Pathophysiology of Congenital Heart Defects

Congenital heart defects are morphologic disorders of the heart and great vessels that are present at birth. Strong breed predilections for congenital heart defects suggest a genetic basis for most defects. Congenital heart defects result in a variety of pathophysiologic alterations that eventually can lead to progressive heart failure, cardiac arrhythmias, and sudden cardiac death, debilitating hypoxemia, or combinations of these adverse outcomes.

Patent Ductus Arteriosus

The ductus arteriosus is a vascular conduit between the pulmonary artery and descending aorta that diverts pulmonary flow away from the fetal lung circulation. Soon after birth, expansion of the fetal lung lowers pulmonary vascular resistance and reverses flow through the ductus. Oxygenated blood is detected by the vascular endothelium of the ductus arteriosus, and this, in turn, inhibits the release of the vasodilating prostaglandin that keeps the ductus patent. The vascular smooth muscle of the ductus arteriosus contracts and functionally closes the ductus within a few hours of birth.

Patent ductus arteriosus (PDA) results from a persistence of the ductus arteriosus after birth. Incomplete development of the medial layer of the ductus arteriosus wall has been implicated in the pathogenesis of PDA in dogs [1]. PDA allows a high-flow left-to-right shunt that overloads the volume in the left atrium and ventricle and overcirculates the lungs. The resultant chronic volume overload induces progressive dilation of the left ventricle with or without wall thickening. Secondary functional mitral regurgitation (MR) and overload-induced systolic dysfunction eventually contribute to the progression of heart failure as PDA becomes long standing. The overload is so overwhelming that most animals will succumb to progressive left-sided congestive heart failure within the first year of life. Closure of PDA is indicated for the vast majority of animals with this defect and is generally undertaken with curative intent unless secondary changes are advanced.

On occasion, increased pulmonary vascular resistance can elevate pulmonary artery pressures sufficiently to reverse flow through a PDA. Suprasystemic pulmonary hypertension results either from a failure of transition of the pulmonary circulation to extrauterine life or progressive pulmonary vascular remodeling caused by chronic pulmonary overcirculation. In the former case, right-to-left or "reverse" PDA is present from birth. In the latter, it typically develops in the first 8 months of life. Regardless of the inciting mechanism, the right-to-left shunt through a PDA causes selective hypoxemia to the caudal portions of the circulation and is responsible for the hallmark sign of differential cyanosis. Clinical consequences of the chronic hypoxemia include moderate to severe activity intolerance, pelvic limb weakness, and progressive polycythemia. Closure of right-to-left or "reverse" PDA causes severe acute cor pulmonale and is contraindicated.

Pulmonic Stenosis

Pulmonic stenosis (PS) in dogs is most often valvular, although supravalvular and subvalvular defects occur, either as isolated defects or in combination. Valvular PS represents a spectrum of abnormalities ranging from simple commissural fusion, consisting of incomplete separation of the valve leaflet commissurae, to valve dysplasia, characterized by varying degrees of narrowing of the valve annulus and/or thickening and immobility of the valve leaflets. In severe cases of PS, secondary hypertrophy of the right ventricular outflow tract (RVOT) can contribute to PS severity by causing dynamic obstruction to ventricular ejection of blood.

Chronic pressure overload caused by PS induces thickening of the right ventricular wall without chamber dilation (i.e., concentric hypertrophy). Right atrial dilation occurs as diastolic filling pressures increase in response to poor ventricular compliance and decreased cardiac output. If primary or secondary tricuspid regurgitation (TR) accompanies PS, then right ventricle dilation may accompany the ventricular wall thickening. Despite its relative importance as a congenital defect, the natural history of untreated PS in animals is not well documented. Dogs with mild to moderate PS may tolerate the defect relatively well for many years. Dogs with severe PS are likely at risk for both sudden cardiac death and progressive right-sided heart failure. Right-sided heart failure can manifest as either congestion behind the right heart (i.e., ascites) or low output failure, or both. Catheter-based or surgical procedures are generally recommended for dogs with moderate to severe PS to lessen the severity of RVOT obstruction, and decrease the risk for sudden death or heart failure.

Some dogs with PS, particularly English bulldogs and boxers, may have an accompanying anomalous left coronary artery. In dogs with this defect, the left coronary artery originates from the right coronary ostia and may course across the right ventricular outflow tract. As a result, the left circumflex coronary artery is at risk for injury during surgical or catheter-based treatments for PS.

Double-Chambered Right Ventricle

Double-chambered right ventricle (DCRV) is an uncommon congenital heart defect of dogs characterized by a fibromuscular diaphragm at the junction of the inflow and outflow portions of the right ventricle [2]. The defect obstructs flow through the mid-portion of the ventricle and causes hypertrophy of the proximal portion of the right ventricle, giving it a "double-chambered" appearance. The pathophysiology and natural history of DCRV are thought to be similar to those of PS.

Subvalvular Aortic Stenosis

Subvalvular aortic stenosis (SAS) is a common congenital defect in certain large and giant breed dogs. The typical defect consists of a discrete subvalvular fibrous membrane located millimeters below the aortic valve leaflets. The membrane traverses the ventricular septum and reflects onto the septal mitral valve leaflet. The defect can be associated with varying degrees of muscular septal hypertrophy and diffuse fibrosis of the left ventricular outflow tract (LVOT) that can contribute to outflow obstruction. The defect is often accompanied by varying degrees of aortic insufficiency. Mitral regurgitation may also be present if the fibrous membrane restricts motion of the septal mitral valve leaflet.

Subvalvular aortic stenosis causes a pressure gradient across the LVOT during left ventricular ejection that, in turn, increases left ventricular systolic pressure. The accompanying increase in ventricular systolic wall stress causes cardiomyocyte hypertrophy, leading to concentric thickening of the left ventricular wall and interventricular septum. Intramural coronary arterial pathology characterized by intimal hyperplasia and medial degeneration has been documented in dogs with SAS [3]. Myocardial oxygen demand is increased by the combination of high systolic wall stress (i.e., afterload) and cardiac hypertrophy. Myocardial oxygen delivery is impaired by abnormal coronary arteries. The resultant mismatch between oxygen demand and delivery causes myocardial ischemia that is exacerbated by activity or exercise. Myocardial ischemia is thought to be the cause of malignant ventricular tachycardia and sudden cardiac death. Median age at sudden death has been reported to be 18 months in dogs with untreated SAS [4]. Chronic β-adrenergic blockade therapy may reduce, but does not eliminate, the risk of sudden death [5]. Surgical intervention has not been shown to decrease the risk of sudden death in dogs with SAS.5 Dogs that avoid early sudden death may develop left-sided congestive heart failure late in life.

Ventricular Septal Defect

Ventricular septal defect (VSD) is a congenital defect that occurs in dogs and cats. The defect allows left-to-right systolic shunt flow from the left to the right ventricle. The magnitude of the pathophysiologic change depends on the size of the defect. Small defects do not allow for equilibration of left and right ventricular systolic pressures and are termed "restrictive." Such defects are associated with low shunt flow. Large defects allow equilibration of ventricular systolic pressures and are associated with high shunt flow. Left-to-right shunt flow causes volume overload of the left heart and pulmonary circulation. The most common anatomic location for VSD in animals is high in the septum behind the septal leaflet of the tricuspid valve. Such defects, termed perimembranous VSD, typically spare the right ventricle from volume overload because shunt flow is ejected directly into the RVOT. Defects located low in the muscular septum may result in volume overload of both sides of the heart. On occasion, VSD occurs dorsal to the supraventricular crest (crista supraventricularis) in the RVOT. Such defects, termed supracristal VSD, are associated with a high incidence of aortic valve leaflet prolapse and concurrent aortic insufficiency. Surgical closure of VSD can be undertaken with the aid of cardiopulmonary bypass with curative intent. Pulmonary artery banding is a palliative surgical procedure intended to decrease shunt flow.

Restrictive VSD is generally well tolerated by both dogs and cats. Large hemodynamically significant defects cause progressive left-sided chamber dilation and congestive heart failure similar to PDA. High shunt flow also can trigger progressive pulmonary vascular remodeling, increased pulmonary vascular resistance, and increased pulmonary arterial pressures. If pulmonary artery pressures reach suprasystemic levels (i.e., exceed systemic arterial pressures), shunt flow reverses and becomes intermittently or continuously right-to-left. This condition, termed Eisenmenger's syndrome, is associated with varying degrees of hypoxemia and polycythemia.

Atrial Septal Defect

Various forms of atrial septal defect (ASD) or atrioventricular septal defect (AVSD) have been described in dogs and cats. Atrial septal defects (ASD) are classified as sinus venosus defects, coronary sinus ASD, ostium secundum (fossa ovalis type) ASD, or patent foramen ovale. Sinus venosus defects are situated cranial and dorsal in the atrial septum at the junction of the cranial vena cava and are frequently associated with anomalous pulmonary venous return. Coronary sinus ASD or unroofed coronary sinus results from an incomplete separation between the coronary sinus and the left atrium; this is often due to the persistence of the left cranial vena cava. Other types of ASD occur directly in the septum primum or the septum secundum, or both. Ostium secundum ASD (fossa ovalis type) occurs in the mid-dorsal portion of the atrial septum. Patent foramen ovale is usually an acquired defect secondary to pressure or volume overload of the right heart. Atrioventricular septal defects represent a spectrum of malformations that involve the septum primum, the inlet portion of ventricular septum, and the atrioventricular valves. Ostium primum ASD is currently classified as a partial AVSD. The defect is characterized by an ostium primum defect and a malformed mitral valve. The mitral valve defect consists of a cleft in the septal leaflet that changes the valve into a trileaflet structure. This malformation usually causes significant mitral regurgitation. Complete AVSD consists of an ostium primum defect above, a VSD below, and a single AV valve that is common to the right and left ventricle. The complete form of AV septal defect was formally termed an endocardial cushion defect.

Atrial septal defects share a common pathophysiology regardless of type. Left-to-right shunt through the defect causes volume overload of the right side of the heart. The right atrium and ventricle dilate in response to chronic volume overload. Increases in right ventricular diastolic pressure lead to progressive right-sided congestive heart failure. As right atrial pressures become elevated, bidirectional shunt and hypoxemia can complicate the clinical picture.

Tetralogy of Fallot

Tetralogy of Fallot (TF) is a complex congenital heart defect consisting of PS, VSD, an overriding aorta, and right ventricular hypertrophy. The defect occurs in both dogs and cats. The pathophysiology and natural history of TF depend on the magnitude of its two primary defects: PS and VSD. Animals with severe pulmonic stenosis and a large VSD will have significant right-to-left shunt resulting in severe hypoxemia. The clinical consequence is moderate to severe cyanosis at rest, profound activity intolerance, and progressive polycythemia. A shortened life span is expected owing to complications related to chronic hypoxemia, polycythemia, and sudden cardiac death. Animals with less severe pulmonic stenosis or restrictive VSD may tolerate the defect to varying degrees. Total correction of TF can be undertaken with the aid of cardiopulmonary bypass with curative intent [5].

Tricuspid Valve Dysplasia

Tricuspid valve dysplasia (TVD) is a congenital malformation of the tricuspid valve that occurs in several large breeds of dog including Labrador retrievers, golden retrievers, and German shepherds. A spectrum of pathologic lesions has been associated with TVD, including shortening, thickening, or notching of leaflets; fusion, absence, or elongation of chordae tendineae; and malformation of papillary muscles. Tricuspid regurgitation (TR) is the most common hemodynamic manifestation, although tricuspid stenosis is possible. Tricuspid regurgitation results from restrictive motion of the valve leaflets and severe progressive dilation of the valve annulus. Severe TR causes volume overload of the right heart and eventual right-sided congestive heart failure. The age at onset of heart failure varies widely among individual dogs. Right-sided congestive heart failure is generally preceded by severe right atrial and ventricular dilation. Pulmonic stenosis or pulmonary hypertension will accelerate the course toward heart failure. Atrial fibrillation is a common late sequela that contributes to progression toward heart failure.