OUP accepted manuscript

Mitrofanova, Lubov; Orshanskaya, V. S.; Ho, Siew Yen; Platonov, Pyotr G.

doi:10.1093/europace/euw361

Cited by 20 publications

(5 citation statements)

References 15 publications

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“…There has been a prevailing dogma that immune cells in heart tissue were mainly derived from the circulation, which led investigators to largely disregard resident immune cells. Most studies have looked at the atrium for signs of inflammation [23, 29], however this approach has been proven to be limited and largely unable to characterize resident immune cells (MoΦ) that are increasingly recognized as an important component of heart tissue [12, 30, 31]. Also, MoΦ in particular have been shown to be capable of influencing the complex balance between inflammation and its’ resolution [32, 33].…”

Section: Discussionmentioning

confidence: 99%

Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery

Aguiar¹,

Gawdat

Legere

et al. 2019

J Transl Med

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BackgroundThe objectives of the study were to characterize and quantify cellular inflammation and structural remodeling of human atria and correlate findings with molecular markers of inflammation and patient surrogate outcome.MethodsVoluntary participants undergoing heart surgery were enrolled in the study and blood samples were collected prior to surgery, and right atrium samples were harvested intraoperatively. Blood samples were analyzed by flow cytometry and complete blood counts. Atrial samples were divided for fixed fibrosis analysis, homogenized for cytokine analysis and digested for single cell suspension flow cytometry.ResultsA total of 18 patients were enrolled and samples assessed. Isolated cells from the atria revealed a CD45+ population of ~ 20%, confirming a large number of leukocytes. Further characterization revealed this population as 57% lymphocytes and 26% monocyte/macrophages (MoΦ), with the majority of the latter cells being classical (CD14++/CD16−). Interstitial fibrosis was present in 87% of samples and correlated significantly with patient age. Older patients (> 65) had significantly more atrial fibrosis and cellular inflammation. AFib patients had no distinguishing feature of atrial fibrosis and had significantly greater CD45+ MoΦ, increased expression of MMP9 and presented with a significant correlation in length of stay to CCL-2/MCP-1 and NLR (neutrophil-to-lymphocyte ratio).ConclusionAtrial fibrosis is correlated with age and not determinate to AFib. However, severity of atrial leukocyte infiltration and markers of matrix degradation are determinant to AFib. This also correlated with CCL2 (or MCP-1) and NLR-indicative of marked inflammation. These data show the potential importance of diagnostic and prognostic assessments that could inform clinical decision making in regard to the intensity of AFib patient management.

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Section: Discussionmentioning

confidence: 99%

Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery

Aguiar¹,

Gawdat

Legere

et al. 2019

J Transl Med

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“…Due to an auto-aggressive behavior of this cytotoxic T cell subset, multiple micro-scars are formed based on cell-necrosis and apoptosis induction, leading to atrial fibrosis. As recently demonstrated, atrial fibrosis is known to impact on cardiac eclectic conduction, generating fibrillation impulses among atrial tissue and resulting in the manifestation of POAF 32 . Of note, the observed significant association of CD4 + CD28 null cells and of both CRP and total leucocyte values in patients developing POAF underlines the aggravated inflammatory state in this subgroup, compared to non-POAF individuals.…”

Section: Discussionmentioning

confidence: 95%

CD4+CD28null T Lymphocytes are Associated with the Development of Atrial Fibrillation after Elective Cardiac Surgery

Sulzgruber

Thaler

Koller

et al. 2018

Sci Rep

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Post-operative atrial fibrillation (POAF) is postulated as a complex interaction of different pathogenic factors, suggesting inflammatory processes as a main trigger of this particular type of atrial fibrillation. Therefore, the study sought to assess the impact of cellular immunity on the development of POAF. Comparing patients developing POAF to individuals free of POAF the fraction of CD4+CD28null T Lymphocytes was significantly higher in individuals developing POAF (11.1% [POAF] vs. 1.9% [non-POAF]; p < 0.001). CD4+CD28null cells were independently associated with the development of POAF with an adjusted odds ratio per one standard deviation of 4.89 (95% CI: 2.68–8.97; p < 0.001). Compared to N-terminal Pro-Brain Natriuretic Peptide, the fraction of CD4+CD28null cells demonstrated an increased discriminatory power for the development of POAF (NRI: 87.9%, p < 0.001; IDI: 30.9%, p < 0.001). Interestingly, a pre-operative statin-therapy was associated with a lower fraction of CD4+CD28null cells (p < 0.001) and showed an inverse association with POAF (p < 0.001). CD4+CD28null cells proved to be predictive for the development of POAF after cardiac surgery. Our results potentially indicate an auto-immune impact of this preexisting, highly cytotoxic T cell subset in the pathogenesis of POAF, which might be modified via the anti-inflammatory potential of a pre-operative statin-therapy.

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“…Исследования последних лет показывают, что в качестве этиологического фактора, наряду с артериальной гипертонией и ИБС, большую роль в развитии и поддержании ФП играют воспалительные процессы в миокарде [16][17][18]. По данным разных авторов, гистологические признаки воспаления у пациентов с фибрилляцией предсердий неуточненной этиологии встречаются в 14-70% случаев [18,19].…”

Section: Discussionunclassified

Hybrid Imaging Techniques in the Diagnosis of Ventricular Myocardial Inflammatory Processes in Patients with Atrial Fibrillation of Unknown Etiology

Ilyushenkova

Сазонова

Баталов

2019

Vestn. rentgenol. radiol.

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Фибрилляция предсердий является наиболее распространенным видом нарушения ритма сердца. Определение этиологического фактора возникновения и поддержания фибрилляции предсердий имеет первостепенное клиническое значение и служит необходимым условием для успешного лечения. Представлен клинический случай диагностики миокардита у пациента с фибрилляцией предсердий, резистентной к медикаментозной терапии. Дополнительно пациенту была выполнена однофотонная эмиссионная компьютерная томография/компьютерная томография с 99m Tc-пирофосфатом для диагностики воспалительного процесса в миокарде и последующего сопоставления результатов с данными гистологического исследования (эндомиокардиальная биопсия). Ключевые слова: фибрилляция предсердий; миокардит; сцинтиграфия миокарда; однофотонная эмиссионная компьютерная томография/компьютерная томография. Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов. Финансирование. Исследование не имело спонсорской поддержки. Для цитирования: Ильюшенкова Ю.Н., Сазонова С.И., Баталов Р.Е. Гибридные методы визуализации в диагностике воспалительных процессов в миокарде желудочков у пациентов с фибрилляцией предсердий неясной этиологии.

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OUP accepted manuscript

Abstract: Histological signs of chronic inflammation affecting ventricular myocardium are strongly associated with AF and demonstrate significant correlation with fibrosis extent that cannot be explained by cardiovascular comorbidities otherwise.

Cited by 20 publications

References 15 publications

Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery

Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery

CD4+CD28null T Lymphocytes are Associated with the Development of Atrial Fibrillation after Elective Cardiac Surgery

Hybrid Imaging Techniques in the Diagnosis of Ventricular Myocardial Inflammatory Processes in Patients with Atrial Fibrillation of Unknown Etiology

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