Use of the Win Ratio Analysis in Critical Care Trials.

Composite outcomes are commonly used in critical care trials to estimate the treatment effect of an intervention. A significant limitation of classical analytic approaches is that they assign equal statistical importance to each component in a composite, even if these do not have the same clinical importance (i.e., in a composite of death and organ failure, death is clearly more important). The win ratio (WR) method has been proposed as an alternative for trial outcomes evaluation, as it effectively assesses events based on their clinical relevance (i.e., hierarchical order) by comparing each patient in the intervention group with their counterparts in the control group. This statistical approach is increasingly used in cardiovascular outcome trials. However, WR may be useful to unveil treatment effects also in the critical care setting, because these trials are typically moderately sized, thus limiting the statistical power to detect small differences between groups, and often rely on composite outcomes that include several components of different clinical importance. Notably, the advantages of this approach may be offset by several drawbacks (such as ignoring ties and difficulties in selecting and ranking endpoints) and challenges in appropriate clinical interpretation (i.e., establishing clinical meaningfulness of the observed effect size). In this perspective article, we present some key elements to implementing WR statistics in critical care trials, providing an overview of strengths, drawbacks, and potential applications of this method. To illustrate, we conduct a reevaluation of the HYPO-ECMO (Hypothermia during Venoarterial Extracorporeal Membrane Oxygenation) trial using the WR framework as a case example.

Sex-specific Prediction of Cardiogenic Shock After Acute Coronary Syndromes: The SEX-SHOCK Score.

BACKGROUND: and aims: Cardiogenic shock (CS) remains the primary cause of in-hospital death after acute coronary syndromes (ACS), with its plateauing mortality rates approaching 50%. To test novel interventions, personalized risk prediction is essential. The ORBI (Observatoire Régional Breton sur l'Infarctus) score represents the first-of-its-kind risk score to predict in-hospital CS in ACS patients undergoing percutaneous coronary intervention (PCI). However, its sex-specific performance remains unknown, and refined risk prediction strategies are warranted. METHODS: This multinational study included a total of 53 537 ACS patients without CS on admission undergoing PCI. Following sex-specific evaluation of ORBI, regression and machine-learning models were used for variable selection and risk prediction. By combining best-performing models with highest-ranked predictors, SEX-SHOCK was developed, and internally and externally validated. RESULTS: The ORBI score showed lower discriminative performance for the prediction of CS in females than males in Swiss (AUC [95% CI]: 0.78 [0.76-0.81] vs. 0.81 [0.79-0.83]; p=0.048) and French ACS patients (0.77 [0.74-0.81] vs. 0.84 [0.81-0.86]; p=0.002). The newly developed SEX-SHOCK score, now incorporating ST-segment elevation, creatinine, C-reactive protein, and left ventricular ejection fraction, outperformed ORBI in both sexes (females: 0.81 [0.78-0.83]; males: 0.83 [0.82-0.85]; p<0.001), which prevailed following internal and external validation in RICO (females: 0.82 [0.79-0.85]; males: 0.88 [0.86-0.89]; p<0.001) and SPUM-ACS (females: 0.83 [0.77-0.90], p=0.004; males: 0.83 [0.80-0.87], p=0.001). CONCLUSIONS: The ORBI score showed modest sex-specific performance. The novel SEX-SHOCK score provides superior performance in females and males across the entire spectrum of ACS, thus providing a basis for future interventional trials and contemporary ACS management.

NLRP3 inflammasome-induced pyroptosis and serum ASC specks are increased in patients with cardiogenic shock.

Cardiogenic shock (CS) is characterized by impaired cardiac function, very high mortality, and limited treatment options. The proinflammatory signaling during different phases of CS is incompletely understood. We collected serum and plasma (n = 44) as well as freshly isolated peripheral blood mononuclear cells (PBMCs, n = 7) of patients with CS complicating acute myocardial infarction on admission and after revascularization (24, 48, and 72 h) and of healthy controls (serum and plasma, n = 75; PBMCs, n = 12). PBMCs of patients with CS had increased gene expression of NLRP3, CASP1, PYCARD, IL1B, and IL18 and showed increased rates of pyroptosis (control, 4.7 ± 0.3 vs. 9.9 ± 1.7% in patients with CS, P = 0.02). Serum interleukin (IL)-1ß levels were increased after revascularization. IL-18 and IL-6 were higher in patients with CS than in healthy controls but comparable before and after revascularization. Proinflammatory apoptosis-associated speck-like proteins containing CARD (ASC) specks were elevated in the serum of patients with CS on admission and increased after revascularization (admission, 11.1 ± 4.4 specks/µL; after 24 h, 19.0 ± 3.9, P = 0.02). ASC specks showed a significant association with 30-day mortality in patients with CS (P < 0.05). The estimated regression coefficients and odds ratios indicated a positive relationship between ASC specks and mortality (odds ratio: 1.029, 95% confidence interval, 1.000 to 1.072; P = 0.02). Pyroptosis and circulating ASC specks are increased in patients with CS and are particularly induced after reperfusion. This underscores their potential role as a biomarker for poor outcomes in patients with CS. ASC specks represent promising new therapeutic targets for patients with CS with high inflammatory burden.NEW & NOTEWORTHY The expression of NLR family pyrin domain containing-3 (NLRP3) inflammasome-related genes and the rate of pyroptosis are increased in PBMCs from patients with CS. Furthermore, patients with CS are characterized by higher serum concentrations of ASC specks and IL-1ß, IL-6, and IL-18. This current study adds circulating ASC specks to the portfolio of biomarkers for the identification of patients with a high inflammatory burden paving the way for precision medicine approaches to improve clinical outcomes.

The Use of Cangrelor in Cardiogenic Shock: Insights from the CAMEO Registry.

INTRODUCTION: Little is known about the use of cangrelor in patients with myocardial infarction (MI) presenting with cardiogenic shock (CS). METHODS: CAMEO (Cangrelor in Acute MI: Effectiveness and Outcomes) is a multicenter observational registry evaluating platelet inhibition in patients with MI. We examined the duration of cangrelor infusion and the amount of time to transition from cangrelor to an oral P2Y12 inhibitor in patients with CS. We also assessed major adverse cardiovascular events (MACEs) and bleeding risks, stratified by dosage duration, time to transition and oral P2Y12 inhibitor potency. RESULTS: Among 2352 cangrelor-treated patients with MI, 249 patients were in CS. Among the patients with CS, 16 (6.4%) received the "bridge" infusion dose, 202 (81.1%) the PCI cangrelor infusion dose, and 30 (12.0%) had a combination of both infusion doses. Patients with CS had a median age of 66 years; 32% were women; 21% were Black patients; 35% had diabetes; 19% received thrombectomy; and 59% received mechanical circulatory support (MCS) (35% intra-aortic balloon pump, 27% Impella). The median duration of infusion was 3.9 (2-21.5 hours) in patients with CS and was 2 (1.6-3.1 hours) for all cangrelor-treated patients. The median duration of transition from cangrelor to oral P2Y12 inhibitor administration was 0.1 (-0.5-21.0 hours) for patients with CS. In multivariable modeling, chronic lung disease and the use of MCS and was associated with longer cangrelor infusions (defined as > 3.9 hours). Among cangrelor-treated patients with CS, 24.1% of these patients had a bleeding event, and 41.8% had a MACE event. After adjustment, a longer cangrelor infusion duration was associated with increased risk of bleeding (P < 0.05). CONCLUSIONS: The median duration of cangrelor infusion was longer for patients presenting with CS. Use of MCS was associated with longer cangrelor infusion durations in patients with CS. Further work is needed to understand the pharmacodynamics of antiplatelet agents in patients with CS.

Outcomes of Patients Transferred to Tertiary Care Centers for Treatment of Cardiogenic Shock: A Cardiogenic Shock Working Group Analysis.

BACKGROUND: Consensus recommendations for cardiogenic shock (CS) advise transfer of patients in need of advanced options beyond the capability of "spoke" centers to tertiary/"hub" centers with higher capabilities. However, outcomes associated with such transfers are largely unknown beyond those reported in individual health networks. OBJECTIVES: To analyze a contemporary, multicenter CS cohort with the aim of comparing characteristics and outcomes of patients between transfer (between spoke and hub centers) and nontransfer cohorts (those primarily admitted to a hub center) for both acute myocardial infarction (AMI-CS) and heart failure-related HF-CS. We also aim to identify clinical characteristics of the transfer cohort that are associated with in-hospital mortality. METHODS: The Cardiogenic Shock Working Group (CSWG) registry is a national, multicenter, prospective registry including high-volume (mostly hub) CS centers. Fifteen U.S. sites contributed data for this analysis from 2016-2020. RESULTS: Of 1890 consecutive CS patients enrolled into the CSWG registry, 1028 (54.4%) patients were transferred. Of these patients, 528 (58.1%) had heart failure-related CS (HF-CS), and 381 (41.9%) had CS related to acute myocardial infarction (AMI-CS). Upon arrival to the CSWG site, transfer patients were more likely to be in SCAI stages C and D, when compared to nontransfer patients. Transfer patients had higher mortality rates (37% vs 29%, < 0.001) than nontransfer patients; the differences were driven primarily by the HF-CS cohort. Logistic regression identified increasing age, mechanical ventilation, renal replacement therapy, and higher number of vasoactive drugs prior to or within 24 hours after CSWG site transfer as independent predictors of mortality among HF-CS patients. Conversely, pulmonary artery catheter use prior to transfer or within 24 hours of arrival was associated with decreased mortality rates. Among transfer AMI-CS patients, BMI > 28 kg/m2, worsening renal failure, lactate > 3 mg/dL, and increasing numbers of vasoactive drugs were associated with increased mortality rates. CONCLUSION: More than half of patients with CS managed at high-volume CS centers were transferred from another hospital. Although transfer patients had higher mortality rates than those who were admitted primarily to hub centers, the outcomes and their predictors varied significantly when classified by HF-CS vs AMI-CS.

Association of Hemometabolic Trajectory and Mortality: Insights From the Cardiogenic Shock Working Group Registry.

Cardiogenic shock (CS) is a hemodynamic syndrome that can progress to systemic metabolic derangements and end-organ dysfunction. Prior studies have reported hemodynamic parameters at the time of admission to be associated with mortality but hemodynamic trajectories in CS have not been well described. We studied the association between hemodynamic profiles and their trajectories and in-hospital mortality in patients with CS due to heart failure (HF-CS) and acute myocardial infarction (MI-CS). Using data from the large multicenter Cardiogenic Shock Working Group (CSWG) registry, we analyzed hemodynamic data obtained at the time of pulmonary artery catheter (PAC) insertion (dataset at baseline) and at PAC removal or death (dataset at final time point). Univariable regression analyses for prediction of in-hospital mortality were conducted for baseline and final hemodynamic values, as well as the interval change (delta-P). Data was further analyzed based on CS etiology and survival status. A total of 2260 patients with PAC data were included (70% male, age 61 ± 14 years, 61% HF-CS, 27% MI-CS). In-hospital mortality was higher in the MI-CS group (40.1%) compared with HF-CS (22.4%, P < .01). In the HF-CS cohort, survivors exhibited lower right atrial pressure (RAP), pulmonary artery pressure (PAP), cardiac output/index (CO/CI), lactate, and higher blood pressure (BP) than nonsurvivors at baseline. In this cohort, during hospitalization, improvement in metabolic (aspartate transaminase, lactate), BP, hemodynamic (RAP, pulmonary artery pulsatility index [PAPi], pulmonary artery compliance for right-sided profile and CO/CI for left-sided profile), had association with survival. In the MI-CS cohort, a lower systolic BP and higher PAP at baseline were associated with odds of death. Improvement in metabolic (lactate), BP, hemodynamic (RAP, PAPi for right-sided profile and CO/CI for left-sided profile) were associated with survival. In a large contemporary CS registry, hemodynamic trajectories had a strong association with short-term outcomes in both cohorts. These findings suggest the clinical importance of timing and monitoring hemodynamic trajectories to tailor management in patients with CS.

High Circulating Dipeptidyl Peptidase 3 Predicts Mortality and Need for Organ Support in Cardiogenic Shock: An Ancillary Analysis of the ACCOST-HH Trial.

BACKGROUND: Cardiogenic shock (CS) is burdened with high mortality. Efforts to improve outcome are hampered by the difficulty of individual risk stratification and the lack of targetable pathways. Previous studies demonstrated that elevated circulating dipeptidyl peptidase 3 (cDPP3) is an early predictor of short-term outcome in CS, mostly of ischemic origin. Our objective was to investigate the association between cDPP3 and short-term outcomes in a diverse population of patients with CS. METHODS AND RESULTS: cDPP3 was measured at baseline and after 72 hours in the AdreCizumab against plaCebO in SubjecTs witH cardiogenic sHock (ACCOST-HH) trial. The association of cDPP3 with 30-day mortality and need for organ support was assessed. Median cDPP3 concentration at baseline was 43.2 ng/mL (95% confidence interval [CI], 21.2-74.0 ng/mL) and 77 of the 150 patients (52%) had high cDPP3 over the predefined cutoff of 40 ng/mL. Elevated cDPP3 was associated with higher 30-day mortality (adjusted hazard ratio [aHR] = 1.7; 95% CI, 1.0-2.9), fewer days alive without cardiovascular support (aHR, 3 days [95% CI, 0-24 days] vs aHR, 21 days [95% CI, 5-26 days]; P < .0001) and a greater need for renal replacement therapy (56% vs 22%; P < .0001) and mechanical ventilation (90 vs 74%; P = .04). Patients with a sustained high cDPP3 had a poor prognosis (reference group). In contrast, patients with an initially high but decreasing cDPP3 at 72 hours had markedly lower 30-day mortality (aHR, 0.17; 95% CI, 0.084-0.34), comparable with patients with a sustained low cDPP3 (aHR, 0.23; 95% CI, 0.12-0.41). The need for organ support was markedly decreased in subpopulations with sustained low or decreasing cDPP3. CONCLUSIONS: The present study confirms the prognostic value of cDPP3 in a contemporary population of patients with CS.

Cardiogenic Shock Intravascular Cooling Trial (CHILL-SHOCK).

BACKGROUND: Cardiogenic shock (CS) is complicated by high mortality rates. Targeted temperature control (TTC) has been proposed as an adjunct therapy in CS. This study aims to examine the safety of TTC in patients presenting with CS. METHODS AND RESULTS: In this open-label, randomized controlled pilot trial, 20 patients with hemodynamic criteria for CS were assigned to standard of care plus TTC vs standard of care alone. The primary outcome was a composite safety outcome, including well-described complications of TTC. Secondary outcomes included mortality at 90 days, invasive hemodynamic and echocardiographic parameters, electrocardiographic measurements, and inotrope dosing. There were no significant differences in the composite analysis of prespecified safety outcomes (3 events in the TTC group vs 0 events in the control group; P = 0.24). Patients randomized to TTC demonstrated a statistically significant increase in cardiac index and cardiac power index compared to the control group at 48-96 hours after randomization (3.6 [3.1, 3.9] L/min/m2 vs 2.6 [2.5, 3.15] L/min/m2; P = 0.029 and 0.61 [0.55, 0.7] W/m2 vs 0.53 [0.435, 0.565] W/m2; P = 0.029, respectively). CONCLUSION: TTC may be a safe adjunct therapy for patients presenting with CS and may yield improvement in specific hemodynamic parameters.

A Novel Predictive Score Model for Successful Weaning From Mechanical Circulatory Support in Patients With Cardiogenic Shock.

BACKGROUND: Clinical evidence regarding predictors of successful weaning from mechanical circulatory support (MCS) is lacking. This study aimed to create a simple risk score to predict successful weaning from MCS in patients with cardiogenic shock. METHODS AND RESULTS: This retrospective single-center cohort study included 114 consecutive patients with cardiogenic shock treated with venoarterial extracorporeal membrane oxygenation or IMPELLA between January 2013 and June 2023. Patients with out-of-hospital cardiac arrest were excluded. The primary end point was successful weaning from MCS, defined as successful decannulation without the need for MCS reimplantation and survival to discharge. Multivariable logistic regression with a stepwise variable selection was performed to generate the prediction model. We first developed a general weaning score model, and then created a simple version of the score model using the same variables. Fifty-five patients were weaned from MCS successfully. The following variables measured during weaning evaluation were selected as the components of the weaning score model: acute myocardial infarction (AMI), mean blood pressure, left ventricular ejection fraction (LVEF), lactate level, and QRS duration. According to the results, we conducted a novel weaning score model to predict successful weaning from MCS: 1.774 - 2.090 × (AMI) + 0.062 × [mean blood pressure (mm Hg)] + 0.139 × [LVEF (%)] - 0.322 × [Lactate (mg/dL)] - 0.066 × [QRS (ms)]. The following variables were selected as the components of the simple version of the weaning score model: AMI, mean blood pressure of ≥80 mm Hg, lactate of <10 mg/dL, QRS duration of ≤95 ms, and LVEF of >35%. CONCLUSIONS: We developed a simple model to predict successful weaning from MCS in patients with cardiogenic shock.

Modes of Death in Patients with Cardiogenic Shock in the Cardiac Intensive Care Unit: A Report from the Critical Care Cardiology Trials Network.

BACKGROUND: There are limited data on how patients with cardiogenic shock (CS) die. METHODS: The Critical Care Cardiology Trials Network is a research network of cardiac intensive care units coordinated by the Thrombolysis In Myocardial Infarction (TIMI) Study Group (Boston, MA). Using standardized definitions, site investigators classified direct modes of in-hospital death for CS admissions (October 2021 to September 2022). Mutually exclusive categories included 4 modes of cardiovascular death and 4 modes of noncardiovascular death. Subgroups defined by CS type, preceding cardiac arrest (CA), use of temporary mechanical circulatory support (tMCS), and transition to comfort measures were evaluated. RESULTS: Among 1068 CS cases, 337 (31.6%) died during the index hospitalization. Overall, the mode of death was cardiovascular in 82.2%. Persistent CS was the dominant specific mode of death (66.5%), followed by arrhythmia (12.8%), anoxic brain injury (6.2%), and respiratory failure (4.5%). Patients with preceding CA were more likely to die from anoxic brain injury (17.1% vs 0.9%; P < .001) or arrhythmia (21.6% vs 8.4%; P < .001). Patients managed with tMCS were more likely to die from persistent shock (P < .01), both cardiogenic (73.5% vs 62.0%) and noncardiogenic (6.1% vs 2.9%). CONCLUSIONS: Most deaths in CS are related to direct cardiovascular causes, particularly persistent CS. However, there is important heterogeneity across subgroups defined by preceding CA and the use of tMCS.

Sex-Based Survival Outcomes in Cardiogenic Shock.

BACKGROUND: Sex-based disparities have been demonstrated in care delivery for females with cardiogenic shock (CS), including lower use of coronary angiography (CAG), percutaneous intervention (PCI) and mechanical circulatory support (MCS). We evaluated whether sex-based disparities exist and are associated with worse CS outcomes in females. METHODS: We studied a retrospective cohort of 1498 consecutive, unique adult cardiovascular intensive care unit (CICU) admissions with CS from 2007-2018. RESULTS: Compared to males, females (n = 566, 37.1%) were older (71.7 vs 67.8 years; P < 0.001) but had similar burdens of medical comorbidities. Acute myocardial infarction (AMI) was present in 54.1% of females and 59.1% of males (P = 0.06). There were no sex-based differences in the use of CAG and PCI, but females received temporary MCS less commonly. Specifically, females with non-AMI CS received MCS devices less commonly (17.6% vs 24.4%; P = 0.04). There was no difference in in-hospital or 1-year mortality rates between the sexes. Compared to males, females who received PCI had lower risks of 1-year mortality (unadjusted HR 0.72; P = 0.03), whereas females who received CAG without PCI had higher risks of 1-year mortality (unadjusted HR 1.41; P = 0.02). CONCLUSIONS: No sex-based disparities in mortality due to CS were demonstrated in this large, diverse cohort of patients with CICU admissions. Females who underwent PCI demonstrated lower risks of 1-year mortality, whereas females who underwent CAG without PCI demonstrated higher risks of 1-year mortality compared to males. This may reflect underuse of PCI as a mortality-reducing therapy in females.

Impact of Right Ventricular Dysfunction on Outcomes in Acute Myocardial Infarction and Cardiogenic Shock: Insights from the National Cardiogenic Shock Initiative.

BACKGROUND: Right ventricular dysfunction (RVD) complicates 30%-40% of cases in acute myocardial infarction (AMI) and cardiogenic shock (CS). There are sparse data on the effects of RVD on outcomes and the impact of providing early left ventricular (LV) mechanical circulatory support (MCS) on RV function and hemodynamics. METHODS AND RESULTS: Between July 2016 and December 2020, 80 sites participated in the study. All centers agreed to treat patients with AMI-CS using a standard protocol emphasizing invasive hemodynamic monitoring and rapid initiation of LV-MCS. RVD was defined as a right atrial (RA) pressure of >12 mm Hg and a pulmonary artery pulsatility index (PAPI) of <1 within 24 hours of the index procedure. The primary outcome was survival to discharge. In a subgroup analysis, data available from the Automated Impella Controller console was used to analyze diastolic suction alarms from LV placement signal and its relation to RVD. A total of 361 patients were included in the analysis, of whom 28% had RVD. The median age was 64 years (interquartile range 55-72 years), 22.7% were female and 75.7% were White. There was no difference in age, sex, or comorbidities between those with or without RVD. Patients with RVD had a higher probability of active CPR during LV-MCS implant (14.7% vs 6.3%), Society for Cardiovascular Angiography and Interventions stage E shock (39.2% vs 23.2%), and higher admission lactate levels (5.1 mg/dL vs 3.0 mg/dL). Survival to discharge was significantly lower among those with RVD (61.8% vs 73.4%, odds ratio 0.89, 95% confidence interval 0.36-0.95, P = .031). This association remained significant in the multivariate analysis. There was no significant difference in hemodynamic variables within 24 hours of LV-MCS support among those with or without RVD. At 24 hours, patients with a CPO of >0.6 W and a PAPi of >1 had a trend toward better survival to discharge compared with those with a CPO of ≤0.6 W and a PAPi of ≤1 (77.1% vs 54.6%, P = .092). Patients with RVD were significantly more likely to have diastolic suction alarms within 24 hours of LV-MCS initiation. CONCLUSIONS: RVD in AMI-CS is common and associated with worse survival to discharge. Early LV-MCS decreases filling pressures rapidly within the first 24 hours and decreases the rate of RVD. Achieving a CPO of >0.6 W and a PAPi of >1 within 24 hours is associated with high survival. Diastolic suction alarms may have usefulness as an early marker of RVD.

Pulmonary Artery Diastolic Pressure as a Surrogate for Pulmonary Capillary Wedge Pressure in Cardiogenic Shock.

BACKGROUND: It is common for clinicians to use the pulmonary artery diastolic pressure (PADP) as a surrogate for the pulmonary capillary wedge pressure (PCWP). Here, we determine the validity of this relationship in patients with various phenotypes of cardiogenic shock (CS). METHODS AND RESULTS: In this analysis of the Critical Care Cardiology Trials Network registry, we identified 1225 people admitted with CS who received pulmonary artery catheters. Linear regression, Bland-Altman and receiver operator characteristic analyses were performed to determine the strength of the association between PADP and PCWP in patients with left-, right-, biventricular, and other non-myocardia phenotypes of CS (eg, arrhythmia, valvular stenosis, tamponade). There was a moderately strong correlation between PADP and PCWP in the total population (r = 0.64, n = 1225) and in each CS phenotype, except for right ventricular CS, for which the correlation was weak (r = 0.43, n = 71). Additionally, we found that a PADP ≥ 24 mmHg can be used to infer a PCWP ≥ 18 mmHg with ≥ 90% confidence in all but the right ventricular CS phenotype. CONCLUSIONS: This analysis validates the practice of using PADP as a surrogate for PCWP in most patients with CS; however, it should generally be avoided in cases of right ventricular-predominant CS.

Triglyceride-glucose index correlates with the occurrence and prognosis of acute myocardial infarction complicated by cardiogenic shock: data from two large cohorts.

BACKGROUND: Triglyceride-glucose (TyG) index, a dependable indicator of insulin resistance, has been identified as a valid marker regarding multiple cardiovascular diseases. Nevertheless, the correlation of TyG index with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains uncertain. Our study aims for elucidating this relationship by comprehensively analyzing two large-scale cohorts. METHODS: Utilizing records from the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care IV, the link between TyG and the incidence and prognosis of AMICS was assessed multicentrally and retrospectively by logistic and correlation models, as well as restricted cubic spline (RCS). Propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting (OW) were employed to balance the potential confounders. Subgroup analyses were performed according to potential modifiers. RESULTS: Overall, 5208 AMI patients, consisting of 375 developing CS were finally included. The TyG index exhibited an apparently higher level in AMI populations developing CS than in those who did not experienced CS [9.2 (8.8-9.7) vs. 9.0 (8.5-9.5)], with a moderate discrimination ability to recognize AMICS from the general AMI (AUC: 0.604). Logistic analyses showed that the TyG index was significantly correlated with in-hospital and ICU mortality. RCS analysis demonstrated a linear link between elevated TyG and increased risks regarding in-hospital and ICU mortality in the AMICS population. An increased mortality risk remains evident in PSM-, OW- and IPTW-adjusted populations with higher TyG index who have undergone CS. Correlation analyses demonstrated an apparent link between TyG index and APS score. Subgroup analyses presented a stable link between elevated TyG and mortality particularly in older age, females, those who are overweight or hypertensive, as well as those without diabetes. CONCLUSIONS: Elevated TyG index was related to the incidence of CS following AMI and higher mortality risks in the population with AMICS. Our findings pointed a previously undisclosed role of TyG index in regard to AMICS that still requires further validation.

Cytoprotection as an Innovative Therapeutic Strategy to Cardiogenic Shock: Exploring the Potential of Cytidine-5-Diphosphocholine to Mitigate Target Organ Damage.

BACKGROUND: Preservation of organ function and viability is a crucial factor for survival in cardiogenic shock (CS) patients. There is not information enough on cytoprotective substances that may delay organs damage in CS. We hypothesize that cytidine-5-diphosphocholine (CDP-choline) can act as a cytoprotective pharmacological measure that diminishes the target organ damage. So, we aimed to perform a review of works carried out in our institution to evaluate the effect of therapeutic cytoprotection of the CDP-choline. SUMMARY: CDP-choline is an intermediate metabolite in the synthesis of phosphatidylcholine. It is also a useful drug for the treatment of acute ischaemic stroke, traumatic brain injury, and neurodegenerative diseases and has shown an excellent pharmacological safety profile as well. We review our institution's work and described the cytoprotective effects of CDP-choline in experimental models of heart, liver, and kidney acute damage, where this compound was shown to diminish reperfusion-induced ventricular arrhythmias, oxidative stress, apoptotic cell death, inflammation, lactic acid levels and to preserve mitochondrial function. KEY MESSAGES: We propose that additional research is needed to evaluate the impact of cytoprotective therapy adjuvant to mitigate target organ damage in patients with CS.

Blood Urea Nitrogen to Left Ventricular Ejection Ratio as a Predictor of Short-Term Outcome in Acute Myocardial Infarction Complicated by Cardiogenic Shock.

INTRODUCTION: Cardiogenic shock (CS) is the most critical complication after acute myocardial infarction (AMI) with mortality above 50%. Both blood urea nitrogen and left ventricular ejection fraction were important prognostic indicators. We aimed to evaluate the prognostic value of admission blood urea nitrogen to left ventricular ejection fraction ratio (BUNLVEFr) in patients with AMI complicated by CS (AMI-CS). METHODS: 268 consecutive patients with AMI-CS were divided into two groups according to the admission BUNLVEFr cut-off value determined by Youden index. The primary endpoint was 30-day all-cause mortality and the secondary endpoint was the composite events of major adverse cardiovascular events (MACEs). Cox proportional hazard models were performed to analyze the association of BUNLVEFr with the outcome. RESULTS: The optimal cut-off value of BUNLVEFr is 16.63. The 30-day all-cause mortality and MACEs in patients with BUNLVEFr≥16.63 was significantly higher than in patients with BUNLVEFr<16.63 (30-day all-cause mortality: 66.2% vs. 17.1%, p < 0.001; 30-day MACEs: 80.0% vs. 48.0%, p < 0.001). After multivariable adjustment, BUNLVEFr≥16.63 remained an independent predictor for higher risk of 30-day all-cause mortality (HR = 3.553, 95% CI: 2.125-5.941, p < 0.001) and MACEs (HR = 2.026, 95% CI: 1.456-2.820, p < 0.001). Subgroup analyses found that the effect of BUNLVEFr was consistent in different subgroups (all p-interaction>0.05). CONCLUSION: The admission BUNLVEFr provided important prognostic information for AMI-CS patients.

A novel echocardiographic parameter considering left ventricular afterload during V-A ECMO support.

BACKGROUND: Left ventricular stroke work index (LVSWI) and cardiac power index (CPI) account for the haemodynamic load of the left ventricle and are promising prognostic values in cardiogenic shock. However, accurately and non-invasively measuring these parameters during veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is challenging and potentially biased by the extracorporeal circulation. This study aimed to investigate, in an ovine model of cardiogenic shock, whether Pressure-Strain Product (PSP), a novel speckle-tracking echocardiography parameter, (1) can correlate with pressure-volume catheter-based LVSWI and CPI, and (2) can be load-independent during the flow modification of V-A ECMO. METHODS: Nine Dorset-cross ewes (51 ± 4 kg) were included. After cardiogenic shock was induced, full support V-A ECMO (X L/min based on 60 mL/kg/min) commenced. At seven time points during 24-h observation, echocardiographic parameters as well as pressure-volume catheter-based LVSWI and CPI were simultaneously measured with X and following X-1 L/min of ECMO flow. PSP was calculated by multiplying global circumferential strain or global radial strain, and mean arterial pressure, for PSPcirc or PSPrad, respectively. RESULTS: PSPcirc showed a stronger correlation with LVSWI (correlation coefficient, CC = .360, p < .001) and CPI (CC = .283, p < .001) than other echocardiographic parameters. The predictability of PSPcirc for pressure-volume catheter-based LVSWI (AUC .82) and CPI (AUC .80) was also higher than other echocardiographic parameters. No statistically significant differences were identified between the two ECMO flow variations in PSPcirc (p = .558). CONCLUSIONS: A novel echocardiographic parameter, PSP, may non-invasively predict pressure-volume catheter-based LVSWI and CPI in a load-independent manner in a cardiogenic shock supported by V-A ECMO.

Spontaneous Coronary Artery Dissection with Cardiogenic Shock in the United States.

Background: Spontaneous coronary artery dissection (SCAD) is defined as a non-traumatic separation of the epicardial coronary artery walls that creates a false lumen. SCAD poses a difficult challenge in management, as decisions regarding revascularization and medical management seem to be tailored to the individual patient. We evaluated and compared outcomes based on cardiogenic shock in patients with SCAD utilizing Nationwide Readmissions Database (NRD) between January 1, 2016, to December 30, 2020. Methods: We utilized the NRD 2016-2019 to carry out this study. We evaluated demographics (e.g., age, gender), conventional risk factors, comorbidities present on the index admission, and in-hospital outcomes using their specific ICD-10-CM codes. The primary outcomes were In-hospital mortality and 30-day readmission, and the secondary outcome was to compare the complications in SCAD patient with cardiogenic shock (CS) compared to those without CS. Results: We analyzed 2473 individuals with SCAD, 2199 of these individuals did not have cardiogenic shock whereas 274 of these individuals did have cardiogenic shock. When comparing SCAD with cardiogenic shock to SCAD without cardiogenic shock, there was a statistically significant increased odds ratio (OR) for death (propensity matched OR 24.93 (7.49-83.05), use of mechanical circulatory support (propensity matched OR 15.30 (6.87-34.04), ventricular tachycardia (propensity matched OR 4.45 (1.92-10.34), utilization of blood transfusions (propensity matched OR 3.82 (1.86-7.87), acute kidney injury (propensity matched OR 4.02 (1.45-11.13), need for mechanical ventilation (propensity matched OR 8.87 (3.53-22.31), and respiratory failure (propensity matched OR 4.95 (1.83-13.41)))))))). There was no statistically significant difference in 30-day readmission rates between the two groups. Conclusions: SCAD is a unique condition that can lead to many complications. In our analysis, we showed that SCAD associated with cardiogenic shock compared to SCAD not associated with cardiogenic shock results in greater odds of complications including death, use of mechanical circulatory support, need for blood transfusions, ventricular tachycardia, acute kidney injury, use of mechanical ventilation, and respiratory failure. SCAD with cardiogenic shock represents a significantly critical clinical scenario that requires a multi-disciplinary approach to prevent the many potential complications associated with this disease process.

Association between Albumin-Corrected Anion Gap and Mortality in Patients with Cardiogenic Shock.

Background: Cardiogenic shock (CS) is a critical illness with a high mortality rate in clinical practice. Although some biomarkers have been found to be associated with mortality in patients suffering from CS in previous studies. The albumin-corrected anion gap (ACAG) has not been studied in depth. Our study aimed to explore the relationship between ACAG and mortality in patients with CS. Methods: All baseline data was extracted from Medical Information Mart for Intensive Care-IV version: 2.0 (MIMIC-IV). According to the prognosis at 30 days of follow-up, they were divided into survivors and non-survivors groups. The survival curves between the two groups were drawn using the Kaplan-Meier method and the log-rank test. Valid factors were selected using the least absolute shrinkage and selection operator (LASSO) logistic analysis model. Analysis was performed to investigate the relationship between mortality and all enrolled patients using restricted cubic spline (RCS) and Cox proportional hazards models. Receiver operating characteristic (ROC) curves were used to assess the predictive ability of ACAG. Evaluation of final result stability using sensitivity analysis. Results: 839 cases were selected to meet the inclusion criteria and categorized into survivors and non-survivors groups in the final analysis. The ACAG value measured for the first time at the time of admission was selected as the research object. Kaplan-Meier (K-M) survival curves showed that cumulative 30- and 90-day survival decreased progressively with elevated ACAG (p < 0.001), and multifactorial Cox regression analyses showed ACAG to be an independent risk factor for increased 30- and 90-day mortality in patients suffering from CS (p < 0.05). RCS curves revealed that all-cause mortality in this group of patients increased with increasing ACAG ( χ 2 = 5.830, p = 0.120). The ROC curve showed that the best cutoff value for ACAG for predicting 30-day mortality in patients with CS was 22.625, with a sensitivity of 44.0% and a specificity of 74.7%. The relationship between ACAG and CS short-term mortality remained stable in all sensitivity analyses (All p < 0.05). Conclusions: The ACAG is an independent risk factor for 30- and 90-day mortality in CS patients and predicts poor clinical outcomes in CS patients. According to our study, elevated ACAG at admission, especially when ACAG > 20 mmol/L, was an independent predictor of all-cause mortality in CS.

Clinical Application of Extracorporeal Membrane Oxygenation in the Treatment of Fulminant Myocarditis.

Fulminant myocarditis (FM) is a rare but serious clinical syndrome which can be characterized by the rapid deterioration of cardiac function, with cardiogenic shock (CS) and arrhythmic electrical storms being common presentations, often requiring adjunctive support with mechanical circulatory devices. With the development of mechanical circulatory support (MCS) devices, there are now more and more studies investigating the application of MCS in FM patients, and the use of extracorporeal membrane oxygenation (ECMO) to treat FM has shown good survival rates. This review elucidates the treatment of FM, and the application and clinical outcomes associated with ECMO intervention.