Current evidence for pharmacologic therapy following stage 1 palliation for single ventricle congenital heart disease

ABSTRACT

Introduction

Infants with single ventricle congenital heart disease are vulnerable to complications between stage 1 and stage 2 of palliation. Pharmaceutical treatment during this period is varied and often dependent on institutional practices as there is little evidence supporting a particular treatment path.

Areas Covered

This review focuses on medical management of patients following stage I palliation. We performed a scoping review of the current literature regarding angiotensin converting enzyme inhibitors and digoxin treatment in the interstage period. In addition, we discuss other medication classes frequently used in these patients.

Expert Opinion

Due to significant heterogeneity of anatomy, rarity of disease, and other confounding factors, there is limited evidence to support most commonly used medications within the interstage period. Digoxin is associated with improved mortality within the interstage period and should be considered; however, no large randomized controlled trial exists supporting its use. Prevention of thrombotic complication with aspirin is also associated with improved outcomes and should be considered unless a contraindication exists. The addition of other prescriptions in this patient population should be considered only after an evaluation of the risks and benefits of each medication, recognizing the burden and risk of polypharmacy in this fragile patient population.

KEYWORDS:

• Congenital heart disease
• hypoplastic left heart syndrome
• infant
• interstage
• neonate
• Norwood procedure
• pediatric cardiology
• single ventricle
• stage 1 palliation

Article highlights

• Hypoplastic left heart syndrome and other single ventricle heart lesions were previously uniformly fatal. Survival with staged surgical palliation is now 70–90%, however, mortality continues to be greatest in the interstage period between stage 1 and stage 2 of palliation. Pharmaceutical therapy following stage 1 palliation is extremely variable with little evidence to support medication practices.

• Due to the risk and significant consequences of thrombosis in this patient population, thromboprophylaxis with at least aspirin should be prescribed.

• Current evidence does not support the use of angiotensin-converting enzyme inhibitors in the interstage period.

• Digoxin prescription in the interstage period is supported by large retrospective studies. Digoxin use should be considered in patients following stage 1 palliation after careful consideration of its risks and benefits and is felt by many to be standard of care.

• Additional research on pharmaceuticals with prospective clinical trials in this specific and fragile patient population is needed. However, there are significant challenges given the rarity and heterogeneity of single ventricle heart disease. To supplement clinical trials, basic science and translational research focused on the mechanisms of ventricular failure and remodeling during the critical neonatal period as well as large database collaborations focusing on the care of infants following stage 1 palliation are needed.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.