HISTORY OF PRESENT ILLNESS
The patient is a 7-week-old boy who was in good health until 3 weeks prior to presentation. At that time, he developed rhinorrhea, congestion, and cough. He had no history of fever. He was evaluated by his pediatrician. A chest roentgenogram demonstrated a left lower lobe infiltrate. He was then started on a 10-day course of erythromycin for treatment of pneumonia. On completion of this antibiotic course, his mother felt that his respiratory status had improved to some extent, but his work of breathing was still increased from his baseline. Furthermore, his cough was persistent in nature. One week later, a repeat chest roentgenogram revealed persistence of the left lower lobe infiltrate and he was referred for further evaluation. His review of symptoms revealed good oral intake and normal urine output.
He was born at 41 weeks gestation with a birth weight of 3000 g. There were no pregnancy or birth-related complications. He had no history of cyanosis or feeding difficulties. He was feeding on formula, taking two ounces every 2 hours. He has two older siblings who are both healthy.
T 37.3°C; P 153 bpm; RR 54/min; BP RUE 93/59 mmHg, LUE 87/62 mmHg, RLE 94/63 mmHg; SpO2 95% in room air
Weight 4.5 kg
Initial examination revealed a well-developed infant in moderate respiratory distress.
Physical examination was remarkable for nasal flaring, intercostal retractions, and intermittent grunting. He had good aeration and scattered rales at both lung bases. Cardiac examination revealed a normal S1 with a prominent P2. A II-III/VI systolic murmur was appreciated at the left sternal border. The liver edge was palpated 4 cm below the right costal margin. The remainder of the physical examination was normal.
Laboratory analysis revealed a peripheral blood count of 8400 white blood cells/mm3 with 35% segmented neutrophils, 60% lymphocytes, and 5% eosinophils. The hemoglobin was 11.4 g/dL and there were 203 000 platelets/mm3. Electrolytes, blood urea nitrogen, and creatinine were all within normal limits. Antigens of respiratory viruses were not detected by immunofluorescence of nasopharyngeal washings.
COURSE OF ILLNESS
An electrocardiogram was performed that suggested a diagnosis (Figure 4-2).
FIGURE 4-2. Left image: Two-dimensional echocardiogram. Right image: Superimposed color Doppler flows, demonstrating systolic blood flow from left to right through the ventricular septal defect (in red-orange; normal aortic outflow shown in blue). (From: Roger Breitbart, MD, Department of Cardiology, Children’s Hospital Boston, with permission.)
DISCUSSION CASE 4-2
The causes of persistent cough in infants are diverse, but the most common etiology are infections. Viral infections, including respiratory syncytial virus, parainfluenza, and influenza, are the most common. Normal children may develop up to eight viral respiratory infections per year, and if each infection lasts 7-14 days, recurrent infections can appear to cause a chronic cough. Bacterial infections may also cause prolonged cough. In infants with a history of conjunctivitis or maternal cervical infection, Chlamydia trachomatis should be considered. The staccato-like cough is the classic description associated with this infection. Bordetella pertussis can occur in infants and presents with a chronic cough, along with apneic pauses, gagging, cyanosis, and bradycardia. Most often, infants are unable to generate the force necessary for the classic “whoop.” Certainly, other bacterial pneumonias should be considered with the lobar infiltrate noted on chest roentgenogram in the case above.
There are several noninfectious causes of persistent cough in infants. Asthma should always be considered, especially if there is associated wheezing and clinical response to bronchodilators. One should consider gastroesophageal reflux as a possible etiology for cough in infancy. Other less common causes of cough in this age group would include congenital malformations, including trachoesophageal fistulas, tracheobronchomalacia, vascular rings, lobar emphysema, bronchogenic cyst, pulmonary sequestration, laryngeal cleft, and airway hemangiomas. Cystic fibrosis should be on the differential diagnosis, particularly if the patient has a history of meconium ileus, steatorrhea, failure to thrive, or a positive family history for this disease.
Congestive heart failure should always be considered, particularly if there are also feeding difficulties, poor growth, tachycardia, tachypnea, nasal flaring, intercostal retractions, grunting, murmur, and/or hepatomegaly. Etiologies in infancy may include volume overload (patent ductus arteriosus, truncus arteriosus, ventricular septal defect, common atrioventricular canal, total anomalous pulmonary venous return), myocardial dysfunction (myocarditis, anomalous left coronary artery), arrhythmias (supraventricular tachycardia), pressure overload (coarctation of the aorta, aortic stenosis), and secondary causes (hypertension, sepsis).
The features of this case that prompted additional evaluation were the presence of a heart murmur, a loud P2, bilateral rales, and hepatomegaly on the physical examination, as well as biventricular hypertrophy seen on the electrocardiogram. Additional suspicious features would have been the recognition of cardiomegaly and increased vascular markings on the chest roentgenogram.
Electrocardiogram revealed a ventricular rate of 150 bpm and biventricular hypertrophy. An echocardiogram revealed a large perimembranous ventricular septal defect (VSD) with left to right shunting. It also demonstrated moderately depressed biventricular function with a shortening fraction of 29%. The diagnosis is a perimembranous VSD.
INCIDENCE AND EPIDEMIOLOGY
Ventricular septal defects account for up to 40% of cardiac anomalies, making them the most common cardiac malformation seen in children. Studies have shown the incidence of VSD in newborns to be 5-50 per 1000 children with a slight female predominance. VSDs are the most common form of congenital heart disease associated with chromosomal disorders, although most patients with VSD do not have a chromosomal abnormality. Other types of genetic disorders that have recently been shown to be associated with VSD include single gene defects, such as mutations in TBX5 and GATA4. Single gene defects account for only 3% of patients with congenital heart disease. VSD has also been associated with environmental factors such as maternal infection or teratogens.
VSDs may be classified into four types: perimembranous, also known as membranous or infracristal (most common, 80%); outlet, also known as subpulmonary, supracristal, conal, infundibular, or doubly committed subarterial (5%-7%); inlet (5%-8%); and muscular (5%-20%). A diagram of various types of VSD is depicted in Figure 4-3. Muscular defects have the greatest likelihood to undergo spontaneous closure. Approximately 75%-80% of small VSDs will close spontaneously, most often by 2 years of age.
FIGURE 4-3. Anatomy of perimembranous ventricular septal defect. (From the Multimedia Library of Congenital Heart Disease, Children’s Hospital, Boston, MA, editor Robert Geggel, MD, www.childrenshospital.org/mml/cvp, with permission.)
The size of the VSD, the pulmonary vascular resistance, and the relative pressures in the right and left ventricles, are all important determinants of the extent of the left to right shunt. Small defects are known as restrictive, because flow across them is limited by virtue of their size. Small VSDs tend to have the loudest murmur and may also have a thrill. Most infants with small VSDs will have no significant symptoms and will thrive.
In contrast, the flow across larger, so-called non-restrictive defects is determined by the relative pulmonary to systemic vascular resistance. At birth, pulmonary vascular resistance is still elevated, resulting in a lack of shunt and the absence of a murmur on auscultation. As pulmonary vascular resistance declines over the next few weeks of life, the classic harsh, holosystolic murmur becomes apparent upon auscultation along the left sternal border. Most often, the murmur is heard around 1–6 weeks of age (see Table 4-6 for hints on physical examination that may suggest the type of VSD). With large defects, infants will often have a hyperactive precordium. In those infants with moderate or large VSDs, other symptoms can include tachypnea, irritability, diaphoresis or fatigue with feeding, and failure to thrive. These symptoms develop secondary to progressive heart failure and pulmonary edema. Not uncommonly, symptoms come to attention immediately following a respiratory infection, which stresses the infant’s small reserve. The infant in the case above presented precisely in this manner, as evidenced by the left lower lobe infiltrate on chest roentgenogram consistent with probable pneumonia.
TABLE 4-6. Physical examination that may suggest the type of VSD.
Patients with unrestricted left to right shunting experience an increase in pulmonary blood flow and increased pulmonary venous return, which may lead to left atrial and ventricular dilation and hypertrophy. The increased pulmonary blood flow can, over time, lead to elevated pulmonary artery pressure and reversal of the shunt across the VSD from right to left. This condition is known as Eisenmenger syndrome, with clinical features including cyanosis, desaturation, and erythrocytosis.
Chest roentgenogram. With small VSDs, the chest roentgenogram may be normal. In contrast, a large VSD may lead to significant cardiomegaly and increased vascular markings (see Figure 4-4). Later, as patients with untreated VSD develop increased pulmonary vascular resistance, there may be reduced vascular markings.
FIGURE 4-4. Four-month-old infant with large membranous ventricular septal defect. An anterior-posterior chest radio-graph (left panel) shows situs solitus, moderate cardiomegaly, symmetrically increased pulmonary blood flow, and hyper-inflation. (From the Multimedia Library of Congenital Heart Disease, Children’s Hospital, Boston, MA, editor Robert Geggel, MD, www.childrenshospital.org/mml/cvp, with permission.)
Electrocardiography. As with chest roentgenogram, the ECG may be normal with small VSDs. However, with moderate-sized VSDs, there will likely be left ventricular hypertrophy secondary to volume overload of the left ventricle and right ventricular hypertrophy secondary to pressure overload of the right ventricle. Importantly, these changes are not always evident in the ECG of infants with moderate-sized VSDs.
Echocardiography. Two-dimensional echocardiography with doppler is essential to pinpoint the size and location of a VSD. Ventricular, pulmonary artery, and interventricular pressure differences can be determined. Echocardiography also identifies associated cardiac defects and extracardiac vascular structures. Three-dimensional echocardiography, which has been studied more recently, may play a valuable role in characterizing the size and shape of the defect, as well as its spatial relationship to surrounding structures, prior to surgical or catheter-based closure of the defect. Transesophageal echocardiography is used intra-operatively or when transthoracic echocardiography provides limited image quality.
MRI. Cardiac MRI can be used if echocardiography does not reveal sufficient detail. On occasion, MRI may be needed to evaluate extracardiac vascular anomalies.
Cardiac catheterization. Cardiac catheterization is necessary only for patients with complicated cardiovascular anatomy or physiology and need not be performed in all VSD patients. Pulmonary blood flow and vascular resistance may be evaluated in more detail than with Doppler echocardiography. This modality is also used for trans-catheter closure of the VSD in certain patients with muscular defects.
As mentioned, infants with small VSDs usually do not require any intervention.
They do require careful surveillance during the first 6 months of life, assessing growth and respiratory status. Many of these small VSDs will close spontaneously and require no further intervention.
Generally, those infants with moderate/large VSDs will develop some degree of congestive heart failure. Often, medical management is the initial therapy and may include diuretics and digoxin. On occasion, afterload reduction with angiotensin-converting-enzyme inhibitors is also required. In those patients with persistent failure to thrive, caloric augmentation may be required. If the patient’s congestive heart failure and growth failure are not controlled with medical management, surgical intervention is required. Standard repair has been with patch closure via sternotomy and cardiopulmonary bypass. Significant postoperative morbidity is uncommon and surgical mortality is currently quite low.
In recent years, transcatheter VSD closure techniques have been developed, particularly for muscular VSDs. In addition, new hybrid techniques, which combine pediatric cardiac surgery, interventional pediatric cardiology, and transesophageal echocardiography, have been introduced.
Endocarditis prophylaxis guidelines were revised in 2007. For patients with uncomplicated VSDs, antibiotic prophylaxis prior to dental, gastrointestinal, and genitourinary procedures is no longer recommended as it may not be effective in preventing endocarditis. Patients should always be counseled that maintenance of optimal oral health and hygiene is advised, and is more likely to prevent endocarditis than antibiotics prior to dental procedures. However, prophylaxis is still recommended for 6 months following complete repair with prosthetic material, and for life if there is a residual defect at the site or adjacent to a prosthetic patch, since this scenario may inhibit endothelialization.
Patients with Eisenmenger syndrome are generally considered inoperable, and are offered symptomatic therapy for reduced exercise capacity and cyanosis. Partial exchange transfusion may be offered for symptomatic polycythemia.
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