Mechanisms of the septic heart: From inflammatory response to myocardial edema.

Sepsis-induced myocardial dysfunction (SIMD), also known as sepsis-induced cardiomyopathy (SICM), is linked to significantly increased mortality. Despite its clinical importance, effective therapies for SIMD remain elusive, largely due to an incomplete understanding of its pathogenesis. Over the past five decades, research involving both animal models and human studies has highlighted several pathogenic mechanisms of SICM, yet many aspects remain unexplored. Initially thought to be primarily driven by inflammatory cytokines, current research indicates that these alone are insufficient for the development of cardiac dysfunction. Recent studies have brought attention to additional mechanisms, including excessive nitric oxide production, mitochondrial dysfunction, and disturbances in calcium homeostasis, as contributing factors in SICM. Emerging clinical evidence has highlighted the significant role of myocardial edema in the pathogenesis of SICM, particularly its association with cardiac remodeling in septic shock patients. This review synthesizes our current understanding of SIMD/SICM, focusing on myocardial edema's contribution to cardiac dysfunction and the critical role of the bradykinin receptor B1 (B1R) in altering myocardial microvascular permeability, a potential key player in myocardial edema development during sepsis. Additionally, this review briefly summarizes existing therapeutic strategies and their challenges and explores future research directions. It emphasizes the need for a deeper understanding of SICM to develop more effective treatments.

Post-diuretic spot urine sodium assessment in acute heart failure: a retrospective analysis.

AIMS: To provide real-world data on post-diuretic spot urine sodium concentration (UNa) assessment in acute heart failure (AHF) and its implications for treatment. METHODS AND RESULTS: Automated query of the electronic medical record identified patients admitted to the cardiac intensive care unit of a single tertiary care hospital between November 2018 and December 2021, who received intravenous loop diuretics. Detailed manual chart review confirmed the AHF diagnosis. Stratification was performed based on whether post-diuretic UNa was assessed within 24 h of admission. AHF was confirmed in 340/380 identified patients. Post-diuretic UNa was assessed in 117 (34%), more frequently when ejection fraction was reduced and heart failure more advanced. Patients with versus without post-diuretic UNa assessment received higher doses of intravenous loop diuretics and more frequently acetazolamide and thiazide-like diuretics (p < 0.001 for all), resulting in similar urine output despite more advanced heart failure [2,488 mL (1,740-4,033 mL) vs. 2,400 mL (1,553-3,250 mL), respectively; p = 0.170]. Diuretic therapy remained more intense at discharge in the post-diuretic UNa group, with also a higher prescription rate of angiotensin-neprilysin inhibitors (p = 0.021). Serum creatinine increases/decreases were similarly frequent irrespectively from UNa assessment, with more dynamic changes observed in patients with UNa ≤ 80 mmol/L versus ≥ 81 mmol/L. After adjustments for baseline characteristics, the risk for death or heart failure readmission was similar in patients with versus without UNa assessment [HR (95%CI) = 1.43 (0.88-2.32); p = 0.150]. CONCLUSION: Post-diuretic UNa assessment in AHF was associated with more intense diuretic regimens, preserving urine output despite its use in a sicker population.

Lung ultrasound and diuretic therapy in chronic heart failure: a randomised trial.

BACKGROUND: Lung congestion is frequent in heart failure (HF) and is associated with symptoms and poor prognosis. Lung ultrasound (LUS) identification of B-lines may help refining congestion assessment on top of usual care. Three small trials comparing LUS-guided therapy to usual care in HF suggested that LUS-guided therapy could reduce urgent HF visits. However, to our knowledge, the usefulness of LUS in influencing loop diuretic dose adjustment in ambulatory chronic HF has not been studied. AIMS: To study whether to show or not LUS results to the HF assistant physician would change loop diuretic adjustments in "stable" chronic ambulatory HF patients. METHODS: Prospective randomised single-blinded trial comparing two strategies: (1) open 8-zone LUS with B-line results available to clinicians, or (2) blind LUS. The primary outcome was change in loop diuretic dose (up- or down-titration). RESULTS: A total of 139 patients entered the trial, 70 were randomised to blind LUS and 69 to open LUS. The median (percentile25-75) age was 72 (63-82) years, 82 (62%) were men, and the median LVEF was 39 (31-51) %. Randomisation groups were well balanced. Furosemide dose changes (up- and down-titration) were more frequent among patients in whom LUS results were open to the assistant physician: 13 (18.6%) in blind LUS vs. 22 (31.9%) in open LUS, OR 2.55, 95%CI 1.07-6.06. Furosemide dose changes (up- and down-titration) were more frequent and correlated significantly with the number of B-lines when LUS results were open (Rho = 0.30, P = 0.014), but not when LUS results were blinded (Rho = 0.19, P = 0.13). Compared to blind LUS, when LUS results were open, clinicians were more likely to up-titrate furosemide dose if the result "presence of pulmonary congestion" was identified and more likely to decrease furosemide dose in the case of an "absence of pulmonary congestion" result. The risk of HF events or cardiovascular death did not differ by randomisation group: 8 (11.4%) in blind LUS vs. 8 (11.6%) in open LUS. CONCLUSIONS: Showing the results of LUS B-lines to assistant physicians allowed more frequent loop diuretic changes (both up- and down-titration), which suggests that LUS may be used to tailor diuretic therapy to each patient congestion status.

Effect of SGLT2 Inhibitor on Cardiomyopathy in a Rat Model of T2DM: Possible involvement of Cardiac Aquaporins.

Diabetic cardiomyopathy (DCM) causes arrhythmia, heart failure, and sudden death. Empagliflozin, an SGLT-2 (Sodium glucose co-transporter) inhibitor, is an anti-diabetic medication that decreases blood glucose levels by stimulating urinary glucose excretion. Several aquaporins (AQPs) including AQP-1-3 and - 4 and their involvement in the pathogenesis in different cardiac diseases were detected. In the current study the effect of Empagliflozin on diabetic cardiomyopathy and the possible involvement of cardiac AQPs were investigated. METHODS: 56 adult male Sprague-Dawley rats were divided into 4 groups: Control, DCM: type 2 diabetic rats, low EMPA+DCM received empagliflozin (10 mg/kg/day) and high EMPA+DCM received empagliflozin (30 mg/kg/day) for 6 weeks. RESULTS: Administration of both EMPA doses, especially in high dose group, led to significant improvement in ECG parameters. Also, a significant improvement in biochemical and cardiac oxidative stress markers (significant decrease in serum CK-MB, and malondialdehyde while increasing catalase) with decreased fibrosis and edema in histopathological examination and a significant attenuation in apoptosis (caspase-3) and edema (AQP-1& -4). CONCLUSION: Both doses of Empagliflozin have a cardioprotective effect and reduced myocardial tissue edema with high dose having a greater effect. This might be due to attenuation of oxidative stress, fibrosis and edema mediated through AQP-1, - 3& - 4 expression.

Case Report: Right Heart Failure Mistaken for Obesity-A Fault of Telemedicine.

As a result of the COVID-19 pandemic, telemedicine has become an important branch of healthcare worldwide. Apart from their undeniable advantages, the virtual visits lack physical examination, which can lead to important diagnostic mistakes. We hereby present a case of a pediatric patient whose weight gain, initially attributed to a sedentary lifestyle was, in fact, due to sub-acute right heart failure in the context of a ruptured sinus of Valsalva aneurysm. The condition was not diagnosed until the patient presented at the emergency. The boy was successfully treated with two percutaneous interventions and returned to his previous stature.

Assessment of Patient Knowledge, Awareness, and Adherence in Heart Failure in a Real-Life Setting: Insights from Data Acquired in Pharmacies.

BACKGROUND: Patient knowledge is crucial for managing and/or monitoring patients with heart failure (HF). However, "real-life" evidence of knowledge level and awareness in HF is yet to be explored. We assessed unselected HF patients' knowledge and awareness in a pharmacy setting. METHODS: One hundred eight HF patients (mean age [SD], 70 (12) years, 61% men) were studied in pharmacies in the north-east region of France in 2019. All patients were interviewed by their pharmacist to quantify their knowledge in HF, self-assessment of symptoms of congestion, as well as their adherence to HF treatment and guideline-recommended lifestyle. RESULTS: Overall, 40% of patients had not consulted their cardiologist in the past 6 months, and 89% never underwent an HF education program. Regarding HF knowledge, nearly half were unsure whether they had HF (43.5%). Only half of the patients knew how to self-assess HF symptoms (57.4%), while a quarter (25%) were unsure of the purpose of HF medications. CONCLUSIONS: In patients with HF assessed in their pharmacies, a majority lacked fundamental knowledge regarding HF, such as self-assessment of congestion, possibly due to a minimal proportion of patients undergoing an HF education program. These results suggest that interventions led by pharmacies may help improve HF education coverage in patients who may have poor access to specialized care.

Vertical Artifacts in Lung Ultrasonography: Some Common Clinician Questions and the Related Engineer Answers.

INTRODUCTION: Vertical artifacts, including B lines, are frequently seen in a variety of lung diseases. Their sonomorphology varies in length, width, shape, and internal reverberations. The reason for this diversity is still unknown and is the cause of discussion between clinicians and ultrasound physics engineers. AIM: The aim of this work is to sum up the most common clinician observations and provide an explanation to each of them derived from ultrasound physics. MATERIALS AND METHODS: Based on clinical and engineering experiences as well as data collected from relevant literature, the sonomorphology of vertical artifacts was analyzed. Thirteen questions and answers were prepared on the common sonomorphology of vertical artifacts, current nomenclature, and clinical observations. CONCLUSIONS: From a clinical standpoint, the analysis of vertical artifacts is very important and requires that further clinical studies be conducted in cooperation with engineers who specialize in physics.

Head-to-head comparison of diagnostic scores for acute heart failure in the emergency department: results from the PARADISE cohort.

BREST and PREDICA scores have recently emerged for the diagnosis of acute heart failure (AHF) in the emergency department (ED). This study aimed to perform a head-to-head comparison in a large contemporary cohort. BREST and PREDICA scores were calculated from, respectively, 11 and 8 routine clinical variables recorded in the ED in 1386 patients from the PArADIsE cohort. The diagnostic performance of the scores for adjudicated AHF diagnosis was assessed by the area under the ROC curve (AUC). Acute HF diagnosis was adjudicated according to the European Society of Cardiology criteria and BNP levels. A BREST score ≤ 3 or PREDICA score ≤ 1 was associated with low probabilities of AHF (5.7% and 2.6%, respectively). Conversely, a BREST score ≥ 9 or PREDICA score ≥ 5 was associated with a high risk of AHF diagnosis (77.3% and 66.9%, respectively) although more than half of the population was within the "gray zone" (4-8 and 2-4 for the BREST and PREDICA scores, respectively). Diagnostic performances of both scores were good (AUC 79.1%, [66.1-82.1] for the BREST score and 82.4%, [79.8-85.0] for the PREDICA score). PREDICA score had significantly higher diagnostic performance than BREST score (increase in AUC 3.3 [0.8-5.8], p = 0.009). Our study emphasizes the good diagnostic performance of both BREST and PREDICA scores, albeit with a significantly higher diagnostic performance of the PREDICA score. Yet, more than half of the population was classified within the "gray zone" by these scores; additional diagnostic tools are needed to ascertain AHF diagnosis in the ED in a majority of patients. Clinical trial registration: NCT02800122.

Cardiac MRI findings in patients with Crohn's disease.

BACKGROUND: Early cardiac death is more common in patients with Crohn's disease (CD) than in healthy adults, but the exact cause is unknown. AIMS: The aim of this study is to investigate the cardiac magnetic resonance imaging (MRI) findings in patients with CD and compare the MRI findings with healthy controls (HCs). This study also aimed to demonstrate the possible cardiac involvement in patients with CD using MRI. METHODS: In this prospective study, participants with CD (n = 20) and HC (n = 20) underwent cardiac MRI. Erythrocyte sedimentation rate (ESR) and hematocrit levels were investigated before MRI in both groups. Two observers evaluated the ventricular functional and morphological parameters in consensus. Myocardial T1/T2-relaxation times were calculated by two observers independently using two different software, and hematocrit-corrected left ventricle extracellular volume (LV-ECV) was calculated. Observer-2 also performed histogram analysis for T1/T2-mapping images. RESULTS: Patients with CD had a significantly higher LV-ECV, mildly decreased right ventricle ejection fraction, and prolonged T2-relaxation time than HC. Moreover, histogram analysis showed that the maximum and mean T2-relaxation times were higher in patients with CD. There was an excellent agreement between observers for the assessment of mean native and post-contrast T1-relaxation time (intraclass correlation coefficient (ICC) of 0.991 and ICC of 0.941, respectively) and mean T2-relaxation time measurements (ICC of 0.983). Moreover, mean T2-relaxation time was found to be significantly correlated with ESR. CONCLUSIONS: This study suggests visually undetectable myocardial involvement due to chronic systemic inflammation in patients with Crohn's disease. Cardiac MRI can help assess and monitor cardiac involvement in patients with CD.

Intravenous Mineralocorticoid Receptor Antagonist Use in Acutely Decompensated Heart Failure with Diuretic Resistance.

Intravenous mineralocorticoid receptor antagonists (MRAs) have been used in some centers for decades to reduce the risk of hypokalemia and boost diuresis in acutely decompensated heart failure (ADHF). We report the well-tolerated use of intravenous MRAs as a rescue procedure in 3 patients admitted for ADHF with important diuretic resistance. Undertaking trials evaluating the effect of this therapeutic strategy in ADHF could represent a promising avenue.

Association between right-sided cardiac function and ultrasound-based pulmonary congestion on acutely decompensated heart failure: findings from a pooled analysis of four cohort studies.

BACKGROUND: Right ventricular (RV) dysfunction and RV-pulmonary artery (PA) uncoupling are associated with the development of pulmonary congestion during exercise. However, there is limited information regarding the association between these right-sided cardiac parameters and pulmonary congestion in acutely decompensated heart failure (HF). METHODS: We performed an individual patient meta-analysis from four cohort studies of hospitalized patients with HF who had available lung ultrasound (B-lines) data on admission and/or at discharge. RV function was assessed by tricuspid annular plane systolic excursion (TAPSE), RV-PA coupling was defined as the ratio of TAPSE to PA systolic pressure (PASP). RESULTS: Admission and discharge cohort included 319 patients (75.8 ± 10.1 years, 46% women) and 221 patients (77.9 ± 9.0 years, 47% women), respectively. Overall, higher TAPSE was associated with higher ejection fraction, lower PASP, b-type natriuretic peptide and B-line counts. By multivariable analysis, worse RV function or RV-PA coupling was associated with higher B-line counts on admission and at discharge, and with a less reduction in B-line counts from admission to discharge. Higher B-line counts at discharge were associated with a higher risk of the composite of all-cause mortality and/or HF re-hospitalization [adjusted-HR 1.13 (1.09-1.16), p < 0.001]. Furthermore, the absolute risk increase related to high B-line counts at discharge was higher in patients with lower TAPSE. CONCLUSIONS: In patients with acutely decompensated HF, impaired RV function and RV-PA coupling were associated with severe pulmonary congestion on admission, and less resolution of pulmonary congestion during hospital stay. Worse prognosis related to residual pulmonary congestion was enhanced in patients with RV dysfunction. TAPSE, tricuspid annular plane systolic excursion; PASP, pulmonary artery systolic pressure.

Proteomic Identification Reveals the Role of Ciliary Extracellular-Like Vesicle in Cardiovascular Function.

Primary cilia are shown to have membrane swelling, also known as ciliary bulbs. However, the role of these structures and their physiological relevance remains unknown. Here, it is reported that a ciliary bulb has extracellular vesicle (EV)-like characteristics. The ciliary extracellular-like vesicle (cELV) has a unique dynamic movement and can be released by mechanical fluid force. To better identify the cELV, differential multidimensional proteomic analyses are performed on the cELV. A database of 172 cELV proteins is generated, and all that examined are confirmed to be in the cELV. Repressing the expression of these proteins in vitro and in vivo inhibits cELV formation. In addition to the randomized heart looping, hydrocephalus, and cystic kidney in fish, compensated heart contractility is observed in both fish and mouse models. Specifically, low circulation of cELV results in hypotension with compensated heart function, left ventricular hypertrophy, cardiac fibrosis, and arrhythmogenic characteristics, which result in a high mortality rate in mice. Furthermore, the overall ejection fraction, stroke volume, and cardiac output are significantly decreased in mice lacking cELV. It is thus proposed that the cELV as a nanocompartment within a primary cilium plays an important role in cardiovascular functions.

Practical management of worsening renal function in outpatients with heart failure and reduced ejection fraction: Statement from a panel of multidisciplinary experts and the Heart Failure Working Group of the French Society of Cardiology.

Renal function is often affected in patients with chronic heart failure with reduced ejection fraction (HFrEF). The complex interplay between heart and renal dysfunction makes renal function and potassium monitoring mandatory. Renin-angiotensin-aldosterone system (RAAS) blockers are a life-saving treatment for patients with HFrEF, regardless of worsening renal function. Uptitration to the maximum-tolerated dose should be a constant goal. This simple fact is all too often forgotten (only 30% of patients with heart failure receive the target dosage of RAAS blockers), and the RAAS blocker effect on renal function is sometimes misunderstood. RAAS blockers are not nephrotoxic drugs as they only have a functional effect on renal function. In many routine clinical cases, RAAS blockers are withheld or stopped because of this misunderstanding, combined with suboptimal assessment of the clinical situation and underestimation of the life-saving effect of RAAS blockers despite worsening renal function. In this expert panel, which includes heart failure specialists, geriatricians and nephrologists, we propose therapeutic management algorithms for worsening renal function for physicians in charge of outpatients with chronic heart failure. Firstly, the essential variables to take into consideration before changing treatment are the presence of concomitant disorders that could alter renal function status (e.g. infection, diarrhoea, hyperthermia), congestion/dehydration status, blood pressure and intake of nephrotoxic drugs. Secondly, physicians are invited to adapt medication according to four clinical scenarios (patient with congestion, dehydration, hypotension or hyperkalaemia). Close biological monitoring after treatment modification is mandatory. We believe that this practical clinically minded management algorithm can help to optimize HFrEF treatment in routine clinical practice.

The effect of sphingosine-1-phosphate on the endothelial glycocalyx during ischemia-reperfusion injury in the isolated rat heart.

OBJECTIVE: Sphingosine-1-phosphate is a natural metabolite that is cardioprotective, but its effects on endothelial glycocalyx damage during ischemia-reperfusion are unknown. Therefore, we investigated the effect of sphingosine-1-phosphate on the endothelial glycocalyx during ischemia-reperfusion. METHODS: Isolated hearts from Wistar rats were perfused on a Langendorff system with Krebs-Henseleit buffer and pretreated with sphingosine-1-phosphate (10 nmol/L) before ischemia-reperfusion. Infarct size was measured by triphenyl tetrazolium chloride staining (n ≥ 6 per group). Cardiac edema was assessed by calculating total water content (n = 7 per group) and histologically quantifying the interstitial compartment (n ≥ 3 per group). The post-ischemic coronary release of syndecan-1 was quantified using ELISA. Syndecan-1 immunostaining intensity was assessed in perfusion-fixed hearts (n ≥ 3 per group). RESULTS: Pretreatment with sphingosine-1-phosphate decreased infarct size in isolated hearts subjected to ischemia-reperfusion (P = .01 vs ischemia-reperfusion). However, sphingosine-1-phosphate had no effect on syndecan-1 levels in the coronary effluent or on the intensity of the syndecan-1 immunostaining signal in cardiac tissue. Heart total water content was not significantly different between control and ischemic groups but was significantly decreased in hearts treated with sphingosine-1-phosphate alone. CONCLUSION: These results suggest that sphingosine-1-phosphate-induced cardioprotection against ischemia-reperfusion injury is not mediated by the maintenance of syndecan-1 in the endothelial glycocalyx.

Comparison of Body Weight Trend Algorithms for Prediction of Heart Failure Related Events in Home Care Setting.

BACKGROUND: Automatic event detection is used in telemedicine based heart failure disease management programs supporting physicians and nurses in monitoring of patients' health data. OBJECTIVES: Analysis of the performance of automatic event detection algorithms for prediction of HF related hospitalisations or diuretic dose increases. METHODS: Rule-Of-Thumb and Moving Average Convergence Divergence (MACD) algorithm were applied to body weight data from 106 heart failure patients of the HerzMobil-Tirol disease management program. The evaluation criteria were based on Youden index and ROC curves. RESULTS: Analysis of data from 1460 monitoring weeks with 54 events showed a maximum Youden index of 0.19 for MACD and RoT with a specificity > 0.90. CONCLUSION: Comparison of the two algorithms for real-world monitoring data showed similar results regarding total and limited AUC. An improvement of the sensitivity might be possible by including additional health data (e.g. vital signs and self-reported well-being) because body weight variations obviously are not the only cause of HF related hospitalisations or diuretic dose increases.