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.

Prevalence and Clinical Characteristics of Patients with Torsades de Pointes Complicating Acquired Atrioventricular Block.

BACKGROUND: Female gender, degree of QT prolongation, and genetic susceptibility are known risk factors for developing torsades de pointes (TdP) during high-grade atrioventricular block (HG-AVB). Our objective was to analyze the prevalence and clinical characteristics of patients presenting with TdP and AVB (TdP [+]) in comparison with non-TdP patients with AVB (TdP [-]). METHODS: All the ECGs from patients prospectively admitted for AVB (2 to 1, HG, and complete) at the University Hospital of Nice were analyzed. Automated corrected QT (QTc), manual measurements of QT and JT intervals, and Tpeak-to-end were performed at the time of the most severe bradycardia. RESULTS: From September 2020 to November 2021, 100 patients were admitted for HG-AVB. Among them, 17 patients with TdP were identified (8 men; 81 ± 10 years). No differences could be identified concerning automated QTc, manual QTc (Bazett correction), baseline QRS width, or mean left ventricular ejection fraction between the two groups. Potassium serum level on admission and mean number of QT-prolonging drugs per patient were not significantly different between the two groups, respectively: 4.34 ± 0.5 mmol/L in TdP [+] versus 4.52 ± 0.6 mmol/L (p = 0.33); and 0.6 ± 0.7 in TdP [+] versus 0.3 ± 0.5 (p = 0.15). In contrast, manual QTcFR (Fridericia correction), JT (Fridericia correction), Tpeak-to-end, and Tpe/QT ratio were significantly increased in the TdP [+] group, respectively: 486 ± 70 ms versus 456 ± 53 ms (p = 0.04); 433 ± 98 ms versus 381 ± 80 ms (p = 0.02); 153 ± 57 ms versus 110 ± 40 ms (p < 0.001); and 0.27 ± 0.08 versus 0.22 ± 0.06 (p < 0.001). CONCLUSIONS: The incidence of TdP complicating acquired AVB was 17%. Longer QTcFR, JT, and Tpeak-to-end were significantly increased in the case of TdP but also in the presence of permanent AVB during the hospitalization.

An exploratory human study investigating the influence of type 2 diabetes on macrophage phenotype after myocardial infarction.

Background: Myocardial infarction (MI) is the primary cause of death in subjects with type 2 diabetes (T2D) and their in-hospital mortality after MI is still elevated compared with those without T2D. Therefore, it is of crucial importance to identify possible mechanisms of worse clinical outcomes and mortality in T2D subjects. Monocyte/macrophage-mediated immune response plays an important role in heart remodelling to limit functional deterioration after MI. Indeed, first pro-inflammatory macrophages digest damaged tissue, then anti-inflammatory macrophages become prevalent and promote tissue repair. Here, we hypothesize that the worse clinical outcomes in patients with T2D could be the consequence of a defective or a delayed polarization of macrophages toward an anti-inflammatory phenotype. Methods and results: In an exploratory human study, circulating monocytes from male patients with or without T2D at different time-points after MI were in vitro differentiated toward pro- or anti-inflammatory macrophages. The results of this pilot study suggest that the phenotype of circulating monocytes, as well as the pro- and anti-inflammatory macrophage polarization, or the kinetics of the pro- and anti-inflammatory polarization, is not influenced by T2D. Conclusion: Further studies will be necessary to understand the real contribution of macrophages after MI in humans.

Prevalence and Clinical Characteristics of Patients with Pause-Dependent Atrioventricular Block.

BACKGROUND: In patients with complete atrioventricular block (AVB), the prevalence and clinical characteristics of patients with pause-dependent AVB (PD-AVB) is not known. Our objective was to assess the prevalence of PD-AVB in a population of patients with complete (or high-grade) AVB. METHODS: Twelve-lead electrocardiogram (ECG) and/or telemonitoring from patients admitted (from September 2020 to November 2021) for complete (or high-degree) AVB were prospectively collected at the University Hospital of Nice. The ECG tracings were analyzed by an electrophysiologist to determine the underlying mechanism of PD-AVB. RESULTS: 100 patients were admitted for complete (or high-grade) AVB (men 55%; 82 ± 12 years). Arterial hypertension was present in 68% of the patients. Baseline QRS width was 117 ± 32 ms, and mean left ventricular ejection fraction was 56 ± 7%. Fourteen patients (14%) with PD-AVB were identified, and presented similar clinical characteristics in comparison with patients without PD-AVB, except for syncope (which was present in 86% versus 51% in the non-PD-AVB patients, p = 0.01). PD-AVB sequence was induced by: Premature atrial contraction (8/14), premature ventricular contraction (5/14), His extrasystole (1/14), conduction block in a branch (1/14), and atrial tachycardia termination (1/14). All patients with PD-AVB received a dual-chamber pacemaker during hospitalization. CONCLUSION: The prevalence of PD-AVB was 14%, and may be underestimated. PD-AVB episodes were more likely associated with syncope in comparison with patients without PD-AVB.

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.