Br Heart J: first published as 10.1136/hrt.34.8.821 on 1 August 1972. Downloaded from British HeartJournal, I972, 34, 82I-827. Myocarditis and cardiomyopathy after arbovirus infections (dengue and chikungunya fever) Ivor Obeyesekere and Yvette Hermon From the Cardiology Unit, General Hospital, Colombo, and the Virus Laboratory, Medical Research Institute, Colombo, Ceylon The varying clinicalfeatures and sequelae in Io patients sufferingfrom myocarditis after dengue and chikungunya fever caused by arboviruses are described. These patients had significantly raised antibody levels in the serum and gave a recent history of 'dengue-like' fever. Afew patients had afavourable outcome with disappearance ofsymptoms, improvement in the electrocardiogram, and no residual cardiomegaly. Others had persistent symptoms, electrocardio- graphic changes, and cardiomegaly which suggested a transition to cardiomyopathy, a chronic cardiac disorder. It seems likely that arbovirus infections play a significant role in the aetiology of the cardiomyopathies which are common in Ceylon. Myocarditis or inflammation of the myocar- rhythm; (3) a recent history of 'dengue-like' dium refers to myocardial lesions and symp- fever; (4) serological evidence of past dengue or toms associated with infectious diseases and chikungunya infection as revealed by the presence specific infections. Among the reported causes of antibody in high titre. are The study included the history, physical bacterial, viral, mycotic, protozoal and examination, serial electrocardiograms, serial x- Rickettsial infections, parasitic infestations, rays of chest, and cardiac catheterization in two http://heart.bmj.com/ and specific bacterial toxins. Of the viruses, patients. The laboratory tests included routine Coxsackie B, and less frequently viruses examination of urine and blood, estimation of causing infectious mononucleosis, infectious transaminases, erythrocyte sedimentation rates, hepatitis, mumps, measles, poliomyelitis, complement-fixation tests for toxoplasmosis and aseptic meningitis, and encephalo-myocar- filariasis, antistreptolysin titres, and tests for ditis have been reported to be pathogenic to systemic lupus erythematosus. man. While dengue and chikungunya fever Serological tests for arbovirus antibody were carried out by means of the haemagglutination- are well recognized, there are very few on September 30, 2021 by guest. Protected copyright. pub- inhibition test to determine evidence of past lished reports concerning their cardiac com- arbovirus infection. Simultaneously, the same plications (Boon and Tan, I967; Hyman, test was carried out on 3 control groups ofpatients I943). Myocarditis, which was thought to be also admitted to the Cardiology Unit, (I) those benign, is now known to lead to a more with rheumatic heart disease, (2) those suffering chronic disorder, cardiomyopathy (Bengtsson, from coronary heart disease, with characteristic I968). electrocardiographic changes and transient rises This paper describes the varying clinical in activity of serum enzymes (SGOT), and (3) features and sequelae of patients suffering those with congenital heart disease. The comple- from myocarditis in association with dengue ment-fixation test was done on IO patients suffer- and chikungunya fever caused ing from myocarditis who showed high haemag- by arboviruses glutination-inhibition antibody levels. The de- and referred to as 'arbovirus myocarditis'. scription of the antigens used and serological techniques are described in the Appendix. Subjects and methods For the purpose of this study io patients were Results selected in whom a diagnosis of arbovirus myo- The results of haemagglutination-inhibition carditis was made. The following diagnostic and complement-fixation tests in IO patients criteria were used. (i) Clinical evidence of myo- with myocarditis are given in Table carditis; (2) the presence of electrocardiographic i. All evidence of myocarditis, ST segment and T wave these (except Case 9) had haemagglutination- changes, and disturbances in conduction and inhibition antibody levels of i: 640 or greater to either dengue (Type I or II) or chikun- Received 25 October 1971. gunya, and all (except Case i) had comple- Br Heart J: first published as 10.1136/hrt.34.8.821 on 1 August 1972. Downloaded from 822 Obeyesekere and Hermon TABLE I Virus serological results ofpatients with acute arbovirus myocarditis Case Age Sex Haemagglutination inhibition titre Complement-fixation titre No. JE DI D2 Chik JE Di D2 Chik I 43 F < 20 640 I60 I280 <4 I6 i6 32 2 24 F i6o 640 640 <20 <4 64 32 < 4 3 33 F 640 2560 i28o <20 32 I28 64 <4 4 48 F 320 320 640 <20 8 I28 i28 <4 5 32 F 320 640 640 <20 i6 64 64 <4 6 44 F 8o 80 80 2560 <4 8 i6 I28 7 5I M I60 640 640 <20 8 64 64 <4 8 20 F I60 I280 i6o <20 8 I28 32 < 4 9 40 M 320 320 320 I60 8 64 I28 i6 o0 5 F 320 640 640 <20 8 64 64 4 II I8 F < 20 8o 80 5I20 I2 54 F 40 i6o I60 640 l 13 36 M I60 320 i60 40 l I4 48 F 40 320 i60 I60 i6I6 3653° FM i68o80 640320 320 <20 Not done 17 i8 F 40 320 i60 40 I8 7 M <20 320 40 <20 I9 32 F i6o i6o 320 <20 20 59 M < 20 i6o 8o 320 ment-fixation antibody levels of I: 64 or past arbovirus infection. It is postulated that greater. Ten other patients with myocarditis dengue and chikungunya fevers, with their had haemagglutination-inhibition titres of prominent myalgic manifestations, involved I:320 and above to dengue or chikungunya. the myocardium and triggered off the chain Table 2 gives the haemagglutination-inhibi- of symptoms resulting in acute myocarditis tion and complement-fixation test results in followed, in some cases, by cardiomyopathy. the 3 control groups. There was a striking and All the I0 patients with acute myocarditis http://heart.bmj.com/ highly significant difference, with only one gave a history of 'dengue-like' illness in the patient with a haemagglutination-inhibition recent or distant past. It was not possible by titre of I: 320 and two with titres of i: i6o. determining the haemagglutination-inhibition A serological diagnosis of arbovirus infec- antibody levels of single sera to determine tion necessarily depends on the examination whether the infections were primary or secon- of paired sera, the first sample being collected dary dengue. However, the complement- in the acute phase and the second convalescent fixation test results confirmed that all these sample 2 or 3 weeks later. The criteria for were secondary or recurrent infections as on September 30, 2021 by guest. Protected copyright. serological diagnosis have been described there was antibody to both Types I and II (Nimmannitya et al., I969). Primary and dengue. Two patients (Cases i and 6) showed secondary or recurrent infection are recog- high haemagglutination-inhibition and com- nized according to the haemagglutination- plement-fixation titres to chikungunya as well inhibition and complement-fixation antibody as dengue haemagglutination-inhibition and responses. In the I0 patients described in this complement-fixation antibody, which indi- paper, a diagnosis of acute arbovirus infection cated infections with both viruses in the past. was not initially sought. By the time these The main clinical features and sequelae of I0 patients presented themselves at the cardi- patients with arbovirus myocarditis are illus- ology unit they already had established cardiac trated by case histories. disorders which followed recent 'dengue-like' illnesses. Five of these patients (Cases I, 5, 6, 7, and 8) also gave definite histories of Case histories similar attacks of fever occurring months or Case I A 43-year-old housewife developed years earlier. Only evidence of past arbovirus sharp pain over the praecordium, difficulty in infection was, therefore, sought and a single taking a deep breath, profuse sweating, and of was dizziness. sample blood sent for detection of A few days previously and also three months arbovirus antibody. The results revealed that before she had had fever with recurrent head- all these patients had high dengue and chikun- aches, backache, and pains in the joints. gunya haemagglutination-inhibition and com- On examination, temperature was 37 40C, pulse plement-fixation antibody which confirmed a rate 78 a minute with frequent ectopics, and Br Heart J: first published as 10.1136/hrt.34.8.821 on 1 August 1972. Downloaded from Myocarditis and cardiomyopathy after arbovirus infections (dengue and chikungunya fever) 823 blood pressure 130/70 mmHg. Both heart sounds TABLE 2 Virus serological results ofpatients were heard. Crepitations were heard at the base with (a) rheumatic heart disease, (b) coronary of the left lung. She ran a low temperature for heart disease, and (c) congenital heart disease five days and complained of extreme fatigue and (controls) breathlessness. The ventricular ectopics persisted for four weeks. Disease Control Age Sex Haemagglutination inhibition titre Two months later, she was symptom free; No. there were no abnormal physical signs in the J7E Di D2 Chik heart. I 20 F < 20 8o < 20 < 20 Comments 2 I2 F < 20 < 20 < 20 < 20 3 I0 F <20 <20 <20 <20 This woman presented with severe chest pain 4 41 F < 20 8o 40 < 20 simulating coronary heart disease. She had ex- Rheumatic 5 10 F < 20 < 20 < 20 < 20 tensive electrocardiographic changes, a raised heut 6 24 F < 20 < 20 < 20 < 20 erythrocyte sedimentation rate, normal serum disease (12) 7 17 F < 20 < 20 < 20 < 20 enzymes, and positive serology for arbovirus in- 8 33 F <20 <20 <20 <20 fection. The pain was probably pericardial in 9 22 M < 20 < 20 < 20 < 20 I0 I9 M 40 320 320 < 20 origin. She made a satisfactory recovery within II 26 F < 20 < 20 < 20 < 20 two months with no symptoms, return of the I2 I7 F < 20 8o 40 < 20 electrocardiogram to normal, and no residual cardiomegaly. (13 45 M <20 <20 <20 <20 114 48 M <20 <20 <20 <20 I5 45 M 8o 40 8o <20 Case 2 An unmarried woman aged 24 years Coronary heart J I6 48 M 8o i6o 8o <20 presented with fever of I0 days' duration, general- disease (8) 17 57 F 8o 8o i6o i6o ized aches and pains, painful joints, palpitations, i8 44 M <20 <20 <20 <20 and sharp pain over the praecordium made worse I9 45 M <20 <20 <20 <20 by deep breathing.