Pulmonary Edema Research Articles

Quantification of pulmonary edema using automated lung segmentation on computed tomography in mechanically ventilated patients with acute respiratory distress syndrome

BackgroundQuantification of pulmonary edema in patients with acute respiratory distress syndrome (ARDS) by chest computed tomography (CT) scan has not been validated in routine diagnostics due to its complexity and time-consuming nature. Therefore, the single-indicator transpulmonary thermodilution (TPTD) technique to measure extravascular lung water (EVLW) has been used in the clinical setting. Advances in artificial intelligence (AI) have now enabled CT images of inhomogeneous lungs to be segmented automatically by an intensive care physician with no prior radiology training within a relatively short time. Nevertheless, there is a paucity of data validating the quantification of pulmonary edema using automated lung segmentation on CT compared with TPTD.MethodsA retrospective study (January 2016 to December 2021) analyzed patients with ARDS, admitted to the intensive care unit of the Department of Anesthesiology and Critical Care Medicine, University Hospital Mannheim, who underwent a chest CT scan and hemodynamic monitoring using TPTD at the same time. Pulmonary edema was estimated using manually and automated lung segmentation on CT and then compared to the pulmonary edema calculated from EVLW determined using TPTD.Results145 comparative measurements of pulmonary edema with TPTD and CT were included in the study. Estimating pulmonary edema using either automated lung segmentation on CT or TPTD showed a low bias overall (− 104 ml) but wide levels of agreement (upper: 936 ml, lower: − 1144 ml). In 13% of the analyzed CT scans, the agreement between the segmentation of the AI algorithm and a dedicated investigator was poor. Manual segmentation and automated segmentation adjusted for contrast agent did not improve the agreement levels.ConclusionsAutomated lung segmentation on CT can be considered an unbiased but imprecise measurement of pulmonary edema in mechanically ventilated patients with ARDS.

Diagnostic Accuracy of Lung Ultrasonography Compared to Chest Radiography, BNP and Physical Examination in Patients with Dyspnea Suggestive of Pulmonary Edema: A Systematic Review and Meta-Analysis

Background: Pulmonary edema (PE) is the result of an abrupt increase in hydrostatic pressure in the pulmonary capillaries that leads to leakage of fluid through microvascular endothelial cells. This leads to a disruption of gas exchange in the lungs. Aims: This meta-analysis aimed to determine the diagnostic accuracy of lung ultrasonography (LUS) in pulmonary edema. Methods: A systematic search was conducted using a strategy based on these search terms (Lung ultrasonography, pulmonary edema, diagnostic accuracy); we searched PubMed, Google Scholar, and the Cochrane Library. Out of 1029, 14 prospective cross-sectional and observational studies with 2239 patients who reported the sensitivity and specificity of lung ultrasonography in diagnosing pulmonary edema were selected. For inclusion and data extraction, an independent review of citations was carried out. The data obtained were analyzed using SPSS, RevMan 5.3, and Stata 14.0 software. A quality assessment was conducted using the QUADAS-2 tool. The reference gold standard was the final clinical diagnosis according to chest radiography, B-type natriuretic peptide, and/or physical examination in dyspneic patients. Results: The overall sensitivity and specificity of lung ultrasonography in the diagnosis of pulmonary edema were 0.86 (95% CI, 0.81-0.90) and 0.91 (95% CI, 0.90-0.93), respectively, with a Younden index of 77.8%. The area under the receiver operating characteristic (ROC) curve was 0.889. Conclusion: The overall diagnostic odds ratio was 68.86. The results of this meta-analysis suggest that lung ultrasonography is an effective non-invasive technique in the diagnosis of acute pulmonary edema with rapid bedside examination and immediate interpretation.

Epidural anesthesia as a sole anesthetic for a parturient with cardiac disease and low ejection fraction – a case report in resource limited setup

Introduction and importance: The effective care of pregnant women with cardiac conditions relies on collaboration among the obstetrician, cardiologist, and anesthesiologist throughout the peripartum period. Limited research exists regarding the safety of specific anesthetic approaches for patients with congestive heart failure (CHF), particularly in the context of pregnancy. Case presentation: This was a 28-year-old woman who was pregnant with her third child (gravida III, para II) and has not had a menstrual period for the past 8 months. She had been receiving antenatal care at a local health center. Currently, she was experiencing symptoms including coughing, difficulty breathing, epigastric pain, and chest pain, which had been present for 1 week. Upon examination, she was diagnosed with New York Heart Association class IV CHF with pulmonary edema, and preeclampsia with severe features, and she was in the third trimester of pregnancy. Clinical discussion: Pre-existing medical conditions can adversely affect pregnancy outcomes for women and their offspring, especially in resource-poor settings in Africa. The goals of anesthetic management are avoidance of myocardial depression, maintaining normovolemia, avoiding an overdose of drugs during induction as the circulation time is slow, and avoiding sudden hypotension when regional anesthesia is the choice. Conclusion: We believe that successful management of anesthesia for this critical case depends on a thorough understanding of the pathophysiology of the disease condition, the selection of anesthetic techniques, and the decision-making of our team. We showed epidural anesthesia could be safely used to manage high-risk cardiac patients, however, further interventional study is needed to prove safety.

Severe postoperative negative pressure pulmonary edema: a case report

BackgroundPostoperative negative pressure pulmonary edema (NPPE) can occur in any patient undergoing general anesthesia. There are several risk factors for it, especially postoperative laryngospasm. The disease is usually benign and quickly reversible. In our case the severity and need for advanced critical care therapy was unusual.CaseWe report a severe case of postoperative negative pressure pulmonary edema in a 62-year-old male patient undergoing elective right-sided retroperitoneoscopic adrenalectomy. The patient developed a severe case of acute respiratory distress syndrome (ARDS) after postoperative laryngospasm, possibly in conjunction with a suspected anaphylactic reaction. The patient was consequently treated with a combination of invasive airway pressure release ventilation (APRV) and a prone positioning regimen. After drastic improvement in respiratory function, the patient was discharged from the intensive care unit after 10 days and from the hospital after 14 days.ConclusionNPPE is a rare but relevant complication of anesthesia and laryngospasm. The disease can basically occur in any patient undergoing general anesthesia and therefore should be considered.

A Rare Complication: Post-Cardioversion Pulmonary Edema

A Rare Complication: Post-Cardioversion Pulmonary Edema

Эффективность алгоритма назначения диуретической терапии под контролем натрийуреза у пациентов с острой декомпенсацией сердечной недостаточности в отделении реанимации и интенсивной терапии: проспективное интервенционное контролируемое исследование

INTRODUCTION: The European Society of Cardiology suggests using early and repeated assessment of sodium content in urine in patients admitted with heart failure to evaluate diuretic therapy. OBJECTIVES: Evaluation of the effectiveness of the algorithm for diuretic therapy under the control of natriuresis in patients with acute decompensation of chronic heart failure (ADCHF) in the intensive care unit (ICU). MATERIALS AND METHODS: A prospective study included 150 patients hospitalized in the ICU with ADCHF. All patients underwent standard physical, laboratory and instrumental examinations. The starting dose of furosemide was 20 mg i/v. After 2 hours, a quantitative assessment of sodium in urine was performed. If the natriuresis was ≥ 70 mmol/l, furosemide was continued at the same dose every 12 hours. If the natriuresis was < 70 mmol/L, the dose of furosemide was doubled. Natriuresis was monitored every 12 hours. RESULTS: In the natriuresis-controlled group the duration of patients' stay in the ICU was significantly shorter (3 vs. 5 days, p = 0.01), achieving euvolemia was significantly more frequent (42 % vs. 12 %, p < 0.05), the daily diuresis in patients was significantly higher on more daily (120 mg vs. 80 mg, p < 0.05) and the total dose of furosemide (420 mg vs. 240 mg, p < 0.05). There was a pronounced decrease in congestion in the group of patients with natriuresis control with less pulmonary (number of B-lines 9.6 ± 1.2 versus 23.4 ± 2.5) and venous congestion (GRADE 0–56 %, 1–20 %, 2–24 %, 3–0 % against 0–20 %, 1–35 %, 2–18 %, 3–27 %) on the 3rd day of hospitalization. CONCLUSION: The inclusion of an algorithm for diuretic therapy under the control of natriuresis in patients with ADCHF in the ICU is effective and contributes to a more pronounced and rapid reduction of congestion, as well as a 1.5-fold reduction of time in the ICU.

Перипартальна кардіоміопатія: сучасні можливості ведення пацієнток із важкою серцевою недостатністю

Peripartum cardiomyopathy (PCMP) is a cardiomyopathy with impaired LV systolic function that develops in pregnant women or in the first months after childbirth. Clinical manifestations can vary from mild or moderate to severe symptoms of heart failure with significant functional limitation and high mortality. The mechanisms of PCMP development are unknown, and there is no specific treatment. In the article, we wanted to demonstrate our own experience of managing a patient with severe PCMP, the course of which was complicated by heart rhythm disturbances, the development of cardiogenic shock and pulmonary edema. This clinical example will highlight basic information about the etiology, pathogenesis, prevention and treatment of PCMP at the current stage.

Case report: Mixed hydrofluoric and nitric acid mist inhalation poisoning

IntroductionHydrofluoric and nitric acids are strongly acidic substances with strong oxidation and are widely used in industrial production. Chemical pneumonia caused by the inhalation of strong acids has occasionally been reported. Severe chemical pneumonia can lead to acute pulmonary edema and life-threatening acute respiratory distress syndrome. The treatment of chemical pneumonia mainly relies on symptomatic and supportive treatment such as anti-inflammatory and anti-infection.Case descriptionThis study reports three cases of chemical pneumonia caused by the inhalation of a mixed hydrofluoric and nitric acid mist during an occupational exposure accident. After appropriate emergency symptomatic treatment, such as oxygenation and excretion promotion, cough, and difficulty in breathing were alleviated but not completely cleared.DiscussionMost of the literature reports damage caused by hydrogen fluoride on the skin and mucosal burns, and reports on lung damage caused by the inhalation of large amounts of hydrogen fluoride gas are relatively rare. Usually in the early stage of this kind of patients can have elevated blood picture, hypoxemia, pulmonary CT inflammatory plaque changes, so as to have obvious respiratory irritation symptoms. When inhaling a large amount of hydrofluorine mixed nitric acid mist, in addition to considering the occurrence of severe pneumonia, we should also be alert to the occurrence of other organ damage and electrolyte disorder.ConclusionAs occupational hydrogen fluoride gas inhalation poisoning often occurs in groups, improving the safety facilities and standard operations of small- and medium-sized enterprises is necessary. For medical workers, it is necessary to be alert to the occurrence of severe toxic pneumonia and severe fluorosis.

Immunomodulatory activity of omadacycline in vitro and in a murine model of acute lung injury.

Cystic fibrosis (CF) is characterized by chronic airway obstruction, infection, and inflammation leading to progressive loss of lung function and eventual respiratory failure. Omadacycline, a tetracycline antibiotic, demonstrates in vitro activity against key CF pathogens, substantial lung penetration, and increasing clinical evidence for the treatment of lung infections in people with CF (PwCF). Preliminary in vitro data demonstrate that omadacycline exhibits anti-inflammatory activity. This study aims to determine the anti-inflammatory effects of omadacycline in vitro and in a murine model of lipopolysaccharide (LPS)-induced lung neutrophilia. In vitro, THP-1-derived macrophages were treated with omadacycline (20-100 µg/mL) 30 minutes prior to LPS stimulation. Pro-inflammatory cytokine (TNF-α, IL-1β/6), chemokine (CXCL-1/2), and MMP-9 levels were analyzed after 24 hours by ELISA. Omadacycline's effects on IL-8-induced human neutrophil chemotaxis were also investigated. In vivo, omadacycline (2.5-30 mg/kg), comparators dexamethasone (1 mg/kg), and azithromycin (30 mg/kg) were administered 1 hour before and 6 hours after intranasal LPS challenge, respectively. Leukocyte counts and differentials in bronchoalveolar lavage fluid (BALF), inflammatory mediator levels in BALF and lung homogenates, pulmonary edema markers, and the severity of lung injury were evaluated 24 hours or 48 hours post-challenge. Treatment with omadacycline in vitro resulted in significant, dose-dependent reductions in IL-6, CXCL-1, and MMP-9 expression and inhibition of IL-8-induced neutrophil chemotaxis. In vivo, omadacycline yielded protective and therapeutic effects by reducing the production of proinflammatory cytokines and chemokines and neutrophil infiltration into the lungs, along with modestly improving lung injury severity. These preclinical results suggest that omadacycline may provide dual anti-bacterial and anti-inflammatory activities relevant to chronic lung infection treatment in PwCF.IMPORTANCENontuberculous mycobacteria, particularly Mycobacterium abscessus complex (MABSC), are a major concern for people with cystic fibrosis (PwCF) due to their association with deteriorating lung function. A substantial barrier to effective treatment is the limited number of safe and effective antibiotics. Omadacycline offers a potential advancement in managing MABSC infections in cystic fibrosis due to its activity, effective penetration into pulmonary secretions, improved tolerability, and good oral bioavailability as shown in healthy volunteers. Our study is the first to explore omadacycline's effects in a model of sterile lung inflammation and acute lung injury. We found that omadacycline not only has potent anti-bacterial properties but also exhibits anti-inflammatory effects, reducing lung inflammation and injury in our preclinical models. These findings underscore omadacycline's potential as a dual-action therapy for lung infections in PwCF, indicating significant potential to improve patient outcomes and guide more effective antimicrobial therapy decisions.

Prim-O-glucosylcimifugin alleviates influenza virus-induced pneumonia in mice by inhibiting the TGF-β1/PI3KCD/MSK2/RELA signalling pathway.

Prim-O-glucosylcimifugin (POG) is a chromone derived primarily from Saposhnikovia divaricata (Turcz) Schischk and Cimicifuga simplex. Previous research has shown that POG possesses antibacterial, anticancer, anti-inflammatory, antioxidant, anticonvulsant, antipyretic, and analgesic properties. However, the specific impact of POG on influenza-virus-induced pneumonia is not well understood. In this study, we investigated the protective effects and underlying mechanisms of POG in pneumonia caused by influenza A virus (IAV). In vitro, POG was found to have a protective effect against infections caused by the respiratory viruses respiratory syncytial virus (RSV), human coronavirus OC43, and influenza A virus. POG inhibited A/FM/1/1947(H1N1) infection with an EC50 ranging from 3.01 to 10.43 in vitro. Intraperitoneal infection of mice with POG at a dose of 5 or 10 mg/kg resulted in a reduction in IAV-induced pneumonia, as evidenced by decreased pulmonary edema, improved lung histopathology, and reduced inflammatory cell accumulation. At the higher dose (10 mg/kg), POG treatment significantly increased survival rates, decreased viral titres in the lungs, improved lung histology, and reduced lung inflammation in IAV-infected mice. POG also effectively alleviated pulmonary fibrosis by reducing the levels of fibrotic markers (hydroxyproline [Hyp] and transforming growth factor β1 [TGF-β1]) and suppressing the expression of alpha smooth muscle actin (α-SMA), p focal adhesion kinase (p-FAK), and TGF-β1 in lung tissues. In addition, POG inhibited the expression of the RELA proto-oncogene (RELA), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD), and mitogen- and stress-activated protein kinase 2 (MSK2) in lung tissues. These results indicate that POG may have a protective effect against IAV-induced pneumonia by downregulating the TGF-β1/PI3KCD/MSK2/RELA signalling pathway in the lungs.

Artificial intelligence to detect pulmonary congestion on chest computed tomography in consecutive dyspnoeic patients

Abstract Background Pulmonary congestion is a hallmark of acute heart failure (AHF), and essential for the diagnosis, treatment, and risk stratification. We have previously shown that a low-dose chest CT has four times greater odds than chest radiographs to detect pulmonary congestion. However, implementation is limited by shortage of radiologists. We hypothesized that artificial intelligence (AI) can detect pulmonary congestion on chest CT and aimed to develop and validate an AI-algorithm to detect pulmonary congestion on chest CT. Methods We extracted all chest CT-scans ordered acutely (N= 4840 unique patients) by medical departments at X Hospital from 2016-2021. A random subset of these CT-scans (N= 2187) was used to develop an AI-algorithm to detect pulmonary congestion, using the radiology reports as reference. The remaining subset (N= 1094) was used for internal validation. We externally validated the AI-algorithm in a different cohort (X), comprising of 236 consecutive dyspnoeic patients admitted to the emergency department, all examined with a low-dose, non-contrast chest CT (LDCT). The primary outcome was pulmonary congestion adjudicated by clinical on-call radiologists with access to the medical record, and two independent, blinded research thoracic radiologists. The default AHF thresholds for the optimal cut-off, rule-in threshold and rule-out threshold was established from the internal validation. Results Of 236 patients (median age 74 years, 57% male), 62 (26%), 64 (27%) and 60 (26%) had pulmonary congestion on LDCT evaluated by the on-call radiologists and the two thoracic research radiologists, respectively. The AI-algorithm included ten discriminating features of pulmonary congestion, and the results demonstrate an AUC of 0.95 [95%CI: 0.93-0.98] to predict pulmonary congestion by the on-call radiologists. The results were confirmed by the two expert research radiologists, with an AUC of 0.91 [95%CI: 0.88-0.95] and 0.94 [95%CI: 0.90-0.97], respectively. The sensitivity and specificity of the AI-default threshold was 89% [95%CI: 78-95%] and 89% [95%CI: 83-93%], respectively. The rule-in threshold demonstrated a sensitivity of 97% [95%CI: 86-100%] and the rule-out threshold had a specificity of 96% [95%CI: 92-98%], Figure 1. Conclusion We developed and validated a novel AI-algorithm with promising potential for the rapid automatic detection of pulmonary congestion as the underlying cause of dyspnoea in consecutive acute patients.

Is the female sex a risk factor for heart failure after myocardial infarction?

Abstract Background In previous observations, female sex was associated with heart failure after myocardial infarction (MI). However, women were older and had more risk factors and were not treated the same as men. Purpose Our aim was to investigate the differential impact of sex on heart failure (including cardiogenic shock) and outcome in a propensity score matched population with MI who had undergone percutaneous coronary intervention (PCI) and the association between sex, heart failure and long-term mortality. Methods Data from 3624 (30.6% women) MI patients who underwent PCI at our institution were analyzed. Propensity-score matching analysis was performed to adjust for differences in baseline characteristics between men and women. After propensity matching, the sample comprised 2170 patients (1085 women and 1085 men). Heart failure was defined by clinical criteria (bilateral pulmonary rales, S3 gallop, edema or cardiogenic shock) and/or pulmonary edema on chest X-ray and/or ejection fraction <30%. The data were analyzed using descriptive statistics. The median follow-up time was 27 months (25th, 75th percentile: 9,48). Results In hospital, 329 (16.4%) patients developed heart failure, with a similar incidence in men and women (156(15.5%) vs. 173(17.2%);p=0.33) (Figure 1). Furthermore, female sex was not associated with heart failure either univariately (OR 1.13;95%CI 0.89-1.43;p=0.31) or after adjustment for confounding factors (aOR 1.27;95% CI 0.96-1.66;p=0.093). Age, hypertension, hyperlipidemia, ST- elevation MI, and P2Y12 receptor inhibitors were associated with heart failure. We followed the patients for up to six years. At the end of the observation period, 330(16.4%) patients had died. The mortality rate was similar in both sexes (159(15.8%) men died compared to 171(17.0%) women; p=0.51) (Figure 2). In addition, sex was not associated with long-term mortality (aHR 1.11;95%CI 0.88-1.40;p=0.38) after adjusting for confounders. In-hospital heart failure was independently associated with long-term mortality (aHR 2.64;95%CI 2.04-3.41;p<0.0001). Hyperlipidemia, age, ST- elevation MI, radial access, P2Y12 receptor inhibitor and GFR were also associated with long-term mortality. Conclusions Our results suggest that sex itself is not associated with heart failure after MI when women are treated similarly to men, have similar risk factors, and are of similar age. It is more likely that women are more frequently affected by heart failure because they are older, have more risk factors, are less likely to be revascularized, and are less likely than men to be treated with guideline-recommended therapy,Heart failure in men and womenLong-term all-cause mortality

May right heart failure cause pulmonary congestion in pulmonary arterial hypertension?

Abstract Aims Recent studies have shown that lung ultrasound-assessed pulmonary congestion is worse in heart failure when pulmonary vascular resistance (PVR) is increased, suggesting a paradoxical relationship between right heart failure and increased lung water content. Accordingly, we wondered if lung ultrasound would reveal otherwise clinically silent pulmonary congestion in patients with pulmonary arterial hypertension (PAH). Methods and results All patients referred for suspicion of PAH in a tertiary center from January 2020 to December 2022 underwent a complete diagnostic work-up including echocardiography, lung ultrasound and right heart catheterization. Pulmonary congestion was identified by lung ultrasound B-lines using an 8-site scan. The study enrolled 102 patients with idiopathic PAH (mean age 53±13; 71% female). WHO functional classes I, II and III were found respectively in 2, 52 and 46% of them. The N-terminal-pro-brain natriuretic peptide (NT-proBNP) was 377 pg/mL [interquartile range, IQR 218, 906]. B-lines were identified in 77 out of 102 patients (75%), with a median of 3 [IQR: 1-5]. At univariable analysis B-lines were positively correlated to male sex, age, NT-proBNP, systolic PA pressure (sPAP), right atrial pressure (RAP), PVR, left ventricular end-diastolic volume and tricuspid annulus plane systolic excursion (TAPSE), and negatively to cardiac output and stroke volume. At multivariable analysis, RAP (p<0.001; Fig 1), TAPSE/sPAP (p=0.001), and NT-proBNP (p=0.04) were independent predictors of B-lines. Conclusion Lung ultrasound commonly discloses pulmonary congestion in PAH. This finding is related to right ventricle to pulmonary artery uncoupling, and may tentatively be explained by increased central venous pressure impeding lymphatic outflow.Figure 1

Heritable heart failure traits in mice undergoing early life stress

Abstract Introduction Adverse childhood experiences, known as early life stress (ELS), are associated with increased cardiovascular disease risk in later life, yet the underlying mechanisms remain elusive. Recent evidence indicates that parental life experiences can be transmitted to the offspring. Whether ELS exerts transgenerational effects on the heart is unknown. Purpose To investigate the effects of ELS on cardiac structure and function in exposed parents and in their offspring, across 3 generations. Methods We used a mouse model of ELS (MSUS) that mimics the exposure to traumatic experiences during childhood in humans. Mouse pups (F1) were separated from their mother (F0) unpredictably each day for 3 hours from postnatal day 1 (PND1) to PND14. During separation, dams were exposed to an additional unpredictable stressor by being subjected to either, a forced swim (18°C water for 5 minutes) or a 20-minute physical tube restraint, anytime (unpredictably) during the 3 hours. From PND15, mice are left undisturbed with their mother until PND21, are then raised normally until adulthood. Control litters were raised normally. A high-resolution Micro-Ultrasound System (Vevo 3100, Visualsonics) was used for the echocardiographic assessment at 6, 12 and 18 months both in the exposed animals (F0) as well as in their offspring (F1) and grandoffspring (F2). Both male and female mice were studied. Heart weight/tibia length and left ventricle weight/tibia length were used to assess cardiac mass while myocardial fibrosis was assessed by Masson's Trichrome and Picriosirius Red stainings. Lung congestion was assessed as lung wet/dry weight ratio. Single cell RNA sequencing (scRNAseq) was used in LV specimens from MSUS mice to unveil cell-specific transcriptional changes. Finally, MSUS mice underwent environmental enrichment (cages containing running wheels, maze) to investigate any rescuing effect on cardiac function. Results F1 mice displayed increased LV mass, impaired diastolic function, myocardial fibrosis and lung congestion. A time-dependent worsening of cardiac performance was observed from 6 to 18 months, both in males and females. ScRNAseq unveiled dysregulation of transcriptional programs underlying inflammation and lipotoxicity in the cardiomyocyte and endothelial cell clusters. The MSUS offspring did not show changes of cardiac function at 6 months, however diastolic dysfunction and lung congestion were observed at 12 and 18 months. A similar impairment of cardiac function was observed in the MSUS grandoffspring (F3). Of interest, 6-week exposure to an environmental enrichment protocol was able to improve LV mass, diastolic function and lung congestion in 12 months-old MSUS mice. Conclusions ELS induces a transgenerational transmission of cardiac phenotypic alterations which can be rescued by EE. Our results shed light on the potential role of ELS on heart failure development and potential mitigation strategies.

Left ventricular dysfunction, pulmonary congestion, or both and cardiovascular risk after acute myocardial infarction

Abstract Background Patients with acute myocardial infarction (AMI) complicated by left ventricular systolic dysfunction (LVSD), pulmonary congestion, or both are at increased risk for adverse cardiovascular events, including long-term heart failure. The EMPACT-MI trial studied the efficacy and safety of early initiation of a sodium-glucose cotransporter-2 inhibitor (SGLT2i) in this population. We set out to evaluate the contemporary real-world risk associated with AMI presenting with LVSD and/or congestion and the projected impact of implementing early SGLT2i post-MI across the spectrum of risk. Purpose To evaluate the independent risk of presenting with LVSD, congestion, or both in patients with AMI. We will further explore the potential impact of the implementation of early initiation of SGLT2i in real-world clinical practice. Methods We conducted a retrospective population-based cohort study in Ontario, Canada, analyzing AMI hospitalizations from April 2009 to March 2022, emulating the EMPACT-MI trial cohort. Patients that survived to hospital discharge were stratified by baseline presentation with LVSD (defined as LVEF<50%), signs or symptoms of congestion or both and compared with a referent group without either risk factor (none). Exclusion criteria were previously established heart failure, prior SGLT2i use, eGFR < 20 ml/min/1.73m2 or chronic dialysis. The primary outcome was a composite of HF hospitalization or all-cause mortality at 30 days and 1 year. We used a multivariable logistic regression model to report an odds ratio (OR) and 95% confidence intervals (CI) adjusted for clinical risk factors. Results Among 36,837 AMI patients, 3% presented with congestion, 55% with LVSD, 10% with both, and 32% with none. Age/sex-adjusted 30-day event rates for the primary endpoint were 30%, 22%, 57%, and 7%, respectively. The corresponding adjusted ORs were 3.34 (95% CI: 2.05-5.46) for congestion, 3.58 (95% CI: 2.72-4.71) for LVSD, and 7.01 (95% CI: 5.09-9.65) for both, versus the reference group (none) (Figure 1). At year 1, a similar pattern of risk was observed (Figure 2). Based on the results of the EMPACT-MI trial being reported at the ACC conference in April 2024, relative and absolute risk differences in outcomes with implementation of early initiation of SGLT2i post-MI in real-world clinical practice across the spectrum of presentation will be reported. Conclusion Patients presenting with pulmonary congestion and/or LVSD remain at high risk of adverse cardiovascular events following AMI. This high-risk group represents an unmet need with a potential impact for improvement with novel interventions such as SGLT2i.

Risk factors for delirium in patients aged 60 years and over with recent myocardial infarction

Abstract Introduction Delirium is a form of acute brain dysfunction and geriatric patients are particularly vulnerable to this health problem. Modifiable and unmodifiable risk factors may influence delirium appearance. Purpose The study aimed to assess the prevalence and characteristic of delirium risk factors in patients ≥ 60 years of age hospitalized due to acute myocardial infarction (AMI). Methods The study included 405 consecutive patients (mean age: 73.1[8.5], males: 248/61.2 %) hospitalized due to AMI divided and characterized according to the in-hospital delirium presence. The following sets of data were analysed: demographic data, length of hospitalization, type of AMI, coronary intervention, multimorbidity, accompanying symptoms, psychiatric conditions, and pharmacotherapy used. Results Of 405 patients, 57 (14%, mean age: 80.9[7.3] years, males: 33/58%) experienced delirium. Patients with delirium were older (80.9[7.3] vs 71.82[8.1] years), all of them presented multimorbidity, they more frequently used polypharmacy (96.5 vs 30.2%) and their hospitalization was longer (8.0[1.4] vs 4.6[1.0] days) as compared to the patients without delirium. Patients with delirium more frequently experience in-hospital reversible problems: periprocedural complications (limited number of radial access, prolonged compression and pain after the procedure, pseudoaneurysm of femoral artery, as well as the following accompanying symptoms: fever (40.4% vs 0.9%), infections (78.9% vs 3.7%), pulmonary oedema (73.7% vs 0.6%), hypoxemia (91.1% vs 98.3%), urinary catheter (96.5% vs 17.2%), dehydration (89.5% vs 6.6%), and insomnia (71.9% vs 0.3%) compared to patients without delirium (Table 1). Delirium was also associated with mild (49.1% vs 0.3%, p<0.0001) and moderate (47.4% vs 9.2%) dementia and symptoms of mild depression (59.6% vs 2.3%) (P<0.0001 for all). Valvular heart disease (OR=4.78; 95%CI: 1.10-2.70; p<0.0001, pulmonary oedema (OR=66.79; 95%CI: 12.04-370.34, p<0.001), and dehydration (OR=37.26; 95%CI: 10.50-132.27, p<0.001) were risk factors for delirium occurrence. Analysis of all factors related to delirium revealed that the coexistence of ≥ 11 concerned 44% of the delirium population (Table 1). Conclusions The in-hospital course of AMI is complicated by delirium occurrence in 14% of patients ≥ 60 years old. Multimorbidity and polypharmacy regard most of the subjects with delirium. The potent reversible complications of the in-hospital course of AMI associated with delirium should be recognized and limited to prevent this problem.Table1.Number of delirium risk factors.

A new hydration strategy can reduce contrast-induced acute kidney injury after PCI in patients with chronic heart failure and chronic kidney disease: a two-center randomized controlled trial

Abstract Backgrounds Adequate hydration is crucial for preventing contrast-induced acute kidney injury (CI-AKI), particularly in patients with chronic kidney disease (CKD). The current guidelines recommend half-volume hydration for patients with chronic heart failure (CHF) to prevent pulmonary edema. Thus, it is challenging to administer hydration therapy in patients with CHF and CKD. This study was aimed to compare different hydration strategies in this subset of patients. Methods This two-center, open-label, randomized clinical trial enrolled 303 CHF (patients with elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion) patients with CKD (estimated glomerular filtration rate [eGFR] of 15-60 mL/min/1.73m2) undergoing selective coronary angiography (CAG) from two tertiary hospitals from October 2020 to December 2023. Patients were randomized into three groups: half-volume hydration group (HH group, 0.5 mL/Kg/h hydration), standard hydration group (SH group, 1 mL/Kg/h hydration), and standard hydration with diuretic group (SH+D group, 1 mL/Kg/h hydration + immediate postoperative intravenous injection of furosemide 20 mg). All patients received hydration from 6 to 12 hours before to 24 hours after the procedure. The primary endpoint was CI-AKI, defined as a serum creatinine (SCr) increase of more than 0.3 mg/dL or 1.5-1.9 times greater than the baseline 48-72 hours after CAG. Safety endpoints included pulmonary edema during hydration, perioperative mortality, and the need for dialysis. Results A total of 101 patients were included in each group. Baseline characteristics (mean age, proportion of males, left ventricular ejection fraction and eGFR) were similar among groups. SCr, cystatin C levels, and SCr level changes between 48 and 72 hours after procedure did not significantly differ among groups (P > 0.05). The incidence of CI-AKI was highest in the HH group (22.8%), lowest in the SH+D group (11.9%), and intermediate in the SH group (17.8%) (P = 0.041). Regarding safety endpoints, there were 2 patients in the HH group, 3 patients in the SH group and 1 patient in the SH+D group experienced heart failure or pulmonary edema during hydration, with no statistically significant differences among the groups (P = 0.874). Perioperative mortality occurred in 1 patient in the HH group and 2 patients in the SH+D group, with no statistically significant differences (P = 0.776). No patient required renal replacement therapy. Conclusions In CHF patients with CKD, the half-volume hydration regimen recommended by guidelines was associated with a higher incidence of CI-AKI compared to standard hydration. However, standard hydration combine with diuretic fails to reduce the risk of heart failure during hydration or perioperative mortality, even if this novel strategy does not increase the risk of CI-AKI compared to standard hydration therapy.

The BET inhibitor Apabetalone protects against heart failure with preserved ejection fraction by suppressing myocardial inflammation

Abstract Background Posttranslational histone modifications, play a major role in cardiac hypertrophy and dysfunction. Apabetalone (APA), a selective inhibitor of bromodomain and extraterminal containing protein family (BET) proteins, prevents bromodomain-containing protein 4 (BRD4) interactions with chromatin thus modulating transcriptional programs in different organs. Purpose We sought to investigate whether APA could be beneficial in cardiometabolic heart failure with preserved ejection fraction (cHFpEF). Methods Mice were subjected to high fat diet feeding and L-NAME treatment for 15 weeks to induce cHFpEF. Histology, mouse echocardiography (Vevo3100) and Treadmill exhaustion test were performed. Unbiased gene expression profiling by PCR array and proteomics analysis (Olink) was employed in left ventricular (LV) myocardial specimens from HFpEF mice and control animals. Cultured cardiomyocytes (CMs) treated with palmitic acid (PA) were used as an in vitro model of metabolic stress. cHFpEF mice were chronically treated with the BET inhibitor APA (150mg/kg/day) or vehicle (DMSO). In order to translate our findings to the human setting, passive stiffness of skinned CMs collected from cHFpEF patients was assessed before and after APA treatment. Results HFpEF mice displayed LV hypertrophy, diastolic dysfunction, myocardial fibrosis, lung congestion and impaired exercise tolerance as compared to controls. Interestingly, diastolic dysfunction - assessed by E/A ratio and isovolumic relaxation time (IVRT) - and lung congestion were significantly reduced in HFpEF mice treated with APA, while exercise tolerance was improved. Transcriptomic analysis in PA-treated CMs and LV mouse specimens from cHFpEF mice showed a profound deregulation of genes controlling inflammation, namely IL-6, TNF-alpha, and IL-1beta. ChIP assays showed BRD4 occupancy on the promoter of several inflammatory genes, including IL6. Treatment with APA suppressed most of inflammatory genes, with a pronounced effect on IL6 expression. Moreover, APA reduced circulating levels of several inflammatory chemokines. The beneficial effects of APA were explained by modulation of IL-6/CaMKII/STAT3 pathway both in cHFpEF hearts and PA-treated CMs. In skinned CMs from cHFpEF patients, both APA and IL6 blockade were able to attenuate passive stiffness. Conclusions Our findings set the stage for preclinical studies and exploratory clinical trials testing APA in patients with cHFpEF.

Progress in cytokine research for ARDS: A comprehensive review.

Acute respiratory distress syndrome (ARDS) is a critical form of acute respiratory failure characterized by diffuse alveolar damage, refractory hypoxemia, and non-cardiogenic pulmonary edema, resulting in high mortality. Dysregulated inflammation, driven by cytokines, is central to ARDS pathogenesis, progression, and prognosis. This review synthesizes current knowledge on the role of cytokines in ARDS and evaluates their potential as therapeutic targets, offering new insights for clinical management. A comprehensive analysis of recent studies was conducted to explore the roles of pro-inflammatory cytokines (e.g., IL-1β, IL-6, IL-8) and anti-inflammatory cytokines (e.g., IL-10, IL-22) in ARDS pathogenesis and to assess current and emerging therapies targeting these cytokines. Pro-inflammatory cytokines are crucial in initiating inflammatory responses and lung injury in early ARDS, while anti-inflammatory cytokines help regulate and resolve inflammation. Targeted therapies, such as IL-1 and IL-6 inhibitors, show potential in managing ARDS, particularly in COVID-19, but their clinical efficacy is still debated. Combination therapy strategies may enhance outcomes, but further large-scale, multicenter randomized controlled trials are required to establish their safety and efficacy. Understanding cytokine regulation in ARDS could lead to innovative therapeutic approaches. Future research should focus on cytokine roles across ARDS subtypes and stages and develop biomarker-driven, individualized treatments.

Prognostic value of alveolar surfactant type-B in acute heart failure: a long-term comparative analysis vs NT-proBNP

Abstract Background In heart failure (HF) biomarkers are an integral component of prognostic assessment. Natriuretic peptides are the gold standard, but they do not directly reflect lung vascular injury. Surfactant type B (Surf-B) is released by type 2 alveolar cells under pressure induced trauma, with few reports just addressing its plasmatic levels in stable chronic HF (CHF). Information on acute HF (AHF) is lacking. Purpose To clarify the prognostic value of Surf-B changes vs NT-proBNP levels after decongestion therapy and to compare their prognostic ability at 1-year follow-up. Methods Patients with acute pulmonary edema (APE) underwent a combined evaluation of Surf-B and NT-proBNP serum levels with quantification of B-lines at hospital admission (time 0), discharge (time 1) and at 1 year (time 2). Results 54 patients (mean age 72.1 ± 11 years; mean LVEF 36% ± 13%; 65% men) were enrolled. At time 1, the average Surf-B, NT-proBNP and B-lines were significantly reduced compared to time 0 (p<0.0001). No correlation between Surf-B and NT-proBNP was observed either at time 0 (r=-0.21; p=0.12) or at time 1 (r=0.05; p=0.71). Despite the significant decrease in Surf-B levels from time 0 to time 1, 18.5% of patients behaved as non-responders exhibiting no changes in Surf-B; conversely, only 5.5% did not show significant reduction in NT-proBNP, despite significant decongestion. 38 patients were followed up to time 2: of these, 13 (34%) reached the composite endpoint of death or hospitalization for HF. Surf-B measured at time 1 was a strong predictor of adverse outcome. Patients with Surf-B above median at discharge displayed a worse survival-free from HF hospitalization compared to the remainders (Log rank p=0.012) (Figure). Also, patients with Surf-B above median at discharge had a more than 4-fold increased risk of the composite endpoint (HR 4.5, 95%CI 1.4-20.2, p=0.023). Conversely, NT-proBNP at discharge was not significantly associated with HF-free survival (Log rank p=0.26) (Figure) and was not a significant predictor of the composite outcome (HR 1.9, 95%CI 0.6-9.3, p=0.25). At ROC analysis, discharge Surf-B levels showed a higher area under the curve (AUC=0.763, p=0.011) than NT-proBNP values (AUC=0.69, p=0.063). Conclusions These data suggest that Surf-B, an organ specific biomarker of lung injury, is highly sensitive to the effectiveness of decongestion therapy, outperforming NT-proBNP. Given the high rate of patients who do not improve their Surf-B levels over time, the reparative processes of alveolar break damage may dissociate from mere decongestion and cardiac healing in AHF.Figure:1yr Kaplan-Meier survival curves