Does inflammation matter in cardiogenic shock?

BackgroundCardiogenic shock (CS) is characterized by high mortality and requires accurate prognostic tools to predict outcomes and guide treatment. The Society for Cardiovascular Angiography and Interventions (SCAI) shock classification indicates shock severity and can be used for outcome prediction. ObjectiveHere, we compare the prognostic performance of SCAI shock classification determined on admission and during intensive care unit (ICU) stay. MethodsWe included all patients with CS or conditions associated with developing CS based on ICD codes. SCAI shock stages were determined on admission and during the first 5 days of ICU stay. Receiver operating curves were used to compare the prognostic performance of SCAI stages on admission, SCAI stages during ICU stay and CS evolution (absent, resolved, persistent and new onset) for in-hospital mortality. ResultsBetween 01/2018 and 06/2022, 1303 patients were identified and 862 patients were included. On admission, 50.6 % patients had SCAI shock stage A, 3.9 % SCAI shock stage B, 17.7 % SCAI shock stage C, 7.0 % SCAI shock stage D and 20.8 % SCAI shock stage E. Shock stage distribution changed dynamically during ICU stay. Compared to SCAI stage on admission (AUC 0.80; 95 % CI 0.77–0.83), highest achieved SCAI stage during ICU (AUC 0.86, 95 % CI 0.83–0.89, p < 0.0001) and shock evolution (AUC 0.87, 95 % CI 0.85–0.90, p < 0.0001) yielded better prognostic performance. ConclusionsSCAI shock stages changed dynamically during ICU stay, and prognostic performance can be improved by considering highest achieved SCAI shock stage as well as the evolution of CS compared to SCAI shock stage on admission.

Cardiology Patient Page. C-reactive protein: a simple test to help predict risk of heart attack and stroke.

To determine whether baseline C-reactive protein (CRP) levels can predict mortality after transcatheter aortic valve implantation (TAVI), we performed a meta-analysis of currently available studies. All studies investigating the prognostic impact of baseline (preprocedural) CRP levels on all-cause mortality after TAVI were identified by means of searching PubMed and Google Scholar through May 2019. For each study, (preferentially, adjusted rather than unadjusted) odds/hazard ratios (ORs/HRs) with corresponding 95% confidence intervals of mortality per standard-deviation (SD) (or unit) increase in CRP levels or those for high vs low CRP levels. Our search identified 14 eligible studies including a total of 3449 patients undergoing TAVI and reporting early (in-hospital to 3-month) and midterm (1-year to 3-year) all-cause mortality after TAVI. Pooled analyses demonstrated associations of high-baseline CRP levels with a marginal, but statistically nonsignificant increase in early mortality (pooled OR/HR per SD increase in CRP levels, 2.72; P = .09 and pooled OR/HR for high vs low CRP levels, 3.32; P = .07) and a statistically significant increase in midterm mortality after TAVI (pooled OR/HR per SD increase in CRP levels, 1.45; P < .0001 and pooled OR/HR for high vs low CRP levels, 1.78; P < .00001). Excluding HRs for high-sensitivity CRP, combining ORs/HRs of 1-year mortality, pooling HRs of ≥2-year mortality, and combining adjusted HRs did not alter the primary results. High-baseline CRP levels may predict increased midterm, but not early, mortality after TAVI.

Background Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a critical form of mechanical circulatory support (MCS) for patients with refractory cardiogenic shock (CS). The combination therapy of VA-ECMO and Impella, known as ECPELLA, provides both systemic circulatory support and left ventricular (LV) unloading. However, whether the LV unloading effect of ECPELLA further reduces myocardial damage and mortality in Society for Cardiovascular Angiography and Interventions (SCAI) Stage E patients remains unclear. Objective To evaluate whether ECPELLA reduces myocardial damage and improves short-term survival in refractory CS patients with ST-elevation myocardial infarction (STEMI) requiring VA-ECMO before reperfusion. Methods Between January 2012 and January 2025, we retrospectively screened 239 acute coronary syndrome patients who required advanced mechanical circulatory support (MCS).Patients with non-STEMI, those who did not receive VA-ECMO during percutaneous coronary intervention (PCI) (n=81), and those with mechanical complications, such as left ventricular free wall rupture (n=8) or ventricular septal perforation (n=1), were excluded. Additionally, patients who had absent vital signs after MCS implantation and were deemed for withdrawal of care (n=7) were also excluded from the study. Ultimately, 77 consecutive STEMI patients who received VA-ECMO before reperfusion were included. Patients were divided into two groups: ECPELLA (n=48) and ECMO with IABP (n=28). Serum CK-MB levels and 30-day all-cause mortality were assessed. Results There were no significant differences between the groups in age, sex, coronary risk factors, left main trunk (LMT) lesion, or the rate of extracorporeal cardiopulmonary resuscitation (E-CPR). However, renal impairment (eGFR &amp;lt;60 mL/min/1.73 m²) was significantly more prevalent in the ECMO with IABP group. Additionally, the IABP-SHOCK II score, a prognostic score for CS, was significantly higher in the ECMO with IABP group than in the ECPELLA group (3 [3–4] vs. 4 [3–6]; p=0.015). The ECPELLA group had significantly higher MCS support flow per unit of body surface area during PCI and the first three days, received a significantly lower catecholamine dose, and demonstrated better lactate clearance. ECPELLA also resulted in significantly lower peak CK-MB levels (330 [115–562] IU/L vs. 500 IU/L; p=0.026). Kaplan-Meier analysis demonstrated a significantly higher 30-day survival rate in the ECPELLA group (p=0.003 by log-rank test). Multivariable Cox proportional hazard analysis, adjusting for age, E-CPR, LMT lesion, renal impairment, IABP-SHOCK II score, and ECPELLA, identified ECPELLA as the only independent factor associated with 30-day all-cause mortality (hazard ratio: 0.52, 95% confidence interval: 0.27–0.98; p=0.044). Conclusion ECPELLA treatment provides greater circulatory support and lower CK-MB levels, which may be associated with improved short-term survival compared to ECMO with IABP support.Figure1 Figure2

Identifying biomarker-driven subphenotypes of cardiogenic shock: analysis of prospective cohorts and randomized controlled trials.

Funding Acknowledgements Type of funding sources: None. Background Mortality from cardiogenic shock (CS) shows great disparities (1). This evidence reflects variations in access to care and medical practice, related to the lack of clear guidelines for appropriate patient selection for mechanical circulatory support (MCS) application. In this regard, the results of most trials or meta-analyses were neutral on survival, and the costs in terms of patient morbidity/mortality are high and unproven (2). Accordingly, a judicious use of MCS is crucial for an adequate resource allocation and to avoid futility. Purpose To characterize trends in use of support devices and compare outcomes between CS patients included in a contemporary national Cardiac Intensive Care Units (CICUs) registry, treated or not with MCS. Methods 324 sequential patients admitted with CS at a CICUs network between March 2020 and August 2022 were identified. We categorized patients according to treatment with MCS (n=204; 63%) and medical therapy (n=120; 37%). We investigated differences in clinical, laboratory, hemodynamics, echocardiographic and prognostic scores on admission, at 24-hours and at discharge. In-hospital outcome and mid-term survival were described for each treatment cohort. Comparison of continuous variables was performed using Student’s t-test. For categorical variables, the χ2 statistic was used. Results CS was a complication of acute myocardial infarction in 141 patients (44%) and of acute on chronic heart failure in 124 patients (38%); 58 patients (18%) presented with other diagnosis. In MCS cohort, we reported more advanced Society for Cardiovascular Angiography and Interventions (SCAI) shock stages and MCS implantation was more prevalent within 24-hours in SCAI C (48,6% on admission; 51,2% at 24-hours). In-hospital mortality did not differ between the two groups (38% in MCS and 37% in medically treated patients, p=0,874). Chronic kidney disease (OR 2.1, 95%CI 1.2-3.5, p=0,009), elevated lactates and SCAI stage at 24-hours (OR and 95%CI were, respectively, 3.45, 1.99-5.97 and 3.67, 2.46-5.47, p&amp;lt;0,001) emerged as major independent predictors of in-hospital mortality in MCS subgroup. A significant protective association persisted for those monitored with pulmonary artery catheter (OR 0.61, 95%CI 0.51-0.92, p=0.001). Among the 196 patients evaluated at mid-term follow up MCS treatment had not markedly improved cumulative survival compared to medical treatment (51,9% in MCS subgroup versus 55,6% in medical therapy, p=0,806). Palliative care team was rarely engaged (14% in MCS cohort vs 27% in medical therapy, p=0,83). Conclusions In this nation-wide study, mortality in MCS patients was high and no statistically significant difference on in-hospital and mid-term survival emerged between patients receiving MCS compared to medical therapy. Hence, a prompt and constant risk-stratification is mandatory to exclude patients too sick to derive any benefits from invasive therapies, avoiding futility.

AimsAge is an important risk factor for mortality among patients with cardiogenic shock and heart failure (HF). We sought to assess the extent to which age modified the performance of the Society for Cardiovascular Angiography and Interventions (SCAI) shock stage for in‐hospital and 1 year mortality in cardiac intensive care unit (CICU) patients with and without HF.Methods and resultsWe retrospectively reviewed unique admissions to the Mayo Clinic CICU during 2007–2015 and stratified patients by age and SCAI shock stage. The association between age and in‐hospital mortality was analysed using multivariable logistic regression, and 1 year mortality was analysed using Cox proportional hazards analysis, both in the entire cohort and among patients with an admission diagnosis of HF or acute coronary syndrome (ACS). The final study population included 10 004 unique patients with a mean age of 67 ± 15 years, including 46.1% with HF and 43.1% with ACS. Older patients more frequently had HF and had more extensive co‐morbidities, higher illness severity, more organ failure, and differential use of critical care therapies. The percentage of patients with SCAI shock stages A, B, C, D, and E were 46%, 30%, 16%, 7%, and 1%, respectively. Patients with HF were older, had greater severity of illness and higher SCAI shock stage, and had higher rates of death at all time points. In‐hospital mortality occurred in 908 (9%) patients, including 549 (12%) patients with HF (61% of all hospital deaths). Age was independently associated with hospital mortality (adjusted odds ratio per 10 years 1.3, 95% confidence interval 1.2–1.4, P < 0.001) and 1 year mortality (adjusted hazard ratio per 10 years 1.2, 95% confidence interval 1.2–1.3, P < 0.001) in the overall cohort. The associations of age with both hospital mortality (adjusted odds ratio 1.6 vs. 1.3 per 10 years older) and 1 year mortality (adjusted hazard ratio 1.5 vs. 1.3 per 10 years older) were higher for patients with ACS compared with patients with HF. Older age was associated with higher adjusted hospital mortality and 1 year mortality in each SCAI shock stage (all P < 0.05). Additive increases in both hospital mortality and 1 year mortality were observed with increasing age and SCAI shock stage.ConclusionsAge is an independent risk factor for mortality that modifies the relationship between the SCAI shock stage and mortality risk in CICU patients, providing robust risk stratification for in‐hospital and 1 year mortality. Although patients with HF had a higher risk of dying, age was more strongly associated with mortality among patients with ACS.

Cardiogenic Shock in Non-Ischemic Cardiomyopathy: Dynamic Mechanical Circulatory Support and Pathophysiology Illustration

Background/Aims Elevated baseline (BL) C-reactive protein (CRP) level can serve as a predictor for treatment response to TNF inhibitors in patients (pts) with radiographic axSpA (r-axSpA). The impact of CRP on b/tsDMARD response in r-axSpA is listed as a topic of interest on the ASAS-EULAR research agenda. Ixekizumab (IXE) has previously demonstrated efficacy in the treatment of r-axSpA in pts with normal and elevated CRP. This analysis further investigates the impact of baseline CRP levels on the ASAS40 individual components, BASDAI, and Axial Spondyloarthritis Disease Activity Score (ASDAS). Methods Biologic-naive adults with r-axSpA were enrolled in the COAST-V study (NCT02696785). At BL, pts were randomised to treatment with IXE Q4W, adalimumab (ADA), or placebo (PBO). Randomisation was stratified by baseline (BL) CRP normal (CRP ≤5 mg/L) or elevated (CRP&amp;gt;5 mg/L). This analysis reports change from BL (CFB) at 16 weeks for ASAS40 individual components, BASDAI, and ASDAS responses. Descriptive results for these outcomes are presented according to CRP levels. Results The mean ages of pts with normal CRP at BL were 43.3, 43.7, and 44.8 years for IXE, ADA, and PBO respectively (subsequently reported in that order, herein), whereas the mean age of pts with elevated CRP at BL was 39.6, 40.3, and 41.7 years. Gender, HLA-B27 positivity distribution and the mean duration of axSpA diagnosis was similar across both CRP groups. Pts with normal CRP had lower mean MRI-SPARCC spine score vs those with elevated CRP (6.8, 6.6, and 6.4 vs 15.8, 24.0, and 15.1 units) for IXE, ADA, and PBO respectively. At BL disease activity was comparable between pts with normal and elevated CRP. In pts treated with IXE, ASAS40 response at week 16 was driven by all 4 individual components with the largest improvements seen in morning stiffness (mean of intensity and duration of morning stiffness questions of BASDAI) and spinal pain, across both normal and elevated CRP. BASDAI 50 was achieved by 34.6%, 24.3%, and 15.4% of pts with normal CRP and by 48.1%, 39.2%, and 18.3% of pts with elevated CRP. ASDAS major improvement was achieved by 19.2% (IXE), 8.1% (ADA) and 3.8% (PBO) of pts with normal CRP and by 36.5%, 35,3% and 5.2% of pts with elevated CRP, respectively. Conclusion In pts with r-axSpA, BL clinical characteristics were similar in the normal and elevated CRP groups with pts experiencing similar disease burden. Across IXE and ADA treatment groups, the elevated CRP group tended to achieve higher treatment responses than the normal CRP group. Whereas in patients with normal CRP, CFB of ASAS individual components, BASDAI and ASDAS improvement was numerically highest in IXE Q4W followed by ADA and PBO. Disclosure R. Sengupta: Consultancies; AbbVie, Celgene, Eli Lilly and Company, Novartis, Pfizer, and UCB Pharma. Grants/research support; AbbVie, Celgene, Eli Lilly and Company, Novartis, Pfizer, and UCB Pharma. P.M. Machado: Consultancies; AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck Sharp &amp; Dohme, Novartis, Orphazyme, Pfizer, Roche, and UCB Pharma. P. Goupille: Consultancies; AbbVie, Biogaran, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, and UCB Pharma. V. Navarro Compán: Consultancies; AbbVie, Eli Lilly and Company, Janssen, Novartis, Pfizer, and UCB Pharma. Grants/research support; ASAS and Novartis. X. Huji: None. M. Sheesh: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. K. Ng: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. M. Ngantcha: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. H. Russ: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. G. Doridot: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. X. Baraliakos: Consultancies; AbbVie, Bristol Myers Squibb, Celgene, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, and UCB Pharma. Grants/research support; AbbVie, Bristol Myers Squibb, Celgene, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, and UCB Pharma.

Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). In a Phase 2 study, changes from baseline in C-reactive protein (CRP) levels as early as Week 4 and partial Mayo scores (PMS) as early as Week 2 were shown to correlate with clinical and endoscopic outcomes at Week 8 in patients with UC receiving tofacitinib.1 We aimed to determine whether CRP levels and/or PMS can be early predictors of clinical or endoscopic outcomes at Week 8 in OCTAVE Induction 1 and 2 (NCT01465763; NCT01458951).2 Methods In OCTAVE Induction 1 and 2, patients received placebo or tofacitinib 10 mg twice daily (BID) for 8 weeks. Mean CRP levels at baseline and Week 4, and PMS at baseline and Weeks 2 and 4, were analysed by secondary endpoint (clinical response, clinical remission, mucosal healing and endoscopic remission) status at Week 8. Univariate logistic regression analyses were performed to evaluate if CRP levels (log-transformed) or PMS were associated with these endpoints. Results In patients treated with tofacitinib 10 mg BID, numerically greater decreases from baseline were observed in CRP levels at Week 4 in patients who achieved a clinical response at Week 8 vs. those who did not achieve a clinical response (Table). Similarly, numerically greater decreases from baseline were observed in PMS at Weeks 2 and 4 in patients who achieved clinical response, clinical remission, mucosal healing and endoscopic remission at Week 8 vs. those who did not achieve these endpoints (Table). Logistic regression results showed that PMS at Weeks 2 and 4, and CRP levels at Week 4, were significantly (p &amp;lt; 0.001) associated with a clinical response at Week 8 (odds ratio [95% confidence interval] 0.578 [0.529, 0.631]; 0.483 [0.437, 0.533]; 0.631 [0.572, 0.695], respectively). This was also true for clinical remission (0.523 [0.467, 0.587]; 0.426 [0.367, 0.495]; 0.582 [0.508, 0.666]), mucosal healing (0.650 [0.600, 0.705]; 0.599 [0.548, 0.655]; 0.576 [0.515, 0.643]) and endoscopic remission (0.659 [0.574, 0.756]; 0.604 [0.513, 0.712]; 0.663 [0.549, 0.802]) at Week 8. Conclusion These post hoc analyses showed that PMS as early as Week 2 and CRP levels as early as Week 4 may be predictors of improved clinical and endoscopic outcomes in patients with moderately to severely active UC treated with tofacitinib 10 mg BID. These results are in alignment with the findings reported from the Phase 2 trial.1 References

CRP-Marker or Maker of Cardiovascular Disease?Jan Nilsson C -reactive protein (CRP) has emerged as an interesting novel and potentially clinically useful marker for increased cardiovascular risk. 1,2This is an attractive concept because atherosclerosis is a disease characterized by chronic arterial inflammation 3,4 and suggests the possibility that subclinical states of atherosclerosis can be identified by an increase in circulating markers of inflammation before acute events occur.Based on data obtained primarily from in vitro studies it has also been proposed that CRP in itself is actively contributing to disease progression and that it should be considered as true risk factor and consequently as a target for intervention.However, in the present issue of Arteriosclerosis, Thrombosis, and Vascular Biology, two independent reports demonstrate that transgenic overexpression of CRP does not affect the development of atherosclerosis in mice, suggesting that this is not the case.

C-reactive protein (CRP), a biomarker of inflammation, has predicted mortality in end-stage respiratory failure and in the critically ill patients. Our aim was to investigate if CRP can predict morbidity and mortality in patients requiring prolonged mechanical ventilation. A prospective study conducted in a ventilator weaning unit of a skilled nursing facility over 13 months included 98 patients older than 18 years of age requiring mechanical ventilation via tracheostomy. Serum CRP and albumin levels were tested on admission. Age, gender, body mass index (BMI), and diagnoses causing respiratory failure were recorded. The outcomes measured were as follows: hospitalization, weaned from mechanical ventilation, and death. Our population had a median age of 77 years and the median BMI, albumin, and mean CRP were 26 kg/m(2), 2.25 g/dL, and 5.75 mg/dL, respectively. The most common diseases leading to respiratory failure were pulmonary, neurologic, and cardiac. The patients with the empiric cutoff CRP of <2 mg/dL (n = 14) had 0% hospitalization rate at 2 weeks and 7% at 30 days, whereas the patients with CRP > or = 2 mg/dL (n = 84) had 26% hospitalization rate at 2 weeks and 38% at 30 days. Mortality for the patients with CRP > or = 2 mg/dL was 26% at 60 days, whereas the CRP < 2 mg/dL patients had no mortality at 60 days (P = 0.034). The patients who survived 60 days (n = 70) had significantly lower median CRP levels than the nonsurvivors (4.1 mg/dL vs 8.5 mg/dL, P = 0.009). The area under the receiver operating characteristic (ROC) curve for CRP levels predicting 2-week hospitalization was not large at 0.617 and the optimum CRP cutoff point was >2.7 mg/dL. The sensitivity and negative predictive value of the 2-week hospitalization outcome were equally high at 96%. The area under the ROC curve for 60-day survival was 0.691, and its optimum CRP cutoff point was >3.7 mg/dL with 85% sensitivity and 91% negative predictive value. CRP was not able to predict weaning success in this setting where the 60-day weaning rate was 9%. A CRP level of < or =2.7 mg/dL may be used to screen for patients who are not likely to develop acute illness requiring early 2-week rehospitalization, and a CRP level of < or =3.7 mg/dL may be used to predict 60-day survival in patients with respiratory failure requiring prolonged mechanical ventilation in the long-term care setting.

Alice K. Jacobs, MD, FACC, FAHA, Chair Jeffrey L. Anderson, MD, FACC, FAHA, Chair-Elect Nancy Albert, PhD, CCNS, CCRN, FAHA Mark A. Creager, MD, FACC, FAHA Steven M. Ettinger, MD, FACC Robert A. Guyton, MD, FACC Jonathan L. Halperin, MD, FACC, FAHA Judith S. Hochman, MD, FACC, FAHA

Timing of cardiogenic shock and clinical outcomes in takotsubo syndrome: A multicenter cohort study.

Background/aim: The objective of this study is to identify clinical predictors of primary non-response (PNR) and secondary loss of response (LOR), in Crohn’s disease (CD) patients treated with anti-tumor necrosis factor α (anti-TNF) agents.Methods: This retrospective, longitudinal, and observational cohort study included 283 patients with CD who received anti-TNF treatments from November 2006 to July 2017 at Samsung Medical Center, Seoul, Korea.Results: A total of 212 patients with CD were eligible and based on clinical responses, divided into three groups: PNR, LOR, and responder groups. PNR occurred in 13 patients (6.1%). C-Reactive protein (CRP) level at initiation of anti-TNF (baseline CRP) was a possible predictor of PNR compared to the non-PNR group (baseline CRP >1 mg/dl, OR = 4.34, 95% CI = 1.06–17.83, p = .042). During maintenance therapy, incidence of LOR was 12.2% at 1-year, 23.6% at 2-years, 36.3% at 3-years, and 52.1% at 5-years. Combining baseline CRP level and CRP reduction rate [(CRP at 12–14 weeks–baseline CRP)/baseline CRP] was a possible predictor of 1-year LOR compared to the responder group (baseline CRP >1 mg/dl and CRP reduction rate > −70%, OR = 18.86, 95% CI = 3.40–104.55, p = .001). In the Cox hazard proportional model, a combination of baseline CRP level and CRP reduction rate was possible predictors of long-term LOR during maintenance therapy (baseline CRP >1 mg/dl and CRP reduction rate > −70%, HR = 5.84, 95% CI = 2.75–12.41, p < .001).Conclusions: Baseline CRP level and CRP reduction rate might be clinical predictors for PNR or LOR to anti-TNF in patients with CD, and could guide proper therapeutic interventions in patients with CD.