A broadly cross-reactive monoclonal antibody against hepatitis E virus capsid antigen

To generate a hepatitis E virus (HEV) genotype 3 (HEV-3)–specific monoclonal antibody (mAb), the Escherichia coli–expressed carboxy-terminal part of its capsid protein was used to immunise BALB/c mice. The immunisation resulted in the induction of HEV-specific antibodies of high titre. The mAb G117-AA4 of IgG1 isotype was obtained showing a strong reactivity with the homologous E. coli, but also yeast-expressed capsid protein of HEV-3. The mAb strongly cross-reacted with ratHEV capsid protein derivatives produced in both expression systems and weaker with an E. coli–expressed batHEV capsid protein fragment. In addition, the mAb reacted with capsid protein derivatives of genotypes HEV-2 and HEV-4 and common vole hepatitis E virus (cvHEV), produced by the cell-free synthesis in Chinese hamster ovary (CHO) and Spodoptera frugiperda (Sf21) cell lysates. Western blot and line blot reactivity of the mAb with capsid protein derivatives of HEV-1 to HEV-4, cvHEV, ratHEV and batHEV suggested a linear epitope. Use of truncated derivatives of ratHEV capsid protein in ELISA, Western blot, and a Pepscan analysis allowed to map the epitope within a partially surface-exposed region with the amino acid sequence LYTSV. The mAb was also shown to bind to human patient–derived HEV-3 from infected cell culture and to hare HEV-3 and camel HEV-7 capsid proteins from transfected cells by immunofluorescence assay. The novel mAb may serve as a useful tool for further investigations on the pathogenesis of HEV infections and might be used for diagnostic purposes. Key points • The antibody showed cross-reactivity with capsid proteins of different hepeviruses. • The linear epitope of the antibody was mapped in a partially surface-exposed region. • The antibody detected native HEV-3 antigen in infected mammalian cells

The modified MIDA-Score predicts mid-term outcomes after interventional therapy of functional mitral regurgitation.

AimsThe preprocedural assessment of outcomes and patients' prognosis after interventional therapy of functional MR (FMR) is uncertain. Therefore, we aim to develop an easy-to-handle scoring system for adequate prediction of individual outcomes in patients with FMR after the interventional treatment.Materials and methodsWe retrospectively used medical data of patients with symptomatic FMR, who underwent transcatheter mitral valve repair (TMVR) from January 2014 to August 2016 in our heart center. All patients had the mean follow-up of 18 months. All clinical and echocardiographic data originate from the "Bonner Mitral Valve Register Database".ResultsWe included 105 patients (76,7±8,8 years, 50,6% female) with symptomatic (NYHA functional class>II) moderate-to-severe or severe FMR at surgical high-risk. We modified the MIDA-Score for degenerative MR (DMR) according to the varying underlying pathomechanisms of FMR, called as "The modified MIDA Score". We found all-cause mortality of 7% within 18 months after the procedure. 34,1% of our cohort was rehospitalized; 90% of those were due to cardiovascular causes. The modified MIDA score was found to be a strong predictor for mortality and rehospitalization in patients with FMR (AUC: 0,89) and superior to the other conventional scoring systems in prediction of mortality (The modified MIDA-Score: AUC: 0,8, EuroSCORE II: AUC: 0,57, STS-Score: AUC: 0,51). The logistic regression analysis showed the modified MIDA score > 9 points to be the strongest predictor for mortality and rehospitalization after TMVR (OR: 3,35, p = 0,011).ConclusionThe modified MIDA score was found to be a promising, easy-to-handle, elementary scoring system for adequate prediction of individual postinterventional prognosis in patients with FMR undergoing TMVR. Further evaluation and validation of this novel scoring system in prospective multicentric studies with a large number of patients is warranted

Treatment of Secondary Mitral Regurgitation - Strategies of a University Network

Secondary mitral regurgitation is common in patients with heart failure and associated with adverse outcome. Treatment was traditionally restricted to general heart failure therapy due to high surgical risk. Development of catheter-based techniques now offers treatment with acceptable risk. Albeit trial evidence is still limited, current European guidelines up-graded the recommendation of transcatheter therapies for patients with increased surgical risk and high probability of treatment response. However, several uncertainties remain with respect to the role of surgical treatment and patient selection for transcatheter therapies. In this review we summarize current status of treatment of secondary mitral regurgitation and show strategies of university networks with the aim to provide further evidence in support of the treatment

CHA2DS2-VASC score predicts coronary artery disease progression and mortality after ventricular arrhythmia in patients with implantable cardioverter-defibrillator

Aim: The CHA2DS2-VASC score has expanded its use beyond the initial purpose of predicting the risk of stroke in patients with atrial fibrillation. We aimed to investigate the value of the CHA2DS2-VASC score as a risk assessment tool to predict relevant coronary artery disease (CAD) leading to percutaneous coronary intervention (PCI), and all-cause mortality after detected ventricular arrhythmia (VA) in patients with an Implantable Cardioverter-Defibrillator (ICD). Methods: A total of 183 ICD-patients who underwent coronary angiography after VA were included and classified according to their CHA2DS2-VASC score in a low(1-3), intermediate(4-5) and high(6-8) score group. We evaluated the predictive value of CHA2DS2-VASC score for the presence of relevant CAD leading to percutaneous coronary intervention (PCI), as well as late all-cause mortality. Results: A total of 60 patients (32.8%) had significant CAD and underwent successful PCI. After adjustment for relevant parameters such as ischemic cardiomyopathy, angina pectoris, left ventricular ejection fraction, CHA2DS2-VASC score remained the only independent predictor of CAD leading to PCI [HR 1.73 (1.07–2.80)]. The Area under curve was 0.64 (0.56–72, p = 0.002). Kaplan-Meier analysis and log-rank showed an increased three-year mortality of ICD-patients with an intermediate or high score after VA (p = 0.003). Multivariate cox-regression analysis revealed that CHA2DS2-VASC score was also independently associated with all-cause mortality following adjustment for clinically relevant variables (HR 2.20, 1.17–4.14). Conclusions: CHA2DS2-VASC score can be a predictor of CAD leading to PCI in ICD-patients after VA. ICD-Patients with a high score have an increased risk for reduced three-year all-cause mortality after VA

Prognostic significance of the get with the guidelines-heart failure (GWTG-HF) risk score in patients undergoing trans-catheter tricuspid valve repair (TTVR)

The Get-With-The-Guidelines-Heart-Failure (GWTG-HF) score is a risk assessment tool to predict mortality in patients with heart-failure (HF). We aimed to evaluate the GWTG-HF score for risk stratification in HF patients with tricuspid regurgitation undergoing trans-catheter tricuspid valve repair (TTVR). In total, 181 patients who underwent TTVR via edge-to-edge repair (86%) or annuloplasty (14%) were enrolled. Patients were categorized into a low- (≤ 43 points), intermediate- (44-53 points) and high-risk score groups (≥ 54 points). TTVR led to an improvement of TR (p < 0.0001) and NYHA (p < 0.0001). Kaplan-Meier analysis and log-rank test revealed that higher GWTG-HF scores were associated with reduced rates of event-free survival regarding mortality (96% vs 89% vs 73%, respectively, p = 0.001) and hospitalization for heart failure (HHF) (89% vs 86% vs 74%, respectively, p = 0.026). After adjusting for important variables like renal function, left ventricular ejection fraction and mitral regurgitation, the GWTG-HF score remained an independent predictor of the composite endpoint of HHF or mortality (hazard ratio 1.04 per 1-point increase, p = 0.029). Other remaining predictors were renal function and mitral regurgitation. The GWTG-HF score used as a risk stratification tool of mortality and HHF maintains its prognostic value in a HF population with severe TR undergoing TTVR

Clinical effects of cognitive behavioral therapy in heart failure patients: a meta-analysis of randomized controlled trials

Abstract Background About 20–40% of people with Heart failure (HF) suffer from some depression, which is 4–5% greater than the overall population. This depression can lead to undesirable outcomes, including elevated mortality rate and frequent hospitalization. Purpose The current study aims to evaluate the impact of cognitive behavioural therapy (CBT) on self-care and the symptoms of depression and anxiety in HF patients. Methods We searched PubMed, Web of Science (WOS), Scopus, and Cochrane Library till 15 October 2022. All relevant randomized controlled trials (RCTs) were included. The data were extracted and pooled using Review Manager software (RevMan 5.4). Continuous data were pooled as mean difference and 95% confidence interval (CI). Results Our search retrieved 1146 records, and 7 studies (611 patients) were finally included. We assessed the Beck Depression Inventory-II (BDI-II) as the primary outcome of the study. Hamilton Rating Scale for Depression (HRSD-17), Change in Beck Anxiety Inventory, Kansas City Cardiomyopathy Questionnaire (KCCQ), and Self-Care of Heart Failure Index (SCHFI) were also assessed as secondary outcomes. With CBT, BDI-II showed a significant reduction after 4 to 6 months follow-up (MD = -4.87, 95% CI: [-8.06; -1.69], P = 0.003) as well as 8 to 9 months follow-up (MD = -5.71, 95% CI: [-8.95; -2.46], P = 0.0006). But no significant difference was shown with 3 months follow-up (M.D=-4.34; 95%CI: [-10.70; 2.03], P = 0.18). Conclusions CBT has long-term (4–9 months) significant favorable outcomes decreasing anxiety and depression compared to non-CBT groups. No significant short-term (less than 3 months) impact on HF patients’ self-care, depression, or anxiety were shown

Sodium thiocyanate treatment attenuates atherosclerotic plaque formation and improves endothelial regeneration in mice.

INTRODUCTION:Atherosclerotic plaque formation is an inflammatory process that involves the recruitment of neutrophil granulocytes and the generation of reactive oxygen species (ROS). ROS formation by myeloperoxidase, a key enzyme in H2O2 degradation, can be modulated by addition of sodium thiocyanate (NaSCN). However, the therapeutic use of NaSCN to counteract atherogenesis has been controversial, because MPO oxidizes NaSCN to hypothiocyanous acid, which is a reactive oxygen species itself. Therefore, this study aimed to investigate the effect of NaSCN treatment on atherogenesis in vivo. METHODS:Apolipoprotein E knockout (ApoE-/-) mice on western-diet were treated with NaSCN for 8 weeks. Blood levels of total cholesterol, IL-10, and IL-6 were measured. Aortic roots from these mice were analyzed histologically to quantify plaque formation, monocyte, and neutrophil granulocyte infiltration. Oxidative damage was evaluated via an L-012 chemiluminescence assay and staining for chlorotyrosine in the aortic walls. Endothelial function was assessed by use of endothelium-dependent vasodilation in isolated aortic rings. Neointima formation was evaluated in wild-type mice following wire injury of the carotid artery. RESULTS:NaSCN treatment of ApoE-/- mice lead to a reduction of atherosclerotic plaque size in the aortic roots but had no effect on monocyte or granulocyte infiltration. Serum levels of the pro-inflammatory cytokine IL-6 decreased whereas anti-inflammatory IL-10 increased upon NaSCN treatment. In our experiments, we found oxidative damage to be reduced and the endothelial function to be improved in the NaSCN-treated group. Additionally, NaSCN inhibited neointima formation. CONCLUSION:NaSCN has beneficial effects on various stages of atherosclerotic plaque development in mice

Risk of mortality following transcatheter aortic valve replacement for low-flow low-gradient aortic stenosis

Background Low-flow low-gradient (LF-LG) aortic stenosis (AS) is associated with high mortality, even after transcatheter aortic valve replacement (TAVR). Further knowledge of risk indicators is needed and a clinical risk score would be desirable for optimizing patient selection and therapeutic strategy. Methods The study cohort comprised of 219 consecutive LF-LG AS patients undergoing TAVR from 2008 to 2018 in two high-volume German centers. Predictive factors for one-year all-cause mortality were defined according to a Cox proportional hazard model. Results At one-year follow-up after TAVR, 28% of patients had died. A multivariate model revealed six independent predictors of one-year mortality: history of myocardial infarction (HR 2.05, 95%CI 1.13-3.72), eGFR = 8 had a prohibitive risk of one-year mortality of 67.6% (95%CI 52.0-82.4%). Conclusion In patients with LF-LG AS, history of myocardial infarction, renal dysfunction, tricuspid regurgitation, a low stroke volume index, self-expandable device, and non-femoral approach were associated with increased 1-year mortality after TAVR. The RRS might serve as a helpful tool for risk prediction and patient selection for TAVR in patients with LF-LG AS

Deep sedation vs. general anesthesia for transcatheter tricuspid valve repair

BackgroundTranscatheter tricuspid valve repair (TTVr) is routinely performed under general anesthesia (GA). This study aimed to investigate whether TTVr procedures can be performed effectively and safely without GA but using deep sedation (DS). MethodsWe performed a retrospective analysis of 104 patients from three centers who underwent TTVr between 2020 and 2021. The primary performance endpoints were technical success and severity of TR assessed at the time of discharge. The safety outcome was a composite of in-hospital complications, including occurrence of death, conversion to surgery, major adverse cardiac and cerebrovascular events, major vascular complications, or occurrence of pneumonia. ResultsSixty-four procedures were performed in GA and 40 procedures were performed in DS. The groups did not differ in age, EuroScore II, TR severity, ventricular function, or hemodynamic parameters. Technical success was achieved in 92.5% of the patients in the DS group and in 93.6% of the patients in the GA group (p = 0.805). In none of the patients intraprocedural conversion from DS to GA was required. There was no difference in total duration of the procedure, and number of devices implanted. The degree of TR was <= 2+ in 77.5% of the patients in the DS group and in 74.2% of the patients in the GA group (p = 0.705). The composite safety endpoint did not differ between the groups (2.5 vs. 6.3%, p = 0.384). The total duration of hospital stay was shorter in patients who underwent TTVr in DS compared to those who underwent TTVr in GA (6 [5, 9] days vs. 8 [6, 11] days; p = 0.011). ConclusionPerforming TTVr in DS was effective with similar procedural results, and was safe with similar low complication rates compared to GA

PASCAL versus MitraClip-XTR edge-to-edge device for the treatment of tricuspid regurgitation: a propensity-matched analysis

Background!#!Transcatheter tricuspid valve repair (TTVR) is a promising technique for the treatment of tricuspid regurgitation (TR). Data comparing the performance of novel edge-to-edge devices (PASCAL and MitraClip-XTR) are scarce.!##!Methods!#!We identified 80 consecutive patients who underwent TTVR using either the PASCAL or MitraClip-XTR system to treat symptomatic TR from July 2018 to June 2020. To adjust for baseline imbalances, we performed a propensity score (PS) 1:1 matching. The primary endpoint was a reduction in TR severity by at least one grade at 30 days.!##!Results!#!The PS-matched cohort (n = 44) was at high-surgical risk (EuroSCORE II: 7.5% [interquartile range (IQR) 4.8-12.1%]) with a mean TR grade of 4.3 ± 0.8 and median coaptation gap of 6.2 mm [IQR 3.2-9.1 mm]. The primary endpoint was similarly observed in both groups (PASCAL: 91% vs. MitraClip-XTR: 96%). Multiple device implantation was the most common form (59% vs. 82%, p = 0.19), and the occurrence of SLDA was comparable between the PASCAL and MitraClip-XTR system (5.7% [2 of 35 implanted devices] vs. 4.4% [2 of 45 implanted devices], p = 0.99). No periprocedural death or conversions to surgery occurred, and 30-day mortality (5.0% vs. 5.0%, log-rank p = 0.99) and 3-month mortality (10.0% vs. 5.0%, log-rank p = 0.56) were similar between both groups. During follow-up, functional NYHA class, 6-min walking distance, and health status improved in both groups.!##!Conclusions!#!Both TTVR devices, PASCAL and MitraClip-XTR, appeared feasible and comparable for an effective TR reduction. Randomized head-to-head comparisons will help to further define the appropriate scope of application of each system