ECG changes after rabbit coronavirus infection

This study examines the electrocardiographic (ECG) changes following rabbit coronavirus (RbCV) infection. We have shown that infection with RbCV results in the development of myocarditis and congestive heart failure and that some survivors of RbCV infection go on to develop dilated cardiomyopathy in the chronic phase. Serial ECGs were recorded on 31 RbCV-infected rabbits. Measurements of heart rate; P-R interval; QRS duration; QTc interval; and P-, QRS-, and T-wave voltages were taken. The recordings were also examined for disturbances of conduction, rhythm, and repolarization. The acute and subacute phases were characterized by sinus tachycardia with depressed R- and T-wave voltages as well as disturbances of conduction, rhythm, and repolarization. In most animals in the chronic phase, the sinus rate returned to near-baseline values with resolution of the QRS voltage changes. The ECG changes observed during RbCV infection are similar to the spectrum of interval/segment abnormalities, rhythm disturbances, conduction defects, and myocardial pathology seen in human myocarditis, heart failure, and dilated cardiomyopathy. Because animals often died suddenly in the absence of severe clinical signs of congestive heart failure during the acute phase, RbCV infection may increase ventricular vulnerability, resulting in sudden cardiac death. RbCV infection may provide a rare opportunity to study sudden cardiac death in an animal model in which the ventricle is capable of supporting ventricular fibrillation, and invasive techniques monitoring cardiac function can be performed.     

Kawasaki syndrome in an adult: endomyocardial histology and ventricular function during acute and recovery phases of illness

Kawasaki syndrome, an acute systemic inflammatory illness of unknown origin usually affecting children, may develop into a serious illness complicated by coronary artery aneurysms or myocarditis. This report describes an adult with Kawasaki syndrome studied by right ventricular endomyocardial biopsy and cardiac catheterization during the acute and recovery phases of illness. The initial biopsy specimen showed acute myocarditis and was associated with hemodynamic evidence of biventricular dysfunction, a severely depressed left ventricular ejection fraction and global hypokinesia. With time, there was spontaneous and rapid resolution of the inflammatory cell infiltrate with concurrent return to normal myocardial function. Right ventricular endomyocardial biopsy studies early in the course of the cardiac disease associated with Kawasaki syndrome may correlate with ventricular function and may be useful for monitoring immunosuppressive therapy in patients with this syndrome.     

The evolution of experimental Trypanosoma cruzi cardiomyopathy in rabbits: further parasitological, morphological and functional studies

Young rabbits (1–2 months of age) inoculated with trypomastigote forms of the Colombia strain of Trypanosoma cruzi have been shown to develop cardiac pathological changes (together with parasitological and immunological alterations) which are very similar to those observed in the acute and chronic phases of Chagas' disease in man. The cardiac alterations in the acute phase are characterized grossly by slight cardiomegaly with dilatation of the right-sided chambers. Microscopically they are characterized by mild focal myocarditis. The chronic phase is characterized by moderate to marked cardiomegaly with hypertrophy and dilatation of both ventricular chambers. There is thinning of the apical region (apical aneurysm), particularly of the left ventricle. Focal myocarditis is seen microscopically with areas of myocytolytic necrosis, atrophic and hypertrophic myofibers, an inflammatory response predominantly composed of mononuclear cells and interstitial fibrosis. Cineventriculography in the left ventricle of rabbits during the chronic phase disclosed regional myocardial dysfunction, with typical apical systolic bulging. The pathogenesis of Chagasic cardiomyopathy is briefly discussed in the light of these findings. Our investigation has further shown that this animal model is particularly suitable for studies on the mechanisms, pathology and treatment of Chagas' heart disease.     

Transient ventricular wall thickening in acute myocarditis: a serial echocardiographic and histopathologic study

The present study was designed to determine whether the wall thickening seen in acute myocarditis is caused by interstitial edema. The study group comprised 25 patients (idiopathic myocarditis, 17; eosinophilic myocarditis, 8) in whom acute myocarditis was diagnosed histologically and who underwent echocardiography and endomyocardial biopsy during both the acute and convalescent phases. The following echocardiographic parameters were measured: interventricular septum and left ventricular posterior wall thickness, left ventricular end-diastolic dimension, and left ventricular ejection fraction. Based on the myocardial biopsy specimens, the degree of interstitial edema was classified into 3 grades [(-), 1(+), 2(+)] and the transverse diameter of cardiac myocytes was measured using light microscopy. The thickness of both the interventricular septum and left ventricular wall decreased from 14.3+/-3.7 mm and 13.3+/-2.4 mm in the acute phase to 9.7+/-1.7 mm (p<0.001) and 10.2+/-1.7 mm (p<0.0001), respectively, in the convalescent phase. Edema was present in 22 patients (88.0%) in the acute phase, but in the convalescent phase, edema was present in only 7 patients (28.0%), indicating a significant reduction in the degree of edema (p<0.0001). Cardiac myocyte diameter did not differ significantly between the acute (13.6+/-1.1 microm) and convalescent (13.8+/-1.8 microm) phases.     

Chronic (or healed) myocarditis mimicking arrhythmogenic right ventricular dysplasia

The aetiology of arrhythmogenic right ventricular dysplasiais still unknown, and there are few reports on familial coincidencein the literature. A case of a previously healthy man with anepisode of acute myocarditis is described. After recovery fromacute myocarditis, the patient was resuscitated from abortedsudden cardiac death 16 months later. Angiographic and electrophysiologicalevaluation suggested the pattern of arrhythmogenic right ventriculardysplasia. The case seems to suggest that arrhythmogenic rightand/or left ventricular dysplasia could be mimicked by chronic(or healed) myocarditis.     

Experimental rat model representing both acute and chronic heart failure related to autoimmune myocarditis

Summary The most important clinical manifestation of myocarditis is congestive heart failure. The precise mechanisms of heart failure during myocarditis have not been elucidated because no animal model that would permit in vivo study of hemodynamics in severe active myocarditis has been available. We monitored hemodynamics and left ventricular function in a rat model of experimental autoimmune myocarditis to determine if this model could be useful for the study of in vivo hemodynamics in severe active myocarditis. Lewis rats were immunized with human cardiac myosin suspended in complete Freund's adjuvant. Baseline hemodynamics were measured using an ultraminiature catheter pressure transducer via the right internal carotid artery, 4 weeks after immunization in one group of rats (acute phase) and 3 months after immunization in another group (chronic phase). Untreated rats served as the control group. Hemodynamic measurements were also obtained after infusion of dobutamine in the acute-phase and chronic-phase groups. The heart weight-to-body weight ratios were significantly higher in both the acute-phase group and the chronic-phase group compared with normal control rats. The baseline left ventricular systolic pressure was significantly lower in the chronic phase group than in the control group. Peak dP/dt and peak -dP/dt were significantly lower in both the acute-phase group and the chronic-phase group compared with the control group. Dobutamine significantly increased left ventricular systolic pressure, peak dP/dt, and peak -dP/dt in the chronic-phase group but caused only minor changes in hemodynamic variables in the acute-phase group. In vivo measurements of hemodynamic variables indicated the presence of left ventricular dysfunction in rats with experimental autoimmune myocarditis. This animal model may be useful for the study of both acute heart failure related to acute myocarditis and chronic heart failure due to diffuse myocardial fibrosis.     

Successful immunoglobulin treatment for fulminant myocarditis and serial analysis of serum thioredoxin: a case report.

A 31-year-old woman suspected to have acute myocarditis was admitted to hospital and was managed with intra-aortic balloon pumping and a percutaneous cardiopulmonary support system because of sustained ventricular tachycardia. After immunoglobulin treatment, cardiac function and systematic inflammation were improved. The left ventricular endomyocardial biopsy revealed massive necrosis and degeneration of myocardial cells, and extensive infiltration of inflammatory cells. The clinicopathology of this patient was thought to be fulminant myocarditis. Serial serum thioredoxin (TRX) analysis showed that the serum level was high during the acute phase, and decreased during the chronic phase. Immunohistochemistry for TRX in the biopsy samples showed that inflammatory cells and cardiomyocytes were positively stained.     

Bidirectional Ventricular Tachycardia Secondary to Subacute Myocarditis

We report a case of subacute myocarditis with severe heart failure referred for urgent cardiac transplantation. The patient had an episode of bidirectional ventricular tachycardia during the acute admission. Subacute myocarditis should be added to the limited differential diagnosis of bidirectional ventricular tachycardia.     

An experimental model for myocarditis and congestive heart failure after rabbit coronavirus infection.

In a model for virus-induced myocarditis and congestive heart failure, rabbit coronavirus infection was divided into acute (days 2-5) and subacute (days 6-12) phases on the basis of day of death and pathologic findings. During the acute phase, the principal histologic lesions were degeneration and necrosis of myocytes, myocytolysis, interstitial edema, and hemorrhage. The severity of these changes increased in the subacute phase. Pleural effusion and congestion of the lungs and liver were also present at this time. Myocarditis was detected by day 9 and peaked by day 12. Heart weights and heart weight-to-body weight ratios were increased, and dilation of the right ventricular cavity became prominent early in infection and persisted. In contrast, dilation of the left ventricle occurred late in the subacute stage. Virus was isolated from infected hearts between days 2 and 12. These data suggest that rabbit coronavirus infection progresses to myocarditis and congestive heart failure.     

Lymphocyte subsets in patients with acute myopericarditis, arrhythmias and dilated cardiomyopathy

To investigate the role of immunoregulatory function in determining the clinical course of acute myopericarditis, lymphocyte subsets were analysed by laser flow cytometry in 20 patients with acute myopericarditis, 30 with various arrhythmias or atrio-ventricular block and 31 with dilated cardiomyopathy. During the healing stage of acute myopericarditis, patients with residual electrocardiographic or left ventricular wall motion abnormalities presented altered frequencies of lymphocyte subsets, increased B 1 and reduced OKT 8 positive cells with an elevated OKT 4/8 ratio. The abnormal pattern was not evident in patients with acute pericarditis nor in those with acute myocarditis who recovered completely without residual abnormalities. This observation suggested that an imbalance of helper/suppressor T cells could modulate the clinical course of acute myopericarditis, either by producing extensive and irreversible myocardial damage during acute illness or by inducing chronic smoulding myocardial inflammation. Patients with ventricular arrhythmias and left ventricular wall motion abnormalities also presented reduced suppressor/cytotoxic T cells, implying that they had been suffering from chronic smoulding myocarditis mediated by immunoregulatory dysfunction. However, we could not determine whether the imbalance of helper/suppressor T cells could mediate the progression from myocarditis to dilated cardiomyopathy, since no association was demonstrated between the abnormal lymphocyte subsets and mononuclear cell infiltration in endomyocardial biopsy sample from patients with dilated cardiomyopathy.     

Effects of the Valsalva maneuver on myocardial ischemia in patients with coronary artery disease.

The influence of the Valsalva maneuver (VM) on myocardial ischemia was evaluated in 24 patients with coronary heart disease. Clinical and hemodynamic responses to the VM were studied during acute ischemia manifested by angina pectoris with transient left ventricular (LV) dysfunction and compared with responses during nonischemic intervals. In the absence of evidence for acute ischemia (angina and increased LV end-diastolic pressure), six patients had abnormal hemodynamic responses to the VM. Five had lack of systolic pressure overshoot and in one, systolic pressure did not decline during straining. When the VM was performed during an ischemic episode, 14 patients had abnormal responses (12 with lack of overshoot in phase IV and two with lack of systolic pressure decline in phase II). In 18 patients a prompt decline in LV end-diastolic pressure occurred with the disappearance of angina during the VM. These changes uniformly occurred during the latter part of straining (VM phase II) as cardiac size and systolic pressure declined. No adverse effects occurred when a VM was performed during acute ischemia. Our observations suggest that the VM abruptly reduces determinants of cardiac oxygen demand, relieving acute ischemia without harmful effects.     

The importance of serial cardiac troponin measurement for evaluating the response to immunosuppressive therapy for myocarditis

A 71-year-old woman was admitted to our department because of acute myocarditis. She was ameliorated with conventional heart failure treatment, however she developed left ventricular dilatation and cardiac troponin T (cTnT) was elevated again to >1.0ng/ml 6 month after the first admission. She was re-admitted because of recurrent decompensated heart failure in spite of conventional treatment. Right ventricular endomyocardial biopsy revealed active myocarditis. Immunosuppressive therapy with prednisolone and azathioprine improved her symptoms and left ventricular function accompanied by a striking decrease of cTnT levels. The decreased cTnT level indicated an effective response to immunosuppression early after the beginning of treatment. These findings suggested that it is possible to evaluate the response to immunosuppressive therapy by serial measurement of cardiac troponin.     

Acute myocarditis in children. Study of 11 clinical cases

The diagnosis of acute myocarditis in children is based on histological criteria. Often viral in origin, it results in acute left ventricular dysfunction, the clinical manifestations of which are very variable. The potential severity of the disease is maximal in its initial phase, justifying rapid and intensive treatment. Long-term outcome is relatively good although there is a risk of chronic left ventricular dysfunction. This retrospective study is based on 11 cases of acute myocarditis admitted to the paediatric unit of Clermont-Ferrand University Hospital between February 1989 and March 1999. The initial symptoms were non-specific. Echocardiography was the key diagnostic procedure. Half of the patients had severe cardiac failure requiring admission to the intensive care unit. Four cases presented with a severe complication: two embolic events, one syncopal atrioventricular block and one cardiac arrest. The cardiac treatment was classical (digitalis, diuretics, angiotensin converting enzyme inhibitors, anticoagulants). The aetiology was established in 3 cases (toxoplasmosis, haemolytic and uraemic syndrome, Kawasaki) and a viral cause was suspected in 6 other cases (adenovirus in 3 cases, herpes virus, RSV and enterovirus in 1 case). There were no deaths in the acute phase. The long-term outcome was globally good: complete regression in 8 cases, 1 chronic left ventricular dysfunction and 2 late deaths due to intractable cardiac failure. This short series illustrates the often misleading presentation of acute myocarditis in childhood, the value of systematic investigation in the hope of a specific treatment becoming available in the near future for the often viral aetiology.     

An experimental model of acute and subacute viral myocarditis in the pig.

Twenty-six young pigs were infected with encephalomyocarditis virus, observed clinically, studied at intervals by noninvasive and invasive methods to assess cardiac function and eventually examined pathologically. All infected animals appeared ill, usually manifesting diminished appetite, lethargy and fever. Spontaneous mortality occurred either 1 to 4 or 20 to 21 days after infection. Electrocardiographic abnormalities, seen in the majority of animals, comprised ST-T wave changes, conduction disturbances or ventricular ectopic rhythm. The majority of animals manifested echocardiographic evidence of left ventricular dilation and decreased systolic function, which improved with time in some animals. Hemodynamic studies revealed elevation of biventricular filling pressures in 3 of 10 animals; as a group, infected animals manifested significantly elevated right ventricular filling pressures. In selected animals, the feasibility of gallium scans as well as left ventriculography and coronary angiography was demonstrated. At autopsy, heart weight/body weight ratio was significantly elevated in infected animals. The heart of all but two animals showed active myocarditis associated with fibrosis and focal calcification in the later stages. In general, the cardiovascular manifestations were parallel with those seen in acute and subacute myocarditis in humans. It is concluded that encephalomyocarditis infection in the pig is a large animal model of viral myocarditis suitable for assessing alterations in the structure and function of the cardiovascular system and the effects of interventions.     

TandemHeart as a Bridge to Recovery in Legionella Myocarditis

Legionnaires'' disease is the designation for pneumonia caused by the Legionella species. Among the rare extrapulmonary manifestations, cardiac involvement is most prevalent, in the forms of myocarditis, pericarditis, postcardiotomy syndrome, and prosthetic valve endocarditis. Mechanical circulatory support has proved to be a safe and effective bridge to myocardial recovery in patients with acute fulminant myocarditis; however, to our knowledge, this support has not been used in infectious myocarditis specifically related to Legionellosis.We describe a case of Legionella myocarditis associated with acute left ventricular dysfunction and repolarization abnormalities in a 48-year-old man. The patient fully recovered after left ventricular unloading with use of a TandemHeart percutaneous ventricular assist device. In addition, we review the English-language medical literature on Legionella myocarditis and focus on cardiac outcomes.     

Role of biochemical markers in diagnosis of myocardial infarction

An ideal cardiac biochemical marker should have not only high sensitivity but also high specificity to myocardial infarction. The creatine kinase-MB, a relatively specific cardiac marker, could be elevated in situations other than acute myocardial infarction, such as renal failure, muscular injury, and myopathy. Although these are more specific than creatine kinase-MB, cardiac troponins have also been reported to be elevated in conditions other than acute myocardial infarction, such as chronic renal failure, acute myocarditis, cardiomyopathy, congestive heart failure, pulmonary embolism, rhabdomyolysis, sepsis, and left ventricular hypertrophy. With the ongoing research in this field, future holds hopes of finding an ideally specific marker of myocardial infarction, but until then biochemical markers should be used in conjunction with clinical assessment and electrocardiography in making the diagnosis of myocardial infarction, and the patients should not be treated merely on the basis of elevated serum levels of cardiac biochemical markers.     

Mechanical bridging to improvement in severe acute "nonischemic, nonmyocarditis" heart failure

Improved myocardial function has been observed in patients with acute myocarditis who have had short-term support with a ventricular assist system. Additionally, a limited number of patients with nonischemic cardiomyopathy have undergone successful device explantation after their myocardial function improved during ventricular assist system support. The authors present their experience with four patients who had acute, severe heart failure without coronary artery disease or biopsy-proven myocarditis. After receiving prolonged ventricular assist system support, all four patients had significantly improved left ventricular function, returning to New York Heart Association functional class I without inotropic therapy. In each case, dobutamine stress echocardiography and invasive hemodynamic tests were performed to confirm improvement of cardiac function before device explantation was undertaken. In all four cases, device explantation was followed by early successful maintenance of left ventricular function. These cases reveal a unique clinical syndrome that may be successfully treated with early institution of ventricular assist system support followed by explantation after myocardial recovery.     

Clinical aspects of myocarditis--symptomatology, diagnosis and pathogenesis]

On the basis of newer knowledge from literature in a survey aspects of symptomatology, diagnostics and course of the myocarditis important for practice are represented. According to the frequency of the virus myocarditis is referred to the importance of immunopathogenetic factors for prognosis and course. Own experiences confirm the transition from an acute myocarditis into a chronic cardiomyopathy which was observed by various investigators. In a 17-year-old female patient the development of a congestive cardiomyopathy after acute myocarditis could be pursued for several years. After-examination of 58 patients after acute myocarditis resulted after 3 years in 62% in cardiac residual symptoms, in which cases anamnestic data and objective findings of the examination well correlated. In 14 patients (24.1%) chronic recidivating courses were found. The importance of the biopsy of the endomyocardium for the diagnostics and differential diagnostics of cardiomyopathies is represented at the instance of a 20-year-old male with subacute rheumatic myocarditis who was hospitalised on account of symptoms of a left heart insufficiency, enlargement of the heart and a picture of a left hypertrophy in the ECG. Bioptically was found a hypertrophy with formation of a large nucleus. After 1 1/2 years clinical improvement and normalisation of size of the heart and ECG. The control biopsy now resulted in normal findings of the heart.     

Strain Doppler echocardiography can identify longitudinal myocardial dysfunction derived from edema in acute myocarditis

Usually, during acute phase of focal myocarditis, edema is located in the epicardial layer of the ventricular wall and it can't be associated with clear evidence of wall motion abnormalities on echocardiography. Among many cardiac imaging techniques, only cardiac magnetic resonance (CMR) and computer tomography permit a direct detection of edema during acute myocarditis.

We report a case where strain Doppler echocardiography was able to identify longitudinal segmental myocardial dysfunction derived from edema in acute phase of myocarditis. The strain Doppler echocardiography was compared with cardiac magnetic resonance.     

Structural and electrical ventricular remodeling in rat acute myocarditis and subsequent heart failure

OBJECTIVE: We reported that experimental autoimmune myocarditis (EAM) rats showed dramatic changes in ventricular action potential and enhanced arrhythmogenicity in the acute phase, but mechanisms for this are still unclear. To investigate the mechanisms of cardiac remodeling in acute myocarditis and subsequent heart failure, physiological and molecular changes were evaluated along the time course of EAM. METHODS: Six-week-old Lewis rats were immunized with porcine cardiac myosin. On days 14, 21, 35 and 60 after immunization, histology, hemodynamics and electrophysiological parameters (i.e., effective refractory period (ERP), monophasic action potential duration (MAPD) and PVC inducibility) were evaluated and compared with control rats. After these studies, the expression levels of Kv(+) and L-Ca(2+) channels, ion transporters and BNP expressions in the left ventricle were examined by quantitative real time RT-PCR and Western blot analysis. RESULTS: EAM rats showed acute myocarditis with massive infiltration of the mononuclear cells on days 14 and 21. Subsequently, a chronic dilated cardiomyopathy (DCM)-like structural change was observed on day 60. Hemodynamic parameters were worse in EAM than controls. ERP and MAPD were longer in EAM than controls, with a peak on day 21, which was parallel to PVC inducibility. mRNA levels of Kv4.2, Kv1.5, KChIP2, frequenin and SERCA2a, and the protein levels of Kv4.2 and Kv1.5, were reduced, especially in the acute phase. CONCLUSIONS: The initial reduction of Ito-related molecules, such as the expression levels of Kv4.2, 1.5, frequenin and KChIP2, and the prolongation of MAPD are considered to be a key mechanism of ventricular remodeling and cause the characteristic clinical findings in EAM in the acute inflammatory phase and chronic DCM phase.