title: Viral persistence in the myocardium is associated with progressive cardiac dysfunction.
abstract: BACKGROUND
  Cardiotropic viral infections have been suspected as one possible cause of myocarditis and dilated cardiomyopathy. Although adverse outcomes in dilated cardiomyopathy patients have been documented, the natural course of heart diseases caused by cardiotropic viruses is unknown.
  
  
  RESULTS
  Consecutive patients (n=172) with biopsy-proven viral infection in endomyocardial biopsies (EMBs) were followed up by reanalysis of EMBs and hemodynamic measurements after a median period of 6.8 months (range, 5.4 to 11.9). Nested polymerase chain reaction (PCR) and reverse transcription-PCR were performed to analyze the genomic sequences. Myocardial inflammation was assessed by histology and immunohistology. At baseline, 32.6% of EMBs in the study group contained enteroviral (EV) RNA, 8.1% adenovirus (ADV) DNA, 36.6% parvovirus B19 (PVB19) DNA, and 10.5% human herpesvirus type 6 (HHV6) DNA. In 12.2% of the samples, dual infection with PVB19 and HHV6 was present. Follow-up analysis of EMBs by PCR documented spontaneous clearance of viral genomes in 36.2% (55/151) of all patients with single infections. Virus-specific clearance rates were 50% for EV, 35.7% for ADV, 22.2% for PVB19, and 44.4% for HHV6. In patients with dual infection with PVB19+ and HHV6(+)-, HHV6 was cleared in 42.8% (9/21), whereas PVB19 persisted in all 21 patients. Clearance of viral genomes was associated with a significant improvement in left ventricular ejection fraction (LVEF), improving from 50.2+/-19.1% to 58.1+/-15.9% (P<0.001). In contrast, LV function decreased in patients with persisting viral genomes (LVEF, 54.3+/-16.1% versus 51.4+/-16.1%, P<0.01).
  
  
  CONCLUSIONS
  In this first biopsy-based analysis of the course of viral heart disease, we show that EV, ADV, PVB19, and HHV6 persistence detected in the myocardium of patients with LV dysfunction was associated with a progressive impairment of LVEF, whereas spontaneous viral elimination was associated with a significant improvement in LV function.
authors.affiliation: Charite, Universitätsmedizin Berlin, Campus Benjamin-Franklin, Medizinische Klinik II, Abteilung für Kardiologie und Pneumologie, Hindenburgdamm 30, 12200 Berlin, Germany. uwe.kuehl@charite.de
authors.forename: Uwe
authors.initials: U
authors.lastname: Kühl
authors.forename: Matthias
authors.initials: M
authors.lastname: Pauschinger
authors.forename: Bettina
authors.initials: B
authors.lastname: Seeberg
authors.forename: Dirk
authors.initials: D
authors.lastname: Lassner
authors.forename: Michel
authors.initials: M
authors.lastname: Noutsias
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Poller
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
mesh_terms: D000256:Adenoviridae / Q000302:isolation & purification; D000328:Adult; D004770:Enterovirus / Q000302:isolation & purification; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000821:virology; D006439:Hemodynamics; D015654:Herpesvirus 6, Human / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D016732:Parvovirus B19, Human / Q000302:isolation & purification; D013318:Stroke Volume; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000473:pathology / Q000503:physiopathology* / Q000821:virology*; D014777:Virus Diseases / Q000150:complications*