What is the interstage mortality rate for single ventricle disease?

Interstage Mortality in Single Ventricle Disease

The interstage mortality rate for single ventricle disease has decreased from 40-50% to currently between 2% and 12%, with recent improvements in care delivery and monitoring programs. 1

Understanding Interstage Mortality

The interstage period refers to the time between discharge after the first stage of palliation (typically Norwood procedure) and before the second stage (Glenn/bidirectional cavopulmonary anastomosis). This is a particularly vulnerable period for infants with single ventricle physiology.

Historical Perspective and Current Rates

• Historically, mortality between first and second stages of palliation for hypoplastic left heart syndrome was 40-50% 1
• With improved care delivery and implementation of learning networks, this has decreased to 2-12% 1
• Despite these improvements, the interstage period remains a high-risk time for these infants

Risk Factors for Interstage Mortality

Several factors have been identified that increase the risk of interstage mortality:

• Moderate to severe atrioventricular valve regurgitation (AVVR) (HR 2.41) 2
• Moderate ventricular dysfunction (HR 5.29) 2
• Right ventricular dominant morphology 2
• Perinatal acidosis 2
• Systemic ventricular dysfunction 1
• Fontan pathway dysfunction 1
• Lymphatic dysfunction 1
• Extracardiac dysfunction 1

Interventions That Improve Interstage Outcomes

Home Monitoring Programs

Home monitoring programs have been developed to improve interstage outcomes:

• The implementation of dedicated single-ventricle home-monitoring programs has been associated with:

  • Improved interstage weight gain 3
  • Earlier second-stage palliation at equivalent patient weight 3
  • Improved 1-year transplant-free survival 3

• Technology-based monitoring systems like the Cardiac High Acuity Monitoring Program (CHAMP) have shown benefits over traditional three-ring binder documentation:

  • Fewer unplanned ICU days per 100 interstage days 4
  • Shorter delays in care 4
  • Lower resource utilization during readmissions 4
  • Lower incidence of interstage growth failure 4

Pharmacotherapy

Medication management plays a critical role in interstage care:

• Digoxin use has been associated with significantly reduced interstage mortality:

  • Interstage mortality of 2.9% in infants discharged on digoxin versus 12.3% in those not on digoxin 5
  • Adjusted hazard ratio of 3.5 (95% CI, 1.1-11.7) 5
  • Number needed to treat to prevent one death: 11 patients 5

• Common medications prescribed during the interstage period include:

  • Aspirin (95.7% of patients)
  • Diuretics (90.4%)
  • ACE inhibitors (37.7%)
  • Proton pump inhibitors (33.4%)
  • H2 receptor blockers (30.6%)
  • Digoxin (27.6%) 6

Pitfalls and Caveats

1. Medication burden: The total number of medications prescribed shows a negative correlation with interstage weight gain (r = -0.19, p=.002) 6

2. Gastric medications: Proton pump inhibitors and prokinetic agents have not been associated with better outcomes and may be associated with poor growth 6

3. Monitoring limitations: Despite home monitoring programs, some centers have not observed significant reductions in interstage mortality, even though 1-year transplant-free survival improved 3

4. Thrombosis risk: The interstage period carries risk of thrombosis, particularly in areas of blood flow stasis such as interconnecting pulmonary artery segments or blind-ended pulmonary artery stumps 1

5. Late referrals: Many individuals with Fontan circulation die from complications either after late consideration for advanced heart failure therapies or having never seen a heart failure specialist 1

By implementing comprehensive monitoring programs and optimizing pharmacotherapy (particularly considering digoxin), clinicians can work to further reduce the interstage mortality rate in this vulnerable patient population.