Imuninė stebėsena širdies transplantacijoje: atmetimo reakcijos poveikis T limfocitų žymenų ekspresijai

Radvilė Malickaitė, Laimutė Jurgauskienė, Stanislava Simanavičienė, Vytė Valerija Maneikienė, Rita Sudikienė, Kęstutis Ručinskas Vilniaus universiteto Širdies ir kraujagyslių ligų klinikos Širdies chirurgijos centras, Santariškių g. 2, LT-08661 Vilnius El. paštas: [email protected] Darbo tikslas: Nustatyti Vilniaus universiteto ligoninės Santariškių klinikų Širdies chirurgijos centre atliekamos širdies transplantacijos įtaką T limfocitų aktyvumo rodikliams, įvertinti imuninės stebėsenos tinkamumą ūminiam transplantato atmetimui prognozuoti. Ligoniai ir metodai: Retrospektyviai analizuotas dvidešimt vieno širdies recipiento imuninių rodiklių kitimas esant normaliai potransplantacinei būklei ir ūminiam transplantato atmetimui. Periferinio kraujo imunokompetentinių ląstelių CD3+CD103+, CD4+CD103+, CD8+CD103+, CD3+CD134+, CD4+CD134+, CD8+CD134+, CD8+CD57+ ir CD8+CD38+ procentas nustatytas tėkmės citometrijos būdu. Ūminis transplantato atmetimas vertintas pagal histologinius endomiokardinės biopsijos radinius. Rezultatai: Esant ūminio atmetimo epizodams, kai endomiokardo biopsijos įvertintos ≥ 2R (3A) laipsniu, reikšmingai didėja integrino CD103 (p < 0,0001), kostimuliacinio receptoriaus CD134 (p = 0,005), antigeno CD57 (p = 0,005) ir ląstelių paviršiaus glikoproteino CD38 (p = 0,015) ekspresija citotoksinių CD8+ limfocitų paviršiuje. Išvados: Imuninė periferinio kraujo limfocitų būklės stebėsena gali būti taikoma po transplantacijos skiriamam imunosupresiniam gydymui įvertinti numatant didelę ūminio atmetimo tikimybę. Reikšminiai žodžiai: kiaušidžių cistos, supiktybėjimo rizika, piktybiškumo rizikos indeksas, ultragarsinis tyrimas, Ca-125 antigenas, chirurginis gydymas Measuring T cell reactivity for predicting heart transplant rejection Radvilė Malickaitė, Laimutė Jurgauskienė, Stanislava Simanavičienė, Vytė Valerija Maneikienė, Rita Sudikienė, Kęstutis Ručinskas Vilnius University, Clinic of Cardiovascular Diseases, Centre of Heart sSurgery, Santariškių str. 2, LT-08661 Vilnius, Lithuania E-mail: [email protected] Objective: We aimed to analyze alterations in peripheral blood T-cell subset activation compared with endomyocardial byopsy findings. Patients and methods: The study included in total twenty-one heart recipients grafted 1997–2007 at the Vilnius Heart sSurgery cCenter. T-cell activation markers CD3+CD103+, CD4+CD103+, CD8+CD103+, CD3+CD134+, CD4+CD134+, CD8+CD134+, CD8+CD57+ ir CD8+CD38+ were detected by two-color flow cytometry. Rejection was graded according to the ISHLT (the International Society of Heart and Lung Transplantation) grading system. Results: In case of ≥ 2R (3A) rejection episodes, a significant increase in the expression of integrin CD103 (p < 0.0001), co-stimulatory receptor CD134 (p = 0.005), antigen CD57 (p = 0.005) and surface glycoprotein CD38 (p = 0.015) on CD8+ T lymphocytes has been revealed. Conclusion: Immune monitoring performed on peripheral blood can be used for the assessment of immunosuppression therapy on transplant recipients’ immune response and for determining the risk of rejection. Key words: heart transplantation, acute rejection, and immune activatio

Prevalence and prognostic relevance of myocardial inflammation and cardiotropic viruses in non-ischemic dilated cardiomyopathy

Background: Non-ischemic dilated cardiomyopathy (DCM) is a heterogeneous disease with a spectrum of etiological factors. However, subsets of the disease are not well-characterized with respect to these factors. The aim of this study was to evaluate the prevalence of myocardial inflammation and cardiotropic viruses in DCM patients and their impact on clinical outcome. Methods: Fifty-seven patients with DCM underwent endomyocardial biopsy between 2010 and 2013. Biopsies were analyzed by polymerase chain reaction (PCR) for the presence of cardiotropic viruses, and inflammatory cell infiltration was assessed by immunohistochemistry. During a 5-year follow-up, 27 (47%) patients reached the primary composite outcome measure: heart transplantation, left ventricle assist device implantation or cardiovascular-related death. Results: rvovirus B19 and human herpesvirus type-6. Four specific sub-groups were distinguished by PCR and immunohistochemistry: virus-positive (chronic) myocarditis, autoreactive inflammatory DCM, viral DCM, non-inflammatory DCM. The presence of a viral genome in myocardium or diagnosis of inflammatory DCM did not predict the outcome of composite outcome measures (p &gt; 0.05). However, univariate Cox regression and survival function estimation revealed an association between inflammation by a high number of T-cells and poor prognosis. Conclusions: This study has shown that two markers — cardiotropic viruses and myocardial inflammation — are prevalent among DCM patients. They are also helpful in identifying sub-groups of DCM. An increased number of T-lymphocytes in the myocardium is a predictor of poor mid-term and long‐term prognosis

Citomegalovirusinės ligos gastrointes-tininė forma po širdies persodinimo

Aleksejus Zorinas1, Kęstutis Ručinskas1, Saulius Miniauskas1, Radvilė Malickaitė1, Gitana Žemaitytė2, Vytė Valerija Maneikienė2, Vytautas Sirvydis11 Vilniaus universiteto Širdies chirurgijos centras, Santariškių g. 2, LT-08661 Vilnius2 Vilniaus universiteto ligoninės Santariškių klinikų Širdies chirurgijos centras,Santariškių g. 2, LT-08661 VilniusEl paštas: [email protected]; [email protected] Citomegalovirusinis (CMV) virškinimo trakto pažeidimas yra vienas iš klinikinių infekcijos poreiškių pacientams po organų persodinimo. Gastrointestininės CMV formos diagnostika dažnai yra sudėtinga, o padariniai sunkūs. Pristatomas CMV ligos po širdies persodinimo atvejis, diagnostikos ypatumai ir gydymo rekomendacijos. Pagrindiniai žodžiai: širdies persodinimas, citomegalo viruso infekcija Subaortic stenosis and mitral valve anomaly: surgical treatment aspects Aleksejus Zorinas1, Kęstutis Ručinskas1, Saulius Miniauskas1, Radvilė Malickaitė1, Gitana Žemaitytė2, Vytė Valerija Maneikienė2, Vytautas Sirvydis11 Vilnius University, Cardiac Surgery Centre, Santariškių str. 2, LT-08661 Vilnius, Lithuania2 Vilnius University Hospital „Santariškių klinikos“, Cardiac Surgery Centre,Santariškių str. 2, LT-08661 Vilnius, LithuaniaE-mail: [email protected]; [email protected] Cytomegalovirus infection can cause lesions of different organs, including gastrointestinal tract. In transplant patients, CMV infection can be associated with severe consequences. This case details the clinical and diagnostic features of gastrointestinal CMV disease in a patient after heart transplantation, in which treatment resulted in a complete resolution of the symptoms. Key words: heart transplantation, cytomegalovirus infectio

Pacientų atranka širdies transplantacijai: šiuolaikiniai kriterijai

Vytė Valerija Maneikienė1, Jelena Čelutkienė2, Gitana Žemaitaitytė1, Kęstutis Ručinskas3, Saulius Miniauskas3, Sigitas Čibiras2, Vytautas Jonas Sirvydis3, Aleksandras Laucevičius2 1 Vilniaus universiteto ligoninės Santariškių klinikų Širdies chirurgijos centras, Santariškių g. 2, LT-08661 Vilnius 2 Vilniaus universiteto Širdies ir kraujagyslių ligų klinika, Santariškių g. 2, LT-08661 Vilnius 3Vilniaus universiteto Širdies chirurgijos centras, Santariškių g. 2, LT-08661 Vilnius El paštas: [email protected] Vilniaus universiteto Širdies chirurgijos centre nuo 1987 metų atliekamos širdies transplantacijos operacijos. Per šį laikotarpį recipientų sąrašuose buvo įrašyti 268 pacientai, atliktos 47 širdies transplantacijos. Šiuolaikiniai medikamentinio, elektrofiziologinio ir chirurginio gydymo metodai gerokai padidino pacientų, laukiančių širdies transplantacijos, išgyvenimą, tačiau širdies transplantacija tebėra veiksmingiausias gydymo metodas terminalinėmis širdies nepakankamumo stadijomis. Pastaraisiais metais Vilniaus universiteto Širdies chirurgijos klinikoje įdiegti nauji diagnostikos metodai (spiroergometrija, NT-pro-BNP nustatymas) leidžia praktiškai pritaikyti šiuolaikinius atrankos kriterijus. Šiame straipsnyje remiantis literatūros apžvalga įvardyti pagrindiniai recipientų atrankos širdies transplantacijai kriterijai, taikomi ir Vilniaus universiteto Širdies chirurgijos centre. Pagrindiniai žodžiai: širdies nepakankamumas, recipientų atranka, transplantacija Evaluation at selection of patients for heart transplantation: current criteria Vytė Valerija Maneikienė1, Jelena Čelutkienė2, Gitana Žemaitaitytė1, Kęstutis Ručinskas3, Saulius Miniauskas3, Sigitas Čibiras2, Vytautas Jonas Sirvydis3, Aleksandras Laucevičius2 1 Vilnius University Hospital „Santariškių klinikos“, Heart Surgery Centre, Santariškių str. 2, LT-08661 Vilnius, Lithuania 2 Vilnius University, Heart and Cardiovascular Diseases Clinic, Santariškių str. 2, LT-08661 Vilnius, Lithuania 3 Vilnius University, Heart Surgery Centre, Santariškių str. 2, LT-08661 Vilnius, Lithuania E-mail: [email protected] Heart transplantations at Vilnius University Heart Surgery Centre have been performed since 1987. During all this period, 268 patients were included into the recipients’ list and 47 heart transplantations were performed. The current medical, electrophysiological and surgical methods have obviously increased the survival of patients who are waiting for heart transplantation. However, heart transplantation is still the most effective method in the end-stage heart failure. In recent years, the new diagnostic methods (spiroergometry, NT-pro-BNP) implemented at Vilnius University Heart Surgery Center enable using current selection criteria in practice. In the article, according to a literature review, all the basic criteria of evaluating and selecting recipients for heart transplantation mentioned above are used at our Center. Key words: heart failure, recipients’ selection, transplantatio

Cardiac resynchronisation therapy: evaluation and prediction of effectiveness

Chronic heart failure (HF) is the main cause determining increasing morbidity and mortality of the patients suffering from cardiovascular diseases related to sudden death or progressive heart insufficiency. Cardiac resynchronization therapy (CRT) is a progressive, modern and very promising method of non-medicament treatment of heart failure. Long-term data of observation (2002 – 2013 years) of the patients at the Clinic of Cardiology and Angiology of Vilnius University Hospital Santariškių Klinikos were collected, stored and analyzed, in order to evaluate the role of resynchronization in the process of the left ventricle recovery and re-modelling, decreasing all-cause morbidity and mortality. The experience gained allowed to form sufficient samples in patient groups that were less analyzed in large multicenter researches or were presented as results of metaanalysis of subgroups (patients with atrial fibrillation with or without the AV node block, CRT upgrade procedure, seniors (≥70 years old) groups). For the first time in Lithuania, we used imaging of adrenergic innervation of the heart with 123 I-MIGB (Iodine-123-metaiodobenzyl-guanidine) to evaluate global and regional adrenergic innervation of the heart in patients with heart failure and electrical conduction disorders; the further clinical course of these patients was prospectively followed-up, while implementing different methods of treatment (optimal medical treatment [OMT] or CRT). Based on obtained data, we have proposed algorithm of clinical decisions for advanced heart failure patients; it allows us to avoid application of expensive and time-exhausting treatment for the patients, who have no internal sources for improvement of their condition, also

Širdies resinchronizuojamojo gydymo efektyvumo įvertinimas ir prognozavimas

Chronic heart failure (HF) is the main cause determining increasing morbidity and mortality of the patients suffering from cardiovascular diseases related to sudden death or progressive heart insufficiency. Cardiac resynchronization therapy (CRT) is a progressive, modern and very promising method of non-medicament treatment of heart failure. Long-term data of observation (2002 – 2013 years) of the patients at the Clinic of Cardiology and Angiology of Vilnius University Hospital Santariškių Klinikos were collected, stored and analyzed, in order to evaluate the role of resynchronization in the process of the left ventricle recovery and re-modelling, decreasing all-cause morbidity and mortality. The experience gained allowed to form sufficient samples in patient groups that were less analyzed in large multicenter researches or were presented as results of metaanalysis of subgroups (patients with atrial fibrillation with or without the AV node block, CRT upgrade procedure, seniors (≥70 years old) groups). For the first time in Lithuania, we used imaging of adrenergic innervation of the heart with 123 I-MIGB (Iodine-123-metaiodobenzyl-guanidine) to evaluate global and regional adrenergic innervation of the heart in patients with heart failure and electrical conduction disorders; the further clinical course of these patients was prospectively followed-up, while implementing different methods of treatment (optimal medical treatment [OMT] or CRT). Based on obtained data, we have proposed algorithm of clinical decisions for advanced heart failure patients; it allows us to avoid application of expensive and time-exhausting treatment for the patients, who have no internal sources for improvement of their condition, also

Osteoporozinis stuburo slankstelių lūžis po širdies operacijos

Kęstutis Šalčius, Gintaras Turkevičius, Vytė Valerija ManeikienėVilniaus universiteto ligoninės Santariškių klinikų Širdies chirurgijos centras,Santariškių g. 2, LT-08661 VilniusEl paštas: [email protected] Osteoporozinis stuburo slankstelių lūžis, įvykęs po širdies operacijos, yra kazuistinis atvejis. Aprašome torokalinės stuburo dalies spontaninį lūžimą, kurio padarinys – stuburo smegenų pažeidimas 61 metų ligonei po širdies operacijos. Pagrindiniai žodžiai: vožtuvų protezavimas, osteoporozė Vertebral bone breaks after heart surgery Kęstutis Šalčius, Gintaras Turkevičius, Vytė Valerija ManeikienėVilnius University Hospital „Santariškių klinikos“, Cardiac Surgery Centre,Santariškių str. 2, LT-08661 Vilnius, LithuaniaE-mail: [email protected] Osteoporotic vertebral break after heart surgery is a very rare complication. We report a case of 61-year-old woman who was diagnosed with later spontaneous backbone break after heart surgery. Key words: valve replacement, osteoporosi

Obligatory nature of diagnostic and treatment guidelines for the physician (how much binding are diagnostic and treatment standards for the physician)

Professional guidelines in Lithuania are legal documents that include the sets of recommendations supposed to direct diagnosing or treatment doctors’ actions. Their legal meanings are rather obscure. In some cases, they are seen as usual legal norms. Their violation implies criminal, civil or administrative sanctions. In other cases, they are seen as some kind of advice on the most preferred way of actions. Also, there are cases when they are seen as a legal permission to take some actions. This multivaluedness of medical guidelines is caused by ambivalent concepts that are used to formulate medical recommendations (“is indicated”, “should be considered”, “is recommended”, “can be reasonable”, etc.). The first step in specification of these concepts has been done by classification of medical recommendations, developed by Feinstein and Cochrane. They specified every such concept with only one kind (class) of recommendations. The next step should be further specification of doctor’s actions he is supposed to commit depending on the class of recommendation and its wording. From the legal point of view, the most important thing seems to be the difference between the actions that must be taken in the case of “strong” and “weak” recommendations. In the first case, the recommendation is obligatory and must be followed. In the second one, the decision to follow or not belongs to doctor’s discretion. Doctor’s duty in this situation is to consider all related scientific knowledge on factors both promoting and preventing the effectiveness of recommendation, which has been considered

A Rare Case of Primary Purulent Pericarditis Caused by <i>Streptococcus constellatus</i>

Background: Bacteria-caused acute pericarditis is a very rare entity. It is usually associated with an underlying infection or compromised immune system. Primary purulent pericarditis in a previously healthy individual is highly unexpected; therefore, it is likely to have a delayed diagnosis and poor outcomes. Case: We report a case of an adult immunocompetent patient with primary bacterial pericarditis caused by a member of the commensal oral flora Streptococcus constellatus. The patient presented with septic shock and cardiac tamponade, and was further complicated with constrictive pericarditis, which was successfully treated with pericardiectomy. Conclusions: Bacterial pericarditis is a fulminant disease with a high mortality and complication rate. Fast recognition and prompt therapy are required to achieve a full recovery

Inflammation-Related Biomarkers Are Associated with Heart Failure Severity and Poor Clinical Outcomes in Patients with Non-Ischemic Dilated Cardiomyopathy

Inflammation-related biomarkers are associated with clinical outcomes in mixed-etiology chronic heart failure populations. Inflammation-related markers tend to be higher in ischemic than in non-ischemic dilated cardiomyopathy (NI-DCM) patients, which might impact their prognostic performance in NI-DCM patients. Therefore, we aimed to assess the association of inflammation-related biomarkers with heart failure severity parameters and adverse cardiac events in a pure NI-DCM patient cohort. Fifty-seven patients with NI-DCM underwent endomyocardial biopsy. Biopsies were evaluated by immunohistochemistry for CD3+, CD45ro+, CD68+, CD4+, CD54+, and HLA-DR+ cells. Blood samples were tested for high-sensitivity C-reactive protein (hs-CRP), interleukin-6, tumor necrosis factor-α (TNF-α), soluble urokinase-type plasminogen activator receptor and adiponectin. During a five-year follow-up, twenty-seven patients experienced at least one composite adverse cardiac event: left ventricle assist device implantation, heart transplantation or death. Interleukin-6, TNF-α and adiponectin correlated with heart failure severity parameters. Patients with higher levels of interleukin-6, TNF-α, adiponectin or hs-CRP, or a higher number of CD3+ or CD45ro+ cells, had lower survival rates. Interleukin-6, adiponectin, and CD45ro+ cells were independently associated with poor clinical outcomes. All patients who had interleukin-6, TNF-α and adiponectin concentrations above the threshold experienced an adverse cardiac event. Therefore, a combination of these cytokines can identify high-risk NI-DCM patients