A 38-year-old African American man presented to the emergency room with shortness of breath, chest and abdominal pains of 4 days duration. An electrocardiogram (ECG) revealed acute antero-lateral myocardial infarction and a conduction delay with A-V dissociation. He was in shock with low cardiac output and renal insufficiency. His physical exam on admission was significant for tachycardia (100-110 ppm), hypotension (80/50 mmHg), an S3 gallop and bilateral rales up to mid-lung fields.
Laboratory data and other tests
Laboratory: WBC 16, Hb/Hct 12.5/38, Plt 210; BUN/creat 30/1.5, glucose 148; CK 900 (MB 7.8), LD 1790. Combined M mode and 2-D echocardiograms demonstrated normal valves, decreased cardiac output, enlarged left atrium and ventricle, moderate mitral regurgitation, right-sided chambers of normal size and severe antero-lateral left ventricular wall hypokinesis. A small posterior pericardial effusion was also noted. Blood and sputum cultures were negative.
Laboratory: WBC 16, Hb/Hct 12.5/38, Plt 210; BUN/creat 30/1.5, glucose 148; CK 900 (MB 7.8), LD 1790. Combined M mode and 2-D echocardiograms demonstrated normal valves, decreased cardiac output, enlarged left atrium and ventricle, moderate mitral regurgitation, right-sided chambers of normal size and severe antero-lateral left ventricular wall hypokinesis. A small posterior pericardial effusion was also noted. Blood and sputum cultures were negative.
The diagnosis of acute CHF secondary to an acute myocardial infarction was made. He was treated with dobutamine, furosemide and oxygen. Shortly after endotracheal intubation he developed cardiac tachyarrhythmias with subsequent electromechanical dissociation. Resuscitation was unsuccessful.
Gross Description
The body was that of a well-developed, well-nourished 38-year-old man measuring 1.70 m and weighing 80 kg. The heart weighed 480 g. Both right and left chambers were dilated (Figure 1). The epicardial surface was mildly roughened. There were no other significant findings except for areas of yellow discoloration in the myocardium and moderate atherosclerosis involving the left anterior descending coronary artery. The lungs were congested, edematous and weighed 2150 g.
The body was that of a well-developed, well-nourished 38-year-old man measuring 1.70 m and weighing 80 kg. The heart weighed 480 g. Both right and left chambers were dilated (Figure 1). The epicardial surface was mildly roughened. There were no other significant findings except for areas of yellow discoloration in the myocardium and moderate atherosclerosis involving the left anterior descending coronary artery. The lungs were congested, edematous and weighed 2150 g.
Figure 1 Myocarditis. Globular dilatation of the heart as aresult of remodeling
Microscopic Description
H&E stained sections of the heart revealed extensive diffuse myocarditis. The infiltrate was predominantly lymphocytic and involved all chambers including the conduction system at the base of the heart, as well as the papillary muscles. The lymphocytes appeared reactive with enlarged irregular nuclei (Figure 2). Extensive confluent and focal transmural myocardial necrosis was noted. Inflammation and necrosis were seen adjacent to the atrio-ventricular conduction system, which explains the conduction block on presentation. Histologic features of organization and granulation tissue formation were consistent with an interval of 10-14 days. Other areas were less than a week old and many foci showed acute active inflammation (24 hours). Active inflammatory pericarditis was also noted. Additional findings included congestion of the lungs, spleen and liver, consistent with the clinical diagnosis of acute congestive heart failure.
H&E stained sections of the heart revealed extensive diffuse myocarditis. The infiltrate was predominantly lymphocytic and involved all chambers including the conduction system at the base of the heart, as well as the papillary muscles. The lymphocytes appeared reactive with enlarged irregular nuclei (Figure 2). Extensive confluent and focal transmural myocardial necrosis was noted. Inflammation and necrosis were seen adjacent to the atrio-ventricular conduction system, which explains the conduction block on presentation. Histologic features of organization and granulation tissue formation were consistent with an interval of 10-14 days. Other areas were less than a week old and many foci showed acute active inflammation (24 hours). Active inflammatory pericarditis was also noted. Additional findings included congestion of the lungs, spleen and liver, consistent with the clinical diagnosis of acute congestive heart failure.
Figure 2 Myocarditis, histologic section. Lymphocytes infiltrate around necrotic myocytes (Hematoxylin and Eosin 40x)
Case Analysis
Inflammation of the human myocardium due to infectious and noninfectious agents is collectively termed as myocarditis. This case represents an atypical presentation of myocarditis in an adult, but would be the commonest one in children. The fulminant presentation is usually secondary to a viral infection of the cardiac tissues, and with appropriate cultures the virus may be grown. The onset and progression tend to be relatively rapid and the outcome is usually fatal over a period of days to weeks. The atypical lymphocytes infiltrating this patient’s heart are consistent with an acute reaction to a viral agent. The adult often presents with a more indolent course and the pathogenesis is invariably immunologic.
Inflammation of the human myocardium due to infectious and noninfectious agents is collectively termed as myocarditis. This case represents an atypical presentation of myocarditis in an adult, but would be the commonest one in children. The fulminant presentation is usually secondary to a viral infection of the cardiac tissues, and with appropriate cultures the virus may be grown. The onset and progression tend to be relatively rapid and the outcome is usually fatal over a period of days to weeks. The atypical lymphocytes infiltrating this patient’s heart are consistent with an acute reaction to a viral agent. The adult often presents with a more indolent course and the pathogenesis is invariably immunologic.
The extensive multifocal, and in some areas, confluent myocardial damage seen in this patient, can resemble clinically a transmural myocardial infarction. Both the ECG and the cardiac enzyme elevations were indicative of myocardial necrosis. However, in contrast to the global injury seen in fulminant myocarditis, the damage seen in a myocardial infarction is generally limited to the territory of a coronary artery. Although the autopsy revealed moderate atherosclerosis of the left anterior descending coronary artery, ischemia played no role in the myocardial damage.
The histology demonstrated that extensive damage was at least 2 weeks old at the time of the patient’s demise, although he allegedly was not symptomatic until 4 days prior to admission. It is not unusual for myocarditis to be clinically “silent” until sufficient myocardium is damaged to lead to the development of CHF, arrhythmia, chest pain, or sudden death. In this case, even if the patient had been admitted several days prior to the onset of his symptoms, the outcome would have probably been the same. The damage was so extensive that supportive therapy with vasopressors and/or intra-aortic balloon pump, would have been only of short term benefit.
Other non-infectious etiologies to consider in this patient include immune-mediated diseases, and toxic and drug related injury. Although, there is no clinical history to support either of these possibilities, they may have fulminant presentations as well. However, the pathology in such acute cases may be of significant value, since it can identify features associated with specific etiologies (e.g. rheumatoid nodules in rheumatoid arthritis involving the conduction system).
In Europe and the United States of America the most important infectious cause of myocarditis are viruses, of which Coxsackie A and B, ECHO and Influenza A and B are the major types. In this patient, even if the viral agent had been identified, specific antiviral treatments are not currently available. In addition, immunosuppressive therapy is of no value in fulminant myocarditis, and may even exacerbate the already severe condition. In South and Central America parasitic infections of the heart account for a significant number of myocarditis cases with Chaga’s disease one of its main causes, along with chronic cardiomyopathy. Furthermore, with increasing numbers of immunocompromised patients, disseminated infections (HIV/AIDS, toxoplasmosis, aspergillosis, candidiasis) will continue to be associated with myocardial damage and dysfunction.
The clinical course of myocarditis depends not only in the causative agent, but also in the type, degree and duration of the damage. The host plays a pivotal role because of the genetic determinants that define its inherent susceptibility and the response to the injury. The various infectious agents may directly affect the myocytes, exert a cytotoxic effect (toxin-mediated), cause injury via an immune-mediated mechanism or cause myocardial dysfunction as it spreads from adjacent inflammatory foci. In addition, these agents can induce a vascular damage that in turn will affect the myocardium.
The specific immune alterations associated with myocarditis are unknown. The expression of major histocompatibility complex (MHC) antigens class I and II during the course of human viral myocarditis supports the possibility of this process having an autoimmune component. Messenger ribonucleic acid of perform, the pore-forming protein that mediates cytotoxicity, has been identified in the cytoplasmic granules of inflammatory cells. Interleukins 1, 6 and 8 as well as tumor necrosis factor also appear to play a role in myocardial damage. Recently, myosin-specific antibodies have been identified in the serum of a large percentage of adult patients with myocarditis. These antibodies may arise as a result of tissue injury or may induce actual tissue damage. Cytomegalovirus (CMV) induced cross-reacting antibodies to myosin have also been described. In certain mouse strains (DBA/2) there is an increased susceptibility to myocarditis following in vivo administration of myosin-specific antibodies. It appears that autoimmune myocarditis mediated by myosin-specific antibodies has a genetic basis, which is complex and has yet to be defined.
Endomyocardial biopsies to evaluate the presence of myocarditis are obtained from the right side of the ventricular septum. The Dallas Classification was developed to standardize the histopathological diagnosis of active and chronic myocarditis. In the acute cases, in addition to the inflammatory infiltrate, there is necrosis and degeneration of myocytes. However, clinical improvement usually precedes histologic recovery. In chronic myocarditis, necrosis is not a required feature, but interstitial fibrosis and loss of myofibers will indicate the degree of severity of the injury. Other terms such as ongoing, resolving and healed myocarditis can be used in subsequent biopsies.
In this case, the outcome was determined by the diffuse and extensive acute inflammatory damage to the myocardium. Although some authors have proposed that fulminant Myocarditis can have a good long-term prognosis, the majority of patients die as a result of severe hemodynamic alterations.
0 comments:
Post a Comment