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Introduction: Early oxygen debt repayment is predictive of successful weaning from veno-arterial extracorporeal membrane oxygenation (V-A ECMO). However, studies are limited by the patient cohort's heterogeneity. This study aimed to understand the early state of oxygen debt repayment and its association with end-organ failure and 30-day survival using cluster analysis., Methods: A retrospective, single-center study was conducted on 153V-A ECMO patients. Patients were clustered using a two-step cluster analysis based on oxygen debt and its repayment during the first 24 h of ECMO. Primary outcomes were end-organ failure and 30-day survival., Results: The overall mortality was 69.3%. For cluster analysis, 137 patients were included, due to an incomplete data set. The mortality rate in this subset was 67.9%. Three clusters were generated, representing increasing levels of total oxygen debt from cluster 1 to cluster 3. Thirty-day survival between clusters was significantly different (cluster 1: 46.9%, cluster 2: 23.4%, and cluster 3: 4.8%, p = 0.001). Patients in cluster 3 showed less decrement in liver enzymes, creatinine, and urea blood levels. There were significant differences in the baseline oxygen debt and the need for continuous veno-venous hemofiltration (CVVH) between survivors and non-survivors (p < 0.05). Forty-seven patients (34.3%) migrated between clusters within the first 24 h of support. Among these patients, 43.4% required CVVH. Notably, patients requiring CVVH and who migrated to a cluster with a higher oxygen debt repayment showed better survival rates compared to those who migrated to a cluster with a lower oxygen debt repayment., Conclusions: Oxygen debt repayment during the first 24 h of V-A ECMO shows to correspond with survival, where the baseline oxygen debt value and the necessity for continuous kidney replacement therapy appear to be influential., (© 2022. The Author(s).)

Introduction: Myocardial infarction with non-obstructive coronary arteries (MINOCA) predominantly affects younger females. Women with a history of gestational hypertension (GH), preeclampsia (PE), and gestational diabetes mellitus (GDM) are subjected to an elevated lifetime risk of cardiovascular disease. However, data on the potential association between these obstetric complications and MINOCA is lacking. Therefore, the current study aimed to provide insight in the prevalence of metabolic and hypertensive pregnancy disorders (MHPD) in MINOCA patients and their clinical characteristics., Methods: In this observational cohort study conducted at the Zuyderland Medical Center and Maastricht University Medical Center in the Netherlands, patients were enrolled if they were identified as having MINOCA. Data on individual patient characteristics, laboratory results, electrocardiography as well as (non-)invasive imaging procedures were derived from the electronic health record system. Patients were asked to complete a questionnaire about prior MHPD including GDM, GH, and PE. Patients were grouped into those with MHPD and those with prior uncomplicated normotensive pregnancy (or pregnancies; NP)., Results: After excluding patients without 1-year follow-up ( n = 53), 86 female MINOCA patients remained eligible for analysis. Of the total female population, 25 (29.1%) patients had MHPD, including GH ( n = 19; 22.1%), PE ( n = 4; 4.7%), and GDM ( n = 7; 8.1%). The MHPD patients showed higher rates of chronic hypertension (84.0 vs. 55.7%; p = 0.013), hypercholesterolemia (64.0 vs. 34.4%; p = 0.012), a family history of CVD (84.0 vs. 45.9%; p = 0.001), gout or rheumatic arthritis (16.0 vs. 1.6%; p = 0.024), and were more often non-smokers (45.8 vs. 78.3%; p = 0.004), compared to the NP patients. Moreover, MHPD patients were more likely to use cardiovascular medications at baseline. A trend toward no specific cause found for the MINOCA event was observed in MHPD patients compared to the NP group (64.0 vs. 42.6%, p = 0.072)., Conclusion: A history of metabolic and hypertensive pregnancy disorders occurred in one-third of female MINOCA patients. In these patients, conventional cardiovascular risk factors were more prevalent compared to NP patients. In most MHPD patients, the specific cause for MINOCA remained unclear., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pustjens, Vranken, Jansen, Winkler, Stein, Hoebers, Kietselaer, Spaanderman, Rasoul, Ghossein-Doha and van 't Hof.)

Background: The optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) admitted with acute coronary syndrome (ACS) and treated with a drug-eluting stent (DES) remains unclear. This is a prespecified sub-study from the Randomised Evaluation of short-term DUal antiplatelet therapy in patients with acute Coronary syndromE treated with a new generation DES (REDUCE) trial that was designed to determine the efficacy and safety of short-term versus standard 12 months DAPT in diabetic patients with ACS undergoing percutaneous coronary intervention (PCI) using the COMBO stent., Methods: In this study we included ACS diabetic patients enroled in the REDUCE trial treated with the COMBO stent and randomly assigned to either 3 or 12 months of DAPT. The primary study endpoint was the composite of all-cause mortality, myocardial infarction (MI), stent thrombosis (ST), stroke, target vessel revascularisation (TVR), and bleeding complications at 12 and 24 months follow-up., Results: A total of 307 diabetic patients were included, of which 162 (52.8%) in the 3 months DAPT group and 145 (47.2%) in the 12 months DAPT group. Patient characteristics, PCI success, and number of stents used were similar in the 3 and 12 months DAPT groups. Occurrence of the primary study endpoint at 12 and 24 months follow-up was comparable between the two groups (3.1 vs. 3.5%, p = 0.865, and 15.8 vs. 14.9%, p = 0.824, respectively). Moreover, the prevalence of the specific clinical outcome parameters (all-cause mortality), MI, ST, stroke, TVR, and bleeding was similar in both study groups., Conclusions: This sub-analysis shows similar clinical outcomes following 3 months DAPT as compared to 12 months DAPT in diabetic patients undergoing PCI for ACS using the COMBO stent. These results suggest that, even in this particular subset of patients, short duration of DAPT might be considered safe. Future larger studies are warranted to provide more precise estimations in terms of safety and efficacy of short term DAPT in these high-risk patients., (© 2022 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Although recent studies revealed suboptimal outcomes in patients with myocardial infarction with nonobstructive coronary arteries (MINOCAs), the underlying etiology remains unknown in most patients. Therefore, adequate treatment modalities have not yet been established. We aimed to assess demographics, treatment strategies, and long-term clinical outcome in MINOCA subgroups. We retrospectively analyzed data from a large, prospective observational study of patients with acute coronary syndrome admitted to the Isala hospital in Zwolle, The Netherlands between 2006 and 2014. Patients with MINOCA were divided into subgroups based on the underlying cause of the event. From 7,693 patients, 402 patients (5%) concerned MINOCA. After the exclusion of missing cases (n = 47), 5 subgroups were distinguished: "true" acute myocardial infarction (10%), perimyocarditis (13%), cardiomyopathy (including Takotsubo cardiomyopathy) (19%), miscellaneous causes (21%), and an indeterminate group (38%). Patients with cardiomyopathy were predominantly women (78%) and showed the highest incidence of major adverse cardiovascular events at 30 days follow-up (7%; p = 0.012), 1 year (19%; p = 0.004), and mortality at long-term follow-up (27%; p = 0.010) compared with any other MINOCA subgroup. The cardiomyopathy group was followed by the indeterminate group, with major adverse cardiovascular events rates of 1% and 5%, respectively, and 17% long-term all-cause mortality. In conclusion, long-term prognosis in MINOCA depends on the underlying etiology. Prognosis is worst in the cardiomyopathy group followed by the indeterminate group. This underlines the importance of revealing the diagnosis to ultimately optimize treatment., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has been used successfully for the past decade in adult patients with acute respiratory distress syndrome (ARDS) refractory to conventional ventilatory support. However, knowledge of the health-related quality of life (HRQoL) in VV-ECMO patients is still limited. Thus, this study aimed to provide a comprehensive overview of the HRQoL following VV-ECMO support in ARDS patients., Methods: A systematic search was performed on PubMed and Web of Science databases from January 1st, 2009 to October 19th, 2020. Studies reporting on HRQoL following VV-ECMO for ARDS in adults were included. Two authors independently selected studies, extracted data, and assessed methodological quality., Results: Eight studies were eligible for inclusion, consisting of seven observational studies and one randomized controlled trial (total N = 441). All eight studies had a quantitative design and reported 265 VV-ECMO survivors to have a reduced HRQoL compared to a generally healthy population. Follow-up time varied between six months to three years. Additionally, only four studies (total N = 335) compared the HRQoL of VV-ECMO (N = 159) to conventionally treated survivors (N = 176), with one study showing a significantly better HRQoL in VV-ECMO survivors, while three studies were stating comparable HRQoL across groups. Notably, most survivors in these studies appeared to experience varying degrees of anxiety, depression, and post-traumatic stress disorder (PTSD)., Conclusions: ARDS survivors supported by VV-ECMO have a decline in HRQoL and suffered from physical and psychological impairments. This HRQoL reduction is comparable or even better to the HRQoL in conventionally treated ARDS survivors., (© 2021. The Author(s).)

Background: Many patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) are discharged without a known aetiology for their clinical presentation. This study sought to assess the effect of this 'indeterminate MINOCA' diagnosis on the prevalence of recurrent cardiovascular events and presentations to the Cardiac Emergency Department (CED)., Methods: We retrospectively analysed all patients meeting the diagnostic MINOCA criteria presenting at a large secondary hospital between January 2017 and April 2019., Participants: Patients were divided into the (1) 'indeterminate MINOCA', or (2) 'MINOCA with diagnosis' group. The primary outcome was the occurrence of major adverse cardiac events (MACE) defined as the composite of all-cause mortality, non-fatal myocardial infarction, stroke and any revascularisation procedure. Secondary outcomes were all recurrent visits at the CED, and MACE including unplanned cardiac hospitalisation., Results: In 62/198 (31.3%) MINOCA patients, a conclusive diagnosis was found (myocardial infarction, (peri)myocarditis, cardiomyopathy, or miscellaneous). MINOCA patients with a confirmed diagnosis were younger compared to those with an indeterminate diagnosis (56.7 vs. 62.3 years, p = 0.007), had higher maximum troponin-T [238 ng/L vs. 69 ng/L, p < 0.001] and creatine kinase (CK) levels [212U/L vs. 152U/L, p = 0.007], and presented more frequently with electrocardiographic signs of ischaemia (71.0% vs. 47.1%, p = 0.002). Indeterminate MINOCA patients more often showed recurrent CED presentations (36.8% vs. 22.6%, p = 0.048), however the occurrence of cardiovascular events was equal (8.8 vs. 8.1%, p = 0.86). Multivariable analysis showed that elevated levels of troponin-T and CK, ST-segment deviation on electrocardiography, reduced left ventricular ejection fraction, regional wall motion abnormalities, and performance of additional examination methods were independent predictors for finding the underlying MINOCA cause., Conclusions: Only in one-third of MINOCA patients a conclusive diagnosis for the acute presentation was identified. Recurrent CED visits were more often observed in the indeterminate MINOCA group, while the occurrence of cardiovascular events was similar across groups., Trial Registration: Retrospectively registered., (© 2021. The Author(s).)

Heparin anticoagulation monitoring by point-of-care activated clotting time (ACT) is essential for cardiopulmonary bypass (CPB) initiation, maintenance, and anticoagulant reversal. Concerns exist regarding the comparability of kaolin activated ACT devices. The current study, therefore, evaluated the agreement of ACT assays using parallel measurements performed on two commonly used devices. Measurements were conducted in a split-sample fashion on both the ACT Plus (Medtronic, Minneapolis, MN) and i-STAT (Abbott Point of Care, Princeton, NJ) analyzers. Blood samples from 100 adult patients undergoing elective cardiac surgery with CPB were assayed at specified time points: before heparinization, following systemic heparinization, after CPB initiation, every 30 minutes during CPB, and following protamine administration. A cutoff value of 400 seconds (s) was used as part of the local protocol. Measurements were compared using t tests or Wilcoxon signed-rank tests, linear regression, and Bland-Altman analyses. Parallel ACT measurements demonstrated a good linear correlation ( r = .831, p < .001). The overall median difference between both measurements was significantly different from zero, amounting to 87 (14-189) ( p < .001), with limits of agreement of -124 and 333s. The i-STAT-derived ACT values were systematically lower than the ACT Plus values, which was more pronounced during CPB. Fourteen patients received additional heparin during CPB at a median ACT Plus value of 414s, with a concomitant median i-STAT value of 316s. Assuming 308s as the theoretical i-STAT cutoff value based on the linear regression equation and an ACT Plus threshold of 400s, 29 patients would have received additional heparin. Based on these results, kaolin point-of-care ACT devices cannot be used interchangeably. Device-specific predefined target values are warranted to avert heparin overdosing during CPB., (© Copyright 2021 AMSECT.)

Background. Postoperative monitoring of deep inferior epigastric perforator (DIEP) flaps for breast reconstruction using noninvasive tissue oximetry enables timely recognition of vascular compromise. This may limit ischemic tissue damage, minimizing postoperative morbidity and healthcare costs. The aim of this review was to provide an economic analysis of tissue oximetry for postoperative monitoring of DIEP flap breast reconstruction. Methods. A systematic literature search was conducted utilizing PubMed and Embase. Articles reporting costs related to tissue oximetry following DIEP flap breast reconstruction, costs directly related to DIEP flap surgical procedure, and costs associated with postoperative complications were included. Risk of bias was assessed using different tools depending on study type. Results. Six articles were included. Four studies provided an overview of total costs associated with DIEP flap breast reconstruction; two studies focused on whether tissue oximetry could facilitate a decrease in hospital costs. Average overall costs for DIEP flap procedure were estimated at $28 000, with additional costs up to $37 530 in case of total flap failure. Tissue oximetry to monitor DIEP flaps could potentially save up to $1667 per procedure. Moreover, it might eliminate the need for specialized postoperative care. Conclusion. Tissue oximetry following DIEP flap breast reconstruction can potentially facilitate a decrease in hospital costs since its readings enable physicians to intervene in an early stage of tissue malperfusion, contributing to minimizing complications. Tissue oximetry may eliminate the need for specialized postoperative care. However, based on the current literature, no firm conclusions can yet be drawn regarding cost-effectiveness of standard implementation.

Aims: Whether patients with MINOCA (myocardial infarction with non-obstructive coronary arteries) have better outcomes than patients with obstructive coronary artery disease remains contradictory. The current study focussed on the clinical profile and prognosis of MINOCA patients., Methods and Results: We performed a retrospective analysis of patients with acute coronary syndrome (ACS) admitted to the Isala hospital in Zwolle, the Netherlands, between 2006 and 2014. A total of 7693 patients were categorized into three groups: MINOCA, single-vessel obstructive ACS (SV-ACS), and multi-vessel obstructive ACS (MV-ACS). MINOCA patients (5.2% of the total population) were more likely to be female (51.5% vs. 30.3% and 26.0% in SV-ACS and MV-ACS, respectively, p < 0.001 for both). The prevalence of risk factors in the MINOCA group was in between the SV-ACS and MV-ACS groups. Logistic regression revealed a lower odds of dying in SV-ACS (odds ratio (OR) = 0.70 (p = 0.04)) and a similar odds in MV-ACS (OR = 0.88, p = 0.45) compared to MINOCA., Conclusions: Patients with MINOCA show an 'intermediate' risk profile with mortality rates in between those of both ACS groups. Hence, MINOCA should be recognised as a potential risk factor for mortality, requiring adequate treatment and follow-up., Competing Interests: The authors declare that they have no known competing financial interests or personal relation which could have affected the work reported in this paper., (© 2020 The Authors.)

Femoral access in extracorporeal life support (ECLS) has been associated with regional variations in arterial oxygen saturation, potentially predisposing the patient to ischemic tissue damage. Current monitoring techniques, however, are limited to intermittent bedside evaluation of capillary refill among other factors. The aim of this study was to assess whether cerebral and limb regional tissue oxygen saturation (rSO 2 ) values reflect changes in various patient-related parameters during venoarterial ECLS (VA-ECLS). This retrospective observational study included adults assisted by femorofemoral VA-ECLS. Bifrontal cerebral and bilateral limb tissue oximetry was performed for the entire duration of support. Hemodynamic data were analyzed parallel to cerebral and limb rSO 2 . A total of 23 patients were included with a median ECLS duration of 5 [1-20] days. Cardiac arrhythmias were observed in 12 patients, which was associated with a decreased mean rSO 2 from 61%±11% to 51%±10% during atrial fibrillation and 67%±9% to 58%±10% during ventricular fibrillation ( P <0.001 for both). A presumably sudden increase in cardiac output due to myocardial recovery (n=8) resulted in a significant decrease in mean cerebral rSO 2 from 73%±7% to 54%±6% and from 69%±9% to 53%±8% for the left and right cerebral hemisphere, respectively ( P =0.012 for both hemispheres). Also, right radial artery partial gas pressure for oxygen decreased from 15.6±2.8 to 8.3±1.9 kPa ( P =0.028). No differences were found in cerebral desaturation episodes between patients with and without neurologic complications. In six patients, limb rSO 2 increased from on average 29.3±2.7 to 64.0±5.1 following insertion of a distal cannula in the femoral artery ( P =0.027). Likewise, restoration of flow in a clotted distal cannula inserted in the femoral artery was necessary in four cases and resulted in increased limb rSO 2 from 31.3±0.8 to 79.5±9.0; P =0.068. Non-invasive tissue oximetry adequately reflects events influencing cerebral and limb perfusion and can aid in monitoring tissue perfusion in patients assisted by ECLS.

Non-invasive tissue oximetry is a monitoring method for continuous assessment of tissue oxygenation, which may aid in detection of hemodynamic instability and otherwise unnoticed hypoxia. Numerous studies focused on using non-invasive tissue oximetry intraoperatively, proposing its predictive value in relation to clinical outcome. Tissue oximetry may be part of standard monitoring practice for brain monitoring during cardiac surgery in many clinical centers; however, the monitoring method can be deployed in numerous clinical settings. This succinct overview aims to determine the role of non-invasive tissue oximetry in current clinical practice.

Postoperative neurological complications (PNCs) following cardiac surgery with cardiopulmonary bypass (CPB) is a detrimental complication, contributing to increased mortality rates and health care costs. To prevent intraoperative cerebral desaturations associated with PNC, continuous brain monitoring using near-infrared spectroscopy has been advocated. However, clear evidence for a defined desaturation threshold requiring intervention during CPB is still lacking. Since cerebral oximetry readings are nonspecific, cerebral tissue oxygenation values need to be interpreted with caution and in the context of all available clinical information. Therefore, maintaining an intact autoregulatory activity during CPB rather than solely focusing on regional cerebral oxygen saturation measurements will collectively contribute to optimization of patient care during CPB.