Growing Evidence for LV Unloading in VA ECMO

Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) is a means of supporting the lungs or the heart and lungs in patients with hemodynamic compromise that is refractory to conventional measures. VA-ECMO is most commonly deployed in a percutaneous fashion with femoral arterial and venous access. While VA-ECMO, particularly in a femoral-femoral configuration, provides both hemodynamic and ventilatory support, it also causes increased afterload on the left ventricle (LV) which in turn may result in LV distension (LVD). LV thrombus formation, ventricular arrhythmias, pulmonary edema, and pulmonary hemorrhage are clinical manifestations of LVD. LV unloading is a means of preventing LVD and its sequelae. If less invasive methods fail to achieve adequate LV unloading, invasive mechanical methods are pursued such as intra-aortic balloon pump counter-pulsation, atrial septostomy, surgical venting, left atrial cannulation, and percutaneous transvalvular micro-axial pump placement. We sought to review indicators of LVD, thresholds, and options for mechanical venting strategies. A Pubmed search was performed to identify current literature about LV unloading for VA ECMO. This was categorized and summarized to determine commonly reported thresholds for mechanical LV unloading. Multiple physiologic and radiographic indicators were reported without uniformity. Common indicators included increased pulmonary artery catheter pressures, decreased Aortic Line Pulse Pressure, as well as multiple Echocardiographic, and radiographic indicators. Although there has been significant interest in the topic, there is currently limited uniformity in thresholds for when to initiate and escalate mechanical LV unloading. While the method of LV unloading is an active area of investigation, the threshold for which to initiate invasive venting strategies is largely unexplored.

The Hole of Hope: Balloon Atrial Septostomy for Left Ventricle Unloading during VA ECMO

Mammalian heart development requires precise allocation of cardiac progenitors. The existence of a multipotent progenitor for all anatomic and cellular components of the heart has been predicted but its identity and contribution to the two cardiac progenitor ‘fields’ has remained undefined. Here we show, using clonal genetic fate mapping, that Mesp1+ cells in gastrulating mesoderm are rapidly specified into committed cardiac precursors fated for distinct anatomic regions of the heart. We identify Smarcd3 as a marker of early specified cardiac precursors and identify within these precursors a compartment boundary at the future junction of the left and right ventricles that arises prior to morphogenesis. Our studies define the timing and hierarchy of cardiac progenitor specification and demonstrate that the cellular and anatomical fate of mesoderm-derived cardiac cells is specified very early. These findings will be important to understand the basis of congenital heart defects and to derive cardiac regeneration strategies.DOI: http://dx.doi.org/10.7554/eLife.03848.001

Left ventricular (LV) unloading has been shown to improve survival for patients requiring veno-arterial extracorporeal membrane oxygenation (VA ECMO) support for cardiogenic shock. A mortality benefit has been shown for ECMO and concomitant placement of a transcatheter unloading LV pump such as an Impella device (colloquially referred to as ECPELLA or ECMELLA) for patients resuscitated with VA ECMO after a short period of cardiac arrest. Despite the described benefit of LV unloading with VA ECMO for cardiopulmonary resuscitation, it remains unclear as to what criteria should be used and what other diagnostic and therapeutic adjuncts may be useful. We describe here the successful utilization of concomitant VA ECMO and Impella in a 43 year old male with acute heart failure and cardiac arrest. Distinguishing itself from the currently reported methods, our methodology incorporates transesophageal echocardiography (TEE) in the emergency department for rapid decision-making in addition to an automatic chest compression device, the Lund University Cardiac Assist System (LUCAS) device (Stryker, Portage, MI) as a bridge to LV unloading in a hybrid operating suite.

Despite advances in reperfusion times, patients presenting with acute myocardial infarction carry an unacceptably high rate of mortality and morbidity. Mechanical unloading of the left ventricle (LV) has been suggested to reduce infarct size after acute myocardial infarction. Although prior studies have investigated LV unloading during ischemia with a delay in reperfusion, little is known about the optimal timing for LV unloading in the setting of acute myocardial infarction. Studies were conducted in 17 adult Yorkshire swine weighing 67±5 kg. A coronary balloon was inflated in the mid left anterior descending for 60 minutes to induce a myocardial infarction. The coronary balloon was then deflated for 120 minutes (reperfusion). The animals were stratified into 3 groups: group 1 (control, reperfusion with no LV unloading, n=5), group 2 (LV unloading during ischemia with delayed reperfusion, n=6), and group 3 (simultaneous LV unloading and reperfusion, n=6). Staining the hearts with Evans blue and 2,3,5-triphenyltetrazolium chloride was used to identify the area at risk and the infarct area respectively. Infarct percent size was defined as the area of infarcted myocardium divided by the area at risk. Of the 3 groups, group 3 demonstrated significantly smaller infarct percent size compared with controls (54.7±20.3% versus 22.2±13.4%; P=0.03). Comparison between group 1 and group 2 did not reveal significant difference (54.7±20.3% versus 43.3±24.6%; P=0.19). In our large animal experimental model, simultaneous reperfusion and mechanical LV unloading yielded the smallest infarct size compared with no LV unloading or LV unloading with delayed reperfusion. In the context of prior studies showing benefit to unloading before reperfusion, these findings raise questions about how this strategy may be translated to humans.

Regional Differences of Gene Expression in Human and Rodent Heart

Venoarterial extracorporeal membrane oxygenation (VA ECMO) is an established method of short-term mechanical support for patients in cardiogenic shock, but can create left ventricular (LV) distension. This paper analyzes the physiologic basis of this phenomenon and treatment methods. This is a retrospective review of the existing literature on VA ECMO and LV distension. We undertook a PubMed review of all peer-reviewed papers focusing on VA ECMO, LV distension, and LV venting. We reviewed these papers and synthesized our findings. We also will discuss the various methods of LV venting and venting strategies we use at Columbia. LV distension is becoming an increasingly appreciated aspect of caring for patients on VA ECMO support. The literature demonstrates that the consequences of failing to anticipate, recognize, and treat LV distension are grave, and will worsen an already distended and hypocontractile LV. Myocardial recovery will be hindered, and LV thrombus formation more likely. Early recognition and aggressive management of LV distension is paramount in helping care for this critically ill patient population.

BackgroundVenoarterial extracorporeal membrane oxygenation (VA ECMO) is a critical therapeutic intervention that is commonly used in the management of paediatric patients with congenital heart disease (CHD). This procedure can be initiated either inraoperatively or postoperatively. However, few studies have reported data on the comparative clinical outcomes associated with different timings of VA ECMO initiation. In this study, patient characteristics and clinical outcomes between intraoperative and postoperative VA ECMO in infants undergoing cardiac surgery were compared and predictors of ECMO initiation were determined, which may improve clinical outcomes.MethodsA total of 47 infants who received postcardiotomy VA ECMO support from September 2019 to December 2023 were included in this retrospective, single-centre observational study. Patients who received VA ECMO support in the operating room (intraoperative, n = 27) were compared with those who received it in the intensive care unit (postoperative, n = 20). Kaplan‒Meier curves were further analysed for survival and perioperative factors were evaluated to predict VA ECMO initiation.ResultsSurvival rates were greater in the intraoperative group (70.37% vs. 25%; P = 0.002), with a reduced risk of mortality (HR: 2.84; 95% CI: 1.23–6.55). The intraoperative group also had a higher ECMO weaning rate (88.89% vs. 45%, P < 0.001) and shorter VA ECMO duration (5.00 ± 1.80 days vs. 7.50 ± 2.76 days; P < 0.001). Continuous renal replacement therapy (CRRT) was needed in 100% of postoperative patients versus 70.40% of intraoperative patients (P = 0.014). The combination of preoperative lactate ≥ 6.495 mmol/L and cardiopulmonary bypass (CPB) time ≥ 138 min predicted the need for intraoperative VA ECMO [AUC (area under the curve): 0.893 (95% CI: 0.805–0.980, P < 0.001)].ConclusionsCompared with postoperative VA ECMO, the use of Intraoperative VA ECMO might improve clinical outcomes in infants undergoing cardiac surgery, highlighting the potential benefits of early intervention. The significant predictive value of the CPB time and preoperative lactate level may inform future clinical practices regarding the timing of ECMO initiation in paediatric patients postcardiotomy.

<i>Circulation: Cardiovascular Interventions</i> Editors’ Picks

Introduction: The extent that left atrium (LA) functional remodeling is impacted by left ventricle (LV) systolic function or clinical history in patients with chronic heart failure (HF) is unresolved. Cardiac imaging and plasma biomarkers may provide valuable information in this regard. Hypothesis: Elastic and active contributions to LV stroke volume (LV SV) are variable, independent of LV systolic function and reflected in natriuretic peptide measurements. Methods: We recruited 27 controls without overt cardiovascular disease and 68 patients with moderate HF, including preserved and reduced LV ejection fraction (LVEF). Cardiac MRI was used to evaluate LV volumes at end diastole and end systole, and LA volumes at end diastole, diastasis and end systole to determine passive and active volume changes. Plasma mid-region pro-atrial and N-terminal pro-brain natriuretic peptides (MR-proANP and NT-proBNP, respectively) were measured. Results: Elastic LA contribution to LV SV was significantly lower in HF (median, IQR: 14%, 8-23%) than controls (24%, 17-30%; p=0.001), but active contribution was not (23%, 0-34% vs 24%, 21-31%; p=0.163). In patients with HF, active LA contribution to LV SV was negatively associated with history of hypertension (β=-0.41, p=0.007) and positively associated with aging (β=0.40, p=0.008) in a multiple linear regression model. Seven of nine subjects with HF and a history of atrial fibrillation (AF), but in sinus rhythm (SR) on the day of study, had active LA contributions to LV SV &gt;15%. Increased LA volume at end diastole (β=0.51, p=0.001) and LVEF (β=-0.33, p=0.008) were independently associated with NT-proBNP (β=0.51, p=0.001) in a model that included age and history of AF. Similarly, LA volume at end diastole (β=0.48, p=0.001) was independently associated with MR-proANP in a model that included age and history of AF. Notably, natriuretic propeptides were not associated with elastic or active LA contributions to LV SV. Conclusions: Heart failure is characterized by preserved LA active contribution to LV SV, regardless of LVEF, which increases with age, and is modifiable by hypertension and AF. Imaging-based assessment can elucidate the contribution of LA function in HF and may provide insight into the impact of AF in patients with HF.

Peripheral veno-arterial extracorporeal membrane oxygenation (VA ECMO) exposes the patient to a pulmonary blood flow bypass and a left ventricle afterload increase. Impella, a catheter-mounted microaxial rotary pump, has been proposed for left ventricle (LV) unloading in combination with VA ECMO. In order to assess the effect of Impella on pulmonary flow and LV preload, we checked Doppler pulmonary artery velocity-time integral (pVTI) and LV diastolic diameter (LVED) by transesophageal echocardiography and end-tidal carbon dioxide (EtCO2) during a step-by-step increase in Impella flow (Impella ramp test). From 134 patients on VA ECMO retrieved from our database, 27 (20%) have benefited secondary Impella implantation, out of which 11 patients had available EtCO2, pVTI, and LVED measurements at various levels of Impella speeds. We observed a proportional increases in pVTI and EtCO2 and decrease in LVED (p ≤ 0.001) during Impella flow increase. There was a significant correlation between EtCO2 and pVTI (Pearson correlation coefficient 0.64; p = 0.006). The study shows that Impella improves pulmonary flow, an effect that can be easily measured by EtCO2 monitoring, and ensures LV discharge, allowing adapting Impella flow adequately to patient's individual needs.

BackgroundPercutaneous mechanical circulatory support (MCS), such as the Impella heart pump is a valuable option for cardiogenic shock (CS), although the use of Impella in CS due to peripartum cardiomyopathy (PPCM) is limited.ObjectiveTo assess outcomes in women with PPCM supported with an Impella device from the global catheter‐based ventricular assist device (cVAD) Registry.Methods and ResultsA total of 15 women with PPCM supported with Impella devices between November 2008 and October 2015 were included. Of the 15 women, five were treated at Hannover medical school and have been reported previously, the rest were managed at various US hospitals. The mean age was 30.0 ± 7.34 years, eight women were Caucasian, and seven were African‐American. The occurrence of PPCM was post‐delivery in eight (53.3%), at delivery in one (6.7%), and during gestation in four women (26.7%). At admission, all women had severe heart failure with a mean ejection fraction of 14.7 ± 6% and 13 women (86.7%) presented with CS. Prior to Impella, 100% were mechanically ventilated, 79% received inotropes/vasopressors, 20% supported with IABP, and 27% received veno‐arterial extracorporeal membrane oxygenation (VA ECMO) during Impella support. Two women (13.3%) died, and 13 (87.7%) survived to discharge. Eight women (53.3%) had a recovery of native heart function and six (40%) were bridged to durable left ventricular assist device (LVAD).ConclusionMCS with Impella devices can be successfully used as a bridge to early improvement, heart recovery, or successful implantation of durable LVAD in women with PPCM complicated by severe LV dysfunction.

Repair of Infracardiac Total Anomalous Pulmonary Venous Return

Background Aortic stenosis (AS) results in high pressure afterload causing detrimental effect especially on the left chambers. Structural and functional changes of the left ventricle (LV) usually corresponds to concomitant remodelling of the left atrium (LA). However, how this pressure afterload specifically affects LA function and whether the study of LA function could help in stratifying patients with different degree of AS it is not known. Purpose We aim to evaluate the differences in LA and LV function according different degree of AS by standard and speckle tracking echocardiographic. Methods From January 2016 to May 2018 we recruited 135 patients referring to our echo-lab with diagnosis of AS (mean age 79.5±4.4; 60/55% female). We divided this population according to AS severity in patients with moderate AS, severe asymptomatic and severe symptomatic AS and matched with 35 control group with no aortic stenosis (n=45, mean age: 77.6±4.5). All patients underwent standard and 2-dimensional speckle tracking echocardiography computing global longitudinal strain (GLS) of LV and peak atrial strain of LA (PALS). Results In all patients PALS was a good predictor of E/e' ratio after correction for LV EF and age (p&lt;0.001, β: −0.48). LVEF and GLS progressively decreased together with worsening of AS degree, as well as parameters of geometry and function of LA (Table1). By excluding patients with LV dysfunction the reduction gradient of parameters of LA geometry and function was still present. However, when severe symptomatic with asymptomatic severe AS are compared, no difference in E/e' ratio was found while both GLS and PALS were significantly reduced (both p&lt;0.0001). Variables Overall population (180) Control (45) Moderate AS (45) Severe asympt AS (45) Severe sympt. AS (45) p LVEF 65.0±11.1 67.7±5.6 69.4±8.5 66.1±10.7 59.5±13.5 0.0001 GLS −20.4±4.1 −23.1±2.4 −21.5±2.9 −21.4±3.2 −17.1±4.3 0.0001 LA vol index 41.6±21.5 28.2±10.4 40.1±19.7 39.8±16.7 52.3±24.9 0.0001 LA strain 23.6±10.9 30.8±10.3 27.8±9.2 24.4±9.7 15.2±7.1 0.0001 LA reservoir 46.4±15.9 51.9±11.5 53.0±15.0 48.3±14.1 37.2±16.1 0.0001 Ee' ratio 14.8±7.0 9.6±2.7 13.7±6.3 15.4±6.2 19.3±7.2 0.0001 Conclusions LA function seems to progressively decrease according to the degree of AS, independently from LV function. Significant difference was found between parameters of LA remodelling and dysfunction between symptomatic and asymptomatic AS patients. The assessment of LA function by strain may help stratify the patients with AS, identifying those who need intensive medical/surgical treatment.

Background: The blood flow from pulmonary veins (PVs) to left ventricle (LV) through left atrium (LA) changes under various conditions, and affects global cardiac function and thrombogenesis. We aimed to clarify the velocity vectors in LA and the blood particles movement from PVs to LV using 4D-Flow MRI. Methods: Thirty two patients with and without organic heart diseases (59±14 years, mean±SD) underwent 4D-Flow with routine MRI and echocardiography. We set a plane traversing each exit of PV, and the velocity vectors in LA were post-processed to delineate streamline images (Fig. A). The percentage of blood particles that reached LV (%LV particles) was also analyzed during a cardiac cycle (Fig. B: initial phase and Fig. C: last phase). Results: (1) The streamline images revealed intra-LA vortex formation in 20 patients but did not in 12 patients. All the vortices showed characteristic counter-clockwise flow patterns in the cranial view. (2) The LV end-diastolic and end-systolic volume, and the LA volume were less in patients with vortex than in those without vortex (104±34 vs. 155±67 ml, 46±28 vs. 88±59 ml, and 41±19 vs. 75±31 ml, p<0.01, respectively). (3) The %LV particles in patients with vortex was higher than that in patients without vortex (14% vs. 2%, medians, p<0.01). The %LV particles from right PVs was also higher than that from left PVs in patients with vortex (22% vs. 5%, p<0.01), whereas it did not differ in patients without vortex (2% vs. 0%, p=ns). ![Figure][1] Conclusions: 4D-Flow MRI can visualize the intra-LA vortex formation and flow dynamics from PVs to LV. The vortex formation may be dependent on the LV and LA volume, and may affect the flow dynamic from PVs to LV. The blood flow from left PVs seems to be more stagnant within LA than that from right PVs. [1]: pending:yes