Morphological Prediction of CPAP Associated Acute Respiratory Instability.

RATIONALE: Multiple mechanisms are involved in the pathogenesis of obstructive sleep apnea (OSA). Elevated loop gain is a key target for precision OSA care and may be associated with treatment intolerance when the upper airway is the sole therapeutic target. Morphological or computational estimation of LG is not yet widely available or fully validated - there is a need for improved phenotyping/endotyping of apnea to advance its therapy and prognosis. OBJECTIVES: This study proposes a new algorithm to assess self-similarity as a signature of elevated loop gain using respiratory effort signals and presents its use to predict the probability of acute failure (high residual event counts) of continuous positive airway pressure (CPAP) therapy. METHODS: Effort signals from 2145 split-night polysomnography studies from the Massachusetts General Hospital were analyzed for SS and used to predict acute CPAP therapy effectiveness. Logistic regression models were trained and evaluated using 5-fold cross-validation. RESULTS: Receiver operating characteristic (ROC) and precision-recall (PR) curves with AUC values of 0.82 and 0.84, respectively, were obtained. Self-similarity combined with the central apnea index (CAI) and hypoxic burden outperformed CAI alone. Even in those with a low CAI by conventional scoring criteria or only mild desaturation, SS was related to poor therapy outcomes. CONCLUSIONS: The proposed algorithm for assessing SS as a measure of expressed high loop gain is accurate, non-invasive, and has the potential to improve phenotyping/endotyping of apnea, leading to more precise sleep apnea treatment strategies.

Physiological control for left ventricular assist devices based on deep reinforcement learning.

BACKGROUND: The improvement of controllers of left ventricular assist device (LVAD) technology supporting heart failure (HF) patients has enormous impact, given the high prevalence and mortality of HF in the population. The use of reinforcement learning for control applications in LVAD remains minimally explored. This work introduces a preload-based deep reinforcement learning control for LVAD based on the proximal policy optimization algorithm. METHODS: The deep reinforcement learning control is built upon data derived from a deterministic high-fidelity cardiorespiratory simulator exposed to variations of total blood volume, heart rate, systemic vascular resistance, pulmonary vascular resistance, right ventricular end-systolic elastance, and left ventricular end-systolic elastance, to replicate realistic inter- and intra-patient variability of patients with a severe HF supported by LVAD. The deep reinforcement learning control obtained in this work is trained to avoid ventricular suction and allow aortic valve opening by using left ventricular pressure signals: end-diastolic pressure, maximum pressure in the left ventricle (LV), and maximum pressure in the aorta. RESULTS: The results show controller obtained in this work, compared to the constant speed LVAD alternative, assures a more stable end-diastolic volume (EDV), with a standard deviation of 5 mL and 9 mL, respectively, and a higher degree of aortic flow, with an average flow of 1.1 L/min and 0.9 L/min, respectively. CONCLUSION: This work implements a deep reinforcement learning controller in a high-fidelity cardiorespiratory simulator, resulting in increases of flow through the aortic valve and increases of EDV stability, when compared to a constant speed LVAD strategy.

Imaging in acute percutaneous mechanical circulatory support in adults. A clinical consensus statement of the Association for Acute CardioVascular Care (ACVC) of the ESC, the European Association of Cardiovascular Imaging (EACVI) of the ESC and the European branch of the Extracorporeal Life Support Organization (EuroELSO).

The use of temporary mechanical circulatory support (tMCS) in cardiogenic shock patients has increased during the last decades with most management strategies relying on observational studies and expert opinion, including hemodynamic monitoring, device selection and timing of support institution/duration. In this context, imaging has a pivotal role throughout the patient pathway, from identification to initiation, monitoring and weaning. This manuscript summarizes the consensus of an expert panel from the European Society of Cardiology Association for Acute CardioVascular Care, the European Association of CardioVascular Imaging and the European Extracorporeal Life Support Organization, providing the rationale for and practical guidance of imaging to tMCS based on existing evidence and consensus on best current practice.

Understanding the complexity of cardiogenic shock management: the added value of advanced computational modeling.

PURPOSE OF REVIEW: The purpose of this review is to explain the value of computational physiological modeling for in-depth understanding of the complex derangements of cardiopulmonary pathophysiology during cardiogenic shock, particularly when treated with temporary mechanical circulatory support (tMCS) devices. RECENT FINDINGS: Computational physiological models have evolved in recent years and can provide a high degree of clinical realism in the simulation of cardiogenic shock and related conservative and interventional therapies. These models feature a large spectrum of practically relevant hemodynamic and respiratory parameters tunable to patient-specific disease states as well as adjustable to medical therapies and support device settings. Current applications work in real-time and can operate on an ordinary computer, laptop or mobile device. SUMMARY: The use of computational physiological models is increasingly appreciated for educational purposes as they help to understand the complexity of cardiogenic shock, especially when sophisticated management of tMCS is involved in addition to multimodal critical care support. Practical implementation of computational models as clinical decision support tools at the bedside is at the horizon but awaits rigorous clinical validation.

ECPELLA as a bridge-to-decision in refractory cardiogenic shock: a single-centre experience.

BACKGROUND: In refractory cardiogenic shock, temporary mechanical support (tMCS) may be crucial for maintaining tissue perfusion and oxygen delivery. tMCS can serve as a bridge-to-decision to assess eligibility for left ventricular assist device (LVAD) implantation or heart transplantation, or as a bridge-to-recovery. ECPELLA is a novel tMCS configuration combining venoarterial extracorporeal membrane oxygenation with Impella. The present study presents the clinical parameters, outcomes, and complications of patients supported with ECPELLA. METHODS: All patients supported with ECPELLA at University Medical Centre Utrecht between December 2020 and August 2023 were included. The primary outcome was 30-day mortality, and secondary outcomes were LVAD implantation/heart transplantation and safety outcomes. RESULTS: Twenty patients with an average age of 51 years, and of whom 70% were males, were included. Causes of cardiogenic shock were acute heart failure (due to acute coronary syndrome, myocarditis, or after cardiac surgery) or chronic heart failure, respectively 70 and 30% of cases. The median duration of ECPELLA support was 164 h (interquartile range 98-210). In 50% of cases, a permanent LVAD was implanted. Cardiac recovery within 30 days was seen in 30% of cases and 30-day mortality rate was 20%. ECPELLA support was associated with major bleeding (40%), haemolysis (25%), vascular complications (30%), kidney failure requiring replacement therapy (50%), and Impella failure requiring extraction (15%). CONCLUSION: ECPELLA can be successfully used as a bridge to LVAD implantation or as a bridge-to-recovery in patients with refractory cardiogenic shock. Despite a significant number of complications, 30-day mortality was lower than observed in previous cohorts.

A patient-specific echogenic soft robotic left ventricle embedded into a closed-loop cardiovascular simulator for advanced device testing.

Cardiovascular medical devices undergo a large number of pre- and post-market tests before their approval for clinical practice use. Sophisticated cardiovascular simulators can significantly expedite the evaluation process by providing a safe and controlled environment and representing clinically relevant case scenarios. The complex nature of the cardiovascular system affected by severe pathologies and the inherently intricate patient-device interaction creates a need for high-fidelity test benches able to reproduce intra- and inter-patient variability of disease states. Therefore, we propose an innovative cardiovascular simulator that combines in silico and in vitro modeling techniques with a soft robotic left ventricle. The simulator leverages patient-specific and echogenic soft robotic phantoms used to recreate the intracardiac pressure and volume waveforms, combined with an in silico lumped parameter model of the remaining cardiovascular system. Three different patient-specific profiles were recreated, to assess the capability of the simulator to represent a variety of working conditions and mechanical properties of the left ventricle. The simulator is shown to provide a realistic physiological and anatomical representation thanks to the use of soft robotics combined with in silico modeling. This tool proves valuable for optimizing and validating medical devices and delineating specific indications and boundary conditions.

Head-to-toe bedside ultrasound for adult patients on extracorporeal membrane oxygenation.

Bedside ultrasound represents a well-suited diagnostic and monitoring tool for patients on extracorporeal membrane oxygenation (ECMO) who may be too unstable for transport to other hospital areas for diagnostic tests. The role of ultrasound, however, starts even before ECMO initiation. Every patient considered for ECMO should have a thorough ultrasonographic assessment of cardiac and valvular function, as well as vascular anatomy without delaying ECMO cannulation. The role of pre-ECMO ultrasound is to confirm the indication for ECMO, identify clinical situations for which ECMO is not indicated, rule out contraindications, and inform the choice of ECMO configuration. During ECMO cannulation, the use of vascular and cardiac ultrasound reduces the risk of complications and ensures adequate cannula positioning. Ultrasound remains key for monitoring during ECMO support and troubleshooting ECMO complications. For instance, ultrasound is helpful in the assessment of drainage insufficiency, hemodynamic instability, biventricular function, persistent hypoxemia, and recirculation on venovenous (VV) ECMO. Lung ultrasound can be used to monitor signs of recovery on VV ECMO. Brain ultrasound provides valuable diagnostic and prognostic information on ECMO. Echocardiography is essential in the assessment of readiness for liberation from venoarterial (VA) ECMO. Lastly, post decannulation ultrasound mainly aims at identifying post decannulation thrombosis and vascular complications. This review will cover the role of head-to-toe ultrasound for the management of adult ECMO patients from decision to initiate ECMO to the post decannulation phase.

Hypotension Prediction Index Is Equally Effective in Predicting Intraoperative Hypotension during Noncardiac Surgery Compared to a Mean Arterial Pressure Threshold: A Prospective Observational Study.

BACKGROUND: The Hypotension Prediction Index is designed to predict intraoperative hypotension in a timely manner and is based on arterial waveform analysis using machine learning. It has recently been suggested that this algorithm is highly correlated with the mean arterial pressure itself. Therefore, the aim of this study was to compare the index with mean arterial pressure-based prediction methods, and it is hypothesized that their ability to predict hypotension is comparable. METHODS: In this observational study, the Hypotension Prediction Index was used in addition to routine intraoperative monitoring during moderate- to high-risk elective noncardiac surgery. The agreement in time between the default Hypotension Prediction Index alarm (greater than 85) and different concurrent mean arterial pressure thresholds was evaluated. Additionally, the predictive performance of the index and different mean arterial pressure-based methods were assessed within 5, 10, and 15 min before hypotension occurred. RESULTS: A total of 100 patients were included. A mean arterial pressure threshold of 73 mmHg agreed 97% of the time with the default index alarm, whereas a mean arterial pressure threshold of 72 mmHg had the most comparable predictive performance. The areas under the receiver operating characteristic curve of the Hypotension Prediction Index (0.89 [0.88 to 0.89]) and concurrent mean arterial pressure (0.88 [0.88 to 0.89]) were almost identical for predicting hypotension within 5 min, outperforming both linearly extrapolated mean arterial pressure (0.85 [0.84 to 0.85]) and delta mean arterial pressure (0.66 [0.65 to 0.67]). The positive predictive value was 31.9 (31.3 to 32.6)% for the default index alarm and 32.9 (32.2 to 33.6)% for a mean arterial pressure threshold of 72 mmHg. CONCLUSIONS: In clinical practice, the Hypotension Prediction Index alarms are highly similar to those derived from mean arterial pressure, which implies that the machine learning algorithm could be substituted by an alarm based on a mean arterial pressure threshold set at 72 or 73 mmHg. Further research on intraoperative hypotension prediction should therefore include comparison with mean arterial pressure-based alarms and related effects on patient outcome.

The physiology of venoarterial extracorporeal membrane oxygenation - A comprehensive clinical perspective.

Venoarterial extracorporeal membrane oxygenation (VA ECMO) has become a standard of care for severe cardiogenic shock, refractory cardiac arrest and related impending multiorgan failure. The widespread clinical use of this complex temporary circulatory support modality is still contrasted by a lack of formal scientific evidence in the current literature. This might at least in part be attributable to VA ECMO related complications, which may significantly impact on clinical outcome. In order to limit adverse effects of VA ECMO as much as possible an indepth understanding of the complex physiology during extracorporeally supported cardiogenic shock states is critically important. This review covers all relevant physiological aspects of VA ECMO interacting with the human body in detail. This, to provide a solid basis for health care professionals involved in the daily management of patients supported with VA ECMO and suffering from cardiogenic shock or cardiac arrest and impending multiorgan failure for the best possible care.

Left ventricular unloading in patients supported with veno-arterial extra corporeal membrane oxygenation; an international EuroELSO survey.

INTRODUCTION: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) improves end-organ perfusion in cardiogenic shock but may increase afterload, which can limit cardiac recovery. Left ventricular (LV) unloading strategies may aid cardiac recovery and prevent complications of increased afterload. However, there is no consensus on when and which unloading strategy should be used. METHODS: An online survey was distributed worldwide via the EuroELSO newsletter mailing list to describe contemporary international practice and evaluate heterogeneity in strategies for LV unloading. RESULTS: Of 192 respondents from 43 countries, 53% routinely use mechanical LV unloading, to promote ventricular recovery and/or to prevent complications. Of those that do not routinely unload, 65% cited risk of complications as the reason. The most common indications for unplanned unloading were reduced arterial line pulsatility (68%), pulmonary edema (64%) and LV dilatation (50%). An intra-aortic balloon pump was the most frequently used device for unloading followed by percutaneous left ventricular assist devices. Echocardiography was the most frequently used method to monitor the response to unloading. CONCLUSIONS: Significant variation exists with respect to international practice of ventricular unloading. Further research is required that compares the efficacy of different unloading strategies and a randomized comparison of routine mechanical unloading versus unplanned unloading.

Extracorporeal cardiopulmonary resuscitation for refractory cardiac arrest: an overview of current practice and evidence.

Cardiac arrest (CA) is a common and potentially avoidable cause of death, while constituting a substantial public health burden. Although survival rates for out-of-hospital cardiac arrest (OHCA) have improved in recent decades, the prognosis for refractory OHCA remains poor. The use of veno-arterial extracorporeal membrane oxygenation during cardiopulmonary resuscitation (ECPR) is increasingly being considered to support rescue measures when conventional cardiopulmonary resuscitation (CPR) fails. ECPR enables immediate haemodynamic and respiratory stabilisation of patients with CA who are refractory to conventional CPR and thereby reduces the low-flow time, promoting favourable neurological outcomes. In the case of refractory OHCA, multiple studies have shown beneficial effects in specific patient categories. However, ECPR might be more effective if it is implemented in the pre-hospital setting to reduce the low-flow time, thereby limiting permanent brain damage. The ongoing ON-SCENE trial might provide a definitive answer regarding the effectiveness of ECPR. The aim of this narrative review is to present the most recent literature available on ECPR and its current developments.

Fulminant myocarditis proven by early biopsy and outcomes.

BACKGROUND AND AIMS: While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear. METHODS: Data were collected from 419 adult patients with clinically suspected fulminant myocarditis admitted to intensive care units across 36 tertiary centres in 15 countries worldwide. The diagnosis of myocarditis was histologically proven in 210 (50%) patients, either by EMB (n = 183, 44%) or by autopsy/explanted heart examination (n = 27, 6%), and clinically suspected cardiac magnetic resonance imaging confirmed in 96 (23%) patients. The primary outcome of survival free of heart transplantation (HTx) or left ventricular assist device (LVAD) at 1 year was specifically compared between patients with early EMB (within 2 days after intensive care unit admission, n = 103) and delayed EMB (n = 80). A propensity score-weighted analysis was done to control for confounders. RESULTS: Median age on admission was 40 (29-52) years, and 322 (77%) patients received temporary mechanical circulatory support. A total of 273 (65%) patients survived without HTx/LVAD. The primary outcome was significantly different between patients with early and delayed EMB (70% vs. 49%, P = .004). After propensity score weighting, the early EMB group still significantly differed from the delayed EMB group in terms of survival free of HTx/LVAD (63% vs. 40%, P = .021). Moreover, early EMB was independently associated with a lower rate of death or HTx/LVAD at 1 year (odds ratio of 0.44; 95% confidence interval: 0.22-0.86; P = .016). CONCLUSIONS: Endomyocardial biopsy should be broadly and promptly used in patients admitted to the intensive care unit for clinically suspected fulminant myocarditis.

Expert consensus on training and accreditation for extracorporeal cardiopulmonary resuscitation an international, multidisciplinary modified Delphi Study.

BACKGROUND: A multidisciplinary group of stakeholders were used to identify: (1) the core competencies of a training program required to perform in-hospital ECPR initiation (2) additional competencies required to perform pre-hospital ECPR initiation and; (3) the optimal training method and maintenance protocol for delivering an ECPR program. METHODS: A modified Delphi process was undertaken utilising two web based survey rounds and one virtual meeting. Experts rated the importance of different aspects of ECPR training, competency and governance on a 9-point Likert scale. A diverse, representative group was targeted. Consensus was achieved when greater than 70% respondents rated a domain as critical (> or = 7 on the 9 point Likert scale). RESULTS: 35 international ECPR experts from 9 countries formed the expert panel, with a median number of 14 years of ECMO practice (interquartile range 11-38). Participant response rates were 97% (survey round one), 63% (virtual meeting) and 100% (survey round two). After the second round of the survey, 47 consensus statements were formed outlining a core set of competencies required for ECPR provision. We identified key elements required to safely train and perform ECPR including skill pre-requisites, surrogate skill identification, the importance of competency-based assessment over volume of practice and competency requirements for successful ECPR practice and skill maintenance. CONCLUSIONS: We present a series of core competencies, training requirements and ongoing governance protocols to guide safe ECPR implementation. These findings can be used to develop training syllabus and guide minimum standards for competency as the growth of ECPR practitioners continues.

Transfusion of red blood cells in venoarterial extracorporeal membrane oxygenation: A multicenter retrospective observational cohort study.

BACKGROUND: Evidence-based recommendations for transfusion in patients with venoarterial extracorporeal membrane oxygenation (VA ECMO) are scarce. The current literature is limited to single-center studies with small sample sizes, therefore complicating generalizability. This study aims to create an overview of red blood cell (RBC) transfusion in VA ECMO patients. METHODS: This international mixed-method study combined a survey with a retrospective observational study in 16 centers. The survey inventoried local transfusion guidelines. Additionally, retrospective data of all adult patients with a VA ECMO run >24 h (January 2018 until July 2019) was collected of patient, ECMO, outcome, and daily transfusion parameters. All patients that received VA ECMO for primary cardiac support were included, including surgical (i.e., post-cardiotomy) and non-surgical (i.e., myocardial infarction) indications. The primary outcome was the number of RBC transfusions per day and in total. Univariable logistic regressions and a generalized linear mixed model (GLMM) were performed to assess factors associated with RBC transfusion. RESULTS: Out of 419 patients, 374 (89%) received one or more RBC transfusions. During a median ECMO run of 5 days (1st-3rd quartile 3-8), patients received a median total of eight RBC units (1st-3rd quartile 3-17). A lower hemoglobin (Hb) prior to ECMO, longer ECMO-run duration, and hemorrhage were associated with RBC transfusion. After correcting for duration and hemorrhage using a GLMM, a different transfusion trend was found among the regimens. No unadjusted differences were found in overall survival between either transfusion status or the different regimens, which remained after adjustment for potential confounders. CONCLUSION: RBC transfusion in patients on VA ECMO is very common. The sum of RBC transfusions increases rapidly after ECMO initiation, and is dependent on the Hb threshold applied. This study supports the rationale for prospective studies focusing on indications and thresholds for RBC transfusion.

Interrater agreement in classifying infections during extracorporeal membrane oxygenation.

Infectious complications are common during extracorporeal membrane oxygenation (ECMO) and may negatively impact outcomes. However, there is considerable variation in the reported rates of incidence, which hampers the use of infections as a quality benchmark for ECMO centers. To assess the contributing role of poor interrater agreement, three independent raters reviewed medical records from all intensive care unit (ICU) patients who received ECMO for >24 h in our tertiary center between October 2019 and October 2021 for suspected episodes of infection, which were rated based on their date of onset and presumed site/diagnosis. To establish a gold standard, any discrepancies were resolved using an expert panel consisting of two intensivists/infectious disease specialists. During 83 ECMO-runs in 77 patients, we observed a total of 62 adjudicated infectious episodes (incidence rate 62, 95% CI: 48-80, per 1000 days at risk). Among 81 episodes suspected by at least one observer, 66 (81%) were identified by two, and only 44 (54%) by all three raters, resulting in Fleiss' kappa of 0.10 (95% CI: 0.00-0.19; slight agreement). However, if raters concurred regarding infection onset, subsequent agreement on infection site was good (concordance 89%; kappa 0.85, 95% CI: 0.72-0.98; near perfect agreement). In conclusion, adjudication of infectious episodes during ECMO is associated with poor interrater agreement regarding occurrence-but not site-of infection. This finding might partially explain the significant disparities observed in reported infection rates during ECMO, emphasizing the need for caution when interpreting infection data in this particular population due to the potential for inherent measurement error.