Myocarditis

MYOCARDITIS. Contents: Classification..................406 Pathological anatomy...............407 Clinical concept of M.............410 Pathogenesis.....................412 Acute M.....................413 Chronic M..................429 Myocarditis (from Greek mys - muscle and kardia - heart), inflammation of the heart muscle. Classification. Myocarditis can manifest in various forms, which are divided 1) according to the c o u r s e into acute and chronic, 2) according to the nature of those tissue elements that undergo the strongest changes into parenchymatous and interstitial, 3) according to the nature of the spread of the process into focal and diffuse, and 4) according to the type of inflammatory process into alterative, exudative, and productive. Transitional and mixed forms are frequent, and assigning them to one type or another often proves difficult. Sometimes an etiological sign is also used to define myocarditis (diphtheritic, typhoidal, syphilitic myocarditis, etc.). As for acute myocarditis, all of them, insofar as their etiology can be determined, have an infectious-toxic origin, with the exception of only very rare isolated cases of a purely toxic nature (e.g., in carbon monoxide poisoning, in uremia). On the other hand, there is almost no infectious disease in which an inflammatory process in the heart muscle is not observed in a certain percentage of cases. The greatest significance both in the sense of frequency and intensity, and in the sense of influence on the outcome of the disease, is myocarditis in diphtheria; lesser in typhoid and typhus fever, scarlet fever, and nonspecific septic infections (streptococcal, diplococcal); even less in other contagious diseases. Sometimes the etiology of myocarditis cannot be established, and then it is treated as idiopathic primary myocarditis. Pathological anatomy. In all the enumerated cases, we are dealing with an acute inflammatory process in the myocardium, the histological picture of which is in its main features fairly homogeneous. It is composed, on the one hand, of various degenerative-necrotic (alterative) changes in the muscle fibers (parenchymatous, fatty, vacuolar, waxy degeneration, lump disintegration, myolysis), and on the other hand, of an exudative-proliferative reaction on the part of the vessels and interstitial tissue, which is expressed by the appearance in the interstitium of diffuse or focal cellular accumulations of varying density and different composition (histiocytes, round and plasma cells, neutrophilic and eosinophilic leukocytes, fibroblasts, etc.) and is usually accompanied by a greater or lesser inflammatory edema. Corresponding to the predominance of changes in the first or second group, myocarditis is designated as parenchymatous or interstitial. It must be borne in mind that a change in the heart muscle expressed only in the degeneration of muscle fibers does not pertain to inflammation and therefore cannot be called myocarditis. Myocarditis designated as parenchymatous, along with alterative changes in the parenchyma, must always contain exudative and productive changes in the stroma (see below). Classical pictures of parenchymatous myocarditis with extensive phenomena of myolysis are observed in diphtheria (myolysis diphtherica Eppingeri). Among the various parts of the heart, the left ventricle is usually the most severely affected. The His-Tawara bundle rarely remains completely untouched, but on the other hand, it is only exceptionally the site of the strongest changes. Conversely, subendocardial hemorrhages, which sometimes accompany myocarditis, occur mostly in the left ventricle, specifically in the region of the branching of the left branch of the bundle, probably due to the greater looseness of the surrounding connective tissue and its more abundant vascularization. It should be noted that not only in various infections, but—what is most important—in various cases of the same infectious disease, the pathological-anatomical picture of the process in terms of the vividness of expression of one or another of the enumerated features can be extremely diverse depending on the age of the patient, the reactive capacity and resistance of his various tissues, the period of the disease, the acuteness of its course, the strength of intoxication, etc. Histological differences between individual infections are also very difficult to catch and inconstant, as a consequence of which an attempt to determine the etiology on the basis of histological data is possible only in exceptional cases, and even then only hypothetically. In severe cases, especially in cases with significant parenchymatous changes, even a grossly anatomical study at autopsy yields much that is characteristic. Strong stretching of the walls, caused by the decrease in the elasticity of the muscles, leads to a corresponding expansion of the cavities and an increase in the volume of the heart, sometimes 3-4 times compared to the norm. The contours of the apex are smoothed out, and the consistency of the organ becomes so flabby that one can with full justification speak of "inflammatory softening" of the walls (Kaufmann). The color of the muscles becomes grayish-yellow, and on a section made parallel to the surface, more or less bright red spots are usually discovered, corresponding to the areas with the strongest vascular-inflammatory reaction. With insignificant destruction of muscle fibers and the predominance of interstitial changes, the flaccidity of the heart and the increase in its volume are expressed more weakly, and in some cases (especially in later stages of myocarditis) with moderate expansion of the cavities, the density of the walls can even be greater than normal. In the case of a favorable outcome of myocarditis, the dead muscle fibers are gradually resorbed and replaced first by cellular and then by fibrous connective tissue. The latter also develops in places of proliferation of cellular elements of the interstitium. Since the necrotic and proliferative foci in acute infectious myocarditis are usually insignificant in size but very numerous and scattered over almost the entire heart muscle, the resulting heart sclerosis is as a rule diffuse in nature, producing no changes visible to the naked eye and determined only microscopically. Only the significant density of the heart musculature ascertained in this connection, in combination with the simultaneous expansion of the cavities, can already at section give rise to the assumption of sclerosis (see also Cardiosclerosis). A special place among acute myocarditis due to its pathogenesis and histological picture is occupied by purulent myocarditis. It arises either hematogenously in various pyemic diseases (on the basis of osteomyelitis, ulcerative endocarditis, puerperal sepsis, etc.) by way of embolic seeding of pathogens into the small arteries and capillaries of the heart, or as a result of the direct transition of the process from the endocardium (in ulcerative endocarditis) or, more rarely, from the pericardium (in purulent pericarditis) to the underlying muscle tissue. In the first case, under the influence of toxic products of bacteria, necrosis of the muscles first occurs around the embolized vessel, with a successive inflammatory reaction at the border of normal tissue. At this time, the entire focus has the appearance on section of a small yellowish spot, often surrounded by a red rim. Subsequently, infiltration of the necrotized area by neutrophils and gradual purulent melting occurs, i.e., the formation of an abscess. If the abscess is located close to the inner or outer surface, it can rupture (depending on its position) into any of the cavities of the heart, causing corresponding consequences (purulent pericarditis, septic embolisms in various organs, sometimes the development of an acute aneurysm of the heart). Upon the transition of the process from the endocardium (resp. pericardium) into the corresponding place of the muscle wall, thanks to necrosis and suppuration proceeding from the surface into the depth, a cavity of one size or another is formed, which, having reached a known depth, can also give rise to the occurrence of an acute aneurysm or even to rupture of the heart. The causative agents of purulent myocarditis, apart from various mundane pyogenic microbes (staphylo-, strepto-, diplococci, etc.), in some rare cases turn out to be gonococci, which sometimes penetrate from the surface of the urinary and genital tracts into the blood stream and cause the development of endocarditis or pyemia. Outcome in recovery in purulent myocarditis is exceptionally rare. If it does occur, granulation tissue appears at the site of the purulent and necrotic foci, passing then into a scar. Thus, here too the outcome is sclerosis of the myocardium, but having a clearly focal character. Some of the above-described infectious-toxic myocarditides (e.g., after typhus, puerperal infection, pneumonia, etc.) can sometimes take a protracted course almost from the very beginning, wherein they do not produce vivid symptoms and significant, rapidly developing destructive or proliferative changes, but are expressed mainly in the gradually proceeding proliferation between the muscle fibers of connective tissue, at first loose and rich in cells, and then passing into fibrous, which is accompanied by atrophy and death of a known part of the parenchyma. The same is described by some also in Basedow's disease.

However, much more frequently such subacute or chronic productive myocarditis has a specific etiology and arises under the influence of pathogens that cause the development of various specific infectious granulomas in the heart muscle. Among these latter forms, rheumatism is most commonly encountered, and more rarely syphilis, tuberculosis, etc. (see Heart). It must be kept in mind that the clinical symptomatology of myocarditis far from always corresponds to an inflammatory process in the heart muscle. Conversely, microscopic examination in these cases very often reveals either persistent changes resulting from a past inflammatory process, or even such pictures that give no grounds whatsoever to speak of inflammation and do not deserve the name of myocarditis. The first category includes all those changes of a sclerotic character which have already been repeatedly mentioned in the previous exposition when describing the outcomes of various forms of myocarditis, and which can sometimes be so significant as to cause serious and prolonged disorders of heart muscle function. In the second group (of non-inflammatory changes), sclerosis also occupies the first place in frequency, but it develops not as an outcome of myocarditis, but on the basis of one or another disease of the coronary arteries of the heart, most commonly atherosclerosis. In some cases, establishing the difference between such vascular sclerosis (often united under the name of cardiosclerosis) and the consequences of myocarditis is rather difficult, all the more so because sometimes both of these factors can exert a joint influence (for example, in syphilitic involvement of the myocardium). Usually, however, the differential diagnosis between them is made without difficulty even macroscopically, since apart from the corresponding arterial involvement, vascular sclerosis is almost always distinguished by greater coarseness of changes and produces scars that are well visible to the naked eye. Some confusion regarding the question of myocarditis is also introduced by pathologists themselves, many of whom designate any proliferations of fibrous tissue in the heart muscle, whatever their origin, as myocarditis chronica fibrosa, s. productiva, which is of course incorrect. Among other pathological conditions that can simulate the clinical picture of chronic or acute myocarditis, the following deserve mention: 1) severe degrees of fatty heart with significant atrophy of the muscle fibers, and 2) those diverse acute degenerative changes of the myocardium (parenchymatous, fatty degeneration, waxy degeneration, etc.), which in severe cases of various infectious diseases (diphtheria, typhus, scarlet fever, etc.) frequently reach a very great intensity and prevalence and arise entirely independently of any inflammatory process.

M. Skvortsov. Clinical Concept of Myocarditis. The diagnosis of "myocarditis" is made very frequently in routine medical practice; for example, according to Gelman, when examining professional groups of the population, outpatient physicians found up to 28% of individuals with "myocarditis" in one or another group. The basis for this diagnosis is usually various signs of heart failure, such as shortness of breath or an irregular heart rhythm (e.g., extrasystole), or generally such subjective or objective pathological phenomena on the part of the heart or even the circulatory organs in general, on the basis of which it is difficult to classify a given case into the category of one or another heart or vascular disease having a clearer clinical picture. The vast majority of these "myocarditis" cases cannot be attributed to myocarditis either from a clinical or, even more so, from a pathological-anatomical point of view, as set forth above. The discrepancy regarding the diagnosis of myocarditis between everyday medical practice and pathological anatomy is explained by the fact that numerous and very diverse pathological states of the cardiovascular system (insofar as they do not fit into the framework of clearer and well-known conditions, such as valvular defects) do not easily lend themselves to correct recognition and precise differentiation. In relation to these very frequent cases, physicians have a certain inclination to assume myocarditis, which is undoubtedly facilitated to a large extent by the obscurity of the clinical picture of myocarditis itself. In view of such obscurity and inaccuracy in applying the diagnosis of myocarditis in the clinic (see also chronic myocarditis below), there is no possibility of obtaining any reliable statistical data that would determine the position of myocarditis among other diseases of the cardiovascular system. There is no doubt that the diagnosis of myocarditis, insofar as it is a definite pathological-anatomical concept, should also be clinically established only in those cases where there is reason to assume precisely those changes in the heart muscle that pathological anatomy considers characteristic of myocarditis (see pathological anatomy above), but it must at the same time be recognized that the clinic at present is not yet in a position to fully fulfill this requirement. First of all, it is not always able to differentiate between purely degenerative forms of myocardial lesions and those where, besides these degenerative, respectively alterative, changes, there are also exudative and productive changes in the interstitial tissue, i.e., between so-called myodegeneratio cordis and myocarditis parenchymatosa, s. alterativa. It is undoubtedly true, however, that pathologically and anatomically an exact boundary is not always easy to draw between these two processes, just as it is not easy to draw it between the corresponding changes in other parenchymatous organs, e.g., the kidneys. This some obscurity of the boundary between degenerative changes in the heart muscle on the one hand, and degenerative plus inflammatory on the other, is especially evident for those myocardial changes that accompany acute infectious diseases. Undoubtedly, infections can cause changes in the chemical or physico-chemical structure of the organ's parenchyma and in the physiological processes occurring within it. This "alteration" can be and often is the sole effect of infection on the myocardium. On the other hand, infection can also cause an inflammatory process in the heart muscle. The histological manifestations of such a process are localized in the interstitial tissue, and these inflammatory changes in the stroma can also be the only changes in the heart muscle caused by infection. But more often there is a combination of both actions, and especially in acute infectious diseases, all sorts of variations of combinations of alterative changes of the parenchyma and inflammatory changes of the interstitial tissue are encountered. Not infrequently, in the initial stages of the disease, there are only alterative (degenerative) changes in the parenchyma, and only later do inflammatory phenomena join in the interstitial tissue. In these cases, one may think of the manifestation of both influences of the infection at various times, but it is entirely possible that there is only a degenerative, respectively necrotic, process here as a result of the direct action of the infection, while inflammation is a secondary, reactive, respectively reparative process. In any case, the clinic regarding those phenomena on the part of the heart that are observed in connection with acute infectious diseases very often has no opportunity to decide to what extent they are caused by purely degenerative changes of the myocardium and to what extent by degenerative plus inflammatory changes. This is explained by the fact that a diffuse inflammatory process of the myocardium with severe alterative changes of the muscle fibers will give the same picture of heart failure as diffuse degenerative changes of the same fibers without any inflammatory changes of the stroma. The general manifestations of the inflammatory process of the myocardium are usually completely overshadowed by the severe symptoms of the general infection. Therefore, the clinician, regarding myocardial changes in acute infectious diseases in those frequent cases where there is no possibility to more accurately determine the nature of these changes, is forced either to refrain from a more precise diagnosis, calling the heart lesion at least myodegeneration, or to apply the term "myocarditis" to all those cases where there is an indication of significant changes on the part of the heart muscle, although it is impossible to determine to what extent they are purely degenerative and to what extent they are also inflammatory. Pathogenesis. As indicated above, myocarditis should be regarded as a consequence of almost exclusively infectious-toxic influences on the heart muscle, since myocarditis is observed in the vast majority of cases in connection with the above-listed infectious diseases. Undoubtedly, the influence of infection as the etiological factor of myocarditis must be conceived as a chemical or physico-chemical action on the myocardium of poisons produced in the body during infection. These poisons can be produced anywhere in the body and brought by the blood to the heart muscle, or the causative agents themselves penetrate into the heart muscle and act on it with their poisons directly. In the first case, a predominantly diffuse process can be expected, in the latter, a more focal process. Undoubtedly, various combinations of both methods are possible. For the clinic, all morphological changes of one or another organ, and in particular of the heart, are significant to a large extent only insofar as they are a manifestation of a process leading to a violation of the function of the given organ. At the base of the violation of organ function lie undoubtedly changes in the chemical composition, physico-chemical, colloidal, and similar structure of its tissues and a violation of the normal processes occurring in them. But these chemical, respectively physico-chemical, changes may not be accompanied by morphological changes accessible to our research methods, and on the other hand, morphological changes are not always a reliable criterion of significance for the function of the organ of those chemical changes by which they are caused. This fully explains those frequent and large discrepancies between the morphological changes of the heart muscle observed in it in various pathological processes and in myocarditis in particular, and their clinical manifestations in general and the degree of violation of heart functions in particular. In other words, the connection between these three aspects of heart muscle disease—physico-chemical changes, their morphological manifestations, and functional impairment—has not yet been established to a sufficient degree. In particular, we still do not know enough of all the morphological substrates of the main manifestation of diffuse heart muscle lesion—heart failure. It should not be overlooked here that morphological changes of the heart muscle (e.g., fatty infiltration) can be (and often apparently really are) not a causal or coordinated phenomenon in relation to the violation of myocardial function, but a consequence of this violation and in particular a consequence of the impairment of the blood supply to the heart muscle caused by it. So far, pathological histology distinguishes only two forms of myocarditic changes—changes predominantly of the parenchyma, i.e., alterative (infiltrative and degenerative or necrotic processes in muscle fibers), and lesions of the interstitium (predominantly exudative and proliferative, respectively reactive and reparative processes). We do not yet have sufficient data to link one or another category of these manifestations of myocarditis with one or another specific functional or other clinical manifestation. It can only be said that the predominance of alterative changes is more characteristic of acute forms, respectively the initial stages of myocarditis, while the predominance of reactive-reparative changes is characteristic of chronic forms or later stages of the disease. Of particular importance for the clinic of myocarditis is the division of the heart muscle into two parts—the system that generates and conducts impulses for contraction and consists of elements distinct from the rest of the musculature, and the remaining part of the musculature that performs this contraction.

The great importance of focal lesions of the conducting system in myocarditis is determined by its special functional significance, by virtue of which the damage to this system, due to the concentration within it over a small extent of the most important functions of the heart muscle, often has the most severe consequences in terms of impairing the function of the entire heart, and furthermore produces special symptoms thanks to which the presence of such localization is comparatively easily recognized. These special symptoms consist of various types of cardiac rhythm disturbances. Damage to the rest of the myocardium, which is the main part by size and performs predominantly mechanical work, is discovered clinically almost exclusively by one or another sign of insufficiency of cardiac activity. Acute Myocarditis. The general symptomatology of acute myocarditis, as follows from what has just been said, is composed of phenomena of insufficiency of the heart's work and irregularity of this work, i. e., cardiac rhythm disturbances. Manifestations of cardiac insufficiency indicate predominantly diffuse involvement of the myocardium, while manifestations of irregularity of cardiac activity indicate predominantly focal involvement and specifically involvement of the system that generates and conducts impulses. In addition, myocarditis, as an infectious-inflammatory process, can also produce general manifestations of infection and inflammation. The weakening of the contractile force and lowering of the tone of the heart muscle caused by a diffuse and sufficiently intensive lesion are manifested by weakening of the apex beat, greater or lesser expansion of cardiac dullness in all directions, radiologically by an increase in the cardiac shadow, a decrease in the magnitude of its pulsation, greater smoothness of its characteristic contours, and auscultatorily by a weakening of the tones, especially the first one; with the usual acceleration of heart contractions in this condition, embryocardia may be observed, i. e., the large and small pauses become equal and the difference in the intensity of the 1st and 2nd tones is smoothed out; systolic murmurs frequently appear, predominantly over the apex and the pulmonary artery. The mechanism of origin of these systolic (so-called febrile) murmurs, which are characterized by great inconstancy, is not entirely clear. In the presence of other signs of a decrease in the contractile force of the heart muscle (enlargement of the heart, weakening of the first tone, etc.), and especially in the presence of some accentuation of the second tone over the pulmonary artery, one should assume mitral insufficiency of muscular origin, but the development of mitral insufficiency in myocarditis is also possible as a result of damage to the papillary muscles. As for the pulse, when cardiac activity is weakened due to myocarditis, there is acceleration, greater lability, especially a tendency to even greater acceleration even with minor physical exertions, and a decrease in filling and tension. The integuments become pale and sometimes cyanotic, the extremities cold, dyspnea appears and weakness increases; in more acute and sharp weakening of cardiac activity, cold sweat, vomiting, and abdominal pain (as a result of acute swelling of the liver) are sometimes observed. As for the subjective manifestations of acute myocarditis, they may be observed in the form of a feeling of weakness, dyspnea, palpitation, and uncharacteristic pain phenomena in the region of the heart. Sometimes these pain phenomena resemble angina pectoris in character and strength. These subjective symptoms are inconstant; they are often masked by the subjective manifestations of the underlying infection or are not revealed at all due to significant damage to the mental sphere by the same infection. Apart from the indicated manifestations of the weakening of the contractile and tonic functions of the heart muscle, diffuse myocarditis yields almost no definite signs directly connected with it. Recently, attention has been drawn to changes in the electrocardiogram observed in the course of acute infectious diseases, which consist in a reduction of all waves of the electrocardiogram ("low voltage"), an elongation of the P-Q (R) interval and the QRS complex, and finally a change in the direction of the T wave in the sense of converting it from positive to negative. These changes develop in acute infectious diseases to a certain extent in parallel with other clinical manifestations of cardiac insufficiency. The second series of manifestations of myocarditis can be defined as focal, i. e., as manifestations of impaired function of limited areas of the myocardium, especially in the region of its system that generates and conducts impulses to contraction. These focal manifestations are the result of the aforementioned foci of the inflammatory process or (more rarely) hemorrhages due to changes in the vascular walls. More or less limited foci of myocarditis produce the more definite and severe signs, the more differentiated in functional terms the section of the heart muscle is that is affected by the inflammatory process. These signs are, as already mentioned, first of all all possible disturbances of the cardiac rhythm depending on the functional significance of the damaged section of this system. Many of them can be recognized even without special methods of investigation: for example, excessive tachycardia or, conversely, bradycardia, which do not correspond to the degree of elevation of body temperature, the character of the infection, and the stage of the given disease. They indicate a disturbance in the function of the sinus node or (excessive tachycardia) that one or another place in the myocardium is generating more frequent impulses than the sinus node and is causing the heart to beat at a corresponding tempo. As the cause of this phenomenon, one can imagine local excitatory or inhibitory influences of the corresponding foci of the inflammatory process. Excessive bradycardia can be the result of the depressing influence of the inflammatory process on the sinus node or the result of the inhibition of the conduction of these impulses through various sections of the conducting system. As a result of the inhibition of impulse conduction through the bundle of His and its two branches, all possible types of heart block are observed—from a simple prolongation of the time interval between atrial and ventricular contraction to complete atrioventricular block. When evaluating excessive tachycardia or bradycardia, as well as arrhythmia, often observed in infectious diseases as a sign of myocarditis, it is necessary to take into account the possibility of the influence on the cardiac rhythm under these conditions of extracardiac nerves and corresponding divisions of the autonomic nervous system, but we still have a less than real idea of such influences in infectious diseases that would cause cardiac rhythm disturbances. Infectious myocarditis with atrial fibrillation and extrasystole has been described, but in comparison with impaired impulse conduction, these types of arrhythmia in myocarditis are relatively less frequent. Manifestations of myocarditis in the sense of general manifestations of the infectious process or an inflammatory focus in the body—for example, febrile temperature, changes in the number and composition of white blood cells, changes in metabolism, etc.—are usually masked by the corresponding manifestations of the infectious disease that caused the given myocarditis. But in those cases where myocarditis develops during the period of recovery from an infectious disease or after it, the general signs just listed may be present in a more or less expressed form, yet presenting nothing characteristic or specific for myocarditis in general and for this or that form of it in particular, as far as the meager clinical observations in this regard allow one to judge. Diagnostics and differential diagnostics of myocarditis in acute infectious diseases. Such frequent and important circulatory disturbances during acute infectious diseases can be caused by: 1. Vascular insufficiency due to a) depression of the function of vasomotor nerve centers (Romberg), b) local decrease in the tone of capillaries, specifically capillaries of the area innervated by the splanchnic nerves (Holzbach), c) disturbance of the endocrine regulation of the vasomotor nervous system (damage to the adrenal glands). 2. Cardiac insufficiency due to a) disturbance of the chemical structure of the heart muscle and the chemical processes occurring in it; histologically, degenerative or necrotic changes in the myocardium may correspond to this change in chemism; b) inflammation of the heart muscle. The separation and recognition of these various forms of circulatory disorders in acute infectious diseases is practically extremely important, since rational therapy is largely determined by this. Apparently, vascular functions disturbances are more frequent in acute infectious diseases, and perhaps also dystrophic, resp. degenerative, changes in the heart muscle. Myocarditis in an expressed form is a less frequent phenomenon. Therefore, myocarditis usually occurs not as an isolated lesion of the cardiovascular system in acute infectious diseases, but almost always in combination with vascular insufficiency and degenerative changes in the heart muscle. Since vascular insufficiency leads to a decrease in venous blood inflow into the right heart and thereby to a decrease in the blood supply to organs, including the heart, the heart also suffers as a result of vascular insufficiency.

From what has been said, it follows that the manifestations of inflammatory changes in the myocardium in acute infectious diseases must be differentiated from the manifestations of vascular insufficiency, from the manifestations of heart failure caused by it, and also from the manifestations of dystrophic, respectively degenerative, changes in the heart muscle. If in one case there is only heart failure and in another only vascular insufficiency, it is possible to distinguish between them to a certain extent. Heart failure is especially characterized by shortness of breath, cyanosis, and phenomena of congestion in those parts of the cardiovascular system which, according to the blood flow, lie higher than the corresponding part of the heart: in left-heart failure, congestion in the lungs; in right-heart failure, congestion in the veins of the systemic circulation (increased pressure in them), congestion in the liver, kidneys, edema, etc. For vascular insufficiency, on the contrary, the characteristic phenomena are a disturbance of the reverse blood flow to the heart and, as a consequence, insufficiency of the entire peripheral part of the circulatory system: low arterial and especially venous pressure, paleness of the integuments, absence of edema, phenomena of inadequate blood supply to the central nervous system, etc. (see Blood circulation, pathology). But if we have a combination, as is usually the case in acute infectious diseases, of both cardiac and vascular insufficiency, then the manifestations of heart failure are smoothed out to a significant degree, and first of all, the congestion characteristic of it is not observed. They apparently do not occur because the blood flow to the heart due to vascular insufficiency is reduced to such an extent that even the weakened heart is able to transfer all the blood flowing to it into the arterial system. As for other clinical manifestations of heart failure in myocarditis, they do not present anything specific for myocarditis and can be caused by more severe dystrophic, respectively degenerative, changes in the myocardium as a result of either the action of toxins or the disturbance of the blood supply to the heart muscle due to vascular insufficiency; some of these manifestations, such as accelerated pulse, its softness, paleness of the integuments, cooling of the extremities, weakness, can also be a direct manifestation of vascular insufficiency. Under such conditions, determining the presence of primary changes in the heart muscle, whether due to an inflammatory or severe degenerative process, can be done to some extent only on the basis of comparing the degree of all other, so to speak, peripheral signs of vascular insufficiency with the degree and severity of the phenomena from the heart itself. As already indicated, it is very difficult to differentiate the clinical manifestations of diffuse parenchymatous myocarditis from more severe, purely degenerative changes in the myocardium as long as the clinical picture is limited to symptoms of heart failure and there are no general or local manifestations of inflammation of the heart muscle itself. As for the above-mentioned electrocardiographic changes, those of them that should be considered as a manifestation of a diffuse change in the heart muscle do not present anything specific for diffuse myocarditis, since they are also observed under other conditions adversely affecting the physico-chemical state of the heart muscle. These electrocardiographic changes do not fully correspond to the patho-anatomical changes found in corresponding cases after death; thus, the indicated electrocardiogram changes should be considered as a manifestation of the physico-chemical changes of the myocardium caused by infection, and although by themselves they are of very great interest, they do not yet have differential diagnostic significance. The second category of manifestations of myocarditis—manifestations of focal disorders of myocardial functions—is of particularly great value for the diagnosis of acute myocarditis in view of the fact that both the general signs of myocarditis in acute infectious diseases and the phenomena of insufficiency of the entire heart caused by it are so little characteristic. True, focal lesions of the myocardium are not specific for inflammatory processes in the heart muscle either, since they very often occur from other origins, most often arteriosclerotic. But the combination with an acute infectious disease of signs of focal myocardial lesion in the absence of data in favor of another origin (e.g., at a patient's age below 40 years) already gives a definite right to assume the presence of myocarditis (true, only focal), especially when these focal manifestations develop before our eyes in connection with the given acute infectious disease. But the presence of focal myocarditis in the presence of signs of impaired function of the entire heart muscle to a certain extent gives even more grounds to consider these diffuse changes in the myocardium as inflammatory. From what has been said, the great importance that the signs of focal lesion of the heart muscle have for the diagnosis of myocarditis follows with certainty. Regarding the diagnosis of acute or subacute myocarditis, special difficulties are still presented by those cases where endocarditis is undoubtedly present and it is necessary to determine whether myocarditis is also present, how pronounced it is, and what role it plays in the general picture of the disease. In such cases, only a careful clarification of the extent to which the existing manifestations of heart failure can be the consequence of the given valvular defect and general infection can help to some extent. If the degree of circulatory disturbance and heart failure cannot be fully explained by these factors, this gives the right to assume coordinated changes in the myocardium itself. And here, of course, manifestations of focal lesion of the heart muscle will speak in favor of the presence of myocarditis. Another diagnostic difficulty is encountered in those cases of acute infectious diseases where there is reason to assume myocardial damage, with a systolic murmur over the apex and other more pronounced signs of mitral insufficiency. In these cases, it is required to decide whether there is only myocarditis with muscular insufficiency of the mitral valve or, in addition to myocarditis, also endocarditis. The resolution of this question often presents insurmountable difficulties, but it must be said that, undoubtedly, in general, physicians insufficiently take into account how often systolic murmurs over the apex are of functional, resp. muscular origin, and are too inclined to consider every systolic murmur in the presence of signs of general infection as a manifestation of endocarditis. Meanwhile, systolic murmurs over the apex and other signs of mitral insufficiency in acute infectious diseases, and in cardiomyopathies accompanying them in particular, are a very frequent phenomenon. Only prolonged observation with strict consideration of all other possible signs of endocardial involvement makes it possible to resolve the issue correctly. In all cases where the picture is not sufficiently clear, it is necessary to refrain from the diagnosis of endocarditis until clear data are obtained. Particular symptomatology of acute myocarditis. Among acute myocarditis, the most frequent is myocarditis in diphtheria. According to Romberg, it is observed clinically in 10-20% of all cases, according to Schwensen in 17-25%, according to Wulfius in 22.5%; pathologo-anatomically, according to the latter author, in 18.8%, and of those 22.5% where the diagnosis was made clinically, myocarditis was found at autopsy in 70%, and of the 18.8% of all cases where it was found patho-anatomically, the diagnosis of myocarditis was made clinically in 83% of cases. Other pathologo-anatomists found myocarditis in diphtheria either more frequently (Fahr - 42%, Hübschmann - 26%) or less frequently (Kretz - only in 1.5%). The large divergence of these numbers can be explained only by the different character of various epidemics. It is customary to consider diphtheritic myocarditis as a type of myocardial inflammation caused by the action of toxin circulating in the blood, and Rolly and Gottlieb established that diphtheritic toxin is indeed fixed by the heart muscle. However, Kirch, by means of cultures, as well as bacterioscopic examination of sections, established that the heart muscle contains diphtheritic bacilli most constantly of all organs. What role these bacilli in the myocardium play in the origin of diphtheritic myocarditis cannot yet be determined; in any case, by the administration of diphtheritic toxin alone, it was possible to obtain experimentally a myocarditis quite similar to diphtheritic myocarditis in humans (N. Anichkov). Between the clinical manifestations of diphtheritic myocarditis and the patho-anatomical changes of the heart muscle, as follows from the above numerical data, there is no complete parallelism. The impression is obtained that the diphtheritic poison, upon acute and energetic action, can disrupt the function of the myocardium and, in particular, the function of the system that generates and conducts impulses (even up to cardiac arrest), without causing almost any morphological changes in the tissue.

That in these cases it is possible to assume the influence of the diphtheritic infection precisely on the heart muscle follows from the fact that atrio-ventricular block—a frequent heart lesion in diphtheria—is not always accompanied by corresponding morphological changes in the conduction system, in particular its isolated fatty infiltration, hemorrhages, and cloddy breakdown. A very frequent and important symptom of diphtheritic myocarditis consists of arrhythmias: sinus arrhythmia (sino-auricular block), extrasystole, atrial fibrillation, and especially various conduction disturbances up to complete atrio-ventricular block. Conduction disturbance, manifested by severe slowing and irregularity of the pulse, as a rule indicates severe myocarditis, frequently leading to death. According to Smith, atrio-ventricular block is observed in approximately 4% of diphtheria cases. Apparently, in a significant portion of cases of sudden death during and after diphtheria, the cause is precisely the complete disturbance of atrio-ventricular conduction with the inability of the lower sections of the conduction system—due to the same changes—to automatically generate sufficiently frequent impulses. Another cause of sudden death in diphtheria, especially late death, Friedemann considers to be the lesion of the nerves regulating the tone of the cardiac and vascular musculature, analogous to the one that causes the paralysis of various other muscle groups characteristic of diphtheria. One of the causes of early death caused by circulatory disturbance can apparently also be vascular insufficiency. Among the electrocardiogram changes in diphtheria, besides the corresponding manifestations of the above-mentioned arrhythmias, one should point out the frequently observed flattening and even disappearance of P, the lengthening of the QRS group, the appearance of a deep Q in leads I and II, and the flattening or disappearance of the T wave, resp. its transition into a negative wave. Diphtheritic myocarditis often lasts for weeks. Recovery is frequently incomplete, and prolonged cardiac weakness remains. Anatomically in such cases, a significant change in the heart muscle of the character of subacute, predominantly interstitial inflammation is determined, which as an outcome yields myocarditic cardiosclerosis. Schwenkenbecher, upon checking the state of the cardiovascular system in individuals who had suffered from diphtheria two years prior to the examination, found in ²/₃ of all cases one or another disturbance of cardiac function (see also Diphtheria). In typhoid fever, pathologico-anatomically there are discovered in the heart muscle almost exclusively more or less pronounced parenchymatous changes—homogenization of muscle fibers, so-called albuminous degeneration, fatty infiltration, and waxy degeneration. Interstitial inflammatory changes are apparently extremely rare. The indicated changes in the parenchyma in connection with clinical data indicating a lesion of the contractile and tonic functions of the myocardium give the right to assume that typhoid infection is characterized by causing almost exclusively diffuse dystrophic changes in the heart muscle fibers. On the other hand, precisely for this same infection, vascular insufficiency of central nervous or peripheral origin is especially characteristic. Therefore, when assessing phenomena on the part of the heart itself, one should keep in mind the possibility of a secondary effect on it of vascular insufficiency. Phenomena on the part of the heart that can be attributed to primary changes in the myocardium in typhoid fever usually appear no earlier than the second week and consist in a pulse acceleration excessive for the given infection and the given level of temperature, in weakness and muffling of heart sounds, especially the first sound, in the dilation of the left and sometimes the right heart, and in the appearance of signs of muscular insufficiency of the mitral valve. If such cases of typhoid fever, where during the 2nd-3rd week the indicated phenomena on the part of the myocardium develop, end in recovery, then after the cessation of fever, signs of relative insufficiency and increased excitability of the heart still remain for many weeks, particularly clearly manifesting themselves under the influence of physical exertion—inclination to tachycardia, cardiac dilation, unstable mitral insufficiency, edema. But still, after typhoid fever, as a rule, sooner or later all these phenomena on the part of the myocardium disappear, and in the overwhelming majority of cases, no persistent heart damage remains. From the above-mentioned phenomena on the part of the heart during the typhoid fever disease itself, the so-called post-typhoid myocarditis is usually distinguished (Hayem, Romberg, Thayer). 1–2 weeks after the cessation of fever in typhoid fever, a tendency to tachycardia as a rule appears. It is frequently discovered upon first getting up and somewhat decreases, but does not disappear, when the convalescent is again transferred to bed rest. In other cases, appearing in the same period, tachycardia remains at figures up to 120–140–170 for several weeks despite absolute rest, significantly increasing with the slightest physical exertion. This tachycardia is often accompanied by a distressing sensation of palpitation. Objectively, besides tachycardia, sinus arrhythmia is sometimes determined, in heavier cases—cardiac dilation and phenomena of muscular mitral insufficiency. The corresponding percussion and auscultation phenomena differ in this case by significant instability. All these phenomena last in proportion to their severity from 2 weeks to 2 months and then mostly gradually pass; however, increased excitability of the heart often remains for a long time. Still, even this "post-typhoid myocarditis" almost never leaves behind any persistent heart damage. Functional changes of the myocardium in typhoid fever are clearly determined electrocardiographically (Aryev and Tigy). Changes in the electrocardiogram usually appear during the 2nd week and consist in a decrease of all waves; P sometimes becomes barely noticeable, R also significantly decreases, T frequently disappears or even turns into a negative wave, in approximately half of the cases P–Q is significantly prolonged (up to 0.27), and this prolongation does not correspond at all to changes in pulse frequency. The entire QRST group is also prolonged, reaching 0.42. All these changes gradually disappear upon the termination of the febrile period, with T becoming normal later than the other waves—sometimes even during 4–6 months after the disease, an increase in it is observed. These electrocardiogram changes also testify with certainty to a diffuse change in the entire musculature of the heart; as for the prolongation of P–Q, there is no reason to assume special local changes of the atrioventricular bundle; since other more pronounced phenomena of block are not observed in typhoid fever, it is more likely that the conductivity of the entire heart muscle is uniformly reduced, and this is manifested most sharply only on the prolongation of P–Q, since this section of the electrocardiogram corresponds to the place of greatest physiological delay of the impulse traveling from the atria to the ventricles. In favor of the connection of these electrocardiographic changes with insufficiency of the heart muscle in typhoid fever, only the undoubted parallelism between the degree of weakening of the 1st sound and the degree of change of the T wave speaks so far (Aryev and Tigy). Clinical experience definitely speaks in favor of the fact that influenza infection often exerts a special harmful effect on the organs of circulation. Besides phenomena indicating a disturbance of the function of the vascular system in the form of central vasomotor or peripheral lowering of vascular tone, phenomena indicating damage to the heart itself are also observed. The impression is obtained that, especially in elderly individuals suffering from arteriosclerosis, and in cardiac patients, influenza infection reflects extremely unfavorably on the heart, sharply worsening its working capacity. In influenza infection, phenomena on the part of the heart set in either during the disease itself or later and consist in pulse lability, excessive tachycardia, cardiac dilation, and muscular mitral insufficiency. According to Romberg, already at the height of the disease various arrhythmias can appear, and during recovery—attacks of cardiac weakness, frequently attacks of pains resembling angina pectoris. Lately, there are also isolated electrocardiographic observations fully confirming Romberg's indications regarding severe rhythm disturbances in influenza infection (Dressler). But it must be recognized that the available observations on cardiac phenomena in influenza infection are generally still insufficient. Pathologico-anatomically, Fahr among 246 autopsies of those who died from influenza infection found pronounced myocarditis in only one case and in 30 cases significant cardiac dilation. Glaus among 260 autopsies of influenza cases also had only one case of myocarditis. Koopmann—7 among 342. Various degenerative changes of the myocardium are encountered more frequently. The impression is obtained that in influenza the clinical manifestations of disturbances of cardiac activity are significantly more frequent. Therefore, the assumption may arise that they are partly caused by a disturbance under the influence of influenza infection of the innervation of the heart and vessels.

This was especially noticeable during the course of the pandemic influenza (Spanish disease), where a sharp complex of cardiovascular disorders (early drop in blood pressure, bradycardia, cyanosis) led a number of authors (Elistratov, Andreyev, Koltypin) to express the opinion that, in their genesis, apart from myocardial changes, a significant role is played by damage to the vascular innervation. The idea of the frequency of myocarditis in scarlet fever varies within wide limits—from zero (Berkholz) to 50% (Hirsch) and even up to 70% (Lederer, Stolte) of all cases. Perhaps this is explained by the fact that various epidemics of scarlet fever, as is known, tend to give predominantly certain complications. Pathologically and anatomically, the so-called cloudy swelling of muscle fibers, granular or fatty degeneration, and small-cell infiltration have been described (Romberg, Lubarsch, Broadbent). Fahr often found small perivascular granulomas, similar to Aschoff nodules, characteristic of rheumatic myocarditis. Clinical phenomena on the part of the heart in scarlet fever, although frequent, are little expressed and little characteristic, and therefore are evaluated differently by various observers. They consist in an increased pulse rate, a dull, weak, unclean first sound, systolic murmurs over the apex and pulmonary artery, and a slight enlargement of the heart. These phenomena usually occur in the 2nd week of the disease; sometimes they are accompanied by a new rise in temperature. All these phenomena usually pass without a trace within 2–6 weeks. Much less frequently, phenomena of myocarditis are observed later; thus, in Kretz's case—7 weeks after a mild scarlet fever. Electrocardiographically, a frequent change during scarlet fever has been noted in the T wave, which in the 2nd and not unfrequently in the 3rd lead becomes biphasic or negative, only to become normal again after the end of the disease, sometimes very late (a month later). Scarlet fever myocarditis has no connection with the complication of scarlet fever by rheumatoid joint lesions, but is observed or manifests itself frequently together with scarlet fever nephritis. It is generally accepted that the outcome of the disease in pneumonia depends on the functional capacity of the heart of the given patient during the course of the disease. Exactly in relation to experimental pneumococcal infection, Romberg and his co-workers established the significance for circulatory disturbance of central vasomotor paresis; therefore, it is assumed that in pneumonia in humans, vasomotor paresis is one of the causes of circulatory failure. Its second cause is considered to be the obstruction of blood flow through the lungs due to the pneumonic process. Finally, the third cause of circulatory disturbance in pneumonia may be myocardial damage. Regarding these myocardial lesions, there are as yet no sufficient patho-anatomical data (only Lipmann found distinct interstitial changes in 2 cases out of 11). Clinically, enlargement of the heart both to the right and to the left is noted, occasionally conduction disturbances of the bundle of His, the transition of the T wave in the 3rd lead into a negative wave with its return to normal shortly after the end of the disease. It is even more difficult to isolate in typhus fever that share in the circulatory disturbance, usually so sharply expressed in this condition, which is due to damage to the heart muscle alongside damage to the nerve centers regulating circulation, and with such a widespread specific lesion of the smallest vessels in the periphery. Undoubtedly, in typhus fever, the same widespread focal vasculitis, or rather perivasculitis, is present in the heart muscle as in other organs and tissues. Localizing in the heart, it is in all probability the cause of those frequent heart rhythm disturbances that are observed in typhus fever in the form of extrasystoles, atrial fibrillation, more rarely conduction disorders, etc. This same myocardial perivasculitis is in all probability also one of the causes of the weakening of heart activity in typhus fever. Acute myocarditis in various degrees and forms of development is frequently observed in other infections as well; however, there are very peculiar differences: in some infections the myocardium is very energetically involved in a degenerative-inflammatory process, parallel with which goes the damage to the endocrine-vegetative apparatus (diphtheria, scarlet fever in severe forms, dysentery, erysipelas, pandemic influenza, typhoid fever, smallpox, typhus fever, relapsing fever); these are a series of toxic-septic infections. In other infections the heart is affected relatively weakly (such are measles, rubella, mumps, chickenpox, cerebrospinal meningitis); in these infections, myocardial damage and clinical heart disorders are observed in a very mild form. - Special attention is deserved by the damage to the heart muscle caused by acute tonsillitis. Until recently, the idea of them was limited to cases where, after tonsillitis, general weakness, a tendency to shortness of breath, palpitation, variable systolic murmurs over the apex, tachycardia, and sometimes arrhythmia appeared. Thanks to electrocardiography, there are now quite concrete data on myocardial function impairment and various arrhythmias after tonsillitis. In combination with the subjective and objective symptoms on the part of the heart just listed, a significant prolongation of P-R (accompanied by gallop rhythm), atrial fibrillation, and extrasystole have been established. All these phenomena turned out to be rapidly passing. - It is necessary to point out that according to the concept of rheumatic infection developing at the present time, the latter can proceed without joint involvement and manifest itself by tonsillitis with subsequent damage only to the myocardium. The electrocardiographic changes that were established in the aforementioned cases after acute tonsillitis in the highest degree resemble those that are so frequently encountered in acute rheumatic infection manifested by acute polyarthritis following preceding tonsillitis. Therefore, the assumption is possible that the above-indicated cases of "myocarditis" after tonsillitis were cases of rheumatic infection without joint involvement. Trichinosis myocarditis also deserves mention, caused apparently not by the trichinae themselves, which have not yet been found in the heart muscle, but by their toxins. This myocarditis is histologically manifested by infiltration with eosinophilic leukocytes and lymphocytes (Stäubli, Simmonds). Its clinical manifestations have not yet been established. - Septic myocarditis is also distinguished, developing in various acute and subacute septic diseases. The clinical manifestations of septic myocarditis are usually covered by the manifestations of the underlying disease, which itself, and without special myocardial damage through the action of corresponding toxins, causes both cardiac and vascular failure. Only rarely, on the basis of individual signs—angina-type pains, pronounced arrhythmia, etc.—is it possible to determine during life the presence of specific damage to the heart muscle. Romberg draws attention to the fact that in the case of a favorable outcome of an acute or subacute septic disease in the recovery period, a lowered resistance of the heart is often observed, manifested by the development of acute heart failure following relatively minor physical exertion. How much these phenomena are caused by the consequences of septic myocarditis, and how much by diffuse degenerative changes in the heart muscle, is impossible to say at present in the absence of corresponding patho-anatomical data. As follows from what has been set forth, clinical as well as patho-anatomical information on inflammatory states of the heart muscle in most acute infectious diseases is still extremely meager. With this state of affairs, it is very difficult clinically to single out among the manifestations of circulatory disorders in acute infectious diseases those caused by myocardial damage. Therefore, when describing myocarditis in typhoid fever, influenza, pneumonia, etc., it has constantly been necessary to speak also of the manifestations of other, non-cardiac types of circulatory disturbance in these infections. Acute and subacute idiopathic myocarditis. Cases of acute and subacute myocarditis proceeding without an accompanying or shortly preceding specific infectious disease are so rare that they are still the subject of casuistic reports. Such cases, where only phenomena of myocarditis and more or less pronounced general signs of an infectious process of an indefinite character were discovered clinically and at autopsy, total about 50. Patho-anatomically, predominantly interstitial diffuse or focal myocarditis and frequently hypertrophy of the heart muscle were discovered in these cases. Such cases were first reported by Fiedler (1900). They are subsequently described under the name of acute idiopathic, or isolated, or primary myocarditis, or Fiedler's myocarditis. The disease sometimes begins under the guise of an acute infectious disease, and sometimes gradually. In the clinical picture, the symptom complex of heart failure dominates, and in these cases of isolated myocarditis it is usually more or less fully expressed, i.e., there are usually characteristic congestive phenomena up to edema. The pulse is more or less accelerated, blood pressure is lowered, and sometimes there are signs of focal myocardial damage.

To these one should in all probability also attribute the severe bradycardia that was sometimes observed in these cases (atrioventricular block due to a lesion of the bundle of His). Pain phenomena in the region of the heart are frequently observed, especially at the beginning of the disease, more or less resembling angina pectoris. The general manifestations of the infection consist of an atypical febrile temperature, varying from high remittent or intermittent to insignificant and non-constant elevations; sometimes there is leukocytosis, slight albuminuria. Apart from the indicated stagnant phenomena on the part of other organs, there are no signs of the disease. A clinically correct diagnosis was almost never made in any case. Most often, coronary sclerosis was suspected; indeed, in the presence of pain phenomena, the clinical picture of the disease most resembles severe coronary sclerosis with fresh infarction of the heart muscle. The etiology of this form of myocarditis is not clear. Sepsis is thought of, most likely streptococcal, with predominant damage to the heart muscle. But in most cases, a definite connection with any process that could be interpreted as primary in the sense of septic infection cannot be established, and there are no convincing bacteriological data either. Others are inclined to consider at least some of these cases as cases of isolated damage to the heart muscle by rheumatic infection. But so far there are no conclusive data in this direction either. In particular, in almost none of the cases of idiopathic myocarditis described over the last decade could Aschoff nodules be found in the myocardium. Almost all the described cases ended in death within a few weeks or several months. Only Krehl describes cases ending in recovery, which, according to their clinical picture, can be considered as belonging to this form. The prognosis of acute and subacute myocarditis depends primarily on their etiology. In addition, of course, in each case the prognosis is determined by how intensively the heart muscle is damaged, how pronounced the vascular insufficiency is, and how severely the underlying infectious disease proceeds. The decisive factor, along with the strength of the infection, is the resistance of the entire organism and its cardiovascular system in particular. This resistance is determined by the state of the organism during the infection, depending on the external conditions of its life and on its constitutional-hereditary data. Prophylaxis and treatment. The prophylaxis of myocarditis developing in connection with acute infectious diseases coincides with the prophylaxis of these diseases. To prevent complications of the onset of acute infection by myocarditis, one should in any case strive for the earliest possible use of specific treatment against the infection itself, if such is available. But it must be recognized that doubts are possible as to whether this really succeeds in preventing the development of this complication. Even with respect to diphtheria, not everyone agrees that serum treatment prevents the complication of myocarditis, but nevertheless there is no doubt that in practice, for the purpose of preventing the complication of myocarditis, it is necessary with all one's might to strive for the earliest and most energetic treatment with serum. If at the height of the disease during the 1st week of diphtheria, phenomena of myocarditis develop, then it is advised to use large doses of antidiphtheritic serum—up to 20,000 units intramuscularly or intravenously, taking into account, of course, the preceding serum treatment. It may be that strict enforcement of physical and mental rest from the very beginning of the development of those infectious diseases that are prone to give the complication of myocarditis will contribute to the prevention of this complication or its development in a less severe form. In any case, the regime of absolute physical and mental rest (not sitting up in bed, and under no circumstances getting up) is necessary when the first signs of circulatory insufficiency in general and cardiac insufficiency in particular are discovered. During convalescence from myocarditis, the transition to sitting up, getting up, and walking should be extremely cautious, because experience shows that premature excessive physical exertion in this period can cause phenomena of acute severe heart failure or even death. In general, it is desirable to maintain a regime of complete rest until all pathological phenomena on the part of the heart disappear. But often this is impossible, because sometimes for a very long time—for months—individual manifestations of the suffered myocarditis remain, e.g., great lability of the pulse. In these cases, the patient is accustomed to movements very carefully and under constant control. The use of baths, and in particular carbon dioxide baths, in the presence of heart failure and in general signs of an active inflammatory process in the heart muscle, is contraindicated; carbon dioxide baths (to strengthen the heart muscle) are appropriate only after recovery. When signs of vascular insufficiency appear during an infectious disease, it is necessary to vigorously combat it, among other things because vascular insufficiency contributes to the development of cardiac insufficiency. It is necessary in these cases to use energetically and systematically preparations of camphor, caffeine, theobromine, strychnine, and especially adrenaline. These agents, acting through the vasomotor centers or directly on the vessels, increase the tone of the vascular musculature. In addition, they also through the nerve centers regulating cardiac activity, or directly, affect the heart as well, enhancing its contractions and perhaps improving its blood supply (preparations of caffeine and especially theobromine). Therefore, these agents, although they have dominant importance in the treatment of vascular insufficiency, should also be used for cardiac insufficiency. As for the use in acute myocarditis complicating acute infectious diseases of cardiac remedies in the narrow sense of the word, i.e., remedies of the digitalis group, there is as yet no general firmly established point of view on their significance under these conditions. There is an idea that they are of little effect in acute infectious diseases, i.e., they do not improve circulation. This notion is in a certain sense confirmed by experimental studies (Schwarz, Herzog), according to which during animal fever the lethal dose of strophanthin increases by 200% and more, and this depends not on a change in the effect of this remedy on the heart, but on its fixation or destruction in other parts of the febrile organism. These observations can raise the doubt whether the notion of the ineffectiveness of digitalis group remedies in febrile patients is the result of insufficient dosage of these remedies for the given patients. At the same time, in the very latest time, prominent clinicians (Krehl, Straub, Friedemann) warmly recommend the treatment of circulatory disorders during infectious diseases, and in particular typhoid fever, with digitalis preparations. They use them at the very first onset of signs of cardiovascular insufficiency and in all more serious cases give preference to intravenous injections of strophanthin. But special attention must be paid to the proper dosage in each case. Starting with small doses (no more than ¹/₄ mg), it is necessary, guided by the effect of the injection on the patient, to work out the dosage required in the given case to improve circulation; the maximum single dose, however, should not exceed ¹/₂ mg, and the daily dose 1 mg. Strophanthin can be replaced by digalen or digipuratum, using them also intravenously or intramuscularly, but their effect is weaker. In severe cases, in addition to the indicated cardiac and vascular remedies, an intravenous solution of grape sugar with the addition of adrenaline or strophanthin should be used, depending on the predominance of manifestations of vascular or cardiac insufficiency. In diphtheria, one can combine the intravenous administration of sugar solution with the subcutaneous administration of antidiphtheritic serum. Myocarditis caused by exogenous and endogenous poisons. Alongside myocarditis of infectious-toxic origin, myocarditis caused by exogenous and endogenous poisons has been described. Of the former, myocarditis due to carbon monoxide poisoning deserves attention, being apparently a fairly typical manifestation of this poisoning. How much the observed clinical phenomena on the part of the circulatory organs in carbon monoxide poisoning—namely, cardiac enlargement, rhythm disturbance, and a drop in blood pressure—are in causal connection with changes in the myocardium has not yet been sufficiently elucidated. Pathologo-anatomical changes consist of sharp degenerative and necrotic changes in muscle fibers, but not of a diffuse, but of a focal character, with a predominant localization in the region of the apex of the left ventricle and especially in the apices of its papillary muscles. These degenerative-necrotic changes are sometimes accompanied by small hemorrhages without disturbing the integrity of the walls of small vessels (consequently, hemorrhages per diapedesin). In addition, exudative and infiltrative-proliferative inflammatory changes are observed in the interstitial tissue in the region of the indicated parenchymal changes. Perhaps these inflammatory changes have a secondary, resp. reparative character.

In such a case, this myocardial lesion in illuminating gas poisoning would not, strictly speaking, deserve the name of myocarditis. As regards endogenous toxic influences, in one case of uremia, the development of a pronounced diffuse interstitial hemorrhagic myocarditis was established. Lüscher is inclined to attribute this myocarditis to the uremic poison. In this case, pericarditis was also established—a complication of uremia long known to the clinic. No infection could be demonstrated. In Basedow's disease and status thymico-lymphaticus, Fahr, Ceelen, and Rieder describe degenerative parenchymal changes and interstitial, more or less diffuse or focal inflammatory changes. All these descriptions of myocarditic changes in these pathological states, while of great interest, still require confirmation and clarification by further observations. Chronic myocarditis. This term is abused in clinical practice even more than the term acute myocarditis. To this day, it is still commonly applied to myocardial changes caused by coronary artery sclerosis (see Cardiosclerosis). It is equally incorrect to apply this term to those cases where, as a result of a past acute or subacute myocarditis, there is a focal development of connective tissue in the heart muscle, but no signs of an active inflammatory process remain, i.e., there is cardiosclerosis as a result of myocarditis. Finally, it is incorrect to apply the term chronic myocarditis to the diffuse development of connective tissue in the heart muscle that occurs with prolonged increased work of a hypertrophied heart muscle, leading to dilation of the corresponding compartment of the heart and to heart failure (see Cardiosclerosis). Chronic myocarditis undoubtedly includes syphilis of the myocardium and tuberculosis thereof (see Heart, syphilis, tuberculosis). Rheumatic infection causes both acute myocardial changes and typical subacute myocarditis, which very frequently assumes a relapsing and chronic character (Talalaev), and it is most probable that those inflammatory changes in the myocardium (partly typical in the form of Aschoff nodules, partly atypical) which are so frequently encountered also in old valvular heart lesions of endocarditic origin should be regarded as manifestations of this chronic, resp. relapsing, rheumatic myocarditis (see Rheumatism). If we exclude all those forms of heart muscle disease that are incorrectly referred to as chronic myocarditis, as well as syphilitic, tuberculous, and rheumatic myocarditis, the form remaining in the literature under the name of chronic myocarditis represents a completely vaguely outlined form of disease. Sometimes cases are mentioned where an acute myocarditis, developed in connection with a specific infection, transitions into a chronic one. But regarding these latter cases, we also do not have sufficient concrete data. Therefore, from a clinical standpoint, it is more correct to refrain from distinguishing and describing chronic myocarditis or chronic myocarditides, other than the above-mentioned syphilitic, tuberculous, and rheumatic forms of this disease, until appropriate concrete material has been gathered.