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Congestion is one of the main predictors of poor outcome in patients with heart failure (HF). Assessing and monitoring congestion is essential for optimizing HF therapy. Among the various available methods, serial measurements of estimated plasma volume (ePVS) using routine blood count and/or body weight (e.g., the Strauss, Duarte, Hakim formulas) may be useful in HF management. Further prospective study is warranted to determine whether ePVS can help optimize decongestion therapy (loop diuretics, mineralocorticoid receptor antagonists, SGLT2i) in various HF settings. This narrative review summarizes the recent evidence supporting the association of ePVS with clinical congestion and outcome(s) and discusses future directions for monitoring ePVS in HF. Graphic abstract

In patients with cryptogenic stroke and patent foramen ovale with atrial septal aneurysm or large interatrial shunt, closure of the PFO and administration of antiplatelet medications resulted in a lower rate of recurrent stroke than antiplatelet therapy alone.

ObjectiveThe primary objective was to assess the characteristics and prognosis of pyogenic spondylodiscitis (PS) in patients with infective endocarditis (IE). The secondary objectives were to assess the factors associated with occurrence of PS.MethodsProspective case–control bi-centre study of 1755 patients with definite IE with (n=150) or without (n=1605) PS. Clinical, microbiological and prognostic variables were recorded.ResultsPatients with PS were older (mean age 69.7±18 vs 66.2±14; p=0.004) and had more arterial hypertension (48% vs 34.5%; p<0.001) and autoimmune disease (5% vs 2%; p=0.03) than patients without PS. The lumbar vertebrae were the most frequently involved (84 patients, 66%), especially L4–L5. Neurological symptoms were observed in 59% of patients. Enterococci and Streptococcus gallolyticus were more frequent (24% vs 12% and 24% vs 11%; p<0001, respectively) in the PS group. The diagnosis of PS was based on contrast-enhanced MRI in 92 patients, bone CT in 88 patients and 18F-FDG PET/CT in 56 patients. In-hospital (16% vs 13.5%, p=0.38) and 1-year (21% vs 22%, p=0.82) mortalities did not differ between patients with or without PS.ConclusionsPS is a frequent complication of IE (8.5% of IE), is observed in older hypertensive patients with enterococcal or S. gallolyticus IE, and has a similar prognosis than other forms of IE. Since PS is associated with specific management, multimodality imaging including MRI, CT and PET/CT should be used for early diagnosis of this complication of endocarditis.

Aims Sodium zirconium cyclosilicate (SZC, formerly ZS‐9) is a selective K+ binder to treat adults with hyperkalaemia. HARMONIZE‐Global examined the efficacy and safety of SZC among outpatients with hyperkalaemia from diverse geographic and ethnic origins. Methods and results This phase 3, randomized, double‐blind, placebo‐controlled study recruited outpatients with serum K+ ≥5.1 mmol/L (measured by point‐of‐care i‐STAT device) at 45 sites in Japan, Russia, South Korea, and Taiwan. Following open‐label treatment with thrice‐daily SZC 10 g during a 48 h correction phase (CP), patients achieving normokalaemia (K+ 3.5–5.0 mmol/L) were randomized 2:2:1 to once‐daily SZC 5 g, SZC 10 g, or placebo during a 28 day maintenance phase (MP). The primary endpoint was mean central‐laboratory K+ level during days 8–29 of the MP. Of 267 patients in the CP, 248 (92.9%) entered the MP. During the CP, mean central‐laboratory K+ was reduced by 1.28 mmol/L at 48 h vs. baseline (P < 0.001). During the MP (days 8–29), SZC 5 and 10 g once‐daily significantly lowered mean central‐laboratory K+ by 9.6% and 17.7%, respectively, vs. placebo (P < 0.001 for both). More patients had normokalaemia (central‐laboratory K+ 3.5–5.0 mmol/L at day 29) with SZC 5 (58.6%) and 10 g (77.3%) vs. placebo (24.0%), with the greatest number of normokalaemic days in the 10‐g group. The most common adverse events with SZC were mild or moderate constipation and oedema. Conclusions Normokalaemia achieved during the CP was maintained over 28 days with SZC treatment among outpatients with hyperkalaemia.

In international trials, glucagon-like protein-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2Is) were effective in improving cardiovascular (CV) outcomes. We assessed the effect of GLP-1RAs and SGLT2Is treatment effect on CV endpoints by geographical region in multiple international trials using random effects weighted least squares meta-regressions. The estimated effects of both SGLT2Is and GLP-1RAs on major adverse CV events (MACE) in North America (SGLT2Is n = 12,399, HR 0.90, 95% CI 0.81-1.01; GLP-1RAs n = 12,515, HR 0.95, 95% CI 0.83- 1.09) and in Europe (SGLT2Is n = 19,435, HR 0.93, 95% CI 0.85-1.02; GLP-1RAs n = 22,812, HR 0.88, 95% CI 0.79-0.99) were numerically lower but not statistically different to the rest of the world (ROW) (SGLT2Is n = 15,127, HR 0.83, 95% CI 0.75-0.92, p-value for interaction 0.26; GLP-1RAs n = 17,494, HR 0.82, 95% CI 0.73-0.92, p-value for interaction 0.28). Effects of SGLT2Is on heart failure readmission or CV death varied significantly by region (P = 0.0094). The effect of SGLT2Is was significantly smaller in Europe (n = 18,653, HR 0.86, 95% CI 0.78-0.95) than in the ROW (n = 12,463, HR 0.68, 95% CI 0.61-0.76, P = 0.0024). The smaller effect in North America (n = 9776, HR 0.76, 95% CI 0.66-0.87) did not differ significantly from that in the ROW (P = 0.2370). The effects of SGLT2Is on HF events are larger in the ROW. Further analyses and studies are needed to better elucidate the differential effects of SGLTIs and GLP-1RAs by geographical regions.

Background Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. Methods Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox’s regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. Findings Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 group (adjusted HR 1.65 (95% CI 1.11–2.46), p  = 0.013), but not in influenza (1.74 (0.99–3.06), p  = 0.052), or no viral infection groups (1.13 (0.68–1.86), p  = 0.63). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. Interpretation VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693.

Despite its well-documented relation with visceral adiposity (VAT) and cardiometabolic risk (CMR), whether waist circumference (WC) should be measured in addition to body mass index (BMI) remains debated. This study tested the relevance of adding WC to BMI for the estimation of VAT and CMR. In the International Study of Prediction of Intra-abdominal Adiposity and Its Relationship with Cardiometabolic Risk/Intra-abdominal Adiposity, 297 physicians recruited 4,504 patients (29 countries). Both BMI and WC were measured, whereas VAT and liver fat were assessed by computed tomography. A composite CMR score was calculated. From the 4,109 patients included in the present analyses (20 ≤ BMI < 40 kg/m2, 47% women), about 30% displayed discordant values for WC and BMI quintiles, despite a strong correlation between the 2 anthropometric variables (r = 0.87 and r = 0.84 for men and women, respectively, p <0.001). Within each single BMI unit, VAT and WC showed substantial variability between subjects (mean difference between 90th and 10th percentiles: 175 cm2/16 cm and 137 cm2/18 cm for VAT/WC in men and women, respectively). Within each BMI category, increasing gender-specific WC tertiles were associated with significantly higher VAT, liver fat, and with a more adverse CMR profile. In conclusion, this large international cardiometabolic study highlights the frequent discordance between BMI and WC, driven by the substantial variability in VAT for a given BMI. Within each BMI category, WC was cross-sectionally associated with VAT, liver fat, and CMR factors. Thus, WC allows a further refinement of the CMR related to any given BMI.

Background: Fluid challenge (FC) is one of the most common practices in Intensive Care Unit (ICU). The present study aimed to evaluate whether echocardiographic assessment of the response to FC at the end of the infusion or 20 min later could affect the results of the FC.

Abstract Rationale Post–cardiac surgery shock is associated with high morbidity and mortality. By removing toxins and proinflammatory mediators and correcting metabolic acidosis, high-volume hemofiltration (HVHF) might halt the vicious circle leading to death by improving myocardial performance and reducing vasopressor dependence. Objectives To determine whether early HVHF decreases all-cause mortality 30 days after randomization. Methods This prospective, multicenter randomized controlled trial included patients with severe shock requiring high-dose catecholamines 3–24 hours post–cardiac surgery who were randomized to early HVHF (80 ml/kg/h for 48 h), followed by standard-volume continuous venovenous hemodiafiltration (CVVHDF) until resolution of shock and recovery of renal function, or conservative standard care, with delayed CVVHDF only for persistent, severe acute kidney injury. Measurements and Main Results On Day 30, 40 of 112 (36%) HVHF and 40 of 112 (36%) control subjects (odds ratio, 1.00; 95% confidence interval, 0.64–1.56; P = 1.00) had died; only 57% of the control subjects had received renal-replacement therapy. Between-group survivors’ Day-60, Day-90, intensive care unit, and in-hospital mortality rates, Day-30 ventilator-free days, and renal function recovery were comparable. HVHF patients experienced faster correction of metabolic acidosis and tended to be more rapidly weaned off catecholamines but had more frequent hypophosphatemia, metabolic alkalosis, and thrombocytopenia. Conclusions For patients with post–cardiac surgery shock requiring high-dose catecholamines, the early HVHF onset for 48 hours, followed by standard volume until resolution of shock and recovery of renal function, did not lower Day-30 mortality and did not impact other important patient-centered outcomes compared with a conservative strategy with delayed CVVHDF initiation only for patients with persistent, severe acute kidney injury. Clinical trial registered with www.clinicaltrials.gov (NCT 01077349).

Maintenance of vascular integrity is critical for homeostasis, and temporally and spatially regulated vascular leak is a central feature of inflammation. Sphingosine-1-phosphate (S1P) can regulate endothelial barrier function, but the sources of the S1P that provide this activity in vivo and its importance in modulating different inflammatory responses are unknown. We report here that mutant mice engineered to selectively lack S1P in plasma displayed increased vascular leak and impaired survival after anaphylaxis, administration of platelet-activating factor (PAF) or histamine, and exposure to related inflammatory challenges. Increased leak was associated with increased interendothelial cell gaps in venules and was reversed by transfusion with wild-type erythrocytes (which restored plasma S1P levels) and by acute treatment with an agonist for the S1P receptor 1 (S1pr1). S1pr1 agonist did not protect wild-type mice from PAF-induced leak, consistent with plasma S1P levels being sufficient for S1pr1 activation in wild-type mice. However, an agonist for another endothelial cell Gi-coupled receptor, Par2, did protect wild-type mice from PAF-induced vascular leak, and systemic treatment with pertussis toxin prevented rescue by Par2 agonist and sensitized wild-type mice to leak-inducing stimuli in a manner that resembled the loss of plasma S1P. Our results suggest that the blood communicates with blood vessels via plasma S1P to maintain vascular integrity and regulate vascular leak. This pathway prevents lethal responses to leak-inducing mediators in mouse models.