Differential Effects of Pharmacologic and Mechanical Support on Right-Left Ventricular Coupling.

BACKGROUND: Percutaneous ventricular assist devices are increasingly relied on to maintain perfusion for cardiogenic shock patients. Optimal medical management strategies however remain uncertain from limited understanding of interventricular effects. This study analyzed the effects of pharmacologic and left-sided mechanical support on right ventricular function. METHODS: A porcine model was developed to assess biventricular function during bolus pharmacologic administration before and after left-sided percutaneous ventricular assist and in cardiogenic shock. RESULTS: The presence of mechanical support increased right ventricular load and stress with respect to the left ventricle. This shifted and exaggerated the relative effects of commonly used vasoactive agents. Furthermore, induction of cardiogenic shock led to differential pulmonary vascular and right ventricular responses. CONCLUSIONS: Left ventricular ischemia and mechanical support altered interventricular coupling. Resulting impacts of pharmacologic agents indicate differential right heart responses and sensitivity to treatments and the need for further study to optimize biventricular function in shock patients.

Impact of Extracorporeal Membrane Oxygenation Bridging Duration on Lung Transplant Outcomes.

BACKGROUND: We sought to characterize the association between venovenous extracorporeal membrane oxygenation (VV-ECMO) bridging duration and outcomes in patients listed for lung transplantation. METHODS: A retrospective observational study was conducted using the Organ Procurement and Transplantation Network (OPTN) database to identify adults (≥18 years old) who were listed for lung transplantation between 2016-2020 and who were bridged with VV-ECMO. Patients were then stratified into groups, determined by risk inflection points, depending on the amount of time spent on pre-transplant ECMO: Group 1 (≤5 days), Group 2 (6-10 days), Group 3 (11-20 days), and Group 4 (>20 days). Waitlist survival between groups was analyzed using Fine-Gray competing risk models. Post-transplant survival was compared using Cox regression. RESULTS: Of 566 eligible VV-ECMO bridge-to-lung-transplant patients (median age=54, 49% male), 174 (31%), 124 (22%), 130 (23%), and 138 (24%) were categorized as Groups 1, 2, 3, and 4, respectively. Overall, median duration of VV-ECMO was 10 days (range=1-211) and 178 patients (31%) died on the waitlist. In the Fine-Gray model, compared to Group 1, patients bridged with longer ECMO durations in Groups 2 (SHR=2.95, 95%CI: 1.63-5.35), 3 (SHR=3.96, 95%CI: 2.36-6.63), and 4 (SHR=4.33, 95%CI: 2.59-7.22, all p<0.001), were more likely to die on the waitlist. Of 388 patients receiving a transplant, pre-transplant ECMO duration was not associated with one-year survival in Cox regression. CONCLUSIONS: Prolonged ECMO bridging duration was associated with worse waitlist mortality but did not impact post-lung transplant survival. Prioritization of very early transplantation may improve waitlist outcomes in this population.

Steady Flow Left Ventricle Unloading Is Superior to Pulsatile Pressure Augmentation Venting During Venoarterial Extracorporeal Membrane Oxygenation Support.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) shunts venous blood to the systemic arterial circulation to provide end-organ perfusion while increasing afterload that may impede left ventricle (LV) ejection and impair cardiac recovery. To maintain flow across the aortic valve and reduce risk of lethal clot formation, secondary mechanical circulatory support (MCS) devices are increasingly used despite limited understanding of their effects on cardiac function. This study sought to quantify the effects of VA-ECMO and combined with either intraaortic balloon pump (IABP) or percutaneous ventricular assist device (pVAD) on LV physiologic state and perfusion metrics in a porcine model of acute cardiogenic shock. Shock was induced through serial left anterior descending artery microbead embolization followed by initiation of VA-ECMO support and then placement of either IABP or pVAD. Hemodynamic measurements, LV pressure-volume loops, and carotid artery blood flow were evaluated before and after institution of combined MCS. The IABP decreased LV end-diastolic pressure by a peak of 15% while slightly increasing LV stroke work compared with decreases of more than 60% and 50% with the pVAD, respectively. The pVAD also demonstrated increased coronary perfusion and systemic pressure gradients in comparison to the IABP. Combined support with VA-ECMO and pVAD improves cardiovascular state in comparison to IABP.

Dynamic load modulation predicts right heart tolerance of left ventricular cardiovascular assist in a porcine model of cardiogenic shock.

Ventricular assist devices (VADs) offer mechanical support for patients with cardiogenic shock by unloading the impaired ventricle and increasing cardiac outflow and subsequent tissue perfusion. Their ability to adjust ventricular assistance allows for rapid and safe dynamic changes in cardiac load, which can be used with direct measures of chamber pressures to quantify cardiac pathophysiologic state, predict response to interventions, and unmask vulnerabilities such as limitations of left-sided support efficacy due to intolerance of the right heart. We defined hemodynamic metrics in five pigs with dynamic peripheral transvalvular VAD (pVAD) support to the left ventricle. Metrics were obtained across a spectrum of disease states, including left ventricular ischemia induced by titrated microembolization of a coronary artery and right ventricular strain induced by titrated microembolization of the pulmonary arteries. A sweep of different pVAD speeds confirmed mechanisms of right heart decompensation after left-sided support and revealed intolerance. In contrast to the systemic circulation, pulmonary vascular compliance dominated in the right heart and defined the ability of the right heart to adapt to left-sided pVAD unloading. We developed a clinically accessible metric to measure pulmonary vascular compliance at different pVAD speeds that could predict right heart efficiency and tolerance to left-sided pVAD support. Findings in swine were validated with retrospective hemodynamic data from eight patients on pVAD support. This methodology and metric could be used to track right heart tolerance, predict decompensation before right heart failure, and guide titration of device speed and the need for biventricular support.

Extracorporeal membrane oxygenation as a bridge to lung transplantation: Practice patterns and patient outcomes.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly relied on to bridge patients with respiratory failure to lung transplantation despite limited evidence for its use in this setting. This study evaluated longitudinal trends in practice patterns, patient characteristics, and outcomes in patients bridged with ECMO to lung transplant. METHODS: A retrospective review of all adult isolated lung transplant patients in the United Network for Organ Sharing database between 2000 and 2019 was performed. Patients were classified as "ECMO" if supported with ECMO at the time of listing or transplantation and "non-ECMO" otherwise. Linear regression was used to evaluate trends in patient demographics during the study period. Trends in mortality were evaluated using Cox proportional hazards modeling, with time period as the primary covariate (2000-2004, 2005-2009, 2010-2014, or 2015-2019) and age, time on the waitlist, and underlying diagnosis as covariates. RESULTS: The number of patients included were 40,866, of whom 1,387 (3.4%) were classified as ECMO and 39,479 (96.6%) as no ECMO. Average age and initial Lung Allocation Score increased significantly during the study period in both cohorts, but occurred at a slower rate in the ECMO population. The hazard of death was significantly lower in more recent years (2015-2019) for both the ECMO and non-ECMO cohorts (aHR (adjusted hazards ratio) 0.59, 95% confidence interval (CI) 0.37-0.96 and aHR 0.74, 95% CI 0.70-0.79) when compared to the early years (2000-2004) of the study period. CONCLUSIONS: Post-transplantation survival for patients bridged to transplantation with ECMO demonstrates ongoing improvement despite cannulation of progressively older and sicker patients.

Characterizing the Racial Discrepancy in Hypoxemia Detection in VV-ECMO: An ELSO Registry Analysis.

Importance: Skin pigmentation influences peripheral oxygen saturation (SpO2) measured by pulse oximetry compared to the arterial saturation of oxygen (SaO2) measured via arterial blood gas analysis. However, data on SpO2-SaO2 discrepancy are limited in venovenous-extracorporeal membrane oxygenation (VV-ECMO) patients. Objective: To determine whether there is racial/ethnical discrepancy between SpO2 and SaO2 in patients receiving VV-ECMO. We hypothesized VV-ECMO cannulation, in addition to race/ethnicity, accentuates the SpO2-SaO2 discrepancy due to significant hemolysis. Design: Retrospective cohort study of the Extracorporeal Life Support Organization Registry from 1/2018-5/2023. Setting: International, multicenter registry study including over 500 ECMO centers. Participants: Adults (≥ 18 years) supported with VV-ECMO with concurrently measured SpO2 and SaO2 measurements. Exposure: Race/ethnicity and ECMO cannulation. Main outcomes and measures: Occult hypoxemia (SaO2 ≤ 88% with SpO2 ≥ 92%) was our primary outcome. Multivariable logistic regressions were performed to examine whether race/ethnicity was associated with occult hypoxemia in pre-ECMO and on-ECMO SpO2-SaO2 calculations. Covariates included age, sex, temporary mechanical circulatory support, pre-vasopressors, and pre-inotropes for pre-ECMO analysis, plus single-lumen versus double-lumen cannulation, hemolysis, hyperbilirubinemia, ECMO pump flow rate, and on-ECMO 24h lactate for on-ECMO analysis. Results: Of 13,171 VV-ECMO patients (median age = 48.6 years, 66% male), there were 7,772 (59%) White, 2,114 (16%) Hispanic, 1,777 (14%) Black, and 1,508 (11%) Asian patients. The frequency of on-ECMO occult hypoxemia was 2.0% (N = 233). Occult hypoxemia was more common in Black and Hispanic versus White patients (3.1% versus 1.7%, P < 0.001 and 2.5% versus 1.7%, P = 0.025, respectively).In multivariable logistic regression, Black patients were at higher risk of pre-ECMO occult hypoxemia versus White patients (adjusted odds ratio [aOR] = 1.55, 95% confidence interval [CI] = 1.18-2.02, P = 0.001). For on-ECMO occult hypoxemia, Black patients (aOR = 1.79, 95%CI = 1.16-2.75, P = 0.008) and Hispanic patients (aOR = 1.71, 95%CI = 1.15-2.55, P = 0.008) had higher risk versus White patients. Furthermore, higher pump flow rate (aOR = 1.29, 95%CI = 1.08-1.55, P = 0.005) and higher on-ECMO 24h lactate (aOR = 1.06, 95%CI = 1.03-1.10, P < 0.001) significantly increased the risk of on-ECMO occult hypoxemia. Conclusions and Relevance: Hispanic and Black VV-ECMO patients experienced occult hypoxemia more than White patients. SaO2 should be carefully monitored during ECMO support for Black and Hispanic patients especially for those with high pump flow and lactate values at risk for occult hypoxemia.

Extracorporeal Membrane Oxygenation Physiological Factors Influence Pulse Oximetry and Arterial Oxygen Saturation Discrepancies.

BACKGROUND: Cannulation strategy, vasopressors, and hemolysis are important physiological factors that influence hemodynamics in extracorporeal membrane oxygenation (ECMO). We hypothesized these factors influence the discrepancy between oxygen saturation measured by pulse oximetry (Spo2) and arterial blood gas (Sao2) in patients on ECMO. METHODS: We retrospectively analyzed adults (aged ≥18 years) on venoarterial or venovenous ECMO at a tertiary academic ECMO center. Spo2-Sao2 pairs with oxygen saturation ≥70% and measured within 10 minutes were included. Occult hypoxemia was defined as Sao2 ≤88% with a time-matched Spo2 ≥92%. Adjusted linear mixed-effects modeling was used to assess the Spo2-Sao2 discrepancy with preselected demographics and time-matched laboratory variables. Vasopressor use was quantified by vasopressor dose equivalences. RESULTS: Of 139 venoarterial-ECMO and 88 venovenous-ECMO patients, we examined 20,053 Spo2-Sao2 pairs. The Spo2-Sao2 discrepancy was greater in venovenous-ECMO (1.15%) vs venoarterial-ECMO (-0.35%, P < .001). Overall, 81 patients (35%) experienced occult hypoxemia during ECMO. Occult hypoxemia was more common in venovenous-ECMO (65%) than in venoarterial-ECMO (17%, P < .001). In linear mixed-effects modeling, Spo2 underestimated Sao2 by 9.48% in central vs peripheral venoarterial-ECMO (95% CI, -17.1% to -1.79%; P = .02). Higher vasopressor dose equivalences significantly worsened the Spo2-Sao2 discrepancy (P < .001). In linear mixed-effects modeling, Spo2 overestimated Sao2 by 25.43% in single lumen-cannulated vs double lumen-cannulated venovenous-ECMO (95% CI, 5.27%-45.6%; P = .03). Higher vasopressor dose equivalences and lactate dehydrogenase levels significantly worsened the Spo2-Sao2 discrepancy (P < .001). CONCLUSIONS: Venovenous-ECMO patients are at higher risk for occult hypoxemia compared with venoarterial-ECMO. A higher vasopressor requirement and different cannulation strategies (central venoarterial-ECMO; single-lumen venovenous-ECMO) were significant factors for clinically significant Spo2-Sao2 discrepancy in both ECMO modes.

A recommended preclinical extracorporeal cardiopulmonary resuscitation model for neurological outcomes: A scoping review.

Background: Despite the high prevalence of neurological complications and mortality associated with extracorporeal cardiopulmonary resuscitation (ECPR), neurologically-focused animal models are scarce. Our objective is to review current ECPR models investigating neurological outcomes and identify key elements for a recommended model. Methods: We searched PubMed and four other engines for animal ECPR studies examining neurological outcomes. Inclusion criteria were: animals experiencing cardiac arrest, ECPR/ECMO interventions, comparisons of short versus long cardiac arrest times, and neurological outcomes. Results: Among 20 identified ECPR animal studies (n = 442), 13 pigs, 4 dogs, and 3 rats were used. Only 10% (2/20) included both sexes. Significant heterogeneity was observed in experimental protocols. 90% (18/20) employed peripheral VA-ECMO cannulation and 55% (11/20) were survival models (median survival = 168 hours; ECMO duration = 60 minutes). Ventricular fibrillation (18/20, 90%) was the most common method for inducing cardiac arrest with a median duration of 15 minutes (IQR = 6-20). In two studies, cardiac arrests exceeding 15 minutes led to considerable mortality and neurological impairment. Among seven studies utilizing neuromonitoring tools, only four employed multimodal devices to evaluate cerebral blood flow using Transcranial Doppler ultrasound and near-infrared spectroscopy, brain tissue oxygenation, and intracranial pressure. None examined cerebral autoregulation or neurovascular coupling. Conclusions: The substantial heterogeneity in ECPR preclinical model protocols leads to limited reproducibility and multiple challenges. The recommended model includes large animals with both sexes, standardized pre-operative protocols, a cardiac arrest time between 10-15 minutes, use of multimodal methods to evaluate neurological outcomes, and the ability to survive animals after conducting experiments.

Racial and ethnical discrepancy in hypoxemia detection in patients on extracorporeal membrane oxygenation.

Objective: To determine whether there is racial/ethnical discrepancy between pulse oximetry (SpO2) and oxygen saturation (SaO2) in patients receiving extracorporeal membrane oxygenation (ECMO). Methods: This was a retrospective observational study at a tertiary academic ECMO center with adults (>18 years) on venoarterial (VA) or venovenous (VV) ECMO. Datapoints were excluded if oxygen saturation ≤70% or SpO2-SaO2 pairs were not measured within 10 minutes. The primary outcome was the presence of a SpO2-SaO2 discrepancy between different races/ethnicities. Bland-Altman analyses and linear mixed-effects modeling, adjusting for prespecified covariates, were used to assess the SpO2-SaO2 discrepancy between races/ethnicities. Occult hypoxemia was defined as SaO2 <88% with a time-matched SpO2 ≥92%. Results: Of 139 patients receiving VA-ECMO and 57 patients receiving VV-ECMO, we examined 16,252 SpO2-SaO2 pairs. The SpO2-SaO2 discrepancy was greater in VV-ECMO (1.4%) versus VA-ECMO (0.15%). In VA-ECMO, SpO2 overestimated SaO2 in Asian (0.2%), Black (0.94%), and Hispanic (0.03%) patients and underestimated SaO2 in White (-0.06%) and nonspecified race (-0.80%) patients. The proportion of SpO2-SaO2 measurements considered occult hypoxemia was 70% from Black compared to 27% from White patients (P < .0001). In VV-ECMO, SpO2 overestimated SaO2 in Asian (1.0%), Black (2.9%), Hispanic (1.1%), and White (0.50%) patients and underestimated SaO2 in nonspecified race patients (-0.53%). In linear mixed-effects modeling, SpO2 overestimated SaO2 by 0.19% in Black patients (95% confidence interval, 0.045%-0.33%, P = .023). The proportion of SpO2-SaO2 measurements considered occult hypoxemia was 66% from Black compared with 16% from White patients (P < .0001). Conclusions: SpO2 overestimates SaO2 in Asian, Black, and Hispanic versus White patients, and this discrepancy was greater in VV-ECMO versus VA-ECMO, suggesting the need for physiological studies.

A case series evaluating the effect of esmolol therapy to treat hypoxemia in COVID-19 patients on VV-ECMO.

When COVID-19 ARDS abolishes pulmonary function, VV-ECMO can provide gas exchange. If oxygenation remains insufficient despite maximal VV-ECMO support, the addition of esmolol has been proposed. Conflict exists, however, as to the oxygenation level which should trigger beta-blocker initiation. We evaluated the effect of esmolol therapy on oxygenation and oxygen delivery in patients with negligible native lung function and various degrees of hypoxemia despite maximal VV-ECMO support. We found that, in COVID-19 patients with negligible pulmonary gas exchange, the generalized use of esmolol administration to raise arterial oxygenation by slowing heart rate and thereby match native cardiac output to maximal attainable VV ECMO flows actually reduces systemic oxygen delivery in many cases.

National Trends, Risk Factors, and Outcomes of Acute In-Hospital Stroke Following Lung Transplantation in the United States: Analysis of the United Network for Organ Sharing Registry.

BACKGROUND: Lung transplantation (LTx) is the definitive treatment for end-stage lung failure. However, there have been no large, long-term studies on the impact of acute in-hospital stroke in this population. RESEARCH QUESTION: What are the trends, risk factors, and outcomes of acute stroke in patients undergoing LTx in the United States? STUDY DESIGN AND METHODS: We identified adult first-time isolated LTx recipients from the United Network for Organ Sharing database, which comprehensively captures every transplant in the United States, between May 2005 and December 2020. Stroke was defined as occurring at any time after LTx but prior to discharge. Multivariable logistic regression with stepwise feature elimination was used to identify risk factors for stroke. Freedom from death in patients with a stroke vs those without a stroke was evaluated with Kaplan-Meier analysis. Cox proportional hazards analysis was used to identify predictors of death at 24 months. RESULTS: Of 28,564 patients (median age, 60 years; 60% male), 653 (2.3%) experienced an acute in-hospital stroke after LTx. Median follow-up was 1.2 (stroke) and 3.0 (non-stroke) years. Annual incidence of stroke increased (1.5% in 2005 to 2.4% in 2020; P for trend = .007), as did lung allocation score and utilization of post-LTx extracorporeal membrane oxygenation (P = .01 and P < .001, respectively). Compared with those without stroke, patients with stroke had lower survival at 1 month (84% vs 98%), 12 months (61% vs 88%), and 24 months (52% vs 80%) (log-rank test, P < .001 for all). In Cox analysis, acute stroke conferred a high hazard of mortality (hazard ratio, 3.01; 95% CI, 2.67-3.41). Post-LTx extracorporeal membrane oxygenation was the strongest risk factor for stroke (adjusted OR, 2.98; 95% CI, 2.19-4.06). INTERPRETATION: Acute in-hospital stroke post-LTx has been increasing over time and is associated with markedly worse short- and long-term survival. As increasingly sicker patients undergo LTx as well as experience stroke, further research on stroke characteristics, prevention, and management strategies is warranted.

Arterial oxygen and carbon dioxide tension and acute brain injury in extracorporeal cardiopulmonary resuscitation patients: Analysis of the extracorporeal life support organization registry.

BACKGROUND: Acute brain injury (ABI) remains common after extracorporeal cardiopulmonary resuscitation (ECPR). Using a large international multicenter cohort, we investigated the impact of peri-cannulation arterial oxygen (PaO2) and carbon dioxide (PaCO2) on ABI occurrence. METHODS: We retrospectively analyzed adult (≥18 years old) ECPR patients in the Extracorporeal Life Support Organization registry from 1/2009 through 12/2020. Composite ABI included ischemic stroke, intracranial hemorrhage (ICH), seizures, and brain death. The registry collects 2 blood gas data pre- (6 hours) and post- (24 hours) cannulation. Blood gas parameters were classified as: hypoxia (<60mm Hg), normoxia (60-119mm Hg), and mild (120-199mm Hg), moderate (200-299mm Hg), and severe hyperoxia (≥300mm Hg); hypocarbia (<35mm Hg), normocarbia (35-44mm Hg), mild (45-54mm Hg) and severe hypercarbia (≥55mm Hg). Missing values were handled using multiple imputation. Multivariable logistic regression analysis was used to assess the relationship of PaO2 and PaCO2 with ABI. RESULTS: Of 3,125 patients with ECPR intervention (median age=58, 69% male), 488 (16%) experienced ABI (7% ischemic stroke; 3% ICH). In multivariable analysis, on-ECMO moderate (aOR=1.42, 95%CI: 1.02-1.97) and severe hyperoxia (aOR=1.59, 95%CI: 1.20-2.10) were associated with composite ABI. Additionally, severe hyperoxia was associated with ischemic stroke (aOR=1.63, 95%CI: 1.11-2.40), ICH (aOR=1.92, 95%CI: 1.08-3.40), and in-hospital mortality (aOR=1.58, 95%CI: 1.21-2.06). Mild hypercarbia pre-ECMO was protective of composite ABI (aOR=0.61, 95%CI: 0.44-0.84) and ischemic stroke (aOR=0.56, 95%CI: 0.35-0.89). CONCLUSIONS: Early severe hyperoxia (≥300mm Hg) on ECMO was a significant risk factor for ABI and mortality. Careful consideration should be given in early oxygen delivery in ECPR patients who are at risk of reperfusion injury.

Early Low Pulse Pressure in VA-ECMO Is Associated with Acute Brain Injury.

BACKGROUND: Pulse pressure is a dynamic marker of cardiovascular function and is often impaired in patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Pulsatile blood flow also serves as a regulator of vascular endothelium, and continuous-flow mechanical circulatory support can lead to endothelial dysfunction. We explored the impact of early low pulse pressure on occurrence of acute brain injury (ABI) in VA-ECMO. METHODS: We conducted a retrospective analysis of adults with VA-ECMO at a tertiary care center between July 2016 and January 2021. Patients underwent standardized multimodal neuromonitoring throughout ECMO support. ABI included intracranial hemorrhage, ischemic stroke, hypoxic ischemic brain injury, cerebral edema, seizure, and brain death. Blood pressures were recorded every 15 min. Low pulse pressure was defined as a median pulse pressure < 20 mm Hg in the first 12 h of ECMO. Multivariable logistic regression was performed to investigate the association between pulse pressure and ABI. RESULTS: We analyzed 5138 blood pressure measurements from 123 (median age 63; 63% male) VA-ECMO patients (54% peripheral; 46% central cannulation), of whom 41 (33%) experienced ABI. Individual ABIs were as follows: ischemic stroke (n = 18, 15%), hypoxic ischemic brain injury (n = 14, 11%), seizure (n = 8, 7%), intracranial hemorrhage (n = 7, 6%), cerebral edema (n = 7, 6%), and brain death (n = 2, 2%). Fifty-eight (47%) patients had low pulse pressure. In a multivariable model adjusting for preselected covariates, including cannulation strategy (central vs. peripheral), lactate on ECMO day 1, and left ventricle venting strategy, low pulse pressure was independently associated with ABI (adjusted odds ratio 2.57, 95% confidence interval 1.05-6.24). In a model with the same covariates, every 10-mm Hg decrease in pulse pressure was associated with 31% increased odds of ABI (95% confidence interval 1.01-1.68). In a sensitivity analysis model adjusting for systolic pressure, pulse pressure remained significantly associated with ABI. CONCLUSIONS: Early low pulse pressure (< 20 mm Hg) was associated with ABI in VA-ECMO patients. Low pulse pressure may serve as a marker of ABI risk, which necessitates close neuromonitoring for early detection.

Effect of anatomical variation on extracorporeal membrane oxygenation circulatory support: A computational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) via femoral cannulation is a vital intervention capable of rapidly restoring perfusion for patients in shock. Despite increasing use to provide circulatory support, its hemodynamic effects are poorly understood and the impact of patient-specific anatomical variation on perfusion is unknown. This study investigates the complex failing heart-mechanical circulatory support circulation and analyzes the effect of patient-specific vascular anatomical variations on hemodynamics and end-organ perfusion. METHODS: Patient-specific vascular geometries were constructed from segmenting clinical computerized tomography angiography images and quantitatively compared using tortuosity, curvature, torsion, and lumen diameter. Computational fluid dynamic simulations were performed on a subset of geometries selected to represent a range of anatomical variation. Heart failure severity was modeled by varying the relative fraction of total flow provided by the heart and the extracorporeal circuit. A 3-element lumped parameter model was applied to accurately and dynamically model distal perfusion boundary conditions. Hemodynamic parameters and end-organ perfusion were analyzed and compared to assess the effect of anatomical variation. RESULTS: Pulsatile antegrade cardiac perfusion and ECMO retrograde perfusion collide in the aorta to form a dynamic watershed region. The size, position, and variation of this region over the cardiac cycle is substantially altered by patient anatomical region. Increased vascular tortuosity reduces the proximal extent of flow from circulatory support and decreases the size of the watershed region. CONCLUSIONS: Patient vascular anatomy is a key determinant of the ECMO-failing heart circulation that alters the location and extent of the watershed region and affects the tissues at risk for differential hypoxia and circuit-derived thromboemboli for a given level of support.

Simulation of Fluid-Structure Interaction in Extracorporeal Membrane Oxygenation Circulatory Support Systems.

Extracorporeal membrane oxygenation (ECMO) is a vital mechanical circulatory support modality capable of restoring perfusion for the patient in circulatory failure. Despite increasing adoption of ECMO, there is incomplete understanding of its effects on systemic hemodynamics and how the vasculature responds to varying levels of continuous retrograde perfusion. To gain further insight into the complex ECMO:failing heart circulation, computational fluid dynamics simulations focused on perfusion distribution and hemodynamic flow patterns were conducted using a patient-derived aorta geometry. Three case scenarios were simulated: (1) healthy control; (2) 90% ECMO-derived perfusion to model profound heart failure; and, (3) 50% ECMO-derived perfusion to model the recovering heart. Fluid-structure interface simulations were performed to quantify systemic pressure and vascular deformation throughout the aorta over the cardiac cycle. ECMO support alters pressure distribution while decreasing shear stress. Insights derived from computational modeling may lead to better understanding of ECMO support and improved patient outcomes.

Hysteretic device characteristics indicate cardiac contractile state for guiding mechanical circulatory support device use.

BACKGROUND: Acute heart failure and cardiogenic shock remain highly morbid conditions despite prompt medical therapy in critical care settings. Mechanical circulatory support (MCS) is a promising therapy for these patients, yet remains managed with open-loop control. Continuous measure of cardiac function would support and optimize MCS deployment and weaning. The nature of indwelling MCS provides a platform for attaining this information. This study investigates how hysteresis modeling derived from MCS device signals can be used to assess contractility changes to provide continuous indication of changing cardiac state. Load-dependent MCS devices vary their operation with cardiac state to yield a device-heart hysteretic interaction. Predicting and examining this hysteric relation provides insight into cardiac state and can be separated by cardiac cycle phases. Here, we demonstrate this by predicting hysteresis and using the systolic portion of the hysteresis loop to estimate changes in native contractility. This study quantified this measurement as the enclosed area of the systolic portion of the hysteresis loop and correlated it with other widely accepted contractility metrics in animal studies (n = 4) using acute interventions that alter inotropy, including a heart failure model. Clinical validation was performed in patients (n = 8) undergoing Impella support. RESULTS: Hysteresis is well estimated from device signals alone (r = 0.92, limits of agreement: - 0.18 to 0.18). Quantified systolic area was well correlated in animal studies with end-systolic pressure-volume relationship (r = 0.84), preload recruitable stroke work index (r = 0.77), and maximum slope of left ventricular pressure (dP/dtmax) (r = 0.95) across a range of inotropic conditions. Comparable results were seen in patients with dP/dtmax (r = 0.88). Diagnostic capability from ROC analysis yielded AUC measurements of 0.92 and 0.90 in animal and patients, respectively. CONCLUSIONS: Mechanical circulatory support hysteretic behavior can be well modeled using device signals and used to estimate contractility changes. Contractility estimate is correlated with other accepted metrics, captures temporal trends that elucidate changing cardiac state, and is able to accurately indicate changes in inotropy. Inherently available during MCS deployment, this measure will guide titration and inform need for further intervention.

A Computational Fluid Dynamics Study of the Extracorporeal Membrane Oxygenation-Failing Heart Circulation.

Extracorporeal membrane oxygenation (ECMO) is increasingly deployed to provide percutaneous mechanical circulatory support despite incomplete understanding of its complex interactions with the failing heart and its effects on hemodynamics and perfusion. Using an idealized geometry of the aorta and its major branches and a peripherally inserted return cannula terminating in the iliac artery, computational fluid dynamic simulations were performed to (1) quantify perfusion as function of relative ECMO flow and (2) describe the watershed region produced by the collision of antegrade flow from the heart and retrograde ECMO flow. To simulate varying degrees of cardiac failure, ECMO flow as a fraction of systemic perfusion was evaluated at 100%, 90%, 75%, and 50% of total flow with the remainder supplied by the heart calculated from a patient-derived flow waveform. Dynamic boundary conditions were generated with a three-element lumped parameter model to accurately simulate distal perfusion. In profound failure (ECMO providing 90% or more of flow), the watershed region was positioned in the aortic arch with minimal pulsatility observed in the flow to the visceral organs. Modest increases in cardiac flow advanced the watershed region into the thoracic aorta with arch perfusion entirely supplied by the heart.

A Scalable Approach to Determine Intracardiac Pressure From Mechanical Circulatory Support Device Signals.

OBJECTIVE: Effective mechanical circulatory support (MCS) relies on cardiac function measures to guide titration. Left ventricular end diastolic pressure (LVEDP) is a useful measure that is indirectly estimated using pulmonary artery catheters (PACs). PACs require additional intervention and provide intermittent and unreliable estimations. MCS device signals can estimate LVEDP but are prone to inter-device variability and require rigorous specialized characterization. We present a scalable and implementable approach to calculate LVEDP continuously using device signals. METHODS: LVEDP was calculated from MCS device measured aortic pressure and motor current, which approximates the pressure head between the aorta and left ventricle. This motor current-pressure head relationship is device-specific but approximated using existing flow calibration and assumed physiologic relationships. Performance was evaluated with comparison from direct measurement of LVEDP in a series of acute animal models. RESULTS: LVEDP measures (n = 178,279) from 18 animals had good correlation (r = 0.84) and calibration (Bland-Altman limits of agreement -7.77 to 7.63 mmHg; mean bias -0.07 ± 0.02 mmHg). The total mean error prediction interval was -3.42 to 3.32 mmHg and RMS error was 3.85 mmHg. CONCLUSION: LVEDP can be continuously calculated using device signals without specialized characterization. Calculated LVEDP values improved upon PAC estimations and were found using a scalable and manufacturer-accessible method. SIGNIFICANCE: This method improves upon existing LVEDP measures without the need for rigorous characterization, external calibration, or additional intervention; this allows widescale deployment of continuous LVEDP measurement for patients on MCS and demonstrates key considerations necessary to translate research-grade technologies.

Emerging Mechanisms of Pulmonary Vasoconstriction in SARS-CoV-2-Induced Acute Respiratory Distress Syndrome (ARDS) and Potential Therapeutic Targets.

The 1918 influenza killed approximately 50 million people in a few short years, and now, the world is facing another pandemic. In December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an international outbreak of a respiratory illness termed coronavirus disease 2019 (COVID-19) and rapidly spread to cause the worst pandemic since 1918. Recent clinical reports highlight an atypical presentation of acute respiratory distress syndrome (ARDS) in COVID-19 patients characterized by severe hypoxemia, an imbalance of the renin-angiotensin system, an increase in thrombogenic processes, and a cytokine release storm. These processes not only exacerbate lung injury but can also promote pulmonary vascular remodeling and vasoconstriction, which are hallmarks of pulmonary hypertension (PH). PH is a complication of ARDS that has received little attention; thus, we hypothesize that PH in COVID-19-induced ARDS represents an important target for disease amelioration. The mechanisms that can promote PH following SARS-CoV-2 infection are described. In this review article, we outline emerging mechanisms of pulmonary vascular dysfunction and outline potential treatment options that have been clinically tested.

Left ventricle unloading strategies in ECMO: A single-center experience.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is a life-saving technology capable of restoring perfusion but is not without significant complications that limit its realizable therapeutic benefit. ECMO-induced hemodynamics increase cardiac afterload risking left ventricular distention and impaired cardiac recovery. To mitigate potentially harmful effects, multiple strategies to unload the left ventricle (LV) are used in clinical practice but data supporting the optimal approach is presently lacking. MATERIALS & METHODS: We reviewed outcomes of our ECMO population from September 2015 through January 2019 to determine if our LV unloading strategies were associated with patient outcomes. We compared reactive (Group 1, n = 30) versus immediate (Group 2, n = 33) LV unloading and then compared patients unloaded with an Impella CP (n = 19) versus an intra-aortic balloon pump (IABP, n = 16), analyzing survival and ECMO-related complications. RESULTS: Survival was similar between Groups 1 and 2 (33 vs 42%, P = .426) with Group 2 experiencing more clinically-significant hemorrhage (40 vs. 67%, P = .034). Survival and ECMO-related complications were similar between patients unloaded with an Impella versus an IABP. However, the Impella group exhibited a higher rate of survival (37%) than predicted by their median SAVE score (18%). DISCUSSION: Based on this analysis, reactive unloading appears to be a viable strategy while venting with the Impella CP provides better than anticipated survival. Our findings correlate with recent large cohort studies and motivate further work to design clinical guidelines and future trial design.