Percutaneous Coronary Intervention versus Optimal Medical Therapy in Patients with Chronic Total Occlusion: A Meta-Analysis.

Background/Objectives: Chronic total occlusion (CTO) is a prevalent finding in patients with coronary artery disease and is associated with increased mortality. Prior reports on the efficacy of percutaneous coronary intervention (PCI) compared to optimal medical therapy (OMT) were controversial. Following the emergence of recently published new evidence, a meta-analysis is warranted. The current meta-analysis assessed the effects of PCI compared to OMT in the treatment of CTO. Methods: A structured literature search was performed. Randomized controlled trials (RCTs) and non-randomized controlled studies of interventions were eligible. The primary outcome was an accumulated composite of cardiac mortality, myocardial infarction and target vessel/lesion revascularization events. Results: Thirty-two studies reporting on 11260 patients were included. Of these, 5712 (50.7%) were assigned to the PCI and 5548 (49.3%) were allocated to the OMT group. The primary outcome occurred in 14.6% of the PCI and 20.1% of the OMT group (12 trials, OR 0.66, 95% CI 0.50 to 0.88, p = 0.005, I2 = 67%). Subgrouping demonstrated a consistent reduction in the primary outcome for the PCI group in RCTs (six trials, OR 0.58, 95% CI 0.33 to 0.99, p = 0.05). The primary outcome reduction was irrespective of the study design, and it was replicable in sensitivity and subgroup analyses. Advantages in other outcomes were rather related to statistical pooling effects and dominated by observational data. Conclusions: CTO-PCI was associated with improved patient-oriented primary outcome compared to OMT in a study-level meta-analysis. This composite outcome effect was mainly driven by target vessel treatment, but a significant reduction in mortality and myocardial infarction was observed, irrespectively. These findings have hypothesis-generating implications. Future RCTs with adequate statistical power are eagerly awaited.

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.

Accredited cardiac arrest centers facilitate eCPR and improve neurological outcome.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a frequent medical emergency with low survival rates even after a return of spontaneous circulation (ROSC). Growing evidence supports formation of dedicated teams in scenarios like cardiogenic shock to improve prognosis. Thus, the European Resuscitation Council (ERC) recommended introduction of Cardiac Arrest Centers (CAC) in their 2015 guidelines. Here, we aimed to elucidate the effects of newly introduced CACs in Germany regarding survival rate and neurological outcome. METHODS: A multicenter retrospective observational cohort study was performed at three university hospitals and outcomes after OHCA were compared before and after CAC accreditation. Primary outcomes were survival until discharge and favorable neurological status (CPC 1 or 2) at discharge. RESULTS: In total 784 patients (368 before and 416 after CAC accreditation) were analyzed. Rates of immediate percutaneous coronary intervention (40 vs. 52%, p = 0.01) and implementation of extracorporeal CPR (8 vs. 13%, p < 0.05) increased after CAC accreditation. Likelihood of favorable neurological status at discharge was higher after CAC accreditation (71 vs. 87%, p < 0.01), whereas overall survival remained similar (35 vs. 35%, p > 0.99). CONCLUSION: CAC accreditation is linked to higher rates of favorable neurological outcome and unchanged overall survival.

Optic Nerve Sheath Diameter for Assessing Prognosis after Out-of-Hospital Cardiac Arrest.

PURPOSE: Evaluate optic nerve sheath and pial diameters (ONSD, ONPD) via sonography and computed tomography (CT) after out-of-hospital cardiac arrest (CA) and to compare their prognostic significance with other imaging and laboratory biomarkers. MATERIALS AND METHODS: A prospective observational study enrolling patients after successful resuscitation between December 2017 and August 2021. ONSD and ONPD were measured with sonography. Additionally, ONSD, and also grey-to-white ratio at basal ganglia (GWRBG) and cerebrum (GWRCBR), were assessed using CT. Lactate and neuron specific enolase (NSE) blood levels were measured. RESULTS: Sonographically measured ONSD and ONPD yielded no significant difference between survival and non-survival (p values ≥0.4). Meanwhile, CT assessed ONSD, GWRBG, GWRCBR, and NSE levels significantly differed regarding both, survival (p values ≤0.005) and neurological outcome groups (p values ≤0.04). For survival prognosis, GWRBG, GWRCBR, and NSE levels appeared as excellent predictors; in predicting a good neurological outcome, NSE had the highest accuracy. CONCLUSIONS: CT diagnostics, in particular GWRBG and GWRCBR, as well as NSE as laboratory biomarker, appear as excellent outcome predictors. Meanwhile, our data lead us to recommend caution in utilizing sonography assessed ONSD and ONPD for prognostic decision-making post-CA.

[Preclinical loading in patients with acute chest pain and acute coronary syndrome - PRELOAD survey]. / Präklinisches Loading bei Patienten mit akutem Thoraxschmerz und akutem Koronarsyndrom ­ PRELOAD-Umfrage.

BACKGROUND: Guidelines on myocardial infarction (MI) recommend antithrombotic and anticoagulatory treatment at time of diagnosis. MI with ST segment elevation (STEMI) is mostly a certain diagnosis. Acute coronary syndrome without ST segment elevation (NSTE-ACS) has diagnostic uncertainty and remains a working diagnosis in the prehospital setting. OBJECTIVE: Assessment of prehospital loading with aspirin and heparin depending on ACS subtype and pretreatment with oral anticoagulants. METHODS: The PRELOAD survey was a nationwide German study. STEMI/NSTE-ACS scenarios were designed and varied in pretreatment: I) no pretreatment, II) new oral anticoagulants (NOAC), III) vitamin K antagonist (VKA). Loading strategy was assessed and included: a) aspirin (ASA), b) unfractionated heparin (UFH), c) ASA + UFH, d) no loading. RESULTS: A total of 708 emergency physicians were included. In NSTE-ACS without pretreatment, 79% chose loading (p < 0.001). ASA + UFH (71.4%) was the preferred option. In corresponding STEMI scenario, 100% chose loading and 98.6% preferred ASA + UFH (p < 0.001). In NSTE-ACS with NOAC pretreatment, 69.8% favored loading (p < 0.001); in VKA pretreatment the corresponding rate was 72.3% (p < 0.001). In each scenario, ASA was the preferred option. In STEMI with NOAC pretreatment, 97.5% chose loading (p < 0.001); analogous rate was 96.8% in STEMI with VKA pretreatment (p < 0.001). ASA was the preferred option again. CONCLUSIONS: Prehospital loading was the preferred treatment strategy despite the diagnostic uncertainty in NSTE-ACS and guidelines recommending loading at time of diagnosis. Pretreatment with oral anticoagulants resulted in a strategy shift to loading with only aspirin. In STEMI patients, this indicates potential undertreatment.

Look before you leap: the importance of ECG in management of out-of-hospital cardiac arrest.

Graphical abstractReconstructed pre-hospital ECG, 25 mm/s 10 mm/mV.

Outcome of Out-of-Hospital Cardiac Arrest Patients Stratified by Pre-Clinical Loading with Aspirin and Heparin: A Retrospective Cohort Analysis.

Background: Out-of-hospital cardiac arrest (OHCA) has a high prevalence of obstructive coronary artery disease and total coronary occlusion. Consequently, these patients are frequently loaded with antiplatelets and anticoagulants before hospital arrival. However, OHCA patients have multiple non-cardiac causes and high susceptibility for bleeding. In brief, there is a gap in the evidence for loading in OHCA patients. Objective: The current analysis stratified the outcome of patients with OHCA according to pre-clinical loading. Material and Methods: In a retrospective analysis of an all-comer OHCA registry, patients were stratified by loading with aspirin (ASA) and unfractionated heparin (UFH). Bleeding rate, survival to hospital discharge and favorable neurological outcomes were measured. Results: Overall, 272 patients were included, of whom 142 were loaded. Acute coronary syndrome was diagnosed in 103 patients. One-third of STEMIs were not loaded. Conversely, 54% with OHCA from non-ischemic causes were pretreated. Loading was associated with increased survival to hospital discharge (56.3 vs. 40.3%, p = 0.008) and a more favorable neurological outcome (80.7 vs. 62.6% p = 0.003). Prevalence of bleeding was comparable (26.8 vs. 31.5%, p = 0.740). Conclusions: Pre-clinical loading did not increase bleeding rates and was associated with favorable survival. Overtreatment of OHCA with non-ischemic origin, but also undertreatment of STEMI-OHCA were documented. Loading without definite diagnosis of sustained ischemia is debatable in the absence of reliable randomized controlled data.

Acute Chest Pain­Diagnostic Accuracy and Pre-Hospital Use of Anticoagulants and Platelet Aggregation Inhibitors

BACKGROUND: Acute chest pain (aCP) can be a symptom of life-threatening diseases such as acute coronary or aortic syndrome, but often has a non-cardiac cause. The recommendations regarding pre-hospital drug treatment of patients with aCP are ambiguous. METHODS: A retrospective cohort study was conducted of 822 patients with aCP who were attended by emergency physicians. The cause of aCP was classified as follows: acute coronary syndrome without ST-segment elevation (NSTE-ACS), acute aortic syndrome, hypertensive crisis, cardiac arrhythmias, musculoskeletal, or other. The suspected and discharge diagnoses were compared, and the pre-hospital administration of acetylsalicylic acid (ASA) and unfractionated heparin (UFH) was analyzed. Furthermore, the parameters that improved diagnostic accuracy were investigated. RESULTS: The positive predictive value of the diagnosis assigned by the emergency physician (EP diagnosis) was 39.7%. NSTEACS was the most commonly suspected cause of aCP (74.7%), but was confirmed after hospital admission in only 26.3% of patients. ASA was administered in 51%, UFH in 55%, and both substances in 46.4% of cases. A large proportion of patients received anticoagulants in the pre-hospital setting although the discharge diagnosis was not NSTE-ACS: ASA 62.9%, UFH 66.0%, both substances 56.5%. CONCLUSION: ASA and UFH are often given to EP-accompanied patients with aCP despite the low accuracy of diagnosis in the pre-hospital setting. Pre-hospital measurement of high-sensitivity troponin T (hs Trop-T) might improve discrimination between NSTE-ACS and other causes of aCP. This is important, as the current guidelines contain no clear recommendations for prehospital drug treatment in NSTE-ACS.

["Long lie trauma" patients: retrospective analysis of a patient cohort presenting to a university hospital emergency department]. / Liegetrauma: retrospektive Analyse einer Patientenkohorte aus einer universitären Notaufnahme.

BACKGROUND: Patients discovered recumbent, helpless and incapacitated, awake or unresponsive are referred to as "long lie trauma" (LLT) in the German medical jargon. Yet, a characterization of this cohort is missing. METHODS: We retrospectively analyzed all LLT patients admitted to the emergency department of the University Hospital Cologne from July 2018 to December 2020. RESULTS: A total of 50 LLT patients (median age 76 years, median time on the ground 13.5 h) were identified. The FD was most often attributed to primary cerebral causes in 40% of the cases (20% ischemic stroke, 16% intracranial hemorrhage, 4% epilepsy), intoxication/overdose (12%), and trauma (10%). It was often associated with infection (52%), injury (22%), hypovolemia (66%), acute kidney injury (20%), and severe rhabdomyolysis (creatine kinase ≥ 5000 U/l, 21%) as well as severe hypothermia < 32 °C (20%). Overall, 69% of the patients were admitted to an intensive care unit and in-hospital mortality was 50%. CONCLUSION: The term "long lie trauma" describes a complex clinical situation, in which various conditions lead to an incapacitated state with acute onset, which then causes further adverse health effects. Trauma or tissue damage were no obligatory requirement in this syndrome. Considering the high morbidity and in-hospital mortality, patients should initially be treated in the emergency room by an interdisciplinary team.

German Cardiac Arrest Registry: rationale and design of G-CAR.

BACKGROUND: In Germany, 70,000-100,000 persons per year suffer from out-of-hospital cardiac arrest (OHCA). Despite medical progress, survival rates with good neurological outcome remain low. For many important clinical issues, no or only insufficient evidence from randomised trials is available. Therefore, a systemic and standardised acquisition of the treatment course and of the outcome of OHCA patients is warranted. STUDY DESIGN: The German Cardiac Arrest Registry (G-CAR) is an observational, prospective, multicentre registry. It will determine the characteristics, initial treatment strategies, invasive procedures, revascularisation therapies and the use of mechanical circulatory support devices with a focus on extracorporeal cardiopulmonary resuscitation. A special feature is the prospective 12-month follow-up evaluating mortality, neurological outcomes and several patient-reported outcomes in the psychosocial domain (health-related quality of life, cognitive impairment, depression/anxiety, post-traumatic stress disorder and social reintegration). In a pilot phase of 24 months, 15 centres will include approximately 400 consecutive OHCA patients ≥ 18 years. Parallel to and after the pilot phase, scaling up of G-CAR to a national level is envisaged. CONCLUSION: G-CAR is the first national registry including a long-term follow-up for adult OHCA patients. Primary aim is a better understanding of the determinants of acute and long-term outcomes with the perspective of an optimised treatment. TRIAL REGISTRY: NCT05142124. German Cardiac Arrest Registry (G-CAR).

Coronary angiography after cardiac arrest without ST-elevation myocardial infarction: a network meta-analysis.

AIMS: This network meta-analysis aimed to assess the effect of early coronary angiography (CAG) compared with selective CAG (late and no CAG) for patients after out-of-hospital cardiac arrest without ST-elevation myocardial infarction (NSTE-OHCA). METHODS AND RESULTS: A systematic literature search was performed using the EMBASE, MEDLINE and Web of Science databases without restrictions on publication date. The last search was performed on 15 July 2022. Randomized controlled trials (RCTs) and non-randomized studies (NRS) comparing the effect of early CAG to selective CAG after NSTE-OHCA on survival and/or neurological outcomes were included. Meta-analyses were performed based on a DerSimonian-Laird random effects model. A total of 18 studies were identified by the literature search. After the exclusion of two studies due to high risk of bias, 16 studies (six RCTs, ten NRS) were included in the final analyses. Meta-analyses showed a statistically significant increase in survival after early CAG compared with selective CAG in the overall analysis [OR: 1.40, 95% confidence interval (CI): (1.12-1.76), P < 0.01, I2 = 68%]. This effect was lost in the subgroup analysis of RCTs [OR: 0.89, 95% CI: (0.73-1.10), P = 0.29, I2 = 0%]. Random effects model network meta-analysis of NRS based on a Bayesian method showed statistically significant increased survival after late compared with early CAG [OR: 4.20, 95% CI: (1.22, 20.91)]. CONCLUSION: The previously reported superiority of early CAG after NSTE-OHCA is based on NRS at high risk of selection and survivorship bias. The meta-analysis of RCTs does not support routinely performing early CAG after NSTE-OHCA.

Prevalence of left ventricular thrombus formation after mitral valve edge-to-edge repair.

The prevalence of left ventricular (LV) thrombus formation following percutaneous mitral valve edge-to-edge repair (TMVR) with the MitraClip system is unclear. Decreased total stroke volume and perfusion of the LV apex after mitral valve repair may facilitate thrombus formation especially in the context of reduced LV function. LV thrombus may cause disabling stroke or other thromboembolic events in this elderly and multimorbid patient cohort. Analyses of the prevalence of and risk factors for left ventricular thrombus formation in patients treated with the MitraClip system due to severe mitral valve regurgitation. All discharge and follow-up transthoracic echocardiographic examinations up to 6 months of 453 consecutive patients treated with the MitraClip system were screened for the presence of LV thrombus. Prevalence of LV thrombus formation was 1.1% (5/453). Importantly, LV thrombi were exclusively found in patients with severely depressed left ventricular systolic function (LV-EF < 30%), comprising a prevalence of 4.4% in this subgroup (5/113). Importantly, two of these patients were under active DOAC therapy with Rivaroxaban and Apixaban, respectively. Apart from LV-EF, we did not identify other factors that might have facilitated LV thrombus formation. LV thrombus formation following percutaneous mitral valve repair occurred exclusively in patients with severely depressed LV-EF. As two patients developed LV thrombus despite of DOAC therapy, anticoagulation with a Vitamin K antagonist should be considered in patients with an indication for oral anticoagulation following TMVR.

The Hypertension Paradox: Survival Benefit After ST-Elevation Myocardial Infarction in Patients With History of Hypertension. A Prospective Cohort- and Risk-Analysis.

Background: Mortality after ST-elevation myocardial infarction (STEMI) is dependent from best-medical treatment after initial event. Objectives: Determining the impact of prescription of guideline-recommended therapy after STEMI in two cohorts, patients with and without history of arterial hypertension, on survival. Methods: 1,025 patients of the Cologne Infarction Model registry with invasively adjudicated STEMI were dichotomized according to their history of arterial hypertension. We recorded prescription rates and dosing of RAS-inhibitors, ß-blockers and statins in all patients. The primary outcome was all-cause death. Mean follow-up was 2.5 years. Results: Mean age was 64 ± 13 years, 246 (25%) were women. 749 (76%) patients had a history of hypertension. All-cause mortality was 24.2%, 30-day and 1-year mortality was 11.3% and 16.6%, respectively. History of hypertension correlated with lower mortality (hazard ratio [HR], @30 days: 0.41 [0.27-0.62], @1 year: 0.37 [0.26-0.53]). After adjusting for age, sex, Killip-class, diabetes mellitus, body-mass index, kidney function and statin prescription at discharge 1-year mortality HR was 0.24 (0.12-0.48). At discharge, prescription rates for RAS-inhibitors, ß-blockers and statins, as well as individual dosing and long-term persistence of RAS-inhibitors were higher in patients with history of hypertension. On the same lines, prescription rates for RAS-inhibitors, ß-blockers and statins at discharge correlated significantly with lower mortality regardless of history of hypertension. Conclusion: Patients with history of hypertension show higher penetration of guideline recommended drug therapy after STEMI, which may contribute to better survival. Better tolerance of ß-blockers and RAS-inhibitors in patients with history of hypertension, not hypertension itself, likely explains these differences in prescription and dosing.

Proteomics-Based Serum Alterations of the Human Protein Expression after Out-of-Hospital Cardiac Arrest: Pilot Study for Prognostication of Survivors vs. Non-Survivors at Day 1 after Return of Spontaneous Circulation (ROSC).

BACKGROUND: Targeted temperature management (TTM) is considered standard therapy for patients after out-of-hospital cardiac arrest (OHCA), cardiopulmonary resuscitation (CPR), and return of spontaneous circulation (ROSC). To date, valid protein markers do not exist to prognosticate survivors and non-survivors before the end of TTM. The aim of this study is to identify specific protein patterns/arrays, which are useful for prediction in the very early phase after ROSC. MATERIAL AND METHODS: A total of 20 adult patients with ROSC (19 male, 1 female; 69.9 ± 9.5 years) were included and dichotomized in two groups (survivors and non-survivors at day 30). Serum samples were drawn at day 1 after ROSC (during TTM). Three panels (organ failure, metabolic, neurology, inflammation; OLINK, Uppsala, Sweden) were utilised. A total of four proteins were found to be differentially regulated (>2- or <-0.5-fold decrease; t-test). Bioinformatic platforms were utilised to analyse pathways and identify signalling cascades and to screen for potential biomarkers. RESULTS: A total of 276 proteins were analysed and revealed only 11 statistically significant protein alterations (Siglec-9, LAYN, SKR3, JAM-B, N2DL-2, TNF-B, BAMBI, NUCB2, STX8, PTK7, and PVLAB). Following the Bonferroni correction, no proteins were found to be regulated as statistically significant. Concerning the protein fold change for clinical significance, four proteins (IL-1 alpha, N-CDase, IL5, CRH) were found to be regulated in a clinically relevant context. CONCLUSIONS: Early analysis at 1 day after ROSC was not sufficiently possible during TTM to prognosticate survival or non-survival after OHCA. Future studies should evaluate protein expression later in the course after ROSC to identify promising protein candidates.

Extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: first results and outcomes of a newly established ECPR program in a large population area.

OBJECTIVES: Out-of-hospital cardiac arrest (OHCA) is associated with excessively high mortality rates. Recent studies suggest benefits from extracorporeal cardiopulmonary resuscitation (ECPR) performed in selected patients. We sought to present the first results from our interdisciplinary ECPR program with a particular focus on early outcomes and potential risk factors associated with in-hospital mortality. METHODS: Between January 2016 and December 2019, 44 patients who underwent ECPR selected according to our institutional ECPR protocol were retrospectively analyzed regarding pre-hospital, in-hospital, and early outcome parameters. Patients were divided into survivors (S) and non-survivors (NS). Statistical analysis of risk factors regarding in-hospital mortality of the patient cohort analyzed was performed. RESULTS: The mean age of the population was 53 ± 12 years, with most patients being male (n = 40). The leading cause of cardiac arrest (CA) was myocardial infarction (n = 24, 55%). The median hospital stay was 1 (1;13) day. Twenty-three percent of patients (n = 10) were discharged from hospital including eight patients (18%) with CPC 1-2. Survivors showed a trend toward shorter pre-hospital CPR duration (60 (59;60) min (S) vs 60 (55;90) min (NS), p = 0.07). CONCLUSION: Establishing ECPR programs in large population areas offers the option to improve survival rates for OHCA patients. Stringent compliance of institutional criteria (mainly age, witnessed arrest, and time of pre-hospital resuscitation) and providing ECPR to strictly selected patients seems to be a vital factor for such programs' success. Pre-clinical settings and therapeutic measures must be adjusted in this regard to improve outcomes for this highly demanding patient cohort.

Absolute serum neurofilament light chain levels and its early kinetics predict brain injury after out-of-hospital cardiac arrest.

OBJECTIVES: To test if the early kinetics of neurofilament light (NFL) in blood adds to the absolute values of NFL in the prediction of outcome, and to evaluate if NFL can discriminate individuals with severe hypoxic-ischemic brain injury (sHIBI) from those with other causes of poor outcome after out-of-hospital cardiac arrest (OHCA). DESIGN AND SETTING: Monocentric retrospective study involving individuals following non-traumatic OHCA between April 2014 and April 2016. NFL concentrations were determined on a SiMoA HD-1 device using NF-Light Advantage Kits. PARTICIPANTS: Of 73 patients screened, 53 had serum samples available for NFL measurement at three timepoints (after 3, 24, and 48 h of admission). Of these 53 individuals, 43.4% had poor neurologic outcome at discharge as assessed by Glasgow-Pittsburgh cerebral performance categories, and, according to a current prognostication algorithm, poor outcome due to sHIBI in 20.7%. MAIN OUTCOME MEASURE: Blood NFL and its early kinetics for prognostication of outcome and prediction of sHIBI after OHCA. RESULTS: An absolute NFL > 508.6 pg/ml 48 h after admission, or a change in NFL > 494 pg/ml compared with an early baseline value predicted outcome, and discriminated severe sHIBI from other causes of unfavorable outcome after OHCA with high sensitivity (100%, 95%CI 70.0-100%) and specificity (91.7%, 95%CI 62.5-100%). CONCLUSIONS: Not only absolute values of NFL, but also early changes in NFL predict the outcome following OHCA, and may differentiate sHIBI from other causes of poor outcome after OHCA with high sensitivity and specificity. Our study adds to published data, overall corroborating that NFL measured in blood should be implemented in prognostication algorithms used in clinical routine.