Clinical presentation is heterogenous. VM may be asymptomatic, result in symptoms that develop in the course of weeks or even months, or trigger acute symptoms of heart failure and cause sudden cardiac death. Children tend to present more acute symptoms than adults.
Cardiac symptoms such as chest pain, tachycardia, dyspnea and cough, particularly under exercise, are commonly observed. Arrhythmias, heart murmurs, third and fourth heart sound as well as mild and filiform pulse may be present and syncopes may be experienced. Patients suffering from heart failure may also show cyanosis. In cases of chronic disease, these symptoms may rather be caused by a DCM resulting from an undiagnosed myocarditis. Indeed, a DCM detected during routine screens may even be the first indication to an existing inflammation of the myocardium.
Diagnostic measures should be taken to confirm viral infection and heart failure and to rule out distinct causes for the latter. In this context, laboratory analyses of blood samples may be very helpful. Lymphocytosis and neutropenia are frequently associated with viral infection; reduced counts of erythrocytes or decreased levels of hemoglobin, however, indicate anemia. Anemia may cause several of the above described symptoms of VM, it may even cause heart failure. Measurements of the erythrocyte sedimentation rate may further support the distinction of infection and anemia. With regards to blood chemistry, increased levels of C-reactive protein indicate current inflammatory processes. Levels of creatinine kinase and troponin I may reveal important information about existing damage to the heart muscle. Finally, blood cultures may be prepared to rule out bacterial infection .
If the tentative diagnosis of viral infection is confirmed by laboratory results, viral titers may be determined. Concrete suspicions for determined viral agents may be confirmed by molecular biological techniques .
Cardiac function should be assessed by applying electrocardiogram and echocardiography. Typical findings include global hypokinesis, an increased end diastolic and systolic left ventricular volume, a reduced ejection fraction and possibly pericardial effusion.
Other imaging techniques such as chest radiography and magnetic resonance imaging may reveal cardiomegaly and possibly existing pulmonary edema. Of note, contrast agent gadolinium may used in magnetic resonance imaging to detect myopericarditis. Inflammation of the myocardium may also be verified by scintigraphy, although this technique is not the method of choice to confirm VM.
Finally, endomyocardial biopsies obtained from the right ventricle are needed to confirm and specify the diagnosis of myocarditis . The procedure is generally considered safe, however, increased risks are associated to myocardial biopsies in young children and infants. Histologic evaluation of the obtained tissue sample allows for the confirmation of active myocarditis (ample infiltration with inflammatory cells and necrosis) or borderline myocarditis (less inflammation) . Also, if no signs for myocarditis are detected, other pathologies would have to be considered. Besides, biopsies may also be applied to monitor the recovery process once treatment is initiated.
Hospitalization is required to treat VM, even if only mild symptoms are experience. The patient should be constantly monitored in order to avoid rapid deterioration, heart failure and sudden cardiac death.
No specific therapies are available to treat VM. Rest is important to lower the body's demands regarding tissue perfusion and oxygen transport. If oxygen saturation falls below critical levels, additional oxygen should be supplied.
With regards to drug therapy, diuretics and possibly vasodilators are administered to reduce afterload. Inotropic compounds such as digoxin may be applied in order to improve contractility and to increase the ejection fraction . Anticoagulative drugs may proof helpful. While the majority of these drugs will initially be administered intravenously, oral medication may be described for stable patients.
If VM patients present with severely limited left ventricular function, the function of the failing heart may be replaced by left ventricular assist devices until transplants are available. These patients may also benefit from extracorporeal membrane oxygenation.
Prognosis depends on the stage of the disease upon detection. Patients that are diagnosed with VM during the acute stage of the disease, when myocardial damage is still minimal, have a good prognosis and may expect recovery without having to face lifelong consequences. Prognosis worsens when significant cardiac damage is present at the time of diagnosis. Only one out of three severe cases of VM will recover ventricular function. Almost as many patients will, however, require a heart transplant due to serious functional impairment.
The patient's general condition, possibly experienced syncopes, ejection fraction less or more than 40%, pulmonary arterial pressure and the presence of bundle branch blocks have been proposed as prognostic criteria .
Viral infection and inflammation of the myocardium interferes with excitation conduction and in more severe cases with contractility of the heart muscle. This may result in arrhythmias and even heart failure.
Different viral pathogens have been associated with VM  . Among them are:
VM is the most common form of mycarditis. Less commonly, inflammations of the myocardium are triggered by other infectious agents such as bacteria or fungi, by intoxication or autoimmune responses. The remaining share of myocarditis is classified as idiopathic. The overall incidence of myocarditis has been estimated to be approximately 1 in 10,000 individuals. Prevalence at time of death is presumed to be considerably higher and estimates of up to 5% have been delivered. Not surprisingly, numbers range even higher when considering those individuals that died from sudden cardiac death. Here, myocarditis accounts for almost 10% of all cases.
Gender distribution shows that more men suffer from myocarditis than women. A significant share of myocarditis patients are children and young adults .
Myocarditis may ultimately lead to DCM and death. Viral infections are less frequently associated with ischaemic or valvular cardiomyopathies. Nowadays, molecular biological methods allow for a better screen for the presence of viral pathogens in myocarditis and DCM patients. In this context, a variety of more than 20 viruses has been associated with VM. Parvovirus B19 have most frequently been identified . To date it is, however, not clear whether the presence of parvovirus B19 actually contributes to inflammation of the myocard . The prevalence of adenoviruses in cases of VM is increasing, but the opposite is the case for enteroviruses.
Three stages of VM are distinguished. Upon viral infection, pathogens may reach the myocardium during viremia. While no effective immune response inhibits viral replication in this stage, the second stage of VM is characterized by immune cell infiltration into the myocardium. Repair processes, fibrosis and DCM are hallmarks of the third stage of VM.
In detail, viral infection of the myocardium in the first stage of the disease results in significant damage to cardiomyocytes. Other cell types such as fibroblasts or endothelial cells may also be infected with viral agents. Viruses enter cells by receptor-mediated endocytosis. Such a receptor could be identified for the coxsackie virus and adenoviruses type 2 and 5. It is termed the coxsackie adenoviral receptor . The pathogen replicates inside its host cells, mediates lysis and infects adjacent cells. This lysis is the main cause for tissue damage before the host's immune system reacts to viral infection. Some cells also undergo apoptosis, a process that should stop virus replication but nevertheless contributes to loss of cardiomyocytes. Severe myocardial damage may not only lead to reduced contractility but can even cause heart failure and death. Virulence of pathogens may not only depend on the virus itself and its subtype, but also on certain conditions to be found in the host organism. In this context, it has been proposed that deficiencies in selenium or copper increase virulence .
As soon as inflammatory cell infiltration can be observed in the infected myocardium, the second stage of VM is reached. During active immune response, cytolytic T lymphocytes, natural killer cells and macrophages are eliminating infected cells. Cellular actions are stimulated by pro-inflammatory cytokines interleukin-1, interleukin-2, tumor necrosis factor-α and interferon-γ. The production of matrix metalloproteinases results in the degradation of extracellular matrix components like collagen and elastin. T cells and their cytokines have been attributed an important intermediary roles in these events. Unfortunately, myocardial inflammation usually contributes to myocardial damage and functional impairment. In this line, anti-inflammatory therapeutic options, particularly anti-T cell therapies, are currently evaluated as possible treatments for myocarditis and DCM, a condition that may develop during the third stage of VM.
If viral loads can be diminished and anti-inflammatory signals outweigh pro-inflammatory ones, repair processes may begin. Cardiac remodelling involves replacement of lost cardiomyocytes with connective tissue. Fibrotic reparation is, however, not sufficient to regain full functionality and may result in DCM and chronic heart failure .
No specific preventive measures for VM are known. However, since those viral agents that may cause VM are transmitted by individuals suffering from the flu or other infectious diseases, by parasites such as ticks or via contaminated food, adequate hygienic measures may help to prevent infection and subsequent VM. In this context, regular vaccination, avoidance of contact to people that caught a cold, safe sex, regular hand-washing and general food hygiene as well as the use of repellents against parasites may be recommended.
Viral myocarditis (VM) may result from infection with a variety of viruses, whereby the disease is most commonly associated with the presence of entero- or adenoviruses. These viruses reach the heart during viremic phases and replicate inside cardiomyocytes and other cardiac cell types. Virus-mediated cell lysis and apoptosis are the main causes for cardiomyocyte loss in this acute stage of the disease. Infection and subsequent inflammation interfere with excitation conduction and contractility and may cause heart failure and death during any stage of the disease. The initial, virus-mediated damage to the myocardium is further aggravated by inflammatory processes that take place upon inflammatory cell infiltration. Only when viral loads are sufficiently decreased and inflammatory processes are more and more inhibited, cardiac remodelling takes place. Fibrotic repair of damaged myocardium may lead to dilated cardiomyopathy (DCM) and chronic heart failure.
Early diagnosis is required for good prognosis. Only if the treatment starts when the myocardial damage is still limited, full recovery can be expected. If symptoms are present, they correspond to those observed in cases of heart failure: chest pain, tachycardia, dyspnea and reduced tolerance to exercise. Arrhythmias and altered heart action may be detected by auscultation and electrocardiogram examination. Imaging techniques may reveal cardiomegaly and associated lung problems.
There is no specific therapy for VM. Treatment aims at reducing the body's demands for oxygen and facilitating heart action. The latter may be achieved by reducing the afterload, i.e., by administering ACE inhibitors and/or diuretics. Inotropic drugs may be applied to increase the ejection fraction. If cardiac function cannot be restored, a heart transplant may be required.
The heart consists of different tissues, one of them being the actual heart muscle, the myocardium. Myocarditis describes an inflammation of the myocardium and if this condition is caused by viral pathogens, a viral myocarditis (VM) is diagnosed.
A great variety of viruses has been associated with VM. Most frequently, enteroviruses such as the coxsackievirus and adenoviruses are detected in patients suffering from VM. While some of them report to have suffered from a cold before experiencing symptoms of VM, this is not necessarily the case.
The main function of the myocardium is to conduct excitation and to contract and actually pump the blood through the body. In cases of VM, excitation conduction may be altered and contractility is reduced. This leads to symptoms of heart failure and these may consist in chest pain, palpitation, breathing problems and cough, particularly when under exercise. Syncopes are sometimes observed.
Some cases of VM stay asymptomatic and are only detected when the physician observes certain alterations in chest radiographies or electrocardiograms that are realized for other reasons or during routine screens.
Blood samples will be drawn to confirm viral infection and possibly myocardial damage. They also allow the physician to rule out differential diagnoses such as anemia or bacterial infections. If the laboratory results support the tentative diagnosis of VM, an electrocardiogram will be realized. Also, imaging techniques such as echocardiography and chest X-rays may be used to detect arrhythmias, interferences with excitation conduction and overall dilation of the heart. This obviously applies if such findings did not trigger the initial assumption of VM. In order to confirm the diagnosis of VM, a biopsy has to be taken. During this procedure, a small tissue sample is taken from the heart with a fine needle. Histologic evaluation of this tissue sample allows the physician to stage an existing myocarditis or even to rule out this type of disease.
There is no specific treatment for VM. Any therapy aims at alleviating the symptoms associated with heart failure. Bed rest is often mandatory. Furthermore, diuretics and vasodilators may be administered to facilitate the ejection of blood by the heart. Other drugs such as digoxin may be used to improve the contractility of the heart muscle.
If VM is diagnosed before viral pathogens and inflammation cause significant damage to the myocardium, a full recovery can be expected. However, if severe damage is done to the heart muscle, its function may not be regained and a heart transplant may be required.