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.

Impact of coronavirus disease (COVID-19) pandemic on physical activity of patients with cardiac implantable electronic devices-A remote monitoring study.

OBJECTIVES: The study aims to investigate the impact of COVID-19 pandemic on physical activity and frequency of implantable cardioverter-defibrillator (ICD) therapies of patients with cardiac implantable electronic devices. METHODS AND RESULTS: Physical activity, heart rate and ICD-therapies were assessed via routine remote monitoring over two years. We focussed on a 338-day period during COVID-19 pandemic that was divided in 6 time-intervals defined by public health interventions and compared to the previous regular year. Paired nonparametric longitudinal analysis was performed to detect differences between time-intervals. To model effects of age, sex and time we applied a nonparametric ANOVA-type-statistic. 147 patients with cardiac implantable electronic devices were analysed. Longitudinal analysis of physical activity in 2019 and 2020 showed a specific weekly and seasonal pattern. Physical activity was reduced during the pandemic (mean daily physical activity 2019: 12.4% vs. 2020: 11.5%; p<0.0001) with the strongest reductions (fold changes 0.885/0.889, p<0.0001/p<0.0001) during the two lockdown-periods. In older patients (>70 years), physical activity was decreased in every time-interval of the year 2020. In time-intervals of eased restrictions, physical activity of younger patients (≤70 years) was not different compared to 2019. No variation in mean heart rate, arrhythmia-burden and count of ICD-therapies was found. CONCLUSION: Physical activity shows fluctuations dependent on days of the week and time of the year. During the pandemic, physical activity was reduced in patients with cardiac implantable electronic devices with the strongest reductions during lockdown-periods. Younger patients resumed former levels of physical activity in times of eased restrictions while older patients remained less active. Thus, activation of the elderly population is important to prevent long-term health impairments due to the pandemic.

Cardiac Fibrosis Is a Risk Factor for Severe COVID-19.

Increased left ventricular fibrosis has been reported in patients hospitalized with coronavirus disease 2019 (COVID-19). It is unclear whether this fibrosis is a consequence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection or a risk factor for severe disease progression. We observed increased fibrosis in the left ventricular myocardium of deceased COVID-19 patients, compared with matched controls. We also detected increased mRNA levels of soluble interleukin-1 receptor-like 1 (sIL1-RL1) and transforming growth factor ß1 (TGF-ß1) in the left ventricular myocardium of deceased COVID-19 patients. Biochemical analysis of blood sampled from patients admitted to the emergency department (ED) with COVID-19 revealed highly elevated levels of TGF-ß1 mRNA in these patients compared to controls. Left ventricular strain measured by echocardiography as a marker of pre-existing cardiac fibrosis correlated strongly with blood TGF-ß1 mRNA levels and predicted disease severity in COVID-19 patients. In the left ventricular myocardium and lungs of COVID-19 patients, we found increased neuropilin-1 (NRP-1) RNA levels, which correlated strongly with the prevalence of pulmonary SARS-CoV-2 nucleocapsid. Cardiac and pulmonary fibrosis may therefore predispose these patients to increased cellular viral entry in the lung, which may explain the worse clinical outcome observed in our cohort. Our study demonstrates that patients at risk of clinical deterioration can be identified early by echocardiographic strain analysis and quantification of blood TGF-ß1 mRNA performed at the time of first medical contact.

Kidney injury molecule-1: potential biomarker of acute kidney injury and disease severity in patients with COVID-19.

AIMS: The aim of the current study was to evaluate whether tubular markers kidney injury molecule-1 (KIM-1) and N-acetyl-ß-glucosaminidase (NAG) are related to acute kidney injury (AKI) and severe disease in patients with COVID-19. METHODS AND RESULTS: In this prospective observational clinical trial we examined a cohort of 80 patients with proof of acute respiratory infection and divided them into a COVID-19 cohort (n = 54) and a control cohort (n = 26). KIM-1 and NAG were measured from urine samples collected in the emergency department. We assessed the development of AKI, admission to the intensive care unit (ICU) and intrahospital death as clinical endpoints. Urinary KIM-1 and NAG were not significantly different between patients with SARS-CoV-2 and those with other respiratory infections (each p = n.s.). Eight patients from the COVID-19 cohort and five of the non-COVID-19-patients suffered from acute kidney injury during their stay. Nine COVID-19 patients and two non-COVID-19 patients were admitted to the ICU. KIM-1 was significantly elevated in COVID-19 patients with, compared to those without AKI (p = 0.005), as opposed to NAG and creatinine (each p = n.s.). Furthermore, KIM-1 was significantly elevated in the patients with COVID-19 that had to be transferred to the ICU (p = 0.015), in contrast to NAG and creatinine (each p = n.s.). CONCLUSION: Assessing KIM-1 in patients with COVID-19 might provide additional value in recognizing AKI at an early stage of disease. Further, KIM-1 might indicate higher risk for clinical deterioration as displayed by admission to the ICU.

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.