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.

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.

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.

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.

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.

The interaction of thrombocytopenia, hemorrhage, and platelet transfusion in venoarterial extracorporeal membrane oxygenation: a multicenter observational study.

BACKGROUND: Thrombocytopenia, hemorrhage and platelet transfusion are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). However, current literature is limited to small single-center experiences with high degrees of heterogeneity. Therefore, we aimed to ascertain in a multicenter study the course and occurrence rate of thrombocytopenia, and to assess the association between thrombocytopenia, hemorrhage and platelet transfusion during VA ECMO. METHODS: This was a sub-study of a multicenter (N = 16) study on transfusion practices in patients on VA ECMO, in which a retrospective cohort (Jan-2018-Jul-2019) focusing on platelets was selected. The primary outcome was thrombocytopenia during VA ECMO, defined as mild (100-150·109/L), moderate (50-100·109/L) and severe (< 50·109/L). Secondary outcomes included the occurrence rate of platelet transfusion, and the association between thrombocytopenia, hemorrhage and platelet transfusion, assessed through mixed-effect models. RESULTS: Of the 419 patients included, median platelet count at admission was 179·109/L. During VA ECMO, almost all (N = 398, 95%) patients developed a thrombocytopenia, of which a significant part severe (N = 179, 45%). One or more platelet transfusions were administered in 226 patients (54%), whereas 207 patients (49%) suffered a hemorrhagic event during VA ECMO. In non-bleeding patients, still one in three patients received a platelet transfusion. The strongest association to receive a platelet transfusion was found in the presence of severe thrombocytopenia (adjusted OR 31.8, 95% CI 17.9-56.5). After including an interaction term of hemorrhage and thrombocytopenia, this even increased up to an OR of 110 (95% CI 34-360). CONCLUSIONS: Thrombocytopenia has a higher occurrence than is currently recognized. Severe thrombocytopenia is strongly associated with platelet transfusion. Future studies should focus on the etiology of severe thrombocytopenia during ECMO, as well as identifying indications and platelet thresholds for transfusion in the absence of bleeding. TRIAL REGISTRATION: This study was registered at the Netherlands Trial Registry at February 26th, 2020 with number NL8413 and can currently be found at https://trialsearch.who.int/Trial2.aspx?TrialID=NL8413.

Patient-centered weaning from venoarterial extracorporeal membrane oxygenation: "A practice-oriented narrative review of literature".

Venoarterial extracorporeal membrane oxygenation (V-A ECMO) is increasingly used in cardiogenic shock for rapid stabilization and bridging towards recovery, long-term mechanical circulatory support or transplant. Although technological advances have instigated its widespread use, the complex, long-lasting ECMO care creates a significant strain on hospital staff and resources. Therefore, optimal clinical management including timely decisions on ECMO removal and further therapy are pivotal, yet require a well-structured weaning approach. Although dedicated guidelines are lacking, a variety of weaning protocols have distillated echocardiographic and hemodynamic predictors for successful weaning. Nevertheless, a strikingly high mortality up to 70% after initial successful weaning raises concerns about the validity of current weaning strategies. Here, we plead for a patient-tailored approach including a bailout strategy when weaning fails. This should account not only for left- but also right ventricular function and interdependence, as well as the temporal course of cardiac recovery in function of extracorporeal support. Patients with a high risk of weaning failure should be identified early, enabling timely transportation to an advanced heart failure center. This review summarizes predictors of successful weaning and discusses all relevant elements for a structured weaning approach with a central role for patient-specific clinical considerations and echocardiography.

Clinical decision support for ExtraCorporeal Membrane Oxygenation: Will we fly by wire?

Prognostic modelling techniques have rapidly evolved over the past decade and may greatly benefit patients supported with ExtraCorporeal Membrane Oxygenation (ECMO). Epidemiological and computational physiological approaches aim to provide more accurate predictive assessments of ECMO-related risks and benefits. Implementation of these approaches may produce predictive tools that can improve complex clinical decisions surrounding ECMO allocation and management. This Review describes current applications of prognostic models and elaborates on upcoming directions for their clinical applicability in decision support tools directed at improved allocation and management of ECMO patients. The discussion of these new developments in the field will culminate in a futuristic perspective leaving ourselves and the readers wondering whether we may "fly ECMO by wire" someday.

RBC Transfusion in Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study.

OBJECTIVES: In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation. DESIGN: Mixed method approach combining multicenter retrospective study and survey. SETTING: Sixteen ICUs worldwide. PATIENTS: Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45-62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5-14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8 g/dL (8.9-13.0 g/dL), decreasing to 8.7 g/dL (7.7-9.8 g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1 g/dL [7.4-9.3 g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3-2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9 g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients. CONCLUSIONS: Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation.

The ABCDE approach to difficult weaning from venoarterial extracorporeal membrane oxygenation.

Venoarterial extracorporeal membrane oxygenation (VA ECMO) has been increasingly applied in patients with cardiogenic shock in recent years. Nevertheless, many patients cannot be successfully weaned from VA ECMO support and 1-year mortality remains high. A systematic approach could help to optimize clinical management in favor of weaning by identifying important factors in individual patients. Here, we provide an overview of pivotal factors that potentially prevent successful weaning of VA ECMO. We present this through a rigorous approach following the relatable acronym ABCDE, in order to facilitate widespread use in daily practice.

Low thyroid function is not associated with an accelerated deterioration in renal function.

BACKGROUND: Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups. METHODS: Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models. RESULTS: A total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) -4.07 (-6.37 to -1.78) and -2.40 (-3.78 to -1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50-4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function. CONCLUSIONS: Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.

Echocardiography in extracorporeal life support: A key player in procedural guidance, tailoring and monitoring.

Extracorporeal life support (ECLS) is a mainstay of current practice in severe respiratory, circulatory or cardiac failure refractory to conventional management. The inherent complexity of different ECLS modes and their influence on the native pulmonary and cardiovascular system require patient-specific tailoring to optimize outcome. Echocardiography plays a key role throughout the ECLS care, including patient selection, adequate placement of cannulas, monitoring, weaning and follow-up after decannulation. For this purpose, echocardiographers require specific ECLS-related knowledge and skills, which are outlined here.

Transient left ventricular outflow tract obstruction with systolic anterior motion of the mitral valve: A stunning cause.

Left ventricular outflow tract obstruction (LVOTO) and systolic anterior motion (SAM) of the mitral valve may have various etiologies, of which hypertrophic cardiomyopathy is the most common. More rarely, an acute coronary syndrome, myocardial stunning, and takotsubo cardiomyopathy may give rise to LVOTO and SAM. Here, we present a 70-year-old female patient with a non-ST-elevation acute coronary syndrome treated with percutaneous coronary intervention. Echocardiography the day after, because of dyspnea and hypotension, revealed apical akinesia, LVOTO, and SAM, which proved completely reversible after treatment with a ß-blocker and a 2-month follow-up period. It was concluded that postischemic apical stunning had caused LVOTO and SAM.

Looking Back, Going Forward: Understanding Cardiac Pathophysiology from Pressure-Volume Loops.

Knowing cardiac physiology is essential for health care professionals working in the cardiovascular field. Pressure-volume loops (PVLs) offer a unique understanding of the myocardial working and have become pivotal in complex pathophysiological scenarios, such as profound cardiogenic shock or when mechanical circulatory supports are implemented. This review provides a comprehensive summary of the left and right ventricle physiology, based on the PVL interpretation.