Effects of healthcare system transformations spurred by the COVID-19 pandemic on management of stroke and STEMI: a registry-based cohort study in France

International audienceOBJECTIVE: To assess the impact of changes in use of care and implementation of hospital reorganisations spurred by the COVID-19 pandemic (first wave) on the acute management times of patients who had a stroke and ST-segment elevation myocardial infarction (STEMI). DESIGN: Two cohorts of patients who had an STEMI and stroke in the Aquitaine Cardio-Neuro-Vascular (CNV) registry. SETTING: 6 emergency medical services, 30 emergency units (EUs), 14 hospitalisation units and 11 cathlabs in the Aquitaine region.PARTICIPANTS: This study involved 9218 patients (6436 patients who had a stroke and 2782 patients who had an STEMI) in the CNV Registry from January 2019 to August 2020.METHOD: Hospital reorganisations, retrieved in a scoping review, were collected from heads of hospital departments. Other data were from the CNV Registry. Associations between reorganisations, use of care and care management times were analysed using multivariate linear regression mixed models. Interaction terms between use-of-care variables and period (pre-wave, per-wave and post-wave) were introduced.MAIN OUTCOME MEASURES: STEMI cohort, first medical contact-to-procedure time; stroke cohort, EU admission-to-imaging time. RESULTS: Per-wave period management times deteriorated for stroke but were maintained for STEMI. Per-wave changes in use of care did not affect STEMI management. No association was found between reorganisations and stroke management times. In the STEMI cohort, the implementation of systematic testing at admission was associated with a 41% increase in care management time (exp=1.409, 95% CI 1.075 to 1.848, p=0.013). Implementation of plan blanc, which concentrated resources in emergency activities, was associated with a 19% decrease in management time (exp=0.801, 95% CI 0.639 to 1.023, p=0.077).CONCLUSIONS: The pandemic did not markedly alter the functioning of the emergency network. Although stroke patient management deteriorated, the resilience of the STEMI pathway was linked to its stronger structuring. Transversal reorganisations, aiming at concentrating resources on emergency care, contributed to maintenance of the quality of care.TRIAL REGISTRATION NUMBER: NCT04979208

Decrease of Pdzrn3 is required for heart maturation and protects against heart failure

International audienceAbstract Heart failure is the final common stage of most cardiopathies. Cardiomyocytes (CM) connect with others via their extremities by intercalated disk protein complexes. This planar and directional organization of myocytes is crucial for mechanical coupling and anisotropic conduction of the electric signal in the heart. One of the hallmarks of heart failure is alterations in the contact sites between CM. Yet no factor on its own is known to coordinate CM polarized organization. We have previously shown that PDZRN3, an ubiquitine ligase E3 expressed in various tissues including the heart, mediates a branch of the Planar cell polarity (PCP) signaling involved in tissue patterning, instructing cell polarity and cell polar organization within a tissue. PDZRN3 is expressed in the embryonic mouse heart then its expression dropped significantly postnatally corresponding with heart maturation and CM polarized elongation. A moderate CM overexpression of Pdzrn3 ( Pdzrn3 OE) during the first week of life, induced a severe eccentric hypertrophic phenotype with heart failure. In models of pressure-overload stress heart failure, CM-specific Pdzrn3 knockout showed complete protection against degradation of heart function. We reported that Pdzrn3 signaling induced PKC ζ expression, c-Jun nuclear translocation and a reduced nuclear ß catenin level, consistent markers of the planar non-canonical Wnt signaling in CM. We then show that subcellular localization (intercalated disk) of junction proteins as Cx43, ZO1 and Desmoglein 2 was altered in Pdzrn3 OE mice, which provides a molecular explanation for impaired CM polarization in these mice. Our results reveal a novel signaling pathway that controls a genetic program essential for heart maturation and maintenance of overall geometry, as well as the contractile function of CM, and implicates PDZRN3 as a potential therapeutic target for the prevention of human heart failure

Decrease of Pdzrn3 is required for heart maturation and protects against heart failure

International audienceHeart failure is the final common stage of most cardiopathies. Cardiomyocytes (CM) connect with others via their extremities by intercalated disk protein complexes. This planar and directional organization of myocytes is crucial for mechanical coupling and anisotropic conduction of the electric signal in the heart. One of the hallmarks of heart failure is alterations in the contact sites between CM. Yet no factor on its own is known to coordinate CM polarized organization. We have previously shown that PDZRN3, an ubiquitine ligase E3 expressed in various tissues including the heart, mediates a branch of the Planar cell polarity (PCP) signaling involved in tissue patterning, instructing cell polarity and cell polar organization within a tissue. PDZRN3 is expressed in the embryonic mouse heart then its expression dropped significantly postnatally corresponding with heart maturation and CM polarized elongation. A moderate CM overexpression of Pdzrn3 (Pdzrn3 OE) during the first week of life, induced a severe eccentric hypertrophic phenotype with heart failure. In models of pressure-overload stress heart failure, CM-specific Pdzrn3 knockout showed complete protection against degradation of heart function. We reported that Pdzrn3 signaling induced PKC ζ expression, c-Jun nuclear translocation and a reduced nuclear ß catenin level, consistent markers of the planar non-canonical Wnt signaling in CM. We then show that subcellular localization (intercalated disk) of junction proteins as Cx43, ZO1 and Desmoglein 2 was altered in Pdzrn3 OE mice, which provides a molecular explanation for impaired CM polarization in these mice. Our results reveal a novel signaling pathway that controls a genetic program essential for heart maturation and maintenance of overall geometry, as well as the contractile function of CM, and implicates PDZRN3 as a potential therapeutic target for the prevention of human heart failure

Glycaemic Variability and Hyperglycaemia as Prognostic Markers of Major Cardiovascular Events in Diabetic Patients Hospitalised in Cardiology Intensive Care Unit for Acute Heart Failure.

(1) Background: Hyperglycaemia and hypoglycaemia are both emerging risk factors for cardiovascular disease. Nevertheless, the potential effect of glycaemic variability (GV) on mid-term major cardiovascular events (MACE) in diabetic patients presenting with acute heart failure (AHF) remains unclear. This study investigates the prognostic value of GV in diabetic patients presenting with acute heart failure (AHF). (2) Methods: this was an observational study including consecutive patients with diabetes and AHF between January 2015 and November 2016. GV was calculated using standard deviation of glycaemia values during initial hospitalisation in the intensive cardiac care unit. MACE, including recurrent AHF, new-onset myocardial infarction, ischaemic stroke and cardiac death, were recorded. The predictive effects of GV on patient outcomes were analysed with respect to baseline characteristics and cardiac status. (3) Results: In total, 392 patients with diabetes and AHF were enrolled. During follow-up (median (interquartile range) 29 (6-51) months), MACE occurred in 227 patients (57.9%). In total, 92 patients died of cardiac causes (23.5%), 107 were hospitalised for heart failure (27.3%), 19 had new-onset myocardial infarction (4.8%) and 9 (2.3%) had an ischaemic stroke. Multivariable logistic regression analysis showed that GV > 50 mg/dL (2.70 mmol/L), age > 75 years, reduced left ventricular ejection fraction (LVEF < 30%) and female gender were independent predictors of MACE: hazard ratios (HR) of 3.16 (2.25-4.43; < 0.001), 1.54 (1.14-2.08; = 0.005), 1.47 (1.06-2.07; = 0.02) and 1.43 (1.05-1.94; = 0.03), respectively. (4) Conclusions: among other well-known factors of HF, a GV cut-off value of >50 mg/dL was the strongest independent predictive factor for mid-term MACE in patients with diabetes and AHF

Infarctus du myocarde avec sus-décalage du segment ST : prise en charge et association au pronostic lors de la pandémie de COVID-19 en France

International audienceSystems of care have been challenged to control progression of the COVID-19 pandemic. Whether this has been associated with delayed reperfusion and worse outcomes in French patients with ST-segment elevation myocardial infarction (STEMI) is unknown.Aim: To compare the rate of STEMI admissions, treatment delays, and outcomes between the first peak of the COVID-19 pandemic in France and the equivalent period in 2019.Methods: In this nationwide French survey, data from consecutive STEMI patients from 65 centres referred for urgent revascularization between 1 March and 31 May 2020, and between 1 March and 31 May 2019, were analysed. The primary outcome was a composite of in-hospital death or non-fatal mechanical complications of acute myocardial infarction.Results: A total of 6306 patients were included. During the pandemic peak, a 13.9±6.6% (P=0.003) decrease in STEMI admissions per week was observed. Delays between symptom onset and percutaneous coronary intervention were longer in 2020 versus 2019 (270 [interquartile range 150-705] vs 245 [140-646]min; P=0.013), driven by the increase in time from symptom onset to first medical contact (121 [60-360] vs 150 [62-420]min; P=0.002). During 2020, a greater number of mechanical complications was observed (0.9% vs 1.7%; P=0.029) leading to a significant difference in the primary outcome (112 patients [5.6%] in 2019 vs 129 [7.6%] in 2020; P=0.018). No significant difference was observed in rates of orotracheal intubation, in-hospital cardiac arrest, ventricular arrhythmias and cardiogenic shock.Conclusions: During the first peak of the COVID-19 pandemic in France, there was a decrease in STEMI admissions, associated with longer ischaemic time, exclusively driven by an increase in patient-related delays and an increase in mechanical complications. These findings suggest the need to encourage the population to seek medical help in case of symptoms.Contexte. Les systèmes de santé à travers le monde ont été fortement mis à l’épreuve afin de contrôler la progression de l’épidémie de la COVID-19. L’éventualité que la réorganisation des soins ait pu influencer les délais de reperfusion ou le devenir des patients présentant des syndromes coronaires aigus avec sus-décalage du segment ST (SCA ST +) n’a pas été explorée en France.Objectif. Comparer le taux d’admissions pour SCA ST+, les délais de traitement et enfin le devenir de ces patients entre la première vague épidémique de la COVID-19 et pendant la période similaire en 2019.Méthodes. Dans ce registre national multicentrique, les patients avec SCA ST+ provenant de 65 centres français admis en urgence pour revascularisation entre le 1e mars et le 31 mai 2020 et entre le 1e mars et le 31 mai 2019 ont été analysés. Le critère de jugement principal était un critère composite regroupant la mortalité intrahospitalière toute cause confondue et les complications mécaniques en lien avec l’infarctus.Résultats. Un total de 6 306 patients ont été inclus. Pendant le pic de la pandémie une réduction de 13,9 ± 6,6 % (P = 0,003) des admissions pour SCA ST+ a été observée par semaine. Les délais entre l’apparition des symptômes et l’angioplastie percutanée était significativement augmentés 270 (150−705) versus 245 (140−646) minutes (P = 0,013). Cette augmentation était exclusivement liée à une augmentation du temps entre l’apparition des symptômes et le premier contact médical 121 (60−360) en 2019 versus 150 (62−420) minutes en 2020 (P = 0,002). Durant cette période a été constaté un plus grand nombre de complications mécaniques (0,9 % vs 1,7 % (P = 0,029) conduisant à une augmentation significative de notre critère de jugement principal 112 patients (5,6) en 2019 vs 129 (7,6 %) en 2020 (P = 0,018).Conclusions. Pendant le premier pic de la pandémie il a été constaté : une diminution du taux de SCA ST + associé à un temps d’ischémie prolongé, poussé par l’augmentation du temps entre l’apparition des symptômes et le premier contact médical et enfin un plus grand nombre de complications mécaniques. Ces observations suggèrent la nécessité d’encourager la population à consulter au moindre symptôme inquiétant

Social and clinical vulnerability in stroke and STEMI management during the COVID-19 pandemic: a registry-based study

Objective This study aims to evaluate whether the first wave of the COVID-19 pandemic resulted in a deterioration in the quality of care for socially and/or clinically vulnerable stroke and ST-segment elevation myocardial infarction (STEMI) patients.Design Two cohorts of STEMI and stroke patients in the Aquitaine neurocardiovascular registry.Setting Six emergency medical services, 30 emergency units, 14 hospitalisation units and 11 catheterisation laboratories in the Aquitaine region in France.Participants This study involved 9218 patients (6436 stroke and 2782 STEMI patients) in the neurocardiovascular registry from January 2019 to August 2020.Primary outcome measures Care management times in both cohorts: first medical contact-to-procedure time for the STEMI cohort and emergency unit admission-to-imaging time for the stroke cohort. Associations between social (deprivation index) and clinical (age >65 years, neurocardiovascular history) vulnerabilities and care management times were analysed using multivariate linear mixed models, with an interaction on the time period (pre-wave, per-wave and post-first COVID-19 wave).Results The first medical contact procedure time was longer for elderly (p<0.001) and ‘very socially disadvantaged’ (p=0.003) STEMI patients, with no interaction regarding the COVID-19 period (age, p=0.54; neurocardiovascular history, p=0.70; deprivation, p=0.64). We found no significant association between vulnerabilities and the admission imaging time for stroke patients, and no interaction with respect to the COVID-19 period (age, p=0.81; neurocardiovascular history, p=0.34; deprivation, p=0.95).Conclusions This study revealed pre-existing inequalities in care management times for vulnerable STEMI and stroke patients; however, these inequalities were neither accentuated nor reduced during the first COVID-19 wave. Measures implemented during the crisis did not alter the structured emergency pathway for these patients.Trial registration number NCT0497920

Fractional Flow Reserve to Guide Treatment of Patients With Multivessel Coronary Artery Disease

International audienc