Patent Ductus Arteriosus

By | 2011-12-20

The circulation in the fetus differs from that in the adult. In fetal animals the ductus arteriosus develops from the left sixth embryonic arch and extends from the pulmonary artery to the descending aorta, where it diverts blood from the nonfunctional fetal lungs back into the systemic circulation. Prior to birth, the ductus diverts approximately 80% to 90% of the right ventricular output back to the left side of the circulation. After parturition and the onset of breathing, pulmonary vascular resistance falls, flow in the ductus reverses, and the resulting rise in arterial oxygen tension inhibits local prostaglandin release, causing constriction of the vascular smooth muscle in the vessel wall and functional closure of the ductus arteriosus. Although the ductus may be probe patent in puppies less than 4 days of age, it usually is closed securely 7 to 10 days after birth. Persistence of a patent ductus arteriosus beyond the early neonatal period is the first or second most commonly diagnosed congenital cardiac defect in dogs. Cats are also affected but much less commonly than dogs.

Pathogenesis Failed ductal closure in dogs is characterized by distinct histologic abnormalities in the ductal wall. The normal fetal ductal wall contains a loose, branching pattern of circumferential smooth muscle throughout its length. In prenatal puppies bred to have a high probability of patent ductus arteriosus (PDA), varying portions of the ductal wall are comprised of elastic fibers rather than contractile smooth muscle fibers. According to the work of Patterson et al., increasing genetic liability to patent ductus arteriosus results in “extension of the noncontractile wall structure of the aorta to an increasing segment of the ductus arteriosus, progressively impairing its capacity to undergo physiologic closure. ” It is tempting to speculate that some defect prevents one or more of the series of processes that permits smooth muscle cells to proliferate in the wall of the ductus prior to birth. In the defect’s mildest form, the ductus closes at the pulmonary arterial end only and a blind, funnel-shaped outpouching of the ventral aspect of the aorta, called a ductus diverticulum, results. This hidden form (forme fruste) of incomplete ductal closure can be diagnosed only by angiography or necropsy, but it indicates that the dog possesses genes for this defect. Increasing genetic liability results in a tapering, funnel-shaped ductus arteriosus that remains patent after the early natal period and that allows blood to flow from the high-pressure aorta to the low-pressure pulmonary artery, thereby creating varying amounts of left-to-right shunting. The most severe but least common form is the cylindrical, nontapering ductus with persistent, postnatal pulmonary hypertension (Eisenmenger’s syndrome) and bidirectional or right-to-left shunting Based on the breeding studies of poodle-type dogs, Patterson et al. concluded that the mode of transmission of patent ductus arteriosus in dogs is most likely polygenic, but other mechanisms of inheritance are possible For additional information on the morphology and pathogenesis of patent ductus arteriosus (PDA), the reader is referred to several outstanding reviews of the subject.

Pathophysiology The direction of flow through the patent ductus arteriosus is determined by the relative resistances of the pulmonary and systemic vascular beds; in the vast majority of cases, it is directed from left to right (from the aorta to pulmonary artery). This results in a continuous cardiac murmur, increased pulmonary blood flow, and volume overloading of the left atrium and left ventricle Because of the relatively high resistance of the systemic circulation after birth, aortic blood pressure is greater than pulmonary pressure, and blood shunts continuously across the patent ductus arteriosus during both systole and diastole For a given pressure gradient, the magnitude of shunting is determined by the morphology (effective resistance) of the ductus arteriosus. In most cases the ductus is widest at the aortic end and tapers to its narrowest (flow limiting) region at the point of attachment to the pulmonary artery. Increased left ventricular stroke volume and rapid runoff of blood from the aorta to the low pressure pulmonary circulation via the patent ductus arteriosus causes increased aortic systolic and decreased aortic diastolic pressures. The resulting widened arterial pulse pressure offers a hemodynamic explanation for the bounding or hyperkinetic (waterhammer, Corrigan’s) arterial pulse detected in dogs with substantial shunts.

All vascular structures involved in the transport of the shunted blood enlarge to accommodate the extra volume flow. Increased volume flow causes dilatation of the proximal aorta and main pulmonary artery and overcirculation of the pulmonary vascular bed. Dilatation of the left atrium and eccentric hypertrophy of the left ventricle develop in proportion to the volume flow of the shunt This mechanism permits compensation for a variable period, but if the shunt is large, myocardial failure (cardiomyopathy of volume overload) develops, together with progressive elevation of left ventricular end-diastolic pressure and overt pulmonary edema. Because the left-to-right shunt occurs at the level of the great vessels, the right ventricle and atrium never handle- the shunted blood, and these structures remain normal unless pulmonary vascular resistance and pulmonary arterial pressure Increase.

In a small percentage of cases, the- lumen of the patent ductus arteriosus remains wide open after birth. The absence of a restrictive ductal orifice allows aortic pressure- to be transmitted to the pulmonary circulation, precluding the normal postnatal decline in pulmonary vascular resistance. In this circumstance the aortic and pulmonary artery pressures equilibrate, and the right ventricle remains concentrically hypertrophied after birth. In Patterson’s colony of dogs, this pattern of pulmonary hypertension and reversed (right-to-left) shunting developed within the first few weeks of life. These observations fit the usual clinical presentation of most dogs diagnosed with a reversed patent ductus arteriosus (PDA), in which the animal usually has no history of a continuous murmur and no evidence of left ventricular enlargement or a large left-to-right shunt earlier in life. Most dogs with reversed patent ductus arteriosus flow have diminished pulmonary blood flow, a normal to small left ventricle, and marked concentric hypertrophy of the right ventricle. On rare occasions, dogs with a moderate to large left-to-right shunting patent ductus arteriosus experience a gradual increase in pulmonary resistance and gradual reversal of the direction of shunting, typically at several months to several years of age. These dogs often have a history of prior left heart failure. Substantial residual left ventricular (LV) enlargement is evident on thoracic radiographs and by echocardiography. Pulmonary blood flow is reduced, but right ventricular hypertrophy is less pronounced than in dogs in which the direction of shunting is reversed at an early age. The precise pathogenesis of pulmonary hypertension is not completely understood, but anatomic descriptions of the pulmonary vasculature are similar in humans and animals. Histologic changes within small pulmonary arteries include hypertrophy of the media, thickening of the intima and reduction of lumen dimensions, and development of plexiform lesions of the vessel wall. Mast of these changes are considered to be irreversible, precluding surgical correction of the reversed PDA.

Clinical findings The clinical features of patent ductus arteriosus have been thoroughly characterized in both a breeding colony and in clinic populations. Compared with male dogs, female dogs have a substantially greater risk of developing a patent ductus arteriosus (2.49 per 1000 versus 1.45 per 1000).The Chihuahua, collie, Maltese, poodle, Pomeranian, English springer spaniel, keeshond, bichon frise, and Shedand sheepdog are most frequendy affected, although other breeds, such as the Cavalier King Charles spaniel, may also be predisposed. Many other breeds, including larger dogs, such as the German shepherd, Newfoundland, and Labrador retriever, may also be prone to patent ductus arteriosus in some regions. Although severely affected pups and kittens may appear stunted, thin, or tachypneic from left heart failure, most are reported to be asymptomatic and developing normally at the time the condition is discovered. Clinical signs are rarely recognized within the first few weeks of life, and most dogs are not diagnosed until the initial examination at 6 to 8 weeks of age.

Left-to-right shunting patent ductus arteriosus A thorough physical examination and chest radiographs usually suffice to suggest the diagnosis. Mucous membranes are pink in the absence of heart failure. The precordial impulse is often exaggerated and more diffuse than normal as a result of left ventricular enlargement. A thrill may be palpated at the heart base, and a continuous murmur is best heard in the same location. The murmur’s point of maximum intensity is located over the main pulmonary artery at the dorsocranial left heart base and may radiate cranially to the thoracic inlet and to the right base, where it is almost always softer. Often only a systolic murmur is audible over the mitral area. This murmur may simply represent radiation of the loudest portion of the continuous murmur from die heart base to this location, or it may indicate that secondary mitral regurgitation has developed as a consequence of severe left ventricular dilatation. In cats, the continuous murmur of a patent ductus arteriosus may be heard best somewhat more caudoventrally than in affected dogs. Increased LV stroke volume and rapid diastolic runoff through the patent ductus arteriosus combine to produce peripheral arterial pulses that are hyperkinetic (bounding).

Electrocardiography typically indicates left ventricular enlargement (increased R-wave voltages in leads II, III, and aVF and in the left chest leads, V2 and V4) and normal mean electrical axis. Widened P waves may also be found, indicating left atrial enlargement. Chest radiographs indicate left atrial and left ventricular enlargement and pulmonary hypervas-cularity in proportion to the magnitude of the left-to-right shunt. On the dorsoventral (DV) projection, die aortic arch, left auricle, and main pulmonary artery may be abnormally prominent. The most specific radiographic finding is the appearance of an aortic bulge (“ductus bump”) near the origin of the ductus, which is caused by abrupt narrowing of the descending aorta just caudal to the origin of the ductus. Moderate to severe LV enlargement sometimes causes the cardiac apex to shift to the right (common in cats).

The diagnosis of a patent ductus arteriosus can be confirmed by echocardiography in almost all cases. Two-dimensional and M-mode echocardiography demonstrate eccentric LV hypertrophy and dilatation of the left atrium, ascending aorta, and pulmonary artery. Reduced myocardial contractility is often observed and is reflected by reduced fractional shortening and/or increased LV end-systolic dimension and e-point to septal separation (EPSS) measurements. The ductus usually can be imaged from the left cranial parasternal window. Doppler interrogation of the pulmonary artery consistently demonstrates high-velocity continuous ductal flow directed toward the pulmonic valve. In the typical case, the peak velocity of this jet is about 4.5 to 5 m/s and occurs at end-systole. Other common echocardiographic findings include a mildly increased LV outflow velocity (1.8 to 2.3 m/s) and modest secondary mitral and pulmonary valve insufficiency. In dogs with patent ductus arteriosus (PDA), associated cardiac defects are uncommon; nonetheless, a careful echocardiographic examination is worthwhile to exclude the concurrent presence of other common congenital defects, such as subaortic stenosis. Cardiac catheterization and angiocardiography are usually not needed to confirm a diagnosis of patent ductus arteriosus and are not advised unless the Doppler echocardiographic evaluation is ambiguous or additional congenital malformations are suspected.

Patent ductus arteriosus with pulmonary hypertension (right-to-left shunting PDA) High pulmonary vascular resistance tbat causes right-to-left shunting through a patent ductus arteriosus defines the clinical syndrome commonly referred to as a reversed PDA. Right-to-left shunting is observed in a very small minority of dogs with a patent ductus arteriosus (PDA), but the prevalence of this phenomenon is probably underestimated and may be greater in dogs living at altitudes higher than 5000 feet above sea level. Obvious clinical signs are usually evident during the first year of life, but many owners do not recognize clinical signs in their pet during the first 6 to 12 months of life, and some animals are not diagnosed until 3 to 4 years of age or later. Reported signs include exertional fatigue, hindlimb weakness, shortness of breath, hyperpnea, differential cyanosis and, more rarely, seizures.

The clinical examination findings are very different from those in the more common left-to-right PDA. Right-to-left flow through a widely patent ductus arteriosus exhibits little turbulence, and the physical examination reveals either no murmur or only a soft, systolic murmur at the left base. The most common auscultatory finding is an accentuated and split second heart sound. Differential cyanosis (cyanosis of the caudal mucous membranes with pink cranial membranes) may be observed, but recognition may require examination after exercise. Differential cyanosis is caused by the location of the patent ductus arteriosus (PDA), which shunts right to left from the pulmonary artery into the descending aorta but spares the proximal branches of the aorta, which provide normal oxygen delivery to the cranial portion of the body. Perfusion of the kidneys with hypoxemic blood triggers elaboration of erythropoietin and secondary polycythemia and hyperviscosity as the packed cell volume (PCV) gradually increases to 65% or greater. Polycythemia may occur during the first year of life, but it often does not become severe until 18 to 24 months of age.

The electrocardiogram of dogs with a reversed patent ductus arteriosus almost always reveals evidence of right ventricular hypertrophy (i.e., right axis deviation and increased S-wave amplitude in leads 1, II, and III and in the left precordial chest leads V2, and V4). Thoracic radiographs indicate right heart enlargement, dilatation of the main pulmonary artery, a visible ductus bump, and variable appearance of the lobar and peripheral arteries. Echocardiography demonstrates right ventricular concentric hypertrophy and a dilated main pulmonary artery. In some cases a wide, cylindrical ductus may be imaged. Pulmonary hypertension can be verified in some cases by Doppler interrogation of tricuspid or pulmonic insufficiency jets. Contrast echocardiography, nuclear scintigraphy, oximetry, or angiography can be used to demonstrate the presence of right-to-left shunting should Doppler interrogation prove inadequate. Contrast echocardiography is performed by injecting air-agitated saline into a cephalic or saphenous vein, thereby opacifying the right heart, pulmonary artery, and descending aorta (best observed by imaging of the abdominal aorta dorsal to the bladder). Cardiac catheterization can demonstrate pulmonary artery hypertension with equilibration of right and left ventricular and aortic systolic pressures. Oximetry verifies decreased oxygen saturation distal to the entrance of the patent ductus arteriosus in the descending aorta. Right ventricular angiography demonstrates right ventricular hypertrophy and usually oudines a wide patent ductus arteriosus that appears to continue distally as the descending aorta. The lobar pulmonary arteries may appear normal, especially during the first year of life, or may show increased tortuosity. Aortic or left ventricular contrast injections permit visualization of an often extensive bronchoesophageal collateral circulation.

Natural history of patent ductus arteriosus Eyster reported that approximately 64% of dogs diagnosed with a left-to-right shunting patent ductus arteriosus die of complications within 1 year of diagnosis if the condition is not surgically corrected. Complications include left heart failure with pulmonary edema, atrial fibrillation, pulmonary hypertension secondary to left heart failure, and mitral regurgitation secondary to left ventricular dilatation. Dogs and cats with patent ductus arteriosus and more modest shunts often survive to maturity, and some live beyond 10 years of age. In humans with an unconnected patent ductus arteriosus (PDA), the gradual development of pulmonary hypertension and shunt reversal is a significant risk, but this gradual transition to right-to-left shunting is uncommon in dogs. When persistent pulmonary hypertension in the neonate leads to reversed shunting, clinical signs result from hypoxemia, polycythemia, hyperviscosity, and cardiac arrhythmias. Congestive heart failure almost never develops, but sudden death and complications from hyperviscosity are common. Animals with reversed patent ductus arteriosus often live 3 to 5 years, and some survive beyond 7 years if the PCV is kept below 65%.

Clinical management Surgical correction is recommended in virtually all young dogs and cats with a left-to-right shunting PDA. Correction may not be warranted in older pets if the shunt volume is small and cardiomegaly is minimal or absent. Consultation with a specialist may be helpful in borderline circumstances. Recommended preoperative studies include ECG and chest radiographs to help assess the severity of the shunt and to determine whether congestive heart failure is present. An echocardiogram should always be performed to verify the diagnosis and to rule out additional defects. The timing of surgery is debatable, but patent ductus arteriosus correction is typically recommended at an early age or as soon as the diagnosis is made, especially if congestive heart failure appears imminent. If pulmonary edema is found on the chest radiograph, the patient should be treated medically for heart failure (furosemide, angiotensin-converting enzyme [ACE] inhibitors) prior to surgery. Positive inotropic support should also be considered. Treatment with prostaglandin inhibitors such as indomethacin (often used in premature human infants to assist closure of a structurally normal but functionally immature PDA) is not effective in dogs and cats, most likely because of the absence of smooth muscle in the ductal wall.

Two approaches to patent ductus arteriosus correction are currently available. For many years, left thoracotomy and surgical closure, typically by ligation, was the only available treatment. Other surgical methods of repair include suture occlusion with metallic clips and surgical division. These techniques and their results have been described in detail in several reports, indicating high surgical success rates and an excellent prognosis after repair. Complications of surgical patent ductus arteriosus repair in dogs most often include hemorrhage, infection, pneumthorax, cardiac arrhythmias, cardiac arrest, and heart failure. Surgical mortality should be less than 3% in uncomplicated cases. Pre-existing congestive heart failure (CHF) dramatically increases the risk of anesthetic or operative death and the rate of serious complications, underscoring the necessity of resolving pulmonary congestion prior to surgery. Positive inotropic support provided through a dobutamine infusion should also be considered for patients in this circumstance. Most dogs experience an uneventful recovery after surgery, and overall cardiac size gradually decreases toward normal, although the heart and great vessels often retain an abnormal shape. Postoperative Doppler examination may indicate a small residual shunt, although the continuous murmur is usually absent and the clinical outcomes are good. A soft left apical systolic murmur, usually from residual secondary mitral regurgitation, is often heard for a variable period after ductus ligation. Echocardiographic LV fractional shortening declines sharply immediately after surgery as a result of diminished preload and increased afterload. Medical therapy is not usually needed if signs of heart failure were not evident pre-operatively. Medical therapies required prior to surgery for congestive heart failure are often required for several months after repair. Postoperative ductal recanalization has been reported but is uncommon, occurring in less than 2% of cases, and it most commonly is associated with infection. Postoperative fever and pulmonary infiltrates may indicate infection at the surgical site and hematogenous pneumonia. The owner should be informed of the suspected heritable nature of the defect and should be advised not to use the animal for breeding.

Less invasive alternative techniques for patent ductus arteriosus occlusion are gaining popularity. Percutaneous embolization of the ductus using expandable metal devices imbedded with thrombogenic Dacron strands can be accomplished in most small animals with a patent ductus arteriosus (PDA), avoiding the morbidity of surgical thoracotomy. The most commonly used embolization device is a helical metal coil that is delivered through a small catheter via the femoral artery or other peripheral vessel. After the device has been deployed in the ductus arteriosus, the attached Dacron feathers induce thrombus formation, thereby occluding the PDA. The purported advantages of patent ductus arteriosus coil embolization over thoracotomy and surgical ligation include lower morbidity, shorter hospitalization, and faster recovery. To date the success rate of this technique has been promising and the major complication rate has been acceptably low, consisting mainly of residual shunting and pulmonary embolization of a coil. Coils that embolize to the lungs can be ignored, pushed to a peripheral location, or removed. The authors preier to remove dislodged coils, which can be quite easily accomplished using heartworm extraction forceps or other retrieval devices. Because device retention within the patent ductus arteriosus is required for successful closure, the ideal candidates for coil occlusion should have a relatively small, funnel-shaped patent ductus arteriosus that tapers to a diameter of 2 or 3 mm at the pulmonary artery end. Occlusion of large-diameter PDAs (4 mm or greater) can be attempted by deploying multiple coils into the ductal ampulla, but coil dislodgment and residual shunting are more problematic in this circumstance. Mushroom-shaped, self-expanding, occluding stents (Amplatzer) developed for human use have been successfully used to accomplish patent ductus arteriosusclosure in dogs. Advantages of this technique include secure retention of the device in the ductus with a correspondingly low rate of dislodgment, ease of delivery through the femoral vein, and suitability for closing large-diameter PDAs with a single implant. The need for specialized equipment (i.e., coils, occluding stents, catheters, fluoroscopy) and an operator experienced in performing cardiac catheterization limits the application of transcatheter patent ductus arteriosus closure techniques to university teaching hospitals and large specialty referral centers. The historical success of the traditional patent ductus arteriosus surgery makes thoracotomy and ligation a perfectly acceptable and, in some circumstances, a preferable alternative to transcatheter closure.

Animals with reversed patent ductus arteriosus have irreversible obstructive pulmonary vascular disease. Morbidity and mortality is usually due to complications related to polycythemia and chronic hypoxemia rather than congestive heart failure. Treatment of these patients consists of exercise restriction, avoidance of stress, and maintenance of the PCV between 58% and 65% by periodic phlebotomy. Long-term management by these techniques is possible. Phlebotomy should be performed cautiously to avoid weakness or collapse, and intravascular volume may be supported during phlebotomy by administration of crystalloid solutions. Attempts to reduce the red cell volume of reversed patent ductus arteriosus cases using drug therapy (e.g., hydroxyurea) have been reported and may be an alternative to repeated phlebotomy. Activity restriction is usually advised, because exercise-induced systemic vasodilatation increases the degree of right-to-left shunting and predisposes to posterior paresis or collapse and cyanosis. Closure of reversed patent ductus arteriosus is strongly contraindicated, because it invariably leads to late operative or early postoperative acute right heart failure and death.