Features and Outcomes of Females and Males Requiring Postcardiotomy Extracorporeal Life Support.

BACKGROUND: Although cardiogenic shock requiring extracorporeal life support (ECLS) after cardiac surgery is associated with high mortality, the impact of sex on outcomes of post-cardiotomy ECLS remains unclear with conflicting results in literature. We compare patient characteristics, in-hospital outcomes, and overall survival between females and males requiring post-cardiotomy ECLS. METHODS: This retrospective, multicentre (34 centres), observational study included adults requiring post-cardiotomy ECLS between 2000 and 2020. Pre-operative, procedural, and ECLS characteristics, complications, and survival were compared between females and males. Association between sex and in-hospital survival was investigated through mixed-Cox proportional hazards models. RESULTS: This analysis included 1823 patients [females:40.8%; median age:66.0 (interquartile range:56.2-73.0 years)]. Females underwent more mitral (females:38.4%, males:33.1%, p=0.019) and tricuspid (females:18%, males:12.4%, p<0.001) valve surgery, while males had more coronary artery surgery (females:45.9%, males:52.4%, p=0.007). ECLS implantation was more common intra-operatively in females (females:64.1%, males:59.1%) and post-operatively in males (females:35.9%, males:40.9%, p=0.036). Ventricular unloading (females:25.1%, males:36.2%, p<0.001) and intra-aortic balloon pump (females: 25.8%, males:36.8%, p<0.001) were most frequently used in males. Females suffered more post-operative right ventricular failure (females:24.1%, males:19.1%, p=0.016) and limb ischemia (females:12.3%, males:8.8%, p=0.23). In-hospital mortality was 64.9% in females and 61.9% in males (p=0.199) with no differences in 5-year survival (females:20%, 95%CI:17-23; males:24%, 95%CI:21-28;p=0.069). Crude hazard ratio for in-hospital mortality in females was 1.12 (95%CI: 0.99-1.27,p=0.069) and did not change after adjustments. CONCLUSIONS: This study demonstrates that females and males requiring post-cardiotomy ECLS have different pre-operative and ECLS characteristics, as well as complications, without a statistical difference in in-hospital and 5-year survival.

Evolution of distal limb perfusion management in adult peripheral venoarterial extracorporeal membrane oxygenation with femoral artery cannulation.

Limb ischaemia is a clinically relevant complication of venoarterial extracorporeal membrane oxygenation (VA ECMO) with femoral artery cannulation. No selective distal perfusion or other advanced techniques were used in the past to maintain adequate distal limb perfusion. A more recent trend is the shift from the reactive or emergency management to the pro-active or prophylactic placement of a distal perfusion cannula to avoid or reduce limb ischaemia-related complications. Multiple alternative cannulation techniques to the distal perfusion cannula have been developed to maintain distal limb perfusion, including end-to-side grafting, external or endovascular femoro-femoral bypass, retrograde limb perfusion (e.g., via the posterior tibial, dorsalis pedis or anterior tibial artery), and, more recently, use of a bidirectional cannula. Venous congestion has also been recognized as a potential contributing factor to limb ischaemia development and specific techniques have been described with facilitated venous drainage or bilateral cannulation being the most recent, to reduce or avoid venous stasis as a contributor to impaired limb perfusion. Advances in monitoring techniques, such as near-infrared spectroscopy and duplex ultrasound analysis, have been applied to improve decision-making regarding both the monitoring and management of limb ischaemia. This narrative review describes the evolution of techniques used for distal limb perfusion during peripheral VA ECMO.

Patient and Management Variables Associated With Survival After Postcardiotomy Extracorporeal Membrane Oxygenation in Adults: The PELS-1 Multicenter Cohort Study.

Background Extracorporeal membrane oxygenation (ECMO) has been increasingly used for postcardiotomy cardiogenic shock, but without a concomitant reduction in observed in-hospital mortality. Long-term outcomes are unknown. This study describes patients' characteristics, in-hospital outcome, and 10-year survival after postcardiotomy ECMO. Variables associated with in-hospital and postdischarge mortality are investigated and reported. Methods and Results The retrospective international multicenter observational PELS-1 (Postcardiotomy Extracorporeal Life Support) study includes data on adults requiring ECMO for postcardiotomy cardiogenic shock between 2000 and 2020 from 34 centers. Variables associated with mortality were estimated preoperatively, intraoperatively, during ECMO, and after the occurrence of any complications, and then analyzed at different time points during a patient's clinical course, through mixed Cox proportional hazards models containing fixed and random effects. Follow-up was established by institutional chart review or contacting patients. This analysis included 2058 patients (59% were men; median [interquartile range] age, 65.0 [55.0-72.0] years). In-hospital mortality was 60.5%. Independent variables associated with in-hospital mortality were age (hazard ratio [HR], 1.02 [95% CI, 1.01-1.02]) and preoperative cardiac arrest (HR, 1.41 [95% CI, 1.15-1.73]). In the subgroup of hospital survivors, the overall 1-, 2-, 5-, and 10-year survival rates were 89.5% (95% CI, 87.0%-92.0%), 85.4% (95% CI, 82.5%-88.3%), 76.4% (95% CI, 72.5%-80.5%), and 65.9% (95% CI, 60.3%-72.0%), respectively. Variables associated with postdischarge mortality included older age, atrial fibrillation, emergency surgery, type of surgery, postoperative acute kidney injury, and postoperative septic shock. Conclusions In adults, in-hospital mortality after postcardiotomy ECMO remains high; however, two-thirds of those who are discharged from hospital survive up to 10 years. Patient selection, intraoperative decisions, and ECMO management remain key variables associated with survival in this cohort. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03857217.

On-Support and Postweaning Mortality in Postcardiotomy Extracorporeal Membrane Oxygenation.

BACKGROUND: Postcardiotomy venoarterial extracorporeal membrane oxygenation (VA ECMO) is characterized by discrepancies between weaning and survival-to-discharge rates. This study analyzes the differences between postcardiotomy VA ECMO patients who survived, died on ECMO, or died after ECMO weaning. Causes of death and variables associated with mortality at different time points are investigated. METHODS: The retrospective, multicenter, observational Postcardiotomy Extracorporeal Life Support Study (PELS) includes adults requiring postcardiotomy VA ECMO between 2000 and 2020. Variables associated with on-ECMO mortality and postweaning mortality were modeled using mixed Cox proportional hazards, including random effects for center and year. RESULTS: In 2058 patients (men, 59%; median age, 65 years; interquartile range [IQR], 55-72 years), weaning rate was 62.7%, and survival to discharge was 39.6%. Patients who died (n = 1244) included 754 on-ECMO deaths (36.6%; median support time, 79 hours; IQR, 24-192 hours), and 476 postweaning deaths (23.1%; median support time, 146 hours; IQR, 96-235.5 hours). Multiorgan (n = 431 of 1158 [37.2%]) and persistent heart failure (n = 423 of 1158 [36.5%]) were the main causes of death, followed by bleeding (n = 56 of 754 [7.4%]) for on-ECMO mortality and sepsis (n = 61 of 401 [15.4%]) for postweaning mortality. On-ECMO death was associated with emergency surgery, preoperative cardiac arrest, cardiogenic shock, right ventricular failure, cardiopulmonary bypass time, and ECMO implantation timing. Diabetes, postoperative bleeding, cardiac arrest, bowel ischemia, acute kidney injury, and septic shock were associated with postweaning mortality. CONCLUSIONS: A discrepancy exists between weaning and discharge rate in postcardiotomy ECMO. Deaths occurred during ECMO support in 36.6% of patients, mostly associated with unstable preoperative hemodynamics. Another 23.1% of patients died after weaning in association with severe complications. This underscores the importance of postweaning care for postcardiotomy VA ECMO patients.

Heterogeneity in Clinical Practices for Post-Cardiotomy Extracorporeal Life Support: a Pilot Survey from the PELS-1 Multicenter Study.

BACKGROUND: High-quality evidence for post-cardiotomy extracorporeal life support (PC-ECLS) management is lacking. This study investigated the real-world PC-ECLS clinical practices. METHODS: This cross-sectional, multi-institutional, international pilot survey explored center organization, anticoagulation management, left ventricular unloading, distal limb perfusion, PC-ECLS monitoring and transfusions practices. Twenty-nine questions were distributed among 34 hospitals participating in the Post-cardiotomy Extra-Corporeal Life Support Study. RESULTS: Of the 32 centers [16 low-volume (50%); 16 high-volume (50%)] that responded, 16 (50%) had dedicated ECLS specialists. Twenty-six centers (81.3%) reported using additional mechanical circulatory supports. Anticoagulation practices were highly heterogeneous: 24 hospitals (75%) reported using patient's bleeding status as a guide, without a specific threshold in 54.2% of cases. Transfusion targets ranged 7-10 g/dL. Most centers used cardiac venting on a case-by-case basis (78.1%) and regular distal limb perfusion (84.4%). Nineteen (54.9%) centers reported dedicated monitoring protocols including daily echocardiography (87.5%), Swan-Ganz catheterization (40.6%), cerebral near-infrared spectroscopy (53.1%) and multimodal assessment of limb ischemia. Inspection of the circuit (71.9%), oxygenator pressure drop (68.8%), plasma free hemoglobin (75%), d-dimer (59.4%), lactate dehydrogenase (56.3%) and fibrinogen (46.9%) are used to diagnose hemolysis and thrombosis. CONCLUSIONS: This study shows remarkable heterogeneity in clinical practices for PC-ECLS management. More standardized protocols and better implementation of available evidence are recommended.

The importance of timing in postcardiotomy venoarterial extracorporeal membrane oxygenation: A descriptive multicenter observational study.

OBJECTIVES: Postcardiotomy extracorporeal membrane oxygenation (ECMO) can be initiated intraoperatively or postoperatively based on indications, settings, patient profile, and conditions. The topic of implantation timing only recently gained attention from the clinical community. We compare patient characteristics as well as in-hospital and long-term survival between intraoperative and postoperative ECMO. METHODS: The retrospective, multicenter, observational Postcardiotomy Extracorporeal Life Support (PELS-1) study includes adults who required ECMO due to postcardiotomy shock between 2000 and 2020. We compared patients who received ECMO in the operating theater (intraoperative) with those in the intensive care unit (postoperative) on in-hospital and postdischarge outcomes. RESULTS: We studied 2003 patients (women: 41.1%; median age: 65 years; interquartile range [IQR], 55.0-72.0). Intraoperative ECMO patients (n = 1287) compared with postoperative ECMO patients (n = 716) had worse preoperative risk profiles. Cardiogenic shock (45.3%), right ventricular failure (15.9%), and cardiac arrest (14.3%) were the main indications for postoperative ECMO initiation, with cannulation occurring after (median) 1 day (IQR, 1-3 days). Compared with intraoperative application, patients who received postoperative ECMO showed more complications, cardiac reoperations (intraoperative: 19.7%; postoperative: 24.8%, P = .011), percutaneous coronary interventions (intraoperative: 1.8%; postoperative: 3.6%, P = .026), and had greater in-hospital mortality (intraoperative: 57.5%; postoperative: 64.5%, P = .002). Among hospital survivors, ECMO duration was shorter after intraoperative ECMO (median, 104; IQR, 67.8-164.2 hours) compared with postoperative ECMO (median, 139.7; IQR, 95.8-192 hours, P < .001), whereas postdischarge long-term survival was similar between the 2 groups (P = .86). CONCLUSIONS: Intraoperative and postoperative ECMO implantations are associated with different patient characteristics and outcomes, with greater complications and in-hospital mortality after postoperative ECMO. Strategies to identify the optimal location and timing of postcardiotomy ECMO in relation to specific patient characteristics are warranted to optimize in-hospital outcomes.

The Relation Between Obesity and Mortality in Postcardiotomy Venoarterial Membrane Oxygenation.

BACKGROUND: Obesity is an important health problem in cardiac surgery and among patients requiring postcardiotomy venoarterial extracorporeal membrane oxygenation (V-A ECMO). Still, whether these patients are at risk for unfavorable outcomes after postcardiotomy V-A ECMO remains unclear. The current study evaluated the association between body mass index (BMI) and in-hospital outcomes in this setting. METHODS: The Post-cardiotomy Extracorporeal Life Support (PELS-1) study is an international, multicenter study. Patients requiring postcardiotomy V-A ECMO in 36 centers from 16 countries between 2000 and 2020 were included. Patients were divided in 6 BMI categories (underweight, normal weight, overweight, class I, class II, and class III obesity) according to international recommendations. Primary outcome was in-hospital mortality, and secondary outcomes included major adverse events. Mixed logistic regression models were applied to evaluate associations between BMI and mortality. RESULTS: The study cohort included 2046 patients (median age, 65 years; 838 women [41.0%]). In-hospital mortality was 60.3%, without statistically significant differences among BMI classes for in-hospital mortality (P = .225) or major adverse events (P = .126). The crude association between BMI and in-hospital mortality was not statistically significant after adjustment for comorbidities and intraoperative variables (class I: odds ratio [OR], 1.21; 95% CI, 0.88-1.65; class II: OR, 1.45; 95% CI, 0.86-2.45; class III: OR, 1.43; 95% CI, 0.62-3.33), which was confirmed in multiple sensitivity analyses. CONCLUSIONS: BMI is not associated to in-hospital outcomes after adjustment for confounders in patients undergoing postcardiotomy V-A ECMO. Therefore, BMI itself should not be incorporated in the risk stratification for postcardiotomy V-A ECMO.

The Role of Monoclonal Antibodies in the Treatment of Atherosclerosis.

Atherosclerosis is an inflammatory disease that involves antibody immune responses. Progression of hyperlipidemia can lead to atherosclerosis and subsequently cardiovascular diseases with high mortality. Additional lipid-lowering therapies other than statins are currently being studied, such as monoclonal antibodies. In this contemporary review, we examine the various monoclonal antibody therapies targeted toward atherosclerotic disease.

An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients.

Background: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. Methods: Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. Results: Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61-0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. Conclusions: Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome. Funding: Bronner P. Gonçalves, Peter Horby, Gail Carson, Piero L. Olliaro, Valeria Balan, Barbara Wanjiru Citarella, and research costs were supported by the UK Foreign, Commonwealth and Development Office (FCDO) and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z]; and Janice Caoili and Madiha Hashmi were supported by the UK FCDO and Wellcome [222048/Z/20/Z]. Peter Horby, Gail Carson, Piero L. Olliaro, Kalynn Kennon and Joaquin Baruch were supported by the Bill & Melinda Gates Foundation [OPP1209135]; Laura Merson was supported by University of Oxford's COVID-19 Research Response Fund - with thanks to its donors for their philanthropic support. Matthew Hall was supported by a Li Ka Shing Foundation award to Christophe Fraser. Moritz U.G. Kraemer was supported by the Branco Weiss Fellowship, Google.org, the Oxford Martin School, the Rockefeller Foundation, and the European Union Horizon 2020 project MOOD (#874850). The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission. Contributions from Srinivas Murthy, Asgar Rishu, Rob Fowler, James Joshua Douglas, François Martin Carrier were supported by CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and coordinated out of Sunnybrook Research Institute. Contributions from Evert-Jan Wils and David S.Y. Ong were supported by a grant from foundation Bevordering Onderzoek Franciscus; and Andrea Angheben by the Italian Ministry of Health "Fondi Ricerca corrente-L1P6" to IRCCS Ospedale Sacro Cuore-Don Calabria. The data contributions of J.Kenneth Baillie, Malcolm G. Semple, and Ewen M. Harrison were supported by grants from the National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC_PC_19059), and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE) (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support. All funders of the ISARIC Clinical Characterisation Group are listed in the appendix.

Improving Extracorporeal Membrane Oxygenation Survival in COVID-19. Effect of a Bundle of Care.

Veno-venous extracorporeal membrane oxygenation (ECMO) support surged during the COVID-19 pandemic. Our program changed the model of care pursuing to protect the multidisciplinary team from the risk of infection and to serve as many patients as possible. Patient-healthcare interactions were restricted, and the ECMO bed capacity was increased by reducing the ECMO specialist-patient ratio to 1:4 with non-ECMO trained nurses support. The outcomes worsened and we paused while we evaluated and modified our model of care. The ECMO bed capacity was reduced to allow a nurse ECMO-specialist nurse ratio 2:1 with an ECMO trained nurse assistant's support. Intensivists, general practitioners, nurse assistants, and physical and respiratory therapists were trained on ECMO. Tracheostomy, bronchoscopy, and microbiological molecular diagnosis were done earlier, and family visits and rehabilitation were allowed in the first 48 hours of ECMO cannulation. There were 35 patients in the preintervention cohort and 66 in the postintervention cohort. Ninety days mortality was significantly lower after the intervention (62.9% vs. 31.8%, p = 0.003). Factors associated with increased risk of death were the need for cannulation or conversion to veno arterial or veno arterio venous ECMO, hemorrhagic stroke, and renal replacement therapy during ECMO. The interventions associated with a decrease in the risk of death were the following: early fiberoptic bronchoscopy and microbiological molecular diagnostic tests. Increasing the ECMO multidisciplinary team in relation to the number of patients and the earlier performance of diagnostic and therapeutic interventions, such as tracheostomy, fiberoptic bronchoscopy, molecular microbiological diagnosis of pneumonia, rehabilitation, and family support significantly decreased mortality of patients on ECMO due to COVID-19.

Coronary Artery Disease and Aspirin Intolerance: Background and Insights on Current Management.

Aspirin is one of the most widely used medications across the global healthcare system and is the foundation in treating ischemic heart disease, as well as secondary prevention for ischemic and valvular heart disease. Challenges arise in treating patients with cardiovascular disease who have concomitant aspirin intolerance. Through an extensive review of the literature, we provide a comprehensive background on the pharmacology of aspirin, the mechanisms behind aspirin intolerance, the importance of aspirin in cardiovascular disease, and the management of aspirin intolerance in both acute coronary syndrome and stable coronary artery disease. Our review includes a multidisciplinary approach from the internist, allergist/immunologist, and cardiologist when evaluating this important patient population.

Somatic Support with Veno-venous ECMO in a Pregnant Woman with Brain Death: A Case Report.

Supporting homeostasis in a pregnant woman with brain death to achieve fetal viability is called somatic support. We present a case of young pregnant woman at 21 weeks' gestation who developed acute respiratory distress syndrome secondary to influenza A H2N3 infection requiring veno-venous extracorporeal membrane oxygenation (VV ECMO) support for refractory hypoxemia. The clinical course was complicated by intracranial hemorrhage and subsequent brain death. After multidisciplinary team discussion with her family, consensus was reached to continue somatic support with VV ECMO to enable fetal development to attain extrauterine viability. The challenging clinical, ethical, and legal concerns are discussed.

An Uncharacteristic Presentation of Evans Syndrome Following Treatment With Dupilumab.

Evans syndrome is a rare autoimmune disorder where patients develop autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and less commonly immune neutropenia. Patients typically present with fatigue, pallor, jaundice, petechiae, or epistaxis. A 27-year-old man with a history of atopic dermatitis for which he recently began treatment with dupilumab presented to the emergency department with a headache and blurry vision. Multiple Roth spots were seen on fundoscopic examination. Laboratory studies were consistent with warm AIHA, confirmed by a positive direct antiglobulin test (DAT), and severe thrombocytopenia. He was diagnosed with Evans syndrome. He was treated with corticosteroids, rituximab, and intravenous immunoglobulin (IVIG). His recovery was prolonged with the slow improvement of anemia and thrombocytopenia. This is an atypical presentation of Evans syndrome with isolated symptoms of new-onset blurry vision and headache along with the finding of Roth spots. Another interesting feature in the case is the recent use of dupilumab. Dupilumab is a monoclonal antibody that inhibits the T-helper cells type 2 (Th2) signaling pathway by blocking interleukin (IL)-4 and IL-13 binding. This alteration in the immune response could have a role in the development of Evans syndrome.

Extracorporeal Membrane Oxygenation for COVID-19: Updated 2021 Guidelines from the Extracorporeal Life Support Organization.

DISCLAIMER: This is an updated guideline from the Extracorporeal Life Support Organization (ELSO) for the role of extracorporeal membrane oxygenation (ECMO) for patients with severe cardiopulmonary failure due to coronavirus disease 2019 (COVID-19). The great majority of COVID-19 patients (>90%) requiring ECMO have been supported using venovenous (V-V) ECMO for acute respiratory distress syndrome (ARDS). While COVID-19 ECMO run duration may be longer than in non-COVID-19 ECMO patients, published mortality appears to be similar between the two groups. However, data collection is ongoing, and there is a signal that overall mortality may be increasing. Conventional selection criteria for COVID-19-related ECMO should be used; however, when resources become more constrained during a pandemic, more stringent contraindications should be implemented. Formation of regional ECMO referral networks may facilitate communication, resource sharing, expedited patient referral, and mobile ECMO retrieval. There are no data to suggest deviation from conventional ECMO device or patient management when applying ECMO for COVID-19 patients. Rarely, children may require ECMO support for COVID-19-related ARDS, myocarditis, or multisystem inflammatory syndrome in children (MIS-C); conventional selection criteria and management practices should be the standard. We strongly encourage participation in data submission to investigate the optimal use of ECMO for COVID-19.

Survival after heart transplantation for Chagas cardiomyopathy using a conventional protocol: A 10-year experience in a single center.

BACKGROUND: Heart transplant (HT) remains the most frequently indicated therapy for patients with end-stage heart failure that improves prognosis in Chagas cardiomyopathy (CCM). However, the lack of benznidazole therapy and availability of RT-PCR follow-up in many centers is a major limitation to perform this life-saving intervention, as there are concerns related with the risk of reactivation. We aimed to describe the outcomes of a cohort of patients with CCM who underwent HT using a conventional protocol with mycophenolate mofetil, without benznidazole prophylaxis or RT-PCR follow-up. METHODS: Retrospective cohort study. Between 2008 and 2018, 43 patients with CCM underwent HT. A descriptive analysis to characterize outcomes as rejection, infectious and neoplastic complications and a survival analysis was carried out. RESULTS: Median of follow-up was 4.3 (IR 4.28) years. Survival at 1 month, 1 year, and 5 years was 95%, 85%, and 75%, respectively, infections being the main cause of death (60%). Reactivations occurred in only three patients (7.34%) and were not related to mortality. CONCLUSION: This cohort showed a favorable survival and a low reactivation rate without an impact on mortality. Our results suggest that performing HT in patients with CCM following conventional guidelines and recommendations for other etiologies is a safe approach.