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High-density lipoprotein (HDL) has beneficial effects in coronary artery disease. Latz and colleagues show that HDL's benefits stem at least in part by activating an anti-inflammatory program dependent on the transcription factor ATF3. High-density lipoprotein (HDL) mediates reverse cholesterol transport and is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. Here we identify the transcriptional regulator ATF3, as an HDL-inducible target gene in macrophages that downregulates the expression of Toll-like receptor (TLR)-induced proinflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo . Our findings may explain the broad anti-inflammatory and metabolic actions of HDL and provide the basis for predicting the success of new HDL-based therapies.

BackgroundMalnutrition is associated with adverse outcomes in patients with aortic stenosis. The Triglycerides × Total Cholesterol × Body Weight Index (TCBI) is a simple scoring model to evaluate the status of nutrition. However, the prognostic relevance of this index in patients undergoing transcatheter aortic valve replacement (TAVR) is unknown. This study aimed to evaluate the association of the TCBI with clinical outcomes in patients undergoing TAVR.MethodsA total of 1377 patients undergoing TAVR were evaluated in this study. The TCBI was calculated by the formula; triglyceride (mg/dL) × total cholesterol (mg/dL) × body weight (kg)/1000. The primary outcome was all-cause mortality within 3 years.ResultsPatients with a low TCBI, based on a cut-off value of 985.3, were more likely to have elevated right atrial pressure (p = 0.04), elevated right ventricular pressure (p < 0.01), right ventricular systolic dysfunction (p < 0.01), tricuspid regurgitation ≥ moderate (p < 0.01). Patients with a low TCBI had a higher cumulative 3-year all-cause (42.3% vs. 31.6%, p < 0.01; adjusted HR 1.36, 95% CI 1.05–1.77, p = 0.02) and non-cardiovascular mortality (15.5% vs. 9.1%, p < 0.01; adjusted HR 1.95, 95% CI 1.22–3.13, p < 0.01) compared to those with a high TCBI. Adding a low TCBI to EuroSCORE II improved the predictive value for 3-year all-cause mortality (net reclassification improvement, 0.179, p < 0.01; integrated discrimination improvement, 0.005, p = 0.01).ConclusionPatients with a low TCBI were more likely to have right-sided heart overload and exhibited an increased risk of 3-year mortality. The TCBI may provide additional information for risk stratification in patients undergoing TAVR.

Cardiogenic shock and cardiac arrest contribute pre-dominantly to mortality in acute cardiovascular care. Here, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as an established therapeutic option for patients suffering from these life-threatening entities. VA-ECMO provides temporary circulatory support until causative treatments are effective and enables recovery or serves as a bridging strategy to surgical ventricular assist devices, heart transplantation or decision-making. However, in-hospital mortality rate in this treatment population is still around 60%. In the recently published ARREST trial, VA-ECMO treatment lowered mortality rate in patients with ongoing cardiac arrest due to therapy refractory ventricular fibrillation compared to standard advanced cardiac life support in selected patients. Whether VA-ECMO can reduce mortality compared to standard of care in cardiogenic shock has to be evaluated in the ongoing prospective randomized studies EURO-SHOCK (NCT03813134) and ECLS-SHOCK (NCT03637205). As an innate drawback of VA-ECMO treatment, the retrograde aortic flow could lead to an elevation of left ventricular (LV) afterload, increase in LV filling pressure, mitral regurgitation, and elevated left atrial pressure. This may compromise myocardial function and recovery, pulmonary hemodynamics—possibly with concomitant pulmonary congestion and even lung failure—and contribute to poor outcomes in a relevant proportion of treated patients. To overcome these detrimental effects, a multitude of venting strategies are currently engaged for both preventive and emergent unloading. This review aims to provide a comprehensive and structured synopsis of existing venting modalities and their specific hemodynamic characteristics. We discuss in detail the available data on outcome categories and complication rates related to the respective venting option.

A decline in hospitalization for cardiovascular events and catheter laboratory activation was reported for the United States and Italy during the initial stage of the Covid-19 pandemic of 2020. We report on the deployment of emergency services for cardiovascular events in a defined region in western Germany during the government-imposed lock-down period. We examined 5799 consecutive patients who were treated by emergency services for cardiovascular events during the Covid-19 pandemic (January 1 to April 30, 2020), and compared those to the corresponding time frame in 2019. Examining the emergency physicians' records provided by nine locations in the area, we found a 20% overall decline in cardiovascular admissions. The greatest reduction could be seen immediately following the government-imposed social restrictions. This reduction was mainly driven by a reduction in discretionary admissions for dizziness/syncope (-53%), heart failure (-38%), exacerbated COPD (-28%) and unstable angina (-23%), while unavoidable admissions for ST-elevation myocardial infarction (STEMI), cardiopulmonary resuscitation (CPR) and stroke were unchanged. There was a greater decline in emergency admissions for patients ≥60 years. There was also a greater reduction in emergency admissions for those living in urban areas compared to suburban areas. During the Covid-19 pandemic, a significant decline in hospitalization for cardiovascular events was observed during the government-enforced shutdown in a predefined area in western Germany. This reduction in admissions was mainly driven by \"discretionary\" cardiovascular events (unstable angina, heart failure, exacerbated COPD and dizziness/syncope), but events in which admission was unavoidable (CPR, STEMI and stroke) did not change.

Right ventricular failure (RVF) after cardiac surgery is associated with an in-hospital mortality rate of up to 75%. Microaxial flow pumps are one of the mechanical circulatory supports (MCS) options available for the treatment of RVF, however the specifics of timing and indication for MCS, as well as predictors for survival, remain unclear due to a dearth of published data. We evaluated the clinical outcome of patients treated with Impella-RP for predictors of mortality and the hemodynamic effects of the pump. This is a single-center retrospective observational study involving adult patients who underwent cardiac surgery with cardiopulmonary bypass between January 2019 and December 2020 in cardiac surgery and required therapeutic management of RVF with an Impella-RP. Overall, 18 patients were included and analyzed for factors that could be associated with mortality, or that could be predictors of patient outcomes for this population. Treatment of RVF with Impella-RP improved the patient hemodynamics significantly and had a survival rate of 61% within 30 days. Patients with isolated CABG or better liver function before implantation had a better survival rate, which may indicate that underlying disease and timing of implantation are significant for successful treatment of RVF.

Prognosis estimation in patients with cardiogenic shock (CS) is important to guide clinical decision making. Aim of this study was to investigate the predictive value of opportunistic CT-derived body composition analysis in CS patients. Amount and density of fat and muscle tissue of 152 CS patients were quantified from single-slice CT images at the level of the intervertebral disc space L3/L4. Multivariable Cox regression and Kaplan–Meier survival analyses were performed to evaluate the predictive value of opportunistically CT-derived body composition parameters on the primary endpoint of 30-day mortality. Within the 30-day follow-up, 90/152 (59.2%) patients died. On multivariable analyses, lactate (Hazard Ratio 1.10 [95% Confidence Interval 1.04–1.17]; p  = 0.002) and patient age (HR 1.04 [95% CI 1.01–1.07], p  = 0.017) as clinical prognosticators, as well as visceral adipose tissue (VAT) area (HR 1.004 [95% CI 1.002–1.007]; p  = 0.001) and skeletal muscle (SM) area (HR 0.987 [95% CI 0.975–0.999]; p  = 0.043) as imaging biomarkers remained as independent predictors of 30-day mortality. Kaplan–Meier survival analyses showed significantly increased 30-day mortality in patients with higher VAT area ( p  = 0.015) and lower SM area ( p  = 0.035). CT-derived VAT and SM area are independent predictors of dismal outcomes in CS patients and have the potential to emerge as new imaging biomarkers available from routine diagnostic CT.

Vitamin K is classically known for hepatic γ-carboxylation via VKORC1, yet accumulating evidence suggests broader redox-regulatory roles. Here, we characterize the VKORC1 paralogue VKORC1L1 as an anti-oxidative enzyme that couples the vitamin K cycle to ferroptosis defense in the endothelium. In human coronary artery endothelial cells (HCAEC), menaquinone-7 (Vitamin K2, MK-7) increased viability and attenuated RSL3-induced lipid peroxidation, ferroptosis, and NF-κB-dependent inflammatory activation. In vivo, a MK-7 enriched diet accelerated reendothelialization after electric carotid injury in C57BL/6J mice without altering hemostasis. Silencing VKORC1L1, but not the coagulation-linked VKORC1, diminished HCAEC proliferation, raised reactive oxygen species, and triggered NF-κB activation. Importantly, MK-7 failed to rescue these effects in VKORC1L1-deficient cells, supporting a functional requirement for VKORC1L1 in vitamin K-mediated cytoprotection. Transcriptomics of VKORC1L1-deficient cells revealed a lipid peroxide/NF-κB/TNF pathway that amplified oxidative inflammation. This signaling axis was blocked by the lipid-radical scavenger ferrostatin-1 or by inhibiting TNF shedding. Collectively, these data identify VKORC1L1 as a redox-responsive component of the endothelial vitamin K cycle that limits lipid peroxides, suppresses ferroptosis, restrains TNF-driven inflammation, and promotes vascular repair.

Lactate and glucose are widely used biochemical parameters in current predictive risk scores for cardiogenic shock. Data regarding the relationship between lactate and glucose levels in cardiogenic shock are limited. Thus, we aimed to analyze glucose and lactate as early markers for in-hospital mortality in cardiogenic shock. In this retrospective cohort study, 312 patients presenting with cardiogenic shock to a tertiary-care hospital between 2016 and 2018 were included. Apparent cardiogenic shock was defined as hypoperfusion with hemodynamic compromise and biochemical marker increase due to diminished tissue perfusion, corresponding to SCAI shock stages. In-hospital mortality was assessed as the primary endpoint. The median age of the study population was 71 (60–79) years and the etiology of cardiogenic shock was acute myocardial infarction in 45.8%. Overall in-hospital mortality was 67.6%. In the receiver operating curve analysis, the area under the receiver-operating curve (AUC) for prediction of in-hospital mortality was higher for lactate (AUC: 0.757) than for glucose (AUC: 0.652). Both values were significantly associated with outcome (groups created with best cutoff values obtained from the Youden index). Correlation analysis showed a significant non-linear association of both values. In a multivariable stepwise Cox regression analysis, lactate remained an independent predictor for in-hospital mortality, whilst glucose, despite being implicated in energy metabolism, was not independently predictive for mortality. Together, these data suggest that lactate at admission is superior for mortality prediction in patients with apparent cardiogenic shock. Glucose was not independently predictive for mortality.

BackgroundAssessing right ventricular (RV) function is paramount for risk stratification, which remains challenging in patients with tricuspid regurgitation (TR). We assessed RV–pulmonary artery (PA) coupling and its predictability of outcomes after transcatheter tricuspid valve repair (TTVR).MethodsStudy participants comprised patients undergoing transcatheter tricuspid valve repair to treat symptomatic TR from June 2015 to July 2021. We calculated an RV–PA coupling ratio using a formula, which is dividing tricuspid annular plane systolic excursion (TAPSE) by echocardiographically estimated (ePASP) or invasively measured PASP (iPASP) at baseline. The primary outcome was all-cause mortality or heart failure rehospitalization within one year.ResultsThe study participants (n = 206) were at high surgical risk (EuroSCORE II: 7.4 ± 4.8%). The primary outcome occurred in 57 patients within one year. The c-statistics for the outcome were 0.565 (95% CI 0.488–0.643) for TAPSE/ePASP and 0.695 (95% CI 0.631–0.759) for TAPSE/iPASP. The correlation between the ePASP and iPASP was attenuated in patients with massive/torrential TR compared to those with severe TR (interaction p = 0.01). In the multivariable Cox proportional model, TAPSE/iPASP was inversely associated with the risk of the primary outcome (per 0.1-point increase: adjusted-HR 0.67, 95% CI 0.56–0.82, p < 0.001), independent of baseline demographics. According to the TAPSE/iPASP quartiles (i.e., ≤ 0.316; 0.317–0.407; 0.408–0.526; ≥ 0.527), the event-free survival was 43.4%, 48.3%, 77.9%, and 85.4% at one year after TTVR.ConclusionRV–PA coupling predicts one-year mortality and heart failure rehospitalization after TTVR in patients with TR. The predictability is improved if invasively-measured PA pressure is included.Assessing right ventricular (RV) function is paramount for risk stratification. The present analysis confirms that RV–PA coupling, measured as TAPSE/PASP, predicts one-year mortality and heart failure rehospitalization in patients undergoing TTVR. There is a significant interaction between TR severity and the correlation of ePASP with iPASP, and therefore the correlation is attenuated in patients with massive to torrential TR. The predictability of RV–PA coupling is improved if PA pressure is measured invasively and included in the formula.

Transcatheter tricuspid valve repair (TTVR) might be an alternative option to reduce tricuspid regurgitation (TR) in patients with sarcopenia. Psoas muscle area (PMA) measured using computed tomography (CT) is known as a marker of sarcopenia. We investigated the association of PMA with procedural and clinical outcomes following TTVR. We retrospectively measured left and right PMA using pre-procedural CT in patients undergoing TTVR. Low PMA was defined as the total PMA < 20.3 cm 2 for men and < 11.8 cm 2 for women. The primary outcome was a composite of all-cause mortality and heart failure hospitalization within one year after TTVR. Of 163 patients, 47 (29%) were considered as having low PMA. Procedural success, defined as residual TR of ≤ 2 + at discharge, and in-hospital mortality were comparable between patients with low and high PMA. Patients with low PMA had a higher incidence of the composite outcome than those with high PMA (49% vs. 21%; p = 0.001) This association was consistent after adjusting for baseline characteristics (adjusted hazard ratio 0.43; 95% confidence interval: 0.23–0.80; p = 0.008). In contrast, the New York Heart Association functional class improved from baseline to three-month follow-up, regardless of PMA. Approximately 30% of patients undergoing TTVR were found to have low PMA. Although TTVR may be a safe therapeutic option to reduce TR and improve heart failure symptoms in patients with sarcopenia, the prognosis after TTVR remains poor in this population. Pre-procedural CT-based assessment of PMA may enhance risk stratification and support better clinical decision-making for TTVR. Graphical abstract Psoas muscle area and outcomes after transcatheter tricuspid valve repair Patients with low psoas muscle area (PMA) had a higher incidence of all-cause mortality (upper right) and heart failure hospitalization (lower right). CT = computed tomography.