Ventricular septal defects in adults.

Ventricular septal defects (VSDs), first described by Dalrymple in 1847 (1), account for 20% of congenital cardiovascular malformations and 10% of those diagnosed in adults (2, 3). Its prevalence is estimated at 1.17 per 1000 live births and at 0.5 per 1000 adults and has increased lately because of improved detection (4, 5). With one exception (subarterial defect), VSDs have no sex preference. They can be associated with atrial septal defect (35%), patent ductus arteriosus (22%), right aortic arch (13%), and, less often, pulmonary stenosis (6). Multiple VSDs (4% to 18% of isolated defects) are more prevalent in association with double-outlet right ventricle and tetralogy of Fallot and play an important role in these complex congenital malformations (79). This review, however, focuses on isolated defects. Anatomy The ventricular septum is a three-dimensional structure with five components: the membranous septum, the trabecular or muscular septum, the infundibular septum, the atrioventricular septum, and the inlet septum. Ventricular septal defects resulting from deficient growth or failure of fusion of these components vary in size from tiny defects to virtual absence of the septum (10). Understanding of the morphologic characteristics of VSD has been complicated by the plethora of existing classification schemes (1, 1113). Capelli and colleagues (14) described these defects in relation to universally recognized structures: the cardiac valves (Figure 1, top). The most common membranous defects (75% to 80%) result from a defect in the membranous septum inferior to the crista supraventricularis and can extend into the muscular septum (perimembranous) (Figure 1, bottom left). Canal or inlet defects are less frequent (8%), are typically large, and lie beneath both atrioventricular valves, primarily the septal leaflet of the tricuspid valve. This defect, often seen in patients with Down syndrome, rarely presents in adulthood without pulmonary hypertension. Muscular or trabecular defects (5% to 20%) are bordered by muscle within the apical, central (Figure 1, bottom right), or outlet portion of the septum and can be small or large, single or multiple, and occasionally oblique with multiple exits resembling Swiss cheese (2, 15). Subarterial defect, also called outlet, infundibular, conoseptal, or supracristal, is the least common (5% to 7%), except in Asia (30%) (2, 3, 16, 17). It results from deficiency in the septum beneath the semilunar valve but above and anterior to the crista supraventricularis. The resultant loss of support of the right or the noncoronary cusp (or both) causes secondary aortic valve prolapse and regurgitation (18, 19). Figure 1. Septal defects. Top. Positions of different ventricular septal defects. 1 = membranous; 2 = subarterial or supracristal; 3 = muscular or trabecular; 4 = inlet or canal. (Modified from Capelli and colleagues [14] with permission of Excerpta Medica.) Bottom left. Membranous ventricular septal defect (VSD), as seen from the left ventricle, partially obliterated by the septal leaflet of the tricuspid valve (SLTV). Bottom right. Muscular VSD as seen from the left ventricle. (Photographs courtesy of Dr. William D. Edwards, Division of Anatomic Pathology, Mayo Clinic Rochester.) Pathophysiology The direction and volume of the shunt in isolated VSDs are determined primarily by the size of the defect rather than by its location and the ratio of pulmonary to systemic vascular resistance. In adults, the shunt is left to right in the absence of pulmonary stenosis and pulmonary hypertension, resulting in volume overload of the left atrium, both ventricles, and pulmonary arteries. The volume of the shunt dictates the clinical presentation and ultimately the natural history of the patient. The association between aortic regurgitation and VSD, first reported in 1921 (20), is more common in young men (21, 22). Aortic regurgitation is an acquired lesion seen more with subarterial defects than with perimembranous defects. It results from deficiency or hypoplasia of the conal septum that leads to abnormal apposition in diastole and prolapse of the poorly supported noncoronary or right coronary cusp through the VSD into the right ventricle (18, 19). This results in distortion of the aortic valve and progressive aortic regurgitation (Figure 2) (23). Aortic regurgitation often increases in severity with age and indicates a worse prognosis (3, 24). Figure 2. Pathophysiology of aortic regurgitation. In early systole (left), ejected blood from the left ventricle (LV) will be shunted through the ventricular septal defect. As a result, the anatomically unsupported coronary cusp and aortic sinus are driven into the right ventricle (RV) (middle); this is known as the Venturi effect. In diastole (right), the intra-aortic pressure forces the aortic valve leaflet to close, but the unsupported cusp (right or noncoronary) is pushed down into the left ventricular outflow tract away from the opposed coronary cusp, resulting in regurgitation. AR = aortic regurgitation; IVS = interventricular septum; PA = pulmonary artery. (Reproduced from Tatsuno and colleagues [23] with permission of the American Heart Association.) Clinical Presentation At presentation in adults, VSD is a small, medium, or large defect with or without pulmonary stenosis, pulmonary hypertension, or aortic regurgitation (2, 15, 25). Small defects are asymptomatic and could represent a larger defect that became smaller because of incomplete spontaneous closure. Medium defects are uncommon unless associated with protective valvular or subvalvular pulmonary stenosis (25% to 30%) (26). Patients often present with dyspnea. Large VSDs present in infancy with heart failure and require surgery unless they spontaneously become smaller. They can also present in association with pulmonary stenosis or can be complicated by pulmonary hypertension (the Eisenmenger complex). The latter group most commonly presents in adolescence with cyanosis, dyspnea, and syncope (27). Patients with VSD and aortic regurgitation most commonly present with a new diastolic murmur of aortic regurgitation, syncope secondary to right ventricular outflow tract obstruction caused by the prolapsing coronary cusp, or heart failure due to progressive left ventricular volume overload. Physical Examination Most VSDs can be identified by auscultation (Figure 3). This varies depending on the size of the defect; its location; and associated pulmonary stenosis, hypertension, and aortic regurgitation. Small defects are associated with a palpable thrill in the third or fourth intercostal space. The aortic closure sound may be normal or masked by the systolic murmur. A systolic click can be heard in the presence of a septal aneurysm. The defect murmur is a typical harsh holosystolic plateau-shaped murmur of relatively high frequency best heard in the left third and fourth intercostal spaces. If the defect is subarterial, the blood is shunted directly into the pulmonary artery and therefore the murmur is heard maximally in the second intercostal space and may become diamond-shaped (crescendodecrescendo) or simply consist of a systolic ejection component. If the defect is muscular, the murmur may stop well before the second sound because the defect decreases in size or obliterates in the later part of systole. The physical examination of patients with VSD and pulmonary stenosis depends on the degree of right ventricular outflow obstruction. If it is mild, then the VSD murmur is holosystolic but the pulmonary closure sound is delayed. However, if the pulmonary stenosis is moderately severe, then the VSD murmur gets shorter as the left-to-right shunt diminishes, and the pulmonary sound is soft and delayed. If the pulmonary stenosis is severe, the VSD murmur is replaced by a long systolic ejection murmur typical of pulmonary stenosis. Figure 3. The cardiac examination in ventricular septal defect ( VSD Top left. Holosystolic murmur of VSD. Top middle. Shortened systolic murmur of muscular VSD. Top right. Typical murmur of VSD with mild pulmonary stenosis (PS) showing the delayed pulmonary closure sound (P2 ). Bottom left. Systolic ejection murmur of severe pulmonary stenosis with delayed and reduced P2. Bottom middle. Eisenmenger complex with absence of the holosystolic murmur of VSD, a loud P2 secondary to pulmonary hypertension, and pulmonary regurgitation (PR) diastolic murmur. Bottom right. VSD murmur followed by diastolic murmur of aortic regurgitation (AR); A2 = aortic closure sound; C = ejection click; S1 = first heart sound. Patients with the Eisenmenger syndrome are often cyanotic, with clubbed fingers and toes. Most have increased venous pressure, predominantly an A wave due to right ventricular hypertrophy and decreased compliance. A V wave is seen in association with a failing right ventricle and tricuspid regurgitation. The right ventricular impulse is prominent secondary to hypertrophy accompanied by a palpable single and loud pulmonary closure sound. A midsystolic pulmonary ejection click is often heard from a dilated pulmonary artery. The systemic pulmonary artery pressure abolishes the left-to-right shunt, and the holosystolic murmur therefore vanishes. A diastolic blowing murmur of pulmonary regurgitation may be heard in the left upper sternal border. Later in life, an additional systolic murmur of tricuspid regurgitation may be heard at the left lower sternal border in association with the onset of right-sided heart failure. Patients with VSD and aortic regurgitation often demonstrate a wide pulse pressure as well as other features of aortic regurgitation. The murmur is to-and-fro, best heard in the upper sternal border, and composed of a systolic VSD murmur that can be plateau-shaped or diamond-shaped and a separate, high-frequency diastolic murmur of aortic regurgitation. This may simulate murmurs of a coronary artery fistula, a ruptured sinus of Valsalva aneurysm, or a pa