Upsala J Med Sci 81: 167-173, 1976 Acute Myopericarditis A Long-term Follow-up Study E. SANNER, G. SIGURDSSON, D. GISLASSON, B. GUDBRANDSSON and M. STEFANSSON From the Department of Medicine, Central Hospital, Eskilstuna, Sweden ABSTRACT A follow-up study was made of 29 patients aged 21 to 45 years, some 15-158 months after acute myopericarditis. The mean follow-up period was 72.9 months. The follow-up investigation included recording of history, physical exami- nation, laboratory tests, radiologic examination of the heart and lungs and electrocardiography. All hut one of the pa- tients were fit for fulltime work. Nine had residual cardiac symptoms, but the physical examination was negative in all but 2 of them. One patient had chronic cardiac insufficiency and hepatic enlargement. Another had sinus tachycardia and cardiac enlargement of moderate degree and impaired working capacity in relation to heart size. Cardiac murmurs without clinical significance were audible in three cases. The resting ECG was pathologic in only 6 cases. Orthostatic ECG evoked ECG abnormalities in 6 more cases. Exercise tolerance tests showed reduced working capacity in relation to heart volume in 5 of the 29 cases (17%). Four of these 5 patients had cardiac enlargement. There was thus good correlation between increase in heart volume and reduction of physical capacity. The prognosis in regard to cardiac function was good, as was also found in other comparable series in which the observation time was somewhat shorter. INTRODUCTION Acute myopencarditis can occur in previously healthy persons in connexion with acute infections of varying aetiology. In many cases the precise aetiology cannot be established ( 1 , 16). In the diffe- rential diagnosis cardiomyopathy , ischaemic heart disease, collagenosis, rheumatic fever, tuberculosis and sarcoidosis must be excluded. Some reports have recently been published on the incidence and course of acute myopericarditis (11, 3, 7, 2, 6). The prognosis of acute myo- pericarditis in regard to cardiac function is con- sidered to be good, however, a few deaths and occasional cases of chronic cardiac insufficiency have been reported (11, 16, 13). Because of the paucity of long-term observations, we have fol- lowed up a selected series of patients who were treated at the medical clinic of Eskilstuna for myopericarditis between 1958 and 1970 (one patient was hospitalized in Stockholm). Our primary inten- tion was to study the long-term prognosis in regard to cardiac function. The observation periods ranged from 15 to 158 months (mean 72.9 months). MATERIAL AND METHODS Patients: The records of 64 cases classified as acute myopericarditis were reviewed. This diagnosis was altered in 2 patients who died soon after admission (of carbon monoxide and thioridazine intoxication). Other reasons for exclusion from the study were death from malignant disease in two cases and uncertain diagnosis in three. Thirteen patients could not be traced (most had left the district). In order to exclude ischaemic heart disease, the 15 patients who were older than 45 years at the time of follow-up were not studied. The clinical material then consisted of 29 patients aged 21 to 45 years (mean 33.9 years), of whom 15 were men aged 21 to 43 (mean 31.7) years and 14 women aged 26 to 45 (mean 36.2) years. None of the patients had diabetes, hypertension, angina pectoris, collagenosis or rheumatic heart disease. No patient was under digitalis treatment at follow-up. Observations in the acute stage The clinical manifestations of acute myopericarditis has been reviewed by Klainer (10). In the present series the commonest clinical manifestations were raised erythro- cyte sedimentation rate (24 cases), praecordial pain (22 cases), fever (21 cases), leukocytosis (16 cases), pharyn- gitis (14 cases), anaemia (13 cases), raised serum trans- ferase (glutamic oxaloacetate transferase) level (9 cases) and joint and muscle pains (8 cases). The antistreptolysin titre was elevated in only 5 of the 26 tested patients, the C-reactive protein test was positive in 3 of 8 cases and the antinuclear factor (ANF) was found in 6 of 10 cases. No LE cells were found in the 13 cases in which the tests were made. Upsala J Med Sci 81 168 E . Sanner et al. Table I. Physical signs and ECG changes during the acute illness Case no. Sex Peri- ECG changes cardial (Minnesota rub Murmur code) 1 d 2 P 3 0 4 P 5 d 6 8 7 d 8 0 9 0 10 6 11 0 12 d 13 0 14 d 15 d 16 0 17 d 18 6 19 P 20 P 21 0 22 d 23 d 24 9 25 6 26 d 27 d 28 0 29 0 9-2,5-2 + 84,5-2,4-2 8-7,5-3,4-2 + + 9-1, &7,5-2 + + 9-1,8-1,5-2 + 5- 1 5-2,4-3 9-1,s-3,4-3 5-2,4-1 9-2 5-3,4-3 + 9-2.5-1 + 5-3' + 8-7.5-2.4-2 + + + 9-2' 5-2 9-2,5-2 3-3 5-2 + 8-7 7-3,5-2,4-1 9-2,s-3 9-2,8-7,5-2 + 8-7,7-2 9-2 9-2,s-1 9-2,s-2 9-2,5-2 + 9-2 Physical findings Auscultation of the chest revealed nothing abnormal in 16 of the 29 patients. In all of the remaining 13 patients various physical signs were found during the acute iU- ness-pericardial rub in 8 cases, systolic murmur in 6 cases, diastolic murmur (aortic insufficiency) in one case (Case 14) (Table I). Bacteriology Beta-haemolytic streptococci were found in throat cultures from 7 of 19 tested patients (Cases 2,6, 10, 13,24, 26 and 27). Urine cultures were positive in 3 of 14 patients (Cases 3, 13 and 24), two of them also had beta-haemolytic streptococci in throat cultures. Blood cultures were done in 9 cases and faeces cultures in 3 cases. All were nega- tive. Virology Attempts to isolate virus from faeces and throat were made in only a few cases and were negative. Serology Serologic studies (for neutralizing antibodies and com- plement fixation) were done in 10 cases and were nega- tive. Mononucleosis tests were done in 3 cases and gave positive result in one case (Case 1). Radiologic examination Chest radiographs (Table 11) were taken during the acute illness in all patients but one (Case 28), who was pregnant. The heart was somewhat enlarged in 5 cases, in one of them to 600 ml/m2 body surface. Some pulmonary conces- tion was seen in 4 cases and pleural effusion in 2 cases. In Case 25 there were pleural adhesions from a healed tuberculous process. Case 19 had acute broncho- pneumonia. Electrocardiography Electrocardiograms were taken on admission and thereaf- ter at least once weekly, using standard leads I, I1 and 111 and praecordial leads CR 1,2,4,5 and 7. In all cases there were some abnormality of the ECG during the acute ill- ness. The Minnesota Code (4) was used for classification (Table I). T-wave changes were the only abnormality in 6 cases. T-wave changes together with ST-segment depres- sion occurred in 8 cases, together with ST-segment eleva- tion in 8 cases. Thus T-wave changes either alone or in combination with ST-segment abnormalities occurred in 22 cases, one of them also having incomplete right bundle- branch block (Case 21). ST-segment elevation occurred in 4 cases and disturbances of rhythm in 8 cases. One of Table 11. Radiographic cardiac and pulmonary findings during the acute illness Heart volume Case (ml) no. Sex totallrelative" Pulmonary changes 1 6 2 P 3 0 4 P 5 6 6 6 7 8 8 P 9 0 10 d 11 0 12 d 13 9 14 6 15 8 16 P 17 d 18 d 19 P 20 0 21 P 22 d 23 d 24 0 25 6 26 d 27 d 28 P 29 P 1 1201570 4701300 5701400 4801320 7801435 1 1901600 7501420 2801215 4541280 56013 10 6701360 7751440 4801290 1480 6551350 1470 5501315 8601460 8401480 4251275 5201300 4901295 1 0001465 6701325 6051310 9351390 1 0901520 No X-rays 600/300 - Bilateral pleural effusion Pulmonary congestion - - Pulmonary congestion Pleural effusion Pulmonary congestion - - Pulmonary congestion and bronchopneumonia - Pleural adhesions Pulmonary emphysema Pleural adhesions - - No X-rays - a mllm2 body surface. Upsala J Med Sci 81 Acute myupericarditis 169 Table 111. Heart volume, work load and working capacity in relation t o heart volume at fullow-up Case Age Heart volume (ml) pulse 170lmin in relation to no. (yrs) Sex totallrelative (kpmlmin)" heart volume Work load at Working capacity 1 21 d 9801490 990 2 26 0 3901270 390 3 28 0 5301360 740 4 31 P 4201270 750 5 35 8 10301530 930 6 28 d 8101430 1 250 7 42 8 7601415 1090 8 43 0 4001300 300 9 43 0 50513 15 625 10 24 d 6801370 1200 11 45 P 9001480 830 12 25 d 7701430 950 13 45 0 5801335 300 14 37 d 9501540 700 15 37 d 8901470 910 16 43 P 7501390 7 10 17 32 6 7201400 1210 18 25 d 9401480 930 19 33 0 4201250 600 20 27 P 5101320 600 21 44 P '6501370 600 22 24 d NO X-rays 625 23 43 d 1070/515 1 320 24 31 0 7001330 625 25 40 d 6901340 775 26 30 d 12101520 1 020 Low 27 33 8 12101580 450 Low 28 38 0 5901360 665 29 30 P 6001380 435 Low Lowb Low Conversion factor from Traditional Units to SI Units 1 kmp/min=O. 163 Watt. Mean load in males=957 kpmlmink244 S.D. (n=15). Mean load in females=584 kpmlmink166 S.D. (n= 14). Neurocirculatory asthenia. these 8 cases had supraventricular tachycardia and 7 cases had sinus tachycardia, among which one having also com- plete right bundle-branch block. Only occasionally were sporadic monofocal ectopic ventricular extra systoles and ectopic supraventricular extra systoles detectable (not tabulated). Atrio-ventricular conduction defects were not seen. METHODS IN FOLLOW-UP STUDIES Anamnesis The medical history was closely explored, particularly in regard to residual cardiopulmonary symptoms. A sociomedical investigation was made of the patient's cur- rent work situation, with emphasis on the possibility of heart-disease sequelae. Physical examination The general examination included auscultation of the heart and lungs and measurement of the blood pressure, using a cuff mercury manometer. Laboratory tests These included analyses in venous blood of haemoglobin, haematocrit, leukocytes, fasting blood sugar, cholesterol, creatinine, bilirubin and serum enzymes (glutamic oxalo- acetatetxansferase and lactate dehydrogenase). Radiologic examination X-rays of the heart and lungs in erect position were com- pared with films taken during the acute illness. All com- parisons were made by the same roentgenologist. The total and the relative heart size (ml/m2 body surface) were calculated according to Jonsell (9). The accepted upper limits of normal value were 500 d / m a for men and 450 ml/mz for women. Electrocardiography A direct writing ink-recorder (Elema-Schonander, Stock- holm) was used with standard leads I, I1 and I11 and praecordial leads CR 1, 2, 4, 5 and 7 for resting and orthostatic ECG. In exercise tolerance tests CH leads were used with the indifferent electrode on the forehead. ECG tracings were made after ten minutes in supine posi- Upsala J Med Sci 81 170 E . Sanner et at. Table IV. Heart volume, ECG and working capacity at follow-up (in cases with pathologicfindings) Pulse ECG after Working capacity Case rate Heart volume ECG 8 min stand- ECG during W 170 in relation to no. Sex atrest totallrelative atrest ing position work heart volume 2 0 110 3901270 Normal Pathologic Normal Normal 4 0 76 4201270 Normal Pathologic Normal Normal 5 d 85 10301530 Pathologic Pathologic Pathologic Low 6 6 75 8 101430 Pathologic Pathologic Pathologic Normal 8 0 86 4001300 Normal Pathologic Normal Normal 9 P 83 50513 15 Pathologic Pathologic Pathologic Normal 11 0 75 9001480 Pathologic Pathologic Pathologic Normal 13 0 115 5801335 Normal Pathologic Pathologic Low' 14 d 105 9501540 Normal Normal Normal Low 18 8 66 9401480 Normal Pathologic Pathologic Normal 21 0 108 6501370 Normal Pathologic Normal Normal 24 0 115 7001330 Pathologicb Pathologicb Pathologicb Normal 26 d 72 1 2101520 Normal Normal Normal Low 27 d 54 12lOl580 Pathologic Pathologic Pathologic Low ' Neurocirculatory asthenia. Right bundle-branch block. tion, immediately after adopting the erect position and after eight minutes' standing. Pulse rate and blood pres- sure were registered simultaneously. Exercise tolerance test In exercise tests the patient sat on an electrically braked bicycle as described by Holmgren & Mattsson (8). The work load was increased stepwise at 6-minute intervals. The pulse rate was measured every second minute of each increment. The work load at 170 beatslmin in steady state (W 170) was calculated according to Sjostrand (12) and Wahlund (15). The working capacity in relation to the heart volume was compared with findings in a series of healthy persons published by Gerz6n et al. (6). Deviation from the regres- sion line exceeding 2 S.D. were classified as pathologic. Physical examination Abnormal physical findings occurred only in 5 pa- tients. Two of them (Cases 12 and 16) had systolic cardiac murmurs without clinical significance. In Case 14 moderate sinus tachycardia and slight hypertension were registered, but at repeated ex- amination the pressure had normalized. In Case 20 a grade 11-111 pansystolic murmur was heard in the third intercostal space, which was considered to be due to physiologic flow and with no haemodynamic significance. Moderate hepatic enlargement was found in Case 5. Only these last 2 patients had both subjective and objective symptoms. Laboratory tests RESULTS These showed moderate sideropenic anaemia in a Subjective symptoms young woman (Case 3). The serum protein level up which they associated with the myocarditis. Sev- ase reading was elevated in the man with hepatic en had praecordial Or pain, dysfunction. All but two of the patients underwent one (Case 20) complained of sporadic Pulse irregu- the laboratory tests and these two were asympto- matic. larity and one (Case 5) of dyspnoea and fatigue. Nine patients (31 %) reported symptoms at follow- was slightly subnormal and the alkaline phosphat- Sociomedical examination All but one of the patients were fully fit for work. In Case 5 the working capacity was impaired as a result of hepatic dysfunction which presumably was of cardiac origin. This patient, however, worked part-time in his previous occupation. Five patients had progressed to better positions, probably be- cause of more advanced training. Four had switched to less physically demanding work, as a result of the myocarditis. Radiologic examination The relative heart size was increased in 5 male patients and one female. One of these patients (Case 27) suffered from cardiac enlargement during the acute illness, and this had now increased (Ta- bles I1 and 111). Electrocardiography Pathologic resting ECG was found in only 6 patients (21%). In 5 of them previously observed T-wave Upsala J Med Sci 81 Acute rnyopericarditis 171 w1 70 kpm Im i n 1600 1200 800 400 MALES kpnlrnin 1600 12 00 8 00 4 00 1 , . , . , . , . . . , . -1 W W M E 200 COO 600 800 lo00 m l FEMALES 1 , . : :’: , , , . , , .’ <* HEART WLWE 200 400 600 800 1000 ml F i g . l a , b. The individual relation between working capacity and the heart volume as compared with normal regression lines ( f 2 S.D.). changes had diminished. Complete right bundle- branch block was still present in Case 24 (Table IV) . The orthostatic ECG was pathologic in 12 pa- tients (41%), 6 of whom showed normal patterns during rest. The new changes in standing were in- version or flattening of T-waves, except in the pa- tient with right bundle-branch block, who showed this pattern also during rest. In Case 13 the resting pulse rate of 115 beatslmin rose to 140 in standing position. The exercise ECG was pathologic in 8 patients (27%), all of whom also had pathologic orthostatic ECG. Two patients with pathologic ST-T changes during work had a normal resting ECG. Complete right bundle-branch block was again seen in Case 24 (Table IV). Working capacity The total work load a t pulse 170 beats/min (W 170) averaged 957 kpmlminf244 S.D. in the male pa- tients and 584 kpmlminfl66 S.D. in the females (Table 111). Five patients (4 males and one female) showed low exercise tolerance in relation to cardiac volume (Fig. l a , b). In one of them (Case 27) the break point was well below a pulse rate of 170 beats/min (450 kpm/min at pulse 98 beatdmin). His working capacity was regarded as equivalent to the highest tolerated load for 6 minutes according to Sjostrand (12). In cases 14 and 26 the low physical capacity was not accompanied by ECG changes (Table IV). Case 13 showed sinus tachycardia and low working capacity, probably because of neurocirculatory asthenia. Her heart size was nor- mal, in contrast to the other patients with impaired exercise tolerance (Table IV). In only one of these 5 patients (Case 5) did the follow-up examination also reveal subjective and objective physical sequelae and pathologic ECG. DISCUSSION During the acute infectious illness all 29 patients showed signs of cardiac disorder, in particular path- ologic ECG a t rest, but also physical signs. A presumptive aetiologic diagnosis was made in 13 cases (45%): 7 had beta-haemolytic streptococci in throat swabs, 4 had elevated antistreptolysin titre without positive throat swabs, one had mo- nonucleosis and one had urinary tract infection. In the remaining cases the symptoms and the physi- cal findings during the acute illness indicated viral infection. A relevant point is that 15 of the 29 pa- tients were treated before 1%6, when virologic studies were relatively rare at this hospital. Our frequency of aetiologic diagnosis tallies with Bergstrom e t al. (2) and GerzCn et al. (6). The physical examination at follow-up was nega- tive in all but 5 of the patients, one of whom had hepatic dysfunction (Case 5). Repeated biopsies in this case yielded normal liver tissue, indicating a cardiac causation. The same patient also had dysp- noea of effort and progressive cardiac enlargement with pleural effusion which necessitated diuretic medication. Moderate sinus tachycardia was found in Case 14. This patient also had moderate cardiac enlarge- ment and impaired physical capacity in tolerance test, but had no subjective symptoms. Systolic Upsala J Med Sci 81 172 E . Sanner et al. murmurs without any clinical significance was heard in 3 patients. One of them (Case 20) com- plained of sporadic pulse irregularity, but the ECG at follow-up showed sinus rhythm without extra systoles. Of the 9 patients who reported residual symp- toms, only Cases 5 and 20 showed deviation from the normal at physical examination, and of these only Case 5 had reduced capacity at function test. Of the five patients with pathologic physical find- ings, only Cases 5 and 14 showed low exercise tolerance. Similar observations were made by Berg- strom et al. (2). By contrast, Bengtsson & Lam- berger (3) reported good correlation between the patients’ symptoms, ECG changes and reduction of working capacity. The cardiac volume in this series was increased at follow-up in 21% of cases. Bengtsson & Lamberger (3) reported 20% in a considerably larger case series. The follow-up resting ECG was pathologic in only 6 of the 29 cases. Two of the six had low working capacity (Cases 5 and 27). Change to stand- ing position gave pathologic ECG in 6 more cases, with altered S T and T tracings. This illustrates the value of the orthostatic test for providing sup- plementary information. Similar findings were published by others ( 1 1 , 3, 2, 6). The pulse rate in the orthostatic test rose by more than 20 beats/min in 1 1 of the 29 cases. One of them (Case 13) had sinus tachycardia at rest and sympatheticotonic ECG changes appeared during standing, indicating neurocirculatory asthenia. The mean pulse increase in the orthostatic test was 15 beats/min, which tal- lies with Bergstrom et al. (2) and GerzCn e t al. (6). Exercise tolerance tests produced no additional ECG changes are compared with the orthostatic tests. Gerzkn et al. (6) found arrhythmia in 5 of 45 cases and in two others T-wave changes, which were not apparent a t rests or during the orthostatic test. Levander-Lindgren ( 1 1) reported that ECG changes arose during work in 22% of her cases. Bergstrom e t al. (2) found abnormal ECG at rest in 33 %, in standing in 53 % and during work in 73 % of cases. Corresponding figures reported by Bengts- son & Lamberger (3) were 19, 10 and 30%. Work tests thus can evoke otherwise unseen ECG changes, though this did not occur in our case series. In 4 of our patients with pathologic ortho- static ECG the S T and T tracings were normal during work. The physical capacity was low in relation to the heart volume in 5 of the 29 cases (17%). The cor- responding frequency reported by Bergstrom e t al. (2) was 13%. Two patients with subnormal physical capacity had normal ECG tracing (resting, standing and working). GerzCn et al. (6) reported residual cardiac symptoms in 35% of their cases, but work tests showed normal capacity in relation to total haemoglobin and to heart volume. Physical working capacity in healthy persons is in linear relation to the heart volume. Myocardial damage of fimctional significance may, however, impair the working capacity while the heart size tends to increase. Calculation of working capacity in relation to heart size may therefore be helpful in detecting deviations from the normal. In our series 4 of the 5 patients whose working capacity was low in relation to heart size had cardiac enlargement. The fifth patient was classified as neurocirculatory asthenia. Bengtsson & Lamberger (3) similarly found good correlation between cardiac enlarge- ment and impaired physical working capacity. The mean work loads a t a pulse rate of 170 beats/min (W 170) were similar to those found by Frisk et al. (5). In 67 healthy males they reported 1050 kpm/min+ 125 S.D. In 58 healthy females they found 750 kpmlminf 100 S.D. In the general popu- lation, however, the physical working capacity shows wide variations. It may have diminished in recent years. Strom (14) reported a study from 1964-1965 in which healthy Swedish students showed mean readings of 1 009 kpmlmin in 61 males and 555 kpmlmin in 22 females. Our conclusion is that the prognosis in this series of patients with earlier myopericarditis is good. The results are in agreement with those in other com- parable series in which the observation time was somewhat shorter. REFERENCES 1 . Bell, R . W. & Murphy, W. M.: Myocarditis in young military personel. Amer Heart J 74: 309, 1%7. 2. Bergstrom, K., Erikson, U . , Nordbring, F., Nordgren, B. & Parrow, A.: Acute non-rheumatic myopencarditis: A follow-up study. Scand J Infect Dis 2: 7, 1970. 3. Bengtsson, E. & Lamberger, B.: Five-year follow-up study of cases suggestive of acute myocarditis. Amer Heart J 72:751, 1966. 4. Blackburn, H . , Keys, A . , Simonson, E., Rautahaju, P. & Punsar, S.: The electrocardiogram in population studies. A classification system. Circulation 21: 1160, 1960. Upsala J Med S c i d l Acute myopericarditis 173 5 . Frisk, A. R., Holmgren, A., Strom, G. & Viktorsson, K. E.: Stockholms stads halsoundersokning 1954.111. Viloekg, arbetsekg och fysisk arbetsformgga. Nord Med 58: 1437, 1957. 6. GerzCn, P., Granath, A., Holmgren, B. & Zetterquist, S.: Acute myocarditis. A follow-up study. Brit Heart J 34: 575, 1972. 7. Helin, M., Savola, J. & Lapinleimu, K.: Cardiac man- ifestations during a coxsackie B5 epidemic. Brit Med J III: 97, 1968. 8. Holmgren, A. & Mattsson, K. H.: A new ergometer with constant work load at varying pedalling rate. Scand J Clin Lab Invest6:137, 1954. 9. Jonsell, S.: A method for the determination of the heart size by teleroentgenography (A heart volume index). Acta Radiol20: 325, 1939. 10. Klainer, A. S.: Clinical aspects of infectious heart disease. Postgrad Med 55: 124, 1974. 11. Levander-Lindgren, M.: Studies in myocarditis. IV. Late prognosis. Cardiologia47: 209, 1965. 12. Sjostrand, T.: Exercise tests. In Clinical Physiology (ed. T. Sjostrand), pp. 515-530. Svenska Bokforlaget Bonniers, Stockholm, 1967. 13. Smith, W. G.: Coxsackie B myopericarditis in adults. Amer Heart J 80: 34, 1970. 14. Strom, G.: N b r a medicinska synpunkter pf~ fysisk trbing. Medicinska Foreningens Tidskrift 45: 168, 1%7. 15. Wahlund, H.: Determination of the physical working capacity. Acta Med Scand, Suppl. 215: 1948. 16. Wenger, N. K.: Infectious myocarditis. Postgrad Med 44: 105,c1%8. Received August 8, 1976 Address for reprints: E. Sanner, M.D. Department of Medicine Central Hospital S-63 1 88 Eskilstuna Sweden Upsala f Med Sci8l