The hemodynamic effect of different left ventricular unloading techniques during veno-arterial extracorporeal life support: a systematic review and meta-analysis.

BACKGROUND: Pulmonary edema and left ventricular thrombosis may arise during veno-arterial extracorporeal life support due to an increase in cardiac load. This mechanical stress can be reduced through different left ventricular unloading techniques. We set out to quantitatively summarize the hemodynamic effects of available methods in patients treated with veno-arterial extracorporeal life support. METHODS: Literature was systematically searched for studies reporting left ventricular unloading during veno-arterial extracorporeal life support as reflected by changes in left atrial pressure, pulmonary capillary wedge pressure, diastolic pulmonary artery pressure, or left ventricular end-diastolic pressure. For studies including ⩾10 patients per group, changes in these parameters were pooled using (1) standardized mean differences and (2) ratio of means. Assessment of potential bias was performed for all studies. RESULTS: Eight studies met the inclusion criteria. Reported techniques included use of intra-aortic balloon pump (n = 1), micro-axial blood pump (Impella®, n = 2), left ventricular venting (n = 1), and atrial septostomy (n = 4). Overall, left ventricular unloading was associated with a statistically significant reduction in preload parameters (standardized mean differences = -1.05 (95% confidence interval = -1.24 to -0.86) and ratio of means = 0.60 (0.47 to 0.76)). Effect sizes were strongest for micro-axial blood pump and atrial septostomy (standardized mean differences = -1.11 (-1.55 to -0.68) and -1.22 (-1.47 to -0.96), and ratio of means = 0.58 (0.39 to 0.86) and 0.54 (0.36 to 0.83), respectively). CONCLUSION: Left ventricular unloading was associated with a significant reduction in left ventricular preload parameters in the setting of veno-arterial extracorporeal life support. This effect may be most pronounced for micro-axial blood pump and atrial septostomy.

Left ventricular unloading during veno-arterial ECMO: a review of percutaneous and surgical unloading interventions.

Short-term mechanical support by veno-arterial extracorporeal membrane oxygenation (VA ECMO) is more and more applied in patients with severe cardiogenic shock. A major shortcoming of VA ECMO is its variable, but inherent increase of left ventricular (LV) mechanical load, which may aggravate pulmonary edema and hamper cardiac recovery. In order to mitigate these negative sequelae of VA ECMO, different adjunct LV unloading interventions have gained a broad interest in recent years. Here, we review the whole spectrum of percutaneous and surgical techniques combined with VA ECMO reported to date.

Differential hypoxemia during venoarterial extracorporeal membrane oxygenation.

Venoarterial extracorporeal membrane oxygenation, indicated for severe cardio-respiratory failure, may result in anatomic regional differences in oxygen saturation. This depends on cannulation, hemodynamic state, and severity of respiratory failure. Differential hypoxemia, often discrete, may cause clinical problems in peripheral femoro-femoral venoarterial extracorporeal membrane oxygenation, when the upper body is perfused with low saturated blood from the heart and the lower body with well-oxygenated extracorporeal membrane oxygenation blood. The key is to diagnose and manage fulminant differential hypoxemia, that is, a state that may develop where the upper body is deprived of oxygen. We summarize physiology, assessment of diagnosis, and management of fulminant differential hypoxemia during venoarterial extracorporeal membrane oxygenation. A possible solution is implantation of an additional jugular venous return cannula. In this article, we propose an even better solution, to drain the venous blood from the superior vena cava. Drainage from the superior vena cava provides superiority to venovenoarterial configuration in terms of physiological rationale, efficiency, safety, and simplicity in clinical circuit design.

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.

Venous Cannula Positioning in Arterial Deoxygenation During Veno-Arterial Extracorporeal Membrane Oxygenation-A Simulation Study and Case Report.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is indicated in reversible life-threatening circulatory failure with or without respiratory failure. Arterial desaturation in the upper body is frequently seen in patients with peripheral arterial cannulation and severe respiratory failure. The importance of venous cannula positioning was explored in a computer simulation model and a clinical case was described. A closed-loop real-time simulation model has been developed including vascular segments, the heart with valves and pericardium. ECMO was simulated with a fixed flow pump and a selection of clinically relevant venous cannulation sites. A clinical case with no tidal volumes due to pneumonia and an arterial saturation of below 60% in the right hand despite VA-ECMO flow of 4 L/min was described. The case was compared with simulation data. Changing the venous cannulation site from the inferior to the superior caval vein increased arterial saturation in the right arm from below 60% to above 80% in the patient and from 64 to 81% in the simulation model without changing ECMO flow. The patient survived, was extubated and showed no signs of hypoxic damage. We conclude that venous drainage from the superior caval vein improves upper body arterial saturation during veno-arterial ECMO as compared with drainage solely from the inferior caval vein in patients with respiratory failure. The results from the simulation model are in agreement with the clinical scenario.

Individualized real-time clinical decision support to monitor cardiac loading during venoarterial ECMO.

Veno-arterial extracoporeal membrane oxygenation (VA ECMO) is increasingly used for acute and refractory cardiogenic shock. Yet, in clinical practice, monitoring of cardiac loading conditions during VA ECMO can be cumbersome. To this end, we illustrate the validity and clinical applicability of a real-time cardiovascular computer simulation, which allows to integrate hemodynamics, cardiac dimensions and the corresponding degree of VA ECMO support and ventricular loading in individual patients over time.

EVALUATION OF QUANTITATIVE THYROID SCINTIGRAPHY FOR DIAGNOSIS AND STAGING OF DISEASE SEVERITY IN CATS WITH HYPERTHYROIDISM: COMPARISON OF THE PERCENT THYROIDAL UPTAKE OF PERTECHNETATE TO THYROID-TO-SALIVARY RATIO AND THYROID-TO-BACKGROUND RATIOS.

Thyroid scintigraphy is commonly used for evaluation of cats with hyperthyroidism, with the thyroid-to-salivary ratio (T/S) being the most common method to quantify the degree of thyroid activity and disease. Calculation of thyroid-to-background ratios (T/B) or percent thyroidal uptake of (99m) TcO(-) 4 (TcTU) has only been reported in a few studies. The purpose of this prospective, cross-sectional study was to evaluate a number of quantitative scintigraphic indices as diagnostic tests for hyperthyroidism, including the T/S, three different T/B, TcTU, and estimated thyroid volume. Of 524 cats referred to our clinic for evaluation of suspected hyperthyroidism, the diagnosis was confirmed (n = 504) or excluded (n = 20) based on results of a serum thyroid panel consisting of thyroxine (T4 ), triiodothyronine (T3 ), free T4 (fT4 ), and thyroid-stimulating hormone (TSH) concentrations. In the hyperthyroid cats, median values for TcTU, T/S, and three T/B ratios were all significantly higher (P < 0.001) than values in euthyroid suspect cats or clinically normal cats. All scintigraphic parameters were relatively sensitive and specific as diagnostic tests for hyperthyroidism, but the T/S ratio had the highest test accuracy. The T/S ratio correlated strongly with the TcTU (r = 0.85). However, the TcTU had a higher and more significant correlation (P < 0.01) with serum T4 (r = 0.76 vs. 0.64), T3 (r = 0.77 vs. 0.64), and estimated thyroid volume (r = 0.62 vs. 0.38). Overall, calculation of TcTU is an accurate diagnostic test, but also appears to be the best parameter to predict the functional volume and metabolic activity of the feline adenomatous thyroid gland.

Pheochromocytoma-Induced Inverted Takotsubo-Like Cardiomyopathy Leading to Cardiogenic Shock Successfully Treated With Extracorporeal Membrane Oxygenation.

Pheochromocytoma classically displays a variety of rather benign symptoms, such as headache, palpitations, and sweating, although severe cardiac manifestations have been described. We report a case of pheochromocytoma-induced inverted takotsubo-like cardiomyopathy leading to shock and cardiac arrest successfully treated with extracorporeal membrane oxygenation (ECMO) as a bridge to pharmacological therapy and curative adrenalectomy. A previously healthy 46-year-old woman presented to the emergency department with abdominal pain, dyspnea, nausea, and vomiting. Clinical evaluation revealed cardiorespiratory failure with hypoxia and severe metabolic acidosis. Computed tomography (CT) scan showed pulmonary edema and a left adrenal mass. Transthoracic echocardiography (TTE) displayed severe left ventricular dysfunction with inverted takotsubo contractile pattern. Despite mechanical ventilation and inotropic and vasopressor support, asystolic cardiac arrest ensued. The patient was resuscitated using manual chest compressions followed by venoarterial ECMO. Repeated TTEs demonstrated resolution of the cardiomyopathy within a few days. Laboratory results indicated transient renal and hepatic dysfunction, and CT scan of the brain displayed occipital infarctions. Biochemical testing and radionuclide scintigraphy confirmed a pheochromocytoma. Pharmacological adrenergic blockade was instituted prior to delayed adrenalectomy after which the diagnosis was histopathologically verified. The patient recovered after rehabilitation. We conclude that pheochromocytoma should be considered in patients presenting with unexplained cardiovascular compromise, especially if they display (inverted) takotsubo contractile pattern. Timely, adequate management might involve ECMO as a bridge to pharmacological therapy and curative surgery.

Thyroid scintigraphy findings in 2096 cats with hyperthyroidism.

Thyroid scintigraphy is currently the reference standard for diagnosing and staging cats with hyperthyroidism, but few studies describing the scintigraphic characteristics in a large number of cats have been reported. The objective of this study was to better characterize thyroid scintigraphy findings by evaluating 2096 consecutive cats with hyperthyroidism that were referred over a 3.5-year period. Of these cats, 2068 (98.7%) had a high thyroid-to-salivary ratio (>1.5), whereas 2014 (96.1%) were found to have a high thyroid-to-background ratio (>6.1). When the patterns of the cats' thyroid disease were recorded, 665 (31.7%) had unilateral disease, 1060 (50.6%) had bilateral-asymmetric disease (two thyroid lobes unequal in size), 257 (12.3%) had bilateral-symmetric disease (both lobes similar in size), and 81 (3.9%) had multifocal disease (≥3 areas of increased radionuclide uptake). The number of areas of (99m) TcO(-) 4 uptake in the 2096 cats ranged from 1 to 6 (median, 2), located in the cervical area in 2057 (98.1%), thoracic inlet in 282 (13.5%), and in the thoracic cavity in 115 (5.5%). Ectopic thyroid tissue (e.g. lingual or mediastinal) was diagnosed in 81 (3.9%) cats, whereas thyroid carcinoma was suspected in 35 (1.7%) of the cats. The results of this study support conclusions that most hyperthyroid cats have unilateral or bilateral thyroid nodules, but that multifocal disease will develop in a few cats that have ectopic thyroid disease or thyroid carcinoma. Both ectopic thyroid disease and thyroid carcinoma are relatively uncommon in hyperthyroid cats, with a respective prevalence of ∼4% and ∼2% in this study.

Evaluation of intraorbital prosthetic pigmentation using 0.3 and 1.5 Tesla magnetic resonance imaging and computed tomography.

PURPOSE: To investigate the magnetic susceptibility artifact associated with pigmented intraorbital prosthetics when performing magnetic resonance imaging (MRI) and computed tomography (CT). Potential artifact reduction techniques were also investigated. STUDY DESIGN: Prospective study. METHODS: Five different-colored 20-millimeter small animal silicone intraorbital prosthetics and two equine prosthetics were evaluated using 0.3 and 1.5 Tesla (T) MRI and CT. MRI sequences included T1- (T1WI) and T2-weighted spin echo (T2WI), T2 gradient echo (T2*), short tau inversion recovery (STIR), and fluid-attenuated inversion recovery (FLAIR). When present, artifact size was measured using computerized software by three separate observers. Artifact reduction techniques included alterations in receiver bandwidth, field of view, slice thickness, and matrix size. RESULTS: The ferrous brown-pigmented prosthetic resulted in a magnetic susceptibility artifact with MRI. No artifact was observed on CT images. Interobserver variability was not statistically significant. For both the 0.3T and 1.5T MRI, the T2* sequence exhibited the largest artifact surface area followed by T2WI, T1WI, STIR, and FLAIR. Decreasing slice thickness showed a decrease in artifact size; however, this difference was not statistically significant. CONCLUSIONS: The ferrous substances in the brown intraorbital prosthetic resulted in a significant magnetic susceptibility artifact when performing MRI. Artifact reduction techniques did not significantly decrease artifact surface area. The use of ferrous brown-pigmented prosthetics and their potential to affect future MR imaging studies should be adequately discussed with pet owners.

Closed-loop real-time simulation model of hemodynamics and oxygen transport in the cardiovascular system.

BACKGROUND: Computer technology enables realistic simulation of cardiovascular physiology. The increasing number of clinical surgical and medical treatment options imposes a need for better understanding of patient-specific pathology and outcome prediction. METHODS: A distributed lumped parameter real-time closed-loop model with 26 vascular segments, cardiac modelling with time-varying elastance functions and gradually opening and closing valves, the pericardium, intrathoracic pressure, the atrial and ventricular septum, various pathological states and including oxygen transport has been developed. RESULTS: Model output is pressure, volume, flow and oxygen saturation from every cardiac and vascular compartment. The model produces relevant clinical output and validation of quantitative data in normal physiology and qualitative directions in simulation of pathological states show good agreement with published data. CONCLUSION: The results show that it is possible to build a clinically relevant real-time computer simulation model of the normal adult cardiovascular system. It is suggested that understanding qualitative interaction between physiological parameters in health and disease may be improved by using the model, although further model development and validation is needed for quantitative patient-specific outcome prediction.

MRI of a split cord malformation in a German shepherd dog.

A 9 yr old spayed female German shepherd dog was referred for MRI of the thoracic and lumbar spine because she had clinical signs of chronic neurogenic bladder dysfunction of an unknown cause. Transverse T2-weighted images identified a type II split cord malformation (i.e., diastematomyelia) in the thoracic spine. Split cord malformations are forms of spinal dysraphism where the abnormal development of spinal cord results in sagittal splitting of a portion of the cord into two hemicords. The location of the lesion in the thoracic spine was consistent with the dog's clinical signs of an upper motor neuron bladder. Split cord malformations that occur in humans have similar MRI characteristics and can result in similar clinical signs as those identified in the dog described in this report.

Distinct morphologies of arterial waveforms reveal preload-, contractility-, and afterload-deficient hemodynamic instability: An in silico simulation study.

Hemodynamic instability is frequently present in critically ill patients, primarily caused by a decreased preload, contractility, and/or afterload. We hypothesized that peripheral arterial blood pressure waveforms allow to differentiate between these underlying causes. In this in-silico experimental study, a computational cardiovascular model was used to simulate hemodynamic instability by decreasing blood volume, left ventricular contractility or systemic vascular resistance, and additionally adaptive and compensatory mechanisms. From the arterial pressure waveforms, 45 features describing the morphology were discerned and a sensitivity analysis and principal component analysis were performed, to quantitatively investigate their discriminative power. During hemodynamic instability, the arterial waveform morphology changed distinctively, for example, the slope of the systolic upstroke having a sensitivity of 2.02 for reduced preload, 0.80 for reduced contractility, and -0.02 for reduced afterload. It was possible to differentiate between the three underlying causes based on the derived features, as demonstrated by the first two principal components explaining 99% of the variance in waveforms. The features with a high correlation coefficient (>0.25) to these principal components are describing the systolic up- and downstroke, and the anacrotic and dicrotic notches of the waveforms. In this study, characteristic peripheral arterial waveform morphologies were identified that allow differentiation between deficits in preload, contractility, and afterload causing hemodynamic instability. These findings are confined to an in silico simulation and warrant further experimental and clinical research in order to prove clinical usability in daily practice.

Long-term Extracorporeal Membrane Oxygenation Bridge to Lung Transplantation After COVID-19.

This report describes a patient with severe acute respiratory syndrome coronavirus 2 infection and irreversible lung destruction who underwent successful lung transplantation after 138 days of bridging with extracorporeal membrane oxygenation support. The case exemplifies that lung transplantation may be a possibility after very long-term coronavirus disease 2019 care, even if the patient is initially an unsuitable candidate.

A review of orbital and intracranial magnetic resonance imaging in 79 canine and 13 feline patients (2004-2010).

OBJECTIVE: To review the distribution of orbital and intracranial disease in canine and feline patients undergoing magnetic resonance imaging (MRI) following referral to a veterinary ophthalmologist and to correlate results of MRI with pathologic conditions including neoplasia, suspected optic neuritis (ON) and orbital cellulitis. Recognized and emerging imaging techniques are reviewed. PROCEDURE: Medical records of 79 canine and 13 feline patients were reviewed. RESULTS: Neoplasia was diagnosed in 53/92 (57.6%) of patients. The most prevalent types of neoplasia were carcinoma (16/53, 30.1%), sarcoma (11/53, 20.8%), lymphoma (8/53, 15.1%) and presumptive meningioma (9/53, 17.0%). Carcinomas and sarcomas were characterized by bony lysis and intracranial/sinonasal extension. Lymphoma was generally unilateral, less invasive and originated from the ventromedial orbit. Intracranial masses representing presumptive meningiomas frequently exhibited a 'dural tail' sign. Diagnosis of suspected ON was made in 13 of 92 (14.1%) patients. Results of MRI in patients with suspected ON included unilateral optic nerve hyperintensity (3/13, 23.0%), bilateral optic nerve hyperintensity (1/13, 7.7%) and optic chiasmal hyperintensity (3/13, 23.0%). Seven suspected ON patients demonstrated intracranial multifocal patchy contrast enhancement (7/13, 53.8%). Diagnosis of orbital cellulitis was made in 12/92 (13.0%) patients. CONCLUSIONS: Orbital neoplasia was the most common pathologic condition detected. Essential Roentgen characteristics are helpful when diagnosing pathologic processes and providing prognoses in cases of orbital or intracranial disease. Magnetic resonance imaging comprises an important diagnostic component in cases of suspected ON. Emerging contrast and functional MRI techniques as well as SI data may increase our ability to characterize disease processes.

Right-Left Ventricular Interaction in Left-Sided Heart Failure With and Without Venoarterial Extracorporeal Membrane Oxygenation Support-A Simulation Study.

Left ventricular (LV) dilatation is commonly seen with LV failure and is often aggravated during venoarterial extracorporeal membrane oxygenation (VA ECMO). In this context, the intricate interaction between left and right heart function is considered to be of pivotal importance, yet mechanistically not well understood. We hypothesize that a preserved or enhanced right heart contractility causes increased LV loading both with and without VA ECMO. A closed-loop in-silico simulation model containing the cardiac chambers, the pericardium, septal interactions, and the pulmonary and systemic vascular systems with an option to connect a simulated VA ECMO circuit was developed. Right ventricular contractility was modified during simulation of severe LV failure with and without VA ECMO. Left atrial pressures increased from 14.0 to 23.8 mm Hg without VA ECMO and from 18.4 to 27.0 mm Hg under VA ECMO support when right heart contractility was increased between end-systolic elastance 0.1 and 1.0 mm Hg/ml. Left-sided end-diastolic volumes increased from 125 to 169 ml without VA ECMO and from 150 to 180 ml with VA ECMO. Simulations demonstrate that increased diastolic loading of the LV may be driven by increased right ventricular contractility and that left atrial pressures cannot be interpreted as a reflection of the degree of LV dysfunction and overload without considering right ventricular function. Our study illustrates that modelling and computer simulation are important tools to unravel complex cardiovascular mechanisms underlying the right-left heart interdependency both with and without mechanical circulatory support.

Hydraulic force is a novel mechanism of diastolic function that may contribute to decreased diastolic filling in HFpEF and facilitate filling in HFrEF.

A hydraulic force generated by blood moving the atrioventricular plane is a novel mechanism of diastolic function. The direction and magnitude of the force is dependent on the geometrical relationship between the left atrium and ventricle and is measured as the short-axis atrioventricular area difference (AVAD). In short, the net hydraulic force acts from a larger area toward a smaller one. It is currently unknown how cardiac remodeling affects this mechanism. The aim of the study was therefore to investigate this diastolic mechanism in patients with pathological or physiological remodeling. Seventy subjects [n = 11 heart failure with preserved ejection fraction (HFpEF), n = 10 heart failure with reduced ejection fraction (HFrEF), n = 7 signs of isolated diastolic dysfunction, n = 10 hypertrophic cardiomyopathy, n = 10 cardiac amyloidosis, n = 18 triathletes, and n = 14 controls] were included. Subjects underwent cardiac MR, and short-axis images of the left atrium and ventricle were delineated. AVAD was calculated as ventricular area minus atrial area and used as an indicator of net hydraulic force. At the onset of diastole, AVAD in HFpEF was -9.2 cm2 (median) versus -4.4 cm2 in controls, P = 0.02. The net hydraulic force was directed toward the ventricle for both but was larger in HFpEF. HFrEF was the only group with a positive median value (11.6 cm2), and net hydraulic force was throughout diastole directed toward the atrium. The net hydraulic force may impede cardiac filling throughout diastole in HFpEF, worsening diastolic dysfunction. In contrast, it may work favorably in patients with dilated ventricles and aid ventricular filling.NEW & NOTEWORTHY It is a previously unrecognized physiological mechanism of the heart that diastolic filling occurs with the help of hydraulics. In patients with heart failure with preserved ejection fraction, atrial dilatation may cause the net hydraulic force to work against cardiac filling, thus further augmenting diastolic dysfunction. In contrast, it may work favorably in patients with dilated ventricles, as in heart failure with reduced ejection fraction.

Experimental extracorporeal membrane oxygenation reduces central venous pressure: an adjunct to control of venous hemorrhage?

BACKGROUND: Venoarterial ECMO has been utilized in trauma patients to improve oxygenation, particularly in the setting of pulmonary contusions and ARDS. We hypothesized that venoarterial ECMO could reduce the central venous pressure in the trauma scenario, thus, alleviating major venous hemorrhage. METHODS: Ten swine were cannulated for venoarterial ECMO. Central venous pressure, mean arterial pressure, portal vein pressure and portal vein flow were recorded at three different flow rates in both a hemodynamic normal state and a setting of increased central venous pressure and right ventricular load, mimicking acute lung injury. RESULTS: Venoarterial ECMO reduced the central venous pressure (CVP( sup)) from 9.4+/-0.8 to 7.3+/-0.7 mmHg (p<0.01) and increased the mean arterial pressure from 103+/-8 to 119+/-10 mmHg (p<0.01) in the normal hemodynamic state. In the state of increased right ventricular load, the CVP(sup) declined from 14.3+/-0.4 to 11.0+/-0.7mmHg (p<0.01) and the mean arterial pressure (MAP) increased from 66+/-6 to 113 +/-5 mmHg (p<0.01). CONCLUSION: Venoarterial ECMO reduces systemic venous pressure while maintaining or improving systemic perfusion in both a normal circulatory state and in the setting of increased right ventricular load associated with acute lung injury. ECMO may be a useful tool in reducing blood loss during major venous hemorrhage in both trauma and selected elective surgery.