MECT and NLS in Diagnosing Myocarditis of Mild or Medium Gravity

P.S. Bortshov, K.L. Fadin,

O.P. Derkatch, P.A. Abdulov,

T.N. Timofeyefa, B.M. Nikolaev

Introduction

The diagnosis of non-rheumatic myocarditis remains a complicated and pertinent

problems, which is conditioned by lack of pathognomic clinical signs and similarity to the

semiotics of the disease to other kinds of cardiac pathology.

The notion of myocarditis brings together inflammatory myocardium conditions,

different in terms of etiology and patho-geneisis both at isolated affects of myocardium

(primary myocarditis) and at some infectious diseases and systemic pathological

processes (secondary myocarditis). The disease may develop with a focal or diffuse lesion

of the myocardium.

The clinical diagnosis of primary myocarditis presents great difficulties, so because of the

lack of direct signs of the inflammatory lesion of the myocardium, the diagnosis is based on

indirect clinical hardware-based syndromes that become apparent within 2 or 3 weeks after

the administered infection. The related syndromes are as follows:

1. Any newly detected pathological changes in ECG;

2. An increased level of cardio selective enzymes and proteins in blood (troponin T and

I);

3. Cardiomegaly as per radiography or echocardiography data;

4. Congestive heart failure;

5. Changed immunologic indexes (a higher CD4/CD8 and circulating immune complex

ration, “yes” response to inhibition of lymphocyte migration

6. Tachycardia, reduced first sound and gallop rhythm.

The needle biopsy of the myocardium is one of such diagnostic techniques. Meanwhile,

the basic morphological sign of the disease in this context is presence of an inflammatory

reaction (lymphocytic and histiocytic infiltration) in the myocardium with damaged

cardiomyocytes and capillary endothelium. However, the endomyocardiac biopsy does

not ensure an exhaustive diagnosis because of a chance to pick up a sample from the

unaffected section of the myocardium and obtain a false negative result. According to

most authors, the endomyocardiac biopsy confirms the clinical diagnosis only in 17-37%

of cases.

In this connection the development and extensive use in clinical practice of noninvasive

method of diagnosis of myocarditis that allow to visualize myocardium inflammation and

determine its intensity and evolution in the course of treatment, arouse active interest.

63We have accumulated some experience in non-invasive diagnosis of myocarditis and

dynamic control of the myocardium condition in the course of treatment. In the

integrated diagnosis of inflammatory cardiac lesion, additionally to conventional methods

of clinical, laboratory, immunologic and ultrasound investigation, we have used the

methods of monophoton emission computer tomography of the myocardium (OECI,

tomoseintigraphy of the myocardium) with autoleukocytes tagged by ottTc-

hexamethylpropyleneaminooxym (HMPAO), and NLS-investigation of the heart.

Material and methods

The tomoscintigraphy of the myocardium was performed on the monophoton emission

computer tomograph ‘Eleinct-Apex-SP-6’ (Israel) every 1-2 and 24 hours after the

autoleukocytes reentered the bloodstream. The leukocytic suspension was extracted from

500ml of the whole blood by centrifugation and leukocytopheresis. The leukocyte count

was 37,000-45000 cells per 1 microlite. Before its administration the leukosuspension

was incubated in a flask with 99ITC-HMPAO (500) for 15 minutes at room temperature.

For better visualization of myocardium inflammation and a perfusion study the

tomosintigraphy was performed once again using 44tTC-tetraphosmine. During

processing of the results the tomographic ‘sections’ of the heart were drawn along the

short axis every 0.8 cm from top to bottom and the outward outlines of the aortic

ventricle were encircled. The inflammation areas were visualized on the scans as foci of

hyper-fixation of tagged leukocytes in at least three adjacent sections.

The NLS-investigation was carried out using a device equipped with a 1.4 GHz digital

trigger sensor. In analyzing the obtained virtual shots special attention was paid to the

emerging zones of the increased chromogenic value of the signal from the myocardium

(5-6 points according to Flandler’s scale). All in all 49 patients affected by myocarditis

of mild or medium gravity were examined (25 women and 24 men aged 15-47). All the

patients underwent a primary clinical hardware-based investigation including MECT with

tagged leukocytes. 9 patients had check examinations of the myocardium condition

carried out during the therapy using tomoscintigraphy of the myocardium and NLS. Six

patients underwent an NLS investigation of the heart within 2-8 months after the primary

radioisotope investigation and three patients had MECT performed repeatedly 1.5-8

months later.

Depending on the variant of the primary accumulation of leukocytes in the myocardium,

all the patients with clinic-lab signs of myocarditis were divided into three groups. The

first group included patients with a diffuse accumulation of tagged leukocytes in the

myocardium (n=16), the second one comprised patients with a focal accumulation (n=20) and

the third one did not have any distinct accumulation of tagged autoleukocytes in the

myocardium (n=13). The groups were comparable by age and gender. The average age

of the patients in the group with a diffuse accumulation of leukocytes was 32.1+ 1.8, in

the group with a focal accumulation - 35.2+2.1 and in the group without a distinct

accumulation - 36.6+2.2.

64Result analysis

The analysis of intracardiac distribution of tagged auto leukocytes showed that all the

patients in the first group had a diffuse lesion of the cardiac walls in at least two regions:

the atril 94% of cases (n=15), left ventricle (LV) 63% (n=10), right ventricle (RV) 63% (n=10)

and interventricular partition (IVP) was visualized most often - in 65% of cases (n=15), and

in the other regions of the heart inflammatory infiltration was detected with certainty less

often than in the first group and was less frank (atrium - 30%, n=6, RV -

25%, n=5 and LV -20%, n=4).

One of the factors possibly related to the pattern of auto leukocyte accumulation in the

myocardium was an extra cardiac spot of leukocyte fixation in the nasopharynx, gall

bladder and uterine appendages regions, which could be regarded as an obscure foci of

chronic infection. It was established that at a diffuse pattern of auto leukocyte

accumulation in the myocardium (which could be interpreted as a sign of diffuse

myocarditis) the extracardiac foci of the infection were visualized in 100% of cases.

With a focal pattern of leukocyte accumulation in the myocardium the foci of chronic

infection were determined in 70% of cases. In the group of patients without a clear

accumulation of the leukocytes in the myocardium the foci of chronic infections were

only detected in 40% of cases. Extra cardiac foci of tagged auto leukocyte fixation were

more often detected in the nasopharynx, however there were no authentic distinctions

among the groups.

Another factor related to the pattern of the auto leukocyte distribution in the myocardium

was the duration of the disease which consecutively increased from group 1 to group 3.

So, in the first group the average duration of the disease (from the initial signs of

myocarditis to MECT performance) was 8+4 months, which is authentically shorter than

in the second group, 16+ (P.2 < 0.05) and in the third group, 28+10 (P.3 < 0.05).

The initial integrated investigation of the patients affected by myocarditis showed that in

75% of the patients (36 cases of 49) the accumulation of auto leukocytes occurred in the

thick layers of the myocardium, either diffuse or focal, which together with some clinical

signs of myocarditis confirms the inflammatory lesion of the cardiac muscle. Typical for

a diffuse myocarditis proved to be the moderately increased activity of cardio selective

enzymes and indexes of the cell section of immunity as well as some changes in ECG,

such as disturbed conductivity (A-V blocades of 1-II degrees). Increased diastolic size of

the left atrium and left ventricle and increased indexes of the humoral section of

immunity were typical for a focal inflammatory process. The minimum clinical

implications of myocarditis were found in 25% of the examined patients, whose

tomoscintigraphy did not display a distinct accumulation of leukocyte in the myocardium.

All the patients were put on medication based on anti-inflammatory and metabolic drugs

for 6 months and their walking regime was restricted for a month. As required, some

antiarrythmic, antiviral or antibacterial drugs were administered. 1.5-3 months after the

65medication was started actually all of the patients began to feel better and the clinical

signs that had made them call in medical aid disappeared.

Three patients had tomoscintigraphy of the myocardium performed repeatedly during the

medication. Meanwhile, 2 patients with a diffuse pattern of tagged leukocyte

accumulation, 1.5-3 months later during check tomoscans still showed some foci of auto

leukocyte fixation in the myocardium, though fewer than at the primary examination.

One patient with fixed accumulation of tagged leukocytes at a repeated MECT procedure

8 months after the medication did not show any foci of intracardiac leukocyte

accumulation.

An NLS-investigation performed on three patients affected by diffuse myocarditis within

1.5-5 months after the medication was started, confirmed zones with an abnormality

hyperchromatic NLS-signal, which fully corresponded to the foci of tagged auto

leukocyte fixation in the myocardiam. Our results are in conformity with some literary

evidence on a possible noninvasive diagnosis of mycarditis using computer nonlinear

investigation. Still in another instance of NLS investigation we obtained a doubtful or

false negative result which was accounted for by some technical problems (increased

signal deviation connected with a convulsion of ciliary arrhythmia that occurred during

the investigation). Two patients with a focal leukocyte accumulation had NLS carried

out 6 and 8 months after MECT and the shots did not display any pathological changes.

Thus, the repeated investigations using tomoscintigraphy of the myocardium and NLS

proved, that a clinical improvement in the patients’ condition that could be seen 1.5-3

months after the medication, was not indicative of a recovery, because the

“morphological sanitation of the myocardium” even at a myocarditis of medium or mild

gravity, arrives much later. The tomoscintigraphy of the myocardium with tagged auto

leukocytes proved to be a more sensitive and informative method of diagnosing

mycarditis in such cases (especially during the primary investigation) than the NLS

investigation. MECT allowed detection of lesions of both ventricles and also atria

despite their small thickness. The inflammatory tissues in thin-walled cardiac chambers

were well visualized though it proved difficult to visualize them during NLS. In addition,

rhythm disturbances rather often occurring in mycarditis patients did not affect the

quality of the MECT scanning images, but they did affect the images obtained during the

NLS examinations. Another negative factor of MECT examination was an inevitable

admixture of erythrocytes in the leuko concentrate, which increased the general

background radiation of organs and tissues and in some cases effaced the boundary

between the organs under investigation and its background. The NLS-investigation can

be probably used as a means of the myocardium condition control during therapy, but not

as a method of primary diagnosis.

As an example we would refer to the data obtained during one of the observations.

Patient K., 32 years old came to the clinic with complaints of a persistent dull heart pain

experienced at rest, irregular heartbeat and respiratory distress at a moderate physical

activity, pasty legs and feet in the evening, fatigue and general weakness. The anamnesis

showed that two months before the patient had had an acute rhino-pharyngitis without

66confinement to bed. For 5 days the patient had a fever with a temperature rising up to

38.5oC and algors in the evenings and in addition developed herpes labialis. The patient

took biseptol, remantadinum and aspirin on her own accord, and gradually started to feel

better; however 3 weeks later the complaints reappeared.

When she was hospitalized her condition was satisfactory. According to the physical

examination the patient had pasty talocrural joints, moderate tachycardia (pulse rate 90

beats per minute), and frequent extra systole (about 5 beats per minute), muted first sound

and third sound on the apex of the heart. The blood test detected moderate leukocytosis

up to 8.8x109.1, stab cell shift within 9%, accelerated ESR within 20mm/h slightly

increased within 12.8 U/L (with the norm being 12.5), LDG within 510 U/L (within 450),

fibrinogen within 5.5 (4.0), immunoglobulin M within 4.5 g/L (2.5), immunoglobulin G

within 24.2 g/l (16.0), within 96 units (66). The reaction to inhibited lymphocyte

migration made 174% (with the norm being 90%). The ECG recorded some episodes of

migration of the pacemaker and frequent ventrical extra systoles. The chest X-ray

pictures detected a stronger lung pattern due to the vascular component. The heart

shadow was not enlarged. The echocardiography did not detect any changes in the heart

cavities and valve system, or any disturbed systolic or diastolic functions of the left

ventricle.

Based on the clinical and instrumental investigations the patient was diagnosed to have an

infectious-allergic mycarditis of medium gravity.

A performed tomoscintigraphy of the mycardium detected a diffuse accumulated of

tagged leukocytes in the right atrium region, posterior and lateral walls of the left

ventricle and interventricle partition. The NLS-spectral similarity to the reference

standard process “Infectious-allergic mycarditis” (D=0.202) allowed objectification of

the clinical diagnosis and determination of the localization and spread of the

inflammatory process. The patient was prescribed an antiviral, anti-inflammatory and

metabolic treatment. 1.5 months later the patient’s general condition improved:

heartache, irregular heartbeat, shortness of breath and feebleness did not trouble her any

longer and her legs were not pasty any more. The laboratory and ECG changes became

smaller though did not disappear completely. 2.5 months later a check NLS examination

of the heart was performed. Check shots displayed some areas with a higher

chromogenics of the NLS signal (4-5 points). The increased chromogenics zones

completely corresponded to the fixation areas of tagged autoleukocytes in the

myocardium.

A peculiarity of this clinical example is that in this particular case the diagnosis of

myocarditis was confirmed by several noninvasive methods; the spread of the process

was determined and physical control over the myocardium condition was set in the course

of treatment. In summing up it should be stressed that the MECT with tagged

autoleukocytes and NLS are noninvasive methods of visual diagnosis of inflammatory

diseases of the myocardium. That gives reasons to recommend using MECT and NLS for

diagnosing myocarditis, for making a differential diagnosis of some other diseases of the

67myocardium of a non-inflammatory pattern, and also for evaluating the condition of the

cardiac muscle in the course of treatment.