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VIRAL MYOCARDITIS AS A PREDICTOR OF DILATED CARDIOMYOPATHY, POSSIBILITIES FOR THE PREVENTION OF DCM

N. Kipshidze, M. Rogava, M. Gudushauri
National Center of Therapy, Tbilisi, Georgia

Decline in pump function of cardiac muscle, that often takes significant and irreversible character, younger age of the patients and severe morphologic changed on the cellular and ultracellular levels of cardiomyocytes, determine, why it is so important to study the condition of the myocardium in myocarditis and dilated cardiomyopathy. Today the theory of transformation of viral myocarditis to dilated cardiomyopathy is accepted undoubtedly. Biopsy, performed in patients with dilated cardiomyopathy post heart transplantation, revealed the presence of persisting viruses, indicating the existance of the autoimmune disease. Since 1976 our Institute is carrying out researches aimed at revealing correlation between viral myocarditis and dilated cardiomyopathy; during this time more then 300 patients with the pathologies have been studied. Together with all necessary clinical and laboratory examinations we determined hystocompatibility of HLA markers, and studied serologic indices to cardiotropic and hepatotropic viruses.

Evaluation of the hystocompatibility of HLA markers revealed that: B12 (12%), B27 939%), B35 (18%), A1 (16%), DR4 (6%) antigens were dominating in the study population – the Georgians (Fig.1).

When viral myocarditis was transformed to dilated cardiomyopathy we observed that B12 (up to 45%) and B27 (28%) significantly dominated in the study population (Fig.2).

This fact allows to use them as transformation markers and start preventive measures in such patients already at very early stages of viral myocarditis.

Group 1. enrolled 172 patients, in whom viral myocarditis was diagnosed based on anamnesis, clinical and laboratory data. In 93% of cases the disease was triggered by Influenza, and first symptoms appeared already during week 1-4 (Table 1).

CLINICAL CHARACTERISTICS OF GROUP 1 PATIENTS

We observed that 60% Group 1 patients had acute myocarditis, 21% of them had sub-acute, and 19% had persisting myocarditis.

In Group 2 134 patients with primary diagnosis of dilated cardiomyopathy were included, 73% of them thought that the disease was initiated after influenza, and 17% could not find the reasons why the condition had developed (Table 2).

CLINICAL CHARACTERISTICS OF GROUP 2 PATIENTS

 It is well known that neither a patient nor physician could mention the initiation of the viral myocarditis; thus, the disease, though already progressing, as a rule, will not be included in the case history. Except endomyocardial biopsy serologic method to determine antigens to viruses may be the only and widely available method to reveal viral infection.

As we know, there are up to 20 different types of viruses, which can initiate myocardium damage in patients with viral myocarditis (it could be a combination of distrophic, autoimmune, necrobiotic and inflamatory damage).  The most active and frequently observed are so called cardiotropic viruses, such as Coxsakie A and B, Adenovirus, Influenza A and B viruses, Cytomegalovirus, Herpes and Echoviruses.

We revealed that in Group 1 63,3% of the patients had positive serologic reaction to one virus, 20,8% - to two viruses, 16% - to three, and 8% of patients were positive to 4 viruses (Table 3).

TYPE OF VIRAL INFECTION IN GROUP 1PATIENTS 

It is worth mentioning here that when infected with 1, 2 or 3 viruses, patients suffer acute and sub-acute forms of myocarditis, while patients infected with 4 viruses had persisting myocarditis.

In Group 2 (DCM) 58,6% of the patients had positive serologic reaction to 1 virus, 20,65% - to 2 and 20,7% were positive to 3 viruses. Correlation of different viruses in this Group is summarized in Table 4.

TYPE OF VIRAL INFECTION IN GROUP 2 PATIENTS 

In 10 cases we revealed simultaneous infection with cardiotropic and hepatotropic viruses. In such mixed cases the course of the disease is, as a rule, rather severe. Mean index of viral myocarditis transformation to dilated cardiomyopathy comprised 38,5%

The analyses of the data achieved for both groups revealed that the type of the virus and the severity of the condition were the main causes of the transformation. In cases of transformation the severe forms of myocarditis comprised 59%.

Coxsakie B virus both alone and in combination with other viruses has the greatest cardiotropic effect and causes the most severe forms of the disease.

When other viruses are combined, infection with 2 and more viruses causes more acute forms of myocarditis, though they are not the factors that initiate viral myocarditis transformation to dilated cardiomyopathy.

Based on everything stated above, we can timely reveal the predictors of viral myocarditis transformation to dilated cardiomyopathy and work out the methods for prevention and treatment of the condition. At present, we are widely using the methods for revealing both HLA markers of transformation and the type of viral infection. Based on these data complex therapy is initiated.

CARDIOTROPIC VIRUSES IN PATIENTS WITH VIRAL MYOCARDITIS

TRANSFORMATION TO DILATED CARDIOMYOPATHY

  Together with conventional methods, we use in our every day practice active immunocorrective therapy (drug intervention and IV laser therapy), correction of disorders of rehologic properties of blood, and Selen and Vitamin B2 insufficiency correction. Following drugs were administered:

·        Aciklovir, Zovirax, Neovir, Gallavit (Rus)

·        Solcoseryl (IV 1000 mg of 20% sol.)

·        Vitamin B2, Selentin.

The laser therapy, is used since 1980, it is a 5 to 12 sessions of 20-35 min intravenous irradiation with λ=632 Helium-Neon Lazer (0,2-0,4 millivatt) daily.

The use of the mentioned above therapeutic strategies permitted to improve the quality of life of our patients and reduce the risk of viral myocarditis transformation to dilated cardiomyopathy by 20% in average.

We examined the possibility of vaccination against Coxsackie B1 and B3 viruses to protect myocardium of mice in different periods of viral infection and myocarditis.

One hundred one-month old BALB/C type clean-linear mice were immunized to Coxsackie B1 and B3 subsequently infected with Coxsackie B1 and B3 viruses.

Microscopic examination of myocardium revealed morphologic changes consistent with viral myocarditis (focal fiber necrosis with mononuclear infiltration and interstitial edema) in all 4 experimental groups, vaccinated animals had only focal changes and diffuse cell reaction in interstitium on the background of spread myocardial dystrophy.

CONCLUSIONS:

In the Georgian population the most significant marker of DCM is HLA B12. In Georgia the Coxsackie virus of B type alone and in combinations with other viruses can be considered the main and the most prevalent cause of VM and its transformation into DCM. The second prevalent causes of VM and DCM are Adenovirus and Influenza viruses and their combinations. The number of one or two or more viruses as well as their combinations doesn’t play decisive role in transformation of VM into DCM. Based on the facts of mixed forms, we think, it is necessary to develop new, adequate and aggressive therapeutic strategies aimed at treatment of all conditions involved, thus improving the quality of lives of patients and decreasing the risk of complications development. As a result of inclusion of immunocorrectors and laser therapy into the conventional treatment the transformation degree of VM in DCM was reduced.

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