Diuretics Versus Volume Expansion in the Initial Management of Acute Intermediate High-Risk Pulmonary Embolism.

AIMS: The very early management of pulmonary embolism (PE), a part from antithrombotic treatment, has been little studied. Our aim was to compare the effects of diuretic therapy (DT) versus volume expansion (VE) in patients hospitalized for PE with RV dysfunction. METHODS AND RESULTS: We conducted a randomized open-label multicentric study including patients with intermediate high-risk PE. Patients were randomized between diuretics or saline infusion. The primary endpoint was time to troponin (Tp) normalization. Secondary endpoints were time to normalization of B-type natriuretic peptide (BNP), changes in echocardiographic RV function parameters and treatment tolerance. Sixty patients presenting intermediate high-risk PE were randomized. Thirty received DT and 30 VE. We noted no changes in Tp kinetics between the two groups. In contrast, faster normalization of BNP was obtained in the DT group: 56 [28-120] vs 108 [48-144] h: p = 0.05, with a shorter time to 50%-decrease from peak value 36 [24-48] vs 54 [41-67] h, p = 0.003 and a higher rate of patients with a lower BNP concentration within the first 12 h (42% vs 12% p < 0.001). RV echocardiographic parameters were unchanged between the groups. One dose 40 mg furosemide was well-tolerated and not associated with any serious adverse events. CONCLUSION: In the acute management of intermediate high-risk PE, initial therapy including diuretic treatment is well-tolerated and safe. Although changes in Tp kinetics and echocardiographic RV dysfunction parameters did not differ, normalization of BNP is achieved more quickly in the DT group. This finding, which need to be confirmed in trials with clinical end points, may reflects a rapid improvement in RV function using one dose 40 mg furosemide. TRIAL REGISTRY: Clinical Trial Registration NCT02531581.

Is pulmonary embolism recurrence linked with the severity of the first event? A French retrospective cohort study.

OBJECTIVES: Severity of a first pulmonary embolism (PE) is sometimes proposed as a criterion for prolonging anticoagulant treatment. However, little evidence supports this idea. We attempted to determine the connection between severity of first PE and the risk of recurrence. PARTICIPANTS: Patients admitted with PE between 2012 and 2018 and for whom anticoagulant treatment had been discontinued were followed. PEs were classified according to the severity into the following two groups: those with associated cardiac involvement (increased cardiac biomarker(s) and/or echocardiographic right ventricular dysfunction) and those with no cardiac involvement which were classified as non-severe. Recurrence-free survivals were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: 417 patients with PEs (186 with cardiac involvement) were followed for at least 1 year after discontinuation of treatment with a mean follow-up of: 3.5±1.9 years. 72 patients (17.3%) experienced venous thromboembolism recurrence: 24 (5.8%), 44 (12 %) and 72 (28.3 %) respectively, at 1, 2 and 5 years. In 63 patients (88%), recurrence was a PE. Mean time to onset of recurrence was 24.9±19.9 months. At 5 years, the recurrence rate is higher when the first PE was associated with cardiac involvement p=0.043. In contrast, in patients with provoked PE, the recurrence rate is higher when the first PE event was associated with cardiac involvement: p=0.032. Multivariate analysis demonstrates that PE severity is an independent factor of recurrence (HR 1.634 (1.015-2.632), p=0.043). CONCLUSION: We report for the first time a possible link between a higher recurrence rate and the severity of the first PE. This result which must be confirmed in a dedicated prospective trial could become an important criterion for the duration of anticoagulant therapy after a PE. TRIAL REGISTRATION NUMBER: NCT04980924.

High Prevalence of Acquired Thrombophilia Without Prognosis Value in Patients With Coronavirus Disease 2019.

Background Recent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID-19) infection. This characteristic is unusual and seems specific to COVID-19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then lead to thrombotic complications. We investigate for the presence of acquired thrombophilia, which could participate in this phenomenon, and report its prevalence. We also wonder if these thrombophilias participate in the bad prognosis of severe COVID-19 infections. Methods and Results In 89 consecutive patients hospitalized for COVID-19 infection, we found a 20% prevalence of PS (protein S) deficiency and a high (ie, 72%) prevalence of antiphospholipid antibodies: mainly lupus anticoagulant. The presence of PS deficiency or antiphospholipid antibodies was not linked with a prolonged activated partial thromboplastin time nor with D-dimer, fibrinogen, or CRP (C-reactive protein) concentrations. These coagulation abnormalities are also not linked with thrombotic clinical events occurring during hospitalization nor with mortality. Conclusions We assess a high prevalence of positive tests detecting thrombophilia in COVID-19 infections. However, in our series, these acquired thrombophilias are not correlated with the severity of the disease nor with the occurrence of thrombotic events. Albeit the strong thrombotic tendency in COVID-19 infections, the presence of frequent acquired thrombophilia may be part of the inflammation storm of COVID-19 and should not systematically modify our strategy on prophylactic anticoagulant treatment, which is already revised upwards in this pathological condition. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT04335162.

QT Interval Prolongation Under Hydroxychloroquine/Azithromycin Association for Inpatients With SARS-CoV-2 Lower Respiratory Tract Infection.

Association between Hydroxychloroquine (HCQ) and Azithromycin (AZT) is under evaluation for patients with lower respiratory tract infection (LRTI) caused by the Severe Acute Respiratory Syndrome (SARS-CoV-2). Both drugs have a known torsadogenic potential, but sparse data are available concerning QT prolongation induced by this association. Our objective was to assess for COVID-19 LRTI variations of QT interval under HCQ/AZT in patients hospitalized, and to compare manual versus automated QT measurements. Before therapy initiation, a baseline 12 lead-ECG was electronically sent to our cardiology department for automated and manual QT analysis (Bazett and Fridericia's correction), repeated 2 days after initiation. According to our institutional protocol (Pasteur University Hospital), HCQ/AZT was initiated only if baseline QTc ≤ 480ms and potassium level> 4.0 mmol/L. From March 24th to April 20th 2020, 73 patients were included (mean age 62 ± 14 years, male 67%). Two patients out of 73 (2.7%) were not eligible for drug initiation (QTc ≥ 500 ms). Baseline average automated QTc was 415 ± 29 ms and lengthened to 438 ± 40 ms after 48 hours of combined therapy. The treatment had to be stopped because of significant QTc prolongation in two out of 71 patients (2.8%). No drug-induced life-threatening arrhythmia, nor death was observed. Automated QTc measurements revealed accurate in comparison with manual QTc measurements. In this specific population of inpatients with COVID-19 LRTI, HCQ/AZT could not be initiated or had to be interrupted in less than 6% of the cases.