Etiology and Pathophysiology

Functional closure of the ductus arteriosus normally occurs within hours after birth and is followed by structural changes that occur over several months, which cause permanent closure. The ductal wall in animals with an inherited PDA is histologically abnormal and unable to constrict. When the ductus fails to close, blood shunts through it from the descending aorta into the pulmonary artery. Shunting occurs during both systole and diastole because aortic pressure normally is higher than pulmonic pressure throughout the cardiac cycle. This left-to-right shunt causes a volume overload of the pulmonary circulation, left atrium (LA), and left ventricle (LV). The shunt volume is directly related to the pressure difference (gradient) between the two circulations and the diameter of the ductus.

Hyperkinetic arterial pulses are characteristic of PDA. Blood runoff from the aorta into the pulmonary system allows diastolic aortic pressure to decrease below normal. The widened pulse pressure (systolic minus diastolic pressure) causes palpably stronger arterial pulses (Fig. 5-2).

FIG 5-2 Continuous femoral artery pressure recording during surgical ligation of a patent ductus arteriosus in a Poodle. The wide pulse pressure (left side of trace) narrows as the ductus is closed (right side of trace). Diastolic arterial pressure rises because blood runoff into the pulmonary artery is curtailed.

(Courtesy Dr. Dean Riedesel.)

Compensatory mechanisms (e.g., increased heart rate, volume retention) maintain adequate systemic blood flow. However, the LV is subjected to a great hemodynamic burden, especially when the ductus is large, because the increased stoke volume is pumped into the relatively high pressure aorta. LV and mitral annulus dilation in turn cause mitral regurgitation and further volume overload. Excess fluid retention, declining myocardial contractility stemming from the chronic volume overload, and arrhythmias contribute to the development of congestive heart failure (CHF).

In some cases, excessive pulmonary blood flow leads to pulmonary vascular changes, increased resistance, and pulmonary hypertension (see p. 109). If pulmonary artery pressure rises to equal aortic pressure, very little blood shunting occurs. However, if pulmonary artery pressure exceeds aortic pressure, shunt reversal (right-to-left flow) occurs. Approximately 15% of dogs with inherited PDA develop a reversed shunt; female Cocker Spaniels may be at increased risk for reversed PDA.

Clinical Features

A left-to-right shunting PDA (discussed here) is by far the most common form; clinical features of reversed PDA are described on p. 110. The prevalence of PDA is higher in certain breeds of dogs, and a polygenic inheritance pattern is thought to be responsible. The prevalence is approximately three times greater in female than male dogs. Reduced exercise ability, tachypnea, or cough is present in some cases, but many animals are asymptomatic when first diagnosed. Typical findings include a continuous murmur heard best high at the left base (see p. 9), often with a precordial thrill, hyperkinetic (bounding, “waterhammer”) arterial pulses, and pink mucous membranes.

Diagnosis

Radiographs usually show cardiac elongation (left heart dilation), left atrial and auricular enlargement, and pulmonary overcirculation (Table 5-2). A bulge often is evident in the descending aorta (“ductus bump”) or main pulmonary trunk, or both (Fig. 5-3). The triad of all three bulges (i.e., pulmonary trunk, aorta, and left auricle), located in that order from the 1 to 3 o’clock position on a dorsoventral (DV) radiograph, is a classic finding but not always seen. There is also evidence of pulmonary edema in animals with left-sided heart failure. Characteristic ECG findings include wide P waves, tall R waves, and often deep Q waves in leads II, aVF, and CV₆LL. Changes in the ST-T segment secondary to LV enlargement may occur. However, the ECG is normal in some animals with PDA.

TABLE 5-2 Radiographic Findings In Common Congenital Heart Defects

FIG 5-3 Lateral (A) and dorsoventral (DV) (B) radiographs from a dog with a patent ductus arteriosus. Note the large and elongated heart and prominent pulmonary vasculature. A large bulge is seen in the descending aorta on the DV view (arrowheads in B). C, Angiocardiogram obtained using a left ventricular injection outlines the left ventricle, aorta, patent ductus (arrowheads), and pulmonary artery.

Echocardiography also shows left heart enlargement and pulmonary trunk dilation. LV fractional shortening can be normal or decreased, and the E point–septal separation is often increased. The ductus itself may be difficult to visualize because of its location between the descending aorta and pulmonary artery. Views from the cranial left parasternal position are useful. Doppler interrogation documents continuous, turbulent flow into the pulmonary artery (Fig. 5-4). The maximum aortic-to-pulmonary artery pressure gradient should be estimated. Cardiac catheterization is generally unnecessary for diagnosis, although it is important during interventional procedures. Catheterization findings include higher oxygen content in the pulmonary artery compared with the right ventricle (oxygen “step-up”) and a wide aortic pressure pulse. Angiocardiography shows left-to-right shunting through the ductus (see Fig. 5-3, C).

FIG 5-4 Continuous turbulent flow into the pulmonary artery from the area of the patent ductus (arrow) is illustrated by systolic (A) and diastolic (B) color flow Doppler frames from the left cranial parasternal position, in an adult female Springer Spaniel. Ao, Ascending aorta; PA, main pulmonary artery; RV, right ventricle.

Treatment and Prognosis

Closure of the left-to-right ductus, usually performed as soon as is feasible, is recommended by either a transcatheter or surgical occlusion method. Surgical ligation is successful in most cases, although a perioperative mortality of about 10% has been reported. Patient age or weight does not appear to affect the outcome of surgery. Several methods of transcatheter PDA occlusion are available. These involve placing a vascular occluding device (e.g., the Amplatz canine ductal occluder) or wire coils with attached thrombogenic tufts within the ductus. Vascular access is usually via the femoral artery, although some have used a venous approach to the ductus. Where available, transcatheter PDA occlusion offers a much less invasive alternative to surgical ligation. Complications can occur (including aberrant coil embolization and residual ductal flow, among others), and not all cases are suitable for transcatheter occlusion. A normal life span can be expected after uncomplicated ductal closure. The concurrent mitral regurgitation usually resolves after ductus ligation or occlusion if the valve is structurally normal.

Animals with CHF are treated with furosemide, an angiotensin-converting enzyme inhibitor (ACEI), rest, and dietary sodium restriction (see Chapter 3). Because contractility tends to decline over time, pimobendan or digoxin may be indicated as well. Arrhythmias are treated as necessary.

If the ductus is not closed, prognosis depends on its size and the level of pulmonary vascular resistance. CHF is the eventual outcome for most patients that do not undergo ductal closure. More than 50% of affected dogs die within the first year. In animals with pulmonary hypertension and shunt reversal, ductal closure is contraindicated because the ductus acts as a “pop-off” valve for the high right-sided pressures. Ductal ligation in animals with reversed PDA produces no improvement and can lead to right ventricular (RV) failure.

Etiology and Pathophysiology

Subvalvular narrowing caused by a fibrous or fibromuscular ring is the most common type of aortic stenosis in dogs. Certain larger breeds of dog are predisposed to this defect. SAS is thought to be inherited as an autosomal dominant trait with modifying genes that influence its phenotypic expression. SAS also occurs in cats; supravalvular lesions have been reported in this species as well.

The spectrum of SAS severity varies widely; three grades of SAS have been described in Newfoundland dogs. The mildest (grade I) is associated with no clinical signs or murmur and only subtle subaortic fibrous tissue ridging seen on postmortem examination. Moderate (grade II) SAS consists of mild clinical and hemodynamic evidence of the disease, with an incomplete fibrous ring below the aortic valve found at postmortem. Dogs with grade III SAS have severe disease and a complete fibrous ring around the outflow tract. Some cases have an elongated, tunnel-like obstruction. There may also be malformations of the mitral valve apparatus. Outflow tract narrowing and dynamic obstruction with or without a discrete subvalvular ridge have also been noted in Golden Retrievers. A component of dynamic LV outflow tract obstruction may be important in other dogs as well.

The obstructive lesion of SAS develops during the first several months of life, and there may be no audible murmur at an early age. In some dogs no murmur is detected until 1 to 2 years of age, and the obstruction may continue to worsen beyond that. Murmur intensity usually increases with exercise or excitement. Because of such factors, as well as the presence of physiologic murmurs in some animals, definitive diagnosis and genetic counseling to breeders can be difficult.

The severity of the stenosis determines the degree of LV pressure overload and resulting concentric hypertrophy. Coronary perfusion is easily compromised in animals with severe SAS and left ventricular hypertrophy. Capillary density may become inadequate as hypertrophy progresses, and high systolic wall tension with coronary narrowing can cause systolic flow to be reversed in small coronary arteries. These factors contribute to the development of myocardial ischemia and fibrosis. Clinical sequelae include arrhythmias, syncope, and sudden death. Many animals with SAS also have aortic or mitral valve regurgitation because of related malformations or secondary changes; this imposes a volume overload on the LV. Left-sided CHF develops in some cases. Animals with SAS are thought to be at higher risk for devel oping aortic valve endocarditis because of jet lesion injury to the underside of the valve (see p. 121 and Figure 6-4).

Clinical Features

Historical signs of fatigue, exercise intolerance or exertional weakness, syncope, or sudden death occur in about a third of dogs with SAS. Low-output signs can result from severe outflow obstruction, tachyarrhythmias or sudden reflex bradycardia, and hypotension resulting from the activation of ventricular mechanoreceptors. Left-sided CHF can develop, usually in conjunction with concurrent mitral or aortic regurgitation, other cardiac malformations, or acquired endocarditis. Dyspnea is the most commonly reported sign in cats with SAS.

Characteristic physical examination findings in dogs with moderate-to-severe stenosis include weak and late-rising femoral pulses (pulsus parvus et tardus) and a precordial thrill low at the left heartbase. A harsh systolic ejection murmur is heard at or below the aortic valve area on the left hemithorax. This murmur often radiates equally or more loudly to the right heartbase because of the orientation of the aortic arch. The murmur frequently is heard over the carotid arteries, and it may even radiate to the calvarium. In mild cases a soft, poorly radiating ejection murmur at the left and sometimes right heartbase may be the only abnormality found on physical examination. Functional aortic stenosis murmurs that are not associated with SAS are common in Greyhounds and other sight hounds. Aortic regurgitation can produce a diastolic murmur at the left base or may be inaudible. Severe aortic regurgitation can increase the arterial pulse strength. There may be evidence of pulmonary edema or arrhythmias.

Diagnosis

Radiographic abnormalities (see Table 5-2) can be subtle, especially in dogs and cats with mild SAS. The LV can appear normal or enlarged. Poststenotic dilation in the ascending aorta can cause a prominent cranial waist in the cardiac silhouette (especially on a lateral view) and cranial mediastinal widening. The ECG is often normal, although evidence of LV hypertrophy (left axis deviation) or enlargement (tall complexes) can be present. Depression of the ST segment in leads II and aVF can occur from secondary myocardial ischemia or to hypertrophy; exercise induces further ischemic ST-segment changes in some animals. Ventricular tachyarrhythmias are common.

Echocardiography reveals the extent of LV hypertrophy and subaortic narrowing. A discrete tissue ridge below the aortic valve is evident in many animals with moderate-to-severe disease (Fig. 5-5). Premature closure of the aortic valve, systolic anterior motion of the anterior mitral leaflet, and increased LV subendocardial echogenicity (probably from fibrosis) are common in animals with severe obstruction. Ascending aorta dilation, aortic valve thickening, and LA enlargement with hypertrophy may also be seen. In mildly affected animals 2-D and M-mode findings may be unremarkable. Doppler echocardiography reveals systolic turbulence originating below the aortic valve and extending into the aorta, as well as high peak systolic outflow velocity (Fig. 5-6). Some degree of aortic or mitral regurgitation is common. Spectral Doppler studies are used to estimate the stenosis severity. Doppler-estimated systolic pressure gradients in unanesthetized animals are usually 40% to 50% higher than those recorded during cardiac catheterization under anesthesia. Severe SAS is associated with peak estimated gradients >100 to 125 mm Hg. The LV outflow tract should be interrogated from more than one position to achieve the best possible alignment with blood flow. The subcostal (subxiphoid) position usually yields the highest-velocity signals, although the left apical position is optimal in some animals. The Doppler-estimated aortic outflow velocity may be only equivocally high in animals with mild SAS, especially with suboptimal Doppler beam alignment. With optimal alignment, aortic root velocities of <1.7 m/sec are typical in normal unsedated dogs; velocities over ∼2.25 m/sec are generally considered abnormal. Peak velocities in the equivocal range between these values may indicate the presence of mild SAS, especially if there is other evidence of disease, such as disturbed flow in the outflow tract or ascending aorta and aortic regurgitation. This is mainly of concern when selecting animals for breeding. In some breeds (e.g., Greyhound, Boxer, Golden Retriever), outflow velocities in this equivocal range (1.8-2.25 m/sec) are common. This may reflect breed-specific variation in LV outflow tract anatomy or response to sympathetic stimulation, rather than SAS. A limitation of using the estimated pressure gradient to assess outflow obstruction severity is that this gradient depends on blood flow. Factors causing sympathetic stimulation and increased cardiac output (e.g., excitement, exercise, fever) will increase outflow velocities, whereas myocardial failure, cardiodepressant drugs, and other causes of reduced stroke volume will decrease recorded velocities. Cardiac catheterization and angiocardiography are rarely used now to diagnose or quantify SAS, except in conjunction with balloon dilation of the stenotic area.

FIG 5-5 Echocardiogram from a 6-month-old German Shepherd Dog with severe subaortic stenosis. Note the discrete ridge of tissue (arrow) below the aortic valve, creating a fixed outflow tract obstruction. A, Aorta; LV, left ventricle; RV, right ventricle.

FIG 5-6 Color flow Doppler frame of the left ventricular outflow region in systole from a 2-year-old female Rottweiler with severe subaortic stenosis. Note the turbulent flow pattern originating below the aortic valve, as well as the thickened septum, papillary muscle, and left ventricular free wall. Right parasternal long axis view; Ao, aorta; LA, left atrium; LV, left ventricle; RA, right atrium.

Treatment and Prognosis

Several palliative surgical techniques have been used in dogs with severe SAS, with limited success. Cardiopulmonary bypass and open-heart surgery are necessary to reach the lesion directly. Although resection of the stenotic area can significantly reduce the LV systolic pressure gradient and possibly improve exercise ability, a long-term survival advantage appears lacking. Transvascular balloon dilation of the stenotic area reduces the measured gradient in some dogs, although narrowing may partially recur. Likewise, no survival benefit has been documented with this procedure.

Medical therapy with a β-blocker is advocated in patients with moderate to severe SAS to reduce myocardial oxygen demand and minimize the frequency and severity of arrhythmias. Animals with a high pressure gradient, marked ST-segment depression, frequent ventricular premature beats, or a history of syncope may be more likely to benefit from this therapy. Whether β-blockers prolong survival is unclear. Exercise restriction is advised for animals with moderate-to-severe SAS. Prophylactic antibiotic therapy is recommended for animals with SAS before the performance of any procedures with the potential to cause bacteremia (e.g., dentistry).

The prognosis in dogs and cats with severe stenosis (catheterization pressure gradient >80 mm Hg or Doppler gradient >100-125 mm Hg) is guarded. More than half of dogs with severe SAS die suddenly within their first 3 years. The overall prevalence of sudden death in dogs with SAS appears to be just over 20%. Infective endocarditis and CHF may be more likely to develop after 3 years of age. Atrial and ventricular arrhythmias and worsened mitral regurgitation are complicating factors. Dogs with mild stenosis (e.g., catheterization gradient <35 mm Hg or Doppler gradient <60-70 mm Hg) are more likely to survive longer and without clinical signs.

Etiology and Pathophysiology

PS is more common in small breeds of dogs. Some cases of valvular PS result from simple fusion of the valve cusps, but valve dysplasia is more common. Dysplastic valve leaflets are variably thickened, asymmetric, and partially fused, with a hypoplastic valve annulus. Right ventricular pressure overload produces right ventricle (RV) hypertrophy as well as secondary dilation. Severe ventricular hypertrophy promotes myocardial ischemia and its sequelae. Excessive muscular hypertrophy below the valve (infundibular area) can create a dynamic subvalvular component to the stenosis. Other variants of PS, including supravalvular stenosis and RV muscular partition (double chamber RV) occur rarely.

High-velocity blood flow across the stenotic orifice creates turbulence leading to poststenotic dilation in the main pulmonary trunk. Right atrial dilation from secondary tricuspid insufficiency and high RV filling pressure predisposes to atrial tachyarrhythmias and CHF. The combination of PS and a patent foramen ovale or ASD can allow right-to-left shunting at the atrial level, but this is rare in dogs and cats.

A single anomalous coronary artery has been described in some Bulldogs and Boxers with PS and is thought to contribute to the outflow obstruction. In such cases, palliative surgical procedures and balloon valvuloplasty may cause death secondary to transection or avulsion of the major left coronary branch.

Clinical Features

Many dogs with PS are asymptomatic when diagnosed, although right-sided CHF or a history of exercise intolerance or syncope may exist. Clinical signs may not develop until the animal is several years old, even in those with severe stenosis. Physical examination findings characteristic of moderate-to-severe stenosis include a prominent right precordial impulse; a thrill high at the left base; normal to slightly diminished femoral pulses; pink mucous membranes; and, in some cases, jugular pulses. A systolic ejection murmur is heard best high at the left base on auscultation. The murmur can radiate cranioventrally and to the right in some cases but usually is not heard over the carotid arteries. An early systolic click is sometimes identified; this probably is caused by abrupt checking of a fused valve at the onset of ejection. A murmur of tricuspid insufficiency or arrhythmias can be heard in some cases.

Diagnosis

Radiographic findings typically seen in animals with PS are outlined in Table 5-2. Marked RV hypertrophy shifts the cardiac apex dorsally and to the left. The heart may appear as a “reverse D” shape on a DV or ventrodorsal (VD) view. A variably sized pulmonary trunk bulge (poststenotic dilation) is best seen at the 1 o’clock position on a DV or VD view (Fig. 5-7). The size of the poststenotic dilation does not correlate with the severity of the pressure gradient. A dilated caudal vena cava is also seen in some animals.

FIG 5-7 Lateral (A) and dorsoventral (DV) (B) radiographs from a dog with pulmonic stenosis, showing right ventricular enlargement (apex elevation on lateral view [arrowhead in A] and reverse D configuration on DV view) along with a pulmonary trunk bulge (arrowheads in B) seen on a DV view. C, Angiocardiogram using a selective right ventricular injection demonstrates poststenotic dilation of the main pulmonary trunk and pulmonary arteries. The thickened pulmonic valve is closed in this diastolic frame.

ECG changes are more common in patients with moderate to severe stenosis. These include an RV hypertrophy pattern, right axis deviation, and sometimes an RA enlargement pattern (P pulmonale) or tachyarrhythmias. Echocardiographic findings characteristic of moderate-to-severe stenosis include RV hypertrophy and enlargement. The interventricular septum often appears flattened as high RV pressure pushes it toward the left (Figure 5-8, A). RA enlargement is often seen as well. A thickened, asymmetrical, or otherwise malformed pulmonic valve usually can be identified (Fig. 5-8, B), although the outflow area may be narrow and difficult to visualize clearly. Poststenotic dilation of the main pulmonary trunk is expected. Pleural effusion and marked right heart dilation often accompany secondary CHF. Paradoxical septal motion is likely in such cases as well. Doppler evaluation along with anatomic findings provides an estimate of PS severity. Cardiac catheterization and angiocardiography also can be used to assess the pressure gradient across the stenotic valve, the right heart filling pressure, and other anatomic features. Doppler-estimated systolic pressure gradients in unanesthetized animals are usually 40% to 50% higher than those recorded during cardiac catheterization. PS is generally considered mild if the Doppler-derived gradient is <50 mm Hg and severe if it is >80 to 100 mm Hg.

FIG 5-8 Echocardiograms from two dogs with severe pulmonic stenosis. (A) Right parasternal short-axis view at the ventricular level in a 4-month-old male Samoyed shows right ventricular hypertrophy (arrows) and enlargement; high right ventricular pressure flattens the septum toward the left in this diastolic frame. (B) Thickened, partially fused leaflets of the malformed pulmonary valve (arrows) are seen in a 5-month-old male Pomeranian. Ao, Aortic root; LA, left atrium; RVOT, right ventricular outflow tract; RVW, right ventricular wall.

Treatment and Prognosis

Balloon valvuloplasty is recommended for palliation of severe (and sometimes moderate) stenosis, especially if infundibular hypertrophy is not excessive. This procedure reduces or eliminates clinical signs and appears to improve long-term survival in severely affected animals. Balloon valvuloplasty, done in conjunction with cardiac catheterization, involves passing a specially designed balloon catheter across the valve and inflating the balloon to enlarge the stenotic orifice. The procedure is most successful in dogs with simple fusion of the pulmonic valve cusps. Dysplastic valves are more difficult to dilate effectively, but good results are possible in some cases. Various surgical procedures also have been used to palliate moderate-to-severe PS in dogs. Balloon valvuloplasty generally is attempted before a surgical procedure because it is less risky. Animals with a single anomalous coronary artery should not undergo balloon or surgical dilation procedures. Coronary anatomy can be verified using echocardiography or angiography.

Exercise restriction is generally advised for animals with moderate-to-severe stenosis. A β-blocker may be helpful, especially in those with prominent RV infundibular hypertrophy. Signs of CHF are managed medically (see Chapter 3). The prognosis in patients with PS is variable and depends on the severity of the lesion. Life span can be normal in those with mild PS, whereas animals with severe PS often die within 3 years of diagnosis. Sudden death or the onset of CHF is common. The prognosis is considerably worse in animals with tricuspid regurgitation, atrial fibrillation or other tachyarrhythmias, or CHF.

Etiology and Pathophysiology

Most VSDs are located in the membranous part of the septum, just below the aortic valve and beneath the septal tricuspid leaflet. VSDs sporadically occur in other septal locations also. A VSD may be accompanied by other AV septal (endocardial cushion) malformations, especially in cats. Usually, VSDs produce a volume overload on the lungs, LA, LV, and RV outflow tract. Small defects may be clinically unimportant. Moderate-to-large defects tend to cause left heart dilation and can lead to left-sided CHF. A very large VSD causes both ventricles to function as a common chamber and induces RV dilation and hypertrophy. Pulmonary hypertension secondary to overcirculation is more likely to develop in animals with a large shunt. Some animals with VSD also have aortic regurgitation, with diastolic prolapse of a valve leaflet. Presumably this occurs because the deformed septum provides inadequate anatomic support for the aortic root. Aortic regurgitation places an additional volume load on the LV.

Clinical Features

The most common clinical manifestations of VSD are exercise intolerance and signs of left-sided CHF. Many animals are asymptomatic at the time of diagnosis. The characteristic auscultatory finding is a holosystolic murmur, heard loudest at the cranial right sternal border (which corresponds to the direction of shunt flow). A large shunt volume can produce a murmur of relative or functional PS (systolic ejection murmur at the left base). With concurrent aortic regurgitation, the corresponding diastolic decrescendo murmur is heard at the left base.

Diagnosis

Radiographic findings associated with VSD vary with thesize of the defect and the shunt volume (see Table 5-2). Large shunts cause left heart enlargement and pulmonary overcirculation. However, large shunts that increase pulmonary vascular resistance and pressure lead to RV enlargement. A large shunt volume (with or without pulmonary hypertension) also can increase main pulmonary trunk size.

The ECG may be normal or suggest LA or LV enlargement. In some cases, disturbed intraventricular conduction is suggested by “fractionated” or splintered QRS complexes. An RV enlargement pattern usually indicates a very large defect, pulmonary hypertension, or a concurrent RV outflow tract obstruction, although sometimes a right bundle-branch block causes this pattern.

Echocardiography reveals left heart dilation (with or without RV dilation) when the shunt is large. The defect often can be visualized just below the aortic valve in the right parasternal long-axis LV outflow view. The septal tricuspid leaflet is located to the right of the defect. Because echo “dropout” at the thin membranous septum can mimic a VSD, the area of a suspected defect should be visualized in more than one plane. Supporting clinical evidence and a murmur typical of a VSD also should be present before the diagnosis is made. Doppler (or echo-contrast) studies usually demonstrate the shunt flow (Fig. 5-9).

FIG 5-9 Color flow Doppler frame in systole showing turbulent flow (from left to right) through a small membranous ventricular septal defect just below the aortic root in a 1-year-old male terrier. Right parasternal long axis view; AO, aortic root; LV, left ventricle.

Cardiac catheterization, oximetry, and angiocardiography allow measurement of intracardiac pressures, indicate the presence of an oxygen step-up at the level of the RV outflow tract, and show the pathway of abnormal blood flow.

Treatment and Prognosis

A small-to-moderate defect usually allows a relatively normal life span. In some cases, the defect closes spontaneously within the first 2 years of life. Closure can result from myocardial hypertrophy around the VSD or a seal formed by the septal tricuspid leaflet or a prolapsed aortic leaflet. Left-sided CHF is more likely in animals with a large septal defect, although pulmonary hypertension with shunt reversal develops in some instead, usually at an early age.

Definitive therapy for VSD usually requires cardiopulmonary bypass or hypothermia and intracardiac surgery, although transcatheter delivery of an occlusion device may be possible in some cases. Large left-to-right shunts are sometimes palliated by surgically placing a constrictive band around the pulmonary trunk to create a mild supravalvular PS. This raises RV systolic pressure in response to the increased outflow resistance. Consequently, less blood shunts from LV to RV. An excessively tight band can cause right-to-left shunting (functionally analogous to a T of F), however. Left-sided CHF is managed medically. Palliative surgery should not be attempted in the presence of pulmonary hypertension and shunt reversal.

Etiology and Pathophysiology

Several types of ASD exist. Those located in the region of the fossa ovalis (ostium secundum defects) are more common in dogs. An ASD in the lower interatrial septum (ostium primum defect) is likely to be part of the AV septal (endocardial cushion or common AV canal) defect complex, especially in cats. Sinus venosus–type defects are rare; these are located high in the atrial septum near the entry of the cranial vena cava. Animals with ASD commonly have other cardiac malformations as well. In most cases of ASD, blood shunts from LA to RA and results in a volume overload to the right heart. However, if PS or pulmonary hypertension is present, right-to-left shunting and cyanosis may occur.

Clinical Features

The clinical history in animals with an ASD is usually rather nonspecific. Physical examination findings associated with an isolated ASD are often unremarkable, although large left-to-right shunts can cause a murmur of relative PS. Fixed splitting (i.e., with no respiratory variation) of the second heart sound (S₂) is the classic auscultatory finding. Rarely, a soft diastolic murmur of relative tricuspid stenosis might be audible.

Diagnosis

Right heart enlargement, with or without pulmonary trunk dilation, is found radiographically in patients with severe shunts (see Table 5-2). The pulmonary circulation may appear to be increased unless pulmonary hypertension has developed. Left heart enlargement is not seen unless another defect, such as mitral insufficiency, is present. The ECG may be normal or show evidence of RV and RA enlargement. Cats with an AV septal defect may have RV enlargement and a left axis deviation.

Echocardiography is likely to show RA and RV dilation, with or without paradoxical interventricular septal motion. Large ASDs can be visualized. Care must be taken not to confuse the thinner fossa ovalis region of the interatrial septum with an ASD because echo dropout also occurs here. Doppler echocardiography allows identification of smaller shunts that cannot be clearly visualized on 2-D exam, but venous inflow streams may complicate this. Cardiac catheterization shows an oxygen step-up at the level of the RA. Abnormal flow through the shunt may be evident after the injection of contrast material into the pulmonary artery.

Treatment and Prognosis

Large shunts can be treated surgically, similarly to VSDs. Otherwise, animals are managed medically if CHF develops. The prognosis is variable and depends on shunt size, concurrent defects, and the level of pulmonary vascular resistance.

Etiology and Pathophysiology

The four components of the T of F are a VSD, PS, a dextropositioned aorta, and RV hypertrophy. The VSD can be quite large. The PS can involve the valve or infundibular area; in some cases, the pulmonary artery is hypoplastic or not open at all (atretic). The large aortic root extends over the right side of the interventricular septum and facilitates RV-to-aortic shunting. Aortic anomalies exist in some animals as well. RV hypertrophy occurs in response to the pressure overload imposed by the PS and systemic arterial circulation. The volume of blood shunted from the RV into the aorta depends on the balance of outflow resistance caused by the fixed PS compared with systemic arterial resistance, which can vary. Exercise and other causes of decreased arterial resistance increase right-to-left shunt volume. Pulmonary vascular resistance is generally normal in animals with T of F. A polygenic inheritance pattern for T of F has been identified in the Keeshond. The defect also occurs in other dog breeds and in cats.

Clinical Features

Exertional weakness, dyspnea, syncope, cyanosis, and stunted growth are common in the history. Physical examination findings are variable, depending on the relative severity of the malformations. Cyanosis is seen at rest in some animals. Others have pink mucous membranes, although cyanosis usually becomes evident with exercise in these cases. The precordial impulse is usually of equal intensity or stronger on the right chest wall than on the left. Inconsistently, a precordial thrill is palpable at the right sternal border or left basilar area. Jugular pulsation may be noted. A holosystolic murmur at the right sternal border consistent with a VSD, or a systolic ejection murmur at the left base compatible with PS, or both may be heard on auscultation. However, some animals have no audible murmur because hyperviscosity associated with polycythemia diminishes blood turbulence and therefore murmur intensity.

Diagnosis

Thoracic radiographs depict variable cardiomegaly, usually of the right heart (see Table 5-2). The main pulmonary artery may appear small, although a bulge is evident in some cases. Reduced pulmonary vascular markings are common, although a compensatory increase in bronchial circulation can increase the overall pulmonary opacity. The malpositioned aorta creates a cranial bulge in the heart shadow on lateral view. RV hypertrophy displaces the left heart dorsally and can simulate left heart enlargement. The ECG typically suggests RV enlargement, although a left axis deviation is seen in some affected cats.

Echocardiography depicts the VSD, a large aortic root shifted rightward and overriding the ventricular septum, some degree of PS, and RV hypertrophy. Doppler studies reveal the right-to-left shunt and high-velocity stenotic pulmonary outflow jet. An echo-contrast study also can document the right-to-left shunt. Typical clinicopathologic abnormalities include increased PCV and arterial hypoxemia.

Treatment and Prognosis

Definitive repair of T of F requires open-heart surgery. Palliative surgical procedures can increase pulmonary blood flow by creating a left-to-right shunt. Anastomosis of a subclavian artery to the pulmonary artery and the creation of a window between the ascending aorta and pulmonary artery are two techniques that have been used successfully.

Severe erythrocytosis and clinical signs associated with hyperviscosity (e.g., weakness, shortness of breath, seizures) can be treated with periodic phlebotomy (see p. 111) or alternatively, hydroxyurea (see p. 111). The goal is to maintain PCV at a level where clinical signs are minimal; further reduction of PCV (into the normal range) can exacerbate signs of hypoxia. A β-blocker may help reduce clinical signs in some dogs with T of F. Decreased sympathetic tone, RV contractility, RV (muscular) outflow obstruction, and myocardial oxygen consumption, along with increased peripheral vascular resistance, are potential benefits, although the exact mechanism is not clear. Exercise restriction is also advised. Drugs with systemic vasodilator effects should not be given.

The prognosis for animals with T of F depends on the severity of PS and erythrocytosis. Mildly affected animals and those that have had a successful palliative surgical shunting procedure may survive well into middle age. Nevertheless, progressive hypoxemia, erythrocytosis, and sudden death at an earlier age are common.

Etiology and Pathophysiology

Pulmonary hypertension develops in a relatively small percentage of dogs and cats with shunts. The defects usually associated with development of pulmonary hypertension are PDA, VSD, AV septal defect or common AV canal, ASD, and aorticopulmonary window. The low-resistance pulmonary vascular system normally can accept a large increase in blood flow without marked increase in pulmonary arterial pressure. It is not clear why pulmonary hypertension develops in some animals, although the defect size in those animals is usually quite large. It is possible that the high fetal pulmonary resistance may not regress normally in these animals or their pulmonary vasculature may react abnormally to an initially large left-to-right shunt flow. In any case, irreversible histologic changes occur in the pulmonary arteries that increase vascular resistance. These include intimal thickening, medial hypertrophy, and characteristic plexiform lesions.

As pulmonary vascular resistance rises, pulmonary artery pressure increases and the volume of blood shunted from left-to-right diminishes. If the right heart and pulmonary pressures exceed those of the systemic circulation, the shunt reverses direction and deoxygenated blood flows into the aorta. These changes appear to develop at an early age (e.g., by 6 months), although exceptions are possible. The term Eisenmenger’s physiology refers to the severe pulmonary hypertension and shunt reversal that develop.

Right-to-left shunts that result from pulmonary hypertension cause pathophysiologic and clinical sequelae similar to those resulting from T of F. The major difference is that the impediment to pulmonary flow occurs at the level of the pulmonary arterioles rather than at the pulmonic valve. Hypoxemia, RV hypertrophy and enlargement, erythrocytosis and its consequences, increased shunting with exercise, and cyanosis can occur. Likewise, right-sided CHF is uncommon but can develop in response to secondary myocardial failure or tricuspid insufficiency. The right-to-left shunt permits venous emboli to cross into the arterial system, potentially resulting in stroke or other arterial embolization.

Clinical Features

The history and clinical presentation of animals with pulmonary hypertension and shunt reversal are similar to those associated with T of F. Exercise intolerance, shortness of breath, syncope (especially in association with exercise or excitement), seizures, and sudden death are common. Cough and hemoptysis may also occur. Cyanosis may be evident only during exercise or excitement. Intracardiac shunts cause equally intense cyanosis throughout the body. Cyanosis of the caudal mucous membranes alone (differential cyanosis) is typically caused by a reversed PDA. Here, normally oxygenated blood flows to the cranial body by way of the brachycephalic trunk and left subclavian artery (from the aortic arch), and the rest of the body receives desaturated blood through the ductus, located in the descending aorta (Fig. 5-11). Rear limb weakness is common in animals with reversed PDA.

FIG 5-11 Angiocardiograms from an 8-month-old female Cocker Spaniel with patent ductus arteriosus, pulmonary hypertension, and shunt reversal. Left ventricular injection (A) shows dorsal displacement of the left ventricle by the enlarged right ventricle. Note the dilution of radiographic contrast solution in the descending aorta (from mixing with nonopacified blood from the ductus) and the prominent right coronary artery. Right ventricular injection (B) illustrates right ventricular hypertrophy and pulmonary trunk dilation secondary to severe pulmonary hypertension. Opacified blood courses through the large ductus into the descending aorta.

A murmur typical of the underlying defect(s) may be heard, but often no murmur or only a very soft systolic murmur is audible because blood viscosity is increased by polycythemia. There is no continuous murmur in patients with reversed PDA. Pulmonary hypertension often causes the S₂ sound to be loud and “snapping” or split. A gallop sound is occasionally heard. Other subtle physical examination findings include a pronounced right precordial impulse and jugular pulsations.

Diagnosis

Thoracic radiographs typically reveal right heart enlargement; a prominent pulmonary trunk; and tortuous, proximally widened pulmonary arteries. A bulge in the descending aorta may be seen in dogs with reversed PDA. The left heart in animals with a reversed PDA or VSD may be enlarged as well. The ECG usually suggests RV and sometimes RA enlargement, with a right axis deviation.

Echocardiography reveals the RV hypertrophy and intracardiac anatomic defects (and sometimes a large ductus), as well as pulmonary trunk dilation. Doppler or echo-contrast study can confirm an intracardiac right-to-left shunt. Reversed PDA flow can be shown by imaging the abdominal aorta during venous echocontrast injection. Peak RV (and in the absence of PS, pulmonary artery) pressure can be estimated by measuring the peak velocity of a tricuspid regurgitation jet. Pulmonary insufficiency flow can be used to estimate diastolic pulmonary artery pressure. Cardiac catheterization also can confirm the diagnosis and quantify the pulmonary hypertension and systemic hypoxemia.

Treatment and Prognosis

Therapy is aimed at managing secondary erythrocytosis to minimize signs of hyperviscosity and attempting to reduce pulmonary arterial pressure, if possible. Exercise restriction is also advised. Erythrocytosis can be managed by periodic phlebotomy or use of oral hydroxyurea. It is unclear whether PCV alone should be used to guide treatment, although maintaining PCV at about 62% has previously been recommended. The ideal PCV for a patient would seem to be that associated with minimal physical manifestations of hyperviscosity (e.g., rear limb weakness, shortness of breath, lethargy). Surgical closure of the shunt is contraindicated. The prognosis is generally poor in animals with pulmonary hypertension and shunt reversal, but some patients have done well for years with medical management.

Phlebotomy can be done when necessary. One method is to remove 5 to 10 ml blood/kg body weight and administer an equal volume of isotonic fluid. Another technique (described by Cote and Ettinger, 2001) involves removing 10% of the patient’s circulating blood volume initially without giving replacement fluid. This volume (ml) is calculated as 8.5% × body weight (kg) × 1000 g/kg × 1 ml/g. After 3 to 6 hours of cage rest, an additional volume of blood is removed if the patient’s initial PCV was >60%. This additional volume would be 5% to 10% of the circulating blood volume if initial PCV was 60% to 70%, or an additional 10% to 18% if initial PCV was >70%.

Hydroxyurea therapy (40 to 50 mg/kg by mouth q48h or 3×/week) can be a useful alternative to periodic phlebotomy in some patients with secondary erythrocytosis. A CBC and platelet count should be monitored weekly or biweekly to start. A PCV between approximately 55% to 60% is the suggested target. Possible adverse effects of hydroxyurea include anorexia, vomiting, bone marrow hypoplasia, alopecia, and pruritus. The dose can be divided q12h on treatment days, or administered twice weekly, or at <40 mg/kg depending on the patient’s response.

Sildenafil citrate is a selective phosphodiesterase-5 inhibitor that may reduce pulmonary resistance via nitric oxide–dependent pulmonary vasodilation. It appears to improve clinical signs and exercise tolerance in some dogs with pulmonary hypertension, although experience in animals is limited. Doses of 0.5 to 2(or 3) mg/kg q12h or q8h seem to be well-tolerated and produce some reduction in Doppler-estimated pulmonary artery pressure. Lower initial doses are suggested, with gradual up-titration. Adverse effects of sildenafil can include possible nasal congestion, hypotension, or sexual adverse effects, especially in intact animals. Other vasodilator drugs tend to produce systemic effects that are similar to or greater than those on the pulmonary vasculature; therefore they are of little benefit and possibly detrimental. Low-dose aspirin (e.g., 5 mg/kg) therapy may also be useful in animals with pulmonary hypertension and reversed shunt, but this is not well-studied.