Prognostic Impact of Admission Time in Infarct-Related Cardiogenic Shock: An ECLS-SHOCK Substudy.

BACKGROUND: The outcomes of patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) and the efficacy and safety of extracorporeal life support (ECLS) may be affected by the timing of hospital admission. OBJECTIVES: The present ECLS-SHOCK substudy sought to investigate the prognostic impact of on-hours vs off-hours admission and the efficacy of ELCS according to the timing of hospital admission time in AMI-CS. METHODS: Patients with AMI-CS enrolled in the multicenter, randomized ECLS-SHOCK trial from 2019 to 2022 were included. The prognosis of patients admitted during regular hours (ie, on-hours) was compared to patients admitted during off-hours. Thereafter, the prognostic impact of ECLS was investigated stratified by the timing of hospital admission. The primary endpoint was 30-day all-cause mortality. Statistical analyses included Kaplan-Meier, univariable, and multivariable logistic regression analyses. RESULTS: Of 417 patients enrolled in the ECLS-SHOCK trial, 48.4% (n = 202) were admitted during off-hours. Patients admitted during off-hours were younger (median age = 62 years [Q1-Q3: 55-69 years] vs 63 years [Q1-Q3: 58-71 years]; P = 0.036) and more commonly treated using initial femoral access for coronary angiography (79.0% [n = 158/200] vs 67.9% [n = 146/215]; P = 0.011). However, off-hours admission was not associated with an increased risk of 30-day all-cause mortality (off-hours vs on-hours: 46.0% [n = 93/202] vs 50.7% [n = 109/215]; OR: 0.83; 95% CI: 0.56-1.22). Furthermore, ECLS had no prognostic impact on 30-day all-cause mortality in patients with AMI-CS admitted during on-hours (50.5% [n = 52/103] vs 50.9% [n = 57/112]; P = 0.95; OR: 0.98; 95% CI: 0.58-1.68) or in patients admitted during off-hours (45.3% [n = 48/106] vs 46.9% [n = 45/96]; P = 0.82; OR: 0.94; 95% CI: 0.54-1.63). Finally, ECLS was associated with an increased risk of bleeding events, especially in patients admitted during on-hours. CONCLUSIONS: The prognosis in AMI-CS was not affected by admission time with a similar effect of ECLS during on- and off-hours.

Temporary mechanical circulatory support in infarct-related cardiogenic shock: an individual patient data meta-analysis of randomised trials with 6-month follow-up.

BACKGROUND: Percutaneous active mechanical circulatory support (MCS) devices are being increasingly used in the treatment of acute myocardial infarction-related cardiogenic shock (AMICS) despite conflicting evidence regarding their effect on mortality. We aimed to ascertain the effect of early routine active percutaneous MCS versus control treatment on 6-month all-cause mortality in patients with AMICS. METHODS: In this individual patient data meta-analysis, randomised controlled trials of potential interest were identified, without language restriction, by querying the electronic databases MEDLINE via PubMed, Cochrane Central Register of Controlled Trials, and Embase, as well as ClinicalTrials.gov, up to Jan 26, 2024. All randomised trials with 6-month mortality data comparing early routine active MCS (directly in the catheterisation laboratory after randomisation) versus control in patients with AMICS were included. The primary outcome was 6-month all-cause mortality in patients with AMICS treated with early routine active percutaneous MCS versus control, with a focus on device type (loading, such as venoarterial extracorporeal membrane oxygenation [VA-ECMO] vs unloading) and patient selection. Hazard ratios (HRs) of the primary outcome measure were calculated using Cox regression models. This study is registered with PROSPERO, CRD42024504295. FINDINGS: Nine reports of randomised controlled trials (n=1114 patients) were evaluated in detail. Overall, four randomised controlled trials (n=611 patients) compared VA-ECMO with a control treatment and five randomised controlled trials (n=503 patients) compared left ventricular unloading devices with a control treatment. Two randomised controlled trials also included patients who did not have AMICS, who were excluded (55 patients [44 who were treated with VA-ECMO and 11 who were treated with a left ventricular unloading device]). The median patient age was 65 years (IQR 57-73); 845 (79·9%) of 1058 patients with data were male and 213 (20·1%) were female. No significant benefit of early unselected MCS use on 6-month mortality was noted (HR 0·87 [95% CI 0·74-1·03]; p=0·10). No significant differences were observed for left ventricular unloading devices versus control (0·80 [0·62-1·02]; p=0·075), and loading devices also had no effect on mortality (0·93 [0·75-1·17]; p=0·55). Patients with ST-elevation cardiogenic shock without risk of hypoxic brain injury had a reduction in mortality with MCS use (0·77 [0·61-0·97]; p=0·024). Major bleeding (odds ratio 2·64 [95% CI 1·91-3·65]) and vascular complications (4·43 [2·37-8·26]) were more frequent with MCS use than with control. INTERPRETATION: The use of active MCS devices in patients with AMICS did not reduce 6-month mortality (regardless of the device used) and increased major bleeding and vascular complications. However, patients with ST-elevation cardiogenic shock without risk of hypoxic brain injury had a reduction in mortality after MCS use. Therefore, the use of MCS should be restricted to certain patients only. FUNDING: The Heart Center Leipzig at Leipzig University and the Foundation Institut für Herzinfarktforschung.

A Bayesian reanalysis of the CULPRIT-SHOCK trial.

AIMS: The optimal revascularization strategy for patients with acute myocardial infarction (AMI), cardiogenic shock (CS), and multivessel disease remains controversial. The CULPRIT-SHOCK trial compared culprit lesion-only vs. immediate multivessel percutaneous coronary intervention (PCI), providing important data but leaving efficacy questions unresolved. To address lingering uncertainties and gain deeper insights, we performed a Bayesian reanalysis of the CULPRIT-SHOCK trial data. METHODS AND RESULTS: We conducted a Bayesian re-analysis of the CULPRIT-SHOCK trial data using non-informative, sceptical, and enthusiastic priors. Relative risks (RRs) with 95% highest posterior density (HPD) intervals were calculated. We defined the minimal clinically important difference (MCID) as RR < 0.84. We performed subgroup analyses for key patient characteristics and assessed secondary outcomes and safety endpoints. Probabilities of benefit, achieving MCID, and harm were computed. Results are presented as median RR with probabilities of effect sizes. Bayesian reanalysis showed a median RR of 0.82 (95% HPD 0.66-1.04) with a non-informative prior, indicating a 95% probability of benefit and 59% probability of achieving MCID. Subgroup analyses revealed potentially stronger effects in males (RR 0.78, 73% probability of MCID), patients without diabetes (RR 0.76, 79% probability of MCID), and those with non-anterior ST-segment elevation MI (STEMI; RR 0.74, 76% probability of MCID). Secondary outcomes suggested potential benefits in mortality (RR 0.85) and need for renal replacement therapy (RR 0.72) but increased risks of recurrent MI (RR 2.84) and urgent revascularization (RR 2.88). CONCLUSION: Our Bayesian reanalysis provides intuitive insights by quantifying probabilities of treatment effect sizes, offering further evidence favouring the culprit lesion-only PCI strategy in AMI patients with CS and multivessel disease. The analysis demonstrates a high probability of overall benefit, with a notable chance of achieving a minimally clinically important difference, particularly in specific subgroups. These findings not only support the consideration of culprit lesion-only PCI in certain patient populations but also underscore the need for careful risk-benefit assessment. Furthermore, our hypothesis-generating subgroup analyses, which show varying probabilities of achieving MCID, illuminate promising avenues for future targeted investigations in this critical patient population.

Do DanGer-SHOCK-like patients benefit from VA-ECMO treatment in infarct-related cardiogenic shock? results of an individual patient data meta-analysis.

AIMS: In a recent meta-analysis of randomized controlled trials, routine use of veno-arterial ECMO (VA-ECMO) did not improve outcomes in patients with acute myocardial infarction-related cardiogenic shock (AMI-CS), while a microaxial flow pump reduced mortality in a selected group of patients with AMI-CS in the DanGer-Shock trial. METHODS AND RESULTS: Individual patient data of patients included in four randomized clinical trials investigating the routine use of VA-ECMO in AMI-CS were centrally analysed. For the purpose of this sub-analysis, DanGer-Shock-like patients were analysed (STEMI only, presumed low likelihood of brain injury). The primary endpoint was 180-day all-cause mortality. A total of 202 patients (106 randomized to VA-ECMO and 96 to control) were included. There were no differences in baseline characteristics, angiographic and interventional features between the two groups. Mortality after 6 months was numerically lower with VA-ECMO between the groups [45% in VA-ECMO group vs. 51% in control group; hazard ratio, 0.84; 95% confidence interval (CI), 0.56-1.26], while major bleeding (OR, 2.24; 95% CI, 1.08-4.64) and peripheral vascular complications (OR, 3.65; 95% CI, 1.15-11.56) were increased with the use of VA-ECMO. CONCLUSION: In this exploratory subgroup analysis in patients with CS, STEMI, and a low likelihood of brain injury, there was no mortality benefit with the routine use of VA-ECMO. However, as indicated by the large confidence intervals, the statistical power was limited to draw definite conclusions.

Effect of Peripheral Interventions in Patients with Peripheral Artery Disease Receiving Rivaroxaban and Aspirin: Analyses from the XATOA Registry.

OBJECTIVE: To assess the characteristics and clinical outcomes of patients with lower extremity peripheral artery disease (PAD) in XATOA receiving dual pathway inhibition (DPI) with rivaroxaban 2.5 mg twice daily plus aspirin according to lower extremity revascularisation (LER) history. METHODS: XATOA is an international, multicentre, prospective, single arm registry study. This subanalysis investigated patients with lower extremity PAD according to LER history. Patients with coronary artery disease, PAD, or both, receiving DPI were followed for 12 or more months. Baseline characteristics and clinical outcomes were assessed according to LER history. A time dependency analysis assessed outcomes by time between the most recent LER procedure and the start of DPI. A multivariable analysis assessed the influence of patient characteristics on clinical outcomes. RESULTS: In XATOA (n = 5 532), 2 820 (51.0%) patients had lower extremity PAD, of whom 1 736 (61.6%) had prior LER and 1 084 (38.4%) had no prior LER. Baseline characteristics were generally similar between patients with or without prior LER. A higher proportion of patients with prior LER experienced any treatment emergency clinical events compared with those without prior LER (15.0% vs. 9.4%, respectively), with greater differences observed between incidence rates of limb events, including major adverse limb events (9.06 vs. 4.09 events per 100 patient years, respectively). Similar rates of myocardial infarction, stroke, and major bleeding were observed in both subgroups. Clinical event rates were generally higher in patients who had previous LER for six months or less compared with patients who had previous LET for more than six months before starting DPI, regardless of LER type. Multivariable analyses showed that prior LER was predictive of limb events. CONCLUSION: This subanalysis of XATOA found that prior LER was associated with increased rates of limb events, consistent with results of COMPASS and VOYAGER PAD. Rates of bleeding were also low regardless of LER history and consistent with the findings from these trials.

German Cardiac Arrest Registry (G-CAR)-results of the pilot phase.

BACKGROUND: In Europe, more than 300,000 persons per year experience out-of-hospital cardiac arrest (OHCA). Despite medical progress, only few patients survive with good neurological outcome. For many issues, evidence from randomized trials is scarce. OHCA often occurs for cardiac causes. Therefore, we established the national, prospective, multicentre German Cardiac Arrest Registry (G-CAR). Herein, we describe the first results of the pilot phase. RESULTS: Over a period of 16 months, 15 centres included 559 consecutive OHCA patients aged ≥ 18 years. The median age of the patients was 66 years (interquartile range 57;75). Layperson resuscitation was performed in 60.5% of all OHCA cases which were not observed by emergency medical services. The initial rhythm was shockable in 46.4%, and 29.1% of patients had ongoing CPR on hospital admission. Main presumed causes of OHCA were acute coronary syndromes (ACS) and/or cardiogenic shock in 54.8%, with ST-elevation myocardial infarction being the most common aetiology (34.6%). In total, 62.9% of the patients underwent coronary angiography; percutaneous coronary intervention (PCI) was performed in 61.4%. Targeted temperature management was performed in 44.5%. Overall in-hospital mortality was 70.5%, with anoxic brain damage being the main presumed cause of death (38.8%). Extracorporeal cardiopulmonary resuscitation (eCPR) was performed in 11.0%. In these patients, the in-hospital mortality rate was 85.2%. CONCLUSIONS: G-CAR is a multicentre German registry for adult OHCA patients with a focus on cardiac and interventional treatment aspects. The results of the 16-month pilot phase are shown herein. In parallel with further analyses, scaling up of G-CAR to a national level is envisaged. Trial registration ClinicalTrials.gov identifier: NCT05142124.

Health-related quality of life in elderly cardiac patients undergoing cardiac rehabilitation and the association with exercise capacity: The EU-CaRE study.

AIMS: The ability to be physically active is pivotal to the quality of life in elderly patients. This study aims to describe the association between exercise capacity and health-related quality of life (HRQoL), anxiety, and depression following an exercise-based cardiac rehabilitation (CR) program in elderly cardiac patients. METHODS: Patients aged ≥65 years with acute and chronic coronary syndrome or heart valve surgery were consecutively included from 8 CR centers in 7 European countries. Exercise capacity (VO2peak(ml/kg/min)) was assessed with a cardiopulmonary exercise test (97%) or a six-minute walk test. Outcome variables included HRQoL (SF-36 physical and mental component scores (PCS and MCS)), anxiety (GAD-7), and depression (PHQ-9). Mixed models were used to address the association between baseline and the development in VO2peak, and outcome variables stratified on sex, and adjusted for baseline values, age, and CR center. RESULTS: A total of 1,633 patients were included (T0), 1,523 (93%) completed end-of-CR assessment (T1), and 1,457 (89%) 1-year follow-up (T2). Women had higher % of predicted VO2peak, but poorer scores in HRQoL, anxiety and depression at all time-points. All scores improved in both sexes at follow-up. We found significant associations between VO2peak at baseline as well as development in VO2peak and all outcome variables at T1 and T2 in men (all p < 0.001). In women, VO2peak was only associated with PCS scores (p < 0.001). CONCLUSIONS: Improvements in exercise capacity was strongly associated with improvements in HRQoL and mental health, however with stronger associations in men. The results highlight the importance of physical fitness for HRQol and mental health. The findings from this study might be useful to better target individual CR programs.

This study explores the association between exercise capacity and the well-being of elderly cardiac patients participating in a cardiac rehabilitation program, focusing on health-related quality of life (HRQoL), anxiety, and depression. Key Findings:Women, despite having higher percentages of predicted exercise capacity, consistently reported poorer HRQoL, anxiety, and depression scores compared to men at all assessed time points.Improvements in exercise capacity were strongly associated with positive changes in HRQoL and mental health, with these associations being more pronounced in men.

Why VA-ECMO should not be used routinely in AMI-Cardiogenic Shock.

This review summarizes the current evidence regarding efficacy and safety of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in the setting of cardiogenic shock. Currently, there is evidence from 4 randomized controlled trials which all do not support a mortality benefit and increased complication rates by VA-ECMO. Based on current evidence, possible subgroups will be discussed and indications in selected very small patient groups be discussed.

Patient knowledge about risk factors, achievement of target values, and guideline-adherent secondary prevention therapies 12 months after acute myocardial infarction.

AIMS: The prospective GULLIVE-R study aimed to evaluate adherence to guideline-recommended secondary prevention, physicians' and patients' estimation of cardiac risk, and patients' knowledge about target values of risk factors after acute myocardial infarction (AMI). METHODS AND RESULTS: We performed a prospective study enrolling patients 9-12 months after AMI. Guideline-recommended secondary prevention therapies and physicians as well as patients' estimation about their risk and patients' knowledge about target values were prospectively collected. Between July 2019 and June 2021, a total of 2509 outpatients were enrolled in 150 German centres 10 months after AMI. The mean age was 66 years, 26.4% were women, 45.3% had ST elevation myocardial infarction, 54.7% had non-ST elevation myocardial infarction, and 93.6% had revascularization (84.0% percutaneous coronary intervention, 7.4% coronary artery bypass graft, 1.8% both). Guideline-recommended secondary drug therapies were prescribed in over 80% of patients, while only about 50% received all five recommended drugs (aspirin, P2Y12 inhibitors, statins, beta-blockers, renin-angiotensin-aldosterone system inhibitors), and regular exercise was performed by only one-third. About 90% of patients felt well informed about secondary prevention, but the correct target value for blood pressure was known in only 37.9% and for LDL-cholesterol in only 8.2%. Both physicians and patients underestimated the objective risk of future AMIs as determined by the thormbolysis in myocardial infarction (TIMI) risk score for secondary prevention. CONCLUSION: There is still room for improvement in patient education and implementation of guideline-recommended non-pharmacological and pharmacological secondary prevention therapies in patients in the chronic phase after AMI.

Influence of prior myocardial infarction on outcome in patients with ischaemic HFrEF: insights from the EVIdence based TreAtment in Heart Failure (EVITA-HF) registry.

BACKGROUND: There is scarce information about the influence of prior myocardial infarction (pMI) on outcomes in patients (pts) with ischaemic HFrEF. We analysed data from the EVIdence based TreAtment in Heart Failure (EVITA-HF) registry. METHODS: EVITA-HF comprises web-based case report data on demography, diagnostic measures, adverse events and 1-year follow-up of patients hospitalized for chronic heart failure ≥ 3 months (CHF) and an ejection fraction ≤ 40%. In the present study, we focused on the outcomes of pts with and without pMI in ischaemic HFrEF. RESULTS: Between February 2009 and November 2015, a total of 2075 consecutive pts with ischaemic HFrEF were included from 16 centres in Germany. A total of 81.2% were male, and the mean age was 71 years. A total of 61.5% of the pts with ischaemic HFrEF had a history of pMI. These pts were treated less often with PCI (20.0 vs. 31.0%, p < 0.001) or CABG (3.8 vs. 7.7%, p < 0.001). They more often received an ICD (40.9 vs. 28.7%, p < 0.001), but less often a CRT-D (11.3 vs. 19.4%, p < 0.001). After multivariate adjustment, pts with pMI had a greater all-cause mortality after 1 year than those without pMI (hazard ratio 1.4; 95% CI, 1.10-1.79, p = 0.007). The combined endpoint of death, resuscitation or ICD shock after 1 year was greater in patients with pMI (20.8 vs. 16.4%, p = 0.03). Mobility was more often reduced in pts with pMI (46.8% vs. 40.1%, p = 0.03), and overall health status was more frequently worse in patients with pMI than in those 12 months ago (23.1 vs. 15.9%, p = 0.01). More than a quarter of the pts with ischaemic HFrEF were anxious or depressive. CONCLUSION: pMI in patients with CHF and ischaemic HFrEF was associated with increased mortality, increased event rates, and worsened health status. Hence, the subgroup of pts with ischaemic HFrEF and pMI is at higher risk and deserves special attention.

Use of sacubitril/valsartan in patients with heart failure in primary care in Germany: the AURORA-HF noninterventional study.

BACKGROUND: Sacubitril/valsartan (Sac/Val) is the first angiotensin receptor-neprilysin inhibitor indicated for symptomatic chronic heart failure (HF) with reduced ejection fraction (HFrEF). Given most patients with HF in Germany are managed by general practitioners, AURORA-HF investigated the baseline characteristics and 1­year follow-up of patients starting Sac/Val in primary care in Germany. METHODS: This was a prospective, multicenter, observational study, with all treatment decisions independent of participation. The only inclusion criteria were adults (age ≥ 18 years) with symptomatic HFrEF. The study comprised four groups, depending on therapy on entry: initiation of (1) Sac/Val or (2) other HF therapy; and no change in HF regimen that (3) included or (4) did not include Sac/Val. Baseline data were captured for all groups; 1­year follow-up was recorded in groups 1 and 2. RESULTS: Of 1278 patients in the baseline analyses, 513 (40.1%) had newly started Sac/Val (449 [87.5%] completing the 1­year follow-up), 265 (20.7%) had newly started other HF regimens (245, 92.5%) with 1­year follow-up, while 249 with Sac/Val (19.5%) and 251 without Sac/Val (19.6%) patients had unchanged therapies. Patients treated with Sac/Val had a higher New York Heart Association (NYHA) class at baseline and more often a left ventricular ejection fraction (LVEF) < 35%. The only baseline parameter significantly correlating with Sac/Val discontinuation during the 1­year follow-up was diabetes mellitus (odds ratio: 2.44; 95% confidence interval: 1.14-5.24). In the Sac/Val group, 30.7% of patients were in NYHA class I/II on study entry, improving to 51.0% at 1­year follow-up. In the no Sac/Val group, the corresponding rates of NYHA I and II classes were 49.8% and 58.2%, respectively. The overall adverse event profile of Sac/Val was good, with only 6.0% patients experiencing serious adverse events leading to permanent discontinuation. CONCLUSION: In patients with symptomatic HFrEF treated in primary care, the group in whom Sac/Val was initiated was characterized by a higher NYHA class and lower LVEF compared to patients in whom Sac/Val was not initiated. Sac/Val was well tolerated, with a high proportion completing 1 year of therapy.

A contemporary training concept in critical care cardiology.

Critical care cardiology (CCC) in the modern era is shaped by a multitude of innovative treatment options and an increasingly complex, ageing patient population. Generating high-quality evidence for novel interventions and devices in an intensive care setting is exceptionally challenging. As a result, formulating the best possible therapeutic approach continues to rely predominantly on expert opinion and local standard operating procedures. Fostering the full potential of CCC and the maturation of the next generation of decision-makers in this field calls for an updated training concept, that encompasses the extensive knowledge and skills required to care for critically ill cardiac patients while remaining adaptable to the trainee's individual career planning and existing educational programs. In the present manuscript, we suggest a standardized training phase in preparation of the first ICU rotation, propose a modular CCC core curriculum, and outline how training components could be conceptualized within three sub-specialization tracks for aspiring cardiac intensivists.

Scrutinizing the Role of Venoarterial Extracorporeal Membrane Oxygenation: Has Clinical Practice Outpaced the Evidence?

The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for temporary mechanical circulatory support in various clinical scenarios has been increasing consistently, despite the lack of sufficient evidence regarding its benefit and safety from adequately powered randomized controlled trials. Although the ARREST trial (Advanced Reperfusion Strategies for Patients with Out-of-Hospital Cardiac Arrest and Refractory Ventricular Fibrillation) and a secondary analysis of the PRAGUE OHCA trial (Prague Out-of-Hospital Cardiac Arrest) provided some evidence in favor of VA-ECMO in the setting of out-of-hospital cardiac arrest, the INCEPTION trial (Early Initiation of Extracorporeal Life Support in Refractory Out-of-Hospital Cardiac Arrest) has not found a relevant improvement of short-term mortality with extracorporeal cardiopulmonary resuscitation. In addition, the results of the recently published ECLS-SHOCK trial (Extracorporeal Life Support in Cardiogenic Shock) and ECMO-CS trial (Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock) discourage the routine use of VA-ECMO in patients with infarct-related cardiogenic shock. Ongoing clinical trials (ANCHOR [Assessment of ECMO in Acute Myocardial Infarction Cardiogenic Shock, NCT04184635], REVERSE [Impella CP With VA ECMO for Cardiogenic Shock, NCT03431467], UNLOAD ECMO [Left Ventricular Unloading to Improve Outcome in Cardiogenic Shock Patients on VA-ECMO, NCT05577195], PIONEER [Hemodynamic Support With ECMO and IABP in Elective Complex High-risk PCI, NCT04045873]) may clarify the usefulness of VA-ECMO in specific patient subpopulations and the efficacy of combined mechanical circulatory support strategies. Pending further data to refine patient selection and management recommendations for VA-ECMO, it remains uncertain whether the present usage of this device improves outcomes.