Visual Diagnosis: Chest Pain in a Boy With Duchenne Muscular Dystrophy and Cardiomyopathy

A 17-year-old boy with Duchenne muscular dystrophy (DMD) due to a deletion of exons 18 to 37 in the DMD gene was diagnosed in our clinic as having cardiomyopathy at age 12 years. His current medications include deflazacort (30 mg/d), lisinopril (10 mg once daily for cardiomyopathy), and metoprolol succinate (50 mg twice daily for disordered automaticity). His cardiac function had been stable, with ejection fractions (EFs) ranging from 47% to 55%.After 1 day of headache and emesis, he presents to a local emergency department with acute onset of chest pain and shortness of breath. Electrocardiography (ECG) reveals ST-segment elevation in the inferolateral leads and ST-segment depression in the midprecordial leads, which prompts further testing (Figure 1). His initial troponin I level is elevated. He is transferred to a tertiary care facility for further evaluation. At the time of admission, his chest pain is substantially improved without intervention, but his troponin I level is now 40.27 ng/mL (40.27 μg/L) (reference range, <0.04 ng/mL [<0.04 μg/L]). Further laboratory evaluation reveals a white blood cell count of 12,900 /μL, 72% neutrophils, 20% lymphocytes, a C-reactive protein level of 299.8 mg/L (2855.3 nmol/L) (reference range, <12.0 mg/L [114.3 nmol/L]), and a lactate level of 7.2 mg/dL (0.8 mmol/L) (reference range, 4.5-19.8 mg/dL [0.5-2.2 mmol/L]). Cardiac magnetic resonance imaging (CMRI) with late gadolinium enhancement (LGE) reveals extensive left ventricular lateral wall epicardial enhancement (Figure 2A) and an EF of 50%. Quantitative T2 mapping reveals an increased T2 signal (80 milliseconds compared with 48 milliseconds in the unaffected interventricular septum) in the same region consistent with acute inflammation and injury (Figure 3A).A diagnosis of acute myocarditis superimposed on left ventricular cardiomyopathy secondary to DMD was made. Chest pain can certainly be a presenting sign of myocarditis, although this is not necessary and may be absent. In this patient's case, the initial ECG is markedly abnormal with ST-segment changes. Although the most common ECG abnormality in myocarditis is diffuse T-wave inversion, the finding of ST-segment elevation, combined with the presenting symptoms, appropriately warrants further evaluation of a cardiac cause of his chest pain. The elevated C-reactive protein and troponin I levels should significantly raise the concern for myocarditis as a possible cause of his symptoms and abnormal laboratory test results. In this case, further evaluation was performed using CMRI, including T2 mapping, which revealed evidence of inflammation and confirmed a case of acute myocarditis superimposed on his underlying cardiomyopathy related to DMD.Chest pain, especially when coupled with shortness of breath, presents an extensive differential diagnosis that includes musculoskeletal, pulmonary, gastrointestinal, cardiac, and psychogenic causes. Musculoskeletal causes can include trauma, costochondritis, muscle strain, and rib or thoracic spine abnormalities. Respiratory causes may include severe cough related to viral or bacterial pneumonia, pleural effusions, and asthma.Although patients with neuromuscular disorders may have multiple causes of chest pain, they still remain at risk for nonneuromuscular causes of chest pain. In patients with neuromuscular disorders who experience shortness of breath, one must consider respiratory muscle weakness and restrictive lung disease secondary to thoracic cage deformities and scoliosis. Some neuromuscular disorders can also cause chest pain secondary to esophageal spasms. Cardiac causes can include pericarditis, myocarditis, arrhythmias (including both supraventricular and ventricular arrhythmias), coronary artery abnormalities, and ischemic heart disease. Although many of these cardiac manifestations are rare, patients with neuromuscular disorders and cardiac manifestations are at the same risk for cardiac causes of chest pain as the general population. As such, they require thorough evaluation for potentially treatable causes of chest pain. In this case, appropriate screening led to evaluation of troponin I and ultimately CMRI, confirming the diagnosis of acute myocarditis.Acute myocarditis is an inflammatory disease that affects the heart muscle. It is underrecognized in the general population because chest pain may resolve by the time the patient is evaluated. The true incidence of myocarditis is not known. Myocarditis is typically secondary to an antecedent viral infection or postviral immune-mediated response. The most common infectious causes include adenovirus, enterovirus (Coxsackie A and B), parvovirus B19, cytomegalovirus, herpesvirus, influenza A virus, and Epstein-Barr virus. Of interest, abnormal DMD has been identified as a susceptibility gene for myocardial viral infections, and dystrophin deficiency has been found to increase enteroviral-induced cardiomyopathy. There have been previous reports of boys with DMD diagnosed as acute myocarditis. However, these boys were younger than this patient and had normal left ventricular function before their diagnosis. In addition, rapid deterioration of left ventricular function in boys with DMD has been found after evidence of myocardial inflammation, defined by LGE on CMRI. In this study, two-thirds of the endomyocardial biopsy specimens obtained from the interventricular septum remote from the area of LGE had evidence of myocarditis, either active or healing.In the current era, endomyocardial biopsy and the Dallas criteria are infrequently used for the diagnosis of acute myocarditis, and a current multi-institution study found that endomyocardial biopsy was performed in less than one-fifth of cases of pediatric myocarditis. Clinicians now typically rely on the history, serologic evidence of a viral infection typical for myocarditis, echocardiogram, and CMRI, which is able to produce evidence of acute inflammation as evidenced by LGE of the involved myocardium. In the standard approach to endomyocardial biopsy, only the right ventricle myocardium is sampled. Combined with the patchy myocardial involvement in acute myocarditis, endomyocardial biopsy has a significant false-negative rate. The advantages of CMRI for the assessment of acute myocarditis include the noninvasive nature of the testing, the ability to study the myocardium of the left and right ventricles, and the ability to detect inflammation and edema using techniques such as LGE and T2 mapping. LGE imaging is performed several minutes after the initial injection of gadolinium and allows visualization of injured myocardium and fibrosis, appearing as hyperintense areas, because the contrast is retained in these tissues longer than healthy myocardium. Quantitative T2 mapping is a technique used to assess for myocardial edema. It is similar to T2-weighted imaging, but it eliminates many of the limitations of T2-weighted sequences and allows for a quantitative, rather than qualitative, assessment of the myocardium.In the DMD population, CMRI typically reveals subepicardial enhancement of the posterobasal regions of the left ventricle, which is thought to be secondary to fibrosis. Although our patient had the expected pattern of LGE consistent with that previously reported in patients with DMD, he also had evidence of increased T2 signal on quantitative T2 mapping consistent with edema from acute injury and inflammation. Quantitative T2 mapping reliably identifies the extent of myocardial involvement in myocarditis and has a high sensitivity and specificity (94% and 97%, respectively). Quantitative T2 mapping can also provide diagnostic data in patients who have difficulty with breath holding (eg, patients with neuromuscular disorders), providing better assessment of the extent of involvement compared with wall motion abnormalities (by echocardiography), LGE, and conventional T2-weighted imaging. As the field of CMRI continues to advance, additional, more sophisticated imaging techniques have in addition to quantitative T2 mapping become available, including myocardial T1 mapping and quantification of diffuse interstitial fibrosis.Treatment of acute myocarditis is controversial and predominantly supportive in the case of a viral cause. Many institutions administer intravenous immunoglobulin, but data regarding the benefit of intravenous immunoglobulin are lacking. Alternatively, corticosteroids are beneficial in some case series and randomized trials, but the fact that many patients recover spontaneously questions whether administering corticosteroids truly improves outcome. In the setting of moderate or severe cardiac dysfunction, inotropic support is warranted. Milrinone is typically used in the acute care setting, and the patient is typically transitioned to an oral regimen that consists of an angiotensin-converting enzyme inhibitor with or without additional heart failure medications (β-blockers or diuretics), depending on the degree of residual ventricular dysfunction. In some cases, mechanical support via extracorporeal membrane oxygenation or left ventricular assist device may be warranted.Evaluation for a viral cause was unnecessary because the patient's CMRI was diagnostic for acute myocarditis, most likely of viral origin. His troponin I level decreased, and he became asymptomatic during 3 days of hospitalization. At discharge, his troponin I level was 14.5 ng/mL (14.5 μg/L), and 1 week later, his troponin I level was 0.2 ng/mL (0.2 μg/L). At that time, his echocardiogram revealed an EF of 57%. Three months after discharge, his EF by CMRI was 55%, and LGE imaging again revealed extensive left ventricular lateral wall epicardial enhancement (Figure 2B). However, his quantitative T2 mapping revealed normalized T2 imaging (53 milliseconds compared with 52 milliseconds in the unaffected interventricular septum), suggesting improvement in the inflammation and injury (Figure 3B). He remained asymptomatic, and no further troponin I levels were measured.Our patient's CMRI findings, in combination with his abnormal ECG findings and elevated troponin I level, led to the diagnosis of acute myocarditis, and his clinical course was consistent with this diagnosis. This case highlights (1) utility of appropriate screening tests to guide further evaluation, (2) the importance of a high index of suspicion for myocarditis in patients with DMD with an acute change in symptoms, and (3) the utility of troponin I levels and novel CMRI techniques in establishing the diagnosis. Although dystrophin deficiency may increase the susceptibility to viral myocarditis and myocarditis may hasten the decline in cardiac function, we would caution against the generalization of LGE on CMRI as evidence of myocarditis or prognosticating rapid decline in cardiac function in all boys with DMD. Rather, we believe that it is important to differentiate LGE due to fibrosis and LGE secondary to active myocarditis.