Background Cardiogenic shock (CS) is a heterogeneous clinical syndrome, making it challenging to predict patient trajectory and response to treatment. This study aims to identify biological/molecular CS subphenotypes, evaluate their association with outcome, and explore their impact on heterogeneity of treatment effect (ShockCO-OP, NCT06376318). Methods We used unsupervised clustering to integrate plasma biomarker data from two prospective cohorts of CS patients: CardShock (N = 205 [2010-2012, NCT01374867]) and the French and European Outcome reGistry in Intensive Care Units (FROG-ICU) (N = 228 [2011-2013, NCT01367093]) to determine the optimal number of classes. Thereafter, a simplified classifier (Euclidean distances) was used to assign the identified CS subphenotypes in three completed randomized controlled trials (RCTs) (OptimaCC, N = 57 [2011-2016, NCT01367743]; DOREMI, N = 192 [2017-2020, NCT03207165]; and CULPRIT-SHOCK, N = 434 [2013-2017, NCT01927549]) and explore heterogeneity of treatment effect with respect to 28-day mortality (primary outcome). Findings Four biomarker-driven CS subphenotypes ('adaptive', ' non-inflammatory', ' cardiopathic ' , and ' in fl ammatory ' ) were identified separately in the two cohorts. Patients in the inflammatory and cardiopathic subphenotypes had the highest 28-day mortality (p (log-rank test) = 0.0099 and 0.0055 in the CardShock and FROG-ICU cohorts, respectively). Subphenotype membership significantly improved risk stratification when added to traditional risk factors including the Society for Cardiovascular Angiography and Interventions (SCAI) shock stages (increase in Harrell's C-index by 4% (p = 0.033) and 6% (p = 0.0068) respectively in the CardShock and the FROG-ICU cohorts). The simplified classifier identified CS subphenotypes with similar biological/molecular and outcome characteristics in the three independent RCTs. No significant interaction was observed between treatment effect and subphenotypes. Interpretation Subphenotypes with the highest concentration of biomarkers of endothelial dysfunction and inflam- mation (inflammatory) or myocardial injury/fibrosis (cardiopathic) were associated with mortality independently from the SCAI shock stages. Funding Dr Sabri Soussi was awarded the Canadian Institutes of Health Research (CIHR) Doctoral Foreign Study Award (DFSA) and the Merit Awards Program (Department of Anesthesiology and Pain Medicine, University of Toronto, Canada) for the current study. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Abstract Aims Cardiogenic shock (CS) is the deadliest manifestation of acute heart failure, with persistently high mortality rates and a lack of recent therapeutic breakthroughs. Accurate risk prediction is crucial in clinical decision‐making and the design of future clinical trials. We aimed to validate the CLIP score, a biomarker‐based risk score comprising cystatin C, lactate, interleukin‐6 and NT‐proBNP, for predicting mortality in acute coronary syndrome (ACS) related CS, and to compare its predictive value with the previously published CardShock risk score. Methods and results The study is a post hoc analysis of the CardShock Study, a prospective, observational European multicentre study on CS. The CLIP score was calculated 12 h after hospital admission, and its ability to predict 90‐day mortality was assessed using are under the curve (AUC) of the receiver‐operating characteristics (ROC) curve analysis. The discriminative ability of the CLIP score was compared with the CardShock risk score by comparing the AUC's. The cohort was dichotomized into low and high risk groups by the optimal cut‐off value derived from the ROC analysis of the CLIP score. Kaplan–Meier curves were constructed to evaluate risk stratification when combining the CLIP and CardShock risk scores. The cohort (n = 121) comprised 77% (n = 93) men and the median age was 67 years (IQR 61–76). A total of 21% (n = 25) of the patients had non‐ACS related CS. The CLIP score demonstrated appropriate predictive accuracy for 90‐day mortality (AUC 0.84, 95% CI 0.77–0.91), comparable with the CardShock risk score (AUC 0.77 [95% CI 0.69–0.85]; P = 0.064 for comparison). A CLIP score cut‐off of 0.28 stratified patients into high risk (65% mortality) and low risk (16% mortality) groups. In addition, incorporating the CLIP score enhanced risk stratification in all CardShock risk score categories. Conclusions The CLIP score, calculated within 12 h of hospital admission, accurately predicted 90‐day mortality in CS and complemented the CardShock risk score. The biomarker‐based score has potential utility in dynamic mortality risk assessment and could inform clinical management and trial design.

Cardiogenic shock (CS) is a medical emergency with high in-hospital mortality. New biomarkers are needed to identify patients at a greater risk of adverse outcomes. This study aimed to investigate the prognostic potential of microRNAs (miRNAs) in assessment of the outcome of cardiogenic shock. Circulating miRNA levels were measured by quantitative PCR in plasma samples collected at baseline from 165 patients of the multicenter, prospective, observational CardShock study and compared between in-hospital and 90-day survivors and non-survivors. Of the 10 studied miRNAs, median levels of miR-20b-5p at baseline were significantly higher in in-hospital and 90-day survivors compared to non-survivors [median 0.014 arbitrary units (AU) (interquartile range (IQR) 0.003-0.024) vs. 0.008 AU (IQR 0.001-0.015), p = 0.013] and [0.015 AU (IQR 0.003-0.025) vs. 0.010 AU (IQR 0.001-0.015), p = 0.012], respectively. In Cox regression analysis, miR-20b-5p levels in the highest quartile were significantly associated with 90-day survival (adjusted hazard ratio 2.47 (95 % confidence interval 1.16-5.28), p = 0.019) when adjusted for CardShock Risk Score variables (age, confusion at presentation, previous myocardial infarction or coronary artery bypass grafting, acute coronary syndrome (ACS) etiology, left ventricular ejection fraction, lactate, and estimated glomerular filtration rate). A similar association of highest quartile miR-20b-5p levels with 90-day survival was also confirmed in ACS patient subcohort (79 % of CS patients). The results of this study indicate that circulating levels of miR-20b-5p at baseline could help in assessing in-hospital and 90-day survival in CS patients.

BACKGROUND: Chloride plays a crucial role in renal salt sensing. This study investigates whether serum chloride is associated with clinical outcomes and decongestive response to acetazolamide in patients with acute decompensated heart failure. METHODS: This post hoc analysis includes all 519 patients from the ADVOR trial (Acetazolamide in Decompensated Heart Failure With Volume Overload), randomized to intravenous acetazolamide or matching placebo on top of intravenous loop diuretics. The impact of baseline serum chloride on the main trial end points and the treatment effect of acetazolamide was assessed, as was the evolution of serum chloride under decongestive treatment. RESULTS: Hypochloremia (<96 mmol/L) and hyperchloremia (>106 mmol/L) were present in 80 (15%) and 53 (10%), respectively, at baseline. Hypochloremia was associated with significantly slower decongestion, a longer length of hospital stay, and increased risk of all-cause mortality and heart failure readmissions. Acetazolamide increased the odds of successful decongestion and reduced length of stay irrespectively of baseline serum chloride levels. No statistically significant interaction between serum chloride levels and the effect of acetazolamide on death or heart failure readmissions was observed. The placebo group exhibited a progressive decline in serum chloride, which was effectively prevented by acetazolamide ( P <0.001). CONCLUSIONS: Hypochloremia is associated with diuretic resistance and worse clinical outcomes. Add-on acetazolamide therapy improves decongestion across the entire range of serum chloride and prevents the drop in chloride levels caused by loop diuretic monotherapy. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03505788

Background: The characterization of the different pathophysiological mechanisms involved in normotensive versus hypertensive acute heart failure (AHF) might help to develop individualized treatments. Methods: The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring the B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT) concentrations in 1152 patients presenting with centrally adjudicated AHF to the emergency department (ED) (derivation cohort). AHF was classified as normotensive with a systolic blood pressure (SBP) of 90–140 mmHg and hypertensive with SBP > 140 mmHg at presentation to the ED. Findings were externally validated in an independent AHF cohort (n = 324). Results: In the derivation cohort, with a median age of 79 years, 43% being women, 667 (58%) patients had normotensive and 485 (42%) patients hypertensive AHF. Hemodynamic cardiac stress, as quantified by the BNP and NT-proBNP, was significantly higher in normotensive as compared to hypertensive AHF [1105 (611–1956) versus 827 (448–1419) pg/mL, and 5890 (2959–12,162) versus 4068 (1986–8118) pg/mL, both p < 0.001, respectively]. Similarly, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF [41 (24–71) versus 33 (19–59) ng/L, p < 0.001]. A total of 313 (28%) patients died during 360 days of follow-up. All-cause mortality was higher in patients with normotensive AHF vs. patients with hypertensive AHF (hazard ratio 1.66, 95%CI 1.31–2.10; p < 0.001). Normotensive patients with a high BNP, NT-proBNP, or hs-cTnT had the highest mortality. The findings were confirmed in the validation cohort. Conclusion: Biomarker profiling revealed a higher extent of hemodynamic stress and cardiomyocyte injury in patients with normotensive versus hypertensive AHF.

Abstract Background Secretoneurin (SN) concentrations have been found to provide strong prognostic information in critically ill patients. Accordingly, in this study we hypothesized that SN would provide prognostic information in patients with cardiogenic shock. Objectives To evaluate the utility of SN concentrations to predict 90-day mortality in two multicenter, prospective clinical trials including patients with cardiogenic shock. Methods We measured SN concentrations with a CE-marked ELISA in patients with cardiogenic shock of all etiologies (Cohort #1, n=168) and in patients with post-myocardial infarction cardiogenic shock (Cohort #2, n=45). Inclusion criteria in both cohorts focused on systolic blood pressure <90 mmHg and evidence of tissue hypoperfusion, including increased lactate concentrations. We used Cohort #1 for primary analysis and Cohort #2 for validation. We assessed association between SN concentrations and mortality by Kaplan-Meier curves and by univariate and multivariable Cox proportional hazard regression analysis. Results Median age was 67 and 69 years (Cohort #1 and #2) and the patients were predominantly male (74% and 67%, respectively). Median SN concentration on study inclusion was 53 pmol/L in Cohort #1 and 50 pmol/L in Cohort #2, and SN concentrations decreased from study inclusion to 72 hours (p=0.03 for trend). 90-day mortality was 42% in Cohort #1 and patients with high SN concentrations had worse outcome (Figure A). Adjusting for variables that were associated with 90-day mortality in univariate analysis and not part of the inclusion selection, i.e., age, sex, comorbidities, blood pressure, estimated glomerular filtration rate, treatment, and N-terminal pro-B-type natriuretic peptide concentrations, SN concentrations on study inclusion were still associated with 90-day mortality: hazard ratio per 100 pmol/L increment 1.97 (1.29-3.01), p=0.002. 90-day mortality was 45% in Cohort #2 and SN concentrations were predictive of 90-day mortality also in Cohort #2 (Figure B). Conclusion SN concentrations provide incremental prognostic information to established risk indices in the early phase of cardiogenic shock.A. Cohort #1 with SN tertilesB. Cohort #2 divided by SN median

BACKGROUND:Elevated BNP and the N-terminal fragment of the proBNP (NT-proBNP) are hallmarks of heart failure (HF). Generally, both biomarkers parallel each other. In patients receiving sacubitril/valsartan, BNP remained stable while NT-proBNP decreased. As BNP and NT-proBNP assays have limited specificity due to cross-reactivity, we quantified by mass spectrometry (MS) the contributing molecular species.METHODS:We included 356 healthy volunteers, 100 patients with acute dyspnoea (49 acute decompensated HF; 51 dyspnoea of non-cardiac origin), and 73 patients with chronic HF and reduced ejection fraction treated with sacubitril/valsartan. BNP and NT-proBNP immunoreactivities (BNPir and NT-proBNPir) were measured by immunoassays (Abbott ARCHITECT and Roche Diagnostics proBNPII) and proBNP-derived peptides and glycosylation at serine 44 by MS on plasma samples.RESULTS:BNPir corresponded to the sum of proBNP1-108, BNP1-32, BNP3-32, and BNP5-32 (R2 = 0.9995), while NT-proBNPir corresponded to proBNP1-108 and NT-proBNP1-76 not glycosylated at serine 44 (R2 = 0.992). NT-proBNPir was better correlated (R2 = 0.9597) than BNPir (R2 = 0.7643) with proBNP signal peptide (a surrogate of proBNP production). In patients receiving sacubitril/valsartan, non-glycosylated NT-proBNP1-76 remained constant (P = 0.84) despite an increase in NT-proBNP1-76 and its glycosylation (P < 0.0001). ProBNP1-108 remained constant (P = 0.12) while its glycosylation increased (P < 0.0001), resulting in a decrease in non-glycosylated proBNP1-108 (P < 0.0001), and in NT-proBNPir.CONCLUSIONS:Glycosylation interfered with NT-proBNPir measurement, explaining the discrepant evolution of these 2 biomarkers in patients receiving sacubitril/valsartan. Both BNPir and NT-proBNPir are surrogates of proBNP1-108 production, NT-proBNPir being more robust in the clinical contexts studied.

BACKGROUND:Chloride plays a crucial role in renal salt sensing. This study investigates whether serum chloride is associated with clinical outcomes and decongestive response to acetazolamide in patients with acute decompensated heart failure. METHODS:This post hoc analysis includes all 519 patients from the ADVOR trial (Acetazolamide in Decompensated Heart Failure With Volume Overload), randomized to intravenous acetazolamide or matching placebo on top of intravenous loop diuretics. The impact of baseline serum chloride on the main trial end points and the treatment effect of acetazolamide was assessed, as was the evolution of serum chloride under decongestive treatment. RESULTS:Hypochloremia (<96 mmol/L) and hyperchloremia (>106 mmol/L) were present in 80 (15%) and 53 (10%), respectively, at baseline. Hypochloremia was associated with significantly slower decongestion, a longer length of hospital stay, and increased risk of all-cause mortality and heart failure readmissions. Acetazolamide increased the odds of successful decongestion and reduced length of stay irrespectively of baseline serum chloride levels. No statistically significant interaction between serum chloride levels and the effect of acetazolamide on death or heart failure readmissions was observed. The placebo group exhibited a progressive decline in serum chloride, which was effectively prevented by acetazolamide (P<0.001). CONCLUSIONS:Hypochloremia is associated with diuretic resistance and worse clinical outcomes. Add-on acetazolamide therapy improves decongestion across the entire range of serum chloride and prevents the drop in chloride levels caused by loop diuretic monotherapy. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03505788.

Novel pharmacologic treatment options reduce mortality and morbidity in a cost-effective manner in patients with heart failure (HF). Undisputedly, the effective implementation of these agents is an essential element of good clinical practice, which is endorsed by the European Society of Cardiology (ESC) guidelines on acute and chronic HF. Yet, physicians struggle to implement these therapies as they have to balance the true and/or perceived risks versus their substantial benefits in clinical practice. Any worsening of biomarkers of renal function is often perceived as being disadvantageous and is in clinical practice one of the most common reasons for ineffective drug implementation. However, even in this context, they clearly reduce mortality and morbidity in HF with reduced ejection fraction (HFrEF) patients, even in patients with poor renal function. Furthermore these agents are also beneficial in HF with mildly reduced ejection fraction (HFmrEF) and sodium-glucose cotransporter 2 (SGLT2) inhibitors more recently demonstrated a beneficial effect in HF with preserved ejection fraction (HFpEF). The emerge of several new classes (angiotensin receptor-neprilysin inhibitor [ARNI], SGLT2 inhibitors, vericiguat, omecamtiv mecarbil) and the recommendation by the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic HF of early initiation and titration of quadruple disease-modifying therapies (ARNI/angiotensin-converting enzyme inhibitor + beta-blocker + mineralocorticoid receptor antagonist and SGLT2 inhibitor) in HFrEF increases the likelihood of treatment-induced changes in renal function. This may be (incorrectly) perceived as deleterious, resulting in inertia of starting and uptitrating these lifesaving therapies. Therefore, the objective of this consensus document is to provide advice of the effect HF drugs on renal function.

Aims Soluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker reflecting the level of immune activation. It has been shown to have prognostic value in acute coronary syndrome and heart failure as well as in critical illness. Considering the complex pathophysiology of cardiogenic shock (CS), we hypothesized suPAR might have prognostic properties in CS as well. The aim of this study was to assess the kinetics and prognostic utility of suPAR in CS. Methods and results SuPAR levels were determined in serial plasma samples (0-96 h) from 161 CS patients in the prospective, observational, multicentre CardShock study. Kinetics of suPAR, its association with 90-day mortality, and additional value in risk-stratification were investigated. The median suPAR-level at baseline was 4.4 [interquartile range (IQR) 3.2-6.6)] ng/mL. SuPAR levels above median were associated with underlying comorbidities, biomarkers reflecting renal and cardiac dysfunction, and higher 90-day mortality (49% vs. 31%; P = 0.02). Serial measurements showed that survivors had significantly lower suPAR levels at all time points compared with nonsurvivors. For risk stratification, suPAR at 12 h (suPAR(12h)) with a cut-off of 4.4 ng/mL was strongly associated with mortality independently of established risk factors in CS: OR 5.6 (95% CI 2.0-15.5); P = 0.001) for death by 90 days. Adding suPAR(12h) > 4.4 ng/mL to the CardShock risk score improved discrimination identifying high-risk patients originally categorized in the intermediate-risk category. Conclusion SuPAR associates with mortality and improves risk stratification independently of other previously known risk factors in CS patients.

BACKGROUND Whether acetazolamide, a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption, can improve the efficiency of loop diuretics, potentially leading to more and faster decongestion in patients with acute decompensated heart failure with volume overload, is unclear. METHODS In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned patients with acute decompensated heart failure, clinical signs of volume overload (i.e., edema, pleural effusion, or ascites), and an N-terminal pro-B-type natriuretic peptide level of more than 1000 pg per milliliter or a B-type natriuretic peptide level of more than 250 pg per milliliter to receive either intravenous acetazolamide (500 mg once daily) or placebo added to standardized intravenous loop diuretics (at a dose equivalent to twice the oral maintenance dose). Randomization was stratified according to the left ventricular ejection fraction (≤40% or >40%). The primary end point was successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of decongestive therapy. Secondary end points included a composite of death from any cause or rehospitalization for heart failure during 3 months of follow-up. Safety was also assessed. RESULTS A total of 519 patients underwent randomization. Successful decongestion occurred in 108 of 256 patients (42.2%) in the acetazolamide group and in 79 of 259 (30.5%) in the placebo group (risk ratio, 1.46; 95% confidence interval [CI], 1.17 to 1.82; P<0.001). Death from any cause or rehospitalization for heart failure occurred in 76 of 256 patients (29.7%) in the acetazolamide group and in 72 of 259 patients (27.8%) in the placebo group (hazard ratio, 1.07; 95% CI, 0.78 to 1.48). Acetazolamide treatment was associated with higher cumulative urine output and natriuresis, findings consistent with better diuretic efficiency. The incidence of worsening kidney function, hypokalemia, hypotension, and adverse events was similar in the two groups. CONCLUSIONS The addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure resulted in a greater incidence of successful decongestion. (Funded by the Belgian Health Care Knowledge Center; ADVOR ClinicalTrials.gov number, NCT03505788.).

AIMS:To describe the baseline characteristics of participants in the Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) trial and compare these with other contemporary diuretic trials in acute heart failure (AHF). METHODS AND RESULTS:ADVOR recruited 519 patients with AHF, clinically evident volume overload, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and maintenance loop diuretic therapy prior to admission. All participants received standardized loop diuretics and were randomized towards once daily intravenous acetazolamide (500 mg) versus placebo, stratified according to study centre and left ventricular ejection fraction (LVEF) (≤40% vs. &gt;40%). The primary endpoint was successful decongestion assessed by a dedicated score indicating no more than trace oedema and no other signs of congestion after three consecutive days of treatment without need for escalating treatment. Mean age was 78 years, 63% were men, mean LVEF was 43%, and median NT-proBNP 6173 pg/ml. The median clinical congestion score was 4 with an EuroQol-5 dimensions health utility index of 0.6. Patients with LVEF ≤40% were more often male, had more ischaemic heart disease, higher levels of NT-proBNP and less atrial fibrillation. Compared with diuretic trials in AHF, patients enrolled in ADVOR were considerably older with higher NT-proBNP levels, reflecting the real-world clinical situation. CONCLUSION:ADVOR is the largest randomized diuretic trial in AHF, investigating acetazolamide to improve decongestion on top of standardized loop diuretics. The elderly enrolled population with poor quality of life provides a good representation of the real-world AHF population. The pragmatic design will provide novel insights in the diuretic treatment of patients with AHF.

Biomarkers are useful for diagnosis, disease monitoring and risk stratification in cardiovascular disease. Cardiogenic shock (CS) is a medical emergency caused by a primary cardiac insult resulting in inadequate cardiac output, hypoperfusion and organ injury. The pathophysiology of CS is complex involving hemodynamic and circulatory disturbances, inflammation and organ dysfunction. CS is associated with high short-term mortality. Biomarkers such as lactate, cardiac troponins and markers of renal function are established in the diagnosis and monitoring of CS. Evaluation of organ injury and dysfunction is essential for the management. Biomarkers of inflammation and novel biomarkers such as growth differentiating factor-15 (GDF-15), sST2 and dipeptidyl dipeptidase 3 (DPP) may improve our understanding of pathophysiology and clinical course. The prognostic properties of these biomarkers aids in risk stratification and are incorporated as clinical tools for mortality risk prediction in CS. In this review, the role of biomarkers in CS will be discussed. Markers of organ injury and dysfunction, metabolism and novel biomarkers will be covered from a clinical perspective.

Background Acute kidney injury (AKI) is a frequent form of organ injury in cardiogenic shock. However, data on AKI markers such as plasma proenkephalin (P-PENK) and neutrophil gelatinase-associated lipocalin (P-NGAL) in cardiogenic shock populations are lacking. The objective of this study was to assess the ability of P-PENK and P-NGAL to predict acute kidney injury and mortality in cardiogenic shock. Results P-PENK and P-NGAL were measured at different time points between baseline and 48 h in 154 patients from the prospective CardShock study. The outcomes assessed were AKI defined by an increase in creatinine within 48 h and all-cause 90-day mortality. Mean age was 66 years and 26% were women. Baseline levels of P-PENK and P-NGAL (median [interquartile range]) were 99 (71–150) pmol/mL and 138 (84–214) ng/mL. P-PENK > 84.8 pmol/mL and P-NGAL > 104 ng/mL at baseline were identified as optimal cut-offs for AKI prediction and independently associated with AKI (adjusted HRs 2.2 [95% CI 1.1–4.4, p = 0.03] and 2.8 [95% CI 1.2–6.5, p = 0.01], respectively). P-PENK and P-NGAL levels at baseline were also associated with 90-day mortality. For patients with oliguria < 0.5 mL/kg/h for > 6 h before study enrollment, 90-day mortality differed significantly between patients with low and high P-PENK/P-NGAL at baseline (5% vs. 68%, p < 0.001). However, the biomarkers provided best discrimination for mortality when measured at 24 h. Identified cut-offs of P-PENK 24h > 105.7 pmol/L and P-NGAL 24h > 151 ng/mL had unadjusted hazard ratios of 5.6 (95% CI 3.1–10.7, p < 0.001) and 5.2 (95% CI 2.8–9.8, p < 0.001) for 90-day mortality. The association remained significant despite adjustments with AKI and two risk scores for mortality in cardiogenic shock. Conclusions High levels of P-PENK and P-NGAL at baseline were independently associated with AKI in cardiogenic shock patients. Furthermore, oliguria before study inclusion was associated with worse outcomes only if combined with high baseline levels of P-PENK or P-NGAL. High levels of both P-PENK and P-NGAL at 24 h were found to be strong and independent predictors of 90-day mortality. Trial registration : NCT01374867 at www.clinicaltrials.gov , registered 16 Jun 2011—retrospectively registered

Background: Inflammatory responses play an important role in the pathophysiology of cardiogenic shock (CS). The aim of this study was to investigate the kinetics of procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) in CS and to assess their relation to clinical presentation, other biochemical variables, and prognosis. Methods: Levels of PCT, CRP and IL-6 were analyzed in serial plasma samples (0-120h) from 183 patients in the CardShock study. The study population was dichotomized by PCTmax >= and < 0.5 mu g/L, and IL-6 and CRPmax above/below median. Results: PCT peaked already at 24 h [median PCTmax 0.71 mu g/L (IQR 0.24-3.4)], whereas CRP peaked later between 48 and 72 h [median CRPmax 137mg/L (59-247)]. PCT levels were significantly higher among non-survivors compared with survivors from 12 h on, as were CRP levels from 24 h on (p < 0.001). PCTmax >= 0.5 mu g/L (60% of patients) was associated with clinical signs of systemic hypoperfusion, cardiac and renal dysfunction, acidosis, and higher levels of blood lactate, IL-6, growth-differentiation factor 15 (GDF-15), and CRPmax. Similarly, IL-6 > median was associated with clinical signs and biochemical findings of systemic hypoperfusion. PCTmax >= 0.5 mu g/L and IL-6 > median were associated with increased 90-day mortality (50% vs. 30% and 57% vs. 22%, respectively; p < 0.01 for both), while CRPmax showed no prognostic significance. The association of inflammatory markers with clinical infections was modest. Conclusions: Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis. (C) 2020 Elsevier B.V. All rights reserved.

Abstract Aims This study aimed to assess the utility of contemporary clinical risk scores and explore the ability of two biomarkers [growth differentiation factor‐15 (GDF‐15) and soluble ST2 (sST2)] to improve risk prediction in elderly patients with cardiogenic shock. Methods and results Patients (n = 219) from the multicentre CardShock study were grouped according to age (elderly ≥75 years and younger). Characteristics, management, and outcome between the groups were compared. The ability of the CardShock risk score and the IABP‐SHOCK II score to predict in‐hospital mortality and the additional value of GDF‐15 and sST2 to improve risk prediction in the elderly was evaluated. The elderly constituted 26% of the patients (n = 56), with a higher proportion of women (41% vs. 21%, P < 0.05) and more co‐morbidities compared with the younger. The primary aetiology of shock in the elderly was acute coronary syndrome (84%), with high rates of percutaneous coronary intervention (87%). Compared with the younger, the elderly had higher in‐hospital mortality (46% vs. 33%; P = 0.08), but 1 year post‐discharge survival was excellent in both age groups (90% in the elderly vs. 88% in the younger). In the elderly, the risk prediction models demonstrated an area under the curve of 0.75 for the CardShock risk score and 0.71 for the IABP‐SHOCK II score. Incorporating GDF‐15 and sST2 improved discrimination for both risk scores with areas under the curve ranging from 0.78 to 0.84. Conclusions Elderly patients with cardiogenic shock have higher in‐hospital mortality compared with the younger, but post‐discharge outcomes are similar. Contemporary risk scores proved useful for early mortality risk prediction also in the elderly, and risk stratification could be further improved with biomarkers such as GDF‐15 or sST2.