(70) Severe Cardiovascular Profile Following Conservative Treatment of Patent Ductus Arteriosus Among Extremely Preterm Infants

Background: Traditionally, among extremely preterm infants (EPIs; < 28 weeks of gestation) with a hemodynamically significant patent ductus arteriosus (HSPDA) definitive treatment (surgical ligation, percutaneous closure) was considered standard of care. In view of the risks of definitive treatment, many health care providers have adopted conservative PDA management strategies (non-intervention). Although widely used among EPIs with a small, non-HSPDA, potential consequences of conservative management among EPIs with evidence of a HSPDA have not been well described.

Objectives: Among EPIs with HSPDA, to characterize associated risk factors for the development of severe cardiovascular compromise (defined below) after initial attempts at conservative management.

Design/Methods: Contemporary (1/2010-12/2019), retrospective review at a large, pediatric referral center among EPIs with a diagnosis of HSPDA beyond window when drug therapy for the ductus is considered most efficacious (postnatal day 21). HSPDA was defined as the need for mechanical ventilation and evidence of left-sided atrial or ventricular chamber enlargement. Following iterative discussion with 22 board-certified pediatric cardiologists, we developed a consensus-based definition of severe cardiovascular compromise: left-sided heart chamber (atrium, ventricle) enlargement (e.g., Z-score >4) with damage to the mitral valve apparatus (e.g., mitral regurgitation), clearly/likely attributable to HSPDA exposure, in the absence of other etiologies. Data extraction and assignment of attributability and severity of HSPDA exposure were independently performed by multiple observers.

Results: Among 180 EPIs with HSPDA, 803 ECHOs were independently reviewed, of which we identified 47 infants (26.1%) with severe cardiovascular compromise. Interrater agreement on evidence of severe cardiovascular compromise, and the attributability of the HSPDA to severe cardiovascular compromise, were high (κ = 0.95, 0.92, respectively). EPIs with severe cardiovascular compromise were born more premature (24.2 vs. 26.1 weeks of gestation; P=0.02) and had longer median exposure to HSPDA (146 vs. 62 days; P< 0.01) than EPIs without severe cardiovascular compromise.

Conclusions: Optimal management strategies for EPI with an HSPDA remain unanswered, reinforcing the critical need for well-designed, pragmatic clinical trials in this high-risk subgroup.