Independent External Validation of a Preoperative Prediction Model for Delirium After Cardiac Surgery: A Prospective Observational Cohort Study

Objective: This investigation provided independent external validation of an existing preoperative risk prediction model. Design: A prospective observational cohort study of patients undergoing cardiac surgery covering the period between April 16, 2018 and January 18, 2022. Setting: Two academic hospitals in Switzerland. Participants: Adult patients (≥60 years of age) who underwent elective cardiac surgery, including coronary artery bypass graft, mitral or aortic valve replacement or repair, and combined procedures. Interventions: None. Measurements and main results: The primary outcome measure was the incidence of postoperative delirium (POD) in the intensive or intermediate care unit, diagnosed using the Intensive Care Delirium Screening Checklist. The prediction model contained 4 preoperative risk factors to which the following points were assigned: Mini-Mental State Examination (MMSE) score ≤23 received 2 points; MMSE 24-27, Geriatric Depression Scale (GDS) >4, prior stroke and/or transient ischemic attack (TIA), and abnormal serum albumin (≤3.5 or ≥4.5 g/dL) received 1 point each. The missing data were handled using multiple imputation. In total, 348 patients were included in the study. Sixty patients (17.4%) developed POD. For point levels in the prediction model of 0, 1, 2, and ≥3, the cumulative incidence of POD was 12.6%, 22.8%, 25.8%, and 35%, respectively. The validation resulted in a pooled area under the receiver operating characteristics curve of 0.60 (median CI, 0.525-0.679). Conclusions: The evaluated predictive model for delirium after cardiac surgery in this patient cohort showed only poor discriminative capacity but fair calibration. Keywords: External validation; cardiac surgery; delirium; predictio

Prior intake of new oral anticoagulants adversely affects outcome following surgery for acute type A aortic dissection

Objectives: Oral anticoagulation prior to emergency surgery is associated with an increased risk of perioperative bleeding, especially when this therapy cannot be discontinued or reversed in time. The goal of this study was to analyse the impact of different oral anticoagulants on the outcome of patients who underwent emergency surgery for acute type A aortic dissection (ATAAD). Methods: This was a single-centre retrospective study of patients treated with oral anticoagulation at the time of surgery for ATAAD. Outcomes of patients on new oral anticoagulant (NOAC) therapy were compared to respective outcomes of patients on Coumadin. Additionally, a survival analysis was performed comparing these 2 groups with patients who were operated on with no prior anticoagulation. Results: Between January 2013 and April 2020, a total of 437 patients (63.8 ± 11.8 years, 68.4% male) received emergency surgery for ATAAD; 35 (8%) were taking oral anticoagulation at the time of hospital admission: 20 received phenprocoumon; 14, rivaroxaban; and 1, dabigatran. Compared to Coumadin, NOAC was associated with a greater need for blood-product transfusions and haemodynamic compromise. Operative mortality was 53% in the NOAC group and 30% in the Coumadin group. A 5-year survival analysis showed no significant difference between the NOAC and the Coumadin group (P = 0.059). Compared to 402 patients treated during the study period without anticoagulation, patients taking NOAC had significantly worse survival (P = 0.001), whereas that effect was not observed in patients undergoing surgery who were taking Coumadin (P = 0.99). Conclusions: Emergency surgery for ATAAD in patients taking NOAC is associated with high morbidity and mortality. NOAC are a major risk factor for uncontrollable bleeding and haemodynamic compromise. New treatment strategies must be defined to improve surgical outcomes in these high-risk patients. Keywords: Acute aortic syndrome; Aortic dissection; Bleeding; Coumadin; DOAC; NOAC; Oral anticoagulation; Type A dissection

Short-Term Therapies for Treatment of Acute and Advanced Heart Failure—Why so Few Drugs Available in Clinical Use, Why Even Fewer in the Pipeline?

Both acute and advanced heart failure are an increasing threat in term of survival, quality of life and socio-economical burdens. Paradoxically, the use of successful treatments for chronic heart failure can prolong life but—per definition—causes the rise in age of patients experiencing acute decompensations, since nothing at the moment helps avoiding an acute or final stage in the elderly population. To complicate the picture, acute heart failure syndromes are a collection of symptoms, signs and markers, with different aetiologies and different courses, also due to overlapping morbidities and to the plethora of chronic medications. The palette of cardio- and vasoactive drugs used in the hospitalization phase to stabilize the patient’s hemodynamic is scarce and even scarcer is the evidence for the agents commonly used in the practice (e.g., catecholamines). The pipeline in this field is poor and the clinical development chronically unsuccessful. Recent set backs in expected clinical trials for new agents in acute heart failure (AHF) (omecamtiv, serelaxine, ularitide) left a field desolately empty, where only few drugs have been approved for clinical use, for example, levosimendan and nesiritide. In this consensus opinion paper, experts from 26 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, The Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, U.K. and Ukraine) analyse the situation in details also by help of artificial intelligence applied to bibliographic searches, try to distil some lesson-learned to avoid that future projects would make the same mistakes as in the past and recommend how to lead a successful development project in this field in dire need of new agents

Short-Term Therapies for Treatment of Acute and Advanced Heart Failure—Why so Few Drugs Available in Clinical Use, Why Even Fewer in the Pipeline?

Both acute and advanced heart failure are an increasing threat in term of survival, quality of life and socio-economical burdens. Paradoxically, the use of successful treatments for chronic heart failure can prolong life but—per definition—causes the rise in age of patients experiencing acute decompensations, since nothing at the moment helps avoiding an acute or final stage in the elderly population. To complicate the picture, acute heart failure syndromes are a collection of symptoms, signs and markers, with different aetiologies and different courses, also due to overlapping morbidities and to the plethora of chronic medications. The palette of cardio- and vasoactive drugs used in the hospitalization phase to stabilize the patient’s hemodynamic is scarce and even scarcer is the evidence for the agents commonly used in the practice (e.g., catecholamines). The pipeline in this field is poor and the clinical development chronically unsuccessful. Recent set backs in expected clinical trials for new agents in acute heart failure (AHF) (omecamtiv, serelaxine, ularitide) left a field desolately empty, where only few drugs have been approved for clinical use, for example, levosimendan and nesiritide. In this consensus opinion paper, experts from 26 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, The Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, U.K. and Ukraine) analyse the situation in details also by help of artificial intelligence applied to bibliographic searches, try to distil some lesson-learned to avoid that future projects would make the same mistakes as in the past and recommend how to lead a successful development project in this field in dire need of new agents

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and non-cardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, UK and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute heart failure arena in recent times and charts a possible development trajectory for the next 20 years

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Is our heart a well-designed pump? The heart along animal evolution

A carrier system for gases and nutrients became mandatory when primitive animals grew larger and developed different organs. The first circulatory systems are peristaltic tubes pushing slowly the haemolymph into an open vascular tree without capillaries (worms). Arthropods developed contractile bulges on the abdominal aorta assisted by accessory hearts for wings or legs and by abdominal respiratory motions. Two-chamber heart (atrium and ventricle) appeared among mollusks. Vertebrates have a multi-chamber heart and a closed circulation with capillaries. Their heart has two chambers in fishes, three chambers (two atria and one ventricle) in amphibians and reptiles, and four chambers in birds and mammals. The ventricle of reptiles is partially divided in two cavities by an interventricular septum, leaving only a communication of variable size leading to a variable shunt. Blood pressure increases progressively from 15 mmHg (worms) to 170/70 mmHg (birds) according to the increase in metabolic rate. When systemic pressure exceeds 50 mmHg, a lower pressure system appears for the circulation through gills or lungs in order to improve gas exchange. A four-chamber heart allows a complete separation of systemic and pulmonary circuits. This review describes the circulatory pumping systems used in the different classes of animals, their advantages and failures, and the way they have been modified with evolution