Blagova O V, Kogan E A, Lutokhina Yu A, Kukleva A D, Ainetdinova D H, Novosadov V M, Rud R S, Zaitsev A Yu, Zaidenov V A, Kupriyanova A G, Alexandrova S А, Fomin V V
The State Education Institution of Higher Professional Training the First I.M. Sechenov Moscow State Medical University (Sechenov University), Moscow, Russia.
City Clinical Hospital № 52, Moscow, Russia.
Kardiologiia. 2021 Jul 1;61(6):11-27. doi: 10.18087/cardio.2021.6.n1659.
Aim To study clinical features of myoendocarditis and its possible mechanisms, including persistence of SARS-Cov-2 in the myocardium, in the long-term period following COVID-19.Material and methods This cohort, prospective study included 15 patients aged 47.8±13.4 years (8 men) with post-COVID myocarditis. The COVID-19 diagnosis was confirmed for all patients. Median time to seeking medical care after COVID-19 was 4 [3; 7] months. The diagnosis of myocarditis was confirmed by magnetic resonance imaging (MRI) of the heart (n=10) and by endomyocardial biopsy of the right ventricle (n=6). The virus was detected in the myocardium with PCR; immunohistochemical (IHC) study with antibody to SARS-Cov-2 was performed; anticardiac antibody level was measured; and echocardiography and Holter monitoring were performed. Hemodynamically significant coronary atherosclerosis was excluded for all patients older than 40 years.Results All patients showed a clear connection between the emergence or exacerbation of cardiac symptoms and COVID-19. 11 patients did not have any signs of heart disease before COVID-19; 4 patients had previously had moderate arrhythmia or heart failure (HF) without myocarditis. Symptoms of myocarditis emerged at 1-5 months following COVID-19. MRI revealed typical late gadolinium accumulation, signs of hyperemia, and one case of edema. The level of anticardiac antibodies was increased 3-4 times in 73 % больных. Two major clinical variants of post-COVID myocarditis were observed. 1. Arrhythmic (n=6), with newly developed extrasystole or atrial fibrillation without systolic dysfunction. 2. Decompensated variant with systolic dysfunction and biventricular HF (n=9). Mean left ventricular ejection fraction was 34.1±7.8 %, and left ventricular end-diastolic dimension was 5.8±0.7 cm. In one case, myocarditis was associated with signs of IgG4‑negative aortitis. SARS-Cov-2 RNA was found in 5 of 6 biopsy samples of the myocardium. The longest duration of SARS-Cov-2 persistence in the myocardium was 9 months following COVID-19. By using antibody to the Spike antigen and nucleocapsid, SARS-Cov-2 was detected in cardiomyocytes, endothelium, and macrophages. Five patients were diagnosed with lymphocytic myocarditis; one with giant-cell myocarditis; three patients had signs of endocarditis (infectious, lymphocytic with mural thrombosis).Conclusion Subacute/chronic post-COVID myocarditis with isolated arrhythmias or systolic dysfunction is characterized by long-term (up to 9 months) persistence of SARS-Cov-2 in the myocardium in combination with a high immune activity. Endocarditis can manifest either as infectious or as nonbacterial thromboendocarditis. A possibility of using corticosteroids and anticoagulants in the treatment of post-COVID myoendocarditis should be studied.
研究新型冠状病毒肺炎(COVID-19)长期随访期内心肌炎的临床特征及其可能机制,包括严重急性呼吸综合征冠状病毒2(SARS-CoV-2)在心肌中的持续存在情况。
本队列前瞻性研究纳入了15例年龄为47.8±13.4岁(8例男性)的COVID-19后心肌炎患者。所有患者的COVID-19诊断均得到证实。COVID-19后寻求医疗护理的中位时间为4[3;7]个月。通过心脏磁共振成像(MRI)(n = 10)和右心室内膜心肌活检(n = 6)确诊心肌炎。采用聚合酶链反应(PCR)在心肌中检测病毒;进行了针对SARS-CoV-2抗体的免疫组织化学(IHC)研究;测定了抗心脏抗体水平;并进行了超声心动图和动态心电图监测。排除了所有年龄大于40岁患者的血流动力学显著的冠状动脉粥样硬化。
所有患者的心脏症状出现或加重均与COVID-19有明确关联。11例患者在COVID-19之前没有任何心脏病迹象;4例患者之前有中度心律失常或心力衰竭(HF)但无心肌炎。心肌炎症状在COVID-19后1 - 5个月出现。MRI显示典型的钆延迟强化、充血迹象,以及1例水肿。73%的患者抗心脏抗体水平升高了3 - 4倍。观察到COVID-19后心肌炎的两种主要临床类型。1. 心律失常型(n = 6),出现新发早搏或房颤且无收缩功能障碍。2. 失代偿型,伴有收缩功能障碍和双心室HF(n = 9)。平均左心室射血分数为34.1±7.8%,左心室舒张末期内径为5.8±0.7 cm。1例患者的心肌炎与IgG4阴性主动脉炎迹象相关。在6例心肌活检样本中的5例中发现了SARS-CoV-2 RNA。COVID-19后SARS-CoV-2在心肌中持续存在最长时间为9个月。通过使用针对刺突抗原和核衣壳的抗体,在心肌细胞、内皮细胞和巨噬细胞中检测到了SARS-CoV-2。5例患者被诊断为淋巴细胞性心肌炎;1例为巨细胞性心肌炎;3例患者有内膜炎迹象(感染性、淋巴细胞性伴壁血栓形成)。
伴有孤立性心律失常或收缩功能障碍的亚急性/慢性COVID-19后心肌炎的特征是SARS-CoV-2在心肌中长期(长达9个月)持续存在并伴有高免疫活性。内膜炎可表现为感染性或非细菌性血栓性心内膜炎。应研究在COVID-19后心肌内膜炎治疗中使用皮质类固醇和抗凝剂的可能性。