Interventional management of the patent ductus arteriosus

Introduction

The decision for definitive closure of a patent ductus arteriosus (PDA) remains one of the biggest controversies in neonatology. Importantly, there is marked center-to-center variation in the incidence of ligation among extremely-low-birth-weight (ELBW) infants, and overall rates of surgical ligation reported by international neonatal networks are decreasing. ^, The reasons behind this secular trend are likely multifactorial, but in many centers surgical ligation is being substituted, and even superseded, by the practice of percutaneous closure. Percutaneous (or transcatheter) PDA closure is an emerging technique that has gained popularity in the most recent years and is being performed in progressively smaller and younger patients. Advancements in the technique with decreased fluoroscopy time, venous retrograde approach, the launch of devices that are more appropriate for the preterm ductal morphology, and increased experience have expanded the use of percutaneous closure, with high rates of technical success and few major adverse events.

Observational studies have associated PDA surgery with adverse neonatal outcomes and neurodevelopmental impairment (NDI) in early childhood, although bias due to residual confounding threatens the validity of these studies. Infants treated with surgical ligation undergo major rapid changes in systemic hemodynamics, which commonly lead to postoperative cardiorespiratory instability. In addition, given that dependence on mechanical ventilation is the sine qua non of referring an infant for definitive PDA closure, the increasing availability and use of advanced noninvasive methods of ventilation may permit earlier endotracheal extubation of extremely preterm infants. Consequently, clinician perceptions of the merits of a definitive intervention may differ, prompting them to avoid interventional PDA closure, with the hope of spontaneous ductal closure.

It’s important to note though that, specifically in ELBW, the rate of spontaneous closure is poor; more than 50% of infants born <750 g still have a PDA around day 50. Additionally, the impact of chronic pulmonary overcirculation on the pulmonary parenchyma and on pulmonary vasculature remodeling must be appreciated. Despite several controversies in the literature regarding the impact of PDA closure on different neonatal outcomes, there is increasing evidence of a correlation between prolonged shunt exposure and the development of bronchopulmonary dysplasia (BPD). Although the TIPP trial showed no decrease in the incidence of BPD with the use of prophylactic indomethacin, one recent study reported that a change toward a strict nonintervention approach to PDA resulted in an absolute increase of 31% in BPD in infants born less than 26 weeks. Prolonged exposure to shunts also has a detrimental impact on pulmonary vascular development, and the presence of an untreated large PDA in the first 2 years of life may result in pulmonary vascular disease in as many as 50% of patients. ^, Philip et al. demonstrated that exposure to a PDA beyond 8 weeks of life is associated with an elevation in pulmonary vascular resistance (PVR) index, greater respiratory severity score, and prolonged use of mechanical ventilation. In preterm infants, who have a smaller cross-sectional area of pulmonary vessels and several other inflammatory risk factors, the elevation in PVR occurs more frequently and at an earlier age, ^{, ,} while prolonged PDA exposure is also a potential contributor in the development of pulmonary vein stenosis. Figure 18.1 summarizes the multiple contributors to the pathophysiology of PDA shunt-related pulmonary hypertension.

Although the risks of prolonged shunts are relatively well established, the timing and indication for definitive closure have not been rigorously evaluated. Simultaneously, although the percutaneous approach is deemed to be less invasive and with less adverse events, the evidence regarding appropriate timing and indication for referral remain unknown. As a result, contemporary practice is dominated by considerable uncertainty regarding the role of definitive closure. In this chapter we review the evidence regarding the benefits and risks of PDA interventional closure in very preterm neonates and provide a pathophysiology-based management paradigm to guide peri-closure care in these high-risk infants.

Definitive PDA closure: Timing, patient selection, and staging

In contemporary practice the “definitive PDA closure decision” remains an enduring controversy for clinicians. There is currently a paucity of knowledge regarding the clinical and echocardiography characteristics of infants with persistent PDA who may benefit from definitive closure. The relative risks and benefits of interventional closure compared with conservative management are unknown. Although dependence on mechanical ventilation remains the primary criterion for definitive closure referral, the relative independent contribution of the PDA to ongoing respiratory insufficiency is, at present, difficult to quantify. Infants with similar echocardiography indices of PDA hemodynamic significance may have varying degrees of respiratory failure (none to severe) owing to differences in nascent lung disease of prematurity, pulmonary arterial pressure, and tolerance of the increased pulmonary blood flow from the ductal shunt.

Limited evidence from clinical trials and careful reflection on contemporary treatment practices provides some boundaries for surgical treatment, mostly by limiting the use of ligation in the first postnatal week. Although the trial by Cassady et al. reported reduced necrotizing enterocolitis (NEC) rates with prophylactic surgical ligation on the first postnatal day in ELBW infants, several factors render this practice now untenable. First , prophylactic indomethacin has both relatively high efficacy for early closure and reduces all grades of intraventricular hemorrhage (IVH), providing a therapeutic alternative with additional benefit. Second , early PDA ligation may result in increased right ventricular (RV) afterload, so early ligation may be harmful in preterm infants with increased pulmonary artery pressure, a common finding in severe respiratory distress syndrome. Finally , the natural history of ductal closure has been described, with many infants experiencing early spontaneous closure. Exposing all infants to the risks of interventional closure is therefore inappropriate.

Persistent ductal shunt may be considered a chronic, consistent contributor to impaired pulmonary compliance. Infants with a persistent PDA may be considered for interventional closure when the clinical and echocardiography evaluations identify a shunt of sufficient volume that may be actively contributing to respiratory insufficiency. Echocardiography markers of ductal significance may include measurements of left heart volume loading (i.e., pulmonary vein D wave velocity, mitral E wave velocity, left atrium to aorta ratio and isovolumic relaxation time), estimates of Qp:Qs (left-to-right ventricular output ratio) and of systemic hypoperfusion (diastolic flow reversal in the descending aorta and/or systemic vessels such as celiac and middle cerebral artery). ^, Persistent dependence on invasive or noninvasive ventilation in combination with moderate-severe echocardiography indicators of hemodynamic significance suggests an impaired ability to compensate for the ductal shunt. It is, however, important to consider preterm infants who have clinical features of chronic end-organ hypoperfusion (systemic hypotension, renal failure, feeding intolerance) in the absence of an acute etiology (e.g., sepsis, NEC) accompanied by echocardiographic indices of a large ductal shunt. In these infants echocardiography indices are often in the “severe” range across all parameters, although there are little data regarding the direct clinical relevance of these deviations from normal. Early interventional closure after failure of medical therapy may be indicated for this subgroup of infants as well as a strategy to prevent BPD and pulmonary vascular remodeling in the most immature high-risk patients.

Impact of definitive PDA closure