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MYOCARDITIS
- FROM SYMPTOMS TO TREATMENT IN SHANGHAI, CHINA
AND IN THE GOTHENBURG COUNTY, SWEDEN.
Elinor Torle, Medical student, Göteborg University 2003
Petter Bryngelsson, Medical student, Göteborg University 2003
Swedish supervisor: Prof. Rune Andersson, Skaraborg Hospital, Skövde, Sweden
Chinese supervisor: Prof. Chang Yachen, Xin Hua Hospital, Shanghai, China
MYOCARDITIS
– FROM SYMPTOMS TO TREATMENT IN SHANGHAI, CHINA
AND IN THE GOTHENBURG COUNTY, SWEDEN
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– FROM SYMPTOMS TO TREATMENT IN SHANGHAI, CHINA
AND IN THE GOTHENBURG COUNTY, SWEDEN
Foreword
In January 2003 we started to draw up the guidelines for this comparative study on myocarditis. What
we didn’t know at the time was the very inconvenient period that was ahead of us when it came to
traveling to China.
In spring 2003, the SARS (Severe Acute Respiratory Syndrome) was raging in a number of Asian
countries. The first cases were reported from the southern parts of China in October 2002 and the virus
was spread in more than 30 countries. By the beginning of July 2003 the virus spread seemed to be
under control and The World Health Organization ceased publishing a daily table of the cumulative
number of reported probable cases of SARS. In total, over 8000 persons were infected by the new
virus and more then 800 people died.
Mainland China was among the areas severely affected by the new virus, and by May, severe
outbreaks were reported from the capital, Beijing. Beijing reported that schools and kindergartens
were closed, as well as internet-cafes and theaters to avoid the virus to be spread. Shanghai however,
managed to keep the number of SARS patients relatively low. This may be somewhat surprising
considering the fact that it is the nations largest city and considering the flow of people passing
through Shanghai every day from affected areas such as Hong Kong and Beijing. Nevertheless,
Shanghai was not unaffected by the SARS epidemic. In fact, one of the main reasons for the city’s
success in preventing a local SARS outbreak is most probably the extremely severe measures taken by
the authorities to limit the risk of exposure to the virus. A lot of effort was put into improving hygiene
at hospitals and in public areas. For example, face masks were mandatory for doctors and other
personnel who were in direct contact with any patients. Furthermore, white coats worn inside the
clinics were banned outside hospitals and people were educated not to spit or sneeze if at all avoidable.
Failure to comply with these demands was economically punished (50 EURO fee). (Shanghai Daily,
2003)
The spring 2003 was also the time for one of the authors of this report, Elinor Torle to study the
Chinese way of dealing with myocarditis in Shanghai. Due to the SARS epidemic and the measures
taken to prevent the spread of the disease, there were a significant impact on the study. After the initial
two weeks of the study, medical students were not allowed to see patients before the patients were
examined and diagnosed by a doctor excluding risk of SARS. Moreover, medical students were not
allowed to visit the out-patient department, nor were they allowed in the respiratory care unit.
Nevertheless, with great assistance from the crew at Xin Hua Hospital it was possible to finish the
Shanghai-based part of the study.
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1
Summary
The evaluation and management of acute myocarditis are among the more difficult challenges that
general internists and cardiologists face today. Symptoms and signs of the illness include unexplained
heart failure or arrhythmia in the setting of a systemic febrile illness or after symptoms of an infection.
The myocarditis can be acute, or present itself as a chronic inflammation in the heart muscle, thereby
causing cardiac dysfunction after several years. According to some studies, myocarditis is a major
cause of sudden unexpected death, accounting for approximately 20 percent of cases in adults less than
40 years of age.
In recent years, good progress has been made by scientists and clinicians all over the world in
understanding the causes, pathogenesis, diagnosis and treatment of myocarditis. However, the
knowledge is still far from complete. The aim of this study is to make a modest contribution to the
understanding of myocarditis by describing and comparing the epidemiology, risk factors, clinical
symptoms, diagnostics and treatments of patients suffering from acute myocarditis in two different
regions of the world. Patients from Xin Hua Hospital in Shanghai, China are compared and contrasted
with similar patients from hospitals in the Gothenburg County in Sweden. Such a comparison is
worthwhile since the two countries are very different on many levels. The countries have different
population structures and the strategies for diagnosing and treating myocarditis tend to differ between
the two. The use of Traditional Chinese Medicin for example, plays a significant role in the treatment
of patients diagnosed with myocarditis in Shanghai.
As far as etiology is concerned, in most cases of myocarditis, no definite cause is ever established.
Nevertheless, we know that it has a wide variety of both infectious and non-infectious causes. When it
comes to epidermiology, the prevalence of acute myocarditis is unknown because most cases are not
recognized on account of non-specific symptoms or no symptoms at all. Nonetheless, it is estimated
that as much as 5% of a virus-infected population may experience some form of cardiac involvement
associated with the acute form of the illness. The treatment of myocarditis generally focuses on
supportive care, since effective antiviral agents are often unavailable and usually inappropriate. The
main treatment goal is the maintenance of cardiac output at levels able to provide adequate tissue
perfusion.
The results in Shanghai, China are based on 47 patients. In Gothenburg County they are based on 31
patients. The mean age was 29 years in both groups. The final diagnosis in all cases was myocarditis.
The gender distribution varied between the two patient groups, 53% males in Shanghai and 97% males
in the Gothenburg County. In Shanghai, 87% had a clear history of a preceding infection and
corresponding percentage in Gothenburg County was 97 %. In both groups of patients, an upper
respiratory infection was the most common preceding infection. The two most frequent symptoms that
made patients seek medical care were dyspnea and palpitations in Shanghai, China. In the Gothenburg
County it was chest pain and fever. At examination with ECG, 94% of the patients in both groups had
pathological signs. The most prevalent change was an elevated ST-line and a negative T-wave. The
differences in the pathological frequencies of both ECHO- and laboratory tests indicate that the
patients from the Gothenburg County were more severely ill than the Chinese patients. Bed rest was
the most common used treatment, recommended to all of the Shanghai patients and to 97% in the
Swedish group. Despite the fact that bacterial etiology is an uncommon cause of myocarditis
antibiotics was given to 50% of all patients in Shanghai and to 64% in the Gothenburg group. All of
the Chinese patients received some kind of Traditional Chinese Medicine. The duration of hospital
care in Shanghai was almost three times as long (mean 17 days) compared with the Gothenburg
patient group (mean 6 days). In Shanghai, two patients were left with long-term sequele and no patient
died. In Gothenburg, two patients died during the hospital stay and five patients were left with longterm sequele.
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FOREWORD......................................................................................................................................................... 3
1
SUMMARY.................................................................................................................................................. 4
2
INTRODUCTION ....................................................................................................................................... 6
2.1
3
AIM OF THE REPORT ............................................................................................................................. 6
LITERATURE REVIEW OF ACUTE MYOCARDITIS........................................................................ 7
3.1
ETIOLOGY ............................................................................................................................................. 7
3.2
EPIDEMIOLOGY ..................................................................................................................................... 8
3.3
DIAGNOSIS ............................................................................................................................................ 8
3.4
PATHOGENESIS ..................................................................................................................................... 9
3.5
TREATMENT.......................................................................................................................................... 9
4
BASIC PRINCIPLES OF TRADITIONAL CHINESE MEDICINE ................................................... 11
5
PATIENTS AND METHOD .................................................................................................................... 12
6
7
5.1
SHANGHAI, CHINA .............................................................................................................................. 12
5.2
GOTHENBURG COUNTY, SWEDEN ....................................................................................................... 12
5.3
DIAGNOSTIC CRITERIA FOR MYOCARDITIS, SHANGHAI, CHINA........................................................... 13
5.4
DIAGNOSTIC CRITERIA FOR MYOCARDITIS, GOTHENBURG COUNTY, SWEDEN.................................... 14
RESULTS................................................................................................................................................... 15
6.1
DEMOGRAPHIC DATA .......................................................................................................................... 15
6.2
ASSOCIATED INFECTION AND SYMPTOMS............................................................................................ 16
6.3
CLINICAL SYMPTOMS AT THE TIME OF DIAGNOSIS .............................................................................. 18
6.4
EXAMINATION- AND LABORATORY RESULTS ...................................................................................... 19
6.5
TREATMENT........................................................................................................................................ 23
6.6
DURATION OF HOSPITAL CARE AND SEQUELE ..................................................................................... 25
DISCUSSION............................................................................................................................................. 26
7.1
EPIDEMIOLOGY ................................................................................................................................... 26
7.2
PREVIOUS DISEASES ............................................................................................................................ 26
7.3
PRECEDING INFECTION OR SYMPTOMS ................................................................................................ 26
7.4
CLINICAL SYMPTOMS AT THE TIME OF DIAGNOSIS .............................................................................. 27
7.5
EXAMINATION- AND LABORATORY RESULTS ...................................................................................... 27
7.6
TREATMENT........................................................................................................................................ 27
7.7
DURATION OF HOSPITAL CARE ............................................................................................................ 28
8 REFERENCES................................................................................................................................................. 29
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2
Introduction
The evaluation and management of acute myocarditis remain two of the most difficult challenges that
general internists and cardiologists face today. The uncertainties include an incomplete understanding
of the pathophysiology of the disease, great variability in clinical presentation, absence of accepted
international diagnostic criteria on which to base the diagnosis, and also disagreement regarding the
appropriate treatment. The syndrome is clinical and the combination of an acute infective illness and
myocardial symptoms and signs should suggest the diagnosis. Symptoms and signs include
unexplained heart failure or arrhythmia in the setting of a systemic febrile illness or after symptoms of
an infection.
The myocarditis can be acute or present itself as a chronic inflammation in the heart muscle and cause
cardiac dysfunction after many years. Cases of idiopathic dilated cardiomyopathy may represent
unrecognized viral myocarditis. The latter is a more common condition and the connection between
virus, myocarditis and dilated cardiomyopathy is of great interest in clinical research. In addition, a
study from 1992 shows signs of myocarditis histologically in 10-20 % of the cases of idiopathic
dilated cardiomyopathy [2]. A significant number of cases of clinically suspected myocarditis prove to
have interstitial fibrosis and therefore representing longstanding disease [10]. These findings help us
understand the mechanism of virus infected myocytes.
In recent years scientists and clinicians all over the world have made good progress in understanding
the causes, pathogenesis, diagnosis and treatment of myocarditis. However, our knowledge is still far
from complete. To treat the patients correctly, it is important to know the true pathophysiology. There
are still some controversies regarding the diagnostic criteria as well as the actual treatment of the
disease. New information extending our understanding of myocarditis is being reported frequently.
More recent studies on animals have enhanced our understanding of the complex interactions between
direct viral injury and the host’s immune response [1]. It is evident however, that future research is
needed in this field. Since the majority of cases are subclinical and self-limited, the true prevalence of
viral myocarditis is unknown.
2.1
Aim of the Report
The aim of this study is to describe and compare the epidemiology, risk factors, clinical symptoms,
diagnostics and treatments of patients suffering from acute myocarditis in Shanghai, China with
similar patients in the Gothenburg County, Sweden. Such a comparison is of interest since the two
countries are very different on many levels. The countries have different population structures and
their inhabitants display different antibodies. Furthermore, the strategies for treating myocarditis tend
to differ between Shanghai, China and the Gothenburg County, Sweden.
Most Chinese research is only published in Chinese languages, this limits the possibility for the
western world to take part of it. However, the Chinese themselves do a lot of research on heart disease
and Traditional Chinese Medicine (TCM), and a special center is committed to promoting Chinese
drugs on the international market. One goal is to have major TCM standardized by 2005 [14]. The use
of TCM plays a significant role in the treatment of patients diagnosed with myocarditis as well as
other heart diseases. This adds an extra aspect to this report and the report therefore contains a short
introduction to the principles of TCM.
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3
Literature Review of Acute Myocarditis
The literature on myocarditis is vast, the knowledge is still far from complete and new information
seems to be reported constantly. The review in this chapter is a modest attempt to briefly summarize
the major findings. Myocarditis is here defined as inflammation of the myocardium accompanied by
myocellular necrosis.
3.1
Etiology
In most cases of myocarditis, no definite cause is ever established. Nevertheless, we know that it has a
wide variety of both infectious and non-infectious causes [7]. A large variety of infections, systemic
diseases, drugs and toxins have been associated with the development of this disease. Representing the
infectious part; viruses, bacteria, protozoa, and even worms have been registered as agents. A selected
representation of the more common etiologies of infectious and non-infectious human myocarditis is
presented below in tables 1 and 2.
Enteroviruses
- Coxsackie A and B
- ECHO
- Influenza
- Polio
Herpes viruses
Adenovirus
Mumps
Rubella
Rubeola
Hepatitis B and C
HIV
Rickettsial
Fungal
- Cryptococcus
Protozoan
- Trypanosomiasis cruzi
- Toxoplasmosis gondii
Bacterial
- Legionella
- Clostridium
Salmonella/Shigella
Spirochetal
Borrelia burgdorferi
Cardiotoxic drugs
Cathecholamines
- Doxorubicin
Systemic Illness
- SLE
- Other Collagen diseases
- Sarcoidosis
Hyper sensitive drug reactions
- Antibiotics (Ampicillin, Tetracycline, Sulfisoxazole)
- Diuretics (Hydrochlorothiazide, Spironolactone)
- Others (Lithium, Indomethacin)
Table 2. Etiologies of Non infectious Human
Myocarditis
Table 1. Etiologies of Infectious
Human Myocarditis
In the United States, enteroviruses [3] and especially group B coxsackie viruses have been the major
virus implicated. When sensitive techniques such as in situ hybridization or the polymerase chain
reaction (PCR) are employed, enterovirus genome has been found in approximately 25% of patients
with myocarditis and in 15% of samples of patients with dilated cardiomyopathy [6]. In South
America the protozoan Trypanosoma cruzi causing Chagas disease is the most common cause of
myocardial inflammation and since this protozoa is endemic to rural and central South America this
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infection probably remains the most common cause worldwide. Although it usually manifests itself as
heart failure secondary to dilated cardiomyopathy, acute myocarditis may be recognized in a minority
of patients [7].
A host of medicines are known as allergic triggers for immune-mediated myocarditis. These include
penicillin and thiazide diuretics [7]. Among the systemic diseases, sarcoidosis, scleroderma and
systemic lupus are the most common autoantigen causing myocarditis [5].
The clinical presentation of myocarditis caused by non-infectious agents is typically different from
that of viral myocarditis in that patients often are older and usually are taking multiple medications. In
general, secondary myocarditis is managed by treating the primary systemic illness. Mason [8] in 1991
proposed a classification scheme for myocarditis that separates the possible etiologies into six distinct
categories as summarized below.
•
Active viral
•
Postviral (Lymphocytic)
•
Hypersensitive
•
Autoimmune
•
Infectious
•
Giant-cell myocarditis
Giant-cell myocarditis represents a disease named after its histological appearance of multinucleated
giant cells of unknown etiology. The prognosis is worse than the other categories and cardiac
transplantation is often necessary [7]. This disease has to be biopsy-proved.
The postviral or lymphocytic myocarditis is believed to result from a pathologic immune response to a
recent enteroviral infection. It is proved to be the most common category detected by endomyocardial
biopsy in the United States [9].
3.2
Epidemiology
The prevalence of acute myocarditis is unknown because most cases are not recognized on account of
non-specific symptoms or no symptoms at all. Nonetheless, it is estimated that as much as 5% of a
virus-infected population may experience some form of cardiac involvement associated with the acute
form of the illness [7].
Important clues come from post-mortem studies. Such studies suggest that myocarditis is a major
cause of sudden unexpected death, accounting for approximately 20 percent of cases in adults less than
40 years of age, including young athletes and elite Swedish orienteers [11]. The endomyocardial
biopsy introduced in the 1980s on living people was the beginning of a new method for diagnosing
patients. The Dallas criterion was introduced in 1986 based on the histological findings. However,
these criteria led to years of underestimation, since the criteria where in fact too precise and narrowly
defined. The specimens were to contain both infiltrating lymphocytes and myocytolysis in order to get
the diagnosis according to the Dallas Criteria. Unfortunately, the “gold standard” for the diagnosis has
a limited sensitivity and specificity. A modified classification system was proposed 1991, still without
total acceptance [11]. According to the literature, men seem to be slightly more predisposed than
women to develop myocarditis [7].
3.3
Diagnosis
The clinical presentations of myocarditis are varied, ranging from asymptomatic with only small
findings on an electrocardiogram or echocardiograph, to fulminated heart failure and death.
Unfortunately there is still no specific clinical feature on which to base the diagnosis, but a clinical
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picture with a combination of acute infective illness and myocardial symptoms should suggest it.
Several non-invasive assessment of the heart can be used to get a picture of its status. ECG, X-ray,
echocardiography and cardiac enzyme measurement are the most used. The most common ECG
abnormality showing signs of infection is non-specific ST and T-wave changes. X-ray may show
evidence of pulmonary oedema and heart size enlargement. Echocardiography may show left
ventricular dysfunction or just a regional abnormality of the motion or a local thickening of the
myocardium. When it comes to the cardiac enzymes CK-MB is frequently elevated in patients with
acute myocarditis and significant ST-segment elevation [13]. Elevated levels of troponin-T occur
even more frequently than CK-MB, but in one study only 34 % (18/53) of those with biopsy proven
myocarditis had increased levels, as did 11% (4/35) of patients without myocarditis [12]. So an
increased level of heart enzymes reflects cardiac injury but is neither sensitive nor specific in the
diagnosis of myocarditis. Non-specific markers of inflammation such as white-cell count, ESR and Creactive protein are often elevated in patients with myocarditis. The use of myocardial biopsy to gain
direct histological evidence and allowing identification of viral agents by PCR or in situ hybridisation
- despite its limitations (i.e. sampling error, complications of invasive procedure, variability in
pathologic interpretation and low negative predictive value) - still remains the best way to get a certain
diagnosis of myocarditis.
3.4
Pathogenesis
The pathogenesis of human viral myocarditis is incompletely understood. For decades it was assumed
that myocyte damage was mediated only by the direct viral infection. During the last ten years a new
hypothesis has become more established. The knowledge it is based on comes from experiments
mainly on mice. From these results it seems that it is the host’s own inflammatory response to the
pathogen that causes the greatest harm to the myocytes. The acute viral myocarditis is initiated by a
viral infection which may cause symptoms, but the following myocardial damage appears to be
mediated primarily by post-infectious autoimmune destruction of myocytes, and not as believed before
by direct viral myocellular damage[7]. During an initial phase lasting up to 4 days, you can see what is
most likely to be a direct cytopathic effect of the virus, such as focal myocyte necrosis, macrophage
activation and cytokine expression. During these first four days of viremia, virus can be detected from
the myocardium. The secondary phase seems to be the effect of altered immune regulation. Now the
virus is cleared by natural killer cells and cytotoxic T and B lymphocytes. By day 14 the virus is
usually eliminated from the myocardium, but cytokines persist. The cytokines exhibit a redundancy of
action by affecting pathways that are both harmful and beneficial to myocyte function - for example
tumor necrosis factor TNF α and nitric oxide synthase. During the second week of illness, both T and
B lymphocytes infiltrate the myocardium coincidentally with the most severe myocardial damage. In
some individuals it seems that an aberrant induction of apoptosis may play a crucial part in whom is
later going to develop cardiomyopathy [7]. The third and final phase usually lasts from day 14 up to
90 days. It is characterized by the absence of virus and in some cases heart failure due to fibrosis and
cardiac dilatation. Most patients with myocarditis recover completely.
3.5
Treatment
The treatment of myocarditis is mainly focused on supportive care. Effective antiviral agents are often
unavailable and usually inappropriate, but whenever it is possible to direct the treatment against a
specific etiologic agent, this should be done. The main treatment goal is the maintenance of cardiac
output at levels able to provide adequate tissue perfusion. Even before definitive diagnosis, supportive
care should be initiated. This involves diuretics to lower ventricular filling pressure, an angiotensin
converting enzyme inhibitor to decrease vascular resistance and a beta blocker once clinical stability
has been achieved [3]. In patients with severe symptoms, supportive care may include the use of
inotropic therapy or implant of ventricular device, which in some cases may be life saving. The most
used therapy we have today is hard work restriction. Bed rest is also common in this patient group.
Immunosuppressive agents could be effective in the second stage when it is autoimmune inflammatory
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response that causes the most damage [1]. But the results from randomized controlled trials so far has
been discouraging. An alternative way to treat viral myocarditis has been by developing virus specific
vaccines. Up to now this has only been done on animals - and the results appear to be very good,
although further studies are needed to confirm that this will be the case even with humans.
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4
Basic Principles of Traditional Chinese Medicine
The theory of yin and yang is a kind of world approach. It holds that all things have two opposite
aspects, yin and yang, which are opposite but at the same time interdependent. The two opposites are
not stationary but in constant motion and they can be seen as day and night, i.e., changing into each
other as well as balancing each other.
This theory is applied on the thinking of Chinese medicine and each body organ has an element of yin
and yang within it. The histological structure and nutrients are yin, and the functional activities are
yang and together they keep the flow of qi circulating in a well defined rhythm in the body. Some
organs are predominantly yang while others are strong in yin and the Traditional Chinese Medicine
(TCM) also includes a wide range of internal invisible organs such as Xin-heart, gan-liver and pispleen, which should not be confused with the common international definitions of the organs. In the
healthy individual the fluctuating balance will be maintained but any prolonged condition of
disturbance will affect the harmony and result in some kind of disease.
For example, the Xin-heart dominates the circulation of blood. When it functions properly the tissue
and organs are well perfused and nourished, but when it malfunctions there is precordial pain,
cyanosis and ischaemia. The disease is due to “stagnation of the blood of Xin-heart”. The Xin-heart
“keeps” the mind including mentality, memory and normal sleep, so when this fails, imbalance in Xinheart is believed to be the cause. The Xin-heart takes the tongue as its orifice and opens through it and
hence, different signs on the tongue represent various conditions of the heart.
The central principle of TCM is to diagnose the cause of the disease, or yin yang imbalance within the
body. This is done through inspection of face and body posture as well as evaluation of the mental
condition, examination of the tongue, body auscultation, and palpation of the pulse and by the smell.
Concerning treatment, the basic idea is to strengthen and protect normal qi and maintain a healthy
body. This can be done by using the relevant acupuncture points to correct the flow of qi and thereby
correct the internal disease, or by using herbal medicines [15].
•
Shenmai San Intravenous drip: Ginseng, Ophiopogon, Schizandra
Increases myocardial contractility and enhances myocardial energy metabolism, with
applications to treatment of shock, arrhythmia and cardiac glycoside poisoning. Other
applications of Shenmai mentioned in literature include viral Myocarditis, reaction to high
altitude, congestive heartfailure and symptoms remaining after a heart attack [18]. Its
antioxidant activity is used as a preventive therapy for future heart attacks in patients with
coronary heart disease [19].
•
Danshen Dripping pills: salvia root, notoginseng, borneol
Quickening blood, transforming stasis, rectifying qi, relieving pains.
•
Xin bao: datura flower, deerhorn, cinnamon bark and notoginseng
Warming and tonifying heart and kidney, enriching qi, assisting yang, quickening blood.
Tachycardia and ischemia and angina pectoris can be treated [16].
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5
5.1
Patients and Method
Shanghai, China
Using the ICD-code for acute viral myocarditis, it was possible to gain access to the patients registered
with acute myocarditis at Xin Hua Hospital in Shanghai, China for the latest years. The search was
limited in time from 1 January 2002 until 4 April 2003. A total number of 135 patients were available
during this period. Out of these, supervisors at Xin Hua Hospital randomly collected 44 patients to
represent the myocarditis patients in Shanghai. There was no selection in age, gender or treatment.
During the first two weeks three young patients were hospitalized at the department of cardiology,
diagnosed with myocarditis and they were followed clinically and included in the material. Hence, the
total number of patients registered in the material is 47. The cardiac inflammations often include both
the myocardium (myocarditis) and the pericardium (pericarditis). However, this study focuses on
patients diagnosed with myocarditis only.
Data was collected with a questionnaire, (see appendix A), to determine symptoms that made the
patient seek medical care, as well as examination results and lab results. Both TCM and Western
medicines were used in the treatment.
Since the study is retrospective, some questions were difficult to answer. This can be partly attributed
to the fact that the questionnaire was based on experience from Swedish consulting standards, while
Chinese doctors tended to make documentation in a different way. In order to obtain information as to
whether the patients studied were representative for the whole population in Shanghai, the
questionnaire initially included a section on education level, religion and socio-economic status. As it
turned out, information about this was not available in the patient’s records.
Xin Hua Hospital is one of many hospitals in Shanghai. It is affiliated to Shanghai Second Medical
University (SSMU). There are five different medical universities in Shanghai, and everyone is
connected to four or five hospitals. Xin Hua Hospital was funded in 1958 and has since then twice
been awarded a “Grade 3A Hospital” by the Ministry of Public Health of China, as well as other
awards and acknowledgements. The scale is from 1-3 and three is the top grade. It is a modern hospital
housing almost all disciplines and at present it has 1318 beds and 2713 employees. The hospital
admits approximately 16000 patients per year and the emergency service includes more than 1.25
million outpatient visits annually. Around 21 200 operations are performed every year. Altogether the
hospital has 36 clinical departments, 13 paramedical departments including 47 specialties and 15
research units. The hospitals most successful program is about digestive diseases. Most advanced
medical equipment, such as MRI, the whole-body CT-scanner, SPECT, ECT Linear Accel-Hyperbaric
Oxygen Chamber, is available at Xin Hua hospital [17].
5.2
Gothenburg County, Sweden
The Swedish part of this project was located to the western region of Sweden in the province of Västra
Götaland. The aim has been to get a broad view of patients diagnosed as having myocarditis, therefore
it include all ages as well as patients with residence both in the countryside and in the city. One of the
authors of the report, Petter Bryngelsson, visited several different hospitals in the Gothenburg County,
namely Sahlgrenska University Hospital, Borås Hospital, Kungälv Hospital, Uddevalla Hospital and
Skaraborg Hospital in Skövde. The following departments have been visited:
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•
Cardiology – Skaraborg Hospital in Skövde
•
The clinics for infectious disease – Sahlgrenska University Hospital/Östra, Borås Hospital,
Uddevalla Hospital and Skövde Hospital
•
Paediatrics - Sahlgrenska University Hospital/Östra, Borås Hospital
•
Internal Medicine - Kungälv Hospital
To get enough patients we did our search during a ten years period which has been limited between 1
Jan 1993 until 31 Dec 2002.
5.3
Diagnostic criteria for myocarditis, Shanghai, China
The following procedure is used at Xin Hua Hospital for diagnosing myocarditis. Symptoms and other
findings are divided into four groups as presented below:
Category A – History and signs
Cardiac symptoms and signs appearing within three weeks after a viral infection, often including
upper respiratory infections or diarrhea. Acute symptoms include severe fatigue, breathlessness and
dizziness. Signs range from first sound muffled, to diastolic gallop, pericardial friction, cardiomegaly,
congestive heart failure and Adam-Stokes syndrome.
Category B - Arrhythmia and electrocardiographic changes
Arrhythmia and electrocardiographic changes appearing three weeks after an infection.
1. Tachycardia, AV-conduction disturbance, sino-atrial conduction disturbance or branch blocks.
2. Ventricular premature beats, atrial- or junctional tachycardia, ventricle tachycardia, atrial or
ventricular flutter.
3. ST-segment depressing >= 0.01mV, ST segment increasing abnormally or abnormal Q-wave
appearance.
Category C - Myocardial injury
1. Pathologic serology, Troponin I (TnI)-, Troponin T (TnT)- or Creatinin kinas-MB (CKMB)
elevation.
2. Echocardiography showing enlarged heart or abnormal wall motion.
Category D - Etiological findings
1. In acute phase, virus, virus gene segments or viral antigen are detected by taking biopsy from
endocardium, myocardium or pericardium.
2. Viral antibody titer – neutralizing antibodies against Coxackie B-virus.
One specimen: A fourfold rise in titers above the mean normal value is considered suspect, 8 times
above it is regarded as positive.
Two specimens: If the level of antibody titers of the second specimen is four times higher than that
of the first one, the result is positive.
A patient with two findings of A, B or C can be clinically diagnosed with acute viral myocarditis. The
patient can be diagnosed etiologically if he or she has D:1 or D:2 findings as described above.
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5.4
Diagnostic criteria for myocarditis, Gothenburg County, Sweden
All patient records with a suspect myocarditis (ICD-9 and ICD-10, Nr 422X, 74C, I40.0, I40.9 and
I30.9) were reviewed. All together 186 patients were found. Out of these 31 patients were diagnosed
with proven myocarditis fulfilling at least one of the following criteria.
Category A - Leakage of heart markers such as Troponin or CKMB.
Category B - Pathological UCG with left ventricular dysfunction, and/or regional abnormality of the
motion and/or local thickening of the myocardium and/or low EF (<50%).
Category C - A PAD or Biopsy fulfilling the criteria for myocarditis according to the opinion from a
pathologist.
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6
Results
6.1
Demographic data
Shanghai, China
The results in Shanghai, China are based on 47 patients and the ages ranged from 11 to 54 years (mean
29) and 53 % were male, as presented in diagrams 1 and 2. Furthermore, 43 out of 47 patients came
from families consisting of three members. One family had two members and one consisted of four
family members. Information about family was missing for two patients.
36 % of the patients were students, 45 % workers, 2 % were retired and in 17 % of the cases studied
there was no information about occupation.
Figure 1 & 2.
Gender distribution, Shanghai
Age distribution, Shanghai
Number of patients
10
8
6
Male
4
Female
2
51-55
46-50
41-45
36-40
31-35
26-30
21-25
16-20
11-15
6-10
0-5
0
Age
Out of the 47 patients studied in Shanghai, 77 % had social insurance, while 6 % were not insured and
for 17% of the patients there was no information about social insurance. Five patients (11 %) were
smokers, 45 patients were Shanghai citizens and two patients lived outside the Shanghai metropolitan
area.
One patient had suffered from myocarditis once before, in 2001 and another had a sister who had been
diagnosed with myocarditis. Three patients had previously had cardiac symptoms such as AV-block
and episodes of dyspnea and palpitations. Four patients had in the past been registered with
hyperthyroid hormone production.
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Gothenburg County, Sweden
The results in Sweden are based on the records of 31 patients. As presented in figure 3 and 4 below,
97% in this group were males and the mean age was 29 (range 7 – 55) years.
Figure 3 & 4.
Gender Distribution, Gothenburg
County
10
8
6
4
2
0
Female
51-55
46-50
41-45
36-40
31-35
26-30
21-25
16-20
11-15
6-10
Male
0-5
Number of Patients
Age Distribution, Gothenburg County
Age
Information on occupation was available in 68 % (21/31) of the patients. The representation of
occupation came from varied groups in society, such as a farmer, a carpenter, a truck driver, a social
worker, a data consultant and students. The students were represented with 29 % (9/31) of the total
number of patients, from all other occupations only one patient was represented in each field. Most
patients had their residence in the countryside 58 % (18/31), 35 % lived in a city and from 6 % (2/31)
we had no information. The mean number of family members was 2.8. 29 % (9/31) used some kind of
tobacco on a daily basis, 13 % (4/31) smoked twenty cigarettes or more per day.
6.2
Associated infection and symptoms
Shanghai, China
In Shanghai, 41 out of 47 patients (corresponding to 87 %) had a clear history of an associated
infection within the weeks before diagnosed with myocarditis. In 6 cases out of 47 there was no
information about associated symptoms or infections. The percentages in figure 5 are therefore based
on a total patient number of 41.
Figure 5.
Pneumonia
Gastroenteriti
s
Bronchitis
80
60
40
20
0
Upper resp.
infection
Percent of patients
Infectious diseases during the weeks before diagnosed with myocarditis,
Shanghai, China (n=41 )
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As figure 5 clearly indicates, upper respiratory infection was the most common clinical symptom
found among 30 patients (73%). Upper respiratory infection includes symptoms such as dripping nose,
sore throat, and snuffles. Gastroenteritis includes diarrhea and epigastric pain. It should be noted
though, that one patient could have had one or more of the above listed symptoms in figure 5. The
time span from associated infection or symptoms until seeking medical care for other symptoms or
worsening of the same symptoms ranged from 1 day until 60 days (mean 17 days). The mean time
span is based on data from 36 patients for which the records included precise data on dates.
Gothenburg County, Sweden
In Sweden, 94 % (29/30) had a clear history of a preceding infection within the weeks before
diagnosed with myocarditis. One patient had no preceding infection and for one patient this data was
missing. The data in figure 6 is therefore based on a total of 29 patients. The time span between debut
of preceding infection and date of seeking medical care ranged from 2 to 19 days (mean 6 days).
Figure 6.
Infectious diseases during the weeks before diagnosed with myocarditis
Gothenburg County (n=30)
30
20
10
Varicella
Sepsis
Pneumonia
Bronchitis
Gastroenteritis
0
Upper
respiratory
infection
Percent of
Patients
40
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6.3
Clinical symptoms at the time of diagnosis
Shanghai, China
Figure 7 below illustrates the frequency of the different symptoms that made patients in Shanghai,
China seek medical care.
Figure 7.
Slow pulse
Irregular pulse
Cough
Vomiting
Abdominal pain
Precordial pain
Epigastric pain
Syncope
Dizzyness
Diarrhea
Fever
Fatigue
Chest pain
Palpitations
90
80
70
60
50
40
30
20
10
0
Dyspnea
Percent of Patients
Clinical symptoms at the time of diagnosis of myocarditis, Shanghai, China
Dyspnea and palpitations proved to be the two most common symptoms that made the patients seek
medical care and which eventually led to hospitalization. As a matter of fact, dyspnea was present in
78% of all patients. Even if some of the symptoms per se did not have any cardiac relation,
examinations performed at the emergency care unit or at the out patient department showed
pathological changes most often on the electrocardiogram (ECG). Examples of such symptoms are
vomiting or diarrhea. One patient could experience more than one of the symptoms in figure 7.
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Gothenburg County, Sweden
Figure 8.
Clinical symptoms at the time of diagnosis, Gothenburg county (n=31)
90
80
Percent of patients
70
60
50
40
30
20
10
Figure 8 shows the symptoms that caused the patient to seek medical care in Gothenburg County. In
some cases there was one reason to why the patients seek medical care, in those cases when there were
multiple reasons each one is represented in the figure. The most common clinical symptom was chest
pain, but other manifestations were also common. 71 % (22/31) of the patients had some kind of
pathological clinical manifestation that did not involve the heart. These observations were taken at the
first meeting with a physician.
6.4
Examination- and laboratory results
Shanghai, China
Table 3 illustrates the different examinations carried out in Shanghai, China, together with the results
from the tests. Only three patients had normal ECG findings, and among the 44 with pathological
findings, T-wave changes were present in 34 % of the cases, ST-elevations in 32 % and ventricular
premature beats in 30 %. Twelve patients displayed pulmonary involvement on lung x-rays
representing enlarged left ventricle (3/12 patients), enlarged branches (8/12 patients), apical changes
as of old Tuberculosis (1/12 patient). Ejection fraction (EF) below normal is one of the criteria for heat
failure representing a heart unable to pump out a sufficient fraction of blood. EF is measured by
Echocardiography (Echo). Twelve patients had pathological EF.
19
Palpitations
Headache
Hemoptys
Ventricular
tachycardia
Cough
Muscular pain
Hyptension
Tachypne
Heavy breath
Shivering
Scin
manifestations
Tachycardia
Enlarged
lymphnodes
Infection in
throat
Fever
Chest pain
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Type of test
Pathological
results/total
Percentage (%)
ECG
44 / 47
94
X-ray
12 / 39
31
EF (<59%)
12 / 41
29
Echo
2 / 41
5
Cor.Ai
0/3
0
Myocard. Biopsy
0/0
0
Table 3. Examinations, Shanghai, China
One of the patients in Shanghai, China had pseudo cordease in the left ventricle and one patient had
enlarged left atrium and ventricle shown on echocardiography. Three patients had a coronary
angiography and they were all normal. No patients were examined with myocardial biopsy.
Gothenburg County, Sweden
At the first examination with ECG, Echo, and X-ray 97 % of the patients (30/31) had some kind of
pathologic involvement of the heart. In one case there was nothing pathological except from pain, but
in a later stage the diagnose myocarditis could be confirmed for this patient after receiving
pathological results on the CK-MB and troponin-T and later a biopsy showing myocarditis.
Type of test
Pathological results/total
Percentage (%)
ECG
29/31
94
X-ray
6/26
23
EF (<50%)
6/13
46
Echo
13/30
43
Cor.Ai
0/0
0
Myocard. Biopsy
2/2
100
Table 4. Examinations, Gothenburg County
Pathological ECG findings were not an obligatory criteria to be included in the study. However 94 %
had some kind of pathological findings on their ECG. Elevation of the ST-line was the most common
first signs. A negative T-wave was also rather common a few days after the initial debut of chest pain.
At follow up visits on average six weeks after the patients left the hospital, a majority (78%) had no
residual signs on their ECG.
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From 26 journals x-ray results of hearts and lungs was found. Twenty of these showed a completely
normal picture. Five showed some kind of infiltration in lungs. One examination showed a slightly
enlarged heart.
From 30 of the journals, results of echocardiography were found and 17 of these showed a normal
picture. 13 showed a pathologic function of the myocardium. The mean ejection fraction (EF) of the
whole group was 50%. Out of those with pathological findings a general hypokinesia was the most
common. In 6 patients this lead to low EF (<50 %).
None of the patients were examined with angiography of the heart. From two patients myocardial
biopsies were taken. In both cases post mortem.
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Shanghai, China
Type of test
Pathological results/total
Percentage (%)
Normal range
Min/Max
Hb
6 / 47
13
120-160 g/L
81/153
WBc
2 / 47
4
4-10 *10^9/L
3.1/16.6
Platelets
3 / 47
6
100-300 *10^9/L
24/369
ALP
9 / 43
21
42-121 IU/L
14/335
ASAT
3 / 45
7
10-42 IU/L
4/302
ALAT
3 / 45
7
0-75 IU/L
2/394
Creatinine
1 / 44
2
44-133 micromol/L
43/335
Ck
6 / 43
14
22-269 IU/L
44/1810
CkMB
6 / 43
14
0-25 IU/L
3.5/67
Tnt (0-0.1)
6 / 42
14
0-0.1 microg/mL
/1.8
CRP
12 / 35
34
0-5 mg/L
/80
ESR
8 / 39
21
0-20 mm/h
/35
Coxackie B 1-6
7 / 34
21
Negative
TSH
3 / 37
8
0.3-4.5 U/ml
0.5/8
fT4
7 / 37
19
8.7-17.8 pmol/L
1/20
Table 5. Laboratory tests, Shanghai, China
The most prevalent pathological results were CRP (34%), ALP (21%), ESR (21%) and positive viral
titer-test against Coxackie B virus (21%).
Gothenburg County, Sweden
Type of test
Hb
WBc
Pathological
results/total
3/30
15/29
Percentage (%)
Normal range
Min/Max
10
120-160 g/L
100/172
52
4-10 *10^9/L
2.9/36
100-300 *10^9/L
27/647
Platelets
5/26
19
ALP
5/14
36
<5 µkat/L
2.2/16
ASAT
17/19
89
ALAT
11/22
50
Creatinine
6/22
27
Ck
11/11
50
CkMB
22/25
88
<3.30 µkat/l
0-25 µkat/l
0.35/127
Tnt (0-0.1)
20/20
100
0-0.1 microg/mL
0.11/15
CRP
27/29
93
0-5 mg/L
3.8/250
ESR
6/13
46
0-20 mm/h
4/55
Coxackie B 1-6
2/4
50
Negative
Blood culture
2/10
20
Negative
0.20 – 0.80 µkat/L
0.20-0.80 µkat/L
60-120 µmol/L
0.3 /292
0.25/152
51/426
3.4/303
Table 6. Laboratory tests, Gothenburg County.
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The most prevalent pathological results were Tnt (100%), CRP (93%), ASAT (89%) and CKMB
(88%). Among the two positive blood cultures, Staphylococcus Aureus was grown from one patient
and a gram negative rod from the other.
On 4 patients culture of stool was taken. Two of these were positive with Campylobacter Jejuni.
6.5
Treatment
Shanghai, China
As is illustrated by figure 9, all of the 47 patients from Xin Hua hospital in Shanghai, China got bed
rest ordination in the acute phase, and were recommended hard work restrictions for up to three
months. Six pupils were recommended not to go to school for 3-6 months. One pupil had school
restrictions up to one year.
Figure 9.
Glucocorticoids
Beta receptor
blockers
Ribavirin
Antibiotics
Antiarrhythmic
treatment
Hard work
restriction
100
90
80
70
60
50
40
30
20
10
0
Bed rest
Percent of patients
Treatment, Shanghai, China ( n=47)
Type of treatment
Anti-arrhythmic treatment (Mexiletine) was used in more than 50% of the patients. One third of the
patients received Beta-blockers to prevent arrhythmic disturbances. 50% got antibiotics and the most
common was Lincomycin taken intravenously followed by cephalosporins orally.
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Figure 10.
Si tai long
Tong xin luo
Xin ke shu
Vitamine B
Ning xin bao
Nuo di kang
Vitamine C
Xin de kong
Coenzyme Q10 p.o
Dansen tablets
Shenmai i.v
K, Mg, Asparatat
Huang qi
Coenzyme A i.v
100
90
80
70
60
50
40
30
20
10
0
ATP tablets
Percent of patients
Traditional Chinese medicine, Shanghai, China (n=47)
Type of treatment
Figure 10 should be seen as a complement to figure 9. All of the patients in Shanghai, China had some
kind of TCM treatment during their hospital stay. As many as 90% were recommended ATP-tablets (
Adeno-tri-phosphate) and Coenzyme A.
Gothenburg County, Sweden
Figure 11.
T reatment, Gothenburg County (n=31)
100
Percent of patients
90
80
70
60
50
40
30
20
10
Antiarrhythmic
treatments
ACE-inhibitors
Diuretics
Inotropic drugs
Beta receptor
blockers
Glucocorticoids
Antibiotics
Hard work
restriction
Pain therapy
Bed rest
0
Bed rest was prescribed to 97 % of the patients when they were diagnosed with myocarditis. The
length varied between 2 - 25 (mean 7) days. Hard work restriction varied between 21 days and 6
months, with a mean on 33 days.
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6.6
Duration of hospital care and sequele
Shanghai, China
As presented in figure 12 the most common length of hospital stay was for a period of 11 to 15 days
(mean 17 days). No patients were treated for less than five days, and only very few remained in the
hospital for more than 30 days. Two patients were left with long term sequele and no patient died.
Figure 12.
60
40
20
41-45
36-40
31-35
26-30
21-25
16-20
11-15
6-10
0
0-5
Percent of patients
Duration of hospital care, Shanghai, China
Days
Gothenburg County, Sweden
In the Gothenburg County on the other hand, the vast majority of patients (65 %) left the hospital after
less than six days of treatment. No patients included in the study stayed in the hospital for more than
36 days (mean 6 days). Two patients died during the hospital stay. Five patients were left with long
term sequele.
Figure 13.
31 – 36
25 – 30
21 – 25
16 – 20
11 – 15
6 – 10
80
70
60
50
40
30
20
10
0
0–5
Percent of patients
Duration of hospital care, Gothenburg County
Days
25
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7
7.1
Discussion
Epidemiology
The age distribution in Shanghai and in Gothenburg County was similar with an identical mean age of
29 years.
The proportion between male and female patients on the other hand differed significantly between the
two regions. In Shanghai the male patients represented 53 % while in the Gothenburg County 97%
were males. The Swedish results in this study show an extreme overrepresentation of males which is
hard to explain. Relatively few studies have been made in the epidemiologic field and exact numbers
regarding incidence and sex distribution are generally not well defined in the review articles of the
studies. Nevertheless, according to literature and reviews, men seem to be slightly more predisposed
than women to develop myocarditis [7]. The only article found considering epidermiology was a
retrospective cohort study (1987- 1996) from Australia documenting the epidemiologies of
cardiomyopathy in childhood. In this study, there was a male predominance among children with
hypertrophic and unclassified cardiomyopathy. Of the children with dilated cardiomyopathy, 56%
were female [20].
Considering the hereditable aspect, one of the Chinese patients had a sister who had been diagnosed
with myocarditis. One interesting observation in Shanghai was the low number of family members.
With only two exceptions the families consisted of three members. This must be a result of the family
politics introduced in 1978, trying to control the growing population in China.
7.2
Previous diseases
In the Shanghai group, one patient had been diagnosed with myocarditis once before in 2001. In the
Swedish part of the study one patient had earlier been diagnosed with perimyocarditis. According to
these data it seems that the risk for relapse is relatively low.
Since hyperthyroid hormone production can give cardiac symptoms and could be a differential
diagnosis to myocarditis, it is interesting to notice that four patients in the Shanghai group previously
had a hyperthyroid hormone production. None of the Swedish patients were registered with this
particular type of hormone divergence.
In Shanghai, hepatitis is far more common than in the Gothenburg County. In fact two patients in the
Shanghai group were diagnosed with hepatitis A, and two patients were infected by hepatitis B virus.
None of the Swedish patients had earlier suffered from hepatitis virus.
In the Swedish group, the prevalence of previous diseases was very low. A result that could be
expected in a group of patients with mean age of 29 years. No obvious correlation was found between
myocarditis and any other disease or predisposing factor. Neither were any specific risk factors for
developing myocarditis identified.
According to literature on the matter, most cases of myocarditis with onset in otherwise healthy people
are believed to have an infectious origin. This theory is supported by our results.
7.3
Preceding infection or symptoms
In both groups upper respiratory infection was the most common preceding infection (illustrated in
figure 5 and 6). Among the Chinese patients, the episode of myocarditis was preceded by upper
respiratory infection in 73% and by gastroenteritis in about 10% (figure 5) of the cases. In Sweden on
the other hand, corresponding data are 37% and 27%. This is surprising since China has a higher
prevalence of gastroenteritis in general.
Coxsackie B virus causing upper respiratory infections is according to literature one of the most
common etiological agents in cases of myocarditis [3] and this could correspond to our findings.
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87% in China had a preceding infection and the clinical spectrum ranges from upper respiratory
infections to pneumonia. Even though preceding infection was not a diagnostic criterion in Sweden,
94% of the patients described one. These data corresponds very well to earlier studies, suggesting that
most myocarditis has a viral origin that begins with a systemic infection.
7.4
Clinical symptoms at the time of diagnosis
The clinical symptoms differ between the two studied regions. In Shanghai, a majority (78%) of the
patients had dyspnea and palpitations when they did seek medical care, while chest pain and fever
seemed to be the most common clinical signs of an ongoing myocarditis in the Gothenburg County.
7.5
Examination- and laboratory results
Despite the major improvements in imaging techniques during the last twenty years ECG still appears
to be a sensitive and inexpensive tool for the initial evaluation of suspected myocarditis. The results
from both Shanghai and Gothenburg suggest what most studies on myocarditis have already
confirmed in the past: a vast majority of the patients which end up with a myocarditis diagnosis have a
pathological ECG at the time of seeking medical care.
The differences in the pathological frequencies of both ECHO- and laboratory tests indicate that the
patients from the Gothenburg County were more severely ill than the Chinese patients. The low
frequency of pathological results from Echo in Shanghai is somewhat surprising. Other studies
indicate that you can visualize abnormalities on Echo in up to 90 % of the patients diagnosed with
myocarditis [21]. The laboratory results differ drastically between Shanghai and Gothenburg. For
instance, in Shanghai 14 % of the patients had pathological results on Tnt, in Gothenburg this figure
was 100%. The reason to this dramatic difference is partly because the diagnostic criterion to be
included in the study differed some between the two patient groups. The laboratory test which most
frequently showed pathological results in both groups was CRP. An elevation of CRP as a common
entity in combination with myocarditis is not only supported by our results but also by most other
studies.
7.6
Treatment
In Shanghai, one third of the patients had chest pain as a clinical symptom when diagnosed with
myocarditis. However, not one received western traditional pain therapy. Most probably some of the
TCM have an analgetic effect that replaces the need for traditional western medicine. In Sweden pain
therapy was the most used drug and more than 80% took some kind of pain reliever. This might
indicate that the Swedish group were more seriously ill. But it might also be an indication of different
mental attitudes to pain in two ethnic groups.
As far as the risk of arrhythmic events is concerned, all patients in Shanghai and almost all in
Gothenburg County got bed rest recommended in the acute phase. This type of therapy has in other
cases and diseases proved to be a direct threat to the health since immobility increases the risk of
developing thrombosis. Great awareness should be taken with regard to the possible need of
anticoagulation in acute myocarditis since the inflamed endomyocardium may be predisposed to
thrombosis. Hard work restrictions were given to all patients in Shanghai and to 75% of the Swedish
patients. Data from animal tests have shown that exercise increases myocardial inflammation, necrosis
and mortality in animals with myocarditis [7].
The use of anti-arrhythmic drugs and beta-receptor blockers focuses on supportive treatment and was
more common used in Shanghai. Almost 90% received some kind of supportive therapy in Shanghai
while in Gothenburg County the corresponding data was 25%. Since all of the included Chinese
patients were hospitalized in a departemente of cardiology this may influence the choice of treatment.
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On the other hand the Swedish patients who were picked from several disciplines (for instance 2
departments of infectious diseases) received antibiotics in a higher grade, 70% contra 50%. Since
bacterial etiology is an uncommon cause of myocarditis, it is surprising that such a high proportion of
the patients in both countries received antibiotics.
Antiviral treatment was not at all used in Gothenburg County while 40 % of the Shanghai patients
received Ribavirin. Anti viral treatment focus on the direct damage on the myocyte, the first stage in
the pathogenesis and could be useful during the first four days.
Glucocorticoides could be effective in the second stage of myocarditis, from day four till day 14, when
it is autoimmune inflammatory response that causes the most damage for the myocytes.
Glucocorticoides was not as common in Shanghai as it was in Gothenburg County.
The third phase of myocarditis, day 14 up to three months, with can lead to fibrosis of the heart muscle
and cardiac dilatation, has no treatment among the western traditional medicines.
The treatment of myocarditis should be examined in the light of the difficulty in diagnosing this entity.
Since the pathogenesis is incompletely understood, the correct treatment is hard to specify. It is likely
that continued understanding of the pathogenesis of the immune system in myocarditis will lead to
more specific and effective therapies for this disease. A future study that compares the traditional
western medicines with the TCM would be interesting.
7.7
Duration of hospital care
The patients in Gothenburg were at least as badly ill as the patients in Shanghai, but they were
hospitalized in average almost three times as long in Shanghai. A contributing factor may be the
hospitals own interest in what happens to their patients. In Shanghai the hospital gets paid by an
insurance company (or individual) for every night the patient stays. In Sweden it is a loss for the
government for every night a patient stays. So the interests towards the duration of hospital stay in the
two countries are the opposite when you look at the situation from a financial view.
No international consensus is available on diagnostic criteria or treatment of myocarditis. In our study
we have noticed several differences in clinical presentation and management of myocarditis. A
binational randomized prospective trial, focusing on diagnostic criteria and the different options of
treatment would be of great value.
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8 References
1
Liu P, Martino T, Opavsky MA, Penninger J. Viral Myocarditis: balance between viral infection
and immune response. Can J Cardiol. 1996;12:935-43.
2
Sole MJ, Lui P. Viral myocarditis: A paradigm for understanding the pathogenesis and treatment
of dilated cardiomyopathy. J Am Coll. Cardiol. 1992:22(suppl.A):99A-105A.
3
Mandell, Douglas and Bennetts. Principles and Practice of Infectious Disease. 5th Edition, 2000.
4
Lonely planet. Shanghai-The Pulse of modern China. 1st edition 2001.
5
Daniel Levi and Juan Alejos. An approach to the Treatment of Pediatric Myocarditis. Pediatric
Drugs 2002;4(10) 637-647.
6
Hyypia T. Etiologic diagnosis of viral heart disease. Scand J Infect Dis. 1993;88(suppl):25-31
cited in
7
Garrie J, HAAS, MD. Etiology, Evaluation and Management of Acute Myocarditis. Cardiology in
review. 2001, 9(2) 88-95.
8
Mason JW. Distinct forms of myocarditis. Circulation 1991;83:1110-1111.
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O´Connell JB. Diagnosis and medical treatment of inflammatory cardiomyopathy. In Topol EJ,
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29
MYOCARDITIS
– FROM SYMPTOMS TO TREATMENT IN SHANGHAI, CHINA
AND IN THE GOTHENBURG COUNTY, SWEDEN
Thanks to:
Prof. Rune Andersson, Skaraborg Hospital, Skövde, Sweden
Prof. Chang Yachen, Xin Hua Hospital, Shanghai, China
Dr.Ying Yu, department of cardiology, Xin Hua Hospital, Shanghai
Director Ou Jianfeng, Vice-Director, President Office Foreign Affaires
Prof. Rong YeZhi, Dept. of Medicine, Xin Hua Hospital, The Research Laboratory for Myocardial
Diseases, Shanghai Second Medical University
Prof. Zhang Maozhen, SSMU, The Research Laboratory for Myocardial Diseases
Prof. Chen Jie, Walllenberg Laboratory, Sahlgrenska Hospital Göteborg.
Prof Michael Fu, Wallenberg Laboratory, Sahlgrenska Hospital Göteborg.
The staff at the department of cardiology, Xin Hua Hospital, Shanghai
To the secretaries and other staff at: the department of infectious diseases Sahlgrenska/Östra, the
departement Cardiology Skövde, the department of infectious diseases Borås, the department of
infectious diseases Uddevalla, the department of infectious diseases Skövde, the departemente of
pediatrics Sahlgrenska/Östra, the department of pediatrics Borås and the departement of internal
medicine Kungälv.
30