FAQ on What an Autopsy Might Reveal

Unlike many human ailments, myocarditis is rarely determined to be the cause of death based on symptoms or physical examinations. Unfortunately, there is no blood test that can be performed that is specific for myocarditis. Without an autopsy, myocarditis is most often assigned as a cause of death due to a high degree of suspicion of its presence based on a strategy involving:

• A patient’s physician or care team who have a careful history of events before death
• Family members who observed what happened in the weeks, days or hours before death
• Suggestive laboratory tests, imaging, and clinical symptoms

With an autopsy, myocarditis can be assigned as the cause of death with a high degree of certainty based on:

• Careful gross analysis of the heart tissue
• Microscopic review of heart tissue looking for specific features of myocarditis
• The exclusion of other potential causes of death across all of the body organs

There is no test that perfectly diagnoses myocarditis, but many tests can give clues. Because myocarditis may affect characteristic electrical activity, inflammation and damage of the heart may be suggested in life by electrocardiography (ECG) scans. Certain shapes of waves or tracings seen on ECGs, or the rate and rhythm of the heart as reflected on the ECG may point to the possibility of myocarditis. The details of these changes should be appraised by a cardiologist, internist, pediatrician or family medicine physician.  Such ECG abnormalities may also suggest pericarditis, that is, inflammation of the heart’s membrane sac.

Another method becoming more common is the use of cardiac MRI, which is an imaging scan of one’s heart. Using special criteria, a radiologist can suggest myocarditis is present based on findings related to heart function and swelling in the heart tissue.

At specialized centers, a heart biopsy can be performed to diagnose myocarditis. The heart tissue is read by a cardiovascular pathologist trained to look for features in the tissue that indicate myocarditis including inflammatory cells in the heart and myocyte injury. While a positive result is diagnostic of myocarditis, the inflammation in myocarditis can be missed by this method as only a small amount of tissue can be studied.

Additional tests that might support the presence of myocarditis include:

• An abnormal white blood cell (inflammatory cell) count
• Elevated C-reactive protein levels (CRP) (marker of inflammation)
• Increased erythrocyte sedimentation rate (ESR) (marker of inflammation)
• Modestly elevated circulating troponin in the blood (marker of heart muscle damage)
• Other markers of heart failure such as N-terminal pro-B-type natriuretic peptide (NT-proBNP)

Many disease processes can be observed only by study of the patient’s tissues, including under a microscope. Pathologists, especially with specialist training, can undertake histological analysis of tissues with a microscope at the time of autopsy. Such tissues are taken in a systematic way from the heart including from the heart muscle of the pumping chambers called ventricles. The cutting and staining of the tissues includes standard stains along with special stains to look for scarring and inflammatory cells. The latter stains may highlight areas of heart muscle injury. Other approaches may even detect the presence of viral genes that are markers of viruses that can attack the heart muscle.  The disease processes associated with myocarditis can only be diagnosed by these direct examinations and with expert study.  While it’s impossible to achieve sufficient tissue samples to assure exclusion of myocarditis as the cause of heart disease by biopsy of tiny samples while a patient is alive, an autopsy provides much greater access to tissue for more thorough analysis.

So, in summary, study of the tissues (including the use of a microscope and special molecular techniques) can reveal a wide range of disease indicators, including:

• Certain kinds of inflammatory cells including lymphocytes, macrophages, giant cells, and eosinophils
• Areas of cell death, particularly heart muscle cells (called cardiomyocytes) that may underlie heart failure or heart rhythm disturbances

The inflammatory cells play a role in fighting against cells infected by certain viruses to keep the body healthy, but they can also unintentionally damage uninfected cells, killing them as well. The microscopic analysis may detect these inflammatory cells, as well as the injured or dead cardiomyocytes, the vital cells that allow the heart to contract.

An experienced pathologist who understands myocarditis in its various forms and phases can identify it after death via histological patterns observable under the microscope and detected through an autopsy. Generally, multiple parts of the heart tissue are reviewed to look for these clues. When myocarditis is present, these are the types of cell infiltrates with their possible causes:

• Lymphocytes and Macrophages: Myocarditis due to viral infection, cancer treatment, or autoimmune disorder
• Eosinophils: Hypersensitivity myocarditis; may also indicate hypereosinophilic syndrome due to adverse drug reactions
• Granulomas: Giant cell myocarditis or cardiac sarcoidosis, tuberculosis or fungus, or deposits of particulates like talc
• Neutrophils: Myocarditis due to bacterial, fungal, or early viral infection, or ischemic cell death as seen in vascular occlusion

Histology can also provide information about the phase of myocarditis, including:

• Acute (recent onset): The presence of an early inflammatory infiltrate, a small amount of myocyte injury and little change to the overall structure of the tissue.
• Subacute: Inflammatory cell infiltrate and associated myocyte injury with apparent edema (excess water spreading the tissues apart). Some early reparative processes in the tissue may be occurring and larger structural changes including dilation (enlargement) of the ventricular chambers that pump blood through the heart and body or thinned ventricular walls
• Chronic: An established change to the heart tissue with scarring, that can be described as interstitial fibrosis and the continued presence of inflammatory cells. Larger structural changes including dilation or thinned ventricular walls can be pronounced. These changes are less specific to myocarditis than acute or subacute changes as they overlap with another disease called dilated cardiomyopathy

Thanks in part to the Myocarditis Foundation’s support, an international group of cardiovascular pathologists have recently created standardized criteria to diagnose lymphocytic myocarditis at autopsy.  This diagnosis relies on injury to heart cells (myocytes) and a lymphocyte infiltrate.

 

Changes in the heart caused by myocarditis are almost impossible to be certain of, even for the most experienced physicians. However, corresponding symptoms and some clinical scenarios may support a request for an autopsy to be performed. These symptoms could be mild or severe:

• Unexplained chest pain
• Rapid or irregular heartbeat
• Shortness of breath
• Faintness or lightheadedness
• Fluid retention in the lower legs
• Fatigue
• Unexplained sudden death
• The use of immune check point inhibitor drugs to treat cancer

Children with myocarditis often present with symptoms that include difficult/rapid breathing, fever, fainting, and/or discoloration of the skin.

Serology, or testing that identifies antibodies in the blood, can also help guide diagnosis. If antibodies to known common viral, bacterial, and other infectious agents that cause myocarditis, it may indicate such a cause of myocarditis. Further investigation is advised including performing an autopsy if the patient passes away.