CASE 1

History

A full-term neonate, the product of an uncomplicated pregnancy and delivery, presents with cyanosis after normal spontaneous vaginal delivery. There is no family history of intrauterine demise, congenital heart disease, or sudden unexplained death. There was no prenatal drug or toxin exposure. The infant’s mother tested negative for group B Streptococcus, cytomegalovirus, human immunodeficiency virus, and hepatitis B; she is immune to rubella.

Physical Exam

Pulse oximetry reveals upper and lower extremity saturation of 75% to 80% on room air. One hundred percent blow-by-oxygen does not affect systemic saturations. Heart rate is 135 bpm. Respiratory rate is 30 breaths/min. Upper and lower extremity blood pressures are normal and equivalent. Physical exam reveals a fully developed term infant without any dysmorphic features. The infant is breathing comfortably without any respiratory distress. Precordial impulse is normal by palpation. There is a harsh 2 to 3/6 systolic ejection type murmur at the left upper sternal border. Lung fields are clear. Radial and pedal pulses are normal and symmetric. There is no radial-femoral pulse delay.

CASE 2

History

A 34-year-old female Russian immigrant is referred for cardiology evaluation with a history of a heart murmur since birth. She has no specific complaints, although she describes a vague history of shortness of breath and fatigue at peak exertion. She denies any cyanosis. She has never been hospitalized or had surgery. There is no family history of congenital heart disease or sudden unexpected death.

Physical Exam

Vital signs include the following: heart rate 76 bpm, respiratory rate 14 breaths/min, right arm blood pressure 111/68 mm Hg; right leg blood pressure 115/72 mm Hg, and oxygen saturation 99%. On physical exam, she is a thin, healthy-appearing female who is in no distress. Carotid artery pulses are normal without bruit. She has no jugular venous distension. Radial and femoral pulses are 2+ and symmetric; there is no radial-femoral pulse delay. Chest is symmetric without deformity. Subxiphoid cardiac impulse is pronounced. There are no palpable thrills. There is an early systolic ejection click at the left upper sternal border. A harsh 3/6 systolic ejection murmur that spills into early diastole is heard throughout the precordium, most prominently at the left upper sternal border; there are no diastolic murmurs. Lungs are clear without wheezes, rales, or rhonchi. Her abdomen is soft, nontender, and flat with no hepatosplenomegaly. Extremities are warm and well perfused with no clubbing or cyanosis. There is trace pedal edema.

CASE 1

The differential diagnosis of cyanosis in a term newborn includes many cardiac and noncardiac etiologies. Cyanosis that resolves or improves significantly with administration of supplemental oxygen suggests a noncardiac etiology. The most common congenital heart defect presenting with cyanosis in a term newborn is transposition of the great arteries. Other causes of irreversible neonatal cyanosis include lesions in which pulmonary blood flow is restricted (eg, tetralogy of Fallot, pulmonary atresia, critical pulmonary valve stenosis) and lesions in which systemic venous return and pulmonary venous return mix completely at the atrial or ventricular level (eg, tricuspid atresia, hypoplastic left heart syndrome, double inlet left ventricle, truncus arteriosus, total anomalous pulmonary venous return). Ductal-dependent left heart obstructive lesions can likewise cause cyanosis with a murmur (eg, critical aortic stenosis with a large ductus arteriosus). Interrupted aortic arch and critical coarctation of the aorta with a patent ductus arteriosus may not present with a significant heart murmur but would manifest lower body cyanosis or desaturation.

In case 1, a harsh systolic murmur and severe desaturation suggest a lesion with obstruction to pulmonary blood flow, likely at the level of the pulmonary outflow tract—tetralogy of Fallot or critical pulmonary valve stenosis—although critical aortic stenosis should also be considered.

CASE 2

The differential diagnosis of a murmur in an otherwise healthy adult is broad. If the murmur has been present consistently since birth, the likelihood of a congenital heart defect is high. The lack of severe symptoms, however, suggests mild disease. Specific defects associated with a heart murmur that may go unrecognized or untreated until adulthood include the following: atrial-level shunts (eg, secundum atrial septal defect [ASD], sinus venosus ASD, primum ASD, unroofed coronary sinus, partial anomalous pulmonary venous return), right heart obstructive lesions (eg, valvar, supravalvar, or subvalvar pulmonary stenosis [PS]; pulmonary artery [PA] stenosis; or double-chamber right ventricle), and left heart obstructive lesions (eg, valvar, supravalvar, or subvalvar aortic stenosis; coarctation of the aorta; or hypertrophic obstructive cardiomyopathy). The harsh quality of the murmur is more likely to be an obstructive lesion than an atrial-level shunt. The location of the murmur (left upper sternal border) and prominent subxiphoid impulse suggest a right heart obstructive lesion. An early systolic click supports the diagnosis of a bicuspid valve (in this case, a bicuspid pulmonary valve). The relative lack of symptoms also favors PS over aortic valve stenosis, assuming a moderate or severe degree of obstruction.

MANAGEMENT OF CRITICAL NEONATAL PS

Initial Testing

In the neonate with a murmur and cyanosis after birth, a chest x-ray is indicated as a first-line test (Figure 24-1). In the presence of critical PS, the cardiac silhouette may be normal or enlarged. There may be prominence of the main PA segment. In the presence of a large, nonrestrictive ductus arteriosus, pulmonary vascularity may be normal or even increased. If the ductus is restrictive or absent, then distal pulmonary vasculature is likely to be diminished. An electrocardiogram (ECG) is not often required for the diagnosis of critical PS in the neonate. However, given the likelihood of transcatheter and possible surgical intervention, an ECG may be acquired. In the presence of severe or critical PS, the electrocardiogram may demonstrate right ventricular (RV) hypertrophy with high-voltage R waves in the right precordial leads (V₁, V₂). Right-axis deviation is often present. Peaked P waves in multiple leads suggest right atrial enlargement.

Transthoracic echocardiography provides definitive diagnosis of critical PS. By definition, critical PS is diagnosed when the antegrade flow across the pulmonary valve is inadequate to provide sufficient oxygenation to support circulation and the metabolic demands of the patient.

A complete transthoracic echocardiogram should be performed to prove otherwise normal anatomy including normal situs and cardiac positioning, normal atrial-ventricular connections, and normal ventricular–great arterial relationships. It also will distinguish between critical PS and pulmonary atresia. In both critical PS and pulmonary atresia, antegrade pulmonary blood flow is inadequate and must be supplemented, initially via a patent ductus arteriosus (PDA). In some cases, a large, nonrestrictive PDA can complicate the ability to identify antegrade pulmonary blood flow using echocardiography and color Doppler, making the differentiation of PS from pulmonary atresia difficult. On occasion with critical PS, pulmonary valve regurgitation may be identified even if antegrade, systolic flow across the pulmonary valve is not obvious. Clinically, however, the presence of a harsh systolic murmur would exclude pulmonary valve atresia as a potential diagnosis. When considering the feasibility and procedural aspects of balloon valvuloplasty, echocardiography is useful for measuring the pulmonary valve annulus size and defining the morphology of the valve, if possible. Pulmonary valve morphology may predict the likelihood of a successful valvuloplasty; thin, doming bicuspid pulmonary valves are more likely to respond to balloon valvuloplasty than thickened, dysplastic trileaflet valves (Figure 24-2).

A right-to-left shunt at the atrial level through the patent foramen ovale or an ASD is almost always present. This atrial shunt results from severe RV hypertension and hypertrophy, leading to elevated filling pressures and elevated right atrial pressures that exceed left atrial pressures. Thus, desaturated systemic venous return mixes with saturated pulmonary venous return and is the cause of the systemic arterial desaturation seen with critical PS.

RV function and the degree of RV hypertrophy should be assessed. Any dynamic subvalvar RV outflow tract obstruction should also be described, because this may result in a persistent RV to PA gradient after otherwise successful pulmonary valvuloplasty. The branch PAs should be shown and defined as being confluent. Poststenotic main PA and branch PA dilatation may be present.

Medical Management

Stabilization of the acutely ill infant with critical pulmonary valve stenosis involves assessing of the infant’s respiratory pattern and work of breathing and supporting the patient with supplemental oxygen and ventilatory support as needed. Intravenous access should be obtained, typically by cannulating the umbilical vein. In the presence of cyanosis that is not responsive to oxygen, prostaglandin E₁ (PGE₁) should be initiated intravenously even if definitive diagnosis with transthoracic echocardiography is not readily available. Once the diagnosis of critical PS is confirmed, the PGE₁ should be continued until after therapeutic intervention. Except in extreme circumstances, inotropic support is typically not necessary in neonates with critical PS.

Therapeutic Intervention

Indications for Intervention

Transcatheter pulmonary valvuloplasty is the first-line and potentially definitive treatment of critical PS. Balloon valvuloplasty is indicated in an urgent fashion once the diagnosis of “critical” PS is made. Critical PS is diagnosed when the severity of obstruction is such that cardiac output is impaired in the absence of a PDA, or when the resulting right-to-left shunting across the atrial septum produces significant desaturation (often less than 85% by pulse oximetry). In such a situation, there is no advantage to delaying intervention. Surgical valvotomy, once the standard of care, has been supplanted by transcatheter valvuloplasty. In some cases, however, when transcatheter valvuloplasty is unsuccessful, surgical valvotomy or RV outflow tract reconstruction may be needed.

Procedural Technique

Balloon pulmonary valvuloplasty is typically performed from a femoral venous approach. A modified Seldinger technique is used to puncture the femoral vein and establish reliable access with hemostatic sheath. Sheath size will depend on the size of the diagnostic catheters and valvuloplasty balloon that will be used; in most neonates, a 4- or 5-Fr internal diameter sheath will suffice.

After vascular access and administration of anticoagulation, an angiographic catheter is advanced into the RV. We typically use a Berman angiographic balloon catheter (Arrow International, Redding, PA). Biplane RV angiography (straight anteroposterior [AP] and lateral or slight cranial AP and straight lateral) using 1 to 1.5 mL/kg of contrast allows for measurement of the pulmonary valve annulus and will define any subvalvar RV outflow obstruction. On occasion, a contrast injection by hand through an end-hole catheter may provide better definition of valve anatomy and may help distinguish between pulmonary atresia and critical PS (Figure 24-3).

Depending on the patient’s clinical stability, hemodynamic catheterization is performed. Ideally this is performed with a balloon-tipped wedge catheter that will reduce the risk of damage to the tricuspid valve from the inevitable catheter and wire exchanges. In smaller neonates, the balloon wedge catheter may not readily follow the direction of the flow and may be difficult to direct across the tricuspid valve. In such cases, either a deflecting wire or a curved stiff end of a wire advanced to just before the tip of the wedge catheter may help direct it across the tricuspid valve. Alternatively, an end-hole directional catheter such as a Cordis Judkins right coronary catheter (Cardinal Health, Milpitas, CA) or a hydrophilic, angled Terumo Glidecath (Terumo Medical, Somerset, NJ) and a soft wire may facilitate hemodynamic catheterization and crossing the tricuspid and pulmonary valves. Depending on the severity of valvar obstruction, traversing the pulmonary valve can be quite difficult. Often this requires the use of an angled hydrophilic wire. On occasion, a smaller diameter coronary wire may be useful to help cross the stenotic valve. Once across the pulmonary valve, the guidewire should be advanced through the PDA and down the descending aorta (Figure 24-4). This position provides optimal wire stability and avoids the risk of trauma to smaller, distal branch PAs with positioning of the wire in the right or left PA.

When the wire is across the pulmonary valve and advanced into the distal descending aorta, the diagnostic catheter is advanced across the valve annulus over the wire until the catheter tip is likewise in the distal descending aorta. The hydrophilic or coronary wire is then removed and exchanged for an exchange-length, more rigid wire to support a balloon for valvuloplasty. In neonates with critical PS, our preference is to use a hydrophilic tipped V-18 wire (Boston Scientific, Natick, MA), which has a diameter of 0.018 inch. A slight curve can be made in the hydrophilic tip using a sheath dilator or the edge of the handle of a scalpel and will allow for some directional control of the wire. Proximal to the hydrophilic tip, the wire becomes quite stiff, which nicely stabilizes the balloon during valvuloplasty. However, the course of the stiff wire through the right heart in a small child can temporarily disrupt tricuspid valve function and lead to hemodynamic compromise, particularly in the setting of critical RV outflow obstruction. In addition, the patient’s cardiac rhythm should be constantly monitored, because the wire may induce ventricular ectopy or disrupt atrioventricular conduction. If the V-18 wire causes any hemodynamic instability, it should be exchanged for a less rigid wire.

Once the exchange-length wire is in position, valvuloplasty is performed. Selecting a balloon for valvuloplasty depends on a number of factors, including the diameter, the length, and inflation pressure. Ultimately the target balloon–to–valve annulus ratio is 1.2 to 1.4 (ie, the nominal balloon diameter should be 120%-140% the diameter of the pulmonary valve annulus). A short balloon should be selected, preferably no longer than 2 cm. Longer balloons may extend across into the RV inlet and damage tricuspid valve function when inflated. Unless starting with a smaller balloon diameter, as described below, the initial valvuloplasty should be performed with a low-pressure balloon, such as the Tyshak series of pediatric valvuloplasty balloons (NuMed, Hopkinton, NY; Figure 24-5). In most cases, the small-diameter Tyshak balloons, although compliant, are able to handle adequate inflation pressure to produce a successful valvuloplasty. In the event that low-pressure valvuloplasty is unsuccessful, one can consider higher pressure dilation such as a Z-MED II balloon (NuMed).