N-acetyl-b-D-glucosaminidase: A potential cardiorenal biomarker with a relevant impact on ICD shock therapies and mortality

Aims Chronic heart failure may lead to chronic kidney disease. Previous studies suggest tubular markers N-acetyl-b-D-glucosaminidase (NAG) and Kidney-injury-molecule-1 (KIM-1) as potential markers for the cardiorenal syndrome (CRS). The prognostic value of NAG and KIM-1 regarding implantable cardioverter defibrillator (ICD) shock therapies is unknown. Methods We included 314 patients with an ICD and collected plasma and urine samples. Urine-values of NAG and KIM-1 got related to urinary creatinine. Outcomes of interest were sustained adequate shock therapies and a combined endpoint of all-cause mortality, rehospitalisation due to congestive heart failure and adequate shock therapies. Follow up time was 32 months (IQR 6-35 months). Results KIM-1 and NAG were positively correlated with NT-proBNP (KIM-1:r= .34,P < .001; NAG:r= .47,P < .001). NAG was significantly elevated in patients with primary prevention compared with secondary prevention ICD indication (P= .003). According to Kaplan Meier analysis, NAG as well as NT-proBNP were significant predictors for adequate ICD shock therapies and for the combined endpoint (eachP < .001). Elevated KIM-1 showed no significant differences (eachP= n.s.). In multivariate cox regression analysis, NAG as well as NT-proBNP were both independent predictors for adequate ICD shock therapies as well as the combined endpoint, beside ejection fraction <35% (eachP < .05). Diabetes, primary prevention ICD indication, coronary artery disease, eGFR and age were no significant predictors for both endpoints (eachP= n.s.). Conclusion Similar to NT-proBNP, NAG showed promising value for overall prognostication in ICD patients. Especially, NAG seems to incorporate an additional prognostic value regarding occurrence of ICD shock therapies

Ventricular arrhythmia burden in patients with implantable cardioverter defibrillator and remote patient monitoring during different time intervals of the COVID-19 pandemic

Purpose The current study investigated whether the changes in patient care in times of the COVID-19 pandemic, especially the reduction of in-person visits, would result in a deterioration of the arrhythmic and clinical condition of patients with an implantable cardioverter defibrillator (ICD) and remote patient monitoring. Methods Data were obtained from a local ICD registry. 140 patients who received ICD implantation at our department and had remote patient monitoring were included. The number of patients with ventricular arrhythmias, appropriate ICD therapy, the number of visits to our outpatient clinic and hospitalization due to acute coronary syndrome, stroke or heart failure were compared during three time intervals of the COVID-19 pandemic (first (LD1) and second (LD2) national lockdown in Germany and the time after the first lockdown (postLD1)) and a time interval 1 year before the pandemic began (preCOV). Each time interval was 49 days long. Results Patients had significantly fewer visits to our outpatient clinic during LD1 (n = 13), postLD1 (n = 22) and LD2 (n = 23) compared to the time interval before the pandemic (n = 43, each p ≤ 0.05). The number of patients with sustained ventricular arrhythmias, appropriate ICD therapy and clinical events showed no significant difference during the time intervals of the COVID-19 pandemic and the time interval 1 year prior. Conclusions The lockdown measures necessary to reduce the risk of infection during the COVID-19 pandemic, led to a reduction of in-person patient visits, but did not result in a deterioration of the arrhythmic and clinical condition of ICD patients with remote patient monitoring

Cardiac MRI Based Left Ventricular Global Function Index: Association with Disease Severity in Patients with ICD for Secondary Prevention

Left ventricular (LV) ejection fraction (LVEF) is the most widely used prognostic marker in cardiovascular diseases. LV global function index (LVGFI) is a novel marker which incorporates the total LV structure in the assessment of LV cardiac performance. We evaluated the prognostic significance of LVGFI, measured by cardiovascular magnetic resonance (CMR), in predicting mortality and ICD therapies in a real-world (ICD) population with secondary ICD prevention indication, to detect a high-risk group among these patients. In total, 105 patients with cardiac MRI prior to the ICD implantation were included (mean age 56 ± 16 years old; 76% male). Using the MRI data for each patient LVGFI was determined and a cut-off for the LVGFI value was calculated. Patients were followed up every four to six months in our or clinics in proximity. Data on the occurrence of heart failure symptoms and or mortality, as well as device therapies and other vital parameters, were collected. Follow up duration was 37 months in median. The mean LVGFI was 24.5%, the cut off value for LVGFI 13.5%. According to the LVGFI Index patient were divided into 2 groups, 86 patients in the group with the higher LVGFI und 19 patients in the lower group. The LVGFI correlates significantly with the LVEF (r = 0.642, p I, the initial device or a medication (each p = n.s.). Further, in Kaplan–Meier analysis no association was evident between the LVGFI and adequate ICD therapy (p = n.s.). In secondary prevention ICD patients reduced LVGFI was shown as an independent predictor for mortality and rehospitalization, but not for ICD therapies. We were able to identify a high-risk collective among these patients, but further investigation is needed to evaluate LVGFI compared to ejection fraction, especially in patients with an elevated risk for adverse cardiac events

The impact of bicuspid aortic valve morphology on von Willebrand factor function in patients with severe aortic stenosis and its change after TAVI

Background Aortic stenosis (AS) can cause acquired von Willebrand syndrome (AVWS) and valve replacement has been shown to lead to von Willebrand factor (vWF) recovery. The aim of the current study was to investigate the prevalence of AVWS in different severe AS phenotypes and its course after transcatheter aortic valve implantation (TAVI). Methods 143 patients with severe AS undergoing TAVI were included in the study. vWF function was assessed at baseline, 6 and 24 h after TAVI. AVWS was defined as a reduced vWF:Ac/Ag ratio ≤ 0.7. Phenotypes were classified by tricuspid (TAV) and bicuspid (BAV) valve morphology, mean transvalvular gradient (Pmean), stroke volume index (SVI), ejection fraction (EF) and indexed effective orifice area (iEOA). Results AVWS was present in 36 (25.2%) patients before TAVI. vWF:Ac/Ag ratio was significantly lower in high gradient compared to low-gradient severe AS [0.78 (IQR 0.67–0.86) vs. 0.83 (IQR 0.74–0.93), p < 0.05] and in patients with BAV compared to TAV [0.70 (IQR 0.63–0.78) vs. 0.81 (IQR 0.71–0.89), p < 0.05]. Normalization of vWF:Ac/Ag ratio was achieved in 61% patients 24 h after TAVI. As in the overall study cohort, vWF:Ac/Ag ratio increased significantly in all severe AS subgroups 6 h after TAVI (each p < 0.05). Regarding binary logistic regression analysis, BAV was the only significant predictor for AVWS. Conclusions BAV morphology is a strong predictor for AVWS in severe AS. TAVI restores vWF function in most patients with severe AS independently of AS phenotype and valve morphology

Urinary N-Terminal Pro-Brain Natriuretic Peptide Predicts Acute Kidney Injury and Severe Disease in COVID-19

Introduction: The ongoing COVID-19 pandemic is placing an extraordinary burden on our health care system with its limited resources. Accurate triage of patients is necessary to ensure medical care for those most severely affected. In this regard, biomarkers could contribute to risk evaluation. The aim of this prospective observational clinical study was to assess the relationship between urinary N-terminal pro-brain natriuretic peptide (NT-proBNP) and acute kidney injury (AKI) as well as severe disease in patients with COVID-19. Methods: 125 patients treated with an acute respiratory infection in the emergency department of the University Hospital Regensburg were analyzed. These patients were divided into a COVID-19 cohort (n = 91) and a cohort with infections not caused by severe acute respiratory syndrome-coronavirus-2 (n = 34). NT-proBNP was determined from serum and fresh urine samples collected in the emergency department. Clinical endpoints were the development of AKI and a composite one consisting of AKI, intensive care unit admission, and in-hospital death. Results: 11 (12.1%) COVID-19 patients developed AKI during hospitalization, whereas 15 (16.5%) reached the composite endpoint. Urinary NT-proBNP was significantly elevated in COVID-19 patients who suffered AKI or reached the composite endpoint (each p < 0.005). In a multivariate regression analysis adjusted for age, chronic kidney disease, chronic heart failure, and arterial hypertension, urinary NT-proBNP was identified as independent predictor of AKI (p = 0.017, OR = 3.91 [CI: 1.28–11.97] per standard deviation [SD]), as well as of the composite endpoint (p = 0.026, OR 2.66 [CI: 1.13–6.28] per SD). Conclusion: Urinary NT-proBNP might help identify patients at risk for AKI and severe disease progression in COVID-19

Decreased GLUT1/NHE1 RNA expression in whole blood predicts disease severity in patients with COVID‐19

Aims We aimed to assess whether expression of whole‐blood RNA of sodium proton exchanger 1 (NHE1) and glucose transporter 1 (GLUT1) is associated with COVID‐19 infection and outcome in patients presenting to the emergency department with respiratory infections. Furthermore, we investigated NHE1 and GLUT1 expression in the myocardium of deceased COVID‐19 patients. Methods and results Whole‐blood quantitative assessment of NHE1 and GLUT1 RNA was performed using quantitative PCR in patients with respiratory infection upon first contact in the emergency department and subsequently stratified by SARS‐CoV‐2 infection status. Assessment of NHE1 and GLUT1 RNA using PCR was also performed in left ventricular myocardium of deceased COVID‐19 patients. NHE1 expression is up‐regulated in whole blood of patients with COVID‐19 compared with other respiratory infections at first medical contact in the emergency department (control: 0.0021 ± 0.0002, COVID‐19: 0.0031 ± 0.0003, P = 0.01). The ratio of GLUT1 to NHE1 is significantly decreased in the blood of COVID‐19 patients who are subsequently intubated and/or die (severe disease) compared with patients with moderate disease (moderate disease: 0.497 ± 0.083 vs. severe disease: 0.294 ± 0.0336, P = 0.036). This ratio is even further decreased in the myocardium of patients who deceased from COVID‐19 in comparison with the myocardium of non‐infected donors. Conclusions NHE1 and GLUT1 may be critically involved in the disease progression of SARS‐CoV‐2 infection. We show here that SARS‐CoV‐2 infection critically disturbs ion channel expression in the heart. A decreased ratio of GLUT1/NHE1 could potentially serve as a biomarker for disease severity in patients with COVID‐19

Dipeptidyl-peptidase 3 and IL-6: potential biomarkers for diagnostics in COVID-19 and association with pulmonary infiltrates

Coronavirus SARS-CoV-2 spread worldwide, causing a respiratory disease known as COVID-19. The aim of the present study was to examine whether Dipeptidyl-peptidase 3 (DPP3) and the inflammatory biomarkers IL-6, CRP, and leucocytes are associated with COVID-19 and able to predict the severity of pulmonary infiltrates in COVID-19 patients versus non-COVID-19 patients. 114 COVID-19 patients and 35 patients with respiratory infections other than SARS-CoV-2 were included in our prospective observational study. Blood samples were collected at presentation to the emergency department. 102 COVID-19 patients and 28 non-COVID-19 patients received CT imaging (19 outpatients did not receive CT imaging). If CT imaging was available, artificial intelligence software (CT Pneumonia Analysis) was used to quantify pulmonary infiltrates. According to the median of infiltrate (14.45%), patients who obtained quantitative CT analysis were divided into two groups (> median: 55 COVID-19 and nine non-COVID-19, ≤ median: 47 COVID-19 and 19 non-COVID-19). DPP3 was significantly elevated in COVID-19 patients (median 20.85 ng/ml, 95% CI 18.34–24.40 ng/ml), as opposed to those without SARS-CoV-2 (median 13.80 ng/ml, 95% CI 11.30–17.65 ng/ml; p < 0.001, AUC = 0.72), opposite to IL-6, CRP (each p = n.s.) and leucocytes (p < 0.05, but lower levels in COVID-19 patients). Regarding binary logistic regression analysis, higher DPP3 concentrations (OR = 1.12, p < 0.001) and lower leucocytes counts (OR = 0.76, p < 0.001) were identified as significant and independent predictors of SARS-CoV-2 infection, as opposed to IL-6 and CRP (each p = n.s.). IL-6 was significantly increased in patients with infiltrate above the median compared to infiltrate below the median both in COVID-19 (p < 0.001, AUC = 0.78) and in non-COVID-19 (p < 0.05, AUC = 0.81). CRP, DPP3, and leucocytes were increased in COVID-19 patients with infiltrate above median (each p < 0.05, AUC: CRP 0.82, DPP3 0.70, leucocytes 0.67) compared to infiltrate below median, opposite to non-COVID-19 (each p = n.s.). Regarding multiple linear regression analysis in COVID-19, CRP, IL-6, and leucocytes (each p < 0.05) were associated with the degree of pulmonary infiltrates, as opposed to DPP3 (p = n.s.). DPP3 showed the potential to be a COVID-19-specific biomarker. IL-6 might serve as a prognostic marker to assess the extent of pulmonary infiltrates in respiratory patients

N-acetyl-ß-D-glucosaminidase is predictive of mortality in chronic heart failure: a 10-year follow-up

Aim: The study focused on biomarkers of kidney injury as predictors of mortality in patients with chronic heart failure (CHF) in a long-term follow-up (median 104 months). Methods/results: KIM-1, NAG and NGAL were assessed from urine, NT-proBNP from blood samples. 149 patients (age 62 +/- 12 years) with CHF (mean EF 30% [IQR 24-40%]) were enrolled. 79 (53%) patients died. Cox regression analysis revealed Log2NAG (HR: 1.46, CI: 1.12-1.89), Log2KIM-1 (HR: 1.23, CI: 1.02-1.49) and Log2NT-proBNP (HR: 1.50, CI: 1.32-1.72) as significant predictors of all-cause mortality as opposed to Log2NGAL (HR: 1.04, CI: 0.90-1.20). Log2NAG remained a significant predictor of all-cause mortality in a multivariate Cox regression model but lost its predictive value in combination with Log2NT-proBNP. Conclusion: The 10-year follow-up suggests NAG as a predictive tubular marker in CHF patients

Radiotherapy of patients with cardiac implantable electronic devices according to the DEGRO/DGK guideline—is the risk of relevant errors overestimated?

Purpose Ionizing radiation is able to cause severe damage to cardiac implantable electronic devices (CIED). In Germany, the DEGRO/DGK guideline recommends close monitoring of patients with CIEDs undergoing radiotherapy (RT). Nevertheless, especially in the era of intensity-modulated techniques and predominant use of 6MV photons, errors of CIEDs are rare events. Therefore, we performed daily CIED controls and hypothesized that no relevant device interaction would occur in our cohort. Methods From 2014 to 2018, we collected data of 51 patients (62 courses) with daily interrogation (n= 1046) of CIED. The dose to the skin above the CIED was measured by semiconductor or ion chamber dosimetry at least once per RT course. In many cases the dose was also calculated. Results The prescribed dose to the planning target volume (PTV) ranged from 7.5 to 78.0Gy (IQR 27.8-61.0Gy). The median measured cumulative dose to the skin above the CIED was 0.17Gy, whereas the median calculated dose was 1.03Gy. No error occurred in the group with maximum beam energy >10MeV. Three events without clinical relevance could be recognized in the group with an intensity-modulated technique at 6MV. None of the three concerned devices were located directly within the PTV. Conclusion Errors of CIEDs during RT are rare events. The approach according to the DEGRO/DGK guideline is safe, but also consumes resources. In our cohort it was not compulsory to relocate any CIED. Clinically relevant events are uncommon, so it remains debatable which procedure is necessary. Daily controls could be avoided in some selected cases without compromising patient safety

Evaluation of a multimarker panel in chronic heart failure: a 10-year follow-up

Aim: We assessed the 10-year prognostic role of 11 biomarkers with different pathophysiological backgrounds. Materials & methods/results: Blood samples from 144 patients with heart failure were analyzed. After 10 years of follow-up (median follow-up was 104 months), data regarding all-cause mortality were acquired. Regarding Kaplan-Meier analysis, all markers, except TIMP-1 and GDF-15, were significant predictors for all-cause mortality. We created a multimarker model with nt-proBNP, hsTnT and IGF-BP7 and found that patients in whom all three markers were elevated had a significantly worse long-time-prognosis than patients without elevated markers. Conclusion: In a 10-year follow-up, a combination of three biomarkers (NT-proBNP, hs-TnT, IGF-BP7) identified patients with a high risk of mortality