scholarly journals Comparative Transcriptomics of Immune Checkpoint Inhibitor Myocarditis Identifies Guanylate Binding Protein 5 and 6 Dysregulation

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2498
Author(s):  
Daniel Finke ◽  
Markus B. Heckmann ◽  
Janek Salatzki ◽  
Johannes Riffel ◽  
Esther Herpel ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Immune Checkpoint ◽  
Binding Protein ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Transcriptional Changes ◽  
Myocardial Biopsies ◽  
Guanylate Binding Protein

Immune checkpoint inhibitors (ICIs) are revolutionizing cancer treatment. Nevertheless, their increasing use leads to an increase of immune-related adverse events (irAEs). Among them, ICI-associated myocarditis (ICIM) is a rare irAE with a high mortality rate. We aimed to characterize the transcriptional changes of ICIM myocardial biopsies and their possible implications. Patients suspected for ICIM were assessed in the cardio-oncology units of University Hospitals Heidelberg and Kiel. Via RNA sequencing of myocardial biopsies, we compared transcriptional changes of ICIM (n = 9) with samples from dilated cardiomyopathy (DCM, n = 11), virus-induced myocarditis (VIM, n = 5), and with samples of patients receiving ICIs without any evidence of myocarditis (n = 4). Patients with ICIM (n = 19) showed an inconsistent clinical presentation, e.g., asymptomatic elevation of cardiac biomarkers (hs-cTnT, NT-proBNP, CK), a drop in left ventricular ejection fraction, or late gadolinium enhancement in cMRI. We found 3784 upregulated genes in ICIM (FDR < 0.05). In the overrepresented pathway ‘response to interferon-gamma’, we found guanylate binding protein 5 and 6 (compared with VIM: GBP5 (log2 fc 3.21), GBP6 (log2 fc 5.37)) to be significantly increased in ICIM on RNA- and protein-level. We conclude that interferon-gamma and inflammasome-regulating proteins, such as GBP5, may be of unrecognized significance in the pathophysiology of ICIM.

scholarly journals 265 Incidence, determinants and prognostic relevance of HS-troponin and natriuretic peptides elevation at admission in hospitalized COVID-19 pneumonia patients

2020 ◽  
Vol 22 (Supplement_N) ◽  
pp. N65-N79
Author(s):  
Luca Arcari ◽  
Michelangelo Luciano ◽  
Luca Cacciotti ◽  
Maria Beatrice Musumeci ◽  
Valerio Spuntarelli ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Natriuretic Peptides ◽  
Multivariable Analysis ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Good Ability ◽  
Myocardial Involvement ◽  
D Dimer

Abstract Aims myocardial involvement in the course of Coronavirus disease 2019 (COVID-19) pneumonia has been reported, though not fully characterized yet. Aim of the present study is to undertake a joint evaluation of hs-Troponin and natriuretic peptides (NP) in patients hospitalized for COVID-19 pneumonia. Methods and results in this multicenter observational study, we analyzed data from n = 111 COVID-19 patients admitted to dedicated “COVID-19” medical units. Hs-Troponin was assessed in n = 103 patients and NP in n = 82 patients on admission; subgroups were identified according to values beyond reference range. increased hs-Troponin and NP were found in 38% and 56% of the cases respectively. As compared to those with normal cardiac biomarkers, these patients were older, had higher prevalence of cardiovascular diseases (CVD) and more severe COVID-19 pneumonia by higher CRP and D-dimer and lower PaO2/FIO2. Two-dimensional echocardiography performed in a subset of patients (n = 24) showed significantly reduced left ventricular ejection fraction in patients with elevated NP only (p = 0.02), whereas right ventricular systolic function (tricuspid annular plane systolic excursion) was significantly reduced both in patients with high hs-Troponin and NP (p = 0.022 and p = 0.03 respectively). On multivariable analysis, independent associations were found of hs-Troponin with age, PaO2/FIO2 and D-dimer (B = 0.419, p = 0.001; B=-0.212, p = 0.013 and B = 0.179, p = 0.037 respectively), and of NP with age and previous CVD (B = 0.480, p &lt; 0.001 and B = 0.253, p = 0.001 respectively). In patients with in-hospital mortality (n = 23, 21%) hs-Troponin and NP were both higher (p = 0.001 and p = 0.002 respectively), while increasing hs-troponin and NP were associated with worse in-hospital prognosis [OR 4.88 (95% CI 1.9-12.2), p = 0.001 (adjusted OR 3.1 (95% CI 1.2-8.5), p = 0.025) and OR 4.67 (95% CI 2-10.8), p &lt; 0.001 (adjusted OR 2.89 (95% CI 1.1-7.9), p = 0.04) respectively]. Receiver operator characteristic curves showed good ability of hs-Troponin and NP in predicting in-hospital mortality (AUC = 0.869 p &lt; 0.001 and AUC = 0.810, p &lt; 0.001 respectively). Conclusion myocardial involvement at admission is common in COVID-19 pneumonia and associated to worse prognosis, suggesting a role for cardiac biomarkers assessment in COVID-19 risk stratification. Independent associations of hs-Troponin with markers of disease severity and of NP with underlying CVD might point towards existing different mechanisms leading to their elevation in this setting.

scholarly journals Evaluation of Cardiac Biomarkers in Dengue Myocarditis in a Tertiary Care Hospital in Eastern India

2020 ◽  
Author(s):  
Debojyoti Bhattacharjee ◽  
Jayati Roy Choudhury ◽  
Kasturi Mukherjee ◽  
Kheya Mukherjee
Keyword(s):  
Viral Infection ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Health Concern ◽  
Left Ventricular Ejection ◽  
Cardiac Complications ◽  
Care Hospital ◽  
Ventricular Ejection Fraction

Introduction: Dengue, a vector borne viral infection transmitted by Aedes mosquito has recently become a major public health concern in the tropical regions of the world. In addition to the two major life threatening complications- Dengue Haemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS), a variety of cardiac complications have been recognised, the most common being myocarditis. Aim: To study and compare the quantity of different cardiac biomarkers in patients of Dengue Fever with and without myocarditis. Materials and Methods: This was a hospital-based retrospective observational study done in a Tertiary Care Hospital, Kolkata, West Bengal, India from June 2019 to November 2019. Dengue patients with diagnosed myocarditis on day 7 of fever based on electro and echocardiogram changes of left ventricular ejection fraction less than 50% were considered as cases (n=41). Age and sex matched dengue patients with normal electro and echocardiogram changes were considered as control (n=43). After obtaining Institutional Ethics Committee Clearance, laboratory data were collected from samples coded and assayed for markers of acute cardiac myocyte damage such as total Creatine Kinase (CK), CK-Muscle Brain (CK-MB), Troponin T (Trop T) and cardiac failure biomarker N-Terminal pro Brain Natriuretic Peptide (NT-proBNP). Statistical analysis of the data was performed using Statistical Package for Social Sciences (SPSS 20). Results: Cardiac biomarkers CK, CK-MB, Trop T and NT-proBNP levels in cases were higher compared to controls (p-value <0.05). Trop T and NT-proBNP were positively correlated to each other (r-value: 0.44). Trop T changes could also predict significantly the rise in NT-proBNP in circulation (p<0.05). Conclusion: It reconfirmed the need of routine monitoring of cardiac biomarkers in conjunction with other cardiac function tests in early diagnosis and or management of myocarditis, a severe complication of Dengue Viral Infection (DENV).

scholarly journals Prevalence of Undiagnosed Obstructive Sleep Apnea Among Patients Hospitalized for Cardiovascular Disease and Associated In-Hospital Outcomes: A Scoping Review

2020 ◽  
Vol 9 (4) ◽  
pp. 989
Author(s):  
Colin Suen ◽  
Jean Wong ◽  
Clodagh M. Ryan ◽  
Samuel Goh ◽  
Tiffany Got ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Scoping Review ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Left Ventricular Ejection ◽  
Hospital Outcomes ◽  
Ventricular Ejection Fraction ◽  
Obstructive Sleep

Background: Obstructive sleep apnea (OSA) is associated with long-term cardiovascular morbidity and is highly prevalent in patients with cardiovascular disease (CVD). The objectives of this scoping review were to determine the prevalence of OSA inpatients hospitalized for CVD and to map the range of in-hospital outcomes associated with OSA. Methods: We searched MEDLINE(R), Embase, and Cochrane Databases for articles published from 1946–2018. We included studies involving non-surgical adults with OSA or at high risk of OSA who were hospitalized for CVD. The outcomes were considered as in-hospital if they were collected from admission up to 30 days post-discharge from hospital. Results: After the screening of 4642 articles, 26 studies were included for qualitative synthesis. Eligible studies included patients presenting with acute coronary syndromes (n = 19), congestive heart failure (n = 6), or any cardiovascular disease (n = 1). The pooled prevalence of OSA in cardiac inpatients was 48% (95% CI: 42–53). The in-hospital outcomes reported were mortality (n = 4), length of stay (n = 8), left ventricular ejection fraction (n = 8), peak troponin (n = 7), peak B-type natriuretic peptide (n = 4), and composite cardiovascular complications (n = 2). Conclusions: OSA is highly prevalent in the cardiac inpatient population. The outcomes reported included mortality, cardiac function, cardiac biomarkers, and resource utilization. There are significant knowledge gaps regarding the effect of treatment and OSA severity on these outcomes. The findings from this review serve to inform further areas of research on the management of OSA among patients with CVD.

Concomitant myopericarditis and takotsubo syndrome following immune checkpoint inhibitor therapy

2020 ◽  
Vol 13 (9) ◽  
pp. e235265 ◽  
Author(s):  
Nicholas Yick Loong Tan ◽  
Nandan S Anavekar ◽  
Brandon M Wiley
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Left Ventricular ◽  
Inhibitor Therapy ◽  
Left Ventricular Ejection ◽  
Cardiac Complications ◽  
Takotsubo Syndrome ◽  
Ventricular Ejection Fraction ◽  
Checkpoint Inhibitor Therapy

A 62-year-old man with metastatic hepatocellular carcinoma presented with ST elevation myocardial infarction had received one dose of nivolumab 3 weeks prior. Cardiac catheterisation was negative for obstructive coronary artery disease. He was transferred to the cardiac intensive care unit due to ventricular arrhythmias and markedly elevated troponin T levels. Transthoracic echocardiogram showed severely depressed left ventricular ejection fraction of 18% (normal 55%–70%) with mid and apical ballooning consistent with takotsubo syndrome (TTS). Intravenous glucocorticoids were administered due to suspicion for superimposed myocarditis. Cardiac MRI 3 days later showed mid-myocardial and subepicardial delayed enhancement in the inferior and lateral walls as well as apex indicative of myopericarditis. He clinically improved on steroids and was discharged with outpatient follow-up. This case highlights major cardiac complications that may arise with immune checkpoint inhibitor therapy. In addition, it emphasises the importance of assessing for concomitant myocarditis even when initial imaging suggests TTS.

A correlative study of cardiac biomarkers and left ventricular ejection fraction (LVEF) from N9831, a phase III randomized trial of chemotherapy and trastuzumab as adjuvant therapy for HER2-positive breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 579-579 ◽  
Author(s):  
L. A. Kutteh ◽  
T. Hobday ◽  
A. Jaffe ◽  
B. LaPlant ◽  
D. Hillman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Troponin T ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Tnf Alpha ◽  
Ventricular Ejection Fraction ◽  
Pre Treatment ◽  
Positive Breast Cancer

579 Background: N9831 and other clinical trials have demonstrated the additive survival benefit of trastuzumab (H) therapy with chemotherapy for patients with resected HER-2 positive breast cancer. Cardiac toxicity (CTox) is increased by this strategy. Prediction of or early detection of CTox is important. Methods: 95 patients provided informed consent. Brain natriuretic peptide (BNP), C-reactive protein (CRP), troponin T (TnT) and I (TnI), TNF-alpha, IL-1b, and IL-6 were to be drawn at baseline, after initiation of doxorubicin/cyclophosphamide (AC), after initiation of paclitaxel (T), and after the initiation of H (may have been given concurrently with T). 67 patients with at least a baseline sample, a post-treatment sample, and a baseline and subsequent evaluation of LVEF were studied. No patient in this group had a grade 3 decline in LVEF. Only 3 of these patients did not receive H. Values above the 99th percentile were considered abnormal for troponin. 40 ng/ml was considered elevated for BNP. Results: Values of CRP, TNF-alpha, IL- 6 and IL1b changed in very few patients and without a discernible pattern. For further evaluation of BNP, TnI, and TnT, 2 definitions of CTox were tested: 1. a >10% drop in LVEF from baseline (n=27) and 2. a drop in LVEF of 10–15% to less than the institutional lower limit of normal (LLN) OR a >15% decline in LVEF (n=14). No pre-treatment marker appeared to predict a > 10% decline in LVEF (definition 1). For patients fulfilling definition 2, pre-treatment BNP > 40 was seen in 21% of patients vs 8% of normals (nls) (p= 0.18) and an abnormal TnI (>0.04) was seen in 21% vs 6% of nls (p=0.10). Only doubling of BNP appeared promising as a serial marker of CTox using definition 2 (27% vs 7% for nls (p = 0.09). Conclusions: Baseline BNP and TnI and serial measures of BNP may be promising for further investigation for the prediction and detection of treatment-related CTox. Due to limitations of the study including the small numbers of patients analyzed, the difficulty in defining CTox, and the variation in the timing of sample procurement and assessment, these data are considered exploratory. Supported by CA-25224, CA-2115, CA 38926, CA31946. No significant financial relationships to disclose.

Effectiveness of using cardiac biomarkers to detect late anthracycline cardiotoxicity in childhood leukemia survivors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9592-9592
Author(s):  
Beata Mladosievicova ◽  
Dagmar Urbanova ◽  
Eva Radvanska ◽  
Eva Mikuskova ◽  
Iveta Simkova
Keyword(s):  
Childhood Leukemia ◽  
Troponin T ◽  
Combined Therapy ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Anthracycline Cardiotoxicity ◽  
Ventricular Ejection Fraction ◽  
Group I

9592 Background: Cardiotoxicity is usually detected only when clinical symptoms or progressive cardiac dysfunction has already occurred. Cardiac biomarkers (troponin T and N-terminal fragment brain natriuretic peptide precursor) have been hypothesized to reflect subclinical anthracycline cardiotoxicity earlier than echocardiography. This study aims to assess the effectiveness of using cTNT and NTproBNP in asymptomatic long-term survivors of childhood leukemia treated with and without antracyclines (ANT). Methods: Sixty-nine childhood leukemia survivors 5 - 25 years after completion of therapy were evaluated with immunochemical analysis of cTnT and NT-proBNP and echocardiography. Patients from group I (n = 36) received combined therapy with anthracyclines (ANT) with total cumulative dose 95-600 (median 221) mg/m2, patients from group II (n = 33) received therapy without anthracyclines (nonANT). Control group consisted from 44 age- and gender-matched apparently healthy subjects. Results: Levels of NTproBNP were significantly higher in ANT group than in controls (median 51,52 vs 17,37 pg/ml; p=0.0026). Patients treated with ANT had significantly increased median values of NTproBNP compared with patients in non ANT group (51,52 vs 12,24 pg/ml; p=0.0002). CTnT levels remained below the diagnostic cut-off levels in all groups. No patient had echocardiographic abnormalities, but significant differences were found in mean values of left ventricular ejection fraction and deceleration time between patients treated with and without ANT. Conclusions: Assessment of plasma NTproBNP concentrations may be an effective tool for detection of late subclinical cardiac damage in survivors of childhood leukemia previously treated with low ANT doses. Higher NTproBNP levels in patients after ANT therapy might reflect an initial stage of cardiotoxicity before the development of echocardiographic abnormalities. This study was supported by a grant from Ministry of Health 2007/42-UK-18, Slovakia.

scholarly journals Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis

2020 ◽  
Vol 41 (18) ◽  
pp. 1733-1743 ◽  
Author(s):  
Lili Zhang ◽  
Magid Awadalla ◽  
Syed S Mahmood ◽  
Anju Nohria ◽  
Malek Z O Hassan ◽  
...  
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Late Gadolinium Enhancement ◽  
Magnetic Resonance ◽  
Immune Checkpoint ◽  
Cardiovascular Events ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Major Adverse Cardiovascular Events ◽  
Gadolinium Enhancement ◽  
Ventricular Ejection Fraction

Abstract Aims Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented. Methods and results From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE. Conclusion These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis.

Abstract 15976: Comparison of Patients With Variant and Typical Takotsubo Cardiomyopathy

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Sijun Kim ◽  
Robert T Palac ◽  
Anthony S Gemignani ◽  
Daniel J O’Rourke ◽  
Harley P Friedman ◽  
...  
Keyword(s):  
Takotsubo Cardiomyopathy ◽  
Diastolic Pressure ◽  
Medical Center ◽  
Systolic Dysfunction ◽  
Academic Medical Center ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Left Ventricular Ejection ◽  
Discharge Diagnosis ◽  
Ventricular Ejection Fraction

Background: Variant, or reverse, Takotsubo cardiomyopathy (TTC) is defined by left ventricular basal and/or mid-ventricular systolic dysfunction with preserved apical function. This condition is increasingly recognized, yet there have been few studies comparing variant and typical TTC. This study aims to contrast the demographic features and clinical outcomes of patients with variant and typical TTC. Methods: All patients at a single academic medical center with a discharge diagnosis of Takotsubo syndrome [ICD-9-CM 429.83] from 2010-2014 were identified. Patients who met the Mayo Clinic criteria for TTC were included and were then grouped into typical or variant TTC categories based on wall motion abnormality patterns. Results: The initial query identified 275 patients with a discharge diagnosis of TTC, of which 145 (52.7%) met diagnostic criteria for TTC. Typical TTC was present in 125 patients (86.2%) and variant TTC in 20 patients (13.8%). The demographic and clinical characteristics of these groups are summarized in table 1. Variant TTC patients were more likely to be male and subject to a physically stressful trigger. Typical TTC patients had lower left ventricular ejection fraction, higher left ventricular end-diastolic pressure, and were more likely to be intubated. Cardiac biomarkers were not significantly different between groups. In-hospital mortality, length of hospital stay, TTC recurrence and follow-up LVEF were similar between groups. Conclusions: There are important differences between patients with variant and typical TTC. Variant TTC is not as strongly associated with female sex, it is more frequently preceded by a physical stressor, and it has a more benign presentation. Long term outcomes are favorable in patients with variant and typical TTC.

Role of biomarkers in cardioncology

2011 ◽  
Vol 49 (12) ◽  
Author(s):  
Daniela Cardinale ◽  
Michela Salvatici ◽  
Maria T. Sandri
Keyword(s):  
Troponin I ◽  
Cardiac Injury ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Left Ventricular Ejection ◽  
Cardiac Events ◽  
Current Standard ◽  
Converting Enzyme Inhibitors ◽  
Ventricular Ejection Fraction

AbstractCardiotoxicity is a serious adverse effect of anticancer drugs, impacting on quality of life and overall survival of cancer patients. According to the current standard for monitoring cardiac function, cardiotoxicity is usually detected only when a functional impairment has already occurred, precluding any chance of preventing its development. Over the last decade, however, a new approach, based on the use of cardiac biomarkers, has emerged, and has proven to be an effective alternative strategy for early detection of subclinical cardiac injury. In particular, the role of troponin I in identifying patients at risk of cardiotoxicity and of angiotensin-converting enzyme inhibitors in preventing left ventricular ejection fraction reduction and late cardiac events represent an effective tool for the prevention of this complication.

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