The presented review is devoted to generalization of results of own researches of the author on a problem of almost not studied pathology - a neuroleptic (antipsychotic) cardiomyopathy (NCMP). NCMP belongs to secondary specific metabolic dilated cardiomyopathies. It is caused by side cardiotoxic effect of antipsychotic preparations. Many parties of epidemiology, pathogenesis, morphology, clinic and diagnostics of NCMP remain still insufficiently developed.
Results: As showed our researches the development of NCMP passes 3 stages: 1) latent, 2) developed and 3) terminal. Each stage has the clinical features, electrocardiograph signs and certain morphology. The lethal outcome in latent and in developed stages either comes from the intercurrent diseases or is the sudden cardiac death of arhythmogenic genesis. The progressing congestive heart failure serves in a terminal stage as an immediate cause of death. Apparently from our researches morphologically NCMP is characterized by a moderate hypertrophy of heart, expansion of its ventricles and absence of the expressed coronary atherosclerosis. At microscopic research of a myocardium at early stages microcirculation violations come to light. Damages of an extracellular matrix (interstitial oedema and myofibrosis) develop then. Dystrophic-degenerative and atrophic changes of cardiomocytes act into the forefront in a terminal stage. It leads to contractile myocardial dysfunction.
Conclusion: On the basis of synthesis of the data obtained in a number of the own researches clinical and morphological criteria of diagnostics of NCMP are allocated and proved. Considering the described features of NCMP the given pathology is allocated in separate independent nosological unit expediently and quite logical.
Neuroleptic (antipsychotic) cardiomyopathy (NCMP) is one of serious complications of psychotropic therapy caused by side cardiotoxic effect of antipsychotic preparations [1-4]. NCMP belongs to secondary specific metabolic dilated cardiomyopathies [5-7]. The disease is characterized by diffusion damage of a myocardium, sharp decrease in its contractile function and as a result the progressing congestive heart failure (CHF) [2,5,6,8-10]. Many parties of epidemiology, pathogenesis, morphology, clinic and diagnostics of NCMP remain still insufficiently developed. The goal of the real review is the short generalization of the results of the own researches of this problem.
Our long-term researches are conducted on different material and various methods including statistical (parametric and nonparametric). At macroscopic studying of heart original own organometric approach is applied . The microscopicn condition of a myocardium is estimated by means of a morphometric method.
According to our section data among the died patients with schizophrenia which obligatory component of therapy is reception of antipsychotic preparations the number of the suffering of NCMP (11.4 %) is considerable and statistically significant above than in gross section material on a psychiatric pathological department in general (2.0 %) . As showed our researches the development of NCMP passes 3 stages: 1) latent, it is clinically completely compensated, 2) developed at which cardiac violations distinctly are defined, but without the expressed signs of CHF, and 3) terminal when the clinic of CHF acts into the forefront [9,12-14]. The lethal outcome in latent and in developed stages either comes from the intercurrent diseases or is the sudden cardiac death (SCD) of arhythmogenic genesis [5,12,14]. The last is observed at 44.2 % of the dead of NCMP according to our data [15,16]. The progressing CHF serves in a terminal stage as an immediate
cause of death.
The disease develops slowly and at the beginning is hardly
noticeable. In a latent stage it is practically shown by nothing
[5,12,14]. During this period the complaints of patients have
uncertain character or are in general absent. Fatigue and short
wind at considerable physical activity is most often noted.
Thus it must be kept in mind known difficulties of detection
of complaints at mental patients connected both with their
inadequate behavior and lack of due criticism to their state
and with quite often certain medicament load. In a latent stage
of NCMP the findings of the examination are not numerous
and aren’t specific. The tachycardia serving as almost constant
phenomenon at reception of neuroleptics is observed as a rule
. De an auscultation in is defined the deafness of cardiac
sounds. Poorly the borders of heart are usually changed. An
arterial hypo- and a norm tonicity significantly prevail from
the arterial pressure. The insignificant arterial hypertension
is only approximately in ⅓ cases observ ed [5,12].
On the electrocardiogram during this period there are
most often the following pathological signs:
Diffusion muscular changes;
Different types of violation of conductivity, in
particular the blockade of the left leg of Gis’s bunch;
Deviation of an electric axis of a heart to the left;
Overload of the right departments of the heart;
Hypertrophy of the left ventricle [5,6,8-10,17].
In the developed stage the clinic of NCMP is rather
distinctly shown, but the signs of terminal CHF are absent or
poorly noticeable. The complaints of patients are more certain:
weakness, fatigue, heart beating, short wind at moderate
physical activity, sometimes passing pains in the cardiac
region. By the physical examination the deafness of cardiac
sounds, some expansion of the borders of a heart, tachycardia,
passing breathlessness notes. During this period the steadily
normal or labile arterial pressure equally often meets, but
there is a tendency to the moderate increase of it [5,12].
The terminal stage of a current of NCMP is characterized
by accession to already listed symptoms of the known
manifestations of the increasing CHF: short wind at a rest or
the small physical activity, orthopnea posture, the increase of
a liver, the peripheral and cavitary oedemata, sometimes an
anasarka etc. The heart borders are expanded that is confirmed
by the roentgen exploration. The cardiac sounds are deaf.
There are almost always a tachycardia and an arrhythmia.
The moderate arterial hypertension is observed by a little
more than at ¼ patients, and the arterial pressure constantly
exceeds 150/100 mm of mercury at 13.6 % of patients [5,12].
On an electrocardiogram in developed and terminal stages of
NCMP there are such most dangerous phenomena:
Violations of conductivity;
Lengthening of an interval of QT in recalculation on
Bazett’s formula - a correct QT interval (QTc);
Overload of the right departments of the heart [5,6,8-
The special attention is deserved by monitoring of
parameters of QTc as highly informative indicator in the
conditions of a decompensation of the heart [18,19].
Apparently from our researches at the macroscopic
(organ) level NCMP is characterized by a moderate cardiac
enlargement, a noticeable expansion of ventricles of a heart
with some prevalence of dilatation of the left one, absence
of the expressed coronary atherosclerosis, especially at
the relatively aged persons (45 years and more senior).
At microscopic research of a myocardium (tissue and
cellular levels) the expressed myofibrosis and small nodular
replacement cardiosclerosis, the chronic interstitial oedema, in
the beginning hypertrophic and then dystrophic - degenerative
and atrophic changes of cardiomocytes come to light. At early
stages microcirculation violations come to light. Damages of
an extracellular matrix (interstitial oedema and myofibrosis)
develop then. Dystrophic-degenerative and atrophic changes
of cardiomocytes act into the forefront in a terminal stage.
The high frequency of NСMP revealed on autopsy at the
patients accepting antipsychotics testifies to what broad
application in medical practice of neuroleptics is the reason
of development of the given cardiac pathology in patients
with schizophrenia. It is seen from our researches clinical
diagnostics of NCMP is difficult as its symptom complex has
no peculiar features . On the basis of synthesis of the
data obtained in a number of the own researches the clinical
criteria of diagnostics of NCMP are allocated and proved
The diagnostic scheme is approximately submitted as follows.
I. Big criteria (absolute):
The treatment by neuroleptics;
The absence of other cardiac pathology.
II. Small criteria (relative):
The cardiac complaints (even minimum);
The increase in the sizes of a heart (be percussion
and the roentgen exploration);
The findings by the physical examination (tachycardia,
arrhythmia, deafness of cardiac sounds);
The changes of an electrocardiogram (especially the
increase in QTS, violations of a rhythm and a conductivity);
The existence of CHF in the absence of other reasons
of its development;
The SCD of patients (it is important for posthumous
It is necessary to emphasize that each of the listed signs
taken separately out of communication with others isn’t
specific to NCMP. However in the set these criteria can become
a reliable basis for clinical verification of this disease. The long
reception of antipsychotic preparations is the main condition
forcing to think of NCMP.
There is basis to consider that for diagnostics of NCMP it is
enough to have available both big signs and at least two small.
However in this direction nevertheless further researches and
accumulation of practical experience are necessary. At the
same time in our opinion the offered criteria of diagnostics
of NCMP and the approximate diagnostic scheme will be able
to become useful for the early identification of this serious
complication of an antipsychotic therapy in order to its timely
Posthumous diagnostics of NCMP also causes certain
difficulties. They are connected mainly with insufficient
development of the morphological criteria allowing the
pathologist to diagnose NCMP . The results of the own
research of morphology of NCMP executed at the different
levels of an organization of an organism light a pathological
picture of this disease rather fully. During a morphogenesis
of NCMP all structural components of a myocardium (the
microcirculatory course, extracellular matrix, cardiomocytes)
are deeply damaged that sharply reduces its contractile
reserves. The revealed pathological shifts of a microstructure
of a cardiac muscle reflect profound tissue changes dystrophicdegenerative,
sclerotic and to a lesser extent compensatory
and adaptive character which are developed in a myocardium
in the course of a morphogenesis of NCMP.
All noted pathological changes are objective reliable
morphological features and a material basis of the contractile
myocardial dysfunction leading to progressing of fatal CHF
eventually [22,23]. As showed our researches each of the
found morphological signs in it taken separately aren’t specific
to NCMP. However in the set the described morphological
changes permit enough confidently to diagnose this disease
anatomic pathologically [18,21]. Thus NСMP possesses all
signs of the concept “illness” that is has own epidemiology,
etiology, pathogenesis, clinic and morphology.
Proceeding from told about NCMP this pathology
is allocated in separate independent nosological unit
expediently and quite logical. On ICD-10 it can be carried to
the heading I42.7 “The cardiomyopathy caused by influence of
medicines and other external factors” with the additional code
reflecting an external cause of illness (a class of antipsychotic
preparations) - Y49.3-Y49.5 [5,18].