bluuebunny/crossref_metadata_2025 huggingface dataset:
Ticagrelor vs. clopidogrel in ST elevation myocardial infarction patients with hemoglobin > 160
Authors: Zheng M Y , Zhang Y K , Hu S T , Gu T S , Jiang C , Zhang J K , Wu X , Liu X , Liu T , Chen K Y
Published: October 2024

Background

While some studies have provided therapeutic guidance for antiplatelet therapy in acute coronary syndrome (ACS) patients with anemia, research regarding ACS patients with elevated hemoglobin remains scarce.

Purpose

This study aims to evaluate the prognostic impact of different dual antiplatelet therapy (DAPT) regimens in ST-segment elevation infarction (STEMI) patients with hemoglobin > 160 g/L.

Methods

The data for this study were derived from the Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023. A total of 3372 patients were included in the study. Patients were divided into either the ticagrelor group or the clopidogrel group based on their priscribed antiplatelet regimens. The primary endpoint was defined as major adverse cardiovascular and cerebrovascular events (MACCE), comprising of cardiac death, myocardial infarction, and ischemic stroke within one month. Secondary endpoints included all-cause death at one-year, net adverse clinical events (NACE) defined as cardiac death, recurrent MI, Bleeding Academic Research Consortium (BARC) level 3 or greater, and revascularization, and cardiac death at one year. Propensity score matching (PSM) was utilized to balance clinical characteristics between the two groups. Multivariable Cox regression analysis was conducted post PSM to evaluate the impact of different antiplatelet regimens.

Result

The study population comprised 3372 patients, with 2200 receiving clopidogrel and 1172 with ticagrelor. The median age in the clopidogrel group was 54.83 years, while in the ticagrelor group, it was 53.61 years (P = 0.005). The clopidogrel group had a higher proportion of females compared to the ticagrelor group (3.9% vs. 2.0%, p=0.003). After PSM, 1086 well-matched pairs were identified. The ticagrelor group demonstrated a significantly lower rate of one-year all-cause mortality (1.38% VS 2.85%, LogRank p = 0.018), MACCE events (6.53% VS 9.48%, LogRank p = 0.015), and cardiac death (1.29% VS 2.76%, LogRank p = 0.015), compared to the clopidogrel group. However, there was no significant difference in the incidence of NACE events between the two groups (8.38% VS 7.76%, p = 0.300). Multivariate Cox regression analysis showed that ticagrelor treatment was associated with a reduced risk of all-cause mortality ( aHR 0.408, 95%CI: 0.214-0.775, p = 0.006), MACCE events (aHR 0.640, 95%CI: 0.473-0.869, p = 0.042), cardiac death (aHR 0.384, 95%CI: 0.198-0.743, p = 0.004).

Conclusions

Among STEMI patients with hemoglobin > 160 g/L, treatment with ticagrelor was associated with significantly lower rates of all-cause mortality, MACCE, and cardiac death compared to the treatment with clopidogrel.
Temporal trends in major bleeding after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction from 2003 to 2017: the Western Denmark Heart Registry
Authors: Thrane P , Olesen K K W , Thim T , Gyldenkerne C , Hansen M K , Stoedkilde-Joergensen N , Kristensen S D , Maeng M
Published: October 2024

Background

Management of patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) has changed during the last two decades. Introduction of more potent platelet inhibitors may carry an increased risk of bleeding complications, while other therapeutic options, such as use of radial artery access and proton pump inhibitors may reduce bleeding risk. The combined impact of these treatment changes on bleeding risk in patients with STEMI remains unknown.

Purpose

To examine temporal trends in 1-year risk of major bleeding after STEMI treated with primary PCI from 2003 to 2017.

Methods

We used the Western Denmark Heart Registry to identify first-time PCI-treated patients undergoing primary PCI for STEMI from 2003 to 2017. Patients were divided into 4 calendar periods based on the time of STEMI. The main outcome was 1-year risk of major bleeding defined as a hospital admission for bleeding using a validated definition with high accuracy. Additionally, the 1-year risk of major bleeding in STEMI patients was compared with the risk in an age- and sex-matched general population cohort without prior coronary artery disease.

Results

From 2003 to 2017, we identified 18,540 patients treated with primary PCI for STEMI (median age 64 years, 75% men)and 92,700 age- and sex-matched individuals. The 1-year risk of major bleeding after STEMI was similar across the different time periods; 4.1% in 2003-2006, 3.8% in 2007-2010, 3.8% in 2011-2014, and 4.5% in 2015-2017. The adjusted HR for bleeding in STEMI patients was 1.03 (95% CI 0.83-1.26) when comparing the latest period with the earliest period. The age- and sex-matched general population exhibited a 1-year risk of major bleeding of around 1% in all time periods (Figure 1).

Conclusions

Despite changes in management, the 1-year risk of major bleeding remained stable around 4% after primary PCI-treated STEMI from 2003 to 2017. This risk was approximately 4 times higher than the bleeding risk observed in an age- and sex-matched general population.
Influence of social factors on prompt reperfusion in patients with ST-segment elevation myocardial infarction: results from the KRAMI multicenter registry
Authors: Park J M , Kim M H , Lee K M , Song Z Y , Lim K H , Park J S , Kim R B , Hwang J Y , Lee J H
Published: October 2024

Background

The time from symptom onset to reperfusion therapy was particularly important for ST-segment elevation myocardial infarction (STEMI) patients. We sought to investigate the impact of social factors on prompt reperfusion in STEMI patients.

Methods

A total of 5,264 patients with a diagnosis of STEMI from Korean Registry of Acute Myocardial Infarction (KRAMI) was participated in present study. The association between social factors and process of symptom onset-to-timely reperfusion was evaluated. Process of symptom-to-reperfusion time was included door-to-balloon (DTB) time, symptom-to-door (STD) time and symptom-to-balloon (STB) time.

Results

In the entire study population, the median times of DTB, STD and STB were 55 min, 117 min and 175 min, respectively. With 3 parameters, only DTB was associated with in-hospital mortality (Fig. 1 and 2). Old age and male were more likely to delay treatment (p for age=0.000; p for gender <0.0001). Moreover, higher education was linked to reduction of STD and STB time (p<0.05). Living alone was associated with prolonged STB time, and symptom appearing outside was linked to delay medical care. Transportation with ambulance was significantly associated with reduction of reperfusion time, and inter-hospital transportation was particularly prominent (STD: OR 5.450, 95% CI 4.796 - 6.193, p<0.0001; STB: OR 4.593, 95% CI 4.038 - 5.225, p<0.0001). In addition, treatment time during off-hours was relatively delayed DTB time.

Conclusions

Door to balloon time is directy related to in-hospital mortality. Social factors, such as age, gender, and education level, and transportation with ambulance were related to timely reperfusion in STEMI patients.
Comparing the ability of GRACE 2.0 scores for predicting mortality in patients with and without diabetes
Authors: Soman B , Chatterjee T , Chrysostomou P , De Silva R , Sathyapalan T , Chattopadhyay S
Published: October 2024

Background

The GRACE 2.0 (G2) was an improvement on GRACE. Neither contains DM in the model. In the GRACE, DM independently predicted in-hospital but not the 6-month post-discharge mortality. Similar analysis for GRACE 2.0 score is unavailable.

Purpose

Assess the ability of the GRACE 2.0 score in predicting mortality in patients with and without diabetes.

Methods

Retrospective cohort analysis of data on non-STEMI and UA patients admitted in two hospitals between 2010 and 2019 entered into the Myocardial Infarction National Audit Project database. All baseline characteristics of the population and G2 scores were recorded. Death at 1 year was recorded from hospital and general practice records. Follow up was censored at the last recorded contact of the patient with a medical professional. The discriminative power of the G2 score in patients with and without diabetes in predicting mortality was determined by comparing the area under the receiver operating characteristic curve (c-statistics). Accuracy of calibration was evaluated by plotting the mean predicted vs observed mortality in each decile of predicted risk.

Results

Of 2841 patients entered, complete data was available for 2768 patients (age 69±14yrs, 62.3% male, 877(31.7%) with diabetes). G2 risk was higher in DM (8.3, IQR 3.9 to 19.0 v 5.5, IQR 2.6 to 13.0; p<0.0001). 337 patients died, 156 with DM. Higher deaths occurred in DM group (17.8% vs 16.3; adjusted OR 1.81, 95% CI 1.41-2.33, p<0.0001) (fig 1D). G2 discriminated between events well in whole cohort (AUC 0.81, p<0.001) with no difference between DM and non-DM patients (AUC DM: 0.78, 95% CI 0.75 to 0.81; non-DM 0.81, 0.79 to 0.83; δAUC 0.0301, p=0.242) (fig1E). Calibration of predictions by G2 was excellent across all deciles of risk for the whole cohort (fig 1A). However, G2 underestimated mortality in DM versus non-DM (fig1B,C), especially in the higher deciles of risk (fig 1 F,G).

Conclusion(s)

Discrimination of the GRACE 2.0 model was excellent for mortality at 1-year with no difference between patient with and without diabetes in our cohort of NSTEMI and UA patients. However, calibration plots suggest GRACE 2.0 underestimates mortality in diabetic compare to non-diabetic patients. This may suggest that risk stratification with GRACE 2.0 in diabetic patients may have to be considered with caution.Figure 1.
The impact of pre-myocardial infarction exercise frequency on prognosis in Non-ST segment elevation myocardial infarction patients
Authors: Gu T S , Hu S T , Zhang Y K , Jiang C , Zhang J K , Wu X , Liu X , Liu T , Chen K Y
Published: October 2024

Background

Non-ST segment elevation myocardial infarction (NSTEMI) presents a significant challenge in cardiovascular care, often requiring urgent management. Understanding the impact of exercise frequency prior to the onset of NSTEMI on post-event prognosis is crucial for developingmedical strategies.

Purpose

This study aimed to investigate the clinical characteristics and outcomes of NSTEMI patients based on their exercise frequency before experiencing NSTEMI, comparing those with regular exercise (once or more per week) versus those with infrequent or no exercise.

Methods

This study included acute myocardial infarction cohorts from 71 secondary or tertiary hospitals between January 1, 2010 and June 30, 2023. Inclusion criteria comprised NSTEMI patients evaluated for exercise frequency using the Community Health Questionnaire before hospitalization. The primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE), net adverse clinical events (NACE), and all-cause mortality, with secondary outcomes comprising the individual components of MACCE and NACE. Propensity score matching (PSM) was employed to adjust for differences in clinical characteristics between the two groups. Multivariable Cox regression and robust multivariable Cox regression were conducted before and after PSM to evaluate the impact of exercise frequency on outcomes.

Results

The final study population consisted of 38753 participants (42.7% in the High-frequency exercise group). The median follow-up duration was 1518 days, the mean age was 67.80±11.47 years, 61.6% were male. Compared to individuals with infrequent exercise before NSTEMI, those with regular exercise exhibited significantly lower risks of MACCE [aHR 0.93(0.90-0.96), p<0.001], NACE [aHR 0.91(0.88-0.95), p<0.001], and all-cause mortality [aHR 0.88(0.85-0.92), p<0.001]. However, regular exercise before NSTEMI was associated with an increased risk of coronary revascularization [aHR 1.14(1.06-1.23), p<0.001]. These findings remained consistent in the robust multivariate Cox regression analysis conducted after adjusting for differences between the two groups with PSM (Figure 1). After PSM, survival analysis indicated that the incidence of primary outcomes was lower in individuals with high exercise frequency before NSTEMI compared to those with low exercise frequency before NSTEMI, with all-cause mortality rates of 26.9% vs. 30.8%, MACCE rates of 37.2% vs. 38.5%, and NACE rates of 37.9% vs. 39.1%, all with log-rank p-values <0.001.

Conclusion

This study highlights the protective role of regular physical activity befor NSTEMI in reducing adverse post-NSTEMI outcomes. Promoting pre-NSTEMI physical activity can be a key element in preventive cardiology, potentially improving prognosis and decreasing the likelihood of cardiovascular events post-NSTEMI.Figure 1
Do DAN-GER-SHOCK eligible patients benefit from VA-ECMO treatment in infarct-related cardiogenic shock ? Results of an individual patient data meta-analysis.
Authors: Zeymer U , Freund A , Hochadel M , Ostadal P , Belohlavek J , Massberg S , Brunner S , Flather M , Adlam D , Schneider S , Desch S , Thiele H
Published: October 2024

Background

In a recent meta-analysis of randomized controlled trials routine use of venous-arterial ECMO (VA-ECMO) did not improve outcome in patients with infarct related cardiogenic shock (CS). Since the rate of patients with cardiac arrest and the need for cardio-pulmonary resuscitation was over 75 %, it has been speculated that a more selective approach might improve the effectiveness of VA-ECMO.

Methods

Patients included in four randomized clinical trials investigating the routine use of VA-ECMO in CS were centrally analysed. For the purpose of this sub-analysis only patients who would have been eligible for inclusion into the Dan-Ger SHOCK trial were analyzed (STEMI only, exclusion of comatose patients after out-of hospital cardiac arrest). The primary endpoint was 180-day total mortality.

Results

A total of 202 patients (106 randomised to VA-ECMO and 96 to control) were included into this analysis. There were no differences in baseline characteristics, angiographic and interventional features between the two groups. The table summarizes the results and revealed non-significant trends towards a reduced mortality with VA-ECMO.

Conclusions

In non-comatose patients with CS and STEMI the routine use of VA-ECMO is associated with a numerically lower mortality after 6 months. However, as indicated by the large confidence intervals the statistical power was limited, to draw definite conclusions. Therefore, a prospective trial with VA-ECMO in these patients seems warranted.Table
The effect of treatment srategy for acute myocardial infarction complicated by cardiac shock using Impella in accordance with institutional protocol
Authors: Tada T
Published: October 2024

Backgrounds

Team-based care for cardiogenic shock (CS) using mechanical circulatory support (MCS) including Impella in accordance with standardized protocol was reported to improve the prognosis of patients with CS.

Methods

Between February 2018 and September 2022, we performed percutaneous coronary intervention (PCI) in 63 patients with acute myocardial infarction (AMI) complicated by CS using Impella. We introduced institutional protocol (Figure 1) to standardize the treatment strategy for CS from June 2019, in which early Impella implantation preceding PCI was recommended. We retrospectively examined the incidence of Impella implantation preceding PCI, in-hospital outcomes including the rates of survival to Impella weaning and to discharge, and the incidence of major cardiovascular events (MACE) including all death, MI, and hospitalization for heart failure at 1-year before and after protocol introduction.

Results

The patients have a mean age of 67.1±13.2 years and 53 patients (84.1%) were male. The patients in preceding period were 16 cases, while 47 in latter period. The rate of Impella implantation preceding PCI was significantly higher in latter period than that in preceding period (61.7% vs. 25%, p=0.027) (Figure 2A). The rate of survival to Impella weaning was significantly higher in latter period than that in preceding period (83% vs. 56.3%. p=0.043). There was no difference in the rate of survival to discharge between each period (50% in preceding period vs. 68.1% in latter period, p=0.236). However, the cumulative MACE free survival rate was significantly higher in latter period than that in preceding period (56.9% vs. 31.3%, Log-rank p=0.020) (Figure 2B).

Conclusion

The introduction of institutional standardized protocol of MCS use might improve 1-year outcomes of patients with AMI complicated by CS treated with Impella.Figure 1Figure 2
Prevalence and prognostic relevance of non-obstructive coronary atherosclerosis in MINOCA: a meta-analysis of 35 studies
Authors: Ciarlantini M , Cavallo D , Suma N , Casuso M , Fedele D , Impellizzeri A , Bodega F , Bela' R , Pastore G , Ryabenko K , Foa' A , Rinaldi A , Angeli F , Paolisso P , Pizzi C
Published: October 2024

Background

Myocardial infarction with non-obstructive coronary arteries (MINOCA) can result from a variety of pathological mechanisms, not always associated with atherosclerosis. It has been suggested to distinguish between patients without obstructive coronary artery disease (NObs-CAD, stenosis diameter 1-49%), and patients with smooth coronary arteries (NCA), but differences in terms of prognosis or therapeutic approaches have not been clearly elucidated.

Objectives

The aim of this study is to evaluate the prevalence and prognostic impact of NObs-CAD as assessed by invasive coronary angiography (ICA) in MINOCA.

Methods

A meta-analysis was performed including studies reporting the prevalence of NObs-CAD versus NCA in MINOCA patients. Data on prognosis stratified by the presence of NObs-CAD were collected. Random-effects models were used to estimate the prevalence of NObs-CAD. Pooled risk ratios (RR) with 95% confidence intervals (CI) for all-cause death, myocardial infarction (MI), and the composite of both outcomes of patients with NObs-CAD compared to NCA were calculated at short-term (<1 month), 1-year and long-term follow-up (more than 1 year).

Results

Thirty-five studies were analysed. The pooled prevalence of NObs-CAD estimated by ICA was 53% [95% CI 47-60%]. Heterogeneity was high (I2=98.0%), but none of the clinical and instrumental characteristics tested in meta-regression analyses had a significant impact on the I2, except for age (residual I2=97.2%, p=0.014) and geographical context. Specifically, studies conducted outside Europe reported a higher prevalence of NObs-CAD with lower I2 values. Thirteen studies provided prognostic data. The presence of NObs-CAD was associated with an increased risk of death or MI compared to NCA, as well as the risk of MI at 1-year follow-up (RR = 1.49 [95% CI 1.17-1.90] and RR = 1.80 [95% CI 1.26-2.59], respectively), whereas the risk of death was comparable. Similar results were observed at long-term, but not at short-term follow-up. Out of 13 studies, 4 provided information regarded the medications at discharge stratified by the presence or absence of NObs-CAD. NObs-CAD patients received more often aspirin (89% vs 69%; p<0.01), P2Y12-inhibitors (52% vs 29%; p<0.01), angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (53% vs 40%; p<0.01), beta-blockers (70% vs 57%; p<0.01), and statins (86% vs 60%; p<0.01) compared to NCA.

Conclusions

Stratification of patients according to the degree of coronary stenosis has prognostic implications in the setting of MINOCA, since NObs-CAD patients present a higher risk of reinfarction. Further dedicated trials are needed to clarify whether these patients may benefit from a tailored approach in terms of secondary prevention strategies.Central illustration
Contemporary characteristics, outcomes and novel risk score for Takotsubo cardiomyopathy: a national inpatient sample analysis
Authors: Wang T K M , Agrawal A , Bhagat U , Bayat A , Sawhney A , Arockiam A D , Haroun E , Gupta R , Faulx M , Desai M Y , Jaber W , Menon V , Griffin B P
Published: October 2024

Background

Takotsubo cardiomyopathy (TC) is an established differential diagnosis in the category of myocardial infarction with non-obstructive coronaries with significant recent interest but limited data on prognostication. We reviewed the characteristics and in-hospital outcomes and developed a novel risk score for TC.

Methods

Adult patients (≥18 years of age) with a diagnosis of acute coronary syndrome (ACS) and TC were identified from the National Inpatient Sample 2016-2020 in the United States. The cohort was divided into ACS with and without TC, and the related baseline data was retrieved. Multivariable regression analysis was performed to identify clinical factors associated with TC and its adverse outcomes and to create a risk-scoring system estimating mortality risk in the TC cohort.

Results

Amongst 7,219,004 adult patients admitted for ACS, 78,214 (1.0%) were diagnosed with TC, with a mean age of 68.2 years, 64,526 (82.5%) being female, and 5,475 (7.0%, compared with 8.4% for other ACS) in-hospital mortality events. Key factors significantly associated with TC diagnosis were female sex (OR 6.78 (95%CI 6.47-7.09), p<0.001) and chronic heart failure (OR 1.60 (95%CI 1.54-1.66), p<0.001). Based on multivariable analyses for in-hospital mortality in TC patients, a novel risk score was developed, with parameters and score assignment listed in the Figure. The score can be divided into three categories: low risk (-3 to +3), moderate risk (4 to 7), and high risk (8 to 19), and its area under curves for in-hospital mortality were 0.716 in the derivation and 0.726 in the validation cohorts.

Conclusion

TC remains a high-risk diagnosis in a minority of ACS hospitalizations, with comparable in-hospital mortality rates to other causes of ACS. A novel score was developed to risk stratify TC inpatients with moderate discrimination and internal validation, warranting external validation.Takotsubo Cardiomyopathy Risk Score
Clinical characteristics and predictors of adverse cardiovascular events from the australia-new zealand spontaneous coronary artery dissection (ANZ-SCAD) registry
Authors: Dang Q , Psaltis P , Burgess S , Chandrasekhar J , Mukherjee S , Fairley S , Marathe J , Zaman S
Published: October 2024

Background

Spontaneous coronary artery dissection (SCAD) is an increasingly recognised cause of acute coronary syndrome (ACS), predominantly affecting women. Our understanding of SCAD remains incomplete with limited prospective data on determinants of major adverse cardiovascular events (MACE).

Purpose

We aimed to describe the clinical characteristics of patients with SCAD from a large, multicentre SCAD registry. We aimed to identify the predictors of MACE (defined as the composite of all-cause death, non-fatal myocardial infarction, stroke, heart failure, and revascularisation).

Methods

Observational, multi-centre prospective and retrospective cohort study recruiting patients with SCAD from 23 hospitals in Australia and New Zealand. Patients aged=>18 years with SCAD and an ACS were eligible for inclusion. Prospectively recruited patients gave their informed consent with a waiver of consent for retrospectively recruited patients. All invasive coronary angiography imaging was adjudicated by an independent core laboratory to confirm the diagnosis of SCAD. Cox proportional hazard analysis was used to evaluate the association between MACE and SCAD recurrence with predefined clinical variables.

Results

From a total 487 patients recruited, 423 (132 prospective and 291 retrospective) patients with SCAD confirmed on core laboratory review were included for analysis. Mean age was 52.4±10.7 years, 89.7% were female and 73.1% were Caucasian. Percutaneous coronary intervention (PCI) was performed in 10.6% of patients. On discharge, 64% of conservatively managed patients were on dual antiplatelet therapy (DAPT). At 15 (interquartile range 5-36) months median follow-up, the accumulated MACE rate was 6.6%. On multivariate analysis, percutaneous coronary intervention (PCI) was associated with a higher risk of MACE [hazard ratio (HR) 3.50, 95% confidence interval (CI) 1.56-7.89, p=0.002], while discharge on at least one antiplatelet medication was associated with a lower risk of MACE (HR 0.13, 95% CI, 0.05-0.36, p<0.001). In patients managed conservatively (n=353), discharge on at least one antiplatelet medication (n=337) was associated with lower MACE (HR 0.27, 95% CI 0.1-0.73, p=0.01), with no difference between single and dual antiplatelet therapy (DAPT) (p=0.74). In patients managed conservatively and on DAPT (n=226), aspirin and clopidogrel was associated with a lower risk of MACE (HR 0.31, 95% CI 0.10-0.93, p=0.038) compared with DAPT consisting of aspirin and ticagrelor (HR 3.25, 95%CI 1.07-9.85 p=0.038) on multivariate analysis.

Conclusion

Patients with SCAD are at significant risk of MACE. In conservatively managed patients treated with DAPT, aspirin and clopidogrel was independently associated with a lower risk of MACE than aspirin and ticagrelor
Effect of nelonemdaz for patients with out-of-hospital cardiac arrest: the AWAKE phase II randomised clinical trial
Authors: Choi J H , Chun C B , Chung S P , Lee Y H , Lee J S , Kim Y H , Lee J S , Lee J S , Ahn C S , Gwag B J
Published: October 2024

Background

Hypoxic brain injury is a major hurdle that limits the survival of out-of-hospital cardiac arrest (OHCA). Nelonemdaz is a dual-target neuroprotectant, serving as a moderate NR2B-selective N-methyl-D-aspartate (NMDA) receptor antagonist while also exhibiting potent free radical scavenger properties. This dual neuroprotective action of nelonemdaz has the potential to reduce hypoxic brain injury in OHCA. We investigated the efficacy and safety of nelonemdaz for patients with OHCA.

Methods

AWAKE trial was a double-blind, placebo-controlled, randomised, multicentre phase II trial at 5 sites in South Korea. OHCA patients undergoing targeted temperature management were randomly assigned to high-dose (5250 mg), low-dose (3250 mg), and placebo groups at a 1:1:1 ratio. The primary outcome was the blood level of neuron-specific enolase (NSE) after 4th administration of drug. Secondary outcomes comprised blood biomarkers including neuron specific enolase (NSE) and S100beta, brain magnetic resonance imaging (MRI), and Cerebral Performance Category (CPC) and Modified Rankin Scale (mRS) up to day 90. Safety is assessed by serious adverse event.

Findings: A total of 105 patients were enrolled between November 18, 2018 to February 23, 2023. Patients with a median age of 61 years and 82% male were assigned to the high-dose (N=37), low-dose (N=35), and placebo (N=33) groups. Primary outcome was evaluated in 93 patients. There was no difference of neuron specific enolase (NSE, ng/mL), which served as the primary endpoint, between high-dose (median and interquartile range; 23·7, 15·0–69·9) and placebo (17·5, 13·6–113·0) groups and also between low-dose (26·6, 16·2–83·4) versus placebo groups (all p>0·05). Among secondary outcomes, fractional anisotropy of brain MRI was significantly higher in high-dose group compared to placebo group (0·465, 0·449–0·485 versus 0·441, 0·431–0·464; p=0·028), and was not different between low-dose (0·462, 0·439–0·480) and placebo groups (p>0·05). At day 90, the common odds ratio (95% confidence interval) indicating a favourable shift in the modified Rankin Scale was 1·25 (0·48–3·24) and 1·22 (0·47–3·20) in the high-dose and low-dose groups respectively, compared to placebo group (all p>0·05). No serious adverse events were reported.

Interpretation: Nelonemdaz did not reduced blood NSE level of OHCA patients. However, patients treated with high-dose nelonemdaz showed better fractional anisotropy that suggests reduced cerebral white matter damage. Patients treated with nelonemdaz also showed a favourable tendency of neurological recovery at day 90 without significant adverse effects. These results justify the initiation of a large-scale phase III trial.Neurological function up to day 90
The impact of early use of echocardiography performed by non-cardiologist in patients with chest pain - the ENDEMIC study
Authors: Jakl M , Grenar P , Medilek K , Novy J , Koci J , Vanek J , Pudil R
Published: October 2024

Background

Echocardiography is well-established method in management of chest pain at Emergency department (ED). However, evidence on the optimal scope of the examination and the education of the examiner is scarce. Early point of care echocardiography (POCE) by ED physician can speed up the diagnostic process compared to echocardiography performed by dedicated specialist, at the cost of a higher risk of misdiagnosis.

Purpose

Primary objective was to assess the impact of POCE on length of stay on emergency department (ED). Secondary objectives were to evaluate the impact of POCE on time to revascularization and on the accuracy of the diagnosis at the initial examination.

Methods

ENDEMIC study is a prospective, randomised, open-label, single centre study. Prior to enrolment, physicians without any previous experiences with POCE were educated according to BSE standard level 1. Patients examined for chest pain of uncertain etiology were enrolled into the study and randomised in even-odd manner for POCE within 90 minutes or for usual management. In all patients the length of ED stay, time to coronary angiography and accuracy of working diagnosis.

Length of ED stay was defined as time form first contact of the patient with ED to the moment when the patient physically leaved the ward. Time to revascularization was retrieved from patient´s medical records and confirmed by telephonic visit. A working diagnosis was considered accurate if it shared both pathophysiological mechanism and diagnostic criteria with the final diagnosis.

All POCE examinations were recorded and revised by certified echocardiography specialist for errors.

Results

The study was early terminated after enrolment of 150 patients, because main objectives were met. The use of POCE resulted in a significant shortening of both time of decision (138.0 [68.5−230.5] min vs. 252.0 [165.5−304.0], p=0.000004) and length of ED stay (209.0 [143.5−260.0] min vs. 271.0 [206.5−336.0], p=0.0002. Moreover, in patients indicated for further follow-up, utilisation of POCE resulted in better concordance of working and final diagnosis: 91,6 % vs. 50 %; RR = 1.83 (1.104-2.565); p = 0.0063. Benefits of POCE were most pronounced in patients requiring hospitalization.

Conclusion

The study showed that echocardiography performed by sufficiently educated physician in patients with acute chest pain results in significant shortening of ED stay along with improved diagnostic accuracy.
Mixed venous to arterial pCO2-gap is poorly correlated to cardiac index in 1526 pulmonary artery catheter monitored critically ill patients
Authors: Vandenbriele C , Beaumont A , Aw T C , Fernandez-Gard R , Ragavan A , Galiatsou E , Rosenberg A
Published: October 2024

Background

The CO2 gap is the difference between mixed venous and arterial CO2, and can be estimated by the difference in partial pressure in CO2 (Pv-aCO2 or ∆PCO2). ∆PCO2 is affected by cardiac output (CO), CO2 production and solubility. The central venous-to-arterial CO2 gap has been proposed as a less invasive surrogate for P(v-a)CO2 and has been investigated as a measure of adequacy of resuscitation, and to guide sepsis management. Nevertheless, the CO2-gap as determinant of CO has never been thoroughly investigated in large cohort of critically ill ICU-patients. This study aims to investigate the relationship between ∆PCO2 and cardiac index (CI) in a retrospective cohort of critically ill patients in a large quaternary cardiothoracic intensive care unit.

Methods

Over 62 months, pulmonary artery catheter monitored critically ill patients were identified and their case files reviewed in retrospect. Extracorporeal membrane oxygenation (ECMO) patients were excluded. P(v-a)CO2 measurements were defined as mixed venous and arterial pCO2 measurements drawn simultaneously or within maximum 30 minutes together with PA-measurements. Correlation coefficients were calculated between P(v-a)CO2 and CI, serum lactate, mixed venous saturations (SvO2), cardiac power index (CPI), inotropic score (IS), central venous pressure (CVP) and minute expiratory volume (MV)(Table 1). We used receiver operator characteristic (ROC) curves to assess the diagnostic performance of P(v-a)CO2 as a surrogate for CI lower than 2,2L/min/m2. Multivariate linear regression analysis was performed with P(v-a)CO2 as an dependent variable.

Results

4414 P(v-a)CO2 measurements were identified from 1526 patients. Median P(v-a)CO2 was 0,86 kPa (0,66-1,1) or 6.45 mmHg (4.95-8.25), and mean CI was 2.7l/min/m2 (2.2-3.2). Correlation coefficients of P(v-a)CO2 with the other variables remained poor (> 0,35). The area under the ROC curve for P(v-a)CO2 as a predictor of CI<2.2l/min/m2 was 0.65, p<0.0001 (Fig. 1B). A value of P(v-a)CO2 > 6.9 mmHg was found to have the highest sensitivity and specificity, with a poor performance of 61.21% sensitivity and 62.73% specificity.

Conclusion

This large retrospective study in 1526 critically ill cardiac ICU-patients did not demonstrate a strong relationship between P(v-a)CO2 and CI, nor with any other hemodynamic variable found in the ICU patient cohort studied (Table 1). This raises scepticism regarding the efficacy of P(v-a)CO2 as a physiological goal in guiding resuscitation and management of this precarious patient group. Therefore, we argue that the PA-catheter remains the cornerstone in assessing critically ill (cardiothoracic) ICU patients.
V-A ECMO weaning with pump-controlled retrograde trial off (PCRTO) approach: an illustration of safety, benefits and feasibility
Authors: Vandenbriele C , Fiorelli F , Passariello M , Riesgo Gil F , Akhtar W , Soliman Aboumarie H , Aron J , Cox C , Vasileios P , Hall D , Rosenberg A , Patel B
Published: October 2024

Introduction

Weaning cardiogenic shock patients off V-A ECMO is a crucial but difficult step in the management of these patients. Conventional weaning strategies reduce the ECMO flow to approximately 1 L/min, yet this still entails significant unloading of the cardiopulmonary circulation.

Background

The PCRTO technique enables controlled retrograde flow of oxygenated blood from the patient’s arterial side into the right ventricle, resulting in an incremental increase of 0.5 L/min in right ventricular preload. This process challenges and evaluates the entire cardiopulmonary system (Figure).

Methods

We prospectively examined the use of the Pump-Controlled Retrograde Trial Off (PCRTO) approach (-0.5 L/min) compared to conventional ECMO weaning (+1 L/min) in a cross over study including 14 V-A ECMO patients across three quaternary high-output cardiogenic shock centers. Both the conventional and the PCRTO-technique are performed under continuous cardiac echo and PA-catheter guidance.

Results

After achieving adequate anticoagulation levels (Xa>0.3), no thrombotic or other complications were observed, confirming 100% safety of this technique. Table 1 provides an overview of our PCRTO-cohort and their evaluation after conventional versus PCRTO weaning. In 43% (6/14) of our cohort, conventional weaning strategies determined feasibility of ECMO-device weaning, while ultimately failing with PCRTO due to e.g. right ventricular failure or oxygenation failure. In contrast, 4/14 patients who failed the conventional weaning showed a positive weaning potential with PCRTO, potentially enabling patients to be liberated from bridging to durable ventricular assist devices or heart transplant.

Conclusions

In conclusion, PCRTO is a safe weaning strategy that increases the likelihood of successful weaning in critically ill V-A ECMO patients by challenging oxygenation/ventilation and cardiac circulation through increased right ventricular preload and reduced left ventricular afterload. Here, PCRTO ultimately led to a different destination scenario in 78,5% of our patient cohort compared to conventional V-A ECMO weaning alone. PCRTO may provide a standardised, reproducible approach to ECMO assessment and liberation which will be useful for future clinical trials in this population.
Clinical significance of residual ischemia in acute myocardial infarction complicated by cardiogenic shock undergoing VA-ECMO
Authors: Kim O
Published: October 2024

Background

Although culprit-only revascularization during the index procedure has been recommended in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS), the reduction of residual ischemia is also emphasized to improve clinical outcomes. However, few data are available about the significance of residual ischemia in patients undergoing mechanical circulatory supports.

Objectives

This study aimed to evaluate the effects of residual ischemia on clinical outcomes in AMI patients undergoing venoarterial-extracorporeal membrane oxygenation (VA-ECMO).

Methods

AMI patients with multivessel disease who underwent VA-ECMO due to refractory CS were pooled from the RESCUE and SMC-ECMO registries. The included patients were classified into three groups according to residual ischemia evaluated using the residual SYNTAX score (rSS): rSS=0, 08. The primary outcome was 1-year all-cause death.

Results

A total of 408 patients were classified into the rSS=0 (N=100, 24.5%), 08 (N=172, 42.2%) groups. The cumulative incidence of the primary outcome differed significantly according to rSS (33.9% vs. 55.4% vs. 66.1% for rSS=0, 08, respectively, overall P<0.001). In a multivariable model, rSS was independently associated with the risk of 1-year all-cause death (HRadj 1.03, 95% CI 1.01–1.05, P=0.003). Conversely, the baseline SYNTAX score was not associated with the risk of the primary outcome. Furthermore, when patients were stratified by rSS, the primary outcome did not differ significantly between the high and low delta SYNTAX score groups.

Conclusions

In AMI patients with refractory CS who underwent VA-ECMO, residual ischemia was associated with an increased risk of 1-year mortality. Therefore, revascularization strategies to minimize residual ischemia should be considered in advanced CS, particularly in cases requiring VA-ECMO.
Impact of Impella5.0/5.5 use on short-term prognosis in patients with AMI-related cardiogenic shock receiving Impella-incorporated MCS in Japan
Authors: Nakamura M , Imamura T , Nakagaito M , Ueno H , Fukahara K , Kinugawa K
Published: October 2024

Background

The short-term prognosis in patients with acute myocardial infarction-related cardiogenic shock (AMI-CS) remains unsatisfactory even in the era of Impella. The survival benefit of Impella 5.0/5.5 use remains uncertain.

Purpose

This study examined the clinical impact of Impella device type on clinical outcomes among patients with AMI-CS receiving Impella support using the prospective multi-center J-PVAD registry data.

Methods

We included patients with AMI-CS who received Impella-incorporated temporary MCS and were enrolled in the J-PVAD registry between Feb 2022 and Dec 2023. The primary outcome was 30-day survival.

Results

A total of 2405 patients (average 71 y; LVEF 30%; Lac 5.6 mmol/L) were included. 1409 (58.6%) patients received Impella alone and the others (41.4%) received ECPELLA support. Patients who received ECPELLA had a lower 30-day survival compared to those receiving Impella alone (46.1% vs 62.3%, p < 0.0001). Of note, patients who received ECMO with Impella5.0/5.5 had a greater survival compared to those who received ECMO with Impella2.5/CP (64.4% vs 43.0%, Figure 1).

Conclusions

Patients who received ECPELLA had a lower 30-day survival compared to Impella alone. Impella 5.0/5.5 use may improve prognosis for those with ECMO support in AMI-CS.
Long-term outcomes of cardiogenic shock survivors: a contemporary retrospective analysis from a tertiary center
Authors: Barbosa Sousa R , Da Silva Correia D , Azevedo S , Almeida Carvalho R , Certo Pereira J , Sousa Paiva M , Bello A R , Presume J , Brizido C , Strong C , Ferreira J , Tralhao A
Published: October 2024

Background

Cardiogenic shock (CS) is a complex syndrome that still portends a dismal short-term prognosis. However, in patients that survive the initial admission and are later discharged, the long-term prognosis remains ill-characterized.

Aim

We aimed to describe the long-term morbidity and mortality outcomes of patients surviving the index admission for CS.

Methods

Retrospective analysis of all consecutive patients admitted to a cardiac intensive care unit (CICU) between December 2016 and December 2022 with a diagnosis of CS. All etiologies were included and further categorized as: acute myocardial infarction (AMI-CS), acute-on-chronic heart failure (HF-CS) and secondary causes [(S-CS): myocarditis, arrhythmic storm, acute pulmonary embolism, among others]. Our primary endpoint was defined as all-cause death, conditional to being discharged alive. Secondary endpoints comprised heart transplant, durable left ventricular assist device (LVAD) implantation, implantable cardioverter-defibrillator (ICD) insertion and hospital readmission during follow-up.

Results

A total of 208 patients were included [median age 68 years (IQR 57-80), 66% males, mean Charlson comorbidity index 4±3], of whom 52% (n=108) had AMI-CS, 27% (n=56) HF-CS and 21% (n=44) S-CS. During the index admission, mean SAPS II score was 49±18 and most patients were in SCAI-C (66%, n=137) stage. Organ support in the form of invasive mechanical ventilation, renal replacement therapy or temporary mechanical circulatory assist devices was necessary in 62% (n=129), 27% (n=56) and 26% (n=55) of patients, respectively. 53% of patients (n=110) survived the index admission [median CICU length of stay 8 (IQR 3-15) days; median hospital length of stay 13 (IQR 4-25) days]. At discharge, mean left ventricular ejection fraction was 38±16% and 28% (n=26) of patients underwent ICD implantation. Median follow-up after discharge was 679 (IQR 373-1056) days, with 4 (4%) patients lost to follow-up. Overall mortality was 22% (n=24) and was numerically higher for AMI-CS when compared to HF-CS and S-CS (9% vs 7% vs 6% respectively, p=0.640). Secondary endpoint analysis showed that 10% (n=11) had a heart transplant, 2% (n=2) received a durable LVAD, 9% (n=10) received an ICD and 26% (n=28) were re-hospitalized during that period.

Conclusions

Although the long-term mortality of patients discharged alive after the index admission for CS is not overwhelming, one in every four will be readmitted and a small proportion will be eligible for advanced heart failure therapies. Healthcare strategies to improve the morbidity and mortality of many CS survivors should be devised.
Effectiveness of an Impella versus intra-aortic balloon pump in patients who received extracorporeal membrane oxygenation: a nationwide inpatient database study
Authors: Nishimoto Y , Ohbe H , Nakata J , Takiguchi T , Nakajima M , Sasabuchi Y , Isogai T , Matsui H , Sato Y , Watanabe T , Yamada T , Fukunami M , Yasunaga H
Published: October 2024

Background/Introduction

Previous studies have suggested that left ventricular (LV) unloading with an intra-aortic balloon pump (IABP) or percutaneous ventricular assist device (Impella) in combination with extracorporeal membrane oxygenation (ECMO) is associated with lower mortality; however, it is unclear which is better.

Purpose

This study aimed to evaluate the effectiveness of LV unloading with an Impella versus IABP on in-hospital mortality and other clinical outcomes.

Methods

Using the Japanese Diagnosis Procedure Combination database from September 28, 2016, to March 31, 2022, we identified inpatients who received an Impella or IABP in combination with ECMO (ECPella or ECMO+IABP group, respectively). The primary outcome was in-hospital mortality and the secondary outcomes were the length of hospital stay, length of ECMO, total hospitalization cost, and complications including major bleeding, an ischemic stroke, vascular complications, and renal replacement therapy during hospitalization. Propensity score matching was performed to compare the outcomes between the groups. We performed sensitivity analyses excluding patients who received extracorporeal cardiopulmonary resuscitation.

Results

Of 14,525 eligible patients, 603 (4.2%) received ECPella and 13,922 (96%) received ECMO+IABP. After propensity score matching, there was no significant difference in in-hospital mortality between the two groups (58.9% versus 56.6%; risk difference, 2.3%; 95% confidence interval, -3.9% to 8.5%). A Kaplan–Meier analysis with the log-rank test showed no significant difference in the 60-day in-hospital mortality between the two groups (P value = 0.114) (Figure 1). The ECPella group had a longer hospital stay (mean 42.8 days versus 33.7 days; risk difference, 9.1 days; 95% confidence interval, 2.6 to 15.6 days), a higher total hospitalization cost (12,573,000 yen versus 6,857,000 yen; risk differences, 5,716,000 yen; 95% confidence interval, 4,439,000 yen to 6,993,000 yen), and more frequent major bleeding (8.1% versus 5.8%; risk difference, 2.0%; 95% confidence interval, 0.007% to 4.0%), vascular complications (4.1% versus 2.2%; risk difference, 2.0%; 95% confidence interval, 0.04% to 3.9%), and renal replacement therapy during hospitalization (50.6% versus 41.1%; risk difference, 9.5%; 95% confidence interval, 3.0% to 15.9%) than the ECMO+IABP group (Figure 2). The results of the sensitivity analyses, excluding 6,360 patients (44%) who received extracorporeal cardiopulmonary resuscitation, showed similar results to those for the main analyses.

Conclusions

This nationwide inpatient database study showed that ECPella was not associated with a survival benefit but was associated with a longer hospital stay, a higher total hospitalization cost, and more complications than ECMO+IABP.Figure 1Figure 2