[GDF15 : un modulateur de l'immunité et biomarqueur prédictif des atteintes cardiovasculaires : une stratégie dans le COVID-19]. / GDF15 : A modulator of immunity and a predictive biomarker of cardiovascular events : A strategy in COVID-19.

In the recently published manuscript entitled "GDF15 a rising modulator of immunity and a strategy in Coronavirus disease 2019 (COVID-19) in relationship with iron metabolism" and we examined the potential properties of Growth and differentiation factor 15 (GDF15) as an emerging modulator of immunity in COVID-19. We commented new aspects of the biology of GDF15 and investigated the potential value of GDF15 as a biomarker. Is GDF15 a biomarker of the inflammatory process and oxidative stress state? Recently, it was reported that 1500 clinical trials related to COVID-19 have been registered, but none have yet found an optimal strategy. In these conditions, more clinical studies are needed before any of these agents can be considered antiviral agents.

Impact of the First COVID-19 Wave on French Hospitalizations for Myocardial Infarction and Stroke: A Retrospective Cohort Study.

The COVID-19 pandemic modified the management of myocardial infarction (MI) and stroke. We aimed to evaluate the effect of the COVID-19 pandemic on the volume and spatial distribution of hospitalizations for MI and stroke, before, during and after the first nationwide lockdown in France in 2020, compared with 2019. Hospitalization data were extracted from the French National Discharge database. Patient's characteristics were compared according to COVID-19 status. Changes in hospitalization rates over time were measured using interrupted time series analysis. Possible spatial patterns of over or under-hospitalization rates were investigated using Moran's indices. We observed a rapid and significant drop in hospitalizations just before the beginning of the lockdown with a nadir at 36.5% for MI and 31.2% for stroke. Hospitalization volumes returned to those seen in 2019 four weeks after the end of the lockdown, except for MI, which rebounded excessively. Older age, male sex, elevated rate of hypertension, diabetes, obesity and mortality characterized COVID-19 patients. There was no evidence of a change in the spatial pattern of over- or under-hospitalization clusters over the three periods. After a steep drop, only MI showed a significant rebound after the first lockdown with no change in the spatial distribution of hospitalizations.

GDF15: a modulator of immunity and a predictive biomarker of cardiovascular events: a strategy in COVID-19 GDF15 : un modulateur de l'immunité et biomarqueur prédictif des atteintes cardiovasculaires : une stratégie dans le COVID-19

Resume Nous avons récemment publié une revue intitulée : “GDF15 a rising modulator of immunity and a strategy in Coronavirus disease 2019 (COVID-19) in relationship with iron metabolism” et nous avons éxaminé les propriétés potentielles du facteur Growth and differentiation factor 15 (GDF15) comme modulateur émergeant de l'immunité dans le COVID-19. Nous nous sommes intéressés aux aspects biologiques du GDF15 comme biomarqueur. Est-ce que le GDF15 est un biomarqueur du processus inflammatoire et de l’état du stress oxydatif ? Récemment, il a été rapporté plus de 1500 projets d’études cliniques ciblés sur le COVID-19 ; mais aucune des stratégies semble optimale. Dans ces conditions, des études cliniques complémentaires sont nécessaires afin que les composés testés soient définis comme des agents antiviraux.

Smoking in Patients With Chronic Cardiovascular Disease During COVID-19 Lockdown.

Objectives: This cross-sectional study aims to investigate health-related behaviors including tobacco consumption among patients with cardiovascular diseases (CVD), during the first COVID-19-related lockdown. Methods: After 5 weeks of COVID-19 lockdown, 220 patients with chronic coronary syndromes (CCS) and 124 with congestive heart failure (CHF) answered a phone questionnaire. Results: Among these 344 patients, 43 (12.5%) were current smokers, and none had quit during the lockdown. When compared with non-smokers, smokers were 15 years younger, more often diabetic, more likely to live in an urban than a rural lockdown location, and more often in the CCS cohort (p = 0.011). Smokers described greater psychological impairment, but their rates of decrease in physical activity and of increase in screen time were similar to non-smokers. More than one-third (13/43) increased their tobacco consumption, which was mainly related to stress or boredom, but not driven by media messages on a protective effect of nicotine. Conclusions: During the first COVID-19 lockdown, we found a decrease in favorable lifestyle behaviors among patients with CVD. Strikingly, one-third of smokers with CCS or CHF increased their tobacco consumption. Given the major impact of persistent smoking in patients with CVD, this highlights the need for targeted prevention strategies, in particular during such periods.

COVID-19 Lockdown in Patients with Chronic Diseases: A Cross-Sectional Study.

BACKGROUND: We aimed to investigate the impact of the first COVID-19 lockdown on medication adherence, physician access, lifestyle behaviours, and mental health in patients with chronic conditions. METHODS: A cross-sectional phone survey was conducted in 1274 housebound adults recruited from 8 regional chronic disease cohorts (CLEO CD study: NCT04390126). RESULTS: Medication adherence was 97%; 305 (41%) patients declared that at least one scheduled visit with a physician was missed during the first lockdown. The main changes in lifestyle behaviours were deterioration in sleep time (duration and/or quality; 71%), increase in screen time (46%), and decrease in physical activity (46%). Nineteen percent experienced psychological distress (Kessler-6 score ≥ 5). An urban living place (OR, 1.76 vs. rural; 95% CI, 1.32-2.33; p = 10-4), worse self-reported mental health (OR, 1.62 vs. about the same or better; 95% CI, 1.17-2.25; p = 0.003), and a K6 score ≥ 5 (OR, 1.52 vs. <5; 95% CI, 1.05-2.21; p = 0.03) were independent factors associated with at least one unhealthy behaviour. CONCLUSIONS: Encouraging results were observed in terms of medication adherence. Caution is needed in chronic disease patients living in urban places as well as those presenting psychological distress and worse self-reported mental health to reduce unhealthy behaviours.

COVID-19 Lockdown in Patients with Chronic Diseases: A Cross-Sectional Study

Background: We aimed to investigate the impact of the first COVID-19 lockdown on medication adherence, physician access, lifestyle behaviours, and mental health in patients with chronic conditions. Methods: A cross-sectional phone survey was conducted in 1274 housebound adults recruited from 8 regional chronic disease cohorts (CLEO CD study: NCT04390126). Results: Medication adherence was 97%;305 (41%) patients declared that at least one scheduled visit with a physician was missed during the first lockdown. The main changes in lifestyle behaviours were deterioration in sleep time (duration and/or quality;71%), increase in screen time (46%), and decrease in physical activity (46%). Nineteen percent experienced psychological distress (Kessler-6 score ≥5). An urban living place (OR, 1.76 vs. rural;95% CI, 1.32–2.33;p = 10−4), worse self-reported mental health (OR, 1.62 vs. about the same or better;95% CI, 1.17–2.25;p = 0.003), and a K6 score ≥5 (OR, 1.52 vs. <5;95% CI, 1.05–2.21;p = 0.03) were independent factors associated with at least one unhealthy behaviour. Conclusions: Encouraging results were observed in terms of medication adherence. Caution is needed in chronic disease patients living in urban places as well as those presenting psychological distress and worse self-reported mental health to reduce unhealthy behaviours.

Impact of first COVID-19 lockdown on paediatric and adult haemophilia patients treated in a French Haemophilia Comprehensive Care Centre.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has created an unprecedented global health crisis. AIM: To investigate the impact of the 1st COVID-19 lockdown on haemophilia patients in terms of symptoms, management, medication adherence, mental health and lifestyle behaviours. METHODS: A prospective cross-sectional phone survey using a two-part questionnaire was conducted in haemophilia patients (adults and children) followed-up in a French Haemophilia Comprehensive Care Centre between May 5, 2020 and June 2, 2020 (CLEO CD study: NCT04390126). RESULTS: Among 284 haemophilia A or B patients with FVIII or FIX < 40% contacted for the study, 239 (84%) including 183 adults and 56 children participated to the survey. In 81% of children and 78% of adults, bleeding episodes remained unchanged or decreased. Medication adherence was 82.0% in adults and 98.2% in children. Non-adherence concerned haemostatic agents in six patients and analgesics in three. Overall, 67% of adults and 71% of children felt as good as before lockdown. In both adults and children, the three major changes in lifestyle behaviours were: increase in screen time (49% and 57%), decrease in physical activity (43% and 48%), and weight gain (32% and 27%), respectively. CONCLUSIONS: Encouraging results were observed in terms of haemophilia symptoms, medication adherence, and mental health. Conversely, a negative impact was observed on lifestyle behaviours in a cohort of French haemophilia patients during the 1st lockdown.

GDF15: an emerging modulator of immunity and a strategy in COVID-19 in association with iron metabolism.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of respiratory and cardiovascular diseases, known as coronavirus disease 2019 (COVID-19). SARS-CoV-2 encodes the structural proteins spike (S), envelope (E), membrane (M), and nucleocapsid (N). The receptor-binding domain on the surface subunit S1 is responsible for attachment of the virus to angiotensin (Ang)-converting enzyme 2 (ACE2), which is highly expressed in host cells. The cytokine storm observed in patients with COVID-19 contributes to the endothelial vascular dysfunction, which can lead to acute respiratory distress syndrome, multiorgan failure, alteration in iron homeostasis, and death. Growth and differentiation factor 15 (GDF15), which belongs to the transforming growth factor-ß (TGF-ß) superfamily of proteins, has a pivotal role in the development and progression of diseases because of its role as a metabolic regulator. In COVID-19, GDF15 activity increases in response to tissue damage. GDF15 appears to be a strong predictor of poor outcomes in patients critically ill with COVID-19 and acts as an 'inflammation-induced central mediator of tissue tolerance' via its metabolic properties. In this review, we examine the potential properties of GDF15 as an emerging modulator of immunity in COVID-19 in association with iron metabolism. The virus life cycle in host cell provides potential targets for drug therapy.

Impact of SARS-CoV-2 positivity on clinical outcome among STEMI patients undergoing mechanical reperfusion: Insights from the ISACS STEMI COVID 19 registry.

BACKGROUND AND AIMS: SARS-Cov-2 predisposes patients to thrombotic complications, due to excessive inflammation, endothelial dysfunction, platelet activation, and coagulation/fibrinolysis disturbances. The aim of the present study was to evaluate clinical characteristics and prognostic impact of SARS-CoV-2 positivity among STEMI patients undergoing primary percutaneous coronary intervention (PPCI). METHODS: We selected SARS-CoV-2 positive patients included in the ISACS-STEMI COVID-19, a retrospective multicenter European registry including 6609 STEMI patients treated with PPCI from March 1st until April 30th, in 2019 and 2020. As a reference group, we randomly sampled 5 SARS-Cov-2 negative patients per each SARS-CoV-2 positive patient, individually matched for age, sex, and hospital/geographic area. Study endpoints were in-hospital mortality, definite stent thrombosis, heart failure. RESULTS: Our population is represented by 62 positive SARS-CoV-2 positive patients who were compared with a matched population of 310 STEMI patients. No significant difference was observed in baseline characteristics or the modality of access to the PCI center. In the SARS-CoV-2 positive patients, the culprit lesion was more often located in the RCA (p < 0.001). Despite similar pre and postprocedural TIMI flow, we observed a trend in higher use of GP IIb-IIIa inhibitors and a significantly higher use of thrombectomy in the SARS-CoV-2 positive patients. SARS-CoV-2 positivity was associated with a remarkably higher in hospital mortality (29% vs 5.5%, p < 0.001), definite in-stent thrombosis (8.1% vs 1.6%, p = 0.004) and heart failure (22.6% vs 10.6%, p = 0.001) that was confirmed after adjustment for confounding factors. CONCLUSIONS: Our study showed that among STEMI patients, SARS-CoV-2 positivity is associated with larger thrombus burden, a remarkably higher mortality but also higher rates of in-stent thrombosis and heart failure.

Impact of COVID-19 Pandemic on Mechanical Reperfusion for Patients With STEMI.

BACKGROUND: The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality. OBJECTIVES: The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of "at-risk" patient cohorts for failure to present or delays to treatment. METHODS: This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020. Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality. RESULTS: A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p < 0.0001). The heterogeneity among centers was not related to the incidence of death due to COVID-19. A significant interaction was observed for patients with arterial hypertension, who were less frequently admitted in 2020 than in 2019. Furthermore, the pandemic was associated with a significant increase in door-to-balloon and total ischemia times, which may have contributed to the higher mortality during the pandemic. CONCLUSIONS: The COVID-19 pandemic had significant impact on the treatment of patients with STEMI, with a 19% reduction in PPCI procedures, especially among patients suffering from hypertension, and a longer delay to treatment, which may have contributed to the increased mortality during the pandemic. (Primary Angioplasty for STEMI During COVID-19 Pandemic [ISACS-STEMI COVID-19] Registry; NCT04412655).

Bedside chest ultrasound to distinguish heart failure from pneumonia-related dyspnoea in older COVID-19 patients.

AIMS: In the older population, acute heart failure is a frequent, life-threatening complication of COVID-19 that requires urgent specific care. We aimed to explore the impact of point-of-care chest ultrasound (CUS) use in older bedridden inpatients during the COVID-19 pandemic as a tool to distinguish between cardiogenic pulmonary oedema and isolated viral pneumonia-related dyspnoea. METHODS AND RESULTS: This prospective series included 16 patients aged 75 or older, hospitalized for acute dyspnoea in an acute geriatric unit of a university hospital and testing positive for a SARS-Cov2 infection. We collected demographic characteristics, medical history, biological screening, clinical symptoms, CUS findings (n = 16) and chest CT-scan conclusions (n = 14). Mean age was 89 years (77-97). All patients presented asthenia and dyspnoea, 56% complained of coughing and diarrhoea, and 50% had fever. Acute heart failure was clinically suspected in seven patients. At CUS, evidence of heart failure was confirmed in three patients (including one without clinical suspicion); interstitial syndrome was confirmed in 12 patients on CUS vs. 9 patients with CT. CONCLUSIONS: In older patients with COVID-19 and acute dyspnoea, the use of point-of-care CUS allowed the clinician to quickly rule out heart failure in nearly half of suspected cases while easily identifying virus-related interstitial syndrome. The use of CUS appears to be suitable for the rapid bedside investigation of dyspnoea in older patients, particularly in the context of the COVID-19 pandemic.

Impact of lockdown on patients with congestive heart failure during the coronavirus disease 2019 pandemic.

AIMS: Cardiovascular co-morbidities like congestive heart failure (CHF) alter the course of coronavirus disease 2019. Factors associated with the outbreak and lockdown can exacerbate CHF. METHODS AND RESULTS: We analysed the answers of 124 randomly selected CHF outpatients (mean age 71.0 ± 14.0 years, 60.5% male) interviewed by phone during the sixth and seventh weeks of the lockdown. Most patients were treated for New York Heart Association class II (38.7%) and reduced ejection fraction HF (70.2%). Psychological distress (Kessler 6 score ≥ 5) was common (18.5%), and 21.8% felt worse than before the lockdown. Few patients (n = 10) adjusted their intake of HF medications, always on medical prescription. Decreased physical activity was common (41.9%) and more frequent in women (P = 0.025) and urban dwellers (P = 0.009). Almost half of respondents (46.0%) declared increased screen time, but only few declared more alcohol intake (4.0%). Weight gain was common (27.4%), and 44.4% of current smokers increased tobacco consumption. Adherence to recommended salt or fluid intake restrictions was reduced in 14.5%. Increase in HF symptoms was commonly reported (21.8%) and tended to be higher in women than in men (P = 0.074). Of the 23 patients who had a phone teleconsultation during the pandemic, 16 had initially planned an in-person consultation that they switched for teleconsultation. CONCLUSIONS: During the lockdown, psychological distress and decreased well-being were common in CHF outpatients, and there was an increase in unhealthy lifestyle behaviours. These changes may negatively impact short-term and long-term prognoses. Medication adherence was maintained, and limitations in access to care were partly counterbalanced by use of telehealth.

Hospital admissions for acute myocardial infarction before and after lockdown according to regional prevalence of COVID-19 and patient profile in France: a registry study.

BACKGROUND: The COVID-19 pandemic has had a profound effect on general health care. We aimed to evaluate the effect of a nationwide lockdown in France on admissions to hospital for acute myocardial infarction, by patient characteristics and regional prevalence of the pandemic. METHODS: In this registry study, we collected data from 21 centres participating in the ongoing French Cohort of Myocardial Infarction Evaluation (FRENCHIE) registry, which collects data from all patients admitted for ST segment elevation myocardial infarction (STEMI) or non-ST segment elevation myocardial infarction (NSTEMI) within 48 h of symptom onset. We analysed weekly hospital admissions over 8 weeks: the 4 weeks preceding the institution of the lockdown and the 4 weeks following lockdown. The primary outcome was the change in the number of hospital admissions for all types of acute myocardial infarction, NSTEMI, and STEMI between the 4 weeks before lockdown and the 4 weeks after lockdown. Comparisons between categorical variables were made using χ2 tests or Fisher's exact tests. Comparisons of continuous variables were made using Student's t tests or Mann-Whitney tests. Poisson regression was used to determine the significance of change in hospital admissions over the two periods, after verifying the absence of overdispersion. Age category, region, and type of acute myocardial infarction (STEMI or NSTEMI) were used as covariables. The FRENCHIE cohort is registered with ClinicalTrials.gov, NCT04050956. FINDINGS: Between Feb 17 and April 12, 2020, 1167 patients were consecutively admitted within 48 h of acute myocardial infarction (583 with STEMI, 584 with NSTEMI) and were included in the study. Admissions for acute myocardial infarction decreased between the periods before and after lockdown was instituted, from 686 before to 481 after lockdown (30% decrease; incidence rate ratio 0·69 [95% CI 0·51-0·70]). Admissions for STEMI decreased from 331 to 252 (24%; 0·72 [0·62-0·85]), and admissions for NSTEMI decreased from 355 to 229 (35%; 0·64 [0·55-0·76]) following institution of the lockdown, with similar trends according to sex, risk factors, and regional prevalence of hospital admissions for COVID-19. INTERPRETATION: A marked decrease in hospital admissions was observed following the lockdown, irrespective of patient characteristics and regional prevalence of COVID-19. Health authorities should be aware of these findings, in order to adapt their message if the COVID-19 pandemic persists or recurs, or in case of future major epidemics. FUNDING: Recherche Hospitalo-Universitaire en Santé iVasc.

Impact of COVID-19 lockdown on lifestyle adherence in stay-at-home patients with chronic coronary syndromes: Towards a time bomb.

BACKGROUND: We aimed to evaluate the impact of coronavirus disease 2019 (COVID-19)-related lockdown on adherence to lifestyle and drug regimens in stay-at-home chronic coronary syndromes patients living in urban and rural areas. METHODS: A cross-sectional population-based study was perfomed in patients with chronic coronary syndromes. A sample of 205 patients was randomly drawn from the RICO (Observatoire des infarctus de Côte d'Or) cohort. Eight trained interviewers collected data by phone interview during week 16 (April 13 to April 19), i.e. 4 weeks after implementation of the French lockdown (start March 17, 2020). RESULTS: Among the 195 patients interviewed (of the 205, 3 had died, 1 declined, 6 lost), mean age was 65.5 ± 11.1 years. Only six patients (3%) reported drug discontinuation, mainly driven by media influence or family members. All 166 (85%) patients taking aspirin continued their prescribed daily intake. Lifestyle rules were less respected since almost half (45%) declared >25% reduction in physical activity, 26% of smokers increased their tobacco consumption by >25%, and 24% of patients increased their body weight > 2 kg. The decrease in physical activity and the increase in smoking were significantly greater in urban patients (P < .05). CONCLUSIONS: The COVID-19-related lockdown had a negative impact on lifestyle in a representative sample of stay-at-home CCS patients.