PDA and wide open aortic oriﬁce.1 TEE is useful in older children and adults in diagnosing a ductal aneurysm.23 In the past, aortography was the preferred method but now computed tomography (CT) or magnetic resonance imaging (MRI) is recommended when the diagnosis cannot be made by a TEE. Spontaneous aneurysms are true, may be fusiform or saccular, while postoperative aneurysms are more likely to be false aneurysms. Although the incidence is higher in infants, ductal aneurysms have been reported in adults who have a history of infective endarteritis, surgical closure, or transcatheter coil occlusion. In 25% of these adults, there is an underlying connective tissue/genetic disorder such as trisomy 21, trisomy 13, Smith–Lemli–Opitz syndrome, type IV Ehlers–Danlos syndrome, or Marfan’s syndrome. Ductal aneurysms may clinically manifest symptoms such as hoarseness due to left vocal cord paralysis from recurrent left laryngeal nerve impingement. They may present with a “thoracic mass” with possible left bronchial obstruction. Serious complications include rupture, erosion (bronchial or esophageal), infection, and thromboembolism. Prompt surgical resection is indicated in adults especially when it is a postsurgical
aneurysm.23 Aggressive management is even more justiﬁed if there is a functional compromise of adjacent structures along with persistent patency of the ductus, with or without thrombi. Ductal calciﬁcation: In adults with a long-standing PDA with or without pulmonary hypertension, calciﬁcation of the ductus can occur. On chest radiography, calciﬁcation is seen at the aortopulmonary junction.24 Other complications: Pulmonary artery enlargement occurs due to intrinsic structural abnormalities of the wall.25 Patients with severe pulmonary hypertension may develop recurrent laryngeal nerve paralysis, even without an aneurysm, due to impingement of the nerve by an enlarged pulmonary artery, as it courses through the triangle formed by the aortic arch and PDA. The PDA may be a source for recurrent peripheral embolizations.26 Rarely, dissection and/or spontaneous rupture of the pulmonary artery may occur in a patient with severe pulmonary hypertension and aneurismally dilated pulmonary artery.27 There are also rare reports of acute aortic dissection associated with persistently patent duct.28,29 PDA in Pregnancy: Echocardiography plays a major role in complete preconception assessment. Women with a ligated or divided isolated PDA usually tolerate pregnancy, labor, and delivery very well, as long as the left ventricular function and the pulmonary arterial pressures are normal.30 Depending on the size of the ductus/degree of shunt, there is an increased risk for developing atrial ﬁbrillation, pulmonary hypertension, congestive heart failure, and bacterial endocarditis/endarteritis. Women with moderate to large PDA are more vulnerable to heart failure and atrial ﬁbrillation. While the maternal morbidity and mortality in unrepaired PDA without Eisenmenger physiology is low, pregnancy in women with severe pulmonary hypertension/Eisenmenger physiology is contraindicated due to extremely high mortality. Endocarditis prophylaxis is indicated at the time of rupture of membranes during delivery in women with unoperated PDA, or in those with residual shunts/associated CHDs that warrant endocarditis prophylaxis.31 Endocaditis Prophylaxis: Infective endocarditis is more commonly seen in second and third decades of life in individuals with a native PDA. These patients as well as those with residual shunts/associated defects should receive endocarditis prophylaxis lifelong. Individ-
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Figure 3. A. and B. Computed tomographic angiography (CTA) showing a patent ductus arteriosus.
uals with an isolated PDA who have undergone device closure and have no residual shunt, or had surgical ligation without recanalization of the ductus, may discontinue the prophylactic use of antibiotics after 6 months.31 Prophylaxis is not clearly indicated for a tiny PDA where the risk of endarteritis is extremely low. Diagnostic Imaging: Before the development of Doppler echocardiography, the diagnosis of PDA could only be made on a physical examination. Over the past 50 years, M-mode 2DTTE, 2DTEE, three-dimensional (3D) echocardiography have advanced along Doppler imaging. Other imaging modalities such as 3D computed tomographic angiography (3DCTA) (Fig. 3A and B) and MRI are able to delineate extracardiac structures more clearly. Currently, it is possible to accurately diagnose even the smallest of the PDAs in infants and young children.32 Echocardiography is the gold standard and other modalities are used as conﬁrmatory tests for more complete assessment of extracardiac structures especially in adults with suboptimal echocardiographic windows. Transthoracic Echocardiography: TTE is quite sensitive and very speciﬁc in making the diagnosis of PDA. Tiny PDAs may be missed on a complete 2D examination with color Doppler but there is a low likelihood of a false positive PDA.33 The echocardiographic diagnosis of a PDA in adults is based on 2D images demonstrating a persistent anatomic connection between the descending aorta and the pulmonary artery (Fig. 4) which may be more apparent with the help of color Doppler (Fig. 5). The best TTE 6
Figure 4. 2DTTE image demonstrating PDA connection, between descending aorta (DAo) and main pulmonary artery (MPA). 2DTTE = two-dimensional transthoracic echocardiography; PDA = patent ductus arteriosus.
images are obtained in the high left parasternal short-axis view above the level of the aortic valve, or in the suprasternal view which may be modiﬁed to achieve a long-axis view of the right ventricular outﬂow tract and the main pulmonary artery. By angling the probe leftward and superiorly in the high parasternal short-axis view, the bifurcation of the pulmonary artery can be visualized (Fig. 6). The aortic end (Fig. 7) and the pulmonary end (Fig. 8) may be seen in this view.34 Echocardiogram may be normal with no left heart enlargement, normal function, and normal estimated right ventricular systolic pressures (RVSPs) in patients with a small PDA. In those with a moderate to large PDA, the echocardiogram shows left atrial/ventricular enlargement with varying degree of impaired left ventricular function and pulmonary hypertension. Hence, follow-up of left ventricular dimensions and quantitative assessment of left ventricular function are
Echocardiography in Patent Ductus Arteriosus
Figure 5. Color ﬂow Doppler with 2DTTE showing PDA jet ﬂowing from the descending aorta (DAo) to the main pulmonary artery (MPA). 2DTTE = two-dimensional transthoracic echocardiography; PDA = patent ductus arteriosus.
Figure 7. 2DTTE showing dimensions of the aortic (0.7 cm) end of a PDA. 2DTTE = two-dimensional transthoracic echocardiography; PDA = patent ductus arteriosus.
Figure 6. Diagrammatic representation of a short-axis view seen on 2DTTE, which shows a PDA jet arising from connection between descending aorta (DA) and left pulmonary artery (LPA). 2DTTE = two-dimensional transthoracic echocardiography; PDA = patent ductus arteriosus.
important in studying the impact of volume overload. RVSPs should be estimated for assessment of degree of pulmonary hypertension. Clinical presentation depends on the size of the ductus (channel), left ventricular function, and pulmonary vascular resistance. When the pulmonary vascular resistance rises signiﬁcantly, a bidirectional shunt occurs with right-to-left ﬂow seen in early systole and a left-to-right ﬂow seen in late systole/diastole. This may then progress to a predominant right-to-left shunt leading to irreversible pulmonary hypertension/Eisenmenger’s physiology. When the color Doppler is properly angled in the main pulmonary artery, its branches may be seen in the left parasternal short-axis plane. The Doppler sample volume is placed just proximal to the bifurcation, and the maximal velocity is recorded. From the high parasternal window, the ultrasound beam aligned directly into the oriﬁce of the PDA records the systolic and diastolic ﬂow. The main pulmonary artery should be interro-
Figure 8. 2DTTE showing dimensions of the pulmonary artery (0.5 cm) end of a PDA. 2DTTE = two-dimensional transthoracic echocardiography; PDA = patent ductus arteriosus.
gated proximally and then distally in an attempt to demonstrate any other patterns. When the main pulmonary artery is dilated in adults, there can be a low velocity retrograde ﬂow in late systole from the swirling of ﬂow within the dilated pulmonary artery. In a normal heart, blood ﬂow in the pulmonary artery moves away from the transducer in systole (as the blood ﬂows from the pulmonary artery into the lungs), and there is no signiﬁcant ﬂow in diastole. When there is a PDA, the blood ﬂows away from the transducer in systole (seen below the baseline), while in diastole the blood ﬂows both toward the transducer (seen above the baseline) and away. A color Doppler jet may 7
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be seen ﬂowing through the left pulmonary artery into the main pulmonary artery with marked spectral dispersion in systole and diastole (throughout the cardiac cycle in adults) which is typical for a PDA with a left-to-right shunt. High Doppler velocity turbulent ﬂow occurs continuously in left-to-right direction across the patent ductus and enters the main pulmonary artery from the posterolateral direction and reaches a peak in late systole. The turbulence is due to both antegrade and a retrograde ﬂow in the main pulmonary artery. Diastolic ﬂow from PDA is seen along the lateral wall of the pulmonary artery. Doppler ﬂow reversal is noted especially along the anterior wall of the pulmonary artery. The continuous variation of the ﬂow between systole and diastole presents as the “machinery” murmur on physical examination with a crescendo– decrescendo pattern that peaks in late systole. This ﬂow pattern is pathognomonic of a PDA in the absence of a surgical shunt (Figs. 9 and 10). Pulsed-wave Doppler from the suprasternal view is used to demonstrate holo-diastolic ﬂow reversal in the descending aorta due to antegrade ﬂow into the ductus in diastole. Flow across the ductus causes pressure equalization between the aorta and the pulmonary artery ﬁrst in diastole but with increasing severity of pulmonary hypertension, the pressure difference between aorta and the pulmonary artery will decrease in systole. In the differential diagnosis of the ﬂow into the main pulmonary artery, one must consider normal pulmonary ﬂow, aortopulmonary window, pulmonary regurgitation, coronary artery ﬁstulas, and anomalous coronary artery. On the other hand, the ﬂow into the descending aorta is similar to diastolic ﬂow reversal seen in aortic regurgitation. Whether the ﬂow is due to a PDA or not can be conﬁrmed by freezing or slowing frames to see the jet of the color Doppler ﬂow arising from
Figure 9. Spectral Doppler ﬂow pattern acquired at the origin of the patent ductus arteriosus (PDA) in an adult.
Figure 10. Spectral Doppler ﬂow pattern acquired at the middle of the patent ductus arteriosus (PDA) jet in an adult.
the bifurcation of the pulmonary artery with the origin of the shunt from the descending thoracic aorta. To see the entire ductus connect to the inferior curvature of the descending aorta, the probe should be rotated clockwise. Unfortunately, this is often difﬁcult and cannot be usually traced in adults due to limited acoustic windows resulting from body habitus, variations in position, alignment, shape, and length of the ductus. A complete echocardiographic examination entails identiﬁcation of the associated defects, including ventricular septal defects, coarctation of aorta, and complex CHD. When visible, the bifurcation of the main pulmonary artery may appear “trifurcate” with the ductus arising along with left and right pulmonary arteries. The pulmonary artery is usually dilated, may become aneurismal and calciﬁed by the fourth decade of life. The estimated RVSP that reﬂects the pressure gradient between the right atrium and the right ventricle is a surrogate for pulmonary artery pressure in the absence of pulmonary stenosis. It can be calculated in all patients based on the tricuspid regurgitant (TR) jet velocity. When the TR jet is inadequate, it may be potentiated by injecting a bolus of normal saline (10 mL) rapidly through a peripheral intravenous catheter, while the sonographer captures the spectral Doppler waveform that has highest velocity. Contrast enhancement increases the amplitude of Doppler signals that are responsible for TR ﬂow. It improves delineation of the TR jet using color ﬂow imaging by reducing the effect of attenuation and improving signal-to-noise ratio.35 A well-known modiﬁed Bernoulli equation is applied to the peak velocity of the TR jet. The assumed right atrial (RA) pressure is then added to the pressure gradient as shown in this standard equation: RVSP ¼ 4 ðTR jet velocityÞ2 þ RA pressure
Echocardiography in Patent Ductus Arteriosus
The echocardiogram in Eisenmenger physiology may also show ﬂattening of the interventricular septum in systole, right heart enlargement, right ventricular hypertrophy. The M-mode may show systolic notching of the pulmonic valve. TTE has its limitations in adults since the use of lower ultrasonic frequencies hampers with the visualization of the PDA in 2D echocardiography. In addition, the ultrasonic delineation of the ductal structure between the descending aorta and the pulmonary artery is extremely difﬁcult due to interference by subcutaneous fat, lung tissue, calciﬁed ribs, and narrow intercostal spaces. Transesophageal Echocardiography: Multiplane TEE allows more manipulation when attempting to identify left heart enlargement (Fig. 11), the ductus arteriosus and its relationship with the descending aorta and pulmonary artery. Color Doppler helps identify the PDA jet ﬂowing into the main pulmonary artery at the aortic level, when the trifurcation is not clearly seen (Fig. 12). Compared with TTE, the TEE has higher sensitivity and negative predictive value than the TTE in conﬁrming the diagnosis of PDA (97% vs. 42% and 98% vs. 68%, respectively). The speciﬁcity and positive predictive value in establishing the diagnosis of PDA are the similar for both.36 The shunt volume calculation is a major part of the hemodynamic evaluation of PDA.37 A combination of information obtained from a TTE and TEE allows more accurate assessment of pulmonary to systemic ﬂow (Qp/Qs) ratio and shunt calculation in adults with an isolated PDA.38 Shunt Calculation: Doppler echocardiography allows indirect measurement of the shunt volume by analysis of the blood ﬂow through the right and left heart. The 2D echocardiogram in the parasternal long-axis view is used to measure the aortic root
Figure 12. TEE at the aortic level showing the course of the PDA jet in the main pulmonary artery. TEE = transesophageal echocardiography; PDA = patent ductus arteriosus.
diameter at the annulus (AoD) and in the parasternal short-axis view to measure the pulmonary valve diameter at the annulus (PaD). Pulsed- and continuous-wave Doppler with color ﬂow mapping is used to obtain maximal continuous ﬂow velocity time integral (VTI). The aortic ﬂow VTI (AoVTI) is obtained in the standard ﬁve-chamber view with the Doppler sample volume placed distal to the tips of the aortic valve. The pulmonary ﬂow VTI (PaVTI) is obtained in the standard parasternal short-axis view at the level of the aortic valve with the sample volume place distal to the pulmonary valve tip and parallel to the ﬂow in the main pulmonary artery. Since the shunt occurs after the ﬂow crosses the pulmonary valve: Transaortic flow/Transpulmonary gradient ¼ Qp=Qs Qp ¼ p ð1=2AoDÞ2 VTI Ao Qs ¼ p ð1=2PaDÞ2 VTI Pa When the oriﬁce of the PDA can be visualized at the pulmonary and the aortic end, measurements are made at those points. The PDA ﬂow VTI can be obtained from the PDA jet and the QPDA can be calculated.37 The modiﬁed Bernoulli equation can be applied in this situation as well. The peak systolic velocity of the PDA allows us to calculate the gradient between the aorta and the pulmonary artery. Pulmonary artery systolic pressure ¼ Systolic blood pressure ðmmHgÞ 4 ðPDA jet velocityÞ2 in mmHg
Figure 11. TEE showing left atrial and left ventricular enlargement due to long-term volume overload in an adult with PDA. TEE = transesophageal echocardiography; PDA = patent ductus arteriosus.
Kronzon et al. reported direct calculation of the shunt volume using proximal isovelocity surface area (PISA). Good visualization of the PDA ﬂow acceleration in adults often requires a TEE 9
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but the diameter of the PDA is difﬁcult to measure in most adults. PISA allows direct calculation of the shunt volume in PDA.39 Continuous-wave Doppler is used to demonstrate the maximal velocity (Vm) from the continuous jet of PDA. Flow acceleration can be clearly demonstrated on the aortic side. The radius (R) is the largest PISA hemispheric radius. The effective defect area (EDA) is calculated by the following equation: Flow rate Velocity ¼ 2pR2 the aliasing velocity ðVaÞ maximal velocity ðVmÞ The left-to-right shunt volume can then be is calculated as follows: EDA VTI ðvelocity time integral of the shunt flowÞ Left-to-right shunt volume/minute ¼ Volume heart rate ¼ ð2pR2 Va VmÞ VTI heart rate Accuracy of the PISA method may be affected by the assumptions made in the calculation, such as the oriﬁce is round, PISA is a true hemisphere, and the oriﬁce size is constant. Over the years, ﬂuoroscopic guidance has been the main imaging method in the cardiac catheterization laboratory for device closure of the PDA. TEE has played a limited role in guiding device closure of PDA due to difﬁculty in completely imaging the anatomic details of the ductus, but it has signiﬁcantly cut back the ﬂuoroscopic time. The ﬁrst step is to identify the ductus at an angle of 135° on 2DTEE. In this view, the ductus may be visualized between the aorta and the left pulmonary artery. After obtaining transgastric views, the probe should be slowly rotated in the clockwise direction to identify the descending thoracic aorta while gently pulling back. Approximately, at a distance of around 25 cm from the incisors, color Doppler may detect continuous high velocity mosaic ﬂow in the ductus connecting the thoracic aorta and the pulmonary artery.38 Flow gradient across PDA is acquired by continuous-wave Doppler PDA ﬂow in the parasternal short-axis view. The lowest velocity obtained from the continuous-ﬂow Doppler tracings taken as the end-diastolic gradient can help in the selection of coils for percutaneous ductal occlusion. According to a study by Chaurasia et al., the end-diastolic gradient correlates inversely with total surface area of the coils, which then indirectly predicts the size and number of coils.40 The PDA with a lower end-diastolic gradient (less than 38 mmHg) may require the use of multiple 10
or larger coils.40 Diastolic ﬂow reversal in the descending thoracic aorta may predict failure of PDA closure by coils. Therefore, correlating the diastolic ﬂow reversal in the descending thoracic aorta with the diastolic trough gradient may indicate the likelihood of success with the procedure.41 Three-Dimensional Echocardiography: Real Time (Live) 3DTTE: Color Doppler with 3DTTE can be helpful in differentiating vascular structures from artifacts and echo dropouts. A comprehensive assessment of the PDA ﬂow jet is possible by acquiring 3D color Doppler ﬂow signals from the PDA, main pulmonary artery and the descending thoracic aorta followed by rotation to view the ﬂow signals from all sides at any desired angulation. These isolated color Doppler images could be rotated from 0° to 180° enabling comprehensive visualization of ﬂows in pulmonary arteries, PDA, and the descending aorta in three dimensions. Color Doppler 3DTTE can also demonstrate ﬂow signals moving from the pulmonary artery into the descending thoracic aorta in systole and back into the pulmonary artery in diastole.42–44 Real Time (Live) 3DTEE: Marek et al. document the usefulness of real time 3DTEE (RT 3DTEE) in 3D imaging of the PDA, before and after Amplatzer device closure. A major limitation is that the cranial part of the aortic arch is invisible because of the near ﬁeld.42 RT 3DTEE using matrix phased-array transducer is useful in obtaining unique views of complex residual PDAs for complete morphological and quantitative assessment of residual PDAs with complex anatomy. Live 3DTEE has a major role in the perioperative monitoring of a transcatheter procedure since it cuts down the ﬂuoroscopy time. It allows delineation of the anatomical details or its variations, conﬁrms the position of the device after closure and rules out any residual shunts.44 Contrast Echocardiography: Peripheral intravenous contrast echocardiography has been used to noninvasively identify an otherwise undetectable PDA that manifests as central right-to-left shunt at the ductal level in cyanotic patients with Eisenmenger’s physiology. When there is cyanosis or signiﬁcant pulmonary hypertension and a right-to-left shunt is suspected, the abdominal aorta should be viewed in a subcostal view after injecting agitated saline. “Bubbles” can be seen opacifying the right heart and then appearing in the descending thoracic/ abdominal aorta.45–47
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Intra-Operative Transesophageal Echocardiogram: Intra-operative TEE is helpful in assessment of concomitant defects preoperatively and then conﬁrming complete closure of the PDA after surgical ligation/operation. Color Doppler is used to rule out any residual shunts.48 This is very important in those with ductal calciﬁcation or aneurysm that may have a tear during the surgery. Sometimes during surgery for mitral valve repair, an intra-operative TEE may diagnose the presence of a PDA. The question arises whether the PDA signiﬁcantly contributed to left heart enlargement and mitral annular dilation leading to increasing severity of mitral regurgitation (especially when the mitral valve morphology is normal). In addition, in an older population, the contribution of ischemic posterior papillary muscle to the severity of mitral regurgitation should also be considered.49
size citing the small cumulative lifetime risk of endarteritis. In contrast, although a small PDA may or may not have an audible classic murmur in an adult with large body habitus, there may be a signiﬁcant shunt with or without cardiac enlargement demonstrated by echocardiography or another imaging modality. These adults may have nonspeciﬁc symptoms that resolve after PDA closure, even though there is no perceptible change in the echocardiographically assessed of cardiac size and function. One possible explanation is that some of these “small PDAs” may be more “dynamic” in nature allowing more exerciseinduced shunting to cause stretching/dilation of the ductal communication, than witnessed on a resting echocardiogram. Over the past 15 years, intervention has been acceptable in such cases in the absence of audible murmurs or left heart volume overload.
PDA Closure with Catheter-Based Interventions: Indications for Intervention: The indications for PDA closure are to reduce the risk of developing pulmonary hypertension due to pulmonary overcirculation, as well as to reduce the risk of endocarditis.14 The absolute contraindications for device closure in adults are irreversible pulmonary vascular disease/severe pulmonary hypertension or active endocarditis. In infancy, PDA closure is also not performed in ductal dependant congenital cardiac anomalies.50 In contrast to the pediatric population where interventional criteria are more widely established and accepted, the criteria in adult patients are somewhat more difﬁcult and tend to have regional and subregional preferences. In general, most practitioners agree that moderate to large PDAs with signiﬁcant shunt should be closed especially in the absence of irreversible pulmonary hypertension. Most of the controversy exists when talking about trivial or small PDAs with no echocardiographic evidence of volume overload or any particular symptoms.31,32 Since 2003, our strategy for PDA closure has changed due to the availability of the Amplatzer occluder device that allowed catheter-based closure of larger PDAs which previously required surgery. In our practice, we do not recommend intervention for trivial PDAs (those termed “silent” due to absence of an audible murmur) unless the patient speciﬁcally requests an intervention. We believe that the risks of having a trivial native PDA are sufﬁciently low compared with the higher risks associated with an interventional device closure. In some centers, interventional cardiologists will close any PDA regardless of the
Procedure: Over the past 30 years, the efﬁcacy and safety of transcatheter device closure of PDA in adults has been established. Improved cardiac catheterization techniques, imaging equipment and the development of newer devices using space-age metal alloy have positively impacted the management of PDAs. There has been a dramatic evolution from surgery to a catheter-based approach for the majority. Transcatheter occlusion is the treatment of choice for most children and adults with PDA because it has many advantages over the surgical closure. Currently in the United States, PDAs can be closed using singular devices or combinations of devices. These include but are not limited to the following: Gianturco coils (both detachable and free), Amplatzer vascular plugs, Amplatzer muscular VSD device, Amplatzer PDA occluder, and the Amplatzer septal occluder. Other than the Amplatzer PDA occluder, the remaining Amplatzer devices are not FDA approved for PDA closure and their use is “off label.” In Europe, Asia, and the South America, there are a whole host of devices available including those made by the PFM Corporation.51–55 There is no singular technique or device that can be used to close all PDA’s successfully and therefore an interventionalist should have knowledge and familiarity of multiple devices and delivery methods. Presently, the procedural success approaches almost 100% in very experienced hands. The catheter-based technique involves advancement of a catheter or delivery sheath across the ductus arteriosus from either a prograde or anterograde approach followed by securely positioning an embolization device in the ductus to occlude it. Patients are usually 11
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Figures 13. A. and B. Cardiac catheterization (lateral projections) demonstrating measurements of a typical Type A patent ductus arteriosus (PDA) in an adult between the aorta and the pulmonary artery (PA).
under general anesthesia to minimize discomfort, mitigate possible movement or hemodynamic instability during device deployment. After achieving full anticoagulation, a complete hemodynamic assessment including shunt calculation, pressure measurements and calculation of the pulmonary vascular resistance are made. This is followed by biplane angiography of the juxtaductal aorta in the right anterior oblique (RAO) and lateral projections. Once measurements of the type, caliber, and location of the PDA are obtained, allowances for distensibility of the PDA are made (Fig. 13A and B). Accordingly, a suitable device is selected and delivered via proA
grade or antegrade approach. A period of about 10 minutes is then allowed before repeat angiography is performed to assess device position or any residual shunts (Fig. 14). There may be a need for extra manipulation or additional secondary devices. The risks associated with device closure include bleeding, infection, device embolization/ migration, aortic arch obstruction, stroke, vascular compromise, and residual shunts. Device closure has several advantages over surgical closure by eliminating the need for prolonged general anesthesia, surgical incisions, postoperative pain, long convalescence, lifelong scarring, and has a B
Figures 14. A. Aortic arch angiogram (lateral view) demonstrating the position of the aortic disc of the Amplatzer duct occluder (ADO) (arrow) in the PDA. B. Similar cine frame is obtained after opening the pulmonary end of the ADO. A small residual shunt is noted through the device but none parallel to it, indicating that device was sized appropriately for the ductal dimensions. Both images illustrate good positioning of the device. Catheter with markers is seen in both A and B. DAo = descending aorta; PDA = patent ductus arteriosus. Courtesy: Citation – Yarrabolu TR, Syamasundar Rao P: Transcatheter closure of patent ductus arteriosus. Pediat Therapeut 2012;S5:005. doi:10.4172/2161-0665.S5-005. Figure 7. Copyright – © Yarrabolu et al. (2012): This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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impaired ventricular function, and renal disease may contribute to the surgical risk. Catheterbased interventions or modiﬁed surgical approach may be tailored to reduce risks when the beneﬁts of closure outweigh the risks.59–61
Figure 15. CTA in an elderly woman, demonstrating a calciﬁed PDA. CTA = computed tomographic angiography; PDA = patent ductus arteriosus.
very low mortality risk. Even when the immediate success rate is lower with catheter-based device implantations as compared with surgical closures, the reinterventions for residual clinical shunts have been very effective at sealing residual leaks. Surgical Closure: The classic surgical approach usually involves cardiopulmonary bypass with an anterior approach through a median sternotomy. Minimally invasive thoracoscopic techniques have also been successfully used.56 In the presence of ductal calciﬁcation, signiﬁcant pleural scarring, or in “window-like” arterial ducts, video-assisted ligation is not an option and open surgical techniques are indicated. When video-assisted ligation is possible, the approach is based on the patient’s and surgeon’s preference. When an open thoracotomy is selected, a muscle-sparing left posterolateral incision is preferred.57 The main indications favoring surgical closure in adults with PDA are calciﬁcation of the ductus, short/wide ductus, aneurysms, or in the presence of concomitant defects requiring surgery.58 PDA Closure in the Elderly: Even in symptomatic elderly patients PDA closure can be controversial due to the risks involved due to technical difﬁculties, ductal calciﬁcation/friability (Fig. 15), ductal aneurysm, atherosclerotic changes, increased bleeding, and embolic complications. Comorbidities such as coronary artery disease, pulmonary vascular disease, signiﬁcantly
Role of Echocardiography in Post Closure Long-Term Follow-Up: TTE and color Doppler are used in long-term follow-up after device closure or surgery. The goals are to ensure (1) Proper device placement: A well-seated device can be visualized between the pulmonary artery bifurcation and the inferior margin of the aorta. It should not be protrude into the pulmonary artery or into the aortic lumen, and (2) Rule out residual shunts: Previously, it was more common to see residual shunt following certain device closures such as the “umbrella device.” Fortunately, endothelialization resolves most of the small residual shunts over time. Conclusions: Echocardiography is the backbone of imaging in adults with congenital heart disease. It plays a major role in diagnosis, management and followup of unoperated and operated PDA in adults.
Acknowledgments: Many thanks to Dr. Indubala Vardhan, our sonographers (Paul Junkel, Terri McAnallen, Albert Amoranto, and Janae Johnson) at the Echocardiography Laboratory, Kaiser Permanente Medical Center, Panorama City, California and the Cardiac Catheterization Laboratory team, Los Angeles Medical Center, for their clinical contributions and support; Mr. Robert Reber for his expertise as an audiovisual engineer; Ms. Hovey Lee and Ms. Winnie Wong at the Medical Library for fulﬁlling our literature searches.
References 1. Perloff JK, Marelli AH: Perloff’s Clinical Recognition of Congenital Heart Disease. 6th ed. Philadelphia, PA: WB Saunders, 2012. 2. McManus BM: Patent ductus arteriosus. In Roberts WC (ed): Adult Congenital Heart Disease. Philadelphia: FA Davis, 1987, pp. 455–476. 3. Fransson SG: The Botallo mystery (proﬁles in cardiology). Clin Cardiol 1999;22:434–436. 4. Perloff JK: Surgical treatment of patent ductus arteriosus: A new historical perspective. Am J Cardiol 2004;94:1153– 1154. 5. Gross RE, Hubbard JP: Surgical ligation of a patent ductus arteriosus. JAMA 1939;112:729–731. 6. Taussig H, Blalock A: Surgery of congenital heart disease. Br Med J 1947;2:462. 7. Porstmann W, Wierny L, Warnke H: Closure of persistent ductus arteriosus without thoracotomy. Ger Med Mon 1967;12:259–261. 8. Wierny L, Plass R, Porstmann W: Transluminal closure of patent ductus arteriosus: Long-term results of 208 cases treated without thoracotomy. Cardiovasc Intervent Radiol 1986;9:279–285. 9. Rashkind WJ, Muilins CE, Hellenbrand WE, et al: Nonsurgical closure of patent ductus arteriosus: Clinical applica-
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14. 15. 16. 17. 18.
21. 22. 23.
26. 27. 28.
tion of the Rashkind PDA Occluder System. Circulation 1987;75:583–592. Cambier PA, Kirby WC, Wortham DC, et al: Percutaneous closure of the small (less than 2.5 mm) patent ductus arteriosus using coil embolization. Am J Cardiol 1992;69:815–816. Pass RH, Hijazi Z, Hsu DT, et al: Multicenter USA Amplatzer patent ductus arteriosus occlusion device trial: Initial and one-year results. J Am Coll Cardiol 2004;44:513–519. Laborde F, Noirhomme P, Karam J, et al: A new videoassisted thoracoscopic surgical technique for interruption of patent ductus arteriosus in infants and children. J Thorac Cardiovasc Surg 1993;105:278–280. Laborde F, Folliquet T, Batisse A, et al: Video-assisted thoracoscopic surgical interruption: The technique of choice for patent ductus arteriosus. Routine experience in 230 pediatric cases. J Thorac Cardiovasc Surg 1995;110:1681– 1684. Campbell M: Natural history of persistent ductus arteriosus. Br Heart J 1968;30:4–13. Alzamora-Castro V, Battilana G, Abugattas R, et al: Patent ductus arteriosus and high altitude. Am J Cardiol 1960;5:761–763. Miao CY, Zuberbuhler JS, Zuberbuhler JR: Prevalence of congenital cardiac anomalies at high altitude. J Am Coll Cardiol 1988;12:224–228. Hanine H, Dagle JM: Genetics of patent ductus arteriosus susceptibility and treatment. Semin Perinatol 2012;36:98–104. Krichenko A, Lee B, Burrows P, et al: Angiographic classiﬁcation of the isolated, persistently PDA and implications for percutaneous catheter occlusion. Am J Cardiol 1989;63:877–880. Schneider DJ: The patent ductus arteriosus in term infants, children, and adults. Semin Perinatol 2012;36:146–153. Takenaka K, Sakamoto T, Shiota T, et al: Diagnosis of patent ductus arteriosus in adults by biplane transesophageal color Doppler ﬂow mapping. Am J Cardiol 1991;68:691–693. Vargas-Barron J, Attie F, Buendia HA, et al: Echocardiographic recognition of pulmonary artery endarteritis in patent ductus arteriosus. Am Heart J 1985;109:368–370. Wood P: The Eisenmenger syndrome or pulmonary hypertension with reversed central shunt. Br Med J 1958;2:755–762. Lund JT, Jensen MB, Hjelms E: Aneurysm of the ductus arteriosus. A review of the literature and the surgical implications [Review]. Eur J Cardiothorac Surg 1991;5:566–570. Vargas-Barron J, Sanches-Ugarte T, Keirns C, et al: Calciﬁcation of patent ductus arteriosus detected by twodimensional echocardiography. Am Heart J 1987;114:446–448. Niwa K, Perloff JK, Bhuta SM, et al: Structural abnormalities of great arterial walls in congenital heart disease: Light and electron microscopic analyses. Circulation 2001;103:393–400. Strozzi M, Sutlic Z, Drinkovic N, et al: The patent ductus arteriosus as a source of recurrent peripheral embolisations. Acta Med Croatica 1993;47:101–102. Zhao Y, Li Z, Henein MY: PDA with Eisenmenger complicated by pulmonary artery dissection. Eur J Echocardiogr 2010;11:E32. Sardesai SH, Marshall RJ, Farrow R, et al: Dissecting aneurysm of the pulmonary artery in a case of unoperated patent ductus arteriosus. Eur Heart J 1990;11:670– 673. Coard KC, Martin MP: Ruptured saccular pulmonary artery aneurysm associated with persistent ductus arteriosus. Arch Pathol Lab Med 1992;116:159–161.
30. Actis Dato G, Cavaglia M, Aidala E, et al: Patent ductus arteriosus. Follow-up of 677 operated cases 40 years later. Minerva Cardioangiol 1999;47:245–254. 31. Warnes CA, Williams RG, Bashore TM, et al: ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2008;52:e143–e263 or in Circulation. 2008;118:2395–2451. 32. Houston AB, Gnanapragasam JP, Lim MK, et al: Doppler ultrasound and the silent ductus arteriosus. Br Heart J 1991;65:97–99. 33. Gutgesell HP, Huhta JC, Latson LA, et al: Accuracy of two-dimensional echocardiography in the diagnosis of congenital heart disease. Am J Cardiol 1985;55:514– 518. 34. Perez JE, Nordlicht SM, Geltman EM: Patent ductus arteriosus in adults: Diagnosis by suprasternal and parasternal pulsed Doppler echocardiography. Am J Cardiol 1984;53:1473–1475. 35. Waggoner AD, Barzilai B, Perez JE: Saline contrast enhancement of tricuspid regurgitant jets detected by Doppler color ﬂow imaging. Am J Cardiol 1990;65:1368– 1371. 36. Shyu KG, Lai LP, Lin SC, et al: Diagnostic accuracy of transesophageal echocardiography for detecting patent ductus arteriosus in adolescents and adults. Chest 1995;108:1201–1205. 37. Driscoll DJ: Left-to-right shunt lesions. Pediatr Clin North Am 1999;46:355–368. 38. Chang ST, Hung KC, Hsieh IC, et al: Evaluation of shunt ﬂow by multiplane transesophageal echocardiography in adult patients with isolated patent ductus arteriosus. J Am Soc Echocardiogr 2002;15:1367–1373. 39. Kronzon I, Tunick PA, Rosenzweig BP: Quantiﬁcation of left-to-right shunt in patent ductus arteriosus with the PISA method. J Am Soc Echocardiogr 2002;15:376– 378. 40. Chaurasia AK, Harikrishnan S, Bijulal S, et al: Usefulness of Doppler derived end diastolic ﬂow gradient across the patent ductus arteriosus in selecting coils for ductal occlusion. Pediatr Cardiol 2012;33:290–294. 41. Torres AJ, Srivastava S, Parness IA, et al: Echocardiographic predictors of failure in patients undergoing coil occlusion of patent ductus arteriosus. J Am Soc Echocardiogr 2003;16:1063–1067. 42. Marek T, Zelizko M, Kautzner J: Ductus arteriosus before and after transcatheter closure real-time 3-dimensional transesophageal echocardiography imaging: Adult patent ductus arteriosus before and after transcatheter closure. Circulation 2009;120:e92–e93. 43. Sinha A, Nanda NC, Khanna D, et al: Live three-dimensional transthoracic echocardiographic delineation of patent ductus arteriosus. Echocardiography 2004;21:443– 448. 44. Chuang YC, Yin WH, Hsiung MC, et al: Successful transcatheter closure of a residual patent ductus arteriosus with complex anatomy after surgical ligation using an Amplatzer ductal occluder guided by live three-dimensional transesophageal echocardiography. Echocardiography 2011;28:E101–E103. 45. Dick C, Asinger RW: Contrast echocardiographic detection of a right-to-left shunting patent ductus arteriosus. J Am Soc Echocardiogr 1989;2:198–201. 46. Panetta C, Schiller N: Evidence of patent ductus arteriosus and right-to-left shunt by ﬁnger pulse oximetry and Doppler signals of agitated saline in abdominal aorta. J Am Soc Echocardiogr 1999;12:763–765. 47. Sohn DW, Kim YJ, Zo JH, et al: The value of contrast echocardiography in the diagnosis of patent ductus arteriosus with Eisenmenger’s syndrome. J Am Soc Echocardiogr 2001;14:57–59.
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48. Ho AC, Tan PP, Yang MW, et al: The use of multiplane transesophageal echocardiography to evaluate residual patent ductus arteriosus during video-assisted thoracoscopy in adults. Surg Endosc 1999;13:975–979. 49. Wang KY, Hsieh KS, Yang MW, et al: The use of transesophageal echocardiography to evaluate the effectiveness of patent ductus arteriosus ligation. Echocardiography 1993;10:53–57. 50. Rao PS: Consensus on timing of intervention for common congenital heart diseases: Part I – Acyanotic heart defects. Indian J Pediatr 2013;80:32–38. 51. Giroud JM, Jacobs JP: Evolution of strategies for management of the patent arterial duct. Cardiol Young 2007;17 (Suppl 1):68–74. 52. Beyer RW, Bier AJ: Ultrasonic guidance for percutaneous closure of patent ductus arteriosus in an adult. J Invasive Cardiol 2009;122:1123–1127. 53. Ali Khan MA, al Yousef S, Mullins CE, et al: Experience with 205 procedures of transcatheter closure of ductus arteriosus in 182 patients, with special reference to residual shunts and long-term follow-up. J Thorac Cardiovasc Surg. 1992;104:1721–1727. 54. Rao PS, Kim SH, Rey C, et al: Results of transvenous buttoned device occlusion of patent ductus arteriosus in adults. International Buttoned Device Trial Group. Am J Cardiol 1998;82:827–829, A10.
55. Donti A, Formigari R, Bonvicini M, et al: Transcatheter closure of the patent ductus arteriosus with new-generation devices: Comparative data and follow-up results. Ital Heart J 2002;3:122–127. 56. Nezafati MH, Soltani G, Mottaghi H, et al: Videoassisted thoracoscopic patent ductus arteriosus closure in 2,000 patients. Asian Cardiovasc Thorac Ann 2011;19:393–398. 57. Therrien J, Connelly MS, Webb GD: Patent ductus arteriosus. Curr Treat Options Cardiovasc Med 1999;4:341– 346. 58. Jatene MB, Abuchaim DC, Tiveron MG, et al: Surgical treatment of patent ductus arteriosus in adults. Rev Bras Cir Cardiovasc 2011;26:93–97. 59. Ananthasubramaniam K: Patent ductus arteriosus in elderly patients: Clinical and echocardiographic features – A case-based review. J Am Soc Echocardiogr 2001;14:321–324. 60. Woodruff WW III, Gabliani G, Grant AO: Patent ductus arteriosus in the elderly. South Med J 1983;76:1436– 1437. 61. Lamba M, Beauchesne LM, Veinot JP: Pulmonary hypertension and patent ductus arteriosus in an 82-year-old female patient. Cardiovasc Pathol 2006;15:352–353.