case report dilated cardiomyopathy induced by chronic starvation...

Case ReportDilated Cardiomyopathy Induced by Chronic Starvation andSelenium Deficiency

Soham Dasgupta1 and Ashraf M. Aly2

1Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA2Department of Pediatric Cardiology, University of Texas Medical Branch, Galveston, TX 77555, USA

Correspondence should be addressed to Ashraf M. Aly; [email protected]

Received 17 July 2016; Accepted 1 November 2016

Academic Editor: Bibhuti Das

Copyright © 2016 S. Dasgupta and A. M. Aly. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Protein energy malnutrition (PEM) has been rarely documented as a cause of cardiovascular abnormalities, including dilatedcardiomyopathy. Selenium is responsible for antioxidant defense mechanisms in cardiomyocytes, and its deficiency in the settingof PEM and disease related malnutrition (DRM) may lead to exacerbation of the dilated cardiomyopathy. We report a rare caseof a fourteen-year-old boy who presented with symptoms of congestive heart failure due to DRM and PEM (secondary to chronicstarvation) alongwith severe seleniumdeficiency. An initial echocardiogram showed severely depressed systolic function consistentwith dilated cardiomyopathy. Aggressive nutritional support and replacement of selenium and congestive heart failure medicationsthat included diuretics and ACE inhibitors with the addition of carvedilol led to normalization of the cardiac function within fourweeks. He continues to have significant weight gain and is currently completely asymptomatic from a cardiovascular standpoint.

1. Introduction

TheWorldHealthOrganization (WHO) definesmalnutritionas “the cellular imbalance between the supply of nutrients andenergy and the body’s demand for them to ensure growth,maintenance, and specific functions [1].” The term proteinenergy malnutrition (PEM) applies to a group of related dis-orders that includemarasmus, kwashiorkor, and intermediatestates of marasmus-kwashiorkor. Marasmus involves inade-quate intake of protein and calories and is characterized byemaciation while kwashiorkor involves normal caloric intakebut inadequate protein intake.We report a rare case of dilatedcardiomyopathy caused by severe malnutrition combinedwith selenium deficiency in a teenager.Themalnutrition seenin this patient can be more accurately defined as “diseaseor injury related malnutrition” and is commonly seen in thesetting of major infection, burns, or trauma [2].

2. Case Report

A fourteen-year-old boy from SouthAmerica was transferredto the burn unit at our institution for severe malnutrition.

The patient had sustained second-degree burns (>25% BSA)two years prior to admission. He did not receive adequatenutrition and medical care because of poverty and limitedresources in his home country. He was noted to be severelycachectic and malnourished at a local hospital and wastransferred to the United States by a charity organization forhigher level of care.

Initial assessment was significant for a weight of19 kg (<3rd percentile on WHO growth chart), height of141 cm (BMI 9.6 kg/m2, 𝑧 score −12.42), blood pressure of92/63mmHg, and a heart rate of 140 bpm. He experiencedshortness of breath with minimal physical activity. Physicalexamination revealed severe cachexia with atrophy of allmuscles without peripheral edema. He was also notedto be moderately dehydrated. Initial investigations weresignificant for mild hyponatremia [133mmol/L (NL 135–145mmol/L)], severe hypoalbuminemia [0.2 g/dL (NL3.5–5.0 g/dL)], hypocalcemia [ionized calcium 3.2mg/dL(NL 4.5–5.3mg/dL)], severe iron deficiency anemia[hemoglobin/hematocrit 6.7 gm/dL/24.8%, MCV 69.3 FL],and selenium deficiency [32 ug/L]. The reported normalserum selenium levels in the United States ranges from 50

Hindawi Publishing CorporationCase Reports in PediatricsVolume 2016, Article ID 8305895, 4 pageshttp://dx.doi.org/10.1155/2016/8305895

2 Case Reports in Pediatrics

0

5

10

15

20

25

30

35

1 4 7 10 15 90 120Number of days

Wei

ght (

kg)

Figure 1: A diagram showing the increase in body weight with time.

to 150 ug/L [3] while the normal serum levels of selenium inhis country of origin is reported to be 80.6–199 ug/L [4]. Thecarnitine level was normal.

Immediate intravenous fluid resuscitation was initiated.Since he was severely malnourished and had limited abilityfor oral intake, high calorie enteral nutrition was admin-istered via a nasogastric tube. An initial echocardiogram(echo) showed a globular dilated left ventricle with a severelydepressed systolic function [ejection fraction (EF) < 25%]consistent with dilated cardiomyopathy. He was initiallytreated with furosemide and enalapril, and carvedilol wasadded a week later since there was minimal improvementin cardiac function in addition to selenium replacement[200mcg (2.5 umol) twice daily intravenously]. He receivedtwo blood transfusions and repeated albumin infusionswithin the first five days. One week later, his cardiac functiondramatically improved [EF 46%]. His selenium level, as wellas other labs, normalized within two weeks. The cardiacfunction normalizedwithin fourweeks.Hisweight continuedto increase and reached 30 kg [BMI 15.1 kg/m2, 𝑧 score−2.40] within fourmonths (Figure 1). All cardiacmedicationswere then discontinued. The patient’s stamina continues toimprove, and he is able to tolerate full oral intake.

3. Discussion

Malnutrition is a significant cause of morbidity andmortalityin developing countries. It is the direct cause of over 300,000deaths annually and is indirectly responsible for about half ofall deaths in children [5]. The median prevalence of under-weight children worldwide in the year 2012 was 15% with3% of them having severe muscle wasting [6]. Malnutritionmay be secondary to a variety of reasons including poverty,pathologic states, political situations in certain countries, andeven acts of rebellion in order to achieve certain goals. Specifi-cally, “disease relatedmalnutrition” is defined asmalnutritionin the setting of severe inflammation and is commonly seenin the setting of major infection, burns, or trauma. Criticalillness or injury promotes an acute inflammatory responsethat has a rapid catabolic effect on lean body mass [7]. Theinflammatory condition in most diseases is chronic in natureand loss of muscle mass and functionmay occur over months

to years. This form of malnutrition is partially attributableto a decrease in nutrient intake and to the effect of theinflammatory state on metabolism. The malnutrition seen inthis case was both disease related and secondary to starvationas a result of his disease and poverty.

Children suffering from severe malnutrition may exhibitcardiovascular abnormalities including hypotension, cardiacarrhythmias, cardiomyopathy, cardiac failure, and even sud-den death [8]. The cardiac myocytes atrophy during star-vation similar to other muscles in the body [8]. Kerpel-Fronius andVarga showed a 60%decrease in theweight of theheart in an autopsy study [9]. Ultrastructural features of ratswith PEM showed hyalinization and vacuolization of cardiacmuscle fibers, loss of cross striations and myofibrils, smallfoci of necrosis, interstitial fibrosis, and mononuclear cellinfiltration [10]. Histological studies of human myocardiumin patients with PEM show atrophy of the muscle fibers withinterstitial edema. The heart has also been reported to bethin-walled, pale, and flabby on gross examination in otherautopsy studies of children with malnutrition [11].

Echocardiographic studies have shown decreased leftventricular (LV) mass in patients with PEM. Singh et al.reported that LV systolic functions were reduced especiallyin children with a loss in bodyweight of more than 40% ofexpected weight [12]. A recent study showed that parametersof LV systolic function were significantly reduced in patientswith PEM as compared to controls [13]. PEM has beenestablished as an independent risk factor for mortality inpatients with heart failure [14].

Chinese investigators first showed that selenium defi-ciency is one of the principal factors responsible for Keshandisease, a dilated cardiomyopathy that affects people livingin rural areas where selenium is deficient [15]. Seleniummediates its effects via incorporation into selenoproteins(Figure 2). Selenium-dependent enzymes mediate a widerange of biological functions such as regulation of theinflammatory response and proliferation/differentiation ofseveral immune cells.

Selenium is also important in the body’s antioxidantdefensemechanism [16].When incorporated into the variousselenoenzymes, selenium increases antioxidant capacity andsuppresses the production of interleukins and tumor necrosisfactor alpha (TNF-𝛼). Lu et al. provided the first evidencethat selenoproteins contribute to the antioxidant defensemechanisms in cardiomyocytes. Venardos and colleaguesdemonstrated that selenium deficiency leads to myocardialinjury secondary to increased protein and lipid peroxidationin a rat model.These data were supported by the experimentsof Tanguy et al., who showed that selenium deficiency in ratslead to myocardial damage and altered recovery of cardiacfunction.

Given these findings, various experimental studies haveaimed to limit myocardial injury through selenium supple-mentation. The Venardos group showed significantly moremyocardial injury in rats fed with a low selenium diet.Furthermore, Tanguy and colleagues confirmed selenium’sprotective characteristics by demonstrating (a) an improvedcardiac function recovery, (b) a significantly reduced infarct

Case Reports in Pediatrics 3

Heart

GP-3Prevents LDL oxidation, vascular inflammation, and atherogenesis

GP-4Protects cellular lipids from oxidation

Trx-1Reduces hypertrophy and oxidative stress

SelKDecreases intracellular ROS

Figure 2: A diagram showing the actions of various selenoproteins on the cardiac myocytes. SelK: selenoprotein K. GP-3: glutathioneperoxidase-3. Trx-1: thioredoxin reductase-1. GP-4: glutathione peroxidase-4. ROS: reactive oxygen species. LDL: low density lipoprotein.

Table 1: A comparison between marasmus and kwashiorkor.

Marasmus (PEM) KwashiorkorSevere deficiency of allnutrients and inadequatecaloric intake

Severe protein deficiencybut normal caloric intake

Peripheral edema is absent Peripheral edema is present

Hair changes absentHair changes common(sparse and easily pulledout)

Skin is dry and wrinkledbut no dermatosis

Dermatosis, flaky paintappearance of skin

Voracious appetite Poor appetiteAbsent subcutaneous fat Reduced subcutaneous fatFatty liver uncommon Fatty liver commonBetter prognosis Worse prognosis

size, and (c) a decreased incidence of postischemic ventric-ular arrhythmias in rats that received the highest seleniumintake.

The patient we described had some features consistentwith marasmus (Table 1). He also had evidence of dilatedcardiomyopathy based on congestive heart failure symptomsand echocardiographic findings. He responded well to stan-dard therapy for dilated cardiomyopathy with furosemide(preload reduction), enalapril (afterload reduction), andcarvedilol (antioxidant effects). Carvedilol is a nonselectivebeta blocker which suppresses reactive oxygen species andhas antioxidant and anti-inflammatory effects [17]. Seleniumsupplementation was added for its documented deficiencyin addition to providing adequate nutritional support. Therewas a remarkable weight gain from 19 kg to 25 kg in just2 weeks and he continues to gain more weight. He iscurrently asymptomatic from a cardiovascular standpointand is tolerating complete oral intake.

4. Conclusion

Cardiac injury leading to dilated cardiomyopathy in cases ofsevere malnutrition is rare but documented in the literature.During the treatment of patients with malnutrition, levelsof trace elements (specially selenium) should be checked.

Adequate nutrition and replacement of deficient elementsshould be initiated as soon as possible. Congestive heartfailure and dilated cardiomyopathy in these patients seemto respond well to preload and afterload reduction with theaddition of carvedilol as an antioxidant.

Abbreviations

WHO: World Health OrganizationPEM: Protein energy malnutritionBSA: Body surface areaBMI: Body mass indexLV: Left ventricularTNF-𝛼: Tumor necrosis factor-𝛼.

Competing Interests

Theauthors have no conflict of interests relevant to this articleto disclose.

References

[1] M. de Onis, C. Monteiro, and G. Clugston, The WorldwideMagnitude of Protein-Energy Malnutrition: An Overview fromtheWHOGlobal Database on Child Growth, vol. 71, no. 6,WorldHealth Organization, Geneva, Switzerland, 1993.

[2] G. L. Jensen, J. Mirtallo, C. Compher et al., “Adult starvationand disease-related malnutrition: a proposal for etiology-baseddiagnosis in the clinical practice setting from the InternationalConsensus Guideline Committee,” Journal of Parenteral andEnteral Nutrition, vol. 34, no. 2, pp. 156–159, 2010.

[3] R. E. Litov andG. F. Combs Jr., “Selenium inpediatric nutrition,”Pediatrics, vol. 87, no. 3, pp. 339–351, 1991.

[4] F. Sempertegui, B. Estrella, W. Vallejo et al., “Selenium serumconcentrations in malnourished Ecuadorian children: A Case-Control Study,” International Journal for Vitamin and NutritionResearch, vol. 73, no. 3, pp. 181–186, 2003.

[5] O. Muller and M. Krawinkel, “Malnutrition and health indeveloping countries,” Canadian Medical Association Journal,vol. 173, no. 3, pp. 279–286, 2005.

[6] Joint UNICEF—WHO—The World Bank Child MalnutritionDatabase: Estimates for 2012 and Launch of Interactive Data Dashboards, http://www.who.int/entity/nutgrowthdb/jme unicefwho wb.pdf.

4 Case Reports in Pediatrics

[7] A. A. Hill, L. D. Plank, P. J. Finn et al., “Massive nitrogen lossin critical surgical illness: effect on cardiac mass and function,”Annals of Surgery, vol. 226, no. 2, pp. 191–197, 1997.

[8] B. Ocal, S. Unal, P. Zorlu, H. T. Tezic, and D. Oguz, “Echocar-diographic evaluation of cardiac functions and left ventricularmass in children with malnutrition,” Journal of Paediatrics andChild Health, vol. 37, no. 1, pp. 14–17, 2001.

[9] F. Kerpel-Fronius and F. Varga, “Dynamics of circulation ininfantile malnutrition,” Pediatrics, vol. 4, no. 3, pp. 301–309,1949.

[10] M. A. Rossi and S. Zucoloto, “Ultrastructural changes innutritional cardiomyopathy of protein-calorie malnourishedrats,” British Journal of Experimental Pathology, vol. 63, no. 3,pp. 242–253, 1982.

[11] B. D. Gelb and J. Abdenur, “Metabolic heart disease,” in TheScience and Practice of Pediatric Cardiology, A. Garson, T. J.Bricker, D. J. Fisher, and J. R. Neish, Eds., p. 1913, Williams &Wilkins, Baltimore, Md, USA, 2nd edition, 1998.

[12] G. R. Singh, K. E. Malathi, R. R. Kasliwal, A. Ommar, S.Padmavati, and S. Ramji, “An evaluation of cardiac functionin malnourished children by non-invasive methods,” IndianPediatrics, vol. 26, no. 9, pp. 875–880, 1989.

[13] N. H. A. Faddan, K. I. E. Sayh, H. Shams, and H. Badrawy,“Myocardial dysfunction in malnourished children,” Annals ofPediatric Cardiology, vol. 3, no. 2, pp. 113–118, 2010.

[14] J. Bergstr and B. Lindholm, “Malnutrition, cardiac disease andmortality,” Peritoneal Dialysis International, vol. 19, supplement2, 1999.

[15] R. A. Johnson, S. S. Baker, J. T. Fallon et al., “An occidental caseof cardiomyopathy and selenium deficiency,”The New EnglandJournal of Medicine, vol. 304, no. 20, pp. 1210–1212, 1981.

[16] C. Benstoem, A. Goetzenich, S. Kraemer et al., “Selenium andits supplementation in cardiovascular disease—what do weknow?” Nutrients, vol. 7, no. 5, pp. 3094–3118, 2015.

[17] D. Paresh, G. Husam, and B. David, “Antioxidant activity ofcarvedilol in cardiovascular disease,” Journal of Hypertension,vol. 25, no. 4, pp. 731–741, 2007.

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