1. Abstract WereportacaseofslowlyprogressiveBecker’smusculardystrophyina52-year-oldmanwhorequiredcardiactransplantationfor intractablecongestiveheartfailure.Areferralwasmadeconcern- ing prognosis of his muscular dystrophy in the multidisciplinary approach to transplant. A review of the literature provides limited guidance on cardiac transplantation in patients with muscular dystrophy although this procedure appears to be well-tolerated in thosewithBecker’smusculardystrophy.Formalassessmentsand neuromuscularfollow-uphavenotbeenclearlydocumentedinpatients having cardiac transplantation, and robust clinical evidence or guidance in this area is lacking.
Keywords: Cardiac;Transplantation;Neuromuscular;Muscular dystrophy; Cardiomyopathy
2. Introduction Musculardystrophiesareaheterogeneousgroupofgeneticmusculardisorderspresentingwithprogressivemuscularweaknesswhich havecharacteristicpathologicalfeaturesinthemusclebiopsyand areoftenassociatedwithotherorganinvolvementsuchascardiac, respiratory,orcentralnervoussystem[1,2].Cardiacinvolvement caninvolveprimarilythemyocardiumorconductivesystemorbe secondary to respiratory muscle involvement by causing cor pulmonale [3, 4]. Improved management of respiratory, cardiac, and othercomplicationsindifferenttypesofmusculardystrophy(MD) has led to increased survival of with many patients surviving into adulthood [2, 3, 5, 6]. With increased life expectancy of MD patients,neuromuscularphysiciansmaybeaskedtoprovideadvice in novel areas that lack a solid evidence base or guideline. Here, we report the case of a 52-year-old Becker muscular dystrophy (BMD) patient evaluated at the request of the cardiology service regarding eligibility for cardiac transplantation. We also present the results of a literature review regarding cardiac transplantation in MD, including any consensus recommendations.
3. Case Report A52-year-old man was first evaluated in the Prosserman Family NeuromuscularClinicatage41forproximallowerlimbweakness manifestasdifficultyinclimbingstairs.Hereportedthathehada normalchildhoodanddevelopmentbutthathewasneverathletic. His 74-year-old mother had difficulty climbing stairs starting at age 72 and examination showed that she had bilateral calf hypertrophy. Three of his sisters are healthy. He developed symptoms at age 28 with minimal difficulty in climbing stairs. The weaknessprogressedslowlyandbyage37,hehaddifficultygettingup fromachairandrequiredsupporttoclimbstairs.Hehadnoother weakness, bulbar or respiratory symptoms. Physical examination revealedanormalcranialnerveexaminationandupperlimbpow- er. In the lower limbs, he had proximal weakness at 4/5 in hip flexors,quadriceps,andhamstrings,normaldistalstrengthandbilateralcalfhypertrophy.Deeptendonreflexeswerereducedinthe upper limbs, absent at the knees and normal at the ankles. Plantar reflexes were flexor. Sensory examination was normal. He had a waddling gait and positive Gower’s sign.
4. Literature Review DuchenneAndBecker’sMuscularDystrophy Since1988,cardiactransplantationhasbeenreportedbothincase reportsandcaseseriesinpatientswithDuchennemusculardystrophy(DMD)andBMDwithend-stageheartfailureasafinaltreat- ment option with successful outcomes [7–26]. The clinical neuromuscular status including the degree of muscular or respiratory weakness and outcome of the transplantation are summarized in Table1.Someofthedystrophinopathypatientswhohadsuccess- ful cardiac transplantation were neurologically asymptomatic at the time of transplantation despite the severe dilated cardiomyopathy necessitating cardiac transplantation [10, 11, 14, 21, 22, 27]. Otherstudiesreportedpatientswithdystrophinopathy-relatedcardiomyopathywithmildtomoderatemuscularweaknesswhotolerated the transplantation procedure well; most of these were BMD patientsratherthanDMD[7,8,12,14,15,18,21,23].Intwocase reportspublishedrecently[24,26],theauthorsreportedtwoDMD patients with severe muscular weakness in addition to respiratory involvement who also completed the cardiac transplantation uneventfully and one had a 53 month follow up after surgery [24]. There are six case series reporting patients with muscular dystrophywhounderwentcardiactransplantation[9,16,17,19,25,28]. Unfortunately, the degree of muscular and respiratory weakness wasnotdocumentedinthesestudies,butmostwereBMDpatients who have less severe muscular and respiratory weakness than DMD patients or those with other muscular dystrophies.
Emery-DreifussMD There are three case reports of cardiac transplantation in Em-eryDreifuss muscular dystrophy (EDMD) patients. One patient had mild proximal upper and lower limb weakness and minimal distal leg weakness and tolerated the transplantation uneventfully [29], but the clinical status was not recorded in the other 2 case reports[9,17].Similarly,theclinicalneuromuscularstatuswasnot reportedintwocaseseriesofEDMDpatientswhohadsuccessful cardiac transplantation [19, 25]. In two additional case of cardiac transplantation in EDMD patients, mild proximal weakness was evident at the time of cardiac transplantation and the surgery was reported as successful [30, 31]. Limb-girdle MD Successful cardiac transplantation has been reported in two case reports [14,20] and two case series [17,32]of limb-girdle muscular dystrophy (LGMD) patients.The severity of neuromuscular weakness and also the type of LGMD was omitted in one case series[17],butintheothercaseseriesreportingsevenmembersof a family with LGMD type 1B, the muscular weakness was noted asmildexceptinonepatient[32].Muscleweaknessinoneofthe case reports was reported as mild [14] , but not specified in the other [20] . Myotonic Dystrophy Cardiactransplantationwithacceptableoutcomesinmyotonicdystrophy have been reported in two case reports of patients having congestive heart failure [33, 34]and two case series [17, 25]of patientswithoutaspecifiedetiologyforheartfailure.Inonecase report, the post-operative course was complicated by prolonged mechanical ventilation and the need for intensive respiratory and peripheral muscular training pre- and post-operatively due to the presence of bulbar, respiratory and limb musculature weakness beforetransplantation[33].Theothercasereportedaprolonged postoperative course due to transient severe respiratory insufficiency necessitating antibiotics and prolonged mechanical ventilationdespitethepresenceofonlymildmuscleweaknesswithout respiratory involvement before cardiac transplantation [34]. The case series reporting myotonic dystrophy patients did not detail the type of myotonic dystrophy or neuromuscular status in terms of skeletal or respiratory muscle weakness [17, 25]. OtherMuscularDystrophies Single case reports of patients with congenital muscular dystrophies (one Fukuyama congenital muscular dystrophy and one alpha-dystroglycanopathy) have been reported in the literature [23, 35] . The alpha-dystroglycanopathy patient was ambulatory before cardiac transplantation and showed improvement in ambulation status after transplantation [23]. The patient with Fukuyama congenital muscular dystrophy had mild lower limb weakness in terms of a positive Gower’s sign, gait impairment and difficulty running prior to cardiac transplantation, and although he tolerated the procedure well, his post-operative course was complicated by convulsions and acute renal failure preventing recovery to the pre-procedural motor function [35].
5. Recommendations for Cardiac Transplant in Muscular Dystrophy TheAmericanHeartAssociationhassuggestedthatcardiactransplantationisnotanoptionforpatientswithsevereneuromuscular diseases given the increased risk of complications due to respiratory and pharyngeal muscle weakness. They suggest that cardiac transplantationcanbeconsideredforthosewithmilderrespiratory and skeletal muscle weakness such as BMD [36]. In a 2018 publication on DMD care, Birnkrant et. al. suggested cardiac transplantation as only a theoretical option for those with severe heart failuregiventhepaucityofdonors.Theysuggestedacase-by-case approach without any specific characterization of severity of MD or other criteria for cardiac transplantation [37].
6. Discussion Inthepast,neuromusculardisorderswereconsideredascontraindications for cardiac transplantation [38], but these conditions includepatientswithawidespectrumofdiseasesmanifestingindiversecombinationsofmusclegroupweaknessandinvolvementof otherorganssuchasheartandnervoussystem[1].Despitethediversityinmusculardystrophies,themostcommonlimitingfactors for transplant are severe respiratory and bulbar muscle weakness, which predispose these patients to prolonged ventilation support andhighercomplicationrates[14,25,33].Informationconcerning the severity and distribution of neuromuscular weakness is miss- ing in the largest case series of neuromuscular patients who had successfulcardiactransplantation[9,16,17,19,25,28],although some reports indicate that outcome of cardiac transplantation in patients with MD is similar to the non-MD patients in terms of ability to tolerate the surgery, post-operative course,complications,andsurvival[9,17,25,28].Mostofthesereportsarebased onpatientswithBMDwhohavemildermuscleweaknessorthose with dystrophinopathy who were asymptomatic or had mild to moderate muscle weakness before surgery [7, 8, 10-12, 14, 15,18,21-23].AseverephenotypeinDMDmaynotprecludecardiac transplantationalthoughtheevidenceislimitedtotwocasereports only [24, 26]. An exception to the hypothesis that patients with milder forms of dystrophycantoleratecardiactransplantationmaybeinmyotonic dystrophy type 1 patients, who experienced difficult post-operative coursesregardlessofthedegreeofmuscleorrespiratoryweakness before transplantation which could be explained by the systemic nature of the myotonic dystrophy pathology making them more prone to the post-operative complications [33, 34]. Experience is limited also in congenital MD with one patient unable to attainthe pre-transplantation level of motor status due to post-surgical complications [35].
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Song I Yang. Cardiac Transplantation in Patients with Muscular Dystrophy: A Case Report and Review of Literature. Annals of Clinical and Medical Case Reports 2021