A female infant born at 38 weeks via uncomplicated spontaneous vaginal delivery presents hours after birth with cyanosis and respiratory distress.
Prenatal history was significant only for intrauterine growth restriction. The infant was intubated and brought to the NICU for stabilization. Physical exam revealed a cyanotic infant with oxygen saturation ranging from 76-83% on 40% FiO2 and PaO2 in mid 30s. Auscultation of the lungs was clear throughout. Cardiac examination revealed a regular rate and rhythm with a non-specific short Gr I/VI systolic murmur at the LUSB. The remainder of the physical exam was normal.
CXR showed a normal sized heart with interstitial edema in both lung fields.
EKG revealed a normal sinus rhythm with left axis deviation and right ventricular hypertrophy.
Select echocardiogram clips are shown below.
On the first day of life she underwent emergent surgical repair of her congenital cardiac lesion. After weaning from cardiopulmonary bypass, systemic blood pressure is 53/31 mmHg, PA pressure 57/29 mm Hg and left atrial pressure is 13 mm Hg. An arterial blood gas showed a pH = 7.47, pCO2 33 mm Hg, paO2 72 mm Hg.
Which of the following is the most appropriate next step in management?
The correct answer is: C. Begin inhaled nitric oxide.
This patient was born with obstructed infra-cardiac total anomalous pulmonary venous connection (TAPVC), as illustrated in Videos 1, 2, and Figure 1, which demonstrate a dilated right heart (Video 1), and a descending vein, the Doppler flow pattern of which exhibits continuous, turbulent flow without phasic respiratory variation. (Video 2 and Figure 1).
Pulmonary hypertension is frequent immediately following repair of total anomalous pulmonary venous return, especially in patients with significant pre-operative pulmonary venous obstruction. Etiologies include anatomic obstruction to pulmonary venous return (either at the anastomosis of the veins to the left atrium or in the veins themselves), high left atrial pressure and elevated pulmonary vascular resistance. Video 3 shows a non-obstructed pulmonary venous confluence anastomosis to the left atrium, demonstrating that there is no anatomic surgical reason for the continued pulmonary hypertension. Echocardiography can accurately evaluate the pulmonary venous anastomosis, while a CT angiography or cardiac catheterization with hemodynamic assessment may be required to evaluate more distal intrinsic abnormalities of the pulmonary veins themselves or elevation in pulmonary vascular resistance, respectively.
In TAPVC, a relatively small, noncompliant, left ventricle and left atrium can result in high left atrial pressures. Creating an opening in the atrial septum or reopening the vertical vein has been suggested to decompress the left atrium. However, these approaches will produce a left-to-right shunt, "volume loading" the right ventricle and pulmonary vascular bed, which may then be transmitted to the left atrium. Epinephrine has nonspecific vasoconstriction effects that may further elevate pulmonary vascular resistance. Inhaled nitric oxide selectively dilates the pulmonary vascular bed. It is effective treatment for postoperative pulmonary hypertension, particularly when there was preoperative pulmonary venous obstruction. Another possible strategy in the medical management of elevated pulmonary vascular resistance is inducing mild hyperventilation to produce respiratory alkalosis.
When pulmonary artery pressures are higher than aortic pressure, eventual right ventricular failure, low cardiac output, metabolic acidosis, and death may result. If medical interventions such as nitric oxide are unsuccessful, extracorporeal membrane oxygenation may be an alternative option.
Nitric oxide was started intra-operatively and was weaned off over the next several days. Pre-discharge echocardiogram showed unobstructed pulmonary venous confluence with a mean gradient of less than 1 mmHg across its area of anastomosis to the left atrium. As of last follow up, the patient was doing well.
Total anomalous pulmonary venous connection (TAPVC) is characterized by an abnormal connection between the pulmonary veins and the left atrium. Rather than entering the left atrium, these aberrant pulmonary veins come together into a confluence, which then drain into the systemic venous circulation by one of four pathways: supracardiac, infracardiac, cardiac, or mixed.1
The prevalence of TAPVC is 1-2% of all congenital heart defects (CHD). It is the fifth most common cyanotic CHD, occurring in approximately 0.6-1.2 per 10,000 live births.2,3 The gender ratio for supracardiac and cardiac TAPVC is roughly equal, however there is a 4:1 male predominance in the infradiaphragmatic subtype.4
The majority of TAPVC are supracardiac (45%); where the pulmonary veins come together as a confluence which is then drained by an ascending vertical vein that terminates in the innominate vein. In cardiac TAPVC (25%), the confluence is connected to the coronary sinus on the right atrium. Lastly, in the infracardiac subtype (21%), the confluence drains below the diaphragm into the systemic circulation via either the portal vein, hepatic vein or ductus venosus.
From an embryologic perspective, TAPVC is due to a failure of the pulmonary venous plexus to connect with the common pulmonary vein before the splanchnic venous plexus has regressed. This results in a persistent connection between the pulmonary veins and the systemic venous system.5
The clinical presentation of TAPVC will vary depending on the level of obstruction at the time of presentation. Obstruction can occur either at the level of the intra-atrial septum or at the anomalous venous channels. The most common site of obstruction in all types of TAPVC is the connection of the vertical vein with the systemic circulation. The infracardiac subtype is most likely to be obstructed at presentation, as opposed to the supracardiac and cardiac types. There are several anatomic reasons for this. If the descending vertical vein drains into the ductus venosus, obstruction will occur as the vessel begins to constrict after birth. Additionally, the descending vein passes through the diaphragm in the esophageal hiatus where there is the potential for extrinsic compression. Finally, the pathway back to the right heart from the portal system is a high resistance circuit secondary to the hepatic microvasculature that must be traversed.
Without surgical intervention approximately 80% of these patients will die within the first year of life.6 The current surgical mortality is between 0-8%,7 with the lowest mortality being associated with patients who are not obstructed at the time of presentation. Surgical mortality rates increase when surgery is performed emergently or on a critically ill patient with pulmonary venous obstruction.
The long term outcome for repaired TAPVC is excellent. As the repair results in normal circulation, these children can be expected to develop and grow normally, with the majority remaining asymptomatic into adulthood.
Rare complications may occur after surgery, the most troublesome being obstruction to one or more of the pulmonary veins. Signs of pulmonary hypertension should prompt a workup for this possibility. Other complications include arrhythmias, which are also relatively rare. Close follow up in the early post-operative period followed by annual evaluations provide opportunities for early identification of possible complications and plan intervention. As long as there is no evidence of pulmonary venous obstruction, arrhythmia or pulmonary hypertension, patients will not require activity restrictions nor prophylaxis for bacterial endocarditis.
Craig JM, Darling RC, Rothney WB. Total pulmonary venous drainage into the right side of the heart; report of 17 autopsied cases not associated with other major cardiovascular anomalies. Lab Invest 1957;6:44-64.
Bernstein D. Total Anomalous Pulmonary Venous Return. In: Kleigman R, Behrman R, Jenson H, Stanton B (eds). Nelson Textbook of Pediatrics, 18th ed. Philadelphia: WB Saunders, 2007.
Reller MD, Strickland MJ, Riehle-Colarusso T, Mahle WT, Correa A. Prevalence of congenital heart defects in metropolitan Atlanta, 1998-2005. J Pediatr 2008;153:807-13.
Satpahty M, Mishra BR. Clinical Diagnosis of Congenital Heart Disease, 2nd ed. New Delhi: Jaypee. 2015.
Hines MH, Hammon JW. Anatomy of total anomalous pulmonary venous connection. Oper Tech Thorac Cardiovasc Surg 2001;6:2-7.
Burroughs JT, Edwards JE. Total anomalous pulmonary venous connection. Am Heart J 1960;59:913-31.
Kirshbom PM, Myung RJ, Gaynor JW, et al. Preoperative pulmonary venous obstruction affects long-term outcome for survivors of total anomalous pulmonary venous connection repair. Ann Thorac Surg 2002;74:1616-20.