Intermediate-Term Effects of Intracardiac Communications Created Noninvasively by Therapeutic Ultrasound (Histotripsy) in a Porcine Model

The authors have demonstrated that histotripsy (pulsed cavitational ultrasound) can create atrial septal defects and ventricular septal defects (VSDs) in an open-chest canine model transcutaneously through the intact chest of neonatal pigs. To assess the potential untoward effects of these applications, the clinical, systemic, and pathologic effects of histotripsy-induced intracardiac communications were analyzed. Six neonatal pigs received noninvasive ultrasound therapy to their ventricular septa, then were allowed to survive 1 month for evaluation of intermediate-term effects. The results were compared with those of six previous animals killed immediately and three others killed 2-3 days after the procedure. Brain magnetic resonance imaging (MRI) and an assessment of cardiac function were performed with long-term survivors, and pathologic specimens were obtained when the animals were killed. In all 15 animals, VSDs 2-6.5 mm wide were successfully created. No fatalities occurred, and all the animals thrived, achieving normal weight gain by the time they were killed. Brain MRI and lung pathology exhibited no evidence of thromboembolic events. No damage to intervening tissue was observed. Pathologic analysis showed demarcated damage to the ventricular septa. Flanking injury and hemorrhage observed acutely were resolved by 1 month, with tissue remodeling present. Transcutaneous histotripsy is a safe and effective technique for creating intracardiac communications noninvasively without intermediate-term untoward effects. With further refinement and development, histotripsy has the potential to become an effective tool for palliation of congenital heart disease.