Noninvasive assessment of pulmonary congestion in heart failure: Need of the hour.

Early pulmonary congestion detection and surveillance in acute heart failure patients can prevent decompensation, minimize hospitalizations, and improve prognosis. In India, the warm and wet types of HF are still the most common types and residual congestion at discharge is still a significant concern. Thus, there is an urgent need for a reliable and sensitive means of identifying residual and subclinical congestion. Two such monitoring systems are available and approved by US FDA. These include CardioMEMS HF System (Abbott, Sylmar, California) and ReDS System (Sensible Medical Innovations, Ltd., Nanya, Israel). CardioMEMS is a wireless pressure-sensitive implantable device, while ReDS is a wearable noninvasive device for measurement of the lung fluid and hence direct detection of PC. This review discusses the role of noninvasive assessment in PC monitoring in patients with heart failure and its implications from an Indian perspective.

Flash pulmonary oedema following arteriovenous fistula surgery: rapid assessment and treatment is key to break the vicious cycle.

An early adolescent boy with chronic kidney disease on haemodialysis was referred to the surgical clinic for the creation of an arteriovenous fistula. He was undergoing treatment for dilated cardiomyopathy and extrapulmonary tuberculosis. The patient was haemodynamically stable during the procedure, but he developed rapidly progressing dyspnoea, tachycardia and tachypnoea about 10 min after the vessels were declamped. His blood pressure rapidly rose above 220/120 mm Hg and saturation dropped below 90%. A multidisciplinary team (MDT) constituted of surgeons, nephrologists and intensivists was quickly activated. The patient was put on a mechanical ventilator and resuscitated with parenteral antihypertensives, diuretics, amiodarone and haemodialysis. The patient improved clinically and was discharged on the third postoperative day. Thus, a rapidly activated MDT approach was key in breaking the vicious cycle caused by hypertensive crisis, myocardial dysfunction and impending ventilatory failurethat occurred following access surgery.

Development of an Image-Based HCS-Compatible Method for Endothelial Barrier Function Assessment.

The recent renascence of phenotypic drug discovery (PDD) is catalyzed by its ability to identify first-in-class drugs and deliver results when the exact molecular mechanism is partially obscure. Acute respiratory distress syndrome (ARDS) is a severe, life-threatening condition with a high mortality rate that has increased in frequency due to the COVID-19 pandemic. Despite decades of laboratory and clinical study, no efficient pharmacological therapy for ARDS has been found. An increase in endothelial permeability is the primary event in ARDS onset, causing the development of pulmonary edema that leads to respiratory failure. Currently, the detailed molecular mechanisms regulating endothelial permeability are poorly understood. Therefore, the use of the PDD approach in the search for efficient ARDS treatment can be more productive than classic target-based drug discovery (TDD), but its use requires a new cell-based assay compatible with high-throughput (HTS) and high-content (HCS) screening. Here we report the development of a new plate-based image cytometry method to measure endothelial barrier function. The incorporation of image cytometry in combination with digital image analysis substantially decreases assay variability and increases the signal window. This new method simultaneously allows for rapid measurement of cell monolayer permeability and cytological analysis. The time-course of permeability increase in human pulmonary artery endothelial cells (HPAECs) in response to the thrombin and tumor necrosis factor α treatment correlates with previously published data obtained by transendothelial resistance (TER) measurements. Furthermore, the proposed image cytometry method can be easily adapted for HTS/HCS applications.

Incidence of Swimming-Induced Pulmonary Edema: A Cohort Study Based on 47,600 Open-Water Swimming Distances.

BACKGROUND: Despite increasing awareness of swimming-induced pulmonary edema (SIPE), large population-based studies are lacking and the incidence is unknown. RESEARCH QUESTION: What is the incidence of SIPE in a mixed group of competitive and recreational swimmers during a large open-water swimming event? METHODS: In four consecutive years (2016-2019), a prospective cohort study was conducted during Sweden's largest open-water swimming event, Vansbrosimningen. All swimmers seeking medical care with acute respiratory symptoms were eligible for the study. SIPE diagnosis was based on clinical findings in 2016 and 2017 and pulmonary edema assessed by lung ultrasound in 2018 and 2019. Data on patient characteristics, clinical findings, and information about the race were collected. RESULTS: Based on 47,573 consecutive swimming distances, 322 patients with acute respiratory symptoms (0.68%; CI, 0.61%-0.75%) were treated at the mobile medical unit. Of these, 211 patients (0.44%; CI, 0.39%-0.51%) received a diagnosis of SIPE. The annual incidence of SIPE was 0.34%, 0.47%, 0.41%, and 0.57%, respectively, from 2016 through 2019. Most patients diagnosed with SIPE were women (90%), despite about equal percentages of men and women participating (47% men and 53% women). The incidence of SIPE overall was 0.75% in women and 0.09% in men. The incidence increased with age, from 0.08% in the youngest age group (18-30 years) to 1.1% in the oldest age group (≥ 61 years). Based on multiple logistic regression analysis, the adjusted odds for SIPE occurring was 8.59 times higher for women compared with men and 12.74 times higher for the oldest age group compared with the youngest age group. INTERPRETATION: The incidence of SIPE over 4 years during a large open-water swimming event in Sweden was 0.44%. The incidence was higher in women than in men and increased with age.

A quantitative CT parameter for the assessment of pulmonary oedema in patients with acute respiratory distress syndrome.

OBJECTIVES: The aim of this study was to establish quantitative CT (qCT) parameters for pathophysiological understanding and clinical use in patients with acute respiratory distress syndrome (ARDS). The most promising parameter is introduced. MATERIALS AND METHODS: 28 intubated patients with ARDS obtained a conventional CT scan in end-expiratory breathhold within the first 48 hours after admission to intensive care unit (ICU). Following manual segmentation, 137 volume- and lung weight-associated qCT parameters were correlated with 71 clinical parameters such as blood gases, applied ventilation pressures, pulse contour cardiac output measurements and established status and prognosis scores (SOFA, SAPS II). RESULTS: Of all examined qCT parameters, excess lung weight (ELW), i.e. the difference between a patient's current lung weight and the virtual lung weight of a healthy person at the same height, displayed the most significant results. ELW correlated significantly with the amount of inflated lung tissue [%] (p<0.0001; r = -0.66) and was closely associated with the amount of extravascular lung water (EVLW) (p<0.0001; r = 0.72). More substantially than the oxygenation index (PaO2/FiO2) or any other clinical parameter it correlated with the patients' mean SOFA- (p<0.0001, r = 0.69) and SAPS II-Score (p = 0.0005, r = 0.62). Patients who did not survive intensive care treatment displayed higher values of ELW in the initial CT scans. CONCLUSIONS: ELW could serve as a non-invasive method to quantify the amount of pulmonary oedema. It might serve as an early radiological marker of severity in patients with ARDS.

Comparison between lung ultrasonography and current methods for volume assessment in Asian chronic hemodialysis patients.

INTRODUCTION: Volume assessment in end-stage kidney disease patients on hemodialysis (HD) remains inadequate by existing methods: clinical examination, bioimpedance spectroscopy, measurement of inferior vena cava diameter by ultrasound (IVCD), and plasma B-type natriuretic peptide (NT-pro BNP). This study aims to compare the performance of lung ultrasound against existing methods for volume assessment in a HD cohort. METHODS: Two nephrologists independently performed 28-point lung ultrasound immediately before and after midweek HD in 50 patients. Lung congestion was classified into mild, moderate, and severe categories based on lung ultrasound findings. Clinical examination for crepitations and oedema, change in hydration status (∆HS) measured by bioimpedance spectroscopy, NT-pro BNP, IVCD during inspiration (IVCDimin), expiration (IVCDimax), and inferior vena cava collapsibility index were also assessed before and after midweek HD. FINDINGS: In all, 61% of patients with normohydration status by bioimpedance spectroscopy had moderate or severe lung congestion on lung ultrasound. There were significant correlations between predialysis lung ultrasound, and NT-pro BNP (r = 0.432, P = 0.004), ∆HS (r = 0.447, P < 0.001), and IVCD parameters (P < 0.05). Some correlations weakened postdialysis (∆HS [r = 0.322, P = 0.01] and IVCDimax [r = 0.307, P = 0.03]), whereas NT-pro BNP and ∆HS paradoxically increased in 28% and 30% of the cohort, respectively. On receiver operator curve analysis, most methods of volume assessment had limited discriminatory power to detect mild lung congestion. DISCUSSION: Lung ultrasound demonstrates some comparability with existing volume assessment methods in Asian dialysis patients. However, it appears more effective at detecting subclinical pulmonary congestion, and tracking fluid changes real-time compared to bioimpedance spectroscopy and NT-pro BNP.

Early Changes Over Time in the Radiographic Assessment of Lung Edema Score Are Associated With Survival in ARDS.

BACKGROUND: The Radiographic Assessment of Lung Edema (RALE) score is associated with the severity of ARDS, and treatments targeted at reducing pulmonary edema such as conservative fluid management cause a reduction in RALE score over time. RESEARCH QUESTION: Are early changes in RALE score over time associated with survival in patients with ARDS? STUDY DESIGN AND METHODS: Data from patients enrolled in three centers in the Lung Imaging for Ventilation sEtting in ARDS (LIVE) trial with available chest radiographs at baseline (day 0) and days 2 or 3 were used. The RALE was scored by two independent reviewers. The primary end point was death by day 90, considering RALE score both at baseline and as a time-varying covariate in a marginal Cox survival model. RESULTS: RALE was scored from 135, 64, and 88 radiographs on days 0, 2, and 3, respectively. Both baseline RALE (hazard ratio [HR] for each one-point increment, 1.04; 95% CI, 1.01-1.08; P = .006) and the change in RALE over time (HR for each one-point decrease per unit of time, 0.99; 95% CI, 0.99-0.99; P = .03) were associated with death by day 90, even after adjustment for age, sex, BMI, Simplified Acute Physiology Score II, vasopressor use, and total volume of fluids received since study entry. INTERPRETATION: The change in RALE during the first days after ARDS onset is independently associated with survival and may be useful as a surrogate end point in future clinical trials of new therapeutics in ARDS.

From bedside to bench: lung ultrasound for the assessment of pulmonary edema in animal models.

Traditionally, the lung has been excluded from the ultrasound organ repertoire and, hence, the application of lung ultrasound (LUS) was largely limited to a few enthusiastic clinicians. Yet, in the last decades, the recognition of the previously untapped diagnostic potential of LUS in intensive care medicine has fueled its widespread use as a rapid, non-invasive and radiation-free bedside approach with excellent diagnostic accuracy for many of the most common causes of acute respiratory failure, e.g., cardiogenic pulmonary edema, pneumonia, pleural effusion and pneumothorax. Its increased clinical use has also incited attention for the potential usefulness of LUS in preclinical studies with small animal models mimicking lung congestion and pulmonary edema formation. Application of LUS to small animal models of pulmonary edema may save time, is cost-effective, and may reduce the number of experimental animals due to the possibility of serial evaluations in the same animal as compared with traditional end-point measurements. This review provides an overview of the emerging field of LUS with a specific focus on its application in animal models and highlights future perspectives for LUS in preclinical research.

Lung water assessment: from gravimetry to wearables.

Several techniques are now available to detect and quantify pulmonary edema, from the laboratory postmortem method (gravimetry) to non-invasive wearable sensors. In critically ill patients with adult respiratory distress syndrome (ARDS), computed tomography scans are often performed to visualize lung lesions and quantify lung aeration, but their value seems somewhat limited to quantify pulmonary edema on a routine basis and of course to track changes with therapy. In this context, transpulmonary thermodilution is a convenient technique. It is invasive but most patients with ARDS have a central line and an arterial catheter in place. In addition to extravascular lung water measurements, transpulmonary thermodilution enables the measurement of hemodynamic variables that are useful to guide fluid and diuretic therapy. Echo probes are about to replace the stethoscope in our pocket and, if B lines (aka comet tails) do not allow a real quantification of pulmonary edema, they are useful to detect an increase in lung water. Finally, wireless and wearable sensors are now available to monitor patients on hospital wards and beyond (home monitoring). They should enable the detection of pulmonary congestion at a very early stage, and if combined with a proactive therapeutic strategy, have potential to improve outcome.

Assessment of lung edema during ex-vivo lung perfusion by single transpulmonary thermodilution: A preliminary study in humans.

BACKGROUND: Single transpulmonary thermodilution (SD) with extravascular lung water index (EVLWI) could become a new tool to better assess lung graft edema during ex-vivo lung perfusion (EVLP). In this study we compare EVLWI with conventional methods to better select lungs during EVLP and to predict post-transplant primary graft dysfunction (PGD). METHODS: We measured EVLWI, arterial oxygen/fraction of inspired oxygen (P/F) ratio, and static lung compliance (SLC) during EVLP in an observational study. At the end of EVLP, grafts were accepted or rejected according to a standardized protocol blinded to EVLWI results. We compared the respective ability of EVLWI, P/F, and SLC to predict PGD. Mann-Whitney U-test, Fisher's exact test, and receiver-operating characteristic (ROC) curve data were used for analysis. p < 0.05 was considered statistically significant. RESULTS: Thirty-five lungs were evaluated by SD during EVLP. Three lungs were rejected for pulmonary edema. Thirty-two patients were transplanted, 8 patients developed Grade 2 or 3 PGD, and 24 patients developed Grade 0 or 1 PGD. In contrast to P/F ratio, SLC, and pulmonary artery pressure, EVLWI differed between these 2 populations (p < 0.001). The area under the ROC for EVLWI assessing Grade 2 or 3 PGD at the end of EVLP was 0.93. Donor lungs with EVLWI >7.5 ml/kg were more likely associated with a higher incidence of Grade 2 or 3 PGD at Day 3. CONCLUSIONS: Increased EVLWI during EVLP was associated with PGD in recipients.

Assessment of early treatment response by rapid cardiothoracic ultrasound in acute heart failure: Cardiac filling pressures, pulmonary congestion and mortality.

BACKGROUND: It is unclear how to optimally monitor acute heart failure (AHF) patients. We evaluated the timely interplay of cardiac filling pressures, brain natriuretic peptides (BNPs), lung ultrasound (LUS) and symptoms during AHF treatment. METHODS: We enrolled 60 patients who had been hospitalised for AHF. Patients were examined with a rapid cardiothoracic ultrasound (CaTUS) protocol, combining LUS and focused echocardiographic evaluation of cardiac filling pressures (i.e. medial E/e' and inferior vena cava index [IVCi]). CaTUS was done at 0, 12, 24 and 48 hours (±3 hours) and on the day of discharge, alongside clinical evaluation and laboratory samples. Patients free of congestion (B lines or pleural fluid) on LUS at discharge were categorised as responders, whereas the rest were categorised as non-responders. Improvement in congestion parameters was evaluated separately in these groups. The effect of congestion parameters on prognosis was also analysed. RESULTS: Responders experienced a significantly larger decline in E/e' (2.58 vs. 0.38, p = 0.037) and dyspnoea visual analogue scale (1-10) score (7.68 vs. 3.57, p = 0.007) during the first 12 hours of treatment, while IVCi and BNPs declined later without no such rapid initial decline. Among patients experiencing a >3 U decline in E/e' during the first 12 hours of treatment, 18/21 were to become responders ( p < 0.001). LUS response was the only congestion parameter independently predicting both 6-month survival regarding all-cause mortality and the composite endpoint of all-cause mortality or rehospitalisation for AHF. CONCLUSION: E/e' seemed like the most useful congestion parameter for monitoring early treatment response, predicting prognostically beneficial resolution of pulmonary congestion.

Assessment of Pulmonary Edema: Principles and Practice.

Pulmonary edema increasingly is recognized as a perioperative complication affecting outcome. Several risk factors have been identified, including those of cardiogenic origin, such as heart failure or excessive fluid administration, and those related to increased pulmonary capillary permeability secondary to inflammatory mediators. Effective treatment requires prompt diagnosis and early intervention. Consequently, over the past 2 centuries a concentrated effort to develop clinical tools to rapidly diagnose pulmonary edema and track response to treatment has occurred. The ideal properties of such a tool would include high sensitivity and specificity, easy availability, and the ability to diagnose early accumulation of lung water before the development of the full clinical presentation. In addition, clinicians highly value the ability to precisely quantify extravascular lung water accumulation and differentiate hydrostatic from high permeability etiologies of pulmonary edema. In this review, advances in understanding the physiology of extravascular lung water accumulation in health and in disease and the various mechanisms that protect against the development of pulmonary edema under physiologic conditions are discussed. In addition, the various bedside modalities available to diagnose early accumulation of extravascular lung water and pulmonary edema, including chest auscultation, chest roentgenography, lung ultrasonography, and transpulmonary thermodilution, are examined. Furthermore, advantages and limitations of these methods for the operating room and intensive care unit that are critical for proper modality selection in each individual case are explored.

Lung ultrasound: a useful tool in the assessment of the dyspnoeic patient in the emergency department. Fact or fiction?

Patients with respiratory distress present a frequent and challenging dilemma for emergency physicians (EPs). The accurate diagnosis and treatment of the underlying pathology is vitally important in these sick patients to ensure the best outcome and minimise harm from unnecessary treatments. Within the last decade, studies have shown lung ultrasonography (LU) to be valuable in the accurate diagnosis of a variety of lung pathologies, including cardiogenic pulmonary oedema, pleural effusion, pneumothorax, haemothorax and pneumonia. However, despite advances in techniques and the evidence for the use of LU in the diagnosis of respiratory pathology, it remains poorly understood and rarely used by EPs. This clinical review article provides an overview of LU and its relevance as a diagnostic aid to the detection of respiratory pathology in the Emergency Department (ED).

Transpulmonary Thermodilution: Its Role in Assessment of Lung Water and Pulmonary Edema.

Tissue edema, in particular pulmonary edema, increasingly is recognized as a perioperative complication affecting outcome. Management strategies directed at avoiding excessive fluid administration, reducing inflammatory response, and decreasing capillary permeability commonly are advocated in perioperative care protocols. In this review, transpulmonary thermodilution (TPTD) as a bedside tool to quantitatively monitor lung water accumulation and optimize fluid therapy is examined. Furthermore, the roles of TPTD as an early detector of fluid accumulation before the development of overt pulmonary edema and in risk stratification are explored. In addition, the ability of TPTD to provide insight into the etiology of pulmonary edema, specifically differentiating hydrostatic versus increased pulmonary capillary permeability, is emerging as an aid in therapeutic decision-making. The combination of hemodynamic and lung water data afforded by TPTD offers unique benefits for the care of high-risk perioperative patients.

Clinical manifestations of severe enterovirus 71 infection and early assessment in a Southern China population.

BACKGROUND: Enterovirus 71 (EV-A71) shows a potential of rapid death, but the natural history of the infection is poorly known. This study aimed to examine the natural history of EV-A71 infection. METHODS: This was a prospective longitudinal observational study performed between January 1st and October 31st, 2012, at three hospitals in Guangdong, China. Subjects with positive EV-A71 RNA laboratory test results were included. Disease progression was documented with MRI, autopsies, and follow-up. Symptoms/signs with potential association with risk of death were analyzed. RESULTS: Among the 288 patients, neurologic symptoms and signs were observed (emotional movement disorders, dyskinesia, involuntary movements, autonomic dysfunction, and disturbance of consciousness). Some of them occurred as initial symptoms. Myoclonic jerks/tremors were observed among >50% of the patients; nearly 40% of patients presented fatigue and 25% were with vomiting. Twenty-eight patients (9.7%) presented poor peripheral perfusion within 53.4 ± 26.1 h; 23 patients (8.0%) presented pulmonary edema and/or hemorrhage within 62.9 ± 28.6 h. Seventeen (5.9%) patients were in a coma. Seven (2.4%) patients died within 62.9 ± 28.6 h. Seventy-seven survivors underwent head and spinal cord MRI and 37.7% (29/77) showed abnormalities. Two fatal cases showed neuronal necrosis, softening, perivascular cuffing, colloid, and neuronophagia phenomenon in the brainstem. CONCLUSIONS: Patients with EV-A71 infection showed high complexity of symptoms and onset timing. Death risk may be indicated by autokinetic eyeball, eyeball ataxia, severe coma, respiratory rhythm abnormality, absent pharyngeal reflex, ultrahyperpyrexia, excessive tachycardia, pulmonary edema and/or hemorrhage, and refractory shock and ataxic respiration. Early assessment of these symptoms/signs is important for proper management.

Epidemiology, pathophysiology, and in-hospital management of pulmonary edema: data from the Romanian Acute Heart Failure Syndromes registry.

AIM: The objective of this study was to evaluate the clinical presentation, inpatient management, and in-hospital outcome of patients hospitalized for acute heart failure syndromes (AHFS) and classified as pulmonary edema (PE). METHODS: The Romanian Acute Heart Failure Syndromes (RO-AHFS) study was a prospective, national, multicenter registry of all consecutive patients admitted with AHFS over a 12-month period. Patients were classified at initial presentation by clinician-investigators into the following clinical profiles: acute decompensated HF, cardiogenic shock, PE, right HF, or hypertensive HF. RESULTS: RO-AHFS enrolled 3224 patients and 28.7% (n = 924) were classified as PE. PE patients were more likely to present with pulmonary congestion, tachypnea, tachycardia, and elevated systolic blood pressure and less likely to have peripheral congestion and body weight increases. Mechanical ventilation was required in 8.8% of PE patients. PE patients received higher doses (i.e. 101.4 ±â€Š27.1 mg) of IV furosemide for a shorter duration (i.e. 69.3 ±â€Š22.3 hours). Vasodilators were given to 73.6% of PE patients. In-hospital all-cause mortality (ACM) in PE patients was 7.4%, and 57% of deaths occurred on day one. Increasing age, concurrent acute coronary syndromes, life-threatening ventricular arrhythmias, elevated BUN, left bundle branch block, inotrope therapy, and requirement for invasive mechanical ventilation were independent risk factors for ACM. CONCLUSIONS: In this national registry, the PE profile was found to be a high-acuity clinical presentation with distinctive treatment patterns and a poor short-term prognosis. Advances in the management of PE may necessitate both the development of novel targeted therapies as well as systems-based strategies to identify high-risk patients early in their course.

Lung ultrasound for the evaluation of pulmonary congestion in outpatients: a comparison with clinical assessment, natriuretic peptides, and echocardiography.

OBJECTIVES: The aim of this study was to define the performance of lung ultrasound (LUS) compared with clinical assessment, natriuretic peptides, and echocardiography, to evaluate decompensation in patients with systolic heart failure (HF) in an outpatient clinic. BACKGROUND: Evaluation of pulmonary congestion in chronic HF is challenging. LUS has been recently proposed as a reliable tool for the semiquantification of extravascular lung water through assessment of B-lines. METHODS: This was a cohort study of patients with moderate to severe systolic HF. Receiver-operating characteristic (ROC) analyses were performed to compare LUS with a previously validated clinical congestion score (CCS), amino-terminal portion of B-type natriuretic peptide (NT-proBNP), E/e' ratio, chest x-ray, and 6-min walk test. RESULTS: Ninety-seven patients were enrolled. Decompensation was present in 57.7% of patients when estimated by CCS, 68% by LUS, 53.6% by NT-proBNP, and 65.3% by E/e' ≥15. The number of B-lines was correlated to NT-proBNP (r = 0.72; p < 0.0001), E/e' (r = 0.68; p < 0.0001), and CCS (r = 0.43; p < 0.0001). In ROC analyses, considering as reference for decompensation a combined method (E/e' ≥ 15 and/or NT-proBNP >1,000 pg/ml), LUS yielded a C-statistic of 0.89 (95% confidence interval: 0.82 to 0.96), providing the best accuracy with a cutoff ≥ 15 B-lines (sensitivity 85%, specificity 83%). A systematic approach using CCS, E/e', NT-proBNP, chest x-ray, and 6-min walk test in different combinations as reference for decompensation also corroborated this cutoff and found a similar accuracy for LUS. CONCLUSIONS: In an HF outpatient clinic, B-lines were significantly correlated with more established parameters of decompensation. A B-line ≥15 cutoff could be considered for a quick and reliable assessment of decompensation in outpatients with HF.