While many forms of congenital heart disease are amenable to surgical repair, there exists for many patients an inability to undergo repair and, thus, cardiac transplantation is required to optimize the chance of survival. Due to the fact that the number of hearts required far outweighs the supply of donor organs, support options such as veno-arterial extracorporeal membrane oxygenation (ECMO), ventricular assist devices, and more recently even total artificial heart implantation have been employed for cardiopulmonary support as a bridge to transplantation. Veno-arterial extracorporeal membrane oxygenation is the primary support method for bridging a patient to heart transplantation if lung function is not adequate, but a more stable form of support is a ventricular assist device if pulmonary function is not impaired. The median duration on veno-arterial extracorporeal membrane oxygenation for children who receive a heart transplant is about 1 week.Reference Almond, Singh and Gauvreau1 Overall, mortality on veno-arterial extracorporeal membrane oxygenation is approximately 40–60% among the paediatric population with cardiac aetiologies.Reference Punn, Axelrod, Sherman-Levine, Roth and Tacy2 Further, prolonged extracorporeal life support after cardiac surgery is associated with significantly decreased chance of survival.Reference Kolovos, Bratton and Moler3 Among paediatric patients with renal failure while on extracorporeal membrane oxygenation, there is a significant association with decreased survival.Reference Duncan, Hraska and Jonas4 It has also been shown that children requiring dialysis while receiving extracorporeal life support have a decidedly worse prognosis, including increased mortality.Reference Duncan, Hraska and Jonas4 Further, requiring renal dialysis is “an independent risk factor associated with failure to wean” from extracorporeal membrane oxygenation.Reference Wu, Lin, Tsai, Haung, Liu and Tsai5 Additionally, a positive nosocomial culture from any site has been significantly associated with decreased survival, with one study showing 88% mortality.Reference Montgomery, Strotman and Ross6 Herein, we present the case of a 13-year-old male with a complex congenital cardiac history who was supported with extracorporeal membrane oxygenation for over 1 year while awaiting cardiac transplantation.
Case presentation
Subsequent to the discovery of a concentric subaortic membrane in the setting of severe left ventricular outflow obstruction, a 13-year-old male underwent excision of this tissue along with redo mitral valve replacement in the Cayman Islands. He had a past medical history significant for transitional atrioventricular canal defect corrected after birth along with subsequent mitral and aortic stenosis requiring multiple mitral valve replacements. The patient also had a history of renal failure requiring intermittent dialysis. Postrepair intraoperative transthoracic echocardiography revealed a normally functioning prosthetic valve along with good left ventricular function. Days following the procedure, the patient showed signs of low cardiac output and veno-arterial extracorporeal membrane oxygenation was initiated. Attempts to wean the patient off veno-arterial extracorporeal membrane oxygenation resulted in suprasystemic pulmonary artery pressures along with cardiac arrythmias, precluding separation from veno-arterial extracorporeal membrane oxygenation. It was determined that this child would need cardiac transplantation in order to survive. The Congenital Heart Center at the University of Florida was contacted, and we accepted the patient for transfer with the tentative plan to transition the patient from extracorporeal membrane oxygenation to a Berlin Heart ventricular assist device (Berlin EXCOR, Berlin Heart, Inc., Berlin, Germany) until an appropriate donor heart could be found. The patient was subsequently transferred to University of Florida Health Shands Children’s Hospital on day 133 of support with veno-arterial extracorporeal membrane oxygenation.
Upon arrival, the patient had evidence of multiple wound infections on the chest related to the extracorporeal membrane oxygenation cannulation sites. Transition to the Berlin Heart was not possible secondary to multiple infectious issues, and the patient remained on extracorporeal membrane oxygenation with the original right atrial and aortic cannulation. The patient had many other comorbidities, including pressure ulcers along his sacrum and renal failure requiring intermittent haemofiltration. Eventually, he required continuous veno-venous haemofiltration and became dialysis dependent. He was placed on empiric antimicrobial therapy including vancomycin and fluconazole. Nine days following admission, he developed gross haematuria in the context of poor kidney function. An autoimmune panel along with antibody testing for Epstein-Barr virus, adenovirus, and Polyomavirus hominis 1 (BK virus) were all negative. A kidney biopsy was deemed unnecessary due to the risks involved, and a heart and kidney transplant was recommended.
Despite continuous administration of empiric antimicrobial therapy, the patient continued to show clinical signs of unresolved infection. Three months into his hospital admission, the extracorporeal membrane oxygenation cannula and urine cultures grew Candida parapsilosis, and he was subsequently started on micafungin and voriconazole therapy. No evidence of yeast bezoar or renal abscess was evident on ultrasound. As serial urine cultures remained positive for yeast, he began receiving amphotericin B bladder irrigation. However, despite multiple 7-day courses of antifungal therapy, yeast persistently grew on urine culture. Four months post-admission, a discussion was had as to whether or not the patient would tolerate a heart transplant in the context of renal insufficiency and persistent infection.
Six months after the admission to the University of Florida, blood cultures were negative for bacteria and fungus, but the cannulae were presumed to be positive for fungal colonization. The decision was made to list the patient for cardiac transplantation. Pre-transplant haemodynamics revealed that the pulmonary vascular resistance was acceptable for cardiac transplantation, and the patient underwent successful cardiac transplantation after 394 days of support with veno-arterial extracorporeal membrane oxygenation. A kidney transplant was attempted the following day but was unsuccessful due to abnormal collateral circulation around the inferior caval vein and massive hepatomegaly. Post-transplantation urine cultures continued to remain positive for fungus. Sternal cultures obtained 19 days following surgery grew Candida parapsilosis, as did cultures from the explanted heart.
Exactly 1 year post admission to University of Florida, the patient’s infections resolved and antifungals were stopped at that time. The patient was soon discharged, and a follow-up visit 4 months later revealed an ejection fraction of 64%. Two years following cardiac transplantation, the patient has adequate cardiac function but remains dialysis dependent. The possibility exists that the patient may undergo another attempt at kidney transplantation in the future.
Discussion
In patients requiring cardiac transplantation who are unable to receive support with a ventricular assist device, support with extracorporeal membrane oxygenation as a bridge to transplantation can be life-saving, as it was in the case of our patient. Examples of extremely prolonged support with extracorporeal membrane oxygenation are rare. In a retrospective cohort study of 223 patients who underwent 241 extracorporeal membrane oxygenation runs (8 October, 1998 through 25 July, 2016), median support time was 4.0 days (range = 0.04–55.8 days, mean = 6.4 ± 7.0 days).Reference Shah, Kays and Ghazarian7 Our patient’s duration on extracorporeal membrane oxygenation for 394 days as a bridge to cardiac transplantation is unprecedented.
In 2000, Gaynor and colleagues reported “the case of a newborn with severe Ebstein’s anomaly and low cardiac output who was supported with extracorporeal membrane oxygenation for 1126 hours, until an appropriate organ became available.” This remarkable accomplishment of supporting a newborn with extracorporeal membrane oxygenation for 47 days was reported in a manuscript entitled “Prolonged extracorporeal membrane oxygenation as a bridge to cardiac transplantation”.Reference Di Russo, Clark and Bridges8 A 2012 publication reported that “the longest duration for any patient maintained by ECMO in published literature is 117 days,” and “the longest duration of ECMO support mentioned in the paediatric literature is 48 days”.Reference Gupta, McDonald and Chipman9
In 2020, a case was reported where a 7-year-old child with severe inhalational burn injury and rapid progression to multisystem organ failure recovered from total acute lung failure after 20 months (605 days) of extracorporeal life support.Reference Nelson-McMillan, Vricella and Stewart10 This child was supported with the following types of extracorporeal life support:
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Days 1–7: venoarterial extracorporeal membrane oxygenation
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Days 7–61: venovenous extracorporeal membrane oxygenation
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Days 61–552: right ventricular assist device with oxygenator including days 61–420 with CentriMag (Abbott Laboratories, Chicago, Illinois, United States of America) with Quadrox (Getinge, Gothenburg, Sweden) and days 420–552 with PediMag (Abbott Laboratories, Chicago, Illinois, United States of America) with Quadrox
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Days 553–605: extracorporeal carbon dioxide removal system.
This child was supported with extracorporeal membrane oxygenation “with no lung function for almost 2 years.” During this prolonged period of support, “Central nervous system function remained normal and lung function recovered.” In 2020, the authors reported that this case “is the longest successful case of extracorporeal membrane oxygenation to date and prompts further discussion regarding “irreversible” lung injury.” The authors summarized their case by stating that “this child received 605 days of extracorporeal support for total acute lung failure and associated right ventricular failure. She has recovered lung and heart function 3 years after profound injury, with ongoing improvement.”Reference Nelson-McMillan, Vricella and Stewart10
A multicentre study showed that among paediatric patients on extracorporeal membrane oxygenation, bacteria represent the most common pathogens causing infection and are found in 12.5% of patients, whereas fungal infections, most commonly with Candida species, were less common and found in only 4.4% of patients.Reference Cashen, Reeder and Dalton11 Further, respiratory infections were found in 11.0% of these patients, whereas blood and urine infections were found in 4.4% and 4.2% of patients, respectively.Reference Cashen, Reeder and Dalton11 Thus, our patient’s case is particularly unique as he had persistent fungal infection, as well as infections of both the blood and urine. Further, despite the significantly increased mortality associated with renal failure, as well as requiring dialysis while on extracorporeal membrane oxygenation, our case illustrates the ability to perform a cardiac transplantation in a patient with concomitant renal failure at the time of transplant.
This case report documents many of the challenges associated with prolonged support with extracorporeal membrane oxygenation, including polymicrobial bacterial and fungal infections, as well as renal dysfunction. It is possible to successfully bridge a patient to cardiac transplantation with prolonged support with extracorporeal membrane oxygenation of over 1 year; however, multidisciplinary collaboration is critical.
Acknowledgements
None.
Financial support
This research received no specific grant from any funding agency, commercial, or not-for-profit sectors.
Conflicts of interest
None.
Ethical standards
The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national guidelines on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.
