Impact of COVID-19 on posttraumatic stress disorder in ICU survivors: a prospective observational comparative cohort study.

BACKGROUND: Posttraumatic stress disorder (PTSD) after a stay in the intensive care unit (ICU) can affect one in five ICU survivors. At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, admission to the ICU for COVID-19 was stressful due to the severity of this disease. This study assessed whether admission to the ICU for COVID-19 was associated with a higher prevalence of PTSD compared with other causes of ICU admission after adjustment for pre-ICU psychological factors. METHODS: This prospective observational comparative cohort study included 31 ICUs. Eligible patients were adult ICU survivors hospitalized during the first wave of COVID-19 pandemic in France, regardless of the reason for admission. The prevalence of presumptive diagnosis of PTSD at 6 months was assessed using the PTSD Checklist for DSM-5 (PCL-5). Sociodemographics, clinical data, history of childhood trauma (Childhood Trauma Questionnaire [CTQ]), and exposure to potentially traumatic events (Life Events Checklist for DSM-5 [LEC-5]) were assessed. RESULTS: Of the 778 ICU survivors included during the first wave of COVID-19 pandemic in France, 417 and 361 were assigned to the COVID-19 and non-COVID-19 cohorts, respectively. Fourteen (4.9%) and 11 (4.9%), respectively, presented with presumptive diagnosis of PTSD at 6 months (p = 0.976). After adjusting for age, sex, severity score at admission, use of invasive mechanical ventilation, ICU duration, CTQ and LEC-5, COVID-19 status was not associated with presumptive diagnosis of PTSD using the PCL-5. Only female sex was associated with presumptive diagnosis of PTSD. However, COVID-19 patients reported significantly more intrusion and avoidance symptoms than non-COVID patients (39% vs. 29%, p = 0.015 and 27% vs. 19%, p = 0.030), respectively. The median PCL-5 score was higher in the COVID-19 than non-COVID-19 cohort (9 [3, 20] vs. 4 [2, 16], p = 0.034). CONCLUSION: Admission to the ICU for COVID-19 was not associated with a higher prevalence of PTSD compared with admission for another cause during the first wave of the COVID-19 pandemic in France. However, intrusion and avoidance symptoms were more frequent in COVID-19 patients than in non-COVID-19 patients. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT03991611, registered on June 19, 2019.

Reproducibility of reading echocardiographic parameters to assess severity of mitral regurgitation. Insights from a French multicentre study.

BACKGROUND: Poor reproducibility in assessment of mitral regurgitation (MR) has been reported. AIM: To investigate the robustness of echocardiographic MR assessment in 2019, based on improvements in technology and the skill of echocardiographists regarding MR quantification. METHODS: Reproducibility in parameters of MR severity and global rating were tested using transthoracic echocardiography in 25 consecutive patients independently analysed by 16 junior and senior cardiologists specialized in echocardiography (400 analyses per parameter). RESULTS: Overall interobserver agreement for mechanism definition, effective regurgitant orifice area (EROA) and regurgitant volume (RVol) was moderate, and was lower in secondary MR. Interobserver agreement was substantial for EROA [0.61, 95% confidence interval (CI) 0.45-0.75] and moderate for RVol with the PISA method (0.50, 95% CI 0.33-0.56) in senior physicians and was fair in junior physicians (0.33, 95% CI 0.19-0.51 and 0.36, 95% CI 0.36-0.43, respectively). Using a multiparametric approach, overall interobserver agreement for grading MR severity was fair (0.30), was slightly better in senior than in junior physicians (0.31 vs. 0.28, respectively) with substantial or almost perfect agreement more frequently observed in senior versus junior physicians (52% vs. 36%, respectively). CONCLUSION: Reproducible transthoracic echocardiography MR quantification remains challenging in 2019, despite the expected high skills of echocardiographers regarding MR at the time of dedicated percutaneous intervention. The multiparametric approach does not entirely alleviate the substantial dispersion in measurement of MR severity parameters, whereas reader experience seems to partially address the issue. Our study emphasizes the continuing need for multimodality imaging and education in the evaluation of MR among cardiologists.

A multiplex analysis of sepsis mediators during human septic shock: a preliminary study on myocardial depression and organ failures.

BACKGROUND: The mechanisms of organ failure during sepsis are not fully understood. The hypothesis of circulating factors has been suggested to explain septic myocardial dysfunction. We explored the biological coherence of a large panel of sepsis mediators and their clinical relevance in septic myocardial dysfunction and organ failures during human septic shock. METHODS: Plasma concentrations of 24 mediators were assessed on the first day of septic shock using a multi-analyte cytokine kit. Septic myocardial dysfunction and organ failures were assessed using left ventricle ejection fraction (LVEF) and the Sequential Organ Failure Assessment score, respectively. RESULTS: Seventy-four patients with septic shock (and without immunosuppression or chronic heart failure) were prospectively included. Twenty-four patients (32%) had septic myocardial dysfunction (as defined by LVEF < 45%) and 30 (41%) died in ICU. Hierarchical clustering identified three main clusters of sepsis mediators, which were clinically meaningful. One cluster involved inflammatory cytokines of innate immunity, most of which were associated with septic myocardial dysfunction, organ failures and death; inflammatory cytokines associated with septic myocardial dysfunction had an additive effect. Another cluster involving adaptive immunity and repair (with IL-17/IFN pathway and VEGF) correlated tightly with a surrogate of early sepsis resolution (lactate clearance) and ICU survival. CONCLUSIONS: In this preliminary study, we identified a cluster of cytokines involved in innate inflammatory response associated with septic myocardial dysfunction and organ failures, whereas the IL-17/IFN pathway was associated with a faster sepsis resolution and a better survival.

Transoesophageal echocardiography current practice in France: A multicentre study.

BACKGROUND: Few data are available on the application of transoesophageal echocardiography (TOE) recommendations in daily practice. AIMS: To evaluate TOE practice based on echocardiography societies' guidelines, and to determine complication rates and factors associated with patient feelings. METHODS: Between April and June 2017, we prospectively included all consecutive patients referred to 14 French hospitals for a transoesophageal echocardiogram (TOE). A survey was taken just after the examination, which included questions about pre-procedural anxiety, and any pain, unpleasant feeling or breathing difficulties experienced during the examination. RESULTS: Overall, 1718 TOEs were performed, mainly for stroke evaluation. A standardized operating procedure checklist was completed in half of the patients before the examination. TOE was unpleasant for 62.4% of patients, but was stopped for agitation or intolerance in 3.5 and 1.4% of cases, respectively. We observed one severe complication (pulmonary oedema). The mean TOE duration was short (9.2±4.6minutes), but was longer with residents than with more experienced physicians (11±4.7 vs. 8.8±4.7minutes for junior physicians [P=0.0027]; vs. 8.9±4.8minutes for senior physicians [P=0.0013]; and vs. 7.5±4.1minutes for associate professors/professors [P<0.0001]). The visual analogue scale (VAS) score after TOE was good (8.3±1.7 out of 10), and was better in patients with general anaesthesia (GA) than in those without GA (9.3±0.9 vs. 8.1±1.7; P<0.0001). In patients without GA, the VAS score was similar with and without local anaesthesia (8.1±1.7 vs. 8.2±1.6; P=0.19). After multivariable adjustment, absence of anxiety before TOE and greater operator experience were consistently associated with a higher VAS score. CONCLUSIONS: TOE is safe, with a low rate of complications and few stops for intolerance. A shorter TOE duration and better patient feelings were observed for experienced operators, highlighting the importance of the learning curve, and paving the way for teaching on a TOE simulator.

Left ventricular systolic dysfunction during septic shock: the role of loading conditions.

PURPOSE: The clinical significance of septic myocardial dysfunction is controversial, a fact that may be explained by the influence of loading conditions. Many indices may be useful to characterize cardiac function during septic shock, but their feasibility and physiological coherence in the clinical setting are unknown. METHODS: Hemodynamic and echocardiographic data with tissue Doppler and speckle tracking were prospectively recorded on the first 3 days of human septic shock. Hypokinesia, normokinesia, and hyperkinesia were defined as a left ventricular ejection fraction (LVEF) of <45, 45-60, and >60%, respectively. Twelve hemodynamic indices exploring contractility and loading conditions were assessed and analyzed. RESULTS: Two hundred and ninety-seven echocardiographies were performed in 132 patients. During the first 24 h (H1-24), 48 (36.4%) patients were hyperkinetic, 55 (41.7%) were normokinetic, and 29 (22.0%) patients were hypokinetic. Thirteen patients had a secondary hypokinesia absent at H1-24 but present at H25-48 or H49-72, for an overall incidence of 42 (31.8%) during the first 3 days. Despite a limited feasibility (<50%), global LV longitudinal peak systolic strain was impaired in a majority (>70%) of the patients assessed, including all those with depressed LVEF, and declined early in patients whose LVEF secondarily deteriorated. Most contractility indices were inversely correlated with afterload indices. Hyperkinetic patients exhibited the worst reduction in afterload indices. Hospital mortality was significantly higher in patients with LV hyperkinesia than in their counterparts: 30 (62.5%) vs. 35 (41.7%), p = 0.02. CONCLUSIONS: Speckle tracking-derived strain was reduced in the majority of patients with septic shock, revealing covert septic myocardial dysfunction, but had poor feasibility. We found an inverse correlation between most of the contractility and afterload indices. Precise evaluation of afterload is crucial for adequate interpretation of LV systolic function in this setting.

New-onset supraventricular arrhythmia during septic shock: prevalence, risk factors and prognosis.

BACKGROUND: The aims of this study were to prospectively assess the prevalence of sustained (lasting more than 30 s) new-onset supraventricular arrhythmia (NOSVA) during septic shock, identify the associated factors (including septic myocardial dysfunction), and evaluate its impact on hemodynamics and prognosis. METHODS: Patients with a diagnosis of septic shock were screened in a medical intensive care unit of a tertiary hospital center in France with a continuous 12-lead EKG for the occurrence of NOSVA. Biological and clinical data (including septic myocardial dysfunction characterized by echocardiography) were collected. We also assessed the hemodynamic tolerance and prognosis of NOSVA. RESULTS: Among the 71 septic shock episodes assessed during the study, NOSVA occurred in 30 [prevalence of 42 %, 95 % confidence interval (CI) 30-53 %]. Among all recorded factors, only renal failure (as assessed by renal SOFA score at day 1) was associated with NOSVA and this difference persisted by multivariable analysis (odds ratio of 1.29, 95 % CI 1.03-1.62, p = 0.03). There was a significant increase in norepinephrine dosage during the first hour after SVA onset. NOSVA was associated with longer catecholamine use during septic shock as compared with patients in sinus rhythm, whereas ICU mortality was identical between groups. CONCLUSIONS: We found a high prevalence of sustained NOSVA during septic shock. NOSVA was not related to septic myocardial dysfunction, but rather to acute renal failure, raising the hypothesis of an acute renocardiac syndrome.

Total liquid ventilation offers ultra-fast and whole-body cooling in large animals in physiological conditions and during cardiac arrest.

INTRODUCTION: Total liquid ventilation (TLV) can cool down the entire body within 10-15 min in small animals. Our goal was to determine whether it could also induce ultra-fast and whole-body cooling in large animals using a specifically dedicated liquid ventilator. Cooling efficiency was evaluated under physiological conditions (beating-heart) and during cardiac arrest with automated chest compressions (CC, intra-arrest). METHODS: In a first set of experiments, beating-heart pigs were randomly submitted to conventional mechanical ventilation or hypothermic TLV with perfluoro-N-octane (between 15 and 32 °C). In a second set of experiments, pigs were submitted to ventricular fibrillation and CC. One group underwent continuous CC with asynchronous conventional ventilation (Control group). The other group was switched to TLV while pursuing CC for the investigation of cooling capacities and potential effects on cardiac massage efficiency. RESULTS: Under physiological conditions, TLV significantly decreased the entire body temperatures below 34 °C within only 10 min. As examples, cooling rates averaged 0.54 and 0.94 °C/min in rectum and esophageous, respectively. During cardiac arrest, TLV did not alter CC efficiency and cooled the entire body below 34 °C within 20 min, the low-flow period slowing cooling during CC. CONCLUSION: Using a specifically designed liquid ventilator, TLV induced a very rapid cooling of the entire body in large animals. This was confirmed in both physiological conditions and during cardiac arrest with CC. TLV could be relevant for ultra-rapid cooling independently of body weight.

Hemodynamic effects of Ivabradine in addition to dobutamine in patients with severe systolic dysfunction.

BACKGROUND: Dobutamine induced tachycardia increases myocardial oxygen consumption and impairs ventricular filling. We hypothesized that Ivabradine may be efficient to control dobutamine induced tachycardia. METHODS: We assessed the effects of Ivabradine in addition to dobutamine in stable heart failure (HF) patients (LVEF < 35%, n = 22, test population) and validated its effects in refractory cardiogenic shock patients (n = 9, validation population) with contraindication to cardiac assistance or transplant. In the test population (62 ± 17 years, LVEF = 24 ± 8%), systolic and diastolic function were assessed at rest and under dobutamine [10 γ/min], before and after Ivabradine [5mg per os]. In the validation population (54 ± 11 years, LVEF = 22 ± 7%), Ivabradine [5mg twice a day] was added to the dobutamine infusion. RESULTS: In the test population, Ivabradine decreased heart rate [HR] at rest and during dobutamine echocardiography (-9 ± 8 bpm, P = 0.0004). The decrease in HR was associated with a decrease in cardiac power output and an increase in diastolic duration at rest (+ 74 ± 67 ms, P = 0.0002), and during dobutamine infusion (+ 75 ± 67 ms, P < 0.0001). Change in LVEF during dobutamine was greater after Ivabradine treatment than before (+ 7.2 ± 4.7% vs. + 3.6 ± 4.2%, P = 0.002). In the validation population, Ivabradine decreased HR (-18 ± 11 bpm, P = 0.008) and improved diastolic filling time (+ 67 ± 42 ms, P = 0.012) without decreasing cardiac output. At 24h, Ivabradine improved systolic blood pressure (+ 9 ± 5 mmHg, P = 0.007), daily urine output (+ 0.7 ± 0.5L, P = 0.008), oxygen balance (ΔScv02 = + 13 ± 15%, P = 0.010), and NT-pro BNP (-2270 ± 1912 pg/mL, P = 0.017). Finally, only 2/9 (22%) patients died whereas expected mortality determined from a historical cohort was 78% (P = 0.017). CONCLUSION: This pilot study demonstrates the safety and potential benefit of a HR lowering agent in cardiogenic shock.

Evaluation of lung recovery after static administration of three different perfluorocarbons in pigs.

BACKGROUND: The respiratory properties of perfluorocarbons (PFC) have been widely studied for liquid ventilation in humans and animals. Several PFC were tested but their tolerance may depend on the species. Here, the effects of a single administration of liquid PFC into pig lungs were assessed and compared. Three different PFC having distinct evaporative and spreading coefficient properties were evaluated (Perfluorooctyl bromide [PFOB], perfluorodecalin [PFD] and perfluoro-N-octane [PFOC]). METHODS: Pigs were anesthetized and submitted to mechanical ventilation. They randomly received an intra-tracheal administration of 15 ml/kg of either PFOB, PFD or PFOC with 12 h of mechanical ventilation before awakening and weaning from ventilation. A Control group was submitted to mechanical ventilation with no PFC administration. All animals were followed during 4 days after the initial PFC administration to investigate gas exchanges and clinical recovery. They were ultimately euthanized for histological analyses and assessment of PFC residual concentrations within the lungs using dual nuclei fluorine and hydrogen Magnetic Resonance Imaging (MRI). Sixteen animals were included (4/group). RESULTS: In the PFD group, animals tended to be hypoxemic after awakening. In PFOB and PFOC groups, blood gases were not significantly different from the Control group after awakening. The poor tolerance of PFD was likely related to a large amount of residual PFC, as observed using MRI in all lung samples (≈10% of lung volume). This percentage was lower in the PFOB group (≈1%) but remained significantly greater than in the Control group. In the PFOC group, the percentage of residual PFC was not significantly different from that of the Control group (≈0.1%). Histologically, the most striking feature was an alveolar infiltration with foam macrophages, especially in the groups treated by PFD or PFOB. CONCLUSIONS: Of the three tested perfluorocarbons, PFOC offered the best tolerance in terms of lung function, gas exchanges and residuum in the lung. PFOC was rapidly cleared from the lungs and virtually disappeared after 4 days whereas PFOB persisted at significant levels and led to foam macrophage infiltration. PFOC could be relevant for short term total liquid ventilation with a rapid weaning.

Effect of transcatheter (via femoral artery) aortic valve implantation on the platelet count and its consequences.

Decrease in blood platelet count has been described after percutaneous coronary intervention and surgical valve replacement, although no study has been performed in the setting of transcatheter aortic valve implantation (TAVI). The aim of this study was to address the incidence, mechanism, and impact of blood platelet count decrease after TAVI. One hundred forty-four consecutive patients (mean age 84 ± 7 years, 64 men) with severe symptomatic aortic stenosis who underwent TAVI from December 2007 to July 2011 were enrolled. Blood platelet count was recorded before and after aortic valve implantation. Decrease in blood platelet count was compared with in-hospital major adverse cardiovascular events (death, stroke, and major or life-threatening bleeding). Blood platelet count decreases occurred in all but 1 patient. The percentage of platelet count decrease averaged 34 ± 15% and was 24% greater than blood protein decrease. Decrease in platelet count was associated with a higher rate of prosthesis migration, longer x-ray and procedural times, and larger contrast amounts (230 ± 128 ml for the third tertile vs 170 ± 77 ml for the second and first tertiles, p = 0.0006), but no association was observed with regard to changes in bilirubin. In-hospital major adverse cardiovascular events (n = 50 [35%]) were observed more frequently in patients with severe platelet count decreases (21% for the first tertile, 35% for the second tertile, and 48% for the third tertile, p = 0.02). Finally, the percentage of blood platelet count decrease was the only predictor of in-hospital major adverse cardiovascular events (odds ratio 1.67, 95% confidence interval 1.05 to 2.67, p = 0.03). In conclusion, a decrease in platelet count is a common phenomenon after TAVI, and its severity is associated with poor outcomes.

Vascular purpura revealing a severe dilated cardiomyopathy with left ventricular apical thrombus.

We present a case of vascular purpura revealing an intra-cardiac left-sided thrombus complicating an end-stage dilated cardiomyopathy. Vascular purpura main etiologies encompass the wide specturm of vasculitides and microvascular-occlusion syndromes. Among them, cardiac embolism represents an unusal but potentially severe etology.