Ref: Cotoia et al. J Anesth Analg Crit Care (2022) 2:41, https://doi.org/10.1186/s44158-022-00068-1

Glutamine (GLN) is classified as a non-essential amino acid and it is released from skeletal muscle to be a constituent of proteins . Furthermore, GLN acts as an immune stimulator as an essential component for lymphocyte proliferation and cytokine production, macrophage phagocytic and secretory activities, and neutrophil bacterial killing . Under stable conditions, GLN can be produced in suffcient amounts and stored in the muscle tissue. Tese stores actually represent greater than 50% of the total free amino acid pool in the body.

However, GLN levels normally decrease in intensive care unit (ICU) patients both due to a hypercatabolic status, especially in trauma and sepsis, and an increased requirement by the gut, the immune system, liver and kidneys which exceeds the individual’s ability to produce it in sufficient amounts. In critically ill patients, GLN may even become a “conditionally essential” amino acid : it is considered a “fuel for the immune system”, where a low blood concentration may impair immune cell function, resulting in poor clinical outcomes and increased risk of mortality, and so its supplementation is recommended in ICU patients . Interestingly, some authors showed that GLN supplements of 10–20 g/day (or with a high dose >0.2g/kg/day) plus standard enteral nutrition (EN) formulas reduced the rates of pneumonia, sepsis and bacteraemia in ICU patients with shortened hospital stays, better immune function and lower hospital costs .

It is important to note that humoral immunity is a process of adaptive immunity mediated by immunoglobulins such as IgA secreted by B lymphocytes . Cell-mediated immunity is responsible for destroying the intracellular pathogens with T lymphocytes, which consequently produce inflammatory mediators such as interleukin. More clinical trial and new studies on these topics are necessary to focus on cell-mediated and humoral immune responses in severely injured trauma patients and rule on GLN depletion on immune functioning . We hypothesize that GLN could enhance both humoral and cell-mediated immunity. The aim of our study is to investigate the effect of GLN-enriched EN on the cell mediated and humoral immune system in ICU polytrauma patients.

Methods:

All consecutive patients with polytrauma who required mechanical ventilation and enteral nutrition (EN) provided within 24 h since the admission in ICU at the University Hospital of Foggia from September 2016 to February 2017 were included.

Thereafter, two groups were identifed: patients treated by conventional EN (25 kcal/kg/die) and patients who have received conventional EN enriched with 50 mg/kg/ideal body weight of alanyl-GLN 20% intravenously.

We analysed the plasmatic concentration of IgA, CD3+/CD4+ T helper lymphocytes, CD3+/CD8+ T suppressor lymphocytes, CD3+/CD19+ B lymphocytes, IL-4 and IL-2 at admission and at 4 and 8 days.

Results:

IgA levels in control and glutamine (GLN) groups. Data are presented as mean ± SD. °, * and  ^ indicate a significant difference in GLN vs control at T0 (p < 0.05), at T4 (p < 0.05), and at T8 (p < 0.01); • indicates a significant difference (p < 0.05) in the GLN group between T4 and T8

CD3+/CD4+ T helper lymphocyte levels in control and glutamine (GLN) groups. Data are presented as mean ± SD. *, °, and ^ indicate a significant difference in GLN vs control at T4 (p < 0.01) and T8 (p < 0.001); ˅, ”, and • indicate statistically highly significant (p < 0.001) in the GLN group

CD3+/CD8+ T suppressor lymphocyte levels in control and glutamine (GLN) groups. Data are presented as mean ± SD. * and °indicate a significant difference in GLN vs control at T4 (p < 0.05) and at T8 (p < 0.001); ˅, ”, and • indicate statistically significant (p < 0.001) in the GLN group; x and ∩ indicate a significant difference in the control group between T0 and T4 (p < 0.001) and T4 and T8 (p = 0.002)

B lymphocyte CD3+/CD19+ levels in control and glutamine (GLN) groups. Data are presented as mean ± SD. “indicate a significant difference in GLN vs control at T8 (p = 0.01); *, ˅, and ” indicate statistically highly significant (p < 0.001) in the GLN group

IL-2 levels in control and glutamine (GLN) groups. Data are presented as mean ± SD. ^, •, and ˅ indicate a significant difference in the GLN group (p < 0.05); * and ° indicate a significant difference in the control group between T0 and T4 (p = 0.002) and T4 and T8 (p = 0.002)

IL-4 levels in control and glutamine (GLN) groups. Data are presented as mean ± SD. °, ”, and ^ indicate a significant difference (p < 0.004) in the GLN group

Results:

We identified 30 patients, with 15 subjects per group. IgA levels increased significantly in GLN vs the control group at T0, T4 and T8. CD3+/CD4+ T helper lymphocyte and CD3+/CD8+ T suppressor lymphocyte levels significantly increased in GLN vs the control group at T4 and T8. CD3+/CD19+ B lymphocyte levels increased significantly in GLN vs the control group only at T8. IL-2 and IL-4 levels showed no significant differences when comparing GLN with the control group.

Conclusions:

Our study showed that there was an improvement in humoral and cell-mediated immunity with GLN supplementation in polytrauma ICU patients using recommended doses.

The post Immunological effects of glutamine supplementation in polytrauma patients in intensive care unit first appeared on Serene.

Ref: A. Ma, M. Dong, J. Cheng et al, Journal of Intensive Medicine 3 (2023) 65–72, https://doi.org/10.1016/j.jointm.2022.05.006

The intensive care unit (ICU) is the “hardest hit” department for hospital-acquired infections, where a range of traumatic procedures can lead to fatal infections. Ventilator-related pneumonia, catheter-related bloodstream infections caused by an arterial or venous puncture, and skin and soft tissue infections (SSTIs) secondary to tracheotomy and surgical wounds are the main types of hospital-acquired infections. Nearly half of these infections are caused by Gram-positive bacteria. The increasing prevalence of multidrug-resistant Gram positive pathogens poses a significant challenge in the ICU. Methicillin-resistant Staphylococcus aureus (MRSA), methicillin susceptible Staphylococcus aureus (MSSA), and vancomycin resistant Enterococci (VRE), which are extremely common in the ICU, are regarded as priority pathogens that cause morbidity and mortality in countless cases. Therefore, it is essential for ICU clinicians to identify resistance patterns in Gram-positive bacteria and use antibiotics that are effective against these resistant phenotypes. Linezolid, a synthetic oxazolidinone antibiotic, has been approved for the treatment of infections caused by VRE, hospital acquired pneumonia caused by MRSA and MSSA, complicated SSTIs caused by Staphylococcus aureus or Streptococcus pneumoniae, and uncomplicated SSTIs caused by Staphylococcus aureus (methicillin-resistant only) or Streptococcus pyogenes. The drug has favorable in vitro and in vivo activity against the mentioned organismsy.

As advanced antibiotics commonly used in the ICU, linezolid and vancomycin are often compared. Although vancomycin is often used as the first choice, side effects pertaining to liver and kidney function, and especially renal injury, lead to certain limitations in its use in ICU patients. Linezolid is more useful than vancomycin in SSTIs and MRSA pneumonia, and is more effective and cost-effective for hospital-acquired MRSA infections. It is also the only antibiotic that is more effective than daptomycin and quinopidine (among others) for vancomycin resistant Enterococcus faecalis infection. Considering the role of linezolid in the treatment of Gram positive bacteria, this real-world study was conducted to characterize the population of critically ill patients in the ICU and infections treated with linezolid in the ICU. It also aimed to evaluate the clinical efficacy of linezolid therapy and to assess the safety of Chinese-made linezolid in ICU patients. This study collected data from 52 hospitals and conducted a retrospective analysis to guide better antibiotic prescribing among clinicians.

Clinical outcome by infecting pathogen. MRSA: Methicillin-resistant Staphylococcus aureus; MSSA: Methicillin-susceptible Staphylococcus aureus; SSTI: Skin and soft tissue infections; VRE: Vancomycin-resistant Enterococci; VSE: Vancomycin-susceptible Enterococci.

Methods:

This multi-center, observational, real-world study was conducted across 52 hospitals between June 9, 2018, and December 28, 2019. Patients who met the following inclusion criteria were included: (1) admitted to the ICU, (2) of any age group, and (3) having a clinical or laboratory diagnosis of a Gram-positive bacterial infection. Clinical efficacy was categorized as success (cured or improved), failed, or non-evaluable. Adverse events and serious adverse events were recorded during treatment.

Results:

A total of 366 ICU patients who met the inclusion criteria were evaluated. Linezolid was used as second and first-line treatment in 232 (63.4%) and 134 (36.6%) patients, respectively. The most common isolated strain was Staphylococcus aureus (methicillin-resistant Staphylococcus aureus: n=37/119, 31.1%; methicillin-susceptible Staphylococcus aureus: n=15/119, 12.6%); this was followed by Enterococci (vancomycin-resistant Enterococci: n=8/119, 6.7%; vancomycin-susceptible Enterococci: n=11/119, 9.2%) and Streptococcus pneumoniae (multi drug resistant: n=4/119, 3.4%; non-multidrug resistant: n=2/119, 1.7%). The main infection sites where pathogens were detected included the lung (n=216/366, 59.6%), skin and soft tissue (n=104/366, 28.4%), and blood (n=50/366, 13.7%). Clinical success was achieved in 301 (82.2%) patients; 34 (9.3%) were cured and 267 (73.0%) improved; treatment failure and non-evaluable outcomes were observed in 29 (7.9%) in 36 (9.8%) patients, respectively. Linezolid-related adverse events were reported in 8 (2.2%) patients. No treatment-related serious adverse events were reported.

Conclusions:

The treatment of Gram-positive bacterial infections in the ICU is extremely important, and the selection of appropriate antibiotics based on patients’ clinical characteristics is the key to prognosis. Based on real-world results, linezolid has been found to be effective and safe in the treatment of Gram-positive bacterial infections in critically ill patients. Linezolid showed better clinical success in pulmonary infections or SSTIs caused by Staphylococcus aureus. Our results will provide intensivists with a reference for the selection of medication. However, due to the limitations of this study including those pertaining to sample size, clinicians will need to individually evaluate patient conditions before using linezolid in the clinic. In addition, they will need to be vigilant regarding possible side effects during administration.

The post Clinical efficacy and safety of linezolid in intensive care unit patients first appeared on Serene.

Ref: Bussini L., et al, J Emerg Crit Care Med 2022;6:25 | https://dx.doi.org/10.21037/jeccm-22-32

Hospital-acquired pneumonia (HAP) and ventilator associated pneumonia (VAP) remain leading causes of morbidity and mortality despite recent advances in prevention, diagnosis, and treatment. HAP is a lung infection occurring in the nosocomial setting which develops after 48 hours of hospitalization and does not appear in incubation at the hospital admission. Among nosocomial pneumonia, VAP is an infection developing in patients admitted to intensive care unit (ICU) after 48 hours of endotracheal intubation.

Indeed, the definition of VAE/VAC—that is an increase in the daily minimum positive end expiratory pressure (PEEP) of ≥3 cmH2O sustained for ≥2 days after ≥2 days of stable or decreasing daily minimum PEEP, or an increase in the fraction of inspired oxygen (FiO2) of ≥20 points sustained for ≥2 days after ≥2 days of stable or decreasing daily minimum FiO2 level—was created to frame the wide spectrum of complications related to mechanical ventilation (MV). Among them, infection-related ventilator associated complications (IVAC) are considered VAE/ VAC associated with possible pulmonary infection or nonpulmonary infection leading to respiratory deterioration (i.e., an abnormal temperature—38 ℃—and/ or white blood cell count—≤4,000 or ≥12,000 cells/mm3 —and administration of 1 or more new antibiotic for ≥4 days). Possible VAP (PVAP) refers to an IVAC with presumable lung infection supported by positive respiratory secretion or pleural fluid cultures for potentially pathogenic organisms, positive assays for respiratory viruses or Legionella, or suggestive histopathology concurrent with the IVAC.

Epidemiology

Though it is one of the most common nosocomial infections, epidemiologic data on HAP in non-ICU patients are limited and fragmented. Estimated incidence ranges from 5 to more than 20 cases per 1,000 admissions and from 2.5 to more than 6.1 cases per 1,000 non-ICU patients.

In the US, various formalized systems for ongoing national surveillance provide systematized information concerning infection rates, including pneumonia. One of the most recent large experience comes from a multicenter retrospective cohort study of 17,819 hospitalized patients from 253 US hospitals in 2012–2019 period. Among all patients enrolled, 26.5% had NVHAP, 25.6% ventilated HAP (V-HAP), and 47.9% VAP.

In Europe and incoming countries, no such reporting systems exist, and epidemiology of VAP/HAP in ICUs is inferred from national and international studies. A more recent report on pneumonia in European ICUs comes from the EU-VAP/CAP study on 2,436 patients from 27 ICUs. Among all patients enrolled, 34% developed pneumonia during ICU stay, with 18.3 VAP episodes per 1,000 ventilator-days.

The INICC is an international research network comprising centers from Latin America, Eastern Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific aimed to measure and prevent nosocomial infection. The Consortium collected prospective data on nosocomial infections from 861,284 patients hospitalized in 703 ICUs in a 6-year period from January 2010 to December 2015.

The overall rate of VAP was 13.1 per 1,000 ventilator-days, higher than rates from hospitals in North America, Western Europe in the same period (0.9 per 1,000 ventilator-days). Such higher rates could be due to the extremely low nurse-to-patient staffing ratios, the hospital overcrowding, the lack of medical supplies, and an insufficient number of experienced nurses or trained healthcare workers .

Overall, prevalence of VAP has decreased in the last decades, principally as a result of implementation of prevention protocols. Main novel strategies have been priority use of high-flow nasal oxygen or non-invasive positive pressure ventilation (NIPPV) in place of intubation/ reintubation, reduced duration of sedation and MV, daily oral care, early enteral feeding, correct in-bed positioning and early mobilization.

# , not indicated in case of VAP; *, the choice of drugs with antiCRE activity should be made upon the presence of specific risk factors, rectal carriage status and taking into account the local or center-specific epidemiology (i.e., prevalence of infections caused by CRE and most common type of carbapenemase between OXA-48, KPC and MBLs); § , consider combination treatment when ceftazidime-avibactam is used in case of VAP; °, mainly based on center-specific epidemiology, previous colonization or infection. HAP, hospital-acquired pneumonia; VAP, ventilator-associated pneumonia; MDR, multi-drug resistant; MSSA, methicillin-susceptible S. aureus; MRSA, methicillinresistant S. aureus; CRE, carbapenem-resistant Enterobacterales.

Conclusions:

HAP/VAP still represents one of the most challenging complications affecting hospitalized patients. This narrative review may provide to clinicians a complete and updated summary on prevention, diagnosis and management of HAP/VAP.

The post Diagnosis, management and treatment of nosocomial pneumonia in ICU first appeared on Serene.

More than 100,000 people with type 1 diabetes in England are to be offered an artificial pancreas, which experts believe could become the “holy grail” for managing the disease.

The groundbreaking device uses an algorithm to determine the amount of insulin that should be administered and reads blood sugar levels to keep them steady.

A world-first trial on the NHS found it was more effective at managing diabetes than current devices and required far less input from patients. The device is now set to be rolled out across the NHS in England after it won approval from the National Institute for Health and Care Excellence (Nice).

Mark Chapman, the interim director of medical technology at Nice, said: “Some people living with type 1 diabetes struggle to manage their condition, even though they are doing everything asked of them by their diabetes team. This technology is the best intervention to help them control their diabetes, barring a cure.”

In draft guidance published on Tuesday, an independent Nice committee recommended its use for managing blood glucose levels in people struggling to manage type 1 diabetes. The technology allows a patient to go about their day-to-day life without having to monitor if their blood glucose levels are too high or too low.

Women who are pregnant are also eligible, because blood glucose levels are harder to manage during this time. In total, about 105,000 people in England are set to be offered the technology.

Managing type 1 diabetes can be challenging, especially in young children, owing to variations in the levels of insulin required and unpredictability around how much patients eat and exercise. Children are particularly at risk of dangerously low (hypoglycaemia) and high (hyperglycaemia) blood sugar levels, which can damage the body or even lead to death.

The artificial pancreas is worn next to the body. It continually monitors blood glucose levels and automatically adjusts insulin delivered via a pump. It also eliminates the need for finger-prick tests to check blood sugar levels to prevent hypoglycaemic and hyperglycaemia attacks.

The draft Nice recommendations require NHS England to agree a cost-effective price for the device on behalf of relevant health bodies. Currently, the average annual cost for the technology is £5,744, higher than Nice considers a cost-effective use of NHS resources.

Although most of the NHS’s estimated £10bn annual spending on diabetes goes on type 2 diabetes, it is hoped the devices will help cut costs by ensuring less need for interventions for type 1 cases.

Prof Partha Kar, national specialty adviser for diabetes at NHS England, said: “This technology has been proven to give the best control for managing type 1 diabetes and should make things like amputations, blindness, and kidney problems possibly a thing of the past.” Kar, who has previously described the device as “not very far away from the holy grail of a fully automated system”, added: “We have seen fantastic results from the real-world trials which have taken place. The quality of life this technology gives to those using it is huge.”

The post NHS in England to offer artificial pancreas to help manage type 1 diabetes first appeared on Serene.

Alqahtani S. et al., J Endocrinol Metab. 2022;12(6):161-167, doi: https://doi.org/10.14740/jem848

Vascular disease including venous thromboembolism (VTE) is a common cause of death among patients with comorbid conditions such as diabetes mellitus . VTE results in a range of events from symptomless distal venous thrombus of deep veins to threatening deep venous thrombus and fatal pulmonary embolism. The  likelihood of VTE and its associated complications are higher in older patients than younger ones and the risk becomes two-fold with every decade of aging . This risk also varies by the sex of the patients with males being affected more by the second episode than females. The yearly incidence of VTE is between 1.5 and 3.0 cases per 1,000 individuals. The incidence of VTE is even higher among diabetic patients. For example, the data suggest the annual rate of VTE among diabetic patients was 432 per 100,000 population . VTE is considered as the third most common cause of cardiovascular disease following stroke and myocardial infarction . It seems that metformin being an antihyperglycemic drug prevents cardiovascular disease beyond glycemic control. However, despite the effects of metformin on glycemic control, its effects on venous thrombosis may be different. Overall, there is limited evidence supporting such beneficial effects with scarce evidence from well-conducted trials. Few epidemiological studies have shown that hypoglycemic agents such as metformin may have a direct effect on VTE . However, such evidence is not qualitatively synthesized both from observational and intervention studies, thereby limiting our understanding of the role of metformin in preventing VTE. Thus, we carried out a systematic review of the epidemiological studies assessing the role of metformin in preventing VTE. The findings of this review will help clinicians and researchers to plan further studies and make evidence-based clinical and policy decisions to treat the patients appropriately and reduce the burden of VTE and its associated morbidity and mortality.

Methods:

A systematic search of three main electronic databases including Embase, PubMed, and EBSCO was undertaken in 2021. Any study conducted between 2000 and 2021 that addressed the role of metformin in preventing venous thrombosis in patients diagnosed with type 2 diabetes mellitus was considered eligible.

Results:

Following a comprehensive review of the research articles based on the eligibility criteria, six articles were incorporated into the review. The findings of the review demonstrate that metformin was found to be associated with 22% to 58% risk reduction for venous thrombosis among diabetic patients. However, due to the observational studies included in the meta-analysis, the protective effect may not be independent of other risk factors or other variables.

Discussion:

This review was undertaken to summarize the evidence regarding the protective effect of metformin on VTE in diabetic patients. Overall the findings of the review demonstrated a protective effect of metformin among diabetic patients in terms of reducing venous thrombus formation. Though, limited evidence exists and perhaps there is a need to conduct more randomized controlled trials, the available evidence is suggestive of beneficial effects of metformin against VTE. This can be further confirmed by undertaking large intervention studies to endorse the findings. According to the current guidelines of the American Diabetes Association/European Association, metformin should be considered as either as a monotherapy or in combination for patients diagnosed with type 2 diabetes mellitus. This is even more beneficial for patients who are at risk of thrombus formation. Metformin being an insulin sensitizer can improve the function of vessels and related vascular abnormalities with few side effects in patients with type 2 diabetes mellitus . The potential mechanisms by which metformin may prevent venous thrombosis are by inhibiting platelet activation in vivo and in vitro [19]. The evidence suggests that platelets are involved in several biological processes such as clotting, vascular lesions, and activation of other platelets . This activity of platelets is markedly suppressed in the presence of metformin and it is mainly by suppression of platelet prothrombinase activity and by reducing extracellular mitochondrial release . This is consistent with the reduced platelet adhesive function after administering metformin. The animal studies suggest that metformin significantly suppressed aggregation of platelets and prevent both arterial and venous thrombosis in rat models [19]. And thrombus formation deteriorated in the rats treated with metformin . Besides, it has been found that metformin reduces the size and weight of arterial and venous thrombi and subsequently reduces the incidence of pulmonary embolism. Also, metformin reduces markers of endothelial activation such as Von Willebrand factor and it also decreases the inflammation and levels of plasminogen activator inhibitor . These potential mechanisms contribute to the protective effect of metformin in reducing thrombus formation and associated mortality in diabetic patients.

Conclusion and Implications:

for Future Overall, the existing studies included in this review demonstrate that metformin may be found protective against VTE, mainly in diabetic patients. Based on the available findings, metformin may be safely used in diabetic patients at risk of thromboembolism; however, we would recommend conducting more epidemiological studies particularly randomized controlled trials to assess the effect of metformin on VTE before making any definitive conclusions about the same. Considering the limited sample size of this review, more studies and their respective reviews are required to confirm these findings and these studies need to be undertaken both in developing and developed countries to confirm these findings and recommend the use of metformin on a broader scale for the prevention of thromboembolism in diabetic patients.

The post Protective Effect of Metformin on Venous Thrombosis in Diabetic Patients: Findings From a Systematic Review first appeared on Serene.

Ref: Michael Böhm, European Heart Journal (2022) 00, 1–12, https://doi.org/10.1093/eurheartj/ehac693

Empagliflozin reduced cardiovascular death and heart failure hospitalization in patients with preserved ejection fraction. Hypertension is the most common comorbidity and etiological trigger of heart failure with preserved ejection fraction (HFpEF) as pressure overload produces left ventricular hypertrophy, diastolic dysfunction, abnormal arterial-ventricular coupling, and other complications such as kidney failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce systolic blood pressure (SBP) in patients with diabetes and hypertension, while in heart failure with reduced ejection fraction (HFrEF), only patients with a high baseline SBP had a significant and meaningful reduction. Registry data show an increase of heart failure outcomes and death for patients with SBP 140– 150 mmHg without differences between HFrEF and HFpEF. This U-shaped blood pressure (BP)-risk association might not be related to a causality rather than reflecting reverse causation as low BP selects patients with more advanced heart failure and frailty. In EMPEROR-Preserved (empagliflozin outcome trial in patients with chronic heart failure with preserved ejection fraction), we studied the effect of empagliflozin on SBP and its effects on heart failure outcomes and estimated glomerular filtration rate (eGFR) decline across baseline SBP levels in heart failure with ejection fraction >40%.

Methods and results:

The association of SBP and the treatment effects of empagliflozin in EMPEROR-Preserved (empagliflozin outcome trial in patients with chronic heart failure with preserved ejection fraction) was evaluated. Randomized patients (n=5988) were grouped according to SBP at baseline (130 mmHg, n=3118). The effect of empagliflozin on blood pressure, cardiovascular death or HF hospitalization (primary outcome), total HF hospitalizations, and rate of decline in estimated glomerular filtration rate was studied. Over a median of 26.2 months, the placebo-corrected decline was small and not significantly different across baseline SBP. On placebo, the risk of cardiovascular death or hospitalization for HF was 8.58 at >130 mmHg, 8.26 at 110–130 mmHg, and 11.59 events per 100 patient-years at 130 mmHg, P=0.08 vs. 110–130 mmHg). There was no evidence for baseline SBP moderating the effect of empagliflozin on risk of HF events (primary endpoint interaction P=0.69, recurrent HF hospitalizations interaction P=0.55). When comparing empagliflozin with placebo, SBP did not meaningfully associate with adverse events such as hypotension, volume depletion, and acute renal failure.

Discussion:

In EMPEROR-Preserved, there was a small placebo-corrected SBP decline by empagliflozin compared with placebo with an overall increase of SBP at low baseline SBP and a small drop of SBP at high baseline SBP on placebo and on empagliflozin possibly reflecting regression to the mean. In HFpEF, the outcome rates of the primary outcome were higher at low SBP ((<110 mmHg) but the treatment effect of empagliflozin on heart failure outcomes was not significantly related to baseline SBP with a similar risk reduction of heart failure hospitalization and cardiovascular death. Empagliflozin had minor effects on hypotension and volume depletion, while some fewer events were observed for acute renal failure (Structured Graphical Abstract).

HFpEF is a heterogeneous condition with hypertension being one of the most prevalent and possible etiological factors promoting the progression of hypertrophy to failure with more patients presenting with a history of hypertension in HFpEF than in HFrEF. A higher prevalence of high BP in HFpEF compared with HFrEF is shown by the finding that 52.0% of the patients had an SBP of >130 mmHg and 7.6% of EMPEROR-Reduced 28.2% were at >130 mmHg and 24.2% had an SBP of <110 mmHg.8 Patients with heart failure are often undertreated when SBP is low, although they have a worse prognosis than those with a higher SBP. Interestingly, the U- and J-shaped association of SBP and DBP on mortality appears to be similar in HFrEF and HFpEF. Herein, we show that the primary outcome and cardiovascular death was increased in patients at SBP <110 mmHg compared with >110 mmHg. This finding is similar to previous HFrEF trials with treatment effects of SGLT2 inhibitors and sacubitril/valsartan being similar across SBP groups. We extended those findings to HFpEF patients by showing that the effect of empagliflozin is similar across baseline SBP groups in EMPEROR-Preserved.

In EMPEROR-Preserved, 90.6% of patients had a history of hypertension. Although high SBP is a major driver for the development of HFpEF, we still found a significant number with normal or low SBP. Nevertheless, the proportion of patients with low SBP <110 mmHg is lower than in HFrEF.8 A reduced myocardial systolic or diastolic function has been speculated to be involved in drops of SBP over time, previously termed ‘decapitated hypertension’,  also observed in PARAGON-HF in HFpEF patients, and associated with increased HF events in HFrEF and HFpEF. Similar findings of an increased risk for cardiovascular outcomes at low SBP have also been shown in patients after myocardial infarction or stroke or known coronary artery disease. Nevertheless, in HFpEF as in HFrEF, SBP appears not to be an effect modifier of the cardio-renal effects of empagliflozin and, thus, might not contribute mechanistically to the treatment effect of empagliflozin.

As the effect of empagliflozin is maintained at SBP <110 mmHg, it is important that the protective effect does not come at a meaningfully increased cost of safety outcomes. There was only a slight increase of incident hypotension or volume depletion, while the incidence of acute renal failure was reduced. These observations are of clinical relevance as physicians are often reluctant to initiate treatment due to the fear of these adverse events at low SBP.

Conclusion:

In EMPEROR-Preserved, empagliflozin was effective and safe without SBP meaningfully moderating empagliflozin’s treatment effects. This analysis of EMPEROR-Preserved shows that empagliflozin can be used safely and effectively without blood pressure being a meaningful moderator of the drug benefit.

The post Empagliflozin, irrespective of blood pressure, improves outcomes in heart failure with preserved ejection fraction: the EMPEROR Preserved trial first appeared on Serene.

Paolisso P., et al,  Journal of the American Society of Echocardiography, Published: January 04, 2023DOI:https://doi.org/10.1016/j.echo.2022.12.022

Background

The echocardiographic parameters required for a comprehensive assessment of cardiac masses (CMs) are still largely unknown.

Objectives

To identify and integrate the echocardiographic features of CMs that can accurately predict malignancy.

Methods

Observational cohort study of 286 consecutive patients who underwent a standard echocardiographic assessment for suspected cardiac mass in Bologna University Hospital between 2004 and 2022. A definitive diagnosis was achieved by histological examination or, in case of cardiac thrombi, with radiological evidence of thrombus resolution after an appropriate anticoagulant treatment. Logistic and multivariable regression analysis was performed to confirm the ability of 6 echocardiographic parameters to discriminate malignant from benign masses. The unweighted count of these parameters was used as a numerical score, ranging from 0 to 6, with a cut-off of >3 balancing sensitivity and specificity with respect to the histological diagnosis of malignancy. Classification tree analysis (CTA) was used to determine the ability of echocardiographic parameters to discriminate sub-groups of patients with a differential risk of malignancy.

Results

Benign masses were more frequently pedunculated, mobile, and adherent to the interatrial septum (p<0.001). Malignant masses showed a greater diameter and exhibited a higher frequency of irregular margins, an inhomogeneous appearance, sessile implantation, polylobate shape, and pericardial effusion (p<0.001). Infiltration, moderate-severe pericardial effusion, non-left localization, sessile, polylobate, and inhomogeneity were confirmed to be independent predictors of malignancy in both univariate and multivariable models. The predictive ability of the unweighted count of >3 was very high (>0.90) and similar to that of the previously published weighted score. The CTA generated an algorithm in which infiltration was the best discriminator of malignancy, followed by non-left localization and sessile shape. The percentage correctly classified by the CTA as malignant was 87.5%. Agreement between observer readings and cardiac mass histology ranged between 85.1-91.5%. The presence of at least 3 echocardiographic parameters was associated with a lower survival.

Conclusions

In the approach to CM, some echocardiographic parameters can serve as markers to accurately predict malignancy, thereby informing the need for second-level investigations and minimizing the diagnostic delay in such a complex clinical scenario.

The post Echocardiographic Markers in the Diagnosis of Cardiac Masses first appeared on Serene.

Ref:  Nishiura N., et al, J Am Heart Assoc. 2023;12:e025751. DOI: 10.1161/JAHA.122.025751

BACKGROUND: The natural history and optimal interventional timing in patients with isolated severe tricuspid regurgitation (TR) have not been well studied. This study aimed to investigate long-term clinical outcomes and risk factors associated with poor prognosis in patients with isolated severe TR.

Tricuspid regurgitation (TR) is a common echocardiographic finding, and it is encountered in 70% to 90% of the general population. TR has been believed to be a benign disease as it is often asymptomatic and can be managed conservatively with treatments such as diuretic therapy. However, it can sometimes cause right-sided heart failure and require surgical or catheter intervention. Recent studies demonstrated that increased TR severity was associated with higher mortality. Although surgical mortality can be adversely affected by delayed surgical intervention, the optimal timing of intervention for TR remains controversial. A recent study also reported that the prognosis of surgically treated moderate or greater TR did not differ significantly from that treated using medical therapy. Thus, the natural history and risk factors associated with poor outcomes in isolated severe TR remain understudied. Therefore, we aimed to determine the long-term clinical outcomes and risk factors associated with poor prognosis in patients with isolated severe TR to determine the optimal timing for intervention.

METHODS AND RESULTS: Consecutive transthoracic echocardiographic examinations in 2877 patients with isolated severe TR were retrospectively reviewed. Patients with significant left-sided valve disease or repeated examinations were excluded. Primary outcome was defined as a composite of all-cause death and hospitalization for heart failure. Among the 613 enrolled patients (mean age, 74±13 years; men, 38%), 141 died, and 62 were hospitalized for heart failure during the median follow-up period of 26.5 (interquartile range, 6.0–57.9) months. The 5-year event-free rate was 60.1%. TR pressure gradient (adjusted hazard ratio [HR], 1.03 [95% CI, 1.01–1.04]), blood urea nitrogen (adjusted HR, 1.02 [95% CI, 1.01–1.04]), left atrial volume index (adjusted HR, 1.01 [95% CI, 1.002–1.02]), and serum albumin (adjusted HR, 0.56 [95% CI, 0.36–0.95]) were identified as independent predictors of adverse events. A risk model based on the 4 clinical factors that included pulmonary hypertension (TR pressure gradient >40 mm Hg), elevated blood urea nitrogen levels (>25 mg/dL), decreased albumin levels (<3.7 g/dL), and left atrial enlargement (left atrial volume index <34 mL/m2) revealed a graded increase in the risk of adverse events (P<0.001).

CONCLUSIONS: The prognosis of isolated severe TR is not always favorable. Careful attention should be paid to patients with concomitant risk factors, such as pulmonary hypertension, elevated blood urea nitrogen levels, decreased albumin levels, and left atrial enlargement.

Diagram of association between advanced TR and multiorgan damages. LA indicates left atrial; LV, left ventricular; and TR, tricuspid regurgitation.

CLINICAL  PERSPECTIVE

What Is New?

• Patients with severe tricuspid regurgitation may experience adverse events in the long-term.
• A risk model based on pulmonary hypertension, renal and/or liver dysfunction, and left atrial enlargement showed a graded increase in the risk of future adverse events.

What Are the Clinical Implications?

• Intervention might be needed in patients with isolated severe tricuspid regurgitation with concomitant risk factors suspecting multiorgan damages.
• Additional studies are required to evaluate the influence of the interventions on clinical outcomes

in patients with severe tricuspid regurgitation with concomitant risk factors.

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Hospitalized patients with COVID-19 who have a history of chronic HF are at an increased risk for all-cause mortality, according to a study published in ESC Heart Failure.

“Advanced chronic HF (NYHA classes III and IV) is the strongest risk predictor of fatal outcome for COVID-19, and its negative impact on prognosis extends into the early post-hospitalization period, when COVID-19 patients with chronic HF feel worse than those without it, are more likely to seek unplanned medical care, and are more likely to develop de novo disease,” Gregory P. Arutyunov, MD, DSc, RAS, head of the department of internal diseases at Pirogov Russian National Research Medical University in Russia and colleagues wrote. “This suggests the need to develop optimal rehabilitation regimens and a multidisciplinary approach to the management of patients with chronic HF following COVID-19 infection.”

Hospitalized patients with COVID-19 who have a history of chronic HF are at an increased risk for all-cause mortality.

To observe the relationship between all-cause mortality rates and chronic HF history in patients hospitalized with COVID-19, Arutyunov and colleagues analyzed 5,616 patients aged 18 years or older (16.3% with chronic HF) hospitalized with COVID-19 in the Analysis of Comorbid Disease Dynamics in Patients with SARS-CoV-2 Infection (ACTIV) international registry. Patients were divided into two groups based on whether they had a history of chronic HF. All-cause mortality rates were collected in-hospital, as well as after 3 and 6 months of follow-up.

Researchers found that in-hospital mortality was higher in patients with a history of chronic HF than in those without a history of chronic HF (OR = 4.614; 95% CI, 3.633-5.859; P < .001). In-hospital all-cause mortality risk was higher in patients with more severe chronic HF, with patients in NYHA functional classes III and IV (OR vs. no chronic HF = 6.124; 95% CI, 4.538-8.266; P < .001) having higher risks than patients in functional classes I and II (OR vs. no chronic HF = 2.446; 95% CI, 1.831-3.267; P < .001). All-cause mortality risk was also higher in patients with ischemic chronic HF than in patients with nonischemic chronic HF (OR = 1.58; 95% CI, 1.05-2.45; P < .03). In addition, the increased all-cause mortality risk for patients with a history of chronic HF remained after 3 and 6 months of follow-up, according to researchers. “This detrimental interplay of chronic HF and COVID-19 requires careful monitoring, as there is a high likelihood of an increased burden of chronic HF and a change in the course of this condition due to COVID-19 infection,” Arutyunov and colleagues wrote. “Patients with chronic HF should be a priority group in national or population-wide vaccination programs.”

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cardiology today, 8^th Jan 2023 Adapted from: Tilly MJ, et al. Europace. 2022;doi:10.1093/europace/euac244

Autoimmune disorders were associated with elevated atrial fibrillation risk, particularly in women, according to a study published in EP Europace.

Using UK Biobank data from 2006 to 2022, 494,072 patients without AF (median age, 58 years; 55% women) were analyzed for rheumatic fever, gastrointestinal (GI) autoimmune diseases, autoimmune diseases of the musculoskeletal system and connective tissues, and neurological autoimmune diseases. After a median of 12.8 years, 5.5% of patients were diagnosed with new-onset AF.

“We found significant associations between new-onset AF and rheumatic fever without heart involvement, GI (Crohn’s disease and ulcerative colitis) and musculoskeletal system (rheumatoid arthritis, psoriatic and enteropathic arthropathies, polyarteritis nodosa, systemic lupus erythematosus and systemic sclerosis) autoimmune diseases, with AF incidence,” Martijn J Tilly, MS, of the department of epidemiology at Erasmus MC, University Medical Center Rotterdam, the Netherlands, and colleagues wrote. “Moreover, we found evidence of significant differences between men and women in these associations.”

The researchers found that patients had higher risk for developing AF if they had rheumatic fever without heart involvement (HR = 1.47; 95% CI, 1.26-1.72), Crohn’s disease (HR = 1.23; 95% CI, 1.05-1.45), ulcerative colitis (HR = 1.17; 95% CI, 1.06-1.31), rheumatoid arthritis (HR = 1.39; 95% CI, 1.28-1.51), polyarteritis nodosa (HR = 1.82; 95% CI, 1.04-3.09), systemic lupus erythematosus (HR = 1.82; 95% CI, 1.41-2.35) or systemic sclerosis (HR = 2.32; 95% CI, 1.57-3.44).

Autoimmune disorders were associated with elevated AF risk, particularly in women.

Women presented autoimmune disorders at higher rates than men for all but ulcerative colitis and ankylosing spondylitis. Rheumatic fever without heart involvement (HR = 1.79; 95% CI, 1.45-2.2), Crohn’s disease (HR = 1.35; 95% CI, 1.05-1.73), musculoskeletal system disorders (HR = 1.51; 95% CI, 1.38-1.66), rheumatoid arthritis (HR = 1.5; 95% CI, 1.35-1.67), psoriatic and enteropathic arthropathies (HR = 2.01; 95% CI, 1.32-3.05), systemic lupus erythematosus (HR = 1.79; 95% CI, 1.34-2.4), systemic sclerosis (HR = 2.51; 95% CI, 1.64-3.85), ankylosing spondylitis (HR = 1.53; 95% CI, 1.13-2.07) and multiple sclerosis (HR = 1.37; 95% CI, 1.07-1.75) were all significant associations for new-onset AF in women.

Although the incidence rate of new-onset AF in the total population was 4.49 per 1,000 person-years, the rate was 6.25 per 1,000 person years in men and 3.08 per 1,000 person-years in women. “Autoimmune diseases are significantly associated with the risk of new-onset AF in this prospective population-based study, comprising almost half a million participants,” Tilly and colleagues wrote. “Our findings further elaborate on and contribute to the current knowledge of the pathophysiological differences in autoimmunity between men and women.”

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