An empiric diagnosis of myocarditis is often based on a combination of clinical findings including altered ECG, increase in myocardial enzymes, and lack of significant CAD.6 The recommended diagnostic cardiac magnetic resonance (CMR) imaging criteria for clinically suspected myocardial inflammation (ie, the Lake Louise Criteria) include at least two of the following:7
• Regional or global myocardial signal intensity increase in T2-weighted images.
• Increased global myocardial early gadolinium enhancement ratio between myocardium and skeletal muscle in gadolinium-enhanced T1-weighted images.
• At least one focal lesion with nonischemic regional distribution in inversion recovery–prepared gadolinium-enhanced T1-weighted images (“late gadolinium enhancement”).
Because of its reported high sensitivity and specificity (100% and 90%, respectively), CMR was used in the case patient to confirm the diagnosis of myocarditis.8 Specifically, CMR with contrast demonstrated normal left ventricular cavity size and mild reduction in overall left ventricular systolic function, with a visually estimated left ventricular ejection fraction of 45% to 50%. Regional hypokinesis of the mid-inferior wall and apical inferior septum was noted. Delayed contrast imaging demonstrated extensive non-CAD scarring and fibrosis, involving the basal anterior wall, basal inferior wall, and basal and midlateral wall in a pattern consistent with acute myocarditis.
Just as there is variability in the specific criteria by which the diagnosis of myocarditis can be made, the array of clinical findings with which it can manifest range from fatigue and other nonspecific symptoms to fulminant congestive heart failure and sudden death.6 Often, but not always, a viral prodrome precedes the onset of “cardiac symptoms” (eg, chest pain, dyspnea, palpitations, or syncope).5 This patient’s multiple risk factors for CAD and a suggestive, albeit atypical, history of chest discomfort, palpitations, and shortness of breath helped to focus the clinicians’ evaluation on the heart.
Potential Causes
Once a diagnosis of myocarditis is rendered, the next challenge is distinguishing its specific source from a plethora of potential etiologies, including infection, toxic exposure, or hypersensitivity/autoimmune reaction. Viral infections (mostly herpes, parvovirus, and cytomegalovirus) are thought to cause most cases of myocarditis in developed countries.5,9
Viral myocarditis results when viruses enter cardiac myocytes and incite a cytotoxic effect with activation of the immune response, including expression of interferon , natural killer cells, and release of nitric oxide. The majority of patients recover, but some develop an adaptive immune response, which further causes cardiac damage. In this response, antibodies to viral and to some cardiac proteins are produced, and effector T lymphocytes proliferate. Viral genome or inflammatory mechanisms may persist, contributing to ventricular dysfunction leading to heart failure and arrhythmias.10
Celiac disease is a chronic gastroenterologic disease caused by an immune response to a gluten protein. Damage to the brush border of the small intestine results in an inability to absorb fat, protein, vitamins, and minerals. Intermittent diarrhea, abdominal pain, and bloating are most commonly reported, but celiac disease may also manifest less obviously with iron deficiency anemia, joint pain, muscle cramps, osteoporosis, and neuropathy.11 Iron deficiency anemia that is refractory to iron replacement may offer insight into diagnosing myocarditis due to celiac disease.12 Although studies have found that more than 4% of patients with myocarditis also had celiac disease, none had the classic GI symptoms of celiac disease.12
Takotsubo cardiomyopathy is a transient left ventricular apical ballooning syndrome of unknown etiology. (For more information, see Fasolino T. Takotsubo cardiomyopathy: a clinical overview). Patients who have experienced emotional or physiologic stress and postmenopausal women appear to be at greatest risk. The clinical symptoms mimic MI, including chest pain with ST-segment elevation in the precordial leads on ECG13 and minor elevation of the cardiac enzyme and biomarker levels.14 However, patients experiencing this stress cardiomyopathy lack evidence of atherosclerotic CAD.15 An echocardiogram or CMR imaging reveals characteristic wall motion hypokinesis, akinesis, or dyskinesis of the left ventricular apex and mid-ventricle that help to differentiate it from other forms of myocarditis.15,16 Patient prognosis is favorable, with 95% of patients experiencing a full recovery; left ventricular dysfunction usually begins to improve in a few weeks.13,14
Sarcoidosis is a systemic disease resulting in noncaseating granulomas in multiple organs.17 Initial presentation typically includes bilateral hilar adenopathy, pulmonary reticular opacities, and/or skin, joint, or eye lesions.18 Patients with cardiac sarcoidosis most commonly present with conduction disturbances and ventricular arrhythmias.17 Although frequently absent, clinical symptoms may include palpitations, syncope, dizziness, or chest pain and clinical heart failure.17,18 It is difficult to distinguish cardiac sarcoidosis from other forms of myocarditis unless signs of systemic sarcoidosis are evident. A patient with suspected cardiac sarcoidosis should have an ECG to detect subclinical conduction abnormalities.17 The patient should wear a Holter monitor for 24 hours to screen for cardiac involvement, and echocardiography should be performed to define cardiac abnormalities.19