The incidence and epidemiology of myocarditis.
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Acute Disease↗
Biomedical subjects
G Friman
Publications and source records attributed to G Friman.
A 10-year retrospective study of infective endocarditis at a university hospital with special regard to the timing of surgical evaluation in S. viridans endocarditis.
A total of 154 episodes of infective endocarditis (IE) in 149 patients were studied retrospectively with special regard to the major aetiological groups and the surgical evaluation. There were 136 episodes of native valve endocarditis (NVE) (88%) and 18 episodes of prosthetic valve endocarditis (PVE) (12%). Three major groups of NVE crystallized: Streptococcus viridans in 37 (27%), Staphylococcus aureus in 39 (29%) and culture negative IE in 28 (21%) episodes. In these groups surgery during the active phase was required in 41, 28 and 18%, respectively. At the operation myocardial abscess was found in as many as 7/15 cases with S. viridans, but in only in 3/11 cases with S. aureus and 1/5 cases with culture negative IE. The mean duration of preoperative antibiotic treatment was 34 d. This long period of unsuccessful pharmacotherapy, preceded by a mean of 47 d from start of symptoms to admission to hospital, has probably resulted in the high frequency of myocardial abscess in S. viridans NVE. Surgical evaluation should be considered when fever persists beyond 10 d of adequate treatment, even in the absence of clinically apparent complications. Among the PVE episodes, 11/18 were managed with pharmacological treatment alone. Uncomplicated PVE may thus often be successfully treated with antibiotics alone.
Abscess↗
Sudden unexpected cardiac deaths among young Swedish orienteers--morphological changes in hearts and other organs.
During the years 1979-1992 an accumulation of sudden unexpected cardiac deaths (SUD) occurred among young Swedish orienteers. A reevaluation of material saved from 16 autopsies was undertaken. Myocarditis was most frequent. It was found in different stages in the majority of cases, indicating subacute or chronic disease with ongoing reparative processes. There were severe morphological changes in all cases. All but one showed a picture of fibrosis and unspecific hypertrophy and/or degenerative changes in myocytes. The hearts were classified into three groups (A-C), based on the morphological picture of the retrieved heart tissue and the macroscopic description. Group A comprised five cases in which areas with active myocarditis combined with areas of healing or healed myocarditis widely distributed in the left ventricle were the only morphological changes found. Group B comprised four cases demonstrating foci of myocarditis in different stages in the left ventricle and changes resembling those found in arrhythmogenic right ventricular dysplasia (ARVD), including degenerative changes with fibrosis and fatty infiltration located in either ventricle. Group C comprised the remaining seven cases. In none of the cases were coronary artery or valvular anomalies present, nor significant coronary sclerosis or changes outside the heart that could cause SUD.
Adolescent↗
Rickettsia helvetica in Ixodes ricinus ticks in Sweden.
In the present study further characterization of the amplified sequence of the citrate synthase gene of the spotted fever group Rickettsia isolated from Ixodes ricinus ticks in Sweden showed that it has 100% homology with the deposited sequence of the citrate synthase gene of Rickettsia helvetica. The restriction fragment length polymorphism (RFLP) pattern of an amplified 382-bp product of the citrate synthase sequence, defined by primers RpCS877 and RpCS1258, yielded fragments for our isolate that could be visualized as a double band that migrated at approximately 44 bp, another double band at 85 bp, and a single band at nearly 120 bp after digestion with the restriction enzyme AluI. When calculating a theoretical PCR-RFLP pattern of the sequence of the citrate synthase gene of R. helvetica from the known positions where the AluI enzyme cuts, we arrived at the same pattern that was obtained for our isolate, a pattern distinctly different from the previously published PCR-RFLP pattern for R. helvetica. Investigation of 125 living I. ricinus ticks showed a higher prevalence of rickettsial DNA in these ticks than we had found in an earlier study. Rickettsial DNA was detected by amplification of the 16S rRNA gene, for which a seminested primer system consisting of two oligonucleotide primer pairs was used. Of the 125 ticks, some were pooled, giving a total of 82 tick samples, of which 20 were found to be positive for the rickettsial DNA gene investigated. When considering the fact that some of the positive samples were pooled, the minimum possible prevalence in these ticks was 20 of 125 (16%) and the maximum possible prevalence was 46 of 125 (36.8%). These prevalence estimates conform to those of other studies of spotted fever group rickettsiae in hard ticks in Europe.
Animals↗
Evaluation of human seroreactivity to Bartonella species in Sweden.
Among the species that compose the expanding genus Bartonella, thus far only B. henselae and B. quintana have reportedly been isolated from humans in Europe. To evaluate the prevalence of Bartonella infection in Sweden, we conducted a retrospective serological examination of 126 human serum samples. These samples were analyzed for antibodies to B. henselae, B. quintana, and B. elizabethae. Serum samples from 100 blood donors, who spanned the ages of 20 to 60 and had no apparent clinical signs of illness, were also studied as a control group. An immunoglobulin G indirect fluorescence antibody assay revealed 4 and 8.3% Bartonella positivity rates for the blood donor and patient group, respectively, when a cutoff titer of >/=64 was chosen. Among the blood donors, four were seropositive to B. elizabethae; one of these also had concordant positive titer to B. henselae. In the patient group, 14 serum samples were positive against Bartonella spp. These serum specimens represented nine patients. In three of these seropositive patients, paired serum samples displayed a fourfold increase in antibody titer to at least one of the three antigens. These three patients are discussed. In this report we also present a case study of a 60-year-old Swedish male with fatal myocarditis. Postmortem serological analysis revealed a high titer against B. elizabethae. PCR and nucleotide sequencing of the myocardial tissue from this patient, and of liver tissue from one of the other three patients, showed sequences similar to B. quintana. The age, geographical origin, animal contacts, and serological response pattern to the different Bartonella antigens differed among the four patients. This study substantiates the presence of Bartonella spp. in Sweden, documents the seroreactivity to three Bartonella antigens in Swedish patients, and reports the first two cases of B. quintana-like infections in Sweden.
Adolescent↗
Effects of selenium supplementation on virus-induced inflammatory heart disease.
The effects of 10 wk of selenium (Se) supplementation (5 ppm) in drinking water on immune responses and resistance to a myocarditic Coxsackie virus B3 (CB3) infection were studied in female Balb/c mice. Se supplementation reduced CB3-induced mortality: at day 14 postinoculation, survival was 58% in the Se-treated group as compared to 25% in the untreated group. Whole-blood glutathione peroxidase (GSH-Px) activity was elevated by 68% (p < 0.001) and Se content in the liver by 24% (p < 0.001). Red (RBC) and white blood cell (WBC) counts, as well as the number of cells in the spleen and thymus, were unaffected. The cellular counts of T-lymphocytes (CD4+, CD8+) and natural killer (NK+) cells in the blood were not affected. However, the CD4+/CD8+ ratio (5.2) tended to increase after Se supplementation (5.9). The spleen lymphoproliferative response to T- and B-cell mitogens were increased by 9 and 43%, respectively (ns), in the Se-supplemented group. The total NK cell activity in blood and spleen showed minor increases, but when the activity in the blood was expressed per cell, the increase amounted to 35% (ns) with Se supplementation. The inflammatory and necrotic lesions in the ventricular myocardium at 7 and 14 d postinoculation were not significantly reduced by Se treatment, probably owing to the increased survival with Se even of mice with the most pronounced heart damage; comparable untreated mice were estimated to have died at day 14. Results indicate that modest doses of Se can improve immune function, which may increase the general resistance to this viral infection.
Animals↗
Acute infection: metabolic responses, effects on performance, interaction with exercise, and myocarditis.
Acute infections are associated with multiple host responses that are triggered by cytokines and correlated to fever, malaise and anorexia. The purpose of this systemic acute phase host reaction ("the acute phase response") is to mobilize nutrients for the increased needs of the activated immune system, as well as for energy production and tissue repair. Important effects include wasting of striated muscle, degradation of performance-related metabolic enzymes and, concomitantly, deteriorated central circulatory function. These effects result in decreased muscle and aerobic performance, the full recovery of which may require several weeks to months following week-long febrile infections. Also during early infection and fever, prior to the development of muscle wasting, performance is compromised by other mechanisms. Strenuous exercise may be hazardous during ongoing infection and fever and should always be avoided. In infection, muscle wasting seems to be less pronounced in the conditioned (trained) host than in the unconditioned host. Acute myocarditis most often has a viral etiology but bacteria and their toxins may also be the cause. Furthermore, slow-growing bacteria, previously difficult to diagnose, have emerged as potential "new" causes of subacute to chronic myocarditis. Since myocarditis may or may not be associated with fever, malaise, or catarrhal symptoms, athletes should be taught the symptoms suggestive of myocarditis. Whenever myocarditis is suspected exercise should be avoided.
Acute-Phase Reaction↗
[Enterovirus infections in new disguise].
Enteroviruses (Coxsackie A and B, echovirus, poliovirus) belong to a group of small RNA-viruses, picomavirus, which are widespread in nature. Enteroviruses cause a number of wellknown diseases and symptoms in humans, from subclinical infections and the common cold to poliomyelitis with paralysis. The development of polio vaccines is the greatest accomplishment within the field of enterovirus research and the background work was awarded the Nobel prize in 1954. New knowledge implies that enteroviruses play a more important part in the morbidity panorama than was previously thought. Chronic (persistent) enteroviruses were formerly unknown. Serologic and molecular biology techniques have now demonstrated that enteroviral genomes, in certain situations, persist after the primary infection (which is often silent). Persistent enteroviral infection or recurrent infections and/or virus-stimulated autoimmunity might contribute to the development of diseases with hitherto unexplained pathogenesis, such as post polio syndrome, dilated cardiomyopathy, juvenile (type 1) diabetes and possibly some cases of chronic fatigue syndrome.
Cardiomyopathy, Dilated↗
An echocardiographic study comparing male Swedish elite orienteers with other elite endurance athletes.
Between 1979 and 1992, there were 16 known cases of sudden unexpected cardiac death among young Swedish orienteers, whose autopsies showed myocarditis to be a common finding. Therefore, 96 elite orienteers and 47 controls underwent echocardiography, showing left ventricular wall motion abnormalities in 9% of the orienteers compared with 4% in the controls.
Adolescent↗
Characterization of a spotted fever group Rickettsia from Ixodes ricinus ticks in Sweden.
A spotted fever group rickettsia isolated from the common tick, Ixodes ricinus, was genetically characterized by PCR and genomic sequencing. This study was performed with nymphal and adult ticks collected in southern and central Sweden. I. ricinus is the only North European tick species of medical importance which is regularly collected from humans. No species of the genus Rickettsia has previously been found in Scandinavian ticks, nor has any case of domestic rickettsial infection in humans or animals been reported. According to the nucleotide sequencing, the present Rickettsia sp. belongs to the spotted fever group of rickettsiae. Ticks are the most common arthropod reservoirs and vectors of the rickettsiae of this group. Among 748 ticks investigated, 13 (1.7%) were positive for a Rickettsia sp. Borrelia burgdorferi was detected in 52 (7%) of the ticks, a prevalence similar to or somewhat lower than that previously been recorded in other Swedish studies. There was no evidence of ehrlichial or chlamydial DNA in these ticks. The Rickettsia sp. was further characterized by 16S ribosomal DNA (rDNA) sequencing and restriction fragment length polymorphism (RFLP). The 16S rDNA sequencing resulted in a sequence identical to that described for Rickettsia helvetica, but the pattern obtained with RFLP of the citrate synthetase gene diverged from previously known patterns. The rickettsial agent of one tick which was positive by PCR was confirmed by transmission electron microscopy. The morphology of this rickettsia was similar to that of the spotted fever and typhus group rickettsiae. This represents the first documented isolate of a Rickettsia sp. from Swedish ticks.
Animals↗
Phylogenetic placement and characterization of a new alpha-2 proteobacterium isolated from a patient with sepsis.
An alpha-2 proteobacterium, previously unknown as determined by its phylogenetic characteristics and the DNA sequence of its 16S rRNA gene, was isolated from a patient who presented an unusual clinical picture, including high remitting fever and multiorgan involvement. The bacterium was detected in multiple plasma samples, obtained during the acute phase of the disease, after cocultivation in cell culture media. Electron microscopy of the organism showed a three-layer laminar cell wall and electron-dense granules within the cytoplasm, as well as a polar flagellum. By means of PCR followed by sequencing of amplified 16S ribosomal DNA fragments, the bacterium was found to differ from all species for which ribosomal sequence information is available. It is here provisionally named the Rasbo bacterium. At a subsequent relapse, the bacterium was identified in pericardial fluid both by PCR/sequencing and by direct electron microscopy. At a second relapse, it was again cultured from plasma. After in vitro adaptation to solid media, the MICs of various antibiotics could be determined. A transient immunoglobulin M (IgM) but no IgG response to the bacterium was found by an indirect immunofluorescence test, as well as by an immobilization test during the acute phase of the disease.
Adult↗
High incidence of Chlamydia pneumoniae in sclerotic heart valves of patients undergoing aortic valve replacement.
Chlamydia pneumoniae has previously been demonstrated in the atherosclerotic lesions of various arteries, including the coronary arteries, and has been proposed to play a role in the pathogenesis of atherosclerosis. A prospective study of the incidence of C. pneumoniae in the sclerotic valves of patients undergoing aortic valve replacement because of aortic stenosis and in the aortic valves of cases dying of non-cardiac reasons and undergoing forensic autopsy was undertaken. The results were correlated to serological markers of past (IgG) or persistent (IgA) C. pneumoniae infection. C. pneumoniae, as determined by the polymerase chain reaction (PCR), was detected in the aortic valve in 19/39 (49%) patients and in 1/11 (9%) autopsy controls (p = 0.018) and confirmed by electron microscopy in one patient. There was no significant difference in the incidence rate of IgG or IgA antibody positivity between PCR-positive and PCR-negative cardiac patients. These results extend the hypothesis of a pathogenic role of C. pneumoniae in atherosclerosis to include also aortic valve sclerosis.
Adult↗
Interaction between infection and exercise with special reference to myocarditis and the increased frequency of sudden deaths among young Swedish orienteers 1979-92.
Infection and fever evoke a cytokine-mediated host response resulting in negative nitrogen balance, muscle protein degradation, which includes the skeletal muscles as well as the heart muscle, and deteriorated muscle function. Physical training has an opposite effect. Moderate physical training also stimulates the immune system, whereas exhaustive and longlasting exercise is followed by a temporary immunodeficiency and an increased susceptibility to respiratory tract infections. Exercise in the acute phase of an infection may promote complications including myocarditis. Exercise in myocarditis is associated with increased organism-associated as well as immune mediated tissue damage. An increased sudden death (SUD) rate among young Swedish male orienteers existed in 1979-92, suggesting (a) common underlying cause(s). Myocarditis was one of the most conspicuous histopathological features. Chlamydia pneumoniae, or a similar organism cross reacting in diagnostic tests, is hypothesized to be a factor causing this increased death rate. High frequency of intense exercise sessions, which was a common practice among the deceased, may have been immunosuppressive, promoting the development of severe myocardial disease.
Adolescent↗
Antiviral treatment with WIN 54 954 reduces mortality in murine coxsackievirus B3 myocarditis.
BACKGROUND: Coxsackieviruses B (CBVs) are dominant causative agents in myocarditis and are associated with pathogenesis is some cases of dilated cardiomyopathy, a clinical entity with a poor survival without heart transplantation. METHODS AND RESULTS: In vitro, the antiviral agent WIN 54 954 was shown to inhibit replication of CBV3 at a minimal inhibitory concentration value of 0.02 mg/L. Administration of WIN 54 954, 100 mg/kg BID PO, beginning on the day of infection resulted in complete protection from enteroviral mortality (P < .01). WIN 54 954 treatment did not abrogate the inflammatory reaction in the myocardium. No difference was found in the expression of surface lymphocyte subset markers. At 3 weeks, macrophages seemed to dominate the inflammatory reaction, regardless of treatment. There was no difference in CBV3 antibody titers, indicating that WIN 54 954 does not interfere with the development of protective immunity. Complement factors C3 and B were synthesized at a higher level during infection and correlated well with the degree of inflammatory reaction. CONCLUSIONS: The results show that WIN 54 954 is a potent antiviral agent with a highly significant effect on survival in CBV-induced myocarditis in the A/J mouse if treatment is started early. It is suggested that the reduction in mortality seen with WIN 54 954 administration is due to an inhibitory effect on virus replication in affected organs that does not interfere with cellular or humoral immunity.
Animals↗
Effects of methyl mercury on cytokines, inflammation and virus clearance in a common infection (coxsackie B3 myocarditis).
A myocarditic coxsackievirus B3 (CB3) infection in Balb/c mice was used to investigate the effects of 12 weeks of methyl mercury (MeHg) exposure (3.69 mg/g diet) on inflammatory heart lesions, virus in the heart, the cytokine response, i.e. cachectin/TNF-alpha and gamma-interferon (IFN-gamma) levels in plasma, and on disease complications and mortality. This dose of MeHg did not influence mortality in this infection model. The inflammatory and necrotic lesions in the ventricular myocardium 7 days after the inoculation covered 2.2% of the tissue section area in infected control mice. This damage was increased (n.s.) by 50% (to 3.3% of the tissue section area) in MeHg-treated mice. The response pattern of lymphocyte subsets in situ in myocardial inflammatory lesions was corroborated using an immune histological technique. MeHg treatment tended to increase (2.2-fold, n.s.) the number of Mac 2+ cells (macrophages) in the heart muscle in this infection. Plasma levels of both TNF-alpha and IFN-gamma increased on day 3 of the infection in MeHg-treated as well as in non-MeHg-treated mice, but the mean IFN-gamma response was more pronounced in the MeHg-treated mice. On day 7 of the infection, when most animals still showed clinical signs of disease, cytokine levels were back to normal. MeHg-exposure in non-infected mice did not affect cytokine levels. In situ hybridization of virus RNA in myocardial tissue showed remaining virus in those mice who had the lowest plasma IFN-gamma levels. A 20% increased (P < 0.05) lymphoproliferative response to the T cell mitogen Con A was observed as a result of the MeHg treatment. Even heart tissue lesions and virus persistence tended to be influenced by MeHg in a direction compatible with the development of chronic disease.
Animals↗
An increase in sudden unexpected cardiac deaths among young Swedish orienteers during 1979-1992.
BACKGROUND: Sixteen cases of sudden unexpected cardiac death, 15 males and one female, are known to have occurred among young Swedish orienteers from 1979 to 1992, of which seven cases occurred between 1989 and 1992. This is considered to be indicative of an increased death rate. RESULTS: Histopathological evaluation showed myocarditis in a higher than expected proportion of cases. In one such case, which we studied before the sudden unexpected death occurred, the victim had suffered a Chlamydia pneumoniae infection verified by serology, and a nucleotide sequence was found in the heart and lung by means of the polymerase chain reaction (PCR) that hybridized with a probe specific for that organism. Male Swedish orienteers do not, however, seem to have an increased rate of exposure to this agent. No further sudden unexpected deaths among young orienteers have occurred over the past 3.5 years. At the beginning of that period, attempts were made to modify training habits and attitudes.
Adolescent↗
Echocardiographic right and left ventricular measurements in male elite endurance athletes.
Echocardiography was used to assess normal values in the right and left ventricular cavity and wall in 127 male elite endurance athletes. M-mode and two dimensional measurements of left ventricle and left and right atria were also obtained. All subjects were high-performance orienteers, cross-country skiers and middle-distance runners. They all had a normal electrocardiogram at rest and no echocardiographic evidence of heart disease. With the use of multiple right ventricular cross-sections and two-dimensional measurements, we found a significantly greater right ventricular inflow tract and right and left atrial measurements in endurance athletes compared with earlier studies of normal, active subjects. The right ventricular free wall was slightly thicker than reported in normal active subjects but the differences were small. Left ventricular diastolic diameter was consistent with previous reports of endurance athletes. Of the 127 subjects, 13% had left ventricular wall thickness above 13 mm but none of the athletes had wall thickness above 15 mm. These data suggest that cardiac enlargement occurs symmetrically in both right and left cavities, probably reflecting increased haemodynamic loading, a mechanism by which athletes sustain a high cardiac output during exercise.
Adult↗
Blood-borne pathogens in sports.
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Disease Outbreaks↗