Abstract
Anorexia nervosa (AN) is an eating disorder that most frequently afflicts females in adolescence. In these subjects, cardiovascular complications are the main cause of morbidity and mortality. Aim of this review is to analyze the hemodynamic, pro-arrhythmic and structural changes occurring during all phases of this illness, including re-feeding. A systematic literature search was performed on studies in the MEDLINE database, from its inception until September 2017, with PUBMED interface focusing on AN and cardiovascular disease. This review demonstrated that the most common cardiac abnormalities in AN are bradycardia and QT interval prolongation, which may occasionally degenerate into ventricular arrhythmias such as Torsades des Pointes or ventricular fibrillation. As these arrhythmias may be the substrate of sudden cardiac death (SCD), they require cardiac monitoring in hospital. In addition, reduced cardiac mass, with smaller volumes and decreased cardiac output, may be found. Furthermore, mitral prolapse and a mild pericardial effusion may occur, the latter due to protein deficiency and low levels of thyroid hormone. In anorectic patients, some cases of hypercholesterolemia may be present; however, conclusive evidence that AN is an atherogenic condition is still lacking, although a few cases of myocardial infarction have been reported. Finally, refeeding syndrome (RFS), which occurs during the first days of refeeding, may engender a critically increased risk of acute, life-threatening cardiac complications.
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Keski-Rahkonen A, Hoek HW, Susser ES, Linna MS, Sihvola E, Raevuori A, Bulik CM, Kaprio J, Rissanen A (2007) Epidemiology and course of anorexia nervosa in the community. Am J Psychiatry 164(8):1259–1265
Bulik CM, Reba L, Siega-Riz AM, Reichborn-Kjennerud T. Anorexia nervosa: definition, epidemiology, and cycle of risk. Int J Eat Disord. 2005;37 Suppl:S2–S9
Keski-Rahkonen A, Hoek HW, Susser ES, Linna MS, Sihvola E, Raevuori A, Bulik CM, Kaprio J, Rissanen A (2007) Epidemiology and course of anorexia nervosa in the community. Am J Psychiatry 164(8):1259–1265
Becker AE, Grinspoon SK, Klibanski A, Herzog DB (1999) Eating disorders. N Engl J Med 340:1092–1098
Fairburn CG, Harrison PJ (2003) Eating disorders. Lancet 361:407–416
Casiero D, Frishman WH (2006) Cardiovascular complications of eating disorders. Cardiol Rev 14(5):227–231
Sachs KV, Harnke B, Mehler PS, Krantz MJ (2016) Cardiovascular complications of anorexia nervosa: a systematic review. Int J Eat Disord 49(3):238–248. https://doi.org/10.1002/eat.22481 (Epub 29 Dec 2015)
Keshaviah A, Edkins K, Hastings ER, Krishna M, Franko DL, Herzog DB, Thomas JJ, Murray HB, Eddy KT (2014) Re-examining premature mortality in anorexia nervosa: a meta-analysis redux. Compr Psychiatry 55(8):1773–1784
Neumarker KJ (1997) Mortality and sudden death in anorexia nervosa. Int J Eat Disord 21:205–212
Crisp AH, Callender JS, Halek C, Hsu LK (1992) Long-term mortality in anorexia nervosa. A 20-year follow-up of the St. George’s and Aberdeen cohorts. Br J Psychiatry 161:104–107
Miller RJH, Chew D (2016) Re-feeding syndrome and alcoholic cardiomyopathy: a case of interacting diagnoses. J Cardiol Cases 14(3):90–93
Jáuregui-Garrido B, Jauregui-Lobera I (2012) Sudden death in eating disorders. Vasc Health Risk Manag 8:91–98
Fohlin L (1977) Body composition, cardiovascular and renal function in adolescent patients with anorexia nervosa. Acta Paediatr Scand Suppl 268:1–20
Spaulding-Barclay MA, Stern J, Mehler PS (2016) Cardiac changes in anorexia nervosa. Cardiol Young 26(4):623–628
Yahalom M, Spitz m, Sandler L (2013) The significance of bradycardia in anorexia nervosa. Int J Angiol 22:83–94
Warren MP, Wande Viele RL (1973) Clinical and metabolic features of anorexia nervosa. Am J Obstet Gynecol 117:435–449
Sharp CW, Freeman CP (1993) The medical complications of anorexia nervosa. Br J Psychiatry 162:452–462
Debra K, Katzman DK (2005) Medical complications in adolescents with anorexia nervosa: a review of the literature. Int J Eat Disord 37(Suppl):S52–S59
López-Guzmán A, Taboada F, Alvarez Escolá C (2002) Sinus bradycardia in anorexia nervosa. Nutr Hosp 17(1):46–47
Golden NH, Katzman DK, Kreipe RE et al, Society for Adolescent Medicine (2003) Eating disorders in adolescents: position paper of the Society for Adolescent Medicine. J Adolesc Health 33(6):496–503
Kanbur N, Goldberg E, Pinhas L, Hamilton RM, Clegg R, Katzman DK (2009) Second-degree atrioventricular block (Mobitz type I) in an adolescent with anorexia nervosa: intrinsic or acquired conduction abnormality. Int J Eat Disord 42(6):575–578
Raghi G, Perucca A, Parravicini U et al (2006) Severe bradycardia in an asymptomatic young subject: is there an indication to permanent cardiac pacing? G Ital Cardiol (Rome) 7:299–302
American Psychiatric Association (2006) Treatment of patients with eating disorders, third edition. American Psychiatric Association. Am J Psychiatry 163(7 Suppl):4–54
Kollai M, Bonyhay I, Jokkel G, Szonyi L (1994) Cardiac vagal hyperactivity in adolescent anorexia nervosa. Eur Heart J 15(8):1113–1118
Tokumura M, Watanabe H, Esaki T (2012) Convalescent resting tachycardia predicts unfavorable outcome of anorexia nervosa. Pediatr Int 54(6):844–848
Walter C, Rottler E, von Wietersheim J, Cuntz U (2015) QT-correlation formulae and arrythmogenic risk in female patients with anorexia nervosa. Int J Cardiol 187:302–303. https://doi.org/10.2016/j.ijcard,2015.03.230
Day CP, McComb JM, Campbell RW (1990) QT dispersion: an indication of arrhythmia risk in patients with long QT intervals. Br Heart J 63(6):342–344
Swenne I, Larsson PT (1999) Heart risk associated with weight loss in anorexia nervosa and eating disorders: risk factors for QTc interval prolongation and dispersion. Acta Paediatr 88(3):304–309
Fanoe S, Kristensen D, Fink-Jensen A, Jensen HK, Toft E, Nielsen J, Videbech P, Pehrson S, Bundgaard H (2014) Risk of arrhythmia induced by psychotropic medications: a proposal for clinical management. Eur Heart J 35(20):1306–1315
Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, Blom N, Brugada J, Chiang CE, Huikuri H, Kannankeril P, Krahn A, Leenhardt A, Moss A, Schwartz PJ, Shimizu W, Tomaselli G, Tracy C (2013) Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes. Heart Rhythm 10(12):e85–e108
Padfield GJ, Escudero CA, DeSouza AM, Steinberg C, Gibbs K, Puyat JH, Lam PY, Sanatani S, Sherwin E, Potts JE, Sandor G, Krahn AD (2016) Characterization of myocardial repolarization reserve in adolescent females with anorexia nervosa. Circulation 133(6):557–565
Nagata JM, Carlson JL, Kao JM, Golden NH, Murray SB, Peebles R (2017) Characterization and correlates of exercise among adolescents with anorexia nervosa and bulimia nervosa. Int J Eat Disord 50(12):1394–1403
Murialdo G, Casu M, Falchero M, Brugnolo A, Patrone V, Cerro PF, Ameri P, Andraghetti G, Briatore L, Copello F, Cordera R, Rodriguez G, Ferro AM (2007) Alterations in the autonomic control of heart rate variability in patients with anorexia or bulimia nervosa: correlations between sympathovagal activity, clinical features, and leptin levels. J Endocrinol Invest 30:356–362
Facchini M, Sala L, Malfatto G, Bragato R, Redaelli G, Invitti C (2006) Low-K+ dependent QT prolongation and risk for ventricular arrhythmia in anorexia nervosa. Int J Cardiol 106:170–176
Guerrier K, Mitan L, Wang Y, Czosek RJ (2016) Risk for prolonged QT interval and associated outcomes in children with early restrictive eating patterns. Cardiol Young 26(4):644–649
Winston AP (2012) The clinical biochemistry of anorexia nervosa. Ann Clin Biochem 49(Pt 2):132–143
Seidler T, Jacobshagen C, Bauer M, Hasenfuss G, Waeschle RM (2011) Distribution of potassium levels on admission for CPR—severe hypokalaemia with dysmorphophobic eating disorders. Resuscitation 82(5):535–537
Fonseca V, Havard CW (1985) Electrolyte disturbances and cardiac failure with hypomagnesaemia in anorexia nervosa. Br Med J (Clin Res Ed) 291(6510):1680–1682
Kutsal E, Aydemir C, Eldes N, Demirel F, Polat R, Taspnar O, Kulah E (2007) Severe hypermagnesemia as a result of excessive cathartic ingestion in a child without renal failure. Pediatr Emerg Care 23(8):570–572
Palla B, Litt IF (1988) Medical complications of eating disorders in adolescents. Pediatrics 81(5):613–623
Abed J, Judeh H, Abed E, Kim M, Arabelo H, Gurunathan R (2014) “Fixing a heart”: the game of electrolytes in anorexia nervosa. Nutr J 13:90
Stheneur C, Bergeron SJ, Frappier JY, Jamoulle O, Taddeo D, Sznajder M, Lapeyraque AL (2017) Renal injury in pediatric anorexia nervosa: a retrospective study. Eat Weight Disord. https://doi.org/10.1007/s40519-017-0401-1
Krantz MJ, Sabel AL, Sagar U, Long CS, Barbey JT, White KV, Gaudiani JL, Mehler PS (2012) Factors influencing QT prolongation in patients hospitalized with severe anorexia nervosa. Gen Hosp Psychiatry 34(2):173–177
Timour Q, Frassati D, Descotes J, Chevalier P, Christé G, Chahine M (2012) Sudden death of cardiac origin and psychotropic drugs. Front Pharmacol 10:3:76
Birmingham CL, Gritzner S (2007) Heart failure in anorexia nervosa: case report and review of the literature. Eat Weight Disord 12:e7–e10
Lamzabi I, Syed S, Reddy VB, Jain R, Harbhajanka A, Arunkumar P (2015) Myocardial changes in a patient with anorexia nervosa: a case report and review of literature. Am J Clin Pathol 143(5):734–737. https://doi.org/10.1309/AJCP4PLFF1TTKENT
Sutton MSJ, Plappert T, Crosby L, Douglas P, Mullen J, Reichek N (1985) Effects of reduced left ventricular mass on chamber architecture, load, and function: a study of anorexia nervosa. Circulation 72(5):991–1000
Romano C, Chinali M, Pasanisi F, Greco R, Celentano A, Rocco A, Palmieri V, Signorini A, Contaldo F, de Simone G (2003) Reduced hemodynamic load and cardiac hypotrophy in patients with anorexia nervosa. Am J Clin Nutr 77(2):308–312
Kastner S, Salbach-Andrae H, Renneberg B, Pfeiffer E, Lehmkuhl U, Schmitz L (2012) Echocardiographic findings in adolescents with anorexia nervosa at beginning of treatment and after weight recovery. Eur Child Adolesc Psychiatry 21(1):15–21
Lelli L, Rotella F, Castellini G, Benni L, Lo Sauro C, Barletta G, Mannucci E, Castellani S, Di Tante V, Galanti G, Ricca V (2015) Echocardiographic findings in patients with eating disorders: a case-control study. Nutr Metab Cardiovasc Dis 25(7):694–696
Franzoni F, Galetta F, Cupisti A, Rolla M, Santoro G, Pentimone F (2003) Ultrasonic tissue characterization of the myocardium in anorexia nervosa. Acta Paediatr 92:297–300
Kuwabara M, Niwa K, Yamada U, Ohta D (2018) Low body mass index correlates with low left ventricular mass index in patients with severe anorexia nervosa. Heart Vessels 33(1):89–93
Galetta F, Franzoni F, Cupisti A, Morelli E, Santoro G, Pentimone F (2005) Early detection of cardiac dysfunction in patients with anorexia nervosa by tissue Doppler imaging. Int J Cardiol 101(1):33–37
Escudero CA, Potts JE, Lam PY, De Souza AM, Mugford GJ, Sandor GG (2016) An echocardiographic study of left ventricular size and cardiac function in adolescent females with anorexia nervosa. Eur Eat Disord Rev 24(1):26–33
Meyers DG, Starke H, Pearson PH, Wilken MK (1986) Mitral valve prolapse in anorexia nervosa. Ann Intern Med 105(3):384–386
Dini FL, Lattanzi F, Fontanive P, Rosa GM, De Tommasi SM (2009) Value of tissue Doppler imaging for risk stratification of patients with chronic systolic heart failure with or without restrictive mitral flow. Eur J Echocardiogr 10(4):562–566
Dini FL, Rosa GM, Fontanive P, Santonato V, Napoli AM, Ciuti M, Di Bello V (2010) Combining blood flow and tissue Doppler imaging with N-terminal pro-type B natriuretic peptide for risk stratification of clinically stable patients with systolic heart failure. Eur J Echocardiogr 11(4):333–340
Besli F, Kecebas M, Caliskan S, Dereli S, Baran I, Turker Y (2015) The utility of inferior vena cava diameter and the degree of inspiratory collapse in patients with systolic heart failure. Am J Emerg Med 33(5):653–657
Carbone F, Bovio M, Rosa GM, Ferrando F, Scarrone A, Murialdo G, Quercioli A, Vuilleumier N, Mach F, Viazzi F, Montecucco F (2014) Inferior vena cava parameters predict readmission in ischemic heart failure. Eur J Clin Invest 44(4):341–349
Morris R, Prasad A, Asaro J, Guzman M, Sanders L, Hauck A, Singh GK, Levy PT (2017) Markers of cardiovascular dysfunction in adolescents with anorexia nervosa. Glob Pediatr Health 4:2333794×17727423
Winston AP, Jamieson CP, Madira W, Gatward NM, Palmer RL (2000) Prevalence of thiamin deficiency in anorexia nervosa. Int J Eat Disord 28(4):451–454
Douyon L, Schteingart DE (2002) Effect of obesity and starvation on thyroid hormone, growth hormone, and cortisol secretion. Endocrinol Metab Clin N Am 31(1):173–189
Romig RA (1985) Anorexia nervosa, ipecac, and sudden death. Ann Intern Med 103(4):641
Cappelli V, Bottinelli R, Polla B, Reggiani C (1990) Altered contractile properties of rat cardiac muscle during experimental thiamine deficiency and food deprivation. J Mol Cell Cardiol 22:1095–1106
Astudillo L, Degano B, Madaule S et al (2003) Development of beriberi heart disease 20 years after gastrojejunostomy. Am J Med 115:157–158
Wooley JA (2008) Characteristics of thiamin and its relevance to the management of heart failure. Nutr Clin Pract 23:487–493
Sriram K, Manzanares W, Joseph K (2012) Thiamine in nutrition therapy. Nutr Clin Pract 27:41–50
Hofer M, Pozzi A, Joray M, Ott R, Hähni F, Leuenberger M, von Känel R, Stanga Z (2014) Safe refeeding management of anorexia nervosa inpatients: an evidence-based protocol. Nutrition 30(5):524–530
Grabowski A, Kilian J, Strank C, Cieslinski G, Meyding-Lamadé U (2007) Takotsubo cardiomyopathy—a rare cause of cardioembolic stroke. Cerebrovasc Dis 24(1):146–148
Valbusa A, Paganini M, Secchi G, Montecucco F, Rosa GM (2013) What happened to a thrombus during apical ballooning syndrome: a case report. Swiss Med Wkly 143:w13797
Volman MN, Ten Kate RW, Tukkie R (2011) Tako Tsubo cardiomyopathy, presenting with cardiogenic shock in a 24-year-old patient with anorexia nervosa. Neth J Med 69(3):129–131
Carlomagno G, Mercurio V, Ruvolo A, Senatore I, Halinskaya I, Fazio V, Affuso F, Fazio S (2011) Endocrine alterations are the main determinants of cardiac remodelling in restrictive anorexia nervosa. ISRN Endocrinol 2011:171460
Ramacciotti CE, Coli E, Biadi O, Dell’Osso L (2003) Silent pericardial effusion in a sample of anorexic patients. Eat Weight Disord 8(1):68–71
Docx MK, Gewillig M, Simons A, Vandenberghe P, Weyler J, Ramet J, Mertens L (2010) Pericardial effusions in adolescent girls with anorexia nervosa: clinical course and risk factors. Eat Disord 18(3):218–225
Kircher JN1, Park MH, Cheezum MK, Hulten EA, Kunz JS, Haigney M, Atwood JE (2012) Cardiac tamponade in association with anorexia nervosa: a case report and review of the literature. Cardiol J 19(6):635–638
Misra M, Freed N, Herzog DB, Goldstein M, Riggs S, Klibanski A (2006) Uncoupling of cardiovascular risk markers in adolescent girls with anorexia nervosa. J Pediatr 149(6):763–769
Ohwada R, Hotta M, Oikawa S, Takano K (2006) Etiology of hypercholesterolemia in patients with anorexia nervosa. Int J Eat Disord 39(7):598–601
Rigaud D, Tallonneau I, Vergès B (2009) Hypercholesterolemia in anorexia nervosa: frequency and changes during refeeding. Diabetes Metab 35(1):57–63
Solmi M, Veronese N, Manzato E, Sergi G, Favaro A, Santonastaso P, Correll CU (2015) Oxidative stress and antioxidant levels in patients with anorexia nervosa: a systematic review and exploratory meta-analysis. Int J Eat Disord 48(7):826–841
Birmingham CL, Lear SA, Kenyon J, Chan SY, Mancini GB, Frohlich J (2003) Coronary atherosclerosis in anorexia nervosa. Int J Eat Disord 34(3):375–377
García-Rubira JC, Hidalgo R, Gómez-Barrado JJ, Romero D, Cruz Fernández JM (1994) Anorexia nervosa and myocardial infarction. Int J Cardiol 15(2):138–140 45(
Abuzeid W, Glover C (2011) Acute myocardial infarction and anorexia nervosa. Int J Eat Disord 44(5):473–476
Crook MA (2014) Refeeding syndrome: problems with definition and management. Nutrition 30(11–12):1448–1455
Sachs K, Andersen D, Sommer J, Winkelman A, Mehler PS (2015) Avoiding medical complications during the refeeding of patients with anorexia nervosa. Eat Disord 23(5):411–421
Blank S, Zadik Z, Katz I, Mahazri Y, Toker I, Barak I (2002) The emergence and treatment of anorexia and bulimia nervosa. A comprehensive and practical model. Int J Adolesc Med Health 14:257–260
Ornstein RM, Golden NH, Jacobon MS, Shenker IR (2003) Hypophosphatemia during nutritional rehabilitation in anorexia nervosa: implications for refeeding and monitoring. J Adolesc Health 32:83–88
Mehanna HM, Moledina J, Travis J (2008) Refeeding syndrome: what it is, and how to prevent and treat it. BMJ 336:1495–1498
Rio A, Whelan K, Goff L, Reidlinger DP, Smeeton N (2013) Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study. BMJ Open 3(1): e002173
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Giovinazzo, S., Sukkar, S.G., Rosa, G.M. et al. Anorexia nervosa and heart disease: a systematic review. Eat Weight Disord 24, 199–207 (2019). https://doi.org/10.1007/s40519-018-0567-1
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DOI: https://doi.org/10.1007/s40519-018-0567-1