Myocarditis and Sudden Cardiac Death in the Young
Extensive Fibrosis Suggested by Cardiovascular Magnetic Resonance In Vivo and Confirmed Post Mortem
A 15-year-old male presented clinically with myocarditis. At follow-up, a 12-lead ECG (Figure 1A) and chest x-ray were performed (Figure 1B). Echocardiography was reported to show at least mildly impaired left ventricular function, and cardiovascular magnetic resonance (CMR) demonstrated a severely dilated impaired left ventricle (end-diastolic volume index, 160 mL/m2; ejection fraction, 42%), normal proximal coronary arteries, and a pattern of late gadolinium enhancement (LGE) which indicated extensive myocardial scarring as a result of myocarditis (Figure 2). The patient remained asymptomatic. Unfortunately, he died suddenly 2 years later. The post mortem distribution of scarring was concordant with the in vivo CMR LGE findings.
CMR inversion recovery images acquired late after application of paramagnetic contrast agents provide a sensitive tool for detection of myocardial fibrosis, which is distinguished by bright late-enhancement regions where the contrast lingers in the extracellular spaces of scarred myocardium. In our patient, full-thickness late enhancement of the lateral wall was seen (Figure 3, A, B, C, and D(i)) with a corresponding wall motion abnormality. Anterolateral papillary muscle scarring (Figure 3, B(i) and D(i), dotted arrows) was noted. If seen in isolation, these findings would be compatible with ischemic heart disease etiology, but additional patchy foci of enhancement in the septum and regions of patchy LGE with sparing of the subendocardium were also demonstrated suggesting nonischemic cardiomyopathy (Figures 3, C(i) and D(i), and 4⇓A(i), dashed arrows). Fibrosis after ischemic infarction includes the subendocardial layer of the myocardium. The patchy foci, epicardial LGE regions, and lateral wall distribution favored a CMR diagnosis of previously established myocarditis.
Patchy fibrotic change was confirmed post mortem, consistent with myocarditis as clinically suspected (Figures 3 and 4⇑). The coronary arteries were normal. In view of the extensive myocardial structural abnormality with no other abnormal findings and the patient’s sudden death, the likely cause of death was concluded to be cardiac. The in vivo CMR findings correlated with the pathological appearances of the heart post mortem, as shown when comparing Figure 3, A, B, C, D (i) showing regions of LGE with Figure 3, A, B, C, D (ii), showing corresponding pathological sections. Figure 4, A(i) shows areas of LGE with corresponding histology Figure 4, A(ii), B.
In Europe, viral infections represent the most important cause of myocarditis, though in chronic myocarditis viremia is often absent. Even when inflammatory changes of the myocardium are asymptomatic, as in most cases, myocardial fibrosis and dilated cardiomyopathy can occur, which results in heart failure. If at autopsy the subendocardial layer of the myocardium is not involved in the fibrosis, ischemic infarction is unlikely and can be excluded as a differential diagnosis of sudden death in the young in the vast majority of affected patients.
Although there were macroscopic abnormalities in our case, these are not always found at autopsy after sudden death as a result of myocarditis. Extensive histological screening is required to reveal isolated areas of myocardial fibrosis that may be related to myocarditis. In patients with acute or chronic myocarditis, arrhythmia may be the only clinical symptom in the natural course of the disease. Factors responsible for the increased incidence of cardiac arrhythmias include structural changes, ventricular hemodynamics, and vascular changes. The potentially malignant tachyarrhythmias and bradyarrhythmias caused by myocarditis are of particular concern. Acutely, inflammatory processes in the cardiac myocytes and interstitium can lead directly to fluctuations in membrane potential, hence arrythmogenesis. Later, fibrosis and scarring of the myocardium with secondary hypertrophy and atrophy of the myocytes can provide a substrate for arrhythmia as it causes slow conduction and favors the development of ectopic pacemakers, late potentials, and re-entry as a result of inhomogeneous stimulus conduction.
Myocarditis accounts for up to 20% of sudden cardiac deaths in young adults. In this case, CMR imaging with LGE provided in vivo tissue characterization as well as functional assessment, which allowed the etiology of the cardiomyopathy to be determined during life. Availability of the images directed the autopsy to enable the location of small areas of change within the myocardium. The extent of LGE on CMR is likely to reflect the burden of arrhythmogenic risk.
Sources of Funding
Dr Babu-Narayan was supported by the British Heart Foundation.
The online-only Data Supplement, consisting of movies, can be found at http://circ.ahajournals.org/cgi/content/full/116/6/e122/DC1.