Hypoplastic Left Heart Syndrome


arly Stage squareHypoplastic Left Heart Syndrome (HLHS) is rare congenital heart defect characterized by faulty or absent development of the left ventricle. Normally, oxygenated blood returns from the lungs to the left side of the heart to be pumped systemically; however, in HLHS the right ventricle must support both pulmonary and systemic circulations.

While the exact cause of HLHS is unknown, a predominant theory involves a primary anatomic defect in the left heart structures causing altered blood flow through the heart which results in a secondary malformation of the left ventricle and outflow tract. The diagnosis is often made prepartum by fetal echocardiography.

HLHS comprises 2 to 3 percent of all congenital heart disease with an estimated total of 960 live births each year in the US. HLHS is uniformly lethal if left untreated; however, there is currently an estimated 70 percent 5-year survival rate for infants who undergo surgical correction. Unfortunately, even when treated, this disease is associated with significant morbidity including an increased risk of thrombotic complications, decrease in exercise tolerance, and neurodevelopmental impairment.

Current Treatment

The treatment of HLHS involves initial medical management with subsequent surgical correction.
Initial Medical Management: Continuous intravenous prostaglandin E1 is used to maintain a PDA to allow adequate systemic perfusion. Nitrogen may be used in some centers to decrease inspired oxygen which increases pulmonary arterial resistance. This therapy encourages systemic rather than pulmonary blood flow and enhances systemic perfusion.

Interventional Therapy: Transcatheter atrial septoplasty is performed in patients with an inadequate atrial septal defect to allow adequate mixing of oxygenated and deoxygenated blood.

Staged Surgical Palliation: Staged surgical repair has the best outcome and is the most common management approach. This 3 stage procedure allows the right heart to take control of both pulmonary and systemic circulations.

  • Stage 1 (i.e. Norwood procedure): performed during the neonatal period to provide unobstructed blood flow from the right ventricle to the systemic circulation, establish controlled pulmonary blood flow, and ensure a connection between blood returning from the lungs and the right ventricle.
  • Stage 2 (bidirectional Glenn procedure): typically performed at 4-6 months of age to create a shunt between the superior vena cava and pulmonary artery.
  • Stage 3 (Fontan procedure): typically performed at 18-30 months of age to create a venous pathway from the inferior vena cava to the pulmonary artery.

Cardiac transplantation is also a treatment option, but is more commonly used in the event of failed surgical palliation.

Focused Ultrasound Research

An important component in the treatment of HLHS is ensuring adequate patency of an atrial septal defect which allows pulmonary venous blood returning to the left heart to be shunted to the right heart. In patients with a restricted or absent atrial septal defect, atrial septoplasty is necessary to create a large enough opening. Aside from its thermal ablative effects, focused ultrasound is also capable of precise mechanical tissue destruction through a process known as histotripsy. This procedure utilizes high intensity, pulsed ultrasound to collapse bubbles of gas in tissue which releases a shockwave capable of liquefying cells in a phenomenon known as inertial cavitation. A preclinical study has already demonstrated the ability of histotripsy to non-invasively create an atrial septal defect. As such, histotripsy has the potential to be an effective tool to create and/or maintain an atrial septal defect in patients with HLHS.

Notable Papers

Devanagondi R1, Zhang X2, Xu Z3, Ives K4, Levin A5, Gurm H6, Owens GE7. Hemodynamic and Hematologic Effects of Histotripsy of Free-Flowing Blood: Implications for Ultrasound-Mediated Thrombolysis. J Vasc Interv Radiol. 2015 Oct;26(10):1559-65. doi: 10.1016/j.jvir.2015.03.022. Epub 2015 May 4.

M. Azmin, C. Harfield, Z. Ahmad, M. Edirisinghe, and E. Stride, “How do microbubbles and ultrasound interact? Basic physical, dynamic and engineering principles.,” Curr. Pharm. Des., vol. 18, no. 15, pp. 2118–2134, 2012.

Owens GE, Miller RM, Owens ST, Swanson SD, Ives K, Ensing G, Gordon D, Xu Z. Intermediate-term effects of intracardiac communications created noninvasively by therapeutic ultrasound (histotripsy) in a porcine model. Pediatr Cardiol. 2012 Jan;33(1):83-9. doi: 10.1007/s00246-011-0094-6. Epub 2011 Sep 11. PubMed PMID:21910018.

Xu Z, Owens G, Gordon D, Cain C, Ludomirsky A. Noninvasive creation of an atrial septal defect by histotripsy in a canine model. Circulation. 2010 Feb16;121(6):742-9. doi: 10.1161/CIRCULATIONAHA.109.889071. Epub 2010 Feb 1. PubMed PMID: 20124126; PubMed Central PMCID: PMC2834201.

W. W. Roberts, T. L. Hall, K. Ives, J. S. Wolf Jr., J. B. Fowlkes, and C. A. Cain, “Pulsed cavitational ultrasound: A noninvasive technology for controlled tissue ablation (histotripsy) in the rabbit kidney,” J. Urol., vol. 175, no. 2, pp. 734–738, 2006.