scholarly journals Peripheral Blood MicroRNAs as Potential Biomarkers of Myocardial Damage in Acute Viral Myocarditis

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 420
Author(s):  
Maria Marketou ◽  
Joanna Kontaraki ◽  
Alexandros Patrianakos ◽  
George Kochiadakis ◽  
Ioannis Anastasiou ◽  
...  

Background: microRNAs (miRs) have emerged as important modulators of cardiovascular development and disease. Our aim was to determine whether cardiac-related miRs such as miR-21-5p and miR-1-3p were differentially expressed in acute viral myocarditis and whether any of them was related with the extent of myocardial damage and left ventricular dysfunction. Methods: We enrolled 40 patients with acute viral myocarditis. Blood samples were taken on admission and miRs expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Results: miR-21-5p, miR-1-3p were significantly elevated in acute myocarditis. miR-21-5p levels showed a strong correlation with global longitudinal strain (r = 0.71, p < 0.01), while miR-1-3p had significant correlations with troponin I (r = 0.79, p < 0.01). Conclusions: The expression of miR-21-5p and miR-1-3p in peripheral blood is increased in acute viral myocarditis, and this increase is correlated with myocardial damage and indicative of left ventricular systolic dysfunction in these patients.

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Eiichiro Kawai ◽  
Seiichi Omura ◽  
Fumitaka Sato ◽  
Nicholas E Martinez ◽  
Viromi Fernando ◽  
...  

Viral myocarditis has been proposed to be initiated by viral replication in the heart (acute phase), followed by immune-mediated damage (subacute phase), where each phase requires anti-viral and immunomodulatory treatments, respectively. There are no specific biomarkers to distinguish acute from subacute phases of myocarditis while serum troponin, echocardiography, and myocardial biopsy data have been used for diagnosis clinically. To determine the phase-specific biomarkers, we used a mouse model for myocarditis induced by Theiler’s murine encephalomyelitis virus (TMEV), which belongs to the genus Cardiovirus, the family Picornaviridae. We conducted multivariate analyses of viral genome, serum cardiac troponin I, echocardiography, histology, and transcriptome using microarray data of the heart tissue harvested on 4 (acute) and 7 (subacute) days post infection (dpi). The level of viral RNA semi-quantified by RT-PCR was 10-fold higher on 4 dpi (ΔCt = 2.5×10-2 ± 4.9×10-3) than 7 dpi (ΔCt = 2.6×10-3 ± 3.0×10-4) (P < 0.05). Serum troponin was undetectable in 4 of 10 mice on 4 dpi and only in 1 of 10 mice on 7 dpi; the serum troponin levels (ng/ml) on 4 dpi (42.9 ± 15.6) were significantly lower than 7 dpi (249.9 ± 62.8) (P < 0.05). The levels of viral RNA and troponin were strongly correlated on 4 dpi (r = 0.79, P < 0.05), but not 7 dpi (P = 0.12), suggesting that viral replication could be a major cause of myocardial damage only on 4 dpi. We found multiple high intensity cardiac lesions using echocardiography with histological myocarditis on 7 dpi, but not 4 dpi. Transcriptome analyses of microarray data showed upregulation of genes associated with innate immune responses in samples from 4 and 7 dpi, compared with controls. Samples from 7 dpi showed upregulation of genes associated with T, B, and antigen presenting cells and downregulation of cardiac myosin-related genes (Myl4, Myl7, and Mybphl), compared with 4 dpi, suggesting that acquired immune responses contribute to cardiomyocyte damage on 7 dpi. In summary, the chronological order of emergence of biomarker candidates was 1) viral genome and innate immunity, 2) troponin, and 3) acquired immunity and echo and histological changes.


2021 ◽  
Vol 14 (7) ◽  
pp. e243946
Author(s):  
Marta Fonseca ◽  
Daniel H Chen ◽  
John Malcolm Walker ◽  
Arjun K Ghosh

A 51-year-old woman presented with a 2-week history of off balance, left lower limb weakness and neglect and neck pain radiating down the right arm. Investigations revealed a metastatic, ROS1 fusion-positive, non-small cell lung cancer, and treatment with entrectinib, a recently approved multikinase inhibitor, was started. Two weeks after, she was admitted to the emergency department with new-onset pressure-like chest pain and dyspnoea. Laboratory evaluation showed elevated troponin and mild left ventricular systolic dysfunction with reduced global longitudinal strain on transthoracic echocardiogram. Cardiac magnetic resonance revealed mild oedema and non-ischaemic fibrosis. A diagnosis of drug-induced myocarditis was made. Cardioprotective medication with an angiotensin-converting enzyme inhibitor and a beta-blocker was started. Entrectinib was temporarily discontinued and restarted at a reduced dose after a multidisciplinary team meeting involving both the oncology and cardio-oncology teams. This is the second described case of entrectinib-induced myocarditis and the first one without eosinophilia.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Jacob C Jentzer ◽  
Hussein Abu-Daya ◽  
Asher Shafton ◽  
Meshe Chonde ◽  
Didier Chalhoub ◽  
...  

Introduction: Left ventricular systolic dysfunction (LVSD) is common after resuscitation from cardiac arrest (CA). The association of echocardiographic LVSD with cardiac rhythm during CA is not well described. Hypothesis: Patients with a shockable rhythm (VT/VF) will have a greater degree of LVSD by echocardiography after CA. Methods: Prospective registry of patients resuscitated from CA underwent transthoracic echocardiography (TTE) within 24 hours after CA. We determined 2D measurements, LVEF, spectral Doppler of mitral inflow and LV outflow, systolic and diastolic tissue Doppler of the mitral annulus velocity, and tricuspid plane annular excursion (TAPSE). We collected data on in-hospital mortality as well as vasopressor doses and troponin I levels. TTE parameters and clinical characteristics were compared between patients with a shockable (VT/VF) arrest rhythm and a non-shockable (asystole/PEA) arrest rhythm and between survivors and non-survivors using t-tests and ANOVA. Results: Of the 55 patients, the 23 (42%) with shockable CA rhythms had significantly higher LV end-systolic dimension (4.1cm vs. 3.3cm, p = 0.0073), lower LV fractional shortening (0.15 vs. 0.28, p <0.0001), and lower LVEF both by visual estimate (36.2% vs. 52.3%, p = 0.0012) and by Simpson’s biplane method (37.5% vs. 52.3%, p = 0.0506). Other measured TTE parameters did not differ between groups, including TAPSE (shockable 1.53 vs. non-shockable 1.82, p = 0.1731). Admission and peak 24 hour vasopressor requirements did not differ between groups. Peak troponin levels were higher (22.26 vs. 3.88, p = 0.0198) in patients with shockable CA rhythms, but admission troponin levels were no different (0.88 vs. 0.51, p = 0.1527). TTE parameters did not differ between survivors and non-survivors (visual LVEF 47.0% vs. 44.2%, p = 0.5968; LV fractional shortening 0.19 vs. 0.25, p = 0.0916). Conclusions: Patients with shockable CA rhythms have more severe LVSD on 24 hour echocardiography despite similar vasopressor requirements and admission troponin levels. Echocardiographic parameters at 24 hours did not predict in-hospital mortality. Early echocardiography after CA appears more useful for differentiating primary CA rhythm than for predicting mortality.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A.D Farcas ◽  
F.P Anton ◽  
D.L Mocan-Hognogi ◽  
C Cainap

Abstract Introduction Survival after chemotherapy in cancer patients can be affected by several factors, including cardiotoxicity. Identification of high-risk patients and early diagnosis of cardiotoxicity would allow preventive therapies that would mitigate its effect. Although troponin I (hsTnI) and NT-proBNP have shown their usefulness, there still is incomplete data regarding the time and frequency of their testing. Aims The goal of our study was to identify new diagnostic biomarkers for early diagnosis of cardiotoxicity and analyze their predictive value for outcome. Methods We included 68 female patients with breast cancer treated with trastuzumab, who underwent clinical, biological and echocardiographic evaluation and signed informed consent. We performed biomarker testing (NT-proBNP, hsTnI, Gal 3 and GDF-15) and echocardiography at inclusion and on the day of the first chemotherapy course (after trastuzumab was administered).The patients was follow for 1 years and cardiovascular events was noted. Results The study group included middle-aged women (34.5±8.4). Although changes in the biomarker levels after the first chemotherapy course were found, these were not statistically significant. The more interesting aspect is that we found some markers increased (NTproBNP 11.12±2.9 vs 16.25±3.17, p=0.12, hsTnI 147.75±32.88 vs 151.09±34.67, p=0.74,) while other decreased (Gal-3 2300.92±982.26 vs 2193.53±377.69, p=0.78, GDF-15- 1014.09±1689 vs 1006±1662, p=0.76). Echocardiography showed no significant differences in systolic performance parameters – ejection fraction (EF) and global longitudinal strain (GLS) – but a significant change in left ventricular end-diastolic filling pressure (LVEDP) estimated by the e/e' ratio (5.68±5.63 vs 10.05±4.42, p=0.000. The LVEDP increase was correlated to NTproBNp (r=0.712, p=0.000) and Gal3 (r=0.44, p=0.009) variability. Univariate analysis showed that only NTproBNP variability predicts 16.3% of the LVEDP variability between the two moments, but the NTproBNP and LVEDP could predict the cardiovascular events during the 1-year follow-up. Conclusion Changes in diastolic performance – e/e' ratio – occur early after chemotherapy and correlate with the variability of serum natriuretic peptides. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Partnership for the transfer of knowledge in biogenomics applications in oncology and related fields - BIOGENONCO, Project co-financed by FEDR through Competitiveness Operational Programme 2014–2020, contract no. 10/01.09.2016.


2017 ◽  
Vol 35 (8) ◽  
pp. 820-825 ◽  
Author(s):  
Paaladinesh Thavendiranathan ◽  
Eitan Amir

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 51-year-old women with left-sided, T2N1, grade 3, estrogen receptor– and progesterone receptor–negative, human epidermal growth factor receptor 2 (HER2)–positive breast cancer was referred to a cardio-oncology clinic for pre–cancer treatment cardiovascular risk assessment. The planned cancer treatment was 3 cycles of FEC (fluorouracil, epirubicin [100 mg/m2 per dose], and cyclophosphamide), followed by 3 cycles of concurrent docetaxel and trastuzumab, followed by maintenance trastuzumab to complete a 1-year course. Other than a prior history of hysterectomy, there was no relevant medical history. Her cardiac history was notable for the absence of prior cardiovascular disease, hypertension, diabetes, or hypercholesterolemia. She was a nonsmoker. At initial clinic visit, her blood pressure was 138/84 with an unremarkable cardiovascular examination. Her echocardiography demonstrated normal sinus rhythm at 73 beats per minute. During cancer treatment, she was observed with echocardiography (baseline left ventricular ejection fraction [LVEF], 61%; global longitudinal strain, −21.5%), cardiac magnetic resonance imaging (CMR, as part of an ongoing study), high-sensitivity troponin I, and B-type natriuretic peptide ( Table 1 ). Given that her baseline evaluations were negative at her initial visit, we discussed whether there were agents to prevent the rare, but serious, complication of congestive heart failure (HF) associated with anthracycline- and trastuzumab-based therapy.


2021 ◽  
Vol 46 (2) ◽  
pp. 57-71
Author(s):  
Dušan Bastać ◽  
Biserka Tirmenštajn-Janković ◽  
Predrag Marušić ◽  
Zoran Joksimović ◽  
Vojkan Čvorović ◽  
...  

SIGNIFICANCE OF THE PROBLEM: The diagnosis of acute viral myocarditis is one of the diagnoses most difficult to make in cardiology and medicine in general. Echocardiography and cardiomagnetic resonance play a crucial role in the clinical diagnosis and the serum titer of antiviral antibodies to cardiotropic viruses is still unjustifiably used for the diagnosis of myocarditis in everyday practice. RESEARCH OBJECTIVES: To analyze the frequency and significance of echocardiographic parameters in the diagnosis of clinically suspected acute viral myocarditis, to determine the role of antiviral antibody titer (AVA) dynamics for the diagnosis of myocarditis and to compare viral serology and echocardiographic function versus echocardiographic function. METHODOLOGY: A retrograde transverse study was performed in the ten-year period from 2006. to 2015, where 126 consecutive patients from the database of the Office of Internal medicine ''Dr. Bastać'' were analyzed, with a working diagnosis of clinically suspected viral myocarditis. They were clinically, ECG, echocardiographically and serologically monitored for 4 to 8 weeks due to the dynamics of AVA titer. The examined group (A) was divided into subgroups: A1 with elevated AVA class IgM titer in 43 (32%) subjects and subgroup A2 without elevated IgM titer in 83 (68%) patients. The control group of healthy (B) of 103 subjects was comparable.Statistical processing was done in the EXCELL database via descriptive statistics, Student's-T test and Chi2 test. RESULTS: 126 patients had clinically suspected myocarditis (≥2 ESC criteria). Diastolic left ventricular dysfunction in 39/126 (31%) patients was the dominant echocardiographic criterion for clinically suspected myocarditis. Reduced ejection fraction (EF <50%) was measured at 19/126 (15%), followed by left ventricular dilatation. Regional systolic dysfunction was found in 21/126 (17%) and changes in myocardial texture in 17 (13%) subjects. The clinical probability of viral etiology was diagnostically supported by elevated titer of IgM antibodies in 43 (32%) subjects (subgroup A1) where IgM antibodies to Parvo B 19 virus predominate in 36/43 patients (84%). Most were without elevated titer of IgM antibodysubgroup A2 83 (68%). Clear dynamics of IgM antibody titer was observed in 23 persons, a decrease in IgM titer with an increase in IgG titer (seroconversion) in 13 patients. Determination of anti-heart autoantibodies (AHA) was done in 17 severe cases, of which 9 had positive AHA. A comparison of subgroups A1 and A2 did not reveal a statistically significant difference in echocardiographic parameters. The whole group A of clinically suspected myocarditis compared to control group B has statistically highly significantly lower parameters of global systolic (EF=8,7±4,6 vs. 63±7,9; p<0,001), longitudinal systolic (S'=6,9±1,3 vs. 9,9±2,1) and diastolic function (E/e'11,9±4,8 vs. 8,7±4,6; p<0,001), and a highly statistically significant increase in left ventricular telediastolic dimension, myocardial mass index, and left atrial size. CONCLUSION: The diagnosis of acute viral myocarditis in clinical practice is made on the basis of the clinical picture, ECG and echocardiography that indicate myocarditis with the exclusion of cardiac comorbidities, based on the ESC criteria for suspected clinical myocarditis. The whole group A had highly statistically significantly lower parameters of systolic and diastolic function compared to control group B. Normal ECG and echocardiography cannot serve to exclude the diagnosis of myocarditis. Comparison of subgroups A1 and A2 did not reveal a statistically significant difference in echocardiographic parameters.


Author(s):  
Mahmood H. Khan ◽  
Mirza Md. Nazrul Islam ◽  
Md. Shafiqul Islam ◽  
Kaisar Nasrullah Khan ◽  
Shamim Chowdhury ◽  
...  

Background: Coronary Heart Disease (CHD) is the most common category of the heart disease and is found to be the single most important cause that leads to premature death in the developed world. Recognizing a patient with ACS is important because the diagnosis triggers both triage and management. cTnI is 100% tissue-specific for the myocardium and it has shown itself as a very sensitive and specific marker for AMI. Ventricular function is the best predictor of death after an ACS. It serves as a marker of myocardial damage and provides information on systolic function as well as diagnosis and prognosis. The study aimed at investigating the impact of LVEF on elevated troponin-I level in patients with first attack of NSTEMI.Methods: This cross-sectional analytical study was conducted in the department of cardiology in Mymensingh Medical College Hospital from December, 2015 to November, 2016. Total 130 first attack of NSTEMI patients were included considering inclusion and exclusion criteria. The sample population was divided into two groups: Group-I: Patients with first attack of NSTEMI with LVEF: ≥55%. Group-II: Patients with first attack of NSTEMI with LVEF: <55%. Then LVEF and troponin-I levels were correlated using Pearson’s correlation coefficient test.Results: In this study mean troponin-I of group-I and group-II were 5.53±7.43 and 16.46±15.79ng/ml respectively. It was statistically significant (p<0.05). The mean LVEF value of groups were 65.31±10.30% and 40.17±4.62% respectively. It was statistically significant (p<0.05). The echocardiography showed that patients with high troponin-I level had low LVEF and patients with low troponin-I level had preserved LVEF. Analysis showed that patients with highest level of troponin-I had severe left ventricular systolic dysfunction (LVEF <35%) and vice versa-the patients with the lowest levels of troponin-I had preserved systolic function (LVEF ≥55%). In our study, it also showed that the levels of troponin-I had negative correlation with LVEF levels with medium strength of association (r= -0.5394, p=0.001). Our study also discovered that Troponin-I level ≥6.6ng/ml is a very sensitive and specific marker for LV systolic dysfunction.Conclusions: The study has enabled the research team to conclude that the higher is the Troponin-I level the lower is the LVEF level and thus more severe is the LV systolic dysfunction in first attack of NSTEMI patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-4 ◽  
Author(s):  
Sunny Patel ◽  
Sepideh Nabatian ◽  
Michael Goyfman

A 66-year-old female was brought to the emergency department for acute-onset left-sided chest pain. Prior to arrival, she was at an outpatient appointment with a vascular surgeon for elective sclerotherapy treatment of her lower extremity varicose veins. After receiving an IV injection of polidocanol, she developed severe chest pain with left arm and jaw numbness for the first time in her life. Upon arrival to the ED, the patient reported that her symptoms had resolved. Electrocardiogram (ECG) on presentation was significant for T-wave inversions in leads V1-V3. An initial set of cardiac enzymes showed a troponin I level of 0.62 ng/mL, which subsequently increased to 2.26 ng/mL. Her echocardiogram was significant for mild left ventricular systolic dysfunction with apical hypokinesis (ejection fraction 50%). A repeat ECG showed new T-wave inversions compared to that from the time of admission. The patient eventually agreed to cardiac catheterization, which revealed patent vessels without coronary artery disease, supporting our diagnosis of Takotsubo syndrome and what is the first reported case of likely polidocanol-induced Takotsubo syndrome in the United States.


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