bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of risk factors for the severity of immune checkpoint inhibitor-associated myocarditis in cancer patients
Authors: Tang X , Li Y , Shi R , Yang Z 
Published: November 2023

Abstract

Purpose
To explore the predictive significance of patients’ clinical features and examination results, including blood laboratory tests, echocardiogram, cardiovascular magnetic resonance (CMR), and electrocardiogram (ECG), for the severity of immune checkpoint inhibitors (ICIs)-associated myocarditis.

Methods
Data from a real-world cohort of 81 cancer patients who developed ICI-associated myocarditis after immunotherapy were retrospectively analyzed. Myocarditis of Common Terminology Criteria for Adverse Events (CTCAE) grades 3-5 and the development of the major adverse cardiovascular event (MACE) were set as endpoints. Logistic regression was used to evaluate each parameter’s value in predicting myocarditis of grades 3-5 and MACE.

Results
Eventually, CTCAE grades 3-5 and MACE developed in 43/81 (53.1%) and 28/81 (34.6) cases, respectively. The occurrence of CTCAE grades 3-5 (HR, 95%CI: 4.48, 2.02-9.91, p&lt;0.001) and MACE (HR, 95%CI: 16.21, 6.93-37.94, p&lt;0.001) were strongly related to patients’ overall survival from ICI-associated myocarditis to death. The likelihood of CTCAE grades 3-5 and MACE increased with the accumulation of organs affected by the ICI-associated adverse events and initial clinical symptoms. Concurrent systematic therapies during ICI treatment did not raise the risk of myocarditis severity, while prior chemotherapy did. Apart from the classical cardiac markers, such as myoglobin, brain natriuretic peptide, and troponin T, a higher neutrophil ratio was also related to poorer cardiac outcomes, whereas a higher lymphocyte and monocyte ratios were predictors of favorable cardiac outcomes. Besides, the CD4+ T cell ratio and CD4/CD8 ratio were negatively related to CTCAE grades 3-5. Several cardiovascular magnetic resonance parameters were associated with myocarditis severity. In contrast, the predictive value of echocardiography and electrocardiogram was weak.

Conclusions
This study comprehensively evaluated the prognostic value of different patients’ clinical factors and examination results and discovered several predictors of severe ICI-associated myocarditis, which will facilitate early detection of severe ICI-associated myocarditis in patients receiving immunotherapy.
Sequential activation of DNA viruses by the RNA virus SARS-CoV-2 in patients with long COVID syndrome
Authors: Gyongyosi M , Hasimbegovic E , Lukovic D , Zlabinger K , Spannbauer A , Samaha E , Bergler-Klein J , Hengstenberg C , Mucher P , Haslacher H , Breuer M , Strassl R , Riesenhuber M , Nitsche C , Zelniker T A 
Published: November 2023

Abstract

Background
Reactivation of Epstein-Barr virus (EBV) has been suggested to play role in long lasting multiorgan symptoms several months after the initial COVID-19 illness.

Purpose
The aim of our prospective study was to 1) to evaluate the reactivation of DNA viruses of EBV, Cytomegalovirus, Herpes simplex, Varicella zoster and Parvovirus-B19 by SARS-CoV-2 in patients with the diagnosis of long-COVID syndrome, 2) to investigate the effect of supposed virus reactivation on clinical conditions and long COVID syndromes.

Methods
Patients with long COVID syndrome were prospectively included into the Vienna PostCoV Registry between March 15th 2021 and September 30th 2021. - The time between COVID-19 infection and first clinical visit was 219±98 days (7±3 months). Clinical symptoms were documented and patients were divided into symptoms-oriented subgroups with dominantly respiratory, cardiovascular or neuropsychologic complaints. Qualitative and quantitative viral IgG and IgM titer of the selected DNA viruses of n=105 patients were compared with age and sex-matched healthy (non-infected, non-vaccinated, n=105) controls, who had neither spike- nor nucleocapsid antibodies, nor clinical history of COVID-19 disease.

Results
Long Covid patients had significantly higher cumulative number of IgM positivity of the DNA viruses (18.1% vs 6.7%, p=0.02), and significantly elevated quantitative EBV IgG (420±296 vs 339±282 mg/dL, p=0.033) and Parvo-B19 IgM (0.28±0.29 vs 0.03±0.12 mg/dL, p&lt;0.001) titer as compared to healthy controls. Significantly more patients with long COVID symptoms had an EBV IgG titer above the detection limit as compared with healthy controls (40% vs 28%, p=0.018), suggesting EBV virus reactivation and chronic EBV infection. EBV IgG titer was significantly higher in patients with dominant respiratory symptoms, while elevated Parvo-B19 IgM titer was observed in patients with dominant cardiovascular complaints. In patients with long-COVID syndrome the quantitative EBV IgG titer increased with the time between infection and blood sampling (logarithmic correlation, p=0.011), suggesting the subclinical continuous EBV activation by the SARS-CoV2 RNA virus, while the quantitative Parvo-B19 IgM titer decreased linearly during the observation period.

Conclusions
In this study of patients with long-COVID syndrome, SARS-CoV-2 infection apparently activated certain types of DNA viruses (EBV, and Parvo-B19), as demonstrated by the significantly higher incidence of cumulative IgM positivity, and elevated EBV IgG and parvovirus-B19 IgM titers, in long-COVID patients compared to healthy controls.
Association between anti-cardiac autoantibodies in acute myocarditis and downstream clinical outcomes
Authors: Iacob A , Lota A , Bakula A , Sattler S , Prasad S 
Published: November 2023

Abstract

Introduction
Myocarditis is an inflammatory heart muscle disease that can result in cardiac dysfunction and arrhythmias. Its aetiology includes infectious, toxic or autoimmune causes. Myocarditis is responsible for sudden cardiac death in young adults (1) and can result in heart failure due to dilated cardiomyopathy in 20% of patients (2). The pathogenesis of myocarditis may involve immune system dysregulation leading to a cascade of inflammation and myocardial damage (3). For those patients that rapidly progress to end-stage dilated cardiomyopathy, an important dilemma is whether there is any prospect of heart function recovery. Therefore, there is an unmet need for a better understanding of key causal pathways and for developing a biological signature of disease progression.

Hypothesis
The progression of acute myocarditis depends on a persistent adaptive immune response against the heart, leading to ongoing inflammation, myocardial fibrosis and ultimately tissue destruction and remodelling.

Aims
We sought to explore anti-cardiac IgG serum levels, their temporal profile throughout follow up and their association with clinical and imaging data, in patients presenting with acute myocarditis.

Methods
We prospectively recruited 80 patients with a clinical diagnosis of acute myocarditis. We measured their total anti-cardiac IgG levels at admisssion, 3- and 12-months follow-up using an enzyme-linked immunosorbent assay (ELISA). We explored the association between the anti-cardiac IgG levels, cardiac MRI parameters (CMR) and clinical data.

Results
We detect an adaptive immune response against the heart in a subgroup of patients with acute myocarditis. 20% of patients develop high systemic titres of anti-cardiac IgG (OD threshold &gt;0.65), within the first 7 days of presentation (Figure 1a). These patients continue to have persistent and significantly higher anti-cardiac IgG levels at 12 months (Figure 1b). Importantly, patients that mount a strong initial adaptive immune response against the heart, are more likely to show evidence of persistent oedema on CMR at 12 months(Figure 1c). Clinical event rates in our cohort have remained low at five-year follow-up. A small signal exists to indicate potentially higher rates of persistent symptoms (70% vs 47%), hospitalisations for heart failure (12% vs 8%) and new heart failure diagnosis (18% vs 11%), in patients that mount a strong adaptive immune response compared to those that do not.

Conclusion
A subset of patients with acute myocarditis develops a strong and persistent adaptive immune response against the heart. This may be associated with more myocardial oedema on cardiac MRI, persistent symptoms and higher rates of heart failure diagnoses and hospitalisations.

Further work
Plasma proteomics (targeted and un-targeted discovery) with validation in myocardial tissue. Analysis of CMR data with a focus on fibrosis assessment. ELISA for IgG subtypes and total IgG against myosin and troponin I.
Role and prognostic relevance of cardiac magnetic resonance imaging in the assessment of left ventricular non-compaction cardiomyopathy: review and meta-analysis
Authors: Gegenava T , Gegenava M 
Published: November 2023

Abstract

Background
Left ventricular non-compaction (LVNC) is a heterogeneous myocardial disorder characterized by prominent myocardial trabeculation with deep inter-trabecular recesses, thin epicardial layer of compacted myocardium and extensive non-compacted inner muscular layer. Although several diagnostic criteria have been proposed, prediction of major adverse cardiovascular and cerebrovascular events (MACCE) still remains challenging in patients with LVNC.

Objectives
Objectives of our study were to perform systemic review and meta-analysis of published literature evaluating role and prognostic significance of the late gadolinium enhancement (LGE) in cardiac magnetic resonance imaging (CMR) study, its association with MACCE and characteristics of CMR derived feature-tracking (FT) strain analysis in patients with LVNC.

Methods
The objectives, literature search strategies, inclusion and exclusion criteria, outcome measurements, and methods of statistical analysis were analyzed according to an established protocol of the cochrane collaboration steps and meta-analysis of observational studies in epidemiology recommendations (MOOSE). Case control studies with evaluated prevalence of LGE in LVNC cardiomyopathy patients with and without MACCE and studies comparing FT strain: left ventricular global longitudinal (LV GLS), global circumferential (GCS) and global radial (GRS) strain between patients with and without LVNC has been included in the analysis.

Results
A total of 936 papers were collected according to our searching criteria, of those 9 studies including 416 LVNC cardiomyopathy patients with MACCE and 673 LVNC patients without MACCE and with evaluated LGE (including three studies with LVNC and heart failure), also 6 studies including 267 LVNC patients and 283 controls with evaluated FT LV GLS, GCS and GRS (measured in four studies) were selected. LGE was more frequently observed in LVNC patients with MACCE as compared to those without MACCE [RR (95 %CI) 2.52 (1.63 to 3.88); p&lt;0.00001] (Fig.1). FT LV GLS was significantly more affected in LVNC patients compared to controls (St. mean difference (95 %CI): 1.40 (0.69 to 2.11); p&lt;0.00001], as well as GCS and GRS (Fig. 2).

Conclusions
In patients with LVNC evaluated with CMR, LGE shows association with adverse cardiovascular and cerebrovascular events. CMR deformation indices: FT LV GLS, GCS, and GRS are significantly affected in patients with LVNC as compared to controls. This new CMR technique may be a complementary tool for timely detection and differentiation of LVNC cardiomyopathy and to avoid life threatening adverse events.Figure 1Figure 2
Prognostic value of the left ventricular mass index by magnetic resonance imaging in patients with hypertrophic obstructive cardiomyopathy undergoing septal myectomy
Authors: Yang Q , Hao C , Zhu C , Zhao S , Yang S , Wang S 
Published: November 2023

Abstract

Research background
Traditional risk factors for hypertrophic cardiomyopathy (HCM) have limited ability to predict poor survival outcomes in the medium to long term after surgical septal myectomy (septal myectomy) in patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing septal myectomy. Additionally, there is a lack of studies reporting the relationship between left ventricular mass index (LVMI), an index of ventricular remodeling in hypertrophic obstructive cardiomyopathy, and medium to long-term prognostic outcomes after septal myectomy.
Research methods: From June 2011 to July 2016, 490 patients with HOCM who completed preoperative cardiac magnetic resonance (CMR) were retrospectively enrolled for mid- to long-term follow-up. The study's primary endpoint included all-cause death. Secondary endpoints included cardiac death and adverse cardiovascular events. Furthermore, CMR measures were applied to study the risk factors for mid- and long-term adverse endpoint events after septal myectomy treatment.
Study results: 486 patients with HOCM completed follow-up and were included in the final analysis. Twenty-one patients (4.3%) died during follow-up (median 73.6, maximum 105.6 months), and 66 patients (16.3%) had an adverse cardiovascular event during follow-up. In the Cox proportional risk regression model, the most significant predictor of all-cause mortality after septal myectomy was CMR-LVMI (risk ratio 1.009, 95% confidence interval 1.003-1.015, P=0.018). In receiver operating characteristic (ROC) analysis, LVMI &gt; Cutoffpredicted all-cause death analyzed separately by male and female subgruop(P&lt;0.05). In Cox proportional risk regression models (incorporating age, maximum septal thickness, left atrial diameter, left ventricular end-diastolic dimension, left ventricular ejection fraction, LV outflow tract peak pressure, pulmonary hypertension, LGE positive and LVMI), the most significant predictor after surgical septal resection was LVMI measured by CMR (hazard ratio 1.025, 95% confidence interval 1.009-1.040, P=0.002). From ROC analysis, LVMI &gt;cutoff accurately predicted the occurrence of all-cause mortality analysed separately by male and female (P&lt;0.05). Additionally, K-M survival curve plots suggested that patients with HOCM above the LVMI threshold group had lower all-cause mortality-free survival (Log-rank: P=0.0.025), hear failure related mortality-free survival (Log-rank: P=0.0.014) in the medium to long term after septal myectomy.

Conclusions
An elevated preoperative left ventricular myocardial mass index suggests adverse ventricular remodeling and is an independent predictor of poor survival outcomes in patients with HOCM in the medium to long term after septal myectomy.ROC analysis of LVMI for all cause deathK-M survival curve devided by LVMI level
The efficacy and safety of direct oral anticoagulants compared with vitamin K antagonist in patients with hypertrophic cardiomyopathy and atrial fibrillation: a systematic review and meta-analysis
Authors: Lyu S , Zhu J , Wang J , Wu S , Yang Y 
Published: November 2023

Abstract

Background
The benefit-risk profile of direct oral anticoagulants (DOAC) therapy in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) have not been well established yet.

Purpose
This study aimed to evaluate the efficacy and safety of DOAC compared with vitamin K antagonists (VKA) in patients with HCM and AF.

Methods
PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov were searched to identify studies comparing DOAC with VKA in patients with HCM and AF.

Results
Five studies involving 8103 patients were included in this meta-analysis. Compared to the VKA group, the DOAC group displayed a significant lower risk of all-cause death [RR (95%CI): 0.44 (0.35-0.55)]. Meanwhile, DOAC therapy group was similar to VKA therapy in reducing ischemic stroke [RR (95%CI): 0.65 (0.33-1.28)] and thromboembolic events [RR (95%CI): 0.95 (0.74-1.22)]. The incidence of major bleeding [RR (95%CI): 0.69 (0.44-1.07)] were comparable between the two groups.

Conclusion
In patients with HCM and AF, DOAC therapy were superior or non-inferior to VKA therapy in reducing the risk of all-cause death and thromboembolic events, without increasing bleeding risk. Further RCTs are needed to provide more evidence for DOAC therapy in this population.Efficacy and safety endpoints in DOAC th
Outcomes in patients with hypertrophic cardiomyopathy developing left ventricular systolic dysfunction after septal reduction therapy
Authors: Bataiosu D , Lee D Z J , Montazeri M , Billia F , Ralph-Edwards T , Rakowski H , Chan R 
Published: November 2023

Abstract

Background
In hypertrophic cardiomyopathy (HCM), systolic dysfunction (SD), defined by a left ventricular ejection fraction (LVEF) &lt;50% is associated with a poor prognosis. After septal reduction therapy (SRT), anticipated alterations in left ventricular geometry and septal desynchrony may lead to reduction in LVEF. The prognostic significance of a reduction in LVEF &lt;50% following SRT has not been established.

Purpose
To investigate the relationship between new development of SD post SRT and outcomes in HCM patients.

Methods
Of the 4110 HCM patients at our referral centre, 179 patients (4.4%) developed SD during follow up. The composite cardiac outcome was defined as the occurrence of new resuscitated cardiac arrest, ventricular tachycardia or ventricular fibrillation, and cardiac death after the onset of SD.

Results
Of the 179 patients who developed systolic dysfunction (SD), 67 patients developed it after undergoing septal reduction therapy (SRT) (4 patients underwent alcohol septal ablation, and 63 patients underwent septal myectomy). Both groups had similar characteristics with respect to age at the time of SD identification (59.9 ± 13.5 years vs. 59.6 ± 14.2 years, P=0.88), gender (76% men vs. 66% men, P=0.18), and genotype (24% had pathogenic or likely pathogenic variants vs. 28%, P=0.07). Despite similar LVEF at the time of presentation with SD between the two groups (44.1 ± 4.2% vs. 44.4% ± 4.9%, P=0.75), patients who underwent SRT had a lower maximal wall thickness (17.4 ± 4.9mm vs. 19.2 ± 5.2mm, P=0.02), larger end-diastolic diameter (5.3 ± 0.8mm vs. 4.8 ± 0.8mm, P&lt;0.001) and end-systolic diameters (3.8 ± 0.7mm vs. 3.2 ± 0.8mm, P&lt;0.001) than patients without SRT. Furthermore, patients who underwent SRT had a longer QRS complex duration (162.3 ± 20.6ms vs. 125.1 ± 31ms, p&lt;0.001) and lower brain natriuretic peptide (BNP) (359.3 ± 632.9pg/ml vs. 690.8 ± 841.8pg/ml, p=0.04) during follow up than patients without prior SRT. During a mean follow up of 4.7 ± 4.1 years, the incidence of the composite cardiac outcome was significantly lower in patients who underwent SRT than in patients without prior SRT (7.5% vs. 20.5%, P=0.02). Notably, there were no observed sudden cardiac deaths observed in those who developed SD post SRT.

Conclusion
The prognosis for patients with HCM who underwent SRT and subsequently developed SD was significantly more favourable than for those who did not have a history of SRT. Thus, changes in left ventricular geometry and LVEF after SRT may not necessarily translate into a worsened prognosis.
Prediction of acute heart failure events in patients with hypertrophic cardiomyopathy using RNA-Sequencing of plasma small non-coding RNAs
Authors: Akita K , Hasegawa K , Maurer M S , Tower-Rader A , Fifer M A , Topkara V K , Reilly M P , Shimada Y J 
Published: November 2023

Abstract

Background
Hypertrophic cardiomyopathy (HCM) often causes acute heart failure (HF) events, which lead to worse quality of life and prognosis of patients with HCM. The recent emergence of cardiac myosin inhibitors to treat HCM highlights the clinical significance of identifying patients with HCM at high risk of developing acute HF events. However, no tools are available to predict acute HF events in HCM. Furthermore, the underlying molecular mechanisms responsible for the development of HF in HCM remain uncertain. Plasma RNA-sequencing (RNA-Seq) determines concentrations of thousands of small non-coding RNAs (sncRNAs) and has the potential to predict acute HF events in HCM.

Purpose
To predict acute HF events in patients with HCM using RNA-Seq of plasma sncRNAs and to determine signaling pathways dysregulated in those who subsequently experience acute HF events.

Methods
In this prospective, multi-center cohort study of patients with HCM, we conducted RNA-Seq of 3,740 plasma sncRNAs on 390 patients with HCM. The primary outcome was acute HF event defined as unplanned hospitalization due to HF. We developed a sncRNA-Seq-based model with linear discriminant analysis to predict acute HF events using data from one institution (training set, n=271). We also developed a reference model using clinical parameters with significant differences between patients with and without acute HF events in the training set. Then we tested the predictive ability in samples from the other institutions (test set, n=119), comparing the area under the receiver-operating-characteristic curve (AUC) between a combined model using the reference model plus the sncRNA-Seq-based model and the reference model using the Delong’s test. We also performed pathway analysis of microRNAs significantly (i.e., nominal P&lt;0.05) associated with acute HF events.

Results
During a median follow-up time of 2.5 (interquartile 1.7–4.9) years, a total of 37 patients in the training set (14%) and 15 in the test set (13%) experienced an acute HF event. The model combining the reference model with the sncRNA-Seq-based machine learning model developed in the training set significantly outperformed the reference model (AUC 0.86 [95% confidence interval (CI) 0.74–0.97] vs. 0.68 [0.52–0.85], P=0.01, Figure) in the test set. The pathway analysis exhibited that both known pathways related to fibrosis, inflammation, and cell proliferation (e.g., the TGF-β signaling pathway) and novel pathways (e.g., the mTOR signaling pathway) were dysregulated with false discovery rate &lt;0.01 in patients with HCM who subsequently experienced acute HF events (Table).

Conclusions
This study serves as the first to demonstrate the ability of plasma sncRNA-Seq to predict acute HF events in patients with HCM. Patients who subsequently experienced acute HF events exhibited dysregulation of both known and novel pathways.FigureTable