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Autologous mitochondrial transplantation for cardiogenic shock in pediatric patients following ischemia-reperfusion injury

Published:November 30, 2020DOI:https://doi.org/10.1016/j.jtcvs.2020.10.151

      Abstract

      Objectives

      To report outcomes in a pilot study of autologous mitochondrial transplantation (MT) in pediatric patients requiring postcardiotomy extracorporeal membrane oxygenation (ECMO) for severe refractory cardiogenic shock after ischemia-reperfusion injury (IRI).

      Methods

      A single-center retrospective study of patients requiring ECMO for postcardiotomy cardiogenic shock following IRI between May 2002 and December 2018 was performed. Postcardiotomy IRI was defined as coronary artery compromise followed by successful revascularization. Patients undergoing revascularization and subsequent MT were compared with those undergoing revascularization alone (Control).

      Results

      Twenty-four patients were included (MT, n = 10; Control, n = 14). Markers of systemic inflammatory response and organ function measured 1 day before and 7 days following revascularization did not differ between groups. Successful separation from ECMO—defined as freedom from ECMO reinstitution within 1 week after initial separation—was possible for 8 patients in the MT group (80%) and 4 in the Control group (29%) (P = .02). Median circumferential strain immediately following IRI but before therapy was not significantly different between groups. Immediately following separation from ECMO, ventricular strain was significantly better in the MT group (−23.0%; range, −20.0% to −28.8%) compared with the Control group (−16.8%; range, −13.0% to −18.4%) (P = .03). Median time to functional recovery after revascularization was significantly shorter in the MT group (2 days vs 9 days; P = .02). Cardiovascular events were lower in the MT group (20% vs 79%; P < .01). Cox regression analysis showed higher composite estimated risk of cardiovascular events in the Control group (hazard ratio, 4.6; 95% confidence interval, 1.0 to 20.9; P = .04)

      Conclusions

      In this pilot study, MT was associated with successful separation from ECMO and enhanced ventricular strain in patients requiring postcardiotomy ECMO for severe refractory cardiogenic shock after IRI.

      Graphical abstract

      Key Words

      Abbreviations and Acronyms:

      BCH (Boston Children's Hospital), COI (conflicts of interest), ECMO (extracorporeal membrane oxygenation), IRB (institutional review board), IRI (ischemia-reperfusion injury), MT (mitochondrial transplantation), OHT (orthotopic heart transplant), VAD (ventricular assist device)
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      Linked Article

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          The last 2 decades have been marked by explosive and exponential research activity aimed at regeneration and improvement of myocardial function in children. Stem cell therapies have been extensively trialed in the setting of ischemia-reperfusion injury, albeit without widespread clinical application.1 In a detailed study recently published in Nature, injection of alive or dead stem cells or a chemical inducer of innate immunity all resulted in activation of innate immunity and improvement in myocardial function.
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      • Commentary: Autologous mitochondrial transplantation: An exciting innovation that needs evidence of efficacy
        The Journal of Thoracic and Cardiovascular SurgeryVol. 162Issue 3
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          Guariento and colleagues1 describe a pilot clinical trial of a conceptually innovative form of regenerative therapy—autologous mitochondrial transplantation (MT)—in ischemia-reperfusion injury. This approach extends an earlier report from this group describing the first in-human use of autogenous MT in extracorporeal membrane oxygenation-dependent patients.2 The authors should be credited as the primary innovators of MT for cardiac regeneration and this study serves as the next step in the translation of this approach after extensive preclinical studies.
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