End-Stage Cardiomyopathy Because of Hereditary Hemochromatosis Successfully Treated With Erythrocytapheresis in Combination With Left Ventricular Assist Device Support
2014; Lippincott Williams & Wilkins; Volume: 7; Issue: 3 Linguagem: Inglês
10.1161/circheartfailure.114.001198
ISSN1941-3297
AutoresEva Rombout‐Sestrienkova, Nicolaas de Jonge, Kateřina Martinakova, C. Klöpping, Karin P. M. van Galen, Aryan Vink, Elly M.C.J. Wajon, W. M. Smit, Cor van Bree, Ger H. Koek,
Tópico(s)Trace Elements in Health
ResumoHomeCirculation: Heart FailureVol. 7, No. 3End-Stage Cardiomyopathy Because of Hereditary Hemochromatosis Successfully Treated With Erythrocytapheresis in Combination With Left Ventricular Assist Device Support Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBEnd-Stage Cardiomyopathy Because of Hereditary Hemochromatosis Successfully Treated With Erythrocytapheresis in Combination With Left Ventricular Assist Device Support Eva Rombout-Sestrienkova, MD, Nicolaas De Jonge, MD, PhD, Kateřina Martinakova, Corinne Klöpping, MD, Karin P.M. van Galen, MD, Aryan Vink, MD, PhD, Elly M.C.J. Wajon, MD, Wim M. Smit, MD, PhD, Cor van Bree, MD and Ger H. Koek, MD, PhD Eva Rombout-SestrienkovaEva Rombout-Sestrienkova From the Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Maastricht, The Netherlands (E.R.-S.); Department of Cardiology (N.D.J., C.K.), Department of Hematology (K.P.M.v.G.), and Department of Pathology (A.V.), University Medical Center Utrecht, Utrecht, The Netherlands; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University Medical Center Maastricht, Maastricht, The Netherlands (E.R.-S., G.H.K.); Faculty of Medicine, Masaryk University, Brno, Czech Republic (K.M.); Department of Cardiology (E.M.C.J.W.) and Department of Internal Medicine (W.M.S.), Medical Spectrum Twente, Enschede, The Netherlands; and Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Groningen, The Netherlands (C.v.B.). , Nicolaas De JongeNicolaas De Jonge From the Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Maastricht, The Netherlands (E.R.-S.); Department of Cardiology (N.D.J., C.K.), Department of Hematology (K.P.M.v.G.), and Department of Pathology (A.V.), University Medical Center Utrecht, Utrecht, The Netherlands; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University Medical Center Maastricht, Maastricht, The Netherlands (E.R.-S., G.H.K.); Faculty of Medicine, Masaryk University, Brno, Czech Republic (K.M.); Department of Cardiology (E.M.C.J.W.) and Department of Internal Medicine (W.M.S.), Medical Spectrum Twente, Enschede, The Netherlands; and Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Groningen, The Netherlands (C.v.B.). , Kateřina MartinakovaKateřina Martinakova From the Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Maastricht, The Netherlands (E.R.-S.); Department of Cardiology (N.D.J., C.K.), Department of Hematology (K.P.M.v.G.), and Department of Pathology (A.V.), University Medical Center Utrecht, Utrecht, The Netherlands; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University Medical Center Maastricht, Maastricht, The Netherlands (E.R.-S., G.H.K.); Faculty of Medicine, Masaryk University, Brno, Czech Republic (K.M.); Department of Cardiology (E.M.C.J.W.) and Department of Internal Medicine (W.M.S.), Medical Spectrum Twente, Enschede, The Netherlands; and Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Groningen, The Netherlands (C.v.B.). , Corinne KlöppingCorinne Klöpping From the Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Maastricht, The Netherlands (E.R.-S.); Department of Cardiology (N.D.J., C.K.), Department of Hematology (K.P.M.v.G.), and Department of Pathology (A.V.), University Medical Center Utrecht, Utrecht, The Netherlands; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University Medical Center Maastricht, Maastricht, The Netherlands (E.R.-S., G.H.K.); Faculty of Medicine, Masaryk University, Brno, Czech Republic (K.M.); Department of Cardiology (E.M.C.J.W.) and Department of Internal Medicine (W.M.S.), Medical Spectrum Twente, Enschede, The Netherlands; and Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Groningen, The Netherlands (C.v.B.). , Karin P.M. van GalenKarin P.M. van Galen From the Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Maastricht, The Netherlands (E.R.-S.); Department of Cardiology (N.D.J., C.K.), Department of Hematology (K.P.M.v.G.), and Department of Pathology (A.V.), University Medical Center Utrecht, Utrecht, The Netherlands; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University Medical Center Maastricht, Maastricht, The Netherlands (E.R.-S., G.H.K.); Faculty of Medicine, Masaryk University, Brno, Czech Republic (K.M.); Department of Cardiology (E.M.C.J.W.) and Department of Internal Medicine (W.M.S.), Medical Spectrum Twente, Enschede, The Netherlands; and Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Groningen, The Netherlands (C.v.B.). , Aryan VinkAryan Vink From the Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Maastricht, The Netherlands (E.R.-S.); Department of Cardiology (N.D.J., C.K.), Department of Hematology (K.P.M.v.G.), and Department of Pathology (A.V.), University Medical Center Utrecht, Utrecht, The Netherlands; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University Medical Center Maastricht, Maastricht, The Netherlands (E.R.-S., G.H.K.); Faculty of Medicine, Masaryk University, Brno, Czech Republic (K.M.); Department of Cardiology (E.M.C.J.W.) and Department of Internal Medicine (W.M.S.), Medical Spectrum Twente, Enschede, The Netherlands; and Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Groningen, The Netherlands (C.v.B.). , Elly M.C.J. WajonElly M.C.J. Wajon From the Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Maastricht, The Netherlands (E.R.-S.); Department of Cardiology (N.D.J., C.K.), Department of Hematology (K.P.M.v.G.), and Department of Pathology (A.V.), University Medical Center Utrecht, Utrecht, The Netherlands; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University Medical Center Maastricht, Maastricht, The Netherlands (E.R.-S., G.H.K.); Faculty of Medicine, Masaryk University, Brno, Czech Republic (K.M.); Department of Cardiology (E.M.C.J.W.) and Department of Internal Medicine (W.M.S.), Medical Spectrum Twente, Enschede, The Netherlands; and Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Groningen, The Netherlands (C.v.B.). , Wim M. SmitWim M. Smit From the Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Maastricht, The Netherlands (E.R.-S.); Department of Cardiology (N.D.J., C.K.), Department of Hematology (K.P.M.v.G.), and Department of Pathology (A.V.), University Medical Center Utrecht, Utrecht, The Netherlands; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University Medical Center Maastricht, Maastricht, The Netherlands (E.R.-S., G.H.K.); Faculty of Medicine, Masaryk University, Brno, Czech Republic (K.M.); Department of Cardiology (E.M.C.J.W.) and Department of Internal Medicine (W.M.S.), Medical Spectrum Twente, Enschede, The Netherlands; and Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Groningen, The Netherlands (C.v.B.). , Cor van BreeCor van Bree From the Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Maastricht, The Netherlands (E.R.-S.); Department of Cardiology (N.D.J., C.K.), Department of Hematology (K.P.M.v.G.), and Department of Pathology (A.V.), University Medical Center Utrecht, Utrecht, The Netherlands; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University Medical Center Maastricht, Maastricht, The Netherlands (E.R.-S., G.H.K.); Faculty of Medicine, Masaryk University, Brno, Czech Republic (K.M.); Department of Cardiology (E.M.C.J.W.) and Department of Internal Medicine (W.M.S.), Medical Spectrum Twente, Enschede, The Netherlands; and Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Groningen, The Netherlands (C.v.B.). and Ger H. KoekGer H. Koek From the Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Maastricht, The Netherlands (E.R.-S.); Department of Cardiology (N.D.J., C.K.), Department of Hematology (K.P.M.v.G.), and Department of Pathology (A.V.), University Medical Center Utrecht, Utrecht, The Netherlands; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University Medical Center Maastricht, Maastricht, The Netherlands (E.R.-S., G.H.K.); Faculty of Medicine, Masaryk University, Brno, Czech Republic (K.M.); Department of Cardiology (E.M.C.J.W.) and Department of Internal Medicine (W.M.S.), Medical Spectrum Twente, Enschede, The Netherlands; and Blood Bank Division, Unit Transfusion Medicine, Sanquin Blood Supply, Groningen, The Netherlands (C.v.B.). Originally published1 May 2014https://doi.org/10.1161/CIRCHEARTFAILURE.114.001198Circulation: Heart Failure. 2014;7:541–543IntroductionA 51-year-old man with a 2-year history of type II diabetes mellitus, erectile dysfunction, and 3-month history of fatigue was referred in March 2011 to the cardiology department of a local hospital because of 1 week of progressive dyspnea, orthopnea, leg edema, and increasing abdominal girth. His only medication was tolbutamide and metformin. He drank alcohol sporadically with maximum of 1 drink/d and had a history of shoulder arthralgias. On physical examination, the patient had brownish-gray skin pigmentation. He was tachypneic with blood pressure of 105/80 mm Hg and regular heart rate of 118 beats per minute. He had jugular venous distension, bilateral pulmonary crackles, II/VI systolic murmur heard at the apex, ascites, and pitting edema in both lower legs. The ECG showed sinus tachycardia with left atrial and ventricular hypertrophy and repolarization abnormalities. A chest radiograph (Figure 1) revealed cardiomegaly and bilateral pleural effusion. The echocardiogram showed a dilated left and right ventricle with severely compromised systolic function (left ventricular ejection fraction, 20%) and no ventricular hypertrophy. There was moderate mitral and tricuspid insufficiency with elevated right sided pressures (40–45 mm Hg). Coronary angiography was notable for no significant coronary artery disease, and the diagnosis of a nonischemic dilated cardiomyopathy (DCM) was made. Laboratory findings included increased levels of urea 9.3 (2.5–6.4) mmol/L, total bilirubin 21 (<17) μmol/L, aspartate aminotransferase 51 (<40) U/L, alanine aminotransferase 52 (<45) U/L, gamma glutamyltransferase 58 (<50) U/L, N-terminal of the prohormone brain natriuretic peptide 350 (<12) pmol/L, and glucose 9.6 (3.6–5.6) mmol/L. Treatment with diuretics and inotropic agents was begun with initial improvements in his hemodynamics. However, a few days later the patient deteriorated and was transferred to a tertiary center. At that time he was in cardiogenic shock with low blood pressure despite inotropic support and subsequently required an intra-aortic balloon pump. Hemodynamic measurements showed a pulmonary artery pressure of 38/24 mm Hg, mean 29, with a pulmonary capillary wedge pressure of 24 and a right atrial pressure of 15 mm Hg and a cardiac output of 3.8 L/min (cardiac index, 1.9 L/min per meter squared). His clinical condition did not improve, so a left ventricle assist device (LVAD) was implanted as a bridge to heart transplantation.Download figureDownload PowerPointFigure 1. Chest radiographs at first admission showing cardiac enlargement, pulmonary congestion, and bilateral pleural effusion.The myocardium tissue of the left ventricular apex, removed during LVAD implantation, showed widespread iron depositions in the cardiomyocytes (Figure 2). These findings were compatible with cardiac hemochromatosis explaining the cause of the DCM. Iron parameters showed elevated serum ferritin (SF) of 3711 (25–250) μg/L and transferrin saturation of 88%. DNA testing confirmed a homozygous substitution of tyrosine for cysteine at position 282 (C282Y) in the hereditary hemochromatosis (HH) HFE protein. After LVAD implantation, the patient recovered rapidly and was discharged from the hospital. Treatment of iron overload was started with phlebotomy, performed once weekly with a removal of 300- to 500-mL whole blood per procedure (Table), decreasing the SF level from 3011 to 1796 μg/L. Because of slow SF decrease and side effects such as frequent palpitations, syncope, and dizziness during phlebotomy, treatment was switched to erythrocytapheresis with a frequency of 1 procedure every 2 to 3 weeks. About 500-mL erythrocytes, fully compensated with the same volume of saline per procedure, were removed. In total, 20 uneventful erythrocytapheresis procedures were performed during a period of 51 weeks. The total removed erythrocyte volume was 9700 mL with an estimated total iron removal of 7760 mg (Table). Treatment was stopped at an SF level of 41 μg/L. The patients' liver enzymes normalized with no signs of cirrhosis. After the normalization of SF, while on the LVAD, his heart function gradually recovered. Because of the potential option of explantation of the assist device, heart failure medication such as angiotensin-converting enzyme inhibitors and β-blockers were optimized and repeated echocardiograms and exercise tests were performed while turning off the pump. When these tests all demonstrated sufficient recovery of cardiac function, it was decided to explant the device. This operation, performed 23 months after initial implantation, went uneventful and the patient was discharged from the hospital 8 days after explantation. Echocardiographic measurements post-LVAD removal were left ventricular end-diastolic diameter 47 (versus 64 pre-LVAD implantation), left ventricular end-systolic diameter 32 mm (versus 53 mm pre-LVAD implantation), and mitral deceleration time 170 ms (versus 100 ms pre-LVAD implantation; Figure 3A and 3B). Currently, 12 months after the explantation of the LVAD he remains in good clinical condition, New York Heart Association I, without signs of heart failure and near normal left ventricular function.Table. Parameters of Treatment of Hereditary Hemochromatosis Patients With Phlebotomy and ErythrocytapheresisPhlebotomyErythrocytapheresisSerum ferritin at the start of treatment, μg/L30111796Serum ferritin at the end of treatment, μg/L179641No procedures2120Treatment duration, wk2851Treatment interval, d1018,5Total volume removed, mL8800 (whole blood)9700 (erythrocytes)Estimated removal of iron per procedure, mg168388Estimated total removal of iron, mg35207760Download figureDownload PowerPointFigure 2. Cardiac tissue removed during LVAD implantation. A, Myocardium of the apex of the left ventricle with brown pigment in the cardiomyocytes. Hematoxylin and eosin staining. Bar, 100 μm. B, Prussian blue iron staining showing the iron in blue. Bar, 100 μm.Download figureDownload PowerPointFigure 3. Apical 4-chamber view echo pre and post LVAD. A, Post-LVAD removal and (B) pre-LVAD implantation.DiscussionHH is a common heritable disease, characterized by an increase in iron absorption from the gut inappropriate to body iron stores, resulting in a progressive accumulation of iron in tissues, especially in the liver and pancreas. Cardiac involvement is less frequent, nevertheless can also occur, causing arrhythmias and in rare cases restrictive or DCM.Standard therapy for patients with primary iron accumulation is phlebotomy. In this case, we described the use of an alternative treatment option, which is erythrocytapheresis. During this procedure, erythrocytes are selectively removed from whole blood by aphaeresis, followed by reinfusion of leukocytes, platelets, and plasma to the patient. This method has been evaluated in 1 randomized1 and a few nonrandomized studies.2,3 Results from all show that erythrocytapheresis is a much more effective and faster method and removes at least twice as much iron per single procedure compared with phlebotomy. This is especially advantageous in situations of life-threatening organ complications because of iron overload as in this case. The other important benefit of this method is individualized fluid management during the procedure, which makes it more suitable for hemodynamically compromised patients. Prognosis of patients with iron overload cardiomyopathy depends on establishing the diagnosis early and beginning therapy early.4 However, in the presented case, the end-stage DCM with severe systolic dysfunction, requiring support from an LVAD, did fully recover after the treatment with erythrocytapheresis. In addition to showing successful treatment of HH with erythrocytapheresis, this case has 2 other main points: (1) HH may cause a DCM and (2) therapy for HH is still worthwhile even when patients present with cardiogenic shock since the patient improved and was able to be explanted without decompensation ≈1 year after LVAD explant.DisclosuresNone.Footnotes*Drs Rombout-Sestrienkova and De Jonge contributed equally to this work.Correspondence to Eva Rombout-Sestrienkova, MD, Sanquin Blood Supply, Blood Bank Division, Martino Gaetanolaan 95, 6229 GS Maastricht, The Netherlands. E-mail [email protected]References1. Rombout-Sestrienkova E, Nieman FHM, Essers BAB, van Noord PAH, Janssen MCH, van Deursen CThBM, Bos LP, Rombout F, van den Braak R, de Leeuw PW, Koek GH. Erythrocytapheresis versus phlebotomy in the initial treatment of HFE hemochromatosis: results from a randomised trial.Transfusion. 2011; 52:470–477.CrossrefMedlineGoogle Scholar2. Muncunill J, Vaquer P, Galmés A, Obrador A, Parera M, Bargay J, Besalduch J. In hereditary hemochromatosis, red cell apheresis removes excess iron twice as fast as manual whole blood phlebotomy.J Clin Apher. 2002; 17:88–92.CrossrefMedlineGoogle Scholar3. Fernández-Mosteirín N, Salvador-Osuna C, García-Erce JA, Orna E, Pérez-Lungmus G, Giralt M. [Comparison between phlebotomy and erythrocytapheresis of iron overload in patients with HFE gene mutations].Med Clin (Barc). 2006; 127:409–412.MedlineGoogle Scholar4. Murphy CJ, Oudit GY. Iron-overload cardiomyopathy: pathophysiology, diagnosis, and treatment.J Card Fail. 2010; 16:888–900.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Lee J, Tchantchaleishvili V and Vidula H (2018) Cardiac Hemochromatosis Treated With Prolonged Extracorporeal Membrane Oxygenation Support and Chelation Therapy, Artificial Organs, 10.1111/aor.13076, 42:5, (575-576), Online publication date: 1-May-2018. Das S, Zhabyeyev P, Basu R, Patel V, Dyck J, Kassiri Z and Oudit G (2018) Advanced iron-overload cardiomyopathy in a genetic murine model is rescued by resveratrol therapy, Bioscience Reports, 10.1042/BSR20171302, 38:1, Online publication date: 28-Feb-2018. Zhabyeyev P and Oudit G (2017) Hemochromatosis Protein (HFE) Knockout Mice As a Novel Model of Hemochromatosis: Implications for Study and Management of Iron-Overload Cardiomyopathy, Canadian Journal of Cardiology, 10.1016/j.cjca.2017.04.013, 33:7, (835-837), Online publication date: 1-Jul-2017. Robinson M, Al-Kindi S and Oliveira G (2017) Heart and heart-liver transplantation in patients with hemochromatosis, International Journal of Cardiology, 10.1016/j.ijcard.2017.06.075, 244, (226-228), Online publication date: 1-Oct-2017. Tauchenová L, Křížová B, Kubánek M, Fraňková S, Melenovský V, Tintěra J, Kautznerová D, Malušková J, Jirsa M and Kautzner J (2016) Successful Treatment of Iron-Overload Cardiomyopathy in Hereditary Hemochromatosis With Deferoxamine and Deferiprone, Canadian Journal of Cardiology, 10.1016/j.cjca.2016.07.589, 32:12, (1574.e1-1574.e3), Online publication date: 1-Dec-2016. Rombout-Sestrienkova E, van Kraaij M and Koek G (2016) How we manage patients with hereditary haemochromatosis, British Journal of Haematology, 10.1111/bjh.14376, 175:5, (759-770), Online publication date: 1-Dec-2016. Daniłowicz-Szymanowicz L, Świątczak M, Sikorska K, Starzyński R, Raczak A and Lipiński P (2021) Pathogenesis, Diagnosis, and Clinical Implications of Hereditary Hemochromatosis—The Cardiological Point of View, Diagnostics, 10.3390/diagnostics11071279, 11:7, (1279) May 2014Vol 7, Issue 3 Advertisement Article InformationMetrics © 2014 American Heart Association, Inc.https://doi.org/10.1161/CIRCHEARTFAILURE.114.001198PMID: 24847131 Manuscript receivedFebruary 15, 2014Manuscript acceptedMarch 18, 2014Originally publishedMay 1, 2014 Keywordshereditary hemo chromatosisnonischemic cardiomiopathyerythrocytapheresisdilated cardiomiopathyleft ventricular assist devicePDF download Advertisement SubjectsHeart FailureTreatment
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