Parvovirus B19–Associated Active Myocarditis With Biventricular Thrombi Results of Endomyocardial Biopsy Investigations and Cardiac Magnetic Resonance Imaging
A previously healthy 39-year-old man was admitted to our department with biventricular cardiac decompensation (New York Heart Association class IV) and acute onset of angina pectoris after a flulike disease 1 week earlier. The ECG on admission displayed ST elevations in II, III, and aVF. Troponin T on admission was increased (2.20 mg/L, normal value<0.03 mg/L), with increased creatine phosphokinase (503 U/L; normal value<171 U/L) and creatine phosphokinase myocardial band (45 U/L; normal value=10 U/L). N-terminal pro-brain natriuretic peptide was highly elevated (15,848 pg/mL; normal value<125 pg/mL). Coronary artery disease was excluded by coronary angiography. Multiple nonsustained ventricular tachycardias were recorded by Holter monitoring and telemetry.
Endomyocardial biopsies obtained from the right ventricular septum demonstrated active myocarditis by histological investigations according to the Dallas criteria (Figure 1A). By immunohistological staining of endomyocardial biopsies1 and quantification using digital image analysis, highly increased focal lymphocytic (CD3+: 267.4/mm2, CD11a/LFA-1+: 498.9/mm2; Figure 1B) and macrophage infiltrates (CD11b/Mac-1+: 481.6/mm2), sarcolemmal human leukocyte antigen class I expression (area fraction of human leukocyte antigen class I=35.6%; Figure 1C), and focal abundance of CD54/ICAM-1 (area fraction=4.7%) and CD106/VCAM-1 (area fraction: 0.22%) were detected. Nested polymerase chain reaction for cardiotropic viruses2 confirmed parvovirus B19 genomes in endomyocardial biopsies, with a parvovirus B19 virus load at 458 viral copies per microgram of nucleic acid as determined by real-time polymerase chain reaction. Cardiac magnetic resonance imaging (MRI) showed a severely depressed left ventricular ejection fraction (17%; Movie I). Left ventricular end diastolic volume (204 mL/m2) and left ventricular end systolic volume (169 mL/m2) were increased (normal values: left ventricular end diastolic volume=53 to 112 mL/m2, left ventricular end systolic volume=15 to 45 mL/m2). Moreover, apical thrombi were detected in both the left and right ventricles (Figure 2A). Hypo-/akinetic regions in the apical, inferoseptal, and inferolateral segments were colocalized with late gadolinium–diethylene triamine pentaacetic acid enhancement (LE)3 (Figure 2A). Increased edema ratio (2.2; scanner-dependent normal value<2.0) was detected in T2-weighted images (Figure 2C), localized at the inferoseptal and lateral wall. Global relative enhancement calculated from the spin echo images4 was highly elevated (7.4; normal value<4.0), consistent with florid myocarditis (Figure 2E).
Cardiac recompensation was initiated with heart failure medication (diuretics, ramipril, carvedilol, eplerenone, and digitalis). In light of the known potential of acute myocarditis, which was confirmed in this case by histology, immunohistology, and cardiac MRI, for spontaneous improvement, we opted for an observational strategy and did not implant an implantable cardioverter defibrillator for primary prevention of sudden cardiac death. The patient was set on anticoagulation with heparin and then with phenprocoumon (international normalized ratio=2.0 to 3.0). The patient was discharged at a recompensated status (New York Heart Association class II).
The patient was reevaluated 8 weeks after discharge in our outpatient clinic. The N-terminal pro-brain natriuretic peptide had decreased substantially from 15 848 to 1435 pg/mL. Cardiac MRI showed an improved left ventricular ejection fraction to 38% (Movie II), left ventricular end diastolic volume had decreased to 117 mL/m2, and left ventricular end systolic volume had decreased to 73 mL/m2. The late enhancement areas had not changed substantially (Figure 2B). However, the edema ratio had decreased to a marginally elevated 2.0 (Figure 2D), and global relative enhancement had decreased substantially to normal values (1.9, Figure 2F). Furthermore, no left or right ventricular thrombi were detectable. Holter monitoring did not record any ventricular tachycardias at follow-up.
Endomyocardial biopsies and MRI investigations are suitable to identify acute myocarditis as a potentially reversible cause of a recent-onset left ventricular dysfunction and, therefore, may be helpful in deciding whether to use implantable cardioverter defibrillator implantation for primary sudden cardiac death prevention in patients with recently diagnosed nonischemic cardiomyopathy.5 Cardiac MRI is potentially useful for monitoring the natural course of cardiac inflammation noninvasively. In this respect, late enhancement may be superposed by cardiac injury processes, whereas edema ratio and, especially, global relative enhancement may reflect more specifically and sensitively the dynamics of the inflammatory process after the onset of acute myocarditis, as recently elucidated in patients with clinically suspected chronic myocarditis.6
These investigations have been supported by the Deutsche Forschungsgemeinschaft through the Sonderforschungsbereich Trans-Regio 19 (TPZ1 to UK and HPS).
The online-only Data Supplement, consisting of Movies I and II, is available with this article at http://circ.ahajournals.org/cgi/content/full/115/13/e378/DC1.
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