Hypoplastic left heart syndrome

Hypoplastic left heart syndrome (HLHS) is associated with a systemic right ventricle and a remnant left ventricle. The disease represents a spectrum, with the left ventricular cavity appearing of various sizes but being insufficient to sustain a bi-ventricular physiology. The competency of the tricuspid valve is important to assess, as it will become the atrio-ventricular valve of the systemic ventricle. HLHS may also be associated with a globular shape of the right ventricle and various degree of fibro-endoelastosis (often appearing as brightness of the endocardium on echocardiography). One may classify based on the aortic and mitral valve anatomy/physiology. Categories include: mitral stenosis / aortic stenosis (MS/AS), mitral stenosis / aortic atresia (MS/AA), mitral atresia / aortic atresia (MA/AA) or mitral atresia / VSD / aortic stenosis. The entire pulmonary venous return is dependent on the size of the inter-atrial communication. As such, an intact or restrictive atrial septum is of particular concern and may be associated with fetal pulmonary vascular remodelling. As these patients are dependent on low pulmonary vascular resistance to complete the single ventricular palliation, a re-modeled pulmonary vascular bed is of great concern. HLHS is a PGE-dependent condition. Indeed, systemic perfusion is dependent on patency of the ductus, until initial surgery to ensure adequate source of systemic blood flow. Because of the decreased systemic perfusion, the intestine are at particular risk of necrotizing enterocolitis, although the data regarding feeding practices are controversial in the pre-operative setting.

More on HLHS here (outside link).

More on fetal HLHS here.

Important Physiological Considerations

Blood enters the left atrium (LA) but encounters an obstruction at the LA/left ventricle (LV) level due to mitral valve (MV) atresia or stenosis. Consequently, flow to the right atrium (RA) depends heavily on the size and restriction of the inter-atrial shunt. If the shunt is restrictive or intact, these patients deteriorate very quickly after birth, often becoming pre-mortem. During fetal life, significant pulmonary venous congestion can develop despite low pulmonary blood flow (i.e.: high pulmonary vascular resistance in fetal life), leading to pulmonary vascular remodeling and congestion of lymphatic channels, which gives the lungs a "nutmeg" appearance on fetal MRI and sometimes on fetal echocardiography.

Post-natally, a septostomy may be necessary in the case of restrictive atrial septum (although very challenging since the left atrium is often severely underdevelopped, making the procedure often unachievable since it can be very difficult to either pass the balloon via the small inter-atrial opening or to even inflate the balloon in the extremely small LA to achieve a septostomy). Urgent cardiac surgery with surgical atrial septostomy may be necessary. 

Post-natally, as pulmonary vascular resistance (PVR) decreases, the Qp:Qs ratio progressively increases, raising the pulmonary venous return to the small LA. This increased pulmonary blood flow can cause the inter-atrial shunt to become more restrictive over time, progressively impeding post-capillary venous drainage and leading to pulmonary alveolar edema and ventilation-perfusion (V/Q) mismatch.

From the RA, blood flows into the right ventricle (RV) and then into the pulmonary artery (PA). Blood may either enter the pulmonary circulation or be shunted right-to-left through a patent ductus arteriosus (PDA) to supply the systemic circulation. Blood entering the systemic circulation will perfuse the lower body anterograde via the ductus, and feeding the transverse and ascending aorta retrograde (like in fetal life). As such, the small hypoplastic underdevelopped ascending aorta is supplied retrograde by the ductus arteriosus maintained patent by prostaglandins. The coronary arteries are also supplied retrograde and eventually their flow comes back to the right atrium via the coronary sinus. The balance between pulmonary and systemic blood flow (Qp and Qs) is determined by the PVR/SVR ratio (SVR; systemic vascular resistance). Pulmonary blood flow depends on pulmonary resistance, PDA size, and coronary blood flow, which is maintained by retrograde filling of the aorta through the PDA and feeds into the coronary sinus back to the RA.

As pulmonary blood flow increases at the expense of systemic flow (due to competition of PVR/SVR balance), the fraction of blood directed to systemic organs decreases, leading to a reduced volume fraction of systemic venous return. Consequently, the proportion of desaturated blood returning to the RA decreases, while the proportion of oxygenated blood returning to the LA increases (assuming no significant ventilation-perfusion mismatch leading to decreased pulmonary venous oxygen saturation). Therefore, rising systemic oxygen saturations in hypoplastic left heart syndrome (HLHS) indicate a relative decrease in systemic blood flow compared to pulmonary blood flow. As time passes, there can be significant pulmonary congestion and spilling within the pulmonary alveolis, leading to marked pulmonary edema. Pulmonary venous saturation will drop due to difficult passage of oxygen through the Alvelo-capillary membrane. The saturations may drop in this context. Hence, why, these patients are brought often for early first stage palliation to avoid excessive pulmonary flow at the expense of systemic ischemia. 

There are limited medical interventions available in the situation of Qp>>>>Qs in HLHS, but certain actions could inadvertently worsen the condition. It is crucial to avoid maneuvers that further reduce PVR relative to SVR. For mechanically ventilated patients (a situation that needs to be astutely monitored), CO₂ levels should be maintained within a range of permissive hypercapnia to avoid drop in PVR secondary to overventilation. Exposure to oxygen and the use of inhaled nitric oxide (iNO) should be avoided, as they are potent pulmonary vasodilators. In the past. the use of hypoxic mix was even considered to increase PVR - a practice that has been abandonned. See here.

Managing these patients is particularly challenging, as metabolic acidosis from decreased perfusion can lead to hyperventilation, which lowers CO₂ levels and further reduces PVR. In some cases, sedation may be used to prevent hyperventilation after intubation and mechanical ventilation. While this approach can help stabilize the PVR/SVR ratio, it may also reduce SVR, providing a temporary benefit. However, agents that increase SVR (vasopressors) could further compromise systemic blood flow and impair systemic ventricular function, especially in the presence of endocardial fibroelastosis (EFE) and tricuspid insufficiency.

• Variants of HLHS:​

• MS-AS (45%): mitral stenosis – aortic stenosis​ - This form exhibits considerable variability in LV size, the amount of antegrade flow, and the degree of LV systolic and diastolic dysfunction, depending on the severity of obstruction caused by the combined effects of mitral and aortic stenosis. The ascending aorta is generally larger than in cases with aortic atresia. There is overlap in the spectrum with patients who have critical aortic stenosis, allowing some to be considered for a two-ventricle repair.

• MS-AA (25%): mitral stenosis – aortic atresia : risk factor for decreased survival after stage 1 palliation; coronary cameral fistulas in half (abnormal coronary – LV fistulas). ​ In this form, the ascending aorta is severely hypoplastic, and systemic output remains ductal-dependent. Depending on the degree of mitral stenosis, LV pressures may be sub-systemic, systemic, or even supra-systemic. The extent of ventricular hypertrophy is variable, but severe LV systolic dysfunction is typically present.

• MA-AA (30%): mitral atresia – aortic atresia​ - This is the most extreme form of hypoplastic left heart syndrome (HLHS). The left ventricle (LV) is either diminutive or absent, and the ascending aorta is severely hypoplastic. Systemic output is entirely ductal-dependent, with retrograde flow in the ascending aorta.

• Rare Variant – Mitral Atresia, Aortic Stenosis, and Ventricular Septal Defect (VSD): This rare variant involves mitral atresia with a VSD, allowing limited flow into the rudimentary LV, which may enable some forward flow in the aortic arch. These patients also present with aortic stenosis.

• Important considerations:​

• Restrictive atrial septum​ / Intact atrial septum​

• EFE outlines that the myocardium has been chronically undersupplied with oxygen and perfusion during fetal life, leading to chronic ischemia and collagen deposition due to secondary fibrosis. This leads to abnormal cardiac performance (systolic and diastolic function can be impaired). Coronary system is being supported by retrograde flow in the small underdevelopped descending aorta via the ductus. 

• In HLHS, tricuspid valve becomes main Atrio-ventricular valve of the future systemic chamber. Increasing severity of tricuspid regurgitation is associated with poorer prognosis. ​ ​ ​ ​

• Pulmonary valve and main pulmonary artery will become the major systemic outflow. 

• Pulmonary circulation will eventually be dependent on passive flow from the systemic venous return to the pulmonary arteries. As such, abnormal pulmonary vasculature may jeopardize the eventual Fontan circulation. Low pulmonary vascular resistance and normal pulmonary venous drainage is key in favouring the Fontan setup. 

• HLHS with highly restrictive (RS) or intact atrial septum (IAS) causes LA and pulmonary vascular hypertension (HTN) during growth​: “Muscularisation” of vessels during organogenesis ; Lymphangiectasia: dilation of lympathic vessels​

• ​HLHS-RS/IAS results in post-natal hemodynamic instability due to impeded LA flow & marked pulmonary venous HTN​

  1. Outcomes poor with > 50 % mortality in neonatal period​

  2. Surgical atrial septostomy, early Norwood, fetal balloon septoplasty, and transcatheter atrial septostomy, have been used with variable results ​

• ​Despite improvement in overall survival reported in different series for HLHS-RS/IAS carry a poor long-term prognosis​

Guidelines for the management of neonates and infants with hypoplastic left heart syndrome: The European Association for Cardio-Thoracic Surgery (EACTS) and the Association for European Paediatric and Congenital Cardiology (AEPC) Hypoplastic Left Heart Syndrome Guidelines Task Force

Echocardiography examples

Example 1

Example 2

Presentation by Dr Sariya Sahussarungsi (NH Fellow) and Laila Wazneh (NNP) - 2024

Presentation on HLHS by Shiran Moore and Laila Wazneh - 2021