Pulmonary Edema Research Articles

NCOR1 orchestrates macrophage inflammation in heart failure with preserved ejection fraction: a translational study

Abstract Background/Introduction Inflammatory response is a key player in heart failure with preserved ejection fraction (HFpEF) but the underlying mechanisms are poorly understood. Recent studies have shown a critical involvement of cardiac macrophage activation in myocardial remodeling thus contributing to HFpEF. Purpose To investigate the role of cardiac macrophage inflammation in experimental and human HFpEF. Methods We employed a translational approach combining human and murine LV myocardial tissue, FACS analysis of cardiac immune cells, in vitro experiments in RAW 264.7 cells exposed to metabolic stress by palmitic acid (PA), bone marrow-derived macrophages from healthy and HFpEF mice, cardiomyocytes (H9c2), endothelial cells (HAECs) as well as ex vivo functional analyses in LV tissues. Human LV myocardial samples were used to evaluate the pro-inflammatory activity of macrophages in the HFpEF myocardium. Induction of HFpEF in mice was done through a validated mouse model combining metabolic (high-fat diet) and hemodynamic stress (L-NAME). Cardiac function was investigated by high resolution ultrasound imaging (Vevo3100) and the LV myocardial samples were used to study the macrophage polarization and their inflammatory activity. Based on interrogation of available RNA-seq datasets – showing the transcriptional repressor NCOR1 as a relevant signature in macrophages during cardiac inflammation, we generated myeloid cell-specific NCOR1 knockout (Ncor1-KO) transgenic mice to investigate the in vivo effects of NCOR1 deletion on the HFpEF phenotype. Results The expression of macrophage markers in human LV specimens showed an increase in pro-inflammatory macrophages (M1) and a decrease in regulatory macrophages (M2) as compared to age-matched control mice. HFpEF mice showed increased expression of vascular adhesion molecules (ICAM1, ICAM2, E-selectin) and a significant recruitment of M1 macrophages as proved by qPCR, WB, and flow cytometry analysis. Of interest, diastolic dysfunction - assessed by E/A ratio and isovolumic relaxation time (IVRT) – and lung congestion were significantly reduced in mice with macrophage NCOR1 deletion as compared to WT littermates, while exercise tolerance was significantly improved. These findings were associated with a reduction of myocardial inflammation (TNF-a, IL6, IL-1b) in Ncor1-KO mice. In vitro assays showed that stimulation of macrophages with PA induced M1 type switch and increased NCOR1, TNF-a, IL-6, and IL-1b levels, whereas NCOR1 depletion prevented detrimental changes of macrophage secretome (Fig.2). Conclusion NCOR1 is a crucial regulator of immune response and macrophage inflammation in the heart. Our findings highlight its potential as a target for therapies aimed at preventing myocardial damage in HFpEF.

Novel method in mice to evaluate left atrial (LA) systolic contribution to left ventricular volume (LV) using pressure-volume (PV) loops

Abstract Background LA myopathy is a critically important non-LV contributor to the progression of HFpEF (heart failure with preserved ejection fraction) in patients and is associated with a severe phenotype, leading to impaired cardiac output reserve and reduced exercise capacity. In normal humans LA systole contributes ~20% of total LV filling, but with HFpEF, this contribution decreases to <16% with a greater reliance on this contribution to LV filling. Purpose We sought to investigate LA function as a critical component of cardiac function analysis by utilizing the LV pressure signal to identify and quantify the contribution of volume during LA systole to the total LV volume in mice with HFpEF. Methods Hypertension (HTN)-associated HFpEF C57BL/6J mice were subjected to chronic aldosterone infusion and 1% NaCl for 4 weeks (SAUNA model). Obesity after a high fat diet (HFD: 60% fat diet) for 16 weeks followed by the SAUNA protocol, induced HTN and obesity associated HFpEF. Blood pressure was monitored weekly. Mice were anesthetized with isoflurane, intubated, chest opened to expose the heart and allow placement of a PV catheter (Transonic) which was introduced into the LV via apical stab with a 27G needle. Calibration of the PV catheter was performed according to the manufacturer’s instructions. Atrial systole was identified using 2nd order derivative of the LV pressure signal. Contribution of LA systole was calculated using volume at the beginning of LA systole identified by the 2nd order derivative of the LV pressure signal and subtracting from the LV end diastolic volume. The % of LA systole contribution was calculated as a % of the total LV stroke volume. Data was analyzed with LabChart pro software (AD Instruments). Results SAUNA mice had normal LVEF, moderate HTN and lung congestion. PV relationships demonstrated Tau was impaired in HFpEF vs. control mice (14±1 vs. 10±0.5 ms) with a shift of the PV loop to the left (Fig. A.) In control mice, the atrial systole contributed 39± 4% to LV volume and was impaired in HFpEF mice 20± 3% a 1.95-fold reduction (P<0.01). Importantly atrial systole contribution was increased in obese mice 53±5 %. However, the combination of obesity and HTN, both common comorbidities in HFpEF, resulted in a reduced LA systole contribution by 1.43-fold to 37± 9%, (P<0.005; Fig B). Conclusion A novel method of % atrial systole from LV PV loop using 2nd order derivative to quantify the volume contribution of atrial systole to total LV stroke volume was identified in mice. LA dysfunction was present in murine HTN-associated HFpEF with/without obesity.

Transcatheter valve replacement as rescue treatment for heart failure in infective endocarditis. A multinational series.

Abstract Background Transcatheter valve replacement (TVR) could be a therapeutic alternative for refractory heart failure in patients with infective endocarditis (IE) unsuitable for open surgery. However, evidence of tis use in this scenario is limited to isolated case reports. Purpose We aimed to describe the clinical characteristics and outcome of IE patients in whom a TVR was performed during the active phase of infection in a multinational case series. Methods This retrospective study was conducted in 23 referral hospitals for IE and TVR procedure in 8 countries. All consecutive adult patients (≥18 y) with definite IE in whom a TVR was performed during antimicrobial treatment of within the 3 three months after its withdrawal were included. The inclusion period was between July 2011 and July 2023. Baseline, IE-related, TVR-related, outcome and follow-up (min. 3 months) variables were collected. Results Forty-five patients [median age 74 years (IQR 64 – 82), 35 males (78%), median Charlson comorbidity index 6 (4 – 7) points] were included in the study: 42 aortic TVR, 2 mitral TVR and 1 tricuspid TVR. In 20 patients (44%) TVR was performed on a native valve and in 25 on a prosthetic valve. The most frequent microorganisms causing IE were streptococci (n=16, 36%), staphylococci (n=13, 29%) and enterococci (n=5, 11%). Acute heart failure was present in 41 (91%). Of them, 23 (51%) developed acute pulmonary oedema or cardiogenic shock. The main reasons for excluding open surgery were: high surgical risk [n=39, 87%; median EuroSCORE 17 (9 – 28)] and technical impossibility (n=3, 7%). TVR was performed during antimicrobial treatment in 27 cases (60%) [median 25 (13 – 54) days after initiation] and within the first three months after its completion in 18 (40%) [median 25 (17 – 68) days after discontinuation]. Four patients (9%) died during admission. Over a median follow-up of 10 (6 -30) months, 7/41 patients (17%) died and there were 2/41 (5%) relapses, one of which required open valve replacement surgery 17 days after TVR procedure. Two other patients underwent open surgery due to paravalvular leaks (11 and 44 days after TVR). All cases of relapse and open surgery occurred when TVR was performed during antibiotic treatment. Conclusion TVR could be an option as rescue treatment for heart failure in selected IE patients unsuitable for open surgery. This represents a paradigm shift in the management of IE and may change the natural history of the disease in patients who would otherwise die.

High altitude exercise stress echocardiograph for identification of susceptibility to acute mountain sickness

Abstract Background Acute high-altitude exposure increases the risk of acute mountain disease (AMS) and high-altitude pulmonary edema. After the initial exposure to high altitude, mountain climbers are worried about whether they will develop AMS. At high altitudes, there are no accurate indicators to predict the near future occurrence of AMS. Objectives To investigate whether treadmill exercise stress echocardiography at high altitude can predict the occurrence of AMS, and to find out some powerful factors associated with the susceptibility to AMS. Methods 36 healthy lowlanders were taken by bus from sea level to an altitude of 3600 m the next morning, during which they rested overnight at an altitude of 2150 m. Treadmill exercise stress echocardiography was performed immediately upon arrival at 2150 m, and the 2018 Lake Louise Questionnaire Score was performed the next day when arrived at the altitude of 3600 m. Heart rate (HR) and blood pressure (BP) were monitored during stress echocardiography. Left ventricular (LV) ejection fraction and E/e’ were calculated at rest and immediately after exercise. Other right ventricular systolic function parameters and pulmonary artery pressure (PAP) were calculated at the same time, which included tricuspid regurgitation velocity (TRV), tricuspid annular peak systolic excursion (TAPSE), systolic PAP (SPAP), right ventricular (RV) dimension by 2D, RV fraction of area change (FAC), right ventricular outflow tract velocity time integral (RVOT VTI). Pulmonary vascular resistance (PVR) was calculated according to the formula: TRV/RVOT VTI*10+0.16. Mean PAP (mPAP) was calculated as the formula: sPAP*0.61+2. All subjects ascended to 3600m within 24 hours by bus. AMS was identified by 2018 Lake Louise Questionnaire Score. Univariable and multivariable logistic regression analysis assessed independent factors associated with AMS. Results At the altitude of 3600m, 13 of 36 subjects had AMS, which defined as AMS (+) group. And the rest was AMS (-) group. There were no significant differences in HR, BP, SO2 and LV systolic and diastolic function between the two groups (P > 0.05). No significant differences were noted at rest except for TV s' (P < 0.05). Immediately after exercise, TRV, TAPSE, SPAP, mPAP, PVR, and RV area at the end of systole were much higher in AMS (+) group (all P < 0.05). While FAC and TVs’/SPAP were much lower in AMS (+) group (P < 0.05). By multivariable logistic regression model, mPAP immediately after exercise was significantly correlated with AMS occurrence (OR =1.332, 95% CI: 0.669-0.993, P= 003). The cutoff value of mPAP to predict AMS was 32 mmHg (AUC: 0.831, specificity: 86.7%, sensitivity: 76.9%). Conclusions The mPAP immediately after exercise upon arrival at an altitude of 2150 m is a strong predictor of near future AMS, and treadmill exercise stress echocardiography is a simple and non-invasive tool to help mountain climbers avoid more severe mountain sickness.

Research examining microcirculatory dynamics in diseases that cause oedema using skin blood flow and skin reperfusion pressure

Oedema is a build-up of fluid in the tissues in the body. It can develop due to diseases including heart failure and kidney disease. It usually occurs in the limbs, where it can cause discomfort, joint stiffness or pain. However, fluid can also accumulate in the brain, which is called cerebral oedema or in the blood vessels serving the lungs, called pulmonary oedema. A type of oedema called pitting oedema is more prevalent than the other type, non-pitting oedema. In order to treat the condition, the underlying cause must be resolved. Treatment can involve diuretics to help the release of fluids, positioning to encourage draining or compression to force fluids away. Researchers at the Faculty of Rehabilitation at Reiwa Health Sciences University led by Dr Haruki Kogo are examining the microcirculatory dynamics of diseases that cause oedema using skin blood flow and skin reperfusion pressure. They have developed a device that can diagnose oedema and confirmed the reproducibility and validity of the device. They have registered the trademark and plan to commercialise the device for use in clinical and research settings. The device is able to measure the depth of the surface imprint in pitting oedema patients, simplifying the evaluation of pitting oedema, which will be extremely useful in clinical settings. The researchers tested the device across two hospitals, comparing the results with results obtained from the popular circumference measurement method and ultrasound imaging measurement. The team found that there was a strong correlation between measurements from the device and the tissue thickness measurement derived from the ultrasound. This confirmed that the device is a reliable gauge for the measurement of oedema.

Study on the Predictive Value of a Pulmonary Edema Imaging Score for Delayed Extubation in Patients after Heart Valve Surgery on Cardiopulmonary Bypass.

Delayed extubation with mechanical ventilation after cardiac valve surgery is an important clinical challenge. Early extubation can improve the survival rate and prognosis of patients. The study aims to explore the predictive value of a chest X-ray pulmonary edema imaging score on the first day after surgery for delayed extubation in patients after cardiac valve surgery on cardiopulmonary bypass. Retrospective analysis of the clinical data of patients undergoing cardiac valve surgery under extracorporeal circulation admitted to the intensive care unit of Zhongshan Hospital Affiliated with Fudan University (Xiamen) from January 2020 to October 2023. The patients were divided into an early extubation group according to the postoperative mechanical ventilation time (time: <24 h) and a delayed extubation group (time: ≥24 h). The radiographic assessment of lung edema (RALE) score was performed on the chest X-ray of the patient on the first day after surgery to analyze the correlation between delayed extubation of mechanical ventilation and the chest radiograph RALE score on the first day after surgery and to verify its predictive performance. Significant differences in age, the incidence of hypertension, body mass index (BMI), left ventricular ejection fraction (LVEF), pump time, RALE score, ventilation time, oxygenation index, PaCO2, and brain natriuretic peptide (BNP) levels after the first 24 h were seen between patients who were extubated before and 24 h post operation (p = 0.013, 0.001, 0.034, <0.001, <0.001, <0.001, <0.001, <0.001, 0.014, and <0.001, respectively). No significant differences were observed in the proportion of males and the lactate level after the first 24 h between the two groups (p = 0.792 and 0.191, respectively). The time of mechanical ventilation was positively correlated with the RALE score in all patients, and the correlation coefficient was 0.419; the difference was statistically significant (p < 0.001). Multivariate binary logistic regression analysis with stepwise regression was performed on each research factor, and it was found that RALE score, pump time, oxygenation index, and postoperative BNP were independent risk factors for predicting delayed extubation in patients undergoing cardiac surgery on cardiopulmonary bypass. A 10-fold cross-validation revealed that the mean accuracy, sensitivity, specificity, and area under the curve (AUC) of the regression model were 0.737, 0.749, 0.741, and 0.825, respectively. The RALE score on the chest radiograph on the first day after surgery is an independent risk factor for predicting delayed extubation in patients after cardiac valve surgery on cardiopulmonary bypass and has good predictive value.

Long-term efficacy and safety of ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) is often accompanied by atrial fibrillation (AF) but data on safety and long-term outcomes after catheter ablation for AF in HCM are scarce. Purpose To investigate safety, long-term efficacy and clinical outcomes following AF ablation in patients with HCM and in matched controls. Methods Patients with HCM (n=76) undergoing a first catheter ablation for AF or atrial flutter between 1999 and 2022 at a University Hospital in Sweden were included (age 64±12 years, 43% female). Diagnosis of HCM was based on the European Society of Cardiology definition (left ventricular wall thickness ≥15 mm or ≥13 mm not solely explained by abnormal loading conditions, and combined with family history, genetic components and/or electrocardiogram abnormalities). Patients with HCM were matched with controls (n=152) based on age, gender, ablation type and intervention-year. Patients were followed for a mean of 5 years and study endpoints included heart failure hospitalization (HFH), stroke and mortality. Cox regression analyses were performed for the association between HCM and the endpoints. Results Among the overall population, 121 (53%) underwent pulmonary vein isolation (PVI), 62 (27%) isthmus ablation and 45 (20%) His-Bundle ablation. Patients with HCM had a shorter mean duration of AF before ablation (48 months vs. 66 months; p=0.047) and more severe symptoms as indicated by a higher EHRA class (EHRA class IV: 30% vs. 10%; p&amp;lt;0.01). Procedural success rate of PVI and isthmus ablation was lower in patients with versus without HCM (88% vs. 97%; p=0.02). Procedure related complications (vascular complications, tamponade) were overall similar in both groups (9% in HCM vs. 5% in controls, p=0.17) except for higher rates of pulmonary oedema in patients with HCM (7% vs 1%, p=0.03). There was a nearly two-fold increase in risk of AF recurrence after PVI or isthmus ablation in patients with HCM compared to controls (OR 1.95; 95% CI 1.06-3.58; p=0.03). During follow-up, patients with HCM had an increased risk of HFH (HR 2.55, 95% CI 1.21-5.36, p=0.01) but not of stroke or mortality (Figure 1). Conclusion AF ablation was overall safe in patients with HCM but less effective. Patients with HCM had an increased risk of the individual endpoint of HFH after AF ablation but not stroke or mortality during long-term follow-up.

Prevention of mechanical valve thrombosis with a combination of the factor Xa inhibitor edoxaban plus aspirin in swine: intermediate results from the EdoValves project

Abstract Background Patients with an implanted mechanical heart valve (MHV) currently have a contraindication to the use of non-vitamin K antagonist oral anticoagulants (NOACs) based on the unfavorable results of the RE-ALIGN trial with dabigatran. We hypothesized that the combination of a Factor Xa inhibitor, acting upstream of thrombin generation, plus aspirin, may effectively prevent valve thrombosis, providing a much more friendly and viable alternative to vitamin K antagonists for such patients. We tested this in a swine model with a recently implanted mechanical valve prosthesis in the mitral position, combining the most unfavorable conditions promoting mechanical valve thrombosis, based on (a) the implanting position; (b) recent surgery; (c) the high thrombogenicity of the animal model. The study was approved by the Animal Ethics Committee of the University of Pisa and the Italian Ministry of Health and conducted according to Good Clinical Practices for Animal Experiments. Methods 17 farm male pigs, weighing ≈30 kg at the beginning, underwent cardiac surgery under general anesthesia and with extracorporeal circulation to receive a 25 mm or 27 mm bileaflet Corcym Bicarbon mechanical heart valve replacement in the mitral position. Pigs were given 1 mg/kg enoxaparin immediately after surgery and started with the oral daily administration of edoxaban 1 mg/kg (30 mg, then escalated to 60 mg with the animal growth) + aspirin 100 mg, both given as crushed tablets with a food pellet since the animal awakening from anesthesia. An initially planned warfarin control group was quickly abandoned because of the extreme difficulty of controlling warfarin activity. Animals were submitted to blood sampling and transthoracic echocardiography at least twice in the follow-up when uneventful for up to three months or in case of health deterioration. The autopsy was performed by a certified pathologist after each spontaneous death or procured sacrifice. Results (Figure 1): Excluding 5 peri-operative deaths, 12 animals survived surgery. Of those, 6 died within the second month: pulmonary edema occurred in 3 cases, due to prosthesis-mismatch in the growing animals; pulmonary infection occurred in 1 subject; heart failure due to valve thrombosis occurred in 2 cases. Six swine were full-term survivors in good health status up to the 3-month planned observational time. No hemorrhagic events were ever documented. Conclusion The combination of edoxaban + aspirin effectively avoided valve thrombosis events in 10 out of 12 (83%) analyzable animals and was safe from bleeding complications. The study is ongoing up to a predicted sample size of ≥20 animals. If further confirmed, these data may open the possibility of an alternative to vitamin K antagonists in humans with the fixed-dose drug combination here used, without the need for continuous anticoagulation monitoring and with expected greater safety.Figure 1

Differences in risk profiles and clinical outcomes according to age in patients with high-risk myocardial infarction: insights from the PARADISE-MI trial

Abstract Introduction Temporal declines in rates of rehospitalization and death after acute myocardial infarction (MI) have not been uniform across age groups. A better understanding of how risk profiles and clinical outcomes differ after MI by age may allow for targeted treatment and prevention strategies. Aims To investigate risk profiles and clinical outcomes following high-risk MI according to age in the Prospective ARNI vs ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI). Methods Adults without prior heart failure (HF) were randomized to sacubitril/valsartan versus ramipril within 0.5 to 7 days of a MI complicated by transient pulmonary congestion and/or left ventricular systolic dysfunction and additional risk-augmenting factors. Associations between age and clinical outcomes were analyzed using Cox proportional hazards regression models, which were additionally adjusted for baseline demographic and clinical covariates (Figure). Results The mean age of the 5,661 PARADISE-MI participants was 64 ± 11 years. Patients aged ≥75 years (n=1051) were more likely women, had more hypertension and atrial fibrillation and lower estimated glomerular filtration rate, were less likely to present with ST-segment elevation MI and regardless of type of MI were less likely to receive primary reperfusion and guideline-based medical therapy (Table). Age was significantly associated with all-cause death (HR 1.54 per 10-year increase; 95% CI, 1.41-1.68) and was more strongly associated with non-CV death (HR 2.09; 95% CI, 1.70-2.56) than with CV death (HR 1.43; 95% CI, 1.29-1.57). Age was also associated with incident HF (HR 1.37; 95% CI, 1.25-1.49) (Figure). Multivariable adjustment attenuated the risk relationship of age with recurrent fatal or non-fatal MI (HR 1.08; 95% CI, 0.96-1.21) and the coronary composite outcome (HR 1.01; 95% CI, 0.93-1.09). The relative treatment effect of sacubitril/valsartan versus ramipril on the primary composite outcome of CV death or incident HF was not significantly modified by age (p-interaction = 0.19). Conclusions Following high-risk MI, age was most strongly associated with subsequent non-CV death followed by CV death and incident HF, but was not independently associated with recurrent coronary events. The heightened risk of CV death and HF with advancing age was not explained by differences in clinical characteristics. Older patients may require closer surveillance and more aggressive treatment after MI to mitigate the elevated risk of CV death and HF.

Predictors of B-line count in hospitalized patients with COVID-19

Abstract Background B-lines on lung ultrasound (LUS) are non-specific signs of increased density within lung tissue, which can be secondary to pulmonary congestion, pneumonia, or fibrosis. LUS is recommended for managing acute heart failure (HF); however, its value in non-HF populations is less clear. Purpose To identify clinical, laboratory, and echocardiographic predictors of B-lines in a population with Coronavirus disease 2019 (COVID-19). Methods In the ECHOVID-19 study, hospitalized non-ICU patients ≥18 years with confirmed laboratory diagnosis of COVID-19 in Eastern Denmark underwent 8-zone LUS and echocardiography. We used trend and regression analyses to identify associations with the number of B-lines and adjusted for potential confounders (age, sex, body mass index, C-reactive protein, and pandemic wave). Results Among 270 (89%) patients with adequate LUS images, the mean age was 69±14 years, 58% were male and 11% had prior HF. Median time from hospital admission to LUS was 4 [2-8] days. In total, 263 (97%) had ≥1 B-line (median B-line number 14 [9-22]) and median left ventricular ejection fraction [LVEF] was 59 [54-63]). In adjusted models, more B-lines were associated with higher levels of C-reactive protein with an incidence rate ratio (IRR) of 16% (95%CI: 8%-24%) per log-unit increase (P&amp;lt;0.001) and higher Early Warning Score (IRR 5% [95%CI: 1%-0%] per point, P=0.02). Higher tricuspid regurgitation gradient was associated with more B-lines: IRR 2% (95%CI: 1%-3%) per mmHg, P&amp;lt;0.001) (Figure 1). Echocardiographic measures of left ventricular (LV) function (including LVEF and global longitudinal strain, left atrial volume, and LV filling pressures (E/e’)) and right ventricular function were not significantly associated with the number of B-lines. B-lines were not associated with N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations, even in patients with established HF. Lastly, B-lines were not associated with 30-day mortality. Conclusions Among hospitalized patients with COVID-19, B-lines on LUS are associated with markers of infectious disease severity and pulmonary hypertension but not with markers of left-sided HF.Figure1.Predictors of B-lines

Standardization of transthoracic impedance values for estimating heart failure and its utility

Abstract Background The use of intrathoracic impedance for examining pleural effusion in heart failure patients has been explored previously. However, due to concerns about its accuracy and complexity, transthoracic impedance values have had limitations in quantifying extravascular lung water. Our dual objectives were to clarify the relationship between intrathoracic conditions and percutaneous transthoracic impedance values, and to establish a basic model for a new machine learning-based estimation system for assessing intrathoracic conditions in patients with heart failure. Methods First, we developed a live porcine congested lung model that induced pleural effusion by substantial fluid loading, and then longitudinally evaluated its correlation with percutaneous transthoracic impedance values. Second, we conducted multi-frequency bioelectrical impedance analysis to simultaneously collect electrical, physical, and hematological data from 63 hospitalized heart failure patients and 82 healthy volunteers Results In the porcine model, pleural effusion correlated with a concurrent decrease in SpO2 and a gradual decrease in impedance. We indexed and generated features from the measured values and developed an intrathoracic estimation model based on electrical measurements and clinical findings using a decision tree-based machine learning approach. Among the 286 features collected per individual, the model used 16 features. Notably, the model demonstrated high accuracy in discriminating patients with pleural effusion, achieving an AUC of 0.905 (95% CI: 0.870-0.940) in cross-validation, significantly outperforming the conventional frequency-based method. Conclusions Transthoracic impedance values, when indexed, reflect intrathoracic conditions and improve estimation. Our results highlighted the potential of machine learning and thoracic impedance measurement for accurate estimation of pleural effusion. This approach provides an effective means of assessing intrathoracic conditions. Figure: The upper figure shows the relationship between impedance values and pleural effusion in the congested lung model. On these results, human data were collected to construct the estimation model. The lower illustrates the accuracy of the model and provides a comprehensive view of the system.

Impact of Remote Dielectric Sensing on Predicting Worsening Heart Failure During Hospitalization for Heart Failure.

Background: A remote dielectric sensing (ReDS) system quickly quantifies pulmonary congestion. Nonetheless, its efficacy in predicting an in-hospital increase in plasma B-type natriuretic peptide levels, the potential surrogate of worsening heart failure, remains undetermined. Methods: Patients who underwent ReDS measurement on admission during their hospitalization in the general wards for heart failure between 2021 and 2022 were eligible. The impact of the baseline ReDS value, completely blinded to the attending clinicians, on the in-hospital increase in plasma B-type natriuretic peptide levels of >100 pg/mL from index admission was evaluated. Results: A total of 147 patients admitted with acute-on-chronic heart failure (median age: 79 years; 76 men) were included. The median ReDS value on admission was 28% (25%, 34%). Eighteen patients experienced the primary outcome: plasma B-type natriuretic peptide levels increasing from 461 (207, 790) pg/mL (baseline) to 958 (584, 1290) pg/mL (maximum) (p < 0.001). The ReDS value on admission was an independent predictor of the primary outcome, with an adjusted odds ratio of 1.07 (95% confidence interval: 1.01-1.14; p = 0.028) with an optimal cutoff of 32%. Conclusions: The ReDS system could be a promising tool for predicting in-hospital worsening heart failure in patients hospitalized for heart failure when measured upon admission. The clinical implication of ReDS-guided management of heart failure during index hospitalization requires further studies.

Maternal Risk Conditions and Outcomes by Levels of Maternal Care.

Objectives: To (1) determine associations between maternal risk conditions and severe adverse outcomes that may benefit from risk-appropriate care and (2) assess whether associations between risk conditions and outcomes vary by level of maternal care (LoMC). Methods: We used the 2017-2019 National Inpatient Sample (NIS) to calculate associations between maternal risk conditions and severe adverse outcomes. Risk conditions included severe preeclampsia, placenta accreta spectrum (PAS) conditions, and cardiac conditions. Outcomes included disseminated intravascular coagulation (DIC) with blood products transfusion or shock, pulmonary edema or acute respiratory distress syndrome (ARDS), stroke, acute renal failure, and a composite cardiac outcome. Then we used 2019 delivery hospitalization data from five states linked to hospital LoMC. We calculated associations between risk conditions and outcomes overall and stratified by LoMC and assessed for effect modification by LoMC. Results: We found positive measures of association between risk conditions and outcomes. Among patients with severe preeclampsia or PAS, the magnitudes of the associations with DIC with blood products transfusion or shock, pulmonary edema or ARDS, and acute renal failure were lower in Level III/IV compared with <Level III facilities. Among patients with cardiac conditions, the magnitudes of the associations with these outcomes, along with stroke, were also lower in Level III/IV compared with <Level III facilities. The proportion of patients with risk conditions that delivered in <Level III facilities was 19.8-46.8%. Conclusions: Odds of severe adverse outcomes among women with selected risk conditions were lower for births occurring at higher-level facilities, supporting the benefit of risk-appropriate care.

The effect of immunosuppressive agent FTY-720 on coagulation, nitroxidergic lung activity and water balance in experimental antiphospholipid syndrome

Antiphospholipid syndrome (APS) is a systemic acquired autoimmune thrombophilia that leads to impaired non-respiratory lung functions due to the circulation of antiphospholipid antibodies, shifting the balance between the coagulation link of hemostasis and the anti-coagulation system towards hypercoagulation. The research examines the modulating effect of FTY-720 on the water balance, coagulation and NO-activity of the lungs under conditions of experimental APS. The functional activity of FTY-720 is largely due to its ability to bind to S1P1 receptors and block signaling pathways mediated by the interaction of the mediator sphingosine-1-phosphate with them. The main effect of FTY-720 is immunosuppression, which develops as a result of the drug’s receptor interaction predominantly with S1P1 receptors, resulting in the retention of autoreactive lymphocytes in lymph nodes, and prevents further spread of inflammation and damage. The experiments were conducted on 85 male rats, divided into groups as follows: The first group of animals (n = 30) was injected with cardiolipin antigen every other day for three weeks for APS modeling; the rats of the second group (n = 25), which served as a control group, were similarly injected with 0.9% NaCl; APS modeling and FTY-720 injection were combined on the remaining animals (n = 30). Three weeks later, arterial (art) and venous (ven) blood was taken, in which APTT and PT were determined using a hemocoagulometer CGL 2110 “Solar” and the corresponding coefficients of APPT of ven/art, PT of ven/ art were calculated. NO-activity was assessed by the content of plasma NO and NO bronchoalveolar lavage obtained by washing the extraction of the bronchopulmonary complex in anesthetized animals. To study the water balance of the lungs, the mass of moist and dried lungs was measured, were determined the total, extra- and intravascular fluid of the lungs. In APS, an increase in APTT and PT of arterial and venous blood was observed, an increase in the level of NO in bronchoalveolar lavages against the background of worsening nitroxidergic activity of the lungs – the NO index of ven/art decreased. There was a positive effect of FTY- 720 on the restoration of non-respiratory lung functions in APS.

Advances in Physiological Research: Consideration on Arterial Hypercapnia in Acute Cardiogenic Pulmonary Edema (ACPE)

The causes of hypercapnia in Acute Cardiogenic Pulmonary Edema are still unknown. Our hypothesis recognizes an alteration of the ventilation-perfusion ratio in the apical areas of the lung as the major cause. The redistribution of blood to the apical lung zone in hypertensive pulmonary circulation determines an excess of perfusion compared to ventilation and consequently hypercapnia. Our suggestion might be in favor of Bilevel-PAP over Continuous Positive Airway Pressure (CPAP) as the first line of therapy.

Pathophysiological Markers of Acute Respiratory Distress Syndrome Severity Are Correlated With Ventilation-Perfusion Mismatch Measured by Electrical Impedance Tomography.

Pulmonary ventilation/perfusion (V/Q) mismatch measured by electrical impedance tomography (EIT) is associated with the outcome of patients with the acute respiratory distress syndrome (ARDS), but the underlying pathophysiological mechanisms have not been fully elucidated. The present study aimed to verify the correlation between relevant pathophysiological markers of ARDS severity and V/Q mismatch. Prospective observational study. General ICU of a university-affiliated hospital. Deeply sedated intubated adult patients with ARDS under controlled mechanical ventilation. Measures of V/Q mismatch by EIT, respiratory mechanics, gas exchange, lung imaging, and plasma biomarkers. Unmatched V/Q units were assessed by EIT as the fraction of ventilated nonperfused plus perfused nonventilated lung units. At the same time, plasma biomarkers with proven prognostic and mechanistic significance for ARDS (carbonic anhydrase 9 [CA9], hypoxia-inducible factor 1 [HIF1], receptor for advanced glycation endproducts [RAGE], angiopoietin 2 [ANG2], gas exchange, respiratory mechanics, and quantitative chest CT scans were measured. Twenty-five intubated ARDS patients were included with median unmatched V/Q units of 37.1% (29.2-49.2%). Unmatched V/Q units were correlated with plasma levels of CA9 (rho = 0.47; p = 0.01), HIF1 (rho = 0.40; p = 0.05), RAGE (rho = 0.46; p = 0.02), and ANG2 (rho = 0.42; p = 0.03). Additionally, unmatched V/Q units correlated with plateau pressure (r = 0.38; p = 0.05) and with the number of quadrants involved on chest radiograph (r = 0.73; p < 0.01). Regional unmatched V/Q units were correlated with the corresponding fraction of poorly aerated lung tissue (r = 0.62; p = 0.01) and of lung tissue weight (rho: 0.51; p = 0.04) measured by CT scan. In ARDS patients, unmatched V/Q units are correlated with pathophysiological markers of lung epithelial and endothelial dysfunction, increased lung stress, and lung edema. Unmatched V/Q units could represent a comprehensive marker of ARDS severity, reflecting the complex organ pathophysiology and reinforcing their prognostic significance.

The predictive capacity of biomarkers for clinical pulmonary oedema in patients with severe falciparum malaria is low: a prospective observational study

BackgroundPulmonary oedema is a feared and difficult to predict complication of severe malaria that can emerge after start of antimalarial treatment. Proinflammatory mediators are thought to play a central role in its pathogenesis.MethodsAn exploratory study was conducted to evaluate the predictive capacity of biomarkers for development of clinical pulmonary oedema in patients with severe falciparum malaria at two hospitals in Bangladesh. Plasma concentrations of interleukin-6 (IL-6), IL-8, tumour necrosis factor (TNF), soluble Receptor of Advanced Glycation End-products (sRAGE), surfactant protein-D (SP-D), club cell secretory protein (CC16), and Krebs von den Lungen-6 (KL-6) on admission were compared with healthy controls. Correlations between these biomarker and plasma lactate and Plasmodium falciparum histidine-rich protein 2 (PfHRP2) levels were evaluated. Receiver Operating Characteristic (ROC) curves were constructed to assess the predictive capacity for clinical pulmonary oedema of the biomarkers of interest.ResultsOf 106 screened patients with falciparum malaria, 56 were classified as having severe malaria with a mortality rate of 29%. Nine (16%) patients developed clinical pulmonary oedema after admission. Plasma levels of the biomarkers of interest were higher in patients compared to healthy controls. IL-6, IL-8, TNF, sRAGE, and CC16 levels correlated well with plasma PfHRP2 levels (rs = 0.39; P = 0.004, rs = 0.43; P = 0.001, rs = 0.54; P < 0.001, rs = 0.44; P < 0.001, rs = 0.43; P = 0.001, respectively). Furthermore, IL-6 and IL-8 levels correlated well with plasma lactate levels (rs = 0.37; P = 0.005, rs = 0.47; P < 0.001, respectively). None of the biomarkers of interest had predictive capacity for development of clinical pulmonary oedema.ConclusionsIL-6, IL-8, TNF, sRAGE, SP-D, CC16 and KL-6 cannot be used in predicting clinical pulmonary oedema in severe malaria patients.

Study on the Consistency of Point-of-Care Ultrasound and Chest X-ray in the Diagnosis of Postoperative Thoracic Abnormalities in Children with Congenital Heart Disease

Objective: This study aimed to explore the consistency of point-of-care ultrasound (POCUS) and chest X-ray in the diagnosis of postoperative thoracic abnormalities in children with congenital heart disease. Methods: The clinical data of 68 children with congenital cardiosurgery in our hospital from January 2021 to August 2024 were retrospective analyzed. Six children were excluded, and 62 cases were finally included. POCUS was performed 24 hours after surgery. After the examination of POCUS, chest X-ray examination was conducted. The results of POCUS and chest X-ray examinations in children, as well as the clinical incidence of postoperative thoracic abnormalities were recorded. The effect of POCUS and chest X-ray in the diagnosis of postoperative thoracic abnormalities was compared. Results: POCUS had slightly higher diagnostic sensitivity of pleural effusion and atelectasis than chest X-ray. The sensitivity of POCUS in diagnosing pulmonary edema was consistent with that of chest X-ray. However, POCUS had slightly lower sensitivity in diagnosing pneumothorax than chest X-ray. The specificity of POCUS in diagnosing pneumothorax and atelectasis was consistent with that of chest X-ray. However, POCUS had slightly higher specificity in the diagnosis of pleural effusion and pulmonary edema than chest X-ray. The kappa values of POCUS and chest X-ray in diagnosing pleural effusion, pneumothorax, atelectasis and pulmonary edema were 0.546, 0.565, 0.502 and 0.701, respectively. Conclusion: POCUS and chest X-ray examinations have good consistency in the diagnosis of postoperative thoracic abnormalities in children with congenital heart disease.

An Uncommon Case of Plasmodium vivax Malaria with Disseminated Intravascular Coagulation: Rare Case Report with Review of Literature.

Malaria is a severe health issue in India despite government efforts. Malaria has many complications, some of which can be life-threatening. Disseminated intravascular coagulation (DIC) is a prominent malaria complication, besides renal failure, cerebral malaria, pulmonary edema, and anemia. We report a young man with Plasmodium vivax malaria who developed septic shock due to DIC. A 25-year-old male had a fever, abdominal pain, vomiting, and nausea for 5 days. On clinical examination, the patient was in distress and had a fever of 102.6°F with a blood pressure of 86/46 mmHg. A complete blood count revealed anemia, leukocytopenia, and severe thrombocytopenia. Peripheral blood smear findings showed a P. vivax parasite in red blood cells with the presence of a few schistocytes. Further coagulation tests showed raised prothrombin, partial thromboplastin time, and d-dimer. DIC and septic shock required critical care unit admission. Conservative treatment with artesunate and lumefantrine completely cured him. This unusual case shows that P. vivax causes severe malaria and its morbid consequences. It stresses early diagnosis and treatment to prevent mortality and morbidity.

Chest Tubes and Pleural Drainage: History and Current Status in Pleural Disease Management.

Thoracostomy and chest tube placement are key procedures in treating pleural diseases involving the accumulation of fluids (e.g., malignant effusions, serous fluid, pus, or blood) or air (pneumothorax) in the pleural cavity. Initially described by Hippocrates and refined through the centuries, chest drainage achieved a historical milestone in the 19th century with the creation of closed drainage systems to prevent the entry of air into the pleural space and reduce infection risk. The introduction of plastic materials and the Heimlich valve further revolutionized chest tube design and function. Technological advancements led to the availability of various chest tube designs (straight, angled, and pig-tail) and drainage systems, including PVC and silicone tubes with radiopaque stripes for better radiological visualization. Modern chest drainage units can incorporate smart digital systems that monitor and graphically report pleural pressure and evacuated fluid/air, improving patient outcomes. Suction application via wall systems or portable digital devices enhances drainage efficacy, although careful regulation is needed to avoid complications such as re-expansion pulmonary edema or prolonged air leak. To prevent recurrent effusion, particularly due to malignancy, pleurodesis agents can be applied through the chest tube. In cases of non-expandable lung, maintaining a long-term chest drain may be the most appropriate approach and procedures such as the placement of an indwelling pleural catheter can significantly improve quality of life. Continued innovations and rigorous training ensure that chest tube insertion remains a cornerstone of effective pleural disease management. This review provides a comprehensive overview of the historical evolution and modern advancements in pleural drainage. By addressing both current technologies and procedural outcomes, it serves as a valuable resource for healthcare professionals aiming to optimize pleural disease management and patient care.