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ournal of Cardiology (2009) 54, 475—479

ASE REPORT

almonella myocarditis in a young adult patientresenting with acute pulmonary edema,habdomyolysis, and multi-organ failure

afid Fayadh Al-aqeedi (MD) ∗, Ahmed Kamha (MD, FRCP),uad K. Al-aani (MD), Ahmed A. Al-ani (MD, FRCP)

epartment of Cardiology & Cardiovascular Surgery, Hamad Medical Corporation, Doha, Qatar

eceived 10 November 2008; received in revised form 11 February 2009; accepted 13 February 2009

KEYWORDSSalmonella typhi;Myocarditis;Rhabdomyolysis;Pulmonary edema;Multi-organ failure

Summary The mortality and morbidity of salmonella infections is seriously under-estimated. Salmonella myocarditis is an unusual complication of salmonella sepsisin adults. Cases that do occur may be associated with high morbidity and mor-tality. We present a rare case of salmonella myocarditis with multi-organ failurein a previously healthy young adult man who was brought to the emergency roomwith fever, diarrhea, shortness of breath, and altered sensorium, discovered to haveacute pulmonary edema and respiratory compromise for which he was assisted withmechanical ventilation for 8 days. Blood culture grew Salmonella typhi. Biochemi-cally he exhibited myocardial, hepatic, and muscular enzymatic surge with renal

failure, features of rhabdomyolysis, and disseminated intravascular coagulation.The patient showed a progressive improvement on treatment with ceftriaxone for2 weeks in addition to decongestive therapy. He was discharged in good conditionafterward.

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© 2009 Japanese Collereserved.

ntroduction

yphoid fever is both a water- and food-borne

astrointestinal infection, common among childrennd young adults in developing countries, with anstimated global prevalence between 16 million

∗ Corresponding author at: Department of Cardiology & Car-iovascular Surgery, Hamad Medical Corporation, P.O. Box 3050,oha, Qatar.

E-mail address: rafayadh@yahoo.com (R.F. Al-aqeedi).

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914-5087/$ — see front matter © 2009 Japanese College of Cardiolooi:10.1016/j.jjcc.2009.02.011

f Cardiology. Published by Elsevier Ireland Ltd. All rights

nd 33 million cases per year, with 700,000 deaths1,2].

Typhoid fever is a life-threatening illnessarely complicated by myocarditis. Inflammatoryyocarditis caused by non-viral infective agents

s nowadays rare. It usually occurs in immuno-uppressed patients with secondary involvement

f the myocardium [3]. Salmonella myocarditisay produce variable clinical manifestations from

atent to severe clinical forms, such as acuteongestive heart failure and sudden cardiac death

gy. Published by Elsevier Ireland Ltd. All rights reserved.

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476

[4,5]. Postmortem studies suggest that myocarditisis a major cause of sudden unexpected death inyoung adults and may account for 20% of cases [6].Rhabdomyolysis associated with Salmonella typhiinfection has only been reported in a few cases[7,8]. However, there have been more reportedcases associated with S. enteritidis [9,10]. Wepresent the case report of a young adult manbrought with fever, diarrhea, shortness of breath,and altered sensorium due to S. typhi infectionculminating in myocarditis, rhabdomyolysis, andmulti-organ failure.

Case report

A 34-year-old Indian man was brought to the emer-gency room by emergency medical services afterbecoming unconscious on a nearby avenue. Notmuch history data were available upon presenta-tion, although on retrospect he had 3 days’ historyof fever and frequent diarrhea, his symptoms hadintensified before admission, and he became con-fused and lethargic.

The patient had had no previous health problemsor coronary artery disease risk factors, he was noton any medications and had no allergies. There wasno history of alcohol, tobacco, or illicit drug use.He had no witnessed convulsions or recent contactwith animals or anyone with a febrile illness.

Physical examination on arrival revealed a welldeveloped but ill-looking young man, dehydrated,orthopneic with blood pressure 98/55 mmHg, heartrate 142 beats/min, respiratory rate 28 min−1, tem-

perature 39.1 ◦C, and O2 saturation 98% on roomair. He was somnolent and he had no meningismusor focal neurological signs. The cardio-respiratoryexamination revealed bilateral fine basal crepi-

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Figure 1 The electrocardiogram (ECG) showed sinus tachycar

R.F. Al-aqeedi et al.

ations with no murmurs or pericardial rub.bdominal and musculoskeletal examinations wereormal with no skin rash. While he was inhe emergency room, he developed increasingreathlessness and crepitation to mid chest withespiratory compromise (O2 saturation 71%), andigns of circulatory hypoperfusion. An assistedechanical ventilation was established and he was

hen admitted to medical intensive care unit (MICU)here a central venous line was inserted.The laboratory investigations upon arrival

howed creatine kinase (CK) and creatinineinase isoenzyme MB (CK-MB) were elevated to341 U/l and 409.5 ng/ml, respectively, troponinwas 0.26 ng/ml (normal: <0.1), troponin I was

.86 ng/ml (normal: <0.08), and myoglobin was2,480 ng/ml. Leukocyte count was 4.5 × 103 �l−1

neutrophils 87.7%, lymphocytes 11%, mono-ytes 1.2%), hemoglobin 12 g/dl, platelet count7 × 109 l−1. In regard to his hepatic function, theerum bilirubin was normal, but liver enzymes werelevated, aspartate aminotransferase 2320 U/l andlanine aminotranferase 559 U/l, however alkalinehosphatase was normal. Total protein was 62 g/lnd serum albumin 31 g/l. His renal functionhowed urea nitrogen 17.9 mmol/l, serum creati-ine 210 �mol/l and corrected calcium 1.77 mmol/lhereas serum sodium, potassium, magnesium,nd phosphorous were normal. The coagulationtudies revealed an international normalized ratiof 1.8 and a partial thromboplastin time of 41.4 s.-Dimer test was elevated 9087 �g/l (normal: upo 280 �g/l). Arterial blood gas analysis showedetabolic acidosis with pH 7.188, pCO 40.1 mmHg,

2O2 74.2 mmHg, and HCO3 14.7 mmol/l. Toxicologycreening for drugs and alcohol was negative.

Liver, spleen, and kidneys were with normal sizesn bedside abdominal ultrasound but mild ascites

dia, heart rate 146 min−1, and nonspecific ST, T changes.

Salmonella myocardits in a young adult patient 477

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igure 2 (A) Admission chest X-ray consistent with acuteulmonary edema. (B) Chest X-ray showing improvementfter intensive therapy.

etected. Computed tomography scan of the headnd cervical spine was normal. Cerebrospinal fluidas clear with normal cytology, protein, and sugarontent, culture revealed no growth and Gram andcid fast bacilli stains were negative. Endotrachealube secretion showed no bacterial growth. Twoottles of blood culture grew S. typhi. A urinaly-is showed significant myoglobulin, 3+ blood and 2+rotein but no active sediment or bacterial growth.erology for both hepatitis B and C viruses wereegative.

The electrocardiogram (ECG) showed sinusachycardia, heart rate 148 min−1, and nonspe-

ific ST, T changes (Fig. 1). Chest X-ray showedilateral perihilar vascular congestion suggestivef pulmonary edema with no gross cardiomegalyCT ratio: 0.5) (Fig. 2A). Transthoracic echocar-

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nitial presentation. Two-dimensional four chambersiews; (A) during end-systole; (B) during end-diastole; (C)-mode view.

iography showed severe left ventricular systolicysfunction with ejection fraction (LVEF) of 23% andkinesia of both mid inferior and anterior segmentsith hypokinesis of the rest of myocardium. No veg-tations were seen (Fig. 3).

The initial diagnosis of complicated heat stroke

as raised until the result of blood culture emergedfter 2 days. Meanwhile he was managed with intra-enous fluid resuscitation, antibiotics together withiuretics and sodium bicarbonate to maintain an

478

alkaline urine. The final diagnosis of S. typhi infec-tion and related myocarditis, rhabdomyolysis, andmulti-organ failure was made based on the clin-ical, echocardiographical findings and laboratoryresults. The patient was extubated after 8 days ofassisted ventilation while he showed a progressiveclinical and biochemical improvement on treat-ment with ceftriaxone for 2 weeks (Fig. 2B). Hishematological and biochemical parameters werenormalized, and a follow up echocardiography per-formed before discharge showed mild improvementwith LVEF of 30% and he was discharged afebrile ingood condition and planned for follow up. Another

Figure 4 Transthoracic echocardiography views 5months after initial presentation. Two-dimensional fourchambers views; (A) during end-systole; (B) during end-diastole; (C) M-mode view.

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chocardiography performed about 5 months afternitial presentation revealed more improvement inV function with EF 42% and mild global hypokinesiaFig. 4).

iscussion

he incidence of myocarditis is unknown andemains underestimated in spite of the develop-ent of various diagnostic modalities. In the caseresented, the diagnosis of S. typhi infection andelated myocarditis was made based on the clin-cal, laboratory, and echocardiographical results.he rise in CK-MB and troponins is noted in myocar-ial damage of any cause [11]; however, Smith etl. found CK elevation in only 5.7% and troponinelevation in 34% of patients with autoimmuneyocarditis [12].In one study of 100 patients with bacteriolog-

cally or serologically documented enteric fever,ohanan et al. found seven cases with clini-al evidence of myocarditis [13]. Rowland foundyocardial involvement in 9 out of 539 patient

1.2%) in another study [14].The common ECG abnormalities in salmonella

yocarditis mentioned in other reports were noteen in our case [15—19]. Moreover the character-stic paradoxical bradycardia in the febrile patientas also not detected. The absence of left ventric-lar dilatation and mild improvement in ventricularunction within a short period are characteristic ofulminant course of myocarditis, with low risk ofrogression to dilatated cardiomyopathy, whereascute myocarditis with less severe hemodynamicompromise more often leads to persistent cardiacilatation [20].

The elevated serum concentrations of CPKnd myoglobinuria causing renal dysfunction areharacteristic features of the syndrome of rhab-omyolysis in this patient. Infections are a wellnown but less common cause of rhabdomyolysis,nd should always be considered in the differen-ial diagnosis. There have only been few reportedases of rhabdomyolysis related to S. typhi infec-ion but more have been reported cases with otheralmonellae species [7—10]. Immunologically medi-ted myocardial damage or bacterial invasion ofuscles and generation of toxins are the proposedathophysiological mechanisms of rhabdomyolysisnd myocarditis in salmonella infections. Balanced

ntravenous fluid therapy and sodium bicarbonateo maintain an alkaline urine to prevent the disso-iation of myoglobin to its nephrotoxic metaboliteerrihemate can be of value in management ofhabdomyolysis-related nephrotoxicity [21,22].

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almonella myocardits in a young adult patient

The presentation with congestive heart failurend pulmonary edema in young patients, without aistory of heart disease, especially when it is con-urrent with infection, should arouse suspicion ofyocarditis. The reversible nature of myocarditis in

yphoid is recognized and early institution of diuret-cs and specific antibiotic therapy can help tide overhe period until the inflammatory process subsides.

The definitive diagnosis of myocarditis mayequire an endomyocardial biopsy. However, in ourase we thought this invasive test might not bendicated just to establish direct proof of inflamma-ion when the disease can be clinically diagnosedased on positive blood culture of S. typhi alongith the biochemical, echocardiographic examina-

ions, and reversible nature of congestive cardiacailure. Moreover, the Dallas criteria used for theistological evaluation of biopsy specimens proba-ly underestimate the true incidence of myocarditis6].

onclusion

lthough rare, rhabdomyolysis and multi-organailure are recognized complications of S. typhinfection in addition to myocarditis. This should beept in mind when reviewing clinical and labora-ory findings, as early recognition and managementf these complications can improve survival.

eferences

[1] Agarwal KS, Singh SK, Kumar N, Srivastav R, Rajkumar A.A study of current trends in enteric fever. J Commun Dis1998;30:171—4.

[2] Engels EA, Falagas ME, Lau J, Bennish ML. Typhoid fevervaccines: a meta-analysis of studies on efficacy and toxicity.Br Med J 1998;316:110—6.

[3] Calabrese F, Thiene G. Myocarditis and inflammatory car-

diomyopathy: microbiological and molecular biologicalaspects. Cardiovasc Res 2003;60:11—25.

[4] Burt CR, Proudfoot JC, Roberts M, Horowitz RH. Fatalmyocarditis secondary to Salmonella septicemia in a youngadult. J Emerg Med 1990;8:295—7.

[

Available online at www.

479

[5] Le-Van-Dien, Arnold K. Typhoid fever with myocarditis. AmJ Trop Med Hyg 1974;23:218.

[6] Feldman AM, McNamara D, Myocarditis. N Engl J Med2000;342:1388—98.

[7] Rheingold OJ, Greenwald RA, Hayes PJ, Tedesco FJ. Myo-globinuria and renal failure associated with typhoid fever.JAMA 1997;238:341.

[8] Barnes P, Goldstein DA, Overturf GD. Rhabdomyoly-sis and pancytopenia in a young man. West J Med1986;144:586—90.

[9] Sion ML, Hatzitolios A, Toulis E, Kounanis A, ProkopidisD. Rhabdomyolysis and acute renal failure associated withSalmonella enteritidis bacteremia. Nephrol Dial Transplant1998;13:532.

10] Singh U, Scheld WM. Infectious etiologies of rhabdomy-olysis: three case reports and review. Clin Infect Dis1996;22:642—9.

11] Kadota S, Takeuchi Y, Izuhara M, Baba O, Shioji K, UegaitoT, Kadota E, Matsuda M. The importance of serial car-diac troponin measurement for evaluating the responseto immunosuppressive therapy for myocarditis. J Cardiol2008;52:154—8.

12] Smith SC, Ladenson JH, Mason JW, Jaffe AS. Evaluation ofcardiac troponin I associated with myocarditis: experimen-tal and clinical correlates. Circulation 1997;95:163—8.

13] Mohanan PA, Pereira P, Raghuveer CV. Myocarditis in entericfever. Indian J Med Sci 1995;49:28—31.

14] Rowland HA. The complication of typhoid fever. J Trop MedHyg 1961;64:143.

15] Nand N, Sharma M, Bhutani M, Singh GP, Sharma VK. Cardiacstatus in typhoid fever. Angiology 1996;47:1095—100.

16] Pelupessy JM, Sangka P. Electrocardiographic pat-tern of typhoid fever in children. Paediatr Indones1989;29:215—20.

17] Akdeniz H, Tuncer I, Irmak H, Demiroz AP. Salmonellamyocarditis in a patient with Wolf—Parkinson—White syn-drome that was confused with an inferior myocardialinfarction. Clin Infect Dis 1997;25:736—7.

18] Rajeshwari K, Yadav S, Puri RK, Khanijo CM. Sick sinus syn-drome: a rare complication of typhoid fever. Indian Pediatr1994;31:995—8.

19] Mathur SL. Sino-atrial block in typhoid fever [letter]. J AssocPhysicians India 1990;38:243—4.

20] Felker GM, Boehmer JP, Hruban RH, Hutchins GM, KasperEK, Baughman KL, Hare JM. Echocardiographic findingsin fulminant and acute myocarditis. J Am Coll Cardiol2000;36:227—32.

21] Al Ani MA. Rhabdomyolysis and acute renal failure asso-

ciated with Salmonella food poisoning. Qatar Med J2003;12:141—3.

22] Prendergast BD, George CF. Drug induced rhabdomy-olysis: mechanism and management. Postgrad Med J1993;69:333—6.

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