ECMO as a bridge to cardiac surgery: stabilizing unstable patients for a definitive procedure.

Introduction: Extracorporeal membrane oxygenation (ECMO) in adults has been used in post-cardiotomy patients who decline hemodynamically. Cardiogenic shock in patients with potential surgically correctable cardiac conditions are at significantly higher risk for post-operative morbidity and mortality. We present experience with a pre-emptive approach of ECMO institution pre-operatively to stabilize patients with cardiogenic shock. Materials and methods: This study expands on a pilot study with a group of twenty patients who were supported with ECMO pre-operatively in different institutions over a period between 2011 and 2021. The patients presented with cardiogenic shock. Peripheral veno-arterial (VA) ECMO support was used in all the patients. Cardiac surgery was performed via median sternotomy utilizing the in situ ECMO cannulae to institute cardiopulmonary bypass (CPB). Results: Seventeen patients were weaned off ECMO support following a mean duration of support of 156 h. Fifteen patients survived to discharge. The 30-day mortality and in-hospital mortality were 25% (expected 67% by European System for Cardiac Operative Risk Evaluation (EuroSCORE) II). The causes of mortality included persistent bleeding in 2 patients due to liver dysfunction, and one with low platelet counts. The other two had multi-organ failure. Conclusions: Variable period of pre-operative ECMO support provides hemodynamic stability and may prevent or reverse the multi-organ dysfunction if instituted on time in patients presenting with cardiogenic shock. This strategy allows cardiac surgery to be performed with acceptable risk.

Projecting Future Climate Impact on National Australian Respiratory-Related Intensive Care Unit Demand.

BACKGROUND AND AIMS: A robust climate-health projection model has the potential to improve health care resource allocation. We aim to explore the relationship between Australian intensive care unit (ICU) demand and various measures of the long-lived large-scale climate and to develop a future nationwide climate-health projection model. METHODS: We investigated patients admitted to ICUs in Australia between January 2003 and December 2019 who were exposed to long-lived large-scale combined climatic measures of temperature and humidity. We analysed the projected demand for respiratory-related ICU average length of stay (in days) per capita (ICUD/C) with four historical and one future projection dataset. These datasets included: i) Australian and New Zealand Intensive Care Society adult patient database, ii) Socioeconomic Data and Applications Center gridded global historical population, iii) Australian Bureau of Statistics national historical population, iv) Japanese 55-year Reanalysis historical climate (JRA55), and v) the fifth Coupled Model Inter-comparison Project future climate projections. RESULTS: 148,638 patients with respiratory issues required intensive care between 2003 and 2019. The annual growth in the population density-weighted wet-bulb-globe temperature-a combined measure of temperature and humidity-is strongly correlated with the annual per capita growth ICUD/C for respiratory-related conditions (r=0.771; p<0.001). This relationship was applied to develop a model projecting future respiratory-related ICU demand with three possible future Representative Concentration Pathways (RCP). RCP2.6 (lowest carbon emission climate scenario) showed only a 33.4% increase in Australian ICUD/C demand by 2090, while the RCP8.5 (highest carbon emission climate scenario) demonstrated almost two-fold higher demand (66.1%) than RCP2.6 by 2090. CONCLUSIONS: The annual growth in population density-weighted wet-bulb-globe temperature correlates with the annual growth in Australian ICUD/C for respiratory-related conditions. A model based on possible future climate scenarios can be developed to predict changes in ICU demand in response to CO2 changes over the coming decades.

Discovery of a Transferrin Receptor 1-Binding Aptamer and Its Application in Cancer Cell Depletion for Adoptive T-Cell Therapy Manufacturing.

The clinical manufacturing of chimeric antigen receptor (CAR) T cells includes cell selection, activation, gene transduction, and expansion. While the method of T-cell selection varies across companies, current methods do not actively eliminate the cancer cells in the patient's apheresis product from the healthy immune cells. Alarmingly, it has been found that transduction of a single leukemic B cell with the CAR gene can confer resistance to CAR T-cell therapy and lead to treatment failure. In this study, we report the identification of a novel high-affinity DNA aptamer, termed tJBA8.1, that binds transferrin receptor 1 (TfR1), a receptor broadly upregulated by cancer cells. Using competition assays, high resolution cryo-EM, and de novo model building of the aptamer into the resulting electron density, we reveal that tJBA8.1 shares a binding site on TfR1 with holo-transferrin, the natural ligand of TfR1. We use tJBA8.1 to effectively deplete B lymphoma cells spiked into peripheral blood mononuclear cells with minimal impact on the healthy immune cell composition. Lastly, we present opportunities for affinity improvement of tJBA8.1. As TfR1 expression is broadly upregulated in many cancers, including difficult-to-treat T-cell leukemias and lymphomas, our work provides a facile, universal, and inexpensive approach for comprehensively removing cancerous cells from patient apheresis products for safe manufacturing of adoptive T-cell therapies.

Cardiology, Research and Training: An Interview With Professor Eugene Braunwald.

Professor Eugene Braunwald, often referred to as the 'Father of Modern Cardiology', has contributed significantly to medicine and cardiology. He is best known for the acclaimed textbook Braunwald's Heart Disease and for being the founding chairman of the Thrombolysis in Myocardial Infarction (TIMI) Study Group. Our primary aim is to highlight his experiences and the guidance that he has to offer to future generations of medical trainees and professionals. An interview with Prof. Braunwald provided the authors with an insight into his journey in medicine. A range of questions were posed pertaining to his struggles and accomplishments in cardiology, his perspectives on the future of cardiology and research, as well as his advice to current and future medical professionals.1 Positive role models are an inspiration to all, regardless of the stage in their career. With hard work, unwavering dedication and a strong desire to make a positive difference to patients and the field, the opportunities are endless. Whether it is clinical or bench research, advances in clinical cardiology and research usually go hand-in-hand. Although primary and secondary prevention of cardiovascular disease remain of critical importance, it is now time to focus on primordial prevention to step back and reduce the development of the risk factors for the future development of cardiovascular disease in the first place. There have been significant advances in cardiology over the past two-thirds of the century during which Prof. Braunwald trained and then led the field. However, there is still much work to be done. Mentors and medical institutions alike must work towards a common goal of 'igniting the fire' within the new generation of clinicians and investigators who will then propel this important specialty to ever greater heights.

Extra corporeal membrane oxygenation (ECMO) as bridge to high-risk cardiac surgery.

Dr. Om Prakash Yadava, CEO and Chief Cardiac Surgeon, National Heart Institute, New Delhi, India, and Editor-in-Chief, Indian Journal of Thoracic and Cardiovascular Surgery, in conversation with Prof. Jai Raman, Professor, Cardiothoracic Surgery at Austin and St. Vincent's Hospitals, Melbourne, Australia, and Oregon Health and Science University, Portland, USA, explore an innovative new concept of supporting and resuscitating the heart on Veno Arterial ECMO before high-risk cardiac surgery in a sick patient.

Radial Artery Patency and Clinical Outcome Study (RAPCOS) Trial.

Dr. O.P. Yadava, CEO and Chief Cardiac Surgeon, National Heart Institute, New Delhi, India, and Editor-in-Chief, Indian Journal of Thoracic and Cardiovascular Surgery, in conversation with Dr. Jai Raman from the University of Melbourne on the Radial Artery Patency and Clinical Outcome (RAPCO) Trial. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12055-020-01111-y.

Detection and Quantification of Myocardial Fibrosis Using Stain-Free Infrared Spectroscopic Imaging.

CONTEXT.­: Myocardial fibrosis underpins a number of cardiovascular conditions and is difficult to identify with standard histologic techniques. Challenges include imaging, defining an objective threshold for classifying fibrosis as mild or severe, and understanding the molecular basis for these changes. OBJECTIVE.­: To develop a novel, rapid, label-free approach to accurately measure and quantify the extent of fibrosis in cardiac tissue using infrared spectroscopic imaging. DESIGN.­: We performed infrared spectroscopic imaging and combined that with advanced machine learning-based algorithms to assess fibrosis in 15 samples from patients belonging to the following 3 classes: (1) patients with nonpathologic (control) donor hearts, (2) patients undergoing transplant, and (3) patients undergoing implantation of a ventricular assist device. RESULTS.­: Our results show excellent sensitivity and accuracy for detecting myocardial fibrosis, as demonstrated by a high area under the curve of 0.998 in the receiver operating characteristic curve measured from infrared imaging. Fibrosis of various morphologic subtypes were demonstrated with virtually generated picrosirius red images, which showed good visual and quantitative agreement (correlation coefficient = 0.92, ρ = 7.76 × 10-15) with stained images of the same sections. Underlying molecular composition of the different subtypes was investigated with infrared spectra showing reproducible differences presumably arising from differences in collagen subtypes and/or crosslinking. CONCLUSIONS.­: Infrared imaging can be a powerful tool in studying myocardial fibrosis and gleaning insights into the underlying chemical changes that accompany it. Emerging methods suggest that the proposed approach is compatible with conventional optical microscopy, and its consistency makes it translatable to the clinical setting for real-time diagnoses as well as for objective and quantitative research.

Long-Term Results of the RAPCO Trials.

BACKGROUND: An internal thoracic artery graft to the left anterior descending artery is standard in coronary bypass surgery, but controversy exists on the best second conduit. The RAPCO trials (Radial Artery Patency and Clinical Outcomes) were designed to compare the long-term patency of the radial artery (RA) with that of the right internal thoracic artery (RITA) and the saphenous vein (SV). METHODS: In RAPCO-RITA (the RITA versus RA arm of the RAPCO trial), 394 patients <70 years of age (or <60 years of age if they had diabetes mellitus) were randomized to receive RA or free RITA graft on the second most important coronary target. In RAPCO-SV (the SV versus RA arm of the RAPCO trial), 225 patients ≥70 years of age (or ≥60 years of age if they had diabetes mellitus) were randomized to receive RA or SV graft. The primary outcome was 10-year graft failure. Long-term mortality was a nonpowered coprimary end point. The main analysis was by intention to treat. RESULTS: In the RA versus RITA comparison, the estimated 10-year patency was 89% for RA versus 80% for free RITA (hazard ratio for graft failure, 0.45 [95% CI, 0.23-0.88]). Ten-year patient survival estimate was 90.9% in the RA arm versus 83.7% in the RITA arm (hazard ratio for mortality, 0.53 [95% CI, 0.30-0.95]). In the RA versus SV comparison, the estimated 10-year patency was 85% for the RA versus 71% for the SV (hazard ratio for graft failure, 0.40 [95% CI, 0.15-1.00]), and 10-year patient survival estimate was 72.6% for the RA group versus 65.2% for the SV group (hazard ratio for mortality, 0.76 [95% CI, 0.47-1.22]). CONCLUSIONS: The 10-year patency rate of the RA is significantly higher than that of the free RITA and better than that of the SV. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00475488.

Association of Radial Artery Graft vs Saphenous Vein Graft With Long-term Cardiovascular Outcomes Among Patients Undergoing Coronary Artery Bypass Grafting: A Systematic Review and Meta-analysis.

Importance: Observational studies have suggested that the use of radial artery grafts for coronary artery bypass grafting may improve clinical outcomes compared with the use of saphenous vein grafts, but this has not been confirmed in randomized trials. Objective: To compare clinical outcomes between patients receiving radial artery vs saphenous vein grafts for coronary artery bypass grafting after long-term follow-up. Design, Setting, and Participants: Patient-level pooled analysis comparing radial artery vs saphenous vein graft in adult patients undergoing isolated coronary artery bypass grafting from 5 countries (Australia, Italy, Serbia, South Korea, and the United Kingdom), with enrollment from 1997 to 2009 and follow-up completed in 2019. Interventions: Patients were randomized to undergo either radial artery (n = 534) or saphenous vein (n = 502) grafts for coronary artery bypass grafting. Main Outcomes and Measures: The primary outcome was a composite of death, myocardial infarction, or repeat revascularization and the secondary outcome was a composite of death or myocardial infarction. Results: A total of 1036 patients were randomized (mean age, 66.6 years in the radial artery group vs 67.1 years in the saphenous vein group; 376 [70.4%] men in the radial artery group vs 351 [69.9%] in the saphenous vein group); 942 (90.9%) of the originally randomized patients completed 10 years of follow-up (510 in the radial artery group). At a median (interquartile range) follow-up of 10 (10-11) years, the use of the radial artery, compared with the saphenous vein, in coronary artery bypass grafting was associated with a statistically significant reduction in the incidence of the composite outcome of death, myocardial infarction, or repeat revascularization (220 vs 237 total events; 41 vs 47 events per 1000 patient-years; hazard ratio, 0.73 [95% CI, 0.61-0.88]; P < .001) and of the composite of death or myocardial infarction (188 vs 193 total events; 35 vs 38 events per 1000 patient-years; hazard ratio, 0.77 [95% CI, 0.63-0.94]; P = .01). Conclusions and Relevance: In this individual participant data meta-analysis with a median follow-up of 10 years, among patients undergoing coronary artery bypass grafting, the use of the radial artery compared with the saphenous vein was associated with a lower risk of a composite of cardiovascular outcomes.

A Systems Approach to Analyzing and Preventing Hospital Adverse Events.

OBJECTIVE: This study aimed to demonstrate the use of a systems theory-based accident analysis technique in health care applications as a more powerful alternative to the chain-of-event accident models currently underpinning root cause analysis methods. METHOD: A new accident analysis technique, CAST [Causal Analysis based on Systems Theory], is described and illustrated on a set of adverse cardiovascular surgery events at a large medical center. The lessons that can be learned from the analysis are compared with those that can be derived from the typical root cause analysis techniques used today. RESULTS: The analysis of the 30 cardiovascular surgery adverse events using CAST revealed the reasons behind unsafe individual behavior, which were related to the design of the system involved and not negligence or incompetence on the part of individuals. With the use of the system-theoretic analysis results, recommendations can be generated to change the context in which decisions are made and thus improve decision making and reduce the risk of an accident. CONCLUSIONS: The use of a systems-theoretic accident analysis technique can assist in identifying causal factors at all levels of the system without simply assigning blame to either the frontline clinicians or technicians involved. Identification of these causal factors in accidents will help health care systems learn from mistakes and design system-level changes to prevent them in the future.

The RADial artery International ALliance (RADIAL) extended follow-up study: rationale and study protocol.

It is generally accepted that radial artery (RA) grafts have better mid-term patency rate compared to saphenous vein grafts. However, the clinical correlates of the improved patency rate are still debated. Observational studies have suggested increased survival and event-free survival for patients who receive an RA rather than a saphenous vein, but they are open to bias and confounders. The only evidence based on randomized data is a pooled meta-analysis of 6 randomized controlled trial comparing the RA and the saphenous vein published by the RADial artery International Alliance (RADIAL). In the RADIAL database, improved freedom from follow-up cardiac events (death, myocardial infarction and repeat revascularization) was found at 5-year follow-up in the RA arm. The most important limitation of the RADIAL analysis is that most of the included trials had an angiographic follow-up in the first 5 years and it is unclear whether the rate of repeat revascularization (the main driver of the composite outcome) was clinically indicated due to per-protocol angiographies. Here, we present the protocol for the long-term analysis of the RADIAL database. By extending the follow-up beyond the 5th postoperative year (all trials except 1 did not have angiographic follow-up beyond 5 years), we aim to provide data on the role of RA in coronary artery bypass surgery with respect to long-term outcomes.