Unveiling the Role of Endothelial Dysfunction: A Possible Key to Enhancing Catheter Ablation Success in Atrial Fibrillation.

Atrial fibrillation, a prevalent type of arrhythmia, is increasingly contributing to the economic burden on healthcare systems. The development of innovative treatments, notably catheter ablation, has demonstrated both impressive and promising outcomes. However, these treatments have not yet fully replaced pharmaceutical approaches, primarily due to the relatively high incidence of atrial fibrillation recurrence post-procedure. Recent insights into endothelial dysfunction have shed light on its role in both the onset and progression of atrial fibrillation. This emerging understanding suggests that endothelial function might significantly influence the effectiveness of catheter ablation. Consequently, a deeper exploration into endothelial dynamics could potentially elevate the status of catheter ablation, positioning it as a primary treatment option for atrial fibrillation.

Comprehensive temporal analysis of right ventricular function and pulmonary haemodynamics in mechanically ventilated COVID-19 ARDS patients.

BACKGROUND: Cardiac injury is frequently reported in COVID-19 patients, the right ventricle (RV) is mostly affected. We systematically evaluated the cardiac function and longitudinal changes in severe COVID-19 acute respiratory distress syndrome (ARDS) admitted to the intensive care unit (ICU) and assessed the impact on survival. METHODS: We prospectively performed comprehensive echocardiographic analysis on mechanically ventilated COVID-19 ARDS patients, using 2D/3D echocardiography. We defined left ventricular (LV) systolic dysfunction as ejection fraction (EF) < 40%, or longitudinal strain (LS) > - 18% and right ventricular (RV) dysfunction if two indices among fractional area change (FAC) < 35%, tricuspid annulus systolic plane excursion (TAPSE) < 1.6 cm, RV EF < 44%, RV-LS > - 20% were present. RV afterload was assessed from pulmonary artery systolic pressure (PASP), PASP/Velocity Time Integral in the right ventricular outflow tract (VTIRVOT) and pulmonary acceleration time (PAcT). TAPSE/PASP assessed the right ventriculoarterial coupling (VACR). RESULTS: Among 176 patients included, RV dysfunction was common (69%) (RV-EF 41.1 ± 1.3%; RV-FAC 36.6 ± 0.9%, TAPSE 20.4 ± 0.4mm, RV-LS:- 14.4 ± 0.4%), usually accompanied by RV dilatation (RVEDA/LVEDA 0.82 ± 0.02). RV afterload was increased in most of the patients (PASP 33 ± 1.1 mmHg, PAcT 65.3 ± 1.5 ms, PASP/VTIRVOT, 2.29 ± 0.1 mmHg/cm). VACR was 0.8 ± 0.06 mm/mmHg. LV-EF < 40% was present in 21/176 (11.9%); mean LV-EF 57.8 ± 1.1%. LV-LS (- 13.3 ± 0.3%) revealed a silent LV impairment in 87.5%. A mild pericardial effusion was present in 70(38%) patients, more frequently in non-survivors (p < 0.05). Survivors presented significant improvements in respiratory physiology during the 10th ICU-day (PaO2/FiO2, 231.2 ± 11.9 vs 120.2 ± 6.7 mmHg; PaCO2, 43.1 ± 1.2 vs 53.9 ± 1.5 mmHg; respiratory system compliance-CRS, 42.6 ± 2.2 vs 27.8 ± 0.9 ml/cmH2O, all p < 0.0001). Moreover, survivors presented significant decreases in RV afterload (PASP: 36.1 ± 2.4 to 20.1 ± 3 mmHg, p < 0.0001, PASP/VTIRVOT: 2.5 ± 1.4 to 1.1 ± 0.7, p < 0.0001 PAcT: 61 ± 2.5 to 84.7 ± 2.4 ms, p < 0.0001), associated with RV systolic function improvement (RVEF: 36.5 ± 2.9% to 46.6 ± 2.1%, p = 0.001 and RV-LS: - 13.6 ± 0.7% to - 16.7 ± 0.8%, p = 0.001). In addition, RV dilation subsided in survivors (RVEDA/LVEDA: 0.8 ± 0.05 to 0.6 ± 0.03, p = 0.001). Day-10 CRS correlated with RV afterload (PASP/VTIRVOT, r: 0.535, p < 0.0001) and systolic function (RV-LS, 0.345, p = 0.001). LV-LS during the 10th ICU-day, while ΔRV-LS and ΔPASP/RVOTVTI were associated with survival. CONCLUSIONS: COVID-19 improvements in RV function, RV afterload and RV-PA coupling at day 10 were associated with respiratory function and survival.

New-Onset Atrial Fibrillation in the Critically Ill COVID-19 Patients Hospitalized in the Intensive Care Unit.

New-onset atrial fibrillation (NOAF) is the most frequently encountered cardiac arrhythmia observed in patients with COVID-19 infection, particularly in Intensive Care Unit (ICU) patients. The purpose of the present review is to delve into the occurrence of NOAF in COVID-19 and thoroughly review recent, pertinent data. However, the causality behind this connection has yet to be thoroughly explored. The proposed mechanisms that could contribute to the development of AF in these patients include myocardial damage resulting from direct virus-induced cardiac injury, potentially leading to perimyocarditis; a cytokine crisis and heightened inflammatory response; hypoxemia due to acute respiratory distress; disturbances in acid-base and electrolyte levels; as well as the frequent use of adrenergic drugs in critically ill patients. Additionally, secondary bacterial sepsis and septic shock have been suggested as primary causes of NOAF in ICU patients. This notion gains strength from the observation of a similar prevalence of NOAF in septic non-COVID ICU patients with ARDS. It is plausible that both myocardial involvement from SARS-CoV-2 and secondary sepsis play pivotal roles in the onset of arrhythmia in ICU patients. Nonetheless, there exists a significant variation in the prevalence of NOAF among studies focused on severe COVID-19 cases with ARDS. This discrepancy could be attributed to the inclusion of mixed populations with varying degrees of illness severity, encompassing not only patients in general wards but also those admitted to the ICU, whether intubated or not. Furthermore, the occurrence of NOAF is linked to increased morbidity and mortality. However, it remains to be determined whether NOAF independently influences outcomes in critically ill COVID-19 ICU patients or if it merely reflects the disease's severity. Lastly, the management of NOAF in these patients has not been extensively studied. Nevertheless, the current guidelines for NOAF in non-COVID ICU patients appear to be effective, while accounting for the specific drugs used in COVID-19 treatment that may prolong the QT interval (although drugs like lopinavir/ritonavir, hydrochlorothiazide, and azithromycin have been discontinued) or induce bradycardia (e.g., remdesivir).

Effectiveness of Lifestyle Interventions during Pregnancy on Preventing Gestational Diabetes Mellitus in High-Risk Women: A Systematic Review and Meta-Analyses of Published RCTs.

BACKGROUND: Until now, it is uncertain whether lifestyle interventions during pregnancy can prevent gestational diabetes mellites (GDM) in high-risk pregnant women. OBJECTIVE: This study aims at investigating the effectiveness of dietary interventions and/or exercise interventions during pregnancy for preventing GDM in high-risk pregnant women. MATERIALS AND METHODS: Eligible randomized controlled trials (RCTs) were selected after a search in CENTRAL, Scopus, and PubMed. Synthesis was performed for the outcome of GDM in women with any identified GDM risk factor. Separate meta-analyses (MA) were performed to assess the efficacy of either nutrition or physical activity (PA) interventions or both combined compared with standard prenatal care for preventing GDM. Subgroup and sensitivity analyses, as well as meta-regressions against OR, were performed to assess potentional heterogeneity. Overall quality, the quality of RCTs, and publication bias were also evaluated. RESULTS: A total of 13,524 participants comprising high-risk pregnant women in 41 eligible RCTs were analyzed for GDM. Women receiving only a nutrition intervention during pregnancy were less likely to experience GDM compared with women following standard prenatal care. Among 3109 high-risk pregnant women undergoing only dietary intervention for preventing GDM, 553 (17.8%) developed GDM; however, the result of the MA was marginally not significant (OR 0.73, 95%CI 0.51, 1.03; p-value 0.07), (Q 21.29, p-value 0.01; I2 58% (95%CI 10, 78%)). Subgroup analyses demonstrated an effect for studies that were conducted in Great Britain (OR 0.65, 95%CI 0.49, 0.81; p-value 0.003), and in Spain (OR 0.50, 95%CI 0.27, 0.94; p-value 0.03), for studies with forms of the Mediterranean diet as the intervention's component (OR 0.61; 95%CI 0.46, 0.81; p-value 0.0005), and for studies including a motivation arm in the intervention (OR 0.71, 95%CI 0.58, 0.87; p-value 0.0008). Among 2742 high-risk pregnant women being analyzed for GDM outcome after receiving only an exercise intervention, 461 (16.8%) were diagnosed with GDM. Women after receiving PA intervention were less likely to develop GDM (OR 0.64, 95%CI 0.51, 0.80; p-value < 0.0001), (Q 11.27, p-value 0.51; I2 0% (95%CI 0, 99%)). Finally, 1308 (17%) cases of GDM were diagnosed among 7673 high-risk pregnant women undergoing both diet and PA intervention. Women in the group of mixed lifestyle intervention had a significant reduction in incidence of GDM (OR 0.70, 95%CI 0.55, 0.90; p-value 0.005), (Q 50.32, p-value < 0.0001, I2 66%, (95% CI 44, 79%)). CONCLUSIONS: The results of this study support the efficacy of lifestyle interventions during pregnancy for preventing GDM in high-risk women if an exercise component is included in the intervention arm, either alone, or combined with diet. A combined lifestyle intervention including physical exercise and a Mediterranean diet accompanied by motivation support may be considered the most effective way to prevent GDM among high-risk women during pregnancy. Future research is needed to strengthen these findings.

Pleural Fluid-to-Blood BNP Ratio May Contribute to Prognosis in Malignant Pleural Mesothelioma.

BACKGROUND: Brain natriuretic peptide (BNP) seems to be produced from malignant mesothelial cells other than cardiomyocytes. We aimed to evaluate whether an increased pleural fluid-to-blood BNP ratio in patients with malignant pleural mesothelioma (MPM) could facilitate prognosis beyond diagnosis. MATERIALS AND METHODS: Patients with MPM were included (observational study). One- and two-year survival and factors affecting it were tested. To evaluate the prognostic significance of the natriuretic peptide precursor B (NPPB) gene expression in MPM, we constructed a survival curve from data derived from The Cancer Genome Atlas. RESULTS: Nineteen consecutive patients with MPM were included (age: 67 (61, 80), male 78.9%). One- and two-year survival were 52.6% and 31.6%, respectively. Age, performance status, and the other variables tested did not differ between survivors and non-survivors. Non-survivors presented higher pleural fluid BNP in two years (699 (210, 5000) vs. 379.5 (5, 567), p = 0.036) and BNP ratios than survivors (1-year: 28.75 (4.05, 150.24) vs. 3.49 (0.3, 26) p = 0.001, 2-years: 22.8 (2.42, 150.24) vs. 3.49 (0.3, 7.76), p = 0.001). One- and two-year survival rates in patients with BNP ratios above/equal to the median value (8.82) were 20% and 0%, and 88.9% and 66.7%, respectively, in patients with BNP ratios below 8.82 (p = 0.006 and p = 0.002, respectively). MPM patients with low NPPB expression presented significantly higher survival rates compared to patients with higher expressions (p = 0.032). CONCLUSION: A high pleural fluid/blood BNP ratio, an easily performed in everyday practice, costless biomarker seems to predict poorer survival better than the commonly reported prognostic factors in MPM.

Metabolic Syndrome and Atrial Fibrillation: Different Entities or Combined Disorders.

Obesity, hypertension, insulin resistance, and dyslipidemia are all clusters of an entity called "Metabolic Syndrome". The global trends of this syndrome's incidence/prevalence continue to increase reciprocally, converting it into a massive epidemic problem in the medical community. Observing the risk factors of atrial fibrillation, a medical condition that is also converted to a scourge, almost all parts of the metabolic syndrome are encountered. In addition, several studies demonstrated a robust correlation between metabolic syndrome and the occurrence of atrial fibrillation. For atrial fibrillation to develop, a combination of the appropriate substrate and a trigger point is necessary. The metabolic syndrome affects the left atrium in a multifactorial way, leading to atrial remodeling, thus providing both the substrate and provoking the trigger needed, which possibly plays a substantial role in the progression of atrial fibrillation. Due to the remodeling, treatment of atrial fibrillation may culminate in pernicious sequelae, such as repeated catheter ablation procedures. A holistic approach of the patient, with simultaneous treatment of both entities, is suggested in order to ensure better outcomes for the patients.

Novel Approaches to the Management of Diabetes Mellitus in Patients with Coronary Artery Disease.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in individuals with diabetes mellitus (DM). Although benefit has been attributed to the strict control of hyperglycemia with traditional antidiabetic treatments, novel antidiabetic medications have demonstrated cardiovascular (CV) safety and benefits by reducing major adverse cardiac events, improving heart failure (HF), and decreasing CVD-related mortality. Emerging data underline the interrelation between diabetes, as a metabolic disorder, and inflammation, endothelial dysfunction, and oxidative stress in the pathogenesis of microvascular and macrovascular complications. Conventional glucose-lowering medications demonstrate controversial CV effects. Dipeptidyl peptidase- 4 inhibitors have not only failed to prove to be beneficial in patients with coronary artery disease, but also their safety is questionable for the treatment of patients with CVD. However, metformin, as the first-line option for type 2 DM (T2DM), shows CVD protective properties for DM-induced atherosclerotic and macrovascular complications. Thiazolidinedione and sulfonylureas have questionable effects, as evidence from large studies shows a reduction in the risk of CV events and deaths, but with an increased rate of hospitalization for HF. Moreover, several studies have revealed that insulin monotherapy for T2DM treatment increases the risk of major CV events and deaths from HF, when compared to metformin, although it may reduce the risk of myocardial infarction. Finally, this review aimed to summarize the mechanisms of action of novel antidiabetic drugs acting as glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors that show favorable effects on blood pressure, lipid levels, and inflammation, leading to reduced CVD risk in T2DM patients.

Levosimendan in the Treatment of Patients with Severe Septic Cardiomyopathy.

(1) Background: The optimal treatment of septic cardiomyopathy (SCM) remains questionable. The aim of the study was to compare the treatment of SCM based on levosimendan versus the best available therapy. (2) Methods: We conducted an observational study including patients with severe septic cardiomyopathy and circulatory failure. (3) Results: Fourteen patients (61%) received levosimendan, and nine received other treatments. The patients in the levosimendan group were more severely ill [APACHE II: 23.5 (14, 37) vs. 14 (13, 28), respectively, p = 0.012], and there was a trend for more decompensated LV function depicted by the LVEF [15% (10, 20) vs. 25% (5, 30), respectively, p = 0.061]. However, they presented a significantly higher increase in LVEF after seven days [15% (10, 20) to 50% (30, 68) (p < 0.0001) vs. 25% (5, 30) to 25% (15, 50) (p = 0.309), and a significantly higher decrease in lactate levels during the first 24 h [4.5 (2.5, 14.4) to 2.85 (1.2, 15), p = 0.036 vs. 2.9 (2, 18.9) to 2.8 (1, 15), p = 0.536]. Seven-day survival (64.3% vs. 33.3%, p = 0.424) and ICU survival (50% vs. 22.2%, p = 0.172) were higher in the first group, although differences did not reach statistical significance. The degree of left ventricular impairment and the magnitude of EF improvement by the seventh-day post-SCM onset were associated with mortality in regression analysis. (4) Conclusions: Our study presents main hemodynamic data supporting the possible efficacy of levosimendan treatment in patients with severe SCM.

Aerosolized Antibiotics to Manage Ventilator-Associated Infections: A Comprehensive Review.

BACKGROUND: Ventilator-associated lower respiratory tract infectious complications in critically ill patients cover a wide spectrum of one disease process (respiratory infection), initiating from tracheal tube and/or tracheobronchial colonization, to ventilator associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). VAP occurence has been associated with increased intensive care unit (ICU) morbidity (ventilator days, as well as length of ICU and hospital stay) and ICU mortality. Therefore, treatments that aim at VAP/VAT incidence reduction are a high priority. AIM: The aim of the present review is to discuss the current literature concerning two major aspects: (a) can aerosolized antibiotics (AA) administered in a pre-emptive way prevent the occurrence of ventilator-associated infections? and (b) can VAT treatment with aerosolized avert the potential evolution to VAP? RESULTS: There were identified eight studies that provided data on the use of aerosolized antibiotics for the prevention of VAT/VAP. Most of them report favorable data on reducing the colonisation rate and the progression to VAP/VAT. Another four studies dealt with the treatment of VAT/VAP. The results support the decrease in the incidence to VAP transition and/or the improvement in signs and symptoms of VAP. Moreover, there are concise reports on higher cure rates and microbiological eradication in patients treated with aerosolized antibiotics. Yet, differences in the delivery modality adopted and resistance emergence issues preclude the generalisability of the results. CONCLUSION: Aerosolized antibiotic therapy can be used to manage ventilator-associated infections, especially those with difficult to treat resistance. The limited clinical data raise the need for large randomized controlled trials to confirm the benefits of AA and to evaluate the impact on antibiotic selection pressure.

Molecular Mechanisms and Therapeutic Implications of Endothelial Dysfunction in Patients with Heart Failure.

Heart failure is a complex medical syndrome that is attributed to a number of risk factors; nevertheless, its clinical presentation is quite similar among the different etiologies. Heart failure displays a rapidly increasing prevalence due to the aging of the population and the success of medical treatment and devices. The pathophysiology of heart failure comprises several mechanisms, such as activation of neurohormonal systems, oxidative stress, dysfunctional calcium handling, impaired energy utilization, mitochondrial dysfunction, and inflammation, which are also implicated in the development of endothelial dysfunction. Heart failure with reduced ejection fraction is usually the result of myocardial loss, which progressively ends in myocardial remodeling. On the other hand, heart failure with preserved ejection fraction is common in patients with comorbidities such as diabetes mellitus, obesity, and hypertension, which trigger the creation of a micro-environment of chronic, ongoing inflammation. Interestingly, endothelial dysfunction of both peripheral vessels and coronary epicardial vessels and microcirculation is a common characteristic of both categories of heart failure and has been associated with worse cardiovascular outcomes. Indeed, exercise training and several heart failure drug categories display favorable effects against endothelial dysfunction apart from their established direct myocardial benefit.

Hemodynamic and Respiratory Changes following Prone Position in Acute Respiratory Distress Syndrome Patients: A Clinical Study.

BACKGROUND: Limited data are available for the oxygenation changes following prone position in relation to hemodynamic and pulmonary vascular variations in acute respiratory distress syndrome (ARDS), using reliable invasive methods. We aimed to assess oxygenation and hemodynamic changes between the supine and prone posture in patients with ARDS and identify parameters associated with oxygenation improvement. METHODS: Eighteen patients with ARDS under protective ventilation were assessed using advanced pulmonary artery catheter monitoring. Physiologic parameters were recorded at baseline supine position, 1 h and 18 h following prone position. RESULTS: The change in the Oxygenation Index (ΔOI) between supine and 18 h prone significantly correlated to the concurrent change in shunt fraction (r = 0.75, p = 0.0001), to the ΔOI between supine and 1 h prone (r = 0.73, p = 0.001), to the supine acute lung injury score and the OI (r = -0.73, p = 0.009 and r = 0.69, p = 0.002, respectively). Cardiac output did not change between supine and prone posture. Moreover, there was no change in pulmonary pressure, pulmonary vascular resistances, right ventricular (RV) volumes and the RV ejection fraction. CONCLUSIONS: The present investigation provides physiologic clinical data supporting that oxygenation improvement following prone position in ARDS is driven by the shunt fraction reduction and not by changes in hemodynamics. Moreover, oxygenation improvement was not correlated with RV or pulmonary circulation changes.

The Role of Left Ventricular Ejection Fraction and Left Ventricular Outflow Tract Velocity-Time Integral in Assessing Cardiovascular Impairment in Septic Shock.

Background: the role of echocardiography in septic shock remains controversial, since depressed cardiac afterload may overestimate left ventricular (LV) systolic performance and mask septic cardiomyopathy (SC). We hypothesized that afterload-adjusted LV ejection fraction (LVEF) and LV outflow tract velocity-time integral (VTI) values for given systemic vascular resistances (SVR) could provide novel insights into recognizing and stratifying the severity of SC. Methods: in this observational, monocentric study, we prospectively included 14 mechanically-ventilated patients under septic-shock who all had a Pulse index Continuous Cardiac Output (PiCCO) system in place for hemodynamic monitoring. Echocardiographic and PiCCO longitudinal examinations (71 measurements overall) were performed simultaneously at the onset of septic shock and every 12 h for 60 h overall. Results: VTI-derived stroke volume (SV) and cardiac output (CO) were significantly correlated with PiCCO measurements (r ≥ 0.993, both p < 0.001). LVEF and VTI showed linear and exponential inverse correlation to SVR (R2 = 0.183 vs. 0.507 and p < 0.001 vs. p < 0.001, respectively). The equations LVEF = 86.168 − 0.011 × SVR and VTI = 41.23 × e(−0.0005×SVR) were found to provide "predicted" values for given SVR. Measured to predicted LVEF ratios (for given SVR), the afterload-adjusted LVEF defined the severity of SC (mild ≥ 90%, 80% ≤ moderate < 90% and severe < 80%). Mild SC demonstrated normal/supra-normal LVEF, normal VTI and SVR. Moderate SC showed lower LVEF and SVR, yet increased LV end-diastolic volume (LVEDV), VTI, SV and CO compared with mild SC (all p < 0.05). Severe SC was distinguished from moderate SC by markedly reduced LVEF, LVEDV, VTI, SV, CO and significantly increased SVR (all p < 0.05). LVEF and VTI decreased over time in mild SC, LVEF decreased in moderate SC, and LVEF and VTI increased over time in severe SC (p ≤ 0.038). LVEF and VTI demonstrated significant performance in identifying severe SC [cut-off < 61.5%, area under the curve (AUC) = 1 ± 0.0, sensitivity/specificity = 100/100, p < 0.001 vs. cut-off < 17.9 cm, AUC = 0.882 ± 0.042, sensitivity/specificity = 80/77, p < 0.001, respectively]. VTI but not LVEF demonstrated significant diagnostic performance in identifying both SVR < 800 dynes·s·cm−5 and SVR > 1500 dynes·s·cm−5 (cut-off > 24.46 cm, AUC = 0.889 ± 0.049, sensitivity/specificity = 75/100, p < 0.001; cut-off < 16.8, AUC = 0.0.857 ± 0.082, sensitivity/specificity = 83/86, p = 0.002, respectively).Conclusions: our study suggests that ICU bedside echocardiographic assessment of LVEF, VTI and their adjusted to corresponding SVR values provides valuable insights for the comprehension of SC phenotypes, underlying vasoplegia and cardiac output fluctuations in septic shock.

Neuromuscular Blockade in the Pre- and COVID-19 ARDS Patients.

Acute respiratory distress syndrome (ARDS) accounts for a quarter of mechanically ventilated patients, while during the pandemic, it overwhelmed the capacity of intensive care units (ICUs). Lung protective ventilation (low tidal volume, positive-end expiratory pressure titrated to lung mechanics and oxygenation, permissive hypercapnia) is a non-pharmacological approach that is the gold standard of management. Among the pharmacological treatments, the use of neuromuscular blocking agents (NMBAs), although extensively studied, has not yet been well clarified. The rationale is to minimize the risk for lung damage progression, in the already-injured pulmonary parenchyma. By abolishing rigorous spontaneous efforts, NMBAs may decrease the generation of high transpulmonary pressures that could aggravate patients' self-inflicted lung injury. Moreover, NMBAs can harmonize the patient-ventilator interaction. Recent randomized controlled trials reported contradictory results and changed the clinical practice in a bidirectional way. NMBAs have not been documented to improve long-term survival; thus, the current guidance suggests their use only in patients in whom a lung protective ventilation protocol cannot be applied, due to asynchrony or increased respiratory efforts. In the present review, we discuss the published data and additionally the clinical practice in the "war" conditions of the COVID-19 pandemic, concerning NMBA use in the management of patients with ARDS.

Simulation to minimise patient self-inflicted lung injury: are we almost there?

Computational modelling has been used to enlighten pathophysiological issues in patients with acute respiratory distress syndrome (ARDS) using a sophisticated, integrated cardiopulmonary model. COVID-19 ARDS is a pathophysiologically distinct entity characterised by dissociation between impairment in gas exchange and respiratory system mechanics, especially in the early stages of ARDS. Weaver and colleagues used computational modelling to elucidate factors contributing to generation of patient self-inflicted lung injury, and evaluated the effects of various spontaneous respiratory efforts with different oxygenation and ventilatory support modes. Their findings indicate that mechanical forces generated in the lung parenchyma are only counterbalanced when the respiratory support mode reduces the intensity of respiratory efforts.

Secondary bacterial infections are a leading factor triggering New Onset Atrial Fibrillation in intubated ICU Covid-19 ARDS patients.

BACKGROUND: Cardiac arrhythmias, mainly atrial fibrillation (AF), is frequently reported in COVID-19 patients, more often in Intensive Care Unit (ICU) patients, yet causality has not been virtually explored. Moreover, non-Covid ICU patients frequently present AF, sepsis being the major trigger. We aimed to examine whether sepsis or other factors-apart from Covid-19 myocardial involvement-contribute to elicit New Onset AF (NOAF) in intubated ICU patients. METHODS: Consecutive intubated, Covid-19ARDS patients, were prospectively studied for factors triggering NOAF. Demographics, data on Covid-19 infection duration, laboratory findings (troponin as well), severity of illness and ARDS were compared between NOAF and control group (no AF) on admission. In NOAF patients, echocardiographic findings, laboratory and secondary infection data on the AF day were compared to the preceding days and/or ICU admission data. RESULTS: Among 105 patients screened, 79 were eligible; nineteen presented NOAF (24%). Baseline characteristics did not differ between the NOAF and control groups. Troponin levels were mildly elevated upon ICU admission in both groups. Left ventricular global longitudinal strain was impaired (<16.5%) in 63% vs 78% in the two groups, respectively. The right ventricle was mildly dilated, and pericardial effusion was present in 52 vs 43%, respectively. NOAF occurred on the 18 ± 4.8 days from Covid-19 symptoms' onset, and the 8.5 ± 2.1 ICUday. A septic secondary infection episode occurred in 89.5% of the patients in the NOAF group ( vs 41.6% in the control group (p < 0.001). In fact, NOAF occurred concurrently with a secondary septic episode in 84.2% of the patients. Sepsis presence was the only factor associated to NOAF occurrence (OR 16.63, p = 0.002). Noradrenaline, lactate and inflammation biomarkers gradually increased in the days before AF (all p < 0.05). Echocardiographic findings did not change on NOAF occurrence. CONCLUSION: Secondary infections seem to be major contributors for NOAF occurrence in Covid-19 patients, probably playing the role of the "second hit" in an affected myocardium from Covid-19.

Rapidly improving acute respiratory distress syndrome in COVID-19: a multi-centre observational study.

BACKGROUND: Before the pandemic of coronavirus disease (COVID-19), rapidly improving acute respiratory distress syndrome (ARDS), mostly defined by early extubation, had been recognized as an increasingly prevalent subphenotype (making up 15-24% of all ARDS cases), associated with good prognosis (10% mortality in ARDSNet trials). We attempted to determine the prevalence and prognosis of rapidly improving ARDS and of persistent severe ARDS related to COVID-19. METHODS: We included consecutive patients with COVID-19 receiving invasive mechanical ventilation in three intensive care units (ICU) during the second pandemic wave in Greece. We defined rapidly improving ARDS as extubation or a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2) greater than 300 on the first day following intubation. We defined persistent severe ARDS as PaO2:FiO2 of equal to or less than 100 on the second day following intubation. RESULTS: A total of 280 intubated patients met criteria of ARDS with a median PaO2:FiO2 of 125.0 (interquartile range 93.0-161.0) on day of intubation, and overall ICU-mortality of 52.5% (ranging from 24.3 to 66.9% across the three participating sites). Prevalence of rapidly improving ARDS was 3.9% (11 of 280 patients); no extubation occurred on the first day following intubation. ICU-mortality of patients with rapidly improving ARDS was 54.5%. This low prevalence and high mortality rate of rapidly improving ARDS were consistent across participating sites. Prevalence of persistent severe ARDS was 12.1% and corresponding mortality was 82.4%. CONCLUSIONS: Rapidly improving ARDS was not prevalent and was not associated with good prognosis among patients with COVID-19. This is starkly different from what has been previously reported for patients with ARDS not related to COVID-19. Our results on both rapidly improving ARDS and persistent severe ARDS may contribute to our understanding of trajectory of ARDS and its association with prognosis in patients with COVID-19.

Ultrasonographic Confirmation of Nasogastric Tube Placement in the COVID-19 Era.

BACKGROUND: Nasogastric tube (NGT) placement is a daily routine in the Intensive Care Unit (ICU), and misplacement of the NGT can cause serious complications. In COVID-19 ARDS patients, proning has emerged the need for frequent NGT re-evaluations. The gold standard technique, chest X-ray, is not always feasible. In the present study we report our experience with the use of ultrasonographic confirmation of NGT position. METHODS: A prospective study in 276 COVID-19 ARDS patients admitted after intubation in the ICU. Ultrasonographic evaluation was performed using longitudinal or sagittal epigastric views. Examinations were performed during the initial NGT placement and every time the patients returned to the supine position after they had been proned or whenever critical care physicians or nurses considered that reconfirmation was necessary. RESULTS: Ultrasonographic confirmation of correct NGT placement was feasible in 246/276 (89.13%) patients upon ICU admission. In 189/246 (76.8%) the tube could be visualized in the stomach (two parallel lines), in 172/246 (69.9%) the ultrasonographic whoosh test ("flash" due to air instillation through the tube, seen with ultrasonography) was evident, while in 164/246 (66.7%) both tests confirmed correct NGT placement. During ICU stay 590 ultrasonographic NGT evaluations were performed, and in 462 (78.14%) cases correct NGT placement were confirmed. In 392 cases, a chest X-ray was also ordered. The sensitivity of ultrasonographic NGT confirmation in these cases was 98.9%, specificity 57.9%, PPV 96.2%, and NPV 3.8%. The time for the full evaluation was 3.8 ± 3.4 min. CONCLUSION: Ultrasonographic confirmation of correct NGT placement is feasible in the initial placement, but also whenever needed thereafter, especially in the COVID-19 era, when changes in posture have become a daily practice in ARDS patients.

Fixed dilated pupils in Covid-19 ARDS patients under rocuronium, reversed after discontinuation.

Neuromuscular Blockade Agents (NMBA) are used in the management of moderate and severe Acute Respiratory Distress Syndrome (ARDS) patients. They have never been reported to present Central Nervous System adverse reactions. Shortage of cis-atracurium during the pandemic, led to the use of rocuronium. We report three patients with Covid-19 ARDS, who presented bilateral dilated, non-reactive pupils, after continuous rocuronium infusion. Brain CT findings were unremarkable and transcranial doppler tracings did not suggest brain edema or hemorrhage. NMBA's discontinuation led to reversal of the pupillary dilation. We believe that impairment of Blood-Brain-Barrier, due to Covid-19, led rocuronium access into the Central Nervous System, leading to this adverse effect. Clinicians should be aware of this adverse reaction when managing patients with Covid-19 ARDS warranting NMBA use.