Basics
Description
Hypoplastic left heart syndrome (HLHS) is a continuum of congenital cardiac defects resulting from severe underdevelopment of the structures of the left side of the heart (left atrium, mitral valve, left ventricle, aortic valve, and ascending aorta).
Epidemiology
- 0.16-0.36 per 1,000 live births
- 8% of congenital heart disease (CHD); 3rd most common cause of critical CHD in the newborn
- 23% of all neonatal mortality from CHD
- Male predominance (67%)
Risk Factors
Genetics
- Familial inheritance: Sibling recurrence risk ranges from 8% to 21%, with higher recurrence observed when cardiovascular malformations are present in either parent. In addition, rare kinships have a frequency approaching autosomal dominant transmission.
Commonly Associated Conditions
- Increased mortality when associated with definable genetic disorders, which comprise 10-28% of HLHS patients:
- Turner syndrome, Noonan syndrome, Smith-Lemli-Opitz syndrome, Holt-Oram syndrome
- Trisomy 13, 18, 21, or microdeletion syndromes
- Major extracardiac anomalies (diaphragmatic hernia, omphalocele)
Pathophysiology
- The etiology appears multifactorial, most likely resulting from an in utero reduction of left ventricular inflow or outflow (mechanisms postulated include premature closure of the foramen ovale and fetal cardiomyopathy).
- As a result, the right ventricle (RV) must supply both the pulmonary and systemic circulations (via the ductus arteriosus) before and after birth.
- The reduction in pulmonary vascular resistance that occurs with lung expansion at birth reduces the proportion of RV output to the systemic circulation. If the ductus arteriosus closes, shock occurs.
Diagnosis
History
- In the current era, HLHS is often diagnosed prenatally.
- Postnatal signs and symptoms:
- Respiratory distress (tachypnea, grunting, flaring, retractions)
- Cyanosis
- Cardiovascular collapse and profound metabolic acidosis when the ductus arteriosus closes
Physical Exam
- CHF secondary to pulmonary overcirculation (e.g., tachycardia, hepatomegaly, gallop)
- Normal S1 and single S2 (A2 absent); a murmur of tricuspid regurgitation may be auscultated
- Varying degrees of cyanosis
- Decreased perfusion and weak peripheral pulses
Diagnostic Tests & Interpretation
Lab
- Chest radiograph: varying degree of cardiomegaly with increased pulmonary vascular markings (if the atrial septum is intact or highly restrictive, lungs will appear hazy with a pulmonary venous obstructive pattern)
- ECG: right axis deviation (+90 to +210 degrees), RV hypertrophy with a qR pattern in the right precordial leads, decreased left ventricular forces with an rS pattern in the left precordial leads
- Echocardiogram: varying degrees of hypoplasia or atresia of the mitral valve, left ventricle, aortic valve, ascending aorta, and aortic arch; patent ductus arteriosus with right-to-left shunt in systole and diastolic flow reversal; atrial septal defect with left-to-right flow
- Cardiac catheterization: no longer routinely performed; similar findings as with echocardiography
Differential Diagnosis
- Cardiac: Other causes of circulatory collapse in the neonate include critical aortic stenosis and coarctation of the aorta, cardiomyopathy (infectious, metabolic, or hypoxic), persistent supraventricular tachycardia, obstructive cardiac neoplasms, and large arteriovenous fistulae.
- Noncardiac: neonatal septicemia, respiratory distress syndrome, inborn errors of metabolism
Treatment
Initial Stabilization
During initial resuscitation and stabilization of a newly diagnosed infant:
- Prostaglandin E1 therapy should be initiated as soon as possible to maintain ductal patency.
- Avoid using oxygen despite low pulse oximetry saturation. Increasing FiO2 will lower pulmonary vascular resistance, preferentially shunting cardiac output away from the systemic circulation toward the lungs, thereby worsening systemic perfusion.
- Should invasive ventilation be required, avoid hyperventilation.
- Permissive hypercapnea is preferred due to the secondary increase in pulmonary vascular resistance and subsequent improvement in systemic perfusion.
- Maintain mildly elevated Paco2 levels (40-50 mm Hg).
Supportive Care
- Although surgical intervention has become the medical standard, supportive measures are sometimes offered, especially when multiple noncardiac congenital anomalies exist or when severe multiorgan system damage is present.
- The preoperative goal is to balance the systemic and pulmonary circulations provided by the RV to a Qp/Qs (ratio of pulmonary to systemic blood flow) of ~1:1, usually achieved with a pulse oximetry measurement of 75%.
- Prostaglandin E1 infusion: 0.05-0.1 mcg/kg/min
- Aggressive treatment of hypocalcemia with calcium boluses, avoidance of metabolic acidosis with fluid boluses, consider sodium bicarbonate
- 0.21 FiO2, goal PaO2 of 35-40 mm Hg
- Careful use of small amounts of inotropic agents (in cases of sepsis or RV failure). Aggressive use of inotropic agents (alpha effect) may worsen systemic perfusion.
Surgery/Other Procedures
- Palliative surgery is generally performed in 3 stages:
- Stage I Norwood palliation (performed in the first few days of life or soon after presentation): transection of the main pulmonary artery with anastomosis of the augmented aortic arch to the pulmonary valve stump to form a neoaortic valve and arch, placement of an aorta-to-pulmonary artery shunt (modified Blalock-Taussig shunt), and often an atrial septectomy. The RV provides both systemic and pulmonary blood flows with postoperative saturations of ~75%.
- Stage I Sano modification: Developed in 2003 as an alternative to the Norwood procedure, the Sano modification replaces the modified Blalock-Taussig shunt with an RV to pulmonary artery conduit, with the RV continuing to supply both pulmonary and systemic circulations.
- Hybrid procedure: An additional alternative to the Norwood procedure uses both median sternotomy (pulmonary artery banding) and interventional cardiac catheterization (PDA stenting) to provide both systemic and pulmonary blood flow while avoiding cardiopulmonary bypass.
- Stage II/Hemi-Fontan or bidirectional Glenn procedure: involves anastomosis of the superior vena cava to the pulmonary artery, resulting in volume unloading of the RV. All prior shunts are usually removed. The oxygen saturations after this procedure are usually 85-90%.
- Stage III/Modified Fontan procedure: baffling the inferior vena cava to the pulmonary artery with placement of a small fenestration in the baffle, permitting a small residual right-to-left shunt. The RV is now supplying only systemic blood flow. The oxygen saturations after this procedure are usually 90-95%.
- There are many surgical modifications to these 3 procedures. In addition, these procedures may be performed at different ages based on an institution's experience. Our approach has been to perform the hemi-Fontan operation at 4-6 months of age and the Fontan operation at 18 months to 2 years of age.
- Orthotopic heart transplantation may be performed either as an initial approach or after a stage I palliation.
Follow-up Recommendations
Admission Criteria
The admission for the first operation usually lasts for about 3-4 weeks after birth. Patients are watched to ensure stable oxygen saturation and weight gain. Nutritional needs often require nasogastric tube feed supplementation.
Prognosis
- Fatal if untreated (95% mortality within the first month of life)
- Improved outcomes may result from early diagnosis and prevention of the presentation as neonatal shock.
- 90% early survival after stage I palliation if treated in a timely fashion at experienced institutions
- 5% mortality at stage II hemi-Fontan (bidirectional cavopulmonary anastomosis) procedure
- Recently, 1% mortality at Fontan operation (with the addition of a fenestration to allow right-to-left shunting)
- Excluding infants who die waiting for a donor organ, the 5-year actuarial survival for either staged palliation (Fontan) or heart transplantation is similar, ~75%.
Complications
Neonatal presentation:
- Circulatory collapse with resultant metabolic acidosis
- Multiorgan system failure (i.e., necrotizing enterocolitis, renal failure, liver failure, CNS injury)
Patient Monitoring
Interval evaluations should include careful consideration of growth parameters, cardiovascular symptoms, and developmental milestones. Examinations should focus on the presence or absence of cyanosis, edema, pleural effusions, diarrhea, ascites, and arrhythmias.
- For patients after staged palliation, frequent echocardiograms and intermittent cardiac catheterizations may be needed to assess for the following:
- RV dysfunction
- Residual or recurrent aortic arch obstruction
- Branch pulmonary artery narrowing
- Venous collateral formation causing increased cyanosis
- Protein-losing enteropathy
- Sinus node dysfunction
- Atrial arrhythmias
- For patients treated alternatively with heart transplantation, other lifelong issues should be addressed:
- Graft rejection and/or coronary vasculopathy
- Infection
- Hypertension
- Lymphoproliferative disease
- Follow-up medications:
- Lifelong subacute bacterial endocarditis (SBE) prophylaxis
- Furosemide is generally administered until the hemi-Fontan.
- Afterload reduction (i.e., angiotensin-converting enzyme inhibitors) may be used to reduce the workload on the heart at any stage.
- Antiplatelet (aspirin) and anticoagulant (Coumadin) therapies are used by most physicians after stage 1 and later in the setting of the low-flow state of the cavopulmonary connection.
- For transplant patients, immunosuppressive regimens are managed differently according to institution preferences.
Additional Reading
- Alsoufi B, Bennetts J, Verma S, et al. New developments in the treatment of hypoplastic left heart syndrome. Pediatrics. 2007;119(1):109-117. [View Abstract]
- Grossfeld P. Hypoplastic left heart syndrome: new insights. Circ Res. 2007;100(9):1246-1248. [View Abstract]
- Mahle WT, Clancy RR, McGaurn SP, et al. Impact of prenatal diagnosis on survival and early neurologic morbidity in neonates with the hypoplastic left heart syndrome. Pediatrics. 2001;107(6):1277-1282. [View Abstract]
- McClure CD, Johnston JK, Fitts JA, et al. Postmortem intracranial neuropathology in children following cardiac transplantation. Pediatr Neurol. 2006;35(2):107-113. [View Abstract]
- Pigula FA, Vida V, Del Nido P, et al. Contemporary results and current strategies in the management of hypoplastic left heart syndrome. Semin Thorac Cardiovasc Surg. 2007;19(3):238-244. [View Abstract]
- Stamm C, Friehs I, Mayer JE, et al. Long-term results of the lateral tunnel Fontan operation. J Thorac Cardiovasc Surg. 2001;121(1):28-41. [View Abstract]
- Tabbutt S, Dominguez TE, Ravishankar C, et al. Outcomes after the stage I reconstruction comparing the right ventricular to pulmonary artery conduit with the modified Blalock Taussig shunt. Ann Thorac Surg. 2005;80(5):1582-1590. [View Abstract]
- Tworetzky W, McElhinney DB, Reddy VM, et al. Improved surgical outcome after fetal diagnosis of hypoplastic left heart syndrome. Circulation. 2001;103(9):1269-1273. [View Abstract]
- Wernovsky G, Ghanayem N, Ohye RG, et al. Hypoplastic left heart syndrome: consensus and controversies in 2007. Cardiol Young. 2007;17(Suppl 2):75-86. [View Abstract]
Codes
ICD09
- 746.7 Hypoplastic left heart syndrome
- 758.6 Gonadal dysgenesis
- 759.89 Other specified congenital anomalies
ICD10
- Q24.8 Other specified congenital malformations of heart
- Q96.9 Turner's syndrome, unspecified
- Q87.1 Congenital malform syndromes predom assoc w short stature
- E78.72 Smith-Lemli-Opitz syndrome
- Q87.2 Congenital malformation syndromes predominantly involving limbs
SNOMED
- 62067003 Hypoplastic left heart syndrome (disorder)
- 38804009 Turner syndrome (disorder)
- 205824006 Noonan's syndrome (disorder)
- 43929004 Smith-Lemli-Opitz syndrome (disorder)
- 19092004 Holt-Oram syndrome (disorder)
FAQ
- Q: What should the differential diagnosis include when an infant with HLHS who's undergone stage I palliation presents with cyanosis and respiratory distress?
- A: Modified Blalock-Taussig shunt thrombosis, anemia, intercurrent lower respiratory tract infection leading to V/Q mismatch, low cardiac output state, sepsis
- Infants with HLHS status post stage I palliation are solely dependent on the modified Blalock-Taussig shunt for pulmonary blood flow. This synthetic tube graft ranges from 3.5 to 4 mm in diameter and is prone to thrombosis, especially during periods of illness, which lead to dehydration (gastroenteritis), poor nutrition, or systemic inflammation.
- Q: Should there be a specific concern if a patient with HLHS who's completed the 3-stage palliation with Fontan procedure presents with complaints of unremitting diarrhea, crampy abdominal pain, ascites, and peripheral edema?
- A: Yes. Protein-losing enteropathy (PLE) is a poorly understood disease process affecting patients with single ventricle after Fontan operation associated with significant morbidity and mortality. PLE is defined as the abnormal loss of serum proteins into the lumen of the gastrointestinal tract and occurs in up to 11% of patients after Fontan palliation. Diuretic therapy and nutritional supplementation are often insufficient management strategies, often requiring the addition of somatostatic analogs (octreotide), sildenafil, and/or the creation of a fenestration in the Fontan circuit to palliate potentially elevated Fontan pressures.