Background Cardiac light chain amyloidosis (AL-CA) patients often die within three months of starting chemotherapy. Chemotherapy for non-immunoglobulin M gammopathy with AL-CA frequently includes bortezomib (Bor), cyclophosphamide (Cy), and dexamethasone (D). We previously reported that NT-ProBNP levels can double within 24h of dexamethasone administration, suggesting a deleterious impact on cardiac function. In this study, we evaluate the role of dexamethasone in early cardiovascular mortality during treatment. Methods and findings We retrospectively assessed 100 de novo cardiac AL patients (62% male, mean age 68 years) treated at our institute between 2009 and 2018 following three chemotherapy regimens: CyBorDComb (all initiated on day 1; 34 patients), DCyBorSeq (D, day 1; Cy, day 8; Bor, day 15; 17 patients), and CyBorDSeq (Cy, day 1; Bor, day 8; D, day 15; 49 patients). The primary endpoint was cardiovascular mortality and cardiac transplantation at days 22 and 455. At day 22, mortality was 20.6% with CyBorDComb, 23.5% with DCyBorSeq, and 0% with CyBorDSeq (p = 0.003). At day 455, mortality was not significantly different between regimens (p = 0.195). Acute toxicity of dexamethasone was evaluated on myocardial function using a rat model of isolated perfused heart. Administration of dexamethasone induced a decrease in left ventricular myocardium contractility and relaxation (p<0.05), supporting a potential negative inotropic effect of dexamethasone in AL-CA patients with severe cardiac involvement. Conclusion Delaying dexamethasone during the first chemotherapy cycle reduces the number of early deaths without extending survival. It is clear that dexamethasone is beneficial in the long-term treatment of patients with AL-CA. However, the initial introduction of dexamethasone during treatment is critical, but may be associated with early cardiac deaths in severe CA. Thus, it is important to consider the dosage and timing of dexamethasone introduction on a patient-severity basis. The impact of dexamethasone in the treatment of AL-CA needs further investigation.

Objectives: To describe early electrocardiogram (ECG) abnormalities after status epilepticus (SE) and evaluate their association with 90-day neurological outcomes. Design: Retrospective analysis of a multicenter, national prospective registry between February 2018 and June 2020. Setting: Sixteen ICUs in France, IctalGroup Research Network. Patients: Adults with available ECG performed less than or equal to 24 hours after the onset of SE and less than or equal to 12 hours after its resolution. Intervention: Double-blinded review of all ECGs was performed by two independent cardiologists. ECGs were categorized as normal/abnormal and then with minor/major early ECG abnormalities according to the Novacode ECG Classification system. Measurements and Main Results: Among 155 critically ill patients with SE, early ECG abnormalities were encountered in 145 (93.5%), categorized as major in 91 of 145 (62.8%). In addition to sinus tachycardia, the main abnormalities were in the ST segment (elevation [16.6%] or depression [17.9%]) or negative T waves (42.1%). Major early ECG abnormalities were significantly associated with respiratory distress and sinus tachycardia at the scene and hyperlactatemia at ICU admission. By multivariable analysis, three variables were significantly associated with 90-day poor outcome: age, preexisting ultimately fatal comorbidity, and cerebral insult as the cause of SE. Early major ECG abnormalities were not independently associated with 90-day functional outcome. Conclusions: In our study, early ECG abnormalities in the acute phase of SE were frequent, often unrecognized and were associated with clinical and biological stigma of hypoxemia. Although they were not independently associated with 90-day functional outcome, ECG changes at the early stage of SE should be systematically evaluated. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03457831.

Background Angiotensin-converting enzyme 2 is the receptor that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses for entry into lung cells. Because ACE-2 may be modulated by angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), there is concern that patients treated with ACEIs and ARBs are at higher risk of coronavirus disease 2019 (COVID-19) pneumonia. Aim This study sought to analyze the association of COVID-19 pneumonia with previous treatment with ACEIs and ARBs. Materials and methods We retrospectively reviewed 684 consecutive patients hospitalized for suspected COVID-19 pneumonia and tested by polymerase chain reaction assay. Patients were split into two groups, according to whether (group 1, n = 484) or not (group 2, n = 250) COVID-19 was confirmed. Multivariable adjusted comparisons included a propensity score analysis. Results The mean age was 63.6 ± 18.7 years, and 302 patients (44%) were female. Hypertension was present in 42.6% and 38.4% of patients in groups 1 and 2, respectively (P = 0.28). Treatment with ARBs was more frequent in group 1 than group 2 (20.7% vs. 12.0%, respectively; odds ratio [OR] 1.92, 95% confidence interval [CI] 1.23–2.98; P = 0.004). No difference was found for treatment with ACEIs (12.7% vs. 15.7%, respectively; OR 0.81, 95% CI 0.52–1.26; P = 0.35). Propensity score-matched multivariable logistic regression confirmed a significant association between COVID-19 and previous treatment with ARBs (adjusted OR 2.36, 95% CI 1.38–4.04; P = 0.002). Significant interaction between ARBs and ACEIs for the risk of COVID-19 was observed in patients aged > 60 years, women, and hypertensive patients. Conclusions This study suggests that ACEIs and ARBs are not similarly associated with COVID-19. In this retrospective series, patients with COVID-19 pneumonia more frequently had previous treatment with ARBs compared with patients without COVID-19.

Contexte et objectif. L’enzyme de conversion de l’angiotensine (ACE) de type 2 est le récepteur du virus SARS-CoV-2 sur les pneumocytes. L’expression de l’ACE-2 est modulée par les inhibiteurs de l’enzyme de conversion (IEC) et les antagonistes des récepteurs à l’angiotensine II (ARA2) largement utilisés en cardiologie. Ceci a interrogé sur d’éventuels liens entre ces traitements et la vulnérabilité aux pneumopathies liées au COVID-19 ou leur sévérité. L’objectif de la présente étude était d’analyser l’association entre un traitement par IEC/ARA2 et les formes graves de COVID-19. Méthodes. Nous avons suivi prospectivement 433 patients consécutifs hospitalisés pour COVID-19 confirmée par PCR ou hautement suspectée sur les données cliniques, biologiques, radiologiques et inclus dans l’étude COVHYP. La survie et les formes graves de COVID-19 (décès, réanimation, ou hospitalisation >30 jours) ont été comparées chez les patients recevant ou non des IEC/ARA2. Le taux de suivi hospitalier a été de 100%, et à un mois ou plus de 96,5%. Résultats L’âge moyen des patients était de 64 ± 17 ans, 40% étaient des femmes. Au suivi moyen de 78 ± 50 jours, 136 (31%) ont eu une forme grave de COVID-19 (64 décès, 73 séjour en réanimation et 49 hospitalisations >30 jours). L’hypertension (55,1% vs 36,7% ; p<0,001) et la présence d’un traitement antihypertenseur étaient associés aux formes graves ainsi qu’à la mortalité globale. L’association univariée entre le traitement par IEC/ARA2 et les formes graves (Odds Ratio 1,74 IC95% [1,14-2,64] ; p=0.01) n’a pas été confirmée après ajustement sur l’âge, le sexe et l’hypertension (OR ajusté 1,13 [0,59-2,15] ; p=0,72). Le diabète, l’hypothyroïdie étaient associés aux formes graves, l’antécédent d’asthme aux formes non graves. Conclusion. Le traitement par IEC/ARA2 n’est pas associé aux formes graves, à la mortalité hospitalière, ni à la mortalité à 1 ou 2 mois des patients hospitalisés pour COVID-19, après ajustement sur les facteurs de confusion. A contrario, les antagonistes du système rénine-angiotensine-aldostérone, principalement les ARA2, ne semblent pas avoir d’effet protecteur sur les pneumopathies graves de la COVID-19.

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