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Heart Transplantation in Kearns-Sayre Syndrome

Di Nora, Concetta MD1; Paldino, Alessia MD2; Miani, Daniela MD1; Finato, Nicoletta MD3; Pizzolitto, Stefano MD3; De Maglio, Giovanna MD3; Vendramin, Igor MD1; Sponga, Sandro MD, PhD1; Nalli, Chiara MD1; Sinagra, Gianfranco MD2; Livi, Ugolino MD, FECTS1

doi: 10.1097/TP.0000000000002860

1 Department of Cardiothoracic Science, Azienda Sanitaria Universitaria Integrata and DAME, University of Udine, Italy.

2 Cardiovascular Department “Ospedali Riuniti” of Trieste and Post Graduate School of Cardiovascular Sciences, University of Trieste, Trieste, Italy.

3 Laboratory Department of Medical and Biological Sciences, University of Udine, Udine, Italy.

Received 17 April 2019. Revision received 18 June 2019.

Accepted 21 June 2019.

C.D.N. analyze the data and draft the paper. A.P. and D. M. collect the data and draft the paper. N.F., S.P., G.D.M., I.V., and S.S. perform the acquisition and analysis of data. C.N. collect and analyze the data. G.S. and U.L. review the paper and final approval of the paper.

The authors declare no funding or conflicts of interest.

Correspondence: Concetta Di Nora, MD, Department of Cardiothoracic Science, Azienda Sanitaria Universitaria Integrata di Udine, Hospital S. Maria della Misericordia, Udine, Italy, 33100. (

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Kearns-Sayre syndrome (KSS) is a systemic disease that belongs to a group of neuromuscular disorders known as mitochondrial encephalomyopathies that typically involves the central nervous system, eyes, skeletal muscles, and heart. Acute onset of congestive heart failure (HF) is a possible expression of a rare form of dilated cardiomyopathy (DCM) secondary to KSS.

We describe a case of a 16-year-old boy affected by KSS that rapidly progressed to HF needing of orthotopic heart transplantation (HTx). His mitochondrial disease was caused by 4309G>A mutation of the mitochondrially encoded tRNA isoleucine gene encoding for mitochondrial tRNA for isoleucine, diagnosed with mitochondrial DNA (mtDNA) analysis by next-generation sequencing. The definitive diagnosis was confirmed when the patient was 3 years old. At that time, he showed short stature and late development of language capacities; then, he rapidly developed ophthalmoplegia caused by bilateral deficit of extrinsic ocular motility, bilateral ptosis, and blindness due to pigmentary retinopathies. Moreover, he showed moderate myopathy with generalized hypotony. The cardiologic follow-up was negative until 2017, when an initial involvement of the left ventricle (LV) was noted in absence of any symptoms (the LV ejection fraction worst: 62% in 2016 versus 48% in 2017), so a low dosage of angiotensin-converting enzyme inhibitor was suggested. However, in September 2018, he was admitted for acute onset of HF. The transthoracic echocardiogram showed moderate dilation with severe reduction of ejection fraction of both ventricles (Figure 1A). In spite of diuretic and and inotropic treatment, his clinical status dramatically worsened. The right heart catheterization confirmed severe reduction of the cardiac index (1.6 L/min/m2), with pulmonary artery pressures in normal range. After a multidisciplinary assessment, including neurologic, endocrinologic, ocular, and renal evaluation, the young patient was referred and received HTx in October 2018. Donor heart was classified as marginal, because of evidence of interventricular septum thickening (12 mm) and an expected ischemic time > 4 hours. For these reasons, the ex vivo normothermic perfusion with Organ Care System (Transmedics) was used, permitting total ischemic time reduction and graft evaluation.1 Detailed donor data are shown in Table 1.





The postoperative course was uneventful, so he was discharged home after 3 weeks. The current immunosuppression therapy includes cyclosporine, mycophenolate, and low dose of corticosteroids. The pathologic findings of the explanted heart are shown in Figure 1B–F.

This is a peculiar case of KSS in a young 16-year-old boy with acute presentation of HF due to DCM that underwent HTx successfully. The cardiac involvement in mitochondrial myopathies has hitherto been limited almost exclusively to the conducting tissue2; conversely, clinical presentation of DCM in KSS has been described solely in few reports, leading the option of HTx exclusively in selected cases.3–6 Considering the scarcity published data on the prevalence of heart involvement in mitochondrial encephalomyopathies, this is the youngest patient that underwent HTx for DCM in KSS with good results in the early and mid-term outcome.

As for these rare diseases, the more data about KSS patients are collected, the more we can learn about the phenotypic and genotypic expression of these patients and the better the outcome of KSS patients. Actually, the prognosis quoad vitam of this disease is strongly dependent by the grade of heart involvement; while the quality of life is strictly associated to the morbidity, that depends on severity of peripheral muscle system and ocular involvement. The routinely serial follow-up is crucial in these systemic diseases to be aware of the possible subtle worsening in the clinical history of these patients. Furthermore, the multidisciplinary approach was determinant to have a qualified and complete evaluation of the disease, allowing us to perform HTx, even the lacking data about this rare disease. Finally, the severe involvement of both ventricles in the idiopathic dilatative phenotype secondary to KSS has been determinant to prefer HTx over durable left ventricular assist device implantation. Being a cardiac muscle disease, the same process resulting in LV cardiomyopathy also impaired right ventricle myocardial performance. Data about long-term follow-up would be needful to confirm this debated choice in such a frail young recipient, as far as in other systemic rare disease.7 Centers always struggle with making decisions on whether to offer a scarce resource to patients with a systemic and progressive disease. The chance of having HTx in patients with mitochondrial encephalopathies is arguing; otherwise, it must be assessed case-by-case. Moreover, it is not so far the hypothesis to have a potential therapy for mitochondrial disorders,8,9 whereas potential treatment may attempt to inhibit mutant mtDNA replication or encourage replication of wild-type mtDNA. The long-term follow-up of this case would be needful to confirm these preliminary encouraging results.

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