Gitelman syndrome (GS) is a rare hereditary tubulopathy affecting the distal tubule leading to significant electrolyte disturbances.1 Although generally a benign condition, rare associations with arrhythmias and sudden cardiac death have been reported. A paucity of literature exists associating GS with cardiomyopathy. We present a child with dilated cardiomyopathy and GS who was successfully treated with orthotopic heart transplantation

Hoffman, Timothy M.

Kihlstrom, Margaret

Schwartz, Stephanie P.

Sharma, Mahesh S.

Solt, Shannon Alexandra

Westreich, Katherine D.

Carolina Digital Repository

Case ReportOrthotopic Heart Transplantationin a Patient With Gitelman Syndromeand Dilated CardiomyopathyShannon Alexandra Solt, DO1, Timothy M. Hoffman, MD1,Mahesh S. Sharma, MD1, Katherine D. Westreich, MD1,Margaret Kihlstrom, MD1, and Stephanie P. Schwartz, MD11 University of North Carolina Medical Center, Chapel Hill, NC, USADOI: 10.1177/2150135120912227AbstractGitelman syndrome (GS) is a rare hereditary tubulopathy affecting thedistal tubule leading to significant electrolyte disturbances.1 Althoughgenerally a benign condition, rare associations with arrhythmias andsudden cardiac death have been reported.1 A paucity of literatureexists associating GS with cardiomyopathy. We present a child withdilated cardiomyopathy and GS who was successfully treated withorthotopic heart transplantation.Case ReportA seven-year-old male with Gitelman syndrome (GS) presented withacute onset right-sided hemiplegia and aphasia. Head computed tomo-graphy revealed an ischemic stroke of the left middle cerebral artery.Echocardiogram demonstrated dilated cardiomyopathy, severelydepressed biventricular function (ejection fraction: 18%), and no atrialshunt (Figure 1). Echocardiogram two years prior revealed normalbiventricular function. Extensive evaluation for an underlying etiol-ogy including viral studies and a comprehensive cardiomyopathysequencing panel were unremarkable.He was stabilized on a milrinone infusion, then transitioned toenteral heart failure medications and magnesium supplementation,as well as prophylactic anticoagulation for potential cardioembolicstroke. At discharge, he had mild expressive aphasia and right-sidedweakness. Within four months, he experienced decompensated heartfailure requiring readmission for transplant evaluation and listing. Hewas bridged to transplant with milrinone and dobutamine infusions, aswell as a high-dose magnesium infusion, and listed status 1A byexemption. Due to his history of stroke, a ventricular assist devicewas not offered as the risk of systemic anticoagulation was felt tooutweigh the benefit of mechanical circulatory support.He was transplanted after seven months of waitlist time. Other thanthe requirement of multiple magnesium and potassium replacements tomaintain serum levels, there were no additional anesthetic or operativemanagement issues related to his GS. Subsequent echocardiogramsrevealed normal graft function. Posttransplant, the use of tacrolimusin the setting of his underlying GS elicited recalcitrant hypomagnese-mia. Postoperative course was complicated by ventricular tachycardiawithout evidence of rejection, reperfusion injury, or coronary arteryabnormality. A lidocaine infusion was initiated and subsequently tran-sitioned to enteral amiodarone. Additionally, he developed significantcramping and tetany in his extremities limiting mobility, whichimproved with higher serum magnesium levels. A magnesium infusiontreated both unique postoperative symptoms. Transition to enteral mag-nesium was challenging with high stool output and resultant metabolicacidosis. Ultimately, he was discharged home 79 days posttransplant(289 hospitalization days including waitlist time) on a regimen of mag-nesium oxide, magnesium chloride, sodium bicarbonate, and spirono-lactone, in addition to amiodarone, enalapril, and immunosuppressionwith steroids, tacrolimus, and mycophenolate mofetil. His neurologicexamination continued to improve throughout hospitalization, and atdischarge, he had only mild right-sided weakness.DiscussionGitelman syndrome is an autosomal recessive tubulopathy arisingfrom mutations in the SLC12A3 gene encoding the thiazide-sensitiveNaCl cotransporter.1,2 The syndrome is characterized by metabolicalkalosis, hypokalemia, hypomagnesemia, and reduced urinary cal-cium excretion.1 While often benign, rare associations with arrhyth-mias and sudden cardiac death have been reported.3,4 No knownassociation between GS and cardiomyopathy exists. This case com-plements two previously published reports describing children withGS or suspected GS with dilated cardiomyopathies requiring hearttransplantation.5,6 While etiologies for these cases were described asprobable viral origin or idiopathic, each additional case reinforces apossible association between GS and dilated cardiomyopathy.Cardiac workup for patients with GS is not well established.Electrocardiograms are suggested for patients with GS and hypomag-nesemia to assess QT interval and subsequent arrhythmia risk.3 Nostandard exists for echocardiography. More data are needed to evalu-ate whether periodic screening echocardiography is indicated.Many patients with GS remain hypomagnesemic despite supple-mentation, often requiring large quantities of magnesium in order toreach the lower limit of normal.1,5 Renal magnesium wasting and highstool output due to enteral magnesium supplementation often exacer-bate hypomagnesemia, leading to the consideration of potassium-sparing diuretics and nonsteroidal anti-inflammatory drugs to curtailrenal potassium and magnesium loss.7,8 Our patient’s posttransplanthypomagnesemia was exacerbated by the use of a calcineurin inhibi-tor, a drug class known to induce urinary magnesium wasting.9Submitted November 25, 2019; Accepted February 15, 2020.Corresponding Author:Shannon Alexandra Solt, University of North Carolina Medical Center, 101Manning Dr, Chapel Hill, NC 27514, USA.Email: sas5025@email.unc.eduFigure 1. Echocardiogram of patient with dilated cardiomyopathy.In the setting of arrhythmias and/or cardiomyopathy, electrolytebalance is critical.3 Hypomagnesemia can cause prolongation of theventricular action potential and subsequent QT interval prolongation.4QTc prolongation is associated with severe ventricular arrhythmias,for which patients posttransplant are already at risk.4 Hypomagnese-mia is known to cause tetany, cramps, paresthesias, and musclepain,1,5 which can complicate postoperative recovery and patientmobilization.Our patient’s postoperative ventricular tachyarrhythmias as wellas pain and cramping in his extremities were presumed to be exa-cerbated by hypomagnesemia. Therefore, we initially sought to keephis serum magnesium levels above 2.0 mEq/L, requiring a magne-sium sulfate infusion of up to 13.5 mg/kg/h. This level was unachie-vable with oral supplementation, as increasing doses of enteralmagnesium (up to 33 mg/kg/d magnesium chloride and 73 mg/kg/d magnesium oxide) led to intolerable stooling patterns which threat-ened volume and acid–base status. He was discharged achieving goalmagnesium levels of 1.2 mEq/L with six to seven loose stools daily.Subsequently, his serum magnesium level has improved to average1.7 mEq/L, and the amount of magnesium supplementation requiredhas dramatically decreased.Salt wasting, an additional characteristic of GS, has the potential toeffect volume status.2 Liberal sodium intake is encouraged. Renin–angiotensin–aldosterone system inhibitors can aggravate renal sodiumwasting and increase the risk of symptomatic hypovolemia but limitrenal potassium losses in the distal tubules.2 While not first-line treat-ment for tubulopathies, they are not contraindicated pending hemody-namic tolerance from a hemodynamic standpoint. In our patient,enalapril was started for afterload reduction posttransplant and waswell tolerated.This report provides an additional case of a patient with GS pre-senting with dilated cardiomyopathy, ultimately receiving a hearttransplantation. It is possible that while previously unrecognized, anassociation exists between GS and dilated cardiomyopathy. Further-more, while the hypomagnesemia induced by GS and calcineurininhibitors is challenging to manage postoperatively, heart transplanta-tion is a viable therapeutic option for this patient population.Authors’ NoteAuthors confirm that permission to publish this report was obtainedfrom the patient’s parents.Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect tothe research, authorship, and/or publication of this article.FundingThe author(s) received no financial support for the research, author-ship, and/or publication of this article.References1. Knoers NV, Levtchenko EN. Gitelman syndrome. Orphanet J RareDis. 2008;3: 22. doi:10.1186/1750-1172-3-22.2. Blanchard A, Bockenhauer D, Bolignano D, et al. Gitelman syn-drome: consensus and guidance from a Kidney Disease: ImprovingGlobal Outcomes (KDIGO) Controversies Conference. Kidney Int.2017;91(1): 24-33. doi:10.1016/j.kint.2016.09.046.3. Foglia PE, Bettinelli A, Tosetto C, et al. Cardiac work up inprimary renal hypokalaemia-hypomagnesaemia (Gitelmansyndrome). Nephrol Dial Transplant. 2004;19(6): 1398-1402.doi:10.1093/ndt/gfh204.4. Bansal T, Abeygunasekara S, Ezzat V. An unusual presentationof primary renal hypokalemia-hypomagnesemia (Gitelman’ssyndrome). Ren Fail. 2010;32(3): 407-410. doi:10.3109/08860221003632873.5. Al-Rasheed AK, Blaser SI, Minassian BA, Benson L, Weiss SK.Cyclosporine A neurotoxicity in a patient with idiopathic renalmagnesium wasting. Pediatr Neurol. 2000;23(4): 353-356. doi:10.1016/s0887-8994(00)00198-3.6. Schmitz ML, Massicotte P, Faulkner SC, et al. Management of apediatric patient on the Berlin Heart Excor ventricular assist devicewith argatroban after heparin-induced thrombocytopenia. ASAIO J.2008;54(5): 546-547. doi:10.1097/MAT.0b013e3181873681.7. Blanchard A, Vargas-Poussou R, Vallet M, et al. Indomethacin,amiloride, or eplerenone for treating hypokaemia in Gitelman syn-drome. J Am Soc Nephrol. 2015;26(2): 468.8. Vaisbich MH, Fujimura MD, Koch VH. Bartter syndrome: benefitsand side effects of long-term treatment. Pediatr Nephrol. 2004;19(8): 858.Solt et al 521

Orthotopic Heart Transplantation in a Patient With Gitelman Syndrome and Dilated Cardiomyopathy

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Orthotopic Heart Transplantation in a Patient With Gitelman Syndrome and Dilated Cardiomyopathy

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