Pathophysiology of sepsis-induced cardiomyopathy.

S100a8/a9 contributes to sepsis-induced cardiomyopathy by activating ERK1/2-Drp1-mediated mitochondrial fission and respiratory dysfunction.

Assessment of quality of care in heart failure (HF) has focused on the development and use of process of care-based performance measures. While it has been presumed that these process measures when applied in actual clinical practice are associated with improved clinical outcomes, this link has not been well-established. A recent analysis of the Organized Program to Initiate Lifesaving Treatment In Hospitalized Patients With Heart Failure (OPTIMIZE-HF) 1 registry/performance improvement program examined the relationship between current performance measures for patients hospitalized with HF and relevant patient clinical outcomes. This study found that none of the current HF performance measures were significantly associated with reduced early mortality risk and only angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use at discharge was associated with 60- to 90-day postdischarge mortality or rehospitalization. b-Blocker therapy at the time of hospital discharge, currently not an HF performance measure, was strongly associated with reduced risk of mortality and mortality/rehospitalization postdischarge. To accurately identify health care providers and hospitals providing care that is associated with more optimal clinical outcomes, additional HF performance measures as well as better methodology for identifying and validating performance measures is needed. HF is the leading cause of hospitalization in persons older than 65 years, with almost 3.6 million hospitalizations attributed to HF as the primary or a secondary discharge diagnosis each year. 2 HF patients are at substantial risk for recurrent exacerbations of symptoms requiring intervention, with up to 50% of discharged patients being rehospitalized within 6 months. An estimated 11.6% of HF patients die within 30 days and 33.1% of patients die within 1 year after their first hospitalization for HF. 3 Uniform highquality health care might reasonably be expected to reduce this burden of morbidity and mortality associated with HF. Evidence-based guidelines for the diagnosis and treatment of patients with HF have been developed. 2,4 To facilitate the measurement of and improvement in quality of care in HF, components of these guidelines have been adapted by the various organizations as performance measures. 5,6 These performance measures are based on clinical practice guidelines but are intended to be confined to those structural aspects or processes of care for which the evidence is so strong that the failure to perform them reduces the likelihood of optimal patient outcomes. 5 It is impor

Funding AcknowledgementsType of funding sources: None.BackgroundPatients with heart failure in the setting of COVID-19 requiring admission to the intensive care unit may present a set of unique challenges. There is limited data to describe the clinical characteristics and outcomes in this subset of the patient population.PurposeThe study"s purpose was to extensively describe the characteristics and outcomes of heart failure patients admitted to the intensive care unit with COVID-19 compared to non-heart failure patients .MethodsWe conducted a multicenter, prospective analysis for all adult critically ill patients with heart failure admitted to intensive care units (ICUs) between March 1 to August 31, 2020, with an objectively confirmed diagnosis of COVID-19.ResultsA total of 723 critically ill patients with COVID-19 had been admitted in ICUs, 59 patients with heart failure, and 664 patients with no heart failure before ICU admission. Heart failure patients had significantly more comorbid conditions such as diabetes mellitus, hypertension, dyslipidemia, atrial fibrillation, and acute coronary syndrome. Higher baseline severity scores (APACHE II & SOFA score) and nutritional risk (NUTRIC Score) were observed in heart failure patients. Also, heart failure patients had more acute kidney injury during ICU admission and required more mechanical ventilation within 24 hours of ICU admission. Patients with heart failure had a similar incidence of thrombosis compared to patients with no heart failure. Critically ill patients with COVID-19 and heart failure had similar ICU length of stay (LOS), mechanical ventilation duration, and hospital LOS compared to patients with no heart failure. During ICU stay, patients with heart failure had more in-hospital and ICU deaths in comparison to the non-heart failure group (64.3% vs. 44.6%, P-value <0.01) and (54.5% vs. 39%, P-value = 0.02) respectively.ConclusionIn this observational study evaluating the clinical characteristics and outcomes of critically ill COVID-19 patients with heart failure, patients with COVID-19 and heart failure had similar ICU LOS, duration of MV and hospital LOS, thrombosis rate compared to patients with no heart failure. However, during ICU stay, patients with heart failure had more in-hospital and ICU deaths than the non-heart failure group.

Proactive Approach to Peri-Induction Hemodynamic Management in Critically Ill Patients

Levosimendan And Septic Cardiomyopathy: A Key That May Have Found Its Lock?

Extracorporeal membrane oxygenation in adult patients with sepsis and septic shock: Why, how, when, and for whom

Clinical characteristics and outcomes of patients with heart failure admitted to the intensive care unit with coronavirus disease 2019 (COVID-19): A multicenter cohort study

Sepsis-induced cardiomyopathy.

Sepsis is one of the primary causes of death in intensive care units. Recently, increasing evidence has identified lncRNA HOTAIR is involved in septic cardiomyopathy. However, the potential mechanism underlying HOTAIR on septic cardiomyopathy is still unknown. H9C2 cells were treated with lipopolysaccharide (LPS) after transfection with sh-HOTAIR, sh-Lin28, pcDNA3.1-HOTAIR, and pcDNA3.1-PDCD4. qRT-PCR was used to examine the level of HOTAIR, Lin28, PDCD4, and sepsis-related inflammatory cytokines. Flow cytometric analysis was applied to detect cell apoptosis. The interaction between Lin28 and HOTAIR or PDCD4 was verified by RNA pull-down and RIP assay. HOTAIR levels were interfered by AAV9-sh-HOTAIR in LPS-induced septic cardiomyopathy mice. ELISA analysis was used to evaluate TNF-α, IL-6, and IL-1β level. Western blot was used to detect the expression of LIN28 and PDCD4 in mouse cardiomyocytes. Echocardiography was used to evaluate the cardiac function. In our study, knockdown of HOTAIR inhibited LPS-induced inflammation and H9C2 cells apoptosis. HOTAIR promoted LPS-induced inflammatory response and apoptosis of H9C2 cells by enhancing PDCD4 stability. RNA pull-down and RIP assay exhibited that Lin28, a highly conserved RNA-binding protein, was combined with HOTAIR and PDCD4. The in vivo experiments verified that the HOTAIR knockdown alleviated the cardiac function injury and secretion of inflammatory factors caused by sepsis. In conclusion, our findings supported that the HOTAIR/Lin28/PDCD4 axis serves as a critical regulator of sepsis, which may open a new direction for the development of sepsis therapeutic.

To evaluate survival outcomes and identify candidate profiles for venoarterial extracorporeal membrane oxygenation in adult patients with sepsis-induced cardiomyopathy. The authors systematically searched PubMed, Embase, and Google Scholar up to October 22, 2024, for English-language studies investigating venoarterial extracorporeal membrane oxygenation in adult patients with septic shock and/or sepsis-induced cardiomyopathy. Two reviewers independently screened studies, assessed quality, and extracted data on demographics, illness severity, and survival. Studies were conducted in intensive care units across multiple international centers. A total of 15 studies, including 1,110 adult patients with septic shock and/or septic cardiomyopathy who underwent extracorporeal membrane oxygenation support, were identified. Venoarterial extracorporeal membrane oxygenation was implemented as a salvage therapy for refractory septic shock and/or sepsis-induced cardiomyopathy. The primary outcome was survival to hospital discharge. Secondary data included age, mean arterial pressure, arterial pH, lactate level, PaO₂/FiO₂ ratio, ejection fraction, inotrope score, and Sequential Organ Failure Assessment (SOFA) score. The pooled survival rate was 42%. At venoarterial extracorporeal membrane oxygenation initiation, patients exhibited severe hemodynamic instability: mean age 52 ± 6 years; mean arterial pressure 62 ± 8 mmHg; pH 7.20 ± 0.07; lactate 9 ± 6 mmol/L; PaO₂/FiO₂ 85 ± 20; ejection fraction 33% ± 15; inotrope score 122 ± 99 μg/kg/min; SOFA score 15 ± 3. Venoarterial extracorporeal membrane oxygenation may provide meaningful survival benefits in carefully selected patients with severe, refractory septic shock and/or sepsis-induced cardiomyopathy. Given the observational nature and the heterogeneity of the included studies, these findings should be interpreted with caution. Further prospective trials are needed to refine patient selection and optimize outcomes.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The heart is one of the most important oxygen delivery organs, and dysfunction significantly increases the mortality of the body. Hence, the heart has been studied in sepsis for over half a century. However, the definition of sepsis-induced cardiomyopathy is not unified yet, and the conventional conception seems outdated: left ventricular systolic dysfunction (LVSD) along with enlargement of the left ventricle, recovering in 7 to 10 days. With the application of echocardiography in intensive care units, not only LVSD but also left ventricular diastolic dysfunction, right ventricular dysfunction, and even diffuse ventricular dysfunction have been seen. The recognition of sepsis-induced cardiomyopathy is gradually becoming complete, although our understanding of it is not deep, which has made the diagnosis and treatment stagnate. In this review, we summarize the research on sepsis-induced cardiomyopathy. Women and young people with septic cardiomyopathy are more likely to have LVSD, which may have the same mechanism as stress cardiomyopathy. Elderly people with ischemic cardiomyopathy and hypertension tend to have left ventricular diastolic dysfunction. Patients with mechanical ventilation, acute respiratory distress syndrome or other complications of increased right ventricular afterload mostly have right ventricular dysfunction. Diffuse cardiac dysfunction has also been shown in some studies; patients with mixed or co-existing cardiac dysfunction are more common, theoretically. Thus, understanding the pathophysiology of sepsis-induced cardiomyopathy from the perspective of critical care echocardiography is essential.

Septic cardiomyopathy is a common complication of severe sepsis, which is one of the leading causes of death in intensive care units. Therefore, finding an effective therapy target is urgent. Neferine is an alkaloid extracted from the green embryos of mature seeds of Nelumbo nucifera Gaertn., which has been reported to exhibit various biological activities and pharmacological properties. This study aims to explore the protective effects of neferine against lipopolysaccharide (LPS)-induced myocardial dysfunction and its mechanisms. The LPS-induced cardiac dysfunction mouse model was employed to investigate the protective effects of neferine. In this study, we demonstrated that neferine remarkably improved cardiac function and survival rate and ameliorated morphological damage to heart tissue in LPS-induced mice. Neferine also improved cell viability and mitochondrial function and reduced cell apoptosis and the production of reactive oxygen species in LPS-treated H9c2 cells. In addition, neferine significantly upregulated Bcl-2 expression and suppressed cleaved caspase 3 activity in LPS-induced mouse heart tissue and H9c2 cells. Furthermore, neferine also upregulated the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) signaling pathway in vivo and in vitro. Conversely, LY294002 (a PI3K inhibitor) reversed the protective effect of neferine in LPS-induced H9c2 cells. Our findings thus demonstrate that neferine ameliorates LPS-induced cardiac dysfunction by activating the PI3K/AKT/mTOR signaling pathway and presents a promising therapeutic agent for the treatment of LPS-induced cardiac dysfunction.

Estimating the Organ Donor Potential in Denmark: A Prospective Analysis of Deaths in Intensive Care Units in Northern Denmark

To describe the practices in intensive care units in Mumbai hospitals regarding limitation and withdrawal of care at the end of life. Review of prospectively collected data. Intensive care units of four major hospitals (two private tertiary referral general hospitals, one mixed public and private cancer referral hospital, and one large public hospital). Hospital and intensive care unit patients who died during the study period. None. We measured the percentage of hospital deaths occurring inside and outside intensive care units and the incidence of withholding intubation, withholding other therapy, and withdrawing therapy for deaths in the intensive care unit. The proportion of hospital deaths that occurred in an intensive care unit was 14% in the cancer hospital, 23% in the public hospital, and 58-73% in the two private hospitals (chi-square test for trends, p < .0001). Of the 143 deaths that occurred in intensive care unit, limitation of care occurred in 49 patients. Twenty-five percent of these patients were not intubated terminally, 67% were initially intubated and ventilated but failed to recover and subsequently had no further escalation of therapy, and 8% had withdrawal of therapy. Therapy was limited in 19% of deaths in the public hospital intensive care unit (odds ratio, 0.44; 95% confidence interval, 0.2-0.97) vs. 40%, 41%, and 50% of deaths in the other three intensive care units. Therapy is limited in a significant proportion of intensive care unit patients. Significant differences in the practice of limitation of therapy exist between public and private hospitals. Lack of access to a limited number of intensive care unit beds, especially in the public hospital, may constitute implicit limitation of care.

Chronic heart failure in intensive care unit: can we accurately predict the risk?