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Keywords:

  • Donor evaluation;
  • donor selection;
  • heart;
  • organ shortage;
  • pediatric;
  • transplant

Abstract

  1. Top of page
  2. Abstract
  3. Case Report
  4. Discussion
  5. Acknowledgments
  6. Disclosure
  7. References

Heart transplantation is the most effective therapy for children with end-stage heart disease; however, its use is limited by the number of donor organs available. This shortage may be further compounded by concerns about organ quality, leading to refusal of potential donor organ offers. We report on the successful transplantation and 5-year follow-up of a heart from a donor with Ullrich congenital muscular dystrophy (UCMD). The candidate was critically ill at the time of the transplant and the donor organ was declined repeatedly on the match run list due to concerns about organ quality, despite having normal cardiac function by echocardiography on minimal inotropic support. We believe the diagnosis of “muscular dystrophy” in the donor combined with a lack of understanding about the specifics of the diagnosis of UCMD enabled our candidate to receive a primary offer for this organ. We are unaware of any previous reports of the use of a heart from a donor with UCMD for orthotopic heart transplantation in adults or children.


Abbreviations
BiVAD

biventricular assist device

UCMD

Ullrich's congenital muscular dystrophy

Case Report

  1. Top of page
  2. Abstract
  3. Case Report
  4. Discussion
  5. Acknowledgments
  6. Disclosure
  7. References

A 5-year-old, 16 kg male with a history of idiopathic dilated cardiomyopathy and nonsustained ventricular tachycardia was admitted to our institution with fatigue, decreased oral intake and poor output. The day after admission he decompensated further and he was intubated, placed onto inotropic support and listed for urgent heart transplantation. A Levitronix® CentriMag biventricular assist device (BiVAD) was placed the next day and the patient's clinical status improved. The BiVAD was removed 12 days postimplantation after marked improvement was noted in ventricular function and the patient's clinical condition. However, over the next 10 days the patient had worsening clinical status with return of severe biventricular dysfunction culminating in ventricular fibrillation arrest. Cardiopulmonary resuscitation (CPR) and direct current shock therapy were utilized and the patient was placed onto extracorporeal membrane oxygenation. In the hours preceding his cardiopulmonary arrest and placement onto extracorporeal membrane oxygenation, a donor heart became available.

The donor was a 7-year-old, 27 kg male with a diagnosis of UCMD. He used nighttime ventilator support at home and suffered respiratory distress with resultant cardiorespiratory arrest with 1 h of reported CPR. Echocardiogram performed as part of the donor evaluation process showed a structurally normal heart with left ventricular ejection fraction of 61% and shortening fraction of 32% on dopamine 2 μg/kg/min and T4 infusion. Troponin I was 0.03 mg/mL and ECG was normal. Our candidate was third in the match run for this donor; however, the two candidates ahead of him turned down the organ citing the refusal code 830—“donor age or quality”. Of the 25 candidates on the match run, there were only 2 other provisional acceptances and 13 refusals citing code 830. Because of the paucity of literature on cardiac involvement in UCMD, we urgently contacted an expert on this rare condition who confirmed that long-term follow-up of a cohort of cases of UCMD (some into the fourth decade of life), including serial echocardiographic evaluation, had not identified cases of clinical cardiomyopathy (personal communication, Professor Francesco Muntoni, Director of the Dubowitz Neuromuscular Centre, UCL Institute of Child Health and Great Ormond Street NHS Trust). Based on this information, the donor organ was accepted for transplantation.

The patient underwent successful transplantation and did not require mechanical circulatory support posttransplantation. Intra-operative echocardiogram showed good systolic ventricular function, as did all follow-up studies. The early posttransplant course was complicated by a peri-transplant stroke, posterior reversible encephalopathy syndrome, systemic hypertension, pancreatitis, renal tubular acidosis and gross motor debilitation; however, the patient was discharged to rehabilitation 4 weeks after transplant and subsequently to home. His initial catheterization on Day 14 showed a mildly elevated right atrial pressure of 8 mmHg with cardiac index of 4.1 L/min/m2 and mixed venous saturation of 70%.

At most recent follow-up, 5.5 years after transplant, the patient was doing well, living at home and attending school at appropriate grade level for age. He is clinically well with no concern for dysrhythmias or heart failure. He has a benign rejection history and no known chronic allograft vasculopathy. All echocardiograms have shown normal left ventricular shortening fraction with qualitatively normal right ventricular systolic function. Most recent hemodynamics show a mean right atrial pressure of 4 mmHg with a pulmonary capillary wedge pressure of 8 mmHg and cardiac index of 3.9 L/min/m2.

Discussion

  1. Top of page
  2. Abstract
  3. Case Report
  4. Discussion
  5. Acknowledgments
  6. Disclosure
  7. References

The use of heart transplantation is limited by the number of donor organs available [1]. Many strategies have been tried in an effort to expand the donor pool including the use of marginal donors, donation after cardiac death and warm blood preservation [2-5]. One common reason for refusal of a potential organ is concern about the quality of the organ [6]. Whereas muscular dystrophies typically do not spare the heart, Ullrich congenital muscular dystrophy (UCMD) is a rare genetic disorder caused by mutations in genes encoding subunits of collagen VI and characterized by contractures of the proximal joints, hyperlaxity of the distal joints, generalized weakness, kyphoscoliosis and respiratory failure [7, 8]. Patients generally present from birth to 12 months of age and respiratory function often declines after 6 years of age [9]. To date no cases of UCMD with cardiac involvement have been reported [9, 10]. However, due to UCMD's rarity, relatively few studies of the disease have been performed. In a review of the literature, we found 11 case series describing the clinical and genetic findings of UCMD patients, with between 5 and 15 patients (average age 12.4 years) in each report [7, 8, 11-19]. Nine of these specifically commented on cardiac status and reported no abnormalities. In another case series of 49 patients with either UCMD or Bethlem myopathy (another collagen VI myopathy), there was no mention of cardiac involvement [20].

On first pass we believe it was reasonable to be wary of accepting a heart from a donor with a diagnosis of “muscular dystrophy”. However, because our patient was critically ill at the time of this organ offer and the donor assessment revealed normal cardiac function on minimal inotropic support, we felt compelled to learn more about the diagnosis of UCMD. Fortunately we were quickly able to review literature and consult a world's expert on UCMD to determine that the potential benefits of transplantation in this setting likely outweighed the risks. By taking these steps to further investigate UCMD, we were able to comprehensively assess the quality of this donor heart and provide a much needed treatment for our patient.

We believe this case is the first to document the successful transplantation of a donor organ with UCMD. More importantly, this case highlights the importance of gathering complete knowledge about the donor, including information about chronic conditions that may initially cause concern for organ acceptance, prior to making a decision about organ acceptance. This may be especially important in the pediatric population where unusual genetic syndromes are more prevalent. Given the shortage of donor organs and the high waitlist mortality in pediatric candidates, an aggressive and proactive approach to evaluation of donor organs is required, especially when the donor carries a rare diagnosis of uncertain significance for the organ donation process. In this case, consultation with an international expert on a very rare diagnosis led to successful use of a donor organ, which might otherwise have been discarded as unsuitable for transplantation.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Case Report
  4. Discussion
  5. Acknowledgments
  6. Disclosure
  7. References

The authors gratefully acknowledge the help of Dr. Ira Bergman and Professor Francesco Muntoni for providing critical clinical information that facilitated successful transplantation. Dr. Feingold's effort on this project was supported by the National Institutes of Health (KL2RR024154, KL2TR000146).

Disclosure

  1. Top of page
  2. Abstract
  3. Case Report
  4. Discussion
  5. Acknowledgments
  6. Disclosure
  7. References

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

References

  1. Top of page
  2. Abstract
  3. Case Report
  4. Discussion
  5. Acknowledgments
  6. Disclosure
  7. References