Half-Life and Clearance of Cardiac Troponin I and Troponin T in Humans.

BACKGROUND: Cardiac troponin (cTn) is key in diagnosing myocardial infarction (MI). After MI, the clinically observed half-life of cTn has been reported to be 7 to 20 hours, but this estimate reflects the combined elimination and simultaneous release of cTn from cardiomyocytes. More precise timing of myocardial injuries necessitates separation of these 2 components. We used a novel method for determination of isolated cTn elimination kinetics in humans. METHODS: Patients with MI were included within 24 hours after revascularization and underwent plasmapheresis to obtain plasma with a high cTn concentration. After at least 3 weeks, patients returned for an autologous plasma retransfusion followed by blood sampling for 8 hours. cTn was measured with 5 different high-sensitivity cTn assays. RESULTS: Of 25 included patients, 20 participants (mean age, 64.5 years; SD, 8.2 years; 4 women [20%]) received a retransfusion after a median of 5.8 weeks (interquartile range, 5.0-6.9 weeks) after MI. After retransfusion of a median of 620 mL (range, 180-679 mL) autologous plasma, the concentration of cTn in participants' blood increased 4 to 445 times above the upper reference level of the 5 high-sensitivity cTn assays. The median elimination half-life ranged from 134.1 minutes (95% CI, 117.8-168.0) for the Elecsys high-sensitivity cTnT assay to 239.7 minutes (95% CI, 153.7-295.1) for the Vitros high-sensitivity cTnI assay. The median clearance of cTnI ranged from 40.3 mL/min (95% CI, 32.0-44.9) to 52.7 mL/min (95% CI, 42.2-57.8). The clearance of cTnT was 77.0 mL/min (95% CI, 45.2-95.0). CONCLUSIONS: This novel method showed that the elimination half-life of cTnI and cTnT was 5 to 16 hours shorter than previously reported. This indicates a considerably longer duration of cardiomyocyte cTn release after MI than previously thought. Improved knowledge of timing of myocardial injury may call for changes in the management of MI and other disorders with myocardial injury.

Single center outcomes after temporary mechanical circulatory assist device prior to Heartmate 3 implantation - a retrospective cohort study.

Objectives. Temporary mechanical circulatory support (TMCS) has become a component in the therapeutic strategy for treatment of cardiogenic shock as a bridge-to-decision. TMCS can facilitate recovery of cardiopulmonary function, end-organ function, and potentially reduce the surgical risk of left ventricular assist device (LVAD) implantation. Despite the improvements of hemodynamics and end-organ function, post-LVAD operative morbidity might be increased in these high-risk patients. The aim of the study was to compare outcomes after Heartmate 3 (HM3) implantation in patients with and without TMCS prior to HM3 implant. Methods. In this retrospective cohort study of all HM3 patients in the period between November 2015 and October 2021, patients with and without prior TMCS were compared. Patients' demographics, baseline clinical characteristics, laboratory tests, intraoperative variables, postoperative outcomes, and adverse events were collected from patient records. Results. The TMCS group showed an improvement in hemodynamics prior to LVAD implantation. Median TMCS duration was 19.5 (14-26) days. However, the TMCS group were more coagulopathic, had more wound infections, neurological complications, and more patients were on dialysis compared with patient without TMCS prior to HM3 implantation. Survival four years after HM3 implantation was 80 and 82% in the TMCS (N = 22) and non-TMCS group (N = 41), respectively. Conclusion. Patients on TMCS had an acceptable short and long-term survival and comparable to patients receiving HM3 without prior TMCS. However, they had a more complicated postoperative course.

Return to Work After Refractory Out-of-Hospital Cardiac Arrest in Patients Managed With or Without Extracorporeal Cardiopulmonary Resuscitation: A Nationwide Register-Based Study.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used for refractory out-of-hospital cardiac arrest (OHCA). However, survivors managed with ECPR are at risk of poor functional status. The purpose of this study was to investigate return to work (RTW) after refractory OHCA. METHODS AND RESULTS: Of 44 360 patients with OHCA in the period of 2011 to 2020, this nationwide registry-based study included 805 patients with refractory OHCA in the working age (18-65 years) who were employed before OHCA (2% of the total OHCA cohort). Demographics, prehospital characteristics, status at hospital arrival, employment status, and survival were retrieved through the Danish national registries. Sustainable RTW was defined as RTW for ≥6 months without any long sick leave relapses. Median follow-up time was 4.1 years. ECPR and standard advanced cardiovascular life support were applied in 136 and 669 patients, respectively. RTW 1 year after OHCA was similar (39% versus 54%; P=0.2) and sustainable RTW was high in both survivors managed with ECPR and survivors managed with standard advanced cardiovascular life support (83% versus 85%; P>0.9). Younger age and shorter length of hospitalization were associated with RTW in multivariable Cox analysis, whereas ECPR was not. CONCLUSIONS: In refractory OHCA-patients employed prior to OHCA, approximately 1 out of 2 patients were employed after 1 year with no difference between patients treated with ECPR or standard advanced cardiovascular life support. Younger age and shorter length of hospitalization were associated with RTW while ECPR was not.

Health-related quality of life and cognitive function after out-of-hospital cardiac arrest; a comparison of prehospital return-of-spontaneous circulation and refractory arrest managed with extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) for selected refractory out-of-hospital cardiac arrest (OHCA) is increasingly used. Detailed knowledge of health-related quality of life (HRQoL) and long-term cognitive function is limited. HRQoL and cognitive function were assessed in ECPR-survivors and OHCA-survivors with prehospital return of spontaneous circulation after standard advanced cardiac life support (sACLS). METHODS: Fifteen ECPR-survivors and 22 age-matched sACLS-survivors agreed to participate in this follow-up study. Participants were examined with echocardiography, 6-minute walk test, and neuropsychological testing, and answered HRQoL (EQ-5D-5L and Short Form 36 (SF-36)), and mental health questionnaires. RESULTS: Most patients were male (73 % and 82 %) and median age at follow-up was similar between groups (55 years and 60 years). Low flow time was significantly longer for ECPR-survivors (86 min vs. 15 min) and lactate levels were significantly higher (14.1 mmol/l vs. 3.9 mmol/l). No between-group difference was found in physical function nor in cognitive function with scores corresponding to the 23rd worst percentile of the general population. SACLS-survivors had HRQoL on level with the Danish general population while ECPR-survivors scored lower in both EQ-5D-5L (index score 0.73 vs. 0.86, p = 0.03, visual analog scale: 70 vs. 84, p = 0.04) and in multiple SF-36 health domains (role physical, bodily pain, general health, and mental health). CONCLUSIONS: Despite substantially longer low flow times with thrice as high lactate levels, ECPR-survivors were similar in cognitive and physical function compared to sACLS-survivors. Nonetheless, ECPR-survivors reported lower HRQoL overall and related to mental health, pain management, and the perception of limitations in physical role.

Use of prone position ventilation in patients with COVID-19 induced severe ARDS supported with V-V ECMO: A danish cohort study with focus on adverse events.

INTRODUCTION: Prone position ventilation (PPV) of patients with adult respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO) may improve oxygenation and alveolar recruitment and is recommended when extensive dorsal consolidations are present, but only few data regarding adverse events (AE) related to PPV in this group of patients have been published. METHODS: Nationwide retrospective analysis of 68 COVID-19 patients admitted from March 2020 - December 2021 with severe ARDS and need of V-V ECMO support. The number of patients treated with PPV, number of PPV-events, timing, the time spent in prone position, number and causes of AE are reported. Causes to stop the PPV regimen and risk factors for AE were explored. RESULTS: 44 out of 68 patients were treated with PPV, and 220 PPV events are evaluated. AE were identified in 99 out of 220 (45%) PPV events and occurred among 31 patients (71%). 1 fatal PPV related AE was registered. Acute supination occurred in 19 events (9%). Causes to stop the PPV regimen were almost equally distributed between effect (weaned from ECMO), no effect, death (of other reasons) and AE. Frequent causes of AE were pressures sores and ulcers, hypoxia, airway related and ECMO circuit related. Most AE occurred during patients first or second PPV event. CONCLUSIONS: PPV treatment was found to carry a high incidence of PPV related AE in these patients. Causes and preventive measures to reduce occurrence of PPV related AE during V-V ECMO support need further exploration.

Short-term outcomes after heart transplantation using donor hearts preserved with ex vivo perfusion.

The standard Conventional Cold Storage (CCS) during heart transplantation procurement is associated with time-dependent ischemic injury to the graft, which is a significant independent risk factor for post-transplant early morbidity and mortality - especially when cold ischemic time exceeds four hours. Since 2018, Rigshospitalet (Copenhagen, Denmark) has been utilising ex vivo perfusion (Organ Care System, OCS) in selected cases. The objective of this study was to compare the short-term clinical outcomes of patients transplanted with OCS compared to CCS. Methods: This retrospective single-centre study was based on consecutive patients undergoing a heart transplant between January 2018 and April 2021. Patients were selected for the OCS group when the cold ischemic time was expected to exceed four hours. The primary outcome measure was six-month event-free survival. Results: In total, 48 patients were included in the study; nine were transplanted with an OCS heart. The two groups had no significant differences in baseline characteristics. Six-month event-free survival was 77.8% [95% CI: 54.9-100%] in the OCS group and 79.5% [95% CI: 67.8-93.2%] in the CCS group (p = 0.91). While the OCS group had a median out-of-body time that was 183 min longer (p < 0.0001), the cold ischemic time was reduced by 51 min (p = 0.007). Conclusion: In a Scandinavian setting, our data confirms that utilising OCS in heart procurement allows for a longer out-of-body time and a reduced cold ischemic time without negatively affecting safety or early post-transplant outcomes.

First-in-Human Implantation of a New Transcatheter Tricuspid Valve Replacement System.

Therapeutic options for patients with isolated severe to torrential tricuspid regurgitation have been limited. Because a surgical option is often not attractive, new catheter-based therapies are emerging. We report the first-in-human percutaneous transcatheter tricuspid valve replacement with the MonarQ system in a 75-year-old female patient with severely symptomatic torrential tricuspid regurgitation. (Level of Difficulty: Advanced.).

Extracorporeal cardiopulmonary resuscitation: a national study on the association between favourable neurological status and biomarkers of hypoperfusion, inflammation, and organ injury.

AIMS: In refractory out-of-hospital cardiac arrest (OHCA) with prolonged whole-body ischaemia, global tissue injury proceeds even after establishment of circulation with extracorporeal cardiopulmonary resuscitation (ECPR). We aimed to investigate the role of biomarkers reflecting hypoperfusion, inflammation, and organ injury in prognostication of patients with refractory OHCA managed with ECPR. METHODS AND RESULTS: This nationwide retrospective study included 226 adults with refractory OHCA managed with ECPR in Denmark (2011-2020). Biomarkers the first days after ECPR-initiation were assessed. Odds ratio of favourable neurological status (Cerebral Performance Category 1-2) at hospital discharge was estimated by logistic regression analyses. Cut-off values were calculated using the Youden's index. Fifty-six patients (25%) survived to hospital discharge, 51 (91%) with a favourable neurological status. Factors independently associated with favourable neurological status were low flow time <81 min, admission leukocytes ≥12.8 × 109/L, admission lactate <13.2 mmol/L, alkaline phosphatase (ALP) < 56 (day1) or <55 U/L (day2), and day 1 creatine kinase MB (CK-MB) < 500 ng/mL. Selected biomarkers (leukocytes, C-reactive protein, and lactate) were significantly better predictors of favourable neurological status than classic OHCA-variables (sex, age, low-flow time, witnessed arrest, shockable rhythm) alone (P = 0.001) after hospital admission. CONCLUSION: Biomarkers of hypoperfusion (lactate), inflammation (leucocytes), and organ injury (ALP and CK-MB) were independently associated with neurological status at hospital discharge. Biomarkers of hypoperfusion and inflammation (at hospital admission) and organ injury (days 1 and 2 after ECPR) may aid in the clinical decision of when to prolong or terminate ECPR in cases of refractory OHCA.

Pressure Difference Estimation in Non-stenotic Carotid Bifurcation Phantoms Using Vector Flow Imaging.

Local pressure differences estimated using vector flow imaging (VFI) and direct catheterization in seven carotid bifurcation phantoms were compared with simulated pressure fields. VFI correlated strongly with simulated peak pressure differences (r = 0.99, p < 0.00001), with an average overestimation of 12.3 Pa (28.6%). The range between the lowest and highest pressure difference of VFI underestimated simulations by 4.6 Pa (8.06%; r = 0.99, p < 0.0001). The catheter method exhibited no correlation (r = -0.09, p = 0.85). Ten repeated measurements on one phantom revealed a small standard deviation (SD) for VFI (SD = 8.4%, mean estimated SD = 11.5%), but not for the catheter method (SD = 785.6%). An in vivo peak systolic pressure difference of 97.9 Pa (estimated SD = 30%) was measured using VFI in one healthy individual. This study indicates that VFI pressure difference estimation is feasible in phantoms and in vivo and realistic estimates of the SD can be attained from the data.

Mechanical circulatory support for refractory out-of-hospital cardiac arrest: a Danish nationwide multicenter study.

BACKGROUND: Mechanical circulatory support (MCS) with either extracorporeal membrane oxygenation or Impella has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). The objective of this study was to describe the gradual implementation, survival and adherence to the national consensus with respect to use of MCS for OHCA in Denmark, and to identify factors associated with outcome. METHODS: This retrospective, observational cohort study included patients receiving MCS for OHCA at all tertiary cardiac arrest centers (n = 4) in Denmark between July 2011 and December 2020. Logistic regression and Kaplan-Meier survival analysis were used to determine association with outcome. Outcome was presented as survival to hospital discharge with good neurological outcome, 30-day survival and predictors of 30-day mortality. RESULTS: A total of 259 patients were included in the study. Thirty-day survival was 26%. Sixty-five (25%) survived to hospital discharge and a good neurological outcome (Glasgow-Pittsburgh Cerebral Performance Categories 1-2) was observed in 94% of these patients. Strict adherence to the national consensus showed a 30-day survival rate of 30% compared with 22% in patients violating one or more criteria. Adding criteria to the national consensus such as signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow < 100 min, pH > 6.8 and lactate < 15 mmol/L increased the survival rate to 48%, but would exclude 58% of the survivors from the current cohort. Logistic regression identified asystole (RR 1.36, 95% CI 1.18-1.57), pulseless electrical activity (RR 1.20, 95% CI 1.03-1.41), initial pH < 6.8 (RR 1.28, 95% CI 1.12-1.46) and lactate levels > 15 mmol/L (RR 1.16, 95% CI 1.16-1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had reduced risk of 30-day mortality (RR 0.63, 95% CI 0.52-0.76). CONCLUSIONS: A high survival rate with a good neurological outcome was observed in this Danish population of patients treated with MCS for OHCA. Stringent patient selection for MCS may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors.

[Extracorporeal membrane oxygenation therapy of acute respiratory distress syndrome in adults in Denmark].

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is an established treatment option in critically ill patients with acute respiratory distress syndrome (ARDS). The overall mortality in patients with ARDS has fallen over the past 30 years. VV-ECMO for selected patients has contributed to this. In Denmark, VV-ECMO is centralised to Aarhus University Hospital and Rigshospitalet, as it is a complex multidisciplinary therapy. The treatment involves many specialities and personnel groups, all with special training and experience. This review presents the current literature in the ARDS and ECMO treatment.

Advances in critical care management of patients undergoing cardiac surgery.

Cardiac surgery has been evolving to include minimally invasive, hybrid and transcatheter techniques. Increasing patient age and medical complexity means that critical care management needs to adapt and evolve. Recent advances have occurred in several areas, including ventilation, haemodynamics and mechanical circulatory support, bleeding and coagulation, acute kidney injury, and neurological management. This narrative review describes standard care, recent advances, and future areas of research in the critical care management of patients undergoing cardiac surgery.