Discussion

Arteriovenous malformations, significant enough to cause haemodynamic manifestations in the newborn period, are rare. The transitional period is characterised by significant changes in the systemic and pulmonary vascular resistance, shunt flow, and heart function. The normal postnatal adaptative process may be compromised in the presence of pathophysiological changes related to arteriovenous malformations with consequent poor tissue oxygen delivery. In particular, fetal volume overload in utero affects cardiomyocyte structure which can predispose particularly to right ventricular dysfunction. Pulmonary overcirculation during fetal life causes flow-induced pulmonary hypertension via remodelling, augmented response to pulmonary vasoconstricting stimuli, and impairment of endothelium-dependent relaxation.^{Reference Steinhorn, Russell, Lakshminrusimha, Gugino, Black and Fineman2} Several types of arteriovenous malformations have been associated with a transitional circulation phenotype^{Reference Giesinger, Elsayed, Castaldo and McNamara4} in which hypoxic respiratory failure and impaired right ventricular performance are the predominant manifestations. This case highlights the dynamic nature of cardiovascular physiology and adaptive heart function responses to embolisation of arteriovenous malformations and the merits of longitudinal TnECHO evaluation by trained haemodynamic specialists.

We have previously developed an algorithm for haemodynamic therapy-guided treatment of cerebral arteriovenous malformation based on phenotypic presentation and physiologic delineation.^{Reference Giesinger, Stanford and Rios8} In this case, the initial presentation of the infant was consistent with suprasystemic pulmonary hypertension. The need for embolisation of a large network of vessels is associated with a high risk for glue embolisation. These have been described in a variety of conditions,^{Reference Bouras, Truant and Beregi5,Reference Ashraf, Haqqi, Shaikh and Wakani9} including a neonate after embolisation for cerebral arteriovenous malformation.^{Reference De Luca, Piastra, Pietrini, Rollo and Conti6} In our case, the large right-to-left transatrial shunt presented a concerning risk of stroke due to paradoxical glue embolisation into the pre-ductal systemic circulation. Therefore, reversal of this shunt using nitric oxide enabled controlled embolisation with preferential delivery of embolised glue to the pulmonary vascular bed, rather than the cerebral circulation, thereby avoiding potential iatrogenic brain injury (Supplementary Fig 1). Access to longitudinal neonatologist performed TnECHO-enabled pre-procedural iNO testing to appraise the reversibility of the elevated pulmonary vascular resistance (PVR) and a minimum duration of iNO is needed to reach this goal. These assessments were not only frequent, but also at inconvenient times of the day. Furthermore, unique measurements that are not routinely done in anatomical cardiology scans aided in the decision-making and precision in regard to the assessment of ventricular outputs and objective measurements of right heart function.

Paradoxical embolism has been described in adults following other thromboembolic events, but also following embolisation procedures.^{Reference Abbar, Vimpere, Khater, Cellier and Diehl7,Reference Abdullah, Sachithanandan and Tan10} To our knowledge, this complication has not been described in neonates. Manipulation of PVR with inhaled nitric oxide pre-emptively, with documented TnECHO evidence of shunt reversal, may have mitigated the risk of a potentially catastrophic complication. The patient developed glue embolism but did not have clinical or radiological evidence of systemic or brain embolisation, supporting the success of this approach.

Continuation of nitric oxide between procedures was not advisable due to the risk of reducing the pulmonary pressure to subsystemic levels thereby encouraging left-to-right ductal and atrial shunt, and therefore, providing two additional sources of pulmonary over-circulation. The immediate fall in both RV and LV outputs is likely multifactorial due to the elimination of the hepatic arteriovenous malformation and the severity of biventricular dysfunction due to elevated pulmonary and systemic afterload. After the first two procedures, the infant developed clinical signs suggestive of pulmonary embolism with worsening hypoxia and RV dysfunction. This diagnosis was confirmed by the identification of multiple glue emboli on chest tomography scan and by worsening of pulmonary hypertension parameters and right ventricular dysfunction on echo. The nature of severe LV dysfunction may relate to increased LV afterload or ventricular interdependence secondary to afterload-related RV dysfunction due to pulmonary embolisation. Embolisation of glue into the coronary arteries is possible, although it would appear to be less likely in the absence of embolic damage to any other systemic organs. It is plausible that the biventricular dysfunction may also have related to transatrial glue embolisation into the coronary arteries, although there was no evidence of regional wall dysfunction. In the post-procedural phase, supportive treatment with milrinone was sufficient to ameliorate the worsening of pulmonary hypertension. Afterload reduction with milrinone was likely also beneficial to the LV following embolisation in order to support myocardial performance.^{Reference Giesinger, Elsayed, Castaldo and McNamara4}

Comprehensive evaluation by TnECHO aids in the characterisation of the underlying physiology, facilitates enhanced monitoring, and informs treatment choices. One important factor to be considered pre-procedure is the presence of intra- and extra-cardiac shunts and its directionality. The nuances presented in this case highlight the value of a dedicated team with neonatal haemodynamic expertise in a specialised centre in order to provide optimal care for neonates with similar conditions.