Viral persistence in the myocardium is associated with progressive cardiac dysfunction
Viral persistence in the myocardium is associated with progressive cardiac dysfunction
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DOI：
10.1161/circulationaha.105.548156
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发表时间：
2005-09-27
期刊：
影响因子：
37.8
通讯作者：
Schultheiss, HPP
中科院分区：
文献类型：
--
作者：
Kühl, U;Pauschinger, M;Schultheiss, HPP
背景-嗜心病毒感染被怀疑是心肌炎和扩张型心肌病的可能病因之一。虽然扩张型心肌病患者的不良后果已被记录在案，但嗜心病毒引起的心脏病的自然过程尚不清楚。方法和结果-在中位6.8个月（范围，5.4 - 11.9）后，对经活检证实的心内膜肌活检（EMBs）病毒感染的连续患者（n = 172）进行EMBs和血流动力学测量的再分析随访。采用巢式聚合酶链反应（巢式PCR）和反转录PCR对基因组序列进行分析。采用组织学和免疫组织学方法评估心肌炎症。在基线时，研究组中32.6%的EMBs含有肠病毒（EV） RNA， 8.1%的腺病毒（ADV） DNA， 36.6%的细小病毒B19 (PVB19) DNA和10.5%的人疱疹病毒6型（HHV6） DNA。12.2%的样本存在PVB19和HHV6双重感染。通过PCR对EMBs进行随访分析，发现36.2%（55/151）的单次感染患者的病毒基因组自发清除。病毒特异性清除率分别为EV 50%、ADV 35.7%、PVB19 22.2%和HHV6 44.4%。在PVB19（+）和HHV6(+)-双重感染的患者中，HHV6被清除的比例为42.8%(9/21)，而PVB19在所有21例患者中持续存在。清除病毒基因组与左心室射血分数（LVEF）的显著改善相关，从50.2 +/- 19.1%改善到58.1 +/- 15.9% （P < 0.001）。相比之下，持续存在病毒基因组的患者左室功能下降（LVEF, 54.3 +/- 16.1% vs 51.4 +/- 16.1%, P < 0.01）。结论：在这首个基于活检的病毒性心脏病病程分析中，我们发现在左室功能障碍患者心肌中检测到的EV、ADV、PVB19和HHV6持续性与左室功能障碍的进行性损害有关，而自发病毒消除与左室功能的显著改善有关。
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.Methods and 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.